Factors Associated With Cardiac Radiation Dose Reduction After Hypofractionated Radiation Therapy for Localized, Left-Sided Breast Cancer in a Large Statewide Quality Consortium.

PURPOSE: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer. METHODS AND MATERIALS: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022. RESULTS: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal. CONCLUSIONS: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage.

Pectoralis Muscle Dosimetry and Posttreatment Rehabilitation Utilization for Patients With Early-Stage Breast Cancer.

PURPOSE: Up to 50% of women treated for localized breast cancer will experience some degree of arm or shoulder morbidity. Although radiation is thought to contribute to this morbidity, the mechanism remains unclear. Prior studies have shown biologic and radiographic changes in the pectoralis muscles after radiation. This study thus aimed to investigate the relationship between radiation to the pectoralis muscles and referrals for rehabilitation services posttreatment for arm and shoulder morbidity. METHODS AND MATERIALS: A retrospective 1:1 matched case-control study was conducted for patients with breast cancer who were and were not referred for breast or shoulder rehabilitation services between 2014 and 2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation. Patients who underwent an axillary lymph node dissection were excluded. Cohorts were matched based on age, axillary surgery, and use of radiation boost. Muscle doses were converted to equivalent dose in 2 Gy fractions assuming an α:ß ratio of 2.5 and were compared between the 2 groups. RESULTS: In our cohort of 50 patients of a median age 60 years (interquartile range, 53-68 years), 36 patients (72%) underwent a sentinel lymph node biopsy in addition to a lumpectomy. Although pectoralis muscle doses were generally higher in those receiving rehabilitation services, this was not statistically significant. Pectoralis major V20-40 Gy reached borderline significance, as did pectoralis major mean dose (17.69 vs 20.89 Gy; P = .06). CONCLUSIONS: In this limited cohort of patients, we could not definitively conclude a relationship between pectoralis muscle doses and use of rehabilitation services. Given the borderline significant findings, this should be further investigated in a larger cohort.

Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives.

STUDY OBJECTIVES: Physician-patient interactions influence the immediate encounter and leave lasting impressions for future health care encounters. We aimed to understand patient experiences and decision-making for considering sleep surgery, in terms of barriers and communication behaviors that facilitate or hinder referral for consideration of sleep surgery management of obstructive sleep apnea (OSA) when continuous positive airway pressure (CPAP) therapy has failed. METHODS: We employed qualitative methods, using semistructured interviews of adults with OSA who presented for sleep surgery consultation after unsatisfactory therapy with CPAP. Open-ended questions traced symptoms and progression of sleep apnea burden, trials of noninvasive OSA therapies, outcomes, and patient expectations and concerns. The interviews were audio-recorded, transcribed, and analyzed using content analysis to identify themes. RESULTS: Ten adult patients with OSA were enrolled March through April 2021 and reached predominant thematic saturation. Barriers to sleep surgery consultation included: (1) delays in OSA diagnosis due to limited OSA awareness among patients or primary providers and patients' perceived inconvenience of sleep testing, (2) patients faulted for slow progress, (3) patient-reported lack of urgency by providers in troubleshooting noninvasive management options, (4) scheduling delays and waitlists, and (5) cost. Patients were receptive to noninvasive treatment options, but inadequate improvement led to frustration after multiple encounters. Patients appreciated empathetic providers who shared information through transparent and understandable explanations and who presented multiple treatment options. CONCLUSIONS: Experiences of patients with OSA highlight the need for shared decision-making through improved communication of unresolved concerns and alternative management options, including timely referral for sleep surgery consultation when indicated. CITATION: Ikeda AK, McShay C, Marsh R, et al. Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives. J Clin Sleep Med. 2023;19(1):111-117.

Patient Factors and Preferences in Choosing Sleep Surgery for Obstructive Sleep Apnea: A Qualitative Study.

OBJECTIVE: There are several obstructive sleep apnea (OSA) treatment options available to patients, including surgery and less invasive therapies. Little is known about the factors that influence patient preferences for treatment. We aimed to understand factors influencing patient experience and decision making for undergoing sleep surgery. STUDY DESIGN: Retrospective qualitative study. SETTING: Tertiary sleep surgery clinic. METHODS: We conducted semistructured interviews with adults who previously underwent any nasal and/or pharyngeal sleep surgery. We asked open-ended questions about their decision-making process within a preconceived thematic framework of chief OSA symptoms, expectations for recovery, and sources of information. The interviews were audio recorded and transcribed, and content was analyzed for defined, emergent, and prevalent themes. RESULTS: Ten patients were interviewed from December 11, 2020 through January 29, 2021. Six patients underwent nasal surgery, 1 underwent pharyngeal surgery, and 3 underwent staged nasal and pharyngeal procedures. All patients were beyond the acute recovery phase. Reasons for pursuing surgical consultation varied from sleep apnea burden to external factors, such as recommendations from significant others. Duration of sleep surgery consideration varied from months to years. Major concerns about sleep surgery involved anesthesia and postoperative pain. External factors influencing patients' decisions to pursue sleep surgery included family and friend support. Postoperative outcomes of surgery included patient satisfaction with decision for surgery, given OSA improvements. CONCLUSION: Understanding patient factors that influence decision making for sleep surgery may guide clinicians in patient-centered counseling that engages patients in decision making, aligning with clinical symptoms and patient preferences.

Knowledge-Based Quality Assurance and Model Maintenance in Lung Cancer Radiation Therapy in a Statewide Quality Consortium of Academic and Community Practice Centers.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of Dose Accuracy in the Near-Surface Region for Whole Breast Irradiation Techniques in a Multi-institutional Consortium.

PURPOSE: To assess the accuracy of dose calculations in the near-surface region for different treatment planning systems (TPSs), treatment techniques, and energies to improve clinical decisions for patients receiving whole breast irradiation (WBI). METHODS AND MATERIALS: A portable custom breast phantom was designed for dose measurements in the near-surface regions. Treatment plans of varying complexities were created at 8 institutions using 4 different TPSs on an anonymized patient data set (50 Gy in 25 fractions) and peer reviewed by participants. The plans were recalculated on the phantom data set. The phantom was aligned with predetermined shifts and laser marks or cone beam computed tomography, and the irradiation was performed using a variety of linear accelerators at the participating institutions. Dose was measured with radiochromic film placed at 0.5 and 1.0 cm depth and 3 locations per depth within the phantom. The film was scanned and analyzed >24 hours postirradiation. RESULTS: The percentage difference between the mean of the measured and calculated dose across the participating centers was -0.2 % ± 2.9%, with 95% of measurements within 6% agreement. No significant differences were found between the mean of the calculated and measured dose for all TPSs, treatment techniques, and energies at all depths and laterality investigated. Furthermore, no significant differences were observed between the mean of measured dose and the prescription dose of 2 Gy per fraction. CONCLUSION: These results demonstrate that dose calculations for clinically relevant WBI plans are accurate to within 6% of measurements in the near-surface region for various complexities, TPSs, linear accelerators, and beam energies. This work lays the necessary foundation for future studies investigating the correlation between near-surface dose and acute skin toxicities.

Cardiac Magnetic Resonance Imaging and Blood Biomarkers for Evaluation of Radiation-Induced Cardiotoxicity in Patients With Breast Cancer: Results of a Phase 2 Clinical Trial.

PURPOSE: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. METHODS: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. RESULTS: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. CONCLUSIONS: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.

Comparative Effectiveness Analysis of 3D-Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy (IMRT) in a Prospective Multicenter Cohort of Patients With Breast Cancer.

PURPOSE: Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT). METHODS AND MATERIALS: Using prospective data regarding patients receiving adjuvant whole breast radiation therapy without nodal irradiation at 23 institutions from 2011 to 2018, we compared the incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting, adjusting for treatment facility as a random effect. RESULTS: Of 1185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly segmented forward-planned IMRT, 458 (59.2%) did; and of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1296 patients treated with hypofractionation and 3DCRT, 432 (33.3%) experienced acute toxicity; of 709 treated with highly segmented forward-planned IMRT, 227 (32.0%) did; and of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with inverse-probability-of-treatment weighting, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% confidence interval, 0.45-0.91) with conventional fractionation and 0.41 (95% confidence interval, 0.26-0.65) with hypofractionation. CONCLUSIONS: This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared with 3DCRT in reducing acute toxicity of breast radiation therapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness.

Mechanical properties of the shoulder and pectoralis major in breast cancer patients undergoing breast-conserving surgery with axillary surgery and radiotherapy.

Breast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p < 0.001) and healthy controls (p = 0.027). The mean prescribed radiotherapy dose to the PM was significantly correlated with passive shear elastic modulus (p = 0.018). Breast cancer patients undergoing more extensive axillary surgery and nodal radiotherapy did not experience long-term functional deficits to shoulder integrity but did experience long-term mechanical changes of the PM.

A Randomized Comparison of Radiation Therapy Techniques in the Management of Node-Positive Breast Cancer: Primary Outcomes Analysis.

PURPOSE: Although inverse-planned intensity modulated radiotherapy (IMRT) and deep inspiration breath hold (DIBH) may allow for more conformal dose distributions, it is unknown whether using these technologies reduces cardiac or pulmonary toxicity of breast radiotherapy. METHODS AND MATERIALS: A randomized controlled trial compared IMRT-DIBH versus standard, free-breathing, forward-planned, three-dimensional conformal radiotherapy in patients with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and 1 year post treatment. RESULTS: Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5 Gy averaged 15.8% with standard radiotherapy and 5.6% with IMRT-DIBH (P < .001). SPECT revealed no differences in perfusion defects in the left anterior descending coronary artery territory, the study's primary endpoint, but did reveal statistically significant differences (P = .02) in left ventricular ejection fraction (LVEF), a secondary endpoint. No differences were found for lung perfusion or function. CONCLUSION: The small but statistically significant benefit in preservation of cardiac LVEF observed here should motivate future studies that include LVEF as a potentially meaningful endpoint. Future studies should disaggregate the impact of IMRT from that of DIBH. Clinical practice should recognize the importance of minimizing cardiac dose, even when already low in comparison to historical levels.

Improving Quality and Consistency in NRG Oncology Radiation Therapy Oncology Group 0631 for Spine Radiosurgery via Knowledge-Based Planning.

PURPOSE: To use knowledge-based planning (KBP) as a method of producing high-quality, consistent, protocol-compliant treatment plans in a complex setting of spine stereotactic body radiation therapy on NRG Oncology Radiation Therapy Oncology Group (RTOG) 0631. METHODS AND MATERIALS: An internally developed KBP model was applied to an external validation cohort of 22 anonymized cases submitted under NRG Oncology RTOG 0631. The original and KBP plans were compared via their protocol compliance, target conformity and gradient index, dose to critical structures, and dose to surrounding normal tissues. RESULTS: The KBP model generated plans meeting all protocol objectives in a single optimization when tested on both internal and protocol-submitted NRG Oncology RTOG 0631 cases. Two submitted plans that were considered to have a protocol-unacceptable deviation were made protocol compliant through the use of the model. There were no statistically significant differences in protocol spinal cord metrics (D10% and D0.03cc) between the manually optimized plans and the KBP plans. The volume of planning target volume receiving prescription dose increased from 93.3% ± 3.2% to 98.3% ± 1.4% (P = .01) when using KBP. High-dose spillage to surrounding normal tissues (V105%) showed no significant differences (2.1 ± 7.3 cm3 for manual plans to 1.8 ± 0.6 cm3 with KBP), and dosimetric outliers with large amounts of spillage were eliminated through the use of KBP. Knowledge-based planning plans were also found to be significantly more consistent in several metrics, including target coverage and high dose outside of the target. CONCLUSION: Incorporation of KBP models into the clinical trial setting may have a profound impact on the quality of trial results, owing to the increase in consistency and standardization of planning, especially for treatment sites or techniques that are nonstandard.

Post-disaster agricultural transitions in Nepal.

In Spring 2015, a series of earthquakes and aftershocks struck Nepal. The earthquakes caused significant changes in labor and land availability, cash income needs, and land quality. We examine how these post-earthquake impacts converged with ongoing agricultural shifts. Earthquake-related socio-economic and landscape changes specifically motivate the adoption of cardamom, Amomum subulatum, a high-value ecologically beneficial, and low labor commercial crop. We investigate reasons for the increased interest in cardamom post-earthquake, and challenges associated with it. We find that adopting cardamom serves as an important post-disaster adaptation. However, more broadly, unevenly distributed interventions coupled with the high capital costs of agricultural transition exacerbate social differentiation in communities after the disaster. Adoption is often limited to economically better off smallholder farmers. This paper extends previous research on disasters and smallholder farming by highlighting the specific potential of disasters to accelerate agricultural transitions and resulting inequality from the changes.

Ischemic Cardiac Events Following Treatment of the Internal Mammary Nodal Region Using Contemporary Radiation Planning Techniques.

PURPOSE: Regional nodal irradiation, including radiation therapy (RT) to the internal mammary node (IMN) region, improves oncologic outcomes in patients with node-positive breast cancer. Concern remains, however, given the proximity of the IMNs to the heart and the association between cardiac RT exposure and toxicity. The objective of the study was to evaluate rates of ischemic cardiac events (ICEs) and associated risk with treatment of the IMN region. METHODS AND MATERIALS: The cardiac outcomes of 2126 patients treated with adjuvant breast RT or breast and nodal RT from 1984 to 2007 at a single institution were reviewed. The primary endpoint was an ICE following RT initiation. The association between IMN RT and ICEs was assessed using Cox proportional hazards models. Treatment with both IMN RT and 3-dimensional (3D) conformal radiation therapy (CRT) began in 1997; therefore, subset analyses of patients with only 3D CRT were performed to minimize bias associated with improved treatment technique. RESULTS: The median follow-up period was 9.3 years. An ICE occurred in 87 patients (4.1%). No increased 10-year rate of ICEs was observed with IMN RT compared with no IMN RT in the total cohort (3.2% [95% confidence interval (CI), 2.4%-4.3%] vs 3.4% [95% CI, 1.5%-7.5%]; hazard ratio [HR], 0.88; P=.73). Similarly, no statistically significant difference was noted in the 3D CRT-planned, left-sided disease subset (5.1% [95% CI, 1.8%-14.1%] vs 4.0% [95% CI, 2.0%-8.0%]; HR, 1.18, P=.76). On multivariate analysis, adjusting for cardiac risk factor imbalances, no significantly increased hazard was noted with IMN RT (HR, 1.84; P=.28) in the 3D CRT-planned, left-sided disease subset. CONCLUSIONS: No statistically significant association between IMN RT and ICEs was demonstrated in a review of patients treated at a single institution from 1984 to 2007. Given the long natural history and low overall rate of ICEs, continued follow-up of this study, as well as additional studies in the 3D CRT era, is warranted to confirm these results. Minimizing cardiac exposure, when treating a limited IMN field, is critical to limit excess risk of ICEs.

An analysis of knowledge-based planning for stereotactic body radiation therapy of the spine.

PURPOSE: Planning for spine stereotactic body radiation therapy (SBRT) is time consuming, and differences in planner experience and technique result in discrepancies in plan quality between facilities. Here, knowledge-based planning is analyzed to determine if it may be effective in improving the quality and efficiency of spine SBRT planning. MATERIALS AND METHODS: Thirty-eight spine SBRT cases were collected from the University of Michigan database and inverse planned to deliver 3 10-Gy fractions to the planning target volume (PTV). These plans were used to train a knowledge-based model (model A) using RapidPlan (Varian Medical Systems). The model was evaluated for outliers and validated in 10 independent cases. Each of these cases was manually planned to compare the quality of the model-generated plans with the manual plans. To further test the robustness of the software, 2 additional models (models B and C) were created with intentional outliers resulting from inconsistent contouring. RESULTS: Using models A, B, and C, all 10 generated plans met all dose objectives for modeled organs at risk (OARs) (spinal cord, cord planning risk volume, and esophagus) without user intervention. The target coverage and OAR dose sparing was improved or equivalent to manual planning by an expert dosimetrist; however, manually created plans typically required 1 to 1.5 hours to produce and model-generated plans required only 10 to 15 minutes with minimal human intervention to meet all dose objectives. CONCLUSIONS: The clinical quality of plans produced by RapidPlan were found to improve on or be similar to the manually created plans in terms of normal tissue objectives and PTV dose coverage and could be produced in a fraction of the time. RapidPlan is a robust technique that can improve planning efficiency in spine SBRT while maintaining or potentially improving plan quality and standardization across planners and centers.

Development of a model web-based system to support a statewide quality consortium in radiation oncology.

PURPOSE: A database in which patient data are compiled allows analytic opportunities for continuous improvements in treatment quality and comparative effectiveness research. We describe the development of a novel, web-based system that supports the collection of complex radiation treatment planning information from centers that use diverse techniques, software, and hardware for radiation oncology care in a statewide quality collaborative, the Michigan Radiation Oncology Quality Consortium (MROQC). METHODS AND MATERIALS: The MROQC database seeks to enable assessment of physician- and patient-reported outcomes and quality improvement as a function of treatment planning and delivery techniques for breast and lung cancer patients. We created tools to collect anonymized data based on all plans. RESULTS: The MROQC system representing 24 institutions has been successfully deployed in the state of Michigan. Since 2012, dose-volume histogram and Digital Imaging and Communications in Medicine-radiation therapy plan data and information on simulation, planning, and delivery techniques have been collected. Audits indicated >90% accurate data submission and spurred refinements to data collection methodology. CONCLUSIONS: This model web-based system captures detailed, high-quality radiation therapy dosimetry data along with patient- and physician-reported outcomes and clinical data for a radiation therapy collaborative quality initiative. The collaborative nature of the project has been integral to its success. Our methodology can be applied to setting up analogous consortiums and databases.

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial.

PURPOSE: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. METHODS AND MATERIALS: As part of an institutional review board-approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanning before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. RESULTS: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). CONCLUSIONS: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates.

Decline of cosmetic outcomes following accelerated partial breast irradiation using intensity modulated radiation therapy: results of a single-institution prospective clinical trial.

PURPOSE: To report the final cosmetic results from a single-arm prospective clinical trial evaluating accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) with active-breathing control (ABC). METHODS AND MATERIALS: Women older than 40 with breast cancer stages 0-I who received breast-conserving surgery were enrolled in an institutional review board-approved prospective study evaluating APBI using IMRT administered with deep inspiration breath-hold. Patients received 38.5 Gy in 3.85-Gy fractions given twice daily over 5 consecutive days. The planning target volume was defined as the lumpectomy cavity with a 1.5-cm margin. Cosmesis was scored on a 4-category scale by the treating physician. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). We report the cosmetic and toxicity results at a median follow-up of 5 years. RESULTS: A total of 34 patients were enrolled. Two patients were excluded because of fair baseline cosmesis. The trial was terminated early because fair/poor cosmesis developed in 7 of 32 women at a median follow-up of 2.5 years. At a median follow-up of 5 years, further decline in the cosmetic outcome was observed in 5 women. Cosmesis at the time of last assessment was 43.3% excellent, 30% good, 20% fair, and 6.7% poor. Fibrosis according to CTCAE at last assessment was 3.3% grade 2 toxicity and 0% grade 3 toxicity. There was no correlation of CTCAE grade 2 or greater fibrosis with cosmesis. The 5-year rate of local control was 97% for all 34 patients initially enrolled. CONCLUSIONS: In this prospective trial with 5-year median follow-up, we observed an excellent rate of tumor control using IMRT-planned APBI. Cosmetic outcomes, however, continued to decline, with 26.7% of women having a fair to poor cosmetic result. These results underscore the need for continued cosmetic assessment for patients treated with APBI by technique.

Dose to the inferior rectum is strongly associated with patient reported bowel quality of life after radiation therapy for prostate cancer.

PURPOSE: To evaluate rectal dose and post-treatment patient-reported bowel quality of life (QOL) following radiation therapy for prostate cancer. METHODS: Patient-reported QOL was measured at baseline and 2-years via the expanded prostate cancer index composite (EPIC) for 90 patients. Linear regression modeling was performed using the baseline score for the QUANTEC normal tissue complication probability model and dose volume histogram (DVH) parameters for the whole and segmented rectum (superior, middle, and inferior). RESULTS: At 2-years the mean summary score declined from a baseline of 96.0-91.8. The median volume of rectum treated to ≥70 Gy (V70) was 11.7% for the whole rectum and 7.0%, 24.4%, and 1.3% for the inferior, middle, and superior rectum, respectively. Mean dose to the whole and inferior rectum correlated with declines in bowel QOL while dose to the mid and superior rectum did not. Low (V25-V40), intermediate (V50-V60) and high (V70-V80) doses to the inferior rectum influenced bleeding, incontinence, urgency, and overall bowel problems. Only the highest dose (V80) to the mid-rectum correlated with rectal bleeding and overall bowel problems. CONCLUSIONS: Segmental DVH analysis of the rectum reveals associations between bowel QOL and inferior rectal dose that could significantly influence radiation planning and prognostic models.

Age and comorbid illness are associated with late rectal toxicity following dose-escalated radiation therapy for prostate cancer.

PURPOSE: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. METHODS AND MATERIALS: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. RESULTS: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. CONCLUSIONS: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

Quantifying dose to the reconstructed breast: can we adequately treat?

To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V(20). Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.