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.
Evaluation and management of Stage III Non-Small Cell Carcinoma Lung including Radiotherapy planning. On a Radiation Oncologist Perspective. MD Radiotherapy discussion - CMC, Vellore
Radiotherapy in Uterine & Cervical Cancer.pptxAtulGupta369
Radiotherapy
uterine carcinoma
cervix carcinoma
brachytherapy in uterine carcinoma
brachytherapy in cervical carcinoma
detailed decription
explanation about recent recommendations
explanations about landmark trials
one shot whole ppt for learning about EBRT and brachytherapy in cervical and uterine carcinoma
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
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.
Evaluation and management of Stage III Non-Small Cell Carcinoma Lung including Radiotherapy planning. On a Radiation Oncologist Perspective. MD Radiotherapy discussion - CMC, Vellore
Radiotherapy in Uterine & Cervical Cancer.pptxAtulGupta369
Radiotherapy
uterine carcinoma
cervix carcinoma
brachytherapy in uterine carcinoma
brachytherapy in cervical carcinoma
detailed decription
explanation about recent recommendations
explanations about landmark trials
one shot whole ppt for learning about EBRT and brachytherapy in cervical and uterine carcinoma
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
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.
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.
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: 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.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
lung cancer: sclc uPTODATE.pptx
1. Limited-stage small cell lung cancer: Initial
management
DR SUMIT KUMAR, ASSISTANT PROFESSOR, NEIGRIHMS
2. INTRODUCTION
SCLC is a poorly differentiated NET that represents approximately 15% of all lung cancers.
Nearly all patients with SCLC are current or former smokers.
Clinical characteristics are quick doubling time, high growth fraction, and the onset of metastases early on.
SCLC typically presents with widespread disease, necessitating systemic therapy as the primary approach..
Limited-stage SCLC often involves radiation therapy for thoracic disease and brain prophylaxis.
In rare cases of a single pulmonary nodule, surgery may be part of the treatment.
Extensive-stage SCLC is primarily treated with chemotherapy and immunotherapy.
Chest and brain radiation therapy may be considered in specific ES –SCLC cases.
3. Treatment flow chart
Small cell lung cancer on biopsy or FNAC of primary/metastatic site
Extensive stage
Cect –chest+abd.+pelvis/Brain mri or Whole body PET/CT
Limited stage
PFT/Bone scan /BMA-if no PET
Limited stage
(T1-T2NOMO
Limited
(IIB-IIIC)
BMB
Consistent with
malignancy
Pathologic mediastinal staging
negative
Medically inoperable Pathologic mediastinal staging
positive
Lobectomy& mediastinal
LND SABR CTRT
R0 R1/R2
CTRT
CT CT
4.
5.
6.
7.
8.
9. DEFINITION OF LIMITED-STAGE DISEASE
LS-SCLC is defined as disease that is limited to the ipsilateral hemithorax and
regional lymph nodes and can be encompassed in a safe radiotherapy field.
Most patients with LS-SCLC will have clinical or pathologic evidence of mediastinal
lymph node involvement.
For staging following test to be done :
CECT of chest, abdomen, and pelvis.
PET-CT-whole body/MRI of the brain (CT brain with contrast if MRI is contraindicated).
Bone scan (only if PET-CT is not available).
Patients who have pleural effusions but otherwise LS disease should undergo
thoracentesis with cytologic analysis to confirm LS disease.
10. OVERVIEW OF TREATMENT AND BENEFITS
The current standard of care for patients with LS-SCLC that involves the lymph nodes
consists of 4 cycles of combination chemotherapy (typically cisplatin plus etoposide [EP])
along with concurrent thoracic radiotherapy during the early part of the chemotherapy
treatment (starting with the 1st or 2nd cycle of chemotherapy).
Prophylactic cranial irradiation (PCI) in CR or significant tumor regression at the completion
of chemotherapy.
Carboplatin can be substituted if cisplatin is contraindicated for reasons such as pre-existing
neuropathy, hearing loss, renal insufficiency, or congestive heart failure.
SCLC is highly responsive to both chemotherapy and radiation therapy.
For patients with LS-SCLC treated with contemporary chemoradiotherapy and PCI, ORR of
80 to 90%, including 50 to 60% complete response rates, are typically reported.
Median survival is approximately 17 months, and the 5-yr survival rate is approximately 20%.
11. STAGE I DISEASE (T1 to T2, N0)
IF histologically hilar and mediastinal lymph nodes are not involved & no contraindications to surgery,
resection of the primary tumor with lobectomy, plus mediastinal lymph node sampling or dissection.
Adjuvant chemotherapy with four cycles of cisplatin-based therapy.
IASLC database
Over 8000 cases of SCLC
349 cases (4 %) underwent surgery and staged
pathologically
Reported 5-yr survival rates for
pathologic stages I, II, and III
SCLC: 48%, 39%, and 15%,
respectively.
National Cancer Database Analysis:
29,994 clinical stages I to III SCLC cases
compare 2,089 patients who had surgery with
nonsurgically treated patients.
Contrasted with clinical trial data showing a 5-yr survival
rate of 26% to 34% for primarily stage III SCLC with
nonsurgical (chemoradiotherapy) treatment.
Nearly doubled median OS for N0
patients treated with surgery (38 vs. 22
months).
Favoured lobectomy over sublobar
resections and pneumonectomies
12. Postoperative chemotherapy —
Study/Analysis Patient Group Adjuvant Treatment 5-Year Survival Rate
National Cancer Database
Study
Early-stage (pT1-2N0M0)
SCLC
Adjuvant Chemotherapy
(with or without
radiation)
Surgery Alone
53%
40%
Surgical Resection Series Patients who underwent
surgical resectionfor SCLC
(Pathologic Stages I-III)
Adjuvant Chemotherapy Stage I: 51%
Stage II: 28%
Stage III: 19%
Contrast with Earlier Studies Surgery Alone 1%
National Cancer Database
3017 patients with LS-SCLC
postoperative thoracic radiation therapy
5-year OS
N2 disease (29 vs 19 %)
N1 disease , no
differences
Study on Adjuvant Radiation Therapy (RT) in LS-SCLC with Nodal Involvement
13. STAGE II TO III DISEASE
Chemotherapy
Initial studies of combined-modality therapy in patients with LS-SCLC used chemotherapy regimens such
as cyclophosphamide, doxorubicin, and vincristine (CAV), followed sequentially by thoracic RT.
146 patients with LS-SCLC received thoracic RT
(40 to 50 Gy) after four cycles of chemotherapy.
randomly assigned to CAV, EP, or CAV alternating
with EP
Outcome CAV EP, CAV
alternating
with EP
Response rates 51 % 77 % 88 %
overall survival
(OS) mth
12.4 11.7 11.8
myelotoxicity less
thoracic RT (42 Gy) was given between
the third and fourth cycles of
chemotherapy
EP compared with CEV)
OUTCOME EP CE
V
Median
survival(mth)
14.5 9.7
2-year survival
rates
25% 8 %
214 patients with LS-
SCLC
Etoposide plus cisplatin (EP) is the standard regimen for chemotherapy in patients with LS-SCLC along with early,
concurrent thoracic radiation therapy (RT
14. Substitution of carboplatin for cisplatin
Meta-analysis that included 663 patients in four trials compared
the efficacy of cisplatin-based versus carboplatin-based regimens
in SCLC
Overall, response rate, PFS, and OS
were similar patients with both LS- and
ES-SCLC
Hematologic toxicity was greater with carboplatin
Nonhematologic toxicity was greater with cisplatin.
Cisplatin remains the standard agent, with carboplatin restricted to patients with contraindications to or poor
tolerance of cisplatin
15. Irinotecan-containing regimens
Phase III trial (JCOG0202),
256 patients without progression were randomly assigned to
consolidation with either irinotecan plus cisplatin or etoposide plus
cisplatin
281 patients were initially treated with induction etoposide plus
cisplatin in conjunction with accelerated hyperfractionated RT
No statistically significant difference in OS,
18. The addition of thoracic radiation therapy (RT) to chemotherapy results in a small, statistically significant
improvement in survival compared with the use of chemotherapy alone.although the combined-modality
approach is associated with an increase in toxicity.
Two large meta-analyses have reported benefit to the use of combined chemotherapy and thoracic RT.
One meta-analysis, which included 11 randomized studies, found that the addition of thoracic RT was
associated with an absolute improvement in local control of 23 percent (two-year local control rate, 47 versus
24 percent). The chemotherapy regimens differed among the studies, as did the thoracic RT doses and
delivery schedules.
Another meta-analysis of 13 randomized trials (including the same 11 studies evaluated in the previously
noted meta-analysis) found that the use of combined chemotherapy and thoracic RT resulted in an absolute
survival benefit of 5.4 percent at three years.
The survival benefit associated with the use of thoracic RT outside of clinical trials was also suggested in a
subsequent review from the National Cancer Database. For patients with LS-SCLC, the five-year survival rate
for the 6752 patients diagnosed in 2000 was significantly higher in patients treated with thoracic RT plus
chemotherapy compared with chemotherapy alone (13.3 versus 5.7 percent).
While the benefit of RT in one of the meta-analyses was greatest for patients younger than 55 years old, with
a trend towards detriment in patients age 70 years and older, modern RT techniques and supportive care
have improved such that the benefits may outweigh toxicities for the older population as well. A retrospective
analysis of approximately 8600 patients age 70 years and older treated between 2003 and 2011 found that
the addition of RT to chemotherapy was associated with improved OS rates (15.7 percent absolute OS benefit
at three years).
Thoracic RT
Study Title/Source Number of Randomized Studies/no pt. Key Findings
Meta-Analysis 1 11
- Addition of thoracic RT associated with a
23% absolute improvement in local control
(two-year local control rate, 47% vs. 24%).
Meta-Analysis 2
13 Included the same 11 studies from
Meta-Analysis 1.
- Combined chemotherapy and thoracic RT
resulted in a 5.4% absolute survival benefit at
three years.
National Cancer Database
Review
For LS-SCLC patients diagnosed in 2000,
- 5-year survival rate was significantly higher in
patients treated with thoracic RT plus
chemotherapy compared to chemotherapy
alone (13.3% vs. 5.7%).
Retrospective Analysis of
Patients Age 70 and Older
(2003-2011)
Approximately 8600
- Addition of RT to chemotherapy associated
with a 15.7% absolute OS benefit at three
years.
19. Treatment volume —limited-field thoracic RT is the current standard of care.
All gross disease present at the time of RT planning (postchemotherapy volume), and all nodal regions
involved at the time of initial diagnosis (prechemotherapy volume).
PET-CT scans should be obtained for staging if RT is planned for patients with suspected LS-SCLC
Thoracic RT : Treatment volume
trial by SWOG
191 patients with a partial response or stable
disease following induction chemotherapy,
Prechemotherapy tumor volumes Postchemotherapy tumor volumes
No apparent difference in severe drug- related toxicity or radiation
pneumonitis
Myelosuppression than the reduced-field group (18 versus 7 percent)
RT FIELD
20. Preffered Regimen —45 Gy given in 1.5 Gy fractions twice daily over three weeks
Alternate regimen- 60 to 70 Gy in fractions of 2 Gy once daily over 6-7 weeks
Thoracic RT : Dose fractionation schedule
Advantage of hyperfractionation
Shorter total treatment time
Potentially reduces the opportunity for tumor cell
regeneration
Toxicities
More acute toxicities to normal tissues
Late toxicities should be similar
21. Thoracic RT : Dose fractionation schedule (trial)
Trial Name Treatment Arm Response Toxicity
CONVERT trial(547 pt.)
Twice-daily RT (45 Gy/30 fractions) vs.
Once-daily RT (66 Gy/33 fractions)
Median survival: 30 vs. 25 months,
HR 1.18 (not statistically significant)
- Grade 3-4 esophagitis: 19% in
both groups .
Radiation pneumonitis: 3%vs. 2%
11 treatment-related deaths (3 in
BD group, 8 in OD group)
CALGB 30610 trial(638 pt.)
Twice-daily RT (45 Gy) vs. Once-daily RT (70
(70 Gy)
PFS: Median 13.5 vs. 14.2 months
OS: Median 29 vs. 31 months,
Similar rates of grade 3 or higher
adverse events in both arms
Phase III Trial (417 pt.)
Twice-daily RT (45 Gy) vs. Once-daily RT (45
(45 Gy)
- 5-year OS: 26% vs. 16% (twice-
daily better)
- Severe esophagitis: 27% (twice-
daily) vs. 11% (once-daily) -
No significant difference in severe
hematologic and pulmonary
toxicities
Randomized Phase II
Trial(182pt.)
Twice-daily RT (45 Gy/30 fractions) vs.
Once-daily RT (65 Gy/26 fractions)
- PFS: Median 13.4 vs. 17.2 months,
Median OS: 34 vs. 39 months (not
statistically significant)
Similar incidence of ≥grade 3
esophagitis and pneumonitis, and
treatment-related death rates in
both groups
Dose-Escalation Trial(170
pt.)
Dose-escalated RT (60 Gy/40 fractions) vs.
Standard RT (45 Gy/30 fractions)
- Improved 2-year OS rates: 75%
vs. 48%,
- No significant differences in local
control, PFS, distant metastasis end
No significant differences toxicity
rates.
In conclusion, the data support both 60 to 70 Gy daily RT or 45 Gy twice daily, with the possibility of escalating
the dose to 60 Gy twice daily, in select patients.
22. THORACIC RT : CONCURRENT VS SEQUENTIAL TREATMENT
Preference for concurrent rather than sequential treatment —treatment start concurrently with
chemotherapy during cycle 1 or 2.
However, concurrent or alternating regimens have been associated with more toxicity (myelosuppression,
esophagitis, pneumonitis) when compared with sequential treatment. This increased toxicity is considered
acceptable based on improved outcomes with concurrent regimens.
Trial Name/Source Treatment Approach Response Toxicity
Japanese Clinical
Oncology Group Study
9104
Concurrent VS
SequentialThoracic RT
Median OS: 27 vs. 20
months (not statistically
significant, p = 0.10)
- Severe esophagitis:
Concurrent group (9%),
Sequential group (4%)
- Similar rates of
pulmonary toxicity and
treatment-related death.
Meta-Analysis of 13
Randomized Trials
Sequential vs.
Alternating/Concurrent
Thoracic RT
No significant differences
in thoracic RT outcomes
between sequential and
alternating/concurrent
approaches.
Not specified (data on
specific toxicity rates and
outcomes not provided).
23. EARLY VERSUS LATE THORACIC RT
Early versus late thoracic RT — We suggest that thoracic radiation therapy (RT) be integrated early
(in cycle 1 or 2) with chemotherapy rather than later in the treatment course.
There have been eight randomized trials and three meta-analyses that have attempted to address the
timing of the delivery of thoracic RT relative to chemotherapy. All the studies that employed standard
cisplatin-based chemotherapy without significant dose reductions convincingly showed that early
(starting with cycle 1 or 2 of chemotherapy) rather than late integration of thoracic RT is associated with
a better outcome.
As an example, a meta-analysis reported in 2004, which included seven randomized trials published
after 1985, showed a significant improvement in two-year OS for early versus late thoracic RT. A
subsequent meta-analysis showed that the most important factor associated with improved five-year
survival was a short interval between the start of any treatment and the completion of thoracic RT
(relative risk, 0.62).
Is there a role for surgery in patients with a good response to treatment? —In the setting of limited
data, not pursue surgery in patients with stage II or III disease, irrespective of response to
chemoradiotherapy, although we acknowledge that other experts may adopt this approach in select
instances.
Study/Analysis Timing of Thoracic RT Key Findings
Meta-Analysis (2004) seven
randomized trials published after 1985
Early (cycle 1 or 2) - Significant improvement in two-year
OS for early vs. late thoracic RT.
Subsequent Meta-Analysis
Early (short interval between start of
any treatment and thoracic RT)
- Short interval between treatment
start and thoracic RT associated with
improved five-year survival (relative
risk, 0.62).
24. PROPHYLACTIC CRANIAL IRRADIATION
Prophylactic cranial irradiation (PCI) following chemotherapy has been demonstrated to decrease the
incidence of symptomatic brain metastases (BM) and increase overall survival in patients with LS-SCLC
.
As such, PCI is the standard of care for most patients with LS- SCLC who achieve a complete or good
partial response following treatment.
25. SPECIAL CONSIDERATIONS
Patients with SVC obstruction — For patients with LS-SCLC and symptoms of superior vena cava
(SVC) obstruction, standard treatment should consist of concurrent chemotherapy plus definitive
thoracic radiation therapy (RT) with curative intent.
If there is any potential delay in planning of RT, then the first cycle of chemotherapy should be initiated
as soon as possible, with definitive RT added in once planning has been completed.
26. SUMMARY AND RECOMMENDATIONS
Introduction and treatment algorithm – A combined-modality approach is indicated for the
management of patients with limited-stage small cell lung cancer (LS-SCLC), following careful
staging to rule out distant metastases.
• For patients with clinical stage I (T1 to 2, N0) disease, invasive staging of mediastinal lymph
nodes is also indicated to identify the small fraction of patients who do not have lymph node
involvement or other metastatic disease.
• Stage I disease
• For patients with clinical stage I (cT1 to 2, N0) LS-SCLC, initial surgery followed by
adjuvant treatment
• If patients are not surgical candidates, chemoradiotherapy is an appropriate
27. SUMMARY AND RECOMMENDATIONS
• Stage II to III patients
• Chemotherapy – For patients with LS-SCLC four cycles of cisplatin plus
etoposide with concurrent RT
• Thoracic RT – Postchemotherapy gross disease and prechemotherapy
nodal volumes conventional fractionation (total dose of 60 to 70 Gy in
fractions of 2 Gy) or accelerated hyperfractionated schedules 45 Gy in twice-
daily fractions over three weeks concurrently with the first or second cycle of
chemotherapy.
• Prophylactic cranial irradiation – Prophylactic cranial irradiation is offered
to most patients with LS-SCLC who achieve a complete or very good partial
response to their initial chemotherapy treatment. Supporting data are
discussed elsewhere
28. This Photo by Unknown Author is licensed under CC BY
This Photo by
Unknown Author is
licensed under CC
BY-SA