Search

Locally advanced lung cancer (LALC) treatment planning is often complex due to challenging tradeoffs related to large targets near organs at risk, making the judgment of plan quality difficult. The purpose of this work was to update and maintain a multi-institutional knowledge-based planning (KBP) model developed by a statewide consortium of academic and community practices for use as a plan quality assurance (QA) tool.Sixty LALC volumetric-modulated arc therapy plans from 2021 were collected from 24 institutions. Plan quality was scored, with high-quality clinical (HQC) plans selected to update a KBP model originally developed in 2017. The model was validated via automated KBP planning, with 20 cases excluded from the model. Differences in dose-volume histogram metrics in the clinical plans, 2017 KBP model plans, and 2022 KBP model plans were compared. Twenty recent clinical cases not meeting consortium quality metrics were replanned with the 2022 model to investigate potential plan quality improvements.Forty-seven plans were included in the final KBP model. Compared with the clinical plans, the 2022 model validation plans improved 60%, 65%, and 65% of the lung V20Gy, mean heart dose, and spinal canal D0.03cc metrics, respectively. The 2022 model showed improvements from the 2017 model in hot spot management at the cost of greater lung doses. Of the 20 recent cases not meeting quality metrics, 40% of the KBP model-replanned cases resulted in acceptable plans, suggesting potential clinical plan improvements.A multi-institutional KBP model was updated using plans from a statewide consortium. Multidisciplinary plan review resulted in HQC model training plans and model validation resulted in acceptable quality plans. The model proved to be effective at identifying potential plan quality improvements. Work is ongoing to develop web-based training plan review tools and vendor-agnostic platforms to provide the model as a QA tool statewide.

Introduction: Little data have been reported about the patient experience during curative radiotherapy for lung cancer in routine clinical practice, or how this relates to treatment toxicity reported by clinicians. The purpose of this study was to compare clinician-reported adverse events (AEs) with patient-reported outcomes (PROs) including both specific symptoms/side effects as well as overall quality of life (QOL) during and after definitive radiotherapy (RT) for locally advanced lung cancer (LALC) in a large statewide cohort. Methods and Materials: Patient-reported outcomes (PROs) were prospectively collected from patients treated with definitive radiotherapy for LALC at 24 institutions within the XXXX Radiation Oncology Quality Consortium between 2012-2018 using the Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI). Physicians prospectively recorded adverse events (AEs) using CTCAE version 4.0. Patient-reported quality of life (QOL) changes from baseline were assessed during and after radiotherapy using the FACT-TOI. Spearman correlation coefficients were calculated for AEs and similar PROs, and multivariable analysis was used to assess associations with QOL. Results: 1361 patients were included and 53% of respondents reported clinically meaningful declines in QOL at the end of RT. Correlation between clinician-reported esophagitis and patient-reported trouble swallowing was moderate (R=0.67) while correlations between clinician-reported pneumonitis and patient-reported shortness of breath (R=0.13) and cough (R=0.09) were weak. Clinician-reported AEs were significantly associated with clinically meaningful declines inpatient-reported QOL, with R=-0.46 for a summary AE-score. QOL was more strongly associated with fatigue (R=-0.41) than lung-specific AEs. Conclusions: AEs are associated with clinically meaningful declines in QOL during and after RT for LALC, but associations between AEs and QOL are only modest. This highlights the importance of PRO data, and future research should assess whether earlier detection of PRO changes could allow for interventions that reduce the frequency of treatment-related clinically meaningful declines in QOL.

To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC).A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes.A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79).Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P.05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P.0001.The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall were contoured consistently per RTOG 1106 OAR-Atlas. The dose-volume histograms (DVHs) of physical prescription dose (DVHp) and biological effective dose (α/β = 2.5; DVH2.5) were generated, respectively. The primary endpoint was PBT toxicities, defined by CTCAE 4.0 under the terminology of bronchial stricture/atelectasis.Of 100 patients enrolled, with a median follow-up of 64 months (95% confidence interval [CI], 50-78), 73% received 70 Gy or greater and 17% developed PBT toxicity (grade 1, 8%; grade 2, 6%; grade 3, 0%; and grade 4, 3%). The median time interval between RT initiation and onset of PBT toxicity was 8.4 months (95% CI, 4.7-44.1). The combined DVHs showed that no patient with a PBT maximum physical dose65 Gy developed any PBT toxicity. Cox proportional hazards analysis and receiver operating characteristic analysis demonstrated that V75 of PBT was the most significant dosimetric parameter for both grade 1+ (P = .035) and grade 2+ (P = .037) PBT toxicities. The dosimetric thresholds for V75 of PBT were 6.8% and 11.9% for grade 1+ and grade 2+ PBT toxicity, respectively.V75 of PBT appeared be the most significant dosimetric parameter for PBT toxicity after conventionally fractionated thoracic 3DCRT. Constraining V75 of PBT can limit clinically significant PBT toxicity.

Purpose To identify and define the incidence, risk factors, clinical characteristics, and treatment approaches to pelvic insufficiency fractures (PIFs) that develop as a consequence of pelvic radiation therapy for gynecologic malignancies. Materials and Methods A systematic literature review (PubMed and Embase indexed from January 1, 1980, to May 1, 2020) of studies describing PIFs that result from radiation therapy for gynecologic malignancies. A random-effects model weighted by the inverse variance was used to calculate the pooled crude incidence, actuarial incidence, and proportion of symptomatic PIFs, and to evaluate the relationship between PIF incidence and various risk factors. Results Thirty-eight studies describing PIFs following radiation therapy for gynecologic malignancies were reviewed. A meta-analysis of 6488 patients (37 studies) identified the crude incidence of PIF as 9.4% (95% confidence interval [CI] 6.8%-12.4%), and a meta-analysis of 2131 patients (9 studies) identified the 5-year actuarial incidence of PIF as 15.3% (95% CI 7.5%-25.0%). Factors that significantly correlated with increased risk of PIF development included evidence of osteoporosis (P Conclusions PIFs cause significant morbidity in gynecologic cancer patients after radiation therapy. In this systematic review, we discuss the incidence and risk factors associated with PIF development as it relates to the different detection methods, radiation techniques, doses, and gynecologic cancers treated. Additional studies are needed to further define prevention and treatment approaches for insufficiency fractures.

Purpose Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer. Methods and Materials Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle. The 3-fraction regimen employed a minimum of 8 Gy per fraction compared with 6 Gy for the 5-fraction regimen. Imaging was obtained every 12 weeks to assess response. Results From October 2015 to February 2017, 12 patients were enrolled in the study (median age 64; range, 55-77 years). The best response by the Response Evaluation in Solid Tumors criteria was partial response in 3 and stable disease in 3, for a disease control rate of 50%. Five patients had a grade 3 immune-related adverse event, including choreoretinitis (n = 1), pneumonitis (n = 1), transaminitis (n = 1), fatigue (n = 1), and peripheral neuropathy (n = 1). The median progression-free survival was 2.3 months, and the median overall survival was 6.9 months (range, 0.4-not reached). There was no clear association between peripheral blood T cell repertoire characteristics at baseline, PD-L1, or tumor mutations and response or outcome. One long-term survivor exhibited oligoclonal T cell populations in a baseline tumor biopsy that were consistently detected in peripheral blood over the entire course of the study. Conclusions HIGRT plus atezolizumab resulted in an overall response rate of 25% and disease control rate of 50% in this pilot study. The incidence of grade 3 adverse events was similar to that of atezolizumab alone. Alhough it was a pilot study with limited sample size, the results generated hypotheses worthy of further investigation.

PURPOSE: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation. METHODS AND MATERIALS: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. RESULTS: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8(+) T cells and decreased PD-1(+)CD8(+), PD-L1(+)CD8(+), and PD-L1(+)CD68(+) subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. CONCLUSIONS: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.

Single-fraction (SF) radiation therapy is effective and convenient for patients with painful noncomplex bone metastases. Prior survey results reported a low recommendation of SF radiation therapy in the US. We sought to assess contemporary treatment recommendations for the management of bone metastases among diverse physicians participating in a statewide quality consortium.Members of the Michigan Radiation Oncology Quality Consortium were surveyed between April and May 2017. Physicians rated the importance of 31 variables on their choice of dose fractionation. The survey also covered 7 patient scenarios.Fifty-six physicians responded who were practicing at 18 of 20 centers surveyed. Respondents recommended 23 dose-fractionation schedules across the 7 scenarios. Highest-rated factors considered when choosing a dose fractionation regimen were performance status, prognosis, spinal cord compression, and prior radiation therapy. Recommendations for SF overall were uncommon (16.1%). On multivariable analysis, factors associated with SF use included academic employment (odds ratio [OR] 2.04; 95% CI, 1.02-4.08; P = .044) and higher palliative case volume (OR 2.59; 95% CI, 1.45-4.63; P = .001). Stereotactic body radiation therapy (SBRT) was recommended in 16.4% of scenarios overall, and on multivariable analysis, significant predictors for SBRT use were academic employment (OR 2.99; 95% CI, 1.39-6.44; P = .005), more recent residency completion (OR 4.37; 95% CI, 1.26-15.17; P = .02), spine location (OR 12.54; 95% CI, 3.96-39.68; P .001), and prior radiation therapy (OR 26.67; 95% CI, 7.86-90.57; P .001). SF rates were higher than in a survey reported in 2009 (16.1% vs 9.4%, P = .0004).SF radiation therapy remains uncommonly recommended, although it may be recommended more now than it was 10 years ago despite the increased utilization of SBRT. We identify multiple key drivers in physician decision making affecting SF recommendations that have not been addressed by prior level one evidence. Further research with evidence-based recommendations to clarify the role of SF and SBRT in management of patients with bony metastases are needed.

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life.

Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients' plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively. Interactions between candidate biomarkers, radiobiological, and clinical parameters were analyzed using data-driven Bayesian network (DD-BN) analysis. We identified alterations in specific miRNAs (miR-532, -99b and -495, let-7c, -451 and -139-3p) correlating with lung toxicity. High levels of soluble tumor necrosis factor alpha receptor 1 (sTNFR1) were detected in a majority of lung cancer patients. However, among RP patients, within 2 weeks of RT initiation, we noted a trend of temporary decline in sTNFR1 (a physiological scavenger of TNFα) and ADAM17 (a shedding protease that cleaves both membrane-bound TNFα and TNFR1) levels. Cytokine signature identified activation of inflammatory pathway. Using DD-BN we combined miRNA and cytokine data along with generalized equivalent uniform dose (gEUD) to identify pathways with better accuracy of predicting RP2 as compared to either miRNA or cytokines alone. This signature suggests that activation of the TNFα-NFκB inflammatory pathway plays a key role in RP which could be specifically ameliorated by etanercept rather than current therapy of non-specific leukotoxic corticosteroids.

Background Patterns and prognostic implications of recurrent adrenocortical carcinoma are poorly understood. In this study, we aim to describe temporal and spatial patterns of adrenocortical carcinoma recurrence. Methods This is a retrospective review of 576 patients with adrenocortical carcinoma evaluated at a single institution. Clinicopathologic and follow-up data were collected longitudinally. Results A total of 354 patients underwent resection of stage I-III adrenocortical carcinoma. We found that 249 (70%) patients developed disease recurrence. The median recurrence-free interval after primary resection was 11 months. The most common sites of initial recurrence were lung and tumor bed. The shortest time to recurrence was associated with lung or multiple site metastases. We found that 142 of 249 patients developed one or more additional sites of recurrence (median 5 months), most commonly involving the lungs. A total of 20 patients developed a third site of recurrence. We found that 100 patients underwent one or more reoperations or metastasectomies and 79 recurred again after reoperation. Same organ or site recurrence was common after reoperation (67%). Although lung metastases occurred early, recurrences to the peritoneal cavity or to multiple sites were associated with worse survival. Metastasectomy beyond three total operations did not improve overall survival. Conclusion Survival varies according to site of recurrence and other clinicopathologic factors. Knowledge of patterns of recurrence may assist in anticipating disease course and lead to better informed selection of treatment.

Background Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. Objective To identify a potential ICE for men receiving PORT. Design, setting, and participants We performed an institutional review board–approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. Outcome measurements and statistical analysis Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance ( c ) indices were used to assess model discrimination. Results and limitations OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45–3.71; p p p c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. Conclusions While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. Patient summary We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.

Purpose Palliative radiation therapy for bone metastases is often viewed as a single entity, despite national guidelines providing input principally only for painful uncomplicated bone metastases. Data surrounding the treatment of bone metastases are often gleaned from questionnaires of what providers would theoretically do in practice or from population-based data lacking critical granular information. We investigated the real-world treatment of bone metastases with radiation therapy. Methods and Materials Twenty diverse institutions across the state of Michigan had data extracted for their 10 most recent cases of radiation therapy delivered for the treatment of bone metastases at their institution between January and February 2017. Uni- and multivariable binary logistic regression was used to assess the use of single fraction (8 Gy × 1) radiation therapy. Results A total of 196 cases were eligible for inclusion. Twenty-eight different fractionation schedules were identified. The most common schedule was 3 Gy × 10 fractions (n = 100; 51.0%), 4 Gy × 5 fractions (n = 32; 16.3%), and 8 Gy × 1 (n = 15; 7.7%). The significant predictors for the use of single fraction radiation therapy were the presence of oligometastatic disease (P = .008), previous overlapping radiation therapy (P = .050), and academic practice type (P = .039). Twenty-nine cases (14.8%) received >10 fractions (median 15, range 11-20). Intensity modulated radiation therapy was used in 14 cases (7.1%), stereotactic body radiation therapy in 11 (5.6%), and image guidance with cone beam computed tomography in 11 (5.6%). Of the cases of simple painful bone metastases (no previous surgery, spinal cord compression, fracture, soft tissue extension, or overlapping previous radiation therapy; n = 70), only 12.9% were treated with 8 Gy × 1. Conclusions Bone metastases represent a heterogeneous disease, and radiation therapy for bone metastases is similarly diverse. Future work is needed to understand the barriers to single fraction use, and clinical trials are necessary to establish appropriate guidelines for the breadth of this complex disease.

PURPOSE: The purpose of this study is to identify dosimetric variables that best predict for acute esophagitis in patients treated for locally advanced non–small cell lung cancer in a prospectively accrued statewide consortium. METHODS AND MATERIALS: Patients receiving definitive radiation therapy for stage II-III non–small cell lung cancer within the Michigan Radiation Oncology Quality Consortium were included in the analysis. Dose-volume histogram data were analyzed to determine absolute volumes (cc) receiving doses from 10 to 60 Gy (V10, V20, V30, V40, V50, and V60), as well as maximum dose to 2 cc (D2cc), mean dose (MD), and generalized equivalent uniform dose (gEUD). Logistic regression models were used to characterize the risk of toxicity as a function of dose and other covariatcs. The ability of each variable to predict esophagitis, individually or in a multivariate model, was quantified by receiver operating characteristic analysis. RESULTS: There were 533 patients who met study criteria and were included; 437 (81.9%) developed any grade of esophagitis. Significant variables on univariate analysis for grade ≥2 esophagitis were concurrent chemotherapy, V20, V30, V40, V50, V60, MD, D2cc, and gEUD. For grade ≥3 esophagitis, the predictive variables were: V30, V40, V50, V60, MD, D2cc, and gEUD. In multivariable modeling, gEUD was the most significant predictor of both grade ≥2 and grade ≥3 esophagitis. When gEUD was excluded from the model, D2cc was selected as the most predictive variable for grade ≥3 esophagitis. For an estimated risk of grade ≥3 esophagitis of 5%, the threshold values for gEUD and D2cc were 59.3 Gy and 68 Gy, respectively. CONCLUSIONS: In this study, we report the novel finding that gEUD and D2cc, rather than MD, were the most predictive dose metrics for severe esophagitis. To limit the estimated risk of grade ≥3 esophagitis to

Purpose To study the dosimetric impact of deformable image registration–based contour propagation on MRI-based cervical cancer brachytherapy planning. Methods and Materials High-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. “Manual-contour” and “propagated-contour” plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD2] EBRT + brachytherapy) parameters. Results The differences between the manual- and propagated-contour plans with respect to the HRCTV D90 and bladder, rectum, and sigmoid D2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98–107%, 95–105%, and 92–108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97–103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans. Conclusions When deformable image registration–propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes.

A substantial barrier to the single-and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, doseevolume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials. (C) 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Purpose Tools for survival prediction for non-small cell lung cancer (NSCLC) patients treated with chemoradiation or radiation therapy are of limited quality. In this work, we developed a predictive model of survival at 2 years. The model is based on a large volume of historical patient data and serves as a proof of concept to demonstrate the distributed learning approach. Methods and Materials Clinical data from 698 lung cancer patients, treated with curative intent with chemoradiation or radiation therapy alone, were collected and stored at 2 different cancer institutes (559 patients at Maastro clinic (Netherlands) and 139 at Michigan university [United States]). The model was further validated on 196 patients originating from The Christie (United Kingdon). A Bayesian network model was adapted for distributed learning (the animation can be viewed at https://www.youtube.com/watch?v=ZDJFOxpwqEA). Two-year posttreatment survival was chosen as the endpoint. The Maastro clinic cohort data are publicly available at https://www.cancerdata.org/publication/developing-and-validating-survival-prediction-model-nsclc-patients-through-distributed, and the developed models can be found at www.predictcancer.org. Results Variables included in the final model were T and N category, age, performance status, and total tumor dose. The model has an area under the curve (AUC) of 0.66 on the external validation set and an AUC of 0.62 on a 5-fold cross validation. A model based on the T and N category performed with an AUC of 0.47 on the validation set, significantly worse than our model (P

Background and purpose Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.

Purpose Dose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT). Methods and Materials SPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed. Dose was converted to the nominal dose equivalent per 2 Gy fraction, and SPECT intensities were normalized. Regional lung segments were defined, and the average dose delivered to each lung region was quantified. Three functional categorizations were defined to represent low-, normal-, and high-functioning lungs. The percent of functional lung category receiving ≥20 Gy and mean functional intensity receiving ≥20 Gy (iV20) were calculated. RILT was defined as grade 2+ radiation pneumonitis and/or clinical radiation fibrosis. A logistic regression was used to evaluate the association between dose-function metrics and risk of RILT. Results By analyzing V/Q normalized intensities and functional distributions across the population, a wide range in functional capability (especially in the ipsilateral lung) was observed in patients with NSCLC before RT. Through multivariable regression models, global lung average dose to the lower lung was found to be significantly associated with RILT, and Q and V iV20 were correlated with RILT when using ipsilateral lung metrics. Through a receiver operating characteristic analysis, combined V/Q low-function receiving ≥20 Gy (low-functioning V/Q20) in the ipsilateral lung was found to be the best predictor (area under the curce: 0.79) of RILT risk. Conclusions Irradiation of the inferior lung appears to be a locational sensitivity for RILT risk. The multivariable correlation between ipsilateral lung iV20 and RILT, as well as the association of low-functioning V/Q20 and RILT, suggest that irradiating low-functioning regions in the lung may lead to higher toxicity rates.

Although large volumes of information are entered into our electronic health care records, radiation oncology information systems and treatment planning systems on a daily basis, the goal of extracting and using this big data has been slow to emerge. Development of strategies to meet this goal is aided by examining issues with a data farming instead of a data mining conceptualization. Using this model, a vision of key data elements, clinical process changes, technology issues and solutions, and role for professional societies is presented. With a better view of technology, process and standardization factors, definition and prioritization of efforts can be more effectively directed.

To evaluate the usage of concurrent chemo-radiotherapy (C-CRT) for the treatment of locally advanced cervical cancer.Patients with locally invasive cervical carcinoma diagnosed between January 1, 2004 and December 31, 2012 from the National Cancer Database (NCDB) were included. Outcomes for patients undergoing radiation therapy only, 'RT alone' group were compared to those receiving chemotherapy concurrent with radiation 'C-CRT group'. Trends in utilization of C-CRT and factors associated with the deviation from standard of care were explored. Lastly, the effect of hospital volume on utilization of C-CRT was investigated.A total of 18,164 patients undergoing definitive radiation therapy were available for analysis. Utilization of C-CRT increased from 72.4% in 2004 to 84.3% in 2012 (p-trend0.001). After adjusting for patient, tumor, and treatment factors, a multivariable logistic regression model revealed increasing age, African-American race, Charlson-comorbidity index of ≥2, Medicaid insurance status, uninsured status, and Stage I disease were each independently associated with the lack of C-CRT. After adjusting for patient characteristics, low volume hospitals were noted to have overall significantly lower rates and greater variation in C-CRT administration. Patients in 'RT alone' group had an overall worse survival rate (adjusted-HR 1.47, 95%CI 1.4-1.56).Rates of C-CRT administration varied significantly across hospitals in the United States. Hospitals with a high case volume had higher rates and more consistent patterns of C-CRT administration. Furthermore, we identified independent factors, all of which represent noteworthy health disparities, associated with lower rates of C-CRT administration.

Purpose Although recurrences and toxicity occur after vaginal cuff (VC) brachytherapy, little is known about dosimetry due to the inability to clearly visualize the VC on computed tomography (CT). T2-weighted (T2W) magnetic resonance imaging (MRI) is superior to CT in this setting, and we hypothesized that it could provide previously unascertainable dosimetric information. Methods and Materials In a cohort of 32 patients who underwent cylinder-based brachytherapy for endometrial cancer with available MR simulation images, the VC was retrospectively contoured on T2W images, and cases were replanned to treat the upper VC to a dose of 7 Gy/fraction prescribed to 5 mm. Relevant dose-volume parameters for the VC were calculated. Results T2W MRI identified significant underdosing not observed on CT or T1-weighted imaging. Over two-thirds (69%) of patients had at least 1 cm 3 of VC that received less than 75% of the prescription dose and half (50%) of patients had a least 1 cm 3 of VC that received less than 50% of the prescription dose. The mean minimum point dose to the VC was 2.4 Gy, or 34% of the intended prescription dose (range: 0.53-6.4 Gy). Conclusions We identified previously unreported VC underdosing in over two-thirds of our patients, with most of these patients having volumes of undistended VC that received less than half of the prescription dose. The maximum dimension was along the craniocaudal axis in some patients or left-right/anterior-posterior axis in others, suggesting that suture material may be restricting access to the vaginal apex and that alternative applicators may be needed when the diameter of the apex is larger than the introitus. Additional follow-up will be needed to determine whether underdosing is associated with isolated VC failure or whether low failure rates across the cohort suggest that some patients are being exposed to excessive dose and unnecessary risk of toxicity.

Objectives Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT. Materials and methods We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT. Results The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23–3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03–1.48), p = .02), and require supportive infusions (1.10 (1.02–1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14–2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment. Conclusion HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

PURPOSE: To develop a brachytherapy audit checklist that could be used to prepare for Nuclear Regulatory Commission or agreement state inspections, to aid in readiness for a practice accredi- tation visit, or to be used as an annual internal audit tool. METHODS AND MATERIALS: Six board-certified medical physicists and one radiation oncol- ogist conducted a thorough review of brachytherapy-related literature and practice guidelines pub- lished by professional organizations and federal regulations. The team members worked at two facilities that are part of a large, academic health care center. Checklist items were given a score based on their judged importance. Four clinical sites performed an audit of their program using the checklist. The sites were asked to score each item based on a defined severity scale for their noncompliance, and final audit scores were tallied by summing the products of importance score and severity score for each item. RESULTS: The final audit checklist, which is available online, contains 83 items. The audit scores from the beta sites ranged from 17 to 71 (out of 690) and identified a total of 7e16 noncompliance items. The total time to conduct the audit ranged from 1.5 to 5 hours. CONCLUSIONS: A comprehensive audit checklist was developed which can be implemented by any facility that wishes to perform a program audit in support of their own brachytherapy program. The checklist is designed to allow users to identify areas of noncompliance and to prioritize how these items are addressed to minimize deviations from nationally-recognized standards. 2015

Purpose Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

Purpose: Adjuvant high-dose-rate vaginal brachytherapy (VB) is commonly used in endometrial cancer. We evaluated the dosimetric and cost differences of using either a single plan or replan prior to each fraction for single- and multi-channel VB. Methods and Materials: We evaluated 84 fractions from 25 patients at our institution (16 singlechannel patients each 3 fractions; 9 multi-channel patients each 4 fractions). All fractions were preceded by a computed tomographic (CT) simulation scan, after which a unique treatment plan was generated, dose points per International Commission on Radiation Units and Measurements (ICRU) 38. We calculated the dose to critical organs based on a decay-and-treat method utilizing the original catheter dwell-times for the initial fraction, and also the interfractional motion of the critical organ points between the initial and the subsequent CT scans. Results: The absolute mean dose difference was 14 cGy for bladder and 15 cGy for rectum between the replan and decay methods for single-channel, and 14 cGy for both organ points for the multi-channel cylinder. The bladder and rectum doses were not found to be significantly different between the replan and decay methods for either single-channel (bladder, P = .08; rectum, P = .19) or multi-channel cylinders (bladder, P = .85; rectum, P = .10). The mean interfractional displacement of the organ points between the initial and subsequent CT scans was 1.10 cm for the bladder and 0.67 cm for the rectum for single-channel, and 0.87 cm and 0.51 cm for multi-channel cylinders. The maximum interfractional motion was seen in the transverse plane for both organ points for both types of cylinders. At our institution, the decay method was 19% and 22% more cost-effective for single-channel and multi-channel cylinders, respectively. Conclusions: Our data show no dosimetric advantage, but higher costs, associated with replanning prior to each fraction for both single- and multi-channel VB. Fractional replanning should not be utilized on a routine basis.