Non-clear cell renal cell carcinoma (RCC) encompasses diverse subtypes, each requiring tailored therapeutic approaches. Papillary RCC may benefit from immunotherapy or vascular endothelial growth factor receptor (VEGFR) inhibitors. Chromophobe RCC often sees mTOR inhibitors or VEGFR inhibitors as initial treatments. For collecting duct and renal medullary carcinomas, cytotoxic chemotherapy is recommended.
Translocation RCC may respond well to lenvatinib plus pembrolizumab, while unclassified RCC patients might consider immunotherapy-based regimens. Sarcomatoid features in non-clear cell RCC lean towards immunotherapy.
Clinical trials are encouraged due to limited high-quality data, emphasizing the need for personalized strategies based on histologic subtypes. Overall, these recommendations aim to optimize outcomes in the diverse landscape of non-clear cell RCC.
The most common type of cancer arising in the kidney: Renal cell carcinoma(RCC)(also known as Hypernephroma or Grawitz tumor).
Renal cell carcinoma accounts for over 3% of all adult malignancies and has several histological subtypes.
Approximately 85% of kidney tumors are renal cell carcinoma, and approximately 70% of these have a Clear cell histology. Its diagnostic work-up, staging and management.
The most common type of cancer arising in the kidney: Renal cell carcinoma(RCC)(also known as Hypernephroma or Grawitz tumor).
Renal cell carcinoma accounts for over 3% of all adult malignancies and has several histological subtypes.
Approximately 85% of kidney tumors are renal cell carcinoma, and approximately 70% of these have a Clear cell histology. Its diagnostic work-up, staging and management.
Highlights in the treatment of Rectal cancer.pptxMona Quenawy
rectal cancer treatment updates in simple way and the advances in the molecular techniques .the role of the neo adjuvant chemoradiotherapy and the state of the art in the management by each stage.radiotherapy role and technique by using the RTOG guidance in target definition
Euthanasia, derived from Greek words meaning "good death," is a complex and controversial ethical and legal issue revolving around the deliberate ending of a person's life to relieve suffering. It is often a topic of intense debate within medical, legal, religious, and ethical circles.
Types of Euthanasia:
Voluntary Euthanasia: This occurs when a competent person makes a voluntary and informed decision to end their life with the assistance of a medical professional or loved one.
Non-voluntary Euthanasia: In this scenario, the decision to end a person's life is made by someone other than the individual, typically when they are unable to make decisions for themselves due to being in a coma or having advanced dementia.
Involuntary Euthanasia: This is the termination of a person's life against their will or without their consent, often performed in situations where the person's suffering is deemed unbearable or where their quality of life is deemed too low by others.
Assisted Suicide: This involves providing a person with the means or information necessary to end their own life, such as prescribing lethal medication, while the individual ultimately carries out the act themselves.
Ethical Considerations:
Autonomy vs. Sanctity of Life: Supporters of euthanasia argue for individual autonomy and the right to die with dignity, while opponents often cite the sanctity of life and the potential for abuse or slippery slope arguments.
Quality of Life: Discussions often revolve around the subjective nature of suffering and the quality of life, with some arguing that euthanasia can alleviate unnecessary suffering, while others raise concerns about the potential devaluation of certain lives.
Medical Ethics: Euthanasia raises questions about the role of healthcare professionals in end-of-life care, the distinction between killing and allowing to die, and the obligations of physicians to relieve suffering while upholding ethical principles.
Legal Status:
The legality of euthanasia varies greatly around the world. Some countries, such as the Netherlands, Belgium, and Canada, have legalized certain forms of euthanasia under strict conditions, while others, including many U.S. states, maintain its illegality. In some regions, there are ongoing debates and court cases seeking to clarify or change existing laws.
Conclusion:
Euthanasia remains a deeply divisive and emotionally charged issue, touching on fundamental questions about life, death, autonomy, and suffering. As medical technology advances and societal attitudes evolve, discussions surrounding euthanasia are likely to persist, challenging individuals, communities, and policymakers to navigate the complexities of this sensitive topic with compassion and integrity.
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Highlights in the treatment of Rectal cancer.pptxMona Quenawy
rectal cancer treatment updates in simple way and the advances in the molecular techniques .the role of the neo adjuvant chemoradiotherapy and the state of the art in the management by each stage.radiotherapy role and technique by using the RTOG guidance in target definition
Euthanasia, derived from Greek words meaning "good death," is a complex and controversial ethical and legal issue revolving around the deliberate ending of a person's life to relieve suffering. It is often a topic of intense debate within medical, legal, religious, and ethical circles.
Types of Euthanasia:
Voluntary Euthanasia: This occurs when a competent person makes a voluntary and informed decision to end their life with the assistance of a medical professional or loved one.
Non-voluntary Euthanasia: In this scenario, the decision to end a person's life is made by someone other than the individual, typically when they are unable to make decisions for themselves due to being in a coma or having advanced dementia.
Involuntary Euthanasia: This is the termination of a person's life against their will or without their consent, often performed in situations where the person's suffering is deemed unbearable or where their quality of life is deemed too low by others.
Assisted Suicide: This involves providing a person with the means or information necessary to end their own life, such as prescribing lethal medication, while the individual ultimately carries out the act themselves.
Ethical Considerations:
Autonomy vs. Sanctity of Life: Supporters of euthanasia argue for individual autonomy and the right to die with dignity, while opponents often cite the sanctity of life and the potential for abuse or slippery slope arguments.
Quality of Life: Discussions often revolve around the subjective nature of suffering and the quality of life, with some arguing that euthanasia can alleviate unnecessary suffering, while others raise concerns about the potential devaluation of certain lives.
Medical Ethics: Euthanasia raises questions about the role of healthcare professionals in end-of-life care, the distinction between killing and allowing to die, and the obligations of physicians to relieve suffering while upholding ethical principles.
Legal Status:
The legality of euthanasia varies greatly around the world. Some countries, such as the Netherlands, Belgium, and Canada, have legalized certain forms of euthanasia under strict conditions, while others, including many U.S. states, maintain its illegality. In some regions, there are ongoing debates and court cases seeking to clarify or change existing laws.
Conclusion:
Euthanasia remains a deeply divisive and emotionally charged issue, touching on fundamental questions about life, death, autonomy, and suffering. As medical technology advances and societal attitudes evolve, discussions surrounding euthanasia are likely to persist, challenging individuals, communities, and policymakers to navigate the complexities of this sensitive topic with compassion and integrity.
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
Role of Neoadjuvant Chemotherapy (NACT) in Ovarian Cancer:
Objective: Administer systemic therapy before definitive surgery.
Goal: Reduce perioperative complications, enhance complete resection chances.
Patient Selection:
Offered to clinically apparent, unresectable ovarian cancer cases.
Considered for poor surgical candidates with medical comorbidities.
Diagnostic Laparoscopy: Used in stage III or IV cases to assess resectability.
Chemotherapy Choice: Prefer intravenous platinum-based regimen, e.g., carboplatin plus paclitaxel.
Assessment and Next Steps:
Serial evaluations during NACT, assessing treatment response after three cycles.
Surgical cytoreduction for optimal resection chances.
Consider Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for optimal surgical results if expertise available.
Medical therapy for disease progression or suboptimal response.
Following Surgery:
Recommend adjuvant platinum-based chemotherapy.
Prefer intravenous chemotherapy (carboplatin and paclitaxel for 3-6 cycles) over intraperitoneal therapy.
Renal cell carcinoma (RCC) often presents with vague symptoms in its early stages, and patients may remain asymptomatic. As the disease progresses, common clinical features may include:
Hematuria: Blood in the urine is a common sign, often presenting as either visible blood or microscopic hematuria.
Flank Pain: Discomfort or pain in the side or lower back, potentially associated with tumor expansion or pressure on surrounding structures.
Palpable Abdominal Mass: A palpable lump or mass in the abdomen may be felt during a physical examination.
Weight Loss and Fatigue: Advanced stages may lead to unintended weight loss and fatigue.
Paraneoplastic Syndromes: Some RCCs produce hormones or cytokines, leading to paraneoplastic syndromes, such as elevated erythropoietin levels causing polycythemia.
Pathology:
Histological Subtypes: Clear cell, papillary, chromophobe, and other rare subtypes exist. Clear cell is the most common and typically associated with worse prognosis.
Genetic and Molecular Alterations: Mutations in tumor suppressor genes (e.g., VHL, PBRM1, BAP1), chromosomal deletions, and alterations in cellular pathways contribute to RCC development.
Tumor Grading: Fuhrman grade and ISUP grading system assess tumor differentiation, with higher grades indicating a poorer prognosis.
Tumor Necrosis: Histologic coagulative tumor necrosis is an independent predictor of outcome.
Imaging:
CT Scan: High-resolution computed tomography (CT) imaging is the primary modality for RCC diagnosis and staging, providing detailed visualization of the tumor, surrounding structures, and potential metastases.
MRI: Magnetic resonance imaging (MRI) offers additional soft tissue contrast and is particularly useful for characterizing renal masses.
Ultrasound: Ultrasound may be used for initial assessment and is effective in detecting solid masses but may have limitations in characterizing complex lesions.
Nuclear Medicine: Positron emission tomography (PET) scans can be used for staging and detecting distant metastases.
Prognosis:
TNM Staging: The tumor, node, metastasis (TNM) staging system stratifies patients based on the extent of disease.
Anatomic Factors: Invasion into the renal vein or inferior vena cava, perinephric fat extension, and involvement of the urinary collecting system impact prognosis.
Histopathological Factors: Clear cell histology, higher tumor grade, and tumor necrosis are associated with a worse prognosis.
Molecular Markers: Various molecular markers, genetic alterations, and gene expression profiles can provide additional prognostic information.
Survival Rates: Prognosis varies widely, with early-stage disease having better survival rates compared to advanced stages. Advances in targeted therapies and immunotherapy have improved outcomes for some patients with advanced RCC.
Osteoradionecrosis is a severe complication arising from head and neck radiotherapy. Mainly affecting the posterior mandible, it often manifests in molars and premolars. Common risk factors include high radiation doses, teeth extractions, and smoking. In the context of treatment, ORN can be categorized into four grades (1-4) based on severity.
Key Points:
Incidence: Occurs in approximately 7.5% of cases, with a median onset time of 8 months post-radiotherapy.
Risk Factors:
Higher incidence with elevated mean radiation doses to the mandible.
Smoking and pre-radiotherapy dental extractions significantly increase the risk.
Treatment Approaches:
Conservative management for early stages.
Surgical interventions include sequestrectomy (Stage 2) and, in severe cases, resection (Stage 3, involving mandibulectomy).
Hyperbaric oxygen therapy may aid in non-healing cases.
Prevention:
Precise dose planning tailored to individual patients crucial for minimizing risks.
Consideration of patient-specific factors, such as smoking and dental history, in treatment planning.
ORN underscores the importance of meticulous treatment planning and individualized approaches to minimize this debilitating complication.
Borderline ovarian malignancy, also known as borderline ovarian tumor or ovarian tumors of low malignant potential (LMP), is a distinct category of ovarian tumors that fall between benign and malignant tumors in terms of their behavior and potential for spreading.
Characteristics and Diagnosis:
Histological Features: Borderline ovarian tumors have certain cellular abnormalities that suggest malignancy but lack the invasive qualities seen in fully malignant tumors.
Age Group: They often occur in women of childbearing age, and their incidence tends to be highest in women in their 30s and 40s.
Clinical Presentation: Borderline ovarian tumors may be asymptomatic or present with nonspecific symptoms like abdominal pain, bloating, or changes in urinary habits.
Imaging and Biopsy: Diagnosis typically involves imaging studies, such as ultrasound, and a biopsy or surgical removal of the tumor for a pathological examination to confirm its borderline nature.
Treatment and Prognosis:
Surgical Approach: The primary treatment for borderline ovarian tumors is usually surgery, which involves removing the affected ovary or ovaries. The goal is to perform a comprehensive surgical staging to assess the extent of disease without removing both ovaries unless necessary.
Chemotherapy: Unlike malignant ovarian tumors, borderline tumors are less likely to spread beyond the ovaries. In cases where there is evidence of disease spread or in certain high-risk situations, chemotherapy may be considered.
Prognosis: The overall prognosis for women with borderline ovarian tumors is generally favorable. The majority of patients have an excellent long-term survival rate, especially if the tumor is confined to the ovaries at the time of diagnosis.
Follow-Up and Recurrence:
Regular Monitoring: Given the potential for recurrence, patients with borderline ovarian tumors often undergo regular follow-up examinations, including imaging studies and blood tests (such as CA-125), to monitor for any signs of disease recurrence.
Reproductive Considerations:
Fertility-Sparing Options: For women who wish to preserve fertility, there may be options for fertility-sparing surgery in carefully selected cases where the tumor is unilateral, well-staged, and the patient desires future childbearing.
Conclusion:
Borderline ovarian malignancy represents a unique category in ovarian tumors, requiring a multidisciplinary approach involving gynecologic oncologists, pathologists, and other healthcare professionals. While generally associated with a favorable prognosis, individual cases can vary, and personalized treatment plans are essential for optimal outcomes. Regular follow-up and clear communication between patients and healthcare providers play a crucial role in managing and monitoring borderline ovarian tumors.
Definition: Small cell lung carcinoma (SCLC) is a type of lung cancer that typically starts in the bronchi (large airways) and tends to grow and spread quickly. It accounts for approximately 10-15% of all lung cancers.
Characteristics: SCLC is characterized by small, oat-shaped cancer cells that rapidly divide and form large tumors. It is often associated with a history of smoking and has a strong correlation with tobacco exposure.
Aggressive nature: SCLC is considered highly aggressive, with a tendency to metastasize (spread) early to the lymph nodes and other distant parts of the body, such as the liver, bones, and brain. This rapid spread makes early detection and treatment crucial.
Limited and extensive stage: SCLC is classified into two stages: limited stage and extensive stage. Limited stage means the cancer is confined to one side of the chest and potentially adjacent lymph nodes, whereas extensive stage indicates that the cancer has spread beyond the chest to distant organs.
Treatment approach: The treatment of SCLC typically involves a combination of chemotherapy and radiation therapy. Surgery is generally not recommended for SCLC due to its aggressive nature and tendency to spread early. Chemotherapy, often in combination with immunotherapy, is the mainstay of treatment and can help shrink tumors and control the disease.
Prognosis: The prognosis for SCLC is generally poorer compared to non-small cell lung carcinoma (NSCLC) due to its more aggressive behavior and earlier metastasis. However, treatment advances and research efforts continue to improve outcomes for SCLC patients.
Supportive care: As with any cancer diagnosis, supportive care plays a critical role in managing SCLC. This includes addressing symptoms, managing pain, providing emotional support, and ensuring optimal quality of life for patients.
It's important to consult with healthcare professionals for an accurate diagnosis, personalized treatment plan, and ongoing monitoring for individuals suspected or diagnosed with small cell lung carcinoma.
Definition: Peritoneal mesothelioma is a rare cancer that develops in the lining of the abdomen, known as the peritoneum. It is primarily caused by exposure to asbestos fibers.
Symptoms: Common symptoms include abdominal pain, swelling, changes in bowel habits, unexplained weight loss, and fatigue. However, these symptoms can be nonspecific and resemble other gastrointestinal conditions, which can make diagnosis challenging.
Diagnosis: Diagnosis involves a combination of imaging tests, such as CT scans and MRIs, as well as biopsies to confirm the presence of peritoneal mesothelioma. These tests help determine the extent and stage of the disease.
Treatment options: The management of peritoneal mesothelioma often involves a multimodal approach, tailored to the individual case. Treatment options may include surgery, chemotherapy, and heated intraperitoneal chemotherapy (HIPEC).
Surgical interventions: Cytoreductive surgery aims to remove visible tumors from the abdomen, including affected organs and tissues. It is often performed in combination with HIPEC, a procedure where heated chemotherapy drugs are circulated in the abdominal cavity to target any remaining cancer cells.
Chemotherapy: Systemic chemotherapy, given intravenously or orally, may be used before or after surgery to help shrink tumors, kill cancer cells, and prevent their spread. In some cases, intraperitoneal chemotherapy (IPC) may be used instead of HIPEC.
Palliative care: Palliative care focuses on providing relief from symptoms and improving the quality of life for patients. It may involve pain management, nutritional support, and psychological support for both the patient and their loved ones.
Diagnosis: Prompt and accurate diagnosis is crucial. It involves imaging tests such as X-rays, CT scans, and MRIs, as well as biopsies to confirm the presence of pleural mesothelioma.
Treatment options: The management of pleural mesothelioma typically involves a multidisciplinary approach, which may include surgery, chemotherapy, and radiation therapy. The choice of treatment depends on the stage and extent of the disease, as well as the patient's overall health.
Surgical interventions: Surgical options may include pleurectomy/decortication (removal of the affected tissue lining the lungs) or extrapleural pneumonectomy (removal of the affected lung, lining, and nearby structures). These procedures aim to remove as much of the cancerous tissue as possible.
Chemotherapy: Chemotherapy drugs are often used to kill or slow the growth of cancer cells. They can be administered orally or through intravenous infusions. Sometimes, chemotherapy is given before surgery to shrink tumors and after surgery to target any remaining cancer cells.
Radiation therapy: This treatment involves the use of high-energy X-rays or other radiation sources to target and destroy cancer cells. It can be used before or after surgery, or as a standalone treatment to alleviate symptoms and manage the disease.
Palliative care: Palliative care focuses on improving the quality of life for patients by managing pain, reducing symptoms, and providing emotional and psychological support. It can be integrated into the treatment plan at any stage of the disease.
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, presents with various clinical features that can help diagnose and stage the disease. These features, along with imaging studies and laboratory tests, aid in determining the extent and severity of HCC. Here are the key clinical features and staging considerations:
Clinical Features:
Abdominal Pain: HCC can cause pain or discomfort in the upper right abdomen due to liver enlargement or tumor growth.
Jaundice: Yellowing of the skin and eyes (jaundice) may occur when the tumor affects liver function or obstructs the bile ducts.
Weight Loss: Unintentional weight loss may result from factors such as decreased appetite or cancer-related wasting.
Fatigue and Weakness: HCC patients often experience persistent fatigue and generalized weakness.
Loss of Appetite and Nausea: HCC can lead to reduced appetite, resulting in nausea and vomiting.
Abdominal Swelling: Ascites, the accumulation of fluid in the abdomen, may cause abdominal distension and discomfort.
Enlarged Liver: As HCC progresses, the liver may become palpable due to its enlargement and the presence of a tumor.
Staging: HCC staging helps determine the extent and spread of the cancer, guiding treatment decisions. The most commonly used staging system for HCC is the Barcelona
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
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2. Renal cell carcinoma (RCC) constitutes a notable segment of adult malignancies, accounting
for 3% to 4% of cases.
Accounts for a minority (approximately 10-30%) of renal cell carcinomas (RCC) are non clear
cell.
Papillary RCC may be associated with hereditary factors, while chromophobe RCC is linked to
Birt-Hogg-Dubé syndrome.
Generally considered to have a more favorable prognosis compared to clear cell RCC,
especially chromophobe and papillary subtypes.
Surgery remains a primary treatment for localized disease, akin to clear cell RCC.
Systemic therapies, including targeted agents and immunotherapy, are being explored based
on subtype-specific studies and extrapolation from ccRCC data.
3.
4. 1. Grouping of Renal Tumors:
Papillary Renal Tumors:
1. Type 1 and Type 2 PRCC no longer recommended.
2. Type 1 now termed classic PRCC.
3. Type 2 recognized as various entities (e.g., FH deficient RCC, acquired cystic disease-associated RCC).
4. Morphologic spectrum expanded, including biphasic PRCC and Warthin-like PRCC.
5. Papillary renal neoplasm with reverse polarity recognized as a separate entity.
2. Oncocytic and Chromophobe Renal Tumors:
New Category: Other Oncocytic Tumors:
1. Includes emerging entities like low-grade oncocytic tumor (LOT) and eosinophilic vacuolated tumor (EVT).
2. Includes oncocytic renal neoplasms of low malignant potential (NOS) and hybrid oncocytic tumors (HOT) in a
hereditary setting.
3. Collecting Duct Tumors:
No specific changes mentioned.
4. Other Renal Tumors:
Clear Cell Papillary Renal Cell Tumor:
1. Replaces clear cell papillary renal cell carcinoma due to benign behavior.
5. Molecularly Defined Renal Carcinomas:
1. TFE3 rearranged RCC and TFEB altered RCC separated into distinct entities.
2. New entities introduced: ESC RCC, ELOC-mutated RCC, ALK rearranged RCC.
6. Grading of Renal Carcinomas:
1. Based on the single high-power field showing the greatest pleomorphism.
2. WHO/ISUP grading varies in significance across RCC subtypes, categorized based on grading value.
5. 1.Von Hippel-Lindau (VHL) Gene:
• ccRCC: Often characterized by VHL gene mutations or inactivation, leading to dysregulation of
hypoxia-inducible factor (HIF) and subsequent angiogenesis.
• ncRCC: VHL mutations are less frequent in non-clear cell subtypes.
2.MET Gene:
• Papillary RCC: Frequently associated with MET gene mutations.
3.CD117 (c-KIT):
• Chromophobe RCC: CD117 expression is often seen in chromophobe RCC but is typically
negative in ccRCC.
4.Carbonic Anhydrase IX (CAIX):
• ccRCC: CAIX is commonly expressed in clear cell RCC, making it a potential marker for
distinguishing ccRCC from other subtypes.
5.PAX8:
• ccRCC: Positive for PAX8, a marker often used in the immunohistochemical evaluation of
renal tumors.
• ncRCC: Also positive for PAX8, making it less helpful in subtype differentiation.
6.Cytokeratins (CKs):
Papillary RCC: Positive for CK7, while clear cell RCC is typically negative.
8. Primary tumor (T)
T category T criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor <_ 7 cm in greatest dimension, limited to the kidney
T1a Tumor <_4 cm in greatest dimension, limited to the kidney
T1b Tumor >4 cm but < 7 cm in greatest dimension, limited to the kidney
T2 Tumor >7 cm in greatest dimension, limited to the kidney
T2a Tumor >7 cm but < 10 cm in greatest dimension, limited to kidney
T2b Tumor>10 cm , limited to kidney
T3 Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia
T3a Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perinal and/ or renal
sinus fat but not beyond Gerota’s fascia
T3b Tumor extends into the vena cava below the diaphragm
T3c Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava
T4 Tumor invades beyond Gerota’s fascia ( including contiguous extension into the ipsilateral adrenal gland)
Regional lymph nodes (N)
N category N criteria
NX Regional lymph node cannot be assessed
N0 No regional lymph node metastases
N1 Metastasis in regional lymph node(s)
Distant metastasis (M0
M ctegory M criteria
M0 No distant metastasis
M1 Distant metastasis
10. Suspicious Mass
STAGE I
T1a
STAGE I
T1b
STAGE
II
STAGE
III
STAGE
IV
Partial nephrectomy
(preferred)
Ablative techniques
Active surveillance
Radical nephrectomy
Partial nephrectomy
Ablative techniques
Active surveillance
Radical nephrectomy
Partial nephrectomy
(preferred)
Radical nephrectomy
Radical nephrectomy
(preferred)
Partial nephrectomy
surveillance
Adjuvant pembrolizumab
surveillance
Clear cell histology
Adjuvant pembrolizumab
surveillance
Non Clear cell histology
H&P
Urinanalysis
Abdomen +/-pelvis CT or MRI
Chest CT Scan
surveillance
11. Clear cell histology
Surgically
unresectable
Potentially surgically
resectable primary
Consider tissue sampling
Systemic therapy ( preferred
in clear cell histology
Tissue sampling
Clinical trial
First line systemic therapy
Metastasectomy or SBRT
BST
Cytoreductive nephrectomy
in selected patient
Stage IV
Non- Clear cell histology
Clinical trial
First line systemic therapy
Metastasectomy or SBRT
BST
12. 1.Nephron-Sparing Surgery (Partial Nephrectomy):
Recommended for:
1. Unilateral stage I–III tumors (where technically feasible).
2. Uninephric state, renal insufficiency, bilateral renal masses, and familial renal cell cancer.
3. Patients at relative risk for progressive chronic kidney disease (young age, medical risk factors).
2.Surgical Techniques:
Open, laparoscopic, or robotic approaches for radical and partial nephrectomies.
3.Lymph Node Dissection:
Optional but should be considered for resectable adenopathy on preoperative imaging
or palpable/visible adenopathy.
4.Adrenalectomy:
Omitted if adrenal gland is uninvolved.
5.Inferior Vena Cava Involvement:
Specialized teams or referral to high-volume centers may be required for extensive
involvement.
6.Thermal Ablation:
1. Options include cryosurgery, radiofrequency ablation, and microwave ablation.
2. Considered for clinical stage T1 renal lesions.
3. Clinical T1b masses in select patients not eligible for surgery.
13. 1.Stereotactic Body Radiation Therapy (SBRT):
Option for medically inoperable patients with stage I, II, or III kidney cancer (Category 2B for
stage I, Category 3 for stage II and III).
2.Active Surveillance:
Considered for clinical stage T1 renal lesions, especially:
• Small renal masses (<3 cm) with high rates of benign tumors.
• T1a tumors (≤4 cm) with a predominantly cystic component.
• Patients with T1 masses and significant competing risks for intervention-related morbidity or mortality.
Involves serial imaging with timely intervention if the mass shows changes indicating
increasing metastatic potential.
Periodic metastatic survey, including blood work and chest imaging, is recommended.
3.Cytoreductive Nephrectomy:
Candidates typically have:
• Excellent performance status (ECOG PS <2).
• No brain metastasis.
Considered prior to systemic therapy.
4.Systemic Therapy:
Recommended before cytoreductive nephrectomy for patients with:
• Large-volume distant metastases.
• Tumors with significant sarcomatoid burdens.
14. Characteristic Clear Cell Carcinoma Non-Clear Cell Carcinoma
Histology Clear cytoplasm
Diverse morphology based on
specific subtype
Prevalence 70-80% of RCC cases
Less common, various subtypes
collectively
Genetics Associated with VHL mutations
Heterogeneous genetic alterations
by subtype
Prognosis Variable, often less favorable
Variable, subtypes may have
different outcomes
Molecular Features VHL mutations common
Genetic variations specific to each
subtype
Clinical Approach
Targeted therapies often
developed
Individualized approach based on
subtype
Examples of Subtypes Clear cell, clear cell papillary
Papillary, chromophobe, collecting
duct, etc.
15. 1. Surgery:
• Nephron-Sparing Surgery: Considered whenever feasible to preserve renal function.
• Radical Nephrectomy: In cases where nephron-sparing surgery is not possible or for more aggressive subtypes.
2. Systemic Therapy:
1. Targeted Therapies: Depending on the specific histologic subtype.
• Papillary RCC: Tyrosine kinase inhibitors (TKIs) like sunitinib or pazopanib.
• Chromophobe RCC: Limited evidence, but potential response to TKIs.
• Collecting Duct Carcinoma: Chemotherapy may be considered.
• Other Subtypes: Limited data, and treatment may vary.
3. Immunotherapy:
• Checkpoint Inhibitors: May be considered for certain subtypes, with immunotherapy agents like nivolumab or pembrolizumab.
4. Clinical Trials:
• Participation in clinical trials exploring novel treatments and targeted therapies is encouraged, given the limited evidence for standard treatments in ncRCC.
5. Radiation Therapy:
• Adjuvant or Palliative Radiation: Depending on the extent and location of the disease.
6. Active Surveillance:
• For selected cases with indolent tumors or those not amenable to immediate intervention.
7. Cytoreductive Nephrectomy:
• Considered in metastatic disease, especially if there's potential for a significant reduction in tumor burden.
8. Genetic Testing:
• Consideration for genetic testing, as certain genetic mutations may guide treatment decisions.
9. Patient Considerations:
• Age, overall health, and comorbidities play a crucial role in treatment decisions.
The general approach to treatment of localized (stage I to III)non-clear cell
renal cell carcinoma (RCC) is similar to that of clear cell RCC.
16. Typically diagnosed between ages 50–70, more common in men.
Radiologically characterized by calcification, often multifocal.
Higher incidence among Black individuals and increased risk in Asian Americans.
Metastatic pRCC associated with worse survival compared to clear cell RCC (ccRCC).
Threefold higher incidence in Black individuals than White individuals.
Asian Americans show an increased risk based on regional data
Limited randomized phase III trials for non-clear cell RCC.
Treatment decisions historically based on retrospective data, phase II trials, and
subgroup analyses.
17. A) Classical features of pRCC type 1, with delicate papillae covered by cells with scant pale cytoplasm and nuclei
arranged in a single layer. (B) Notice the frequent psammomatous calcifications (arrows) and macrophages filled with
hemosiderin pigment;
pRCC is relatively hypovascular in comparison with cRCC
18. Characteristic Type 1 pRCC Type 2 pRCC
Histological Characteristics
Single-layered cells, oval nuclei,
scant basophilic cytoplasm
Large pseudostratified cells,
eosinophilic, prominent nucleoli
Immunohistochemistry
CK7, MUC1, vimentin expressions
common
CK20, E-cadherin expressions more
frequent
Molecular Profile
Largely driven by MET pathway
alterations
Multiple subtypes, distinct
molecular profiles
Genomic Clusters (NGS)
Lower-grade, higher rates of
chromosomal gains in 7p and 17p
Different copy number alterations,
subtypes identified
Cell Origin Diversity
Primarily from proximal tubule (PT)
cells
Multiple cell origins, some tumors
from collecting duct (CD) cells
Clinical Associations Generally lower grade
May have higher-grade subtypes,
varied clinical associations
Examples Classic pRCC
Includes HLRCC, translocation RCC,
diverse subtypes
19. 1. Abandonment of Type 1 and Type 2 Subtyping:
• Traditional subtyping of PRCC into Type 1 and Type 2 is no longer recommended.
• "Type 1 PRCC" is now termed "classic PRCC."
2. Recognition of Distinct Entities:
• Tumors previously labeled as "Type 2" PRCC exhibit morphologic variability and diverse clinical behaviors.
• Many tumors with prominent papillary architecture previously classified as "Type 2" are now recognized as separate entities:
1. Sporadic FH-deficient RCC
2. MiTF family translocation RCC
3. ALK-rearranged RCC
4. Acquired cystic disease-associated RCC (ACD-RCC)
5. Eosinophilic solid and cystic RCC
3. Prognostic Value of WHO/ISUP Grade:
• Recent evidence questions the clinical significance of "Type 1 and 2" PRCC, emphasizing the prognostic value of WHO/ISUP grade.
• Emerging biomarkers like ABCC2 are also considered for prognosis.
4. Expanded Morphologic Spectrum:
• The morphologic spectrum of PRCC is expanded to include new patterns:
1. Biphasic (alveolar/squamoid) PRCC with solid growth
2. Papillary renal neoplasm with reverse polarity (formerly "oncocytic low-grade PRCC")
3. Warthin-like PRCC mimicking salivary gland Warthin tumor
5. Association with Immunohistochemical Features and Molecular Alterations:
• Specific patterns like papillary renal neoplasm with reverse polarity are consistently positive for GATA3 and negative for vimentin.
• Molecular alterations, such as recurrent KRAS mutations, are observed, even in small tumors.
20. Preferred Regimens
•Clinical trial
•Cabozantinib
Other Recommended Regimens
•Lenvatinib + everolimus
•Nivolumabb
•Nivolumabb + cabozantinib
•Pembrolizumabb
•Sunitinib
Useful in Certain Circumstances
•Axitinib
•Bevacizumab
•Bevacizumab + erlotinib for selected patients with advanced papillary RCC
including hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated RCC
(HERED-RCC-D)
•Bevacizumabg + everolimus
•Erlotinib
•Everolimus
•Nivolumabb + ipilimumabb (category 2B)
•Pazopanib
•Temsirolimuse (category 1 for poor-prognosis risk group; category 2A for other risK
21. Trial Name Comparative Arms Findings
ARCC Trial IFN vs. Temsirolimus Temsirolimus showed superiority over IFN in terms of PFS and OS in pRCC.
RAPTOR Trial Everolimus
Everolimus demonstrated an OS benefit, with a longer duration of SD contributing to positive
outcomes.
SUPAP Trial Sunitinib
Sunitinib demonstrated effectiveness in terms of response rates, PFS, and OS in patients with
pRCC.
AXIPAP Trial Axitinib Axitinib showed activity in both type 1 and type 2 pRCC, with significant responses and PFS.
ESPN Trial Sunitinib vs. Everolimus Sunitinib showed superior PFS compared to everolimus in nccRCC, including pRCC.
ASPEN Trial Sunitinib vs. Everolimus
Sunitinib showed improved PFS compared to everolimus in the intention-to-treat cohort, with
significant benefits in pRCC.
SAVOIR Trial Savolitinib vs. Sunitinib
Savolitinib showed a numerically superior response rate to sunitinib in a biomarker-driven
approach for MET inhibition in pRCC.
PAPMET Trial Cabozantinib vs. Sunitinib Cabozantinib demonstrated superior median PFS and response rates compared to sunitinib.
KEYNOTE-427 Trial Pembrolizumab
Pembrolizumab monotherapy demonstrated activity in non-clear cell histology, including a
significant ORR in pRCC.
CheckMate-374 Trial Nivolumab
Nivolumab demonstrated an ORR and impressive OS in patients with treatment-refractory
advanced/metastatic nccRCC.
CheckMate-920 Trial
Nivolumab plus
Ipilimumab
Nivolumab plus ipilimumab showed activity in previously untreated advanced/metastatic
nccRCC.
22. • Among other histologies mostly papillary.
Phase III, randomized, open-label study
ARM 1 ARM 1
IFN (3 million units [MU] subcutaneously
three times weekly,
N: 207
Other histology: 36
temsirolimus (25 mg intravenously weekly)
N:209
Other histology: 37
FOR OTHER
Median Months :1.8
Overall response: 8.3%
OS:4.3
Clinical Benefit:8.3%
FOR OTHER
Median Months :7.0
Overall response: 5.4%
OS:11.6
Clinical Benefit: 40.5%
Dutcher J.P., De Souza P., McDermott D., Figlin R.A., Berkenblit A., Thiele A., Krygowski M., Strahs A., Feingold J., Hudes G. Effect
of temsirolimus versus interferon-α on outcome of patients with advanced renal cell carcinoma of different tumor
histologies. Med. Oncol. 2009;26:202–209.
23. The RAPTOR study, a phase 2 trial, evaluated first-line everolimus in previously untreated patients with papillary metastatic renal
cell carcinoma (mRCC). Key findings:
Patient Characteristics:
• 92 patients enrolled; 78% were men.
• Mean age: 60 years.
• Papillary histology confirmed in 78% (type 1, 32%; type 2, 64%).
Treatment and Endpoints:
• Everolimus 10 mg once daily until progression or toxicity.
• Primary endpoint: 6-month PFS rate (34%).
Results:
• Median PFS: 4.1 months (95% CI 3.6-5.5).
• 65% achieved stable disease.
• Median OS: 21.4 months (95% CI 15.4-28.4).
• Type 1 histology: Median PFS 7.9 months; Median OS 28.0 months.
• Type 2 histology: Median PFS 5.1 months; Median OS 24.2 months.
Adverse Events:
• Common grade >2 events: Asthenia (13%), anemia (7%), fatigue (5%).
Interpretation:
• Everolimus showed clinical benefit in papillary mRCC.
• Central pathological review emphasized for this rare tumor.
24. • Participants: 108 patients with metastatic non-clear-cell renal cell carcinoma (papillary,
chromophobe, or unclassified).
• Patients were randomly assigned (1:1) to receive everolimus (10 mg/day) or sunitinib (50 mg/day;
6-week cycles of 4 weeks with treatment followed by 2 weeks without treatment)
Parameter Sunitinib (N=51) Everolimus (N=57)
PFS 8.3 months (80% CI 5.8–11.4) 5.6 months (5.5–6.0)
Hazard Ratio 1.41 (80% CI 1.03–1.92), p=0.16
Adverse Events
Hypertension 24% 2%
Infection 12% 7%
Diarrhea 10% 2%
Pneumonitis 9% 9%
Stomatitis 9% -
Hand-Foot Syndrome 8% -
25. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell
carcinoma: a randomised, open-label, phase 2 trial
Prof Sumanta K. Pal, MD,1 Prof Catherine Tangen, DrPH,2,3 Ian M. Thompson, Jr., MD,4
•Study Design:
• Randomized, open-label, phase II trial.
• 152 patients enrolled (April 2016 to December 2019).
•Treatment Arms:
• Sunitinib (46), Cabozantinib (44), Crizotinib (28), Savolitinib
(29).
•Patient Characteristics:
• Median age: 66 years; 76% male.
• 147 eligible patients in the intention-to-treat population.
• Prior therapy received by 7%.
Sunitinib: 50 mg 4 weeks on, 2 weeks off, with
dose reductions to 37.5 mg and 25 mg permitted.
Cabozantinib: 60 mg oral daily with dose
reductions to 40 mg and 20 mg permitted.
Crizotinib:250 mg twice daily with dose reductions
to 200 mg twice daily and 250 mg once daily
permitted.
Savolitinib: 600 mg oral daily with dose reductions
to 400 mg and 200 mg oral daily permitted
27. Type: French multicentre phase II study
Patients: Untreated mPRCC patients with measurable disease, ECOG performance status ≤ 1, and adequate organ
functions.
Treatment: Axitinib administered orally at 5 mg twice daily.
Patients Screened: 56
Patients Included: 44 (13 type 1, 30 type 2, 1 non-specified)
Follow-up: Median 32.0 months (13.1-39.9)
24w-PFR (Primary Endpoint): 45.2% (95% CI, 32.6% to +∞)
Objective Response Rate: 28.6% (95% CI, 15.7%-44.6%)
Type 1: 7.7%
Type 2: 35.7%
Progression-Free Survival (Overall Median): 6.6 months (95% CI, 5.5-9.2)
Type 1: 6.7 months
Type 2: 6.2 months
Overall Survival: Median 18.9 months (95% CI, 12.8-not reached)
Grade 3-4 Treatment-Related Adverse Events: Rare, except for hypertension (27%)
Negrier S., Rioux-Leclercq N.,., et al. Axitinib in first-line for patients with metastatic papillary renal cell
carcinoma: Results of the multicentre, open-label, single-arm, phase II Eur. J. Cancer. 2020;129:107–116.
Conclusion:
Axitinib demonstrated encouraging efficacy in
mPRCC patients, particularly in type 2 PRCC.
Manageable toxicity profile.
Axitinib may be a promising first-line treatment
option and warrants further investigation,
potentially in combination with immunotherapy
28. • Study Type: Single-arm, international phase II trial
• Patients Enrolled: 158
• Histology: Advanced non-clear cell RCC of varying histologies
• Treatment: Lenvatinib plus pembrolizumab
• Results (Papillary Histology Subgroup):
• Patients with Papillary Histology: 93
• Objective Responses: 54%
• Complete Responses: 9%
• One-Year Progression-Free Survival (PFS): 67%
• Follow-up:
• Median Follow-up: 15 month
29. • Phase II
• N= 47
• Patients: Advanced non–clear-cell RCC, 0-1 prior systemic therapies (excluding immune
checkpoint inhibitors).
• Treatment: Cabozantinib 40 mg once daily plus nivolumab 240 mg q2w or 480 mg q4w.
Results:
• Cohort 1 (Papillary, Unclassified, Translocation-Associated RCC):
• ORR: 47.5% (median follow-up: 13.1 months).
• Median progression-free survival: 12.5 months.
• Median overall survival: 28 months.
• Mutations: NF2 and FH.
• Promising efficacy, with common mutations in NF2 and FH associated with objective
responses.
• Cohort 2 (Chromophobe RCC):
• No responses; one patient had stable disease > 1 year.
• Safety:
• Grade 3/4 treatment-related adverse events: 32%.
• Discontinuation due to toxicity: 13% for cabozantinib, 17% for nivolumab.
• Conclusion: Cabozantinib plus nivolumab demonstrated promising efficacy in non–clear-cell RCC
variants, especially those with papillary features.
32. • Introduction:
• 5% of kidney cancers are chRCC.
• Estimated 3,700 new cases in the USA (2020).
• Clinical Presentation:
• Less aggressive than clear cell RCC.
• Often asymptomatic, detected incidentally.
• Common metastases to liver and lungs.
• Genetic Syndromes:
• Linked to Birt-Hogg-Dubé syndrome and others.
• Pathology:
• Arises from collecting duct cells.
• Microscopic variants: pale and eosinophilic cells.
• Immunohistochemistry markers: CD117, CK7.
• Molecular Characteristics:
• Aneuploidy with chromosome losses.
• Loss of HNF1B and TP53 mutation noted.
• Infrequent PDL1 expression (5.6%).
• Conclusion:
• Ongoing research on genetic and molecular features.
• Accurate diagnosis involves clinical, pathological, and
molecular assessments.
High-power photomicrograph of the classic variant of chRCC demonstrates uninucleated (black
arrow) and binucleated (red arrow) cells with a polymorphous character, including raisinoid
nuclei and perinuclear clearing. (Hematoxylin-eosin stain; original magnification, ×200.)
33. • Clinical Presentation:
• Often incidental finding.
• Local symptoms: abdominal/flank pain (34–67%), abdominal mass (27%),
hematuria (17–40%).
• Systemic symptoms: fever, cachexia, fatigue, weight loss (20–33%).
• Majority low-stage cancers at diagnosis.
• Epidemiology:
• Estimated global RCC incidence in 2018: 400,000 with 175,000 deaths.
• U.S. annual chRCC incidence: 3,250 cases.
• Mean age at diagnosis: 58–60 years.
• Slight male sex predilection.
• Birt-Hogg-Dubé (BHD) Syndrome:
• Associated with chRCC.
• Autosomal dominant with FLCN gene mutations on chromosome 17.
• RCC incidence 7x higher in BHD.
• RCCs in BHD: bilateral, multifocal, slow-growing.
• Often hybrid oncocytic tumors or pure chRCCs.
• Imaging Features (CT):
• Well-circumscribed mass, smooth/lobular contours.
• Solid or mostly solid appearance.
• Calcification in 14–34%.
• Central scar in 19–34%.
• Isoattenuating to slightly hyperattenuating on noncontrast CT.
• Moderate enhancement, peaks in nephrographic phase.
• Enhances less than ccRCC but more than papRCC.
chRCC may have a central scar (black * in
34. Chromophobe renal
cell carcinoma
Localised disease Metastatic disease
Radical nephrectomy
(ablation if feasible for
tumors <3 cms)
Surveillance
No proven benefit
with adjuvant therapy
Consider cytoreductive nephrectomy if
ECOG PS 0-1 AND SYMPTOMATIC
RENAL MASS
Systemic therapy:
Sunitinib or Everolimus
Preferred first-line options
Also consider:
Genomic testing, clinical trials,
temsirolimus, immunotherapy for
sarcomatoid variants
35. • The general approach for
the treatment of localized chRCC is
surgery, similar to that of ccRCC
• Localized chRCC has better prognosis
when compared to ccRCC.
• The 5-year recurrence-free survival
and cancer-specific survival rates
were 89.3 % and 93 %, respectively.
• However, advanced stage IV chRCC
has no survival benefit compared to
ccRCC
Axial contrast-enhanced excretory phase CT image
shows a hypoenhancing mass (arrow) with
nonenhancing central necrosis (*).
36.
37. • Collecting Duct RCC:
• Aggressive tumor with similarities to urothelial carcinoma.
• Responds to platinum-based chemotherapy.
• Limited clinical trial data; further studies needed.
• Phase II trial with gemcitabine plus cisplatin showed 26% objective responses, median survival
~11 months.
• Renal Medullary Carcinoma:
• Aggressive variant associated with sickle cell trait.
• Limited treatment data; platinum-based chemotherapy commonly used.
• Response rates around 30% in observational studies.
• Two-year overall survival in one series: 13%.
• Limited activity with anthracyclines, bortezomib, and VEGFR inhibitors.
• General Recommendations:
• Cytotoxic chemotherapy (cisplatin plus gemcitabine, carboplatin plus gemcitabine, or
carboplatin plus paclitaxel) suggested for both histologies.
• Immunotherapy with checkpoint inhibitors investigational; limited data available.
• Encourage enrollment in clinical trials for both types.
38. • Initial Treatment:
• Suggest immunotherapy-based regimens for high objective response rates.
• Options include combination therapy (nivolumab plus ipilimumab; lenvatinib plus pembrolizumab)
or single-agent immunotherapy (pembrolizumab or nivolumab).
• Alternative for Immunotherapy Decline:
• VEGFR inhibitors, either as single-agents (e.g., sunitinib or cabozantinib) or combination therapy
(lenvatinib plus everolimus), are reasonable.
• Immunotherapy Regimens:
• Nivolumab plus ipilimumab: Observational data report 20-44% objective response rates.
• Lenvatinib plus pembrolizumab: Phase II trial showed 52% objective response in unclassified RCC.
• Pembrolizumab: Phase II trial reported 31% objective response and durable responses.
• Nivolumab: Phase II trial demonstrated 30% objective response in unclassified RCC.
• VEGFR Inhibitors:
• Sunitinib: Improved progression-free survival (PFS) twofold relative to everolimus in randomized
trials.
• Cabozantinib: Retrospective study reported 13% objective responses and 36% 12-month overall
survival in unclassified RCC subset.
• Other Regimens:
• Lenvatinib plus everolimus: Phase II trial showed partial responses in unclassified RCC.
• Bevacizumab plus everolimus: Phase II trial reported 43% objective response rate and 14 months
median PFS in unclassified RCC with papillary features.
39. • Initial Therapy:
• Suggest lenvatinib plus pembrolizumab for high objective response rates.
• Single-agent VEGFR inhibitor (e.g., sunitinib) is a reasonable alternative for those
declining or ineligible for immunotherapy.
• Translocation RCC Characteristics:
• Rare non-clear cell carcinoma variant with TFE3 gene fusions.
• Fusions activate microphthalmia-associated transcription factor (MITF).
• Limited Data on Optimal Therapy:
• Rarity hinders data collection.
• Lenvatinib plus pembrolizumab phase II trial showed a 67% objective response rate.
• No direct comparison with single-agent VEGFR inhibitors in randomized trials.
• Lenvatinib Plus Pembrolizumab:
• KEYNOTE-B61 phase II trial demonstrated 67% objective response in papillary histology.
• International trial with 158 patients, systemic therapy-naïve advanced non-clear cell RCC.
• Sunitinib:
• Observational studies support initial use in translocation RCC.
• Nonrandomized study showed 27% partial responses with sunitinib.
• Longer progression-free survival compared to cytokine therapy (median PFS eight versus
two months).
40. Histologic Subtypes:
• Main subtypes include papillary, chromophobe, collecting duct, unclassified, and translocation carcinomas.
• Sarcomatoid features can be present in any histologic subtype.
Treatment Approach:
• Tailored to histologic subtype due to limited data.
• Encourage enrollment in clinical trials whenever possible.
Papillary RCC:
• Immunotherapy-based therapy (e.g., nivolumab plus ipilimumab) or VEGFR inhibitor as initial therapy.
• Consider nivolumab plus ipilimumab for immunotherapy, extrapolating from clear cell RCC data.
• Cabozantinib is suggested for those opting for targeted antiangiogenic therapy or ineligible for
immunotherapy.
• Preferred therapy for hereditary leiomyomatosis-related papillary RCC: bevacizumab plus erlotinib.
Chromophobe RCC:
• Limited evidence due to rarity.
• Initial treatment with mTOR inhibitor (e.g., everolimus) or VEGFR inhibitor (e.g., sunitinib).
• Alternatives include combination therapy (lenvatinib plus pembrolizumab or lenvatinib plus everolimus).
41. Collecting Duct and Renal Medullary Carcinoma:
Cytotoxic chemotherapy as initial therapy over VEGFR inhibitors.
Platinum-based chemotherapy options: cisplatin plus gemcitabine, carboplatin
plus gemcitabine, or carboplatin plus paclitaxel.
Translocation RCC:
Lenvatinib plus pembrolizumab preferred over single-agent VEGFR inhibitor.
Consider single-agent VEGFR inhibitor (e.g., sunitinib) for those declining or
ineligible for immunotherapy.
Unclassified RCC:
Immunotherapy-based regimens recommended over VEGFR inhibitors.
Options: combination therapy (nivolumab plus ipilimumab; lenvatinib plus
pembrolizumab) or single-agent immunotherapy (pembrolizumab or
nivolumab).
VEGFR inhibitors are reasonable alternatives for those declining or ineligible for
immunotherapy.
Non-Clear Cell RCC with Sarcomatoid Features: