This meta-analysis combines data from 5 randomized controlled trials investigating adjuvant chemotherapy and chemoradiation for pancreatic cancer. It includes individual patient data from 875 patients across 4 trials, as well as previously unpublished updated follow-up data from 261 additional patients in the ESPAC1 trial. The analysis found that chemotherapy significantly reduced the risk of death, with median survival of 19 months with chemotherapy versus 13.5 months without. However, chemoradiation did not significantly reduce the risk of death compared to no adjuvant treatment, with median survivals of 15.8 months and 15.2 months respectively. Subgroup analyses suggested chemoradiation may be more effective for patients with positive resection margins, while chemotherapy was less effective for this
1. This meta-analysis included 7 studies comparing outcomes for GBM patients receiving extended adjuvant temozolomide (more than 6 cycles) versus standard 6 cycles.
2. The results showed that overall survival and progression-free survival were significantly higher in patients receiving more than 6 cycles of temozolomide compared to 6 cycles.
3. However, there was high heterogeneity between the studies. The meta-analysis concluded that regimens aiming to prolong temozolomide exposure or increase cumulative dose cannot replace the standard 5-day regimen in clinical practice.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
Critical evaluation of an article titled " Systematic review of basket trials, umbrella trials, and platform trials: A landscape analysis of master protocols"
Gemcitabine and Cisplatin In Metastatic Carcinoma Gallbladder. A Single Insti...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: effica...Enrique Moreno Gonzalez
This document summarizes a prospective, randomized, phase II clinical trial that evaluated the efficacy and safety of neoadjuvant chemotherapy with or without rh-endostatin for breast cancer. 68 patients received either 3 cycles of docetaxel and epirubicin (DE) chemotherapy alone or DE chemotherapy combined with rh-endostatin. The combination therapy showed a higher objective response rate of 91% compared to 68% for chemotherapy alone, with more complete responses but no increase in adverse effects. The combination appeared to work better in premenopausal patients and those with better performance status.
This document summarizes the results of a study that evaluated the health care resource utilization and costs of patients with symptomatic multiple myeloma in the United Kingdom. The study found that the average total cost per treatment line was £34,296, with most costs attributed to anti-tumor drugs. The average cost per month of active treatment was £5,168. For patients receiving best supportive care after discontinuing active treatment, the average total cost was £1,444 if they progressed or £2,480 if they did not progress before death.
Personalized Medicine in Diagnosis and Treatment of Cancer Maryam Rafati
The document discusses next generation sequencing (NGS) and its applications in personalized medicine for cancer diagnosis and treatment. It provides examples of several families with hereditary cancer syndromes who were analyzed using NGS to identify pathogenic variants. The results demonstrated higher response rates and prolonged progression-free and overall survival for cancer patients receiving personalized treatments based on biomarkers identified by NGS, compared to non-personalized treatments. NGS can detect somatic and germline mutations to classify cancers at a molecular level and guide precision oncology.
1. This meta-analysis included 7 studies comparing outcomes for GBM patients receiving extended adjuvant temozolomide (more than 6 cycles) versus standard 6 cycles.
2. The results showed that overall survival and progression-free survival were significantly higher in patients receiving more than 6 cycles of temozolomide compared to 6 cycles.
3. However, there was high heterogeneity between the studies. The meta-analysis concluded that regimens aiming to prolong temozolomide exposure or increase cumulative dose cannot replace the standard 5-day regimen in clinical practice.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
Critical evaluation of an article titled " Systematic review of basket trials, umbrella trials, and platform trials: A landscape analysis of master protocols"
Gemcitabine and Cisplatin In Metastatic Carcinoma Gallbladder. A Single Insti...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: effica...Enrique Moreno Gonzalez
This document summarizes a prospective, randomized, phase II clinical trial that evaluated the efficacy and safety of neoadjuvant chemotherapy with or without rh-endostatin for breast cancer. 68 patients received either 3 cycles of docetaxel and epirubicin (DE) chemotherapy alone or DE chemotherapy combined with rh-endostatin. The combination therapy showed a higher objective response rate of 91% compared to 68% for chemotherapy alone, with more complete responses but no increase in adverse effects. The combination appeared to work better in premenopausal patients and those with better performance status.
This document summarizes the results of a study that evaluated the health care resource utilization and costs of patients with symptomatic multiple myeloma in the United Kingdom. The study found that the average total cost per treatment line was £34,296, with most costs attributed to anti-tumor drugs. The average cost per month of active treatment was £5,168. For patients receiving best supportive care after discontinuing active treatment, the average total cost was £1,444 if they progressed or £2,480 if they did not progress before death.
Personalized Medicine in Diagnosis and Treatment of Cancer Maryam Rafati
The document discusses next generation sequencing (NGS) and its applications in personalized medicine for cancer diagnosis and treatment. It provides examples of several families with hereditary cancer syndromes who were analyzed using NGS to identify pathogenic variants. The results demonstrated higher response rates and prolonged progression-free and overall survival for cancer patients receiving personalized treatments based on biomarkers identified by NGS, compared to non-personalized treatments. NGS can detect somatic and germline mutations to classify cancers at a molecular level and guide precision oncology.
Сравнение эффективности препаратов Карбоплатин (Carboplatin) и Паклитаксел (P...oncoportal.net
Сравнение эффективности препаратов Карбоплатин (Carboplatin) и Паклитаксел (Paclitaxel) при добавлении препарата Бевацизумаб (Bevacizumab) и без него для лечения одной их форм рака легкого у пациентов старше 65 лет
in Older Patients With Advanced Non–Small Cell Lung Cancer
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
Ten years experience in the management of borderline ovarianTariq Mohammed
This study summarizes the experience of managing 138 patients with borderline ovarian tumors at the Tom Baker Cancer Centre over a 10-year period. The patients were divided into two groups based on whether they received complete or incomplete surgical staging. The recurrence rate was similar between the groups, at 5.6% for those with complete staging and 8.2% for incomplete staging. Surgical staging was still found to be important as it identified two patients with invasive implants that required chemotherapy. Microinvasion was identified as a risk factor for recurrence. The study concludes that while the need for restaging surgery remains controversial, close follow-up is important for patients undergoing conservative surgery.
1. The document analyzes changes in treatment strategies for metastatic colorectal cancer in Germany between 2005-2007 based on data from large population surveys. It finds that results from clinical trials showing increased effectiveness of new drugs like oxaliplatin and irinotecan were quickly implemented in clinical practice.
2. The treatment objective of achieving secondary resection of metastases after chemotherapy increased significantly from 18% to 27% during this period, as clinical trials showed biologicals improving resectability rates. Biologicals were used more often when secondary resection was the goal compared to other objectives.
3. A multivariate analysis found that while many factors influenced treatment choices, the objective of secondary resection and patient age had the most significant impact
This study performed a cost-effectiveness analysis of adjuvant chemoradiotherapy for resected gastric cancer based on results from the Intergroup 0116 trial. The analysis found that the incremental cost of adding chemoradiotherapy was $20,100 and provided an additional 0.53 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio of $38,400 per quality-adjusted life year gained. A probabilistic sensitivity analysis predicted a 67% likelihood that the ratio would be less than $50,000 per quality-adjusted life year, which compares favorably to other widely used cancer treatments.
This document summarizes a drug use evaluation (DUE) of daptomycin from June to October 2014. Data was collected from 21 patients on daptomycin, but 10 patients were excluded for reasons such as duplication, not completing therapy, or having an actual body weight less than 130% of ideal body weight. The remaining 10 patients were included in the analysis. Most patients were dosed using adjusted body weight and had indications of MRSA infections or reactions to vancomycin. Adverse reactions occurred in 2 patients. Outcomes included resolution of infection in 5 patients, discontinuation due to adverse reactions in 2 patients, and discontinuation due to lack of efficacy in 3 patients. The study had a small sample size making it
Aim: to evaluate the effi cacy and tolerability of electro-hyperthermia (ET) for the treatment of relapsed malignant glioma.
Methods: this was a retrospective observational clinical study. Patients were included in the study if they had >18 years, informed consent signed, histological diagnosis of malignant glioma, failure of previous temozolamide-based chemotherapy and radiotherapy, indication for treatment with ET.
Hyperthermia was performed with short radiofrequency waves of 13.56 MHz using a capacitive coupling technique keeping the skin surface at 26 C°. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumors was above 40 C° for more than 90% of the treatment duration (20-60 minutes gradually).
1. The study analyzed treatment patterns over time in patients receiving first-line chemotherapy for advanced or metastatic esophageal or gastric cancer based on data from 2,808 patients documented in Therapiemonitor from 2006-2013.
2. Treatment intensity increased over time, with 49.3% of patients receiving triplet chemotherapy in 2013 compared to just 10.1% in 2006. HER2 testing rates increased from 49.1% in earlier studies to 79.1% in 2012-2013, though testing was still not always performed according to guidelines.
3. Usage of fluoropyrimidine/cisplatin combinations with trastuzumab declined from 67% in 2010-2011 to 50% in 2012-2013
Global Academic Program of MD Anderson Cancer Centerspa718
The Global Academic Programs (GAP) at MD Anderson Cancer Center supports the institution's mission of eliminating cancer globally through its Sister Institution Network of 33 cancer centers in 24 countries. GAP facilitates collaboration between MD Anderson and its sister institutions across key areas of patient care, research, prevention, and education. Notable activities include referring international patients for second opinions and treatment through the Sister Institution Referral Assistance Center, funding collaborative research projects through the Sister Institution Network Fund, increasing global cancer publications and clinical trials, implementing tobacco control programs, and convening an annual conference to foster networking.
This journal club discussion summarizes a randomized controlled trial that compared the glucose-lowering drug rosiglitazone to metformin and glyburide in patients with recently diagnosed type 2 diabetes. The study was well-designed, experimental in nature, and included over 4,000 patients followed for a median of 4 years. The primary outcome was time to monotherapy failure based on fasting glucose levels. The results showed that rosiglitazone delayed monotherapy failure better than the other drugs and had a lower incidence of progression to higher fasting glucose levels. However, the study also reported some safety concerns with rosiglitazone like increased risk of heart failure. Overall, the discussant found the study to be valid and that the
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
This document summarizes a meta-analysis that evaluated the efficacy and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Eight randomized controlled trials involving 583 patients were included. The analysis found that compared to Western medicine alone, Astragalus injection improved treatment efficacy, improved patient quality of life, reduced leukopenia, reduced neurotoxicity, and reduced nausea and vomiting. The quality of the included studies was acceptable. In conclusion, Astragalus injection can reduce toxicity and improve the efficacy of conventional Western medicine in treating colorectal cancer.
Abstract—Colorectal cancer is leading cancer-related public health problem. This study was conducted to determine the effect of High-Dose-Rate intraluminal brachytherapy (HDR-BT) with or without interstitial brachytherapy during neoadjuvant chemoradiation for locally advanced rectal cancer. This randomized contrial was conducted on 28 patients attended with locally advanced rectal cancer (T3, T4 or N+) treated initially with concurrent capecitabine (800 mg/m2 twice daily for 5 days per week) and pelvic external beam radiation therapy (45Gy in 25 Fractions) after one week MRI for all patients; received intraluminal HDR-BT with 4Gy x 2 Fractions with one week interval for those had gross residual disease within 1cm of rectal wall and receiveed intraluminal and interstitial brachytherapy with 4Gy x 2 Fractions with one week interval for those had gross residual disease far from 1cm of rectal wall. All patients underwent surgery within 4-8 week after completion of neoadjuvant therapy. In the control group which were not randomized, twenty-eight patients underwent neoadjuvant chemoradiation (45Gy in 25 Fraction with concurrent capecitabine 800mg/m2 twice daily for 5 days per week) followed by surgery. It was found that in HDR-BT group pathologic complete response (pCR), pathologic partial response (pPR) and pathologic response rates (pCR+pPR) based on AJCC TNM staging for colorectal cancer were %35.7, %35.7, and %71.4 respectively. The pCR, pPR, and pRR were %25, %17, and %42 in the control group respectively. pCR, pPR, and pRR were improved with HDR-BT. However, only response rate improvement was statistically significant (p=0.031). There was no a statistically significant difference in the complications between the two groups (p > 0.05). So it can be concluded that HDR intraluminal with or without interstitial brachytherapy may be an effective method of dose escalation technique in neoadjuvant chemoradiation therapy of locally advanced rectal cancer with higher response rate and manageable side effects.
This study compared different chemotherapy and radiotherapy regimens for patients with early unfavorable Hodgkin's lymphoma. The study found:
1) 4 cycles of ABVD chemotherapy followed by 30Gy radiotherapy was as effective as 4 cycles of BEACOPP chemotherapy followed by either 30Gy or 20Gy radiotherapy.
2) However, 4 cycles of ABVD followed by a reduced radiotherapy dose of 20Gy was inferior to the other regimens and resulted in worse patient outcomes.
3) A reduction of radiotherapy dose from 30Gy to 20Gy is only possible when combined with a more intensive chemotherapy regimen like BEACOPP, not a less intensive regimen like ABVD.
Percutaneous image-guided cryoablation of spinal metastases: A systematic reviewAhmad Ozair
Percutaneous cryoablation (PCA) is a minimally invasive technique that has been recently used to treat spinal metastases with a paucity of data currently available in the literature. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective or retrospective studies concerning metastatic spinal neoplasms treated with current generation PCA systems and with available data on safety and clinical outcomes were included. In the 8 included studies (7 retrospective, 1 prospective), a total of 148 patients (females = 63%) underwent spinal PCA. Tumors were located in the cervical (3/109 [2.8%], thoracic (74/109 [68.8%], lumbar (37/109 [33.9%], and sacrococcygeal (17/109 [15.6%] regions. Overall, 187 metastatic spinal lesions were treated. Thermo-protective measures (e.g., carbo-/hydro-dissection, thermocouples) were used in 115/187 [61.5%] procedures. For metastatic spinal tumors, the pooled mean difference (MD) in pain scores from baseline on the 0–10 numeric rating scale was 5.03 (95% confidence interval [CI]: 4.24 to 5.82) at a 1-month follow-up and 4.61 (95% CI: 3.27 to 5.95) at the last reported follow-up (range 24–40 weeks in 3/4 studies). Local tumor control rates ranged widely from 60% to 100% at varying follow-ups. Grade I-II complications were reported in 9/148 [6.1%] patients and grade III-V complications were reported in 3/148 [2.0%]) patients. PCA, as a stand-alone or adjunct modality, may be a viable therapy in appropriately selected patients with painful spinal metastases who were traditionally managed with open surgery and/or radiation therapy.
- Larotrectinib, a TRK inhibitor, showed marked antitumor activity in 55 patients with TRK fusion-positive cancers of various types who were enrolled in three clinical studies.
- The overall response rate was 75% according to independent review and 80% according to investigators. At one year, 71% of responses were ongoing and 55% of patients remained progression-free.
- Adverse events were predominantly grade 1. No grade 3-4 adverse events related to larotrectinib occurred in more than 5% of patients, and no patients discontinued treatment due to drug-related adverse events.
Metronomic chemotherapy involves the chronic administration of chemotherapy drugs at low, minimally toxic doses on a frequent schedule with no prolonged breaks. This strategy aims to control cancer by targeting tumor vasculature and is an attractive option in resource-limited areas due to its low cost, oral administration, and minimal side effects compared to conventional chemotherapy. Combining metronomic chemotherapy with drug repositioning and targeted therapies may lead to improved cancer control through multi-pronged effects on cancer cells, vasculature, and the immune system. However, determining the optimal biological dose and identifying surrogate markers pose challenges to realizing the full potential of this approach.
CCRT has:
1. Synergistic benefit against head and neck cancers
2. Associated with high level of response in in-operable disease
3. Tumour-radiosensitizing properties of chemotherapy or novel agents
4. Preservation of function is a major endpoint of interest
This study: efficacy of CCRT with a single agent
carboplatin in locally advanced head and neck cancers
A spherical aluminum oxide abrasive is the best choice for polishing resins like polycarbonate and acrylic. Here's why. Learn more: http://nanophase.com/markets/optical-surface-polishing/
"Nano Alumina Slurries for Improved Polishing on Thermoset and Thermoplastic Resins" was presented by Abigail Hooper at Optifab 2015 in Rochester, NY.
Fe3O4 nano-particles were synthesized using chemical co-precipitation at temperatures ranging from 30-60°C. X-ray diffraction analysis showed the particles had different sizes and structural properties depending on the synthesis temperature. The sample prepared at 50°C was found to be the most stable. Future work will include VSM and HRTEM studies to determine actual particle size distributions and EPR studies of the samples at different temperatures.
This study evaluated the roles of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic cancer. 541 patients were randomized to one of four groups: chemoradiotherapy, chemotherapy, both, or observation. The results showed no survival benefit for adjuvant chemoradiotherapy, with a median survival of 15.5 months compared to 16.1 months without chemoradiotherapy. However, there was evidence of a survival benefit for adjuvant chemotherapy, with a median survival of 19.7 months compared to 14 months without chemotherapy. This study provided evidence that adjuvant chemotherapy may improve survival for patients with resected pancreatic cancer, but did not show a benefit for chemoradiotherapy.
This document summarizes adjuvant chemotherapy for breast cancer. It discusses the rationale for adjuvant chemotherapy based on the Fisher hypothesis that breast cancer is a systemic disease at diagnosis. Evidence from large meta-analyses shows that adjuvant chemotherapy improves outcomes compared to no treatment or CMF chemotherapy alone. The addition of anthracyclines or taxanes to chemotherapy regimens provides further benefits. Molecular profiling tools can help select patients who will most benefit from chemotherapy based on tumor biology. Guidelines recommend chemotherapy for higher risk patient subgroups based on tumor characteristics and gene expression profiles.
Сравнение эффективности препаратов Карбоплатин (Carboplatin) и Паклитаксел (P...oncoportal.net
Сравнение эффективности препаратов Карбоплатин (Carboplatin) и Паклитаксел (Paclitaxel) при добавлении препарата Бевацизумаб (Bevacizumab) и без него для лечения одной их форм рака легкого у пациентов старше 65 лет
in Older Patients With Advanced Non–Small Cell Lung Cancer
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
Ten years experience in the management of borderline ovarianTariq Mohammed
This study summarizes the experience of managing 138 patients with borderline ovarian tumors at the Tom Baker Cancer Centre over a 10-year period. The patients were divided into two groups based on whether they received complete or incomplete surgical staging. The recurrence rate was similar between the groups, at 5.6% for those with complete staging and 8.2% for incomplete staging. Surgical staging was still found to be important as it identified two patients with invasive implants that required chemotherapy. Microinvasion was identified as a risk factor for recurrence. The study concludes that while the need for restaging surgery remains controversial, close follow-up is important for patients undergoing conservative surgery.
1. The document analyzes changes in treatment strategies for metastatic colorectal cancer in Germany between 2005-2007 based on data from large population surveys. It finds that results from clinical trials showing increased effectiveness of new drugs like oxaliplatin and irinotecan were quickly implemented in clinical practice.
2. The treatment objective of achieving secondary resection of metastases after chemotherapy increased significantly from 18% to 27% during this period, as clinical trials showed biologicals improving resectability rates. Biologicals were used more often when secondary resection was the goal compared to other objectives.
3. A multivariate analysis found that while many factors influenced treatment choices, the objective of secondary resection and patient age had the most significant impact
This study performed a cost-effectiveness analysis of adjuvant chemoradiotherapy for resected gastric cancer based on results from the Intergroup 0116 trial. The analysis found that the incremental cost of adding chemoradiotherapy was $20,100 and provided an additional 0.53 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio of $38,400 per quality-adjusted life year gained. A probabilistic sensitivity analysis predicted a 67% likelihood that the ratio would be less than $50,000 per quality-adjusted life year, which compares favorably to other widely used cancer treatments.
This document summarizes a drug use evaluation (DUE) of daptomycin from June to October 2014. Data was collected from 21 patients on daptomycin, but 10 patients were excluded for reasons such as duplication, not completing therapy, or having an actual body weight less than 130% of ideal body weight. The remaining 10 patients were included in the analysis. Most patients were dosed using adjusted body weight and had indications of MRSA infections or reactions to vancomycin. Adverse reactions occurred in 2 patients. Outcomes included resolution of infection in 5 patients, discontinuation due to adverse reactions in 2 patients, and discontinuation due to lack of efficacy in 3 patients. The study had a small sample size making it
Aim: to evaluate the effi cacy and tolerability of electro-hyperthermia (ET) for the treatment of relapsed malignant glioma.
Methods: this was a retrospective observational clinical study. Patients were included in the study if they had >18 years, informed consent signed, histological diagnosis of malignant glioma, failure of previous temozolamide-based chemotherapy and radiotherapy, indication for treatment with ET.
Hyperthermia was performed with short radiofrequency waves of 13.56 MHz using a capacitive coupling technique keeping the skin surface at 26 C°. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumors was above 40 C° for more than 90% of the treatment duration (20-60 minutes gradually).
1. The study analyzed treatment patterns over time in patients receiving first-line chemotherapy for advanced or metastatic esophageal or gastric cancer based on data from 2,808 patients documented in Therapiemonitor from 2006-2013.
2. Treatment intensity increased over time, with 49.3% of patients receiving triplet chemotherapy in 2013 compared to just 10.1% in 2006. HER2 testing rates increased from 49.1% in earlier studies to 79.1% in 2012-2013, though testing was still not always performed according to guidelines.
3. Usage of fluoropyrimidine/cisplatin combinations with trastuzumab declined from 67% in 2010-2011 to 50% in 2012-2013
Global Academic Program of MD Anderson Cancer Centerspa718
The Global Academic Programs (GAP) at MD Anderson Cancer Center supports the institution's mission of eliminating cancer globally through its Sister Institution Network of 33 cancer centers in 24 countries. GAP facilitates collaboration between MD Anderson and its sister institutions across key areas of patient care, research, prevention, and education. Notable activities include referring international patients for second opinions and treatment through the Sister Institution Referral Assistance Center, funding collaborative research projects through the Sister Institution Network Fund, increasing global cancer publications and clinical trials, implementing tobacco control programs, and convening an annual conference to foster networking.
This journal club discussion summarizes a randomized controlled trial that compared the glucose-lowering drug rosiglitazone to metformin and glyburide in patients with recently diagnosed type 2 diabetes. The study was well-designed, experimental in nature, and included over 4,000 patients followed for a median of 4 years. The primary outcome was time to monotherapy failure based on fasting glucose levels. The results showed that rosiglitazone delayed monotherapy failure better than the other drugs and had a lower incidence of progression to higher fasting glucose levels. However, the study also reported some safety concerns with rosiglitazone like increased risk of heart failure. Overall, the discussant found the study to be valid and that the
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
This document summarizes a meta-analysis that evaluated the efficacy and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Eight randomized controlled trials involving 583 patients were included. The analysis found that compared to Western medicine alone, Astragalus injection improved treatment efficacy, improved patient quality of life, reduced leukopenia, reduced neurotoxicity, and reduced nausea and vomiting. The quality of the included studies was acceptable. In conclusion, Astragalus injection can reduce toxicity and improve the efficacy of conventional Western medicine in treating colorectal cancer.
Abstract—Colorectal cancer is leading cancer-related public health problem. This study was conducted to determine the effect of High-Dose-Rate intraluminal brachytherapy (HDR-BT) with or without interstitial brachytherapy during neoadjuvant chemoradiation for locally advanced rectal cancer. This randomized contrial was conducted on 28 patients attended with locally advanced rectal cancer (T3, T4 or N+) treated initially with concurrent capecitabine (800 mg/m2 twice daily for 5 days per week) and pelvic external beam radiation therapy (45Gy in 25 Fractions) after one week MRI for all patients; received intraluminal HDR-BT with 4Gy x 2 Fractions with one week interval for those had gross residual disease within 1cm of rectal wall and receiveed intraluminal and interstitial brachytherapy with 4Gy x 2 Fractions with one week interval for those had gross residual disease far from 1cm of rectal wall. All patients underwent surgery within 4-8 week after completion of neoadjuvant therapy. In the control group which were not randomized, twenty-eight patients underwent neoadjuvant chemoradiation (45Gy in 25 Fraction with concurrent capecitabine 800mg/m2 twice daily for 5 days per week) followed by surgery. It was found that in HDR-BT group pathologic complete response (pCR), pathologic partial response (pPR) and pathologic response rates (pCR+pPR) based on AJCC TNM staging for colorectal cancer were %35.7, %35.7, and %71.4 respectively. The pCR, pPR, and pRR were %25, %17, and %42 in the control group respectively. pCR, pPR, and pRR were improved with HDR-BT. However, only response rate improvement was statistically significant (p=0.031). There was no a statistically significant difference in the complications between the two groups (p > 0.05). So it can be concluded that HDR intraluminal with or without interstitial brachytherapy may be an effective method of dose escalation technique in neoadjuvant chemoradiation therapy of locally advanced rectal cancer with higher response rate and manageable side effects.
This study compared different chemotherapy and radiotherapy regimens for patients with early unfavorable Hodgkin's lymphoma. The study found:
1) 4 cycles of ABVD chemotherapy followed by 30Gy radiotherapy was as effective as 4 cycles of BEACOPP chemotherapy followed by either 30Gy or 20Gy radiotherapy.
2) However, 4 cycles of ABVD followed by a reduced radiotherapy dose of 20Gy was inferior to the other regimens and resulted in worse patient outcomes.
3) A reduction of radiotherapy dose from 30Gy to 20Gy is only possible when combined with a more intensive chemotherapy regimen like BEACOPP, not a less intensive regimen like ABVD.
Percutaneous image-guided cryoablation of spinal metastases: A systematic reviewAhmad Ozair
Percutaneous cryoablation (PCA) is a minimally invasive technique that has been recently used to treat spinal metastases with a paucity of data currently available in the literature. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective or retrospective studies concerning metastatic spinal neoplasms treated with current generation PCA systems and with available data on safety and clinical outcomes were included. In the 8 included studies (7 retrospective, 1 prospective), a total of 148 patients (females = 63%) underwent spinal PCA. Tumors were located in the cervical (3/109 [2.8%], thoracic (74/109 [68.8%], lumbar (37/109 [33.9%], and sacrococcygeal (17/109 [15.6%] regions. Overall, 187 metastatic spinal lesions were treated. Thermo-protective measures (e.g., carbo-/hydro-dissection, thermocouples) were used in 115/187 [61.5%] procedures. For metastatic spinal tumors, the pooled mean difference (MD) in pain scores from baseline on the 0–10 numeric rating scale was 5.03 (95% confidence interval [CI]: 4.24 to 5.82) at a 1-month follow-up and 4.61 (95% CI: 3.27 to 5.95) at the last reported follow-up (range 24–40 weeks in 3/4 studies). Local tumor control rates ranged widely from 60% to 100% at varying follow-ups. Grade I-II complications were reported in 9/148 [6.1%] patients and grade III-V complications were reported in 3/148 [2.0%]) patients. PCA, as a stand-alone or adjunct modality, may be a viable therapy in appropriately selected patients with painful spinal metastases who were traditionally managed with open surgery and/or radiation therapy.
- Larotrectinib, a TRK inhibitor, showed marked antitumor activity in 55 patients with TRK fusion-positive cancers of various types who were enrolled in three clinical studies.
- The overall response rate was 75% according to independent review and 80% according to investigators. At one year, 71% of responses were ongoing and 55% of patients remained progression-free.
- Adverse events were predominantly grade 1. No grade 3-4 adverse events related to larotrectinib occurred in more than 5% of patients, and no patients discontinued treatment due to drug-related adverse events.
Metronomic chemotherapy involves the chronic administration of chemotherapy drugs at low, minimally toxic doses on a frequent schedule with no prolonged breaks. This strategy aims to control cancer by targeting tumor vasculature and is an attractive option in resource-limited areas due to its low cost, oral administration, and minimal side effects compared to conventional chemotherapy. Combining metronomic chemotherapy with drug repositioning and targeted therapies may lead to improved cancer control through multi-pronged effects on cancer cells, vasculature, and the immune system. However, determining the optimal biological dose and identifying surrogate markers pose challenges to realizing the full potential of this approach.
CCRT has:
1. Synergistic benefit against head and neck cancers
2. Associated with high level of response in in-operable disease
3. Tumour-radiosensitizing properties of chemotherapy or novel agents
4. Preservation of function is a major endpoint of interest
This study: efficacy of CCRT with a single agent
carboplatin in locally advanced head and neck cancers
A spherical aluminum oxide abrasive is the best choice for polishing resins like polycarbonate and acrylic. Here's why. Learn more: http://nanophase.com/markets/optical-surface-polishing/
"Nano Alumina Slurries for Improved Polishing on Thermoset and Thermoplastic Resins" was presented by Abigail Hooper at Optifab 2015 in Rochester, NY.
Fe3O4 nano-particles were synthesized using chemical co-precipitation at temperatures ranging from 30-60°C. X-ray diffraction analysis showed the particles had different sizes and structural properties depending on the synthesis temperature. The sample prepared at 50°C was found to be the most stable. Future work will include VSM and HRTEM studies to determine actual particle size distributions and EPR studies of the samples at different temperatures.
This study evaluated the roles of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic cancer. 541 patients were randomized to one of four groups: chemoradiotherapy, chemotherapy, both, or observation. The results showed no survival benefit for adjuvant chemoradiotherapy, with a median survival of 15.5 months compared to 16.1 months without chemoradiotherapy. However, there was evidence of a survival benefit for adjuvant chemotherapy, with a median survival of 19.7 months compared to 14 months without chemotherapy. This study provided evidence that adjuvant chemotherapy may improve survival for patients with resected pancreatic cancer, but did not show a benefit for chemoradiotherapy.
This document summarizes adjuvant chemotherapy for breast cancer. It discusses the rationale for adjuvant chemotherapy based on the Fisher hypothesis that breast cancer is a systemic disease at diagnosis. Evidence from large meta-analyses shows that adjuvant chemotherapy improves outcomes compared to no treatment or CMF chemotherapy alone. The addition of anthracyclines or taxanes to chemotherapy regimens provides further benefits. Molecular profiling tools can help select patients who will most benefit from chemotherapy based on tumor biology. Guidelines recommend chemotherapy for higher risk patient subgroups based on tumor characteristics and gene expression profiles.
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
This document discusses adjuvant systemic therapy options for breast cancer. It provides an overview of chemotherapy, endocrine therapy, targeted therapy and radiotherapy approaches. It also discusses ongoing clinical trials evaluating newer adjuvant treatments and biomarkers to help determine optimal treatment approaches for individual patients.
The document discusses different methods for producing alumina nanoparticles, including sol-gel, spray pyrolysis, and emulsion combustion methods. Sol-gel produces nanoparticles below 30 nm and allows control of particle properties. Spray pyrolysis controls particle size below 400 nm using an ultrasonic spray of precursor solutions decomposed at 700°C. Emulsion combustion combines emulsion and combustion processes to continuously produce hollow spherical alumina nanoparticles 200-800 nm in size with 10 nm shells.
Anticancer drugs work by killing cancer cells or modifying their growth. Most were discovered between 1950-1970 after nitrogen mustard was first used in the 1940s. Cancer treatment includes chemotherapy, radiotherapy, immunotherapy, and surgery. The aims of cancer therapy are to cure or prolong remission, provide palliation, or use adjuvant chemotherapy after surgery/radiotherapy. Anticancer agents are classified as cytotoxic drugs, targeted drugs, or hormonal drugs. Cytotoxic drugs include alkylating agents, platinum agents, antimetabolites, microtubule damaging agents, topoisomerase inhibitors, and antibiotics. They work by various mechanisms such as cross-linking DNA, inhibiting DNA/RNA synthesis, or interfering with microtubule
Synthesis of nanoparticles- physical,chemical and biologicalPriya Nanda
This document discusses various methods for synthesizing nanoparticles, including physical, chemical, and biological approaches. Physical methods include ball milling, melt mixing, physical vapor deposition techniques like sputtering and laser ablation. Chemical methods involve reducing metal salts or using sol-gel processes. Biological methods use microorganisms, plant extracts, proteins like ferritin, or biomolecular templates to synthesize nanoparticles. The document compares top-down lithography approaches to bottom-up assembly and provides many examples of synthesizing specific nanomaterials.
This phase 3 study compared eribulin mesilate to treatment of physician's choice (TPC) in women with metastatic breast cancer who had received 2-5 prior chemotherapy regimens. 762 women were randomly assigned to eribulin (508 patients) or TPC (254 patients), which included chemotherapy, hormonal therapy, or symptomatic treatment. The primary endpoint was overall survival. Eribulin showed a significant improvement in median overall survival compared to TPC (13.1 months vs 10.6 months). The most common adverse events in both groups were fatigue and neutropenia. Peripheral neuropathy was the most common reason for discontinuing eribulin. This study demonstrates that eribulin provides a survival benefit compared
The document summarizes a study that aimed to predict clinical failure in patients with metastatic prostate cancer by identifying genes related to prostate cancer. Researchers analyzed gene expression levels of androgen receptor, estrogen receptor, and stem cell markers in cancer and stromal cells collected via laser capture microdissection from biopsy samples of 76 patients. Logistic regression analysis showed that expression of Sox2, Her2, and CRP in cancer cells and AR and ER in stromal cells highly predicted prostate-specific antigen recurrence. Ten factors were identified as prognostic for cancer-specific survival, including expression of Oct1, TRIM36, Sox2, c-Myc, AR, Klf4, ER, and clinical parameters. Patients were divided into risk
The document summarizes a study that aimed to predict clinical failure in patients with metastatic prostate cancer by identifying genes related to prostate cancer. Researchers analyzed gene expression levels of androgen receptor, estrogen receptor, and stem cell markers in cancer and stromal cells collected via laser capture microdissection from biopsy samples of 76 patients. Logistic regression analysis showed that expression of Sox2, Her2, and CRP in cancer cells and AR and ER in stromal cells highly predicted prostate-specific antigen recurrence. Ten factors were identified as prognostic for cancer-specific survival, including expression of Oct1, TRIM36, Sox2, c-Myc, AR, Klf4, ER, as well as PSA, Gleason score
34320294 jak inhibitors more than just glucocorticoids (1)EVELIN LÁZARO
This editorial discusses recent trials investigating immunomodulatory therapies for COVID-19. It finds that treatment with glucocorticoids (dexamethasone) and JAK inhibitors reduces mortality in hospitalized patients receiving supplemental oxygen or ventilation. Combining JAK inhibitors with glucocorticoids may widen the window of benefit compared to either treatment alone. The editorial concludes that anti-inflammatory therapies reduce mortality in COVID-19 patients with moderate to severe disease, and that JAK inhibitors are a particularly promising option due to their oral administration, safety profile, and potential for combination with glucocorticoids.
This document summarizes a study comparing outcomes of patients who underwent upfront surgery versus neoadjuvant therapy followed by surgery for esophageal cancer. The study analyzed 49 patients treated between 2015-2019 at a hospital in India. It found no significant differences in patient characteristics or postoperative complications between the two groups. However, the neoadjuvant therapy group had a higher rate of pathological complete response (20% vs 0%) and lower rate of adjuvant chemotherapy (41% vs 68%). After a median follow-up of 28 months, there was no significant difference in survival time or rates between the two groups. The study concludes that neoadjuvant therapy prior to surgery is a feasible approach and can achieve higher rates of pathological complete response
This study compared outcomes for head and neck cancer patients based on age. Younger patients (≤40 years old) had significantly better 5-year survival rates (65%) than middle-aged (41-64 years old, 52%) or older patients (≥65 years old, 38%). Younger patients also developed fewer recurrent tumors or new primary tumors. However, the reasons for the differences in outcomes based on age are unclear. The study aimed to analyze outcomes while controlling for other factors like smoking history, tumor stage, and treatment received to better understand the independent impact of age.
- The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency conducted whole-genome analysis on tumors from 100 patients with advanced or incurable cancers to inform treatment decisions.
- Fresh tumor and blood samples were obtained from patients and underwent whole-genome and RNA sequencing. Computational analysis identified potential driver mutations, genes and pathways.
- A multidisciplinary team discussed genomic findings weekly and established guidelines for interpreting and communicating results to integrate them into patient care. Genomic findings were considered actionable in 55 of 78 cases that underwent whole-genome analysis, and motivated treatment changes in 23 cases.
- The experience demonstrated that a multidisciplinary team can implement an approach where whole-genome
Secondary Malignancy after Treatment of Prostate Cancer. Radical Prostatectom...asclepiuspdfs
Background: This study aims to determine whether the treatment of locally confined prostate cancer (PCa) with external radiotherapy (EBRT) increases the risk to develop secondary malignancies (SM) compared to radical prostatectomy (RPE). Materials and Methods: Data from patients who were treated curatively with RPE or EBRT from 2010 to 2018 and who did not have distant metastases, previous malignancy, or previous treatment with radiotherapy or chemotherapy at the time of diagnosis were reviewed to determine the incidence of SM over a median follow-up period of 47 months (range 12–96 months). Regression models were used to correlate the clinicopathological factors with the incidence of SM.
This study assessed the prognostic value of lymph node ratio (LNR) and extramural vascular invasion (EMVI) in predicting survival outcomes for 922 patients who underwent curative colon cancer resection between 2006-2012. The results showed that both increasing LNR and presence of EMVI were independently associated with decreased overall and disease-free survival on multivariate analysis. LNR was found to have greater prognostic value compared to the current pN staging system based on Akaike information criterion. Subgroup analysis by EMVI status also confirmed LNR and EMVI as significant predictors of survival.
1) Radiation therapy has a questionable role in treating primary renal cell carcinoma (RCC) but is commonly used to palliatively treat brain and other metastatic lesions.
2) Stereotactic body radiation therapy (SBRT) enables high doses of radiation to tumors while sparing normal tissues and has shown promise for treating primary or metastatic RCC, with local control rates of 90-98% in studies.
3) While some studies found adjuvant radiation after surgery reduced local recurrence in advanced RCC, prospective randomized trials found no survival benefit and increased toxicity, so radiation is not routinely recommended after surgery.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
This document summarizes the results of a survey of 115 Japanese medical facilities that treat gynecologic cancers, regarding their palliative care practices. The survey found that about 30% of facilities had a dedicated palliative care ward. Most facilities had a palliative care team but about half of physicians on the team had other duties as well. End-of-life care was typically managed in the gynecology department. The median time between a patient's last chemotherapy treatment and death was 85 days. Over 15% of patients received chemotherapy within 30 days of death and over 7% within 14 days of death. The survey identified some gaps in palliative care coordination and opportunities to improve symptom management at the end of life.
Evidence for Cure by Adjuvant Therapy in Colon Cancer: Observations Based on ...alessandrolealmd
This document summarizes a study analyzing individual patient data from 20,898 patients in 18 randomized trials testing fluorouracil-based adjuvant therapy for stage II-III colon cancer. The key findings were:
1) Adjuvant chemotherapy provided a significant and consistent overall survival benefit over 8 years of follow-up, indicating chemotherapy cures some patients rather than just delaying recurrence.
2) Recurrence rates after 5 years were less than 1.5% per year, and after 8 years were less than 0.5% per year for patients treated in clinical trials, demonstrating low long-term recurrence risks.
3) Significant disease-free survival benefit from adjuvant chemotherapy was seen in the first 2 years
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
Evaluation of immunosuppressive ahai.pdfleroleroero1
This study evaluated the outcomes of 42 dogs treated for immune-mediated hemolytic anemia (IMHA) using different immunosuppressive regimens. The dogs were treated with prednisolone alone or in combination with cyclosporine or azathioprine. Treatment regimen had a significant effect on survival during hospitalization, but the small number of subjects prevented determining the cause. Higher serum bilirubin and urea concentrations were associated with poorer prognosis. This was the first report to find a significant difference in outcomes between immunosuppressive drugs commonly used to treat IMHA in dogs.
The survey analyzed treatment patterns for multiple myeloma in Germany between 2008-2011 based on data from 478 patients. Key findings include:
- Bortezomib-chemotherapy regimens are now preferred for first-line treatment regardless of planned autologous stem cell transplantation (ASCT), which was performed in around 30% of eligible patients.
- Thalidomide- and lenalidomide-based therapies are commonly used in the second-line setting in 31% of patients.
- Cytogenetic testing increased from 23% in 2008 to 53% in 2011 and influences treatment decisions, though age and comorbidities remain major factors.
- Supportive care needs decreased
This document summarizes a meta-analysis of individual patient data from three large randomized controlled trials (ProCESS, ARISE, and ProMISe) that evaluated the effectiveness of early goal-directed therapy (EGDT) compared to usual care for treating septic shock. The meta-analysis included a total of 3,723 patients from 138 hospitals in 7 countries. The primary outcome was all-cause mortality at 90 days, with secondary outcomes including in-hospital mortality, length of stay, and costs. The meta-analysis found no significant difference in 90-day mortality between EGDT and usual care. EGDT was associated with longer intensive care unit and cardiovascular support, but higher costs. Subgroup analyses found no
The Efficacy of PARP Inhibitors According to Prior Taxanes Chemotherapy in Pr...semualkaira
No prospective data are available about the best treatment algorithm in mCRPC patients that had received intensified regimens in the castration-sensitive setting. We analyzed the efficacy of a PARPi for mCRPC patients according to prior taxanes treatment.
This document provides guidelines for managing diabetes during Ramadan fasting. It was created by the International Diabetes Federation and Diabetes and Ramadan International Alliance. The guidelines cover epidemiology of diabetes and Ramadan fasting, physiology changes during fasting, risk stratification for fasting, diabetes education, and medication adjustments. The goal is to enhance healthcare provider knowledge to safely support patients with diabetes who choose to fast during Ramadan.
This review article summarizes the 2011 evidence-based practice guideline published by the American Society of Hematology for the diagnosis and treatment of immune thrombocytopenia (ITP). The guideline was created using a rigorous evidence-based approach and provides treatment recommendations using the GRADE system where evidence exists. It identifies a lack of evidence in several key areas of ITP therapy, such as comparative studies of front-line therapies and management of bleeding. The guideline covers diagnosis and treatment of ITP in both children and adults, including recommendations for initial treatment, management of non-responders, treatment of specific secondary forms of ITP, and treatment during pregnancy.
Two types of acute diarrhoeal emergencies are cholera, which causes acute watery diarrhoea, and Shigella dysentery, which causes acute bloody diarrhoea. Both are transmitted through contaminated water, food, hands, and vomit or stool of sick individuals. The first steps in managing a diarrhoeal outbreak are determining if there are an unusual number of similar cases, identifying whether patients have cholera or Shigella by their symptoms, and being prepared for a potential increase in cases.
The document provides guidelines for diabetic eye care developed by the International Council of Ophthalmology (ICO). It aims to improve eye care quality worldwide by addressing screening and management of diabetic retinopathy for different resource settings. The guidelines describe classifying and screening for diabetic retinopathy, detailed eye exams, treating retinopathy and macular edema, and managing special circumstances. It includes tables outlining follow-up schedules and treatment recommendations based on retinopathy severity and resource level.
This document discusses special considerations for managing chronic myeloid leukemia (CML) during pregnancy and in the pediatric population. For pregnancy:
- Tyrosine kinase inhibitors (TKIs) used to treat CML are teratogenic and known to cause fetal toxicities. TKI therapy during pregnancy has been associated with higher rates of miscarriage and fetal abnormalities.
- If a patient wants to conceive, discontinuing TKI therapy may be considered if a deep molecular response has been maintained for at least 2 years. Close monitoring would be needed if CML recurs during pregnancy.
- For pediatric CML management, no evidence-based recommendations exist since CML is relatively rare in children. Specialized care at a cancer center is
This document discusses several minor blood group systems beyond ABO and Rh, including I/i, Lewis, P, MN, and SsU. It provides details on the antigens and antibodies in each system, including frequencies, clinical significance, and serological characteristics. The key points are:
- Over 500 antigens beyond ABO have been identified on red blood cells.
- The I/i, Lewis, P, MN, and SsU systems involve antigens that are inherited based on allelic genes and their interactions.
- Antibodies in these systems are usually naturally occurring and clinically insignificant, though some like anti-S, anti-s, and anti-U can cause hemolytic disease of the new
This document provides a focused update to the 2013 ACCF/AHA guidelines for the management of heart failure. It was developed by a writing group comprised of experts from the ACC, AHA, HFSA, and other organizations. The update provides new recommendations on the use of biomarkers for diagnosis and prognosis of heart failure as well as for treatment of stages A through D. It also includes new recommendations on treating anemia, hypertension, and sleep disordered breathing in heart failure patients. The update was reviewed and approved by several committees and is intended to provide guidance for clinicians on best practices in heart failure management.
These guidelines provide recommendations for managing dyslipidemia and preventing cardiovascular disease. They were developed by a writing committee and task force of experts based on reviews of current literature. The guidelines note that medical decisions should be made using clinical judgment and local resources, as rapid changes in the field may lead to periodic revisions. The document aims to assist healthcare professionals while not replacing their independent judgment.
This document provides an overview of the process and methods used to develop recommendations for the testing, management, and treatment of hepatitis C virus (HCV) infection. A panel of HCV experts from various medical fields develops the guidance using an evidence-based approach. Recommendations are rated based on the strength of evidence. The guidance is intended to be a living document that is regularly updated as new treatments and information become available. Strict processes are in place to manage conflicts of interest among panel members.
This document provides information on drugs that are contraindicated (Pregnancy Category X) for use during pregnancy. It lists the generic and brand names of drugs across several therapeutic categories including cardiovascular, dermatological, gastrointestinal, infections/infestations, musculoskeletal, neoplasms, nutrition, OB/GYN, pain/pyrexia, respiratory, and urogenital systems. For some drugs, it specifies the trimester or stage of pregnancy during which they should be avoided. The document also explains the pregnancy categories (A, B, C, D, X) used to qualify contraindications and precautions for drug use during pregnancy.
Muslims believe that death comes by divine decree and marks the beginning of an eternal journey in the afterlife. Some terminally ill Muslim patients receive care in intensive care units that prolong their lives through significant medical intervention when they may instead suffer without meaningful benefit. There is limited information available about Islamic beliefs regarding end of life issues for Muslims living in non-Muslim countries. Withdrawal of futile treatment is permitted in Islamic law for terminally ill patients to allow death to take its natural course. "Do not resuscitate" orders are also permitted in certain situations according to Islamic rulings if three physicians agree treatment would be non-beneficial. However, hydration and pain management should continue until death.
This document reviews recent guidelines for treating painful diabetic neuropathy (DPN) and compares their recommendations. It finds that the main drug classes recommended as first-line treatment are anticonvulsants like pregabalin and gabapentin, antidepressants like tricyclic antidepressants and duloxetine, and opioids. Pregabalin and duloxetine are the only drugs approved to treat neuropathic pain in diabetes. The guidelines differ in their methodologies, with some based more quantitatively on clinical trial evidence while others incorporate additional factors. Patient characteristics may also influence which treatment is most appropriate.
This document provides guidance from NICE on the assessment and treatment of acute stroke. It outlines recommendations for promptly admitting patients to specialist stroke units, performing brain imaging, providing thrombolysis or mechanical clot retrieval if appropriate, administering antiplatelets or anticoagulants, managing blood pressure and blood sugar, assessing swallowing function and providing nutrition, and carrying out carotid imaging and endarterectomy if indicated. The pathway is designed to optimize stroke care from initial presentation through the acute and subacute phases of recovery.
1) A randomized clinical trial of 576 adults with acute sore throat found that a single dose of oral dexamethasone did not increase the proportion of patients with complete resolution of symptoms at 24 hours compared to placebo.
2) However, at 48 hours significantly more patients in the dexamethasone group experienced complete resolution of symptoms than those in the placebo group.
3) The study found no other significant differences between the dexamethasone and placebo groups in secondary outcomes such as duration of symptoms, health care use, time off work, or medication use.
This document provides guidelines for managing diabetes during Ramadan fasting. It was created by the International Diabetes Federation and Diabetes and Ramadan International Alliance. The guidelines cover epidemiology of diabetes during Ramadan, physiology of fasting and how it impacts diabetes, risk stratification of patients, education recommendations, and medication adjustments for various diabetes medications and high-risk patient groups, such as those with type 1 diabetes. The goal is to enhance healthcare professionals' knowledge to best support patients during Ramadan fasting.
May-Hegglin anomaly is part of a spectrum of disorders called MYH9-related disease. Mutations in the MYH9 gene cause macrothrombocytopenia (low platelet count with large platelets) and basophilic inclusions in white blood cells. A diagnosis can be facilitated by platelet electron microscopy and MYH9 gene sequencing. While each disorder in the spectrum has some unique characteristics, they are all characterized by macrothrombocytopenia and are now considered manifestations of MYH9-related disease.
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7shruti jagirdar
Unit 4: MRA 103T Regulatory affairs
This guideline is directed principally toward new Molecular Entities that are
likely to have significant use in the elderly, either because the disease intended
to be treated is characteristically a disease of aging ( e.g., Alzheimer's disease) or
because the population to be treated is known to include substantial numbers of
geriatric patients (e.g., hypertension).
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...Université de Montréal
“Psychiatry and the Humanities”: An Innovative Course at the University of Montreal Expanding the medical model to embrace the humanities. Link: https://www.psychiatrictimes.com/view/-psychiatry-and-the-humanities-an-innovative-course-at-the-university-of-montreal
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
1. Meta-analysis of randomised adjuvant therapy trials for pancreatic
cancer
DD Stocken1
, MW Bu¨chler2
, C Dervenis3
, C Bassi4
, H Jeekel5
, JHG Klinkenbijl5
, KE Bakkevold6
, T Takada7
,
H Amano7
and JP Neoptolemos*,8,9
on behalf of the Pancreatic Cancer Meta-analysis Group
1
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK; 2
University of Heidelberg, Heidelberg, Germany; 3
Agia Olga
Hospital, Athens, Greece; 4
University of Verona, Verona, Italy; 5
University Hospital Rotterdam, Rotterdam, The Netherlands; 6
University of Bergen, Bergen,
Norway; 7
Teikyo University School of Medicine, Teikyo, Japan; 8
University of Liverpool, Liverpool, UK
The aim of this study was to investigate the worldwide evidence of the roles of adjuvant chemoradiation and adjuvant chemotherapy
on survival in potentially curative resected pancreatic cancer. Five randomised controlled trials of adjuvant treatment in patients with
histologically proven pancreatic ductal adenocarcinoma were identified, of which the four most recent trials provided individual
patient data (875 patients). This meta-analysis includes previously unpublished follow-up data on 261 patients. The pooled estimate
of the hazard ratio (HR) indicated a 25% significant reduction in the risk of death with chemotherapy (HR ¼ 0.75, 95% confidence
interval (CI): 0.64, 0.90, P-valuesstratified (Pstrat) ¼ 0.001) with median survival estimated at 19.0 (95% CI: 16.4, 21.1) months with
chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2- and 5-year survival rates were estimated at 38 and 19%, respectively,
with chemotherapy and 28 and 12% without. The pooled estimate of the HR indicated no significant difference in the risk of death
with chemoradiation (HR ¼ 1.09, 95% CI: 0.89, 1.32, Pstrat ¼ 0.43) with median survivals estimated at 15.8 (95% CI: 13.9, 18.1)
months with chemoradiation and 15.2 (95% CI: 13.1, 18.2) without. The 2- and 5-year survival rates were estimated at 30 and 12%,
respectively, with chemoradiation and 34 and 17% without. Subgroup analyses estimated that chemoradiation was more effective and
chemotherapy less effective in patients with positive resection margins. These results show that chemotherapy is effective adjuvant
treatment in pancreatic cancer but not chemoradiation. Further studies with chemoradiation are warranted in patients with positive
resection margins, as chemotherapy appeared relatively ineffective in this patient subgroup.
British Journal of Cancer (2005) 92, 1372–1381. doi:10.1038/sj.bjc.6602513 www.bjcancer.com
Published online 5 April 2005
& 2005 Cancer Research UK
Keywords: pancreas; resection; post-operative; chemotherapy; chemoradiation; radiotherapy
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57. Pancreatic ductal adenocarcinoma is one of the top five causes of
cancer death in the Western world (Bramhall et al, 1995; Parkin
et al, 2001). Long-term survival remains poor with a 5-year
survival rate of 0.4% (Bramhall et al, 1995) to 4% (Jemal et al,
2003). Resection is associated with improved survival, but this is
only possible in approximately 10% of patients (Sener et al, 1999).
Postoperative adjuvant therapy may further improve long-term
survival, but its routine use has yet to be properly established
(Neoptolemos et al, 2003). Adjuvant therapy can be in the form of
chemoradiation or chemotherapy or both.
Until the recent European Study Group for Pancreatic Cancer
(ESPAC)1 trial, studies of adjuvant therapy have either combined
patients with both pancreatic and periampullary cancers, have
been underpowered to detect the modest survival differences
expected of postoperative adjuvant treatment or have been
nonrandomised (Neoptolemos et al, 2003). The ESPAC1 trial was
designed and powered to answer two questions: the roles of
adjuvant chemoradiation and adjuvant chemotherapy, randomis-
ing 289 patients into a 2 Â 2 factorial design and the recent
publication of the final results showed no survival benefit for
chemoradiation but a significant survival benefit for chemotherapy
(ESPAC1-2 Â 2) (Neoptolemos et al, 2001a, 2004). The results of
individual studies can be conflicting in isolation and the recent
results of the ESPAC1 trial have highlighted the need to perform
this meta-analysis to assess all available worldwide evidence
addressing these questions. In particular, the ESPAC group
randomised an additional 261 patients outside of the 2 Â 2
factorial design (ESPAC1-plus) (Neoptolemos et al, 2001a) and
the updated evidence from these patients are also presented here
for the first time. Also, combining trial results in this meta-analysis
increases statistical power and has allowed reliable assessment of
all available randomised evidence (Stewart and Parmar, 1993;
Stewart and Clarke, 1995; Clarke and Godwin, 1998; Parmar et al,
1998), in particular, the assessment of the magnitude of treatment
effects within predefined prognostic subgroups.
This meta-analysis was an international collaboration collating
individual patient data from randomised controlled trials
(Kalser and Ellenberg, 1985; Gastrointestinal Study Group, 1987;
Bakkevold et al, 1993; Klinkenbijl et al, 1999; Neoptolemos
et al, 2001a, 2004; Takada et al, 2002) with the primary aim to
Received 1 November 2004; revised 14 February 2005; accepted 15
February 2005; published online 5 April 2005
*Correspondence: Professor JP Neoptolemos, Department of Surgery,
Royal Liverpool University Hospital, 5th floor UCD Building, Daulby
Street, Liverpool L69 3GA, UK; E-mail: j.p.neoptolemos@liverpool.ac.uk
This study has not yet been presented
9
For Pancreatic Meta-analysis Group see Appendix A
British Journal of Cancer (2005) 92, 1372 – 1381
& 2005 Cancer Research UK All rights reserved 0007 – 0920/05 $30.00
www.bjcancer.com
ClinicalStudies
58. investigate the roles of adjuvant chemoradiation and adjuvant
chemotherapy on survival.
PATIENTS AND METHODS
Data collection
A protocol for the meta-analysis including objectives, inclusion
criteria for trials and data analysis was followed. A systematic
literature search, using ISI Web of Knowledge, Medline and
EMBASE search tools, was carried out as part of a review
(Neoptolemos et al, 2003) to identify randomised controlled trials
published worldwide. Information regarding ongoing trials was
also requested from members of ESPAC group across 11 European
countries. Trials were eligible if they randomised patients to
adjuvant therapy for resected pancreatic cancer recruiting only
patients aged 418 years with histologically proven ductal
adenocarcinoma of the pancreas and the trial had closed to
recruitment. Identified trial groups were contacted for access to
their individual patient data and trial protocols.
Meta-analysis of individual patient data provides increased
accuracy (Stewart and Parmar, 1993; Stewart and Clarke, 1995;
Clarke and Godwin, 1998; Parmar et al, 1998) and as such trial
groups were encouraged to supply individual patient data
including prognostic information and additional follow-up for
survival, where possible. Patient characteristics and baseline
histology data were requested including date of birth, sex, date
of operation, date of randomisation, tumour type and size, grade of
disease, microscopic resection margin status (Neoptolemos et al,
2001b), nodal status, smoking and preoperative diabetes status as
well as survival information based on the date last seen alive, date
and cause of death and randomised treatment group.
Only patients with pancreatic ductal adenocarcinoma were
included since the survival rate of other less common types of
pancreatic or ‘periampullary’ cancer such as ampullary carcinoma
and intrapancreatic bile duct cancer have much more favourable
prognoses (Magee et al, 2002). Patients were grouped according to
the type of randomised adjuvant treatment (chemoradiation or
chemotherapy). The treatments investigated by the individual
trials were commonly used regimens that were fairly well tolerated
by patients and as such reported no significant detriment to
quality of life.
Statistical methods
The main outcome measure for analysis was overall survival
measured from date of operation to the date of death (from all
causes) or censor date. All analyses were carried out on an
intention-to-treat basis in that patients were analysed according to
their allocated treatment group irrespective of treatment they
received. Any ineligible patients deleted from published analyses
were reinstated where data were available. Reanalysis was carried
out comparing Kaplan–Meier estimates of survival (Kaplan and
Meier, 1958) using standard and stratified log-rank tests (Peto
et al, 1977). The log-rank expected numbers of deaths and variance
were used to calculate individual and pooled hazard ratios (HR)
together with confidence intervals (CIs). Hazard ratios indicating
the effect of treatment on the risk of death are graphically
presented (Early Breast Cancer Trialists Collaborative Group,
1990), with w2
tests used to test for statistical heterogeneity
(interaction) across trials and across prespecified clinical sub-
groups of patients.
Resection margin status was recognised as an influential
prognostic factor by which to stratify randomisation (Kalser and
Ellenberg, 1985; Gastrointestinal Study Group, 1987; Bakkevold
et al, 1993; Neoptolemos et al, 2001a, 2004). Other stratification
factors at randomisation were tumour location (head vs body/tail;
Kalser and Ellenberg, 1985; Gastrointestinal Study Group, 1987),
pancreatic vs ampullary (Klinkenbijl et al, 1999; Neoptolemos et al,
2001a, 2004; Takada et al, 2002), centre (Klinkenbijl et al, 1999;
Neoptolemos et al, 2001a, 2004; Takada et al, 2002), gender
(Bakkevold et al, 1993) and type of surgery, differentiation and
stage of disease (Kalser and Ellenberg, 1985; Gastrointestinal Study
Group, 1987). Reported influential prognostic factors for pancrea-
tic adenocarcinoma were performance status and extent of tumour
(Kalser and Ellenberg, 1985; Gastrointestinal Study Group, 1987)
and tumour grade, regional lymph node status and tumour size
(Neoptolemos et al, 2001a, 2004). As such, clinical subgroups were
specifically those defined by resection margin status (negative,
positive), tumour grade (well, moderate, poor differentiation),
nodal status (negative, positive), tumour size (o2 cm, 42 cm)
and age (o60 years, 460 years). Trials were grouped according
to the type of adjuvant treatment used (chemoradiation or
chemotherapy).
RESULTS
Trials and patients
Searches identified four published studies of adjuvant systemic
chemotherapy, 14 published studies of adjuvant external beam
radiotherapy and 12 studies of combination adjuvant chemoradia-
tion plus maintenance chemotherapy (Neoptolemos et al, 2003).
Two of the four adjuvant chemotherapy studies were randomised
controlled trials and two were retrospective surveys. Two of the 14
radiotherapy studies were randomised controlled trials, six were
nonrandomised and a further six used intraoperative radiotherapy.
One of the 12 combination studies was a randomised controlled
trial, with the other 11 being nonrandomised or retrospective
studies. As such, two adjuvant systemic chemotherapy studies
(Bakkevold et al, 1993; Neoptolemos et al, 2001a, 2004), two adju-
vant chemoradiation studies (Klinkenbijl et al, 1999; Neoptolemos
et al, 2001a, 2004) and one study of adjuvant chemoradiation plus
maintenance chemotherapy (Kalser and Ellenberg, 1985; Gastro-
intestinal Study Group, 1987) were prospective, randomised trials
identified for inclusion in this meta-analysis. One additional trial
of adjuvant systemic chemotherapy (Takada et al, 2002) was
published following the review article and was eligible for
inclusion. The results of a Radiation Therapy Oncology Group
(RTOG) trial (Regine, 2001) of adjuvant chemoradiation plus
chemotherapy were not available at the time of this meta-analysis.
Five randomised controlled trials were available for inclusion
(Table 1) randomising a total of 1386 patients, of whom 939 had
pancreatic cancer. One of the adjuvant systemic and adjuvant
chemoradiation studies was the ESPAC1 trial using a 2 Â 2 factorial
design to answer both questions using the same sample of patients.
As such, three trials investigated the use of adjuvant chemoradia-
tion as follows: (i) the Gastrointestinal Study Group (GITSG)
showed that adjuvant chemoradiotherapy with maintenance
chemotherapy may help improve survival (Kalser and Ellenberg,
1985; Gastrointestinal Study Group, 1987); (ii) the European
Organisation for Research and Treatment of Cancer (EORTC)
showed no significant advantage for adjuvant chemoradiotherapy
(Klinkenbijl et al, 1999); and (iii) the ESPAC group showed no
benefit for adjuvant chemoradiation (Neoptolemos et al, 2001a,
2004). The following three trials investigated the use of adjuvant
chemotherapy: (i) the Norwegian Pancreatic Trials Group showed
an overall significant increase in median survival advantage for
chemotherapy but not 5-year survival (Bakkevold et al, 1993); (ii)
the Japanese Pancreatic Group concluded that combination
chemotherapy did not improve survival in pancreatic patients
(Takada et al, 2002); and (iii) the ESPAC group showed a survival
advantage for adjuvant chemotherapy (Neoptolemos et al, 2001a,
2004). The ESPAC group also randomised an additional 261
Pancreas cancer adjuvant treatment
DD Stocken et al
1373
British Journal of Cancer (2005) 92(8), 1372 – 1381& 2005 Cancer Research UK
ClinicalStudies
59. pancreatic cancer patients (ESPAC1-plus) outside of the 2 Â 2
factorial design (69 for chemoradiation vs observation and 192 for
chemotherapy vs observation) and the updated evidence from
these patients are presented here for the first time as separate
study. The interim results of the ESPAC1-2 Â 2 and ESPAC1-plus
trials were first published together after a median (interquartile
range) follow-up of 10 (1, 25) months (Neoptolemos et al, 2001a).
The final results of the ESPAC1-2 Â 2 factorial trial were published
separately after a median (interquartile range) follow-up of 47 (33,
62) months (Neoptolemos et al, 2004). This meta-analysis includes
the updated results of the ESPAC1-plus trial with a median
(interquartile range) follow-up of 39.2 (19.4, 63.9) months, and
thus contributes wholly original and previously unpublished data.
The GITSG trial was not able to provide individual patient data
due to the age of the trial. The four remaining trials supplied data
from 875 pancreatic cancer patients, ranging from 47 to 289
patients within individual trials (Table 2). Eligibility criteria
required patients to start adjuvant treatment within 8 weeks of
surgery. Patient demographics (age and sex) and important
tumour characteristics (resection margin and lymph nodal status
on pathology) were provided for all studies. Overall, patients were
predominantly male (58%) and aged 460 years of age (55%). As
expected, the majority of patients had negative resection margins
(68%), ranging from 100% in the Norwegian trial to 17% in the
Japanese trial, and approximately half (53%) had regional lymph
nodal involvement, ranging from 33% in the Norwegian trial to
60% in the Japanese trial. Both the GITSG and Norwegian trials
recruited only patients with negative resection margins, but
interestingly the Japanese trial recruited more patients with
positive resection margins, against the natural distribution of this
factor within this disease. Grade of disease was not available for the
Norwegian trial and tumour size was unavailable for the GITSG
and Japanese trials. Despite this, over half (52%) of the patients
had moderately differentiated tumours, with 19% having poorly
differentiated tumours and almost three-quarters (74%) had
tumours with maximum dimension 42 cm. Postoperative com-
plications were reported in 27% of all patients, ranging from 22 to
38% in individual trials. Survival data were provided for all
patients and as expected, the majority of patients (80%) had died
with over three-quarters of patients within each trial having died.
The median follow-up for alive patients was at least 24 months
within individual trials and 44 (interquartile range: 24.9–63.8)
months overall.
Adjuvant chemoradiation
The EORTC (Klinkenbijl et al, 1999) and ESPAC (Neoptolemos
et al, 2001a, 2004) trials were designed to investigate the role of
adjuvant chemoradiation using similar schedules of 2 Â 20 Gy
radiotherapy with 5-fluorouracil (5FU) and folinic acid (FA) as a
radiosensitiser randomising a total of 478 patients (385 deaths).
Table 3 shows the reanalysis of these trial data and Figure 1 shows
Table 1 Details of published randomised controlled trials of adjuvant treatment for pancreatic ductal adenocarcinoma
Trial Recruitment Comparison Adjuvant treatment
Number of patients and
IPD available Published conclusions
GITSGa
, 1985, 1987 Feb ’74–May ’82
All R0 resections
CRT vs OBS 2 Â (20 Gy in 10
fractions+500 mg mÀ2
5FU
days 1–3)+weekly 5FU to
recurrence
49 pancreatic patients
randomized
No IPD available
Significant increase in median
survival (20 vs 11 mo,
P ¼ 0.035) in 43 eligible
patients
Norway, 1993 April ’84–April ’87
All R0 resections
CT vs OBS AMF (40 mg mÀ2
doxorubicin,
6 mg mÀ2
mytomycin C,
500 mg mÀ2
5FU) once every 3
weeks for six courses
61 patients (47 pancreatic, 14
ampullary) randomised
46 additional nonrandomised
patients
IPD for 47 pancreatic patients.
Significant increase in median
survival (23 vs 11 mo, P ¼ 0.02)
in 60 pancreatic and ampullary
patients combined
EORTC, 1999 Sept ’87–April ’95
R0+R1 resections
CRT vs OBS 2 Â (20 Gy in 10
fractions+25 mg kgÀ1
5FU/FA
days 1–5)
218 patients (120 pancreatic,
98 ampullary) randomised
IPD for 120 pancreatic patients
NS increase in median survival
(25 vs 19 mo, P ¼ 0.21) in 207
eligible patients
NS increase in median survival
in 114 eligible pancreatic (17 vs
13 mo, P ¼ 0.099)
Japan, 2002 April ’86–June ’92
R0ÀR3 resections
CT vs OBS 6 mg mÀ2
mytomycin C day
1+310 mg mÀ2
5FU days 1–5
and days 15–20 followed by
100 mg mÀ2
oral 5FU daily to
recurrence
508 patients (173 pancreatic,
335 bile duct/gallbladder/
ampullary) randomised
IPD for 158 eligible pancreatic
patients
Significant survival benefit in
gallbladder
No difference in 158 eligible
pancreatic
No difference in 48 eligible
ampullary
ESPAC1-2 Â 2, 2001,
2004
Feb ’94–June 2000
R0+R1 resections
CRT vs no CRT
CT vs no CT
2 Â (20 Gy in 10
fractions+500 mg mÀ2
5FU/FA
days 1–3)
(20 mg mÀ2
FA+425 mg mÀ2
5FU days 1–5) Â six cycles
289 pancreatic patients
randomised
IPD for 289 pancreatic patients
NS decrease in survival for CRT
(P ¼ 0.053) in 289 patients
Significant increase in survival
for CT (P ¼ 0.009) in 289
eligible patients
ESPAC1-plus, 2001,
updated (unpublished)
Feb ’94–June 2000
R0+R1 resections
CRT vs no CRT
CT vs no CT
2 Â (20 Gy in 10
fractions+500 mg mÀ2
5FU/FA
days 1–3)
(20 mg mÀ2
FA+425 mg mÀ2
5FU days 1–5) Â six cycles
261 pancreatic patients
randomised (69 for CRT, 192
for CT)
IPD for 261 pancreatic patients
NS decrease in survival for CRT
(P ¼ 0.078) in 69 patients
Overall significant increase in
survival for CT (Po0.001) in
192 patients
Total 1386 patients randomised
939 pancreatic patients
randomised
IPD for 875 pancreatic patients
GITSG ¼ Gastrointestinal Study Group; EORTC ¼ European Organisation for Research and Treatment of Cancer; ESPAC ¼ European Study Group for Pancreatic Cancer;
R0 ¼ resection margin negative; R1 ¼ resection margin positive; CRT ¼ adjuvant chemoradiation; CT ¼ adjuvant chemotherapy; OBS ¼ surgery alone; 5FU ¼ 5-fluorouracil;
FA ¼ folinic acid; NS ¼ nonsignificant. a
Individual Patient Data (IPD) not available.
Pancreas cancer adjuvant treatment
DD Stocken et al
1374
British Journal of Cancer (2005) 92(8), 1372 – 1381 & 2005 Cancer Research UK
ClinicalStudies
60. the estimates of the HRs of the effect of chemoradiation treatment
with 95% CIs. The EORTC trial showed a nonsignificant trend in
favour of chemoradiation with a 30% reduction in the risk of death
and the ESPAC1-2 Â 2 and the ESPAC1-plus trials showed
nonsignificant trends in favour of no chemoradiation with 28
and 8% increase in the risk of death, respectively. There was
borderline heterogeneity between these results (w2
¼ 6.1, P ¼ 0.05),
but when combining the trials, the pooled estimate of the HR
indicated no significant difference in the risk of death with
chemoradiation (HR ¼ 1.09, 95% CI: 0.89, 1.32, P-valuesstratified
(Pstrat) ¼ 0.43) being dominated by the ESPAC1 data. The lack of
significant benefit for chemoradiation was shown in the survival
distributions of patients in the EORTC and ESPAC1 trials
combined by treatment (Figure 2) with median survivals estimated
at 15.8 (95% CI: 13.9, 18.1) months with chemoradiation and 15.2
(95% CI: 13.1, 18.2) without. The 2- and 5-year survival rates were
estimated at 30 and 12%, respectively, with chemoradiation and 34
and 17% without.
Summary statistics estimated from results presented in the
GITSG trial paper (Kalser and Ellenberg, 1985) showed a border-
line reduction in the risk of death with chemoradiation of 46%
(HR ¼ 0.54, 95% CI: 0.27, 1.05), more in line with the EORTC
results (Table 3). Including these results, using published summary
information rather than independent patient data (Figure 1)
increased the heterogeneity between the results (w2
¼ 10.0,
P ¼ 0.02), with the pooled HR again indicating no significant
difference in the risk of death with chemoradiation (HR ¼ 1.02,
95% CI: 0.85, 1.24, Pstrat ¼ 0.81).
Adjuvant chemotherapy
The Norwegian (Bakkevold et al, 1993), Japanese (Takada et al,
2002) and ESPAC (Neoptolemos et al, 2001a, 2004) trials were
designed to investigate the role of adjuvant chemotherapy using
5FU-based chemotherapy combinations (doxorubicin, mytomycin
C and intravenous 5FU combination (Bakkevold et al, 1993);
mytomycin C, intravenous 5FU and oral 5FU combination (Takada
et al, 2002); intravenous 5FU and FA combination (Neoptolemos
et al, 2001a, 2004)) randomising a total of 686 patients (550
deaths). Table 3 shows the reanalysis of these trial data and
Figure 3 shows the estimates of the HRs of the effect of
chemotherapy treatment with CIs. The Norwegian trial showed a
nonsignificant trend in favour of treatment with a 20% reduction
in the risk of death, the Japanese trial showed a nonsignificant
Table 2 Patient characteristics in randomised controlled trials of adjuvant treatment for pancreatic ductal adenocarcinoma
Trial
Characteristic
GITSG,
N ¼ 43
Norway,
N ¼ 47
EORTC,
N ¼ 120
Japan,
N ¼ 158
ESPAC1-2 Â 2,
N ¼ 289
ESPAC1-plus,
N ¼ 261
Totala
,
N ¼ 875
Sex
Male 26 (61%) 26 (55%) 65 (54%) 93 (59%) 170 (59%) 157 (60%) 511 (58%)
Female 17 (39%) 21 (45%) 55 (46%) 65 (41%) 119 (41%) 104 (40%) 364 (42%)
Age (years)
p60 18 (41%) 15 (33%) 57 (47%) 62 (40%) 128 (44%) 133 (51%) 395 (45%)
460 25 (59%) 31 (67%) 63 (53%) 94 (60%) 161 (56%) 128 (49%) 477 (55%)
Resection margins
Negative (R0) 43 (100%) 47 (100%) 79 (66%) 26 (17%) 238 (82%) 201 (77%) 591 (68%)
Positive (R1) — — 40 (34%) 127 (83%) 51 (18%) 60 (23%) 278 (32%)
Tumour grade
Well differentiated 15 (35%) NA 39 (33%) 43 (29%) 62 (24%) 48 (19%) 192 (25%)
Moderate 26 (60%) 45 (38%) 64 (43%) 148 (56%) 152 (61%) 409 (52%)
Poor 2 (5%) 34 (28%) 12 (8%) 52 (20%) 50 (20%) 148 (19%)
Papillary — 0 14 (9%) — — 14 (2%)
Other — 1 (1%) 16 (11%) — — 17 (2%)
Lymph nodal status
Negative 31 (72%) 31 (67%) 54 (45%) 62 (40%) 119 (43%) 127 (51%) 393 (47%)
Positive 12 (28%) 15 (33%) 66 (55%) 92 (60%) 155 (57%) 122 (49%) 450 (53%)
Max tumour size (cm)
p2 NA 13 (28%) 47 (39%) NA 53 (20%) 58 (25%) 171 (26%)
42 33 (72%) 72 (61%) 208 (80%) 178 (75%) 491 (74%)
Postop complication
No NA 29 (62%) NA 124 (78%) 201 (74%) 177 (72%) 531 (73%)
Yes 18 (38%) 34 (22%) 70 (26%) 70 (28%) 192 (27%)
Status
Alive 9 (21%) 10 (21%) 28 (23%) 24 (15%) 52 (18%) 63 (24%) 177 (20%)
Dead 34 (79%) 37 (79%) 92 (77%) 134 (85%) 237 (82%) 198 (76%) 698 (80%)
Follow-up of alive patients
Median (months) 412 24.2 33.1 66.8 46.7 39.2 44.1
Interquartile range — 15.9–31.4 18.9–55.5 48.1–85.0 33.0–62.0 19.4–63.9 24.9–63.8
Range 10.9–46.2 9.4–85.3 1.7–105.9 0.0–93.5 0.4–98.0 0.0–105.9
GITSG ¼ Gastrointestinal Study Group; EORTC ¼ European Organisation for Research and Treatment of Cancer; ESPAC ¼ European Study Group for Pancreatic Cancer;
R0 ¼ resection margin negative; NA ¼ not available. a
Total excludes the GITSG trial with no individual patient data (IPD).
Pancreas cancer adjuvant treatment
DD Stocken et al
1375
British Journal of Cancer (2005) 92(8), 1372 – 1381& 2005 Cancer Research UK
ClinicalStudies
61. Table 3 Reanalysis of survival data in randomised controlled trials of adjuvant treatment for pancreatic ductal adenocarcinoma
Trial
No. of
patients
No. of
deaths
Median survival
in months
(95% CI)
2-Year survival
rate (%) HR (95% CI)
Log-rank v2
,
significance
Chemoradiation (CRT) question
GITSGa
No CRT 22 19 10.9 (NA) 15 P ¼ 0.035
CRT 21 15 20.0 (NA) 42 0.54 (0.27, 1.05)a
(one-sided)
EORTC
No CRT 57 48 12.6 (10.3, 16.3) 23.20
CRT 63 44 17.5 (13.3, 23.8) 35.70 0.70 (0.46, 1.06) 2.91, P ¼ 0.088
ESPAC1-2 Â 2
No CRT 144 112 17.9 (14.8, 23.6) 41.40
CRT 145 125 15.9 (13.7, 19.9) 28.50 1.28 (0.99, 1.66) 3.75, P ¼ 0.053
ESPAC1-plus
No CRT 36 29 13.0 (11.5, 15.7) 23.50
CRT 33 27 12.5 (9.4, 16.6) 24.60 1.08 (0.64, 1.83) 0.09, P ¼ 0.77
Chemotherapy (CT) question
Norway
No CT 24 18 10.4 (6.6, 13.1) 24.30
CT 23 19 17.7 (11.0, 25.6) 30.60 0.80 (0.42, 1.53) 0.49, P ¼ 0.48
Japan
No CT 77 62 12.4 (10.5, 19.0) 29.60
CT 81 72 12.8 (9.8, 16.8) 24.20 1.18 (0.84, 1.66) 0.95, P ¼ 0.33
ESPAC1-2 Â 2
No CT 142 125 15.5 (13.0, 17.7) 30.00
CT 147 112 20.1 (16.5, 22.7) 39.70 0.71 (0.55, 0.92) 6.82, P ¼ 0.009
ESPAC1-plus
No CT 95 76 12.7 (10.2, 16.6) 26.80
CT 97 66 24.0 (18.8, 29.4) 48.90 0.54 (0.39, 0.76) 14.19, Po0.001
CI ¼ confidence interval; HR ¼ hazard ratio; GITSG ¼ Gastrointestinal Study Group; EORTC ¼ European Organisation for Research and Treatment of Cancer;
ESPAC ¼ European Study Group for Pancreatic Cancer; CRT ¼ adjuvant chemoradiation; CT ¼ adjuvant chemotherapy; NA ¼ not available. a
Individual patient data (IPD)
not available – data extracted from summary statistics provided in publication, HR estimated from data provided.
Survival by adjuvant chemoradiation
Events/patients
CRT No CRT
CRT events
(O−E) Var.
Hazard ratio and CI
CRT : no CRT
Reduction
(% and s.d.)
EORTC 44/63 48/57
(69.8%) (84.2%)
−8.1 22.5 30% s.d. 18
125/145 112/144
(86.2%) (77.8%)
14.8 58.1
27/33 29/36
(81.8%) (80.6%)
1.1 13.6
Subtotal: 196/241 189/237
(81.3%) (79.7%)
7.7 94.3 −9% s.d. 11
(2P=0.43)
= 6.1; P=0.05Heterogeneity between three groups
2
2
GITSG* 15/21 19/22
(71.4%) (86.4%)
−5.3 8.5 46% s.d. 26
Subtotal: 211/262 208/259
(80.5%) (80.3%)
2.5 102.8 −2% s.d. 10
(2P=0.81)
=10.0; P=0.02Heterogeneity between four groups
95% or 95% confidence intervals
0.0 0.5 1.0 1.5 2.0
CRT better No CRT better
* IPD not available
−28% s.d.15
−8% s.d. 28
2
3
ESPAC1-2×2
ESPAC1-plus
Figure 1 Hazard ratio plot of the effect of chemoradiation in the EORTC, ESPAC1 and GITSG randomised trials (CRT ¼ adjuvant chemoradiation;
’ ¼ individual estimate of the hazard ratio; } ¼ pooled stratified estimate of the hazard ratio).
Pancreas cancer adjuvant treatment
DD Stocken et al
1376
British Journal of Cancer (2005) 92(8), 1372 – 1381 & 2005 Cancer Research UK
ClinicalStudies
62. trend in favour of no treatment with an 18% increase in the risk of
death and the ESPAC1-2 Â 2 and ESPAC1-plus trials showed a
significant trend in favour of chemotherapy with 29 and 46%
reduction in the risk of death with chemotherapy, respectively.
There was significant heterogeneity between these results
(w2
¼ 11.7, P ¼ 0.009) due to the inclusion of the Japanese trial,
with an unusually high proportion of patients with positive
resection margins. When excluding this trial, the heterogeneity
between the Norwegian and ESPAC1 studies was markedly reduced
(w2
¼ 2.5, P ¼ 0.29) to a nonsignificant level. The pooled estimate of
the HR, excluding the Japanese trial, indicates a 35% significant
reduction in the risk of death with chemotherapy (HR ¼ 0.65, 95%
CI: 0.54, 0.80, Pstrato0.001) being dominated by the ESPAC1
results. When combining all data including the Japanese trial, the
pooled estimate of the HR indicated a 25% significant reduction in
the risk of death with chemotherapy (HR ¼ 0.75, 95% CI: 0.64, 0.90,
Pstrat ¼ 0.001). The overall benefit for chemotherapy was shown by
the survival distributions of patients in the Norwegian, Japanese
and ESPAC1 trials combined by treatment (Figure 4) with median
survival estimated at 19.0 (95% CI: 16.4, 21.1) months with
chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2- and
5-year survival rates were estimated at 38 and 19%, respectively,
with chemotherapy and 28 and 12% without.
100
75
50
25
0
0 12 24 36 48 60
No CRT
CRT
No. at risk
No CRT
CRT
237
241
146
151
77
64
49
34
32
20
17
10
Months
%Survival
Survival by adjuvant chemoradiation
Pooled data from EORTC and ESPAC trials
Figure 2 Kaplan–Meier survival estimates by adjuvant chemoradiation in
the EORTC and ESPAC1 trials (CRT ¼ adjuvant chemoradiation).
Japan 72/81 62/77
( 88.9%) ( 80.5%)
5.6 33.3
Subtotal: 269/348 281/338
( 77.3%) ( 83.1%)
−37.8 132.6 25% s.d. 8
(2P =0.001)
=11.7; P =0.009Heterogeneity between four groups 2
3
95% or 95% confidence intervals
0.0 0.5 1.0 1.5 2.0
CT better No CT better
Survival by adjuvant chemotherapy
Events/patients
CT No CT
CT events
(O−E) Var.
Hazard ratio and CI
CT : no CT
Reduction
(% and s.d.)
Norway 19/23 18/24
( 82.6%) ( 75.0%)
−2.1 8.9
112/147 125/142
( 76.2%) ( 88.0%)
−19.9 57.8 29% s.d. 11
66/97 76/95
( 68.0%) ( 80.0%)
−21.5 32.5
Subtotal: 197/267 219/261
( 73.8%) ( 83.9%)
−43.4 99.2 35% s.d. 8
(2P =0.00001)
= 2.5; P =0.29Heterogeneity between three groups
2
2
20% s.d.30
−18% s.d.19
ESPAC1-2×2
ESPAC1-plus 46% s.d.13
Figure 3 Hazard Ratio plot of the effect of chemotherapy in the Norwegian, ESPAC1 and Japanese trials (CT ¼ adjuvant chemotherapy; ’ ¼ individual
estimate of the hazard ratio; } ¼ pooled stratified estimate of the hazard ratio).
100
75
50
25
0
0 12 24 36 48 60
No CT
CT
No. at risk
No CT
CT
338
348
184
230
88
125
44
75
29
49
16
33
Months
%Survival
Survival by adjuvant chemotherapy
Pooled data from Norwegian, Japanese and
ESPAC trials
Figure 4 Kaplan–Meier survival estimates by adjuvant chemotherapy in
the Norwegian, ESPAC1 and Japanese trials (CT ¼ adjuvant chemotherapy).
Pancreas cancer adjuvant treatment
DD Stocken et al
1377
British Journal of Cancer (2005) 92(8), 1372 – 1381& 2005 Cancer Research UK
ClinicalStudies
63. Chemoradiation effect within prognostic subgroups
Figure 5 shows the estimates of the HRs with CIs of the effect of
chemoradiation within the prognostic subgroups, and overall HRs
stratified by age, resection margin status, tumour grade, lymph
node status and tumour size. The pooled estimates of the HRs
stratified by each prognostic factor (Pstrat ranging fro 0.25 to 0.59)
confirm the overall lack of benefit seen in the estimate of the HR
stratified by trial (Pstrat ¼ 0.43). There was no significant hetero-
geneity within the subgroups, except for a significant difference in
the effect of chemoradiation dependent upon resection margin
status (w2
¼ 4.2, P ¼ 0.04), where chemoradiation was estimated to
Survival by adjuvant chemoradiation
Hazard ratio and CI
CRT:No CRT
Reduction
(% and s.d.)
Age ഛ60 years 82/95
(86.3%)
0.5 43.6 −1% s.d. 15
Age Ͼ60 years 107/142
(75.4%)
4.7 51.3 −10% s.d. 15
Subtotal:
Subtotal:
Subtotal:
Subtotal:
Subtotal:
189/237
(79.7%)
5.3 94.9
−6% s.d. 11
(2P=0.59)
144/183
(78.7%)
12.9 73.5 −19% s.d. 13
Resection margin pos (R1) 45/53
(84.9%)
−7.0 21.1 28% s.d. 19
189/236
(80.1%)
5.9 94.6 −6% s.d. 11
(2P=0.54)
42/61
(68.9%)
1.8 18.6
Moderate 95/114
(83.3%)
11.3 49.9
Poor 44/47
(93.6%)
−4.9 21.0 21% s.d. 19
181/222
(81.5%)
8.2 89.5 −10% s.d. 11
(2P=0.39)
71/101
(70.3%)
6.0 37.3
5.0 54.7 −10% s.d. 14
186/229
(81.2%)
11.1 92.0 −13% s.d. 11
(2P=0.25)
44/58
(75.9%)
3.2 21.3
135/162
(83.3%)
2.7 67.4 −4% s.d. 12
179/220
(81.4%)
5.9 88.7 −7% s.d. 11
(2P=0.53)
= 0.2; P=0.66
2
1
−8.5% s.d. 10.7
(2P=0.43)
0.0 0.5 1.0 1.5 2.0
No CRT betterCRT better
−−10% s.d. 24
−−25% s.d. 16
−18% s.d. 18
−16% s.d. 16
Well differentiated
Lymph node neg
Lymph node pos
Size ഛ2cm
Size Ͼ2cm
Stratified by trial
95% or 95% confidence intervals
7.7 94.3196/241
(81.3%)
189/237
(79.7%)
180/220
(81.8%)
137/163
(84.0%)
43/57
(75.4%)
189/230
(82.2%)
109/130
(83.8%)
80/100
(80.0%)
185/223
(83.0%)
42/50
(84.0%)
108/122
(88.5%)
35/51
(68.6%)
Interaction between two groups
= 0.1; P=0.74
2
1
Interaction between two groups
= 4.2; P=0.04
2
1
Interaction between two groups
= 0.2; P=0.70
2
1
Interaction between two groups
= 3.1; P=0.21
2
2
Heterogeneity between three groups
196/241
(81.3%)
41/53
(77.4%)
155/188
(82.4%)
196/241
(81.3%)
102/126
(81.0%)
94/115
(81.7%)
Resection margin neg (R0)
Events/patients
CRT No CRT
CRT events
(O-E) Var.
115/128
(89.8%)
Figure 5 Hazard ratio plot of the effect of chemoradiation by prognostic subgroups in the EORTC and ESPAC1 trials (CRT ¼ adjuvant chemoradiation;
’ ¼ individual estimate of the hazard ratio; } ¼ pooled stratified estimate of the hazard ratio).
Pancreas cancer adjuvant treatment
DD Stocken et al
1378
British Journal of Cancer (2005) 92(8), 1372 – 1381 & 2005 Cancer Research UK
ClinicalStudies
64. be effective in patients with positive resection margins. However,
this effect within this subgroup has a wide CI spanning unity.
Chemotherapy effect within prognostic subgroups
Figure 6 shows the estimates of the HRs with CIs of the effect of
chemotherapy, respectively, within the prognostic subgroups, and
overall HRs stratified by age, resection margin status, tumour
grade, lymph node status and tumour size. The pooled estimates of
the HRs stratified by each prognostic factor confirm the significant
decrease in the risk of death with adjuvant chemotherapy (between
23 and 36%, Pstrat o0.005) seen in the estimate of the HR stratified
by trial (decreased risk of 25%, Pstrat ¼ 0.001). There was no
significant heterogeneity within the subgroups, except for a
Survival by adjuvant chemotherapy
Hazard ratio and CI
CT:No CT
Reduction
(% and s.d.)
Age ഛ60 years 125/147
(85.0%)
−22.6 60.3 31% s.d. 11
Age Ͼ60 years 154/189
(81.5%)
−14.0 72.9 17% s.d. 11
Subtotal:
Subtotal:
Subtotal:
Subtotal:
Subtotal:
279/336
(83.0%)
−36.6 133.2
24% s.d. 8
(2P=0.002)
187/222
(84.2%)
−38.9 85.8 36% s.d. 9
Resection margin pos (R1) 92.114
(80.7%)
2.0 45.6 −4% s.d. 15
279/336
(83.0%)
−36.9 131.3 25% s.d. 8
(2P=0.001)
55/66
(83.3%)
−10.3 25.2
Moderate 131/159
(82.4%)
−11.8 65.5
Poor 56/59
(94.9%)
−8.0 21.9 31% s.d. 18
242/284
(85.2%)
−30.1 112.6 23% s.d. 8
(2P=0.005)
109/147
(74.1%)
−12.2 54.8
−26.4 73.4 30% s.d. 10
269/322
(83.5%)
−38.6 128.2 26% s.d. 8
(2P=0.0007)
38/54
(70.4%)
−5.1 18.5
166/186
(89.2%)
−36.8 73.8 39% s.d. 9
204/240
(85.0%)
−41.9 92.3 36% s.d. 8
(2P=0.00001)
= 0.7; P =0.39
2
1
24.8% s.d. 7.6
(2P=0.001)
0.0 0.5 1.0 1.5 2.0
No CT betterCT better
3434% s.d. 16
16% s.d. 11
20% s.d. 12
24% s.d. 20
Well differentiated
Lymph node neg
Lymph node pos
Size ഛ2cm
Size Ͼ2cm
Stratified by trial
95% or 95% confidence intervals
−37.8 132.7269/348
(77.3%)
281/338
(83.1%)
183/243
(75.3%)
145/188
(77.1%)
38/55
(69.1%)
260/336
(74.4%)
145/172
(84.3%)
115/164
(70.1%)
221/282
(78.4%)
36/44
(81.8%)
135/162
(83.3%)
50/76
(65.8%)
Interaction between two groups
= 0.6; P=0.44
2
1
Interaction between two groups
= 7.3; P =0.007
2
1
Interaction between two groups
= 1.1; P =0.290
2
1
Interaction between two groups
= 1.2; P =0.54
2
2
Heterogeneity between three groups
266/345
(77.1%)
91/109
(83.5%)
175/236
(74.2%)
268/347
(77.2%)
140/181
(77.3%)
128/166
(77.1%)
Resection margin neg (R0)
Events/patients
CT No CT
CT events
(O-E) Var.
160/175
(91.4%)
Figure 6 Hazard ratio plot of the effect of chemotherapy by prognostic subgroups in the Norwegian, ESPAC1 and Japanese trials (CT ¼ adjuvant
chemotherapy; ’ ¼ individual estimate of the hazard ratio; } ¼ pooled stratified estimate of the hazard ratio).
Pancreas cancer adjuvant treatment
DD Stocken et al
1379
British Journal of Cancer (2005) 92(8), 1372 – 1381& 2005 Cancer Research UK
ClinicalStudies
65. significant difference in the effect of chemotherapy dependent
upon resection margin status (w2
¼ 7.3, P ¼ 0.007), where chemo-
therapy was estimated to be less effective in patients with positive
resection margins.
DISCUSSION
The recent publication of the ESPAC1 trial results (Neoptolemos
et al, 2004) highlighted the need to perform this meta-analysis
to assess all available worldwide evidence assessing the role
of adjuvant treatment following resection of pancreatic cancer.
The aim was to provide the most up to date and reliable summary
of available evidence of the roles of adjuvant chemoradiation
and adjuvant chemotherapy. There have been five published
randomised controlled trials (Kalser and Ellenberg, 1985; Gastro-
intestinal Study Group, 1987; Bakkevold et al, 1993; Klinkenbijl
et al, 1999; Neoptolemos et al, 2001a, 2004; Takada et al, 2002),
of which four provided individual patient data (Bakkevold et al,
1993; Klinkenbijl et al, 1999; Neoptolemos et al, 2001a,
2004; Takada et al, 2002). Two trials investigated the role of
adjuvant chemotherapy (Bakkevold et al, 1993; Takada et al,
2002), one investigated the role of adjuvant chemoradiotherapy
(Klinkenbijl et al, 1999), one investigated both chemoradiotherapy
and maintenance chemotherapy (Kalser and Ellenberg, 1985;
Gastrointestinal Study Group, 1987) and one trial investi-
gated both (Neoptolemos et al, 2001a, 2004). This interna-
tional collaboration has provided the largest series of randomised
individual patient data investigating the use of adjuvant therapy
to date, which has allowed particular assessment of the magni-
tude of any treatment benefit within predefined prognostic
subgroups.
The GITSG (Kalser and Ellenberg, 1985; Gastrointestinal
Study Group, 1987), EORTC (Klinkenbijl et al, 1999) and ESPAC1
(Neoptolemos et al, 2001a, 2004) trials were designed to investi-
gate the role of adjuvant chemoradiation randomising a total
of 521 patients (419 deaths) and concluded no significant survival
benefit with chemoradiation, confirmed within established
prognostic factor subgroups. The Norwegian (Bakkevold et al,
1993), Japanese (Takada et al, 2002) and ESPAC1 (Neoptolemos
et al, 2001a, 2004) trials were designed to investigate the role of
adjuvant chemotherapy using 5FU-based chemotherapy combina-
tions randomising a total of 686 patients (550 deaths) and
concluded a significant survival benefit with chemotherapy,
confirmed within established prognostic factor subgroups. This
is despite the fact that the Japanese trial used a treatment regimen
that was largely based on oral 5FU, which because of its hepatic
metabolism has very poor efficacy compared to intravenously
administered 5FU or specially designed oral fluoropyrimidines
(Shore et al, 2003).
The assessment of treatment benefit within prespecified
prognostic groups is informative for future trial design and patient
eligibility. Significant differences in the effect of both chemoradia-
tion and chemotherapy treatments were seen between patients
with negative and positive resection margins. Chemoradiation was
estimated to be more effective and chemotherapy was estimated to
be less effective in patients with positive resection margins;
however, neither of these treatment effects was significant within
this specific subgroup of patients. The testing of treatments within
specific subgroups was purely exploratory, so results should be
interpreted with caution due to a lack of statistical power.
Nevertheless, this meta-analysis has highlighted the need for
further studies to test the effect of treatments, including
chemoradiation, specifically in patients with positive resection
margins. The ESPAC1-2 Â 2 factorial trial (Neoptolemos et al,
2004) showed separation of the survival curves in favour of
adjuvant chemotherapy commencing at around 8 months but
against chemoradiation with the survival curves not beginning to
separate until 14 months following resection. Thus, the initial use
of chemoradiation appeared to have delayed the effective use of
systemic chemotherapy and thereby reduced median and 5-year
survival in patients who received the sequential combination. This
meta-analysis, however, has pointed to a potential role for
chemoradiation, but only in patients with positive resection
margins.
There was heterogeneity between trials ascribed to differing
patient populations with specific tumour characteristics, specifi-
cally the recruitment of resection margin-positive patients.
Heterogeneity was influenced by the inclusion of the GITSG
(Kalser and Ellenberg, 1985; Gastrointestinal Study Group, 1987)
trial, the only trial investigating the effect of chemoradiation in
patients with only negative resection margins and the Japanese
(Takada et al, 2002) trial with an unusually high proportion of
patients with positive resection margins. This meta-analysis has
been dominated by the evidence from the ESPAC1 (Neoptolemos
et al, 2001a, 2004) trials. The ESPAC group randomised 289
pancreatic cancer patients for both chemoradiation and che-
motherapy treatments as part of a 2 Â 2 factorial design and
showed a survival advantage for adjuvant chemotherapy but no
benefit for adjuvant chemoradiation. The ESPAC group also
randomised an additional 261 patients outside of the 2 Â 2 factorial
design, originally analysed with a median 10 month follow-up and
presented here for the first time with a median follow-up of 39.2
months and with similar results.
This meta-analysis provides the most current overview of
evidence estimating the effect of adjuvant treatment following
‘curative’ resection of pancreatic cancer, including recent pub-
lished and unpublished data from the ESPAC1 trial. Pancreatic
tumours do not appear to respond well to adjuvant chemoradia-
tion and routine use is not warranted as standard treatment. There
may be scope for future studies to investigate more modern
chemoradiation techniques including conformal radiotherapy
(Regine, 2001) and also further investigation of the potential role
for chemoradiation in patients with positive resection margins.
There is now strong evidence of a survival benefit for adjuvant
chemotherapy and standard care of patients with resectable
pancreatic cancer should now be based on curative surgery
followed by adjuvant systemic chemotherapy. These results
advocate the need for further randomised trials to find the optimal
chemotherapy regimen.
ACKNOWLEDGEMENTS
We thank all patients who took part in these trials and contri-
buted to this research. This meta-analysis was supported by
Cancer Research UK (ESPAC grant) and the Ministero dell’
Istruzione e della Ricerca (Cofin No. 2003063754), Roma, Italy.
JP Neoptolemos, MW Bu¨chler, C Dervenis and C Bassi are the
lead ESPAC investigators who along with DD Stocken (Biostatis-
tician) were responsible for initiating the project and developing
the protocol. In addition to the data from the ESPAC1
trial, individual patient data were provided by the lead investiga-
tors of the EORTC trial (J Jeekel and JHG Klinkenbijl), the
Norwegian Pancreatic Trials Group (KE Bakkevold) and the
Japanese Pancreatic Group (T Takada and H Amano). DD Stocken
managed the project and was responsible for receiving and
analysing the data and drafted the initial report. All authors
contributed to interpretation of the results and discussion and
commented on drafts of this paper.
Pancreas cancer adjuvant treatment
DD Stocken et al
1380
British Journal of Cancer (2005) 92(8), 1372 – 1381 & 2005 Cancer Research UK
ClinicalStudies
66. REFERENCES
Bakkevold KE, Arnesjo B, Dahl O, Kambestad B (1993) Adjuvant
combination chemotherapy (AMF) following radical resection of
carcinoma of the pancreas and papilla of Vater. Results of a controlled,
prospective, randomised multicentre study. Eur J Cancer 29: 698–703
Bramhall SR, Allum WH, Jones AG, Allwood A, Cummins C, Neoptolemos
JP (1995) Incidence, treatment and survival in 13, 560 patients with
pancreatic cancer: an epidemiological study in the West Midlands. Br J
Surg 82: 111–115
Clarke M, Godwin J (1998) Systematic reviews using individual patient
data: a map for the minefields? Ann Oncol 9: 827–833
Early Breast Cancer Trialists’ Collaborative Group (1990) Introduction and
Methods Sections Reproduced From: Treatment of Early Breast Cancer.
Worldwide Evidence 1985–1990 Vol 1, Oxford: Oxford University Press
Gastrointestinal Tumor Study Group (1987) Further evidence of effective
adjuvant combined radiation and chemotherapy following curative
resection of pancreatic cancer. Cancer 59: 2006–2010
Jemal A, Murray T, Samnels A, Ghafoor A, Ward E, Thun M (2003) Cancer
statistics, 2003. CA Cancer J Clin 53: 5–26
Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined
radiation and chemotherapy following curative resection. Arch Surg 120:
899–903
Kaplan EL, Meier P (1958) Non parametric estimation from incomplete
observations. J Am Stat Assoc 53: 457–481
Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH,
Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J (1999)
Adjuvant radiotherapy and 5-fluorouracil after curative resection of
cancer of the pancreas and periampullary region. Phase III trial of the
EORTC GITCCG. Ann Surg 230: 776–784
Magee CJ, Ghaneh P, Neoptolemos JP (2002) Surgical and medical therapy
for pancreatic carcinoma. Best Pract Res Clin Gastroenterol 16: 435–455
Neoptolemos JP, Cunningham D, Friess H, Bassi C, Stocken DD, Tait DM,
Dunn JA, Dervenis C, Lacaine F, Hickey H, Raraty MGT, Ghaneh P,
Buchler MW (2003) Adjuvant therapy in pancreatic cancer: historical
and current perspectives. Ann Oncol 14: 675–692
Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C,
Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A,
Spooner D, Kerr DJ, Freiss H, Bu¨chler MW (2001a) Adjuvant
chemoradiotherapy and chemotherapy in resectable pancreatic cancer:
a randomised controlled trial. Lancet 358(9293): 1576–1585
Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P,
Bassi C, Dervernis C, Fernandez-Cruz L, Lacaine F, Buckels J, Deakin M,
Adab F, Sutton R, Imrie C, Ihse I, Tihanyi T, Olah A, Pedrazzoli S,
Spooner D, Kerr DJ, Freiss H, Bu¨chler MW (2001b) Influence of
Resection margins on survival for patients with pancreatic cancer treated
by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1
randomized controlled trial. Ann Surg 234: 758–768
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger
H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap
A, Spooner D, Kerr DJ, Bu¨chler MW (2004) A randomized trial of
chemoradiotherapy and chemotherapy after resection of pancreatic
cancer. N Engl J Med 350(12): 1200–1210
Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The
global picture. Eur J Cancer 37: S4–S66
Parmar MKB, Torri V, Stewart L (1998) Extracting summary statistics to
perform meta-analyses of the published literature for survival endpoints.
Stat Med 17: 2815–2834
Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N,
McPherson K, Peto J, Smith PG (1977) Design and analysis of
randomised clinical trials requiring prolonged observation of each
patient II. Analysis and example. Br J Cancer 35: 1–39
Regine WF (2001) Postoperative adjuvant therapy: past, present and future
trial development. In MD Anderson Solid Tumor Oncology Series Evans
DB, Pisters PWT, Abbruzzese JL, Pollock RE (eds) pp 235–242. New
York, USA: Springer-Verlag
Sener S, Fremgen A, Menck H, Winchester D (1999) Pancreatic cancer: a
report of treatment and survival trends for 100, 313 patients diagnosed
from 1985–1995, using the National Cancer database. J Am Coll Surg 189:
1–7
Shore S, Raraty M, Ghaneh P, Neoptolemos JP (2003) Chemotherapy for
pancreatic cancer. Aliment Pharmacol Therap 18: 1049–1069
Stewart LA, Clarke MJ (1995) on behalf of the Cochrane Working Party
group on Meta-analysis using Individual Patient Data. Practical
methodology of meta-analyses (overviews) using updated individual
patient data. Stat Med 14: 2057–2079
Stewart LA, Parmar MKB (1993) Meta-analysis. Lancet 341: 964
Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H,
Nagakawa T, Nakayama T (2002) Is postoperative adjuvant chemo-
therapy useful for gall-bladder carcinoma? Cancer 95(8): 1685
Appendix A
Pancreatic Meta-analysis Group
European Study Group for Pancreatic Cancer (ESPAC): C Bassi, H
Beger, MW Bu¨chler, G Butturini, C Dervenis, JA Dunn, M Falconi,
L Fernandez-Cruz, H Friess, H Hickey, DJ Kerr, F Lacaine, JP
Neoptolemos, A Pap, D Spooner, DD Stocken.
European Organisation for Research and Treatment of Cancer
(EORTC): JP Arnaud, L Collette, ML Couvreur, LT De Wit, DG
Gonzalez, A Hennipman, J Jeekel, JHG Klinkenbijl, T Sahmoud, R
Van Pel, CH Veenhof, J Wils.
Norwegian Pancreatic Group: B Arnesjø, KE Bakkevold, O Dahl, B
Kambestad.
Japanese Pancreatic Group: H Amano, H Kato, T Matsushiro, T
Nagakawa, T Nakayama, Y Nimura, T Takada, H Yasuda.
Pancreas cancer adjuvant treatment
DD Stocken et al
1381
British Journal of Cancer (2005) 92(8), 1372 – 1381& 2005 Cancer Research UK
ClinicalStudies