Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity.

We tested the efficacy and toxicity of cisplatin plus accelerated fractionation with a concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC). Patients had stage III to IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Radiation therapy schedules were 70 Gy in 35 fractions over 7 weeks (SFX) or 72 Gy in 42 fractions over 6 weeks (AFX-C). Cisplatin doses were 100 mg/m(2) once every 3 weeks for two (AFX-C) or three (SFX) cycles. Toxicities were scored by using National Cancer Institute Common Toxicity Criteria 2.0 and the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. Overall survival (OS) and progression-free survival (PFS) rates were estimated by using the Kaplan-Meier method and were compared by using the one-sided log-rank test. Locoregional failure (LRF) and distant metastasis (DM) rates were estimated by using the cumulative incidence method and Gray's test. In all, 721 of 743 patients were analyzable (361, SFX; 360, AFX-C). At a median follow-up of 7.9 years (range, 0.3 to 10.1 years) for 355 surviving patients, no differences were observed in OS (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.18; P = .37; 8-year survival, 48% v 48%), PFS (HR, 1.02; 95% CI, 0.84 to 1.24; P = .52; 8-year estimate, 42% v 41%), LRF (HR, 1.08; 95% CI, 0.84 to 1.38; P = .78; 8-year estimate, 37% v 39%), or DM (HR, 0.83; 95% CI, 0.56 to 1.24; P = .16; 8-year estimate, 15% v 13%). For oropharyngeal cancer, p16-positive patients had better OS than p16-negative patients (HR, 0.30; 95% CI, 0.21 to 0.42; P < .001; 8-year survival, 70.9% v 30.2%). There were no statistically significant differences in the grade 3 to 5 acute or late toxicities between the two arms and p-16 status. When combined with cisplatin, AFX-C neither improved outcome nor increased late toxicity in patients with LA-HNC. Long-term high survival rates in p16-positive patients with oropharyngeal cancer support the ongoing efforts to explore deintensification.

Nguyen-Tan PF ，Zhang Q ，Ang KK ，Weber RS ，Rosenthal DI ，Soulieres D ，Kim H ，Silverman C ，Raben A ，Galloway TJ ，Fortin A ，Gore E ，Westra WH ，Chung CH ，Jordan RC ，Gillison ML ，List M ，Le QT ... -  《-》

Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.

Ang KK ，Zhang Q ，Rosenthal DI ，Nguyen-Tan PF ，Sherman EJ ，Weber RS ，Galvin JM ，Bonner JA ，Harris J ，El-Naggar AK ，Gillison ML ，Jordan RC ，Konski AA ，Thorstad WL ，Trotti A ，Beitler JJ ，Garden AS ，Spanos WJ ，Yom SS ，Axelrod RS ... -  《-》

Concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: radiation therapy oncology group phase II trial 99-14.

Ang KK ，Harris J ，Garden AS ，Trotti A ，Jones CU ，Carrascosa L ，Cheng JD ，Spencer SS ，Forastiere A ，Weber RS ... -  《JOURNAL OF CLINICAL ONCOLOGY》

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Locally Advanced Head and Neck Carcinoma: NRG Oncology Radiatio

To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year. Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years. The pretreatment QOL/PS scores were correlated with outcome and p16 status in patients with oropharyngeal cancer (OPC). Of 818 analyzable patients, the 1-year change from baseline score for FACT-HN total was -0.41 (CIS arm) and -5.11 (CET/CIS arm) (P=.016), representing a 3.2% between-arm change of the FACT-HN total score. The mean EQ-5D index and PSS-HN scores were not significantly different between arms. The p16-positive OPC patients had significantly higher baseline and 1-year scores for PSS-HN, FACT-HN total, physical and functional subscales, and 2-years for the EQ-5D index compared with p16-negative OPC patients. Higher pretreatment PSS-HN diet, PSS-HN eating, FACT-HN, and EQ-5D index scores were associated with better overall survival (OS) and progression-free (PFS) survival on multivariate analysis. Higher baseline FACT-HN total, functional, physical subscale, and EQ-5D index scores were associated with improved OS and PFS in p16-positive OPC patients but not in p16-negative and non-OPC patients. There was no clinically meaningful difference in QOL/PS between arms. The p16-positive OPC patients had significantly higher QOL/PS than did p16-negative patients. Pretreatment QOL/PS is a significant independent predictor of outcome in locally advanced HNC.

Truong MT ，Zhang Q ，Rosenthal DI ，List M ，Axelrod R ，Sherman E ，Weber R ，Nguyen-Tân PF ，El-Naggar A ，Konski A ，Galvin J ，Schwartz D ，Trotti A ，Silverman C ，Singh A ，Godette K ，Bonner JA ，Jones CU ，Garden AS ，Shenouda G ，Matthiesen C ，Le QT ，Bruner D ... -  《-》

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

Noronha V ，Joshi A ，Patil VM ，Agarwal J ，Ghosh-Laskar S ，Budrukkar A ，Murthy V ，Gupta T ，D'Cruz AK ，Banavali S ，Pai PS ，Chaturvedi P ，Chaukar D ，Pande N ，Chandrasekharan A ，Talreja V ，Vallathol DH ，Mathrudev V ，Manjrekar A ，Maske K ，Bhelekar AS ，Nawale K ，Kannan S ，Gota V ，Bhattacharjee A ，Kane S ，Juvekar SL ，Prabhash K ... -  《-》