The document discusses immunotherapy in urologic oncology, including relevant immunology concepts, mechanisms of how cancer cells evade the immune system, immunotherapy strategies like therapeutic vaccination and immune checkpoint blockade, and applications of immunotherapy in renal cancer, upper tract urothelial carcinoma, bladder cancer, penile cancer, and testicular cancer. It provides details on immunotherapeutic agents and their mechanisms of action, efficacy, and side effect profiles.
This document discusses the management of localized and locally advanced prostate cancer. It covers risk stratification methods including D'Amico, NCCN and EAU classifications. Treatment options for localized prostate cancer include active surveillance, radical prostatectomy, external beam radiotherapy and brachytherapy. Patient selection factors, follow-up protocols and potential complications are reviewed for different treatment modalities. Risk assessment tools like Partin tables, Kattan and Briganti nomograms are also described to guide treatment decisions in localized prostate cancer.
This document discusses the management of metastatic renal cancer. It notes that approximately 1/3 of newly diagnosed renal cancers are metastatic and 20-40% of localized cancers eventually metastasize. Metastatic renal cancer is usually fatal with 5-year survival rates under 5%. The document outlines treatment approaches including local therapies like cytoreductive nephrectomy and metastasectomy as well as systemic therapies like immunotherapy, targeted therapy and chemotherapy. It provides details on specific immunotherapy agents, targeted therapies including several tyrosine kinase inhibitors, and recommendations on treatment sequencing.
Management of Testicular Cancers document provides an overview of testicular cancer including:
- Epidemiology showing highest rates in Western countries and increasing worldwide incidence. India has a low incidence of 0.5 cases per 100,000 men.
- Risk factors include cryptorchidism, family history, and genetic conditions. Germ cell tumors are the most common type.
- Staging uses AJCC TNM system and International Germ Cell Consensus Classification for metastatic disease.
- For stage I seminoma, surveillance is an option but adjuvant radiotherapy to para-aortic region is still commonly used with dog leg fields showing similar outcomes to para-aortic fields alone and reducing toxicity
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
This document discusses the management of locally advanced prostate cancer. It defines locally advanced prostate cancer as regional or lymph node involvement without distant metastasis. For imaging, endorectal MRI is useful for staging but has limitations. Treatment options discussed include radical prostatectomy with pelvic lymph node dissection, radiation therapy with long-term androgen deprivation therapy, and newer developments like focal ablation and intermittent androgen deprivation. Guidelines recommend multimodal therapy like surgery followed by radiation for locally advanced prostate cancer.
This document summarizes highlights from the Ohio Colorectal Cancer Prevention Initiative. The initiative screened over 3,300 colorectal cancer patients and found that 15.9% had defective DNA mismatch repair (dMMR). Further testing identified 4% as having Lynch syndrome (LS) and 2% as having double somatic mutations. Similar results were found in screening over 300 endometrial cancer patients. Cascade genetic testing of relatives identified over 180 additional individuals with LS. The initiative demonstrated the value of universal tumor screening in identifying hereditary cancer cases and facilitating prevention through genetic testing of relatives.
This document discusses the management of localized and locally advanced prostate cancer. It covers risk stratification methods including D'Amico, NCCN and EAU classifications. Treatment options for localized prostate cancer include active surveillance, radical prostatectomy, external beam radiotherapy and brachytherapy. Patient selection factors, follow-up protocols and potential complications are reviewed for different treatment modalities. Risk assessment tools like Partin tables, Kattan and Briganti nomograms are also described to guide treatment decisions in localized prostate cancer.
This document discusses the management of metastatic renal cancer. It notes that approximately 1/3 of newly diagnosed renal cancers are metastatic and 20-40% of localized cancers eventually metastasize. Metastatic renal cancer is usually fatal with 5-year survival rates under 5%. The document outlines treatment approaches including local therapies like cytoreductive nephrectomy and metastasectomy as well as systemic therapies like immunotherapy, targeted therapy and chemotherapy. It provides details on specific immunotherapy agents, targeted therapies including several tyrosine kinase inhibitors, and recommendations on treatment sequencing.
Management of Testicular Cancers document provides an overview of testicular cancer including:
- Epidemiology showing highest rates in Western countries and increasing worldwide incidence. India has a low incidence of 0.5 cases per 100,000 men.
- Risk factors include cryptorchidism, family history, and genetic conditions. Germ cell tumors are the most common type.
- Staging uses AJCC TNM system and International Germ Cell Consensus Classification for metastatic disease.
- For stage I seminoma, surveillance is an option but adjuvant radiotherapy to para-aortic region is still commonly used with dog leg fields showing similar outcomes to para-aortic fields alone and reducing toxicity
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
This document discusses the management of locally advanced prostate cancer. It defines locally advanced prostate cancer as regional or lymph node involvement without distant metastasis. For imaging, endorectal MRI is useful for staging but has limitations. Treatment options discussed include radical prostatectomy with pelvic lymph node dissection, radiation therapy with long-term androgen deprivation therapy, and newer developments like focal ablation and intermittent androgen deprivation. Guidelines recommend multimodal therapy like surgery followed by radiation for locally advanced prostate cancer.
This document summarizes highlights from the Ohio Colorectal Cancer Prevention Initiative. The initiative screened over 3,300 colorectal cancer patients and found that 15.9% had defective DNA mismatch repair (dMMR). Further testing identified 4% as having Lynch syndrome (LS) and 2% as having double somatic mutations. Similar results were found in screening over 300 endometrial cancer patients. Cascade genetic testing of relatives identified over 180 additional individuals with LS. The initiative demonstrated the value of universal tumor screening in identifying hereditary cancer cases and facilitating prevention through genetic testing of relatives.
This document discusses muscle invasive bladder cancer (MIBC) and metastatic bladder cancer. It covers topics such as how MIBC is diagnosed, staging of MIBC using the TNM system, treatment with radical cystectomy and pelvic lymph node dissection, and use of neoadjuvant and adjuvant chemotherapy. It also discusses criteria for bladder preservation approaches and standards of care for treating metastatic bladder cancer with cisplatin-based chemotherapy.
This document discusses several landmark trials comparing different treatment approaches for esophageal cancer. The CALGB 9781 trial compared trimodality therapy (chemotherapy, radiation therapy, and surgery) to surgery alone and found improved overall survival and progression-free survival with trimodality therapy. Median overall survival was 4.48 years with trimodality therapy versus 1.79 years with surgery alone. The trial was closed early due to poor accrual, resulting in a small sample size.
Androgen Deprivation Therapy for Prostate CancerAlexander Small
This document summarizes a tumor board review on androgen deprivation therapy for prostate cancer. It begins with a case presentation of a patient with metastatic prostate cancer and then provides: 1) A brief history of the discovery of the connection between androgens and prostate cancer; 2) An overview of the androgen axis and various methods of androgen deprivation therapy including surgical castration, medical castration, anti-androgens, and GnRH agonists/antagonists; 3) A discussion of the adverse effects of androgen deprivation therapy including quality of life impacts, increased risks of osteoporosis and cardiovascular disease; 4) Considerations around treatment timing; and 5) Conclusions regarding optimal androgen deprivation therapy
Management of prostate cancer involves assessing risk levels based on PSA, Gleason score, and percentage of positive biopsy cores. Treatment options include active surveillance for low risk prostate cancer with potential delayed treatment if cancer progresses. Radical prostatectomy is the gold standard for localized prostate cancer and provides the possibility of cure with minimal side effects when performed by an experienced surgeon. While providing excellent cancer control, radical prostatectomy carries risks of erectile dysfunction and urinary incontinence.
This document discusses radiation cystitis, which is inflammation of the bladder caused by radiation therapy for pelvic cancers. It can cause symptoms like bleeding, urgency and frequency. The risks increase with higher radiation doses to the bladder and concurrent chemotherapy. Treatment options discussed include pentosan polysulfate, formalin, aminocaproic acid, conjugated estrogens, phenazopyridine and hyperbaric oxygen therapy. Surgical intervention may be needed for severe cases with complications or an unresponsive, contracted bladder.
The document discusses the role of radiation therapy in treating oligometastatic prostate cancer, noting that radiation can potentially achieve durable responses or even cure in some cases when metastases are limited. It reviews definitions of oligometastatic prostate cancer, the rationale for local and metastasis-directed radiation therapy, clinical evidence from studies on the use of external beam radiation therapy and stereotactic body radiation therapy to treat the primary tumor and metastases, and outcomes from these studies including local control rates, progression-free survival, and overall survival. The document concludes that radiation therapy plays an important role in the treatment of oligometastatic prostate cancer.
Locally advanced prostate cancer (LAPC) involves spread outside the prostate capsule or involvement of nearby structures. While no consensus exists on optimal treatment, combination therapy with radical prostatectomy (RP), radiation therapy (RT), and androgen deprivation (AD) provides the best outcomes. For selected patients with low-volume LAPC, RP alone may be sufficient, but extended pelvic lymph node dissection is important. Adjuvant or neoadjuvant RT and long-term AD after RP can improve local control and reduce recurrence rates. For patients unable to undergo surgery, RT with concurrent and adjuvant AD is the standard treatment and provides improved survival compared to monotherapy. Multimodal therapy increases side effects but provides superior outcomes over the
This document summarizes information about PSMA PET-CT scans for imaging prostate cancer. It explains that PSMA is overexpressed in prostate cancer cells and is a good target for imaging. A new development is using radiolabeled PSMA ligands like Ga-68 for PET imaging, which can detect prostate cancer with high sensitivity and specificity, including small lymph nodes and bone metastases. The benefits of Ga-68 include its generator production and labeling chemistry allowing automated preparation with a short half-life for reduced radiation dose. PSMA PET is useful for staging, recurrence detection, and assessing treatment response in prostate cancer.
The document provides an overview of genomics in breast cancer and summarizes the Oncotype DX genomic assay. It discusses how the assay analyzes the expression levels of 21 genes in breast tumor tissue to provide a Recurrence Score that quantifies a patient's risk of recurrence and predicts who will benefit from chemotherapy. Clinical studies have shown the assay stratifies patients into low, intermediate, and high risk groups and identifies those unlikely to benefit from chemotherapy while high risk patients see significant reduction in recurrence with chemotherapy. The assay is recommended in clinical guidelines and widely covered by insurance.
ANDROGEN DEPRIVATION THERAPHY ON PRASTATE CAEko indra
Androgen deprivation therapy (ADT) reduces androgen hormone levels to prevent prostate cancer growth. It can be administered medically or surgically. Medically, it involves using LH-RH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the androgen receptor. Surgically, bilateral orchiectomy quickly reduces testosterone levels. ADT is indicated for high risk and metastatic prostate cancer, and is often used with radiation therapy. The goal is to lower testosterone levels below 50 ng/dL to achieve a castration effect.
This document discusses treatment options for non-muscle invasive bladder cancer, including transurethral resection of bladder tumor (TURBT), bacillus Calmette-Guerin (BCG) immunotherapy, and intravesical chemotherapy. It provides details on the administration and schedule of BCG, lists its contraindications and potential side effects, and discusses options for patients who fail or are intolerant to BCG therapy, including interferon and investigational immunotherapies.
This presentation provides an overview of androgen deprivation therapy (ADT), also known as hormone therapy, for prostate cancer. It discusses the basic principles, including how prostate cancer cells rely on androgens like testosterone to grow. ADT aims to stop androgen production or block their effects. Methods include surgical removal of the testes, medications to reduce testosterone production, and anti-androgens to inhibit testosterone's action. Side effects from lowering testosterone levels can include hot flashes, fatigue, reduced libido and sexual dysfunction, as well as increased risks of osteoporosis, obesity, and cardiovascular issues over the long term.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
ROLE OF NEOADJUVANT CHEMORADIATION IN LOCALLY ADVANCED BREAST CANCERKanhu Charan
This retrospective study analyzed 187 breast cancer patients treated with neoadjuvant chemoradiation followed by mastectomy from 1970-1984. It found that the 10-year locoregional control, disease-free survival, and overall survival rates were 91%, 47%, and 55% respectively. Only pathological nodal involvement was an independent negative prognostic factor for disease-free and overall survival. The study demonstrates comparable long-term locoregional control with this approach compared to other trials, suggesting neoadjuvant chemoradiation followed by mastectomy can achieve good outcomes.
Neoadjuvant therapy, including chemotherapy and chemoradiotherapy, is being investigated for the treatment of esophageal cancer. While some studies have shown improved survival rates with neoadjuvant therapy compared to surgery alone, the evidence from clinical trials remains conflicting. Achieving a complete pathological response after neoadjuvant therapy is associated with significantly improved long-term survival. Further research is still needed to determine the optimal neoadjuvant approaches and to improve outcomes by reducing distant metastases.
1. Resection offers the only chance for cure of pancreatic cancer, but most patients are unresectable at diagnosis. For resectable patients, surgery without delay followed by adjuvant chemotherapy and radiation improves survival compared to surgery alone.
2. For unresectable locally advanced disease, chemoradiation provides a survival benefit over chemotherapy alone. Median survival is approximately 11-12 months with chemoradiation versus 9 months with chemotherapy.
3. Post-operative chemoradiation following pancreatic cancer resection reduces the risk of recurrence and improves long-term survival compared to surgery or chemotherapy alone. The 2-year survival rate is approximately 40-50% with adjuvant chemoradiation versus 20-30
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Prophylactic cranial irradiation (PCI) is used to prevent brain metastases in cancers with a high risk of spreading to the brain. It is indicated for small cell lung cancer and certain leukemias. PCI significantly reduces the rate of brain metastases in small cell lung cancer, especially when administered early at higher doses. For extensive stage small cell lung cancer, MRI surveillance may be an alternative to PCI. While PCI reduces brain metastases in leukemia, the risk of brain involvement is low for some types such as AML. The standard dose for PCI is 1200-1800 cGy in fractions, with timing and volumes depending on the cancer type. Potential toxicities include neurocognitive effects, endocrine disorders, and secondary cancers.
Immunotherapeutic drugs can be broadly classified into four types: checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccines. However, immunotherapeutic drugs still have some problems, such as off-target side effects and poor pharmacokinetics.
Oncolytic Virus Therapy Development - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy is cancer treatment using a native or reprogrammed virus that has the potential to targeting and killing cancerous cell. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides customized, standardized, and reliable and high-quality oncolytic virus therapy development services for clients globally.
This document discusses muscle invasive bladder cancer (MIBC) and metastatic bladder cancer. It covers topics such as how MIBC is diagnosed, staging of MIBC using the TNM system, treatment with radical cystectomy and pelvic lymph node dissection, and use of neoadjuvant and adjuvant chemotherapy. It also discusses criteria for bladder preservation approaches and standards of care for treating metastatic bladder cancer with cisplatin-based chemotherapy.
This document discusses several landmark trials comparing different treatment approaches for esophageal cancer. The CALGB 9781 trial compared trimodality therapy (chemotherapy, radiation therapy, and surgery) to surgery alone and found improved overall survival and progression-free survival with trimodality therapy. Median overall survival was 4.48 years with trimodality therapy versus 1.79 years with surgery alone. The trial was closed early due to poor accrual, resulting in a small sample size.
Androgen Deprivation Therapy for Prostate CancerAlexander Small
This document summarizes a tumor board review on androgen deprivation therapy for prostate cancer. It begins with a case presentation of a patient with metastatic prostate cancer and then provides: 1) A brief history of the discovery of the connection between androgens and prostate cancer; 2) An overview of the androgen axis and various methods of androgen deprivation therapy including surgical castration, medical castration, anti-androgens, and GnRH agonists/antagonists; 3) A discussion of the adverse effects of androgen deprivation therapy including quality of life impacts, increased risks of osteoporosis and cardiovascular disease; 4) Considerations around treatment timing; and 5) Conclusions regarding optimal androgen deprivation therapy
Management of prostate cancer involves assessing risk levels based on PSA, Gleason score, and percentage of positive biopsy cores. Treatment options include active surveillance for low risk prostate cancer with potential delayed treatment if cancer progresses. Radical prostatectomy is the gold standard for localized prostate cancer and provides the possibility of cure with minimal side effects when performed by an experienced surgeon. While providing excellent cancer control, radical prostatectomy carries risks of erectile dysfunction and urinary incontinence.
This document discusses radiation cystitis, which is inflammation of the bladder caused by radiation therapy for pelvic cancers. It can cause symptoms like bleeding, urgency and frequency. The risks increase with higher radiation doses to the bladder and concurrent chemotherapy. Treatment options discussed include pentosan polysulfate, formalin, aminocaproic acid, conjugated estrogens, phenazopyridine and hyperbaric oxygen therapy. Surgical intervention may be needed for severe cases with complications or an unresponsive, contracted bladder.
The document discusses the role of radiation therapy in treating oligometastatic prostate cancer, noting that radiation can potentially achieve durable responses or even cure in some cases when metastases are limited. It reviews definitions of oligometastatic prostate cancer, the rationale for local and metastasis-directed radiation therapy, clinical evidence from studies on the use of external beam radiation therapy and stereotactic body radiation therapy to treat the primary tumor and metastases, and outcomes from these studies including local control rates, progression-free survival, and overall survival. The document concludes that radiation therapy plays an important role in the treatment of oligometastatic prostate cancer.
Locally advanced prostate cancer (LAPC) involves spread outside the prostate capsule or involvement of nearby structures. While no consensus exists on optimal treatment, combination therapy with radical prostatectomy (RP), radiation therapy (RT), and androgen deprivation (AD) provides the best outcomes. For selected patients with low-volume LAPC, RP alone may be sufficient, but extended pelvic lymph node dissection is important. Adjuvant or neoadjuvant RT and long-term AD after RP can improve local control and reduce recurrence rates. For patients unable to undergo surgery, RT with concurrent and adjuvant AD is the standard treatment and provides improved survival compared to monotherapy. Multimodal therapy increases side effects but provides superior outcomes over the
This document summarizes information about PSMA PET-CT scans for imaging prostate cancer. It explains that PSMA is overexpressed in prostate cancer cells and is a good target for imaging. A new development is using radiolabeled PSMA ligands like Ga-68 for PET imaging, which can detect prostate cancer with high sensitivity and specificity, including small lymph nodes and bone metastases. The benefits of Ga-68 include its generator production and labeling chemistry allowing automated preparation with a short half-life for reduced radiation dose. PSMA PET is useful for staging, recurrence detection, and assessing treatment response in prostate cancer.
The document provides an overview of genomics in breast cancer and summarizes the Oncotype DX genomic assay. It discusses how the assay analyzes the expression levels of 21 genes in breast tumor tissue to provide a Recurrence Score that quantifies a patient's risk of recurrence and predicts who will benefit from chemotherapy. Clinical studies have shown the assay stratifies patients into low, intermediate, and high risk groups and identifies those unlikely to benefit from chemotherapy while high risk patients see significant reduction in recurrence with chemotherapy. The assay is recommended in clinical guidelines and widely covered by insurance.
ANDROGEN DEPRIVATION THERAPHY ON PRASTATE CAEko indra
Androgen deprivation therapy (ADT) reduces androgen hormone levels to prevent prostate cancer growth. It can be administered medically or surgically. Medically, it involves using LH-RH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the androgen receptor. Surgically, bilateral orchiectomy quickly reduces testosterone levels. ADT is indicated for high risk and metastatic prostate cancer, and is often used with radiation therapy. The goal is to lower testosterone levels below 50 ng/dL to achieve a castration effect.
This document discusses treatment options for non-muscle invasive bladder cancer, including transurethral resection of bladder tumor (TURBT), bacillus Calmette-Guerin (BCG) immunotherapy, and intravesical chemotherapy. It provides details on the administration and schedule of BCG, lists its contraindications and potential side effects, and discusses options for patients who fail or are intolerant to BCG therapy, including interferon and investigational immunotherapies.
This presentation provides an overview of androgen deprivation therapy (ADT), also known as hormone therapy, for prostate cancer. It discusses the basic principles, including how prostate cancer cells rely on androgens like testosterone to grow. ADT aims to stop androgen production or block their effects. Methods include surgical removal of the testes, medications to reduce testosterone production, and anti-androgens to inhibit testosterone's action. Side effects from lowering testosterone levels can include hot flashes, fatigue, reduced libido and sexual dysfunction, as well as increased risks of osteoporosis, obesity, and cardiovascular issues over the long term.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
ROLE OF NEOADJUVANT CHEMORADIATION IN LOCALLY ADVANCED BREAST CANCERKanhu Charan
This retrospective study analyzed 187 breast cancer patients treated with neoadjuvant chemoradiation followed by mastectomy from 1970-1984. It found that the 10-year locoregional control, disease-free survival, and overall survival rates were 91%, 47%, and 55% respectively. Only pathological nodal involvement was an independent negative prognostic factor for disease-free and overall survival. The study demonstrates comparable long-term locoregional control with this approach compared to other trials, suggesting neoadjuvant chemoradiation followed by mastectomy can achieve good outcomes.
Neoadjuvant therapy, including chemotherapy and chemoradiotherapy, is being investigated for the treatment of esophageal cancer. While some studies have shown improved survival rates with neoadjuvant therapy compared to surgery alone, the evidence from clinical trials remains conflicting. Achieving a complete pathological response after neoadjuvant therapy is associated with significantly improved long-term survival. Further research is still needed to determine the optimal neoadjuvant approaches and to improve outcomes by reducing distant metastases.
1. Resection offers the only chance for cure of pancreatic cancer, but most patients are unresectable at diagnosis. For resectable patients, surgery without delay followed by adjuvant chemotherapy and radiation improves survival compared to surgery alone.
2. For unresectable locally advanced disease, chemoradiation provides a survival benefit over chemotherapy alone. Median survival is approximately 11-12 months with chemoradiation versus 9 months with chemotherapy.
3. Post-operative chemoradiation following pancreatic cancer resection reduces the risk of recurrence and improves long-term survival compared to surgery or chemotherapy alone. The 2-year survival rate is approximately 40-50% with adjuvant chemoradiation versus 20-30
Advances in management of castration resistant prostate cancerAlok Gupta
Given this patient's advanced age and comorbidities, I would recommend abiraterone acetate as the second line treatment option post enzalutamide progression. Abiraterone has shown survival benefit with good tolerability in older patients with comorbidities in the COU-AA-301 trial. Cabazitaxel could be considered but may have higher toxicity risks in this patient. Close monitoring would be needed.
Prophylactic cranial irradiation (PCI) is used to prevent brain metastases in cancers with a high risk of spreading to the brain. It is indicated for small cell lung cancer and certain leukemias. PCI significantly reduces the rate of brain metastases in small cell lung cancer, especially when administered early at higher doses. For extensive stage small cell lung cancer, MRI surveillance may be an alternative to PCI. While PCI reduces brain metastases in leukemia, the risk of brain involvement is low for some types such as AML. The standard dose for PCI is 1200-1800 cGy in fractions, with timing and volumes depending on the cancer type. Potential toxicities include neurocognitive effects, endocrine disorders, and secondary cancers.
Immunotherapeutic drugs can be broadly classified into four types: checkpoint inhibitors, cytokines, monoclonal antibodies, and vaccines. However, immunotherapeutic drugs still have some problems, such as off-target side effects and poor pharmacokinetics.
Oncolytic Virus Therapy Development - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy is cancer treatment using a native or reprogrammed virus that has the potential to targeting and killing cancerous cell. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides customized, standardized, and reliable and high-quality oncolytic virus therapy development services for clients globally.
This intro is geared towards interested novices who wish to find a resource that can serve as a starting point for further self-study. This is not meant to replace a doctor's advice. Please approach a medical professional for any health condition.
Co-Chairs, Nasser Altorki, MD, and Jonathan D. Spicer, MD, PhD, FRCSC, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Can the Addition of Immunotherapy to Multimodal Management of Stage I-III NSCLC Help Break the Stalled Cycle of Poor Outcomes?” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3m1OV2m. CME/MOC credit will be available until February 27, 2023.
The document discusses Aethlon Medical announcing a new exosome detection assay that can distinguish exosomes by their chemical structures. Exosomes are extracellular vesicles that play roles in cancer and viral diseases like HIV/AIDS. The assay may help diagnose immunosuppressive diseases and cancers more quickly. Aethlon Medical also created a device called the Hemopurifier that can selectively remove exosomes from blood circulation, showing potential benefits for treating cancer, hepatitis C virus, and drug-resistant HIV.
This white paper discusses improving the clinical development of cancer immunotherapies. It outlines the current immunotherapy landscape including checkpoint inhibitors, adoptive T cell therapies, cancer vaccines, and biomarkers. The paper emphasizes that while immunotherapy has promising results for some patients and cancer types, more research is needed to understand which patients will benefit most from which approaches and how to best leverage various immune system components in the fight against cancer. Operational considerations and cautions for clinical development are also discussed.
Download Global cancer immunotherapy market outlook 2020KuicK Research
\"Global Cancer Immunotherapy Market Outlook 2020\" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
Global cancer immunotherapy market outlook 2020KuicK Research
The document provides an overview of the global cancer immunotherapy market outlook for 2020. It discusses how cancer immunotherapies work by modulating the immune system to treat cancer. The market has seen significant growth with many approved and pipeline immunotherapies across classes like monoclonal antibodies, cytokines, vaccines, and immune checkpoint inhibitors. The market is expected to continue growing in coming years due to increased research and funding leading to new treatment modalities and biomarkers to expand the use of immunotherapies for additional cancer types.
Immuno-oncology Discoveries, University of Chicagouchicagotech
The University of Chicago has a leading Immuno-Oncology program that takes a multi-faceted approach to cancer immunotherapy through innovative translational research. The program focuses on immune stimulation, checkpoint blockade, vaccines, and diagnostics to develop new immunotherapies. Representative technologies highlighted include using LIGHT to stimulate anti-tumor immune responses, reversing T-cell anergy with DGK inhibitors, developing senescent cell and antibody-based vaccines, and biomarkers to identify responsive patients. The university has extensive clinical trial capabilities and core facilities to support research and translation.
Celltrion Healthcare Company Brochure(2016)celltrionh
Celltrion Healthcare is a biopharmaceutical company committed to developing and distributing more affordable biosimilar therapies. It has been developing biosimilar products since 1999 to increase patient access to treatments. Celltrion specializes in research and development of monoclonal antibodies and biologics, while Celltrion Healthcare conducts worldwide marketing, sales, and distribution. Their biosimilar products have been approved in over 70 countries. Celltrion is devoted to developing novel biologics and high-quality biosimilar monoclonal antibodies to increase global healthcare access.
This article summarizes a study that found cowpea mosaic virus nanoparticles can induce an immune response against tumors when administered to mice. The nanoparticles activated neutrophils in the tumor which secreted chemokines recruiting more immune cells to the tumor. This led to activation of T lymphocytes and destruction of tumor cells, delaying tumor growth. The nanoparticles offer a simple, scalable approach to cancer immunotherapy without targeting a specific antigen, and induce localized immune responses without toxicity to normal tissues. However, questions remain about how such a specific anti-tumor response occurs and why neutrophils rather than lymphocytes are the primary responders. Answering these questions could advance cancer immunotherapy.
Cancer immunotherapies from the perspectives of oncology nursesZeena Nackerdien
This presentation, tailored for oncology nurses, provides an overview of immunotherapy classes, how they work, and how key side effects are typically managed. (Disclaimer: Content is based on peer-reviewed literature; however, it is not a substitute for medical advice. Please consult your doctor)
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
iOncologi_Pitch Deck_2024 slide show for hostingerssuser9354ce
iOncologi is developing novel cancer immunotherapies including stem cell therapies and mRNA-nanoparticle vaccines. Their stem cell therapy has shown ability to overcome resistance to immune checkpoint inhibitors in preclinical studies and received FDA approval for clinical trials in glioblastoma patients. Their mRNA-NP vaccine platform is in early phase clinical trials for refractory solid cancers. iOncologi seeks capital to further clinical evaluation and develop allogeneic 'off-the-shelf' stem cell therapies.
Monoclonal Antibodies As Therapeutic Agents In Oncology Anddrmisbah83
This document discusses monoclonal antibodies as therapeutic agents for cancer and antibody gene therapy. It describes how monoclonal antibodies work to target cancer cells, lists some common monoclonal antibody drugs approved for cancer treatment, and discusses potential side effects. It also introduces the concept of using antibody gene therapy as a new strategy for cancer treatment by delivering antibody genes directly to tumors using vectors like adenovirus or mesenchymal stem cells.
This document discusses cancer vaccines as a novel approach to treating and preventing cancer. It defines cancer vaccines and explains the different types, including dendritic cell vaccines, antigen vaccines, tumor cell vaccines, DNA vaccines, and anti-idiotype vaccines. Several examples of cancer vaccines currently in clinical trials are provided, such as OncoVAX for colon cancer and Provenge for prostate cancer. While progress has been made, more research is still needed before cancer vaccines can be widely used in clinical settings.
This document discusses various types of cancer immunotherapy, including dendritic cell vaccines, antibody therapy, and cytokine therapy. Dendritic cell vaccines work by activating dendritic cells with tumor antigens, which then provoke an immune response against cancer cells. Antibody therapy targets specific cancer antigens and uses mechanisms like complement-dependent cytotoxicity to kill cancer cells. Cytokines like interferons are also used to treat cancer by activating immune cells and inducing anti-tumor responses. Immunotherapy holds promise for harnessing the power of the immune system to fight cancer.
A Review Immuno Oncology Agents for Cancer Therapyijtsrd
Until recently, cancer treatment had four main types of treatment surgery, radiotherapy, chemotherapy and targeted therapies. Over the past decade, immuno oncology IO has emerged as a new and important alternative to cancer treatment by promoting the immune system to kill cancer cells. This newly developed cancer treatment is growing rapidly, with much accelerated approval by the US Food and Drug Administration and the European Medicines Agency in 2019. Cancer immunotherapy sometimes called immuno oncology is to stimulate the immune system to treat cancer, to improve it. in the natural immune system. It is the use of basic research on cancer immunology and the growing subspeciality of oncology. Cancer immunotherapy uses the fact that cancer cells often contain tumor antigens, the molecules on their surface can be detected by antibody proteins of the immune system, which bind to them. Tumor antigens are usually proteins or other macromolecules e.g., carbohydrates . Normal antibodies bind to foreign viruses, but mutated antibodies bind to tumor antigens that mark and target cancer cells so that the immune system can block or kill. The clinical success of cancer immunotherapy varies greatly between different types of cancer for example, some subfamilies of stomach cancer respond well to treatment while immunotherapy does not work in other subspecies. Unnati Adhate | Rushikesh Bachhav "A Review Immuno-Oncology Agents for Cancer Therapy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-7 | Issue-1 , February 2023, URL: https://www.ijtsrd.com/papers/ijtsrd52724.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/52724/a-review-immunooncology-agents-for-cancer-therapy/unnati-adhate
Similar to Immunotherapy in Urologic Oncology.ppt (20)
This document provides an overview of renal failure, including:
- Classification of acute and chronic renal failure
- Definitions, causes, pathophysiology and treatment of acute kidney injury (AKI) and chronic kidney disease (CKD)
- Prerenal, intrarenal and postrenal causes of AKI
- Clinical manifestations and pathophysiology of CKD including accumulation of waste, fluid and electrolyte disturbances, and calcium/phosphorus disorders
- Treatment focuses on slowing CKD progression, managing complications, and dialysis or transplant for advanced disease.
This is a presentation carried out during one of the Masters Urology classes at the University of Nairobi on Monday 27th April 2020 betweeen 0830-1030 hours. The online session had a maximum of 75 participants.
The respiratory control system comprises sensors in the brain and carotid bodies that detect levels of oxygen, carbon dioxide, hydrogen ions, and pH in the blood and cerebrospinal fluid. This information is sent to the central controller in the brain which coordinates the diaphragm and respiratory muscles as effectors to regulate breathing. Central chemoreceptors in the medulla are directly stimulated by increased carbon dioxide and hydrogen ions in the cerebrospinal fluid, triggering faster breathing. Peripheral chemoreceptors in the carotid and aortic bodies also sense decreased oxygen and increased carbon dioxide in the blood to stimulate the respiratory control center.
This document discusses lung volumes, aspects of ventilation, and regional differences in respiration. It explains how lung volumes like tidal volume, vital capacity, residual volume, and functional residual capacity are measured using a spirometer. Total ventilation is the product of tidal volume and breathing frequency. Alveolar ventilation accounts for ventilation lost to anatomic dead space. Regional ventilation differs depending on body position, with more ventilation occurring in lower lung zones when upright and more on the dependent side when lying laterally.
The document summarizes the structure and function of the lungs. It discusses the airways and alveoli, how stability is maintained through surfactant, how particles are filtered, the blood-gas interface with its thin barrier, and blood flow. The lungs have a large surface area for gas exchange and an efficient capillary network that allows red blood cells to transfer gases in the short time they spend circulating through.
This document discusses autoimmunity, including its definition as an inappropriate immune response against self cells/tissues due to self-tolerance failure. Various triggers are described, such as genetic factors like certain HLA alleles associated with diseases, environmental factors like molecular mimicry between pathogens and self-antigens, and non-genetic host factors including immunodeficiencies. Numerous autoimmune diseases are detailed along with their antibody targets and clinical features. Diagnosis involves clinical exams, labs to detect autoantibodies, and biopsies. Treatment focuses on reducing inflammation through steroids, blocking cytokines/integrins/B cells, or more extreme measures like immunosuppressants.
This document discusses growth monitoring through anthropometric measurements and growth chart interpretation. It defines key terms like growth, growth monitoring, and anthropometry. It describes taking measurements of weight, length/height, head circumference, mid-upper arm circumference, and interpreting growth indicators like height-for-age, weight-for-height, and weight-for-age on growth charts. Abnormal growth patterns like horizontal, downward, and below standard deviation lines indicate malnutrition, illness, or inadequate nutrition requiring further investigation and treatment.
This document discusses tuberculosis (TB) in children. It covers the causative agent, classification, risk factors, global and local burden, and strategies for management. TB is caused mainly by Mycobacterium tuberculosis and is a major global health problem exacerbated by HIV. In Kenya, TB prevalence was 103,159 in 2012, with 39% co-infected with HIV. The Stop TB strategy aims to reduce the global TB burden by 50% by 2015 through improved detection and treatment programs.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
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• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
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This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
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5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
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10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
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1. IMMUNOLOGY AND IMMUNOTHERAPY IN
UROLOGIC ONCOLOGY
PRESENTER: Dr. Keagan Kirugo, PGY 4 Urology
SUPERVISORS:
Dr. Peter Oyiro; Consultant Haemato-oncologist and Lecturer, UoN,
Department of Clinical Medicine and Therapeutics.
Dr. James Ikol; Consultant Urologist and Head of Urology Unit, KNH
DATE: 28/03/2022
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2. 1. Relevant immunology
2. Mechanism of evasion by cancer cells
3. Mechanism of immunotherapy
4. Immunotherapeutic strategies
5. Immunotherapy in Renal Cancer
6. Immunotherapy in UTUC
OBJECTIVES
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3. 7. Immunotherapy in Bladder Cancer
8. Immunotherapy in Penile Cancer
9. Immunotherapy in Testicular Cancer
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4. Introduction
The immune system plays a major role in cancer prevention and
delaying cancer progression.
It comprises adaptive and innate immune system.
The adaptive immune system comprises lymphocytes; T cells
which carries out cell mediated immunity and B cells which
produces antibodies.
RELEVANT IMMUNOLOGY
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5. During lymphopoiesis, rearrangement results in lymphocytes with
a diverse repertoire of unique receptors which recognize a wide
range of antigen sequences both self and non self. The
lymphocytes specific to self are usually deleted or inactivated.
During a primary response to a non self antigen, lymphocytes
specific to that antigen undergo clonal expansion, effector T and B
cells are activated, and the long-lived memory B cells persist.
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6. University of Nairobi ISO 9001:2008 6 Certified http://www.uonbi.ac.ke
Adapted from Dranoff G. Cytokines in cancer pathogenesis and cancer
therapy. Nat Rev Cancer. 2004;4(1):11-22. Crossref | PubMed
7. T cell Antigen Recognition
T cell antigens are presented to the T cells by specialized antigen
presenting cells (APCs), the most efficient of which is the dendritic
cell.
Recognition is sequence specific bound in the MHC molecule.
T cells must have the ability to respond to non self antigens but
must be tolerant to self antigens to avoid autoimmunity.
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8. University of Nairobi ISO 9001:2008 8 Certified http://www.uonbi.ac.ke
Adapted from https://courses.lumenlearning.com/wm-biology2/chapter/t-and-b-
lymphocytes/
9. MHC is present in virtually all nucleated cells, permitting CD8+ T
cells to scan intracellular antigens and identify or kill infected cells
and those expressing altered cell peptides.
The T cell receptor (TCR) does not recognize antigens alone but sees
both the MHC and peptide complexed with it, therefore the whole
complex defines the specificity of the TCR.
Once activated, T cells can mediate cytotoxicity.
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10. Cancer cells can evade detection and eradication by the immune
system by:
1. Reducing antigen expression
2. Secreting immune-suppressing cytokines
3. Upregulating inbuilt regulatory signals
EVASION OF THE IMMUNE
SYSTEM BY CANCER CELLS
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11. 1. Eliminating viruses that drive neoplasia
2. Resolving acute inflammation to pathogens, preventing a
chronic inflammatory environment that can influence
neoplastic transformation.
3. Identifying and eliminating transformed cells
MECHANISM OF
IMMUNOTHERAPY
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12. IMMUNOTHERAPEUTIC
STRATEGIES
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1. Therapeutic Vaccination
Dendritic cell-based activation
Personalized neoantigen specific cancer vaccines
Autologous tumour cell vaccines
13. Dendritic cell-based vaccination
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Adapted from Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy:
the beginning of the end of cancer? BMC
Med. 2016;14(1):73. Crossref | PubMed
14. Tumour antigens are procured from either resection or peripheral
blood mononuclear cells.
The target is selected using DNA and RNA sequencing to identify
tumour specific mutations.
HLA-typing is carried out with prediction of personalized HLA-
binding peptides.
The personal vaccine is manufactured and administered with a
priming period of frequent repeated vaccines and subsequent
booster doses.
Personalized neoantigen-
specific cancer vaccines
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15. The tumour itself may also represent a source of endogenous
antigens, given that anti-cancer T cells can be produced
spontaneously.
Accessing this source of antigens affords convenience.
Autologous tumour cell vaccines
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16. Limited response due to:
1. Continued uncertainties regarding which antigens should be
used, how they should be delivered, which adjuncts are needed
and how a T cell response should manifest.
2. Presence of agents that disrupt pathogens in the tumour
microenvironment may dampen or disable anti-tumour immune
responses before clinically relevant tumour killing can occur.
Disadvantages of therapeutic
vaccines
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17. 2. Targeting immunological checkpoints
Immune checkpoints are regulators of the immune system and
enable self-tolerance. This prevents unwanted attacks on cells.
Inhibitory checkpoint molecules are targets for cancer
immunotherapy.
Examples are Programmed death-ligand 1 (PD-L1) and programmed
death receptor 1 (PD-1)
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18. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule
that suppresses T cell effector function following initial activation by
costimulatory signals.
Programmed death ligand-1 (PD-L1, also known as B7-H1), which
binds to the programmed death-1 receptor (PD-1) on the T cell
surface to inhibit T cell function
Treatments based on monoclonal antibodies that target PD-L1 or
PD-1 are now approved in many tumour types
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19. University of Nairobi ISO 9001:2008 19 Certified http://www.uonbi.ac.ke
Adapted from
https://www.researchgate.net/publication/311968982_Potential_role_of_immunotherapy_in_
advanced_non-small-cell_lung_cancer/figures?lo=1
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Adapted from Dong H. The Basic Concepts in Cancer Immunology and
Immunotherapy. In: Dong H, Markovic SN, eds. The Basics of Cancer
Immunotherapy. Cham: Springer International Publishing; 2018:1-19.
21. 1. VEGF TARGETED THERAPY
Vascular endothelial growth factor (VEGF) is a pro-angiogenic
peptide growth factor that activates a major tyrosine kinase-
signalling pathway.
VEGF is overexpressed in most sporadic renal cell carcinoma (RCC),
due to hypoxia-inducible factor-1 (HIF-1) overexpression caused by
inactivation of the Von Hippel-Lindau (VHL) tumour suppressor
gene.
IMMUNOTHERAPY IN RENAL
CANCERS
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22. VEGF-targeted therapies increase progression-free survival and/or
overall survival, either as a first- or second-line treatments for
patients with clear cell metastatic RCC.
EXAMPLE
Bevacizumab
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24. 2. TYROSINE KINASE INHIBITORS
Protein kinases, a class of enzymes that govern various biological
phenomena at a cellular level, are responsible for signal
transduction in cells that regulate cellular proliferation,
differentiation, and growth.
Protein kinase enzyme mutation results in abnormal cell division
leading to a pathological condition like cancer.
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25. MECHANISM OF ACTION
Kinases control cell growth and division: blocking the kinases
leads to cell death.
They also prevent neovascularization of cancer cells, reducing
their supply of oxygen and nutrients which in turn slows down
or stops the growth of the cancer.
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26. EXAMPLES
Sorafenib: Has broad spectrum activity in a spectrum of settings in
clear cell RCC patients previously treated with cytokine and targeted
therapies.
Sunitinib: More effective than interferon alpha in treatment naïve
patients.
It is available locally in its original form under brand name SUTENT.
Both sorafenib and sunitinib have limited oncological efficacy in on
clear cell RCC.
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27. Sunitinib is available at Nairobi Hospital under a free access
program (Managed Access System). The program has been
decentralized to Mombasa, Kisumu and Nakuru.
A lot of bureaucracy involved in importing Axitinib.
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29. Pazopanib: First line treatment in clear cell RCC and superior to
sunitinib.
Axitinib: Used in the treatment of metastatic RCC or as
neoadjuvant therapy.
It has efficacy in PFS as 2nd line treatment failure of VEGF therapy cf
sorafenib.
Therefore, administered after treatment with another TKI or after
interferon or interleukin treatment
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30. Cabozatinib: Used in intermediate and poor risk untreated clear cell
RCC.
Better response rates and PFS but not OS cf sunitinib.
Levacitinib: Combined with everolimus, confers a modest
improvement in PFS.
Tivozanib: Has been approved but current evidence is considered
inferior cf alternate choices.
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Papillary Metastatic RCC
32. SIDE EFFECTS
Common
Skin: Hand and foot skin reaction
Musculoskeletal: Arthralgia, myalgia
CVS: Hypertension
Endocrine: Hypothyroidism
CNS: Lethargy
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33. University of Nairobi ISO 9001:2008 33 Certified http://www.uonbi.ac.ke
Adapted from https://onlinelibrary.wiley.com/doi/10.1111/j.1346-8138.2010.01059.x
34. LESS COMMON
GIT: Altered liver function
CVS: VTE
ENDOCRINE: Overactive thyroid
CNS: Confusion
HAEMATOLOGY: Anaemia
EYE: Altered vision
EAR: Tinnitus
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35. TKIs have been described as dirty because of the SEs. Most patients
locally cannot tolerate sunitinib, especially ladies. Weight-dose
discrepancy?
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36. 2. MTOR INHIBITORS
Mechanistic target of rapamycin (mTOR) is a cellular protein that
regulates cell division and growth and is overactive in cancer cells.
It is a downstream of the tyrosine kinase signaling pathway.
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37. MOA
Blocking mTOR leads to slowing or stopping cancer growth directly.
It acts indirectly by inhibiting angiogenesis therefore slowing or
stopping tumour growth.
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38. EXAMPLES
Temsirolimus: Treatment of metastatic renal cancer.
As monotherapy, it prolongs OS cf interferon alpha in untreated,
poor risk metastatic RCC.
Everolimus: Inferior to Cabozatinib in PFS and OS in patients
treated with one or more lines of VEGF therapy. However,
everolimus prolongs PFS after VEGF targeted therapy cf placebo or
when patient are intolerant to VEGF targeted therapies.
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39. Everolimus and Lenvatinib has demonstrated a PFS of 14.6/12 cf
5.5/12 in the everolimus group. This combination has therefore
been approved for use in metastatic RCC post one line of TKI.
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40. SIDE EFFECTS
Common
GIT: sore mouth, altered taste, loss of appetite diarrhea, nausea,
indigestion
SKIN: dermatitis
CNS: lethargy, headache, insomnia
HAEMAT: anaemia, neutropenia, thrombocytopenia
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41. University of Nairobi ISO 9001:2008 41 Certified http://www.uonbi.ac.ke
Adapted from
https://www.hmpgloballearningnetwork.com/site/thederm/site/cathlab/event/derm-
dx-what-red-rash-leg
42. CVS: Oedema
MUSCULOSKELETAL: Arthralgia
Less Common
GIT: altered liver function, reactivation of Hepatitis B infection
RENAL: altered renal function
NS: peripheral neuropathy
SKIN: swelling and redness of hands and feet
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43. SYSTEMIC TREATMENT FOR ADVANCED OR METASTATIC RENAL
CANCER
Interferon alpha and bevacizumab
Interferon was previously used to treat advanced RC but is currently
rarely used. This is because interferon alpha monotherapy is
inferior to VEGF targeted therapy or mTOR inhibition in metastatic
RCC.
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44. Adding bevacizumab to interferon alpha is more effective than IF
alpha monotherapy in treatment naive, low risk and intermediate
risk RCC.
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45. Interleukin 2 Monotherapy
It is effective in selected cases with good performance status, clear
cell RCC and lung metastasis only.
It has more side effects than IF alpha. Administered in CCU.
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46. Immune Checkpoint Blockade
PD-1 Inhibitors
Nivolumab is a monoclonal antibody that targets PD-1.
Superior OS cf everolimus in patients failing one or two lines of
VEGF targeted therapy.
Pembrolizumab
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49. SIDE EFFECTS
Common
SKIN: skin changes
CNS: fatigue
GIT: nausea, diarrhoea
CVS: hypertension
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50. Anti-CTLA 4 Antibody Treatment
Ipilimumab is a monoclonal antibody that targets CTLA 4.
CTLA 4 protein on the surface of T cells can sometimes stop the
anticancer action.
Blockage of CTLA 4 allows the T cells to go on and destroy the
cancer cells.
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51. SIDE EFFECTS
GIT: diarrhoea, altered liver function
SKIN: dermatitis
ENDO:
RESP:
CVS:
CNS: neuropathy
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53. COMBINATION THERAPIES
World over, combination therapies are the standard.
1. Immune Checkpoint Inhibitors
Nivolumab and ipilimumab in untreated patients with clear cell RCC
of an intermediate or poor risk leads to superior OS cf sunitinib.
Associated with 15% grade 3-5 toxicity and 1.5% treatment related
deaths.
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55. 2. TKIs and Immune Checkpoint Inhibitors
JAVELIN 101 Study: Avelumab and Axitinib had a PFS of 13.8/12 cf
sunitinib at 8.4/12.
Pembrolizumab and Axitinib showed a PFS of 15.1/12 and 11.1/12
in the sunitinib arm in 1st line treatment of clear cell advanced RCC
patients.
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61. First line for the Cisplatin Ineligible
Pembrolizumab and atezolizumab are approved for patients with
advanced or metastatic urothelial ca who are ineligible to cisplatin
first line chemotherapy.
Restricted to PDL-1 positive.
UTUC
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62. Second line for the Platinum Pretreated
Pembrolizumab, atezolizumab, nivolumab, avelumab and
durvalumab have been used in patients progressing during or after
platinum-based chemotherapy.
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63. NON-MUSCLE INVASIVE BLADDER CANCER
BCG IMMUNOTHERAPY
Live attenuated M. bovis
Intravesical route.
It reduces risk of disease progression and recurrence when
administered post TURBT.
BLADDER CANCER
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65. For optimal efficacy, it must be administered in a maintenance
schedule for at least one year of treatment.
3-year maintenance therapy is more effective than one year in
preventing recurrence in high-risk patients but not in intermediate
risk.
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66. MOA
It attaches to the urothelium via fibronectin receptor mediating an
immune response by chemotaxis and cytokine production.
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69. INTERFERON
IF alpha and systemic immunotherapy provide alternate treatment
options.
No clear difference in recurrence or progression with BCG and IF
alpha cf BCG. Alternating BCG with IF alpha may increase time to
recurrence however the quality of the 5 trials used in the
metanalysis was poor.
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70. MUSCLE INVASIVE BLADDER CANCER
Check point inhibitors have no role currently in MIBC treatment.
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71. METASTATIC DISEASE
Denosumab has been approved as supportive treatment in bone
mets in all cancer types including urothelial.
It is a monoclonal antibody that binds to and neutralizes apoptosis
regulator gene.
Superior to zoledronic acid in reducing and delaying skeletal related
events.
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72. SIPULEUCEL-T
First ever cancer vaccine to achieve FDA approval in April 2010 as tx
for mCRPC.
APCs stimulate T-cell immune response targeted against prostatic
acid phosphatase (PAP)
Harvested APCs are incubated with recombinant fusion protein
antigen, which contains both PAP and GM–CSF.
PROSTATE CANCER
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73. No PSA decline and no difference in PFS in minimally invasive
mCRPC when compared to placebo.
No longer available in Europe.
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74. CHIMERIC ANTIGEN RECEPTOR (CAR)-T THERAPY
Experimental stages.
Proven efficacy in haematological cancers with potential to
become viable tx option in solid cancers including prostate.
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75. PD/PD-L1
Trial with enzalutamide.
PL-L1 being expressed in prostate ca cells post enzalutamide.
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76. 5-FU and Imiquimod have a role in non-invasive penile cancer.
VGX-3100 targets the genetic code of HPV 16 and HPV 18 has been
used in women with ca cervix associated with HPV.
PDL-1 Inhibitors e.g., Nivolumab may be efficacious as 62.2 % of the
tumour demonstrating PDL-1.
PENILE CANCER
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77. Highly treatable with chemotherapy but immunotherapy is
developing a role in those refractory to platinum-based CTX or
relapsing after autologous stem cell treatments.
PDL1 inhibitors (Pembrolizumab and nivolumab) have been used in
this role with newer check point inhibitors poised for use in trial in
similar fashion.
TESTICULAR CANCER
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78. COVID-19 should not prevent immunotherapy.
COVID-19
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79. 1. Buchbinder, E., & Hodi, F. S. (2015). Cytotoxic T lymphocyte
antigen-4 and immune checkpoint blockade. The Journal of
clinical investigation, 125(9), 3377–3383.
2. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy.
Nat Rev Cancer. 2004;4(1):11-22. Crossref | PubMed
3. Velcheti V, Schalper K. Basic overview of current immunotherapy
approaches in cancer. Am Soc Clin Oncol Educ Book.
2016;35:298-308. Crossref | PubMed
REFERENCES
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80. 4. Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy:
the beginning of the end of cancer? BMC Med. 2016;14(1):73.
Crossref | PubMed
5. Aishwarya Shinde, Kanan Panchal, Sumeet Katke, Rishi Paliwal,
Akash Chaurasiya; Tyrosine kinase inhibitors as next generation
oncological therapeutics: Current strategies, limitations and future
perspectives, Therapies, 2021.
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81. 6. ESMO Clinical Practice Guideline update on the use of
immunotherapy in early stage and advanced renal cell carcinoma
2021
7. Prof. Nicholas Abinya’s talk on “MANAGEMENT OF ADVANCED
KIDNEY CANCER IN THE ERA OF IMMUNOTHERAPIES AND
PRECISION ONCOLOGY ” given as part of KESHO CMEs on March
17th, 2022.
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82. 8. Partin A, Dmochowski R, Kavoussi L, Peters C. Campbell-Walsh-
Wein Urology. 12th ed. Amsterdam, Netherlands. Elsevier.
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