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Purpose: Journal impact factor (IF) is often used to measure research quality and importance. We assessed trial factors associated with the publication of cancer trials in journals with higher IF and publications receiving higher citations. Materials and Methods: Cancer-specific phase III RCTs were screened through https://clinicaltrials.gov. We identified trials with published primary endpoints, along with their corresponding journal IF and relative citation ratio (RCR). Results: Seven-hundred ninety manuscripts were included in our study. Trials that met their primary endpoint were more commonly published in journals with higher IF (Median IF: positive trials 35.4 vs. negative trials 26.3, P < 0.001). Furthermore, trials that led to subsequent FDA drug approvals were also published in journals with higher IF (Median IF: 59.1 vs. 26.3 in trials not leading to FDA approvals, P < 0.001). When analyzing RCR, trial positivity (meeting primary endpoint) was not associated with increased citations on multivariable analysis (P = 0.56). Lastly, publications of trials leading to FDA approvals (P < 0.001), and publications of trials in journals with higher IF (P < 0.001) were associated with increased RCR. Conclusions: Positive trials are commonly published in journals with high IF, but do not necessarily lead to increased citations. Moreover, trials published in journals with higher IF are more likely to receive increased citations.

In this review, we present the context of older adult (OA) cancer patients within the broader cancer population, including cancer burdens and trial representation. We first describe the proportion of older adults in clinical trials, with studies showing strong evidence that the proportion of OA in cancer trials is much less than the proportion of OA in the overall cancer population. We highlight the lack of generalizability that can lead to challenges in treatment decisions for OA as well as concerns regarding health inequity. We then discuss barriers to OA enrollment related to trial structure and design, physician perspective, and patient and/or caregiver perspective. We expand on this further by outlining these barriers throughout the process of trial design, patient enrollment/trial implementation, and data analysis in post-market settings. We summarize guidelines from national societies, regulatory agencies, and other institutional bodies, then present a compilation of on-the-ground actionable recommendations to address the challenges of clinical trial design, focusing on geriatric assessments and OA-specific trials. We conclude by providing an outline for future directions, noting specifically the potential impact that radiotherapy and radiation oncology may have on clinical trials related to OA patients.

We aimed to investigate whether implicit linguistic biases exist in letters of recommendation (LORs) for applicants to radiation oncology (RO) residency. LORs (n = 487) written for applicants (n = 125) invited to interview at a single RO residency program from the 2015 to 2019 application cycles were included for analysis. Linguistic Inquiry and Word Count (LIWC) software was used to evaluate LORs for length and a dictionary of predetermined themes. Language was evaluated for gender bias using a publicly available gender bias calculator. Non-parametric tests were used to compare linguistic domain scores. The median number of the LORs per applicant was 4 (range 3–5). No significant differences by applicant gender were detected in LIWC score domains or gender bias calculator (P > 0.05). However, LORs for applicants from racial/ethnic backgrounds underrepresented in medicine were less likely to include standout descriptors (P = 0.008). Male writers were less likely to describe applicant characteristics related to patient care (P < 0.0001) and agentic personality (P = 0.006). LORs written by RO were shorter (P < 0.0001) and included fewer standout descriptors (P = 0.014) but were also more likely to include statements regarding applicant desirability (P = 0.045) and research (P = 0.008). While language was globally male-biased, assistant professors were less likely than associate professors (P = 0.0064) and full professors (P = 0.023) to use male-biased language. Significant linguistic differences were observed in RO residency LORs, suggesting that implicit biases related to both applicants and letter writers may exist. Recognition, and ideally eradication, of such biases are crucial for fair and equitable evaluation of a diverse applicant pool of RO residency candidates. Electronic supplementary material The online version contains supplementary material available at 10.1007/s13187-020-01907-x.

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

Purpose:Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with ten or more brain metastases (BM). However, the clinical and dosimetric consequences of this practice are not well established.Methods: We performed a single institution, retrospective analysis of 30 patients who received GK SRS for ten or more BM in one session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. Results: Our cohort had a median number of 13 treated lesions (range 10 to 26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70 to 3.8 Gy). Mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r=0.23, p=0.21), but was closely associated with tumor volume (Pearson r=0.95, pConclusion: The mean dose to the whole brain in patients treated with GK SRS for 10 or more BM remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent WBRT.

Background Little is known about the readability and utility of patient education materials for stereotactic radiosurgery (SRS). Therefore, the goal of this investigation was to evaluate such materials from high-performing neurosurgery hospitals and professional societies through an analysis of readability and educational content. Methods In this cross-cross sectional study, 61 websites associated with the top 50 neurosurgery and neurology hospitals according to U.S. News & World Report (USNWR) and 11 predetermined professional medical societies were queried. Identified SRS education materials were analyzed by 6 readability indices. Educational content was assessed by 10 criteria based on surveys of patients’ perspectives about SRS. Results Fifty-four materials were identified from the target population (45 from USNWR hospital websites and 9 from professional society websites). Mean readability of materials ranged from 11.7 to 15.3 grade level, far more difficult than national recommendations of sixth and eighth grade. Materials were found to have deficiencies in educational content. Compared with high-performing hospitals, materials from websites of professional societies were longer (P = .002), and more likely to discuss risks and benefits specific to SRS (P = .008), alternative treatment options (P = .05) and expected outcomes or postprocedure descriptions (P = .004). Hospital materials were also more likely to favor brand-specific terminology (eg, GammaKnife) over generic terminology (eg, radiosurgery; P = .019). Conclusion Publicly available online patient educational materials for SRS are written at reading levels above national recommendations. Furthermore, many lack information identified as important by patients. Reevaluation and improvement of online SRS educational materials on a national scale are warranted.

BACKGROUND: As exemplified in patients with adenoid cystic carcinoma (ACC), metastatic salivary gland cancers display heterogenous behavior. Although anatomic site of metastasis has been suggested to be prognostic for survival in this population, this is not adequately characterized in the current literature. METHODS: Using the National Cancer Database (NCDB), patients with newly diagnosed metastatic salivary gland cancers with distant metastasis to a single organ were identified. RESULTS: Eight hundred and fifty-eight patients (n = 284 bone-only, n = 322 lung-only, n = 252 other-site-only) were identified. Anatomic site of distant metastasis was not associated with survival in the cohort as a whole; however, on pre-planned subgroup analysis, lung-only metastasis, relative to bone-only metastasis, was the only factor associated with improved survival in patients with ACC (HR: 0.52, 95%CI: 0.30-0.93, p = 0.029). CONCLUSIONS: Anatomic site of metastasis is strongly associated with survival in patients with metastatic ACC and should be considered in future studies aiming to optimize therapy in this population.

Comprehensive patient education is necessary for shared decision-making. While patient–provider conversations primarily drive patient education, patients also use published materials to enhance their understanding. In this investigation, we evaluated the readability of 2585 patient education materials published in high-impact medical journals from 1998 to 2018 and compared our findings to readability recommendations from national groups. For all materials, mean readability grade levels ranged from 11.2 to 13.8 by various metrics. Fifty-four (2.1%) materials met the American Medical Association recommendation of sixth grade reading level, and 215 (8.2%) met the National Institutes of Health recommendation of eighth grade level. When stratified by journal and material type, general medical education materials from Annals of Internal Medicine were the most readable ( P < .001), with 79.8% meeting the eighth grade level. Readability did not differ significantly over time. Efforts to standardize publication practice with the incorporation of readability evaluation during the review process may improve patients’ understanding of their disease processes and treatment options.

OBJECTIVES Our understanding of odontogenic cancers is limited primarily to case studies given the rarity of these head and neck neoplasms. Using the National Cancer Database, we report the treatment patterns and survival outcomes for one of the largest cohorts of patients with odontogenic cancers. METHODS Patients with odontogenic tumors who did not have metastatic disease and received at least part of their care at the reporting facility were included. Patient and treatment variables were assessed using logistic regression. Survival was assessed using Cox proportional hazard models. RESULTS We identified 437 patients with odontogenic cancers, the majority of which had malignant ameloblastoma (n = 203) or odontogenic carcinoma (n = 217). Median follow-up was 44.8 months. On multivariate analysis, improved survival was associated with age

Purpose Although mentorship is described extensively in academic medical literature, there are few descriptions of mentorship specific to radiation oncology. The goal of the current study was to investigate the state of mentorship in radiation oncology through a scoping review of the literature. Methods and Materials A search protocol was defined according to Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Predefined search terms and medical subject headings were used to search PubMed for English language articles published after January 1, 1990, on mentorship in radiation oncology. Additionally, in-press articles from major radiation oncology and medical education journals were searched. Three reviewers determined article eligibility. Included articles were classified based on predefined evaluation criteria. Results Fourteen publications from 2008 to 2019 met inclusion criteria. The most commonly described form of mentorship was the dyad (64.3%), followed by team (14.3%) and peer (7.1%); 2 articles did not specify mentorship type (14.3%). The most commonly mentored participants were residents (35.7%), followed by medical students (35.7%) and attendings (21.4%); 1 study included participants of all levels (7.1%). Thirteen studies (92.9%) identified an experimental study design, most of which were cross-sectional (42.9%), followed by cohort studies (28.6%) and before/after (21.4%). Median sample size, reported in 12 of 13 experimental studies, was 132 (coefficient of variation, 1.06). Although outcomes varied widely, the majority described successful implementation of mentorship initiatives with high levels of participant satisfaction. Conclusions Although few initiatives are currently reported, the present study suggests that these initiatives are successful in promoting career development and increasing professional satisfaction. The interventions overwhelmingly described mentorship dyads; other forms of mentorship are either less common or understudied. Limitations included interventions not being evaluated in a controlled setting, and many were assessed using surveys with low response rates. This review highlights rich opportunities for future scholarship to develop, evaluate, and disseminate radiation oncology mentorship initiatives.

Purpose/objectives Three‐dimensional (3D) printing is recognized as an effective clinical and educational tool in procedurally intensive specialties. However, it has a nascent role in radiation oncology. The goal of this investigation is to clarify the extent to which 3D printing applications are currently being used in radiation oncology through a systematic review of the literature. Materials/methods A search protocol was defined according to preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. Included articles were evaluated using parameters of interest including: year and country of publication, experimental design, sample size for clinical studies, radiation oncology topic, reported outcomes, and implementation barriers or safety concerns. Results One hundred and three publications from 2012 to 2019 met inclusion criteria. The most commonly described 3D printing applications included quality assurance phantoms (26%), brachytherapy applicators (20%), bolus (17%), preclinical animal irradiation (10%), compensators (7%), and immobilization devices (5%). Most studies were preclinical feasibility studies (63%), with few clinical investigations such as case reports or series (13%) or cohort studies (11%). The most common applications evaluated within clinical settings included brachytherapy applicators (44%) and bolus (28%). Sample sizes for clinical investigations were small (median 10, range 1–42). A minority of articles described basic or translational research (11%) and workflow or cost evaluation studies (3%). The number of articles increased over time (P

Purpose Simulation-based medical education (SBME) is gaining prominence as a tool to meet Accreditation Council for Graduate Medical Education–mandated competency-based assessment educational goals. SBME is used in radiation oncology, although the type and extent are not clear. This study reports a systematic literature review designed to clarify the type and extent of radiation oncology SBME. Methods and Materials The systematic review focused on radiation oncology SBME literature. The methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were identified according to the PICOS (population, intervention, comparison, outcome, and setting) framework. The population included undergraduate, graduate, and continuing medical education learners. Studies were limited to English-language studies published on or after January 1, 1990, in peer-reviewed journals. PubMed, MedEdPORTAL, and in-press articles were searched. The PubMed search was conducted using predefined search terms. References and similar articles were examined. Medical Subject Headings terms in selected articles were reviewed to ensure relevant terms were included. Results Fifty-four SBME publications met the inclusion criteria. Only 9 of 54 studies (17%) self-identified as SBME. SBME types included screen-based simulators (56%), simulated environments (13%), virtual reality and haptic systems (13%), simulated patients (11%), part-task trainers (6%), and computer-based systems with mannequins (2%). A variety of radiation oncology skill sets were addressed, including contouring (54%), treatment planning (20%), clinical decision making (17%), anatomy and/or radiology (13%), radiation biology and/or physics (13%), communication skills and/or patient education (13%), brachytherapy (13%), and immobilization (11%). A target learning population was defined in 47 studies, including residents (53%), attending physicians (36%), medical students (21%), medical physicists (11%), radiation therapists (9%), nurses (6%), administrative staff (4%), and dosimetrists (4%). Learner feedback was reported in 32 studies. Conclusions Overall, this systematic literature review provides context and guidance for future radiation oncology SBME development. Appropriately framing SBME reports in the radiation oncology literature will facilitate development, implementation, and evaluation of SBME interventions. SBME resources should be centralized to facilitate dissemination and share resources.

This cross-sectional study evaluates the gender distribution among chief executives and senior leaders at US health care organizations.

Early stage glottic cancer has traditionally been treated with 3D conformal radiotherapy (3DCRT). However, intensity-modulated radiotherapy (IMRT) has been recently adopted as an alternative to decrease toxicity. Here, we compared the usage and outcomes of IMRT and 3DCRT for patients with early stage squamous cell carcinoma (SCC) of the glottic larynx. Using the National Cancer Database, we identified patients with Stage I&ndash, II SCC of the glottis who received 55&ndash, 75 Gy using IMRT (n = 1623) or 3DCRT (n = 2696). Median follow up was 42 months with a 5-year overall survival (OS) of 72%. Using a nominal logistic regression, race, ethnicity, year of diagnosis and fraction size were associated with the receipt of IMRT (p &lt, 0.05). Using Kaplan&ndash, Meier methods and Cox proportional hazards models as well as a propensity matched cohort, there was no difference in OS for patients who received IMRT versus 3DCRT (hazard ratio (HR), 1.08, 95% confidence interval (95% CI), 0.93&ndash, 1.26, p = 0.302). However, there was a survival benefit for patients receiving slight hypofractionation as compared to conventional fractionation (HR, 0.78, 95% CI, 0.69&ndash, 0.92, p = 0.003). IMRT was associated with similar survival as 3DCRT, supporting the implementation of this potentially less toxic modality without compromising survival.

BACKGROUND This retrospective study evaluated the relationship between histologic subtype and treatment outcomes following SRS for the treatment of multiple brain metastases (MBM). METHODS We analyzed patients with MBM, defined here as >= 3 lesions, treated with SRS at our institution. Primary histologies examined were NSCLC, breast, and melanoma. Patients were categorized according to histology-specific subtypes (NSCLC-EGFR, ALK, KRAS, PD-L1%; breast-HER2, ER, PR; melanoma-BRAF). The primary outcome was local control (defined by RANO-BM) and secondary outcomes included intracranial progression-free survival (iPFS) and overall survival (OS). RESULTS 141 patients met inclusion criteria (66 NSCLC, 61 breast, and 14 melanoma). HER2+ and BRAF V600E+ lesions had increased rates of local control following SRS (P=0.0048 and P=0.0256, respectively) compared to other breast/melanoma subtypes. EGFR mutation was not associated with increased local control with SRS (71 vs 74%), but increased iPFS (P=0.0031). On multivariable analysis, EGFR+ was independently associated with a decreased time-dependent risk of death (P=0.011). The use of progressively newer generations of EGFR-directed therapies was associated with stepwise decreasing risk of intracranial progression and death. HER2+ disease had improved iPFS and OS (P=0.0058 and P< 0.0001, respectively; it was not an independent risk factor for progression or death; however, the use of HER2-directed antibodies was associated with decreased risk of death (p=0.036). The use of tyrosine kinase inhibitors (i.e. lapatanib) was not associated with improvements, although this was a small subset. CONCLUSIONS Some histologic subtypes appear to have better control with SRS, with HER2+ breast cancer and BRAF V600E+ melanoma associated with improved outcomes – this requires further validation; a volumetric analysis is pending. This the protective effect of EGFR mutation appears to be partly related to use of EGFR inhibitors, with the use of newer-generation therapies leading to improved outcomes; although local control with SRS remains excellent regardless of the mutation.

Signet-ring cell carcinoma (SRCC) is a subtype of adenocarcinoma characterized histologically by cells with abundant intracellular mucin production, creating a distinctive “signet-ring” appearance. SRCC typically arises in tissues of the gastrointestinal tract. In the breast, SRCC is a rare subtype of invasive lobular carcinoma defined by the presence of signet-ring cells. Mammary SRCC has unique patterns of metastatic spread compared to more common breast cancers, more often spreading viscerally to involve the serosal surfaces of stomach, urinary tract, and spleen. We report a case of metastatic mammary SRCC presenting in the stomach, thereby mimicking primary gastric SRCC. Recognition of this unusual presentation is critical as treatments for these malignancies are vastly different; misdiagnosis could lead to significant morbidity and mortality for patients.

PURPOSE Radiotherapy (RT) is an essential component in the adjuvant treatment of glioblastoma (GBM); however, despite an initial benefit in tumor control, recurrence is nearly universal. The inflammasome is a multimeric cytosolic complex that has been shown to be activated in immune cells following RT. We investigated the relationship of inflammasome activation and disease progression after RT in GBM. METHODS We performed survival analysis for patients with recurrent GBM using the TCGA dataset, stratifying according to expression of inflammasome pathway molecules Caspase 1 (CASP1), IL-1β, and NLRP3. IL-1β expression and colocalization with CD11b+ myeloid cells were analyzed at different time points following RT in a murine glioma GL261 model. We detected the secreted IL-1β, CASP1 activity, and NLRP3 expression in both tumor and infiltrating immune cells, and the downstream effects of their interplay, including cellular apoptosis, proliferation, and viability. RESULTS High expression of CASP1, IL-1β, and NLRP3 are associated with poor survival in recurrent GBM. In a mouse model, recurrent tumors after treatment with RT display higher levels of the inflammasome effector molecule IL-1β, which colocalizes with infiltrating CD11b+ myeloid cells. Using a co-culture system of tumor cell and M2 macrophages, we found that RT enhances inflammasome activation in both cell types, and this interaction restores the proliferative capacity of surviving tumor cells following treatment. RT induces the inflammasome pathway activation in the setting of an associated immune microenvironment rich in tumor-associated macrophages and myeloid-derived suppressor cells (TAM/MDSCs) and not in tumor cells alone. CONCLUSIONS Inhibition of the oncoprogressive crosstalk between GBM tumor cells and M2 macrophages, possibly through disruption of the inflammasome pathway, might be a potential therapeutic strategy with RT.

Importance Appropriate informed consent processes are crucial to preservation of patient autonomy and shared decision making. Although half of patients with cancer receive radiotherapy, it is unknown whether current consent practices are comprehensible for patients. Objective To characterize use, specificity, and readability of clinical informed consent forms for radiotherapy, hypothesizing that forms would be higher than the recommended sixth- to eighth-grade readability level. Design, Setting, and Participants This nationwide cross-sectional survey study and readability analysis was conducted from 2016 to 2018 and included 89 academic radiation oncology departments that were part of the 2016 Electronic Residency Application Service. Department leaders (clinical directors, chairs, and personal contacts of study authors) at academic radiation oncology departments were contacted via email. Main Outcomes and Measures Readability levels were measured by 7 validated readability indices, including the Ford, Caylor, Sticht (FORCAST) index for nonnarrative texts. Difficult words were identified usingThe Living Word Vocabulary, which describes the readability grade levels of 40 000 common words. Results Of 89 departments, 67 (75%) responded to questions and 57 (64%) provided 113 forms for analysis. Departments providing forms did not differ substantially from others in terms of region, residency size, research output, rural vs urban location, or public vs private institution status. All departments obtained patient written informed consent before radiotherapy; 38 (57%) used body site–specific forms. Using the most conservative (low-score) estimate, mean form readability ranged from grade level 10.6 to 14.2. By 7 distinct indices, only 9 (8%) of 113 forms met the recommended eighth-grade readability level, and 4 (4%) forms met a sixth-grade level. Not a single form met either recommendation based on the FORCAST index. Forms used an average of 7.2 difficult words. Body site–specific forms had considerably better readability than general consent forms. Conclusions and Relevance This nationwide study of informed consent practices for cancer treatment with radiotherapy demonstrates that while all US academic radiotherapy departments use written consent forms, it is rare for templates to meet the recommended readability levels for patient materials. These data suggest the need for reevaluation and modification of the approach to radiotherapy consent, ideally with guidance and templates designed by national professional organizations.