Hyperfractionated (eg, twice daily [BID]) radiation therapy with chemotherapy may improve survival times in patients with some advanced head and neck cancers, a new study confirms, and the American Society for Radiation Oncology (ASTRO)’s new oropharyngeal cancer guideline includes hyperfractionation as a definitive radiotherapy treatment option. Newly-reported results from the phase 3 CONVERT trial failed to show that twice-daily concurrent chemoradiotherapy prolongs overall survival time compared to once-daily treatment in patients with small-cell lung cancer (SCLC) but more patients completed their prescribed radiation dose than was the case for patients in the once-daily treatment arm. Hyperfractionated chemoradiation was not more toxic for patients with SCLC with the possible exception of elevated risk of grade 4 neutropenia. Optimal radiation doses and fractionation schedules remain controversial, however, and more research is needed to establish safety in patients with head and neck cancers. 

In hyperfractionated radiotherapy, a patient’s total radiation dose is split into lower-dose fractions that are delivered in quick sequence, more frequently than once daily (QD). The goal of hyperfractionation is to reduce toxicity while improving tumor control. The total dose is often delivered over a period of days or weeks, comparable to conventional radiotherapy regimens, with the goal of exceeding the total dose delivered in standard treatment.1,2 However, hyperfractionation can also be used to deliver a similar total dose in an overall shorter time period.3

The use of hyperfractionation has been explored for decades, with mixed results.2 In patients with small-cell lung carcinoma (SCLC), twice-daily radiation (1.5 Gy fractions, for total dose of 45 Gy) with concurrent chemotherapy has been tied to longer survival times than 45 to 72 Gy total doses delivered in 1.8 or 2.0 Gy fractions.3 In this study, hyperfractionation cut the total duration of radiation therapy from a median of 50 days to 22 days.3 Treatment in an academic cancer center was associated with a higher likelihood of undergoing hyperfractionated chemoradiation, and in multivariate analyses both treatment at an academic center and hyperfractionated treatment were associated with improved survival times (hazard ratio [HR] 0.88 and 0.92, respectively; P <.001 and P =.008).However, more recent studies have not confirmed a survival advantage for hyperfractionation in SCLC.

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“The adoption of BID radiation remains very limited, but is more commonly utilized in the academic setting,” the study investigators concluded.3 “In this hospital-based study, BID fractionation was associated with improved survival over once daily fractionation, even at doses [greater than or equal to] 60 Gy.”