Patterns of failure for recurrent head and neck squamous cell carcinoma treated with salvage surgery and postoperative IMRT reirradiation.

Purpose/Objectives: The purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT for recurrent head and neck squamous cell cancer (HNSCC). Materials/Methods: Patterns of LRR for 61 patients treated consecutively between 2003 and 2014 who received post-operative IMRT reirradiation to ≥ 60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were defined as in-field, marginal, or out-of-field. Logistic regression analyses were performed to identify predictors for LRR. Results: A total of 55 patients were eligible for analysis and 23 (42 %) had documented LRR after reirradiation. Location of recurrent disease prior to salvage surgery (lymphatic vs. mucosal) was the most significant predictor of LRR after post-operative reirradiation with salvage rate of 67 % for lymphatic vs. 33 % for mucosal sites (p = 0.037). Physician classification of LRR yielded 14 (61 %) in-field failures, 3 (13 %) marginal failures, and 6 (26 %) out-of-field failures, while DIR yielded 10 (44 %) in-field failures, 4 (17 %) marginal failures, and 9 (39 %) out-of-field failures. Most failures (57 %) occurred within the original site of recurrence or first echelon lymphatic drainage. Of patients who had a free flap placed during salvage surgery, 56 % of failures occurred within 1 cm of the surgical flap. Conclusion: Our study highlights the role of DIR in enhancing the accuracy and consistency of POF analysis. Compared to traditional visual inspection, DIR reduces interobserver variability and provides more nuanced insights into dose-specific and spatial parameters of locoregional recurrences. Additionally, the study identifies the location of the initial recurrence as a key predictor of subsequent locoregional recurrence after salvage surgery and re-IMRT.

Outcomes after salvage for HPV-positive recurrent oropharyngeal cancer treated with primary radiation.

PURPOSE: HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) carries a favorable prognosis for patients, yet nearly 30% of patients will experience disease relapse. We sought to detail patterns of failure, associated salvage therapy, and outcomes for patients with recurrent HPV-positive OPSCC. METHODS AND MATERIALS: This is a single institution retrospective study of patients with recurrent HPV-positive OPSCC irradiated from 2002 to 2014. The primary study outcome was overall survival (OS, calculated using the Kaplan-Meier method). Secondary aims included patterns of first failure with descriptive details of salvage therapy. Solitary recurrences were defined as initial presentation of recurrence in a single site (primary, neck or oligometastatic), and multi-site was defined as local and regional and/or multiple sites of distant recurrence. Survival outcomes were compared using the log-rank test. RESULTS: The cohort consisted of 132 patients. The median follow-up was 59 months for surviving patients. Estimated 2-year and 5-year OS rates were 47% and 32%, respectively. Comparative 2-year and 5-year OS rates were 65% and 46% versus 19% and 9% for the solitary group and multi-site group, respectively (p < .001). CONCLUSIONS: Patients with recurrent HPV-positive OPSCC experience 5-year survival of approximately 32%. However, patients with a "solitary" recurrence including disease at the primary site, neck or oligometastatic site have more favorable long-term outcomes.

A Dosimetric Comparison of Oral Cavity Sparing in the Unilateral Treatment of Early Stage Tonsil Cancer: IMRT, IMPT, and Tongue-Deviating Oral Stents.

INTRODUCTION: Tongue-deviating oral stents (TDOS) are commonly used during unilateral neck radiation therapy to reduce unnecessary dose to nontarget oral structures. Their benefit in the setting of highly conformal treatment techniques, however, is not defined. The goal of this study was to investigate the potential benefit of TDOS use on dosimetric parameters in unilateral intensity modulated radiation therapy (IMRT) and intensity modulated proton therapy (IMPT). METHODS: A total of 16 patients with T1-2 tonsil cancer treated at a single institution were selected, of which 8 were simulated/treated with a TDOS and 8 without a TDOS. All received definitive unilateral IMRT to a dose of 66 Gy in 30 fx. IMPT plans were generated for each patient for study purposes and optimized according to standard institutional practice. RESULTS: For IMRT plans, the presence of a TDOS (vs without) was associated with a significantly lower oral mucosa mean dose (31.4 vs 35.3 Gy; P = .020) and V30 (42.7% vs 57.1%; P = .025). For IMPT plans, the presence of TDOS (vs without) was not associated with any improvement in oral mucosa mean dose (18.3 vs 19.9 Gy; P = .274) or V30 (25.0% vs 26.2%; P = .655). IMPT plans without TDOS compared with IMRT plans with TDOS demonstrated reduced oral mucosa mean dose (P < .001) and V30 (P < .001). CONCLUSION: The use of a TDOS for the unilateral treatment of well-lateralized tonsil cancers was associated with oral mucosa sparing for IMRT, but not for IMPT. Moreover, mucosa sparing was improved for IMPT plans without a TDOS compared to IMRT plans with a TDOS.

Racial and Ethnic Disparities Among Participants in US-Based Phase 3 Randomized Cancer Clinical Trials.

Although improving representation of racial and ethnic groups in United States clinical trials has been a focus of federal initiatives for nearly 3 decades, the status of racial and ethnic minority enrollment on cancer trials is largely unknown. We used a broad collection of phase 3 cancer trials derived from ClinicalTrials.gov to evaluate racial and ethnic enrollment among US cancer trials. The difference in incidence by race and ethnicity was the median absolute difference between trial and corresponding Surveillance, Epidemiology, and End Results data. All statistical tests were 2-sided. Using a cohort of 168 eligible trials, median difference in incidence by race and ethnicity was +6.8% for Whites (interquartile range [IQR] = +1.8% to +10.1%; P < .001 by Wilcoxon signed-rank test comparing median difference in incidence by race and ethnicity to a value of 0), -2.6% for Blacks (IQR = -5.1% to +1.2%; P = .004), -4.7% for Hispanics (IQR = -7.5% to -0.3%; P < .001), and -4.7% for Asians (IQR = -5.7% to -3.3%; P < .001). These data demonstrate overrepresentation of Whites, with continued underrepresentation of racial and ethnic minority subgroups.

Prognostic impact of leukocyte counts before and during radiotherapy for oropharyngeal cancer.

INTRODUCTION: Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. MATERIALS AND METHODS: Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011-2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. RESULTS: The radiotherapy type (IMRT vs. IMPT) was not associated with lymphopenia (grade 3 P > .99; grade 4 P = .55). In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99-15.7, P = .001), pretreatment leukocytosis (HR 4.85, 95% CI 1.73-13.6, P = .003), grade 4 lymphopenia during radiotherapy (HR 3.28, 95% CI 1.14-9.44, P = .03), and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01-8.18, P = .05), but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99-7.00, P = .05). Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis. CONCLUSIONS: Treatment modality did not affect blood counts during radiotherapy. Pretreatment neutrophilia, pretreatment leukocytosis, and grade 4 lymphopenia during radiotherapy were associated with worse outcomes after, but establishing causality will require additional work with increased statistical power.