This ppt is providing detail of current status and future direction of treatment deintensification strategies of head and neck cancer in era of HPV positive sq cell carcinoma.
This document discusses neoadjuvant chemotherapy in head and neck cancer. It provides background on when neoadjuvant chemotherapy is given, what regimens are used, and evidence from studies comparing neoadjuvant chemotherapy plus radiation/surgery versus radiation/surgery alone. Several large studies found that adding docetaxel, cisplatin and fluorouracil as neoadjuvant chemotherapy improved overall and progression-free survival compared to cisplatin and fluorouracil alone. However, other studies found no difference in outcomes between neoadjuvant chemotherapy followed by chemoradiation versus chemoradiation alone. Concomitant chemoradiation appears superior to induction chemotherapy for larynx preservation.
The document discusses HPV and its association with head and neck cancers. It notes that HPV, particularly HPV-16, has been found in 25% of oropharyngeal cancers. Patients with HPV-positive cancers tend to be younger, have fewer risk factors like smoking, and have improved survival rates compared to HPV-negative cancers. While the standard treatments still apply, HPV status may allow for less aggressive options in some cases. Future research focuses on developing HPV-targeted treatments since the viruses genes continue to be expressed in late-stage cancers.
Axillary radiotherapy provides comparable regional control to axillary lymph node dissection for breast cancer patients with positive sentinel nodes, with fewer side effects. The AMAROS trial found similar 5-year axillary recurrence, disease-free survival, and overall survival between the radiotherapy and dissection groups. However, radiotherapy resulted in significantly less lymphedema. While control was excellent with both treatments, the trial was underpowered to definitively show non-inferiority due to lower-than-expected axillary recurrences.
Management of carcinoma nasopharynx presents many challenges:
1) Detection is difficult due to its deep, silent location and treatment is challenging due to proximity to critical structures.
2) Radiotherapy alone was historically used but results in 5-year OS of only 35-50%.
3) The current standard of care is chemoradiotherapy which provides excellent tumor control and improves outcomes over radiotherapy alone, with 5-year OS of 70-80% for early stages and 50% for advanced stages.
1) Total neoadjuvant therapy (TNT) involves chemotherapy before and after chemoradiotherapy for locally advanced rectal cancer, aiming to increase downstaging and improve outcomes.
2) A review found TNT achieved a 22% pathological complete response rate compared to 13% for chemoradiotherapy alone, with possibly improved survival.
3) However, most evidence comes from observational studies. Two randomized controlled trials found TNT reduced distant metastases and improved disease-free survival compared to chemoradiotherapy alone.
Hemostatic radiotherapy uses single high doses or fractionated lower doses of external beam radiation to control tumor bleeding. Radiation works by shrinking the tumor and relaxing its aggressiveness, which stops bleeding in 80% of patients within 24-48 hours of treatment starting. Studies have found hemostatic radiotherapy effective at controlling hemorrhaging in 78-100% of advanced cancer patients, usually with doses of 4-10 Gy in a single fraction or 30 Gy over 10 fractions. While radiation achieves short-term hemostasis, most patients experience local recurrence or metastases within two years.
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 document discusses neoadjuvant chemotherapy in head and neck cancer. It provides background on when neoadjuvant chemotherapy is given, what regimens are used, and evidence from studies comparing neoadjuvant chemotherapy plus radiation/surgery versus radiation/surgery alone. Several large studies found that adding docetaxel, cisplatin and fluorouracil as neoadjuvant chemotherapy improved overall and progression-free survival compared to cisplatin and fluorouracil alone. However, other studies found no difference in outcomes between neoadjuvant chemotherapy followed by chemoradiation versus chemoradiation alone. Concomitant chemoradiation appears superior to induction chemotherapy for larynx preservation.
The document discusses HPV and its association with head and neck cancers. It notes that HPV, particularly HPV-16, has been found in 25% of oropharyngeal cancers. Patients with HPV-positive cancers tend to be younger, have fewer risk factors like smoking, and have improved survival rates compared to HPV-negative cancers. While the standard treatments still apply, HPV status may allow for less aggressive options in some cases. Future research focuses on developing HPV-targeted treatments since the viruses genes continue to be expressed in late-stage cancers.
Axillary radiotherapy provides comparable regional control to axillary lymph node dissection for breast cancer patients with positive sentinel nodes, with fewer side effects. The AMAROS trial found similar 5-year axillary recurrence, disease-free survival, and overall survival between the radiotherapy and dissection groups. However, radiotherapy resulted in significantly less lymphedema. While control was excellent with both treatments, the trial was underpowered to definitively show non-inferiority due to lower-than-expected axillary recurrences.
Management of carcinoma nasopharynx presents many challenges:
1) Detection is difficult due to its deep, silent location and treatment is challenging due to proximity to critical structures.
2) Radiotherapy alone was historically used but results in 5-year OS of only 35-50%.
3) The current standard of care is chemoradiotherapy which provides excellent tumor control and improves outcomes over radiotherapy alone, with 5-year OS of 70-80% for early stages and 50% for advanced stages.
1) Total neoadjuvant therapy (TNT) involves chemotherapy before and after chemoradiotherapy for locally advanced rectal cancer, aiming to increase downstaging and improve outcomes.
2) A review found TNT achieved a 22% pathological complete response rate compared to 13% for chemoradiotherapy alone, with possibly improved survival.
3) However, most evidence comes from observational studies. Two randomized controlled trials found TNT reduced distant metastases and improved disease-free survival compared to chemoradiotherapy alone.
Hemostatic radiotherapy uses single high doses or fractionated lower doses of external beam radiation to control tumor bleeding. Radiation works by shrinking the tumor and relaxing its aggressiveness, which stops bleeding in 80% of patients within 24-48 hours of treatment starting. Studies have found hemostatic radiotherapy effective at controlling hemorrhaging in 78-100% of advanced cancer patients, usually with doses of 4-10 Gy in a single fraction or 30 Gy over 10 fractions. While radiation achieves short-term hemostasis, most patients experience local recurrence or metastases within two years.
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 document discusses the use of radiotherapy in the treatment of acute lymphoblastic leukemia (ALL). It provides an overview of ALL, including classification, risk groups, and treatment approaches involving induction, intensification, maintenance, and central nervous system prophylaxis. It then focuses on the role of radiotherapy, describing protocols for cranial irradiation to prevent central nervous system relapse, including dose schedules. It also discusses radiotherapy for meningeal leukemia at diagnosis, testicular irradiation, and total body irradiation used for bone marrow transplantation conditioning.
Mr. Sunil, a 72-year-old male, presented with a 3-month history of a left neck swelling. Further examinations revealed metastatic squamous cell carcinoma in the left neck lymph nodes. He was diagnosed with carcinoma of unknown primary (CUP) and underwent radical neck dissection, followed by chemotherapy and radiotherapy. CUP describes metastatic cancers where the primary site cannot be identified despite various examinations and evaluations. Treatment options for CUP include surgery, radiation therapy, chemotherapy, or concurrent chemoradiation depending on the lymph node involvement and other factors. Prognosis depends on the stage and presence of extracapsular extension, with 5-year survival rates ranging from 30% for upper cervical nodes to 5%
The document discusses the role of chemotherapy in carcinoma of the stomach. It outlines several key trials investigating neoadjuvant, adjuvant and perioperative chemotherapy approaches. The MAGIC trial showed significantly improved 5-year survival with perioperative chemotherapy compared to surgery alone. The French FNCLCC trial also demonstrated improved disease-free and overall survival with perioperative chemotherapy. Adjuvant chemoradiation was shown in the INT0116/SWOG 9008 trial to improve 5-year overall and disease-free survival compared to surgery alone. The Japanese S-1 trial found significant benefit in 5-year disease-free and overall survival with adjuvant S-1 chemotherapy compared to observation after surgery.
Carcinoma nasopharynx anatomy to managementDrAyush Garg
The document provides information on carcinoma of the nasopharynx, including its anatomy, epidemiology, etiology, clinical features, patterns of spread, diagnostic evaluation, and metastatic workup. The key points are:
1) Nasopharyngeal carcinoma is most common in Southern Chinese populations and has a bimodal age distribution. Viral, genetic, and environmental factors like Epstein-Barr virus and salted fish contribute to its etiology.
2) The tumor can spread superiorly into the skull base, anteriorly into the nasal cavity/sinuses, and posteriorly into neck muscles and brain. Distant metastases most often involve bones and lungs.
3) Diagnostic evaluation includes endoscopic
This document discusses treatment de-escalation strategies for HPV-positive oropharyngeal cancer. It provides details on the natural history of HPV and its life cycles. It also summarizes several clinical trials that aimed to de-escalate treatment intensity through strategies like reduced radiation doses, substituting chemotherapy agents, and limiting treatment volumes. One study found that substituting cetuximab for cisplatin reduced survival rates. Another trial found that induction chemotherapy followed by reduced radiation if patients responded well was feasible but came with increased toxicity. A third study found that transoral surgery followed by hyperfractionated radiotherapy with docetaxel achieved high rates of local control and survival with acceptable toxicity levels.
The document discusses several trials evaluating preoperative chemoradiotherapy versus postoperative chemoradiotherapy or radiotherapy alone for rectal cancer. Some key trials found that preoperative therapy improved local recurrence rates and survival compared to postoperative or no adjuvant therapy. Longer intervals between preoperative radiotherapy and surgery were associated with higher rates of tumor downstaging. Adding oxaliplatin or chemotherapy without radiation improved survival outcomes in some trials. Ongoing studies are exploring chemotherapy alone and targeted agents in rectal cancer.
Radiotherapy For Non Small Cell Lung Cancerfondas vakalis
- The document discusses treatment options for non-small cell lung cancer (NSCLC), including surgery, radiotherapy, chemotherapy, and combinations.
- For early stage NSCLC (stages I-II), surgery is the standard treatment but radiotherapy is an alternative for medically inoperable patients. Adjuvant chemotherapy may improve outcomes for stage II.
- For locally advanced NSCLC (stage III), combined modality treatment is usually recommended, with concurrent chemoradiotherapy being superior to sequential treatment for stage IIIB.
Nasopharyngeal carcinoma is typically treated with radiation therapy. Concurrent chemotherapy and radiation is the standard for locally advanced disease and improves survival compared to radiation alone. Intensity-modulated radiation therapy provides better tumor coverage and reduces side effects. Surgery has a limited role except for biopsy or salvaging recurrent tumors. Temporal lobe necrosis is a serious potential complication, so fractional doses above 2Gy should be avoided. Close follow-up is needed due to risk of recurrence or late effects.
Preoperative chemoradiotherapy is commonly used to treat rectal cancer. It can reduce the tumor size and increase the likelihood of sphincter-sparing surgery. Studies have shown that preoperative chemoradiotherapy results in lower local recurrence rates compared to postoperative chemoradiotherapy or radiotherapy alone, without increasing distant metastases or mortality. Short-course radiotherapy followed by surgery within a week is also effective at reducing local recurrence compared to surgery alone, especially when combined with total mesorectal excision.
1) A landmark randomized clinical trial published in 1999 found that concurrent weekly cisplatin chemotherapy during pelvic radiation improved progression-free survival and overall survival rates for patients with bulky stage IB cervical cancer compared to radiation alone. The study demonstrated a 79% 5-year progression-free survival rate and 85% 5-year overall survival rate for patients receiving concurrent chemoradiation versus 74% and 63% respectively for radiation alone.
2) Another 1999 randomized clinical trial found that for high-risk cervical cancer patients, pelvic radiation with concurrent cisplatin and fluorouracil chemotherapy resulted in improved overall survival compared to pelvic and para-aortic radiation alone, establishing concurrent chemoradiation as the new standard
This document discusses the approach towards re-irradiation of common cancers. It begins by noting that local recurrence after radiation therapy and second primary tumors in irradiated areas are challenges, though re-irradiation can provide durable disease control in some cases. It then discusses key considerations for re-irradiation of head and neck cancers, gliomas, gynecological cancers, bone metastases, and brain metastases. Important factors include the initial radiation dose, interval since prior radiation, intent of re-irradiation, cumulative organ doses, and risk versus benefit. Advanced radiation techniques like IMRT can help minimize toxicity risks from re-irradiation. Careful patient selection and multidisciplinary evaluation are emphasized for meaningful survival benefits from re-
The document discusses organ preservation using radiation therapy techniques like brachytherapy. It provides examples of various cancers where brachytherapy can be used to preserve organs like penis, breast, bone, soft tissue sarcomas, anal canal, tongue and others. Brachytherapy provides conformal dose distribution allowing dose escalation to tumor and sparing of adjacent normal tissues, thus helping organ preservation and improved quality of life for patients. Expertise is required for brachytherapy planning and procedures to achieve optimal outcomes of local tumor control and organ preservation.
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 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.
the role of brachytherapy in oral cavity carcinoma.
physics of brachytherapy
radiobiology of brachytherapy
clinical application in tongue, buccal mucosa cancer
Radiotherapy techniques, indications and evidences in oral cavity and oropha...Dr.Amrita Rakesh
This document discusses indications, evidence, and radiation therapy techniques for oral cavity and oropharyngeal cancers. It covers:
- Anatomy of the oral cavity and oropharynx.
- Staging principles and indications for surgery vs systemic therapy.
- Principles of surgery including adequate resection margins and neck management.
- Use of adjuvant radiation therapy or chemoradiation to improve local control, especially for high-risk features like positive margins or extracapsular extension.
- Radiation techniques for oral cavity cancers including field design, dose recommendations, and advantages of IMRT for sparing parotid glands.
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 the anatomy and clinical presentation of nasopharyngeal carcinoma (NPC). It describes the anatomy of the nasopharynx including its walls, foramina, and spaces. It then covers the epidemiology, etiology, local extension patterns, lymph node spread, distant metastasis, clinical presentation, diagnostic workup and staging of NPC. It also provides details of the treatment approach including radiation therapy techniques such as conventional 2D radiation versus intensity modulated radiation therapy (IMRT).
- Renal cell carcinoma (RCC) incidence has increased in recent years, with 20-50% of localized cases progressing to metastatic cancer.
- Several risk stratification models (UISS, SSIGN, Leibovich) are used to predict survival and guide surveillance and treatment eligibility.
- Early adjuvant trials of VEGF TKIs like sunitinib and sorafenib showed minimal improvement in disease-free survival at significant cost of toxicity.
- The KEYNOTE-564 trial showed significant improvement in disease-free survival for high-risk RCC patients treated with adjuvant pembrolizumab compared to placebo.
- The document summarizes a clinical trial that compared cisplatin chemotherapy plus radiotherapy (standard treatment) to cetuximab (EGFR inhibitor) plus radiotherapy for low-risk HPV-positive oropharyngeal cancer.
- The trial found that using cetuximab instead of cisplatin resulted in no reduction in toxicity but significantly worse tumor control outcomes, including lower 2-year overall survival and higher recurrence rates.
- The results suggest that cisplatin remains the standard of care for concurrent chemotherapy with radiotherapy for HPV-positive oropharyngeal cancer and that treatment de-escalation strategies removing systemic chemotherapy need caution.
This document discusses the use of radiotherapy in the treatment of acute lymphoblastic leukemia (ALL). It provides an overview of ALL, including classification, risk groups, and treatment approaches involving induction, intensification, maintenance, and central nervous system prophylaxis. It then focuses on the role of radiotherapy, describing protocols for cranial irradiation to prevent central nervous system relapse, including dose schedules. It also discusses radiotherapy for meningeal leukemia at diagnosis, testicular irradiation, and total body irradiation used for bone marrow transplantation conditioning.
Mr. Sunil, a 72-year-old male, presented with a 3-month history of a left neck swelling. Further examinations revealed metastatic squamous cell carcinoma in the left neck lymph nodes. He was diagnosed with carcinoma of unknown primary (CUP) and underwent radical neck dissection, followed by chemotherapy and radiotherapy. CUP describes metastatic cancers where the primary site cannot be identified despite various examinations and evaluations. Treatment options for CUP include surgery, radiation therapy, chemotherapy, or concurrent chemoradiation depending on the lymph node involvement and other factors. Prognosis depends on the stage and presence of extracapsular extension, with 5-year survival rates ranging from 30% for upper cervical nodes to 5%
The document discusses the role of chemotherapy in carcinoma of the stomach. It outlines several key trials investigating neoadjuvant, adjuvant and perioperative chemotherapy approaches. The MAGIC trial showed significantly improved 5-year survival with perioperative chemotherapy compared to surgery alone. The French FNCLCC trial also demonstrated improved disease-free and overall survival with perioperative chemotherapy. Adjuvant chemoradiation was shown in the INT0116/SWOG 9008 trial to improve 5-year overall and disease-free survival compared to surgery alone. The Japanese S-1 trial found significant benefit in 5-year disease-free and overall survival with adjuvant S-1 chemotherapy compared to observation after surgery.
Carcinoma nasopharynx anatomy to managementDrAyush Garg
The document provides information on carcinoma of the nasopharynx, including its anatomy, epidemiology, etiology, clinical features, patterns of spread, diagnostic evaluation, and metastatic workup. The key points are:
1) Nasopharyngeal carcinoma is most common in Southern Chinese populations and has a bimodal age distribution. Viral, genetic, and environmental factors like Epstein-Barr virus and salted fish contribute to its etiology.
2) The tumor can spread superiorly into the skull base, anteriorly into the nasal cavity/sinuses, and posteriorly into neck muscles and brain. Distant metastases most often involve bones and lungs.
3) Diagnostic evaluation includes endoscopic
This document discusses treatment de-escalation strategies for HPV-positive oropharyngeal cancer. It provides details on the natural history of HPV and its life cycles. It also summarizes several clinical trials that aimed to de-escalate treatment intensity through strategies like reduced radiation doses, substituting chemotherapy agents, and limiting treatment volumes. One study found that substituting cetuximab for cisplatin reduced survival rates. Another trial found that induction chemotherapy followed by reduced radiation if patients responded well was feasible but came with increased toxicity. A third study found that transoral surgery followed by hyperfractionated radiotherapy with docetaxel achieved high rates of local control and survival with acceptable toxicity levels.
The document discusses several trials evaluating preoperative chemoradiotherapy versus postoperative chemoradiotherapy or radiotherapy alone for rectal cancer. Some key trials found that preoperative therapy improved local recurrence rates and survival compared to postoperative or no adjuvant therapy. Longer intervals between preoperative radiotherapy and surgery were associated with higher rates of tumor downstaging. Adding oxaliplatin or chemotherapy without radiation improved survival outcomes in some trials. Ongoing studies are exploring chemotherapy alone and targeted agents in rectal cancer.
Radiotherapy For Non Small Cell Lung Cancerfondas vakalis
- The document discusses treatment options for non-small cell lung cancer (NSCLC), including surgery, radiotherapy, chemotherapy, and combinations.
- For early stage NSCLC (stages I-II), surgery is the standard treatment but radiotherapy is an alternative for medically inoperable patients. Adjuvant chemotherapy may improve outcomes for stage II.
- For locally advanced NSCLC (stage III), combined modality treatment is usually recommended, with concurrent chemoradiotherapy being superior to sequential treatment for stage IIIB.
Nasopharyngeal carcinoma is typically treated with radiation therapy. Concurrent chemotherapy and radiation is the standard for locally advanced disease and improves survival compared to radiation alone. Intensity-modulated radiation therapy provides better tumor coverage and reduces side effects. Surgery has a limited role except for biopsy or salvaging recurrent tumors. Temporal lobe necrosis is a serious potential complication, so fractional doses above 2Gy should be avoided. Close follow-up is needed due to risk of recurrence or late effects.
Preoperative chemoradiotherapy is commonly used to treat rectal cancer. It can reduce the tumor size and increase the likelihood of sphincter-sparing surgery. Studies have shown that preoperative chemoradiotherapy results in lower local recurrence rates compared to postoperative chemoradiotherapy or radiotherapy alone, without increasing distant metastases or mortality. Short-course radiotherapy followed by surgery within a week is also effective at reducing local recurrence compared to surgery alone, especially when combined with total mesorectal excision.
1) A landmark randomized clinical trial published in 1999 found that concurrent weekly cisplatin chemotherapy during pelvic radiation improved progression-free survival and overall survival rates for patients with bulky stage IB cervical cancer compared to radiation alone. The study demonstrated a 79% 5-year progression-free survival rate and 85% 5-year overall survival rate for patients receiving concurrent chemoradiation versus 74% and 63% respectively for radiation alone.
2) Another 1999 randomized clinical trial found that for high-risk cervical cancer patients, pelvic radiation with concurrent cisplatin and fluorouracil chemotherapy resulted in improved overall survival compared to pelvic and para-aortic radiation alone, establishing concurrent chemoradiation as the new standard
This document discusses the approach towards re-irradiation of common cancers. It begins by noting that local recurrence after radiation therapy and second primary tumors in irradiated areas are challenges, though re-irradiation can provide durable disease control in some cases. It then discusses key considerations for re-irradiation of head and neck cancers, gliomas, gynecological cancers, bone metastases, and brain metastases. Important factors include the initial radiation dose, interval since prior radiation, intent of re-irradiation, cumulative organ doses, and risk versus benefit. Advanced radiation techniques like IMRT can help minimize toxicity risks from re-irradiation. Careful patient selection and multidisciplinary evaluation are emphasized for meaningful survival benefits from re-
The document discusses organ preservation using radiation therapy techniques like brachytherapy. It provides examples of various cancers where brachytherapy can be used to preserve organs like penis, breast, bone, soft tissue sarcomas, anal canal, tongue and others. Brachytherapy provides conformal dose distribution allowing dose escalation to tumor and sparing of adjacent normal tissues, thus helping organ preservation and improved quality of life for patients. Expertise is required for brachytherapy planning and procedures to achieve optimal outcomes of local tumor control and organ preservation.
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 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.
the role of brachytherapy in oral cavity carcinoma.
physics of brachytherapy
radiobiology of brachytherapy
clinical application in tongue, buccal mucosa cancer
Radiotherapy techniques, indications and evidences in oral cavity and oropha...Dr.Amrita Rakesh
This document discusses indications, evidence, and radiation therapy techniques for oral cavity and oropharyngeal cancers. It covers:
- Anatomy of the oral cavity and oropharynx.
- Staging principles and indications for surgery vs systemic therapy.
- Principles of surgery including adequate resection margins and neck management.
- Use of adjuvant radiation therapy or chemoradiation to improve local control, especially for high-risk features like positive margins or extracapsular extension.
- Radiation techniques for oral cavity cancers including field design, dose recommendations, and advantages of IMRT for sparing parotid glands.
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 the anatomy and clinical presentation of nasopharyngeal carcinoma (NPC). It describes the anatomy of the nasopharynx including its walls, foramina, and spaces. It then covers the epidemiology, etiology, local extension patterns, lymph node spread, distant metastasis, clinical presentation, diagnostic workup and staging of NPC. It also provides details of the treatment approach including radiation therapy techniques such as conventional 2D radiation versus intensity modulated radiation therapy (IMRT).
- Renal cell carcinoma (RCC) incidence has increased in recent years, with 20-50% of localized cases progressing to metastatic cancer.
- Several risk stratification models (UISS, SSIGN, Leibovich) are used to predict survival and guide surveillance and treatment eligibility.
- Early adjuvant trials of VEGF TKIs like sunitinib and sorafenib showed minimal improvement in disease-free survival at significant cost of toxicity.
- The KEYNOTE-564 trial showed significant improvement in disease-free survival for high-risk RCC patients treated with adjuvant pembrolizumab compared to placebo.
- The document summarizes a clinical trial that compared cisplatin chemotherapy plus radiotherapy (standard treatment) to cetuximab (EGFR inhibitor) plus radiotherapy for low-risk HPV-positive oropharyngeal cancer.
- The trial found that using cetuximab instead of cisplatin resulted in no reduction in toxicity but significantly worse tumor control outcomes, including lower 2-year overall survival and higher recurrence rates.
- The results suggest that cisplatin remains the standard of care for concurrent chemotherapy with radiotherapy for HPV-positive oropharyngeal cancer and that treatment de-escalation strategies removing systemic chemotherapy need caution.
This document discusses stereotactic body radiation therapy (SBRT) for head and neck cancers. It provides an overview of SBRT indications, efficacy, toxicity profiles, quality of life outcomes, fractionation schedules, target definition, constraints, and the role of cetuximab. Several studies on SBRT for recurrent head and neck cancers, primary cancers metastatic to the head and neck region, and target volume delineation are summarized. Toxicities are generally low but carotid blowout syndrome remains a concern, especially for tumors adjacent to carotid arteries.
This study compared short-course radiotherapy to long-course chemoradiation for patients with T3 rectal cancer. It found that long-course treatment resulted in a lower risk of local tumor recurrence, though the difference was not statistically significant. Both treatments had similar rates of distant tumor recurrence and overall survival. Long-course treatment seemed to provide a greater benefit for distal tumors, with fewer local recurrences, but again the difference was not statistically significant due to the small number of distal tumors.
Management Of Recurrent Ovarian Ca (ROC)
The document discusses the management of recurrent ovarian cancer. It provides details on the incidence and patterns of recurrence for ovarian cancer. For patients with platinum-sensitive recurrent ovarian cancer, the standard treatment is second line chemotherapy. Several chemotherapy regimens are discussed including carboplatin with paclitaxel, gemcitabine, or pegylated liposomal doxorubicin. For partially platinum-sensitive recurrent ovarian cancer, the OVA-301 trial showed improved overall survival with the combination of carboplatin and pegylated liposomal doxorubicin compared to carboplatin alone. Management of recurrent ovarian cancer aims to prolong survival, delay progression,
This document summarizes the treatment of anal canal cancer. It discusses:
1. The treatment has evolved from radical surgery (abdominoperineal resection) to nonsurgical chemoradiotherapy using 5-fluorouracil and mitomycin C, allowing for organ preservation in most patients.
2. Definitive chemoradiotherapy is now the standard of care, using a dose of 50.4 Gy radiation with concurrent 5-fluorouracil and mitomycin C. This approach provides high rates of pathologic complete response and survival compared to radiation alone.
3. Ongoing research is exploring modifying the chemoradiotherapy regimen by replacing mitomycin C with cisplatin, 5-fluoroura
Neoadjuvant therapy in colorectal carcinomaAnkita Singh
- Several studies have shown that neoadjuvant therapy decreases local recurrence rates in colorectal cancer when compared to surgery alone. One study showed a statistically significant decrease in local recurrence with the addition of chemotherapy to preoperative radiotherapy.
- Evidence indicates that long-course chemoradiotherapy, induction chemotherapy followed by long-course chemoradiotherapy, and short-course radiotherapy are the three accepted neoadjuvant approaches, with long-course chemoradiotherapy being the most commonly used currently. Short-course radiotherapy has also shown non-inferior oncologic outcomes compared to long-course chemoradiotherapy in some studies.
The document summarizes evidence and guidelines for managing locally advanced rectal cancer. It discusses that neoadjuvant chemoradiation is preferred over postoperative chemoradiation based on trials showing lower local recurrence rates and less toxicity. Long-course neoadjuvant chemoradiation followed by surgery 6-8 weeks later is the standard approach. Post-treatment assessment of tumor response helps predict outcomes, with complete response indicating a good prognosis. Adjuvant chemotherapy after surgery may further improve survival based on meta-analyses of trials. Guidelines recommend a multidisciplinary, tailored approach incorporating staging, treatment response, and patient factors.
This study compared different chemotherapy and radiotherapy regimens for patients with early unfavorable Hodgkin's lymphoma. The study found:
1) 4 cycles of ABVD chemotherapy followed by 30Gy radiotherapy was as effective as 4 cycles of BEACOPP chemotherapy followed by either 30Gy or 20Gy radiotherapy.
2) However, 4 cycles of ABVD followed by a reduced radiotherapy dose of 20Gy was inferior to the other regimens and resulted in worse patient outcomes.
3) A reduction of radiotherapy dose from 30Gy to 20Gy is only possible when combined with a more intensive chemotherapy regimen like BEACOPP, not a less intensive regimen like ABVD.
INDUCTION CHEMOTHERAPY WITH TPF IN HEAD & NECK CANCERS Paul George
Three key points about induction chemotherapy for head and neck cancer:
1) Several trials have shown that a taxane-based induction chemotherapy regimen of docetaxel, cisplatin, and fluorouracil (TPF) improves overall survival compared to cisplatin and fluorouracil (PF) alone when followed by concurrent chemoradiotherapy. TPF also decreases locoregional and distant failures.
2) A large meta-analysis found TPF significantly improved overall survival, progression-free survival, organ preservation, and reduced cancer mortality compared to PF. However, no evidence shows TPF plus radiotherapy is superior to concurrent chemoradiotherapy alone.
3) While TPF is now considered standard
This document summarizes the management of pancreatic carcinoma. It discusses the anatomy, epidemiology, risk factors, hereditary syndromes, pathophysiology including pre-cancerous lesions, types of pancreatic cancer, staging, prognostic factors, diagnostic techniques, treatment including surgery, chemotherapy, targeted therapy, radiotherapy and historical prospective studies. It provides a comprehensive overview of pancreatic carcinoma covering all relevant aspects of the disease.
Omission of RT in elderly breast cancer patientsBharti Devnani
This journal club presentation summarized the PRIME II randomized controlled trial which evaluated the efficacy of postoperative whole-breast radiotherapy for women aged 65 years or older with early-stage, hormone receptor-positive breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. The results showed that radiotherapy achieved a significant but relatively small reduction in local breast recurrence at 5 years compared to no radiotherapy. However, the 5-year rate of recurrence was low enough that omission of radiotherapy could be considered for select low-risk patients based on tumor characteristics and patient preferences. Treatment decisions require individualization based on prognostic factors and risk-benefit assessment.
This document discusses the management of colorectal liver metastases, which is an area of uncertainty or "grey zone" in treatment. It provides background on the burden of metastatic colorectal cancer and outlines an algorithm for evaluating whether a patient with liver metastases is fit for surgery. This includes assessing the patient's fitness, tumor staging, extrahepatic disease, future liver remnant volume, and tumor response to neoadjuvant chemotherapy. For fit patients, treatment may involve surgery with or without neoadjuvant therapy, followed by adjuvant chemotherapy. Other local therapies and surgical techniques like two-stage hepatectomy are also discussed.
This document summarizes information about anal cancer, including epidemiology, risk factors, staging, histology, and treatment approaches. It notes that anal cancer accounts for about 2% of gastrointestinal cancers. Risk factors include HPV, HIV/AIDS, and receptive anal intercourse. Treatment typically involves chemoradiation with 5-FU and mitomycin C, which results in high response rates. Additional trials have explored optimal radiation doses and chemotherapy regimens.
This document discusses anal carcinoma. It covers the overview, risk factors which include HPV and anal intercourse, and the strong association with HPV-16 and HPV-18. It also discusses risk reduction through treatment of high-grade anal intraepithelial neoplasia, a precursor to anal cancer. The anatomy of the anal region and canal is described. Sentinel nodes are the inguinal nodes. Primary treatment of non-metastatic anal cancer involves chemotherapy with radiotherapy to improve local control and reduce colostomies.
This document summarizes key landmark clinical trials in breast cancer. It discusses trials related to prevention using tamoxifen and raloxifene, radiation therapy trials for DCIS and early stage breast cancer, breast-conserving therapy including accelerated whole-breast irradiation, neoadjuvant chemotherapy trials, and HER2 targeted neoadjuvant therapy trials. The trials demonstrated the effectiveness of tamoxifen and radiation therapy in breast cancer prevention and treatment, and showed that hypofractionated radiation regimens and partial breast irradiation are not inferior to standard radiation protocols. Neoadjuvant chemotherapy was found to increase breast-conserving surgery rates and pathologic complete response rates. Dual HER2 blockade neoadjuvant regim
Fractionated radiosurgery for low grade astrocytomasGil Lederman
1. A study evaluated 143 patients with grade II astrocytomas who received fractionated stereotactic radiation therapy. Sixty percent underwent radiation after biopsy or surgery, while 39% received it at relapse.
2. Overall survival was 58% at 5 years and 50% at 8 years. Sixty percent experienced relapse, usually in the high dose radiation area. Toxicity was mild in most patients.
3. Quality of life, as measured by Karnofsky performance scores, improved in most patients after radiation. Pre-treatment contrast enhancement on scans was the only significant predictor of disease-free and overall survival.
Fractionated radiosurgery for low grade astrocytomasGil Lederman
1. A study evaluated 143 patients with grade II astrocytomas who received fractionated stereotactic radiation therapy. Sixty percent underwent radiation after biopsy or surgery, while 39% received it at relapse.
2. Overall survival was 58% at 5 years and 50% at 8 years. Sixty percent experienced relapse, usually in the high dose radiation area. Toxicity was mild.
3. Quality of life, as measured by Karnofsky performance scores, improved in most patients after radiation. Motor deficits and headaches decreased. The study found that contrast enhancement before radiation was the only significant predictor of outcome.
1) Short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer, reducing the relative risk of local recurrence by 61% compared to selective postoperative chemoradiotherapy.
2) The addition of postoperative chemotherapy to preoperative chemoradiotherapy does not affect disease-free survival or overall survival in patients with stage T3 or T4 resectable rectal cancer.
3) Short-course preoperative radiotherapy followed by delayed surgery results in lower tumor stage, greater tumor regression grade, and higher pathologic complete response rates compared to long-course radiotherapy followed by delayed surgery, with potential improvements in overall survival and time to recurrence.
Similar to Treatment Deintensification in HPV positive head and neck cancer (20)
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Treatment Deintensification in HPV positive head and neck cancer
1. Treatment Deintensification in Human Papilloma
Virus-associated Oropharyngeal Squamous Cell
Carcinoma
Dr Rushi Panchal,
Consultant Radiation Oncologist,
M S Patel Cancer Hospital & Shree Krishna Hospital
Karamsad Anand Gujarat
2. Introduction
• From 1988 to 2004, the rates of human papillomavirus
(HPV)-associated OPSCC rose more than 200 percent.
Epidemic of HPV Positivity
• Proportion of oropharyngeal squamous cell carcinoma
associated with HPV has increased from 40.5% in studies
recruiting before the year 2000 to 72.2%.
• Prevalence in India : 15-25%.
3. Introduction
• It has various differences
in its clinicopathologic
features that have
potentially important
implications for staging,
prognosis, and therapy.
• More likely to present
with an T1/T2, & N2/N3
rather T3/4 & N0/1.
T1/T2 is 64% Vs 44% &
N2/N3 is 69% Vs 51%
compared with those
with HPV negative
tumours.
• Significantly less likely to
have a second
4. • HPV DNA integrates with the host DNA,
allowing for the production of viral
proteins E6 and E7. These proteins
interfere with the activation of host
tumour suppressor proteins p53 and Rb,
respectively. Inactivation of Rb by E7
results in the overexpression of p16, a
marker commonly used to identify HPV-
associated cases.
• In the typical HPV negative squamous cell
carcinomas, p53 mutations are very frequent, along
with decreased levels of p16 and increased levels of
pRb. By contrast, HPV positive carcinomas are
associated with wild-type p53, upregulation of p16
and down regulation of pRb.
Pathogenesis in HPV+ Oropharyngeal cancer
5. Management of Ca Oropharynx in pre HPV+ Era
• Early disease (T1 N0 and T2 N0) can be treated by a single modality (surgery or
radiotherapy) & Non-operative management was usually the preferred
approach.
• Loco-regional advanced disease ( T1-2, N2-3/ T3-4,N0-N+) often necessitates
multimodality therapy of either
a. primary concurrent chemoradiation (platinum based/Cetuximab)
or
b. altered fractionation (Hyper>accelerated)
or
c. primary surgical resection (+/- reconstruction) with postoperative RT or CT+RT
when indicated.
6. HPV TESTING FOR HPV-MEDIATED
OROPHARYNGEAL CANCER
• IHC for Expression of p16
is surrogate of HPV
(widely available).
• Other tests include HPV
detection through PCR
(provide additional
sensitivity )and in situ
hybridization-ISH
(provide additional
specificity) and are being
used in case of equivocal
p16 or unclear clinical
scenario.
8. The data reveal a significant
difference in overall survival HR
0.49 [95% CI 0.35–0.69] and
disease specific survival HR 0.41
[95% 0.3–0.56] in favour of the
HPV+ category.
The estimated risk of death for
HPV-positive OPSCC patients is
50 percent lower than for those
with HPV-negative disease.
Survival
9. Survival
5 year OS (AJCC 7th) HPV +Ve OPSCC HPV –Ve OPSCC
I 88 76
II 84 68
III 82 53
IVa 81 45
IVb 60 34
10. Nomogram for OS & DFS in oropharyngeal cancer, Fakhry et al 2017 JCO
35:4057-4065.
11.
12.
13.
14. • HPV associated OPSCC patients are younger and have a
significantly better prognosis. The current standard of care for
OPSCC is derived from older trials with HPV-negative disease result
in excellent cancer control BUT they are also associated with
substantial long-term toxicity potentially representing
overtreatment of favourable-risk HPV patients. There is now great
interest in evaluating less intensive (i.e., de-intensified) treatment
regimens to improve the therapeutic ratio.
Aim of De-escalation
15. Aim of De-escalation
• Acute and late toxicities are both significant problems (grade ≥ 3 toxicity are
approximately 80% and 25%–60%, respectively ) and the possibility of de-escalating
treatment intensity provides an opportunity to reduce mucositis, gastric tube
dependence, osteoradionecrosis, chronic pain, scarring, fibrosis, swallowing
dysfunction, pharyngeal strictures, xerostomia, dental decay, hypothyroidism,
carotid stenosis and stroke, which negatively impact their quality of life. At 24
months after the receipt of radiotherapy (with or without chemotherapy) to the
head and neck, 15% of patients were found to have grade ≥ 2 swallowing
dysfunction, and 8% of patients had progressive dysphagia. Moreover, chronic
effects have been shown to occur in a radiation dose-dependent fashion. Increasing
dose to the supraglottic larynx is also associated with an increased likelihood of
swallowing dysfunction. Stricture and feeding tube dependence increase when the
volume of pharyngeal constrictors receiving 70Gy exceeds 50% and 30%,
respectively, and aspiration increases when >50% of the pharyngeal constrictors
receive 65Gy. Dysphagia increases with every 10Gy above 55Gy given to the superior
and middle pharyngeal constrictors. Therefore, a notable strategy for lessening
treatment morbidity is to reduce the dose and volume of normal tissue irradiated.
16. • The introduction of minimal invasive techniques (TORS/TLM) offers the ability to
reducing the extent of surgery could decrease the risk of surgical morbidity(e.g.
speech/swallow dysfunction, pain, loss of tissue and delayed recovery time).
• Modifying chemotherapy ameliorates haematological toxicity, neurotoxicity,
nephrotoxicity, ototoxicity and emetogenicity. The addition of chemotherapy to
radiation is known to increase rates of acute and chronic toxicity. Rate of grade ≥ 3
toxicity is 52% Vs. 89.5%in the RT alone Vs. CT+RT cohort. Trend for worsened
mucositis was observed by Adding chemotherapy. demonstrated a 10% increase in
the placement of a gastrostomy tube when compared to radiotherapy alone.
Disturbingly, 10-year results of RTOG 91-11 demonstrated increased non-cancer
mortality in the concomitant chemo-radiation arm (30.8%) compared to radiation-
alone arm (16.9%).
• Efforts should be made to reduce radiation related morbidity, and radiation dose
reduction below 55Gy may lead to improved functional outcomes regard to
dysphagia.
Aim of De-escalation
17. Tobacco usage and risk stratification
K. Kian Ang et Al, n engl j med,2010.
3-year OS of
93%
3-year OS of
70%
3-year OS of
46%
18. De-escalation treatment strategies
• Concern for treatment-induced morbidity has prompted the initiation of
multiple trials aiming to reduce treatment-related toxicity each with their own
“pros” and “cons.
• Exploring cetuximab as an alternative to cisplatin when given concurrently with
radiation.
• Reduction of radiation dose when given in combination with chemotherapy as
primary treatment (guided by induction chemotherapy response).
• Reduce total radiotherapy/concurrent chemotherapy dose.
• Reduction of adjuvant chemotherapy or radiotherapy dose following primary
treatment with surgery (guided by histopathological features in the resected
specimen.
19. cetuximab as an alternative to cisplatin when given
concurrently with radiation
Active but not recruiting
20. • Primary End Point: Over all Survival
It is a randomised clinical trial with a non-inferiority design to compare overall
survival when treated with radiotherapy plus cetuximab versus radiotherapy plus
cisplatin. Study group investigated the hypothesis that cetuximab would maintain
a high proportion of patient survival and reduce acute and late toxicity.
21.
22. • In a post-hoc analysis of the
treatment effect, the one- sided 95%
upper CI for the HR was greater than
1·45 for all demographic and clinical
subgroups. Relative to treatment
with cisplatin, patients with a Zubrod
performance score of 1 did
significantly worse when treated with
cetuximab (HR 2·66, one- sided 95%
upper CI 4·32. due to lower mean
dose of cetuximab (1879 mg/m2 vs
1961 mg/m2), and a slightly higher
mean dose of cisplatin (192 mg/m2 vs
182 mg/m2).
24. Toxicity Profile
• An alternative measure of the overall acute toxicity burden for patients is provided by the Tscore—the mean number of grade 3–4 acute
adverse events per patient.13 Patients in the cetuximab group had a significantly lower T- -score than did those in the cisplatin group (raw T--score
2·35 vs 3·19; p<0·0001), corresponding to a 40% lower acute toxicity burden.
• With regard to late toxicity in the cetuximab versus cisplatin groups, neither overall number of one or more grade 3–4 adverse events (62 of
375 patients, 16·5%, 95% CI 12·9–20·7 vs 78 of 383 patients, 20·4%, 16·4–24·8, p=0·1904; table 2) or mean number of grade 3–4 adverse
events (raw A--score 0·27 vs 0·38; p=0·1189) were significantly different.
25. • Acneiform rash was significantly more
frequent in the cetuximab group,
whereas myelosuppression, anaemia,
nausea, vomiting, anorexia,
dehydration, hyponatraemia, kidney
injury, and hearing impairment were
significantly more frequent in the
cisplatin group.
Toxicity Profile
26. • There were no notable differences between
groups for treatment -related grade 3–4 adverse
events over time. At 1 year after treatment, 30
(8·5%, 95% CI 5·8–12·0) of 351 patients in the
cetuximab group and 36 (10·0%, 7·1–13·6) of 360
patients in the cisplatin group had grade 3–4
adverse events.
• At treatment completion, 225 (57·3%, 95% CI
52·2–62·2) of 393 patients in the cetuximab group
and 243 (61·5%, 56·5–66·3) of 395 patients in the
cisplatin group had a feeding tube. These
proportions dropped to 30 (8·4%, 5·8–11·8) of 356
patients in the cetuximab group and 34 (9·2%,
6·5–12·7) of 368 patients in the cisplatin group at
1 year after treatment (p=0·79).
• Patient- reported severity of swallowing problems
increased in both the cetuximab and cisplatin
groups from pre treatment to end of treatment,
but no difference was observed between groups
in change scores from baseline (mean 47·4 vs
48·0; p=0·86). At 1 year, the cetuximab group had
a statistically significant increase in symptoms from
pre treatment compared with the cisplatin group
(7·6 vs 2·5; p=0·0382), but this difference was
below the estimated clinically important
27. • After median follow-up duration of 4·5 years Radiotherapy plus cetuximab did not meet the criteria for
non-inferiority for overall survival when compared with radiotherapy plus cisplatin rather Radiotherapy
plus cetuximab treatment led to inferior overall survival when compared with radiotherapy plus cisplatin
treatment in locally advanced HPV + ( in both low- risk and intermediate -risk groups ) OPSCC. Cetuximab
was estimated to increase the risk of death by 45% (hazard ratio 1·45, 95% CI 1·03–2·05), the risk of cancer
progression or death by 72% (1·72, 1·29–2·29), and locoregional failure by 105% (2·05, 1·35–3·10).
• Profiles of moderate to severe acute and late toxicities were different for patients treated with cetuximab
versus cisplatin, but proportions of one or more such events were similar.
• RTOG 1016 Establishes the first standard of care( no prior phase III trial ) in HPV-positive oropharyngeal
carcinoma.
Accelerated IMRT 70Gy/6weeks + 100mg/m2 cisplatin x 2.
Outcome are very good (85%OS at 5 years),albeit with moderate to high toxicity burden.
• Cetuximab should not be substituted for cisplatin for patients with HPV-positive oropharyngeal cancer
who are platinum eligible. it might not be appropriate to extrapolate the results of RTOG 1016 to HPV-
negative head and neck squamous cell carcinoma.
Conclusion
28. • Setting: open label multicentric randomized controlled phase 3 trial (Ireland, the Netherland, and the UK) n=334, 2012-
2016.
• Inclusion Criteria: locally advanced – 7th
AJCC T3N0–T4N0, and T1N1–T4N3
Age: >18 Years
HPV+ Low risk OPC (Non smoker or <10PY)
ECOG:0/1
• Primary outcome: Overall severe (grade 3-5) toxicity events at 24 months from the end of treatment.
Secondary outcomes were overall survival, time to recurrence, quality of life, swallowing, and acute and late
severe toxicities reported separately; suspected recurrences were assessed by imaging and biopsy.
29. • We observed no notable imbalances in
baseline characteristics (age, tumour site,
tumour stage, smoking history, performance
status, and comorbidities) between the two
groups
• The mean age was 57 years. 80% of patients
were men, 65% had T1–T2 disease (TNM 7),
76% had N2–N3 disease (TNM 7), and 46%
were either current or past smokers, with a
median lifetime smoking history of 8 pack-
years
30. • Patients had a median follow up of 25·9 months (95% CI 25·5–26·0). The primary outcome of mean number of events per
patient of reported overall severe (grades 3–5) toxicity & rates of all grade toxicity & did not differ significantly between
treatment groups.
• Cisplatin also caused more haematological, metabolic, and renal toxicity than did cetuximab. For cetuximab, the most
common severe toxicities were also gastrointestinal (mean 1·9 acute and 0·2 late events per patient). Cetuximab also caused
more skin toxicity and infusion reactions in the acute phase than did cisplatin.
31. there was a significant
difference between
cisplatin and cetuximab
in 2-year overall survival
97·5% vs 89·4%, hazard
ratio 5·0 [95% CI 1·7–
14·7]; p=0·001 and 2-year
recurrence (6·0% vs
16·1%, HR 3·4 [1·6–7·2];
p=0·0007.
Conclusion:
•Compared with the standard cisplatin regimen,
cetuximab showed no benefit in terms of reduced
toxicity, but Instead showed significant
detriment in terms of tumor control in patients
with low-risk HPV-positive oropharyngeal
cancer.
•Cisplatin and radiotherapy should be used as
the standard of care for HPV-Positive low risk
patients who are able to tolerate cisplatin.
The mean global quality-of-life score
on EORTC QLQ-C30 did not differ
significantly between treatment groups
at any of the timepoints (mean
difference at 24 months of 1·51 points
in favour of cisplatin, p=0·9976
33. IC ( Cisplatin + paclitaxel + Cetuximab ) x 3
cCR PR/SD
54Gy/27# with weekly Cetuximab 69.3Gy/33# with weekly Cetuximab
• Primary end point: 2 year PFS.
• Secondary end points included 2-year OS, clinical and radiologic
responses at the primary and nodal sites after IC and after overall
treatment, and safety and toxicity of treatment.
Patients with HPV16 and/or p16-positive,Resectable stage III-IV OPSCC received three cycles of IC with
cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity- modulated
radiation therapy (IMRT) 54Gy(22% reduced dose of 70Gy) with weekly cetuximab(substituted for
Cisplatin); those with less than cCR to IC at the primary site or nodes received 69.3Gy and cetuximab to
those regions.
34. • The median age was 57 years (range,
35 to 73 years) and the majority had
stage T1-3 (89% of 80 eligible
patients), N0-N2b (69% of eligible
patients) OPSCC and were not
current smokers (84%). Ninety-six
percent were p16 positive.
35.
36. ACUTE TOXICITY
The IC regimen of cisplatin, paclitaxel,
and cetuximab was well tolerated. 96%
of patients received all planned cycles,
without major delays or increase in
toxicity burden.
With 54 Gy of radiation and concur-
rent cetuximab vs 69.3 Gy of radiation
and cetuximab, the most frequent
grade 3 adverse events were mucositis
(30% vs 47%), dysphagia (15% vs 29%),
acneiform rash (12% vs 24%), radiation
dermatitis (7% vs 12%), and
lymphopenia (12% vs 29%). The
incidence of grade 4 toxicity was
less than 5% in both cohorts
37. Subset Analysis
• 2-year PFS estimate for patients with a primary-site
cCR treated to 54 Gy of radiation (n = 51) was 80%
(95% CI, 65% to 89%). The 2-year OS for these 51
patients was 94% (95% CI, 82% to 98%). For all 80
evaluable patients, 2-year PFS was 78% (95% CI, 67%
to 86%) and OS was 91% (95% CI, 82% to 96%).
• patients treated with IC and reduced-dose radiation
with low-volume disease T1-T3, N1-N2b and </= 10
pack-years of cigarette smoking to have high rate of
disease control, with a 2-year PFS of 96% (95% CI, 76%
to 99%) and OS of 96% (95% CI, 76% to 99%).
All recurrences
occurred in
patients with
>10 pack years
smoking
history.
38. Conclusion
• This prospective study of radiation de-intensification in patients with HPV-associated OPSCC
demonstrates that three cycles of IC with cisplatin, paclitaxel, and cetuximab result in an
excellent cCR of 70%, reducing tumour burden to subclinical disease. We hypothesized that IC
response would identify patients suitable for radiation dose reduction, and among the 51
patients with primary- site cCR treated with 54Gy of radiation, the 2-year PFS estimate was 80%.
• In this trial, baseline tumour and patient characteristics appeared more predictive of outcome
than radiation dose or IC response.
• The authors do not provide details on how many patients were able to receive reduced-dose RT
to both the primary and nodal sites. Complete response rates to neoadjuvant chemotherapy did
not correlate with smoking status (complete response rate was only 45% in never smokers). This
study does not answer the question whether neoadjuvant chemotherapy is needed to de-
intensify RT—is this trade-off necessary?
40. • Eligibility criteria :
• p16-positive squamous cell carcinoma of the oropharynx or MUO Neck.
• human papillomavirus or p16 positive;
• T0 to 3, N0 to N2c, M0
• <10 pack-years smoking history or >10 -30 pack-years and abstinent for the past 5 years
RADIOTHERAPY : 54-60Gy/30# (54Gy was delivered to anatomic regions at risk for subclinical disease)
CHEMOTHERAPY: Weekly Cisplatin 30mg/m2 once a week x 6
• Primary end point: The primary endpoint of this study was the pathologic complete response (pCR) rate. { biopsy of primary site or
minimally invasive resection (transoral surgery) if primary site partial response & dissection of pre-treatment nodal region - selective
nodal dissection regardless of radiological response Within 6 to 14 weeks after CRT }
• Secondary Endpoint: 2 year LC/RC/CSS/DMFS/OS & PRO-CTCAE & QOL
There are multiple ongoing clinical
trials that attempt to de-intensify
treatment; however, the decrease
in overall intensity is small or the
reduction in one treatment
modality is offset with an increase
of another.
41. The majority of patients were never
smokers or had </=10 pack years
95%. Sixty-four percent were
HPV+/p16+, and 36% were
HPV+/p16+.
All patients received the intended
de-intensified radiation dose of 60
Gy. 93% received 4 weekly doses of
cisplatin &70% received the
planned 6 doses. There were no
toxicity-related treatment delays.
42. Pathological Response
• With a median follow-up of 14.6
months (range, 4-31 months)
overall pCR rate was 86% (37 of
43).
• The pCR rate at the primary site
and in the neck was 98% (40 of
41; 2 patients were T0) and 84%
(33 of 39; 4 patients were N0),
respectively.
43. Toxicity Profile
No patient experienced grade 5 Toxicity. As expected,
chemotherapy-related hematologic toxicity was
minimal. 39% of patients (17 of 44) required a feeding
tube for a mean duration of 15 weeks (range, 5-22
weeks). No patient required a long-term feeding tube.
Rosenbek aspiration scores were similar before
treatment, 4 to 8 weeks after treatment, and 3 to 6
months after surgery for thin (1.3, 1.9, 1.4), pureed (1.0,
1.2, 1.1), and solid substances (1.0, 1.0, 1.1).
Grade 3/4 hematologic toxicities were 11%.
The rates of grade ≥3 toxicities compare favourably to
historical controls
There were no significant differences in modified barium
swallow studies before and after CRT.
44. • The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly
low-dose cisplatin is very high in favourable -risk oropharyngeal squamous cell
carcinoma, with evidence of decreased toxicity compared with standard
therapies.
• reasonable to expect a more favourable long-term toxicity profile with this de-
intensified regimen. Radiation dose was reduced by 16% (70 to 60 Gy), and the
cumulative chemotherapy dose was reduced by 60% (300 mg/m2 to 180
mg/m2).
• We believe the 10-Gy reduction in radiation dose is meaningful because cancer
control and long-term toxicity are predominately correlated to radiation dose.
The dose-response of normal tissue toxicity rises steeply in the high dose range,
so that modest decreases in total dose (in the range used in this study) can have
a major impact on long-term toxicity.
Conclusion
45. • Design: Single Arm, phase 2
• Eligibility: St III/IV Sq. cell P16+ve Oropharynx Carcinoma
2#NACT (n=44)
Paclitaxel (175mg/m2) + Carboplatin (AUC 6)
IMRT with daily IGRT + Conc Paclitaxel 30 mg/m2, Weekly
CR/PR
24(55%)
median follow up =
30mths
<PR/No response
20(45%)
54Gy/27#
43 Gy to uninvolved nodal
areas (SIB)
60Gy/30#
48 Gy to uninvolved areas
(SIB)
• Primary End point: PFS at 2 years
Radiation target volumes were defined
by the extent of disease before
chemotherapy, as assessed by imaging
and physical examination, including
endoscopy, and adjusted to conform to
anatomy after chemotherapy and
acknowledged anatomical boundaries
to tumour spread.
46. 2-year progression-free survival was 92% (95% CI 77–97). Adverse
events during induction chemotherapy were generally mild 26 (39%) of
44 patients had grade 3 adverse events, but no grade 4 events were
reported. The most common were leukopenia and neutropenia. and
during chemoradiotherapy were dysphagia (four [9%]) and mucositis
(four [9%]). One (2%) of 44 patients was dependent on a gastrostomy
tube at 3 months and none was dependent 6 months after treatment.
There were no cases of neutropenic fever. Three (7%) of 44 patients
required dose reductions of paclitaxel and carboplatin in cycle two of
induction chemotherapy because of neutropenia.
47. • Induction chemotherapy followed by chemoradiotherapy with the
radiation dose reduced by 15–20% from the standard yielded similar
2-year progression-free and overall survival to standard
radiotherapy regimens in patients with HPV-positive oropharyngeal
carcinoma, with an acceptable toxicity profile.
• Radiotherapy de-escalation has the potential to improve the
therapeutic ratio and long-term function for these patients.
Conclusion
48. Surgical treatment is the
only modality that
allows pathological
information about
adverse prognostic
factors (e.g.
ECE/LVSI/PNI) & that
influence adjuvant
treatment
recommendations.
Future research is
required to confirm
whether the traditional
risk stratification applies
equally to the HPV
positive cohort. If this is
not the case, equivalent
criteria will need to be
validated, and may be
potentially reliant on
novel markers.
49. TORS patients were less
likely to have positive
margins than were
patients who had
nonrobotic surgery (20.2%
vs 31.0%, P < .001). High-
volume TORS centres had
lower rates of positive
margins (15.8% vs 26.1%,
P < .001) and unplanned
readmissions (3.1% vs
6.1%, P < .03) than did
low-volume centres.
Transoral robotic surgery:
a population- level
analysis. Otolaryngol Head
Neck Surg. 2014
Minimal invasive surgery
is established as an
effective treatment for
early stage OPSCC.
Furthermore, similar to
CRT, HPV-associated
OPSCC is also associated
with a better prognosis
when treated with
primary surgery. The
deintensification of RT
and chemotherapy after
TLM or TORS has been
arbitrary, institution
specific, and has not been
studied in a controlled
manner.
50. Because of the use of
magnification the “host-
tumor” interface is better
visualized, allowing for
more precise negative
margin resections,
maximizing tumour
removal, and limiting
removal of normal
healthy tissue, resulting
in enbloc resection “
surgically targeted
therapy “
The major potential
benefits of primary TLM
and TORS are reduction
in surgical morbidity and
reduction in the intensity
of CRT without
compromising oncologic
outcomes
51. Surgical resection with or without adjuvant chemo-
radiotherapy (based on histopathology risk factors)
• The ADEPT, ECOG 3311 and PATHOS
trials will all randomise adjuvant
treatment strategies
(radiotherapy/chemotherapy) based
on objective histopathological
features from the resected
tumour/neck dissection addressing
the role of de-escalation of
chemoradiotherapy following initial
surgical management. ongoing trials
explore reducing the dose of
adjuvant radiotherapy or eliminating
adjuvant chemotherapy in patients
with pathologic evidence of
extracapsular extension (ECE)—a
departure from the standard of care
adjuvant chemoradiation established
for these patients based on the
combined analysis of EORTC 22931
and RTOG 9501.
52. • ECOG 3311 is a phase II trial in which 377 patients
with p16 +OPSCC are stratified into four arms
according to their surgical pathology. Patients with
intermediate histopathological risk factors will be
randomised to either low-dose (50 Gy) or standard-
dose IMRT (60 Gy).
• Patients deemed low-risk (margin-negative
resection, N0 or N1 disease, no ECE) after resection
are observed, intermediate-risk patients (negative
but ≤ 1 mm margin, +ECE, N2a, or 2–4 involved
lymph nodes) receive adjuvant radiotherapy alone
with 50 versus 60 Gy using standard daily
fractionation, and high-risk patients (>1 mm ECE,
positive margins, or ≥ 5 lymph nodes positive) are
treated with 66 Gy and weekly cisplatin.
• Results of this trial will determine if the combination
of minimally invasive surgical techniques with
reduced intensity adjuvant therapy proves to be less
toxic than current standard of care management,
and may justify a follow up phase III trial comparing
TORS and reduced dose post-operative radiation
therapy with standard chemoradiation.
53. • PATHOS is a UK based phase II trial that has just
received funding for 88 HPV+ Patients stratified
with intermediate or high-risk histopathological
features will be randomised respectively by RT
dose (low dose versus standard dose IMRT) or by
addition of chemotherapy to RT (standard dose
IMRT versus standard dose IMRT + cisplatin) and
the main outcome will be to assess early stage
swallow function.
• While the low-risk classification is the same as ECOG
3311, the other risk group criteria vary. The
intermediate-risk criteria are negative margin, ≥
pT3 disease, or pT1-2 disease with pN2a/b,
perineural invasion, lymphovascular invasion, or
negative but close margin (<5 mm). These patients
receive either 60 Gy in 2 Gy fractions over 6 weeks
or 50 Gy in 2 Gy fractions over 5 weeks. The high-
risk criteria include positive margin or ECE, and
these patients are assigned to receive 60 Gy with
or without concurrent cisplatin.
54. Trial Strength weakness HPV analysis*
RTOG-1016 Inferiority design of
trial
RT dose not reduced p16
De-ESCALaTE RT dose not reduced p16
TROG-12.01 RT dose not reduced p16
ECOG-1308 Small sample size (90
patients)
p16/HPV16
DNA ISH
University of Chicago Commercial sponsor (Novartis) +
Small sample size (80 patients)
p16
Quarterback trial Non-OPSCC cases
included in study
p16/HPV PCR
ADEPT Randomisation based
on histological analysis
p16
ECOG 3311 Randomisation based
on histological analysis
p16
PATHOS Randomisation based Small sample size (88 p16
55. Conclusion
• HPV status is strongly associated with positive therapeutic response and survival compared with HPV-
negative OPSCC, independent of the treatment modality chosen and even after adjustment for stage.
• Appropriate selection of patients for treatment de-intensification is critical in order to avoid jeopardizing
the excellent outcomes that are achieved with the current standard of care therapy in this patient
population.
• Therefore de-intensification is presently not recommended outside of a clinical trial. The approach to
treatment is currently the same for OPSCC of the same stage for AJCC 7 stage cancers. (For example, many
stage I and II HPV associated cancers in AJCC 8 will still be locoregionally advanced and require combined
modality treatment, whereas non-HPV associated stage I and II AJCC 8 cancers will be treated with single
modality surgery or radiation therapy), unless deintensification trials indicate it is safe to de- escalate
treatment. Additional data and longer follow-up will be required.
• A better understanding of the molecular alterations underlying HPV-associated disease should be elucidated
to provide further opportunities for targeted therapies with less toxicity. If these approaches prove
adequate, the quality of life of patients should be significantly improved.
• In the future, these patients will likely be managed with de-intensified therapies, whether it is through de-
intensification of surgery and adjuvant treatment, omission, substitution or reduction of the dose of
chemotherapy, and/or the reduction radiotherapy dose.