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.
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.
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.
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.
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.
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.
The treatment of nasopharyngeal carcinoma (NPC) has traditionally included a multimodality approach including radiotherapy (RT) and systemic chemotherapy. RT has long been favored as the mainstay of ...local treatment for disease in this challenging anatomic location owing to the morbidity of extensive surgical resection in the nasopharynx. However, NPC presents a unique treatment challenge for radiation oncologists because such tumors typically involve complex anatomic structures near several critical organ structures such as the brainstem, spinal cord, temporal lobes, salivary glands, cochleae, oral cavity, mandible and optic structures. Thus, radiation is not without toxicity, and critical organs in these areas clearly benefit from the use of conformal and precise treatment delivery. The unique physical properties of proton radiotherapy (PRT) make it especially well-suited for treating tumors in this anatomically complex area and offer promising potential for acute and chronic toxicity reduction while maintaining excellent disease control.
Over the past 2 decades, major technical advances in radiation therapy planning and delivery have made it possible to deliver higher doses to select high-risk volumes. This has helped to expand the ...role of radiation therapy in the treatment of gastrointestinal malignancies. Whereas dose escalation was previously limited by the radiosensitivity of normal tissues within and adjacent to the gastrointestinal tract, advances in target delineation, patient immobilization, treatment planning, and image-guided treatment delivery have greatly improved the therapeutic ratio. More conformal radiation modalities can offer further dose optimization to target volumes while sparing normal tissue from toxicity.
To quantify and determine the relationship between oncology departmental/division heads and private industry vis-à-vis potential financial conflict of interests (FCOIs) as publicly reported by the ...Centers for Medicare and Medicaid Services Open Payments database.
We extracted the names of the chairs/chiefs in medical oncology (MO) and chairs of radiation oncology (RO) for 81 different institutions with both RO and MO training programs as reported by the Association of American Medical Colleges. For each leader, the amount of consulting fees and research payments received in 2015 was determined. Logistic modeling was used to assess associations between the 2 endpoints of receiving a consulting fee and receiving a research payment with various institution-specific and practitioner-specific variables included as covariates: specialty, sex, National Cancer Institute designation, PhD status, and geographic region.
The majority of leaders in MO were reported to have received consulting fees or research payments (69.5%) compared with a minority of RO chairs (27.2%). Among those receiving payments, the average (range) consulting fee was $13,413 ($200-$70,423) for MO leaders and $6463 ($837-$16,205) for RO chairs; the average research payment for MO leaders receiving payments was $240,446 ($156-$1,234,762) and $295,089 ($160-$1,219,564) for RO chairs. On multivariable regression when the endpoint was receipt of a research payment, those receiving a consulting fee (odds ratio OR: 5.34; 95% confidence interval CI: 2.22-13.65) and MO leaders (OR: 5.54; 95% CI: 2.62-12.18) were more likely to receive research payments. Examination of the receipt of consulting fees as the endpoint showed that those receiving a research payment (OR: 5.41; 95% CI: 2.23-13.99) and MO leaders (OR: 3.06; 95% CI: 1.21-8.13) were more likely to receive a consulting fee.
Leaders in academic oncology receive consulting or research payments from industry. Relationships between oncology leaders and industry can be beneficial, but guidance is needed to develop consistent institutional policies to manage FCOIs.
Abstract
Background
Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with ...patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.
Materials and Methods
A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.
Results
Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 range, 1.1-66.0 months. Median overall survival (OS) from primary diagnosis was 31.5 2.9-99.8 months and median OS from BrM diagnosis was 4.2 0.2-33.8 months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131).
Conclusion
This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.
This article reports an institutional experience with brain metastases from biliary tract cancer and provides clinical and genomic characterizations of these patients.
Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic ...outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers.
Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan-Meier method.
A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity.
Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.
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