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Purpose/Objective (s): Due to manual OAR contouring challenges, various automatic contouring solutions have been introduced. Historically, common clinical auto-segmentation algorithms used were atlas-based, which required maintaining a library of self-made contours. Searching the collection was computationally intensive and could take several minutes to complete. Deep learning approaches have shown significant benefits compared to atlas-based methods in improving segmentation accuracy and efficiency in auto-segmentation algorithms. This work represents the first multi-institutional study to describe and evaluate an AI algorithm for the auto-segmentation of organs at risk (OARs) based on a deep image-to-image network (DI2IN). Materials/Methods: The AI-Rad Companion Organs RT (AIRC) algorithm(Siemens Healthineers, Erlangen, Germany) uses a two-step approach for segmentation. In the first step, the target organ region in the optimal input image is extracted using a trained deep reinforcement learning network (DRL), which is then used as input to create the contours in the second step based on DI2IN. The study was initially designed as a prospective single-center evaluation. The automated contours generated by AIRC were evaluated by three experienced board-certified radiation oncologists using a four-point scale where 4 is clinically usable and 1 requires re-contouring. After seeing favorable results in a single-center pilot study, we decided to expand the study to six additional institutions, encompassing eight additional evaluators for a total of 11 physician evaluators across seven institutions. Results: One hundred and fifty-six patients and 1366 contours were prospectively evaluated. The five most commonly contoured organs were the lung (136 contours, average rating = 4.0), spinal cord (106 contours, average rating = 3.1), eye globe (80 contours, average rating = 3.9), lens (77 contours, average rating = 3.9), and optic nerve (75 contours, average rating = 4.0). The average rating per evaluator per contour was 3.6. On average, 124 contours were evaluated by each evaluator. 65% of the contours were rated as 4, and 31% were rated as 3. Only 4% of contours were rated as 1 or 2. Thirty-three organs were evaluated in the study, with 19 structures having a 3.5 or above average rating (ribs, abdominopelvic cavity, skeleton, larynx, lung, aorta, brachial plexus, lens, eye globe, glottis, heart, parotid glands, bladder, kidneys, supraglottic larynx, submandibular glands, esophagus, optic nerve, oral cavity) and the remaining organs having a rating of 3.0 or greater (female breast, proximal femur, seminal vesicles, rectum, sternum, brainstem, prostate, brain, lips, mandible, liver, optic chiasm, spinal cord, spleen). No organ had an average rating below 3. Conclusion: AIRC performed well with greater than 95% of contours accepted by treating physicians with no or minor edits. It supported a fully automated workflow with the potential for time savings and increased standardization with the use of AI-powered algorithms for high-quality OAR contouring. [ABSTRACT FROM AUTHOR]

Purpose: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high‐intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT‐BC trial assesses the safety and feasibility of an evidence‐based, dose‐escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition. Methods: Participants included women with breast cancer underwent a 3‐month thrice weekly exercise regimen involving dose escalation of high‐intensity compound exercises. Coprimary outcomes included safety and adherence. Pre‐ and post‐regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test. Results: Fourty participants completed a 3‐month exercise regimen, with a median age of 57 years (range, 27–74 years) and 73% having stage 0–2 BC. BC therapies concurrent with exercise included anti‐estrogen therapy (80%), radiotherapy (30%), and non‐hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self‐limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y‐Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed. Conclusion: A 3‐month dose‐escalated resistance training regimen comprising high‐intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient‐reported quality of life. [ABSTRACT FROM AUTHOR]

Adaptive radiotherapy (ART) was introduced in the late 1990s to improve the accuracy and efficiency of therapy and minimize radiation-induced toxicities. ART combines multiple tools for imaging, assessing the need for adaptation, treatment planning, quality assurance, and has been utilized to monitor inter- or intra-fraction anatomical variations of the target and organs-at-risk (OARs). Ethos™ (Varian Medical Systems, Palo Alto, CA), a cone beam computed tomography (CBCT) based radiotherapy treatment system that uses artificial intelligence (AI) and machine learning to perform ART, was introduced in 2020. Since then, numerous studies have been done to examine the potential benefits of Ethos™ CBCT-guided ART compared to non-adaptive radiotherapy. This review will explore the current trends of Ethos™, including improved CBCT image quality, a feasible clinical workflow, daily automated contouring and treatment planning, and motion management. Nevertheless, evidence of clinical improvements with the use of Ethos™ are limited and is currently under investigation via clinical trials. [ABSTRACT FROM AUTHOR]

Adaptive radiotherapy (ART) was introduced in the late 1990s to improve the accuracy and efficiency of therapy and minimize radiation-induced toxicities. ART combines multiple tools for imaging, assessing the need for adaptation, treatment planning, quality assurance, and has been utilized to monitor inter- or intra-fraction anatomical variations of the target and organs-at-risk (OARs). Ethos™ (Varian Medical Systems, Palo Alto, CA), a cone beam computed tomography (CBCT) based radiotherapy treatment system that uses artificial intelligence (AI) and machine learning to perform ART, was introduced in 2020. Since then, numerous studies have been done to examine the potential benefits of Ethos™ CBCT-guided ART compared to non-adaptive radiotherapy. This review will explore the current trends of Ethos™, including improved CBCT image quality, a feasible clinical workflow, daily automated contouring and treatment planning, and motion management. Nevertheless, evidence of clinical improvements with the use of Ethos™ are limited and is currently under investigation via clinical trials. [ABSTRACT FROM AUTHOR]

A recent Twitter poll of over 150 radiation oncology participants acknowledged nearly 90% of participants had not done hand calculations in the previous year.[15] However, rote memorization and hand calculations represent a substantial portion of the resident physics course and board exam. Here we will arbitrarily define "basic fundamental physics" to include the explicit constituents of the "Basic Physics" section of the radiation oncology physics examination blueprint from the American Board of Radiology - "fundamental physics, atomic and nuclear structure, production of kV x-ray beams, production of MV x-ray beams, and radiation interactions". Keywords: radiation oncology resident physics education; resident education EN radiation oncology resident physics education resident education 1 6 6 09/06/23 20230901 NES 230901 THREE DISCIPLINE COLLABORATIVE RADIATION THERAPY (3DCRT) DEBATE SERIES Radiation Oncology is a highly multidisciplinary medical specialty, drawing significantly from three scientific disciplines - medicine, physics, and biology. [Extracted from the article]

Introduction: Imaging is integral part of cervical cancer management. Currently, MRI is used for staging, follow up and image guided adaptive brachytherapy. The ongoing IQ-EMBRACE sub-study is evaluating the use of MRI for functional imaging to aid in the assessment of hypoxia, metabolism, hemodynamics and tissue structure. This study reviews the current and potential future utilization of functional MRI imaging in diagnosis and management of cervical cancer. Methods: We searched PubMed for articles characterizing the uses of functional MRI (fMRI) for cervical cancer. The current literature regarding these techniques in diagnosis and outcomes for cervical cancer were then reviewed. Results: The most used fMRI techniques identified for use in cervical cancer include diffusion weighted imaging (DWI) and dynamic contrast enhancement (DCE). DCE-MRI indirectly reflects tumor perfusion and hypoxia. This has been utilized to either characterize a functional risk volume of tumor with low perfusion or to characterize at-risk tumor voxels by analyzing signal intensity both pre-treatment and during treatment. DCE imaging in these situations has been associated with local control and disease-free survival and may have predictive/prognostic significance, however this has not yet been clinically validated. DWI allows for creation of ADC maps, that assists with diagnosis of local malignancy or nodal disease with high sensitivity and specificity. DWI findings have also been correlated with local control and overall survival in patients with an incomplete response after definitive chemoradiotherapy and thus may assist with post-treatment follow up. Other imaging techniques used in some instances are MRspectroscopy and perfusion weighted imaging. T2-weighted imaging remains the standard technique used for diagnosis and radiation treatment planning. In many instances, it is unclear what additional information functional-MRI techniques provide compared to standard MRI imaging. Conclusions: Functional MRI provides potential for improved diagnosis, prediction of treatment response and prognostication in cervical cancer. Specific sequences such as DCE, DWI and ADC need to be validated in a large prospective setting prior to widespread use. The ongoing IQ-EMBRACE study will provide important clinical information regarding these imaging modalities. [ABSTRACT FROM AUTHOR]

Background: Patients with high-risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost.Methods: The authors compared quality-adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external-beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low-dose-rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479).Results: Treatment strategies were compared using the incremental cost-effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost-effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost-effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost.Conclusions: EBRT with LDR brachytherapy boost may be a cost-effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high-value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost-effective care, despite no change in overall survival. [ABSTRACT FROM AUTHOR]

The task group (TG) on magnetic resonance imaging (MRI) implementation in high‐dose‐rate (HDR) brachytherapy (BT)—Considerations from simulation to treatment, TG 303, was constituted by the American Association of Physicists in Medicine's (AAPM's) Science Council under the direction of the Therapy Physics Committee, the Brachytherapy Subcommittee, and the Working Group on Brachytherapy Clinical Applications. The TG was charged with developing recommendations for commissioning, clinical implementation, and on‐going quality assurance (QA). Additionally, the TG was charged with describing HDR BT workflows and evaluating practical consideration that arise when implementing MR imaging. For brevity, the report is focused on the treatment of gynecologic and prostate cancer. The TG report provides an introduction and rationale for MRI implementation in BT, a review of previous publications on topics including available applicators, clinical trials, previously published BT‐related TG reports, and new image‐guided recommendations beyond CT‐based practices. The report describes MRI protocols and methodologies, including recommendations for the clinical implementation and logical considerations for MR imaging for HDR BT. Given the evolution from prescriptive to risk‐based QA, an example of a risk‐based analysis using MRI‐based, prostate HDR BT is presented. In summary, the TG report is intended to provide clear and comprehensive guidelines and recommendations for commissioning, clinical implementation, and QA for MRI‐based HDR BT that may be utilized by the medical physics community to streamline this process. This report is endorsed by the American Brachytherapy Society. [ABSTRACT FROM AUTHOR]

Aim: To investigate the potential role of a novel spatially fractionated radiation therapy (SFRT) method where heterogeneous dose patterns are created in target areas with virtual rods, straight or curving, of variable position, diameter, separation and alignment personalised to a patient's anatomy. The images chosen for this study were CT scans acquired for the external beam part of radiotherapy.Methods: Ten patients with locally advanced cervical cancer were retrospectively investigated with SFRT. The dose prescription was 30 Gy in 5 fractions to 90% target volume coverage. Peak-and-valley (SFRT_1) and peak-only (SFRT_2) strategies were applied to generate the heterogeneous dose distributions. The planning objectives for the target (CTV) were D90% ≥ 30 Gy, V45Gy ≥ 50-55% and V60Gy ≥ 30%. The planning objectives for the organs at risk (OAR) were: D2cm3 ≤ 23.75 Gy, 17.0 Gy, 19.5 Gy, 17.0 Gy for the bladder, rectum, sigmoid and bowel, respectively. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms.Results: The D2cm3 was 22.4 ± 2.0 (22.6 ± 2.1) and 13.9 ± 2.9 (13.2 ± 3.0) for the bladder and the rectum for SFRT_1 (SFRT_2). The results for the sigmoid and the bowel were 2.6 ± 3.1 (2.8 ± 3.0) and 9.1 ± 5.9 (9.7 ± 7.3), respectively. The hotspots in the target volume were V45Gy = 43.1 ± 7.5% (56.6 ± 5.6%) and V60Gy = 15.4 ± 5.6% (26.8 ± 6.6%) for SFRT_1 (SFRT_2). To account for potential uncertainties in the positioning, the dose prescription could be escalated to D90% = 33-35 Gy to the CTV without compromising any constraints to the OARs CONCLUSION: In this dosimetric study, the proposed novel planning technique for boosting the cervix uteri was associated with high-quality plans, respecting constraints for the organs at risk and approaching the level of dose heterogeneity achieved with routine brachytherapy. Based on a sample of 10 patients, the results are promising and might lead to a phase I clinical trial. [ABSTRACT FROM AUTHOR]

PURPOSE Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. METHODS Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. RESULTS In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015- 2017 to 85.6% in 2018 (P, .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% (P, .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P, .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P50.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P 5 .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. CONCLUSION Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints. [ABSTRACT FROM AUTHOR]

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I–II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998–2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (−) patients (HR 0.69, 95% CI 0.52–0.92, p =.01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75–1.41, p =.85). CMT is associated with improved OS for ALK (−) PTCLs; while no such benefit was seen for the ALK (+) subgroup. [ABSTRACT FROM AUTHOR]

Hybrid imaging with F-18 fludeoxyglucose positron emission tomography/magnetic resonance imaging (FDG PET/MRI) has increasing clinical applications supplementing conventional ultrasound, CT, and MRI imaging as well as hybrid PET/CT imaging in assessing cervical, endometrial, and ovarian cancer. This article summarizes the existing literature and discusses the emerging role of hybrid PET/MRI in gynecologic malignancies. Thus, far, the published literature on the applications of FDG PET/MRI shows that it can have a significant impact on patient management by improving the staging of the cancers compared with PET/CT, influencing clinical decision and treatment strategy. For disease restaging, current literature indicates that PET/MRI performs equivalently to PET/CT. There appears to be a mild-moderate inverse correlation between standard-uptake-value (SUV) and apparent-diffusion-coefficient (ADC) values, which could be used to predict tumor grading and risk stratification. It remains to be seen as to whether multi-parametric PET/MRI imaging could prove valuable for prognostication and outcome. PET/MRI provides the opportunity for reduced radiation exposure, which is particularly relevant for a young female in need of multiple scans for treatment monitoring and follow-up. Fast acquisition protocols and optimized methods for attenuation correction are still evolving. Major limitations of PET/MRI remains such as suboptimal detection of small pulmonary nodules and lack of utility for radiation treatment planning, which pose an impediment in making PET/MRI a viable one-stop-shop imaging option to compete with PET/CT. [ABSTRACT FROM AUTHOR]

We report our PET/MRI experience from a pilot study that compared the diagnostic performance of 18F-FDG PET/MRI versus PET/CT in staging of cervical cancer. Methods: Six adults with newly diagnosed cervical cancer underwent a single 18F-FDG injection with a dual-imaging protocol: standard-of-care PET/CT followed by research PET/MRI. The diagnostic interpretation and SUVmax for the 2 modalities were compared. Results: Both modalities detected all primary tumors (median size, 3.9 cm) and all 4 metastases present in 2 of the 6 patients (median size, 0.9 cm). PET/MRI provided greater diagnostic confidence than PET/CT and upstaged the disease in 4 patients. On the basis of the imaging findings alone, the additional information from PET/MRI would have led to a change in clinical management in 3 of 6 patients. The primary lesion showed a median SUV of 12.8 on PET/CT and 18.2 on PET/MRI (P = 0.03). SUVs, however, correlated strongly between the 2 modalities (ρ = 0.96, P < 0.001). Conclusion: Our pilot study supports the notion that PET/MRI has the potential to impact clinical decisions and treatment strategies in women with cervical cancer. Further studies are, however, warranted to define the value that PET/MRI adds to PET/CT. [ABSTRACT FROM AUTHOR]

Background: The TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation. Methods: A retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0‐1, 2‐4, and 5‐6 adverse factors were categorized into groups (A, B, and C). The Chow model included non‐breast primary, site of metastases other than bone only, and KPS; patients with 0‐1, 2, or 3 adverse factors were categorized into groups (I, II, and III). Results: A total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7‐2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively. Conclusion: Neither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.Methods: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.Results: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.Conclusions: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes. [ABSTRACT FROM AUTHOR]

Purpose: Varian Halcyon linear accelerator version 2 (The Halcyon 2.0) was recently released with new upgraded features. The aim of this study was to report our clinical experience with Halcyon 2.0 for a dual‐isocenter intensity‐modulated radiation therapy (IMRT) planning and delivery for gynecological cancer patients and examine the feasibility of in vivo portal dosimetry. Methods: Twelve gynecological cancer patients were treated with extended‐field IMRT technique using two isocenters on Halcyon 2.0 to treat pelvis and pelvic/or para‐aortic nodes region. The prescription dose was 45 Gy in 25 fractions (fxs) with simultaneous integrated boost (SIB) dose of 55 or 57.5 Gy in 25 fxs to involved nodes. All treatment plans, pretreatment patient‐specific QA and treatment delivery records including daily in vivo portal dosimetry were retrospectively reviewed. For in vivo daily portal dosimetry analysis, each fraction was compared to the reference baseline (1st fraction) using gamma analysis criteria of 4 %/4 mm with 90% of total pixels in the portal image planar dose. Results: All 12 extended‐field IMRT plans met the planning criteria and delivered as planned (a total of 300 fractions). Conformity Index (CI) for the primary target was achieved with the range of 0.99–1.14. For organs at risks, most were well within the dose volume criteria. Treatment delivery time was from 5.0 to 6.5 min. Interfractional in vivo dose variation exceeded gamma analysis threshold for 8 fractions out of total 300 (2.7%). These eight fractions were found to have a relatively large difference in small bowel filling and SSD change at the isocenter compared to the baseline. Conclusion: Halcyon 2.0 is effective to create complex extended‐field IMRT plans using two isocenters with efficient delivery. Also Halcyon in vivo dosimetry is feasible for daily treatment monitoring for organ motion, internal or external anatomy, and body weight which could further lead to adaptive radiation therapy. [ABSTRACT FROM AUTHOR]

Many Americans use smartphone-based mobile applications to acquire health information. Our study evaluated the readability of mobile application-based patient educational materials (PEMs) about five prevalent cancers in the United States. The Apple and Google mobile application marketplaces were queried for breast, colon, lung, prostate, and stomach cancer-related applications, which were subsequently screened for PEMs and assessed with 10 validated readability assessments. Twenty-one pertinent applications yielded 249 articles that were written at an 11.8 ± 2.3 grade level; only 12 (4.8%) articles were written below an eighth grade level. The majority of cancer-related PEMs were written at too difficult reading levels for American patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of this study was to present our evaluation of the cost‐effectiveness of salvage therapies for patients with recurrent head and neck cancer. Methods: A Markov model was developed with 5 salvage treatment strategies: (1) platinum‐based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity‐modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost‐effectiveness ratio (ICER), with effectiveness in quality‐adjusted life years (QALYs), and evaluated with a willingness‐to‐pay (WTP) threshold of $100 000 per QALY gained. Results: In the base case analysis, no treatment strategy was cost‐effective at a WTP threshold. The most cost‐effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost‐effective. Conclusion: None of the treatment strategies were cost‐effective. However, SBRT‐based reirradiation has potential to be cost‐effective. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T-cell lymphoma, nasal-type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States.Methods: Six hundred forty-two stage I-II NKTCL patients from 1998 to 2012 were identified from the National Cancer Data Base. Binary logistic regression analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of the treatment selection and RT dose. Overall survival (OS) analyses were completed with the Kaplan-Meier and Cox multivariate methods, including a propensity score adjustment for a potential indication bias.Results: Of the 642 included NKTCL patients, 70% were at stage I, 79% were white, and 66% were ≤ 60 years old. Fifty-five percent received chemotherapy plus RT, 19% received RT alone, and 27% received chemotherapy alone. The median RT dose was 50 Gy (interquartile range, 43.2-54 Gy), 37% received < 45 Gy, and 43% received < 50 Gy. A multivariate survival analysis showed improved OS in comparison with chemotherapy alone for RT alone at ≥50 Gy (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.70; P < .01), for chemotherapy plus RT at <50 Gy (HR, 0.55, 95% CI, 0.36-0.86; P < .01), and for chemotherapy plus RT at ≥50 Gy (HR, 0.41; 95% CI, 0.27-0.63; P < .01).Conclusions: Stage I-II NKTCL patients in the United States commonly receive chemotherapy alone or suboptimal-dose RT. The omission of RT or the use of suboptimal RT is negatively associated with OS. Efforts to continue improving evidenced-based management are warranted. Cancer 2017;123:3176-85. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low. [ABSTRACT FROM AUTHOR]

Background: We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. Methods and materials: The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. results: For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = -0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = -0.015), and V60 (p = -0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = -0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10. conclusion: The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease. Methods: This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated. Results: Median follow-up was 22.9±15.5 months (range: 2.6-68.6). For the entire cohort, LC was observed for 76.6% of the target lesions; the 2- year OS and PFS were 77% and 28% respectively. After a median of 7.9 months from SABR, 39 patients presented a first progression. In univariate analysis, patients with multiple recurrences prior to SABR (p=0.001) and those who received chemotherapy for metastatic progression (p=0.014) had poorer PFS from time of SABR. Median PFS for patients with no prior treatment for L-OMD vs. prior chemotherapy +/- local treatment vs. local treatment only was: not reached vs. 8.83 (± 2) vs. 32.5 (±2.75) months. The main pattern of first progression was out of field progression: in-field progression alone occurred in 7 patients (12%) and with synchronous regional/distant progression in 10 patients (17%. In all patients, chemotherapy was withheld until progression post-SABR. Treatment was well tolerated; only one patient experienced grade 3 bronchial toxicity, three months after completion of SABR. Conclusions: SABR achieves high rates of local control with limited toxicities in patients with lung oligometastatic disease from a colorectal primary. This retrospective data indicates that patients with newly diagnosed lung oligometastatic disease may be safely treated with SABR as first treatment, with chemotherapy held in reserve. In heavily pretreated patients, SABR may allow patients a treatment break from systemic therapy, which may be beneficial both psychologically and physically. Future randomized SABR studies should evaluate sequencing of chemotherapy, the role of immunotherapies, and the quality of life of patients undergoing SABR. [ABSTRACT FROM AUTHOR]

Background:Proton beam therapy (PBT) is increasingly being used globally to treat a variety of malignancies. This is the first review assessing PBT for gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed. Material and methods:Systematic searches of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology were conducted for publications. There were no restrictions on publication dates. Sixteen original investigations were identified and analyzed for this review. Results:The available evidence for PBT in treating gynecologic cancers is of both low quantity and quality. The most studied scenarios for PBT include treatment of para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy, and these also represent indications with the greatest opportunity for demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown significantly decreased dose to OARs, such as the rectum, bladder, bowel, kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more pronounced within the low-dose volumes than the higher dose volumes, which radiobiologically could be expected to lower second malignancy rates. Clinical data, though no level 1 evidence, show appropriate stage-specific tumor control and outcomes with PBT treatment, along with low toxicity rates. Conclusion:The existing data, albeit limited, warrant and can help guide larger scale and higher quality studies addressing whether PBT could provide clinically meaningful differences in toxicities and outcomes in women with gynecologic neoplasms. [ABSTRACT FROM PUBLISHER]

Background: Patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs) have superior outcomes in comparison with patients with non-HPV-induced OPCs. This study confirms that a previously proposed HPV risk-adapted restaging system better reflects disease outcomes.Methods: The National Cancer Data Base was used to analyze 8803 HPV+ OPC patients. Univariate and multivariate analyses were performed to identify the utility of both American Joint Commission on Cancer (AJCC) staging and HPV risk-adapted staging in predicting the outcomes of patients with HPV+ OPC and other factors influencing survival.Results: With a median follow-up of 27.1 months, 3.2% had AJCC stage I disease and 6.6%, 19.4%, and 70.9% had stage II, III, and IV disease, respectively. When the patients were restaged according to HPV risk-adapted staging, 76.6% had stage I disease, 9.9% had stage II disease, and 13.5% had stage III disease. The 4-year overall survival rates according to HPV risk-adapted staging were 85.8%, 77.3%, and 64.6% for stages I, II, and III, respectively, but the rates for AJCC stages I, II, III, and IV were 90.1%, 86.1%, 87.0%, and 80.1%, respectively. Patients with HPV+ metastatic disease at diagnosis had a significantly improved median survival of 20.5 months versus 11.1 months with HPV- disease (P < .01). In the multivariate analysis, survival was also affected by the age at treatment, a nontonsillar or base-of-tongue primary site, private insurance, an annual income ≥ $48,000/y, and the comorbidity index (all P values < .01).Conclusions: Outcomes of HPV+ OPC are significantly improved in comparison with HPV- OPC outcomes, and the current AJCC staging system does not accurately reflect disease outcomes. This study has retrospectively confirmed that an HPV risk-adapted restaging structure more accurately stratifies patients. Under this new risk-stratified staging system, patients may be more accurately stratified for investigation into treatment escalation or de-escalation studies. Cancer 2016;122:2021-30. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization. Methods Using the National Cancer Data Base, we identified 3552 patients with ATC. Factors associated with surgery, high-dose radiotherapy (RT; ≥59.4 Gy), and chemotherapy utilization were evaluated using multivariable logistic regression. From this, an inverse probability-weighted propensity score was incorporated into multivariable Cox regression analyses for OS. Results Numerous factors predictive for high-dose RT, total thyroidectomy, and chemotherapy utilization are described. Factors associated with improved survival were absence of clinical or pathologic lymph node involvement, absence of metastasis, tumor size ≤6 cm, negative surgical margins, surgery, RT, and chemotherapy. On conditional landmark analysis, improved survival seen with chemotherapy and surgery other than total thyroidectomy was lost, but persisted for total thyroidectomy and high-dose RT. Conclusion Even after correction for selection and immortal time bias, high-dose RT resulted in improved survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2083-E2090, 2016 [ABSTRACT FROM AUTHOR]

Vaginal cancer is an uncommon malignancy and can be either recurrent or primary. In both cases, brachytherapy places a central role in the overall treatment course. Recent technological advances have led to more advanced brachytherapy techniques, which in turn have translated to improved outcomes for patients with malignancies of the vagina. The aim of this manuscript is to outline the incorporation of modern brachytherapy into the treatment of patients with vaginal cancer including patient selection along with the role of brachytherapy in conjunction with other treatment modalities, various brachytherapy techniques, treatment planning, dose fractionation schedules, and normal tissue tolerance. [ABSTRACT FROM AUTHOR]

BACKGROUND Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early-stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early-stage follicular lymphoma in the era of modern therapy. METHODS A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score-adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used. RESULTS Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 ( P<.0001), with corresponding significant increases in observation and single-agent chemotherapy. Patients who received RT had 5-year and 10-year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT ( P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47-0.63 [ P<.0001]). CONCLUSIONS RT is an increasingly underused treatment approach in the era of modern therapy for patients with early-stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines. Cancer 2015;121:3325-3334. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested an association between radiation therapy (RT) of the left breast and increased incidence of coronary artery disease. However, the increased sparing afforded with modern RT may decrease long-term cardiac risk. The aims of our study were to evaluate the association between the RT and cardiac events in breast cancer patients who underwent contemporary RT and to examine whether breast arterial calcification (BAC) seen on mammogram predicts for cardiac events. Methods and Materials: In our observational, descriptive pilot study, 2,439 patients with breast cancer between 1986 and 2007 and a minimum of 3 years since completing RT were asked to complete a questionnaire regarding cardiac events since RT completion. The preoperative and follow-up mammograms were coded for presence/absence of BAC by an experienced radiologist blinded to questionnaire results. Cardiac events were compared between patients who received left- and right-sided adjuvant radiation. Results: At a mean follow-up of 7.5 years (range 3-24), 687 patients completed the questionnaire, with 602 eligible for analysis. Baseline characteristics (age, body mass index [BMI], surgery type, cardiovascular risk factors, and time since RT) were similar in patients who received left- versus right-sided RT. Hypertension before RT and during follow-up, baseline cardiovascular disease, age >50, BMI >30 kg/m2, and subsequent development of diabetes were significantly associated with posttreatment cardiac events. BACs were associated with cardiac events reported before breast cancer diagnosis; however, no association was found between left-sided breast RT or BAC and subsequent cardiac events. Conclusion: In a large single-institutional observational study, no association was found between left-sided breast RT or BAC and subsequent cardiac events. [ABSTRACT FROM AUTHOR]

Purpose: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV). Material and methods: Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption. Results: For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001). Conclusions: This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration. [ABSTRACT FROM AUTHOR]

Background This retrospective study aims to assess the usefulness of SUVmax from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT. Methods This study includes 95 patients of median age 77 years, with primary, biopsy-confirmed peripheral stage IA/IB NSCLC. All patients were treated with 60Gy in 3 fractions with a median treatment time of six days. Local, regional, and distant failures were evaluated independently according to the terms of RTOG1021. Local, regional, and distant control, overall- and progression-free survival were estimated by the Kaplan-Meier method. Cox proportional hazards regression was performed to determine whether SUVmax, age, KPS, gender, tumor size/T stage, or smoking history influenced outcomes. SUVmax was evaluated as both a continuous and as a dichotomous variable using a cutoff of <5 and ≥5. Results Median follow-up for the cohort was 16 months. Median OS and PFS were 25.3 and 40.3 months, respectively. SUV with a cutoff value of 5 predicted for OS and PFS (p = .024 for each) but did not achieve significance for LC (p = .256). On Cox univariate regression analysis, SUV as a dichotomous variable predicted for both OS and PFS (p = .027 and p = .030, respectively). Defined as a continuous variable, SUVmax continued to predict for OS and PFS (p = .032 and p = .003), but also predicted LC (p = .045) and trended toward significance for DC (p = .059). SUVmax did not predict for OS as a dichotomous or continuous variable. It did, however, predict for PFS as a continuous variable (p = .008), neared significance for local control (p = .057) and trended towards, significance for distant control (p = .092). Conclusions SUVmax appears to be a statistically and clinically significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT. Prospective studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to determine the dose contributions from image guided adaptive brachytherapy (IGABT) to individual suspicious pelvic lymph nodes (pLNN) in cervical cancer patients. Data were collected in two cancer centers, University of Pittsburgh Cancer Institute (UPCI) and University Medical Center Utrecht (UMCU). Material and methods: 27 and 15 patients with node positive cervical cancer treated with HDR (high dose rate) or PDR (pulsed dose rate)-IGABT were analyzed. HDR-IGABT (UPCI) was delivered with CT/MRI compatible tandem-ring applicators with 5.0-6.0 Gy x five fractions. PDR-IGABT (UMCU) dose was delivered with Utrecht tandem-ovoid applicators with 32 x 0.6 Gy x two fractions. Pelvic lymph nodes with short axis diameter of ≥ 5 mm on pre-treatment MRI or PET-CT were contoured for all BT-plans. Dose contributions to individual pLNN expressed as D90 (dose to 90% of the volume) were calculated from dose-volume histograms as absolute and relative physical dose (% of the reference dose) for each fraction. For each node, the total dose from all fractions was calculated, expressed in EQD2 (equivalent total dose in 2 Gy fractions). Results: Fifty-seven (UPCI) and 40 (UMCU) individual pLNN were contoured. The mean D90 pLNN was 10.8% (range 5.7-25.1%) and 20.5% (range 6.8-93.3%), respectively, and therefore different in the two centers. These values translate into 2.7 Gy (1.3-6.6 Gy) EQD2 and 7.1 Gy (2.2-36.7 Gy) EQD2, respectively. Differences are caused by the location of the individual nodes in relation to the spatial dose distribution of IGABT, differences in total dose administered and radiobiology (HDR versus PDR). Conclusions: The IGABT dose contribution to individual pelvic nodes depends on patient and treatment related factors, and varies considerably. [ABSTRACT FROM AUTHOR]