Cardiac and pulmonary dosimetric parameters in lung cancer patients undergoing post-operative radiation therapy across a state-wide consortium

PURPOSE/OBJECTIVES: The recently published Lung ART trial reported increased rates of cardiac and pulmonary toxicity in the post-operative 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 post-operative RT for positive surgical margins. The purpose of this study is to examine heart and lung dose exposure in patients receiving post-operative radiation therapy for non-small cell lung cancer (NSCLC) across a statewide consortium. MATERIALS/METHODS: From 2012 to 2022, demographic and dosimetric data were prospectively collected for 377 patients at 27 academic and community centers within [redacted] undergoing PORT for non-metastatic NSCLC. Dosimetric parameters for target coverage and Organ at Risk (OAR) exposure were calculated using data from dose volume histograms, and rates of 3D-CRT and IMRT utilization were assessed. RESULTS: Fifty-one percent of patients in this cohort had N2 disease at the time of surgery, 25% had a positive margin. Sixty-six percent of patients were treated with IMRT compared to 32% with 3D-CRT. Planning target volume (PTV) was significantly smaller in patients treated with 3D-CRT (149.2 cc vs. 265.4 cc, p\u3c0.0001). Median mean heart dose for all patients was 8.7 Gy (IQR 3.5, 15.3), median heart V5 was 35.2% (IQR 18.5, 60.2) and median heart V35 was 9% (IQR 3.2, 17.7). Median mean lung dose (MLD) was 11.4 Gy (IQR 8.1, 14.3), median lung 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 vs. negative surgical margins. CONCLUSIONS: With increased rates of IMRT use, cardiac and lung dosimetric parameters in this state-wide consortium are slightly lower than those reported in Lung ART. These data provide useful benchmarks for treatment planning in patients undergoing post-operative RT for positive surgical margins

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 \u3e20 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(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 \u3c .0001), and the percentage of patients receiving MHD \u3e20 Gy was reduced from 21.1% to 10.3% (P \u3c .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

Prospective Evaluation of Limited-Stage Small Cell Lung Cancer Radiotherapy Fractionation Regimen Usage and Acute Toxicity in a Large Statewide Quality Collaborative

PURPOSE: National guidelines on limited stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy/30 fractions delivered twice-daily, however use of this regimen is uncommon compared to once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily RT regimens. METHODS AND MATERIALS: Demographic, clinical, and treatment data along with physician toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the [quality consortium] between 2012 and 2021 for patients with LS-SCLC. We modeled the influence of RT fractionation and other patient-level variables clustered by treatment site on the odds of a treatment break specifically due to toxicity with multilevel logistic regression. Common Terminology Criteria for Adverse Events, version 4.0, incident Grade 2 or worse toxicity was longitudinally compared between regimens. RESULTS: There were 78 patients (15.6% overall) treated with twice-daily RT and 421 patients treated with once-daily RT. Patients receiving twice-daily RT were more likely to be married/living with someone (65% vs 51%, p=0.019) and to have no major comorbidities (24% vs 10%, p=0.017). Once-daily RT fractionation toxicity peaked during RT and twice-daily toxicity peaked within 1 month after RT. After stratifying by treatment site and adjusting for patient-level variables, once-daily treated patients had a 4.11 (95% confidence interval 1.31-12.87) higher odds of treatment break specifically due to toxicity than twice-daily treated patients. CONCLUSION: Hyperfractionation for LS-SCLC remains infrequently prescribed despite the lack of evidence demonstrating superior efficacy or lower toxicity of once-daily RT. With peak acute toxicity after RT and lower likelihood of a treatment break with twice-daily fractionation in real-word practice, providers may start utilizing hyperfractionated RT more frequently

Prospective Evaluation of Limited Stage Small Cell Lung Cancer (LS-SCLC) Fractionation Regimen Usage and Toxicity in a Large Statewide Quality Collaborative

PURPOSE: National guidelines on limited stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy/30 fractions delivered twice-daily, however use of this regimen is uncommon compared to once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily RT regimens. METHODS AND MATERIALS: Demographic, clinical, and treatment data along with physician toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the [quality consortium] between 2012 and 2021 for patients with LS-SCLC. We modeled the influence of RT fractionation and other patient-level variables clustered by treatment site on the odds of a treatment break specifically due to toxicity with multilevel logistic regression. Common Terminology Criteria for Adverse Events, version 4.0, incident Grade 2 or worse toxicity was longitudinally compared between regimens. RESULTS: There were 78 patients (15.6% overall) treated with twice-daily RT and 421 patients treated with once-daily RT. Patients receiving twice-daily RT were more likely to be married/living with someone (65% vs 51%, p=0.019) and to have no major comorbidities (24% vs 10%, p=0.017). Once-daily RT fractionation toxicity peaked during RT and twice-daily toxicity peaked within 1 month after RT. After stratifying by treatment site and adjusting for patient-level variables, once-daily treated patients had a 4.11 (95% confidence interval 1.31-12.87) higher odds of treatment break specifically due to toxicity than twice-daily treated patients. CONCLUSION: Hyperfractionation for LS-SCLC remains infrequently prescribed despite the lack of evidence demonstrating superior efficacy or lower toxicity of once-daily RT. With peak acute toxicity after RT and lower likelihood of a treatment break with twice-daily fractionation in real-word practice, providers may start utilizing hyperfractionated RT more frequently.http://deepblue.lib.umich.edu/bitstream/2027.42/176789/2/1-s2.0-S1879850023001145-main.pdfPublished onlineDescription of 1-s2.0-S1879850023001145-main.pdf : Published versio

Association Between Physician and Patient Reported Symptoms in Patients Treated with Definitive Radiotherapy for Locally Advanced Lung Cancer in a Statewide Consortium

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

Randomized trial of laryngeal organ preservation evaluating two cycles of induction chemotherapy with platinum, docetaxel, and a novel Bcl-xL inhibitor

BackgroundSingle cycle induction chemotherapy (IC) with platinum and 5-flurouracil (PF) and treatment based on clinical response predicts organ preservation in laryngeal cancer. Other agents offer intriguing alternatives with potentially increased ease of administration, reduced risk for severe toxicities, and increased platinum sensitivity.MethodsWe report the results of a phase II bioselection trial in advanced resectable laryngeal cancer utilizing an IC regimen of two cycles of platinum plus docetaxel (TP) with a Bcl-2 inhibitor. The primary endpoint was organ preservation rate at 12 weeks post chemoradiation.ResultsFifty-four patients were enrolled. Response to IC was 72%. The organ preservation rate was 59% with a laryngectomy free survival of 46%. Induction related grade ≥3 toxicities were observed in 56% of patients with two grade 5 events.ConclusionsTwo cycles of TP IC plus a Bcl-2 inhibitor did not improve laryngeal preservation compared to a single cycle of PF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172949/1/hed27043_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172949/2/hed27043.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172949/3/hed27043-sup-0001-TableS1.pd