Evaluation of Culture Conducive to Academic Success by Gender at a Comprehensive Cancer Center.

INTRODUCTION: The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic. MATERIALS AND METHODS: We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated. RESULTS: A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS. CONCLUSIONS: Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty.

Validation of Anticorrelated TGFß Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy.

PURPOSE: Loss of TGFß signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGFß and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, ßAlt, predicts patient outcome in response to genotoxic therapy. Here we sought to verify this biology in live specimens and additional datasets. EXPERIMENTAL DESIGN: Human head and neck squamous carcinoma (HNSC) explants were treated in vitro to test whether the signatures report TGFß signaling, indicated by SMAD2 phosphorylation, and unrepaired DNA damage, indicated by persistent 53BP1 foci after irradiation or olaparib. A custom NanoString assay was implemented to analyze the signatures' expression in explants. Each signature gene was then weighted by its association with functional responses to define a modified score, ßAltw, that was retested for association with response to genotoxic therapies in independent datasets. RESULTS: Most genes in each signature were positively correlated with the expected biological response in tumor explants. Anticorrelation of TGFß and alt-EJ signatures measured by NanoString was confirmed in explants. ßAltw was significantly (P < 0.001) better than ßAlt in predicting overall survival in response to genotoxic therapy in The Cancer Genome Atlas (TCGA) pancancer patients and in independent HNSC and ovarian cancer patient datasets. CONCLUSIONS: Association of the TGFß and alt-EJ signatures with their biological response validates TGFß competency as a key mediator of DNA repair that can be readily assayed by gene expression. The predictive value of ßAltw supports its development to assist in clinical decision making.

Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.

Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known. Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict. Design, Setting, and Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict. Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001). Conclusions and Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict. Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PURPOSE: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). METHODS: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. RESULTS: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. CONCLUSION: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

PURPOSE AND OBJECTIVES: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. METHODS AND MATERIALS: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. RESULTS: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. CONCLUSIONS: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.

The advantages and drawbacks of routine magnetic resonance imaging for long-term post-treatment locoregional surveillance of oral cavity squamous cell carcinoma.

PURPOSE: Assess the clinical utility and accuracy of routine surveillance head and neck magnetic resonance imaging (HN-MRI) for the detection of locoregional recurrence in patients with a history of oral cavity squamous cell carcinoma (OCSCC) without concurrent suspicious symptoms or signs 6 months or more after treatment. MATERIALS AND METHODS: For OCSCC patients who underwent routine (defined as: without concurrent suspicious symptoms or signs) surveillance HN-MRI at 6 months or more after treatment completion, we retrospectively determined the detection rate of locoregional disease and false positive rate. RESULTS: Out of an original cohort of 533 OCSCC patients, 46 patients, who were disease-free 6 months after treatment, had undergone 108 routine HN-MRIs from 6 to 48 months after surgery without the presence of concurrent suspicious symptoms or signs and had 6 months of subsequent follow up. 1 out of 46 (2.2%) had a true positive regional recurrence. 10 out of 46 (21.7%) patients experienced a false positive locoregional finding. CONCLUSIONS: Routine HN-MRI for locoregional surveillance of OCSCC, when used in patients without concurrent suspicious symptoms or exam findings over 6 months since treatment, may be unnecessary and costly given the very low rate of recurrence and high false positive rate. Our study supports the National Comprehensive Cancer Network guideline of limiting imaging after 6 months of primary treatment completion to patients with suspicious clinical findings. Nonetheless, managing physicians should continue to be empowered to use surveillance imaging based on risk profiles and unique circumstances for each patient.

ACR Appropriateness Criteria® thyroid carcinoma.

The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteriaare evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 ((131)I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.

Dose recalculation and the Dose-Guided Radiation Therapy (DGRT) process using megavoltage cone-beam CT.

PURPOSE: At the University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). MATERIALS AND METHODS: A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. RESULTS: Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D(1) increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D(5) dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. CONCLUSIONS: An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.