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PURPOSE:To assess the optimal structure of an introductory curriculum (IC) for radiation oncology residents, including the perceived utility of a 2-day off-site "boot camp," and evaluate the success of a pilot introductory radiation oncology curriculum (IROC) based on these initial data. METHODS AND MATERIALS:In the first phase, anonymous, web-based surveys were sent to US radiation oncology program directors and residents. Likert-type scores (1, not at all; 5, extremely) are reported as the median and interquartile range. Using the phase 1 results, IROC was developed, piloted, and evaluated. RESULTS:Of the 89 program directors and 697 residents, 47 (53%) and 165 (24%) responded, respectively. Of the 89 program directors, 37 (79%) reported offering a formal IC. However, only 83 residents (50%) reported having a formal IC. Program directors reported resident preparation for clinical training as "moderate" (median 3, interquartile range 2-3) on entering residency and "moderate" (median 3, interquartile range 3-4) after IC completion (P = .03). However, residents only believed they were "slightly" prepared (median 2, interquartile range 1-2) on entering residency and "moderately" (median 3, interquartile range 2-3) prepared after IC completion (P

• Infants treated with proton therapy have similar disease control to their older counterparts. • Young age may not be an adverse prognostic factor if patients receive standard radiation doses. • Rhabdomyosarcoma of the nasal ala in infants may signify a distinctly poor prognosis. • Toxicity data suggest evidence of hypoplasia among survivors. In infants with rhabdomyosarcoma, young age is considered an adverse prognostic factor and treatment is often attenuated to reduce side effects. Proton therapy may improve the therapeutic ratio in these patients. We report outcomes in infants with rhabdomyosarcoma treated with proton therapy. Between 2009 and 2019, 37 infants <24 months old with non-metastatic rhabdomyosarcoma received proton therapy. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan–Meier product limit. The log-rank test assessed significance between selected prognostic factors. Toxicity was graded per CTCAEv5.0. Median follow-up was 5.1 years. Overall, 76% of patients had an unfavorable primary site. Median dose was 50.4GyRBE. At 5 years, LC, PFS, and OS rates were 83%, 78%, and 83%. On univariate analysis, 5-year LC and OS were inferior for favorable versus unfavorable disease sites (67% vs 89%, 67% vs 89%, respectively; p <.05) and 5-year OS was superior in stage 3 versus stage 1–2 disease (91% vs 69%; p =.05), owing to inclusion of nasal ala patients among stage 1. Of 9 recurrences, 7 were in-field, 4 occurring in infants with nasal ala primaries. Recategorizing nasal ala as an unfavorable site resulted in 100% 5-year LC and OS for favorable sites. Six infants experienced late grade 3 toxicity. None developed grade 4 or 5 late toxicity. Young age alone may not be an adverse prognostic factor provided infants receive local therapy similar to older children. Consideration should be given to classifying nasal ala primaries as an unfavorable site. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective outcomes review.Objective: To analyze and report long-term outcomes in a cohort of patients treated with radiotherapy (RT) for symptomatic hemangioma of a vertebral body.Summary Of Background Data: Data are scarce on the rate of tumor control with long-term (>5 yr) follow-up after RT for symptomatic hemangioma of a vertebral body.Methods: We retrospectively reviewed the medical records of patients treated at our institution between 1971 and 2008 for symptomatic hemangioma of a vertebral body, updated their follow-up, analyzed complications, and calculated the tumor control rate. Tumor control by imaging was defined as no increase in tumor size on computed tomography (CT) or magnetic resonance (MR) scan. Clinical tumor control was defined as no symptoms of recurrent tumor.Results: Ten patients were eligible for analysis. All patients had pain from visible hemangioma at the time of radiotherapy for which surgical resection or interventional radiology procedures were likely to result in high morbidity. Tumors were located in the lumbar (40%), thoracic (50%), or cervical (10%) areas of the spine. The mean radiotherapy dose delivered was 47 Gy.Mean imaging follow-up after completion of radiotherapy was 8.1 years; mean clinical follow-up was 21.2 years. The tumor control rate was 90% (9/10). One patient who may have developed a tumor recurrence had radiographic and clinical evidence of tumor progression 30 years after radiotherapy. The actuarial rate of tumor control was 100% at 5, 10, 20, and 25 years. There was no grade more than or equal to three treatment toxicities, no evidence of malignant transformation, and no evidence of second tumors in treatment area (with the possible exception of the one tumor recurrence).Conclusion: RT for symptomatic hemangioma of the spine provides long-term tumor control with a low risk of serious complications. Radiotherapy is a good option when surgery or an interventional radiology procedure is high-risk. Our preferred dose is 45 Gy at 1.8 Gy/fraction.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Purpose: The number of US fourth-year medical students applying to radiation oncology has decreased during the past few years. We conducted a survey of fourth-year medical students to examine factors that may be influencing the decision to pursue radiation oncology., Methods and Materials: An anonymous online survey was sent to medical students at 9 participating US medical schools., Results: A total of 232 medical students completed the survey. Of the 153 students who stated they were never interested in radiation oncology, 77 (50%) reported never having been exposed to the specialty as their reason for not pursuing radiation oncology. The job market was the most commonly cited factor among students who said they were once interested in but ultimately chose not to pursue radiation oncology. Conversely, the recent low pass rates for board examinations and a perception of a lack of diversity within radiation oncology had the least influence., Conclusions: Despite discussion of potential measures to address this disquieting trend, there have been minimal formal attempts to characterize and address potential causes of a decreasing interest in radiation oncology. This study's data are consistent with previous research regarding the trend of decreased medical student interest in radiation oncology and may be used as part of ongoing introspective assessment to inform future change within radiation oncology., (© 2021 The Authors.)

Given the integral role of stimulator of interferon genes (STING, TMEM173 ) in the innate immune response, its loss or impairment in cancer is thought to primarily affect antitumor immunity. Here we demonstrate a role for STING in the maintenance of cellular homeostasis through regulation of the cell cycle. Depletion of STING in human and murine cancer cells and tumors resulted in increased proliferation compared with wild-type controls. Microarray analysis revealed genes involved in cell-cycle regulation are differentially expressed in STINGko compared with WT MEFs. STING-mediated regulation of the cell cycle converged on NFκB- and p53-driven activation of p21. The absence of STING led to premature activation of cyclin-dependent kinase 1 (CDK1), early onset to S-phase and mitosis, and increased chromosome instability, which was enhanced by ionizing radiation. These results suggest a pivotal role for STING in maintaining cellular homeostasis and response to genotoxic stress. SIGNIFICANCE: These findings provide clear mechanistic understanding of the role of STING in cell-cycle regulation, which may be exploited in cancer therapy because most normal cells express STING, while many tumor cells do not. See related commentary by Gius and Zhu, p. 1295 ., (©2018 American Association for Cancer Research.)

Purpose: Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity., Methods and Materials: 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated., Results: With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity ( P  > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity., Conclusions: More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 85% of all lung cancers are non-small cell histology [non-small cell lung cancer (NSCLC)]. Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than 15% of patients survive beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN-stimulated gene expression, including an IFN-related DNA damage resistance signature, predicts for sensitivity to SAR. Importantly, tumor cell-intrinsic expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition. Mol Cancer Ther; 17(4); 732-9. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs., (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. Methods: A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status. Results: Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; P =.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43; P <.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; P =.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P <.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14). Conclusions: Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Emerging evidence indicates that ionizing radiation (IR) and chemotherapy activate Type I interferon (IFN) signaling in tumor and host cells. However, the mechanism of induction is poorly understood. We identified a novel radioprotective role for the DEXH box RNA helicase LGP2 (DHX58) through its suppression of IR-induced cytotoxic IFN-beta [1]. LGP2 inhibits activation of the RIG-I-like receptor (RLR) pathway upon binding of viral RNA to the cytoplasmic sensors RIG-I (DDX58) and MDA5 (IFIH1) and subsequent IFN signaling via the mitochondrial adaptor protein MAVS (IPS1). Here we show that MAVS is necessary for IFN-beta induction and interferon-stimulated gene expression in the response to IR. Suppression of MAVS conferred radioresistance in normal and cancer cells. Germline deletion of RIG-I, but not MDA5, protected mice from death following total body irradiation, while deletion of LGP2 accelerated the death of irradiated animals. In human tumors depletion of RIG-I conferred resistance to IR and different classes of chemotherapy drugs. Mechanistically, IR stimulated the binding of cytoplasmic RIG-I with small endogenous non-coding RNAs (sncRNAs), which triggered IFN-beta activity. We demonstrate that the small nuclear RNAs U1 and U2 translocate to the cytoplasm after IR treatment, thus stimulating the formation of RIG-I: RNA complexes and initiating downstream signaling events. Taken together, these findings suggest that the physiologic responses to radio-/chemo-therapy converge on an antiviral program in recruitment of the RLR pathway by a sncRNA-dependent activation of RIG-I which commences cytotoxic IFN signaling. Importantly, activation of interferon genes by radiation or chemotherapy is associated with a favorable outcome in patients undergoing treatment for cancer. To our knowledge, this is the first demonstration of a cell-intrinsic response to clinically relevant genotoxic treatments mediated by an RNA-dependent mechanism., Competing Interests: The authors declare no conflicts of interest.

Background: Meckel cave tumors are often asymptomatic and have a sufficiently characteristic magnetic resonance imaging/computed tomography signature that allows treatment/surveillance decisions to be made without biopsy confirmation. Radiographic diagnosis requires the surgeon to be fully aware of the plethora of unusual Meckel cave lesions that mimic benign tumors when they are malignant, inflammatory, or infectious and in need of a completely different and often timely intervention. When such a diagnosis is considered, it behooves the surgeon and benefits the patient to have a percutaneous biopsy technique available., Objective: To use our recent experience with a patient with idiopathic inflammatory sensory neuropathy and another with Meckel cave lymphoma to review the management of tumors of the Meckel cave., Methods: The technique of percutaneous biopsy of Meckel cave tumors through the foramen ovale with biopsy needles is detailed., Conclusion: Obtaining tissue biopsy percutaneously prevents patients with Meckel cave tumors best treated with nonsurgical management from undergoing open surgical resection with its concomitant morbidity.