This document provides information on the management of diffuse gliomas, including:
1. It defines diffuse gliomas and discusses their WHO classification, typically involving infiltration of normal brain tissue without clear borders.
2. Symptoms can include raised intracranial pressure, seizures, focal neurological deficits, and others depending on the tumor location.
3. Managing diffuse gliomas requires a multidisciplinary team including radiologists, neurosurgeons, oncologists and others.
4. Trial evidence is discussed regarding the use of radiotherapy and chemotherapy at different doses and timings for diffuse low-grade gliomas.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Induction chemotherapy followed by concurrent chemoradiation (CT-RT) has been studied as an alternative to primary CT-RT for locally advanced head and neck cancers. Meta-analyses have found induction chemotherapy provides no survival benefit compared to primary CT-RT and is associated with increased toxicity. Recent large randomized trials could not demonstrate an improvement with induction chemotherapy due to inadequate accrual and poor compliance with subsequent CT-RT. While induction chemotherapy may improve organ preservation or outcomes for select subgroups like HPV-negative cancers, current evidence indicates primary CT-RT remains the standard of care for most patients.
This document discusses malignant gliomas, specifically focusing on glioblastoma. It provides information on:
- The incidence and types of malignant gliomas, with glioblastomas accounting for 60-70% of cases.
- Signs and symptoms, which commonly include headaches, seizures, and changes in mental status.
- Diagnosis is typically made through brain imaging like MRI that shows irregular, enhancing masses.
- Standard treatment is surgical resection followed by radiation and chemotherapy with temozolomide. However, survival remains poor with a median of 14-15 months.
- Recurrence is common and additional treatment options for recurrent glioblastoma include repeat surgery, stereotactic radiosurgery
HOLISTIC APPROACH IN WHOLE BRAIN RADIATION IN BRAIN METSKanhu Charan
1. Whole brain radiotherapy is commonly used to treat brain metastases but can cause long-term side effects like memory loss and decreased quality of life.
2. A new study aims to spare structures like the hippocampus, cochlea, and parotid glands using IMRT and VMAT to reduce side effects while maintaining tumor coverage.
3. Dosimetry results found that IMRT and VMAT reduced hippocampal, parotid, and cochlear doses by 45-82% compared to conventional radiotherapy, allowing for improved quality of life.
This document summarizes the management of high grade gliomas. It discusses the classification, molecular markers, diagnostic evaluation, treatment including surgery, radiation, chemotherapy, prognostic factors and response assessment for these aggressive brain tumors. Key points include the distinction between glioblastoma and anaplastic astrocytoma/oligodendroglioma, the role of maximal safe resection followed by concurrent chemoradiation using temozolomide as the standard of care, and important prognostic markers like MGMT promoter methylation status. Pseudoprogression and pseudoresponse on imaging are also reviewed.
Prophylactic cranial irradiation (PCI) is used to prevent brain metastases in cancers with a high risk of spreading to the brain. It is indicated for small cell lung cancer and certain leukemias. PCI significantly reduces the rate of brain metastases in small cell lung cancer, especially when administered early at higher doses. For extensive stage small cell lung cancer, MRI surveillance may be an alternative to PCI. While PCI reduces brain metastases in leukemia, the risk of brain involvement is low for some types such as AML. The standard dose for PCI is 1200-1800 cGy in fractions, with timing and volumes depending on the cancer type. Potential toxicities include neurocognitive effects, endocrine disorders, and secondary cancers.
Altered Fractionation Radiotherapy in Head-Neck CancerJyotirup Goswami
Altered fractionation radiotherapy has been shown to improve outcomes for head and neck cancer patients compared to conventional fractionation. Meta-analyses demonstrate significant benefits including improved 5-year locoregional control and overall survival. However, most modern trials do not address fractionation. Hypofractionation shows promise with comparable tumor control and toxicity but reduced treatment time. Ongoing research combines altered fractionation with chemotherapy and radiosensitizers to further improve outcomes while minimizing toxicity.
Reirradiation can provide local tumor control for recurrent head and neck cancer when surgery is not possible. Modern radiation techniques like IMRT allow higher radiation doses to be safely delivered to the tumor while minimizing risks of severe toxicity. Outcomes from reirradiation include a median survival of 10-12 months and 2-year local control rates of 40-64%. Patient selection is important to balance potential benefits of local tumor control against risks of treatment-related side effects.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Induction chemotherapy followed by concurrent chemoradiation (CT-RT) has been studied as an alternative to primary CT-RT for locally advanced head and neck cancers. Meta-analyses have found induction chemotherapy provides no survival benefit compared to primary CT-RT and is associated with increased toxicity. Recent large randomized trials could not demonstrate an improvement with induction chemotherapy due to inadequate accrual and poor compliance with subsequent CT-RT. While induction chemotherapy may improve organ preservation or outcomes for select subgroups like HPV-negative cancers, current evidence indicates primary CT-RT remains the standard of care for most patients.
This document discusses malignant gliomas, specifically focusing on glioblastoma. It provides information on:
- The incidence and types of malignant gliomas, with glioblastomas accounting for 60-70% of cases.
- Signs and symptoms, which commonly include headaches, seizures, and changes in mental status.
- Diagnosis is typically made through brain imaging like MRI that shows irregular, enhancing masses.
- Standard treatment is surgical resection followed by radiation and chemotherapy with temozolomide. However, survival remains poor with a median of 14-15 months.
- Recurrence is common and additional treatment options for recurrent glioblastoma include repeat surgery, stereotactic radiosurgery
HOLISTIC APPROACH IN WHOLE BRAIN RADIATION IN BRAIN METSKanhu Charan
1. Whole brain radiotherapy is commonly used to treat brain metastases but can cause long-term side effects like memory loss and decreased quality of life.
2. A new study aims to spare structures like the hippocampus, cochlea, and parotid glands using IMRT and VMAT to reduce side effects while maintaining tumor coverage.
3. Dosimetry results found that IMRT and VMAT reduced hippocampal, parotid, and cochlear doses by 45-82% compared to conventional radiotherapy, allowing for improved quality of life.
This document summarizes the management of high grade gliomas. It discusses the classification, molecular markers, diagnostic evaluation, treatment including surgery, radiation, chemotherapy, prognostic factors and response assessment for these aggressive brain tumors. Key points include the distinction between glioblastoma and anaplastic astrocytoma/oligodendroglioma, the role of maximal safe resection followed by concurrent chemoradiation using temozolomide as the standard of care, and important prognostic markers like MGMT promoter methylation status. Pseudoprogression and pseudoresponse on imaging are also reviewed.
Prophylactic cranial irradiation (PCI) is used to prevent brain metastases in cancers with a high risk of spreading to the brain. It is indicated for small cell lung cancer and certain leukemias. PCI significantly reduces the rate of brain metastases in small cell lung cancer, especially when administered early at higher doses. For extensive stage small cell lung cancer, MRI surveillance may be an alternative to PCI. While PCI reduces brain metastases in leukemia, the risk of brain involvement is low for some types such as AML. The standard dose for PCI is 1200-1800 cGy in fractions, with timing and volumes depending on the cancer type. Potential toxicities include neurocognitive effects, endocrine disorders, and secondary cancers.
Altered Fractionation Radiotherapy in Head-Neck CancerJyotirup Goswami
Altered fractionation radiotherapy has been shown to improve outcomes for head and neck cancer patients compared to conventional fractionation. Meta-analyses demonstrate significant benefits including improved 5-year locoregional control and overall survival. However, most modern trials do not address fractionation. Hypofractionation shows promise with comparable tumor control and toxicity but reduced treatment time. Ongoing research combines altered fractionation with chemotherapy and radiosensitizers to further improve outcomes while minimizing toxicity.
Reirradiation can provide local tumor control for recurrent head and neck cancer when surgery is not possible. Modern radiation techniques like IMRT allow higher radiation doses to be safely delivered to the tumor while minimizing risks of severe toxicity. Outcomes from reirradiation include a median survival of 10-12 months and 2-year local control rates of 40-64%. Patient selection is important to balance potential benefits of local tumor control against risks of treatment-related side effects.
EBCTCG METAANALYSIS
INDICATION OF POST OP RADIOTHERAPY
Immobilization devices
Conventional planning
Alignment of the Tangential Beam with the Chest Wall Contour
Doses To Heart & Lung By Tangential Fields
CAN WE MARCH WITH MARCH META-ANALYSIS?Kanhu Charan
Altered fractionation radiotherapy, especially hyperfractionated radiotherapy, provides improved overall survival compared to conventional fractionation for head and neck cancers. The 2017 MARCH meta-analysis update, which included over 11,000 patients, confirmed the benefits of altered fractionation. Specifically, hyperfractionated radiotherapy resulted in an 8.1% absolute improvement in 5-year survival. Concurrent chemotherapy with conventional radiation was found to be better than altered fractionation alone, but hyperfractionated radiotherapy seems comparable to chemotherapy with standard radiation.
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
This presentation provides an overview of the standard of care and new advances in the treatment of high-grade glioma, specifically glioblastoma multiforme (GBM) and anaplastic astrocytoma. The key points discussed include:
- The current standard of care for GBM is maximal safe surgical resection followed by concurrent radiation therapy and temozolomide chemotherapy, then adjuvant temozolomide.
- The landmark EORTC/NCIC trial established temozolomide combined with radiation as the standard of care, improving median survival from 12 to 14.6 months.
- MGMT promoter methylation status is the strongest predictor of outcome, with methylated tumors responding better
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
This document discusses reirradiation in recurrent head and neck cancer. It notes that radiation therapy plays a central role in head and neck cancer treatment but recurrence still occurs in 20-35% of patients. Reirradiation presents challenges due to prior radiation exposure and damage to normal tissues. The document discusses treatment options, appropriate patient selection, techniques like IMRT to minimize dose to organs at risk, optimal timing and dosing of reirradiation, and management of toxicities.
Hypofractionated Radiotherapy in Breast Cancer.pptxAsha Arjunan
1) The document outlines studies evaluating hypofractionated whole breast radiotherapy (HF-WBI) for breast cancer treatment. The Ontario Clinical Oncology Group trial found local recurrence rates and overall survival were similar between HF-WBI (42.5 Gy in 16 fractions) and standard WBI (50 Gy in 25 fractions), with lower late toxic effects for HF-WBI.
2) The UK START trials also found similar local recurrence rates between HF-WBI schedules (39-41.6 Gy) and standard WBI (50 Gy), with lower normal tissue effects for HF-WBI. The UK FAST trial found mild/marked breast changes were higher for 30 Gy compared to 50 Gy but not for
This document discusses normal tissue tolerance doses from radiation therapy. It describes the formation of a task force to establish tolerance protocols, with an emphasis on partial volume effects. The earliest publication of tolerance doses is cited from 1972. 28 critical organ sites were included and considered in terms of dose, time factors, and partial volumes irradiated. The significance of these parameters and a quantitative model for normal tissue complication probability are provided. Limitations of the available data and ongoing areas of research are also outlined.
This presentation is intended to refer while doing planning of SBRT Prostate for all practical aspects from Simulation - contouring - planning - treatment. I am sure it will be very useful presentation for any radiation oncologist who are willing to start workflow of SBRT Prostate in the department of radiation oncology
The document discusses medulloblastoma, the most common malignant brain tumor in children. It covers the pathology, molecular subtypes, clinical features, workup, management including surgery, radiation therapy, chemotherapy, and prognosis of medulloblastoma. Risk stratification is based on factors like age, extent of resection, and molecular markers to determine appropriate adjuvant treatment.
1) Brain metastases are the most common intracranial tumors in adults and develop in nearly 30% of cancer patients. They indicate stage IV cancer with a median survival of under 1 year.
2) Treatment options include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). WBRT after surgery or SRS is considered the standard of care to prevent neurologic deaths from brain failure.
3) For a single brain metastasis, surgery or SRS with WBRT provides the best outcomes. For multiple metastases, WBRT is often used but SRS has emerged as an alternative for select patients with few metastases.
1. Radiation therapy plays an important role in the treatment of Wilms tumor, especially for advanced or high-risk cases.
2. It is used preoperatively, postoperatively, and for metastatic disease to reduce the risk of recurrence.
3. The indications and techniques for radiation therapy depend on factors like tumor stage, histology, response to chemotherapy, and whether metastases are present. Precise radiation treatment planning is required to effectively target tumors while sparing healthy tissues.
This document outlines the radiotherapy planning process for pituitary adenoma. It discusses indications for radiotherapy including when medical therapy fails or tumors cause vision problems or compression symptoms. Key steps include pre-radiotherapy evaluation with endocrine and visual assessments, immobilization using customized masks, imaging with CT and MRI to delineate targets and organs at risk, target delineation of GTV, CTV and PTV, dose prescription to targets and nearby structures, and follow up to monitor treatment response and outcomes. The goal of radiotherapy is to control tumor growth and hormone production while minimizing damage to surrounding normal tissues.
The document discusses craniospinal irradiation (CSI), which delivers radiation to the entire cranial-spinal axis to treat intracranial tumors. It was pioneered in the 1950s and is commonly used to treat tumors that may spread through the cerebrospinal fluid such as medulloblastoma. The document outlines the techniques, challenges, indications, and evolving approaches for CSI such as reduced dose protocols and hyperfractionated regimens. It discusses topics like patient positioning, target volumes, critical structures, field arrangements, and the use of newer technologies like virtual simulation.
Brachytherapy improves local control rates for soft tissue sarcomas of the extremities when used as adjuvant therapy after surgery. Interstitial brachytherapy results in 5-year local control rates of 82% for high-grade lesions compared to 69% without brachytherapy. Deeper and larger tumors have worse outcomes, while doses over 60 Gy provide better local control, disease-free survival, and overall survival. Recent data shows intensity-modulated radiation therapy may provide similar local control to brachytherapy with fewer complications. Brachytherapy remains useful for sites where target volumes are extensive or critical structures preclude external beam radiation.
The document provides guidelines for contouring the clinical target volume (CTV) and organs at risk for carcinoma of the cervix treated with 3D conformal radiation therapy or intensity-modulated radiation therapy. The CTV includes the involved lymph nodes (GTV N) and relevant draining nodal groups. The CTV for the primary tumor (CTV-P) includes the gross tumor, uterus, cervix, parametrium, vagina, and ovaries. Detailed guidelines are provided for contouring the lymph node regions, uterus, vagina, and parametrium. A planning target volume (PTV) is created by adding a 10 mm margin to the total CTV. Additional margins are used to create an
1) Accelerated partial breast irradiation (APBI) delivers radiation to only the portion of the breast surrounding the tumor site after breast-conserving surgery, shortening treatment time compared to whole breast irradiation (WBI).
2) Several phase III trials have found APBI to have local control rates comparable to WBI with reduced toxicity, though some trials found slightly higher recurrence rates with APBI.
3) Toxicity and cosmetic outcomes vary by technique, with brachytherapy generally showing better results than external beam techniques.
Brain metastasis is common in cancer patients, occurring via hematogenous spread most often to grey-white matter junctions in the brain. Symptoms include headache, seizures, and neurological deficits. MRI is the preferred imaging modality. Treatment depends on number of metastases and includes surgery for solitary or limited lesions, stereotactic radiosurgery for up to 4 small lesions, and whole brain radiation for multiple metastases. Prognosis is typically less than one year survival even with treatment, though longer survival can occur in select patients with solitary metastases. Neurocognitive decline is a concern, and hippocampal-avoidance whole brain radiation may help preserve cognition compared to standard whole brain radiation.
ROLE OF RADIATION IN BRAIN TUMORS FOR NEUROSURGEONSKanhu Charan
The document discusses neuro-oncology and the role of radiotherapy. It provides statistics on cancer incidence and mortality worldwide. It then covers topics such as the neuro-oncology team, brain tumor types and characteristics, risk factors, clinical presentation, diagnostic techniques including imaging and histopathology, tumor grading, and the roles of surgery, chemotherapy, and radiotherapy in treatment.
Accelerated partial breast irradiation is an alternative to whole breast irradiation in carcinoma breast patients Post breast conserving surgery with equivalent outcome, less duration & less burden on the patient.
The document discusses low grade glioma and provides details about a case. It begins with definitions of diffuse infiltrating gliomas and some key facts. It then provides details of a 39-year-old male patient who presented with frontal headache and personality changes. MRI showed a left temporal lesion measuring 6cm without enhancement. The document discusses the imaging protocol and findings in detail. It provides neuropathology findings of diffuse glioma, IDH mutant, and 1p/19q codeletion, consistent with oligodendroglioma grade II. The document discusses surgery details, post-op imaging, and recommendations for adjuvant treatment including radiation, chemotherapy options and dose.
Hypofractionated radiotherapy regimens are being re-explored for their potential logistical benefits compared to conventionally fractionated radiotherapy. Several studies have evaluated hypofractionation for prostate cancer, finding comparable rates of tumor control and acceptable toxicity profiles. The CHHiP trial directly compared 57Gy in 19 fractions to 74Gy in 37 fractions for prostate cancer, finding no significant differences in patient-reported bowel symptoms up to 2 years post-treatment.
EBCTCG METAANALYSIS
INDICATION OF POST OP RADIOTHERAPY
Immobilization devices
Conventional planning
Alignment of the Tangential Beam with the Chest Wall Contour
Doses To Heart & Lung By Tangential Fields
CAN WE MARCH WITH MARCH META-ANALYSIS?Kanhu Charan
Altered fractionation radiotherapy, especially hyperfractionated radiotherapy, provides improved overall survival compared to conventional fractionation for head and neck cancers. The 2017 MARCH meta-analysis update, which included over 11,000 patients, confirmed the benefits of altered fractionation. Specifically, hyperfractionated radiotherapy resulted in an 8.1% absolute improvement in 5-year survival. Concurrent chemotherapy with conventional radiation was found to be better than altered fractionation alone, but hyperfractionated radiotherapy seems comparable to chemotherapy with standard radiation.
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
This presentation provides an overview of the standard of care and new advances in the treatment of high-grade glioma, specifically glioblastoma multiforme (GBM) and anaplastic astrocytoma. The key points discussed include:
- The current standard of care for GBM is maximal safe surgical resection followed by concurrent radiation therapy and temozolomide chemotherapy, then adjuvant temozolomide.
- The landmark EORTC/NCIC trial established temozolomide combined with radiation as the standard of care, improving median survival from 12 to 14.6 months.
- MGMT promoter methylation status is the strongest predictor of outcome, with methylated tumors responding better
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
This document discusses reirradiation in recurrent head and neck cancer. It notes that radiation therapy plays a central role in head and neck cancer treatment but recurrence still occurs in 20-35% of patients. Reirradiation presents challenges due to prior radiation exposure and damage to normal tissues. The document discusses treatment options, appropriate patient selection, techniques like IMRT to minimize dose to organs at risk, optimal timing and dosing of reirradiation, and management of toxicities.
Hypofractionated Radiotherapy in Breast Cancer.pptxAsha Arjunan
1) The document outlines studies evaluating hypofractionated whole breast radiotherapy (HF-WBI) for breast cancer treatment. The Ontario Clinical Oncology Group trial found local recurrence rates and overall survival were similar between HF-WBI (42.5 Gy in 16 fractions) and standard WBI (50 Gy in 25 fractions), with lower late toxic effects for HF-WBI.
2) The UK START trials also found similar local recurrence rates between HF-WBI schedules (39-41.6 Gy) and standard WBI (50 Gy), with lower normal tissue effects for HF-WBI. The UK FAST trial found mild/marked breast changes were higher for 30 Gy compared to 50 Gy but not for
This document discusses normal tissue tolerance doses from radiation therapy. It describes the formation of a task force to establish tolerance protocols, with an emphasis on partial volume effects. The earliest publication of tolerance doses is cited from 1972. 28 critical organ sites were included and considered in terms of dose, time factors, and partial volumes irradiated. The significance of these parameters and a quantitative model for normal tissue complication probability are provided. Limitations of the available data and ongoing areas of research are also outlined.
This presentation is intended to refer while doing planning of SBRT Prostate for all practical aspects from Simulation - contouring - planning - treatment. I am sure it will be very useful presentation for any radiation oncologist who are willing to start workflow of SBRT Prostate in the department of radiation oncology
The document discusses medulloblastoma, the most common malignant brain tumor in children. It covers the pathology, molecular subtypes, clinical features, workup, management including surgery, radiation therapy, chemotherapy, and prognosis of medulloblastoma. Risk stratification is based on factors like age, extent of resection, and molecular markers to determine appropriate adjuvant treatment.
1) Brain metastases are the most common intracranial tumors in adults and develop in nearly 30% of cancer patients. They indicate stage IV cancer with a median survival of under 1 year.
2) Treatment options include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). WBRT after surgery or SRS is considered the standard of care to prevent neurologic deaths from brain failure.
3) For a single brain metastasis, surgery or SRS with WBRT provides the best outcomes. For multiple metastases, WBRT is often used but SRS has emerged as an alternative for select patients with few metastases.
1. Radiation therapy plays an important role in the treatment of Wilms tumor, especially for advanced or high-risk cases.
2. It is used preoperatively, postoperatively, and for metastatic disease to reduce the risk of recurrence.
3. The indications and techniques for radiation therapy depend on factors like tumor stage, histology, response to chemotherapy, and whether metastases are present. Precise radiation treatment planning is required to effectively target tumors while sparing healthy tissues.
This document outlines the radiotherapy planning process for pituitary adenoma. It discusses indications for radiotherapy including when medical therapy fails or tumors cause vision problems or compression symptoms. Key steps include pre-radiotherapy evaluation with endocrine and visual assessments, immobilization using customized masks, imaging with CT and MRI to delineate targets and organs at risk, target delineation of GTV, CTV and PTV, dose prescription to targets and nearby structures, and follow up to monitor treatment response and outcomes. The goal of radiotherapy is to control tumor growth and hormone production while minimizing damage to surrounding normal tissues.
The document discusses craniospinal irradiation (CSI), which delivers radiation to the entire cranial-spinal axis to treat intracranial tumors. It was pioneered in the 1950s and is commonly used to treat tumors that may spread through the cerebrospinal fluid such as medulloblastoma. The document outlines the techniques, challenges, indications, and evolving approaches for CSI such as reduced dose protocols and hyperfractionated regimens. It discusses topics like patient positioning, target volumes, critical structures, field arrangements, and the use of newer technologies like virtual simulation.
Brachytherapy improves local control rates for soft tissue sarcomas of the extremities when used as adjuvant therapy after surgery. Interstitial brachytherapy results in 5-year local control rates of 82% for high-grade lesions compared to 69% without brachytherapy. Deeper and larger tumors have worse outcomes, while doses over 60 Gy provide better local control, disease-free survival, and overall survival. Recent data shows intensity-modulated radiation therapy may provide similar local control to brachytherapy with fewer complications. Brachytherapy remains useful for sites where target volumes are extensive or critical structures preclude external beam radiation.
The document provides guidelines for contouring the clinical target volume (CTV) and organs at risk for carcinoma of the cervix treated with 3D conformal radiation therapy or intensity-modulated radiation therapy. The CTV includes the involved lymph nodes (GTV N) and relevant draining nodal groups. The CTV for the primary tumor (CTV-P) includes the gross tumor, uterus, cervix, parametrium, vagina, and ovaries. Detailed guidelines are provided for contouring the lymph node regions, uterus, vagina, and parametrium. A planning target volume (PTV) is created by adding a 10 mm margin to the total CTV. Additional margins are used to create an
1) Accelerated partial breast irradiation (APBI) delivers radiation to only the portion of the breast surrounding the tumor site after breast-conserving surgery, shortening treatment time compared to whole breast irradiation (WBI).
2) Several phase III trials have found APBI to have local control rates comparable to WBI with reduced toxicity, though some trials found slightly higher recurrence rates with APBI.
3) Toxicity and cosmetic outcomes vary by technique, with brachytherapy generally showing better results than external beam techniques.
Brain metastasis is common in cancer patients, occurring via hematogenous spread most often to grey-white matter junctions in the brain. Symptoms include headache, seizures, and neurological deficits. MRI is the preferred imaging modality. Treatment depends on number of metastases and includes surgery for solitary or limited lesions, stereotactic radiosurgery for up to 4 small lesions, and whole brain radiation for multiple metastases. Prognosis is typically less than one year survival even with treatment, though longer survival can occur in select patients with solitary metastases. Neurocognitive decline is a concern, and hippocampal-avoidance whole brain radiation may help preserve cognition compared to standard whole brain radiation.
ROLE OF RADIATION IN BRAIN TUMORS FOR NEUROSURGEONSKanhu Charan
The document discusses neuro-oncology and the role of radiotherapy. It provides statistics on cancer incidence and mortality worldwide. It then covers topics such as the neuro-oncology team, brain tumor types and characteristics, risk factors, clinical presentation, diagnostic techniques including imaging and histopathology, tumor grading, and the roles of surgery, chemotherapy, and radiotherapy in treatment.
Accelerated partial breast irradiation is an alternative to whole breast irradiation in carcinoma breast patients Post breast conserving surgery with equivalent outcome, less duration & less burden on the patient.
The document discusses low grade glioma and provides details about a case. It begins with definitions of diffuse infiltrating gliomas and some key facts. It then provides details of a 39-year-old male patient who presented with frontal headache and personality changes. MRI showed a left temporal lesion measuring 6cm without enhancement. The document discusses the imaging protocol and findings in detail. It provides neuropathology findings of diffuse glioma, IDH mutant, and 1p/19q codeletion, consistent with oligodendroglioma grade II. The document discusses surgery details, post-op imaging, and recommendations for adjuvant treatment including radiation, chemotherapy options and dose.
Hypofractionated radiotherapy regimens are being re-explored for their potential logistical benefits compared to conventionally fractionated radiotherapy. Several studies have evaluated hypofractionation for prostate cancer, finding comparable rates of tumor control and acceptable toxicity profiles. The CHHiP trial directly compared 57Gy in 19 fractions to 74Gy in 37 fractions for prostate cancer, finding no significant differences in patient-reported bowel symptoms up to 2 years post-treatment.
Hypofractionated radiotherapy regimens provide comparable tumour control to conventional fractionation for several cancer types based on multiple studies. For prostate cancer, studies found hypofractionated regimens of 57Gy in 19 fractions and 60Gy in 20 fractions resulted in similar biochemical control and toxicity outcomes as 74Gy in 37 fractions at median follow ups of 5 years. However, a larger study found 64.6Gy in 19 fractions significantly increased grade 3 gastrointestinal toxicity compared to 78Gy in 39 fractions for intermediate-high risk prostate cancer. Estimated alpha/beta ratios from studies on breast and other cancers support hypofractionation for tissues with low alpha/beta ratios.
1. SABR has emerged as an alternative to surgery for medically operable early-stage NSCLC based on case-control studies showing equivalence in outcomes.
2. Randomized trials are still needed to provide level 1 evidence of equivalence since residual differences remain between surgery and SABR cohorts in existing studies.
3. Ongoing trials such as STABLE-MATES, VALOR, and SABRTOOTH aim to address this evidence gap through randomized comparisons of SABR to surgery.
This document discusses the management of intermediate and high risk prostate cancer. It begins by providing background on prostate cancer epidemiology and risk stratification. It then covers various treatment options including observation, active surveillance, radical prostatectomy, radiotherapy, and androgen deprivation therapy. Several studies comparing the efficacy of radiotherapy alone versus radiotherapy with short or long-term ADT are summarized. For intermediate risk prostate cancer, the document recommends 4-6 months of ADT with radiotherapy based on trial results. For high risk prostate cancer, 2-3 years of ADT with radiotherapy is recommended.
Osteosarcoma is the most common primary bone cancer, often arising in the appendicular skeleton of teenagers and young adults. It is typically a high grade tumor associated with rapid bone proliferation and spread. Treatment involves complete surgical resection with limb-sparing surgery when possible, along with chemotherapy both before and after surgery. Radiation therapy may be used for unresectable or incompletely resected tumors. Prognostic factors include tumor size, location of metastases, and response to preoperative chemotherapy. While survival has improved with modern multimodal treatment, new strategies are still needed given the risk of recurrence and lung metastases.
1. Low grade gliomas are relatively slow growing brain tumors that typically occur in younger people and have better survival rates than high grade gliomas.
2. Treatment options for low grade gliomas include observation, biopsy, surgical resection, radiotherapy, chemotherapy, and molecular therapy depending on factors such as tumor location, size, and the patient's age and health status.
3. The main treatment goals are maximal tumor resection while preserving brain function, relieving symptoms like seizures, obtaining a diagnosis, and improving outcomes by delaying malignant transformation or progression to a high grade glioma.
This document discusses the radiotherapeutic management of prostate cancer. It begins by introducing the multidisciplinary team involved in diagnosis and treatment. It then covers diagnosis, including various screening tests and pathology findings. Treatment options discussed include observation, surgery, radiation therapy and hormonal treatment. The document focuses on the evolution of radiation techniques from conventional to IMRT and brachytherapy. It compares outcomes and side effects of different local treatment modalities and discusses the role of neoadjuvant hormonal therapy.
Evolution of treatment strategies of brain tumorsAnil Gupta
The document discusses the evolution of treatment strategies for brain gliomas. It begins by providing background on gliomas and their classification. It then discusses advances in surgery, including neuronavigation, fluorescent guided resection, and intraoperative imaging. It also covers the evolution of radiotherapy techniques from early 2D approaches to modern 3D conformal radiotherapy and intensity modulated radiotherapy. Adjuvant therapies like chemotherapy and targeted drugs are also mentioned. Overall the document traces the development of surgical and radiation based approaches for glioma treatment over time.
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
This document discusses high grade gliomas, which include anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and glioblastoma multiforme. It describes the epidemiology, clinical features, prognosis, and management of these tumors. The optimal treatment involves maximal safe surgical resection followed by concurrent chemoradiation and adjuvant chemotherapy. Radiotherapy techniques such as 3D conformal radiation therapy and intensity-modulated radiation therapy aim to deliver a dose of 60 Gy to the tumor volume while sparing surrounding normal brain tissue. However, dose escalation above standard doses has not shown a survival benefit.
Colon cancer is the second and third most common cancer in males and females. Screening programs have led to a reduction in late-stage diagnoses and mortality. Precise identification of prognostic patient groups allows for more targeted adjuvant therapy, improving disease-free and overall survival. Molecular markers of tumor aggressiveness aid in selecting optimal treatment approaches, increasing response rates, progression-free, and overall survival. A multidisciplinary team approach is essential for managing metastatic colon cancer with the goal of surgical cure in organ-limited disease.
This document discusses diagnostic approaches for indeterminate biliary strictures. It notes that obtaining a histological diagnosis can be challenging due to low tumor cellularity and desmoplastic reactions. Multiple sampling techniques during ERCP like brush cytology, forceps biopsy, and needle biopsy have low and variable sensitivities ranging from 8-57% individually. Combining sampling methods can improve yields to around 63%. Newer devices like a scraping device and needle introducer with forceps have shown promise with sensitivities around 65-85% but require further study. Obtaining an adequate tissue sample remains a challenge in diagnosing these strictures.
This document discusses the management of oligometastatic breast cancer. It begins by providing historical context on the evolution of understanding and treatment of breast cancer. It then defines oligometastatic breast cancer as limited metastases that may be amenable to local treatment. The document reviews evidence that local ablative therapy combined with systemic therapy can improve outcomes for select patients. It also discusses several studies that provide randomized evidence supporting the use of stereotactic ablative radiotherapy to treat limited metastatic sites. In conclusion, the document emphasizes that careful patient selection is important to identify those most likely to benefit from localized treatment of oligometastatic disease.
This document summarizes research on using CyberKnife and TomoTherapy for treating liver cancer. It discusses studies from Korea, Taiwan, China, Belgium, and the US on using these technologies for inoperable primary or recurrent hepatocellular carcinoma and liver metastases. Key findings included high response rates and local control. Current research interests discussed standardizing treatment protocols and criteria across countries through guidelines. Future directions may involve regional collaboration on studies to further optimize these radiotherapy approaches for liver cancer.
1) The document discusses optimal adjuvant treatment for early stage high risk endometrial carcinoma.
2) It defines early stage high risk disease as having multiple adverse risk factors like grade 3 histology, deep myometrial invasion, lymphovascular space invasion, or lymph node metastases.
3) Treatment recommendations include pelvic radiation or vaginal brachytherapy based on risk factors, with chemotherapy also considered for very high risk cases. Ongoing trials are exploring integrating molecular markers into risk assessment and treatment decisions.
The document discusses the role of radiation therapy in treating oligometastatic prostate cancer, noting that radiation can potentially achieve durable responses or even cure in some cases when metastases are limited. It reviews definitions of oligometastatic prostate cancer, the rationale for local and metastasis-directed radiation therapy, clinical evidence from studies on the use of external beam radiation therapy and stereotactic body radiation therapy to treat the primary tumor and metastases, and outcomes from these studies including local control rates, progression-free survival, and overall survival. The document concludes that radiation therapy plays an important role in the treatment of oligometastatic prostate cancer.
This document discusses translational medicine research on biomarkers and targets for hepatocellular carcinoma (HCC). It contains the following key points in 3 sentences:
The document outlines an HCC study that aims to discover biomarkers through proteomics and gene expression analysis of clinical samples, identify targets through whole genome sequencing and clinical data analysis, and improve understanding of disease biology. It summarizes the study's goals as biomarker discovery for diagnosis, prognosis, and treatment response as well as target identification and assessment. The study utilizes a translational medicine workflow involving collection of clinical samples and molecular studies to identify biomarkers and targets which can then be validated in cell lines, animal models, and clinical trials.
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATROKanhu Charan
This document appears to be a newsletter or e-book with summaries of oncology research articles and case studies from March 2024 to mid-April 2024. It includes summaries on topics like radiotherapy dosing in head and neck cancer, genetic factors in breast cancer treatment, algorithms for surveillance of colorectal polyps, emerging tracers in neuro-oncology, target delineation workflows for various cancer sites, radiation therapy options for pituitary adenoma, comparisons of APBI guidelines for breast cancer, and associations between Chlamydia psittaci and orbital MALT lymphoma. The document also notes that April is National Oral Cancer Awareness Month.
TARGET DELINEATION OF THORACIC NODAL. STATIONKanhu Charan
The document discusses the different thoracic nodal stations that are relevant for staging lung cancer. It lists 24 different nodal station groups in the thoracic region, including supraclavicular, upper paratracheal, prevertebral, lower paratracheal, subaortic, para aortic, carinal, paraesophageal, and hilar nodal stations. Accurate identification of involved nodal stations is important for determining the stage and treatment planning for lung cancer patients.
TARGET DELINEATION IN RECTUM CANCER BY DR KANHUKanhu Charan
This document outlines the workflow for target delineation in radiation oncology for carcinoma of the rectum. It defines the gross tumor volume for the primary tumor (GTVp) and involved nodes (GTVn), as well as the clinical target volumes (CTVs) which add margins around the GTVs to cover microscopic disease. It describes the borders of the mesorectum and lists the lymph node regions included in the CTV for involved nodes. It concludes by specifying the planning target volumes (PTVs) which expand the CTVs and listing the dose schedules.
TARGET DELINEATION IN ANAL CANAL CANCER BY DR KANHUKanhu Charan
1. The document discusses target delineation and radiation therapy workflow for anal cancer, including definitions of gross tumor volume (GTV) and clinical target volumes (CTVs) based on anatomical locations.
2. It provides guidelines for determining margins around the GTV and nearby anatomical structures to create the CTVs for the primary tumor (CTVp), involved nodes (CTVn), and elective nodal regions (CTVnLR) to cover possible microscopic disease.
3. Treatment planning volumes (PTVs) are created by adding margins to the CTVs, with the PTV-HR receiving the full prescription dose and the PTV-LR receiving a lower dose.
TARGET DELINEATION IN VULVAL CANCER BY DR KANHUKanhu Charan
The document outlines the steps and guidelines for target delineation in vulval cancer radiation therapy planning. It discusses delineating the gross tumor volume (GTV), clinical target volume (CTV), organs at risk (OAR), and planning target volume (PTV). Specific guidelines are provided for contouring depending on the location and extent of the primary tumor, including the vulva, mons pubis, vagina, anorectum, urethra, and clitoris. Radiation dose parameters and OAR constraints are also reviewed. The target delineation workflow aims to adequately cover suspected disease while minimizing dose to surrounding healthy tissues.
TARGET DELINEATION IN CERVIX CANCER BY DR KANHUKanhu Charan
This document outlines the 10 step workflow for target delineation in cervical cancer radiotherapy treatment planning. It describes the clinical target volumes that should be contoured for the primary gross tumor (GTVp), primary clinical target (CTVp), nodal gross tumor (GTVn), nodal clinical targets (CTVn) and elective nodal volumes. It provides explanations and guidelines for delineating each target volume, including the parametrium and nodal regions. Diagrams and images are included to illustrate the anatomical locations and boundaries of the target volumes.
Oncology cartoons by Dr Kanhu Charan PatroKanhu Charan
This document provides guidance on target volume delineation for vulval cancer from the Royal College of Radiologists. It outlines the clinical target volume (CTV) for different disease sites, including the vulva, mons pubis, vagina, anorectum, urethra and pelvic nodes. Contouring workflows and organ-at-risk constraints are also discussed. Recommendations are given for radiation dose and treatment of resectable and unresectable head and neck cancer. The final item notes that smoking increases the risk of kidney cancer.
RADIATION THERAPY IN BILIARY TRACT CANCERKanhu Charan
This document provides information on biliary tract cancers and the role of chemoradiotherapy in their treatment. It discusses the anatomy and types of biliary cancers, risk factors, presentation, diagnosis, staging, and standard treatment approaches including surgery. It then focuses on the evidence and guidelines for use of radiation therapy, including as adjuvant therapy after surgery for positive margins or nodes, as radical/definitive therapy for unresectable disease, and for palliation of symptoms from local or metastatic disease. Key findings are that chemoradiation improves local control and survival as adjuvant or radical therapy, and brachytherapy and external beam radiation are effective for palliation. Optimal regimens involve fluorouracil or capec
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUMEKanhu Charan
Dr Kanhu Charan Patro provides summaries of statistical concepts in 3 sentences or less, beginning each summary with the date. Summaries from January 19th to February 15th are presented, covering topics such as p-values, censoring in survival analysis, hazard ratios, and ISRS guidelines for stereotactic radiosurgery. On February 15th, a 3 sentence summary of World Cancer Day is provided, noting the date it is held, the organization that leads it, and the 2024 slogan of "Close the care gap".
Molecular Profile of Endometrial cancer.Kanhu Charan
The document discusses molecular analysis and classification of endometrial cancer, which impacts staging and treatment decisions. It describes aggressive histological subtypes and how molecular markers like POLE mutations, MMRd, and p53 abnormalities determine low, intermediate, or high risk stratification. Ongoing PORTEC trials are exploring the impact of molecular profiling on adjuvant treatment, with POLE mutations potentially downstaging while p53 mutations upstage disease. Molecular analysis provides predictive significance for personalized adjuvant therapies in endometrial cancer.
ONCOLOGY CARTOONS JANUARY 2024 BY DR KANHU CHARAN PATROKanhu Charan
This document discusses cervical cancer awareness month in January and provides 3 recommendations: 1) Be loyal to your partner to reduce risk of HPV infection, 2) Maintain genital hygiene, 3) Get vaccinated against HPV to prevent cervical cancer, and 4) Get screened regularly to detect cervical cancer early.
TYPES OF STATISTICAL DATA BY DR KANHU CHARAN PATROKanhu Charan
This document discusses types of data in statistics. It defines qualitative and quantitative data, and describes different types of quantitative data like discrete, continuous, ordinal, and nominal. Examples of love and fight data are provided to illustrate these concepts. The document concludes with a short poem about not fighting in marriage.
WHY STEREOTATXY IN CRANIAL AVM / DR KANHU CHARAN PATROKanhu Charan
This document discusses stereotactic radiosurgery (SRS) for the treatment of cerebral arteriovenous malformations (AVMs). It begins by explaining what an AVM is and the risks they pose if untreated, such as bleeding in the brain. It then covers treatment options for AVMs and why SRS is often preferred for certain cases, such as when the AVM is in an eloquent or deep brain area. The document provides details on patient selection, imaging and planning for SRS, anticipated outcomes, and risks of treatment complications. It emphasizes the importance of multidisciplinary discussion and informed consent when determining if SRS is appropriate for a patient's individual AVM.
1) SBRT is an effective treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). In a study of 70 HCC patients with PVTT treated with SBRT, median survival was 10 months and 6-month and 12-month survival rates were 67.3% and 40% respectively.
2) Patients who received SBRT combined with transarterial chemoembolization (TACE) had significantly longer survival compared to those who did not receive TACE after SBRT.
3) SBRT is a promising bridging therapy prior to liver transplantation or hepatectomy by downstaging PVTT to make these curative procedures possible.
DR KANHU CHARTAN PATRO/ FOR ENT SURGEONSKanhu Charan
1. Radiotherapy plays a crucial role in the treatment of head and neck cancers, both as a primary treatment and in combination with surgery. It is used for cancers of the nasopharynx, larynx, hypopharynx, and as postoperative treatment for most oral cancers.
2. Advances in radiotherapy technology such as IMRT have allowed for better tumor targeting while minimizing doses to surrounding healthy tissues, reducing treatment toxicities. Imaging techniques such as PET-CT provide improved visualization of tumors and affected lymph nodes, helping determine accurate target volumes.
3. Organ preservation approaches using radiotherapy and chemotherapy are increasingly used to treat head and neck cancers, avoiding disfiguring surgeries while achieving high
DECEMBER 2023 ONCOLOGY CARTOONS DRKANHU CHARAN PATROKanhu Charan
Here are the key points about the hepatitis B vaccine and liver cancer:
- Hepatitis B virus (HBV) infection can lead to chronic hepatitis B and significantly increase the risk of developing liver cancer later in life.
- The hepatitis B vaccine is effective at preventing HBV infection and therefore helps prevent liver cancers caused by the virus. It was the first vaccine referred to as an "anti-cancer" vaccine by the FDA.
- Around 25% of people with chronic HBV infection may develop liver cancer according to the CDC. Getting vaccinated helps avoid this risk.
- The hepatitis B vaccine is available and affordable in India, ranging from around 45 rupees per pediatric dose to 250 rupees for the
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...Université de Montréal
“Psychiatry and the Humanities”: An Innovative Course at the University of Montreal Expanding the medical model to embrace the humanities. Link: https://www.psychiatrictimes.com/view/-psychiatry-and-the-humanities-an-innovative-course-at-the-university-of-montreal
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
1. MANAGEMENT OF DIFFUSE GLIOMAS
6/20/2021 1
DR KANHU CHARAN PATRO
MD,DNB(RADIATION ONCOLOGY),MBA,FAROI(USA),PDCR,CEPC
HOD,RADIATION ONCOLOGY
Mahatma Gandhi Cancer Hospital And Research Institute, Visakhapatnam
drkcpatro@gmail.com M-9160470564
2. Definition
The term diffuse infiltrating means there is no
identifiable border between the tumour and
normal brain tissue, even though the borders
may appear well-marginated on imaging
6/20/2021 2
7. The team
• Neuroradiologists
• Neurosurgeons
• Neurologists
• Neuropathologist
• Radiotherapy oncologists
• Medical oncologists
6/20/2021 7
8. Some facts
• Diffuse astrocytomas, also referred to as low-grade infiltrative
astrocytomas, are designated as WHO II tumours of the brain.
• Commonly, astrocytomas are confined to white matter although they
can infiltrate and expand the adjacent cortex in later stages.
• However, oligodendroglioma is frequently a cortical-based tumor.
• Although contrast enhancement has been classically associated
with a higher degree of malignancy, contrast enhancement may be
seen in up to 20% of LGG
6/20/2021 8
22. T2-FLAIR
mismatch sign
• The T2-FLAIR mismatch sign describes the
MRI appearance considered a highly specific
radiogenomic signature for diffuse
astrocytoma (IDH-mutant, 1p/19q-non-
codeleted molecular status), as opposed to
other lower-grade gliomas.
• It is particularly helpful in distinguishing a
diffuse astrocytoma from
an oligodendroglioma that will not
demonstrate T2-FLAIR mismatch.
• On T2 weighted images, these tumours have
extensive areas of fairly homogeneous and
strikingly high signal.
• On T2-FLAIR, instead, the majority of these
areas become relatively hypointense in signal
due to incomplete suppression.
• At the margins of the tumour, a rim of
hyperintensity is usually seen.
6/20/2021 22
26. Surgery recommendation
• It is assumed that surgery should aim for the greater extent of resection as it
would Increase survival and potentially alter the natural history of the
disease: gross total removal or subtotal tumor removal (when feasible and
safe) is superior to biopsy in terms of decreasing the rate of tumor
progression and also have positive impact in overall survival estimation of
resection less than 50% would lead to consider biopsy.
• A retrospective multicentric study analyzing 1097 patients (in which the
assessed population was divided into three subgroups depending on the
extent of resection: 100%, 50–99% and less than 50%) showed that the
amount of residual lesion impacted on the course of the disease (OS was
10.5 and 14 years for patients with a less than 50 and 50–99% Extent of
resection, being unreached instead after 15 years for patients with no
residual tumor).
• Biopsy is indicated when diagnosis is needed in deep lesions (including
brainstem), diffuse and/or multicentric tumor or any other contraindication
for open resection.
• Biopsy can be stereotactic (framed or frameless) or open. Neuronavigated
non-framed biopsy is gaining acceptance.
6/20/2021 26
31. Oligodendroglioma
6/20/2021 31
Micrograph of an oligodendroglioma showing the characteristic branching,
small, chicken wire-like blood vessels and fried egg-like cells, with clear cytoplasm
and well-defined cell borders. H&E stain. Those with uniformly rounded nuclei and
perinuclear halo (‘‘fried egg’’) are considered oligodendrogliomas.
32. Diffuse astrocytoma
6/20/2021 32
1. Nuclear irregularities with fibrillary processes
are diagnosed as astrocytoma
2. Infiltrative, diffuse growth pattern with the
formation of secondary structures of Scherer
Moderately cellular
3. Irregular cell distribution
4. Nuclear atypia is typical, yet variable: enlarged
elongated hyperchromatic irregular nuclei
5. Variable amount of cytoplasm: may be scant
(naked nuclei) to moderate with processes
creating a fibrillary background
6. No mitotic activity (a single mitosis in a sizable
specimen is allowed)
7. No necrosis or microvascular proliferation
8. Variable microcystic change
9. Variable calcification
33. Gemistocytic astrocytoma
6/20/2021 33
1. Gemistocytes are cells swollen with
hyaline, pink cytoplasm that is reactive
for GFAP
2. Their hyperchromatic and angulated
nuclei are at the rim of the cells,
producing a bizarre caricature of a
reactive astrocyte.
3. A variant of diffuse astrocytic tumor is
gemistocytic astrocytoma,
characterized by [20% cells with
abundant eccentrically placed
cytoplasm, this variant tends to show a
rapid malignant progression
34. Gemistocytic
astrocytoma
6/20/2021 34
Gemistocytic astrocytomas are
characterised by a significant
gemistocytes population, which are large
cells with their cytoplasm filled with
eosinophilic material displacing the
nucleus eccentrically.
It is important to note that other
gliomas (e.g. fibrillary
astrocytoma and oligodendrogliomas)
can have occasional gemistocytes,
without being designated a
gemistocytic astrocytoma.
Some authors use a cut off of 20% of the
tumour cells being gemistocytes before
designating it as a gemistocytic
astrocytoma.
Although there are no specific features
which allow pre-biopsy diagnosis,
gemistocytic astrocytomas are almost
always supratentorial and usually
located in the frontal lobes
36. Radiotherapy trials
6/20/2021 36
TRIAL INCLUSION ARM RESULT
RTOG 9802 1. Age<40 years
2. GTS
No adjuvant 1. OS rates at 2 and 5 years were: 99
and 93%, respectively.
2. PFS rate at 5 year: 48%
3. In patients without unfavorable
prognostic factors the 2- and 5-year
PFS rates were 100 and
70%.respectively.
Shaw EG. J Neurosurg
(2008)
37. Radiotherapy trials
6/20/2021 37
TRIAL INCLUSION ARM RESULT
EORTC 22844 1. Low-grade
astrocytomas
Low dose RT
(45 Gy)
VS
High dose RT
(59.4 Gy)
1. No significant difference in the 5-
years OS between low-dose arm
(58%) and high dose arm (59%).
2. No significant difference in the 5-
years PFS (47% verss 50%)
Karim AB. Int J Radiat Oncol Biol Phys
1996
38. Radiotherapy trials
6/20/2021 38
TRIAL INCLUSION ARM RESULT
EORTC 22845
Interim
1. Low-grade
astrocytoma
Early RT
(54 Gy)
VS
No RT
1. Early RT showed an improvement in
TTP (4.8 versus 3.4 years; p = 0.02).
HR = 0.68 (95% CI 0.50–0.94).
2. No differences in OS: HR = 1.15 (95%
CI 0.67–1.74).
3. The 5-year OS rate were: 63 versus
66% (p = 0.49).
(Karim AB. Int J Radiat Oncol Biol
Phys(2002)
39. Radiotherapy trials
6/20/2021 39
TRIAL INCLUSION ARM RESULT
EORTC 22845 1. WHO grade II RT (54 Gy)
after biopsy
resection,
VS
No RT until
progression
1. Early RT was associated with an
improvement PFS (5.3 versus 3.4
years): HR = 0.59; 95% CI 0.45–0.77
(p = 0.0001).
2. No difference in OS (7.4 versus 7.2
years): HR = 0.97; 95% CI 0.71–1.34
8 (p = 0.872)
3. Seizure control also improved in
patients treated with early
radiotherapy.
Van den Bent MJ. Lancet
2005)
40. Radiotherapy trials
6/20/2021 40
TRIAL INCLUSION ARM RESULT
NCCTG/RTOG/
ECOG
1. WHO grade II
gliomas
Low dose RT
(50.4 Gy)
VS
High dose RT
(64.8 Gy)
1. No differences in 2- and 5-year OS
between low dose (94 and 75%) and
high dose arm (85 and 64%) (p =
0.48)
2. Patients treated with high doses
showed higher rates of severe
radionecrosis (5 versus 2.5%)
Shaw EG. J Clin Oncol.
(2002)
41. Radiotherapy trials
6/20/2021 41
TRIAL INCLUSION ARM RESULT
RTOG 9802 1. Age >40 years
and/or subtotal
resection
RT (54 Gy)
VS
RT (54 Gy)
And 6 cycles
of adjuvant
PCV
1. Post-RT + PCV conferring a survival
advantage over RT alone: median OS
13.3 versus 7.8 years (HR: 0.59; 95%
CI 0.42–0.83; p = 0.003).
2. Median PFS was prolonged in
patients who received PCV (10.4
versus 4.0 years): HR: 0.50; 95% CI
0.36–0.68 (p0.001)
Buckner JC. N Engl J
Med(2016)
42. Radiotherapy trials
6/20/2021 42
TRIAL INCLUSION ARM RESULT
RTOG 0424 LGG with >3 risk
factors for
recurrence (age >
40 years,
astrocytoma
histology,
bihemispheric
tumor, tumor
diameter[6 cm,
neurologic
function status
Concurrent
radiation
(54 Gy) with
TMZ f/b
monthly TMZ
1. The 3-year OS rate was 73% (95% CI
65.3–80.8%), significantly higher
than the historical control OS rate of
54% (p0.001).
2. The 5-year OS rate was 57.1% (95%
CI 47.7–66.5%), and the median OS
has not yet been reached.
3. The 3-year PFS was 59.2% (95% CI
50.7–67.8%) and median PFS was
4.5 years (95% CI 3.5–NA).
Fisher BJ. J Radiat Oncol Biol
43. Radiotherapy trials
6/20/2021 43
TRIAL INCLUSION ARM RESULT
EORTC 22033 LGG with at least
one high-risk
feature (aged>40
years,
progressive
disease, tumour
Size>5 cm, tumour
crossing the
midline, or
neurological
symptoms)
RT ( 50.4 Gy
VERSUS
Dose-dense
oral TMZ
(75 mg/m2
once daily for
21 days,
every
28 days, for a
maximum
of 12 cycles)
1. There was no significant difference
in PFS between TMZ group (39
months) and RT group (46 months):
HR: 1.16; 95% CI 0.9–1.5 (p = 0.22).
2. Median OS has not been reached.
3. Better PFS in IDH-mutant
noncodeleted patients treated with
radiotherapy: 55 versus 36 months.
HR 1.86; 95% CI 1.21–2.87 (p =
0.0043)
Baumert BG Lancet Oncol.
44. Radiotherapy trials
6/20/2021 44
TRIAL INCLUSION ARM RESULT
Wahl M,et al LGG and gross
residual disease
Monthly
cycles of TMZ
for up to 1
year or until
disease
progression
1. The median PFS and OS were 4.2
and 9.7 years, respectively.
2. Patients with 1p/19q codeletion
demonstrated a 0% risk of
progression during treatment
Neuro
Oncol.(2017)
46. IDH wild type LGG
• Low-grade gliomas that lack a mutation in IDH make up a relatively small
proportion of all low-grade gliomas and carry a significantly worse prognosis
compared with IDH mutant tumors
• There are no randomized trials to guide treatment in patients with IDH-wildtype
low-grade gliomas, and these tumors are underrepresented in historical studies
of low-grade glioma, including the RTOG 9802 trial reviewed above.
• Some of these tumors bear molecular similarity to glioblastoma (e.g., TERT
mutations, loss of heterozygosity of chromosome 10).
• In such cases, we propose to treat patients with immediate postoperative
therapy, regardless of extent of resection or other prognostic factors, with
radiation and chemotherapy.
• Whether to treat IDH-wildtype with RT ? PCV or with concurrent chemo-
radiotherapy with TMZ followed by adjuvant TMZ is an open question that
requires further studies.
• The rational to use the same regimen as in glioblastoma, the Stupp regimen is
the fact that IDH-wt astrocytoma has the same biology and natural history is
very similar to primary GBM
6/20/2021 46
47. Follow up
• Follow-up with FLAIR or T2-weighted MRI is the standard of
care.
• These MRI sequences are widely available and can be used
routinely in clinical protocols. Routine follow-up should also
include T1-weighted images before and after intravenous
contrast administration to detect malignant transformation
• Follow-up recommendation would be clinical evaluation with
particular attention to neurological function, seizures and
corticosteroid use
• MRI and Mini–Mental State Examination (MMSE) after the
completion of therapy, and then every 3–4 months for 1 year,
every 6 months for 2 years, and every year thereafter until
tumor progression is recommended outside clinical trials
(Level V), unless more frequent monitoring is clinically
indicated
6/20/2021 47
48. RANO response criteria for low-grade glioma
• CR
– Complete disappearance of the lesion on T2 or FLAIR imaging (if enhancement had been present, it must have resolved completely)
– No new lesions, no new T2 or FLAIR abnormalities apart from those consistent with radiation effects, and no new or increased enhancement;
– Patients must be off corticosteroids or only on physiological replacement doses
– Patients should be stable or improved clinically
• PR
– Greater than or equal to 50% decrease in the product of perpendicular diameters of the lesion on T2 or FLAIR imaging sustained for at least 4
weeks compared with baseline;
– No new lesions, no new T2 or FLAIR abnormalities apart from those consistent with radiation effects, and no new or increased enhancement;
– Patients should be on a corticosteroid dose that should not be greater than the dose at time of baseline scan, and should be stable or
improved clinically
• Minor response
– A decrease of the area of non-enhancing lesion on T2 or FLAIR MR imaging between 25% and 50% compared with baseline;
– No new lesions, no new T2 or FLAIR abnormalities apart from those consistent with radiation effect, and no new or increased enhancement;
– Patients should be on a corticosteroid dose that should not be greater than the dose at time of baseline scan, and should be stable or
improved clinically
• Stable disease
– Stable disease is present if the changes do not qualify for complete, partial, or minor response, or progression and requires:
– Stable area of non-enhancing abnormalities on T2 or FLAIR imaging;
– Patients should be on a corticosteroid dose that should not be greater than the dose at time of baseline scan, and should be stable or
improved clinically
• Progression
– Development of new lesions or increase of enhancement (radiological evidence of malignant transformation);
– A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best
response after initiation of therapy, not attributable to radiation effect or to comorbid events;
– Definite clinical deterioration not attributable to other causes apart from the tumour, or decrease in corticosteroid dose; or
– Failure to return for evaluation because of death or deteriorating condition, unless caused by documented non-related disorders
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49. Recommendations
1. The revised WHO classification of 2016 integrates molecular markers in the routine
histological diagnosis of CNS tumors.
2. The main molecular factors for subdividing LGG are IDH mutations, 1p19q
codeletions, ATXR and TERT mutations.
3. LGG may be subdivided into three groups:
A. Grade 2 diffuse astrocytoma IDH wt,
B. Grade 2 diffuse Astrocytoma IDH mut without 1p19q codeletion,
C. Grade 2 Oligodendroglioma that requires the following molecular features: IDH
mut and 1p19q codeletion.
4. MRI is the modality of choice for characterizing LGG but advanced MRI techniques,
such as Diffusion weighted imaging (DWI), MR Spectroscopy and Perfusion MRI,
complements the anatomic information obtained from conventional MRI.
5. Surgical resection is considered the first step to be done when dealing with LGG.
Currently is assumed that surgery should aim for the greater extent of resection.
6. As the management of LGG is complex, It is recommended that all cases of low-
grade glioma be discussed in a multidisciplinary committee before selecting a
therapeutic option
7. You can observe in LOW-risk groups
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