Factors associated with acute esophagitis during radiation therapy for lung cancer.

INTRODUCTION: Limiting acute esophagitis remains a clinical challenge during the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Demographic, dosimetric, and acute toxicity data were prospectively collected for patients undergoing definitive radiation therapy +/- chemotherapy for stage II-III NSCLC from 2012 to 2022 across a statewide consortium. Logistic regression models were used to characterize the risk of grade 2 + and 3 + esophagitis as a function of dosimetric and clinical covariates. Multivariate regression models were fitted to predict the 50 % risk of grade 2 esophagitis and 3 % risk of grade 3 esophagitis. RESULTS: Of 1760 patients, 84.2 % had stage III disease and 85.3 % received concurrent chemotherapy. 79.2 % of patients had an ECOG performance status ≤ 1. Overall rates of acute grade 2 + and 3 + esophagitis were 48.4 % and 2.2 %, respectively. On multivariate analyses, performance status, mean esophageal dose (MED) and minimum dose to the 2 cc of esophagus receiving the highest dose (D2cc) were significantly associated with grade 2 + and 3 + esophagitis. Concurrent chemotherapy was associated with grade 2 + but not grade 3 + esophagitis. For all patients, MED of 29 Gy and D2cc of 61 Gy corresponded to a 3 % risk of acute grade 3 + esophagitis. For patients receiving chemotherapy, MED of 22 Gy and D2cc of 50 Gy corresponded to a 50 % risk of acute grade 2 + esophagitis. CONCLUSIONS: Performance status, concurrent chemotherapy, MED and D2cc are associated with acute esophagitis during definitive treatment of NSCLC. Models that quantitatively account for these factors can be useful in individualizing radiation plans.

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.

Cardiac and Pulmonary Dosimetric Parameters in Patients With Lung Cancer Undergoing Postoperative Radiation Therapy Across a Statewide Consortium.

PURPOSE: The recently published Lung Adjuvant Radiotherapy Trial (Lung ART) reported increased rates of cardiac and pulmonary toxic effects in the postoperative radiation therapy (PORT) arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of contemporary real-world practice, which remains relevant for patients undergoing PORT for positive surgical margins. The purpose of this study was to examine heart and lung dose exposure in patients receiving PORT for non-small cell lung cancer across a statewide consortium. METHODS AND MATERIALS: From 2012 to 2022, demographic and dosimetric data were prospectively collected for 377 patients at 27 academic and community centers within the Michigan Radiation Oncology Quality Consortium undergoing PORT for nonmetastatic non-small cell lung cancer. Dosimetric parameters for target coverage and organ-at-risk exposure were calculated using data from dose-volume histograms, and rates of 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) utilization were assessed. RESULTS: Fifty-one percent of patients in this cohort had N2 disease at the time of surgery, and 25% had a positive margin. Sixty-six percent of patients were treated with IMRT compared with 32% with 3D-CRT. The planning target volume was significantly smaller in patients treated with 3D-CRT (149.2 vs 265.4 cm3; P < .0001). The median mean heart dose for all patients was 8.7 Gy (interquartile range [IQR], 3.5-15.3 Gy), the median heart volume receiving at least 5 Gy (V5) was 35.2% (IQR, 18.5%-60.2%), and the median heart volume receiving at least 35 Gy (V35) was 9% (IQR, 3.2%-17.7%). The median mean lung dose was 11.4 Gy (IQR, 8.1-14.3 Gy), and the median lung volume receiving at least 20 Gy (V20) was 19.6% (IQR, 12.7%-25.4%). These dosimetric parameters did not significantly differ by treatment modality (IMRT vs 3D-CRT) or in patients with positive versus negative surgical margins. CONCLUSIONS: With increased rates of IMRT use, cardiac and lung dosimetric parameters in this statewide consortium were slightly lower than those reported in Lung ART. These data provide useful benchmarks for treatment planning in patients undergoing PORT for positive surgical margins.

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.

Effect of Education and Standardization of Cardiac Dose Constraints on Heart Dose in Patients With Lung Cancer Receiving Definitive Radiation Therapy Across a Statewide Consortium.

PURPOSE: Cardiac radiation exposure is associated with an increased rate of adverse cardiac events in patients receiving radiation therapy for locally advanced non-small cell lung carcinoma (NSCLC). Previous analysis of practice patterns within the Michigan Radiation Oncology Quality Consortium (MROQC) revealed 1 in 4 patients received a mean heart dose >20 Gy and significant heterogeneity existed among treatment centers in using cardiac dose constraints. The purpose of this study is to analyze the effect of education and initiation of standardized cardiac dose constraints on heart dose across a statewide consortium. METHODS AND MATERIALS: From 2012 to 2020, 1681 patients from 27 academic and community centers who received radiation therapy for locally advanced NSCLC were included in this analysis. Dosimetric endpoints including mean heart dose (MHD), mean lung dose, and mean esophagus dose were calculated using data from dose-volume histograms. These dose metrics were grouped by year of treatment initiation for all patients. Education regarding data for cardiac dose constraints first occurred in small lung cancer working group meetings and then consortium-wide starting in 2016. In 2018, a quality metric requiring mean heart dose <20 Gy while maintaining dose coverage (D95) to the target was implemented. Dose metrics were compared before (2012-2016) versus after (2017-2020) initiation of interventions targeting cardiac constraints. Statistical analysis was performed using the Wilcoxon rank sum test. RESULTS: After education and implementation of the heart dose performance metric, mean MHD declined from an average of 12.2 Gy preintervention to 10.4 Gy postintervention (P < .0001), and the percentage of patients receiving MHD >20 Gy was reduced from 21.1% to 10.3% (P < .0001). Mean lung dose and mean esophagus dose did not increase, and target coverage remained unchanged. CONCLUSIONS: Education and implementation of a standardized cardiac dose quality measure across a statewide consortium was associated with a reduction of mean heart dose in patients receiving radiation therapy for locally advanced NSCLC. These dose reductions were achieved without sacrificing target coverage, increasing mean lung dose, or increasing mean esophagus dose. Analysis of the clinical ramifications of the reduction in cardiac doses is ongoing.

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.

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.

Contemporary Practice Patterns for Palliative Radiation Therapy of Bone Metastases: Impact of a Quality Improvement Project on Extended Fractionation.

PURPOSE: Radiation therapy effectively palliates bone metastases, although variability exists in practice patterns. National recommendations advocate against using extended fractionation (EF) with courses greater than 10 fractions. We previously reported EF use of 14.8%. We analyzed practice patterns within a statewide quality consortium to assess EF use in a larger patient population after implementation of a quality measure focused on reducing EF. METHODS AND MATERIALS: Patients treated for bone metastases within a statewide radiation oncology quality consortium were prospectively enrolled from March 2018 through October 2020. The EF quality metric was implemented March 1, 2018. Data on patient, physician, and facility characteristics; fractionation schedules; and treatment planning and delivery techniques were collected. Multivariable binary logistic regression was used to assess EF. RESULTS: Twenty-eight facilities enrolled 1445 consecutive patients treated with 1934 plans. The median number of treatment plans per facility was 52 (range, 7-307). Sixty different fractionation schedules were used. EF was delivered in 3.4% of plans. Initially, EF use was lower than expected and remained low over time. Significant predictors for EF use included complicated metastasis (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.04-4.02; P = .04), lack of associated central nervous system or visceral disease (OR, 2.27; 95% CI, 1.2-4.2; P = .01), nonteaching versus teaching facilities (OR, 8.97; 95% CI, 2.1-38.5; P < .01), and treating physicians with more years in practice (OR, 12.82; 95% CI, 3.9-42.4; P < .01). CONCLUSIONS: Within a large, prospective population-based data set, fractionation schedules for palliative radiation therapy of bone metastases remain highly variable. Resource-intensive treatments including EF persist, although EF use was low after implementation of a quality measure. Complicated metastases, lack of central nervous system or visceral disease, and treatment at nonteaching facilities or by physicians with more years in practice significantly predict use of EF. These results support ongoing efforts to more clearly understand and address barriers to high-value radiation approaches in the palliative setting.

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.