Virtual interviews and equity: The pediatric pulmonary fellow perspective.

BACKGROUND AND OBJECTIVES: The SARS-CoV-2 pandemic shifted medical training programs to utilize virtual interviews (VIs) starting with the 2020 interview cycle. Fellowship interviews continue in the virtual format. It is unknown how this shift has affected equity for applicants as compared to in-person interviews. Equity in this study includes consideration of the opportunity for an applicant to accept, access, and conduct a VI. This study assessed pediatric pulmonary fellows' perception of equity associated with VIs and preferences for future cycles. METHODS: An anonymous survey link was emailed to Pediatric Pulmonology Program Directors to disseminate to incoming and first-year pediatric pulmonary fellows who participated in the 2022-2023 and 2021-2022 VI seasons. Responses were summarized by frequency and percentages. Inductive coding was used to thematically analyze free-text responses. RESULTS: Nearly 30% of eligible incoming and first-year pulmonary fellows (n = 35/119, 29.4%) completed the survey. Seventy-four percent felt that VIs reduce inequities as compared to in-person interviews. Sixty percent felt that VIs were the most equitable format, and 51% chose a VI as their preferred future format. Important practice considerations to promote equity for future VIs included providing applicants with instruction for the expected dress code, followed by providing applicants with virtual technology (91% and 89% of respondents ranked as at least "somewhat important," respectively). CONCLUSION: VIs were perceived as a more equitable interview format by pediatric pulmonology fellows compared to in-person interviews in our study. To increase equity for VIs, program directors can consider additional adaptations such as providing standardized instruction for dress code and providing the required technology.

Identification of an optimal mutant allele frequency to detect activating KRAS, NRAS, and BRAF mutations in a commercial cell-free DNA next-generation sequencing assay in colorectal and pancreatic adenocarcinomas.

Background: Evaluation for activating mutations in KRAS, NRAS, and BRAF in colorectal cancer (CRC) and in KRAS in pancreatic ductal adenocarcinoma (PDAC) is essential for clinical care. Plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) allows convenient assessment of a tumor's molecular profile, however low tumor DNA shedding limits sensitivity. We investigated mutant allele frequency (MAF) of other oncogenic dominant genes to identify a threshold for accurate detection of KRAS, NRAS, and BRAF (RAS/RAF) mutations in cfDNA. Methods: Molecular and clinical data were obtained from the Duke Molecular Registry of Tumors and the SCRUM-Japan GOZILA study. Patients with CRC or PDAC and a KRAS, NRAS, or BRAF activating single nucleotide variant (SNV) present on tissue NGS and with available cfDNA assays were included. Recursive partitioning and Wilcoxon-rank statistics methods identified potential cut-points for discriminative MAF values. Results: One hundred and thirty-five CRC and 30 PDAC cases with 198 total cfDNA assays met criteria. Greatest non-RAS/RAF dominant gene MAF of 0.34% provided maximum discrimination for predicting RAS/RAF SNV detection. Sensitivity for RAS/RAF SNVs increased with dominant gene MAF, with MAF ≥1% predicting sensitivity >98%, MAF between 0.34 and 1% predicting sensitivity of 84.0%, and MAF £0.34% predicting sensitivity of 50%. For 43 cfDNA assays that did not detect RAS/RAF SNVs, 18 assays detected 34 other oncogenic variants, of which 80.6% were not also detected on tissue. Conclusions: Non-RAS/RAF dominant oncogenic mutation MAF ≥1% on cfDNA NGS predicts high sensitivity to detect RAS/RAF oncogenic SNVs in CRC and PDAC. MAF £0.34% indicates an assay may not reliably detect RAS/RAF SNVs, despite detection on tissue testing. Most variants from assays that did not detect RAS/RAF had MAF <1% and were not detected on tissue, suggesting potential confounding. These data suggest a practical approach to determining cfDNA assay adequacy, with implications for guiding clinical decisions in CRC and PDAC.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Pan-Cancer Proteomics Analysis to Identify Tumor-Enriched and Highly Expressed Cell Surface Antigens as Potential Targets for Cancer Therapeutics.

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) provides unique opportunities for cancer target discovery using protein expression. Proteomics data from CPTAC tumor types have been primarily generated using a multiplex tandem mass tag (TMT) approach, which is designed to provide protein quantification relative to reference samples. However, relative protein expression data are suboptimal for prioritization of targets within a tissue type, which requires additional reprocessing of the original proteomics data to derive absolute quantitation estimation. We evaluated the feasibility of using differential protein analysis coupled with intensity-based absolute quantification (iBAQ) to identify tumor-enriched and highly expressed cell surface antigens, employing tandem mass tag (TMT) proteomics data from CPTAC. Absolute quantification derived from TMT proteomics data was highly correlated with that of label-free proteomics data from the CPTAC colon adenocarcinoma cohort, which contains proteomics data measured by both approaches. We validated the TMT-iBAQ approach by comparing the iBAQ value to the receptor density value of HER2 and TROP2 measured by flow cytometry in about 30 selected breast and lung cancer cell lines from the Cancer Cell Line Encyclopedia. Collections of these tumor-enriched and highly expressed cell surface antigens could serve as a valuable resource for the development of cancer therapeutics, including antibody-drug conjugates and immunotherapeutic agents.

Adaptive Positron Emission Tomography Radiation Therapy in Patients With Locally Advanced Vulvar Cancer: A Prospective Study.

Purpose: In this prospective trial, we aim to determine whether fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT)-based adaptive radiation therapy (ART) improves dosimetry outcomes for patients treated with definitive radiation for locally advanced vulvar cancer. Methods and Materials: Patients were enrolled in 2 sequential institutional review board-approved prospective protocols for PET/CT ART from 2012 to 2020. Patients were planned with pretreatment PET/CT to 45 to 56 Gy in 1.8 Gy/fraction, followed by a boost to gross disease (nodal and/or primary) to a total of 64 to 66 Gy. Intratreatment PET/CT was obtained at 30 to 36 Gy, and all patients were replanned to the same dose goals with revised organ at risk (OAR), gross tumor volume, and planned target volume contours. Radiation therapy consisted of either intensity modulated radiation therapy or volumetric modulated arc therapy. Toxicity was graded by Common Terminology Criteria for Adverse Events, version 5.0. Local control, disease-free survival, overall survival, and time to toxicity were estimated using the Kaplan-Meier method. Dosimetry metrics for OARs were compared using the Wilcoxon signed rank test. Results: Twenty patients were eligible for analysis. Median follow-up among surviving patients was 5.5 years. Local control, disease-free survival, and overall survival at 2 years were 63%, 43%, and 68%, respectively. ART significantly reduced the following OAR doses: bladder, maximum dose (Dmax; median reduction [MR], 1.1 Gy; interquartile range [IQR], 0.48-2.3 Gy; P < .001) and D2cc (MR, 1.5 Gy; IQR, 0.51-2.1 Gy; P < .001); bowel, Dmax (MR, 1.0 Gy; IQR, 0.11-2.9 Gy; P < .001), D2cc (MR, 0.39 Gy; IQR, 0.023-1.7 Gy; P < .001), and D15cc (MR, 0.19 Gy; IQR, 0.026-0.47 Gy; P = .002); and rectal, mean dose (MR, 0.66 Gy; IQR, 0.17-1.7 Gy; P = .006) and D2cc (MR, 0.46 Gy; IQR, 0.17-0.80 Gy; P = .006). No patients experienced any grade ≥3 acute toxicities. There were no reported late grade ≥2 vaginal toxicities. Lymphedema at 2 years was 17% (95% confidence interval, 0%-34%). Conclusions: Doses to bladder, bowel, and rectum were significantly improved with ART, though the median magnitudes were modest. Which patients benefit most from adaptive treatment is a matter for future investigation.

Divergent Interpretations of Imaging After Stereotactic Body Radiation Therapy for Lung Cancer.

PURPOSE: Conflicting information from health care providers contributes to anxiety among cancer patients. The purpose of this study was to investigate discordant interpretations of follow-up imaging studies after lung stereotactic body radiation therapy (SBRT) between radiologists and radiation oncologists. METHODS AND MATERIALS: Patients treated with SBRT for stage I non-small cell lung cancer from 2007 to 2018 at Duke University Medical Center were included. Radiology interpretations of follow-up computed tomography (CT) chest or positron emission tomography (PET)/CT scans and the corresponding radiation oncology interpretations in follow-up notes from the medical record were assessed. Based on language used, interpretations were scored as concerning for progression (Progression), neutral differential listed (Neutral Differential), or favor stability/postradiation changes (Stable). Neutral Differential required that malignancy was specifically listed as a possibility in the differential. Encounters were categorized as discordant when either radiology or radiation oncology interpreted the surveillance imaging as Progression when the other interpreted the imaging study as Stable or Neutral Differential. The incidence of discordant interpretations was the primary endpoint of the study. RESULTS: From 2007 to 2018, 139 patients were treated with SBRT and had available follow-up CT or PET-CT imaging for the analysis. Median follow-up was 61 months and the median number of follow-up encounters per patient was 3. Of 534 encounters evaluated, 25 (4.7%) had overtly discordant interpretations of imaging studies. This most commonly arose when radiology felt the imaging study showed Progression but radiation oncology favored Stable or Neutral Differential (24/25, 96%). No patient or treatment variables were found to be significantly associated with discordant interpretations on univariate analysis including type of scan (CT 22/489, 4.5%; PET-CT 3/45, 7%; P = .46). CONCLUSIONS: Surveillance imaging after lung SBRT is often interpreted differently by radiologists and radiation oncologists, but overt discordance was relatively low at our institution. Providers should be aware of differences in interpretation patterns that may contribute to increased patient distress.