This document summarizes advances in the treatment of T cell lymphomas. It discusses that T cell lymphomas are a heterogeneous group that require different treatment strategies. Autologous stem cell transplantation improves outcomes for patients who achieve complete remission. Allogeneic stem cell transplantation may provide long-term remissions for nodal T cell lymphomas but has higher non-relapse mortality. Novel agents like romidepsin and bendamustine show promising response rates in relapsed/refractory disease. Overall, stem cell transplantation improves survival when given in the frontline or chemotherapy-sensitive setting, but optimal primary chemotherapy regimens need further refinement to get more patients to transplant.
This document summarizes several presentations on recent developments in Hodgkin lymphoma. It begins with a discussion of a study comparing the predictive value of interim PET scans done after one or two cycles of therapy. The study found PET scans after one cycle had a higher negative predictive value. Another section summarizes a trial finding patients with low stage disease and a negative PET scan after 3 cycles of ABVD had excellent prognosis without further treatment. Later sections discuss outcomes of combining brentuximab vedotin with standard therapies for relapsed/refractory and advanced stage disease. Results showed improved survival correlated with response to brentuximab vedotin.
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.
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
- Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin's lymphoma in Western Europe, with an annual incidence that has been increasing in recent decades.
- FL arises from germinal center B cells and is characterized by the t(14;18) translocation in 85% of cases, resulting in overexpression of the anti-apoptotic BCL2 protein.
- FL is graded based on the percentage of large centroblasts observed, with higher grades indicating a poorer prognosis overall. Risk stratification tools like FLIPI and FLIPI2 can help predict patient outcomes.
This document summarizes the use of allo-HSCT and immunotherapy in the treatment of relapsed or refractory classical Hodgkin lymphoma. It provides statistics on Hodgkin lymphoma incidence and outcomes with first-line therapy in Russia. It then discusses the role and indications for allo-HSCT versus auto-HSCT based on guidelines. The document also reviews outcomes from different conditioning regimens and GVHD prophylaxis for allo-HSCT. It summarizes the efficacy of novel immunotherapies like brentuximab vedotin and PD-1 inhibitors for relapsed disease, including as bridge therapy to allo-HSCT. Finally, it discusses treatment options for post-transplant relapse including donor lymph
The study evaluated 155 patients with T-cell lymphoblastic lymphoma treated with a pediatric-inspired ALL protocol. 91% of patients achieved a complete or unconfirmed response. With a median follow-up of 5.9 years, the 5-year disease-free survival was 71%, event-free survival was 61%, and overall survival was 66%. High serum LDH levels were associated with decreased event-free and overall survival. A 4-gene risk classifier identified patients with a high-risk genetic profile who had significantly shorter event-free, disease-free, and overall survival.
This document summarizes several presentations on recent developments in Hodgkin lymphoma. It begins with a discussion of a study comparing the predictive value of interim PET scans done after one or two cycles of therapy. The study found PET scans after one cycle had a higher negative predictive value. Another section summarizes a trial finding patients with low stage disease and a negative PET scan after 3 cycles of ABVD had excellent prognosis without further treatment. Later sections discuss outcomes of combining brentuximab vedotin with standard therapies for relapsed/refractory and advanced stage disease. Results showed improved survival correlated with response to brentuximab vedotin.
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.
This document outlines the treatment of advanced/metastatic renal cell carcinoma (RCC). It discusses that nephrectomy may still have a role in metastatic RCC for some patients. Active surveillance is an option for favorable risk metastatic RCC patients. Several trials found no differences between tyrosine kinase inhibitors as first line options for metastatic RCC. Second line options after progression on TKIs include mTOR inhibitors, VEGF inhibitors, and immune checkpoint inhibitors. Recent data supports immune checkpoint inhibitors like nivolumab plus ipilimumab as the new standard of care for first line treatment of metastatic RCC based on improved overall survival compared to sunitinib in clinical trials.
- Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin's lymphoma in Western Europe, with an annual incidence that has been increasing in recent decades.
- FL arises from germinal center B cells and is characterized by the t(14;18) translocation in 85% of cases, resulting in overexpression of the anti-apoptotic BCL2 protein.
- FL is graded based on the percentage of large centroblasts observed, with higher grades indicating a poorer prognosis overall. Risk stratification tools like FLIPI and FLIPI2 can help predict patient outcomes.
This document summarizes the use of allo-HSCT and immunotherapy in the treatment of relapsed or refractory classical Hodgkin lymphoma. It provides statistics on Hodgkin lymphoma incidence and outcomes with first-line therapy in Russia. It then discusses the role and indications for allo-HSCT versus auto-HSCT based on guidelines. The document also reviews outcomes from different conditioning regimens and GVHD prophylaxis for allo-HSCT. It summarizes the efficacy of novel immunotherapies like brentuximab vedotin and PD-1 inhibitors for relapsed disease, including as bridge therapy to allo-HSCT. Finally, it discusses treatment options for post-transplant relapse including donor lymph
The study evaluated 155 patients with T-cell lymphoblastic lymphoma treated with a pediatric-inspired ALL protocol. 91% of patients achieved a complete or unconfirmed response. With a median follow-up of 5.9 years, the 5-year disease-free survival was 71%, event-free survival was 61%, and overall survival was 66%. High serum LDH levels were associated with decreased event-free and overall survival. A 4-gene risk classifier identified patients with a high-risk genetic profile who had significantly shorter event-free, disease-free, and overall survival.
This document discusses indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia. It provides information on treatment options and clinical trials for these conditions. The document lists faculty members and their disclosures. It then provides data from clinical trials comparing rituximab maintenance therapy to watchful waiting in asymptomatic follicular lymphoma, and comparing rituximab maintenance to retreatment in low tumor burden follicular lymphoma. Outcomes for different chemotherapy regimens in lymphoma are also presented.
Review of advisories and contingency plan for covid 19 pandemic in radiothera...Anil Gupta
The document reviews advisories and contingency plans for radiotherapy facilities during the COVID-19 pandemic. It summarizes guidelines from various radiation oncology societies on risk stratification of cancer patients, prioritization of treatments, and treatment modifications. It also discusses specific recommendations for tumor sites like head and neck, breast, and gynecological cancers. Screening of patients and staff, treatment scheduling and coordination between departments is emphasized. Treatment principles of remote, avoid, defer, and shorten treatments are recommended to balance cancer and COVID-19 risks.
1) High grade gliomas include grade III anaplastic astrocytomas, anaplastic oligodendrogliomas, and grade IV glioblastomas.
2) The standard of care for glioblastoma is maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide chemotherapy. Molecular markers like MGMT promoter methylation and IDH1 mutation provide prognostic information.
3) For anaplastic gliomas, the treatment involves surgical resection followed by radiotherapy. For anaplastic gliomas with 1p/19q codeletion, PCV chemotherapy is given before or after radiotherapy based on trials showing improved outcomes.
1. Lung neuroendocrine tumors (NETs) have been increasing in incidence and include typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC).
2. Diagnosis of lung NETs can be difficult due to non-specific symptoms and frequently involves histopathological examination. Treatment depends on tumor grade and stage.
3. For localized disease, surgery is the primary treatment. For advanced or metastatic NETs, options include somatostatin analogues, targeted therapies like everolimus, chemotherapy, and peptide receptor radionuclide therapy.
This document provides an overview of the management of gliomas. It discusses the general management and specific management of low grade and high grade gliomas.
For low grade gliomas, the main treatment options are observation, surgery, radiation, and chemotherapy. Surgery aims for maximal safe resection followed by radiation therapy. Chemotherapy with PCV may provide a survival benefit for high risk patients based on one trial, but requires further study.
For high grade gliomas, prognostic factors like age, performance status, extent of resection, and molecular markers are discussed. Treatment involves maximal safe surgery followed by concurrent chemoradiation and adjuvant chemotherapy with temozolomide, which has become the standard of care based on clinical trials
Low grade glioma evidence based managementGaurav Kumar
Management of low grade gliomas (LGG) focuses on the WHO grading system and risk stratification. Current trends include:
1. Immediate postoperative radiotherapy (PORT) for high risk LGG with residual tumor >1cm, preop size >4cm, or age >40 based on improved progression free survival shown in clinical trials.
2. A PORT dose of 54Gy in 30 fractions is recommended based on Phase III trials showing no benefit to higher doses.
3. Adjuvant chemotherapy like temozolomide may be considered for high risk patients, especially those with 1p/19q codeletions and IDH1/2 mutations, though radiotherapy remains standard of
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 key findings from the 2016 ASCO conference regarding neuro-oncology updates. It discusses several studies on treatments for glioblastoma, anaplastic gliomas, low-grade gliomas, and brain metastases. For newly diagnosed glioblastoma in elderly patients, short-course radiation alone was found inferior to temozolomide and short-course radiation. For recurrent glioblastoma, adding lomustine to bevacizumab did not provide a survival advantage. The document also reviews findings on adjuvant temozolomide for anaplastic gliomas without 1p/19q co-deletion and a study comparing surgery with stereotactic radiosurgery versus surgery with whole brain radiation for
High Through-Put DNA Methylation Analysis of Lung Cancer: Plasma cfDNA for Bi...Kate Barlow
• Technology pipeline for methylation biomarker
development
• High throughput DNA methylation-qPCR workflows
• Liquid biopsy – cfDNA methylation testing
While T4 stage, fewer than 12 lymph nodes, and absence of MMR-D are factors considered in deciding adjuvant chemotherapy for Stage II CRC, they are not definitive standards. Currently, there are no established molecular markers that clearly identify patients with high or low risk of recurrence or benefit from chemotherapy for Stage II colon cancer. Researchers are working to develop improved algorithms incorporating clinical, pathological, and emerging molecular markers to better guide treatment decisions.
This is NHL clinical update on 57th ASH Annual Meeting and Exposition (December 5-8, 2015).
It includes only clinical aspects include both chemotherapy and antibody therapy.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
This study evaluated the efficacy and toxicity of the Hyper-CVAD regimen in treating adult acute lymphocytic leukemia (ALL). 204 adult patients with newly diagnosed ALL received alternating cycles of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and high-dose methotrexate and cytarabine, along with central nervous system prophylaxis and supportive care. Results showed that 91% of patients achieved complete remission and the 5-year survival and complete remission rates were 39% and 38% respectively, demonstrating superior outcomes compared to previous regimens. The Hyper-CVAD regimen was found to be an effective therapy for adult ALL that
This document provides an overview of non-small cell lung cancer (NSCLC). It discusses that lung cancer is the leading cause of cancer death. The majority of cases are late-stage at diagnosis and have a poor prognosis. Smoking is responsible for 90% of lung cancers. Advances in screening and targeted therapies have improved outcomes for some patients. Molecular testing is important to identify drivers and direct treatment, such as EGFR mutations that predict response to tyrosine kinase inhibitors.
Radiotherapy in low grade gliomas benefit with local control advantage
Patients with high risk factors need immediate radiation after surgery
RT dose of 50-54 Gy in 2 Gy/Fr
Fractionated radiosurgery in optic nerve glioma and small volume disease
This document summarizes information about Hodgkin's and non-Hodgkin's lymphoma, including:
- Hodgkin's lymphoma accounts for about 30% of malignant lymphomas and is typically treated initially with ABVD chemotherapy plus radiation therapy. Non-Hodgkin's lymphoma is more common and heterogeneous.
- For advanced Hodgkin's lymphoma, BEACOPP chemotherapy is more effective than COPP/ABVD but also more toxic, increasing risks of infertility, premature menopause, and leukemia.
- Long-term survivors of Hodgkin's lymphoma face elevated risks of secondary cancers decades later due to effects of treatment.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with rapid growth and early metastasis. SCLC is usually responsive to initial chemotherapy but often relapses within two years. The standard first-line treatment is platinum-based chemotherapy such as etoposide plus cisplatin or carboplatin. Adding thoracic radiotherapy to chemotherapy improves survival for limited-stage disease. Many clinical trials have evaluated additional agents or alternative regimens but no significant improvements in outcomes have been achieved compared to standard etoposide plus platinum chemotherapy.
This document discusses indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia. It provides information on treatment options and clinical trials for these conditions. The document lists faculty members and their disclosures. It then provides data from clinical trials comparing rituximab maintenance therapy to watchful waiting in asymptomatic follicular lymphoma, and comparing rituximab maintenance to retreatment in low tumor burden follicular lymphoma. Outcomes for different chemotherapy regimens in lymphoma are also presented.
Review of advisories and contingency plan for covid 19 pandemic in radiothera...Anil Gupta
The document reviews advisories and contingency plans for radiotherapy facilities during the COVID-19 pandemic. It summarizes guidelines from various radiation oncology societies on risk stratification of cancer patients, prioritization of treatments, and treatment modifications. It also discusses specific recommendations for tumor sites like head and neck, breast, and gynecological cancers. Screening of patients and staff, treatment scheduling and coordination between departments is emphasized. Treatment principles of remote, avoid, defer, and shorten treatments are recommended to balance cancer and COVID-19 risks.
1) High grade gliomas include grade III anaplastic astrocytomas, anaplastic oligodendrogliomas, and grade IV glioblastomas.
2) The standard of care for glioblastoma is maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide chemotherapy. Molecular markers like MGMT promoter methylation and IDH1 mutation provide prognostic information.
3) For anaplastic gliomas, the treatment involves surgical resection followed by radiotherapy. For anaplastic gliomas with 1p/19q codeletion, PCV chemotherapy is given before or after radiotherapy based on trials showing improved outcomes.
1. Lung neuroendocrine tumors (NETs) have been increasing in incidence and include typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC).
2. Diagnosis of lung NETs can be difficult due to non-specific symptoms and frequently involves histopathological examination. Treatment depends on tumor grade and stage.
3. For localized disease, surgery is the primary treatment. For advanced or metastatic NETs, options include somatostatin analogues, targeted therapies like everolimus, chemotherapy, and peptide receptor radionuclide therapy.
This document provides an overview of the management of gliomas. It discusses the general management and specific management of low grade and high grade gliomas.
For low grade gliomas, the main treatment options are observation, surgery, radiation, and chemotherapy. Surgery aims for maximal safe resection followed by radiation therapy. Chemotherapy with PCV may provide a survival benefit for high risk patients based on one trial, but requires further study.
For high grade gliomas, prognostic factors like age, performance status, extent of resection, and molecular markers are discussed. Treatment involves maximal safe surgery followed by concurrent chemoradiation and adjuvant chemotherapy with temozolomide, which has become the standard of care based on clinical trials
Low grade glioma evidence based managementGaurav Kumar
Management of low grade gliomas (LGG) focuses on the WHO grading system and risk stratification. Current trends include:
1. Immediate postoperative radiotherapy (PORT) for high risk LGG with residual tumor >1cm, preop size >4cm, or age >40 based on improved progression free survival shown in clinical trials.
2. A PORT dose of 54Gy in 30 fractions is recommended based on Phase III trials showing no benefit to higher doses.
3. Adjuvant chemotherapy like temozolomide may be considered for high risk patients, especially those with 1p/19q codeletions and IDH1/2 mutations, though radiotherapy remains standard of
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 key findings from the 2016 ASCO conference regarding neuro-oncology updates. It discusses several studies on treatments for glioblastoma, anaplastic gliomas, low-grade gliomas, and brain metastases. For newly diagnosed glioblastoma in elderly patients, short-course radiation alone was found inferior to temozolomide and short-course radiation. For recurrent glioblastoma, adding lomustine to bevacizumab did not provide a survival advantage. The document also reviews findings on adjuvant temozolomide for anaplastic gliomas without 1p/19q co-deletion and a study comparing surgery with stereotactic radiosurgery versus surgery with whole brain radiation for
High Through-Put DNA Methylation Analysis of Lung Cancer: Plasma cfDNA for Bi...Kate Barlow
• Technology pipeline for methylation biomarker
development
• High throughput DNA methylation-qPCR workflows
• Liquid biopsy – cfDNA methylation testing
While T4 stage, fewer than 12 lymph nodes, and absence of MMR-D are factors considered in deciding adjuvant chemotherapy for Stage II CRC, they are not definitive standards. Currently, there are no established molecular markers that clearly identify patients with high or low risk of recurrence or benefit from chemotherapy for Stage II colon cancer. Researchers are working to develop improved algorithms incorporating clinical, pathological, and emerging molecular markers to better guide treatment decisions.
This is NHL clinical update on 57th ASH Annual Meeting and Exposition (December 5-8, 2015).
It includes only clinical aspects include both chemotherapy and antibody therapy.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
This study evaluated the efficacy and toxicity of the Hyper-CVAD regimen in treating adult acute lymphocytic leukemia (ALL). 204 adult patients with newly diagnosed ALL received alternating cycles of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and high-dose methotrexate and cytarabine, along with central nervous system prophylaxis and supportive care. Results showed that 91% of patients achieved complete remission and the 5-year survival and complete remission rates were 39% and 38% respectively, demonstrating superior outcomes compared to previous regimens. The Hyper-CVAD regimen was found to be an effective therapy for adult ALL that
This document provides an overview of non-small cell lung cancer (NSCLC). It discusses that lung cancer is the leading cause of cancer death. The majority of cases are late-stage at diagnosis and have a poor prognosis. Smoking is responsible for 90% of lung cancers. Advances in screening and targeted therapies have improved outcomes for some patients. Molecular testing is important to identify drivers and direct treatment, such as EGFR mutations that predict response to tyrosine kinase inhibitors.
Radiotherapy in low grade gliomas benefit with local control advantage
Patients with high risk factors need immediate radiation after surgery
RT dose of 50-54 Gy in 2 Gy/Fr
Fractionated radiosurgery in optic nerve glioma and small volume disease
This document summarizes information about Hodgkin's and non-Hodgkin's lymphoma, including:
- Hodgkin's lymphoma accounts for about 30% of malignant lymphomas and is typically treated initially with ABVD chemotherapy plus radiation therapy. Non-Hodgkin's lymphoma is more common and heterogeneous.
- For advanced Hodgkin's lymphoma, BEACOPP chemotherapy is more effective than COPP/ABVD but also more toxic, increasing risks of infertility, premature menopause, and leukemia.
- Long-term survivors of Hodgkin's lymphoma face elevated risks of secondary cancers decades later due to effects of treatment.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with rapid growth and early metastasis. SCLC is usually responsive to initial chemotherapy but often relapses within two years. The standard first-line treatment is platinum-based chemotherapy such as etoposide plus cisplatin or carboplatin. Adding thoracic radiotherapy to chemotherapy improves survival for limited-stage disease. Many clinical trials have evaluated additional agents or alternative regimens but no significant improvements in outcomes have been achieved compared to standard etoposide plus platinum chemotherapy.
1. Several novel agents have shown efficacy against T cell lymphomas based on key clinical trials, including brentuximab vedotin, mogamulizumab, romidepsin, pralatrexate, lenalidomide, and bendamustine.
2. Brentuximab vedotin combined with chemotherapy resulted in high overall response rates of 85-100% in trials. Mogamulizumab demonstrated a 35% overall response rate for relapsed peripheral T cell lymphoma and cutaneous T cell lymphoma.
3. Romidepsin trials showed overall response rates of 25-38% in relapsed/refractory T cell lymphomas, with median durations
This document discusses improvements in treatment and outcomes for acute lymphoblastic leukemia (ALL) in children. It notes that the cure rate for ALL has increased from less than 10% in the 1960s to around 90% currently due to several factors: large randomized clinical trials to test chemotherapy regimens more effectively; understanding of genetic subtypes to tailor treatment intensity; monitoring of minimal residual disease to identify high-risk patients; and introduction of new targeted drugs like imatinib for resistant ALL subtypes. The success of the pediatric approach relies on high enrollment in collaborative multi-center studies to continually refine treatment protocols.
Small cell lung cancer (SCLC) is an aggressive type of lung cancer linked to smoking. It is a neuroendocrine tumor that is highly sensitive to chemotherapy and radiation initially but often recurs. The two main types are limited stage, confined to one lung, and extensive stage, which has spread. Platinum-based chemotherapy is standard and some patients receive prophylactic brain radiation. For extensive stage with response to chemotherapy, radiation to the chest improves survival. Topotecan helps with symptoms for relapsed SCLC compared to multi-agent chemo. Immunotherapy like pembrolizumab shows benefit for some after standard therapies fail.
1. TKI such as imatinib combined with reduced-intensity chemotherapy can achieve high CR rates in Philadelphia chromosome-positive acute lymphoblastic leukemia, even in elderly patients.
2. Allogeneic stem cell transplantation remains the standard of care for eligible patients and is associated with improved long-term outcomes when combined with TKI treatment before and after transplantation.
3. The addition of TKI both before and prolonged use after transplantation is associated with higher molecular response rates and lower relapse rates.
This document provides information about Dr. Jason Westin, an assistant professor at MD Anderson Cancer Center whose research focuses on improving therapy and outcomes for patients with lymphoma. His specific research interests include diffuse large B-cell lymphoma, developing systems to identify optimal therapeutic combinations for individual patients, drug synergy and antagonism, scale free networks in cancer therapy, and developing sensitive disease monitoring methods. The document also summarizes several of Dr. Westin's presentations on novel targeted therapies in T-cell lymphoma from 2014, including studies on drugs such as brentuximab, mogamulizumab, lenalidomide, alisertib, selinexor, romidepsin, panobinostat, and inhibitors of the
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...Gianfranco Tammaro
This document summarizes treatment approaches for non-Hodgkin lymphomas over time:
1. Prior to 1997, treatment included surgery, watchful waiting for indolent lymphomas, radiotherapy for stage I disease, and polychemotherapy. Chemotherapy regimens like CHOP became the standard.
2. After 1997, immunotherapy was introduced with monoclonal antibodies like rituximab, improving response rates and survival. Rituximab combined with chemotherapy became the standard first-line treatment for B-cell lymphomas.
3. Recent studies are exploring new drug combinations, such as lenalidomide and rituximab for untreated indolent lymphomas, which achieved high response rates
This document summarizes prognostic factors and treatment approaches for follicular lymphoma. Some key points:
- Prognostic factors include age, histologic grade, FLIPI score, gene expression profiling, and metabolic tumor volume on PET scans.
- First-line treatment for symptomatic advanced disease is usually rituximab plus chemotherapy such as bendamustine, followed by rituximab maintenance for 2 years.
- The PRIMA trial showed improved progression-free survival with 2 years of rituximab maintenance compared to observation alone in patients achieving response to first-line treatment.
- The GALLIUM trial found improved progression-free survival for first-line treatment of follicular
- Primary gastric lymphoma is rare but increasing in incidence and can involve any part of the GI tract. Approximately 50-60% of non-Hodgkin's lymphomas originate from extranodal sites, with the stomach being the most common.
- Radiation therapy is commonly used as curative treatment for early stage gastric lymphoma, with 5-year survival rates of 80-89% reported. It can also be used as adjuvant therapy after surgery or chemotherapy to improve disease-free survival.
- Recent advances in radiation therapy planning and delivery techniques like 3D-CRT, IMRT, IGRT and CyberKnife have improved the therapeutic ratio by better sparing nearby critical organs.
Larry W. Kwak discusses ongoing research for targeted therapy of Hodgkin's lymphoma. The goals are to [1] improve remission rates and decrease risk of death, [2] minimize side effects and maintain or prolong remissions, and [3] develop additional options for relapsed or refractory disease. Research is exploring targeted agents like HDAC inhibitors, OX40 receptor ligation, and oral panobinostat to alter the tumor microenvironment and induce apoptosis. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown durable responses in refractory Hodgkin's lymphoma with manageable toxicity. Introduction of targeted therapies into frontline treatment, such as brentuxim
Larry W. Kwak discusses ongoing research goals and therapeutic options for Hodgkin's lymphoma, including improving remission rates and minimizing side effects. He describes targeted therapies under investigation, such as deacetylase inhibitors that induce cell cycle arrest and apoptosis as well as alter the tumor microenvironment. Kwak also discusses the use of oral HDAC inhibitors like mocetinostat, which have shown clinical activity in Hodgkin's lymphoma. Finally, he examines the efficacy of the antibody-drug conjugate brentuximab vedotin in treating relapsed and refractory Hodgkin's lymphoma.
This document describes the case of a 35-year-old male who presented with a swelling in his left inguinal region. Investigations revealed multiple enlarged lymph nodes and a diagnosis of follicular lymphoma. The document then provides details on the classification, pathology, genetics, clinical features, staging, prognostic factors, diagnostic workup, and management options for early stage and advanced stage follicular lymphoma. Management depends on disease extent and involves immunotherapy, chemotherapy, radiation therapy or a watch-and-wait approach. Rituximab improves outcomes when added to chemotherapy.
Journal club: Durvalumab as Consolidation therapy in Advanced NSCLCAnimesh Agrawal
This study evaluated the addition of durvalumab consolidation therapy following chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer. The study found that durvalumab improved progression-free survival compared to placebo, with median progression-free survival of 16.8 months versus 5.6 months respectively. Overall survival was also improved with durvalumab, though final analysis is still pending. Safety profiles were similar to other PD-L1 inhibitors, with immune-related adverse events in approximately 25% of durvalumab patients. This study provides evidence that durvalumab consolidation improves outcomes for stage III NSCLC following chemoradiotherapy.
Evaluation and management of Stage III Non-Small Cell Carcinoma Lung including Radiotherapy planning. On a Radiation Oncologist Perspective. MD Radiotherapy discussion - CMC, Vellore
Journal Club: Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia 2 Dr. Aryan (Anish Dhakal)
The study aims to analyze the long-term results of a large cohort of MEN2 patients with the C634Y mutation who had undergone prophylactic thyroidectomy in a tertiary referral hospital, and to analyze the results in terms of age and calcitonin levels.
This document summarizes strategies for treating mantle cell lymphoma (MCL), including:
- When to treat: stratifying based on prognostic factors like the Mantle Cell International Prognostic Index (MIPI)
- What to treat with: conventional chemotherapy like R-CHOP plus newer drugs like bortezomib; more intensive regimens including Hyper-CVAD have shown improved survival
- Rituximab improves outcomes and its addition to chemotherapy is recommended
- Bendamustine plus rituximab has efficacy comparable to R-CHOP for MCL
Patterns of failure and treatment related toxicity in EFRT IN CA CERVIXradiation oncology
This study evaluated patterns of failure and toxicity in 39 patients with advanced cervical cancer treated with extended field radiation therapy (EFRT) and concurrent chemotherapy. The results showed that distant failure was the most common pattern of failure (49% of patients). Treatment-related acute toxicity over grade 3 occurred in 38% of patients, while only 5% experienced significant late toxicity. The 5-year overall and disease-free survival rates were 26% and 19.4% respectively. Involvement of more lymph nodes and higher level nodal involvement were associated with poorer survival outcomes. The study concluded that advanced cervical cancer should be considered a systemic disease and current radiotherapy doses are adequate to control primary tumors and involved nodes with acceptable toxicity.
Metastatic renal cell carcinoma (mRCC) has a poor response to chemotherapy and radiotherapy. Immunotherapy can achieve response rates of 12-39% while cytoreductive nephrectomy prior to immunotherapy may improve response rates and survival outcomes. Two large randomized controlled trials found that cytoreductive nephrectomy before immunotherapy resulted in longer time to disease progression, higher response rates to immunotherapy, and increased overall survival compared to immunotherapy alone. However, the site and number of metastases may impact prognosis, with lung metastases associated with better outcomes than bone or multiple metastases. Future therapies continue to be explored including targeted anti-angiogenic agents and immunotherapies.
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...daranisaha
To evaluate the benefit of radiotherapy, compared with other treatment in ocular marginal zone lymphoma, retrospectively we analyzed our experience, with the end-points: efficacy, measured for complete response, Progression-Free Survival (PFS) and Overall Survival
Cyclin D1 plays a direct role in DNA repair by interacting with proteins involved in homologous recombination. It was found to directly interact with and help recruit RAD51 to DNA damage sites, facilitating efficient DNA repair. Cyclin D1 also interacts with the C-terminus of BRCA2, helping recruit RAD51 by preventing inhibitory phosphorylation of BRCA2 by cyclin A/CDK2. Depletion of cyclin D1 impairs RAD51 focus formation and homologous recombination after DNA damage. These findings establish a novel function of cyclin D1 in promoting accurate DNA repair through homologous recombination.
This document summarizes a presentation on controversies in hepatobiliary pancreatic surgery. It discusses 4 topics: 1) Whether resectable hilar cholangiocarcinoma should be resected or treated with orthotopic liver transplantation, 2) How to treat node-positive intrahepatic cholangiocarcinoma, 3) Options for unresectable intrahepatic cholangiocarcinoma, and 4) Managing large hepatocellular carcinoma in early cirrhosis. For each topic, one or more case examples are described and various treatment approaches are outlined and discussed. Supporting data from studies on outcomes with different strategies are also presented.
- 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.
- Neoadjuvant therapy, or preoperative therapy, has several advantages over upfront surgery for pancreatic cancer. It guarantees all patients receive non-surgical therapy, helps select patients most suitable for effective surgery based on their response, and allows for early cytotoxic effects on micrometastatic disease.
- Some key benefits are that it ameliorates risks of postoperative complications limiting adjuvant therapy, downstages borderline resectable tumors in about a third of cases, and improves surgical margin clearance and time to local recurrence.
- Treatment decisions should be individualized based on a comprehensive analysis of a patient's tumor anatomy, biology and physiology at each phase to optimize outcomes. Neoadjuvant therapy is an
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 document provides an overview of cholangiocarcinoma, a rare and deadly form of cancer. It discusses risk factors and increasing incidence rates. For localized disease, surgical resection is standard but outcomes remain poor. For advanced disease, gemcitabine-based chemotherapy is the standard first-line treatment based on results from the ABC-02 trial showing improved survival with gemcitabine and cisplatin. Retrospective data on second-line therapies and combination of pazopanib and trametinib show some benefit. Adding radiation therapy may also improve outcomes based on another retrospective review. Next generation sequencing is helping identify molecular alterations to guide targeted therapy trials. Ongoing clinical trials at MD Anderson include testing new
Immunotherapy shows promise for colorectal cancer (CRC) patients with microsatellite instability-high (MSI-H) tumors. MSI-H tumors have a higher number of mutations and immune cell infiltrate that make them more visible to immunotherapy. Clinical trials have found response rates of 30-40% for pembrolizumab in metastatic MSI-H CRC patients. Ongoing trials are exploring combination therapies targeting immune checkpoints like PD-1 and CTLA-4 for MSI-H CRC. Immunotherapy may provide an effective treatment option for this patient subgroup.
Surgical Approach to Non Small Cell Lung Cancerspa718
1) Surgery is still the mainstay of curative treatment for NSCLC, though diagnostic role has decreased with less invasive techniques preferred if doubt remains after needle biopsies.
2) Pre-operative assessment is key to determine operability and extent of surgery. N2 involvement means surgery is not recommended initially.
3) Lobectomy is the standard resection but sublobar options are available for selected patients based on cardiopulmonary reserve and disease characteristics like small GGO lesions. Pneumonectomy should be avoided with sleeve lobectomy preferred.
4) Minimally invasive surgery like VATS is becoming the preferred approach over thoracotomy for select patients when oncologic principles can be maintained
Radiation therapy plays an evolving role in the treatment of lung cancer beyond just causing DNA double strand breaks.
1) Stereotactic body radiation therapy (SBRT) can provide curative treatment for early stage lung cancer with high local control rates.
2) For locally advanced lung cancer, dose escalation with conventional fractionation in RTOG 0617 did not improve overall survival, highlighting the importance of fractionation and sequencing with other therapies.
3) Radiation induces tumor cell death that can elicit anti-tumor immune responses, known as abscopal effects, especially when combined with immunotherapy like anti-CTLA4 and anti-PD1/PDL1 agents which play complementary roles.
Update on Management of Triple Negative Breast Cancerspa718
This document provides an update on the management of triple negative breast cancer from Dr. Banu Arun at MD Anderson Cancer Center. It discusses that triple negative breast cancer is a heterogeneous disease comprised of several molecular subtypes with different characteristics and potential treatment targets. Clinical trials exploring chemotherapy regimens, platinum agents, PARP inhibitors, anti-angiogenic drugs, and immunotherapies are summarized. Ongoing research aims to better define the subtypes in order to personalize treatment for triple negative breast cancer patients.
Technical Advances in radiotherapy for Lung (and liver) Cancerspa718
This document summarizes recent technical advances in radiotherapy for lung and liver cancer, including: 4DCT imaging to account for tumor motion; motion management techniques like gating and breath-holding; intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) to improve dose conformity; image-guided radiation therapy (IGRT) to reduce margins and enable adaptations; and proton therapy which may further reduce normal tissue dose due to its physical properties, though proton techniques are still evolving to address motion and anatomical changes. The document outlines the benefits and challenges of each technique through examples and studies.
Controversies in Surgical Approach to Breast Cancerspa718
This document discusses several controversies in surgical approaches to breast cancer:
1. Detecting small lesions in women with dense breast tissue using mammography alone may be inadequate, and supplemental tests like ultrasound or MRI may improve detection rates.
2. For patients with early-stage breast cancer and positive sentinel lymph nodes, axillary lymph node dissection may not always be necessary, especially for those receiving breast-conserving surgery and radiation based on studies like ACOSOG Z0011 and AMAROS.
3. The use of intraoperative radiation therapy (IORT) following breast-conserving surgery remains controversial, as some studies have found higher local recurrence rates compared to whole breast radiation, though recurrence risks may
Lung cancer is a leading cause of cancer death. Immunotherapy using immune checkpoint inhibitors that target proteins like PD-1 and PD-L1 has shown promise in treating lung cancer. A study presented at ASCO 2015 found that treatment with the PD-L1 inhibitor atezolizumab resulted in improved survival for NSCLC patients with higher levels of PD-L1 expression on tumor cells compared to docetaxel chemotherapy. Another study showed nivolumab, a PD-1 inhibitor, improved survival over docetaxel as a treatment for advanced non-squamous NSCLC after chemotherapy, with greater benefit seen in patients with higher PD-L1 expression levels. These results suggest PD-L1 expression can help identify
This document summarizes several presentations from the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting regarding breast cancer research. Key findings include:
1) The MARIANNE study found that the combination of trastuzumab emtansine and pertuzumab was more effective for treating HER2-positive metastatic breast cancer than trastuzumab and taxane chemotherapy.
2) The PALOMA-3 trial demonstrated that adding palbociclib to fulvestrant improved progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer.
3) The TITAN study found no significant difference in disease-free or overall survival between the
This document summarizes advances in radiotherapy for breast cancer over the past 50 years. It discusses how radiotherapy combined with surgery and systemic therapies has improved local control and survival outcomes. Modern techniques like 3D conformal radiotherapy and intensity-modulated radiotherapy can reduce acute side effects compared to older 2D techniques. Ongoing research is exploring hypofractionated whole breast irradiation and accelerated partial breast irradiation to reduce treatment time. Large trials are still needed to establish optimal radiotherapy approaches.
This document discusses research on using regulatory T cells (Tregs) for graft-versus-host disease (GVHD) prevention after allogeneic hematopoietic cell transplantation (HCT). Key points include:
1) Tregs show promise in controlling GVHD while retaining the graft-versus-leukemia effect in mouse models of allogeneic HCT.
2) Studies demonstrate that higher levels of Tregs early after HCT in patients correlate with less severe acute GVHD.
3) Researchers have developed methods to successfully expand Tregs from umbilical cord blood (CB) through CD25 selection and CD3/CD28 bead stimulation while maintaining a functional
The document discusses immunotherapy strategies for multiple myeloma. It summarizes that while current therapies have improved survival, most patients still relapse. It then reviews several immunotherapeutic approaches including allogeneic stem cell transplantation, vaccination strategies targeting antigens like MAGE and idiotype, dendritic cell-based vaccines, and monoclonal antibodies targeting proteins like CS1, CD38, and CD138. Emerging cellular immunotherapies using chimeric antigen receptor (CAR) T cells and natural killer cells targeting myeloma antigens are also discussed. Clinical trials of these approaches demonstrate feasibility and some early signs of efficacy but also highlight ongoing challenges to further improve outcomes.
This document discusses immunotherapy for lymphomas, specifically chimeric antigen receptor T-cell (CAR-T) therapy. It provides an overview of CAR-T development and studies in adults with B-cell lymphomas. It describes identification and management of toxicities from CAR-T therapy such as cytokine release syndrome and neurologic symptoms. The document also summarizes current CAR studies targeting CD19 and discusses unmet needs in CAR-T research such as improving efficacy, antigens, and decreasing tumor immunosuppression.
This document discusses individualized allogeneic immunotherapy for acute myeloid leukemia (AML) after low toxicity conditioning. It notes that while allogeneic hematopoietic stem cell transplantation (allo HSCT) is an effective treatment for AML, toxicity remains a major issue. Low toxicity conditioning is achievable and important for older/unfit patients, but low toxicity does not mean only reduced intensity - disease control is still critical. Individualized conditioning may be needed to balance low toxicity with adequate disease control. The document advocates for personalized, optimized allo HSCT approaches tailored to patient, disease, and donor factors to further improve outcomes of AML patients.
This document summarizes recent updates on the treatment of acute lymphoblastic lymphoma from the American Society of Clinical Oncology and European Hematology Association conferences. It discusses:
1) Long-term data showing the combination of dasatinib and chemotherapy can achieve long-term remissions in Philadelphia chromosome-positive adults.
2) New chemotherapy regimens including rituximab that achieved high one-year remission rates in trials for frontline ALL treatment.
3) The use of blinatumomab, a bispecific antibody, to achieve high remission rates in patients with minimal residual disease after frontline therapy.
4) Several new trials combining tyrosine kinase inhibitors like nilot
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
MATATAG CURRICULUM: ASSESSING THE READINESS OF ELEM. PUBLIC SCHOOL TEACHERS I...NelTorrente
In this research, it concludes that while the readiness of teachers in Caloocan City to implement the MATATAG Curriculum is generally positive, targeted efforts in professional development, resource distribution, support networks, and comprehensive preparation can address the existing gaps and ensure successful curriculum implementation.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
1. Advances in the treatment of
T cell lymphomas
Yok-Lam Kwong
Department of Medicine
Queen Mary Hospital
2. Mature T and NK cell malignancies
T-cell prolymphocytic leukaemia
T-cell large granular lymphocyte leukaemia
Chonic lymphoproliferative disroder of NK cells
Aggressive NK cell leukaemias
Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood
Adult T-cell leukaemia/lymphoma
Extranodal NK/T-cell lymphoma, nasal type
Enteropathy associated T-cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis like T-cell lymphoma
Mycosis fungoides
Sezary syndrome
Primary cutaneous CD30 positive T-cell lymphoproliferative disorders
Primary cutaneous peripheral T-cell lymphomas
Peripheral T-cell lymphoma, NOS
Angioimmunoblastic T-cell lymphoma
Anaplastic large cell lymphoma, ALK positive
Anaplastic large cell lymphoma, ALK negative
3. 393 cases of lymphomas in 5
hospitals in Hong Kong in 2006
4. Overview of the management of TCL
1. All TCL are not the same
2. Different subtypes of TCL may need different
treatment strategies
3. There may be intrinsic differences in some
types of TCL in different patient populations
4. Owing to relative rarity of these lymphomas,
large controlled trials have not been
conducted to evaluate the efficacy of different
treatment protocols
5. Specific subtypes of TCL that may require
different treatment strategies
1. Adult T cell lymphoma / leukaemia
2. Enteropathy associated T cell lymphoma
3. Hepatosplenic T cell lymphoma
4. Subcutaneous panniculitis-like T cell
lymphoma
5. Mycosis fungoides
6. Primary cutaneous T cell lymphomas
6. The three most common subtypes of
T-cell lymphomas
1. Peripheral T cell lymphoma, not
otherwise specified (PTCL-NOS)
2. Angioimmunoblastic T cell
lymphoma (AITL)
3. Anaplastic large cell lymphoma
(ALCL)
7. Problems of treatment of TCL
1.CHOP designed for conventional aggressive
B-cell lymphoma still used
2. Response is suboptimal, and remissions are
often short-lived
3. Dose dense or escalation on a CHOP
backbone has not been shown to be beneficial
4. High dose chemotherapy + autologous
hematopoietic stem cell transplantation
(HSCT) may improve outcome. However, many
patients do not actually make it to HSCT
because of disease progression
9. Results From a Prospective, Open-Label, Phase II Trial of
Bendamustine in Refractory or Relapsed T-Cell
Lymphomas: The BENTLY Trial
Damaj et al.
Histologically confirmed peripheral T-cell lymphoma
(PTCL) or cutaneous T-cell lymphoma
Disease progression afterone or more lines of prior
chemotherapy
Bendamustine: 120 mg/m2
per day on days 1, 2 every 3
weeks for six cycles.
Primary end point: overall response rate (ORR)
Secondary end points: duration of response (DOR),
progression-free-survival (PFS), and overall survival (OS).
10. Results
60 patients, 27 (45%) of whom were refractory to their last
prior chemotherapy
Histology: PTCL-NOS and AITL, advanced stage in 87% of
patients.
Median number of previous chemotherapy: 1 (1 – 3)
ORR: 50%
CR: 17 patients (28%)
PR: 13 patients (22%)
DoR: 3.5 months
PFS: 3.6 months
OS: 6.2 months
Grade III/IV adverse effects
Neutropenia:30%; thrombocytopenia: 24%;
Infections: 20%
12. Schetelig et al Haematologica 2003;88:1272-1278
EBMT-based survey
29 patients with AITL in 16 transplant centers
Median age at HSCT: 53 years.
Upfront: N=14 (48%)
2nd / 3rd-line therapy: N=15 (52%)
Conditioning regimens:
BEAM: 16 patients
ICE: 7 patients
Others: 6 patients
TRM: 1 patient
Outcome
CR increased from 45% before HSCT to 76% afterwards
Median observation time: 5 years (range 2.5 to 10 years)
14 patients have died (13 from progressive disease)
15 patients are alive
5-year overall survival: 44% (95% CI, 22% to 66%)
5-year event-free survival was 37% (95% CI, 17% to 57%)
AITL
13. AITL
Kyriakou et al J Clin Oncol 2008;26:218-24.
Retrospective, EBMT multicenter study of 146 patients with
AITL undergoing autologous HSCT
PBHSC: 143 patients; BM: 3 patients
Conditioning: BEAM in most cases
Median follow-up of 31 months (range, 3 to 174 months)
95 patients (65%) remained alive
51 patients (35%) died (disease progression: 42, TRM: 9)
Non-relapse mortality at 1 yr: 5% and at 2 yr: 7%
Actuarial overall survival (OS): 67% at 2 yr and 59% at 4 yr
Cumulative incidence of relapse: 40% at 2 yr and 51% at 4 yr
Progressive free survival according to status
CR: 70% at 2 yr and 56% at 4 yr
Chemotherapy sensitive disease: 42% at 2 yr and 30% at 4 yr
Chemotherapy refractor disease: 23% at 2 yr and 23% at 4 yr
1. HSCT offers the possibility of long-term disease-free
survival to patients with AITL.
2. Early transplantation is necessary to achieve optimal
results.
14. Yang et al Biol Blood Marrow Transplant 2009;15:118-25
Retrospective analysis of autologous HSCT
64 patients
Median age 44 years (range: 15-63 years)
Risk categorization
a-IPI: 8 patients (12.5%) at high risk
PIT: 16 patients (26.6%) at 2 – 3
Median follow-up of 29.7 months
3-year overall survival (OS): 53%
3-year progression-free survival (PFS) 44.3%
Risk factors on univariate analysis for OS
poor performance status, high lactate dehydrogenase (LDH) levels,
high a-IPI score, high PIT classes, failure to achieve complete
response (CR) at transplantation, and nonfrontline transplantation
Risk factors on multivariate analysis for OS
Non-CR at transplantation (hazard ratio [HR] 2.23; 95% CI 1.78-7.93)
2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42)
PTCL-NOS
15. Mercadal et al Ann Oncol 2008;19:958-63.
Forty-one patients (men: 30; women: 11)
Median age: 47 years
Mega-CHOP, responders received autologous HSCT
28 patients (68%) received planned treatment
CR: 20 patients (50%), PR: 4 patients (10%)
HSCT in 17 patients
Median follow-up of 3.2 years for the whole cohort
4 yr progression free survival: 30%
4-yr overall survival: 39%
Prognostic factor: International Prognostic Index
Survivals were not different between patients receiving and not
receiving autologous HSCT
PTCL-NOS
16. Reimer et al J Clin Oncol 2009;27:106-13
Prospective multicenter study
CHOP (4–6 cycles)
CR and PR patients are eligible for autologous HSCT
Conditioning regimen: Cy – TBI
83 patients were enrolled (PTCL-NOS: 32; AITL: 27)
55 / 83 patients (66%) received autologous HSCT
progressive disease was the main reason for no HSCT
Overall response rate after HSCT: 66% (56% CR and 8% PR).
Median follow-up time of 33 months, 43 patients were alive
3-year overall survival for CR patients: 48%
3-year overall survival for HSCT patients: 71%
3-year overall survival for non-HSCT patients: 11%
1. Substantial impact on outcome for upfront autologous HSCT
2. Treatment needs to be improved so that more patients can
receive HSCT
PTCL-NOS , AITL
18. Sieniawski et al Blood 2010;115:3664-3670
26 patients
EATL
5-year PFS: 52%
5-year OS: 60%
Significantly better than conventional CHOP treatment alone
19. Rodriguez et al Ann Oncol 2007;18:652-7
Retrospective analysis of T-cell lymphoma transplanted at CR1
74 patients at a median age o f46 years.
Stage III / IV: 88%
B sympotms: 53%
Increased LDH: 52%
IPI (2–3 risk factors): 65%
PIT (> 2 risk factors): 14%
Median follow-up of 67 months
5-year overall survival (OS): 68%
5-year progression free survival (PFS): 63%.
Significant risk factor for OS and PFS on multivariate analysis
PIT > 2 risk factors
1. High risk patients benefited from autologous HSCT
2. Patients with unfavorable PIT scores did not appear to
benefit from autologous HSCT, and might be considered for
other innovative therapies
T-cell lymphoma
20. Numata et al Bone Marrow Tranplant 2010;45:311-316
Retrospective analysis
39 patients with T-cell lymphoma
AITL: 11
ALCL: 9
NK/T: 7
PTCL-NOS: 12
Condition at HSCT: CR: 17; Non-CR: 12
Median follow up of 78 months
5-year OS: 62.1%
CR patients - 5-year OS: 71.4%
Non-CR patients - 5-year OS: 27.3%
P=0.046
T-cell lymphoma
22. Conclusions
1. Autologous HSCT improves outcome of patients with
T-cell lymphomas
2. The improvement, however, is seen mainly in patients
who attain a complete remission, or who have
chemotherapy sensitive disease in an up-front setting
3. The challenge therefore is to get the majority of
patients with T-cell lymphoma into a remission with
optimal chemotherapy
4. Patients with PIT of 2 or more risk factors do not
appear to benefit, and may be considered candidates
for experimental therapy
24. Kyriakou et al J Clin Oncol 2009;27:3951-8
EBMT
45 patients undergoing allogeneic HSCT
Median age 48 years (range, 23 to 68 years)
Risk categories
34 patients had received ≥ 2 chemotherapies
11 patients had failed a previous autologous HSCT
Myeloablative conditioning: 25
Reduced intensity conditioning: 20
Sibling donors: 26
None-sibling donors: 19
Chemotherapy-sensitive disease: 27
Chemotherapy-refractory: 18
Non-relapse mortality (NRM): 18% (3m), 22% (6m), and 25% (12m)
NRM significantly correlated with poor performance status
Relapse rate: 16% (2 yr), 20% (3 yr)
Progressive free surival: 62% (1 yr), 53% (3 yr)
Overall survival: 66% (1 yr) and 64% (3 yr)
AITL
25. Molina et al J Clin Oncol 2005;23:6163-71
8 patients
Failed a median of 7 (5 – 12) regimens
Marrow involvement confirmed by TCR rearrangement: 6 patients
Conditioning: Cy-TBI (N=3); BuCy (N=1); Flud/Mel (N=4)
Sibling donor (N=4); MUD (N=4)
CR: 8/8 (100%)
TRM: 2/8 (25%) (GVHD and RSV pneumonia)
Median follow up of 56 months
6 patients were alive and without evidence of lymphoma
Allogeneic HSCT may induce durable clinical, molecular, and
cytogenetic remissions in patients with advanced cutaneous T-cell
lymphoma refractory to standard therapies
Mycosis fungoides and Sezary syndrome
26. Duarte et al J Clin Oncol 2010;28:4492-9
EBMT
60 patients (men: 37, women: 23)
Median age: 46.5 years (range 22 – 66 years)
MF (n = 36); SS (n = 24)
Risk categories
44 had TMN stage IV disease
40 patients had advanced disease
Sibling donor (N=45); MUD (N=15)
Myeloablative: 16; Reduced intensity conditioning: 44
T cell depletion: 25
Overall survival: 66% (1 yr) and 54% (3 yr)
RIC gave higher OS
(RIC decreased NRM, without increaseing relapse)
Advanced-phase disease gave lower PFS and OS
(by increasing relapses)
Sibling better than MUD for PFS and OS
T-cell depletion increased relapses
DLI might be effective in relapses
Mycosis fungoides and Sezary syndrome
27. Jacobsen et al Ann Oncol 2011;22:1608-13
Retrospective analysis
52 patients
Median age: 46 (24 – 72) years
Myeloablative: 31, Reduced intensity conditioning: 21
Nodal (AITL, PTCL-NOS, ALCL): 31
Extranodal (NK/T, EATL, HSTCL, SPTCL, MF): 21
Median follow-up of 49 months
Non-relapse mortality: 27% (3 yr)
Relapse: 43% (3 yr)
3-year progression-free survival was 30%
3-yr PFS: 45% for nodal
3-yr PFS: 6% for extranodal
Overall survival: 41% (3 year)
Allogeneic HSCT can produce long-term remissions in nodal T-cel;l
lymphomas
T-cell lymphomas
28. Conclusions
1. Allogeneic HSCT improves outcome of patients with
nodal T-cell lymphomas
2. Non relapse mortality is increased in patients with
poor performance status
3. In CTCL, HSCT from a sibling donor with reduced
intensity conditioning and performed early in the
disease cause leads to the best outcome
4. Efforts should continue for the definition of an optimal
primary chemotherapy
29. • Novel, potent, bi-cyclic class 1
selective histone deacetylase
inhibitor
• Approved in 2009 by US FDA for
patients with cutaneous T-cell
lymphoma who received at least
one prior systemic therapy and in
2011 for patients with PTCL who
received at least one prior therapy
• Approval in PTCL was primarily
based on results from a phase 2,
single-arm, open-label study in
relapsed/refractory PTCL, GPI-06-
00021
29
Romidepsin
31. Phase II Trial of Romidepsin in patients with T-Cell
Lymphomas
Piekarz et al.
Relapsed/refractory mature T-cell lymphoma
Romidepsin: 14 mg/m2
per day on days 1, 8 and 15 every 4
weeks.
Primary end point: overall response rate (ORR)
Secondary end points: duration of response (DOR),
toxicity profile
32. Results
45 patients; median age 59
Histology: PTCL-NOS (57%) and AITL (15%)
Stage IV: 72%
Median number of prior chemotherapies: 2 (1 – 6)
Prior HSCT: 38%
ORR: 38%
CR: 8 patients (18%)
PR: 9 patients (20%)
Overall median DoR: 8.9 months (2-27) [for CR pt – 29.7 months]
Most common non-haematological adverse effects
Nausea(51%); fatigue (40%)
Grade III/IV Haematological toxicities
Neutropenia:26%; thrombocytopenia: 15%
Infections:2%
33. Phase II Study of Romidepsin in Relapsed/Refractory T-
Cell Lymphomas
Coiffier et al.
Relapsed/refractory mature T-cell lymphoma
Romidepsin: 14 mg/m2
per day on days 1, 8 and 15 every 4
weeks.
Primary end point: overall response rate (ORR)
Secondary end points: duration of response (DOR),
toxicity profile
34. Results
130 patients; median age 61
Histology: PTCL-NOS (53%); AITL (21%); ALK1-ve ALCL (16%)
Stage III/IV: 70%
Median number of prior chemotherapies: 2 (1 – 8)
Prior HSCT: 16%
ORR: 25%
CR: 19 patients (15%)
PR: 14 patients (11%)
Overall median DoR: 17 months
Median PFS: 4 months [18 months for CR patients]
Most common non-haematological adverse effects
Nausea(59%); fatigue (55%)
Grade III/IV Haematological toxicities
Neutropenia:18%; thrombocytopenia: 23%
Infections:6%
35. • Durable responses in patients with the more
common subtypes of relapsed/refractory PTCL
– Rate of CR/CRu similar across 3 subtypes
• 14% in PTCL-NOS to 19% in AITL and ALK-1 negative ALCL
– Nearly half (46%) of patients experienced disease
control
– Median DOR of 17 months, with responses ongoing up
to 34 months
• Thrombocytopenia (25%), neutropenia (18%), and
any infection (15%) were the most common ≥
grade 3 adverse events
– Only infections, thrombocytopenia, dyspnea, and
fatigue led treatment discontinuations in >1 patient.
Conclusions
FDA approval of Romidepsin in R/R T-cell lymphoma
38. Pralatrexate in Patients with Relapsed or Refractory
Peripheral T-Cell Lymphomas: PROPEL Study
O’Connor et al.
Relapsed/refractory mature T-cell lymphoma
Pralatrexate: 30 mg/m2
per week for 6 weeks in 7-week
cycle
Primary end point: overall response rate (ORR)
Secondary end points: duration of response (DOR),
toxicity profile
39. Results
111 patients; median age 58
Histology: PTCL-NOS (53%); ALK1-ve ALCL (15%); AITL (12%);
transformed MF (11%)
Median number of prior chemotherapies: 3 (1 – 12)
Prior HSCT: 16%
ORR: 29%
CR: 12 patients (11%)
PR: 20 patients (18%)
Overall median DoR: 10.1 months
Median PFS: 3.5 months
Median OS: 14.5 months
Most common non-haematological adverse effects
Mucositis(71%, Gr3/4:22%); fatigue (36%); oedema(34%)
Grade III/IV Haematological toxicities
Neutropenia:22%; thrombocytopenia: 33%
Sepsis:5%