IMPORTANCE Major weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy (RT). How baseline and posttreatment body composition affects outcome is unknown. OBJECTIVE To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control. DESIGN, SETTING, AND PARTICIPANT Retrospective study of 2840 patients with pathologically proven HNSCC undergoing curative RT at a single academic cancer referral center from October 1, 2003, to August 31, 2013. One hundred ninety patients had computed tomographic (CT) scans available for analysis of skeletal muscle (SM). The effect of pre-RT and post-RT SM depletion (defined as a CT-measured L3 SM index of less than 52.4 cm2 /m2 for men and less than 38.5 cm2 /m2 for women) on survival and disease control was evaluated. Final follow-up was completed on September 27, 2014, and data were analyzed from October 1, 2014, to November 29, 2015. MAIN OUTCOMES AND MEASURES Primary outcomes were overall and disease-specific survival and locoregional control. Secondary analyses included the influence of pre-RT body mass index (BMI) and interscan weight loss on survival and recurrence. RESULTS Among the 2840 consecutive patients who underwent screening, 190 had whole-body positron emission tomography–CT or abdominal CT scans before and after RT and were included for analysis. Of these, 160 (84.2%) were men and 30 (15.8%) were women; their mean (SD) age was 57.7 (9.4) years. Median follow up was 68.6 months. Skeletal muscle depletion was detected in 67 patients (35.3%) before RT and an additional 58 patients (30.5%) after RT. Decreased overall survival was predicted by SM depletion before RT (hazard ratio [HR], 1.92; 95% CI, 1.19–3.11; P = .007) and after RT (HR, 2.03; 95% CI, 1.02–4.24; P = .04). Increased BMI was associated with significantly improved survival (HR per 1-U increase in BMI, 0.91; 95% CI, 0.87–0.96; P < .001). Weight loss without SM depletion did not affect outcomes. Post-RT SM depletion was more substantive in competing multivariate models of mortality risk than weight loss–based metrics (Bayesian information criteria difference, 7.9), but pre-RT BMI demonstrated the greatest prognostic value. CONCLUSIONS AND RELEVANCE Diminished SM mass assessed by CT imaging or BMI can predict oncologic outcomes for patients with HNSCC, whereas weight loss after RT initiation does not predict SM loss or survival.

In the original version of the Data Descriptor the surname of author Hesham Elhalawani was misspelled. This has now been corrected in the HTML and PDF versions.

For nearly two decades, adaptive radiation therapy (ART) has been proposed as a method to account for changes in head and neck tumor and normal tissue to enhance therapeutic ratios. While technical advances in imaging, planning and delivery have allowed greater capacity for ART delivery, and a series of dosimetric explorations have consistently shown capacity for improvement, there remains a paucity of clinical trials demonstrating the utility of ART. Furthermore, while ad hoc implementation of head and neck ART is reported, systematic full-scale head and neck ART remains an as yet unreached reality. To some degree, this lack of scalability may be related to not only the complexity of ART, but also variability in the nomenclature and descriptions of what is encompassed by ART. Consequently, we present an overview of the history, current status, and recommendations for the future of ART, with an eye towards improving the clarity and description of head and neck ART for interested clinicians, noting practical considerations for implementation of an ART program or clinical trial. Process level considerations for ART are noted, reminding the reader that, paraphrasing Elbert Hubbard, "Art is not a thing, it is a way." "When an artist uses a conceptual form of art, it means that all of the planning and decisions are made beforehand and the execution is a perfunctory affair. The idea becomes a machine that makes the art."-Sol LeWitt (1) The concept of "adaptive radiation therapy" (ART) has been widely praised, serially modeled in silico, and heavily discussed, but to date, at a practical level, remains rarely implemented in vivo outside the research setting. We aim to discuss the "state of the ART" in head and neck therapy, with an emphasis on specification of the intent with which ART is performed; the terms of ART used, or a disambiguation of the nomenclature; technical

BackgroundFailure of locoregional control is the main cause of recurrence in advanced head and neck cancer. This multi-center trial aims to improve outcome in two ways. Firstly, by redistribution of the radiation dose to the metabolically most FDG-PET avid part of the tumour. Hereby, a biologically more effective dose distribution might be achieved while simultaneously sparing normal tissues. Secondly, by improving patient selection. Both cisplatin and Epidermal Growth Factor Receptor (EGFR) antibodies like Cetuximab in combination with Radiotherapy (RT) are effective in enhancing tumour response. However, it is unknown which patients will benefit from either agent in combination with irradiation. We will analyze the predictive value of biological markers and 89Zr-Cetuximab uptake for treatment outcome of chemoradiation with Cetuximab or cisplatin to improve patient selection.MethodsARTFORCE is a randomized phase II trial for 268 patients with a factorial 2 by 2 design: cisplatin versus Cetuximab and standard RT versus redistributed RT. Cisplatin is dosed weekly 40 mg/m2 for 6 weeks. Cetuximab is dosed 250mg/m2 weekly (loading dose 400 mg/m2) for 6 weeks. The standard RT regimen consists of elective RT up to 54.25 Gy with a simultaneous integrated boost (SIB) to 70 Gy in 35 fractions in 6 weeks. Redistributed adaptive RT consists of elective RT up to 54.25 Gy with a SIB between 64-80 Gy in 35 fractions in 6 weeks with redistributed dose to the gross tumour volume (GTV) and clinical target volume (CTV), and adaptation of treatment for anatomical changes in the third week of treatment.Patients with locally advanced, biopsy confirmed squamous cell carcinoma of the oropharynx, oral cavity or hypopharynx are eligible.Primary endpoints are: locoregional recurrence free survival at 2 years, correlation of the median 89Zr-cetuximab uptake and biological markers with treatment specific outcome, and toxicity. Secondary endpoints are quality of life, swallowing function preservation, progression free and overall survival.DiscussionThe objective of the ARTFORCE Head and Neck trial is to determine the predictive value of biological markers and 89Zr-Cetuximab uptake, as it is unknown how to select patients for the appropriate concurrent agent. Also we will determine if adaptive RT and dose redistribution improve locoregional control without increasing toxicity.ClinicalTrials.gov Identifier: NCT01504815