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We sought to develop a computer-aided detection (CAD) system that optimally augments human performance, excelling especially at identifying small inconspicuous brain metastases (BMs), by training a convolutional neural network on a unique magnetic resonance imaging (MRI) data set containing subtle BMs that were not detected prospectively during routine clinical care. Patients receiving stereotactic radiosurgery (SRS) for BMs at our institution from 2016 to 2018 without prior brain-directed therapy or small cell histology were eligible. For patients who underwent 2 consecutive courses of SRS, treatment planning MRIs from their initial course were reviewed for radiographic evidence of an emerging metastasis at the same location as metastases treated in their second SRS course. If present, these previously unidentified lesions were contoured and categorized as retrospectively identified metastases (RIMs). RIMs were further subcategorized according to whether they did (+DC) or did not (-DC) meet diagnostic imaging-based criteria to definitively classify them as metastases based upon their appearance in the initial MRI alone. Prospectively identified metastases (PIMs) from these patients, and from patients who only underwent a single course of SRS, were also included. An open-source convolutional neural network architecture was adapted and trained to detect both RIMs and PIMs on thin-slice, contrast-enhanced, spoiled gradient echo MRIs. Patients were randomized into 5 groups: 4 for training/cross-validation and 1 for testing. One hundred thirty-five patients with 563 metastases, including 72 RIMS, met criteria. For the test group, CAD sensitivity was 94% for PIMs, 80% for +DC RIMs, and 79% for PIMs and +DC RIMs with diameter <3 mm, with a median of 2 false positives per patient and a Dice coefficient of 0.79. Our CAD model, trained on a novel data set and using a single common MR sequence, demonstrated high sensitivity and specificity overall, outperforming published CAD results for small metastases and RIMs – the lesion types most in need of human performance augmentation. [ABSTRACT FROM AUTHOR]

There is a need to foster future generations of radiation oncology physician scientists, but the number of radiation oncologists with sufficient education, training, and funding to make transformative discoveries is relatively small. A large number of MD/PhD graduates have entered he field of radiation oncology over the past 2 decades, but this has not led to a significant cohort of externally funded physician scientists. Because radiation oncologists leading independent research labs have the potential to make transformative discoveries that advance our field and positively affect patients with cancer, we created the Duke Radiation Oncology Research Scholar (RORS) Program. In crafting this program, we sought to eliminate barriers preventing radiation oncology trainees from becoming independent physician scientists. The RORS program integrates the existing American Board of Radiology Holman Pathway with a 2-year post-graduate medical education instructor position with 80% research effort at the same institution. We use a separate match for RORS and traditional residency pathways, which we hope will increase the diversity of our residency program. Since the inception of the RORS program, we have matched 2 trainees into our program. We encourage other radiation oncology residency programs at peer institutions to consider this training pathway as a means to foster the development of independent physician scientists and a diverse workforce in radiation oncology. [ABSTRACT FROM AUTHOR]

The spectrum hypothesis posits that there are distinct clinical states of metastatic progression. Early data suggest that aggressive treatment of more biologically indolent metastatic disease, characterized by metastases limited in number and destination organ, may offer an opportunity to alter the disease course, potentially allowing for longer survival, delay of systemic therapy, or even cure. The development of stereotactic body radiation therapy (SBRT) has opened new avenues for the treatment of oligometastatic disease. Early data support the use of SBRT for treating oligometastases in a number of organs, with promising rates of treated metastasis control and overall survival. Ongoing investigation is required to definitively establish benefit, determine the appropriate treatment regimen, refine patient selection, and incorporate SBRT with systemic therapies. [ABSTRACT FROM AUTHOR]

Objective Our purpose was to address challenges associated with single-isocenter radiosurgery for multiple intracranial targets (SIRMIT) including increased sensitivity to rotational uncertainties (resulting from distance of the targets from isocenter) as well as potential for decreased plan quality from larger multileaf collimator width > 4 cm from isocenter. Methods and materials We evaluated the effect that a 6 degrees-of-freedom couch correction had on localization uncertainty for SIRMIT using thermoplastic mask immobilization. Required setup margin was determined from rotation of the skull and mask (setup kV cone beam computed tomography relative to planning computed tomography). Intraoperational margin was determined from skull rotation within the mask (difference between pre- and posttreatment cone beam computed tomography). We also investigated 4 isocenter placement strategies: volume centroid, centroid of equally weighted points (1 per target), centroid of points weighted by inverse of volume, and Eclipse’s built-in method. Results When no 6 degrees-of-freedom couch correction is performed after initial setup, a 0.35-mm margin is required per centimeter of target-isocenter separation to account for 95% of rotational uncertainties at initial setup. This margin is reduced to 0.10 mm/cm of target-isocenter separation to account for intraoperative rotational uncertainties when the initial setup uncertainty is eliminated via image guided 6 degrees-of-freedom couch correction. Analysis of 11 multitarget plans (37 targets) showed that conformity index and gradient index improved with decreasing distance from isocenter, this trend being more pronounced for targets < 1 mL. Alternative isocenters aimed at decreasing distance of small targets improved their gradient index, but resulted in poorer dose indices for large targets. Mean distance from isocenter was smallest for the centroid of equally weighted points (4.1 ± 1.6cm vs 4.2-4.5cm). Conclusions Rotational corrections via image guidance are necessary for SIRMIT with a thermoplastic mask for immobilization. There is a clear tradeoff between dosimetric quality of small and large targets that should be considered carefully when placing the isocenter. [ABSTRACT FROM AUTHOR]

Objectives To examine the efficacy of prophylactic cranial irradiation (PCI) in elderly patients with small cell lung cancer (SCLC) (≥ 70 years of age) from a pooled analysis of four prospective trials. Materials & Methods One hundred fifty-five patients with SCLC (limited stage, LSCLC, and extensive stage, ESCLC) participated in four phase II or III trials. Ninety-one patients received PCI (30 Gy/15 or 25 Gy/10) and 64 patients did not receive PCI. Survival was compared in a landmark analysis that included only patients who had stable disease or better in response to primary therapy. Results Patients who received PCI had better survival than patients who did not receive PCI (median survival 12.0 months vs. 7.6 months, 3-year overall survival 13.2% vs. 3.1%, HR = 0.53 [95% CI 0.36–0.78], p = 0.001). On multivariate analysis of the entire cohort, the only factor that remained significant for survival was stage (ESCLC vs. LSCLC, p = 0.0072). In contrast, the multivariate analysis of patients who had ESCLC revealed that PCI was the sole factor associated with a survival advantage (HR = 0.47 [95% CI 0.24–0.93], p = 0.03). Grade 3 or higher adverse events (AEs) were significantly greater in patients who received PCI (71.4% vs. 47.5%, p = 0.0031), with non-neuro and non-heme being the specific AE categories most strongly correlated with PCI delivery. Conclusions PCI was associated with a significant improvement in survival for our entire elderly SCLC patient cohort on univariate analysis. Multivariate analysis suggested that the survival advantage remained significant in patients with ESCLC. PCI was also associated with a modest increase in grade 3 or higher AEs. [ABSTRACT FROM AUTHOR]

Summary: The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteriaare evidence-based guidelines for specific clinical conditions that are reviewed every 2years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 (131I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Methods: Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. Results: 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p =0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p =0.05).). Furthermore, exposure of larger volumes of lung to lower (median V5=70%, p =0.09, median V10=63%, p =0.07), intermediate (median V20=50, p =0.04) and high (median V60=25%, p =0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose (median 31Gy) p =0.019. Conclusion: Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation. [Copyright &y& Elsevier]

The most common treatment of pulmonary metastasis for solid tumors employs systemic chemotherapy, hormonal therapy, or biologic agents. Some series have suggested that aggressive surgical resection of pulmonary metastasis may improve patient outcomes in terms of quality of life and overall survival. Recently, data from clinical trials and retrospective series support the use of aggressive local control with high conformal dose radiotherapy (stereotactic body radiation therapy) in patients with limited metastases or oligometastases. Further evidence suggests that these patients represent a distinct clinical and biological class of patients. This review focuses on the role of ablative doses of radiotherapy in the treatment of pulmonary metastases. Specifically we discuss the rationale, treatment delivery, and local control that have led to the ongoing randomized clinical trials attempting to demonstrate a benefit over the current palliative standard of care. [Copyright &y& Elsevier]

Abstract: Purpose: Hypofractionated image guided radiation therapy (HIGRT) is increasingly used for limited metastases. Reported studies have mostly treated small volume tumors. Here, we report the toxicity and oncologic outcomes following treatment of large volume metastases. Methods and Materials: HIGRT patients treated from October 2005 to March 2010 were reviewed. Gross tumor volumes (GTV) and planning target volumes (PTV) were obtained from planning software. A metastasis was considered large volume if the treated PTV exceeded 50 cc. Patients were treated with either 10-fraction (4-5 Gy per fraction) or 3-5 fraction (8-14 Gy per fraction) regimens. Toxicity was obtained from both prospectively collected databases and retrospectively from patient charts. Results: Sixty-four patients with 93 treated lesions >50 cc were identified. The median GTV and PTV volumes were 41 and 119 cc, respectively. The median number of treated large volume lesions was 1, and a maximum of 3 large volume lesions were treated in a single patient. Primary malignancies included non–small cell lung cancer, renal cell, colorectal, breast, bladder, pituitary, small cell lung cancer, sarcoma, head-and-neck cancer, and hepatocellular cancer. Treated sites included lung (n = 33), regional lymph nodes (n = 20), bone (n = 17), adrenal (n = 9), and liver (n = 6). The most frequently used treatment regimen was 50 Gy in 5 Gy fractions. The median follow-up was 27 months for surviving patients. Treated lesion control was 78%. Low rates of acute and late grade 3 or higher toxicity were reported, with 3 and 5 patients experiencing each, respectively. Conclusions: HIGRT to large volume oligometastatic disease is tolerable and feasible with promising tumor control. Local radiation therapy should be considered in patients with large volume, limited metastatic disease. [Copyright &y& Elsevier]

Summary: Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3–4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100mg/m2 every 21days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63Gy for high-risk patients and at least 57Gy for low risk patients. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. Materials and methods: Forty-one postoperative patients with stage III–IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. Results: After a median follow-up of 72months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p =0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. Conclusions: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation. [Copyright &y& Elsevier]

Purpose: The use of induction chemotherapy (IC) for locoregionally advanced head-and-neck cancer is increasing. The response to IC often causes significant alterations in tumor volume and location and shifts in normal anatomy. Proper determination of the radiotherapy (RT) targets after IC becomes challenging, especially with the use of conformal and precision RT techniques. Therefore, a consensus conference was convened to discuss issues related to RT planning and coordination of care for patients receiving IC. Methods and Materials: Ten participants with special expertise in the various aspects of integration of IC and RT for the treatment of locoregionally advanced head-and-neck cancer, including radiation oncologists, medical oncologists, and a medical physicist, participated. The individual members were assigned topics for focused, didactic presentations. Discussion was encouraged after each presentation, and recommendations were formulated. Results: Recommendations and guidelines emerged that emphasize up-front evaluation by all members of the head-and-neck management team, high-quality baseline and postinduction planning scans with the patient in the treatment position, the use of preinduction target volumes, and the use of full-dose RT, even in the face of a complete response. Conclusion: A multidisciplinary approach is strongly encouraged. Although these recommendations were provided primarily for patients treated with IC, many of these same principles apply to concurrent chemoradiotherapy without IC. A rapid response during RT is quite common, requiring the development of two or more plans in a sizeable fraction of patients, and suggesting the need for similar guidance in the rapidly evolving area of adaptive RT. [Copyright &y& Elsevier]

Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising. [ABSTRACT FROM AUTHOR]

Purpose: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation.Methods and Materials: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n=14), cisplatin plus FHX (n=23), paclitaxel plus FHX (n=42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n=26), and irinotecan plus FHX (n=10).Results: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage.Conclusion: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials. [ABSTRACT FROM AUTHOR]

Chat Generative Pre-Trained Transformer (ChatGPT), an artificial intelligence program that uses natural language processing to generate conversational-style responses to questions or inputs, is increasingly being used by both patients and health care professionals. This study aims to evaluate the accuracy and comprehensiveness of ChatGPT in radiation oncology–related domains, including answering common patient questions, summarizing landmark clinical research studies, and providing literature reviews with specific references supporting current standard-of-care clinical practice in radiation oncology. We assessed the performance of ChatGPT version 3.5 (ChatGPT3.5) in 3 areas. We evaluated ChatGPT3.5's ability to answer 28 templated patient-centered questions applied across 9 cancer types. We then tested ChatGPT3.5's ability to summarize specific portions of 10 landmark studies in radiation oncology. Next, we used ChatGPT3.5 to identify scientific studies supporting current standard-of-care practice in clinical radiation oncology for 5 different cancer types. Each response was graded independently by 2 reviewers, with discordant grades resolved by a third reviewer. ChatGPT3.5 frequently generated inaccurate or incomplete responses. Only 39.7% of responses to patient-centered questions were considered correct and comprehensive. When summarizing landmark studies in radiation oncology, 35.0% of ChatGPT3.5′s responses were accurate and comprehensive, improving to 43.3% when provided the full text of the study. ChatGPT3.5′s ability to present a list of studies related to standard-of-care clinical practices was also unsatisfactory, with 50.6% of the provided studies fabricated. ChatGPT should not be considered a reliable radiation oncology resource for patients or providers at this time, as it frequently generates inaccurate or incomplete responses. However, natural language programming-based artificial intelligence programs are rapidly evolving, and future versions of ChatGPT or similar programs may demonstrate improved performance in this domain. [ABSTRACT FROM AUTHOR]

Purpose Bolus-tracked multiphasic contrast computed tomography (CT) is often used in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiation therapy pancreas CT simulation, and its impact on gross tumor volume (GTV) delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas stereotactic body radiation therapy (SBRT) GTVs contoured in the different contrast phases of triphasic CT simulation scans. Methods and materials Triphasic, bolus-tracked planning CT simulation scans of 10 consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial or delayed phase. GTVs were contoured on each phase by a gastrointestinal-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and 2 radiation oncologists rank-ordered the phases according to their value for the lesion-contouring task. Results Tumor-to-pancreas enhancement was on average much larger for the LA and PV than the delayed phase or early arterial phases; the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences among the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18% to 75% across all 3 phases, improving to 43% to 91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3 to 1.8 cm for all 3 phases, improving slightly to 0.1 to 1.4 cm when considering just the LA and PV phases. Conclusions For pancreas SBRT, we recommend combining the GTVs from a multiphasic CT simulation with bolus-tracking, including, at a minimum, a Boolean “OR” of the LA and PV phases. [ABSTRACT FROM AUTHOR]

Introduction In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection. Methods and materials Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed. Results Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤ 5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity. Discussion NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases. [ABSTRACT FROM AUTHOR]

Purpose: The NRG-BR001 trial is the first National Cancer Institute-sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates.Methods and Materials: The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) against OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests.Results: Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs.Conclusions: Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements. [ABSTRACT FROM AUTHOR]

Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments. [ABSTRACT FROM AUTHOR]

The Oncotype DX Genomic Prostate Score (GPS) assay has been validated as a strong prognostic indicator of adverse pathology, biochemical recurrence, distant metastasis (DM), and prostate cancer (PCa)–related death (PCD) in men with localized PCa after radical prostatectomy. However, it has yet to be tested in men undergoing external beam radiation therapy (EBRT), for whom assessing PCa progression risk could inform decisions on treatment intensity. We analyzed whether GPS results are associated with time to biochemical failure (BCF), DM, and PCD after EBRT in men with localized PCa and whether the association is modified by race. We conducted a retrospective study of men with localized PCa treated with EBRT at the VA Health Care System in Durham, NC from 2000 to 2016. Study endpoints were time to BCF per the Phoenix criteria, DM, and PCD. The association of GPS results, per 20-unit increase or dichotomous variable (0-40 vs 41-100), was evaluated with each endpoint using univariable and multivariable Cox proportional hazards models. Results were then stratified by race. A total of 238 patients (69% Black) met the eligibility criteria. Median follow-up for patients who did not experience BCF was 7.6 years. GPS results per 20-unit increase were significantly associated with BCF (hazard ratio [HR], 3.62; 95% confidence interval [CI], 2.59-5.02), DM (HR, 4.48; 95% CI, 2.75-7.38), and PCD (HR, 5.36; 95% CI, 3.06-9.76) in univariable analysis. GPS results remained significant in multivariable models adjusted for baseline clinical and pathological factors, with HRs being similar to the univariable analysis. There was no significant interaction between the GPS assay and race (P =.923). HRs for BCF were similar in Black men (HR, 3.88; 95% CI, 2.40-6.24) versus non-Black men (HR, 4.01; 95% CI, 2.42-6.45). Among men treated with EBRT, the GPS assay is a strong, independent prognostic indicator of time to BCF, DM, and PCD, and performs similarly in Black and non-Black men. [ABSTRACT FROM AUTHOR]

Purpose: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy.Methods and Materials: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model.Results: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy.Conclusions: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy. [ABSTRACT FROM AUTHOR]

Abstract: Using previous dosimetric analysis methods, we identified the volume of bowel receiving 30Gy (V 30) correlated with acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiation therapy and concurrent chemotherapy. For V 30 >450cc and⩽450cc, acute GI toxicity was 33% and 8%, respectively (p =0.003). [Copyright &y& Elsevier]

Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V10 and PBM-V20) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3–4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3–4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V5, V10, V15, and V20 were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V10, V15, and V20 (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients. [Copyright &y& Elsevier]

Purpose: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX2) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX2 in a subset of patients previously irradiated to the head and neck. Methods and materials: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX2. Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). Results: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. Conclusion: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival. [Copyright &y& Elsevier]

Purpose: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT.Methods and Materials: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only).Results: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008).Conclusions: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: Fiberoptic laryngoscopy (FOL) is a critical tool for the diagnosis, staging, assessment of treatment response, and detection of recurrence for head and neck (H&N) malignancies. No standardized recommendations exist for procedural FOL education in radiation oncology. We therefore implemented a pilot simulation workshop to train radiation oncology residents in pertinent H&N anatomy and FOL technique.Methods and Materials: A 2-phase workshop and simulation session was designed. Residents initially received a lecture on H&N anatomy and the logistics of the FOL examination. Subsequently, residents had a practical session in which they performed FOL in 2 simulated environments: a computerized FOL program and mannequin-based practice. Site-specific attending physicians were present to provide real-time guidance and education. Pre- and postworkshop surveys were administered to the participants to determine the impact of the workshop. Subsequently, postgraduate year (PGY)-2 residents were required to complete 6 supervised FOL examinations in clinic and were provided immediate feedback.Results: Annual workshops were performed in 2017 to 2019. The survey completion rate was 14 of 18 (78%). Participants ranged from fourth-year medical students to PGY-2 to PGY-5 residents. All PGY-2 residents completed their 6 supervised FOL examinations. On a 5-point Likert scale, mean H&N anatomy knowledge increased from 2.4 to 3.7 (standard deviation = 0.6, P < .0001). Similarly, mean FOL procedural skill confidence increased from 2.2 to 3.3 (standard deviation = 0.7, P < .0001). These effects were limited to novice (fourth-year medical students to PGY-2) participants. All participants found the exercise clinically informative.Conclusions: A simulation-based workshop for teaching FOL procedural skills increased confidence and procedural expertise of new radiation oncology residents and translated directly to supervised clinical encounters. Adoption of this type of program may help to improve resident training in H&N cancer. [ABSTRACT FROM AUTHOR]

Purpose: Testosterone recovery (TR) after androgen deprivation therapy (ADT) and radiation therapy (RT) is not well characterized. We studied TR in men who received RT and either short-term ADT (STADT) or long-term ADT (LTADT) and aimed to create a nomogram to predict TR.Methods and Materials: We identified consecutive localized prostate cancer patients treated with ADT-RT at 2 academic medical centers from January 2011 to October 2016 with documented baseline testosterone. TR was time from last ADT injection to testosterone normalization. The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models identified TR predictors. A nomogram was trained with site 1 and externally validated with site 2.Results: A total of 340 patients were included; 69.7% received STADT for a median duration of 6 months; 30.3% received LTADT for a median duration of 24.3 months. Median follow-up was 26.7 months. Median time for TR was 17.2 months for STADT and 24.0 months for LTADT patients (P = .004). The 2-year cumulative incidence of TR was 53.1% after LTADT versus 65.7% after STADT (P = .004). On multivariate analysis, shorter duration ADT (hazard ratio [HR], 0.96; P = .004), higher pretreatment testosterone (HR, 1.004; P < .001), and lower body mass index (HR, 0.95; P = .002) were associated with shorter time to TR. Older age (HR, 0.97; P = .09) and white race (HR, 0.67; P = .06) trended as longer TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. The concordance index was 0.71 (95% confidence interval, 0.64-0.78) for the validation cohort.Conclusions: In this population of localized prostate cancer patients, TR after ADT-RT was variable. Using baseline testosterone, ADT duration, body mass index, age, and race, a predictive nomogram can estimate the likelihood of TR. [ABSTRACT FROM AUTHOR]

Purpose: Standard therapy for locally advanced rectal cancer includes neoadjuvant chemoradiation and surgery. Complete response (CR) rates after chemoradiation can be as high as 29%, suggesting that nonoperative management (NOM) may be reasonable with appropriately selected patients. We sought to identify potential NOM candidates.Methods and Materials: Using the Veterans Administration Central Cancer Registry, patients with stage II to III rectal cancer receiving chemoradiation with or without subsequent surgery were identified. Clinical CR (cCR) was assessed by physical examination, endoscopy, or imaging. Kaplan-Meier and log-rank tests were used to assess survival; multivariate analysis was performed using Cox proportional hazards.Results: A total of 1313 patients were identified. Of these, 313 received chemoradiation alone (CRT cohort); 1000 received chemoradiation followed by surgery (CRT + S cohort). Median follow-up was 67.2 months. Median overall survival (OS) was 68.5 months. Median OS was 30.6 months for CRT and 89.3 months for CRT + S (P < .001). Median disease-specific survival (DSS) was 44.8 months for CRT and not reached (NR) for CRT + S (P < .001). Sixty-five CRT patients (20.8%) had a cCR. Median OS for CRT cCR patients was 73.5 months (P = .128 vs CRT + S); median DSS was NR (P = .161 vs CRT + S). One hundred thirty-seven (10.5%) CRT + S patients had a pathologic CR (pCR). Median OS with pCR was 133.7 months (P < .001 vs CRT cCR), and median DSS was NR (P = .276 vs CRT cCR).Conclusions: CRT patients with cCR had similar OS and DSS versus CRT + S patients and similar DSS versus CRT + S patients with a pCR. This suggests that patients with locally advanced rectal cancer with a cCR to CRT have an excellent prognosis and may be candidates for organ preservation. [ABSTRACT FROM AUTHOR]

Purpose: To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT).Methods and Materials: Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up.Results: Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059).Conclusions: HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc. [ABSTRACT FROM AUTHOR]