Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

Diagnostic Delay in HPV-Related Oropharyngeal Squamous Cell Carcinoma.

Introduction Human papillomavirus-related (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment.

Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions. Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney U test and Fisher's exact test. Results: A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/ß = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen. Conclusions: Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.

The American Society for Radiation Oncology Workforce Taskforce Review of the United States Radiation Oncology Workforce Analysis.

Over the past decade, concerns have arisen in radiation oncology regarding potential workforce supply and demand imbalance. The American Society for Radiation Oncology commissioned an independent analysis in 2022, looking at supply and demand in the United States radiation oncology workforce and projecting future trends for 2025 and 2030. The final report, titled Projected Supply and Demand for Radiation Oncologists in the U.S. in 2025 and 2030, is now available. The analysis included evaluating radiation oncologist (RO) supply (new graduates, exits from the specialty), potential changes in demand (growth of Medicare beneficiaries, hypofractionation, loss of indications, new indications) as well as RO productivity (growth of work relative value units [wRVUs] produced), and demand per beneficiary. The results demonstrated a relative balance between radiation oncology supply and demand for radiation services; the growth in ROs was balanced by the rapid growth of Medicare beneficiaries over the same period. The primary factors driving the model were found to be growth of Medicare beneficiaries and change in wRVU productivity, with hypofractionation and loss of indication having only a moderate effect; although the most likely scenario was a balance of workforce supply and demand, scenarios did demonstrate the possibility of over- and undersupply. Oversupply may become a concern if RO wRVU productivity reaches the highest region; beyond 2030, this is also possible if growth in RO supply does not parallel Medicare beneficiary growth, which is projected to decline and will require corresponding supply adjustment. Limitations of the analysis included uncertainty regarding the true number of ROs, the lack of inclusion of most technical reimbursement and its effect as well as failing to account for stereotactic body radiation therapy. A modeling tool is available to allow individuals to evaluate different scenarios. Moving forward, continued study will be needed to evaluate trends (particularly wRVU productivity and Medicare beneficiary growth) to allow for continued assessment of workforce supply and demand in radiation oncology.

Adaptive hypofractionted and stereotactic body radiotherapy for lung tumors with real-time MRI guidance.

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gating/tracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively.

Radiation Oncology Residency Training Program Integration of Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Program Director Survey.

PURPOSE: The aim of this study was to investigate United States (US) radiation oncology (RO) program directors' (PDs) attitudes and practices regarding racial/ethnic diversity, equity, and inclusion (DEI) to better understand potential effects on underrepresented in medicine (UIM) residents in RO. METHODS AND MATERIALS: A 28-item survey was developed using the validated Ethnic Harassment Experiences Scale and the Daily Life Experiences subscale, as well as input from DEI leaders in RO. The survey was institutional review board-approved and administered to RO PDs. PDs were provided with the American Association of Medical Colleges definition of UIM, that is, "Underrepresented in medicine means those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population." Descriptive statistics were used in analysis. RESULTS: The response rate was 71% (64/90). Institutional Culture and Beliefs: 42% responded that they had a department DEI director. A minority (17%, n = 11) agreed "I believe that people from UIM backgrounds have equal access to quality tertiary education in the US." The majority (97%, n = 62) agreed "My program values residents from UIM backgrounds." Support and Resources: The majority (78%, n = 50) agreed "My program has resources in place to assist/provide support for resident physicians from UIM backgrounds." Interview and Recruitment: Most PDs (53%) had not taken part in activities aimed at recruiting UIM residents and 17% had interviewed no UIM applicants in the past 5 years for residency. Resident Experiences of Racism: 17% (n = 11) agreed "UIM residents in my program have reported incidents of racism to me," and 28% (n = 18) agreed "I believe that UIM residents in my program have been treated differently because of their race/ethnicity by faculty, staff, coresidents or patients." CONCLUSIONS: Most PDs reported that they did not believe that UIM residents were treated differently in their department because of their race/ethnicity, and only a minority had received reports of racial discrimination experienced by residents. These data contrast resident experiences and suggest a disconnect between DEI perceptions and resident experiences among US RO PDs that should be addressed through increased programmatic action and evaluation.

Using Holistic Residency Applicant Review and Selection in Radiation Oncology to Enhance Diversity and Inclusion-An ASTRO SCAROP-ADROP-ARRO Collaboration.

Disproportionate sex, racial, and ethnic diversity remains in the radiation oncology physician workforce despite widespread awareness and longitudinal efforts to improve representation. In this collaborative review, we define the rationale and components of holistic review and how it can be best used to provide a comprehensive evaluation of applicants to residency programs in radiation oncology. We initially discuss the current state of diversity in the field of radiation oncology and highlight the components of the residency selection process that may serve to perpetuate existing biases. Subsequently, the Accreditation Council for Graduate Medical Education and Association of American Medical Colleges holistic review framework is reviewed in detail to demonstrate the balanced assessment of potential applicants. The implementation of holistic review in medical school and residency selection to date is examined to underscore the potential value of holistic review in the radiation oncology residency selection process. Finally, recommendations for the practical implementation of holistic review in radiation oncology trainee selection are outlined.

Assessment of Lymphoma and Other Hematologic Malignancies Training Needs Among Radiation Oncology Residents: a Brief Report.

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients.

A Practical Workflow for Magnetic Resonance-Guided Stereotactic Body Radiation Therapy to the Pancreas.

The increased adoption of stereotactic body radiation therapy has allowed for delivery of higher doses, potentially associated with better outcomes but at the risk of higher toxicity. The intimate association of radiosensitive organs at risk (eg, stomach, duodenum, bowel) has historically limited the delivery of ablative doses to the pancreas. The advent of magnetic resonance-guided radiation therapy with improved soft-tissue contrast allows for gated delivery without an internal target volume and online adaptive replanning to maximize the therapeutic ratio. Patient selection requires additional resources, including increased patient on-table time, physician time, and physics support. Within our center's workflow, integrating an educational video at consultation as well as optimizing biofeedback mechanisms have significantly improved the experience for our patients.

Radiation Oncology Resident Perspectives on Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Resident Survey.

PURPOSE: In this study, radiation oncology residents were surveyed on perceptions of diversity, equity, inclusion, and belonging in their residency training programs. METHODS AND MATERIALS: A 23-item survey was developed by the Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee resident members and faculty advisors. The survey was divided into 4 sections: institutional culture, support and resources, interview and recruitment, and experiences of bias. The survey was sent individually to residents from all Accreditation Council for Graduate Medical Education-accredited radiation oncology programs. RESULTS: The survey was issued to 757 residents. A total of 319 residents completed the survey, for a response rate of 42%. All postgraduate years and geographic regions were represented. Significant racial, ethnic, and gender differences were present in survey response patterns. White residents (94%, 164 of 174) and male residents (96%, 186 of 194) were more likely to strongly agree/agree that they were treated with respect by their colleagues and their coworkers than other racial groups (P < .005) or gender groups (P < .008). Only 3% (5 of 174) of White residents strongly agreed/agreed that they were treated unfairly because of their race/ethnicity, while 31% (5 of 16) of Black residents and 10% (9 of 94) of Asian residents strongly agreed/agreed (P < .0001). Similarly, Hispanic residents were more likely to strongly agree/agree (24%, 5 of 21) than non-Hispanic residents (7%, 20 of 298) (P = .003). Regarding mentorship, there were no differences by gender or ethnicity. There were differences by race in residents reporting that they had a supportive mentor (P = .022), with 89% (154 of 174) of White residents who strongly agreed/agreed, 88% (14 of 16) of Black residents, and 91% of Asian residents (86 of 94). CONCLUSIONS: This survey reveals that experiences of support, mentorship, inclusion, and bias vary significantly among radiation oncology residents based on race, ethnicity, and gender. Radiation oncology has opportunity for growth to ensure an equitable experience for all residents.

Radiation therapy prior to CAR T-cell therapy in lymphoma: impact on patient outcomes.

INTRODUCTION: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with refractory or recurrent (R/R) diffuse large B-cell lymphomas (DLBCL). Nonetheless, most patients ultimately progress. The use of bridging or salvage radiotherapy (RT) in combination with CAR T-cell therapy has been proposed as potential strategies to improve patient outcomes, but consensus is currently lacking as to which, if either, approach is effective. AREAS COVERED: We reviewed the immunologic and molecular mechanisms of resistance and the current retrospective data on patterns-of-failure, clinical risk factors, and treatment outcomes in patients undergoing CAR T-cell therapy, with and without bridging or salvage RT. EXPERT OPINION: We believe that current basic and clinical evidence supports the use of comprehensive, ablative bridging irradiation (CABI), as opposed to low-dose bridging or salvage radiotherapy, as a promising strategy to improve CAR T-cell therapy outcomes in patients with R/R DLBCL. This potential benefit is likely greatest in patients with high tumor burden and/or localized disease, who are both at elevated risk of local recurrence and can often be safely and comprehensively treated with ablative radiation doses (EQD2 > 39 Gy). Hypothesis-driven clinical trials are needed prospectively assess the impact of radiation on outcomes in patients undergoing CAR T-cell therapy.

Delivery of Online Adaptive MRI-Guided Radiation Therapy for a Deaf Patient.

MRI-guided radiation therapy (MRgRT) enables real-time imaging during treatment and daily online adaptive planning. It is particularly useful for areas of treatment that have been previously excluded or restricted from ablative doses due to potential damage to adjacent normal tissue. In certain cases, ablative doses to metastatic lesions may be justified and treated with MRgRT using video-assisted gated breath-hold adjustments throughout delivery. The workflow relies on patient biofeedback and auditory cues. A 74-year-old deaf male with a history of prostate cancer status post prostatectomy was found to have an enlarged cervical lymph node, which was excised with histopathology demonstrating Merkel cell carcinoma. Approximately one year after treatment with two cycles of pembrolizumab, which was subsequently discontinued due to toxicity, surveillance imaging demonstrated an enlarging left adrenal nodule. It was initially stable for an additional seven months with pembrolizumab rechallenge but was again found enlarged on subsequent imaging. The patient underwent MRg stereotactic body radiation therapy (MRgSBRT) to a total dose of 60 Gy in five fractions to this isolated site of progression. The patient was equipped with mirrored glasses to view the tracking structure with respect to gating the boundary structure, and the traditional reliance on verbal cues for coaching was reimagined to rely on visual cues instead. Follow-up positron emission tomography/CT (PET/CT) two weeks after treatment demonstrated interval resolution of the left adrenal metastatic nodule and a return to symmetric bilateral adrenal gland metabolic activity. The necessary MRgSBRT treatment for single metastatic lesions near normal tissue structures relies on verbal cues and coaching. However, deaf patients are unable to receive this treatment according to the traditional workflow model. Unique opportunities exist for the implementation of culturally competent care for the Deaf community, relying more heavily on visual cues, in radiation oncology practice.

Assessment of MRI-Linac Economics under the RO-APM.

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (-89%) and pancreatic cancer (-83%). The total annual reimbursement discrepancy amounted to -78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of -47% for lung cancer and -46% for pancreatic cancer, mitigating the overall annual reimbursement difference to -54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM.

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas After Chimeric Antigen Receptor T-Cell Therapy.

PURPOSE: Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies. METHODS AND MATERIALS: This is a retrospective analysis of patients with R/R large B-cell lymphoma who were treated with anti-CD19 CAR T at a National Cancer Institute-designated Comprehensive Cancer Center between 2015 and 2019. Pre- and posttreatment positron emission/computed tomography scans were analyzed to assess the progression of existing (local failures) versus new, nonoverlapping lesions (de novo failures) and identify lesions at a high risk for progression. RESULTS: A total of 469 pretreatment lesions in 63 patients were identified. At a median follow-up of 12.6 months, 36 patients (57%) recurred. Most (n = 31; 86%) had a component of local failure, and 13 patients (36%) exhibited strictly local failures. Even when progressing, 84% of recurrent patients continued to have a subset of pretreatment lesions maintain positron emission/computed tomography resolution. Lesions at a high risk for local failure included those with a diameter ≥5 cm (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.55-3.55; P < .001), maximum standardized uptake value ≥10 (OR, 2.08; 95% CI, 1.38-3.12; P < .001), or those that were extranodal (OR, 1.49; 95% CI, 1.10-2.04; P = .01). In the 69 patients eligible for survival analysis, those with any lesion ≥5 cm (n = 46; 67%) experienced inferior progression-free survival (hazard ratio, 2.41; 95% CI, 1.15-5.04; P = .02) and overall survival (hazard ratio, 3.36; 95% CI, 1.17-9.96; P = .02). CONCLUSIONS: Most patients who recur after CAR T experience a component of local progression. Furthermore, lesions with high-risk features, particularly large size, were associated with inferior treatment efficacy and patient survival. Taken together, these observations suggest that lesion-specific resistance may contribute to CAR T treatment failure. Locally directed therapies to high-risk lesions, such as radiation therapy, may be a viable strategy to prevent CAR T failures in select patients.

Gonadal-sparing total body irradiation with the use of helical tomotherapy for nonmalignant indications.

BACKGROUND: The aim was to demonstrate the feasibility and technique of gonadal sparing total body irradiation (TBI) with helical tomotherapy. Total body irradiation is a common part of the conditioning regimen prior to allogeneic stem cell transplantation. Shielding or dose-reduction to the gonads is often desired to preserve fertility, particularly in young patients undergoing transplant for non-malignant indications. Helical tomotherapy (HT) has been shown to be superior to traditional TBI delivery for organ at risk (OA R) doses and dose homogeneity. MATERIALS AND METHODS: We present two representative cases (one male and one female) to illustrate the feasibility of this technique, each of whom received 3Gy in a single fraction prior to allogeneic stem cell transplant for benign indications. The planning target volume (PTV) included the whole body with a subtraction of OA Rs including the lungs, heart, and brain (each contracted by 1cm) as well as the gonads (testicles expanded by 5 cm and ovaries expanded by 0.5 cm). RESULTS: For the male patient we achieved a homogeneity index of 1.35 with a maximum and median planned dose to the testes of 0.53 Gy and 0.35 Gy, respectively. In-vivo dosimetry demonstrated an actual received dose of 0.48 Gy. For the female patient we achieved a homogeneity index of 1.13 with a maximum and median planned dose to the ovaries of 1.66 Gy and 0.86 Gy, respectively. CONCLUSION: Gonadal sparing TBI is feasible and deliverable using HT in patients with non-malignant diseases requiring TBI as part of a pre-stem cell transplant conditioning regimen.

No Longer a Match: Trends in Radiation Oncology National Resident Matching Program (NRMP) Data from 2010-2020 and Comparison Across Specialties.

PURPOSE: To report trends in the number and types of applicants and matched trainees to radiation oncology in comparison to other specialties participating in the National Resident Matching Program (NRMP) between 2010 and 2020. METHODS AND MATERIALS: Data from the NRMP and Electronic Residency Application System (ERAS) were obtained for 18 medical specialties between 2010 and 2020. We assessed the numbers and types of applicants and matched trainees relative to available positions in the NRMP and Supplemental Offer and Acceptance Program (SOAP). RESULTS: In the 2020 NRMP, 122 US MD senior graduates preferentially ranked radiation oncology, a significant decrease from a median of 187 between 2010 to 2019 (interquartile range [IQR], 170-192; P < .001). Across all 18 specialties, radiation oncology experienced the greatest declines in the 2020 NRMP cycle relative to 2010 to 2019, in both the number of ERAS applicants from the United States and Canada (-31%) and the percentage of positions filled by US MD or DO senior graduates (-28%). Of 189 available positions, 81% (n = 154) filled in the NRMP prior to the SOAP, of which 65% (n = 122) were "matched" by US MD senior graduates who preferentially ranked radiation oncology as their top choice of specialty, representing a significant decrease from a median of 92% between 2010 to 2019 (IQR, 88%-94%; P = .002). The percentages of radiation oncology programs and positions unfilled in the NRMP prior to the SOAP were significantly increased in 2020 compared with 2010 to 2019 (programs: 29% vs 8% [IQR, 5%-8%; P < .001]; positions: 19% vs 4% [IQR, 2%-4%; P <.001]). Despite >99% (n = 127 of 128) of US MD or DO senior applicants preferring radiation oncology successfully matching to a radiation oncology position in the 2020 NRMP, 16 of 35 remaining unfilled positions were filled via the SOAP. Radiation oncology was the top user of the SOAP across all specialties participating in the 2020 NRMP, filling 15% of total positions versus a median of 0.9% (IQR, 0.3%-2.3%; P <.001). CONCLUSIONS: The supply of radiation oncology residency positions now far exceeds demand by graduating US medical students. Efforts to nullify a market correction revealed by medical student behavior via continued reliance on the SOAP to fill historical levels of training positions may not be in the best of interest of trainees, individual programs, or the specialty as a whole.

Pretreatment CT and 18 F-FDG PET-based radiomic model predicting pathological complete response and loco-regional control following neoadjuvant chemoradiation in oesophageal cancer.

INTRODUCTION: To develop a radiomic-based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer. METHODS: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in-house data-chjmirocterization algorithm was used to extract 3D-radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, Fc  = α * FPET  + (1 - α) * FCT , 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco-regional control (LRC), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis, and compared using log-rank test. RESULTS: Median follow-up was 59 months. pCR was achieved in 34 (50%) patients. Five-year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0-1 indicative of complete response or minimal residual disease was significantly associated with improved 5-year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04-0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5-year LRC favouring low-score group (91.1% vs. 80%, 95% CI 0.09-1.77, P = 0.2). CONCLUSION: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes.