Cardiac and Pulmonary Dosimetric Parameters in Lung Cancer Patients Undergoing Post-Operative Radiation Therapy in the Real-World Setting

Purpose/Objective(s): The recently published Lung ART trial reported increased rates of cardiac and pulmonary toxicity in the post-operative radiation therapy arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of real-world practice. 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 2020, 377 patients at 27 academic and community centers within the Michigan Radiation Oncology Quality Consortium (MROQC) underwent surgical resection followed by post-operative radiation therapy for non-metastatic NSCLC. Demographic and dosimetric data were prospectively collected for these patients. Rates of 3D-CRT and IMRT use were analyzed. Mean heart dose (MHD), heart V5, heart V35, mean lung dose (MLD), lung V20, target volume and minimum dose to 95% PTV were calculated for these patients and the reported dosimetric parameters were stratified by treatment modality. Results: 51% of patients in this cohort had N2 disease at the time of surgery, 18% had a positive margin. 65.8% of patients were treated with IMRT compared to 32.1% treated with 3D-CRT. Average MHD for all patients was 10.3 Gy, mean Heart V5 was 40.3% and mean heart V35 was 12.6%. Average MLD was 11.2 Gy and mean lung V20 was 18.9%. These dosimetric parameters did not significantly differ based on treatment modality, with MHD and MLD 9.9 Gy and 10.1 Gy, respectively, for patients treated with 3D-CRT compared to 10.6 Gy and 11.8 Gy for patients treated with IMRT. Conclusion: Cardiac and lung dosimetric parameters for patients receiving post-operative radiation therapy for NSCLC are similar to the dosimetric characteristics reported in Lung ART. The mean heart and mean lung doses observed are slightly lower (MHD 10.3 Gy, MLD 11.2 Gy) compared to Lung ART (MHD 13 Gy, MLD 13 Gy), possibly owing to increased use of IMRT. These data support application of Lung ART\u27s findings outside of the clinical trial setting

Use of Chemotherapy in Patients Receiving Hypofractionated Whole-Breast Irradiation: An Analysis within a State-Wide Quality Consortium

Purpose/Objective(s): Randomized clinical trials support the use of hypofractionated whole breast irradiation (H-WBI) in select patients with early stage breast cancer following breast conserving surgery. Patients who received chemotherapy (CHT) are not well represented on these trials. This study investigates whether receiving CHT prior to WBI is associated with increased toxicity or worse cosmetic outcomes. Materials/Methods: We identified 7,014 women in a state-wide radiation oncology quality consortium database who received WBI with a surgical cavity boost between 11/2011 and 8/2018. Toxicity data were available for 6,870 patients. Significant acute toxicity was defined as patient-reported moderate/severe breast pain (≥4/10), physician-reported CTCAE ≥grade 2 breast pain, or the development of moist desquamation between 7 days prior to and 42 days following the completion of radiotherapy. We determined rates of physician-reported fair/poor cosmetic outcome per the Harvard criteria in 2,012 patients who had ≥1 year of follow-up. Rates of significant acute toxicity and fair/poor cosmetic outcome were compared among patients receiving conventionally fractionated treatment (C-WBI) or H-WBI. Multivariable modeling, adjusting for age, race, BMI, breast volume, separation along the central axis, comorbidity index, smoking status, radiation planning technique, breast D50, triple negative breast cancer, pTis disease, treatment at an academic institution, and receipt of CHT, were used to quantify the strength of association, given as an odds ratio [95%CI], between patient or treatment related factors and clinical endpoints. Results: C-WBI and H-WBI most commonly comprised 45-50.4 Gy in 25-28 fractions and 40-42.72 Gy in 15-16 fractions, respectively. A boost of 10-16 Gy in 5-8 fractions and 10 in 4 fractions was most common for C-WBI and H-WBI, respectively. CHT was administered prior to radiation therapy in 1266 (35%) of the 3,628 patients who received C-WBI and in 558 (17%) of the 3,242 patients who received H-WBI. Crude rates of significant acute toxicity were 43% and 40% for patients receiving CHT followed by C-WBI and C-WBI without CHT, respectively, and 29% and 27% for patients receiving CHT followed by H-WBI and H-WBI without CHT, respectively. CHT was not associated with worse acute toxicity for patients receiving C-WBI (OR=0.94 [0.79-1.12], p=0.50) or H-WBI (OR=0.79 [0.63-1.00], p=0.054). CHT was not associated with increased rates of fair/poor cosmetic outcomes at 1 year (OR=1.21 [0.82-1.78], p=0.33), independent of fractionation. Conclusion: In this large, multi-center cohort, rates of significant acute toxicity and fair/poor cosmetic outcomes were not worse in patients receiving chemotherapy prior to whole breast irradiation, compared to patients who did not receive chemotherapy, regardless of fraction size

Analysis of the 2017 American Society for Radiation Oncology (ASTRO) Research Portfolio

© 2018 Elsevier Inc. Purpose: Research in radiation oncology (RO) is imperative to support the discovery of new uses of radiation and improvement of current approaches to radiation delivery and to foster the continued evolution of our field. Therefore, in 2016, the American Society of Radiation Oncology performed an evaluation of research grant funding for RO. Methods and Materials: Members of the Society of Chairs of Academic Radiation Oncology Programs (SCAROP) were asked about funded and unfunded grants that were submitted by their departments between the fiscal years 2014 and 2016. Grants were grouped according to broad categories defined by the 2017 American Society of Radiation Oncology Research Agenda. Additionally, active grants in the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools database were collated using RO faculty names. Results: Overall, there were 816 funded (44%) and 1031 unfunded (56%) SCAROP-reported grants. Total grant funding was over $196 million. The US government funded the plurality (42.2$85 million in funding. From the 31 responding SCAROP institutions, there was a 28% average success rate for RO proposals submitted to the NIH during this period. Conclusions: Though RO researchers from responding institutions were relatively successful in obtaining funding, the overall amount awarded remains small. Continued advocacy on behalf of RO is needed, as well as investment to make research careers more attractive areas for emerging faculty

Factors Associated with Patient-Reported and Physician-Assessed Acute Toxicity after Hypofractionated Breast Radiotherapy, a Report from a Large Multi-Center Cohort Study

Purpose/Objective(s): In 2018 ASTRO published an update to the 2011 evidence-based guideline for the use of hypofractionated whole breast irradiation (HF-WBI), increasing the patient populations for whom expert consensus supports the use of HF-WBI. While individualized decision making is encouraged, this updated guideline has been expanded to support HF-WBI for patients \u3c50 years, receipt of chemotherapy, larger separation distance, and a diagnosis of DCIS. For some of these indications, however, only moderate data exist. Thus, we now assess patient and physician reported toxicity data in a large prospective registry for populations not well represented on the trials and in whom there is less experience with this approach. Materials/Methods: Prospective data were evaluated from 2,083 patients receiving HF-WBI plus boost, treated between 1/1/2016 – 8/31/2018 at 24 academic and community centers participating in a statewide consortium. A composite toxicity endpoint was defined as occurrence of self-reported (4-10 modified brief pain inventory) or physician-assessed moderate or severe breast pain (CTCAE v. 4.0 grade 2-3) when patient report absent, and/or physician-assessed presence of moist desquamation. Logistic regression models were constructed isolating the effect of specific criteria from the 2011 HF-WBI guidelines, specifically age \u3c50 years, separation distance \u3e25cm, chemotherapy use, and DCIS. This was further adjusted for patient BMI, breast volume, race, comorbidity, smoking status, and IMRT. Results: Mean age was 62 years, mean separation was 22cm. Twenty-two percent of patients were treated for DCIS with the remaining 78% treated for invasive cancer; 17% of patients received chemotherapy. Of the 2,083 patients, 376 patients had more than one 2011 guideline discordance (for ex. \u3c50 years with chemotherapy), therefore 1707 patients were included in this analysis. On multivariable analysis, patients age \u3c 50 years were estimated to be 82% more likely to experience toxicity than older patients (OR=1.82, 95% CI: 1.11-2.97, p=0.02). While unadjusted difference on univariate analysis showed increased toxicity with separation \u3e 25 cm, multivariable analysis revealed no significant difference in toxicity for separation \u3e 25 cm(p=0.25), DCIS (p=0.6753), or treatment following chemotherapy p=0.10). Conclusion: Young breast cancer patients may be at increased risk of acute toxicity compared with other patients when receiving HF-WBI. Additional work is needed to determine why patients \u3c50 years, who were notably underrepresented in the prospective trials establishing the safety and efficacy of HF-WBI, may experience increased breast pain and dermatitis. Work is underway in our group to determine if this same increased risk is appreciated for patients \u3c50 years receiving conventionally fractionated radiotherapy

The impact of chemotherapy on toxicity and cosmetic outcome in patients receiving whole breast irradiation: an analysis within a state-wide quality consortium

PURPOSE: We investigated whether the use of chemotherapy prior to whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxicity or worse cosmetic outcome compared to WBI alone. METHODS AND MATERIALS: We identified 6,754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a state-wide consortium. We reported rates of four toxicity outcomes: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxicity measure (including moist desquamation and either patient-reported or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at one year following WBI. Successive multivariable models were constructed to estimate the impact of chemotherapy on these outcomes. RESULTS: Rates of moist desquamation, patient-reported pain, composite acute toxicity, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2,859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3,895 patients receiving HWBI. Receipt of chemotherapy prior to CWBI was not associated with higher rates of patient-reported pain, composite acute toxicity, or impaired cosmetic outcome compared to CWBI without chemotherapy but was associated with more moist desquamation (OR=1.32 [1.07-1.63], p=0.01). Receipt of chemotherapy prior to HWBI was not associated with higher rates of any of the four toxicity outcomes compared to HWBI alone. CONCLUSIONS: In this cohort, use of chemotherapy prior to WBI was generally well tolerated. CWBI with chemotherapy, but not to HWBI with chemotherapy, was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at one year were comparable in patients receiving chemotherapy prior to either CWBI or HWBI. These data support the use of HWBI following chemotherapy

Are We Missing Acute Toxicities Associated with Hypofractionated Breast Irradiation? A Report from a Large Multi-Center Cohort Study

Purpose/Objective(s): The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) has been established through multiple randomized trials. However, data on acute toxicities associated with HF-WBI remain more limited. Since 2013, our group has prospectively collected data on acute toxicities associated with HF-WBI based on weekly evaluation during treatment and assessment at 1 month after completion of radiotherapy. In October 2015, we intentionally shifted the post-treatment assessment time-point from 1 month to 2 weeks post-completion of treatment. This change was intended to evaluate whether a closer follow-up (f/u) might result in the detection of otherwise unobserved acute toxicities for patients receiving HF-WBI. In this study we report whether 2-week f/u has resulted in increased sensitivity for detecting acute toxicity as compared with 4-wk f/u. Materials/Methods: We prospectively compared acute toxicity for patients treated with HF-WBI at 25 participating institutions. We compared patients treated between 1/1/2013 and 8/31/2015 (before 2-week f/u up was adopted – “4 wk f/u cohort”) to patients treated between 1/1/2016 – 8/31/2018 (after adoption of a 2-week f/u – “2 wk f/u cohort”). Acute toxicity was considered the maximum reported composite toxicity from 7 days prior to the completion of radiotherapy until 42 days (6 weeks) following completion. Composite toxicity was defined as self-reported or physician-assessed moderate or severe breast pain, and/or physician-assessed presence of moist desquamation. Multivariable logistic regression models were used to assess difference in toxicity by cohort using ASTRO HF-WBI 2018 Guideline v. 2011 Guideline, and further adjusted for BMI, breast volume, race, presence of comorbidity, smoking status, and use of IMRT. Results: 2243 patients who received post-lumpectomy radiation and boost were analyzed, 1369 patients in the 2-wk f/u cohort and 874 in the 4-wk f/u cohort. Occurrence of composite acute toxicity was similar between the 2 cohorts, 28.4% for 2-wk f/u cohort vs 26.9% for the 4-wk f/u cohort, adjusted p=0.66. When analyzing only patients who met all ASTRO HF-WBI Guideline v. 2011 criteria, no difference in acute toxicity was noted; 26.5% with 2-wk f/u vs 25.0% with 4-wk f/u, adjusted p=0.83. Finally, with 2 wk f/u compared with 4 wk f/u, additional acute toxicities were not detected for patients who were younger \u3c50 years (p=0.72), received chemotherapy (p=0.93), had ductal carcinoma in-situ (p=0.13), or had separation \u3e25 cm, (p=0.43), yet otherwise guideline compliant. Conclusion: A closer post-treatment follow-up for patients receiving HF-WBI did not reveal a significant increased incidence of acute toxicities at 2 weeks compared to 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI and the appropriateness of the interval of follow-up

Association between Adverse Events and Quality of Life in Patients Treated with Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer

Purpose/Objective(s): Clinician-reported adverse events (AEs) and declines in patient-reported quality of life (QOL) are common during and after definitive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC), but associations between these two outcomes are not well known. The purpose of this study was to assess associations between AEs and patient reported outcomes (PROs) including QOL at different time points during and after definitive radiotherapy for LA-NSCLC in a state-wide consortium. Materials/Methods: Eligible patients included those treated with definitive RT for LA-NSCLC at 24 institutions within the Michigan Radiation Oncology Quality Consortium (MROQC) between 2012-2018 (n=1367). The Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) was collected at baseline, end of treatment, and at 1, 3 and 6 months post-RT. The FACT-TOI includes 3 QOL components: Physical Well Being (PWB), Functional Well Being (FWB), and Lung Cancer Subscale (LCS). Clinicians graded AEs using CTCAE weekly during RT and at the same follow-up visits. An AE score was calculated as the sum of AE grades for pneumonitis, pleuritic pain, cough, dyspnea, esophagitis and esophageal pain at each time point. Spearman correlation coefficients were calculated for AEs and similar PROs, and between AEs and change in each QOL component from baseline. Changes in QOL were compared at different time points for patients with grade ≥ 2 esophagitis (versus grade ≤ 1) and grade ≥ 2 pneumonitis (versus grade ≤ 1) using Student’s t-tests. Results: All QOL domains declined from baseline to the end of RT then recovered at different rates up to 6 months after RT. Mean AE scores at end of RT and 1, 3, and 6 months post-RT were 3.3, 2.3, 2.2, and 2.3, respectively. Correlation coefficients ranged from 0.36 to 0.66 for AEs and similar PROs. Among AEs, esophagitis had the strongest correlation with change in PWB (r=-0.32), while dyspnea had the strongest correlation with change in FWB (r=-0.21) and LCS (r=-0.31). Correlations for AE score were slightly greater, with r=-0.39 for PWB, r=-0.25 for FWB, and r=-0.36 for LCS. The difference in average change in QOL from baseline between the two esophagitis groups was clinically meaningful and statistically significant during the last week of RT for PWB, and at 1 month post-RT for PWB and FWB but not for LCS (statistically significant only). Differences between the pneumonitis groups were clinically meaningful at 6 months post-RT for PWB and LCS, but they were not statistically significant. Conclusion: Patients with higher quantity and severity of clinician-reported AEs have greater average declines in self-reported QOL during and after RT for LA-NSCLC. The associations between AEs and QOL were modest, however, suggesting that treatment-related AEs account for only a portion of QOL changes that patients experience, and reinforce the complementary nature of PROs and AEs

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