1. GISTs were historically misdiagnosed and poorly treated, but advances in molecular genetics and targeted therapies have transformed management.
2. Imatinib revolutionized treatment by specifically targeting KIT and PDGFRA mutations in most GISTs, achieving high response rates and prolonged disease control.
3. Continuous long-term imatinib treatment is now standard for advanced/metastatic GIST due to the near-universal risk of rapid progression upon treatment cessation.
This presentation summarizes the state of the art with respect to the management of GIST. It covers the basics of surgical and medical management including the role of neoadjuvant and adjuvant targeted therapy. www.ellenhornmd.com
1) Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract that arise from interstitial cells of Cajal.
2) GISTs most commonly occur in the stomach and small intestine and present with GI bleeding, abdominal pain, or mass.
3) Diagnostic workup includes CT, endoscopy, and biopsy to establish a diagnosis, assess resectability, and identify mutations for targeted therapy.
4) Complete surgical resection is the main treatment, while adjuvant imatinib therapy helps maintain remission and unresectable tumors may be downstaged with neoadjuvant imatinib.
4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ: Ακτινοθεραπεία στον καρκίνο του τραχήλου της ...isrodoy isr
This document discusses gastrointestinal stromal tumors (GIST) and the use of adjuvant imatinib therapy. It provides background on GIST epidemiology and risk factors for recurrence. Studies show adjuvant imatinib for 1 year after surgery significantly reduces recurrence rates compared to placebo, especially for high-risk patients. The SSGXVIII trial found adjuvant imatinib for 3 years further reduced recurrence rates compared to 1 year of treatment, with no significant difference in overall survival yet. Adjuvant imatinib for 3 years may provide additional benefit over 1 year, especially for high-risk GIST patients.
Gastrointestinal stromal tumor, also called GIST is the most common mesenchymal tumor of GI tract. Over the years, the management of these tumors have evolved. This ppt shows the importance of mutation testing, wild type GIST, Newer drugs like avapritinib and ripretinib etc. Along with that it also shows Indian perspective and need of dedicated GIST clinics in India
This document provides an overview of gastro-intestinal stroma tumors (GISTs). It discusses the origins and characteristics of GISTs, how they present clinically and appear pathologically. Key points include that GISTs arise from interstitial cells of Cajal in the gastrointestinal tract. Clinical symptoms depend on tumor size and location. Pathologically, GISTs are defined by mutations in KIT or PDGFRA genes and are classified based on mitotic rate, which influences prognosis. Imaging can help identify and characterize GISTs, which most commonly metastasize to the liver and peritoneum. Differential diagnosis includes other submucosal masses and tumors in the GI tract.
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that arise in the gastrointestinal tract. They range in size from a few millimeters to over 30 cm. Microscopically, GISTs contain eosinophilic structures that stain brightly with PAS. Symptoms are non-specific and include abdominal pain, bleeding, and early satiety. Diagnostic evaluations include CT, EUS, and biopsy. Treatment depends on tumor size and risk of recurrence or metastasis. For resectable disease, surgery is typically recommended, while imatinib is recommended for unresectable, metastatic, or recurrent tumors. Long-term surveillance is important due to the risk of recurrence within the first
- The patient is a 36-year-old man who underwent neoadjuvant chemoradiotherapy in 2015 for rectal cancer.
- In 2021, he presented with frequent urination. Imaging showed a large recurrent mass involving abdominal structures.
- Biopsy of the skin deposit was suspicious for metastatic mucinous carcinoma.
- The case discusses the current treatment approaches for locally advanced rectal cancer, including neoadjuvant and total neoadjuvant therapy options, and choices for chemotherapy and radiotherapy.
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
This presentation summarizes the state of the art with respect to the management of GIST. It covers the basics of surgical and medical management including the role of neoadjuvant and adjuvant targeted therapy. www.ellenhornmd.com
1) Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract that arise from interstitial cells of Cajal.
2) GISTs most commonly occur in the stomach and small intestine and present with GI bleeding, abdominal pain, or mass.
3) Diagnostic workup includes CT, endoscopy, and biopsy to establish a diagnosis, assess resectability, and identify mutations for targeted therapy.
4) Complete surgical resection is the main treatment, while adjuvant imatinib therapy helps maintain remission and unresectable tumors may be downstaged with neoadjuvant imatinib.
4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ: Ακτινοθεραπεία στον καρκίνο του τραχήλου της ...isrodoy isr
This document discusses gastrointestinal stromal tumors (GIST) and the use of adjuvant imatinib therapy. It provides background on GIST epidemiology and risk factors for recurrence. Studies show adjuvant imatinib for 1 year after surgery significantly reduces recurrence rates compared to placebo, especially for high-risk patients. The SSGXVIII trial found adjuvant imatinib for 3 years further reduced recurrence rates compared to 1 year of treatment, with no significant difference in overall survival yet. Adjuvant imatinib for 3 years may provide additional benefit over 1 year, especially for high-risk GIST patients.
Gastrointestinal stromal tumor, also called GIST is the most common mesenchymal tumor of GI tract. Over the years, the management of these tumors have evolved. This ppt shows the importance of mutation testing, wild type GIST, Newer drugs like avapritinib and ripretinib etc. Along with that it also shows Indian perspective and need of dedicated GIST clinics in India
This document provides an overview of gastro-intestinal stroma tumors (GISTs). It discusses the origins and characteristics of GISTs, how they present clinically and appear pathologically. Key points include that GISTs arise from interstitial cells of Cajal in the gastrointestinal tract. Clinical symptoms depend on tumor size and location. Pathologically, GISTs are defined by mutations in KIT or PDGFRA genes and are classified based on mitotic rate, which influences prognosis. Imaging can help identify and characterize GISTs, which most commonly metastasize to the liver and peritoneum. Differential diagnosis includes other submucosal masses and tumors in the GI tract.
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that arise in the gastrointestinal tract. They range in size from a few millimeters to over 30 cm. Microscopically, GISTs contain eosinophilic structures that stain brightly with PAS. Symptoms are non-specific and include abdominal pain, bleeding, and early satiety. Diagnostic evaluations include CT, EUS, and biopsy. Treatment depends on tumor size and risk of recurrence or metastasis. For resectable disease, surgery is typically recommended, while imatinib is recommended for unresectable, metastatic, or recurrent tumors. Long-term surveillance is important due to the risk of recurrence within the first
- The patient is a 36-year-old man who underwent neoadjuvant chemoradiotherapy in 2015 for rectal cancer.
- In 2021, he presented with frequent urination. Imaging showed a large recurrent mass involving abdominal structures.
- Biopsy of the skin deposit was suspicious for metastatic mucinous carcinoma.
- The case discusses the current treatment approaches for locally advanced rectal cancer, including neoadjuvant and total neoadjuvant therapy options, and choices for chemotherapy and radiotherapy.
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
This is an overview of the adjuvant Tx of pancreatic CA. A Lecture that was given in the annual conference of NCI Egypt: 45 years against cancer in Egypt. Cairo, April, 2013
The document discusses gastrointestinal stromal tumors (GISTs), which arise from interstitial cells of Cajal in the gastrointestinal tract. GISTs most commonly occur in the stomach and small intestine. Over 85% of GISTs have activating mutations in the KIT gene. Surgery is the primary treatment for localized GISTs, while targeted therapy with tyrosine kinase inhibitors such as imatinib is used for advanced or metastatic GISTs. Prognosis depends on factors like tumor size, mitotic rate, and mutation status, with smaller, lower grade GISTs having a better prognosis. Lifelong follow-up is important due to the risk of recurrence even after complete resection.
1) Aggressive fibromatosis is a rare soft tissue tumor that typically affects young adults. Surgery is the main treatment but recurrence is common.
2) New evidence shows systemic therapies like sorafenib, hormonal therapies, and chemotherapy can control the disease. A large trial found sorafenib significantly reduced recurrence compared to placebo.
3) Further research is still needed to determine optimal chemotherapy regimens and biomarkers to predict response to various treatments. "Wait and watch" may be suitable for less aggressive cases. Management of fibromatosis remains challenging due to the lack of high-quality data from India and validated patient-reported outcome measures.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
Gastric cancer discussion slides final version.pptnew.pptzoezettemarc
1) Peri-operative chemotherapy with ECX before and after surgery improves overall survival compared to surgery alone in resectable gastric cancer based on the MAGIC trial.
2) The ACTS-GT trial showed adjuvant S-1 chemotherapy improves 3-year survival compared to observation alone after D2 gastrectomy for stage II-III gastric cancer.
3) Combination chemotherapy improves survival over best supportive care alone in advanced gastric cancer, with regimens including anthracyclines and cisplatin or oxaliplatin showing better efficacy.
This document discusses recent updates in treating metastatic colorectal cancers. It presents several case studies of patients diagnosed with colorectal cancer and large metastatic tumors. It then reviews the epidemiology of colorectal cancer in India, including rising incidence rates. The document outlines different classifications and treatment approaches for patients with metastatic disease, including the goal of increasing overall survival. It also discusses the increasing number of treatment options and challenges of personalizing therapy based on a patient's molecular profile.
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
How the role of radiotherapy has evaluated in pancreatic cancer. Now it has become indispensable for treatment in pancreatic cancer. Radiotherapy can be used in the form of EBRT/SBRT/IORT.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
This document provides information on a case presentation of anal squamous cell carcinoma, including staging, diagnostic workup, management, prognostic factors, and follow up. Key points include:
- The mean age of diagnosis is 62 years and most common symptom is rectal bleeding. Imaging includes CT, MRI, and PET scans to stage disease.
- Treatment depends on disease stage but typically involves chemoradiation with concurrent 5-FU and mitomycin C or cisplatin. Several trials have shown improved outcomes with chemoradiation compared to radiation alone.
- Follow up involves examination and imaging to monitor for recurrence or metastasis. Prognostic factors include tumor size, response to initial treatment, and presence of late
This deals with novel molecular findings and their implications in Ewings sarcoma. The role of dose dense and dose intense chemotherapy and role of high dose chemotherapy. Additionally it also deals with survivor ship issues
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 key landmark clinical trials investigating treatments for metastatic gastric cancer.
- The ToGA trial found that adding trastuzumab (Herceptin) to standard chemotherapy (cisplatin and fluoropyrimidine) significantly improved overall survival and progression-free survival in patients with HER2-positive metastatic gastric cancer compared to chemotherapy alone. Median overall survival was 13.8 months with chemotherapy plus trastuzumab versus 11.1 months with chemotherapy alone.
- The REAL-2 trial demonstrated that cisplatin plus capecitabine was as effective as cisplatin plus fluorouracil for advanced gastric cancer, with less toxicity. Cisplatin plus capecitabine has since
1) The study evaluated the effectiveness of gamma knife (GK) surgery as primary or adjuvant treatment for posterior third ventricular tumors in 17 patients over 12 years.
2) Tumor control was achieved in 13 of 14 patients (92.8%) with an average follow up of 31 months, with 7 patients showing tumor reduction and 6 showing no change.
3) Primary GK achieved 100% tumor control for benign diseases and showed good control of malignant pinealoblastomas and metastases for up to 27 months.
Cette présentation faite le 27 Avril 2017 à l'Hôpital Saint Joseph organisée par le Dr Vincent de Parades fait le point sur les nouvelles approches multidisciplinaires dans la prise en charge des cancers colorectaux en insistant sur la prise en charge de la maladie métastatique hépatique et de la carcinome péritonéale pour terminer sur les nouvelles approches par immunothérapie. Cette EPU a connu un large succès d'audience avec plus de 60 participants. Merci à toutes et tous.
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
Rectal cancer treatment typically involves surgery. Local recurrence after conventional surgery occurs in 15-65% of cases on average. Long course preoperative chemoradiotherapy has been shown to reduce local recurrence rates compared to short course preoperative radiotherapy or radiotherapy alone. It increases local tumor control and survival rates with some toxicities but does not reduce colostomy rates. Preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy in reducing local recurrence rates without affecting overall survival.
- The document discusses liver and hepatobiliary cancers, focusing on hepatocellular carcinoma (HCC). It covers the epidemiology, risk factors, screening and diagnosis of HCC as well as staging systems and treatment options.
- Risk factors for HCC include hepatitis B and C infection, alcohol consumption, and aflatoxin intake. Screening ultrasound and AFP tests are used for early diagnosis in high-risk patients. The BCLC staging system guides treatment which includes resection, transplantation, ablation, and embolization.
- For intermediate stage HCC, transarterial chemoembolization provides the best outcomes, with 70-80% of patients surviving 1 year and 50% surviving 3 years. However
This document discusses the history and treatment of gastrointestinal stromal tumors (GISTs). It notes that GISTs were originally misclassified until 1983 when they were identified as distinct tumors. Treatment progressed slowly until 1998 when the association between GISTs and c-KIT was discovered, leading to the development of imatinib in 2001. Imatinib was approved for metastatic/unresectable GIST in 2002 and as adjuvant therapy for high-risk GIST in 2008 and 2012. The document discusses risk assessment tools and provides guidelines for adjuvant imatinib therapy for intermediate-high risk GIST of 3 years duration. It also discusses neoadjuvant imatinib and subsequent treatment options including sunitinib
This is an overview of the adjuvant Tx of pancreatic CA. A Lecture that was given in the annual conference of NCI Egypt: 45 years against cancer in Egypt. Cairo, April, 2013
The document discusses gastrointestinal stromal tumors (GISTs), which arise from interstitial cells of Cajal in the gastrointestinal tract. GISTs most commonly occur in the stomach and small intestine. Over 85% of GISTs have activating mutations in the KIT gene. Surgery is the primary treatment for localized GISTs, while targeted therapy with tyrosine kinase inhibitors such as imatinib is used for advanced or metastatic GISTs. Prognosis depends on factors like tumor size, mitotic rate, and mutation status, with smaller, lower grade GISTs having a better prognosis. Lifelong follow-up is important due to the risk of recurrence even after complete resection.
1) Aggressive fibromatosis is a rare soft tissue tumor that typically affects young adults. Surgery is the main treatment but recurrence is common.
2) New evidence shows systemic therapies like sorafenib, hormonal therapies, and chemotherapy can control the disease. A large trial found sorafenib significantly reduced recurrence compared to placebo.
3) Further research is still needed to determine optimal chemotherapy regimens and biomarkers to predict response to various treatments. "Wait and watch" may be suitable for less aggressive cases. Management of fibromatosis remains challenging due to the lack of high-quality data from India and validated patient-reported outcome measures.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
Gastric cancer discussion slides final version.pptnew.pptzoezettemarc
1) Peri-operative chemotherapy with ECX before and after surgery improves overall survival compared to surgery alone in resectable gastric cancer based on the MAGIC trial.
2) The ACTS-GT trial showed adjuvant S-1 chemotherapy improves 3-year survival compared to observation alone after D2 gastrectomy for stage II-III gastric cancer.
3) Combination chemotherapy improves survival over best supportive care alone in advanced gastric cancer, with regimens including anthracyclines and cisplatin or oxaliplatin showing better efficacy.
This document discusses recent updates in treating metastatic colorectal cancers. It presents several case studies of patients diagnosed with colorectal cancer and large metastatic tumors. It then reviews the epidemiology of colorectal cancer in India, including rising incidence rates. The document outlines different classifications and treatment approaches for patients with metastatic disease, including the goal of increasing overall survival. It also discusses the increasing number of treatment options and challenges of personalizing therapy based on a patient's molecular profile.
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
How the role of radiotherapy has evaluated in pancreatic cancer. Now it has become indispensable for treatment in pancreatic cancer. Radiotherapy can be used in the form of EBRT/SBRT/IORT.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
This document provides information on a case presentation of anal squamous cell carcinoma, including staging, diagnostic workup, management, prognostic factors, and follow up. Key points include:
- The mean age of diagnosis is 62 years and most common symptom is rectal bleeding. Imaging includes CT, MRI, and PET scans to stage disease.
- Treatment depends on disease stage but typically involves chemoradiation with concurrent 5-FU and mitomycin C or cisplatin. Several trials have shown improved outcomes with chemoradiation compared to radiation alone.
- Follow up involves examination and imaging to monitor for recurrence or metastasis. Prognostic factors include tumor size, response to initial treatment, and presence of late
This deals with novel molecular findings and their implications in Ewings sarcoma. The role of dose dense and dose intense chemotherapy and role of high dose chemotherapy. Additionally it also deals with survivor ship issues
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 key landmark clinical trials investigating treatments for metastatic gastric cancer.
- The ToGA trial found that adding trastuzumab (Herceptin) to standard chemotherapy (cisplatin and fluoropyrimidine) significantly improved overall survival and progression-free survival in patients with HER2-positive metastatic gastric cancer compared to chemotherapy alone. Median overall survival was 13.8 months with chemotherapy plus trastuzumab versus 11.1 months with chemotherapy alone.
- The REAL-2 trial demonstrated that cisplatin plus capecitabine was as effective as cisplatin plus fluorouracil for advanced gastric cancer, with less toxicity. Cisplatin plus capecitabine has since
1) The study evaluated the effectiveness of gamma knife (GK) surgery as primary or adjuvant treatment for posterior third ventricular tumors in 17 patients over 12 years.
2) Tumor control was achieved in 13 of 14 patients (92.8%) with an average follow up of 31 months, with 7 patients showing tumor reduction and 6 showing no change.
3) Primary GK achieved 100% tumor control for benign diseases and showed good control of malignant pinealoblastomas and metastases for up to 27 months.
Cette présentation faite le 27 Avril 2017 à l'Hôpital Saint Joseph organisée par le Dr Vincent de Parades fait le point sur les nouvelles approches multidisciplinaires dans la prise en charge des cancers colorectaux en insistant sur la prise en charge de la maladie métastatique hépatique et de la carcinome péritonéale pour terminer sur les nouvelles approches par immunothérapie. Cette EPU a connu un large succès d'audience avec plus de 60 participants. Merci à toutes et tous.
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
Immunotherapy maintenence for advanced urothelial cancerChandan K Das
- JAVELIN Bladder 100 was a phase 3 trial investigating avelumab maintenance therapy after platinum-based chemotherapy in patients with advanced urothelial carcinoma.
- The trial found avelumab maintenance significantly improved overall survival compared to best supportive care alone, with a 31% reduction in risk of death. Progression-free survival was also significantly improved.
- Subgroup analyses found overall survival benefits were consistent across all patient subgroups, including those with PD-L1-negative tumors. Response rates were also higher with avelumab maintenance.
- The safety profile of avelumab was manageable, with most treatment-related adverse events being grade 1-2 in severity and no new safety signals
Rectal cancer treatment typically involves surgery. Local recurrence after conventional surgery occurs in 15-65% of cases on average. Long course preoperative chemoradiotherapy has been shown to reduce local recurrence rates compared to short course preoperative radiotherapy or radiotherapy alone. It increases local tumor control and survival rates with some toxicities but does not reduce colostomy rates. Preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy in reducing local recurrence rates without affecting overall survival.
- The document discusses liver and hepatobiliary cancers, focusing on hepatocellular carcinoma (HCC). It covers the epidemiology, risk factors, screening and diagnosis of HCC as well as staging systems and treatment options.
- Risk factors for HCC include hepatitis B and C infection, alcohol consumption, and aflatoxin intake. Screening ultrasound and AFP tests are used for early diagnosis in high-risk patients. The BCLC staging system guides treatment which includes resection, transplantation, ablation, and embolization.
- For intermediate stage HCC, transarterial chemoembolization provides the best outcomes, with 70-80% of patients surviving 1 year and 50% surviving 3 years. However
This document discusses the history and treatment of gastrointestinal stromal tumors (GISTs). It notes that GISTs were originally misclassified until 1983 when they were identified as distinct tumors. Treatment progressed slowly until 1998 when the association between GISTs and c-KIT was discovered, leading to the development of imatinib in 2001. Imatinib was approved for metastatic/unresectable GIST in 2002 and as adjuvant therapy for high-risk GIST in 2008 and 2012. The document discusses risk assessment tools and provides guidelines for adjuvant imatinib therapy for intermediate-high risk GIST of 3 years duration. It also discusses neoadjuvant imatinib and subsequent treatment options including sunitinib
Gastrointestinal stromal tumors (GISTs) are rare sarcomas that arise from the gastrointestinal tract. Most commonly found in the stomach, they represent 0.2% of gastrointestinal tumors. While often asymptomatic, they can present with bleeding, pain, or obstruction. Diagnosis involves imaging such as endoscopy or CT scan followed by biopsy showing immunohistochemistry positive for CD117 in 95% of cases. Treatment involves surgical resection with clear margins although adjuvant therapy with imatinib is often used for higher risk tumors. Outcomes have improved greatly in the past two decades with 5-year survival rates now over 50% with appropriate treatment.
GISTs are rare tumors that arise from interstitial cells of Cajal in the gastrointestinal tract. The most common sites are the stomach, small intestine, and colon/rectum. Immunohistochemistry shows positivity for CD117 in 80-90% of cases. Surgery is the standard treatment for localized resectable GISTs, while imatinib is the standard first-line treatment for unresectable or metastatic GISTs due to its inhibitory effects on c-KIT and PDGFR-α mutations. Close monitoring with imaging is important after surgery or medical treatment due to the risk of recurrence.
This document summarizes the current state of targeted therapies for metastatic renal cell cancer. It discusses several front-line standard of care options including sunitinib, pazopanib, and bevacizumab with interferon. Ongoing areas of investigation mentioned include more potent VEGF inhibitors, biomarkers of response and resistance, alternative dosing schedules, and immunotherapy combinations with targeted agents.
Colon cancer is the second and third most common cancer in males and females. Screening programs have led to a reduction in late-stage diagnoses and mortality. Precise identification of prognostic patient groups allows for more targeted adjuvant therapy, improving disease-free and overall survival. Molecular markers of tumor aggressiveness aid in selecting optimal treatment approaches, increasing response rates, progression-free, and overall survival. A multidisciplinary team approach is essential for managing metastatic colon cancer with the goal of surgical cure in organ-limited disease.
Consensus or Controversy Should Mutational Analysis (Ma) Be Considered as a R...CrimsonpublishersCancer
Unique amongst most solid malignancies, gastrointestinal stromal tumors (GISTs) are addicted to a few specific oncogenic drivers and are uniformly resistant to cytotoxic chemotherapeutics but sensitive to tyrosine kinase inhibitors (TKIs). Similar to all cancers, GISTs are heterogenous and subclassified into distinct entities according molecular alterations. It is unquestionable that mutational status offers both prognostic as well as predictive value to guide clinical management of GISTs in both advanced/metastatic and curative/(neo)adjuvant settings. One would therefore assume that mutational analysis would be routine and adopted routinely in terms of timing in the clinical management of GIST, but in practice the assessment of mutational analysis is not adopted routinely. In this paper we will discuss the impact of mutational analysis on clinical management of GIST, as well as review currently guidelines for mutational analysis and review possible reasons for lack of uptake of routine testing in practice.
This document summarizes a presentation on the management of metastatic colorectal cancer (mCRC) in 2017. It discusses several key points:
1) Patient stratification is important in determining treatment approach for mCRC, taking into account factors like disease extent and symptoms.
2) A multidisciplinary team approach is mandatory for developing optimal treatment plans.
3) Assessment of predictive biomarkers like RAS mutations helps determine which first-line treatments may be most effective.
4) Tumor location (right vs left-sided colon cancer) can impact treatment outcomes and response to certain drugs like anti-EGFR therapies.
5) Multiple clinical trials over time have led to improved survival outcomes and more
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.
Breast cancer a focus on bone health integrityMohamed Abdulla
This document summarizes information about bone health and integrity in the context of breast cancer. It discusses how breast cancer commonly spreads to bone, causing skeletal-related events like fractures. It notes that bone-targeted therapies like bisphosphonates and denosumab can help prevent these events by inhibiting bone resorption. Clinical trials show these drugs reduce the risk of skeletal complications when used adjuvantly or for metastatic breast cancer in bone. The document thus emphasizes the importance of bone health for breast cancer patients and the role of anti-resorptive therapies.
1. Small cell lung cancer (SCLC) is the most common type of lung cancer worldwide, accounting for about 16% of cases. It is an aggressive cancer that often spreads rapidly.
2. SCLC is classified as either limited stage disease, confined to one lung and nearby lymph nodes, or extensive stage disease, with metastases to distant organs.
3. Treatment depends on the stage - limited stage is treated with chemotherapy and concurrent thoracic radiotherapy, while extensive stage is treated primarily with chemotherapy along with prophylactic cranial irradiation for patients who respond well initially.
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
Poster presentation at the 2016 WORLD GASTROINTESTINAL SYMPOSIUM on tepotinib a selective inhibitor of c-MET by S. Faivre, J.-F. Blanc, P. Merle, A. Fasolo, A. Iacobellis, V. Grando, T. Decaens, J. Trojan, E. Villa, U. Stammberger, R. Bruns, E. Raymond
1Oncology Unit, Beaujon University Hospital, Clichy, France; 2Service d’hépato-gastroentérologie et d’oncologie digestive, Groupe Hospitalier Saint André, Bordeaux, France; 3Service d'Hépato-Gastro-Entérologie, Hôpital de la Croix Rousse, Lyon, France; 4Dipartimento di Oncologia Medica, Ospedale San Raffaele IRCSS, Milan, Italy; 5Servizio di Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy; 6Service Hépatologie, Hôpital Jean-Verdier, Bondy, France; 7Service d'hepato-gastro-enterologie, CHU de Grenoble - Hôpital Nord, Grenoble, France; 8Gastrointestinal Oncology, Goethe University Hospital, Frankfurt, Germany; 9Policlinico di Modena, Modena, Italy; 10Merck KGaA, Darmstadt, Germany
Chemotherapy in ca urinary bladder dr prasanta dashPrasanta Dash
This document discusses chemotherapy options for metastatic bladder cancer. It notes that the prognosis remains poor with a median survival of 14 months. It reviews response rates of single agents like cisplatin, methotrexate, and doxorubicin. It then discusses combination regimens like MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), noting response rates of around 50% and median survival of approximately 12 months based on several studies. Larger phase 3 trials found MVAC improved median survival compared to cisplatin or cisplatin/cyclophosphamide regimens.
Bladder preservation for CA Urinary BladderAnil Gupta
This document summarizes the case of a 74-year-old male patient with urinary bladder cancer who underwent bladder preservation treatment. He initially presented with hematuria and imaging found two bladder lesions, one of which was muscle-invasive. He received neoadjuvant chemotherapy followed by radical radiotherapy to the bladder, achieving a good response. Over 2.5 years of follow-up, he has remained with no evidence of disease and an intact, functional bladder. The document then discusses bladder cancer treatment approaches and evidence for bladder preservation with chemoradiotherapy as an alternative to radical cystectomy for select patients.
Upper GI bleed is a common, scary and life threatening medical condition usually caused by peptic ulcer disease or oesophageal varices. Uncommon causes include neoplasms, aortoenteric fistulas, vascular lesions, Dieulafoy's lesion etc. Patients usually present with hematemesis or melena. GIST is the third most common tumor of stomach and also the most common mesenchymal tumor. GIST may be asymptomatic and discovered incidentally or they may cause nonspecific symptoms like early satiety and fullness. Although major presentation of GIST is upper GI bleed, GIST as a cause of upper GI bleed is very rare. We here present a patient admitted to us with massive upper GI bleed due to gastrointestinal stromal tumor.
This document discusses the treatment of Ewing's sarcoma. It begins with an introduction to Ewing's sarcoma, describing its identification in 1921 and its characteristics. It then discusses the pathology, genetics, clinical presentation, routes of spread, diagnostic workup, staging, and prognostic factors. The bulk of the document focuses on treatment options, including induction chemotherapy, local therapy options of surgery or radiation, maintenance chemotherapy, and surveillance. It also covers treatment of metastatic and recurrent disease. The document provides detailed information on chemotherapy regimens, radiation techniques, and ongoing research directions.
This document discusses treatment options for a 55-year-old postmenopausal woman with newly diagnosed, hormone receptor-positive, HER2-negative metastatic breast cancer. Based on evidence from clinical trials, fulvestrant alone or in combination with a CDK 4/6 inhibitor plus an aromatase inhibitor are both recommended first-line treatment options. Fulvestrant has shown superior progression-free survival compared to anastrozole alone in the first-line setting. Adding a CDK 4/6 inhibitor to endocrine therapy further improves progression-free survival and response rates and is now considered a standard first-line treatment option for this patient population.
5. EPIDEMIOLOGY
• 80 % of GI Sarcoma.
• GIST = 1% to 3% of all malignant GI tumors.
• Annual incidence rate across the world = 10 to
15 cases / million people.
Cassier PA et al Br J Cancer 2010;103(2):165–170
6.
7.
8.
9. The Development of A Molecular Understanding of GIST
• CD117 antigen a marker for the presence of KIT
protein.
• KIT protein is present in nearly 95% of GIST.
• KIT mutations lead to uncontrolled, ligand-
independent phosphorylation by the KIT kinase.
Wang L et al. Arch Pathol Lab Med 2000;124:1471.
• KIT mutations - 85% of GIST lesions.
– 70% of cases in exon 11 of KIT, others are exon 9, 13,
17.
• 10 % have mutation in PDGFR- A.
Heinrich MC et al Science 2003;299:708
10.
11.
12.
13.
14.
15. Principles of surgery
• Mainstay of therapy for patients with primary
non metastatic GIST
• Initial therapy if the tumor is technically
resectable with minimum morbidity or loss of
function.
25. IMMUNOHISTOCHEMICAL MARKERS IN DIAGNOSIS OF
GIST
• KIT MUTATION
• PDGFRA MUTATION
• ADDITIONAL MARKERS
• CD-34
• H-Caldesmon
• SMA
• EMERGING MARKERS:-DOG1(Discovered On GIST).DOG 1 IN
D/D of GIST
• PKC-THETA
26. Emerging Marker: PKCθ
PKCθ, protein kinase C theta.
Images reproduced with permission from Blay P et al. Clin Cancer Res. 2004;10:4089-4095.
1. Blay P et al. Clin Cancer Res. 2004;10:4089-4095.
2. Motegi A et al. Pathol Int. 2005;55:106-112.
3. Duensing A et al. Cancer Res. 2004;64:5127-5131.
GIST
×10
KIT PKCθ
5% of GIST lack detectable KIT expression
85% to 100% of GIST stain positive for PKCθ1,2
Other similar mesenchymal neoplasias do not stain positive
for PKCθ3
27. Emerging Marker: DOG1
*DOG1.1 antibody was used to detect DOG1; DOG1, discovered on GIST-1; Images reproduced with permission
from Espinosa I et al. Am J Surg Pathol. 2008;32:210-218.
Espinosa I et al. Am J Surg Pathol. 2008;32:210-218.
87% of GIST stain positive for DOG1
Other similar mesenchymal neoplasms do not stain positive for DOG1
DOG1 and KIT show similar staining patterns consistent with ICC staining in the
small bowel
DOG1.1* KIT
28.
29.
30. PROGNOSTIC FACTORS OF GIST
• TUMOR SIZE
• MITOTIC RATE
• LOCATION OF PRIMARY TUMOR
• COMPLETENESS OF RESECTION
• TUMOR RUPTURE
• CELLULAR PROLLIFERATION INDEX
• DIFFUSE MUCOSAL INVASION
• ANEUPLOIDY
• TELOMERASE EXPRESSION
• EXTENT OF DISEASE
32. SURGERY
• R0 resection
• No routine lymphadenectomy
• No tumour rupture or spillage
• Peritoneum & Liver carefully examined
• LAP safe in low risk and localised
33. Influence of Tumour Rupture on Recurrence Free
Survival
No rupture
Rupture
Probabilityofrelapse-freesurvival
p=0.00001
Time [years]
Rutkowski et al. EJSO 2011 Jul 5 [Epub ahead of print].
34. Are Any GIST Benign?
• Surgery is the principal treatment and only curative therapy for
localised, resectable primary disease
• All lesions ≥ 2 cm should be resected
• In the past, lesions < 2 cm have been followed
(often by endoscopy) rather than resected
• Rationale for observation now called into question
– All GIST have malignant potential
– tumours < 2 cm and < 5 mitoses / 50 HPF may have low risk of
recurrence, but it is IMPOSSIBLE to assess mitotic rate on small
endoscopic biopsy samples
Casali et al. Ann Oncol 2008;19 (suppl 2):ii35–ii38.
Demetri et al. J Natl Compr Canc Netw. 2007;5 (suppl 2):S1-29.
34
35. GIST Recurrence After Surgery
• Recurrence of moderate to high-risk GIST following
surgery is common
– Majority of high-risk patients experience recurrence
– Median time to recurrence for those who recur is 2
years
• Five-year survival rates of primary GIST patients before
Imatinib era was approximately 30–60%
• Recurrent disease should be treated as metastatic
disease
DeMatteo et al. Hum Pathol. 2002;33:466-477.
Pierie et al. Arch Surg. 2001;136:383-389.
Rossi et al. Int J Cancer. 2003;107:171-176.
DeMatteo et al. Ann Surg. 2000;231:51-58.
Ng et al. Cancer. 1992;69:1334-1341.
35
36. Management of Metastatic, Unresectable, or Recurrent GIST:
The Paradigm Changes for Advanced Disease
• Failure of Traditional Systemic and Locoregional Cytotoxic
Chemotherapy.
• Rates of objective antitumor response to a variety of
chemotherapy agents for patients with GIST in the range
of 0% to, at best, less than 5%. Goss GA et al. Proc Am Soc Clin Oncol 2000;19 .
• RT rarely plays any role in the management of patients
with metastatic GIST.
• Multifocal hepatic metastases or multiple sites of intra-
abdominal metastatic disease- Role of Sx dismal.
37. • What to use ?
• Why to use ?
• When to use ?
• Till when to use ?
• What next to use ?
38. This TKI…. active in Lab
Addition of imatinib to GIST cells in culture rapidly
and completely blocked the constitutive activation of
KIT, arrested cell proliferation, and induced apoptosis
in the tumor cells.
Tuveson DA et al Oncogene 2001;20:5054.
39.
40.
41. Case report to clinical practice
• single-patient pilot study in Helsinki, Finland,
with close intellectual collaboration from U.S.-
based investigators.
• Treatment with four 100-mg capsules of
STI571 once daily was started in March 2000.
42.
43. Summary of Clinical Studies of Imatinib Mesylate in Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors (GISTs)
Study (Ref.) N Imatinib Dosage (mg) Results
Joensuu et al., 2001 (74) 1 400 daily Major response, durable for more than 2 y
van Oosterom et al., 2001 (75) 40 (36 GIST) 400 to 1,000 daily Partial remissions in 19/36 (53%) GIST patients
with additional minor responses in 6/36 (17%)
Total clinical benefit rate = 70%
No responses in non-GIST patients
Demetri et al., 2002 (61) 147 400 or 600 daily Partial remissions in 97/147 (66%) with additional
minor responses and durable stable disease in
25/147 (17%)
Total clinical benefit rate 83%, no differences for
different doses
Verweij et al., 2003 (76) 51 (27 GIST) 800 daily Complete remissions in 4%, partial remissions in
67%, with additional minor responses and durable
stable disease in 18%
Total clinical benefit rate 89%
Verweij et al., 2003 (87) 946 400 or 800 daily Complete remissions in 5%, partial remissions in
45%, with additional minor responses and durable
stable disease in 32%
Total clinical benefit rate 82%, no differences for
different doses
Blanke et al., 2008 (86) 746 400 or 800 daily Complete remissions in 2%, partial remissions in
46%, with additional minor responses and durable
stable disease in 26%
Total clinical benefit rate 74%, no differences for
different doses
58. ® at 1 yr
Randomised at 3 years
Randomised at 1 year
(Blay et al, JCO 2007)
Randomised at 3 years
(Le Cesne et al, Lancet Oncol 2010)
Discontinue Imatinib?
Randomised at 1 year
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
Months
Survivalprobability
CONT group
19 evts / 26 patients
1-year PFS: 85%
Median PFS : 29 months ; CI95 = [18 - 41]
STOP group
29 evts / 32 patients
1-year PFS: 28%
Median PFS : 7 months ; CI95 = [3 - 9]
Log-rank P value < 0.0001
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48 54 60 66 72
Months
Survivalprobability
CONT group
9 evts / 25 patients
1-year PFS: 92% ; CI95 = [72 - 98]
2-years PFS: 80% ; CI95 = [58 - 91]
STOP group
21 evts / 25 patients
1-year PFS: 32% ; CI95 = [15 - 50]
2-years PFS: 16% ; CI95 = [5 - 33]
Log-rank P value < 0.0001
59. Randomised at 5 years
(Le Cesne et al. ASCO 2011, abstract 10015)
Treatment should be continued indefinitely, since treatment interruption is generally
followed by relatively rapid tumour progression in virtually all cases (Casali et al, ESMO
guidelines, Annals of Oncology 2010)
Randomization at 10 yrs? (ongoing BFR14 amendment)
BFR14: Imatinib Discontinuation
Randomization at 5 yrs
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36
Months
Survivalprobability
CONT group
0 evts / 13 patients
1-year PFS: 100%
STOP group
7 evts / 14 patients
1-year PFS: 65% ; CI95 = [31 - 85]
Log-rank P value = 0.0056
60. BFR14
(i) Interruption of imatinib after 1, 3, or 5 years of
treatment in patients with nonprogressive GIST was
associated with a high risk of progression even in
patients with a complete response.
(ii) Rechallenge with imatinib restored tumor control in
most patients, but the tumor response seldom reached
that before treatment interruption.
(iii) Patients receiving continuous imatinib had a high
rate of prolonged tumor control, which increased with
longer imatinib treatment.
61. Post OP Imatinib
• Complete resection possible in 85% of pts
with primary GIST but approx 50% will
develop mets or recurrence.
• Even in R0 resection look for Risk scoring.
62.
63. Very low risk Low risk Intermediate risk High risk
NIH consensus
criteria1
<2 cm and <5 mitotic
index
2−5 cm and <5 mitotic
index
5−10 cm and <5 mitotic
index or
<5 cm and 6−10 mitotic
index
>5 cm and >5 mitotic
index or
>10 cm and any
mitotic index or
any size and >10
mitotic index
Modified NIH
consensus
classification2
Any location: <2 cm
and 5 mitotic index
Any location: 2.1−5 cm
and 5 mitotic index
Gastric: 2.1−5 cm and
>5 mitotic index or
5.1−10 cm and 5
mitotic index
Any location: <5 cm
and 6−10 mitotic index
Any location: Tumor
rupture, or >10 cm, or
>10 mitotic index, or
>5 cm and >5 mitotic
index
Non-gastric: 2.1−5
cm and >5 mitotic
index, or 5.1−10 cm
and 5 mitotic index
Mitotic index, number of mitoses per 50 high-power fields. RFS, recurrence-free survival
1. Fletcher CD et al. Hum Pathol 2002;33:459-465. 2. Miettinen M et al. Arch Pathol Lab Med 2006;130:1466-1478.
3. Joensuu H. Hum Pathol 2008;39:1411-1419.
Risk Classification Systems
Mitotic index, number of mitoses per 50 high-power fields. RFS, recurrence-free survival
1. Fletcher CD et al. Hum Pathol 2002;33:459-465.
2. Joensuu H. Hum Pathol 2008;39:1411-1419.
73. Algorithm: Management of Unresectable
or Metastatic GIST1–3
CR, complete response; PR, partial response; RFA, radiofrequency ablation; SD, stable disease; TKI, tyrosine kinase inhibitor.
1. Reichardt P. EJC Suppl. 2006;4(suppl 1):19-26.
2. National Comprehensive Cancer Network. Clinical Practice Guidelines. Soft tissue Sarcoma. V.2.2011.
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
3. Casali P et al. Ann Oncol 2010: 21:v98-v102.
Progression
Progression
Metastatic
KIT exon 9+
Imatinib 800 mg/d
Dose-escalate
Imatinib 800 mg/d
Metastatic
Imatinib 400 mg/d
Unresectable
Imatinib 400 mg/d
CR, PR, or SD
Secondary surgery
Continue imatinib
CR or SD
Continue imatinib
CR, PR, or SD
Continue imatinib
• Continue imatinib at same dose or
• Increase imatinib dose as tolerated or
• Switch to sunitinib
• Consider surgery, RFA
• Increase imatinib dose as tolerated or
• Change to sunitinib
• Consider clinical trial
Limited/Local Generalized/Systemic
73
74. Suggested Treatment Algorithm for GIST Patients Who
Experience Progression on Imatinib
*May not be available in all countries
Patel S. Cancer Treat Rev 2011.
77. • After maximal response (usually occurring within
4 to 6 months), definitive surgery could be
performed.
• Marginally resectable or resectable with high risk
of morbidity.
• Imatinib to be started soon after surgery
irrespective of surgical margins.
78. Adverse effect of Imatinab
Adverse effects of Imatinib are generally mild
(grade 1 or 2).
– Edema - approx 74% ; especially notable in the loose subcutaneous tissues of
the facial periorbital region),
– Diarrhea - 45%,
– Myalgia or musculoskeletal pain - 40%,
– Skin rashes -30%,
– Headache -25%.
– Myelotoxicity is markedly less common in GIST patients than in
patients with CML.
83. Phase III GRID Trial
(GIST – Regorafenib In Progressive Disease)
Phase III Data on Bayer’s Regorafenib Met Primary Endpoint Showing Significant
Improvement in Progression-Free Survival in Patients with GIST.
• INCLUSION criteria: Pt whose disease progressed despite prior treatment with imatinib and
sunitinib.
• Patients were randomized in a 2:1 ratio to receive either regorafenib (160 mg once daily,
three weeks on/ one week off) plus best supportive care (BSC) or placebo plus BSC to
evaluate efficacy and safety
• The GRID study met its primary endpoint of improvement in
progression-free survival (PFS) (HR=0.27, p<0.0001).
• The median PFS was 4.8 months in the regorafenib arm
versus 0.9 months in the placebo arm.
84. Mutation Type Likely Influences Efficacy of Adjuvant
Therapy
• PDGFRA mutation D842V is considered imatinib
resistant
– Frequency, 8.7% of the tumours in SSGXVIII
• KIT exon 9 mutation may require 800 mg/d dose1
– Frequency, 7.1% of the tumours in SSGXVIII
• Wt GIST (9.0% in SSGXVII)
– Many may not be imatinib sensitive (NF1 or Carney/Carney-Stratakis
syndrome-associated GIST); succinate dehydrogenase (SDHA, SDHB,
SDHC) mutations2,3 ?
1.GIST Meta-Analysis Group (MetaGIST). J Clin Oncol. 2010;28(7):1247-1253.
2.Janeway KA et al. PNAS 2011;108:314-8.
3.Pantaleo MA et al. JNCI 2011;103:1-5.
84
85. FUTURE
• TAILORED THERAPY ( PDGFRA D842 mutation)
• Blood level testing of imatinib
• Intermediate risk group
• Adjuvant ? 3 yrs
• Other drives and other inhibitors
86.
87.
88. History , physical examination
Abdominal/pelvic CT
with contrast, and/or MRI
Chest imaging
Endoscopic ultrasound
Endoscopy as indicated
FDG PET in indicated cases
90. Negative microscopic margins
Adjuvant Imatinib
At least 12 months
DeMatteo et al. Adjuvant imatinib mesylate increases recurrence free survival
in patients with completely resected localized primary gastrointestinal stromal
tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001. 2007
ASCO
optimal duration has not yet been determined.
Observe
91. ACOSOG Z9001 (american college of surgeons oncology group)
Follow-up of 1.2 years
End point Recurrence
At 1.2 yrs 21% of the expected events had occurred
RFS
Imatinib - 91%
Placebo - 83%
OS - Same
Subset analysis ( high risk group )
RFS
Imatinib - 96%
Placebo - 67-86%
92. Management not well defined
No evidence for re-excision.
Options
Re-excision,
Watchful waiting,
? Adjuvant imatinib.
Positive Microscopic Margin
96. Unresectable or Metastatic disease
On Rx with TKI Response, stable d/s
Limited – 1 or more (limited) foci of progression
Generalised – diffuse, multiple foci of progression
systemic d/s
progression