This document discusses whether patients with refractory anemia with excess blasts (RAEB) or oligoblastic acute myeloid leukemia (AML) should receive induction chemotherapy prior to allogeneic stem cell transplantation. While historically it was believed that less disease is better for transplantation, recent retrospective studies have found no benefit and potential harms to giving chemotherapy induction prior to transplant. Hypomethylating agents are a less toxic alternative to reduce disease burden before transplant. The conclusion is that for MDS and oligoblastic AML, allogeneic transplant is the most curative option and induction chemotherapy before transplant has not been shown to improve outcomes, so patients should proceed directly to transplantation.
1) Hematopoietic stem cell transplantation (HSCT) can cure thalassemia patients by replacing defective bone marrow with healthy donor marrow.
2) A study of 98 thalassemia patients who received HSCT found that 94% survived with a novel reduced toxicity conditioning regimen having similar outcomes as standard regimens.
3) HSCT can cure thalassemia patients of all ages, including those over 10 years old, with survival rates over 90% found in the study. Gene therapy may also provide a cure in the future without requiring donors.
Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
Yes: Suporn Chancharunee, MD
No: Nina Shah, MD
Lenalidomide has shown promising activity against various types of lymphoma in clinical trials. It achieved objective response rates of 44% in relapsed/refractory peripheral T-cell lymphoma and 53% in mantle cell lymphoma. Bortezomib also achieved durable responses as a single agent in relapsed/refractory mantle cell lymphoma. The addition of rituximab to standard chemotherapy such as CHOP has improved outcomes in diseases like DLBCL and increased 5-year survival rates. Combining epratuzumab with rituximab has also shown high response rates in recurrent indolent lymphomas. Radioimmunotherapy with 90Y-ibritumomab tiuxetan following R-
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
This document summarizes new therapies presented at an ASCO/ICML conference for lymphomas. For aggressive NHLs, novel targeted drugs and cell therapies were discussed. Studies showed improved outcomes for DLBCL with regimens adding drugs like lenalidomide or bortezomib to R-CHOP. Intensive therapies did not clearly improve survival for double hit lymphomas over R-CHOP. For indolent NHLs, new drugs and initial therapy strategies were reviewed. The document provided details on clinical trials and outcomes for various lymphoma subtypes and treatments.
The document discusses whether high-risk non-Hodgkin's lymphoma (NHL) patients should receive upfront autologous stem cell transplantation (auto-SCT). Several studies from 1995-2013 have produced inconclusive evidence on whether auto-SCT improves outcomes for good-risk patients. For poor-risk patients, the evidence is also inconclusive but high-quality studies are still warranted. A 2013 study found auto-SCT consolidation associated with higher event-free and overall survival for high-risk NHL patients, but the number of patients was low. The document concludes that auto-SCT may be investigated further for high-risk patients based on prognostic factors like PET scans and molecular markers, and that tandem
This document discusses whether patients with refractory anemia with excess blasts (RAEB) or oligoblastic acute myeloid leukemia (AML) should receive induction chemotherapy prior to allogeneic stem cell transplantation. While historically it was believed that less disease is better for transplantation, recent retrospective studies have found no benefit and potential harms to giving chemotherapy induction prior to transplant. Hypomethylating agents are a less toxic alternative to reduce disease burden before transplant. The conclusion is that for MDS and oligoblastic AML, allogeneic transplant is the most curative option and induction chemotherapy before transplant has not been shown to improve outcomes, so patients should proceed directly to transplantation.
1) Hematopoietic stem cell transplantation (HSCT) can cure thalassemia patients by replacing defective bone marrow with healthy donor marrow.
2) A study of 98 thalassemia patients who received HSCT found that 94% survived with a novel reduced toxicity conditioning regimen having similar outcomes as standard regimens.
3) HSCT can cure thalassemia patients of all ages, including those over 10 years old, with survival rates over 90% found in the study. Gene therapy may also provide a cure in the future without requiring donors.
Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
Yes: Suporn Chancharunee, MD
No: Nina Shah, MD
Lenalidomide has shown promising activity against various types of lymphoma in clinical trials. It achieved objective response rates of 44% in relapsed/refractory peripheral T-cell lymphoma and 53% in mantle cell lymphoma. Bortezomib also achieved durable responses as a single agent in relapsed/refractory mantle cell lymphoma. The addition of rituximab to standard chemotherapy such as CHOP has improved outcomes in diseases like DLBCL and increased 5-year survival rates. Combining epratuzumab with rituximab has also shown high response rates in recurrent indolent lymphomas. Radioimmunotherapy with 90Y-ibritumomab tiuxetan following R-
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
This document summarizes new therapies presented at an ASCO/ICML conference for lymphomas. For aggressive NHLs, novel targeted drugs and cell therapies were discussed. Studies showed improved outcomes for DLBCL with regimens adding drugs like lenalidomide or bortezomib to R-CHOP. Intensive therapies did not clearly improve survival for double hit lymphomas over R-CHOP. For indolent NHLs, new drugs and initial therapy strategies were reviewed. The document provided details on clinical trials and outcomes for various lymphoma subtypes and treatments.
The document discusses whether high-risk non-Hodgkin's lymphoma (NHL) patients should receive upfront autologous stem cell transplantation (auto-SCT). Several studies from 1995-2013 have produced inconclusive evidence on whether auto-SCT improves outcomes for good-risk patients. For poor-risk patients, the evidence is also inconclusive but high-quality studies are still warranted. A 2013 study found auto-SCT consolidation associated with higher event-free and overall survival for high-risk NHL patients, but the number of patients was low. The document concludes that auto-SCT may be investigated further for high-risk patients based on prognostic factors like PET scans and molecular markers, and that tandem
1) The document summarizes research on donor selection for haploidentical hematopoietic stem cell transplantation (HSCT). It finds that donor-specific anti-HLA antibodies were associated with primary graft failure after unmanipulated haploidentical HSCT.
2) Specifically, the research studied 345 HSCT recipients and found that 25.2% had donor-specific anti-HLA antibodies, and those with higher antibody levels had higher rates of graft rejection and poor graft function.
3) Patients who experienced primary graft failure due to these antibodies had inferior survival outcomes compared to those without graft failure. The results suggest donor-specific antibodies should be considered when selecting a haploidentical donor.
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
The document discusses treatment options for patients with relapsed myeloma. It provides details on current treatment goals, classes of drugs used to treat relapsed myeloma, and clinical trial data on combinations of these drugs. Specifically, it summarizes clinical trial results showing improved progression-free and overall survival for combinations of bortezomib, lenalidomide, and dexamethasone compared to dexamethasone alone in relapsed patients. It also discusses factors to consider when selecting a salvage therapy for relapsed myeloma, including disease characteristics, prior treatments, and toxicity risks.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
Recent Advances In The Development Of Innovative Therapies The Celgene Pipelinespa718
This document summarizes recent advances in Celgene's drug pipeline for cancer and inflammatory diseases. It discusses:
1) Celgene's focus on targeting unmet medical needs in hematologic and solid tumor malignancies as well as inflammatory disorders.
2) Recent accomplishments including approval and clinical trial results showing survival benefits for their drugs Lenalidomide (Revlimid), Pomalidomide (Pomalyst), and Abraxane in multiple myeloma, myelodysplastic syndromes, lymphomas, and cancers like pancreatic and lung.
3) Near-term milestones including data readouts for Phase 3 trials of Apremilast in psoriasis and psoriatic arthritis, which
- 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 cellular therapy approaches for multiple myeloma, including:
1) Allogeneic stem cell transplantation can exploit the graft-versus-myeloma effect but is associated with transplant-related mortality; reduced intensity conditioning regimens may improve outcomes.
2) Vaccine strategies targeting antigens like MAGE and idiotype have shown safety and immune responses in clinical trials but limited clinical responses so far.
3) Adoptive transfer of chimeric antigen receptor (CAR) T cells and natural killer (NK) cells show pre-clinical activity against myeloma and are being tested in early clinical trials.
4) Ex-vivo expanded cord blood NK cells are being tested in a clinical
This document discusses hematopoietic stem cell transplantation (HSCT) for aplastic anemia. It addresses preparative regimens using cyclophosphamide with or without anti-thymocyte globulin (ATG), the effect of donor type on outcomes, and alternatives to matched sibling donors. Survival rates after HSCT from matched sibling donors are shown to be over 80% with cyclophosphamide conditioning. Outcomes with matched unrelated donors remain good at around 60% overall survival. Cord blood and haploidentical transplantation have been used as alternatives but require further study in aplastic anemia.
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
Ideal induction regimen for AML in adolescents and young adults spa718
This document discusses considerations for treatment of acute myeloid leukemia (AML) in adolescent and young adult (AYA) patients between ages 15-29. It covers several key points:
1) Overcoming the kinetics of AML through dose-escalated chemotherapy and addition of a third agent.
2) Understanding the disease biology through studies like TCGA and determining the right targeted partners.
3) Whether all younger age groups require the same treatment approach given differences in biology and outcomes between teenagers, 20s, etc.
4) The role of consolidation and bone marrow transplantation.
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.
This document summarizes key findings from several studies related to acute myeloid leukemia (AML) in elderly patients:
1) A phase 3 trial found that azacitidine extended overall survival compared to conventional care regimens in older patients with newly diagnosed AML, with median OS of 10.4 months for azacitidine vs 6.5 months for conventional care.
2) Subanalyses found azacitidine provided particularly long OS benefits vs conventional care for patients with poor-risk cytogenetics (median OS 6.4 vs 3.2 months) or myelodysplasia-related changes (1-year OS 55.1% vs 31.3% for LDAC preselected
1) The document summarizes findings from multiple studies comparing the use of bone marrow versus peripheral blood stem cells as the stem cell source for haploidentical hematopoietic stem cell transplantation.
2) Results showed no significant differences in rates of acute or chronic graft-versus-host disease, non-relapse mortality, overall survival, or progression-free survival between the two stem cell sources.
3) Peripheral blood stem cells were associated with similar hematologic recovery times but were easier to collect and transplant compared to bone marrow.
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
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.
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIESspa718
This document discusses treatment strategies for follicular lymphoma. It begins by outlining options for limited versus advanced stage disease, including watch and wait for asymptomatic low tumor burden or chemotherapy/immunotherapy for symptomatic high tumor burden. Key clinical questions are presented regarding the role of watch and wait in the rituximab era and optimal frontline therapies. Several studies comparing rituximab combined with different chemotherapy regimens are summarized, with one finding superior outcomes for R-CHOP compared to R-CVP or R-FM. Data is also presented showing superior progression-free and overall survival for bendamustine-rituximab compared to CHOP-rituximab. Toxicity profiles also favor bend
Audio and slides for this presentation are available on YouTube: http://youtu.be/rAgnoymx0DQ
Dr. Ann LaCasce talks about the various treatments for lymphoma, including chemotherapy and radiation therapy methods, as well as the role of clinical trials. This presentation was first given at a lymphoma workshop presented by the Lymphoma Research Foundation (www.lymphoma.org).
Audio and slides for this presentation are available on YouTube: http://youtu.be/pkB_mfPtjrA
Andrea K. Ng, MD, of Dana-Farber/Brigham and Women's Cancer Center Department of Radiation Oncology, gives an overview of the different types of radiation therapy, the side effects, and how it is used in the treatment of lymphoma. This presentation was given at the 2013 Lymphoma Research Foundation North American Forum on Sept. 29, 2013. http://www.dana-farber.org | http://www.lymphoma.org
1) The document summarizes research on donor selection for haploidentical hematopoietic stem cell transplantation (HSCT). It finds that donor-specific anti-HLA antibodies were associated with primary graft failure after unmanipulated haploidentical HSCT.
2) Specifically, the research studied 345 HSCT recipients and found that 25.2% had donor-specific anti-HLA antibodies, and those with higher antibody levels had higher rates of graft rejection and poor graft function.
3) Patients who experienced primary graft failure due to these antibodies had inferior survival outcomes compared to those without graft failure. The results suggest donor-specific antibodies should be considered when selecting a haploidentical donor.
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
The document discusses treatment options for patients with relapsed myeloma. It provides details on current treatment goals, classes of drugs used to treat relapsed myeloma, and clinical trial data on combinations of these drugs. Specifically, it summarizes clinical trial results showing improved progression-free and overall survival for combinations of bortezomib, lenalidomide, and dexamethasone compared to dexamethasone alone in relapsed patients. It also discusses factors to consider when selecting a salvage therapy for relapsed myeloma, including disease characteristics, prior treatments, and toxicity risks.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
Recent Advances In The Development Of Innovative Therapies The Celgene Pipelinespa718
This document summarizes recent advances in Celgene's drug pipeline for cancer and inflammatory diseases. It discusses:
1) Celgene's focus on targeting unmet medical needs in hematologic and solid tumor malignancies as well as inflammatory disorders.
2) Recent accomplishments including approval and clinical trial results showing survival benefits for their drugs Lenalidomide (Revlimid), Pomalidomide (Pomalyst), and Abraxane in multiple myeloma, myelodysplastic syndromes, lymphomas, and cancers like pancreatic and lung.
3) Near-term milestones including data readouts for Phase 3 trials of Apremilast in psoriasis and psoriatic arthritis, which
- 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 cellular therapy approaches for multiple myeloma, including:
1) Allogeneic stem cell transplantation can exploit the graft-versus-myeloma effect but is associated with transplant-related mortality; reduced intensity conditioning regimens may improve outcomes.
2) Vaccine strategies targeting antigens like MAGE and idiotype have shown safety and immune responses in clinical trials but limited clinical responses so far.
3) Adoptive transfer of chimeric antigen receptor (CAR) T cells and natural killer (NK) cells show pre-clinical activity against myeloma and are being tested in early clinical trials.
4) Ex-vivo expanded cord blood NK cells are being tested in a clinical
This document discusses hematopoietic stem cell transplantation (HSCT) for aplastic anemia. It addresses preparative regimens using cyclophosphamide with or without anti-thymocyte globulin (ATG), the effect of donor type on outcomes, and alternatives to matched sibling donors. Survival rates after HSCT from matched sibling donors are shown to be over 80% with cyclophosphamide conditioning. Outcomes with matched unrelated donors remain good at around 60% overall survival. Cord blood and haploidentical transplantation have been used as alternatives but require further study in aplastic anemia.
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
Ideal induction regimen for AML in adolescents and young adults spa718
This document discusses considerations for treatment of acute myeloid leukemia (AML) in adolescent and young adult (AYA) patients between ages 15-29. It covers several key points:
1) Overcoming the kinetics of AML through dose-escalated chemotherapy and addition of a third agent.
2) Understanding the disease biology through studies like TCGA and determining the right targeted partners.
3) Whether all younger age groups require the same treatment approach given differences in biology and outcomes between teenagers, 20s, etc.
4) The role of consolidation and bone marrow transplantation.
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.
This document summarizes key findings from several studies related to acute myeloid leukemia (AML) in elderly patients:
1) A phase 3 trial found that azacitidine extended overall survival compared to conventional care regimens in older patients with newly diagnosed AML, with median OS of 10.4 months for azacitidine vs 6.5 months for conventional care.
2) Subanalyses found azacitidine provided particularly long OS benefits vs conventional care for patients with poor-risk cytogenetics (median OS 6.4 vs 3.2 months) or myelodysplasia-related changes (1-year OS 55.1% vs 31.3% for LDAC preselected
1) The document summarizes findings from multiple studies comparing the use of bone marrow versus peripheral blood stem cells as the stem cell source for haploidentical hematopoietic stem cell transplantation.
2) Results showed no significant differences in rates of acute or chronic graft-versus-host disease, non-relapse mortality, overall survival, or progression-free survival between the two stem cell sources.
3) Peripheral blood stem cells were associated with similar hematologic recovery times but were easier to collect and transplant compared to bone marrow.
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
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.
FOLLICULAR LYMPHOMA; UPDATES ON TREATMENT STRATEGIESspa718
This document discusses treatment strategies for follicular lymphoma. It begins by outlining options for limited versus advanced stage disease, including watch and wait for asymptomatic low tumor burden or chemotherapy/immunotherapy for symptomatic high tumor burden. Key clinical questions are presented regarding the role of watch and wait in the rituximab era and optimal frontline therapies. Several studies comparing rituximab combined with different chemotherapy regimens are summarized, with one finding superior outcomes for R-CHOP compared to R-CVP or R-FM. Data is also presented showing superior progression-free and overall survival for bendamustine-rituximab compared to CHOP-rituximab. Toxicity profiles also favor bend
Audio and slides for this presentation are available on YouTube: http://youtu.be/rAgnoymx0DQ
Dr. Ann LaCasce talks about the various treatments for lymphoma, including chemotherapy and radiation therapy methods, as well as the role of clinical trials. This presentation was first given at a lymphoma workshop presented by the Lymphoma Research Foundation (www.lymphoma.org).
Audio and slides for this presentation are available on YouTube: http://youtu.be/pkB_mfPtjrA
Andrea K. Ng, MD, of Dana-Farber/Brigham and Women's Cancer Center Department of Radiation Oncology, gives an overview of the different types of radiation therapy, the side effects, and how it is used in the treatment of lymphoma. This presentation was given at the 2013 Lymphoma Research Foundation North American Forum on Sept. 29, 2013. http://www.dana-farber.org | http://www.lymphoma.org
Hodgkin's lymphoma and non-Hodgkin's lymphomas are cancers of the lymphatic system. Hodgkin's lymphoma is characterized by the presence of Reed-Sternberg cells and usually involves the lymph nodes above the diaphragm. Non-Hodgkin's lymphomas can be of B-cell or T-cell origin and often spread beyond the lymph nodes to other organs. Staging investigations are used to determine the extent of disease, which guides treatment, which may include chemotherapy, radiation therapy, stem cell transplantation or watchful waiting. Prognosis depends on disease stage and other risk factors.
Lymphoma is cancer that arises in the lymphatic system. The lymphatic system contains lymph nodes and vessels that help fight infection and disease. There are two main types of lymphoma - Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is diagnosed using biopsies of swollen lymph nodes and contains abnormal B-cells called Reed-Sternberg cells. Non-Hodgkin's lymphoma can involve many types of abnormal white blood cells and can spread beyond lymph nodes. Both types are staged based on spread and tested using lymph node biopsies, imaging, and bone marrow samples. Treatment depends on type and stage but may include chemotherapy, radiation, and stem cell transplants
This document discusses radiation therapy (RT) for various types of non-Hodgkin's lymphoma. It covers RT dose recommendations when used alone or as part of combined modality therapy for different lymphoma stages and histologies. It discusses techniques for total body irradiation and strategies for treating primary extranodal lymphomas in different anatomical sites. Overall, the document provides guidance on using RT to effectively treat various lymphomas based on stage, histology, and other clinical factors.
This document provides information on various types of leukemia and lymphomas. It discusses the classification, presentation, investigations, treatment and prognosis of acute lymphoblastic leukemia, chronic lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, Hodgkin's lymphoma and non-Hodgkin's lymphoma. Key differences between leukemia and lymphoma are also noted. The document contains detailed information on clinical features, pathogenesis, risk factors and management for each condition.
This document discusses techniques used to study lymphomas, including immunophenotyping, cytogenetics, and molecular analysis. Immunophenotyping helps differentiate between benign and malignant processes and between B and T cell neoplasms by identifying cell surface markers. Cytogenetics identifies translocations and deletions that help classify lymphomas. Molecular analysis identifies immunoglobulin and T-cell receptor gene rearrangements in B and T cell malignancies, respectively. The document also summarizes the history of lymphoma classification systems and the current WHO system, which classifies lymphomas based on morphology, immunophenotype, molecular abnormalities, and clinical profile.
Audio and slides for this presentation are available on YouTube: http://youtu.be/Q_wdfcJO3XE
Ann LaCasce, MD, MMSc, of Dana-Farber/Brigham and Women's Cancer Center Adult Lymphoma Program, talks about new clinical trials and treatments available for lymphoma patients. This presentation was originally given at the Lymphoma Research Foundation North American Forum on Sept. 28, 2013. http://www.dana-farber.org | http://www.lymphoma.org
From Queens Library's expert-led panel, Cancer Awareness: What You Need to Know, featuring professionals from New York Hospital Queens, North Shore LIJ, the American Cancer Society, and the Leukemia and Lymphoma Society
The document discusses haematological malignancies, describing:
1. How genetic mutations in haemopoietic stem cells disrupt normal blood cell differentiation, causing diseases depending on the affected differentiation pathway.
2. The main types of leukaemias including acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and chronic lymphocytic leukaemia (CLL).
3. Other haematological malignancies like myeloproliferative disorders, lymphomas, and multiple myeloma.
- German chemist Paul Ehrlich coined the term "chemotherapy" to refer to treatment of disease with chemical drugs. By the 1950s, the term was primarily used to refer to drugs used to treat cancer.
- Chemotherapy involves using drugs to treat cancer and typically involves drugs that interfere with cell division, such as methotrexate or fluorouracil.
- The choice of chemotherapy depends on factors like the location and stage of the tumor and the patient's health. While it can cure some cancers, it is most effective against cancer before metastasis.
This document discusses the changing landscape and treatment of lymphomas with a focus on the role of radiotherapy. Some key points:
- Non-Hodgkin lymphomas present many challenges due to their diversity and changing outcomes over time. Radiotherapy is an effective local therapy for tumor control and can cure localized disease.
- For stage I/II follicular lymphoma and mucosa-associated lymphoid tissue lymphoma, radiotherapy alone provides excellent long-term local control and survival.
- For localized diffuse large B-cell lymphoma, combined modality treatment with chemotherapy and radiotherapy improves outcomes. Ongoing studies are evaluating the role of radiotherapy in the rituximab era.
1. Hodgkin's lymphoma is a type of lymphoma that was initially described as an inflammatory disease but is now recognized and treated as a malignant lymphoma.
2. Treatment has evolved from radiation alone to a combined approach using chemotherapy and radiation or chemotherapy alone. Common chemotherapy regimens include ABVD and BEACOPP. Radiation therapy doses and fields depend on disease stage and other factors.
3. Side effects of treatment depend on factors like radiation dose, fields, and prior chemotherapy. Acute side effects are usually mild and resolve over time. Late effects can include hypothyroidism, infertility, and in rare cases pneumonitis or pericarditis. Ongoing research aims to reduce treatment
Non-Hodgkin's lymphoma is a cancer of the lymphatic system that can affect B-cells or T-cells. It is classified based on the type of cell and aggressiveness. Common symptoms include swollen lymph nodes, fever, night sweats, and unintended weight loss. While the exact causes are unknown, risk factors include chemical exposure, infections, and immunodeficiency. Diagnosis involves imaging tests and biopsy. Treatment options include chemotherapy, radiation, immunotherapy, and bone marrow transplants, with survival rates varying based on cell type and staging.
This document provides information about lymphoma, including Hodgkin's disease and non-Hodgkin's lymphoma. It discusses the epidemiology, etiology, clinical manifestations, diagnosis, staging, treatment and prognosis of these cancers. Hodgkin's disease is characterized by Reed-Sternberg cells and is categorized using the Rye or REAL classification systems. Non-Hodgkin's lymphoma subtypes include Burkitt lymphoma, lymphoblastic lymphoma, and diffuse large B-cell lymphoma. Staging is important for determining appropriate chemotherapy regimens and radiation treatment. Outcomes depend on disease stage and subtype, with localized disease having higher survival rates.
What is Lymphoma?
Malignant lymphoma is a term given to tumors of the lymphoid system and specifically of lymphocytes and their precursor cells
i.e.
Cancer of the lymphatic system.
Many lymphomas are known to be due to specific genetic mutations.
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.
The document discusses various types of lymphoma and leukemia. It defines lymphoma as lymphoid proliferations in discrete tissue masses, while leukemia involves widespread involvement of the bone marrow and large numbers of tumor cells in the blood. Key types discussed include non-Hodgkin's lymphoma, Hodgkin's disease, follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Burkitt lymphoma, and mantle cell lymphoma. Classification systems and characteristic features such as morphology, immunophenotype, genetics, and clinical presentation are summarized for several of these.
This document discusses the classification and characteristics of various types of non-Hodgkin lymphoma (NHL). It describes the historical classifications of NHL from the 1940s to the current 2008 WHO classification. It then provides details on specific NHL subtypes, including small lymphocytic lymphoma/chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and marginal zone B-cell lymphoma. For each subtype, it discusses immunophenotype, genetic abnormalities, clinical features, histopathology, immunostaining patterns, and differential diagnosis.
Lymphoma can be divided into two main types: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells and typically presents with enlarged, painless lymph nodes. Risk factors include certain viruses and age. Treatment involves chemotherapy and/or radiation therapy depending on the stage. Non-Hodgkin lymphoma is more likely to involve extralymphatic sites and the bone marrow. It can be further divided into low-grade and high-grade subtypes depending on aggressiveness. Treatment typically involves chemotherapy regimens like CHOP.
Evidence-Based Clinical Updates in the Treatment of Patients with Relapsed/Re...Carevive
For information about AMA PRA Category 2 CreditTM,
you may consult page 10 of the AMA’s booklet “The
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Metronomic chemotherapy involves the chronic administration of low, minimally toxic doses of chemotherapy drugs on a frequent schedule with no prolonged breaks. This contrasts with conventional chemotherapy which uses maximum tolerated doses with breaks to allow for bone marrow recovery. Metronomic chemotherapy aims to target the tumor vasculature through its anti-angiogenic effects and has shown efficacy in palliative settings with less toxicity. Several drugs have been used in metronomic chemotherapy regimens with the most common being cyclophosphamide and methotrexate. Ongoing research is focused on optimizing dosing schedules and biomarkers to evaluate treatment response and resistance.
This document discusses potential new drugs for inflammatory bowel disease (IBD) beyond current biological therapies. It outlines several therapeutic pipelines targeting cytokines like TNF, IL-12/IL-23, IL-13 and IL-6. Anti-adhesion molecules targeting integrins and MadCAM-1 are also discussed. The document explores manipulating the microbiome through probiotics, antibiotics or fecal transplantation, as well as using prognostic genomics to predict treatment responses. Overall it concludes that future IBD treatment will be personalized based on biomarkers and tissue signatures to select therapies beyond TNF blockers.
This document discusses approaches to personalized cancer therapy. It describes precision medicine as targeting patient subgroups rather than individuals based on genetic markers. The right target, drug or drug combinations, and patient are key to accomplish this. An example is given of a novel CDK4/6 inhibitor being tested in breast cancer subgroups. Another example discusses an anti-CD22 antibody-drug conjugate showing promise for certain lymphomas. The document also outlines molecular subtypes in lung cancer and how targeted therapies like crizotinib have been effective in subsets of patients with genetic alterations like ALK rearrangement.
Multiple myeloma is a cancer of plasma cells that remains largely incurable. While initial treatments can achieve remission, patients will typically relapse with fewer treatment options available. Current therapies for relapsed and refractory multiple myeloma have limited efficacy and serious side effects. There remains an unmet need for additional effective and tolerable treatments. Carfilzomib is a novel proteasome inhibitor that has shown clinical activity with durable responses and an acceptable safety profile in patients with relapsed and refractory multiple myeloma who have limited treatment options.
Lenalidomide maintenance compared with placebo in responding elderlyravi jaiswal
This randomized phase III trial compared lenalidomide maintenance therapy versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) who achieved a response to first-line R-CHOP induction therapy. The trial found that lenalidomide maintenance led to a statistically significant improvement in progression-free survival compared to placebo, with a median PFS not reached in the lenalidomide arm versus 58.9 months in the placebo arm. There was no significant difference in overall survival between the arms. Lenalidomide maintenance was associated with more grade 3-4 adverse events compared to placebo. The benefit of lenalidomide maintenance was seen across patient subgroups.
Stem Cell Transplantation in Hodgkin’s Lymphoma Past, Present and FutureAmir Abbas Hedayati Asl
Treatment for HL has improved significantly since the ABVD chemotherapeutic combination was invented over 30 years ago .
Despite using the same ABVD regimen in most patients treated in the first line, we now have a much better understanding of disease biology and the late side effects of therapy, and we have moved toward a personalized, risk-adapted approach.
This approach promises to deliver low toxicities and high cure rates for lower risk patients while reserving aggressive regimens for those high risk patients who really need them.
For the minority of patients who fail first-line therapy, novel drugs like the antibody-drug conjugate BV and immunotherapies with nivolumab and pembrolizumab have produced high response rates and durability of benefit.
Further research is needed to determine whether these novel drugs could make life better for both patients with HL who are undergoing treatment and for the growing cohort of HL survivors.
cancer genetics, tumor marker and targeted therapy in cancerShivshankar Badole
This document discusses cancer genetics, tumor markers, and targeted cancer therapy. It begins by explaining how cancer results from gene mutations that disrupt cell cycle control. It then describes different types of genetic alterations like gene amplifications and chromosome translocations. It also discusses proto-oncogenes, oncogenes, and tumor suppressor genes. The document next covers tumor markers and their use in cancer detection and monitoring. Finally, it examines targeted cancer therapies, how they differ from chemotherapy, examples of targeted drugs, their side effects and limitations, and specific targets like BCR-ABL in CML and HER-2 in breast cancer.
The document summarizes several key studies presented at the 2016 American Society of Hematology (ASH) Annual Meeting. It discusses results from the GALLIUM and ALCANZA studies showing improved outcomes for obinutuzumab and brentuximab vedotin, respectively, in follicular lymphoma and cutaneous T-cell lymphoma. It also summarizes positive results from maintenance rituximab in mantle cell lymphoma and lenalidomide in high-risk chronic lymphocytic leukemia. Finally, it discusses advances in CAR T-cell therapy and results from studies of pacritinib and transplant approaches in myeloma.
University of Missouri - Columbia, POSH Inhibitor-Based Cancer Therapykphodel
This document summarizes research into developing a non-toxic cancer treatment by inhibiting POSH and JNK1/JNK2. The treatment shows promise in killing various leukemia and lymphoma cell lines as well as drug-resistant cancer cells in mice. It may also have applications for autoimmune diseases and viral infections by selectively eliminating T-cells and reducing HIV viral release. Next steps include further testing in mice and canines along with developing targeted delivery methods before potential human trials. The researchers are seeking partners for licensing, sponsored research, and collaboration.
The Importance of Biomarkers in Hematology/Oncology Drug Development - Presentation by Steven Fruchtman, Former Chief Medical Officer, Syndax Pharmaceuticals, at the marcus evans Evolution Summit 2014 held in Palm Beach, FL May 7-9
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses epidemiology, signs and symptoms, and risk factors of cancer. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through intravenous methods. Side effects can include skin, gastrointestinal and blood problems. Limitations include cancer cells developing resistance. Present therapies also include immunotherapy and nanotechnology.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology, signs and symptoms, and risk factors of cancer. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves targeted drugs administered through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide a more selective treatment approach compared to chemotherapy.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology of cancer in India, signs and symptoms, and risk factors. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide more selective treatment compared to chemotherapy.
Cancer chemotherapy for medical studentstaklo simeneh
This document provides information about cancer chemotherapy. It defines cancer and discusses the mechanisms of oncogenes and tumor suppressor genes in carcinogenesis. It describes different cancer treatment modalities including chemotherapy, which can be used as primary treatment for advanced cancer, neoadjuvantly to shrink tumors before other therapies, or adjuvantly after other local therapies. The document discusses cell cycle kinetics and how different classes of chemotherapy drugs work at different cell cycle phases. It also covers common side effects of chemotherapy and classifications of anticancer drugs including cytotoxic, targeted, and hormonal agents. Specific drug classes like alkylating agents and their mechanisms of inducing DNA damage are explained in detail.
Chemotherapy is the main treatment for disseminated cancers. It involves using multiple drugs in cycles to target rapidly dividing cancer cells. Common drugs include alkylating agents, antimetabolites, microtubule inhibitors, and monoclonal antibodies. Combination chemotherapy aims to maximize responses while avoiding overlapping toxicities. Doses are based on body surface area and adjusted for individual factors. Treatment intervals allow time for normal tissues to recover between cycles. Toxicities include myelosuppression, nausea/vomiting, and alopecia. Response is evaluated based on tumor shrinkage or progression.
This document discusses immunotherapies for hepatocellular carcinoma (HCC). It begins by explaining that HCC typically develops in the context of chronic liver disease and cirrhosis. For early-stage HCC, surgical resection and liver transplantation can be curative, while radiofrequency ablation and transarterial chemoembolization are common local therapies for intermediate-stage HCC. Systemic therapies were historically ineffective for advanced HCC, but tyrosine kinase inhibitors like sorafenib were found to provide a survival benefit. More recent immunotherapies like nivolumab, pembrolizumab, and combinations with ipilimumab have shown response rates of 15-31% in advanced HCC
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.
1) Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be performed in elderly patients aged 60 years and older with hematological malignancies.
2) A prospective study of 75 patients aged 60-70 years who received a reduced-intensity conditioning allo-HSCT found 2-year overall survival of 36% and non-relapse mortality of 9%.
3) Outcomes can be improved by careful patient selection considering factors like age, comorbidities, disease risk, and through tailored conditioning regimens and graft-versus-host disease prophylaxis.
1. Three major advancements in the field of
Lymphoma Treatment in the 21st century
Dr. Raymond SM Wong
Department of Medicine & Therapeutics
Prince of Wales Hospital
The Chinese University of Hong Kong
2. Major Advancements in Lymphoma Treatment
1. Improvement of efficacy of antibody-directed
therapy
• Antibody-drug conjugates
2. Targeting B-cell receptor (BCR) signaling
• BCR Signal Transduction Inhibitor Therapy
3. Combating the epigenome
• Epigenetic drugs
4. Overall Survival among 399 Patients with DLBCL Assigned to
CHOP vs R-CHOP
Coiffier B et al. N Engl J Med 2002;346:235-242.
5. Antibody-Drug Conjugates
• Most monoclonal antibodies are not sufficiently potent to be
therapeutically active on their own
• Antibody–drug conjugates (ADCs) use antibodies to deliver a
potent cytotoxic compound selectively to tumor cells, thus
improving the therapeutic index of chemotherapeutic agents
• Becoming an increasingly important sub-class of antibody-related
therapeutics
6. Brentuximab vedotin
• Anti-CD30 monoclonal antibody
linked to monomethyl auristatin
E (MMAE), a microtubule-disrupting
agent, by a cleavable
linker
• Approved for use in relapsed
classical Hodgkin lymphoma’s
and in systemic anaplastic large
cell lymphoma
7. Hodgkin’s Lymphoma
• Conventional treatment relies on
standard chemotherapy, radiation
therapy, and autologous or allogeneic
stem cell transplantation in cases of
relapsed disease
• In spite of a high cure rate, patients
who are not cured with first- or second-line
therapy, including stem cell
transplantation, have an estimated
median survival of < 3 years
• No new drugs have been approved for
HL by the US FDA in more than 30 years
14. B-cell receptor signaling
Bruton’s tyrosine kinase (BTK)
• is a non-receptor kinase
• its function is essential to
normal B cells
• is phosphorylated by SYK
and then phosphorylates
phospholipase Cγ2, leading
to activation of protein
kinase C beta and, in turn,
CARD11
Phosphoinositide 3-kinase (PI3K)
• PI3K/AKT pathway is critical
for essential cellular
processes such as
metabolism, growth, and
proliferation
• The p110 delta and p110
gamma isoforms are
expressed primarily in cells
of hematopoietic origin
15. Mechanism of Action of Idelalisib and Ibrutinib
Fruman DA, Cantley LC. N Engl J Med 2014;370:1061-1062.
16. Ibrutinib
• An orally available, selective inhibitor of Bruton's tyrosine
kinase.
• It blocks BCR signaling in normal peripheral B cells and
showed antitumor activity in several types of non-Hodgkin's
lymphoma
• Bruton tyrosine kinase is
commonly overexpressed
in mantle cell lymphoma
17. Ibrutinib phase 2 trial in mantle cell lymphoma
Wang ML et al. N Engl J Med
2013;369:507-516.
18. Idelalisib (GS-1101 or CAL-101)
• An oral agent that primarily
inhibits the delta isoform of PI3K
• Just been approved by FDA to treat
patients with
• relapsed chronic lymphocytic
leukemia (CLL)
• relapsed follicular lymphoma
(FL)
• relapsed small lymphocytic
lymphoma (SLL)
19. Phase 2 study of Idelalisib for indolent lymphoma
Gopal AK, et al. NEJM 2014
23. Targeting the epigenome
• Recurrent mutations in epigenetic enzymes, such as chromatin
modifiers and DNA methyltransferases, have been discovered
in NHL
24. Alteractions of chromatin states in NHL due to
mutations in chromatin-related protein
• CRC: chromatin remodeler
• DNMT: DNA
methyltransferase
• HAT: Histone
acetyltransferase
• HDAC: Histone deacetylase
• HMT: Histone
methyltransferase
• PcG: polycomb group
• TF: Transcription factor
Hassler MR, et al. 2013
25. Vorinostat
• an histone deacetylase inhibitor
• also known as suberoylanilide hydroxamic acid, SAHA
• Approved by FDA for the treatment of cutaneous T-cell
lymphoma failed other treatment
26. Phase 2 trial of Vorinostat for CTCL
Duvic M, et al. Blood 2007
27. Phase 2 trial of Vorinostat for CTCL
Duvic M, et al. Blood 2007
30. Summary
• The rapid improvement of our understanding of the molecular
basis of various lymphomas have led to the development of
many new treatment
• Many of these new agents have shown promising results in
clinical trials and are going into clinical practice
• Despite early success as well as substantial and durable
responses in some patients, there is still much work to be done
• The greatest impact these new treatment will likely to come
from combination therapy, possibly in the frontline setting
• Further studies are needed to answer these key questions and
ultimately lead to the development of highly effective
mechanism based drug regimens
Targeted therapy of HRS cells. HRS cells express a variety of receptors and antigens that can be targeted by monoclonal antibodies. Many of these receptors trigger well-defined signaling pathways that promote HRS cell survival. These signaling pathways can be targeted by a variety of small molecules.