Palliative radiotherapy in locally advanced head and neck cancer after failure of induction chemotherapy: Comparison of two fractionation schemes

Abstract

Context:Among patients with locally advanced head and neck squamous cell cancers (LAHNSCC), the prognosis after nonresponse or progression despite induction chemotherapy (IC) is dismal, and further treatment is often palliative in intent. Given that nonresponse to chemotherapy could indicate subsequent radioresistance, we intended to assess the outcomes with two different fractionation schemes.Aims:To compare the outcomes of two fractionation schemes- ’standard’ (consisting 3GyX5 daily fractions for 2 consecutive weeks) versus ‘hybrid’ (6GyX3 fractions on alternate days during the 1st week, followed by 2GyX5 daily fractions in the 2nd week).Settings and Design:Prospective randomized controlled two-arm unblinded trial.Materials and Methods:Patients with locally advanced oropharyngeal, laryngeal, and hypopharyngeal cancers treated with a minimum of two cycles of taxane, platinum, and fluorouracil-based IC were eligible if residual disease volume amounted <30 cm3. Kaplan-Meier survival curves were compared by the log-rank test. Response rates were compared using the unpaired t-test. Quality of life (QOL) was measured via patient reported questionnaires.Results:Of the initially enrolled 51 patients, 45 patients (24 from standard arm, and 21 from the hybrid arm) were eligible for analysis. Despite being underpowered to attain statistical significance, there still seemed to be a trend towards improvement in progression-free (Hazard ratio (HR) for progression: 0.5966; 95% CI 0.3216-1.1066) and overall survival (HR for death: 0.6062; 95% CI 0.2676-1.3734) with the hybrid arm when compared to the standard arm. Benefits were also observed with regards to response rates and QOL. Rate of complications were similar in both arms.Conclusions:In comparison to the routinely used palliative fractionation scheme of 30 Gray (Gy) in 10 fractions (Fr), the use of hybrid fractionation which integrates hypofractionation in the 1st week, followed by conventional fractionation in the 2nd week, could possibly offer better response rates, QOL increments, and potential survival benefits among LAHNSCC patients even after failing to respond to IC.

Use and Reporting of Patient-Reported Outcomes in Trials of Palliative Radiotherapy

“…A total of 225 published trials, representing 24 281 patients, and 67 trial registrations met the general eligibility criteria (eAppendix 2 in the Supplement). Among the published trials, 116 trials (52%) used PROs. PROs were primary end points in 45 trials (20% of all published trials; 31% of 145 trials clearly stating their primary end point; 39% of 116 trials including a PRO) and secondary end points in 71 trials (31% of all published trials; 61% of trials including a PRO).…”

“…Among the published trials, 116 trials (52%) used PROs. PROs were primary end points in 45 trials (20% of all published trials; 31% of 145 trials clearly stating their primary end point; 39% of 116 trials including a PRO) and secondary end points in 71 trials (31% of all published trials; 61% of trials including a PRO). In published trials, a more recent year of trial publication was associated with a more frequent use of a PRO as a secondary (odds ratio [OR], 1.04 [95% CI, 1.00-1.07]; P = .03), but not as a primary (OR, 1.01 [95% CI, 0.97-1.05]; P = .7) end point, per logistic regression (Figure 1).…”

An Extended Hypofractionated Palliative Radiotherapy Regimen for Head and Neck Carcinomas

“…One study ( 21 ) was not found through PubMed search. Eleven were retrospective studies ( 4 – 7 , 9 , 12 , 14 , 18 , 22 – 24 ) reviewed multiple radiation therapy regimens ( 4 , 11 , 12 , 22 , 23 ). The studies are shown in Table 4 and the relation between the EQD 2 for late effects in normal and for tumor tissue is shown in Figure 2 .…”

“…Published regimens include the QUAD-shot consisting of 3.5 Gy twice-daily fractions given over two consecutive days to a total of 14 Gy per cycle, with a 3- to 4-week break between cycles, with a maximum of three cycles ( 4 – 10 ). Other examples include 30 Gy in 10 fractions given over 2 weeks ( 11 – 13 ), 48 Gy in 12 fractions 3–4 times a week ( 14 ), 20 Gy in five fractions over five consecutive days ( 15 – 17 ), the “0–7–21” regimen (24 Gy in three fractions of 8 Gy each, given on days 0, 7, and 21) ( 18 ), 40 Gy in 10 fractions, twice weekly ( 19 ), 50 Gy in 20 fractions split course ( 12 ), and 50 Gy in 16 fractions, five fractions/week ( 20 ).…”