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Background Time interval between neoadjuvant (combined) chemotherapy and radiation (nCRT) and surgery has been linked to pathologic response rates and outcomes in patients with various solid cancers. The optimal timing between nCRT and esophagectomy in patients with esophageal squamous cell carcinoma (SCC), however, is not known. Our aim was to analyze the relation between elapsed time from completion of nCRT to esophagectomy and postsurgical mortality and overall survival. Methods We reviewed the National Cancer Database for patients with SCC ( n  = 1,244) of the esophagus diagnosed between 2003 and 2011 who were treated with nCRT followed by esophagectomy within 26 weeks after completion of nCRT. Results Thirty-day mortality was 5.6% and 90-day mortality was 11.1%. The duration of post-nCRT interval was not a predictor of 30-day and 90-day postoperative mortality in multivariate models, but 30-day postoperative mortality was predictable based on increasing Charlson-Deyo comorbidities (adjusted odds ratio [aOR] 1.77, P  = .054) and improved in academic institutions (aOR 0.66, P  = .005). Similar findings were found for 90-day mortality (comorbidity index aOR 1.58, P  = .046) and for treatment at an academic facility (0.82, P  = .062). In a multivariate survival analysis, the duration of the post-nCRT interval was not found to be a predictor of overall survival ( P  = .769), whereas increasing age (hazard ratio [HR] 1.02, P  = .005), increasing comorbidity score (HR 1.38, P  = .005), treatment at an academic hospital (HR 0.84, P  = .001), and post-treatment nodal status (HR 1.73, P < .001) were predictors. Conclusion Perioperative mortality and overall survival are not affected by the time interval between completion of nCRT and esophagectomy among patients with SCC histology. [ABSTRACT FROM AUTHOR]

Purpose Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of locoregional recurrence and distant metastasis are high, and patients should be selected carefully to maximize the benefit of additional aggressive local therapy while minimizing the risk of adverse side effects. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Options are limited for patients with intrathoracic recurrence of non-small cell lung cancer (NSCLC) who previously received radiation. We report our 5-year experience with the toxicity and efficacy of proton beam therapy (PBT) for reirradiation. Materials and methods: Thirty-three patients underwent PBT reirradiation for intrathoracic recurrent NSCLC at a single institution. All patients had had RT for NSCLC (median initial dose 63Gy in 33 fractions), with median interval to reirradiation of 36months. Median reirradiation dose was 66Gy (RBE) in 32 fractions. Toxicity was scored with CTCAE v4.0, and survival outcomes were estimated using Kaplan–Meier. Results: Thirty-one patients (94%) completed reirradiation. At a median 11months’ follow-up, 1-year rates of overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were 47%, 28%, 54%, and 39%. Rates of severe (grade ⩾3) toxicity were 9% esophageal, 21% pulmonary; 1 patient had grade 4 esophagitis, and 2 had grade 4 pulmonary toxicity. Nine patients experienced a second in-field failure. Conclusions: PBT is an option for treating recurrent NSCLC. However, the rates of locoregional recurrence and distant metastasis are high and the potential for toxicity significant. The risks and benefits of PBT must be carefully weighed in each case. [Copyright &y& Elsevier]

Exposure to corticosteroids increases the risks of avascular necrosis (AVN) of the bone after hematopoietic cell transplantation (HCT). However, whether this effect is dependent on the dose of corticosteroids is not well known. We conducted a case-controlled study, which included 74 recipients of autologous or allogeneic HCT with AVN and 147 controls without AVN that were matched by age, sex, and year of HCT to cases. Cases with AVN included 8 autologous HCT recipients, 58 myeloablative allogeneic HCT recipients, and 8 recipients of nonmyeloabalative allogeneic HCT. Corticosteroid exposure was expressed as cumulative doses of prednisone. Cases received higher cumulative doses of prednisone than controls, and among allogeneic HCT recipients, cases were more likely to have developed acute and chronic graft-versus-host disease (aGVHD, cGVHD). Cumulative dose of prednisone was an independent risk factor for AVN. Compared to no corticosteroid exposure, exposure to <3870 mg cumulative dose of prednisone was associated with 4.0 (95% confidence intervals, 1.5-11.2) times higher risk, 3870-9735 mg with 5.6 (2.1-15.2) times higher risk and >9735 with 8.6 (3.2-23.5) times higher risk of AVN. Exposure to higher doses of corticosteroids increases the risk of AVN in HCT recipients. [ABSTRACT FROM AUTHOR]

Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE. An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE timing. Thematic analysis was used for qualitative responses. One hundred thirteen Radiation Oncology Education Collaborative Study Group members completed the survey (28.2% response rate); RO attendings comprised 68.1% of respondents. Most practiced in an academic setting (85.8%) in North America (80.5%). Institution-specific materials were the most common PE resource used by radiation oncologists (67.6%). Almost half (40.2%) reported that their PE practices differed based on clinical encounter type, with paper handouts commonly used for in-person and multimedia for telehealth visits. Only 57.7% reported access to non-English PE materials. PE practices among radiation oncologists differed according to RT clinical workflow timing (consultation versus simulation versus first RT, respectively): one-on-one teaching: 88.5% versus 49.4% versus 56.3%, P <.01, and paper handouts: 69.0% versus 28.7% versus 16.1%, P <.01. Identified challenges for PE delivery included limited time, administrative barriers to the development or implementation of new materials or practices, and a lack of customized resources for tailored PE. Effective strategies for PE included utilization of visual diagrams, multimedia, and innovative education techniques to personalize PE delivery/resources for a diverse patient population, as well as fostering interprofessional collaboration to reinforce educational content. Radiation oncologists and interprofessional RO team members engage in PE, with most using institution-specific materials often available only in English. PE practices differ according to clinical encounter type and RT workflow timing. Increased adoption of multimedia materials and partnerships with patients to tailor PE resources are needed to foster high-quality, patient-centered PE delivery. [ABSTRACT FROM AUTHOR]

Black women with breast cancer often present with more aggressive disease compared with other races, contributing to an increased risk of cancer mortality. Despite this inequity, Black women remain severely underrepresented in breast cancer clinical trials. We aim to characterize factors that influence a woman's decision to enroll in a clinical trial, with the goal of identifying clinical interventions to aid in the recruitment of vulnerable groups. A cross-sectional, descriptive study was conducted using a questionnaire adapted from 2 prevalidated surveys investigating factors influencing clinical trial enrollment. The survey was administered to women with curable breast cancer during a single follow-up visit at 4 different sites within a university medical system where all patients are screened for clinical trial eligibility. Chi-square tests and Mann-Whitney U tests were used to assess associations or differences between the populations. One hundred ninety-four out of 209 women completed the survey, giving a compliance rate of 93%. Twenty-six percent of women self-identified as Black, most women were located at community sites (67.1%), most women had diagnoses of early-stage disease (I: 57.7%, II: 29.4%), and 81% of women had some collegiate-level education. Black women were younger at diagnosis (P =.005) and less likely to be married (P =.012) but more often lived with family members (P =.003) and had a lower median income (P <.001). According to the survey, Black women were less likely to trust their care team (P =.032), more likely to believe that research ultimately harms minorities (P <.001), and had a stronger belief in God's will determining illness and wellness (P <.001). Recurring themes of trust in the health care team, patient education, and advancement of cancer treatments were discussed in the focus groups. Failure to offer clinical trials and mistrust in research institutions may pose the greatest hindrances to the enrollment of Black women in clinical trials. Empowering women through education and fostering trustworthy relationships can encourage greater clinical trial participation. [ABSTRACT FROM AUTHOR]

The American Association of Physicists in Medicine Radiation Oncology Medical Physics Education Subcommittee (ROMPES) has updated the radiation oncology physics core curriculum for medical residents in the radiation oncology specialty. Thirteen physicists from the United States and Canada involved in radiation oncology resident education were recruited to ROMPES. The group included doctorates and master's of physicists with a range of clinical or academic roles. Radiation oncology physician and resident representatives were also consulted in the development of this curriculum. In addition to modernizing the material to include new technology, the updated curriculum is consistent with the format of the American Board of Radiology Physics Study Guide Working Group to promote concordance between current resident educational guidelines and examination preparation guidelines. The revised core curriculum recommends 56 hours of didactic education like the 2015 curriculum but was restructured to provide resident education that facilitates best clinical practice and scientific advancement in radiation oncology. The reference list, glossary, and practical modules were reviewed and updated to include recent literature and clinical practice examples. ROMPES has updated the core physics curriculum for radiation oncology residents. In addition to providing a comprehensive curriculum to promote best practice for radiation oncology practitioners, the updated curriculum aligns with recommendations from the American Board of Radiology Physics Study Guide Working Group. New technology has been integrated into the curriculum. The updated curriculum provides a framework to appropriately cover the educational topics for radiation oncology residents in preparation for their subsequent career development. [ABSTRACT FROM AUTHOR]

Purpose: Although supported by most men and women, paternity leave is heavily underused across industries owing in part to external pressures and inconsistent availability. The goal of this study was to assess the use of paternity leave in radiation oncology (RO) practices and identify any associated barriers.Methods and Materials: A 36-item survey was distributed via e-mail to 536 male domestic RO attending and resident physicians. Questions assessed paternity leave policies, use, and departmental support. Data were collected using Research Electronic Data Capture from January to February 2021. Descriptive statistics were obtained for analysis, and logistic regression was performed to analyze the association between practice type and presence of policy.Results: The survey response rate was 20% (n = 108), with 98% of participants completing all applicable questions. Respondents included 63 attending physicians (58%) and 45 resident physicians (42%). The median age of all respondents was 35 years. Among all participants, 51 (47%) stated their practice had a formal paternity leave policy. The median time allowed for leave was 4 weeks (range, 0.5 weeks to unlimited), whereas the median time taken was 2 weeks (range, 0.5-12 weeks). Sixteen men felt pressure to take less leave than what was allowed by their policy, and 46% of men stated that in retrospect, they would have taken more time off for paternity leave.Conclusions: To the authors' knowledge, this is the first study to investigate the use of paternity leave in RO practices in the United States. Integrating expanded family leave policies, including specifically allowing for paternity leave and accompanying these policies with cultural changes acknowledging the importance of family leave, would be beneficial to improving quality of life and work-life balance for parents. [ABSTRACT FROM AUTHOR]

Abstract: The hematopoietic cell transplantation specific comorbidity index (HCT-CI) has been recently proposed to predict the probability of nonrelapse mortality (NRM) and overall survival (OS) in allogeneic HCT recipients while taking into account any pretransplant comorbidity. We tested the validity of the HCT-CI in a cohort of 373 adult HCT recipients (184 matched-related donor and 189 unrelated umbilical cord blood) who received a myeloablative (N = 150) or nonmyeloablative (N = 223) conditioning regimen. HCT-CI scores of 0, 1, 2, and ≥3 were present in 58 (16%), 56 (15%), 64 (17%), and 195 (52%) patients, respectively. Pulmonary conditions were the most common comorbidity. Cumulative incidence of NRM at 2 years was 10%, 20%, 24%, and 28% for HCT-CI scores of 0, 1, 2, and ≥3, respectively (P = .01). The corresponding probability of OS at 2 years was 72%, 67%, 51%, and 48%, respectively (P < .01). On multivariate analyses adjusted for recipient age, disease risk, donor source, and conditioning regimen intensity, the relative risks for NRM for HCT-CI scores of 1, 2, and ≥3 (compared to a score of 0) were 2.0 (95% confidence intervals, 0.8–5.3), 2.6 (1.0–6.7), and 3.2 (1.4-7.4), respectively. The risks for overall mortality were 1.2 (0.6-2.1), 2.0 (1.1-3.4), and 2.1 (1.3-3.3), respectively. In subgroup analyses, the HCT-CI score did not consistently predict NRM and OS among different donor sources and conditioning regimens. The HCT-CI, although a useful tool for capturing pretransplant comorbidity and risk-assessment, needs to be further validated prior to adopting it for routine clinical use. [Copyright &y& Elsevier]

Abstract: Common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. They are biologically significant due to their role in a number of genomic alterations that are frequently found in many different types of cancer. The first CFS to be cloned and characterized was FRA3B, the most active CFS in the human genome. Instability within this region extends for over 4.0Mbs and contained within the center of this CFS is the FHIT gene spanning 1.5Mbs of genomic sequence. There are frequent deletions and other alterations within this gene in multiple tumor types and the protein encoded by this gene has been demonstrated to function as a tumor suppressor in vitro and in vivo. In spite of this, FHIT is not a traditional mutational target in cancer and many tumors have large intronic deletions without any exonic alterations. There are several other very large genes found within CFS regions including Parkin (1.37Mbs in FRA6E), GRID2 (1.47Mbs within 4q22.3), and WWOX (1.11Mbs within FRA16D). These genes also appear to function as tumor suppressors but are not traditional mutational targets in cancer. Each of these genes is highly conserved and the regions spanning them are CFSs in mice. We have now examined lists of the largest human genes and found forty that span over one megabase. Many of these are derived from chromosomal bands containing CFSs. BACs within these genes are being utilized as FISH probes to determine if these are also CFS genes. Thus far we have identified the following as CFS genes: CNTNAP2 (2.3Mbs in FRA7I), DMD (2.09Mbs in FRAXC), LRP1B (1.9Mbs in FRA2F), CTNNA3 (1.78Mbs in FRA10D), DAB1 (1.55Mbs in FRA1B), and IL1RAPL1 (1.36Mbs in FRAXC). Although, these genes are also not traditional mutational targets in cancer they do exhibit loss of expression in multiple tumor types suggesting that they may also function as tumor suppressors. Many of the large CFS genes are involved in neurological development. Parkin is mutated in autosomal recessive juvenile Parkinsonism and deletions in mice are associated with the mouse mutant Quaking (viable). Spontaneous mouse mutants in GRID2 and DAB1 are associated with Lurcher and Reelin, respectively. In humans, alterations in IL1RAPL1 cause X-linked mental retardation and loss of WWOX is associated with Tau phosphorylation. We propose that the instability-induced alterations in these genes contribute to cancer development in a two-step process. Initial alterations will primarily occur within intronic regions, as these genes are greater than 99% intronic. These are not benign. Instead, they alter the repertoire of transcripts produced from these genes. As cancer progresses deletions will begin to encompass exons resulting in gene inactivation. These two types of alterations occurring in multiple large CFS genes may contribute significantly to the heterogeneity observed in cancer. There are also important potential linkages between normal neurological development and the development of cancer mediated by alterations in these genes. [Copyright &y& Elsevier]

Patient understanding of the radiation treatment process, including anticipated logistics, side effects, and outcomes of treatment, is often limited. We lack data on optimal radiation oncology provider approaches to patient education. Our objective was to assess patient education practices and preferences of interdisciplinary radiation oncology providers to inform recommendations for providers and institutions. An anonymous, web-based survey was developed in collaboration with the Radiation Oncology Education Collaborative Study Group (ROECSG) Patient Education Working Group and distributed to all members of the ROECSG listserv via Qualtrics in October 2022. The survey contained 17 items: 13 multiple choice and 4 open-ended. Descriptive statistics summarized survey responses. Thematic analysis was used to analyze qualitative responses. 123 ROECSG members completed the survey (31% response rate). Most respondents were radiation oncology attendings (64%), worked in an academic/university affiliated setting (86%), and were in North America (82%). Aside from verbal communication, the most common educational approaches used were institution-specific materials (61%) and electronic health system-generated materials (38%). 41% of respondents highlighted that their patient education practices differed according to whether assessments were in-person or virtual; printed handouts versus Internet images/videos were used most often for in-person versus virtual visits, respectively. A majority (86%) stated that their institution utilized disease site-specific patient education materials. Over half (58%) reported that their institution had non-English materials available. Review of patient education materials by staff (53%) was the most common assessment method, though 19% reported no assessment of materials at their institution. Among institutions with an assessment process, respondents were largely "unsure" (56%) of the assessment frequency. On qualitative analysis, a central theme surrounding challenges for providing patient education was lack of time for providers to deliver and patients to review materials provided. Respondents also identified administrative roadblocks such as inadequate leadership support, training, and funding for developing education materials. Key strategies for successful patient education included using visual/multimedia materials, personalizing content for patients/caregivers (e.g., based on their learning styles, preferences, and language), reiterating information at multiple timepoints by multiple team members, and utilizing active education (e.g., teach-back method, encouraging notetaking, involving caregivers). Many radiation oncology providers use institution-specific and disease site-specific materials to provide patient education, with personalization of content for patients differing for in-person versus virtual environments. Increased adoption of visual/multimedia materials and partnerships with organizational leadership may facilitate access to and contribute towards the development of high-quality, tailored patient education resources. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Palladium-103 (103Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after 103Pd monotherapy. Methods and Materials: Fifty men with intermediate-risk prostate cancer underwent 103Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests. Results: Postimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI (p = 0.019 for V 100 and p < 0.01 for D 90). Prostate volumes were smaller on the CT/MRI scans (p < 0.00001). The base sector contributed the greatest difference, with doses based on CT/MRI lower than those based on CT (p < 0.01 for V 100 and D 90). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples. Conclusions: CT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after 103Pd monotherapy implants. [Copyright &y& Elsevier]

Abstract: Background and purpose: Improved radiation delivery and planning has allowed, in some instances, for the retreatment of thoracic tumors. We investigated the dose limits of the aorta wherein grade 5 aortic toxicity was observed after reirradiation of lung tumors. Material and methods: In a retrospective analysis, 35 patients were identified, between 1993 and 2008, who received two rounds of external beam irradiation that included the aorta in the radiation fields of both the initial and retreatment plans. We determined the maximum cumulative dose to 1 cm3 of the aorta (the composite dose) for each patient, normalized these doses to 1.8Gy/fraction, and corrected them for long-term tissue recovery between treatments (NIDR ). Results: The median time interval between treatments was 30months (range, 1–185months). The median follow-up of patients alive at analysis was 42months (range, 14–70months). Two of the 35 patients (6%) were identified as having grade 5 aortic toxicities. There was a 25% rate of grade 5 aortic toxicity for patients receiving composite doses ⩾120.0Gy (vs. 0% for patients receiving <120.0Gy) (P =0.047). Conclusions: Grade 5 aortic toxicities were observed with composite doses ⩾120.0Gy (NIDR ⩾90.0Gy) to 1cm3 of the aorta. [Copyright &y& Elsevier]