Top Line: There’s a lot of rad bio theory behind radiation hyperfractionation in the re-irradiation setting, and there is perhaps no site more appealing to use this strategy than in the head and neck.
The Study: We now have a rarity in this space: a large prospective randomized trial. This multi-center Chinese phase 3 trial randomized 144 patients from 3 centers with recurrent nasopharyngeal carcinoma to re-irradiation with “standard” fractionation (60 Gy in 27 daily fractions) versus hyperfractionation (65 Gy in 54 twice-daily fractions with at least 6-hour intervals). There had to have been at least 12 months since prior RT (median time ~3 years). All patients had recurrent primary tumors and 45% had nodal disease. Those with resectable disease were excluded (as they should undergo resection). Also, patients with late grade 3+ toxicity from radiation were excluded. The target volumes consisted of gross primary and nodal disease with a 3mm PTV, and these received the full prescription dose. A small 5mm CTV was also treated around the primary tumor to a slightly lower dose of 54Gy in either 27 or 54 fractions, respectively. There was no elective volume. About half received induction chemo prior to re-irradiation. The logical co-primary endpoints were overall survival and grade 3+ late toxicity. During treatment, acute toxicity was similar, but as hypothesized, there was a significant advantage in terms of late grade 3 toxicity with hyperfractionation (34%, n=23/68) versus standard fractionation (57%, n=39/68). In particular, there was a significant decrease in grade 5 events with hyperfractionation (7% v 24%) driven by fewer hemorrhages and less mucosal necrosis. What wasn’t necessarily anticipated was the resulting significant advantage in overall survival at 3 years with hyperfractionation(75%) versus standard fractionation (55%), again with a primary reason being the significantly lower rate of grade 5 toxicity. Overall, half as many patients in the hyperfractionation group died of late complications than in the standard arm (21% v 44%). Nearly half of patients had locoregional relapse, and the rate was similar between groups (49% v 46%). In other words, hyperfractionation didn’t provide superior tumor control, it just resulted in less severe toxicity.
TBL: If the joint decision is made with a patient to undergo highly-toxic curative intent definitive reirradiation for recurrent nasopharyngeal cancer, hyperfractionation has comparable tumor control and better survival due to a lower risk of life-threatening complications. | You, Lancet 2023
The Study: We now have a rarity in this space: a large prospective randomized trial. This multi-center Chinese phase 3 trial randomized 144 patients from 3 centers with recurrent nasopharyngeal carcinoma to re-irradiation with “standard” fractionation (60 Gy in 27 daily fractions) versus hyperfractionation (65 Gy in 54 twice-daily fractions with at least 6-hour intervals). There had to have been at least 12 months since prior RT (median time ~3 years). All patients had recurrent primary tumors and 45% had nodal disease. Those with resectable disease were excluded (as they should undergo resection). Also, patients with late grade 3+ toxicity from radiation were excluded. The target volumes consisted of gross primary and nodal disease with a 3mm PTV, and these received the full prescription dose. A small 5mm CTV was also treated around the primary tumor to a slightly lower dose of 54Gy in either 27 or 54 fractions, respectively. There was no elective volume. About half received induction chemo prior to re-irradiation. The logical co-primary endpoints were overall survival and grade 3+ late toxicity. During treatment, acute toxicity was similar, but as hypothesized, there was a significant advantage in terms of late grade 3 toxicity with hyperfractionation (34%, n=23/68) versus standard fractionation (57%, n=39/68). In particular, there was a significant decrease in grade 5 events with hyperfractionation (7% v 24%) driven by fewer hemorrhages and less mucosal necrosis. What wasn’t necessarily anticipated was the resulting significant advantage in overall survival at 3 years with hyperfractionation(75%) versus standard fractionation (55%), again with a primary reason being the significantly lower rate of grade 5 toxicity. Overall, half as many patients in the hyperfractionation group died of late complications than in the standard arm (21% v 44%). Nearly half of patients had locoregional relapse, and the rate was similar between groups (49% v 46%). In other words, hyperfractionation didn’t provide superior tumor control, it just resulted in less severe toxicity.
TBL: If the joint decision is made with a patient to undergo highly-toxic curative intent definitive reirradiation for recurrent nasopharyngeal cancer, hyperfractionation has comparable tumor control and better survival due to a lower risk of life-threatening complications. | You, Lancet 2023