BackgroundLarge anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase.The purposes of the study were to estimate:- the PG overdose and the xerostomia risk increase during a “standard” IMRT (IMRTstd);- the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia.Material and methodsFifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched.ResultsCompared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p < 0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p < 0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p < 0.001).ConclusionDuring the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

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Introduction: Large anatomical variations can be observed during the treatment course intensitymodulated radiotherapy (IMRT) for head and neck cancer (HNC), leading to potential dose variations. Adaptive radiotherapy (ART) uses one or several replanning sessions to correct these variations and thus optimize the delivered dose distribution to the daily anatomy of the patient. This review, which is focused on ART in the HNC, aims to identify the various strategies of ART and to estimate the dosimetric and clinical benefits of these strategies. Material and methods: We performed an electronic search of articles published in PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a total of 134 articles assessed for eligibility, 29 articles were ultimately retained for the review. Eighteen studies evaluated dosimetric variations without ART, and 11 studies reported the benefits of ART. Results: Eight in silico studies tested a number of replanning sessions, ranging from 1 to 6, aiming primarily to reduce the dose to the parotid glands. The optimal timing for replanning appears to be early during the first two weeks of treatment. Compared to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6 Gy and the maximum dose to the spinal cord from 0.1 to 4 Gy while improving target coverage and homogeneity in most studies. Only five studies reported the clinical results of ART, and three of those studies included a non-randomized comparison with standard IMRT. These studies suggest a benefit of ART in regard to decreasing xerostomia, increasing quality of life, and increasing local control. Patients with the largest early anatomical and dose variations are the best candidates for ART. Conclusion: ART may decrease toxicity and improve local control for locally advanced HNC. However, randomized trials are necessary to demonstrate the benefit of ART before using the technique in routine practice.

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See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18 F-misonidazole ( 18 F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18 F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18 F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral a 5 0.05, power 1-b 5 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18 F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18 F-FMISO-positive group).