In Regard to Thomson et al.

To the Editor:

We read with interest the timely American Society for Radiation Oncology–European Society for Radiotherapy and Oncology practice recommendations on risk-adapted radiation therapy (RT) for head and neck squamous cell cancers (HNSCCs) during the COVID-19 pandemic, appropriately developed using a modified rapid Delphi process for consensus building.

Although we largely concur with the statement, our reservation is in regard to case-specific RT dose-fractionation recommendations. Continuation of standard fractionation (1.8-2.0 Gy/fraction) for resected oral cancers seems logical, but we were surprised to note strong agreement (oropharynx) and agreement (glottis and larynx) to stay with conventional dose-fractionation for definitive and even palliative RT in the early pandemic scenario. Reassuringly, in the later pandemic stage, there was strong agreement to switch to more hypofractionated schedules for all subsites—unfortunately, without recommending any specific schedule. Panelists considered it unsafe to combine chemotherapy with higher (>2.5-2.8 Gy) dose per fraction. Although three-weekly high-dose cisplatin (80-100 mg/m2) was preferred by 60% of panelists, in accordance with category 1 evidence-based recommendations, 40% used weekly cisplatin (30-40 mg/m2) in daily practice, reflecting ground reality. In the early pandemic stage, the panel agreed not to alter the chemotherapy schedule, although many members would consider switching to weekly cisplatin. In the late pandemic setting, there was agreement to omit concomitant chemotherapy for human papilloma virus–positive oropharyngeal cancer and near agreement to omit concurrent chemotherapy for all.

Radiobiological modeling indicates a lower (6.4 Gy) α/β ratio for HNSCC than the traditional textbook value (10 Gy), supporting the case for an acceptable therapeutic index with hypofractionated-accelerated schedules. In northern England, there is considerable experience with 55 Gy in 20 fractions over 4 weeks even with chemotherapy.4, 5, 6 The same regimen is currently being tested in an ongoing, multicentric, phase 3 randomized controlled trial of accelerated hypofractionated versus normofractionated (HYPNO study) RT in HNSCC (NCT0765503). Notably, the Royal College of Radiology omitted 55 Gy in 20 fractions over 4 weeks as an option for definitive curative-intent RT of HNSCC in their 2016 guideline. However, the recent Royal College of Radiology advisory includes this as one of the evidence-based and preferred options for HNSCC under the pandemic scenario. Given clinical equipoise and significant resource-sparing potential, the HYPNO schedule of hypofractionated-accelerated RT should be widely considered across the world for definitive treatment of HNSCC in the COVID context. With the majority of HNSCC cases worldwide occurring in relatively resource-constrained low- and middle-income countries, which are also witnessing rapid increase in COVID-19 cases, we are slightly concerned that this consensus statement has come out as overly conservative toward altered RT dose-fractionation schedules in pandemic times.