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Hyperfractionated radiation improved outcomes in head and neck cancers
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Hyperfractionated radiation therapy significantly improved local-regional control and prolonged OS compared with standard fractionation in patients with locally advanced squamous cell carcinoma of the head and neck, according to the final results of the RTOG 9003 trial.
Hyperfractionated therapy did not increase late toxicity, researchers added.
The analysis included 1,076 patients with stage III or IV squamous cell carcinoma (SCC) of the head and neck, or stage II base-of-tongue SCC.
Researchers randomly assigned patients to one of four fractionation schemes: hyperfractionation (81.6 Gy in 68 fractions twice daily for 7 weeks), continuous accelerated fractionation (72 Gy in 42 fractions for 6 weeks), accelerated fractionation with split (67.2 Gy in 42 fractions for 6 weeks, with a 2-week resting period after receiving 38.4 Gy) or standard fractionation (70 Gy in 35 fractions daily for 7 weeks).
Median follow-up was 14.1 years, during which 568 patients (52.7%) experienced local-regional failure. The majority of local-regional failure occurred within the first 5 years (97.4%).
Two-hundred patients (18.6%) developed secondary primary cancers, 50% of which occurred within the first 3 years, and 75% of which occurred in the first 5.5 years after treatment. There were no significant differences in secondary primary cancer occurrence between the treatment arms.
Analyses censored for 5-year local-regional control indicated that, of the experimental arms, local-regional control differed only in the hyperfractionation arm vs. the standard fractionation arm (HR=0.79; 95% CI, 0.62-1.00). Patients who received hyperfractionation demonstrated significantly improved OS compared with those who received standard fractionation (HR=0.81; P=.05).
Toxicity was similar between the experimental fractionation arms and standard fractionation with regard to occurrence of grade 3 to grade 5 toxicity at 5 years, as well as the use of a feeding tube after 180 days and at 1 year.
Johnathan J. Beitler
However, analyses that compared 7-week vs. 6-week schedules indicated accelerated fractionation was associated with increased grade 3 to grade 5 toxicity at 5 years (P=.06). Researchers noted a trend for increased grade 3 to grade 5 toxicity vs. grade 0 to grade 2 toxicity in the continuous accelerated arm compared with the standard fractionation arm (P=.09).
“The results suggest that twice-daily radiation may improve cure and limit late side effects for patients,” researcher Johnathan J. Beitler, MD, MBA, FASTRO, professor of radiation oncology, otolaryngology and hematology/medical oncology at the Winship Cancer Institute of Emory University School of Medicine, said in a press release. “Twice-daily radiation might be worth considering in place of concurrent chemoradiotherapy for those patients who are at low risk for distant metastases and those patients who cannot tolerate systemic therapy.”
Disclosure: Beitler reports receiving research funding due to his role as a Georgia Research Alliance Cancer Scientist.
Perspective
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Daniel J. Haraf, MD
The results of RTOG 9003 confirmed the fact that hyperfractionation resulted in improved local control. A trend toward improved control was seen with the concomitant boost as well, but it also had higher grade 3 to grade 5 late toxicity. However, we are now in an era in which concomitant chemotherapy and radiation are the standard for advanced head and neck cancers. Recent studies such as GORTEC 99-02 (Bourhis J. Lancet Oncol. 2012;13:145-153) have suggested that acceleration of radiotherapy is not helpful with concomitant chemotherapy and radiation.
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