PURPOSE The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

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PurposeGrade 4 lymphopenia (G4L) during radiation therapy (RT) is associated with higher rates of distant metastasis and decreased overall survival in a number of malignancies, including esophageal cancer (EC). Through a reduction in integral radiation dose, proton RT (PRT) may reduce G4L relative to photon RT (XRT). The purpose of this study was to compare G4L in patients with EC undergoing PRT versus XRT.Methods and materialsPatients receiving curative-intent RT and concurrent chemotherapy for EC were identified. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count <200/mm3. Univariate and multivariable logistic regression analyses (MVA) were performed to assess patient and treatment factors associated with lymphopenia. A propensity-matched (PM) cohort was created using logistic regression, including baseline covariates.ResultsA total of 144 patients met the inclusion criteria. The median age was 66 years (range, 32-85 years). Of these patients, 79 received XRT (27% 3-dimensional chemo-RT and 73% intensity modulated RT) and 65 received PRT (100% pencil-beam scanning). Chemotherapy consisted of weekly carboplatin and paclitaxel (99%). There were no significant differences in baseline characteristics between the groups, except for age (median 4 years older in the PRT cohort). G4L was significantly higher in patients who received XRT versus those who received PRT (56% vs 22%; P < .01). On MVA, XRT (odds ratio [OR]: 5.13; 95% confidence interval [CI], 2.35-11.18; P < .001) and stage III/IV (OR: 4.54; 95% CI, 1.87-11.00; P < .001) were associated with G4L. PM resulted in 50 PRT and 50 XRT patients. In the PM cohort, G4L occurred in 60% of patients who received XRT versus 24% of patients who received PRT. On MVA, XRT (OR: 5.28; 95% CI, 2.14-12.99; P < .001) and stage III/IV (OR: 3.77; 95% CI, 1.26-11.30; P = .02) were associated with G4L.ConclusionsXRT was associated with a significantly higher risk of G4L in comparison with PRT. Further work is needed to evaluate a potential association between RT modality and antitumor immunity as well as long-term outcomes.

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Purpose Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider–assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5–0.7, moderate; and >0.7, strong. Results CTCAE dermatitis moderately correlated with STATerythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

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