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.
•NBTXR3 is a radioenhancer composed of functionalized hafnium oxide nanoparticles.•This report describes the first patient with pancreatic cancer treated with NBTXR3.•First demonstration of local ...endoscopic delivery of NBTXR3 to a deep visceral tumor.•Multidisciplinary care critical for treating pancreatic cancer patients with NBTXR3.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the leading causes of cancer-related deaths in the world. For patients with PDAC who are not eligible for surgery, radiation therapy improves local disease control, yet safely delivering therapeutic doses of radiation remains challenging due to off-target toxicities in surrounding normal tissues. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide crystalline nanoparticles, has recently shown clinical activity in soft tissue sarcoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, and advanced solid malignancies with lung or liver metastases. Here we report the first patient with pancreatic cancer treated with NBTXR3.
A 66-year-old male with unresectable locally advanced PDAC was enrolled on our clinical trial to receive NBTXR3 activated by radiation therapy. Local endoscopic delivery of NBTXR3 was followed by intensity modulated radiation therapy (IMRT). Follow-up assessment consisted of physical examination, laboratory studies including CA19-9, and CT of the chest, abdomen, and pelvis.
The patient received NBTXR3 by local endoscopic delivery without any acute adverse events. Radiation treatment consisted of 45 Gy in 15 daily fractions using IMRT. The patient began radiation twelve days after NBTXR3 injection. Daily CT-on-rails imaging demonstrated retention of NBTXR3 within the tumor for the duration of treatment. At initial follow-up evaluation, the lesion remained radiographically stable and the patient did not demonstrate treatment-related toxicity.
This report demonstrates initial feasibility of local endoscopic delivery of NBTXR3 activated by radiation therapy for patients with pancreatic cancer who are not eligible for surgery.
Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines ...and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.
Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.
60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p
0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa.
(p=0.028),
(p=0.0295)
(p=0.034)
(p=0.029) were enriched in anal cancer specimens when compared to HR normal.
Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal
,
, and
abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.
Despite the increasing utilization of sphincter and/or organ-preservation treatment strategies, many patients with low-lying rectal cancers require abdominoperineal resection (APR), leading to ...permanent ostomy. Here, we aimed to characterize overall, sexual-, and bladder-related patient-reported quality of life (QOL) for individuals with low rectal cancers. We additionally aimed to explore potential differences in patient-reported outcomes between patients with and without a permanent ostomy.
We distributed a comprehensive survey consisting of various patient-reported outcome measures, including the FACT-G7 survey, ICIQ MLUTS/FLUTS, IIEF-5/FSFI, and a specific questionnaire for ostomy patients. Descriptive statistics and univariate comparisons were used to compared demographics, treatments, and QOL scores between patients with and without a permanent ostomy.
Of the 204 patients contacted, 124 (60.8%) returned completed surveys; 22 (18%) of these had a permanent ostomy at the time of survey completion. There were 25 patients with low rectal tumors (≤5 cm from the anal verge) who did not have an ostomy at the time of survey completion, of whom 13 (52%) were managed with a non-operative approach. FACTG7 scores were numerically lower (median 20.5 vs. 22,
= 0.12) for individuals with an ostomy. Sexual function measures IIEF and FSFI were also lower (worse) for individuals with ostomies, but the results were not significantly different. MLUTS and FLUTS scores were both higher in individuals with ostomies (median 11 vs. 5,
= 0.06 and median 17 vs. 5.5,
= 0.01, respectively), suggesting worse urinary function. Patient-reported ostomy-specific challenges included gastrointestinal concerns (e.g., gas, odor, diarrhea) that may affect social activities and personal relationships.
Despite a limited sample size, this study provides patient-centered, patient-derived data regarding long-term QOL in validated measures following treatment of low rectal cancers. Ostomies may have multidimensional negative impacts on QOL, and these findings warrant continued investigation in a prospective setting. These results may be used to inform shared decision making for individuals with low rectal cancers in both the settings of organ preservation and permanent ostomy.
The aim of this study was to examine the experiences of radiation oncology applicants and to evaluate the prevalence of behaviors that may be in conflict with established ethical standards.
An ...anonymous survey was sent to all 2013 applicants to a single domestic radiation oncology residency program through the National Resident Matching Program (NRMP). Questions included demographics, survey of observed behaviors, and opinions regarding the interview and matching process. Descriptive statistics were presented. Characteristics and experiences of respondents who matched were compared with those who did not match.
Questionnaires were returned by 87 of 171 applicants for a 51% response rate. Eighty-two questionnaires were complete and included for analysis. Seventy-eight respondents (95.1%) reported being asked at least 1 question in conflict with the NRMP code of conduct. When asked where else they were interviewing, 64% stated that this query made them uncomfortable. Forty-five respondents (54.9%) reported unsolicited post-interview contact by programs, and 31 (37.8%) felt pressured to give assurances. Fifteen respondents (18.3%) reported being told their rank position or that they were "ranked to match" prior to Match day, with 27% of those individuals indicating this information influenced how they ranked programs. Half of respondents felt applicants often made dishonest or misleading assurances, one-third reported that they believed their desired match outcome could be improved by deliberately misleading programs, and more than two-thirds felt their rank position could be improved by having faculty from their home institutions directly contact programs on their behalf.
Radiation oncology applicants report a high prevalence of behaviors in conflict with written NRMP policies. Post-interview communication should be discouraged in order to enhance fairness and support the professional development of future radiation oncologists.
Purpose
To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following ...radiotherapy.
Methods
This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015–2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan–Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors.
Results
A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (
n
= 33), ablation (
n
= 11), selective internal radiotherapy (
n
= 7), and external beam radiotherapy (
n
= 8). At a median follow-up of 15.1 months (range, 3.4–54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child–Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months;
p
= 0.03).
Conclusions
Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.
Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction ...chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.
Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant.
Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR.
We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.
The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of ...available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.
Background
Single‐institution studies have shown the oncologic benefit of ablative liver radiotherapy (A‐RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of ...A‐RT across the United States and its associated outcomes are unknown.
Methods
We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A‐RT for receipt of biologically effective doses (BED10) ≥ 80.5 Gy and conventional RT (Conv‐RT) for lower doses. Associations with A‐RT use and overall survival were identified using logistic and Cox regressions, respectively.
Results
Of 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv‐RT (median BED10, 53 Gy; median, 20 fractions) and 27% A‐RT (median BED10, 100 Gy; median, 5 fractions). Use of A‐RT increased from 5% in 2004 to 48% in 2018 (Ptrend < .001). With a median follow‐up of 52.3 months, median survival estimates for Conv‐RT and A‐RT were 12.8 and 23.7 months (P < .001), respectively. On multivariable analysis, stage III and IV disease correlated with a higher risk of death, whereas chemotherapy and A‐RT correlated with a lower risk.
Conclusions
Although A‐RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A‐RT is associated with longer survival versus Conv‐RT.
Lay Summary
Bile duct cancer is a rare, deadly disease that often presents at advanced stages.
Single‐institution retrospective studies have demonstrated that use of high‐dose radiotherapy may be associated with longer survival, but larger studies have not been conducted.
We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high‐dose radiotherapy lived longer than those who received lower doses.
Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes.
In this analysis of 27,571 patients in the United States with unresected intrahepatic cholangiocarcinoma diagnosed between 2004 and 2018, use of liver radiotherapy remained constant despite growing evidence supporting that its use is associated with longer survival. Among patients who received liver radiotherapy, higher doses have been increasingly used; patients who received higher doses had longer survival than those receiving lower doses (median 23.7 vs 12.8 months, respectively).
A lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. We sought to gain a ...nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URMs) in these influential positions.
From March to June 2016, we conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was used to invite all chairs who were women (n = 13) or URMs (n = 3) and 11 male chairs who were not URMs. Multiple analysts coded the verbatim transcripts.
Five themes were identified: (1) commitment to DEI promotes quality health care and innovation; (2) gaps remain despite some progress with promoting diversity in RO; (3) women and URM faculty continue to experience challenges in various career domains; (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race; and (5) expansion of the career pipeline is needed.
The chairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school.
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