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.

What's known on the subject? and What does the study add? Very few comparative studies to date evaluate the results of treatment options for prostate cancer using the most sensitive measurement tools. PSA has been identified as the most sensitive tool for measuring treatment effectiveness. To date, comprehensive unbiased reviews of all the current literature are limited for prostate cancer. This is the first large scale comprehensive review of the literature comparing risk stratified patients by treatment option and with long‐term follow‐up. The results of the studies are weighted, respecting the impact of larger studies on overall results. The study identified a lack of uniformity in reporting results amongst institutions and centres. A large number of studies have been conducted on the primary therapy of prostate cancer but very few randomized controlled trials have been conducted. The comparison of outcomes from individual studies involving surgery (radical prostatectomy or robotic radical prostatectomy), external beam radiation (EBRT) (conformal, intensity modulated radiotherapy, protons), brachytherapy, cryotherapy or high intensity focused ultrasound remains problematic due to the non‐uniformity of reporting results and the use of varied disease outcome endpoints. Technical advances in these treatments have also made long‐term comparisons difficult. The Prostate Cancer Results Study Group was formed to evaluate the comparative effectiveness of prostate cancer treatments. This international group conducted a comprehensive literature review to identify all studies involving treatment of localized prostate cancer published during 2000–2010. Over 18 000 papers were identified and a further selection was made based on the following key criteria: minimum/median follow‐up of 5 years; stratification into low‐, intermediate‐ and high‐risk groups; clinical and pathological staging; accepted standard definitions for prostate‐specific antigen failure; minimum patient number of 100 in each risk group (50 for high‐risk group). A statistical analysis (standard deviational ellipse) of the study outcomes suggested that, in terms of biochemical‐free progression, brachytherapy provides superior outcome in patients with low‐risk disease. For intermediate‐risk disease, the combination of EBRT and brachytherapy appears equivalent to brachytherapy alone. For high‐risk patients, combination therapies involving EBRT and brachytherapy plus or minus androgen deprivation therapy appear superior to more localized treatments such as seed implant alone, surgery alone or EBRT. It is anticipated that the study will assist physicians and patients in selecting treatment for men with newly diagnosed prostate cancer.

Purpose: Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H&N) cancer patients. Methods: Two sets of IMPT plans were generated for 14 H&N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests. Results: CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D 95% ), improved dose homogeneity (i.e., smaller D 5% − D 95% ), and lower or equivalent dose to organs at risk. Conclusions: CTV-based robust optimization provided significantly more robust dose distributions to targets and organs than PTV-based conventional optimization in H&N using IMPT. Eliminating the use of PTV and planning directly based on CTV provided better or equivalent normal tissue sparing.

Background Due to its physical properties, intensity-modulated proton therapy (IMPT) used for oropharyngeal carcinoma patients has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities. Methods We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010–2014. Patients were matched on unilateral/bilateral treatment, disease site, HPV status, T and N stages, smoking status and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis. Results Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32 months. There were no imbalances in patient/tumor characteristics with the exception of age (mean age of 56.8 years for IMRT patients and 61.1 years for IMPT patients, p-value = 0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR) = 0.55; 95% confidence interval (CI): 0.12–2.50, p-value = 0.44) or in progression free survival (HR = 1.02; 95% CI: 0.41–2.54; p-value = 0.96). The age-adjusted odds ratio (OR) for the presence of a Gastrostomy (G)-tube during treatment and at 3 months post-treatment are respectively (OR = 0.53; 95%CI: 0.24–1.15; p-value = 0.11) and (OR = 0.43; 95%CI: 0.16–1.17; p-value = 0.10). When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the odds ratios at 3 months and 1 year were respectively (OR = 0.44; 95%CI: 0.19–1.0; p-value = 0.05) and (OR = 0.23; 95%CI: 0.07–0.73; p-value = 0.01). Conclusion Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.

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