The document discusses treatment options for a 66-year-old man from Nigeria diagnosed with locally advanced head and neck squamous cell carcinoma. The man was treated initially with induction chemotherapy consisting of a PF regimen, followed by concurrent chemoradiation with gemcitabine and radiotherapy, achieving a partial response. The document then outlines general treatment modalities and strategies for locoregionally advanced head and neck cancer.
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
This document summarizes the state of the art in head and neck cancer treatment. It discusses epidemiology, risk factors, staging, treatment modalities including surgery, radiotherapy, chemotherapy, targeted therapy. It highlights recent findings like the role of HPV and molecular targeted agents. It also discusses the benefits of concurrent chemoradiation compared to radiotherapy alone as well as induction chemotherapy followed by chemoradiation for locally advanced disease.
Cetuximab Plus Radiotherapy For Head And Neck Cancerfondas vakalis
1) The document discusses a randomized controlled trial comparing radiotherapy alone versus radiotherapy plus cetuximab for locally advanced squamous cell carcinoma of the head and neck.
2) The trial found that adding cetuximab to radiotherapy improved locoregional control and overall survival compared to radiotherapy alone, with a 13% reduction in risk of locoregional recurrence and 11% reduction in risk of death.
3) Toxicities were similar between the two groups except patients receiving cetuximab experienced more rash, with 13 patients discontinuing due to rash or hypersensitivity reactions.
Induction chemotherapy for locally advanced head and neck cancers spa718
The document discusses studies on induction chemotherapy for head and neck squamous cell carcinomas. It summarizes that two large randomized controlled trials, TAX 323 and TAX 324, found that induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) improved progression-free survival and overall survival compared to induction chemotherapy with cisplatin and fluorouracil alone. A larger study called GSTCC also found improved overall survival for patients receiving induction TPF before concurrent chemoradiotherapy compared to concurrent chemotherapy alone.
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
C:\Documents And Settings\User\Desktop\Head And NeckGamal Abdul Hamid
This document summarizes recent advances in the treatment of head and neck cancer. It discusses the incidence, risk factors, staging, and historical treatment approaches including chemotherapy and chemoradiation. Recent randomized trials show improved outcomes with induction taxane-based chemotherapy followed by chemoradiation compared to chemotherapy and radiation alone. Ongoing trials are further exploring the benefits of induction chemotherapy prior to definitive treatment.
RR-17%
mPFS-4.5 mon
mOS-9.2 mon
Phase III trial
Rec/met HNSCC
N=326
Mtx vs Mtx+BV
No benefit
[1] The document discusses targeted therapies for head and neck squamous cell carcinoma (HNSCC).
[2] It summarizes genetic alterations commonly seen in HNSCC and targeted agents used to treat HNSCC including EGFR inhibitors like cetuximab, IGF inhibitors, VEGF receptor inhibitors, and other non-receptor targets.
[3] The document analyzes clinical trials of cetuximab, panitumumab
Head and neck cancer accounts for 5-6% of all cancers, with over 90% being squamous cell carcinomas. Risk factors include tobacco, alcohol, and HPV. Treatment options include surgery, radiation therapy, chemotherapy, or combinations. While early stage cancer has a good prognosis with single modality treatment, advanced stages generally require combined modality treatment, though 5-year survival remains below 35%. New targeted therapies and improved radiation techniques have provided benefits in recent years.
This document summarizes the state of the art in head and neck cancer treatment. It discusses epidemiology, risk factors, staging, treatment modalities including surgery, radiotherapy, chemotherapy, targeted therapy. It highlights recent findings like the role of HPV and molecular targeted agents. It also discusses the benefits of concurrent chemoradiation compared to radiotherapy alone as well as induction chemotherapy followed by chemoradiation for locally advanced disease.
Cetuximab Plus Radiotherapy For Head And Neck Cancerfondas vakalis
1) The document discusses a randomized controlled trial comparing radiotherapy alone versus radiotherapy plus cetuximab for locally advanced squamous cell carcinoma of the head and neck.
2) The trial found that adding cetuximab to radiotherapy improved locoregional control and overall survival compared to radiotherapy alone, with a 13% reduction in risk of locoregional recurrence and 11% reduction in risk of death.
3) Toxicities were similar between the two groups except patients receiving cetuximab experienced more rash, with 13 patients discontinuing due to rash or hypersensitivity reactions.
Induction chemotherapy for locally advanced head and neck cancers spa718
The document discusses studies on induction chemotherapy for head and neck squamous cell carcinomas. It summarizes that two large randomized controlled trials, TAX 323 and TAX 324, found that induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) improved progression-free survival and overall survival compared to induction chemotherapy with cisplatin and fluorouracil alone. A larger study called GSTCC also found improved overall survival for patients receiving induction TPF before concurrent chemoradiotherapy compared to concurrent chemotherapy alone.
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
C:\Documents And Settings\User\Desktop\Head And NeckGamal Abdul Hamid
This document summarizes recent advances in the treatment of head and neck cancer. It discusses the incidence, risk factors, staging, and historical treatment approaches including chemotherapy and chemoradiation. Recent randomized trials show improved outcomes with induction taxane-based chemotherapy followed by chemoradiation compared to chemotherapy and radiation alone. Ongoing trials are further exploring the benefits of induction chemotherapy prior to definitive treatment.
RR-17%
mPFS-4.5 mon
mOS-9.2 mon
Phase III trial
Rec/met HNSCC
N=326
Mtx vs Mtx+BV
No benefit
[1] The document discusses targeted therapies for head and neck squamous cell carcinoma (HNSCC).
[2] It summarizes genetic alterations commonly seen in HNSCC and targeted agents used to treat HNSCC including EGFR inhibitors like cetuximab, IGF inhibitors, VEGF receptor inhibitors, and other non-receptor targets.
[3] The document analyzes clinical trials of cetuximab, panitumumab
Concurrent Chemoradiation in Postoperative Setting In LAHNC. A comparision of...Santam Chakraborty
A journal club presentation comparing and contrasting the EORTC and RTOG trials of concurrent chemoradiation in Head Neck Cancers in the post operative setting.
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.
Treatment Of Stage Iii Nsclc The Role Of Radiation Therapyfondas vakalis
1. Chemo-radiotherapy is the standard of care for stage III non-small cell lung cancer (NSCLC) based on randomized clinical trial outcomes, though local control and toxicity remain issues.
2. Advances in radiation therapy techniques like 3D conformal radiation therapy and intensity modulated radiation therapy may help improve local control and reduce toxicity by better sparing healthy tissues.
3. Patient-specific factors like tumor volume, nodal disease extent, co-morbidities, and dosimetry parameters should be considered to select optimal combined modality treatments and minimize risks.
This document discusses treatment approaches for locally advanced non-small cell lung cancer (NSCLC). It presents a case of stage IIIB NSCLC and reviews the history and evolution of combined modality therapy using chemotherapy and radiotherapy. Concurrent chemoradiotherapy is now the standard of care and research focuses on optimizing radiotherapy dose/fractionation and integrating targeted therapies and prophylactic cranial irradiation to further improve outcomes.
Biomarkers in head and neck cancers final ajeetAjeet Gandhi
This document provides an overview of biomarkers in head and neck cancers. It discusses how biomarkers can be used for early diagnosis, predicting response to therapy, and identifying therapeutic targets. Key points include:
- Biomarkers like HPV status, ERCC1, and beta-tubulin isoform III may help predict response to chemotherapy and radiation. HPV+ tumors have a better prognosis.
- The EGFR pathway is commonly dysregulated in head and neck cancers but targeting it has had limited success due to resistance mechanisms. EGFRvIII mutations may reduce sensitivity to cetuximab.
- Ongoing research explores using biomarkers to guide more personalized treatment, such as reducing therapy for HPV+ tumors or targeting pathways
This document summarizes various clinical and biochemical factors that can predict outcomes of external beam radiotherapy for prostate cancer. It discusses factors such as radiation dose, stage, Gleason score, PSA kinetics, risk groups, percent positive biopsies, prostate cancer volume, perineural invasion, radiographic T3 disease, radiation technique, treatment delays, and fractionation schedules. The document also proposes that prostate cancer may have a lower alpha-beta ratio, suggesting hypofractionated regimens could have advantages by escalating biologically effective dose while reducing treatment length and acute effects.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
This document summarizes the key points from a presentation on recent cancer research:
1. Several studies presented findings on improving outcomes for prostate cancer, glioblastoma, rectal cancer, and other cancers through optimized use of radiation therapy and chemotherapy.
2. One study found long-term androgen deprivation therapy improved outcomes more than short-term therapy for prostate cancer. Another found radiation improved survival for node-positive prostate cancer.
3. For glioblastoma, a study identified molecular subgroups with more favorable prognosis, while another found improved outcomes with dose-escalated radiation and temozolomide.
4. For rectal cancer, studies explored organ-sparing approaches and found hypofraction
This document summarizes chemotherapy options for head and neck squamous cell carcinoma (HNSCC). It discusses commonly used chemotherapies like methotrexate, 5-fluorouracil, cisplatin, carboplatin and taxanes. It also covers multi-agent chemotherapy regimens and the roles of neoadjuvant, concurrent and adjuvant chemotherapy when combined with radiation or surgery. Recent advances with targeted therapies like trastuzumab are also mentioned.
This document discusses chemoradiation for head and neck cancers. It notes that locoregional control is important for curative treatment as most deaths are due to local or regional spread. The evolution of combining chemotherapy with radiation is described, from initial trials in the 1960s-1980s showing improved larynx preservation and disease-free survival. Current standard concurrent chemoradiation regimens use cisplatin given with radiation. Adjuvant chemoradiation after surgery is also discussed, with two large trials showing improved progression-free and overall survival compared to radiation alone for high-risk patients.
Multimodality Treatment Of Stage Iii Nsclcfondas vakalis
1) Multimodality treatment including chemotherapy and radiotherapy has improved outcomes for stage III non-small cell lung cancer (NSCLC) over the past decade, increasing median survival by 5 months and 1-2 year survival by 10%.
2) Induction chemotherapy with a platinum agent and third-generation drug for 2-3 cycles followed by radiotherapy remains a good standard treatment for fit patients.
3) Concurrent chemoradiotherapy and combined modality approaches may offer further benefits but require more evidence, as they present increased toxicity risks that need to be weighed against uncertain survival gains.
This document provides information on a case presentation of anal squamous cell carcinoma, including staging, diagnostic workup, management, prognostic factors, and follow up. Key points include:
- The mean age of diagnosis is 62 years and most common symptom is rectal bleeding. Imaging includes CT, MRI, and PET scans to stage disease.
- Treatment depends on disease stage but typically involves chemoradiation with concurrent 5-FU and mitomycin C or cisplatin. Several trials have shown improved outcomes with chemoradiation compared to radiation alone.
- Follow up involves examination and imaging to monitor for recurrence or metastasis. Prognostic factors include tumor size, response to initial treatment, and presence of late
Role of induction chemotherapy in Squamous Cell Carcinoma head and Neck ...Kunal Jha
Induction chemotherapy, or neoadjuvant chemotherapy, is the use of chemotherapy prior to definitive surgery or radiation therapy for head and neck cancer. It has several potential benefits, including improving tumor response to subsequent therapy and increasing the chance of organ preservation. While induction chemotherapy is commonly used when organ preservation is the goal, guidelines for its optimal use outside of this setting are still being defined. Larger prospective trials are still needed to further establish the efficacy and role of induction chemotherapy for head and neck cancer.
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
The document discusses combined chemoradiotherapy for non-small cell lung cancer (NSCLC). It describes the evolution of radiotherapy techniques from older 2D techniques to modern 3D conformal radiation and IMRT. Studies show combined chemoradiotherapy improves survival over radiotherapy alone or sequential chemotherapy and radiotherapy by reducing locoregional recurrence rates. However, concurrent chemoradiotherapy is associated with increased toxicity risks which must be balanced against survival benefits.
Personalized medicine in radiation oncology aims to individualize radiotherapy treatment through better imaging, genetics, and biomarkers. Newer radiotherapy techniques like IMRT and IGRT allow for more precise targeting of tumors while minimizing dose to normal tissues. Biomarkers can help characterize tumor hypoxia, proliferation, and a patient's inherent radiosensitivity at the genetic level. Radiogenomics research seeks genetic polymorphisms associated with radiation response and side effects. The goal is to predict treatment outcomes and tailor radiotherapy for each patient's unique biology and genetics.
The document discusses evidence for dose escalation in prostate cancer radiotherapy. It summarizes several randomized controlled trials that found dose escalation improved biochemical control rates with acceptable toxicity. The largest trial, RT01, found a significant improvement in progression-free survival but also greater bowel toxicity for the higher dose. Ongoing trials are further exploring dose escalation using newer techniques like intensity-modulated radiotherapy to better spare surrounding tissues.
1) Randomized trials show that for locally advanced prostate cancer, early hormone therapy combined with radiotherapy improves prostate cancer specific survival and overall survival compared to hormone therapy alone.
2) A randomized trial found that hormone therapy plus radiotherapy reduced the risk of prostate cancer death by 56% and reduced the risk of overall mortality by 23% compared to hormone therapy alone.
3) Radiotherapy is associated with improved outcomes for locally advanced prostate cancer compared to surgery, though the role of surgery remains unclear.
Lung cancer is a leading cause of cancer death. Immunotherapy using immune checkpoint inhibitors that target proteins like PD-1 and PD-L1 has shown promise in treating lung cancer. A study presented at ASCO 2015 found that treatment with the PD-L1 inhibitor atezolizumab resulted in improved survival for NSCLC patients with higher levels of PD-L1 expression on tumor cells compared to docetaxel chemotherapy. Another study showed nivolumab, a PD-1 inhibitor, improved survival over docetaxel as a treatment for advanced non-squamous NSCLC after chemotherapy, with greater benefit seen in patients with higher PD-L1 expression levels. These results suggest PD-L1 expression can help identify
This document discusses treatment approaches for bladder cancer including radiotherapy and cystectomy. It summarizes results from several studies comparing outcomes of radiotherapy versus cystectomy, and studies combining radiotherapy with chemotherapy. The key findings are:
1) Long-term survival rates after radiotherapy or cystectomy are comparable.
2) A study found neoadjuvant chemotherapy prior to radiotherapy improved 2-year loco-regional disease-free survival compared to radiotherapy alone.
3) Bladder preserving therapy can provide good long-term bladder function for patients who are not candidates for cystectomy.
Concurrent Chemoradiation in Postoperative Setting In LAHNC. A comparision of...Santam Chakraborty
A journal club presentation comparing and contrasting the EORTC and RTOG trials of concurrent chemoradiation in Head Neck Cancers in the post operative setting.
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.
Treatment Of Stage Iii Nsclc The Role Of Radiation Therapyfondas vakalis
1. Chemo-radiotherapy is the standard of care for stage III non-small cell lung cancer (NSCLC) based on randomized clinical trial outcomes, though local control and toxicity remain issues.
2. Advances in radiation therapy techniques like 3D conformal radiation therapy and intensity modulated radiation therapy may help improve local control and reduce toxicity by better sparing healthy tissues.
3. Patient-specific factors like tumor volume, nodal disease extent, co-morbidities, and dosimetry parameters should be considered to select optimal combined modality treatments and minimize risks.
This document discusses treatment approaches for locally advanced non-small cell lung cancer (NSCLC). It presents a case of stage IIIB NSCLC and reviews the history and evolution of combined modality therapy using chemotherapy and radiotherapy. Concurrent chemoradiotherapy is now the standard of care and research focuses on optimizing radiotherapy dose/fractionation and integrating targeted therapies and prophylactic cranial irradiation to further improve outcomes.
Biomarkers in head and neck cancers final ajeetAjeet Gandhi
This document provides an overview of biomarkers in head and neck cancers. It discusses how biomarkers can be used for early diagnosis, predicting response to therapy, and identifying therapeutic targets. Key points include:
- Biomarkers like HPV status, ERCC1, and beta-tubulin isoform III may help predict response to chemotherapy and radiation. HPV+ tumors have a better prognosis.
- The EGFR pathway is commonly dysregulated in head and neck cancers but targeting it has had limited success due to resistance mechanisms. EGFRvIII mutations may reduce sensitivity to cetuximab.
- Ongoing research explores using biomarkers to guide more personalized treatment, such as reducing therapy for HPV+ tumors or targeting pathways
This document summarizes various clinical and biochemical factors that can predict outcomes of external beam radiotherapy for prostate cancer. It discusses factors such as radiation dose, stage, Gleason score, PSA kinetics, risk groups, percent positive biopsies, prostate cancer volume, perineural invasion, radiographic T3 disease, radiation technique, treatment delays, and fractionation schedules. The document also proposes that prostate cancer may have a lower alpha-beta ratio, suggesting hypofractionated regimens could have advantages by escalating biologically effective dose while reducing treatment length and acute effects.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
This document summarizes the key points from a presentation on recent cancer research:
1. Several studies presented findings on improving outcomes for prostate cancer, glioblastoma, rectal cancer, and other cancers through optimized use of radiation therapy and chemotherapy.
2. One study found long-term androgen deprivation therapy improved outcomes more than short-term therapy for prostate cancer. Another found radiation improved survival for node-positive prostate cancer.
3. For glioblastoma, a study identified molecular subgroups with more favorable prognosis, while another found improved outcomes with dose-escalated radiation and temozolomide.
4. For rectal cancer, studies explored organ-sparing approaches and found hypofraction
This document summarizes chemotherapy options for head and neck squamous cell carcinoma (HNSCC). It discusses commonly used chemotherapies like methotrexate, 5-fluorouracil, cisplatin, carboplatin and taxanes. It also covers multi-agent chemotherapy regimens and the roles of neoadjuvant, concurrent and adjuvant chemotherapy when combined with radiation or surgery. Recent advances with targeted therapies like trastuzumab are also mentioned.
This document discusses chemoradiation for head and neck cancers. It notes that locoregional control is important for curative treatment as most deaths are due to local or regional spread. The evolution of combining chemotherapy with radiation is described, from initial trials in the 1960s-1980s showing improved larynx preservation and disease-free survival. Current standard concurrent chemoradiation regimens use cisplatin given with radiation. Adjuvant chemoradiation after surgery is also discussed, with two large trials showing improved progression-free and overall survival compared to radiation alone for high-risk patients.
Multimodality Treatment Of Stage Iii Nsclcfondas vakalis
1) Multimodality treatment including chemotherapy and radiotherapy has improved outcomes for stage III non-small cell lung cancer (NSCLC) over the past decade, increasing median survival by 5 months and 1-2 year survival by 10%.
2) Induction chemotherapy with a platinum agent and third-generation drug for 2-3 cycles followed by radiotherapy remains a good standard treatment for fit patients.
3) Concurrent chemoradiotherapy and combined modality approaches may offer further benefits but require more evidence, as they present increased toxicity risks that need to be weighed against uncertain survival gains.
This document provides information on a case presentation of anal squamous cell carcinoma, including staging, diagnostic workup, management, prognostic factors, and follow up. Key points include:
- The mean age of diagnosis is 62 years and most common symptom is rectal bleeding. Imaging includes CT, MRI, and PET scans to stage disease.
- Treatment depends on disease stage but typically involves chemoradiation with concurrent 5-FU and mitomycin C or cisplatin. Several trials have shown improved outcomes with chemoradiation compared to radiation alone.
- Follow up involves examination and imaging to monitor for recurrence or metastasis. Prognostic factors include tumor size, response to initial treatment, and presence of late
Role of induction chemotherapy in Squamous Cell Carcinoma head and Neck ...Kunal Jha
Induction chemotherapy, or neoadjuvant chemotherapy, is the use of chemotherapy prior to definitive surgery or radiation therapy for head and neck cancer. It has several potential benefits, including improving tumor response to subsequent therapy and increasing the chance of organ preservation. While induction chemotherapy is commonly used when organ preservation is the goal, guidelines for its optimal use outside of this setting are still being defined. Larger prospective trials are still needed to further establish the efficacy and role of induction chemotherapy for head and neck cancer.
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
The document discusses combined chemoradiotherapy for non-small cell lung cancer (NSCLC). It describes the evolution of radiotherapy techniques from older 2D techniques to modern 3D conformal radiation and IMRT. Studies show combined chemoradiotherapy improves survival over radiotherapy alone or sequential chemotherapy and radiotherapy by reducing locoregional recurrence rates. However, concurrent chemoradiotherapy is associated with increased toxicity risks which must be balanced against survival benefits.
Personalized medicine in radiation oncology aims to individualize radiotherapy treatment through better imaging, genetics, and biomarkers. Newer radiotherapy techniques like IMRT and IGRT allow for more precise targeting of tumors while minimizing dose to normal tissues. Biomarkers can help characterize tumor hypoxia, proliferation, and a patient's inherent radiosensitivity at the genetic level. Radiogenomics research seeks genetic polymorphisms associated with radiation response and side effects. The goal is to predict treatment outcomes and tailor radiotherapy for each patient's unique biology and genetics.
The document discusses evidence for dose escalation in prostate cancer radiotherapy. It summarizes several randomized controlled trials that found dose escalation improved biochemical control rates with acceptable toxicity. The largest trial, RT01, found a significant improvement in progression-free survival but also greater bowel toxicity for the higher dose. Ongoing trials are further exploring dose escalation using newer techniques like intensity-modulated radiotherapy to better spare surrounding tissues.
1) Randomized trials show that for locally advanced prostate cancer, early hormone therapy combined with radiotherapy improves prostate cancer specific survival and overall survival compared to hormone therapy alone.
2) A randomized trial found that hormone therapy plus radiotherapy reduced the risk of prostate cancer death by 56% and reduced the risk of overall mortality by 23% compared to hormone therapy alone.
3) Radiotherapy is associated with improved outcomes for locally advanced prostate cancer compared to surgery, though the role of surgery remains unclear.
Lung cancer is a leading cause of cancer death. Immunotherapy using immune checkpoint inhibitors that target proteins like PD-1 and PD-L1 has shown promise in treating lung cancer. A study presented at ASCO 2015 found that treatment with the PD-L1 inhibitor atezolizumab resulted in improved survival for NSCLC patients with higher levels of PD-L1 expression on tumor cells compared to docetaxel chemotherapy. Another study showed nivolumab, a PD-1 inhibitor, improved survival over docetaxel as a treatment for advanced non-squamous NSCLC after chemotherapy, with greater benefit seen in patients with higher PD-L1 expression levels. These results suggest PD-L1 expression can help identify
This document discusses treatment approaches for bladder cancer including radiotherapy and cystectomy. It summarizes results from several studies comparing outcomes of radiotherapy versus cystectomy, and studies combining radiotherapy with chemotherapy. The key findings are:
1) Long-term survival rates after radiotherapy or cystectomy are comparable.
2) A study found neoadjuvant chemotherapy prior to radiotherapy improved 2-year loco-regional disease-free survival compared to radiotherapy alone.
3) Bladder preserving therapy can provide good long-term bladder function for patients who are not candidates for cystectomy.
1. The document discusses individualized systemic therapy for non-small cell lung cancer (NSCLC), focusing on biomarkers like ERCC1, BRCA1, and EGFR mutations that can help customize chemotherapy based on a patient's tumor genetics.
2. Clinical trials show that targeting therapies like EGFR tyrosine kinase inhibitors provide significant benefits for NSCLC patients with EGFR mutations, with response rates over 70% in some studies.
3. Ongoing research aims to identify additional biomarkers to further personalize treatment selection and overcome resistance to targeted therapies.
The document summarizes information about lung cancer, including:
1) Lung cancer subtypes are small cell carcinoma (13%), large cell carcinoma (5%), adenocarcinoma (38.3%), and squamous cell carcinoma (19.7%).
2) Adjuvant chemotherapy in resected early-stage non-small cell lung cancer (NSCC) improves survival compared to surgery alone, though benefits vary by stage. Platinum-based regimens like cisplatin and vinorelbine are commonly used.
3) For locally advanced unresectable NSCLC, concurrent chemoradiotherapy is superior to sequential chemotherapy and radiotherapy, improving median and 5-year survival.
Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder CancerBJUI
This document summarizes bladder-sparing trimodality therapy for muscle-invasive bladder cancer. It discusses the evolution of bladder-sparing approaches including maximal transurethral resection of bladder tumor (TURBT), radiation therapy, and chemotherapy. Long-term outcomes from studies at Massachusetts General Hospital show 5-year overall survival of 52% and disease-specific survival of 64% with 29% of patients requiring cystectomy. Factors associated with improved outcomes include lower clinical stage, complete TURBT, and complete response to induction therapy.
Radiation therapy plays an evolving role in the treatment of lung cancer beyond just causing DNA double strand breaks.
1) Stereotactic body radiation therapy (SBRT) can provide curative treatment for early stage lung cancer with high local control rates.
2) For locally advanced lung cancer, dose escalation with conventional fractionation in RTOG 0617 did not improve overall survival, highlighting the importance of fractionation and sequencing with other therapies.
3) Radiation induces tumor cell death that can elicit anti-tumor immune responses, known as abscopal effects, especially when combined with immunotherapy like anti-CTLA4 and anti-PD1/PDL1 agents which play complementary roles.
This document discusses treatment approaches for ovarian cancer. It notes that surgery followed by platinum-based chemotherapy is the standard first-line treatment. Recent trials show neoadjuvant chemotherapy followed by interval debulking surgery may be an alternative approach with less morbidity. Dose-dense chemotherapy regimens and the addition of targeted therapies like bevacizumab to chemotherapy are also discussed as approaches to improve outcomes. Ongoing trials are further exploring the benefits of intraperitoneal chemotherapy and optimal integration of targeted therapies.
This document discusses balanced treatment approaches for esophageal cancer. It recommends that surgery plus additional therapy is required for pT3 N1 tumors. Definitive chemoradiotherapy is an acceptable standard for squamous cell carcinoma. Preoperative and postoperative combination chemotherapy is also an acceptable approach for resectable esophageal or GEJ adenocarcinoma. Preoperative concurrent chemoradiotherapy is a standard for resectable adenocarcinoma of the esophagus or GEJ. The role of preoperative chemotherapy alone for resectable squamous cell carcinoma is unclear and not recommended.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
This document summarizes evidence for adjuvant and neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC). Meta-analyses show adjuvant cisplatin-based chemotherapy improves 5-year survival by 4-5% after surgery for stages II-III NSCLC. Individual trials also found benefits, though some only for certain stages. Neoadjuvant chemotherapy may improve survival by 5% at 5 years for resectable stage IIIA NSCLC. Ongoing trials aim to personalize chemotherapy based on biomarkers and add targeted therapies.
EBRT in breast cancer: Evolution to cutting edgePramod Tike
EBRT in breast cancer has evolved significantly over time. Randomized controlled trials have shown that post-operative radiotherapy after breast-conserving surgery reduces local recurrence rates compared to surgery alone. Hypofractionated radiotherapy regimens have been shown to be as effective as conventional fractionation with reduced toxicity. Newer radiotherapy techniques such as forward-planned intensity-modulated radiation therapy (IMRT) allow improved dose distribution and reduced normal tissue exposure. Partial breast irradiation is being investigated as an alternative to whole breast irradiation for selected low-risk patients.
This document summarizes information about radiotherapy for non-small cell lung cancer (NSCLC). It discusses the role of radiotherapy for early, locally advanced, and metastatic NSCLC. It describes stereotactic body radiotherapy (SBRT) for early-stage disease and concurrent chemoradiotherapy (CTRT) for locally advanced stages. It also reviews evidence on optimal radiotherapy techniques and dosing, as well as trials investigating induction, consolidation, and adjuvant chemotherapy combined with radiotherapy.
This document summarizes information about radiotherapy for non-small cell lung cancer (NSCLC). It discusses the role of radiotherapy for early, locally advanced, and metastatic NSCLC. It describes stereotactic body radiotherapy (SBRT) for early-stage disease and concurrent chemoradiotherapy (CTRT) for locally advanced stages. It also reviews evidence on optimal radiotherapy techniques and dosing, as well as trials investigating induction, consolidation, and adjuvant chemotherapy combined with radiotherapy.
This study evaluated the roles of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic cancer. 541 patients were randomized to one of four groups: chemoradiotherapy, chemotherapy, both, or observation. The results showed no survival benefit for adjuvant chemoradiotherapy, with a median survival of 15.5 months compared to 16.1 months without chemoradiotherapy. However, there was evidence of a survival benefit for adjuvant chemotherapy, with a median survival of 19.7 months compared to 14 months without chemotherapy. This study provided evidence that adjuvant chemotherapy may improve survival for patients with resected pancreatic cancer, but did not show a benefit for chemoradiotherapy.
Post-operative Radiotherapy for Esophageal Cancerfondas vakalis
The document discusses evidence from randomized trials and studies on the use of postoperative radiotherapy and chemoradiotherapy for esophageal cancer. It summarizes several key trials that have shown postoperative radiotherapy improves overall survival for stage III and node-positive esophageal cancer patients by decreasing locoregional recurrence rates. The largest trial discussed found that postoperative chemoradiotherapy improved both overall and relapse-free survival compared to surgery alone for gastric adenocarcinoma patients. Non-randomized studies also suggested benefits of postoperative chemoradiotherapy over radiotherapy alone or surgery alone for esophageal squamous cell carcinoma.
Rectal cancer treatment typically involves surgery. Local recurrence after conventional surgery occurs in 15-65% of cases on average. Long course preoperative chemoradiotherapy has been shown to reduce local recurrence rates compared to short course preoperative radiotherapy or radiotherapy alone. It increases local tumor control and survival rates with some toxicities but does not reduce colostomy rates. Preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy in reducing local recurrence rates without affecting overall survival.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
The document discusses head and neck cancer, focusing on individualizing treatment. It notes that head and neck cancer incidence is increasing, with some caused by HPV. EGFR is a molecular target in these cancers. Studies combining EGFR inhibitors like cetuximab with chemoradiation in locally advanced disease showed increased toxicity but uncertain efficacy benefits. Biomarker-selected treatment de-intensification may be appropriate for HPV-positive cancers.
Similar to MCO 2011 - Slide 17 - J.B. Vermorken - Systemic therapy (20)
1) The study examines how and why certain breast cancer cells metastasize to bone through a "seed pre-selection" process.
2) It finds that high Src activity (denoted by a "Src activity signature" or SRS) in primary tumors associates with bone metastasis.
3) In ER-/ERBB2- breast cancers, cytokines CXCL12 and IGF1 in the tumor microenvironment activate Src which promotes cell survival and bone metastasis. Long term exposure to these cytokines in vitro selects for breast cancer cells with higher Src activity and bone metastatic ability.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
This document summarizes the management of urinary bladder cancer. It discusses staging, histopathologic types, and treatment options for non-muscle invasive and muscle invasive bladder cancer as well as metastatic disease. Standard first-line chemotherapy for metastatic bladder cancer includes gemcitabine and cisplatin or MVAC. Newer chemotherapy regimens and agents are also discussed.
The document discusses new drugs for the treatment of lymphomas. It outlines several monoclonal antibodies that target antigens on B-cells, including CD20, CD19, CD22 and CD37. Ofatumumab and GA-101 are new anti-CD20 monoclonal antibodies that exhibit enhanced binding and cell-killing properties compared to Rituximab. Inotuzumab Ozogamicin is an antibody-drug conjugate targeting CD22 that is internalized and releases a cytotoxic drug, showing promising activity in early clinical trials.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy improves outcomes for DLBCL compared to chemotherapy alone. Strategies discussed to improve outcomes include increasing chemotherapy dose intensity and the potential role of the drug bortezomib for the activated B-cell subtype.
This document discusses treatment of diffuse large B-cell lymphoma (DLBCL). It notes that DLBCL is a heterogeneous disease with genetic subgroups that have different prognoses and responses to treatment. The addition of the antibody rituximab to chemotherapy like CHOP has improved outcomes for DLBCL compared to chemotherapy alone in the post-rituximab era. Strategies to further improve outcomes include targeting specific genetic subgroups like the activated B-cell subtype using drugs like bortezomib that inhibit pathways like NF-kB.
The document discusses the current state of cancer vaccines, focusing on HPV vaccines. It outlines the types of vaccines as prophylactic, preventive, or therapeutic. HPV vaccines have proven highly effective as prophylactic vaccines in preventing cervical cancer. Clinical trials demonstrated up to 100% efficacy of the HPV vaccines Gardasil and Cervarix in preventing precancerous lesions. However, challenges remain regarding cross-protection against other HPV types, long-term duration of protection, and reducing production costs to increase global access.
- Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in women. Risk factors include age over 60, obesity, talcum powder use, fertility drugs, genetic predispositions like BRCA mutations.
- Surgical staging is essential for determining prognosis and appropriate treatment. For early stage disease adjuvant chemotherapy is recommended. Advanced stage disease is treated with cytoreductive surgery followed by platinum/taxane chemotherapy.
- Prognosis depends on stage and completeness of cytoreduction. Median survival is 39 months for optimal vs 17 months for suboptimal cytoreduction. Secondary surgery and chemotherapy may provide benefit for recurrence in some patients.
This document summarizes key information about ovarian cancer, including epidemiology, staging, treatment milestones, prognostic factors, and recent clinical trials. It notes that the median age of diagnosis is 63 years and discusses improvements in 5-year survival over time. New developments discussed include the role of surgery, chemotherapy regimens, targeted therapies like bevacizumab, and trials in recurrent settings.
Nearly 500,000 new cases of cervical cancer occur worldwide each year, with the majority in developing countries. Infection with HPV is responsible for virtually all cervical cancer cases. Screening includes Pap smears and HPV testing, while vaccination may prevent up to 70% of cases but is not widely available due to cost. Diagnosis is through biopsy and histopathological examination, while staging uses the FIGO system based on tumor size and spread. Treatment depends on stage but commonly includes surgery such as hysterectomy with or without radiation or chemotherapy.
- Cervical cancer is a major cause of cancer deaths worldwide, with over 500,000 new cases and 260,000 deaths estimated annually. Most deaths occur in developing countries where screening and prevention programs are lacking.
- Early detection through screening programs can make cervical cancer highly curable, but the majority of cases in developing nations are diagnosed at late stages when survival rates are low. Vaccination and screening can help prevent a large percentage of cervical cancer cases.
- Risk factors for cervical cancer include human papillomavirus infection and lack of access to healthcare. While HPV infection is necessary, most infections clear without causing cancer. Other factors like multiple pregnancies, smoking, and HIV infection can increase the risk.
The document summarizes the current state of metastatic breast cancer treatment. It discusses how survival rates have improved over time and metastatic breast cancer is now considered a chronic, treatable disease rather than an immediately terminal condition. Treatment involves systemic therapies like chemotherapy, endocrine therapy, targeted therapies, as well as radiation, surgery, and supportive care. Selection of optimal first-line systemic treatment depends on disease characteristics and patient factors. Ongoing research focuses on tailoring and sequencing treatments to overcome resistance and further extend patient survival and quality of life.
1) Breast cancer is heterogeneous with different subtypes defined by receptor status and gene expression profiles. The subtypes have different biological behaviors and clinical outcomes.
2) Accurate diagnosis requires biopsy (FNA or core) followed by receptor testing before treatment decisions. Surgery options include breast conserving therapy or mastectomy with/without reconstruction.
3) For early breast cancer, sentinel lymph node biopsy guides the need for further axillary lymph node dissection. Omission of further dissection may be adequate for sentinel node positive patients.
- The document discusses liver and hepatobiliary cancers, focusing on hepatocellular carcinoma (HCC). It covers the epidemiology, risk factors, screening and diagnosis of HCC as well as staging systems and treatment options.
- Risk factors for HCC include hepatitis B and C infection, alcohol consumption, and aflatoxin intake. Screening ultrasound and AFP tests are used for early diagnosis in high-risk patients. The BCLC staging system guides treatment which includes resection, transplantation, ablation, and embolization.
- For intermediate stage HCC, transarterial chemoembolization provides the best outcomes, with 70-80% of patients surviving 1 year and 50% surviving 3 years. However
The document discusses guidelines for screening, diagnosis, staging, adjuvant therapy, advanced disease treatment, and follow-up for colorectal cancer from both the ESMO and NCCN perspectives. It provides recommendations for screening the general and high-risk populations. It also outlines the diagnostic and staging workup, including endoscopy, biopsy, imaging, and surgical staging. Guidelines are presented for adjuvant therapy based on cancer stage. Recommendations are provided for managing both synchronous and metachronous metastatic disease, as well as rectal cancer treatment.
1) A trial found that adding bevacizumab to chemotherapy for stage III colon cancer extended disease-free survival compared to chemotherapy alone, delaying cancer relapse but not preventing it completely.
2) There was no overall survival benefit observed from adding bevacizumab, suggesting it delays but does not alter the underlying biology of the disease.
3) The interpretation is that relapses were delayed by bevacizumab treatment but then occurred at a steady rate later on, similar to the chemotherapy alone group.
This document provides an overview of squamous cell carcinoma of the head and neck (SCCHN), including its anatomical sites, incidence and mortality rates, risk factors, staging guidelines, and treatment approaches. It discusses the roles of surgery, radiation therapy, chemotherapy, concurrent chemoradiation, and targeted therapies like cetuximab in managing localized and advanced SCCHN. Concurrent chemoradiation is now standard for improving local control and organ preservation compared to radiation alone. The addition of cetuximab to radiation was shown to improve locoregional control and overall survival.
The document provides guidelines for the treatment of advanced non-small cell lung cancer. It recommends that first-line therapy should consist of platinum-based combination chemotherapy for patients with good performance status. For patients with EGFR mutations, an EGFR tyrosine kinase inhibitor is the preferred first-line treatment. It also recommends the addition of bevacizumab or cetuximab to platinum-based chemotherapy for certain patients.
1. Systemic Treatment in Head & Neck Cancer Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium ESO-ESMO Masterclass in Clinical Oncology Zürich, April 4, 2011
5. Case 1: Locoregionally Advanced Head and Neck Cancer Treatment: 11.07.2003 PF regimen cycle I 01.08.2003 PF regimen cycle II PR (CT-scan) 26.08.2003 PF regimen cycle III 06.10.2003 RT 70 Gy in 35 sessions concomitant gemcitabine 100 mg/m²/week > 90% PR starting 01.10.03 for 7 times (CT-scan)
9. 1 st. TL 1 st. PLs 1 st. RT SCPL Laser CO² ASCO 1982 trial VA trial EORTC trial RTOG trial EORTC 1873 1903 1878 1970s 1994 1996 2003 2005 2007 CTscan MRI surgery radiotherapy laser Milestones in Larynx/Hypopharynx Management trial GORTEC
10. Milestones in Systemic Therapies (± RT) in Head and Neck Squamous Cell Cancer 1960s Methotrexate (ICT, CRT) 1970s Bleomycin, 5-fluorouracil, cisplatin Combination chemotherapy regimens 1980s Carboplatin Organ preservation trials start (ICT) 1990s Paclitaxel, docetaxel CCRT>RT 2000s Targeted therapies (MoAb) ICT revisited Sequential therapy (ICT CCRT)?
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14. 63 randomized trials MACH-NC = Individual patients data base 7,307 deaths (68 %) 10,741 patients Lancet 2000;355:949-55 IGR 10.00 Meta-Analysis of Chemotherapy in Head & Neck Cancer MACH-NC
15. MACH-NC: Results - Overall Survival Chemotherapy Risk P Absolute benefit timing reduction value at 5 years Adjuvant 2% NS 1% Neoadjuvant* 5% NS 2% Concomitant 19% < 0.0001 8% Total 10% < 0.0001 4% * 15 studies with PF 5% Pignon et al, 2000 (63 trials / 10.741 patients)
20. Enhancement of Radiation Effects Selective Targeting of Hypoxic Cells Induction of Pro-Apoptotic Mechanisms Anti- Angiogenesis Strategies Inhibition of Cox-2 Replacement of Mutated Tumor Suppressor Genes Inhibition of EGFR Several biological mechanisms that have potential to alter sensitization strategies (Choy and MacRae, 2003)
24. Cetuximab + RT in locally advanced SCCHN: Study design Bonner et al. N Engl J Med 2006; 354: 567-578 RT as before + ERBITUX initial 400 mg/m 2 2-h infusion then 250 mg/m 2 1-h infusion weekly for at least 7 doses RT once or twice daily or concomitant boost for 7 – 8 weeks Patients with measurable locally advanced SCCHN (stratified by KPS;node+/0;T1-3/4; RT regimen) Randomization Follow-up until disease progression or up to 5 years
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26. 5-Years Survival Update and QoL Assessment 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 10 20 30 40 50 60 70 Time (months) Probability of overall survival Bonner JA, et al. Presented at ASTRO 2008 ERBITUX + RT RT ERBITUX + RT RT 5-year survival rate 46% 36% p=0.018, HR=0.73 (0.56-0.95) 29.3 49.0 ERBITUX + RT does not adversely affect QoL, while significantly improving overall survival Curran D, et al. J Clin Oncol 2007; 25: 2191 –2197 a Post-baseline scores for the EORTC QLQ-C30 Global health status/QoL score a 100 80 60 40 20 0 RT RT + ERBITUX Baseline Week 4 Month 4 Month 8 Month 12
27. Compliance with Cetuximab or Chemotherapy when Administered with RT 1 Bonner JA, et al. N Engl J Med 2006; 354: 567 –578; 2 Huguenin P, et al. J Clin Oncol 2004; 22: 4665–4673; 3 Calais G, et al. J Natl Cancer Inst 1999; 91: 2081 – 2086; 4 Wendt TG, et al. J Clin Oncol 1998; 16: 1318 –1324 CRT arms of studies comparing CRT vs RT alone Cisplatin / 5-FU / FA 4 46% 51% 71% 90% 0 20 40 60 80 100 Carboplatin / 5-FU 3 Cisplatin 2 Cetuximab 1 Patients receiving all planned doses (%) 10 70 50 30 90 Weekly doses (median 8 doses) 2 cycles at weeks 1 and 5 3 cycles at weeks 1, 4, and 7 3 cycles at weeks 1, 3, and 6 2nd cycle 3rd cycle 3rd cycle
28. Overall Conclusion No direct comparison *level I evidence; **level II evidence; + with mono Platin therapy Chemoradiation Bioradiation ( cetuximab ) 50 trials, 9615 pts (MA)* 1 trial, 424 pts (Bonner trial)** HR of death 0.74 (0.67-0.82) + HR of death 0.74 (0.57-0.97) Main effect on local failure Modest effect on DM Only effect on local failure No effect on DM Efficacy irrespective of site and of fractionation schedule Effect may be site and RT schedule specific Significant acute toxicity which may inflict on late toxicity, in particular swallowing dysfunction Skin reaction?? Late toxicity as RT Compliance of receiving cetuximab 90% in the Bonner trial
29. Analysis of Failures in Phase III CRT or BRT Trials Trials Group Year Published Locoregional failure (%) Distant metastases (%) % of failures due to DM INT 2003 22 23 51 EORTC 2005 18 21 54 RTOG 2005 16 20 65 GORTEC Bonner 2005 2006 57 53 18 17 32 30 Modified from Posner and Vermorken, 2008
30.
31. Randomized Trials of ICT in LA-HNC Revisited Trial Arms Outcome CA 139-322 (2005) PF vs PPF CCR (TTP , OS*) Resectable/nonresectable CRT (CDP) Improved with PPF EORTC 24971/TAX 323 PF vs TPF PFS (RR, OS)° Nonresectable (2007) RT Improved with TPF TAX 324 (2007) PF vs TPF OS (PFS , RR)° Resectable/nonresectable CRT (Cb) Improved with TPF GORTEC 2000-01 PF vs TPF LP (OS, DFS) + Resectable (2006) T(P)L vs RT Improved with TPF *significant only in unresectable disease (JCO); °NEJM; + ASCO 2006
32. SCCHN: Docetaxel in Locally-Advanced Disease Overall Survival TAX 324 30% reduction in risk of death TAX 323 27% reduction in risk of death TPF PF 50 Survival Time (months) Survival Probability (%) Survival Time (months) 0 6 12 18 24 30 36 42 48 54 60 66 72 0 10 20 30 40 60 70 80 90 100 TPF PF Survival Time (months) Survival Time (months) 0 6 12 18 24 30 36 42 48 54 60 66 72 Posner et al, 2007 Resectable/unresectable disease Vermorken et al, 2007 Unresectable disease
33. EORTC 24971/TAX 323 Toxicity NCIC-CTC Grade 3-4 PF (n=179) TPF (n=173) Toxicity % % Anemia/ thrombocytopenia 13/ 18 9/ 3 Neutropenia 53 77 Nausea/vomiting 7/4 <1/<1 Diarrhea 3 3 Stomatitis 11 5 Infection 6 7 Febrile neutropenia 3 5 Hearing loss 3 0 Toxic deaths 5.5 2.3 Primary prophylactic antibiotics were given per protocol for TPF Vermorken et al, N Engl J Med 2007; 357: 1695-1704
34. EORTC 24971/TAX 323 Quality of Life Analysis: QLQ-C30 Global Health Bernier et al. ASCO 2006; Abstract 5522 PF TPF (N=142) (N=143) Cycle 2 Least Square Mean QLQ-C30 Score [99% CI] 100 90 80 70 60 50 40 30 20 10 0 Cycle 4 6 mos. Post RT 9 mos. Post RT Least Square Mean TPF vs PF: p=0.01 CI=Confidence Interval; RT=Radiotherapy
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37. Randomized Trials of Sequential Therapy versus Concurrent Chemoradiation Only Group Regimen TPF (or PF) x 3 CRT (cisplatin) TTCC (Sp) CRT (cisplatin) TPF x 3 CRT (carboplatin) Boston (US) CRT (cisplatin) TPF x 2 THFX Chicago (US) THFX XRT (cetuximab) TPF x 3 XRT (PF) GCTCC (It) XRT (cetuximab) XRT (PF)
42. The 3-year rates of overall survival were 93.0% (95% CI, 88.3 to 97.7) in the low-risk group, 70.8% (95% CI, 60.7 to 80.8) in the intermediate-risk group, and 46.2% (95% CI, 34.7 to 57.7) in the high-risk group. Ang K et al. N Engl J Med 2010;361:24-35
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45. Development of Chemotherapy in R/M SCCHN 1977: cisplatin shows efficacy in 1 st -line SCCHN CABO, cisplatin, methotrexate, bleomycin, vincristine *significant Clavel et al. Ann Oncol 1994; Forastiere et al. JCO 1992; Gibson et al. JCO 2005; Grose et al. Cancer Treat Rep 1985; Vermorken et al. NEJM 2008; Wittes et al. Cancer Treat Rep 1977 N Regimen ORR (%) Median OS (months) Significant OS benefit Grose et al 1985 100 Methotrexate Cisplatin 16 8 5.0 4.5 No Forastiere et al 1992 277 Cisplatin + 5-FU Carboplatin + 5-FU Methotrexate 32* 21 10 6.6 5.0 5.6 No Clavel et al 1994 382 CABO Cisplatin + 5-FU Cisplatin 34* 31* 15 7.3 7.3 7.3 No Gibson et al 2005 218 Cisplatin + 5-FU Cisplatin + paclitaxel 27 26 8.7 8.1 No Vermorken et al 2008 442 Platinum + 5-FU Platinum + 5-FU + Cetuximab 20 36* 7.4 10.1* Yes
47. EXTREME: Responses to Treatment and Survival Variable PF+cetuximab n=222 PF n=220 HR or OR (95% CI) P value Survival – mo overall progression-free 10.1 (8.6 -11.2) 5.6 (5.0 - 6.0) 7.4 (6.4-8.3) 3.3 (2.9-4.3) HR 0.80 (0.60-0.99) HR 0.54 (0.43-0.67) 0.04 <0.001 Best response - % overall disease control 36 (29-42) 81 (75-86) 20 (15-25) 60 (53-67) OR 2.33 (1.50-3.60) OR 2.88 (1.87-4.44) <0.001 <0.001 Time to TRT failure-mo 4.8 (4.0-5.6) 3.0 (2.8-3.4) HR 0.59 (0.48-0.73) <0.001 Duration of response 5.6 (4.7-6.0) 4.7 (3.6-5.9) HR 0.76 (0.50-1.17) 0.21 PF=cisplatin or carboplatin + 5-FU; HR=hazard ratio; OR: odds ratio Vermorken et al. N Engl J Med 2008: 359: 1116-27
48. EXTREME: Symptom Control Mean change from boaseline t worst post-baseline score Pain Swallowing problems Sense problems Speech problems Social eating problems Problems with social contact p=0.0027 p=0.0162 p=0.5702 p=0.0787 p=0.0694 p=0.7732 p=0.2237 -9.99 +3.51 -9.17 +5.21 -2.60 +4.42 -7.81 +1.33 -9.98 +0.24 -2.64 - 0.43 -2.55 +4.37 Problems with reduced sexuality Worsening symptoms Improving symptoms Cetuximab + chemotherapy Chemotherapy alone Mesia et al, Ann Oncol 2010 (doi 10,1093/annonc/mdq077)
49. EXTREME: Most relevant grade 3/4 adverse events Modified from Vermorken et al, N Engl J Med 2008: 359: 1116-27
50. EXTREME: Quality of life a a <50% of patients completed a baseline questionnaire; = 95% CIs for difference in treatment groups 100 80 60 40 20 0 -20 Global health status/QoL Erbitux + CTX CTX Erbitux + CTX CTX Baseline (n=109) (n=94) Cycle 3 (n=80) (n=63) 6 months (n=45) (n=20) Mesia et al, Ann Oncol 2010 (doi 10,1093/annonc/mdq077 )
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52. Adding Cetuximab to Chemotherapy Shows Consistent Efficacy in 1st-line R/M SCCHN Vermorken JB, et al. N Engl J Med 2008;359:1116–1127; Burtness B, et al. J Clin Oncol 2005;23:8646–8654; Bourhis J, et al. J Clin Oncol 2006;24:2866–2872; Hitt R, et al. ASCO 2007 (Abstract No. 6012; updated information presented); Buentzel J, et al. ASCO 2007 (Abstract 6077) a p<0.001; b p=0.04; c p=0.03; d Median OS not reached after a median follow-up of 5.6 months; e TTP Author Phase Regimen ORR (% ) Median PFS (months ) Median OS (months) Burtness et al. III CDDP + cetuximab CDDP + placebo 26 c 10 4.2 2.7 9.2 8.0 Bourhis et al. I/II PF + cetux i ma b 36 5.1 e 9.8 Vermorken et al. III PF + cetuximab PF 36 a 20 5.6 a 3.3 10.1 b 7.4 Hitt et al. II Pacli + cetuxima b 60 5.0 NR d Buentzel et al. II Pacli/Carbo + cetuximab 56 5.0 e 8.0
53. Completed Randomized Trials in First-Line Recurrent/Metastatic SCCHN Study/Reference N Regimen RR (%) PFS (mo) OS (mo) ECOG 5397/ Burtness et al 2005 117 Cisplatin + cetuximab Cisplatin + placebo 26 a 10 4.2 2.7 9.2 8.0 EXTREME/ Vermorken et al 2008 442 PF 1 + cetuximab PF 1 36 a 20 5.6 b 3.3 10.1 c 7.4 SPECTRUM/ Vermorken et al 2010 657 PF 2 + panitumumab PF 2 36 a 25 5.8 b 4.6 11.1 9.0 PF 1 = cisplatin or carboplatin plus 5-FU; PF 2 = cisplatin plus 5-FU a, b, c : significant differences
54. EGFR Inhibitor Response Rates in SCCHN Prior CT= for recurrent/metastatic disease Drug Phase/ prior CT Reference Response Rate Cetuximab II Pt- refract Vermorken, JCO, 2007 13% Erlotinib II 0-1 lines Soulieres, JCO, 2004 4% Gefitinib II 0-1 lines Cohen, JCO, 2003 11% II 0-5 lines Cohen, CCR, 2005 2% II 0-1 lines Kirby, BJC, 2006 9% III Pt + (A) Stewart, JCO, 2009 8% Lapatinib II unclear Abidoye, ASCO 2006 0% Cetuximab II prior Pt Seiwert, ASCO 2010 13% BIBW 2992 II prior Pt Seiwert, ASCO 2010 22%
55. Completed Randomized Trials in 2nd-Line Recurrent/Metastatic SCCHN Study/Reference N Regimen RR (%) PFS OS (mo) IMEX Stewart et al, 2009 486 Gefitinib (250 mg) Gefitinib (500 mg) Methotrexate 2.7 7.6 3.9 ND ND ND 5.6 6.0 6.7 ECOG 1302 Argiris et al, 2009 270 D + Gefitinib D + placebo 12 6 3.3 2.2 6.8 6.2 Zalute Machiels et al, 2010 286 Z + BSC (-MTX) BSC (optional MTX) 6 1 2.3* 1.9* 6.7° 5.2° BSC = best supportive care; Z = zalutumumab; MTX = methotrexate; ND = no data *HR (95% CI): 0.62 (0.47-0.83), p=0,0010; °HR (95% CI): 0.77 (0.57-1.05), p=0.0648
59. Novel Agents Not Targeting EGFR in Recurrent or Metastatic SCCHN Target Single agent Combination Bevacizumab Angiogenesis No data Promising/ongoing Sorafenib Angiogenesis Low/mod activity Ongoing Sunitinib Angiogenesis Low activity - Dasatinib Src, others Low activity Planned Bortezomib Proteasome Low activity Low activity Vorinostat HDAC Low activity - Figitumumab IGF-1R Low activity - Cixutumumab IGF-1R Ongoing Ongoing Everolimus mTOR Ongoing Ongoing
60. Treatment Combined anti-EGFR Treatment with Gefitinib and Cetuximab P. Matar et al Clin Cancer Res 2004; 10: 6487-6501 Courtesy of Dr. Baselga, 2006
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63. Targets for Next-generation Therapy Tumor cell Nucleus 3 3. Signal transduction pathways Ras, raf, MAPK, MEK, ERK, AKT protein kinase C, PI3K 1 1. Growth factors and growth-factor receptors HER family, c-kit/SCFR 2 2. Extracellular matrix/ angiogenic pathways VEGFR, integrins, MMPs 4 4. Cell-survival pathways Cyclin-dependent kinases, mTOR, cGMP, COX-2, p53, Bcl-2 5. Protein production Proteasome 5
Editor's Notes
M225, a murine monoclonal antibody, competitively binds to the EGFR and inhibits EGFR pathways. Clinical trials using murine monoclonal antibodies have been complicated by the development of the human antimouse antibody (HAMA) immune response. The HAMA response not only carries the risk of serious allergic reactions but also increases the clearance of the murine proteins. Thus, the clinical utility of murine monoclonal antibodies has been limited. Cetuximab is a human:murine chimeric anti-EGFR IgG monoclonal antibody that binds exclusively to the EGFR. Chimeric antibodies are composed of the variable regions of murine antibody (the regions responsible for antigen binding) and the constant region of the human Fc fragment.[1] Chimeric monoclonal antibodies have demonstrated specificity and a diminished incidence of immunologic reactions.[2,3] Cetuximab binds to the EGFR with a binding affinity that is approximately one log higher than natural ligands.[4] Cetuximab prevents binding of endogenous ligands and induces receptor internalization, which ultimately blocks the activities of the EGFR pathway. Owens RJ, Young RJ. The genetic engineering of monoclonal antibodies. J Immunol Methods 1994; 168:149–165. Shitara K, Kuwana Y, Nakamura K, et al. A mouse/human chimeric anti-(ganglioside GD3) antibody with enhanced tumor activities. Cancer Immunol Immunother . 1993; 36:373–380. LoBuglio AF, Wheeler RH, Trang J, et al. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci U S A . 1989; 86:4220–4224. Goldstein NI, Prewett M, Zuklys K, et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res . 1995; 1:1311–1318.
Clavel M, et al. Ann Oncol 1994;5:521–526; Forastiere A, et al. J Clin Oncol 1992;10:1245–1251; Gibson MK, et al. J Clin Oncol 2005;23:3562–3567;Grose WE, et al. Cancer Treat Rep 1985;69:577–581; Vermorken JB, et al. N Engl J Med 2008;359:1116–1127; Wittes RE, et al. Cancer Treat Rep 1977;61359–61366.
Petrelli NJ et al. J Clin Oncol 2009;27:6052–6069; Gr é goire et al Annals of Oncology 21 (Supplement 5): v184–v186, 2010
14/04/11 m Adding Erbitux to different chemotherapies has demonstrated consistent efficacy in several trials in first-line R/M SCCHN. In a randomized, phase III trial of Erbitux plus cisplatin vs cisplatin alone (n=117), Burtness and colleagues demonstrated that the addition of Erbitux to cisplatin significantly increased the overall response rate compared with cisplatin alone (26% vs 10%, p=0.03). The addition of Erbitux to cisplatin also produced longer progression-free survival (median 4.2 vs 2.7 months) and longer overall survival (median 9.2 vs 8.0 months) compared with cisplatin alone, although these differences did not reach statistical significance. In a phase I/II trial of Erbitux combined with platinum (cisplatin or carboplatin) plus 5-FU (n=53) in the first-line treatment of R/M SCCHN, Bourhis and colleagues reported an overall response rate of 36%, with a 4% complete response rate. Median duration of response (95% CI) was 4.2 months (3.4 –9.9 months ), median time to progression (95% CI) was 5.1 months (4.2 –6.1 months ), and median survival (95% CI) was 9.8 months (8.0 –13.8 months ). In a phase II trial of Erbitux combined with paclitaxel in the first-line treatment of R/M SCCHN (n=42), Hitt and colleagues reported an overall response rate of 60%, with a 24% complete response rate. Median time to progression was 6.2 months, median progression-free survival was 5.0 months. These three trials, together with the EXTREME study, demonstrate that Erbitux combined with either platinum or taxane provides consistent clinical benefits in the first-line treatment of R/M SCCHN.
As a final slide I would like to put these data into perspective with other reports of anti-EGFR agents. Jan Vermorken reported in 2007 the response rate for Cetuximab to be 13% For Erlotinib the response reported rate is 4.3% For Gefitinib it varies dpending on the report between 1.8 and 10.6%. The phase III IMEX study puts it at 7.9% In our study we now confirm the cetuximab response rate of 13% Furthermore BIBW 2992 shows a response rate that is substantially above that of other small molecule TKIs
Epidermal growth factor receptor (EGFR) is one of several targets for next-generation therapy for metastatic colorectal cancer.