1) Chemotherapy has played a major role in treating advanced-stage Hodgkin lymphoma. Early regimens like MOPP achieved high response rates but significant toxicity.
2) The ABVD regimen became the standard second-generation therapy, providing improved efficacy over MOPP with less toxicity.
3) Higher-intensity regimens like escalated BEACOPP further improved outcomes for advanced disease but had greater toxicity. Recent trials aim to reduce chemotherapy cycles with PET-guided radiotherapy.
The document summarizes the conclusions from the 13th International Breast Cancer Conference held in St Gallen in March 2013. The conference panel reviewed evidence and treatment recommendations for early breast cancer. Key conclusions included: 1) breast conserving surgery is usually preferable to mastectomy if radiation can be given; 2) axillary dissection is not always needed if sentinel nodes are positive; and 3) systemic adjuvant therapies like chemotherapy depend on tumor subtype, with luminal A usually needing endocrine therapy only.
This document discusses the management of carcinoma of the esophagus. It begins by outlining treatment approaches for localized versus metastatic disease, including definitive and palliative therapies. It then reviews the evolution of esophageal cancer treatment, including non-surgical approaches using radiation therapy alone or combined modality therapy, as well as surgical treatments. Several studies evaluating different treatment regimens are summarized, including the benefits of concurrent chemoradiation therapy over radiation alone. The role of preoperative chemoradiation is discussed. Techniques for radiation therapy delivery are also outlined. The document concludes by discussing palliative care approaches for esophageal cancer patients.
1) The PORTEC-1 and PORTEC-2 trials compared pelvic radiotherapy to no additional treatment or vaginal brachytherapy for patients with endometrial carcinoma. PORTEC-1 found pelvic radiotherapy reduced vaginal recurrence while PORTEC-2 found vaginal brachytherapy achieved excellent vaginal control with fewer side effects compared to pelvic radiotherapy.
2) The PORTEC-3 trial randomized 686 patients with high risk endometrial cancer to chemoradiotherapy or radiotherapy alone. It found chemoradiotherapy improved failure-free survival compared to radiotherapy alone, especially for stage III patients, but with increased toxicity.
3)
The RAPIDO trial tested a new experimental treatment for locally advanced rectal cancer that involved short-course radiotherapy followed by chemotherapy before surgery, compared to the standard treatment of long-course chemoradiotherapy followed by surgery and then chemotherapy. The results showed that the experimental treatment led to a lower rate of disease-related treatment failures and distant metastases, along with a doubled rate of pathologic complete responses, without increasing toxicities or compromising survival rates. This provides evidence that the experimental approach may be a new standard of care for high-risk locally advanced rectal cancer.
Neoadjuvant chemoradiotherapy with carboplatin and paclitaxel followed by surgery improves overall survival compared to surgery alone for resectable esophageal cancer. In this randomized controlled trial, the median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24 months in the surgery alone group. The chemoradiotherapy regimen was associated with a low rate of toxicity. A pathological complete response was more common in the chemoradiotherapy group. Long-term follow-up confirmed the survival benefit and lower rates of locoregional and distant disease progression for chemoradiotherapy plus surgery.
1) Preoperative chemotherapy or chemoradiotherapy can downstage tumors and increase resection rates for stomach cancer compared to surgery alone.
2) The MAGIC trial showed perioperative chemotherapy improved survival rates over surgery alone by reducing tumor size and stage.
3) The TOPGEAR trial is currently testing adding preoperative chemoradiotherapy to perioperative chemotherapy to further improve outcomes. Interim results found it to be safe and feasible.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
This document summarizes the current state of neoadjuvant treatment options for esophageal and gastric cancer. It finds that neoadjuvant therapy prior to surgery should be considered for all patients with greater than T1 or node-positive disease. For esophageal cancer, most patients should receive neoadjuvant chemoradiation. For gastric cancer, there is strong support for adjuvant chemotherapy following surgery. Future areas of research include immunotherapy, targeted therapies, and combination approaches.
The document summarizes the conclusions from the 13th International Breast Cancer Conference held in St Gallen in March 2013. The conference panel reviewed evidence and treatment recommendations for early breast cancer. Key conclusions included: 1) breast conserving surgery is usually preferable to mastectomy if radiation can be given; 2) axillary dissection is not always needed if sentinel nodes are positive; and 3) systemic adjuvant therapies like chemotherapy depend on tumor subtype, with luminal A usually needing endocrine therapy only.
This document discusses the management of carcinoma of the esophagus. It begins by outlining treatment approaches for localized versus metastatic disease, including definitive and palliative therapies. It then reviews the evolution of esophageal cancer treatment, including non-surgical approaches using radiation therapy alone or combined modality therapy, as well as surgical treatments. Several studies evaluating different treatment regimens are summarized, including the benefits of concurrent chemoradiation therapy over radiation alone. The role of preoperative chemoradiation is discussed. Techniques for radiation therapy delivery are also outlined. The document concludes by discussing palliative care approaches for esophageal cancer patients.
1) The PORTEC-1 and PORTEC-2 trials compared pelvic radiotherapy to no additional treatment or vaginal brachytherapy for patients with endometrial carcinoma. PORTEC-1 found pelvic radiotherapy reduced vaginal recurrence while PORTEC-2 found vaginal brachytherapy achieved excellent vaginal control with fewer side effects compared to pelvic radiotherapy.
2) The PORTEC-3 trial randomized 686 patients with high risk endometrial cancer to chemoradiotherapy or radiotherapy alone. It found chemoradiotherapy improved failure-free survival compared to radiotherapy alone, especially for stage III patients, but with increased toxicity.
3)
The RAPIDO trial tested a new experimental treatment for locally advanced rectal cancer that involved short-course radiotherapy followed by chemotherapy before surgery, compared to the standard treatment of long-course chemoradiotherapy followed by surgery and then chemotherapy. The results showed that the experimental treatment led to a lower rate of disease-related treatment failures and distant metastases, along with a doubled rate of pathologic complete responses, without increasing toxicities or compromising survival rates. This provides evidence that the experimental approach may be a new standard of care for high-risk locally advanced rectal cancer.
Neoadjuvant chemoradiotherapy with carboplatin and paclitaxel followed by surgery improves overall survival compared to surgery alone for resectable esophageal cancer. In this randomized controlled trial, the median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24 months in the surgery alone group. The chemoradiotherapy regimen was associated with a low rate of toxicity. A pathological complete response was more common in the chemoradiotherapy group. Long-term follow-up confirmed the survival benefit and lower rates of locoregional and distant disease progression for chemoradiotherapy plus surgery.
1) Preoperative chemotherapy or chemoradiotherapy can downstage tumors and increase resection rates for stomach cancer compared to surgery alone.
2) The MAGIC trial showed perioperative chemotherapy improved survival rates over surgery alone by reducing tumor size and stage.
3) The TOPGEAR trial is currently testing adding preoperative chemoradiotherapy to perioperative chemotherapy to further improve outcomes. Interim results found it to be safe and feasible.
This document summarizes the use of PET-CT in staging and assessing treatment response in Hodgkin's lymphoma. It discusses that PET-CT is an important tool for initial staging, assessing response to chemotherapy, and prognostic indicator when done after partial chemotherapy. The sensitivity and specificity of PET-CT is higher than CT alone for detecting nodal and organ involvement. PET-CT may avoid the need for bone marrow biopsy in some cases. Interim PET imaging helps distinguish residual mass as viable tumor or necrosis/fibrosis. The document also reviews chemotherapy regimens like ABVD, BEACOPP and Stanford V in early and advanced Hodgkin's lymphoma.
This document summarizes the current state of neoadjuvant treatment options for esophageal and gastric cancer. It finds that neoadjuvant therapy prior to surgery should be considered for all patients with greater than T1 or node-positive disease. For esophageal cancer, most patients should receive neoadjuvant chemoradiation. For gastric cancer, there is strong support for adjuvant chemotherapy following surgery. Future areas of research include immunotherapy, targeted therapies, and combination approaches.
Neoadjuvant therapy, including chemotherapy and chemoradiotherapy, is being investigated for the treatment of esophageal cancer. While some studies have shown improved survival rates with neoadjuvant therapy compared to surgery alone, the evidence from clinical trials remains conflicting. Achieving a complete pathological response after neoadjuvant therapy is associated with significantly improved long-term survival. Further research is still needed to determine the optimal neoadjuvant approaches and to improve outcomes by reducing distant metastases.
ASCO AND SNO GUIDELINES FOR GLIOMA MANAGEMENTKanhu Charan
This document provides guidelines for the management of gliomas from the American Society of Clinical Oncology (ASCO) and the Society for Neuro-Oncology (SNO). It defines grading criteria for gliomas and provides treatment recommendations based on tumor type, grade, molecular markers and other factors. The recommendations cover initial treatment, adjuvant therapy and options for recurrent gliomas, with an emphasis on radiation therapy, chemotherapy regimens and clinical trial enrollment.
The document discusses adjuvant radiotherapy for locally advanced stomach cancers. It provides background on stomach cancer incidence and need for adjuvant therapy after surgery. Guidelines recommend adjuvant chemoradiation with 45Gy after surgery for advanced or node-positive disease. Target volumes include the stomach bed and regional lymph nodes. Organs at risk include kidneys, liver, lungs and spinal cord. Intensity modulated radiotherapy planning aims to meet dose constraints for targets and organs at risk.
Omission of RT in elderly breast cancer patientsBharti Devnani
This journal club presentation summarized the PRIME II randomized controlled trial which evaluated the efficacy of postoperative whole-breast radiotherapy for women aged 65 years or older with early-stage, hormone receptor-positive breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. The results showed that radiotherapy achieved a significant but relatively small reduction in local breast recurrence at 5 years compared to no radiotherapy. However, the 5-year rate of recurrence was low enough that omission of radiotherapy could be considered for select low-risk patients based on tumor characteristics and patient preferences. Treatment decisions require individualization based on prognostic factors and risk-benefit assessment.
This document discusses hypofractionation in the treatment of head and neck cancers. It begins by outlining outcomes for different stages of disease, then discusses how fraction size, total dose, and treatment time impact treatment. Hypofractionation can counter tumor repopulation and improve local control. Studies show hypofractionation is effective for early disease, palliative cases, and can be safely delivered using simultaneous integrated boost with IMRT. Severe toxicity is low while disease control remains high. Extreme hypofractionation with SBRT also provides good local control with acceptable toxicity.
This document summarizes the results of two randomized controlled trials (PORTEC-1 and PORTEC-2) that compared pelvic external beam radiotherapy (EBRT) to vaginal brachytherapy (VBT) or no additional treatment (NAT) for patients with endometrial carcinoma. PORTEC-1 showed that EBRT improves local control over NAT but does not provide a survival benefit and is associated with long-term side effects. PORTEC-2 found that VBT achieves similar local control as EBRT with fewer side effects, establishing VBT as the preferred adjuvant treatment for high intermediate risk patients.
- This document summarizes a randomized controlled trial that compared mFOLFOX6 alone versus mFOLFOX6 plus bevacizumab as first-line treatment for RAS mutant unresectable colorectal liver-limited metastases.
- 241 patients were randomly assigned to receive either mFOLFOX6 plus bevacizumab (arm A) or mFOLFOX6 alone (arm B). The primary endpoint was the rate of conversion to radical liver resection.
- After treatment, 28 patients in arm A and 8 patients in arm B were determined to be eligible for radical liver resection. However, 2 patients refused surgery. The trial aims to determine if the addition of bevacizumab results in
- Reirradiation or retreatments after initial radiotherapy is possible for 10% of cancer patients who experience a second cancer. However, if the radiation tolerance of a normal organ or tissue was exceeded in the initial treatment, reirradiation cannot be done safely.
- Early-responding tissues like skin generally recover better than late-responding tissues like fibrosis and can tolerate reirradiation with reduced doses. Spinal cord and lung data from rodent and monkey studies show some reirradiation is possible. Kidney and bladder do not recover from late damage.
- Clinical studies on reirradiation are limited but show it can provide local control and possibly survival for head and neck cancers, though with high risks of toxicity and functional
1. The document discusses treatment options and strategies for rectal cancer patients who achieve a clinical complete response after neoadjuvant chemoradiation therapy.
2. Key points discussed include patient selection criteria for active surveillance versus surgery, optimal timing of response assessment, and surveillance schedules for patients undergoing a watch-and-wait approach.
3. Studies presented showed that outcomes for complete responders managed non-operatively can be comparable to those having surgery, though local recurrence rates are higher with the non-operative approach. Strict patient selection and close surveillance are important.
This document discusses treatment options for gastric cancer, including surgery, chemotherapy, and radiation therapy. It covers various lymph node dissection classifications (D0-D2) and their roles in different stages of disease. Adjuvant therapies like chemotherapy and chemoradiation are recommended after surgery to improve survival outcomes. Perioperative and postoperative chemotherapy are supported by clinical trials to be beneficial in resectable gastric cancer.
This study aimed to audit the outcome of omitting pelvic lymphadenectomy during optimal interval cytoreduction in patients with advanced epithelial ovarian cancer. Ten patients who underwent neoadjuvant chemotherapy and optimal interval cytoreduction without lymphadenectomy were analyzed. At a median follow up of 1 year, 5 patients had relapsed - 3 with nodal recurrence. This 30% nodal recurrence rate was statistically significant. Therefore, the study concludes that while initial data showed low nodal positivity, omitting lymphadenectomy led to a higher nodal recurrence rate, and further randomized studies are needed.
The CROSS trial found that neoadjuvant chemoradiotherapy followed by surgery significantly improved long-term overall and progression-free survival compared to surgery alone for patients with resectable esophageal or esophagogastric junction cancer. At a minimum follow-up of 5 years, median overall survival was 48.6 months for chemoradiotherapy plus surgery versus 24 months for surgery alone. Both squamous cell carcinoma and adenocarcinoma subtypes benefited. Neoadjuvant chemoradiotherapy using carboplatin and paclitaxel is now considered the standard of care for these patients.
Primary CNS lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma confined to the brain, eyes, or spinal cord. It makes up around 2% of brain tumors. The median age is 55-65 years. Around 90% are diffuse large B-cell lymphomas. Treatment typically involves high-dose methotrexate chemotherapy combined with whole brain radiation therapy. Several studies have found that adding other chemotherapy drugs like cytarabine or thiotepa can improve response rates and survival compared to methotrexate alone. Ongoing research aims to improve outcomes further while reducing toxicity, such as by adding temozolomide to standard treatment.
This document describes a study protocol for a randomized phase III clinical trial comparing neoadjuvant chemoradiation followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell carcinoma of the esophagus. The trial aims to enroll 350 patients total with 175 patients in each arm. The primary objective is to compare median survival rates and quality of life between the two treatment groups. Secondary objectives include comparing pathological responses, progression-free survival, number of complete resections, treatment toxicity, and costs. The chemoradiation regimen involves weekly paclitaxel and carboplatin chemotherapy with concurrent radiation over 5 weeks. Patients will then undergo surgery and be followed up for survival and quality of life outcomes
Total neoadjuvant therapy for rectal cancer 2016Mohamed Abdulla
1) Total neoadjuvant therapy, consisting of chemotherapy followed by chemoradiation and surgery, may improve outcomes for rectal cancer over the traditional approach.
2) Ongoing clinical trials are investigating selective use of radiation and whether radiation can be omitted from some neoadjuvant regimens based on risk factors and response.
3) Near total neoadjuvant therapy with upfront chemotherapy alone may achieve pathologic complete responses in a third of patients and warrants further exploration as an alternative to traditional chemoradiation.
Advances in induction in Acute Lymphocytic Leukemiaspa718
This document summarizes key findings from recent studies on improving induction therapy for acute lymphocytic leukemia (ALL). It describes trials showing that intensified chemotherapy regimens based on pediatric protocols improved outcomes for young adults compared to historical regimens. A trial incorporating the targeted therapy ponatinib into frontline therapy for Philadelphia chromosome-positive ALL achieved high rates of complete response and molecular response. Combining the epigenetic agents decitabine and vorinostat with chemotherapy showed tolerability and clinical benefit for relapsed/refractory ALL. Overall, the document discusses advances demonstrating that pediatric-inspired and targeted regimens are feasible and effective for certain adult ALL patients.
Adjuvant therapy in pancreatic cancer.pptxSujan Shrestha
This document summarizes the evolution of adjuvant therapy trials for pancreatic cancer. It discusses several major trials including ESPAC-1 which established 5FU + leucovorin as standard adjuvant therapy, CONKO-001 which showed gemcitabine was beneficial, ESPAC-3 which found similar survival for 5FU vs gemcitabine, ESPAC-4 which found gemcitabine + capecitabine improved survival, the PRODIGE/UNICANCER trial which showed modified FOLFIRINOX significantly improved survival over gemcitabine, and the APACT trial which found nab-paclitaxel + gemcitabine did not significantly improve DFS over gemcitabine alone.
Neoadjuvant therapy, including chemotherapy and chemoradiotherapy, is being investigated for the treatment of esophageal cancer. While some studies have shown improved survival rates with neoadjuvant therapy compared to surgery alone, the evidence from clinical trials remains conflicting. Achieving a complete pathological response after neoadjuvant therapy is associated with significantly improved long-term survival. Further research is still needed to determine the optimal neoadjuvant approaches and to improve outcomes by reducing distant metastases.
ASCO AND SNO GUIDELINES FOR GLIOMA MANAGEMENTKanhu Charan
This document provides guidelines for the management of gliomas from the American Society of Clinical Oncology (ASCO) and the Society for Neuro-Oncology (SNO). It defines grading criteria for gliomas and provides treatment recommendations based on tumor type, grade, molecular markers and other factors. The recommendations cover initial treatment, adjuvant therapy and options for recurrent gliomas, with an emphasis on radiation therapy, chemotherapy regimens and clinical trial enrollment.
The document discusses adjuvant radiotherapy for locally advanced stomach cancers. It provides background on stomach cancer incidence and need for adjuvant therapy after surgery. Guidelines recommend adjuvant chemoradiation with 45Gy after surgery for advanced or node-positive disease. Target volumes include the stomach bed and regional lymph nodes. Organs at risk include kidneys, liver, lungs and spinal cord. Intensity modulated radiotherapy planning aims to meet dose constraints for targets and organs at risk.
Omission of RT in elderly breast cancer patientsBharti Devnani
This journal club presentation summarized the PRIME II randomized controlled trial which evaluated the efficacy of postoperative whole-breast radiotherapy for women aged 65 years or older with early-stage, hormone receptor-positive breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. The results showed that radiotherapy achieved a significant but relatively small reduction in local breast recurrence at 5 years compared to no radiotherapy. However, the 5-year rate of recurrence was low enough that omission of radiotherapy could be considered for select low-risk patients based on tumor characteristics and patient preferences. Treatment decisions require individualization based on prognostic factors and risk-benefit assessment.
This document discusses hypofractionation in the treatment of head and neck cancers. It begins by outlining outcomes for different stages of disease, then discusses how fraction size, total dose, and treatment time impact treatment. Hypofractionation can counter tumor repopulation and improve local control. Studies show hypofractionation is effective for early disease, palliative cases, and can be safely delivered using simultaneous integrated boost with IMRT. Severe toxicity is low while disease control remains high. Extreme hypofractionation with SBRT also provides good local control with acceptable toxicity.
This document summarizes the results of two randomized controlled trials (PORTEC-1 and PORTEC-2) that compared pelvic external beam radiotherapy (EBRT) to vaginal brachytherapy (VBT) or no additional treatment (NAT) for patients with endometrial carcinoma. PORTEC-1 showed that EBRT improves local control over NAT but does not provide a survival benefit and is associated with long-term side effects. PORTEC-2 found that VBT achieves similar local control as EBRT with fewer side effects, establishing VBT as the preferred adjuvant treatment for high intermediate risk patients.
- This document summarizes a randomized controlled trial that compared mFOLFOX6 alone versus mFOLFOX6 plus bevacizumab as first-line treatment for RAS mutant unresectable colorectal liver-limited metastases.
- 241 patients were randomly assigned to receive either mFOLFOX6 plus bevacizumab (arm A) or mFOLFOX6 alone (arm B). The primary endpoint was the rate of conversion to radical liver resection.
- After treatment, 28 patients in arm A and 8 patients in arm B were determined to be eligible for radical liver resection. However, 2 patients refused surgery. The trial aims to determine if the addition of bevacizumab results in
- Reirradiation or retreatments after initial radiotherapy is possible for 10% of cancer patients who experience a second cancer. However, if the radiation tolerance of a normal organ or tissue was exceeded in the initial treatment, reirradiation cannot be done safely.
- Early-responding tissues like skin generally recover better than late-responding tissues like fibrosis and can tolerate reirradiation with reduced doses. Spinal cord and lung data from rodent and monkey studies show some reirradiation is possible. Kidney and bladder do not recover from late damage.
- Clinical studies on reirradiation are limited but show it can provide local control and possibly survival for head and neck cancers, though with high risks of toxicity and functional
1. The document discusses treatment options and strategies for rectal cancer patients who achieve a clinical complete response after neoadjuvant chemoradiation therapy.
2. Key points discussed include patient selection criteria for active surveillance versus surgery, optimal timing of response assessment, and surveillance schedules for patients undergoing a watch-and-wait approach.
3. Studies presented showed that outcomes for complete responders managed non-operatively can be comparable to those having surgery, though local recurrence rates are higher with the non-operative approach. Strict patient selection and close surveillance are important.
This document discusses treatment options for gastric cancer, including surgery, chemotherapy, and radiation therapy. It covers various lymph node dissection classifications (D0-D2) and their roles in different stages of disease. Adjuvant therapies like chemotherapy and chemoradiation are recommended after surgery to improve survival outcomes. Perioperative and postoperative chemotherapy are supported by clinical trials to be beneficial in resectable gastric cancer.
This study aimed to audit the outcome of omitting pelvic lymphadenectomy during optimal interval cytoreduction in patients with advanced epithelial ovarian cancer. Ten patients who underwent neoadjuvant chemotherapy and optimal interval cytoreduction without lymphadenectomy were analyzed. At a median follow up of 1 year, 5 patients had relapsed - 3 with nodal recurrence. This 30% nodal recurrence rate was statistically significant. Therefore, the study concludes that while initial data showed low nodal positivity, omitting lymphadenectomy led to a higher nodal recurrence rate, and further randomized studies are needed.
The CROSS trial found that neoadjuvant chemoradiotherapy followed by surgery significantly improved long-term overall and progression-free survival compared to surgery alone for patients with resectable esophageal or esophagogastric junction cancer. At a minimum follow-up of 5 years, median overall survival was 48.6 months for chemoradiotherapy plus surgery versus 24 months for surgery alone. Both squamous cell carcinoma and adenocarcinoma subtypes benefited. Neoadjuvant chemoradiotherapy using carboplatin and paclitaxel is now considered the standard of care for these patients.
Primary CNS lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma confined to the brain, eyes, or spinal cord. It makes up around 2% of brain tumors. The median age is 55-65 years. Around 90% are diffuse large B-cell lymphomas. Treatment typically involves high-dose methotrexate chemotherapy combined with whole brain radiation therapy. Several studies have found that adding other chemotherapy drugs like cytarabine or thiotepa can improve response rates and survival compared to methotrexate alone. Ongoing research aims to improve outcomes further while reducing toxicity, such as by adding temozolomide to standard treatment.
This document describes a study protocol for a randomized phase III clinical trial comparing neoadjuvant chemoradiation followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell carcinoma of the esophagus. The trial aims to enroll 350 patients total with 175 patients in each arm. The primary objective is to compare median survival rates and quality of life between the two treatment groups. Secondary objectives include comparing pathological responses, progression-free survival, number of complete resections, treatment toxicity, and costs. The chemoradiation regimen involves weekly paclitaxel and carboplatin chemotherapy with concurrent radiation over 5 weeks. Patients will then undergo surgery and be followed up for survival and quality of life outcomes
Total neoadjuvant therapy for rectal cancer 2016Mohamed Abdulla
1) Total neoadjuvant therapy, consisting of chemotherapy followed by chemoradiation and surgery, may improve outcomes for rectal cancer over the traditional approach.
2) Ongoing clinical trials are investigating selective use of radiation and whether radiation can be omitted from some neoadjuvant regimens based on risk factors and response.
3) Near total neoadjuvant therapy with upfront chemotherapy alone may achieve pathologic complete responses in a third of patients and warrants further exploration as an alternative to traditional chemoradiation.
Advances in induction in Acute Lymphocytic Leukemiaspa718
This document summarizes key findings from recent studies on improving induction therapy for acute lymphocytic leukemia (ALL). It describes trials showing that intensified chemotherapy regimens based on pediatric protocols improved outcomes for young adults compared to historical regimens. A trial incorporating the targeted therapy ponatinib into frontline therapy for Philadelphia chromosome-positive ALL achieved high rates of complete response and molecular response. Combining the epigenetic agents decitabine and vorinostat with chemotherapy showed tolerability and clinical benefit for relapsed/refractory ALL. Overall, the document discusses advances demonstrating that pediatric-inspired and targeted regimens are feasible and effective for certain adult ALL patients.
Adjuvant therapy in pancreatic cancer.pptxSujan Shrestha
This document summarizes the evolution of adjuvant therapy trials for pancreatic cancer. It discusses several major trials including ESPAC-1 which established 5FU + leucovorin as standard adjuvant therapy, CONKO-001 which showed gemcitabine was beneficial, ESPAC-3 which found similar survival for 5FU vs gemcitabine, ESPAC-4 which found gemcitabine + capecitabine improved survival, the PRODIGE/UNICANCER trial which showed modified FOLFIRINOX significantly improved survival over gemcitabine, and the APACT trial which found nab-paclitaxel + gemcitabine did not significantly improve DFS over gemcitabine alone.
Olaparib is an oral PARP inhibitor that has shown efficacy in the treatment of breast and ovarian cancers associated with BRCA mutations. In breast cancer, phase III trials OlympiA and OlympiAD demonstrated that olaparib improves invasive disease-free survival and progression-free survival, respectively, in patients with germline BRCA mutations. In ovarian cancer, phase III trials SOLO-1, PAOLA-1, and PRIMA found that olaparib improves progression-free survival when used as maintenance therapy or in combination with chemotherapy in patients with BRCA mutations. Olaparib is now approved for several indications based on these trials and provides an important targeted treatment option for cancers associated
This document summarizes treatment approaches for early-stage Hodgkin lymphoma. It describes the evolution from radiotherapy alone to combined modality therapy with chemotherapy and radiotherapy. Key findings include:
1) Combined modality therapy is superior to radiotherapy alone in achieving high cure rates of over 90% for early-stage disease.
2) 4 cycles of ABVD chemotherapy followed by involved-field radiotherapy is as effective as subtotal nodal radiotherapy plus chemotherapy.
3) For selected early-stage favorable disease, 2 cycles of ABVD chemotherapy and 20Gy radiotherapy may be sufficient treatment.
4) For early-stage unfavorable disease, 4 cycles of ABVD chemotherapy with 30Gy
Mr. PR, a 58-year-old male, presented with changes in bowel habits and anemia. Further investigation revealed stage IV rectal cancer with liver and lung metastases. He received FOLFOX chemotherapy with bevacizumab, showing an excellent response. He was then switched to maintenance capecitabine and bevacizumab. Clinical trials demonstrate that bevacizumab improves outcomes when added to first-line chemotherapy for metastatic colorectal cancer. However, it should not be combined with anti-EGFR agents in patients with KRAS wild-type tumors.
This document summarizes the initial therapies for chronic lymphocytic leukemia (CLL) including chemoimmunotherapy regimens like FCR and BR as well as targeted therapies like BTK inhibitors. Key points discussed include trial results establishing FCR as the standard therapy but with risks of myeloid neoplasms and infections in older patients. The document also reviews trials demonstrating the efficacy of ibrutinib for CLL treatment with improved progression-free and overall survival compared to chemoimmunotherapy or chlorambucil, though it can cause atrial fibrillation, bleeding risks, and infections. Complications and management of ibrutinib therapy are also summarized.
The document discusses pancreatic ductal adenocarcinoma (PDA) and different treatment approaches. It summarizes several key trials evaluating neoadjuvant therapy, adjuvant therapy, and chemotherapy for resectable, borderline resectable, locally advanced, and metastatic PDA. The take home message is that more randomized controlled trials are needed to determine the optimal treatment approach for different PDA stages, but neoadjuvant therapy appears beneficial for locally advanced and borderline resectable disease, while gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy provide good outcomes for metastatic PDA.
This study compared the effectiveness of two chemotherapy regimens, BEACOPP and COPP-ABVD, for treating advanced Hodgkin's lymphoma. 49 patients received either BEACOPP (25 patients) or COPP-ABVD (24 patients). The rate of freedom from treatment failure at 5 years was higher for BEACOPP at 76% compared to 69% for COPP-ABVD. Overall survival rates at 5 years were also higher for BEACOPP at 88% versus 83% for COPP-ABVD. While BEACOPP resulted in better tumor control and survival, it also had more acute toxicity including grade 4 leukopenia in some cycles.
This document summarizes the results of a clinical trial investigating the efficacy and safety of pembrolizumab (anti-PD-1 antibody) in patients with advanced melanoma that progressed after treatment with ipilimumab. The overall response rate was 26% in the 2 mg/kg group and 10% in the 10 mg/kg group, with responses ongoing after 1 year. Pembrolizumab demonstrated a manageable safety profile, with grade 3-4 drug-related adverse events occurring in 12% of patients. This trial provides evidence that pembrolizumab is an effective treatment option for patients with advanced melanoma who have progressed on ipilimumab.
Among the trials reviewed in 2016:
1) A study of grade 2 gliomas in young patients found that progression-free survival and overall survival were longer for those who received radiation therapy plus chemotherapy compared to radiation therapy alone.
2) A prostate cancer study found that among men with localized prostate cancer, survival was similar for those undergoing surveillance with PET-CT scans compared to planned neck dissection, but surveillance resulted in fewer operations and was more cost-effective.
3) A soft-tissue sarcoma study found that overall survival was improved for patients receiving eribulin compared to an active control, suggesting eribulin could be a new treatment option for advanced soft-tissue sarcoma.
Pazopanib is an oral multi-targeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma. Results from a phase III randomized controlled trial found that pazopanib significantly prolonged progression-free survival compared to placebo in treatment-naive and cytokine-pretreated patients with metastatic renal cell carcinoma. Common adverse events included diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Economic evaluations found sunitinib to be cost-effective compared to interleukin-2 and interferon-alpha for first-line treatment of metastatic renal cell carcinoma from US and Swedish societal perspectives. However, direct comparisons of cost-effectiveness between pazopanib and other targeted therapies are limited due to
1) A study compared the efficacy and safety of Roxadustat versus erythropoiesis-stimulating agents for treating anemia in chronic kidney disease patients. A meta-analysis found that Roxadustat significantly increased hemoglobin and improved iron metabolism but had a higher risk of serious adverse events.
2) Another study compared splenectomy versus eltrombopag as second-line treatments for immune thrombocytopenic purpura and found that while splenectomy had a faster response time, the overall response rates were similar between the two treatments after 2 years.
3) A meta-analysis on treatments for aplastic anemia found that rabbit antithymocyte globulin and horse antithym
Vonoprazan triple and dual therapy was found to be noninferior to lansoprazole triple therapy for eradicating Helicobacter pylori infection according to a randomized clinical trial conducted in the US and Europe. Vonoprazan triple therapy achieved an 84.7% eradication rate of non-resistant strains compared to 78.5% for lansoprazole triple therapy. Vonoprazan triple therapy also had a higher 65.8% eradication rate of clarithromycin-resistant strains than lansoprazole triple therapy's 31.9% rate. Adverse effects were generally mild to moderate and similar between treatment groups.
Tonight’s speakers: Dr. Dan Sargent and Kim Ryan
Disclaimer: “This Report is not an official event of the 2012 Gastrointestinal Cancers Symposium. Not sponsored or endorsed by any of the cosponsoring organizations of the 2012 Gastrointestinal Cancers Symposium.”
- The document summarizes adjuvant therapies for malignant melanoma that have been presented by Dr. v.veeranath reddy and moderated by Dr. G.Puranik at a journal club meeting.
- Traditional adjuvant therapies included wide local excision, lymph node dissection, and radiotherapy to lymph node basins. However, evidence for their impact on survival is lacking.
- Recent therapies that have shown improved survival include targeted BRAF and MEK inhibitors for BRAF mutant tumors, and immuno therapies like anti-PD-1 inhibitors for BRAF wild type tumors. These are now established as first line therapies for stage 4 disease.
- Ongoing adjuvant trials are investigating
Sickle Cell Disease (SCD) is major health problem in
Tanzania. Every year, approximately 11000 babies are born
with SCD1, and this number is expected to double by the year
2050. Tanzania has the fourth greatest number of annual
SCD births in all of Africa, and the fifth greatest in the world.
In addition, almost 20% of the Tanzanian population carries a
copy of the sickle gene in a form of sickle cell trait (AS).
Despite these staggering statistics, Tanzania has made
progress in the fight against SCD over the past decade. In
2008, the Ministry of Health and Social Welfare by then,
recognized SCD as a priority disease in the National strategy
for Non-communicable disease 2009- 2015, calling for all
sector to cooperate in combating the disease. A chapter on
SCD was also included in the national Non-communicable
Disease Treatment Manual.
Hydroxyurea is useful in the management of individuals with SCD. It reduces the complications
of SCD in infants, children and adults based on its ability to:
o Increase haemoglobin F levels
o Increase steady state hemoglobin counts
o Lower WBC and PLTs hence moderate the chronic inflammation state in SCD
Indications for starting hydroxyurea:
All children 9 months and above with proven SCD
Adolescents and adults with the following:
o Recurrent VOC ( 3 or more severe episodes requiring admission in the last 12
months)
o Severe and/or recurrent ACS (2 or more episodes in a lifetime)
o History of stroke or abnormal TCD (≥199cm/sec)
o Severe symptomatic chronic anemia that interferes with daily activities or quality of
life
o To reduce the risk of new or recurrent stroke where chronic transfusion therapy is not
feasible.
o Recurrent priapism
o Patient with chronic kidney disease on erythropoietin to improve anemia
#SickleCell disease#Indications for Hydroxyurea#Hamisi Mkindi#CKD#Investigations:
FBP - absolute neutrophil count (ANC) > 1,500/µl, platelet > 100,000/ul, Hb> 6g/dl.
If Hb is less than 6gm/dl do Reticulocyte Count[Do not start hydroxyurea in patients with
Hgb< 6 g/dl AND absolute reticulocyte count (ARC)<100,000/µL]
Serum Creatinine - should be within normal range,
Serum ALT – should not be greater than twice the upper limit of normal,
Bilirubin Total and direct
Urine Pregnancy Test in women
HPLC - Quantification of HbF (if this test cannot be done, Hydroxyurea should be prescribed
nevertheless and an elevated baseline HbF should not affect the decision to initiate
hydroxyurea)
The document discusses development plans for AR-67, a third generation camptothecin analog, in glioblastoma multiforme (GBM) and pancreatic cancer. It provides background on AR-67's current phase 2 data in GBM which showed around a 10% overall response rate. It then outlines considerations for AR-67's development pathway, including understanding the competitive GBM treatment landscape, reviewing data on irinotecan in GBM as a comparable drug, and regulatory requirements. The document proposes a clinical development plan for AR-67 in GBM and pancreatic cancer with timelines and cost estimates, and discusses opportunities and risks for AR-67 based on its pharmacokinetic profile relative to other approved camptot
This document discusses recent treatments for lupus nephritis and summarizes a case study. It reviews definitions of glomerular pathology, the pathogenesis of lupus nephritis including the role of immune complexes, and the WHO classification system. It summarizes recent clinical trials comparing cyclophosphamide and mycophenolate mofetil as induction therapies, and azathioprine versus mycophenolate mofetil for maintenance. Rituximab was not found to be superior to placebo as an add-on therapy in one trial. The document recommends treatment and reviews considerations for a specific unemployed African American male patient with new onset nepus nephritis.
Similar to HODGKINS LYMPHOMA ADVANCED STAGE MANAGEMENT (20)
This document summarizes ductal carcinoma in situ (DCIS), a non-invasive breast cancer confined to the breast ducts. It discusses the increasing incidence of DCIS due to mammogram screening, challenges in management, histologic features, mammographic appearance, prognostic factors, and treatment options including observation, breast-conserving surgery with or without radiation, and mastectomy. Controversy remains regarding optimal treatment, with the goal being eradication of cancer and prevention of invasive breast cancer.
CARCINOMA OVARY- EARLY STAGE MANAGEMENTNabeel Yahiya
This document discusses staging, treatment, and survival rates for ovarian cancer. It notes that over 70% of patients present with advanced stage III or IV disease, and less than 40% of women are cured. Primary treatment consists of surgical staging and cytoreduction followed by chemotherapy. Platinum-based chemotherapy, particularly carboplatin and paclitaxel, is now the standard first-line treatment and has improved progression-free and overall survival rates compared to previous single agents or regimens. Adjuvant chemotherapy is also now recommended for early stage high risk disease to further reduce relapse rates.
The pituitary gland is a small structure located at the base of the brain that regulates several important hormonal functions. It has anterior and posterior lobes with different embryological origins. The anterior lobe secretes hormones that control other endocrine glands, while the posterior lobe stores and releases hormones involved in water balance and milk release. Pituitary adenomas are tumors that can develop in the pituitary gland and cause hormonal imbalances or mass effects. Treatment depends on the size and secretory activity of the tumor, and may involve surgery, medication, radiation therapy, or observation.
This document discusses pain management in cancer patients. It notes that 75% of advanced cancer patients experience pain, with one third having a single pain site and one third having two or more pain sites. Pain management involves a multidimensional evaluation and may include modification of the pathological process, non-drug methods, interruption of pain pathways, modification of lifestyle, and use of analgesics like opioids, non-opioids, and adjuvants. Strong opioids combined with non-opioids and adjuvants are recommended for severe pain.
This document discusses high grade gliomas, which include anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and glioblastoma multiforme. It describes the epidemiology, clinical features, prognosis, and management of these tumors. The optimal treatment involves maximal safe surgical resection followed by concurrent chemoradiation and adjuvant chemotherapy. Radiotherapy techniques such as 3D conformal radiation therapy and intensity-modulated radiation therapy aim to deliver a dose of 60 Gy to the tumor volume while sparing surrounding normal brain tissue. However, dose escalation above standard doses has not shown a survival benefit.
This document summarizes the management of indolent lymphomas including follicular lymphoma grade 1-2, marginal zone lymphoma involving extranodal sites (MALT lymphoma), nodal sites, and the spleen, and lymphoplasmacytic lymphoma. For early stage follicular lymphoma, radiation therapy alone is usually sufficient and can cure 20% of patients. For advanced disease, chemoimmunotherapy with rituximab-containing regimens is preferred. MALT lymphoma often responds to antibiotics for H. pylori or local radiation therapy. Splenic marginal zone lymphoma commonly presents with fatigue in elderly men.
carcinoma breast RADIOTHERAPY TECHNIQUESNabeel Yahiya
This document discusses various radiation therapy techniques for breast carcinoma, including indications for radiation, simulation techniques, post-mastectomy radiation techniques, nodal irradiation techniques, contouring guidelines, boost techniques after breast conservation surgery, intensity modulated radiation therapy (IMRT), and accelerated partial breast irradiation (APBI). It covers topics such as treatment positioning and fields, target volume delineation, dose schedules, and techniques for nodal irradiation and tumor bed boosting.
The document discusses carcinoma of the pancreas. It covers the anatomy, epidemiology, risk factors, genetics, screening, staging, pathologic conditions, clinical presentation, evaluation, management approaches for resectable, borderline resectable, and unresectable disease, surgical procedures including Whipple procedure and distal pancreatectomy, complications, adjuvant therapy approaches studied in trials such as ESPAC-1, and the role of chemoradiation following gemcitabine chemotherapy.
This document summarizes the management of rectal cancer. It discusses various imaging modalities used for clinical staging such as transrectal ultrasound, CT scan, and MRI. It then covers staging, prognostic factors, principles of pathologic review, and various treatment options including surgery (local excision, transabdominal resection, low anterior resection), total mesorectal excision, laparoscopic resection, and the role of combined modality therapy with chemotherapy and radiotherapy.
Vaginal cancer is a rare malignancy representing 1-2% of gynecologic cancers. Most cases are metastatic from cervical or endometrial cancer. Risk factors include HPV infection and prior pelvic radiation. Symptoms include abnormal bleeding and discharge. Diagnosis involves biopsy of any suspicious lesions. Treatment typically involves radiation therapy, with surgery reserved for early stage or recurrent disease. Prognosis depends on stage, with 5-year survival rates of 70-80% for stage I but dropping to 0% for stage IV disease. Recurrence rates after radiation range from 10-45% depending on stage.
This document discusses squamous cell carcinoma (SCC), a type of non-melanoma skin cancer. It notes that SCC comprises about 20% of non-melanoma skin cancers. Risk factors for SCC include cumulative sun exposure, fair skin, genetic conditions, immunosuppression, arsenic exposure, and other skin damage or diseases. Actinic keratosis is a precancerous lesion that can progress to SCC. Diagnosis involves biopsy and imaging if needed to assess spread. Treatment depends on risk factors and location but commonly includes surgery, Mohs surgery, radiation, or a combination for more advanced cases.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
7. MOPP
• Devised by Devita and Longo in 1970s
1st CCT regimen to be started with a CURATIVE intent
• Doses:
– Nitrogen Mustard 6 mg/m2 I/V D1 and D8
– Vincristine (Oncovine) 1.4 mg/m2 IV D1 and D8
– Procarbazine 100 mg/m2 D1 to D14
– Prednisone 40 mg/m2 D1 to D 14
• Cycles repeated every 21 days for 6 such cycles
8. • MOPP Regimen -The First Generation
• Complete remission rates of 73% to 81%
• long-term freedom from progression of 36% to 52%,
• long-term OS of 50% to 64% were obtained in
advanced stages
9. • Despite the good initial results with MOPP therapy
• several groups investigated alternative regimens to
improve the efficacy or reduce toxicities
• substitution of an alkylating agent like
cyclophosphamide or chlorambucil for mustargen
• vinca alkaloid like vinblastine or vincristine as well as
alteration of the doses of procarbazine and
prednisone
10. Alternate regimens: ChlVPP (LVPP)
– Chlorambucil 6mg/m2 PO D1-D14 (total dose limited to
10mg/m2 usually)
– Vinblastine 6 mg/m2 IV D1 and D8
– Procarbazine 100 mg/m2 PO D1 to D14
– Prednisone 40 mg PO D1 to D 14
• Contains three oral agents with better ease of administration.
• Acute side effects like myelopsuppresssion, nausea and
vomiting, neuropathy, and alopecia, are much less.
• CR are in the range of 80% and long term results similar to
those expected from MOPP regimen.
11. Other MOPP variants
• MVPP : Designed to
overcome neurotoxicity of
Vincristine by use of
vinblastine
– Nitrogen Mustard
6mg/m2 IV D1 and D8
– Vinblastine 6 mg/m2 IV
D1 and D8
– Procarbazine 100 mg/m2
PO D1 to D14
– Prednisone 40 mg PO D1
to D14
• BCVPP : Designed to
overcome the toxicity of
nitrogen mustard:
– BCNU 100mg/m2 IV D1
– Cyclophosphamide 600
mg/m2 IV D1
– Vinblastine 5 mg/m2 PO
D1
– Procarbazine 50 mg/m2
PO D1 and 100 mg/m2
D2 to D20
– Prednisone 40mg PO D1
to D20
12. • several MOPP-like regimens showed similar efficacy
with less acute gastrointestinal and neurologic
toxicity.
• BUT
• (i) still only about 50% patients could be cured
• (ii) the alkylating-based combination was associated
with an increased risk of sterility and acute leukemia
13. • Bonadonna et al. introduced the ABVD (doxorubicin,
bleomycin, vinblastine, dacarbazine) regimen
• The Second Generation
14. • The authors selected these agents because of:
– Each of the new drugs potentially non cross resistant with
MOPP
– Doxorubicin and Bleomycin has independent efficacy in HD
– Vinblastine is effective in patients failed on Vincristine
– Therapeutic efficacy of DTIC in previously treated HD had
been demonstrated by Frei et al in 1972.
– In addition DTIC has little myelotoxicity so can be
combined with adriamycin or bleomycin with little
synergistic toxicity.
15. • Dosage and Frequency:
– Adriamycin 25 mg/m2 IV D1 and D15
– Bleomycin 10 U/m2 IV D1 and D15
– Vinblastine 6 mg/m2 IV D1 and D15
– Dacarbazine 375 mg/m2 D1 and D15
16. • The Milan group compared three cycles of MOPP or
ABVD
• followed by extended-field irradiation and three
additional cycles of the same chemotherapy
17. • A significant difference in favor of ABVD could be
achieved with freedom from progression rates of
63% MOPP versus 81% of ABVD
• MOPP and ABVD were highly active regimens and
had nonoverlapping toxicities.
• combinations of MOPP and ABVD was tried to
further increase treatment results.
18. • The Milan group randomized patients in stage IV
• MOPP or MOPP/ABVD for up to 12 cycles.
• freedom from progression at 8 years (36% MOPP
versus 65% MOPP/ABVD; P < 0.005).
• Subsequently three large cooperative trial groups
(ECOG, CALGB, and EORTC) have confirmed these
results
19. • The CALGB tested in a three-arm trial 6 to 8 cycles of
MOPP
• 6 to 8 cycles of ABVD
• 12 cycles of MOPP alternating with ABVD.
• At 10 years, the FFS rates were 38% for MOPP, 55%
for ABVD, and 50% for MOPP/ABVD.
• OS was not significantly different, although there was
a trend in favor of ABVD or MOPP/ABVD compared
with MOPP alone.
20. • The EORTC trial
• MOPP/ABVD showed a significantly higher FFS rate
at 6 years (43% MOPP, 60% MOPP/ABVD)
• Thus, ABVD alone and MOPP/ABVD are more
effective than MOPP alone.
• In addition ABVD alone had the advantage of less
acute and long-term toxicities
21. Duration of Therapy
• Bonadonna et al. initially applied up to 12 cycles of
MOPP and later in the alternating program 8 cycles
without reduction in efficacy.
• The CALGB trial demonstrated that 8 cycles of ABVD
was comparable to 12 cycles of alternating
MOPP/ABVD.
22. Hybrid Regimens: The Third
Generation
• The theoretic basis for multidrug regimens is the
predicted advantage of the early introduction of all
active agents to avoid resistant tumor cell clones.
• This idea is based on a model proposed by Goldie
and Coldman who related the drug sensitivity of
tumors to their spontaneous mutation rate.
23. • The NCIC compared the MOPP-ABV hybrid with
alternating MOPP/ABVD
• At 5 years there was no significant difference in the
OS rates between both arms
• however, the hybrid regimen was associated with
higher hematologic and nonhematologic toxicities.
24. • Dose Schedule:
– Nitrogen Mustard 6 mg/m2 IV D1
– Vincristine 1.4 mg/m2 IV D1
– Procarbazine 100 mg/m2 PO D1 to D7
– Prednisone 40 mg PO D1 to D 14
– Adriamycin 35 mg/m2 IV D8
– Vinblastine 6mg /m2 IV D8
– Bleomycin 10 U/m2 IV D8
25. • The Milan group compared their MOPP/ABV hybrid
with alternating MOPP/ABVD.
• Freedom from progression and OS rates at 10 years
revealed no significant difference between the hybrid
and alternating arms
26. • U.S. Intergroup trial in which they compared ABVD
with the MOPP/ABV hybrid in 856 adult patients with
stage IIIA, IIIB, IV
• no statistical difference observed between the ABVD
and the MOPP/ABV arms as far as FFS and OS were
concerned
• greater toxicity was seen during therapy and after
completion of treatment in the MOPP/ABV
27. • the Goldie-Coldman hypothesis could not be proven in
advanced-stage Hodgkin lymphoma
• this could be because the optimal hybrid regimen was
not identified
• ABVD has emerged as the standard against which newer
treatments must be compared
• With ABVD, 60% to 70% of patients will be free of disease
at 5 years.
• ABVD is much less likely to cause severe myelotoxicity,
acute leukemia, or sterility than treatment programs that
contain significant doses of alkylating agents.
28. New Chemotherapy Regimens: The
Fourth Generation
• Pulmonary toxicity of bleomycin, which is especially
pronounced in children and in combination with
mediastinal irradiation, remains a major concern
with ABVD
29. • 20% to 60% response rate in refractory Hodgkin
lymphoma was reported with single-agent etoposide.
• Based on these considerations, several etoposide-
containing drug regimens were developed
37. Results Stanford V
• In a pilot study recruiting 126 patients with a FU of 6.9 years.
• The estimated 5-year freedom from progression was 89%
• Overall survival was 96% at a median observation time of 4.5
years
38. • Randomized Phase III Trial of ABVD Versus Stanford V With or
Without Radiation Therapy in Locally Extensive and Advanced-
Stage Hodgkin Lymphoma: An Intergroup Study Coordinated
by the Eastern Cooperative Oncology Group (E2496)
• There was no significant difference in the overall response
rate between the two arms
• with complete remission rates of 73% for ABVD and 69% for
Stanford V.
• At a median follow-up of 6.4 years, there was no difference in
FFS: 74% for ABVD and 71% for Stanford V at 5 years
39. GHSG HD9 study
• compared two different doses (baseline and escalated)
(BEACOPP) chemotherapy regimen in 1,196 patients with
advanced-stage Hodgkin's lymphoma (HL).
• eight cycles of (COPP) alternating with (ABVD)
• eight cycles of BEACOPP baseline
• eight cycles of BEACOPP escalated.
40. • At 10 years, freedom from treatment failure (FFTF) was 64%,
70%, and 82%
• OS rates of 75%, 80%, and 86% for patients treated with
COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP
escalated (arm C)
• The 10-year follow-up of the HD9 trial demonstrates a
stabilized significant improvement in long-term FFTF and OS
for BEACOPP escalated in advanced-stage HL.
41. The HD15 trial (2003-2008)
• designed to find out whether it is possible to reduce the
number of chemotherapy in patients who are given
additional radiotherapy
• 8 x escalated BEACOPP were compared to
• 6 x escalated BEACOPP and to 8 x BEACOPP 14.
• After completion of chemotherapy, a PET examination was
performed and PET-positive residual tumor tissues larger than
2.5 cm were irradiated.
42. RESULTS
• Treatment with six cycles of BEACOPP(escalated)
followed by PET-guided radiotherapy
• was more effective in terms of freedom from
treatment failure
• less toxic than eight cycles of the same
chemotherapy regimen.
43. ROLE OF RT
• radiotherapy may be used as an adjuvant after
complete remission with standard chemotherapy.
• radiotherapy may be an integrated component of a
combined modality program, possibly with reduced
or brief chemotherapy
• radiotherapy can serve as a non-cross resistant
treatment for patients with partial or uncertain
response after chemotherapy
44. • SWOG study -Sixty-one percent of patients who
achieved complete remission were randomized to
low-dose involved-field radiotherapy or no further
treatment
• no significant differences in remission duration or OS
were detected
45. • The GHSG analyzed the role of low-dose (20 Gy)
involved-field radiotherapy
• versus two cycles of additional consolidation
chemotherapy in 288 patients in complete remission
after initial chemotherapy with COPP/ABVD.
• There were no significant differences in freedom
from progression or OS rates between the two
treatment arms
46. UKLG LY09 Trial
• study analyzed the outcomes of nonrandomized consolidation
radiotherapy (RT)
• given after chemotherapy in the initial treatment of advanced
Hodgkin's lymphoma (HL)
• Postchemotherapy RT for consolidation was given to patients
with bulk disease
• partial response after chemotherapy
47. • PFS and OS was better who received RT
• HD12 trial of the German Hodgkin Study Group
• eight cycles of BEACOPP(escalated) was compared with
• four cycles of BEACOPP(escalated) followed by four cycles of
the baseline dose of BEACOPP (BEACOPP(baseline); 4 + 4),
and RT with no RT in the case of initial bulk or residual disease
• FFTF was inferior without RT particularly in patients who had
residual disease after chemotherapy
• not in patients with bulk in complete response after
chemotherapy
52. Progressive and Relapsed Disease
• relapse generally occurs within 1 to 5 years following
primary therapy
• new histology should be obtained as the risk for
second tumors NHL or solid tumors are increased
• clinical and radiographic restaging is recommended
53. Prognostic Factors
• the treatment modality used in first-line therapy, age
• relapse sites
• quantity of disease at relapse
• presence or absence of systemic symptoms
• duration of first remission is a major determinant of
a second complete response
54. • Primary progressive Hodgkin lymphoma -patients
who never achieved a complete remission or relapse
within 3 months after the end of treatment.
• Early relapses between 3 and 12 months of complete
remission (approximately 15% of all cases)
• Late relapses after an achieved complete remission
lasting at least 12 months (approximately 15% of all
cases).
56. Salvage Radiotherapy
• in patients without B symptoms
• who have not been given radiation previously or
• who relapse locally outside the initial radiation field.
57. • Wirth et al. reported the experience of salvage
radiotherapy in 51 patients
• 45% achieved a complete response following
irradiation.
• Five-year failure-free survival and OS were 26% and
57%, respectively
• who relapsed in supradiaphragmatic nodal sites
without B symptoms has good prognosis
58. • HDT/ASCT VS CONVENTIONAL
CHEMOTHERAPY
• BRITISH NATIONAL LYMPHOMA INVESTIGATION
• Improved EFS and PFS with HDT/ASCT
• No improvement in OS
• TRM was high
59. • Bad prognosis
• Less than 1 yr to relapse
• Presence of extanodal site at relapse
• B symptoms
• Stage at relapse
60. High Dose Chemotherapy
• Given along with stem cell support.
• Usually limited to primary progressive HL and early relapse
after salvage CCT failure
• Regimens used:
– CBV regimen (Cyclophosphamide, BCNU, Etoposide)
– BEAM (BCNU, Etoposide, Ara-C, Melphalan)
• Complications:
– Treatment related mortality : 14% -5%
– Infections: Early and delayed
– MDS / AML risk : 4% -15% within 5yrs.
– Cardiac and Pulmonary complications
– Sterility : Universal
61. • Cyto reduction-
• With 2nd line chemotherapy before HDT/ASCT
• GVD ( gemcitabine, vinorelbine ,liposomal
doxorubicine)
• GCD ( Gemcitabine, carboplatin, dexamethasone )
• Bendamustine, lenalidomide ,everolimus
62. • Brentuximab vedotin a CD-30 directed antibody
conjugate can be used
• It is advocated in who fails after HDT/ASCT or who
are not fit for it