K Misiukiewicz1, V Gupta2, B A Miles3, R Bakst4, E Genden5, I Selkridge6, J T Surgeon6, H Rainey6, N Camille6, E Roy6, D Zhang7, F Ye7, R Jia8, E Moshier8, M Bonomi9, M Hwang10, P Som11, M R Posner12. 1. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA; The Departments of Hematology/Oncology in the Icahn School of Medicine at Mount Sinai, USA; Medicine in the Icahn School of Medicine at Mount Sinai, USA. 2. Radiation Oncology in the Icahn School of Medicine at Mount Sinai, USA. 3. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA; Otolaryngology in the Icahn School of Medicine at Mount Sinai, USA. 4. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA; Radiation Oncology in the Icahn School of Medicine at Mount Sinai, USA. 5. Otolaryngology in the Icahn School of Medicine at Mount Sinai, USA. 6. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA. 7. Pathology in the Icahn School of Medicine at Mount Sinai, USA. 8. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA; Biostatistics in the Icahn School of Medicine at Mount Sinai, USA. 9. The Departments of Hematology/Oncology in the Icahn School of Medicine at Mount Sinai, USA; Medicine in the Icahn School of Medicine at Mount Sinai, USA. 10. Medicine in the Icahn School of Medicine at Mount Sinai, USA. 11. Radiology in the Icahn School of Medicine at Mount Sinai, USA. 12. The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai, USA; The Departments of Hematology/Oncology in the Icahn School of Medicine at Mount Sinai, USA; Medicine in the Icahn School of Medicine at Mount Sinai, USA. Electronic address: marshall.posner@mssm.edu.
Abstract
BACKGROUND:Human Papillomavirus oropharyngeal carcinoma (HPVOPC) has better progression free (PFS) and overall survival (OS) than non-HPVOPC. Standard-dose chemoradiotherapy (sdCRT) results in significant acute toxicity and late morbidity. We hypothesized that after induction chemotherapy (IC), reduced dose chemoradiation (rdCRT) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity. METHODS:Patients with p16+, previously untreated, locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles ofIC with docetaxel, cisplatin and fluorouracil (TPF). Clinical responders who were HPV positive by type-specific PCR were randomized 1:2 to sdCRT (7000 cGy) or rdCRT (5600 cGy) with weekly carboplatin. The endpoints of the study were 3 year PFS and OS. RESULTS:23 patients were enrolled, 22 were evaluable for TPF toxicity and 20 were randomized, 8 to sdCRT and 12 to rdCRT. Sixteen (80%) were HPV 16+ and 4 (20%) were other high risk (HR) variants. Fourteen (70%) had high risk features: T4, N2c, or N3. Median follow up was 56 months (range 42-70). Three-year PFS/OS for sdCRT and rdCRT are 87.5% vs 83.3% (log-rank test p = 0.85), respectively. All 3 failures are locoregional within 4 months of completion of CRT; 2 were in HR variants (50%). CONCLUSIONS:rdCRT after IC resulted in similar PFS/OS compared sdCRT. These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC. Molecular HPV with variant testing and smoking history are necessary for de-escalation trials.
RCT Entities:
BACKGROUND: Human Papillomavirus oropharyngeal carcinoma (HPVOPC) has better progression free (PFS) and overall survival (OS) than non-HPVOPC. Standard-dose chemoradiotherapy (sdCRT) results in significant acute toxicity and late morbidity. We hypothesized that after induction chemotherapy (IC), reduced dose chemoradiation (rdCRT) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity. METHODS:Patients with p16+, previously untreated, locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles of IC with docetaxel, cisplatin and fluorouracil (TPF). Clinical responders who were HPV positive by type-specific PCR were randomized 1:2 to sdCRT (7000 cGy) or rdCRT (5600 cGy) with weekly carboplatin. The endpoints of the study were 3 year PFS and OS. RESULTS: 23 patients were enrolled, 22 were evaluable for TPFtoxicity and 20 were randomized, 8 to sdCRT and 12 to rdCRT. Sixteen (80%) were HPV 16+ and 4 (20%) were other high risk (HR) variants. Fourteen (70%) had high risk features: T4, N2c, or N3. Median follow up was 56 months (range 42-70). Three-year PFS/OS for sdCRT and rdCRT are 87.5% vs 83.3% (log-rank test p = 0.85), respectively. All 3 failures are locoregional within 4 months of completion of CRT; 2 were in HR variants (50%). CONCLUSIONS:rdCRT after IC resulted in similar PFS/OS compared sdCRT. These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC. Molecular HPV with variant testing and smoking history are necessary for de-escalation trials.
Authors: Lisa M Pinatti; Hana N Sinha; Collin V Brummel; Christine M Goudsmit; Timothy J Geddes; George D Wilson; Jan A Akervall; Chad J Brenner; Heather M Walline; Thomas E Carey Journal: Head Neck Date: 2020-10-19 Impact factor: 3.147
Authors: Brett A Miles; Marshall R Posner; Vishal Gupta; Marita S Teng; Richard L Bakst; Mike Yao; Kryzsztof J Misiukiewicz; Raymond L Chai; Sonam Sharma; William H Westra; Seunghee Kim-Schulze; Bheesham Dayal; Stanislaw Sobotka; Andrew G Sikora; Peter M Som; Eric M Genden Journal: Oncologist Date: 2021-03-18
Authors: Mai Takahashi; Michael Hwang; Krysztof Misiukiewicz; Vishal Gupta; Brett A Miles; Richard Bakst; Eric Genden; Isaiah Selkridge; John Botzler; Vruti Virani; Erin Moshier; Marcelo R Bonomi; Marshall R Posner Journal: Front Oncol Date: 2022-04-08 Impact factor: 5.738
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Authors: Flora Yan; Hannah M Knochelmann; Patrick F Morgan; John M Kaczmar; David M Neskey; Evan M Graboyes; Shaun A Nguyen; Besim Ogretmen; Anand K Sharma; Terry A Day Journal: Cancers (Basel) Date: 2020-06-11 Impact factor: 6.639