Physician- and Patient-Reported Outcomes of the MC1635 Phase 3 Trial of Ultrahypofractionated Versus Moderately Hypofractionated Adjuvant Radiation Therapy After Breast-Conserving Surgery.

PURPOSE: Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). METHODS AND MATERIALS: Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. RESULTS: One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. CONCLUSIONS: UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization.

BACKGROUND: Setup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization. METHODS: Ninety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) - (Planned D95%) < - 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) - (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) - (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) - (Planned mean) > 1.5%. RESULTS: On average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively. CONCLUSIONS: On average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.

Gender differences in academic productivity, educational positions, and leadership appointments of physicians in the U.S.

BACKGROUND: Promotions in academic medicine are frequently based on number of publications and leadership positions held. While prior study has established women publish less than men, many evaluations are limited to individual specialties and do not evaluate involvement with educational activities. OBJECTIVE: To compare gender differences in academic output, intramural leadership positions, and educational leadership positions of academic physicians. METHODS: The curriculum vitae and de-identified demographic data of all permanent physicians employed at a multi-site academic medical center were reviewed from April to May 2020. Multivariable logistic and Poisson regressions evaluated leadership positions and number of publications. RESULTS: Of 3,359 physicians in the demographic database, 32.3% (n = 1,087) were women and 72.5% were white (n = 2,510). Of the 3,015 physicians in the curriculum vitae database, 32% (n = 962) were women. Women were more likely (p < 0.001) to be assistant professor (54% vs. 42.7%) and less likely to be associate (18.1% vs. 20.3%) or full professor (14.6% vs. 29.1%). Women assistant professors published 22% fewer articles (ratio estimate = 0.78, p < 0.001), associate professors 18% less (coefficient = 0.82, p < 0.001), and full professors 23% less (coefficient = 0.77, p < 0.001). Fewer women were program directors for residencies (1.6% vs. 2.9%, p = 0.02) or fellowships (5.4% vs. 7.4%, p = 0.04), and held fewer division or department leadership positions (OR 0.8, 95% CI as [0.6, 1.0], p = 0.03). CONCLUSION: Women physicians do not outperform men across any education, leadership, or publication category. A cultural shift is needed to redefine traditional metrics for leadership appointments if academic medicine hopes to achieve equity.

A Prospective Study of Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer Patients.

PURPOSE: Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus-related oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: From March 2016 through May 2019, patients were enrolled in this institutional review board-approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. RESULTS: There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis-free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P < .02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation = 12.5 Gy). CONCLUSIONS: Mucosal sparing radiation is well tolerated in select resected human papillomavirus-related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events.

Pilot/Phase II Trial of Hypofractionated Radiation Therapy to the Whole Breast Alone Before Breast Conserving Surgery.

Purpose: Our purpose was to report the results of a phase II trial of patients with breast cancer treated with hypofractionated whole breast radiation therapy (RT) before breast-conserving surgery (BCS). Methods and materials: Between 2019 and 2020, patients with cT0-T2, N0, M0 breast cancer were enrolled. Patients were treated with hypofractionated whole breast RT, 25 Gy in 5 fractions, 4 to 8 weeks before BCS. Pathologic assessment was performed using the residual cancer burden (RCB). Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Quality of life was assessed with Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, The Breast Cancer Treatment Outcome Scale, Linear Analogue Self-Assessment, and Patient-Reported Outcomes Measurement Information System. Results: Twenty-two patients were enrolled. Median follow-up was 7.6 months (range, 0.2-16.8). Seven (32%) and 2 (9%) patients experienced grade 2+ or 3 toxicities, respectively. Overall quality of life Linear Analogue Self-Assessment and Patient-Reported Outcomes Measurement Information System did not change significantly from baseline (P = .21 and P = .72, respectively). There was no clinically significant change (≥1 point) in any of The Breast Cancer Treatment Outcome Scale domains. Only 1 (5%) patient experienced a clinical deterioration that corresponded to a "fair" outcome on the Harvard Cosmesis Scale. At pathologic evaluation, 14 (64%) patients had RCB-0 or RCB-I, including 3 (14%) patients with a pathologic complete response (RCB-0). Eight patients (36%) had RCB-II. No local or distant recurrences have been observed. Conclusions: Extremely hypofractionated whole breast RT before BCS is a feasible approach. There were low rates of toxicities and good cosmesis. Further investigation into this approach with RT before BCS is warranted.

Patient-reported outcomes for patients with breast cancer undergoing radiotherapy: A single-center registry experience.

Background: We present Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for patients undergoing adjuvant radiotherapy for breast cancer with curative intent. We describe the frequency and severity of PRO-CTCAE and analyze them with respect to dose fractionation. Methods: Patients were included in this study if they were treated with curative intent for breast cancer and enrolled on a prospective registry. Patients must have completed at least one baseline and one post-radiation survey that addressed PRO-CTCAE. For univariate and multivariate analysis, categorical variables were analyzed by Fisher's exact test and continuous variables by Wilcoxon rank sum test. PRO-CTCAE items graded ≥2 and ≥3 were analyzed between patients who received hypofractionation (HF) versus standard conventional fractionation (CF) therapy by the Chi-square test. Results: Three hundred thirty-one patients met inclusion criteria. Pathologic tumor stage was T1-T2 in 309 (94%) patients. Eighty-seven (29%) patients were node positive. Two hundred forty-seven patients (75%) experienced any PRO-CTCAE grade ≥2, and 92 (28%) patients experienced any PRO-CTCAE grade ≥3. CF was found to be associated with an increased risk of grade ≥3 skin toxicity, swallowing, and nausea (all p < 0.01). HF (OR 0.48, p < 0.01) was significant in the multivariate model for decreased risk of any occurrence of PRO-CTCAE ≥3. Conclusions: Our study reports one of the first clinical experiences utilizing multiple PRO-CTCAE items for patients with breast cancer undergoing radiation therapy with curative intent. Compared with CF, HF was associated with a significant decrease in any PRO-CTCAE ≥3 after multivariate analysis.

Exploratory study of seed spots analysis to characterize dose and linear-energy-transfer effect in adverse event initialization of pencil-beam-scanning proton therapy.

BACKGROUND: Both dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil-beam-scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important. PURPOSE: To perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis. METHODS: A total of 113 head-and-neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature-based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose-LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate-to-high dose (≥∼40-Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose-LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve. RESULTS: The product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave-one-out cross-validation) for the very limited patient data included in this study. CONCLUSION: Our exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study.

Unplanned implant removal in locally advanced breast cancer.

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation.

Impact of adjuvant trastuzumab on locoregional failure rates in a randomized clinical trial: North Central Cancer Treatment Group N9831 (alliance) study.

BACKGROUND: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2-positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. RESULTS: The median follow-up was 13.0 years. The first site of failure was local-only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%-5.7%). LFR10 was 5.5% (95% CI 4.3%-7.2%), 4.9% (95% CI 3.7%-6.4%), and 2.8% (95% CI 1.9%-4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P = .62; C vs A: HR 0.72, P = .12). For estrogen receptor-positive patients, LFR10 was 3.7% (95% CI 2.8%-4.8%) and for estrogen receptor-negative patients, it was 6.1% (95% CI 5.0%-7.4%; HR 0.61, P = .004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%-7.8%), 3.0% (95% CI 2.1%-4.3%), and 5.5% (95% CI 4.0%-7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P < .001; M vs L+RT: HR 0.88, P = .57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%-8.9%), 4.1% (95% CI 2.4%-7.0%), and 4.3% (95% CI 2.9%-6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P = .14; M vs M+RT: HR 1.2, P = .6). CONCLUSION: Low 10-year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.

Patient-reported quality-of-life outcomes in relation to provider-assessed adverse events during head and neck radiotherapy.

PURPOSE: To assess the relationship between patient-reported quality-of-life (QOL) outcomes and provider-assessed adverse events (AEs) during head-and-neck (H&N) radiotherapy (RT). METHODS: Sixty-five patients undergoing H&N RT prospectively completed 12-domain linear analogue self-assessments (LASA) at baseline, before biweekly appointments, and at last week of RT. At the same time points, provider-assessed AEs were graded using Common Terminology Criteria for Adverse Events v4.0. LASA scores were stratified by maximum-grade AE and analyzed using Kruskal-Wallis methodology. Agreement between LASA scores and maximum-grade AE was assessed using Bland-Altman analysis. RESULTS: Patient-reported QOL outcomes showed clinically meaningful decreases in most domains, predominantly fatigue (77.8% of patients), social activity (75.4%), and overall QOL (74.2%). Provider-assessed AEs showed 100% grade 2 AE, 35.4% grade 3 AE, and 3.1% grade 4 AE. At baseline, patients with higher grade AEs reported worse physical well-being (WB) (P = .04). At week 1, the following QOL domains were worse for patients with higher grade AEs: overall QOL (P = .03), mental WB (P = .02), and physical WB (P = .03). Bland-Altman analysis showed that QOL scores were relatively worse than AE burden at baseline and relatively better at RT completion. CONCLUSIONS: Worse QOL was associated with higher-grade AEs at baseline and early in RT. The impact of AEs on QOL appears to lessen with time. Patient-reported QOL outcomes and provider-assessed AEs provide complementary information.

Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer.

BACKGROUND AND PURPOSE: IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits. MATERIALS AND METHODS: OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t-tests for other clinical outcomes. RESULTS: 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12-0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07-0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection. CONCLUSION: IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT.

Risk of Recurrence and 10-Year Outcomes in Surgically Treated Nonmelanoma Skin Cancer in Cardiac and Liver Transplant Recipients.

OBJECTIVES: To report long-term outcomes of nonmelanoma skin cancer (NMSC) in immunosuppressed cardiac and liver transplant recipients (CLTR). MATERIALS AND METHODS: The authors reviewed CLTR at the Mayo Clinic in Arizona from 1986 to 2013. Patient and tumor characteristics were recorded. Survival rates were calculated using the Kaplan-Meier method. Patient-specific and lesion-specific analyses were performed. Univariate and multivariate cox regressions were performed for comparisons. RESULTS: Seven-hundred and forty-seven patients underwent cardiac (138) or liver (609) transplantation and of these, 97 patients (13%) developed 382 invasive NMSC. The median follow-up was 11 (range, 3 to 27) years for surviving patients. Primary treatment was mainly surgery alone. At 10 years, the local recurrence (LR) rate was 20% (95% confidence interval, 15%-28%), and 14% of patients had multiple LRs. At 10 years, LR rates were higher for T3/T4 tumors when compared with T1/T2 tumors (32.5% vs. 20%, P=0.05). At 10 years, overall survival was 79% (95% confidence interval, 64%-88%). On multivariate analysis, age 61 years and more demonstrated inferior overall survival (P<0.01). CONCLUSIONS: This is the first study describing the AJCC 8th edition stage-based patterns of recurrence and long-term outcomes of surgically managed NMSC in a large cohort of immunosuppressed CLTRs. T3 and T4 tumors recur more often than early stage tumors. Further study is required to identify factors related to recurrence and guide upfront treatment intensification in this high-risk population.

Clinical evaluation of fitness to drive in patients with brain metastases.

BACKGROUND: Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). METHODS: We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. RESULTS: The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. CONCLUSIONS: There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.

N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial.

OBJECTIVE: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy. PATIENTS AND METHODS: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%. RESULTS: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall. CONCLUSION: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02123511.

Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults.

OBJECTIVES: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger. MATERIALS AND METHODS: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts. RESULTS: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001). CONCLUSION: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.

Linking Education to Action: A Program to Increase Research Participation Among African American Women.

BACKGROUND: Underrepresentation of African American women as research participants contributes to health disparities. Contemporary studies have focused on clinical trial (CT) participation; epidemiologic and genetic studies utilizing medical records and/or biological samples have received less attention. In partnership with The Links, Incorporated (The Links), a national service organization of professional African American women, this study sought to examine attitudes regarding chart review (CR) studies, genetic studies/biobanking (GEN), and CTs; develop; and evaluate an online education-to-action program. METHODS: In phase 1, focus groups were convened with members of The Links to inform the content and format of the program. Phases 2 and 3 involved designing and evaluating the program, respectively. RESULTS: Thirty-four women across three focus groups shared attitudes and perceptions regarding research and provided guidance for program development. Subsequently, 244 women completed the program (77% response rate), including pre- and post-assessments. Participants indicating that they "definitely" or "probably" (responses combined) intend to participate in research increased from 36.5% to 69.3% (pre/post-program). Agreement with the statement "research in the U.S. is ethical" increased (52.9% to 74.4%) as did factual knowledge regarding each of the study types. There was a decrease in reporting "little or no understanding" of study types (Pre/Post: GEN: 66%/24.9%, CR: 62.9%/18.4%, CTs: 40.7%/15.5%). Pre-program, few were "very positive" about the study types (14.3% GEN, 15.0% CR, 28.6% CTs); post-program ratings increased and equalized (42.8% GEN, 43.0% CR, 42.5% CTs). CONCLUSIONS: An online education-to-action program targeting professional African American women improved knowledge, perceptions of ethics, and intent to participate in biomedical research.

Choosing wisely after publication of level I evidence in breast cancer radiotherapy.

BACKGROUND: Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT. To assess response to level I evidence and adherence to ASTRO recommendations, we evaluated the pattern of RT use for early-stage breast cancer at our National Comprehensive Cancer Network institution from 2006 to 2008 and 2011 to 2013 and compared the results with national trends. METHODS: Data from a prospective database were extracted to include patients treated with BCT, aged ≥50 years, with histologic findings of invasive ductal carcinoma, stage T1-T2N0M0, estrogen receptor-positive, and HER2 normal. We retrospectively reviewed the medical records and estimated costs based on 2016 Hospital Outpatient Prospective Payment System (technical fees) and Medicare Physician Fee Schedule (professional fees). RESULTS: Among 55 cases from 2006 to 2008, treatment regimens were 11% hypofractionated, 69% traditional schedule, and 20% RT omission (29% of patients were aged >70 years). Among 83 cases from 2011 to 2013, treatment regimens were 54% hypofractionated, 19% traditional schedule, and 27% RT omission (48% of patients were aged >70 years). 3DCRT was used for all WBRT treatments. Direct medical cost estimates were as follows: 15 fractions 3DCRT, $7,197.87; 15 fractions IMRT, $11,232.33; 25 fractions 3DCRT, $9,731.39; and 25 fractions IMRT, $16,877.45. CONCLUSION: Despite apparent resistance to shorter radiation schedules in the United States, we demonstrate that rapid practice change in response to level I evidence is feasible. Wider adoption of evidence-based guidelines in early-stage breast cancer may substantially lower health care costs and improve convenience for patients without sacrificing oncologic outcomes.

Patient-reported distress and survival among patients receiving definitive radiation therapy.

OBJECTIVE: Patient-reported distress (PRD) has not been well assessed in association with survival after radiation therapy (RT). The aims of this study were to evaluate the association between PRD level and survival after definitive RT and to identify the main causes of distress in definitive RT patients. METHODS AND MATERIALS: A total of 678 consecutive patients receiving definitive RT at our institution from April 2012 through May 2015 were included. All patients answered a PRD questionnaire that contained 30 items related to possible causes of distress, which could be rated from 1 (no distress) to 5 (high distress). Additionally, patients were asked to rate their overall distress level from 0 (no distress) to 10 (extreme distress). This overall distress level was our primary patient-reported distress measure and was examined as a continuous variable and as a categorical variable with 3 PRD levels (low, 0-3 [n = 295]; moderate, 4-6 [n = 222]; and high, 7-10 [n = 161]). RESULTS: As a continuous variable in multivariable Cox regression analysis, a higher overall PRD level was associated with poorer survival after RT (hazard ratio [HR], 1.39; P = .004). As a categorical variable, compared with patients with low distress, survival was poorer for patients with moderate distress (HR, 1.62; P = .038) or high distress (HR, 1.49; P = .12), but the latter difference was not significant. When the moderate and high distress levels were combined, survival was significantly poorer compared with the low distress level (HR, 1.57; P = .034). The top 5 specific causes of distress that patients mentioned were "How I feel during treatment," "Fatigue," "Out-of-pocket medical costs," "Pain that affects my daily functioning," and "Sleep difficulties." CONCLUSIONS: PRD before or during RT is a prognostic factor associated with decreased survival. Distress screening guidelines and interventions should be implemented for patients receiving definitive RT.