Racial Differences in Treatments and Toxicity in Non-Small Cell Lung Cancer Patients Treated with Thoracic Radiation Therapy

Background: Racial disparities are of particular concern for lung cancer patients given historical differences in surgery rates for African-American lung cancer patients that resulted in lower overall survival and higher recurrence rates compared with rates in White patients. Objectives: The overall objective of this study was to examine racial differences in thoracic radiation therapy (RT) treatments and toxicities in a large cohort of patients from a multi-institutional consortium database of non-small cell lung cancer (NSCLC) patients. Methods: A large multi-institutional statewide prospectively collected patient-level database of locally advanced (stage II or III) NSCLC patients who received thoracic RT from March 2012 to November 2019 was analyzed to assess the associations between race and treatment and toxicity variables. Race (White or African-American) was defined by patient self-report or if not available then by the electronic medical record system classification. Race categories other than White or African-American comprised a small minority of patients and were excluded from this analysis. Patient-reported toxicity was determined by validated tools including the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Provider-reported toxicity was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Uni-variable and multi-variable regression models were then fitted to assess relationships between primary outcomes by race and indicators of high-quality treatment and secondary analysis of symptoms. Spearman rank correlation coefficients were calculated between provider reported toxicity and similar patient reported outcomes for each race category. Results: A total of 1441 patients from 24 institutions with mean age of 68 years (range 38-94) were evaluated; 226 patients were African-American, of whom 61% were treated at three facilities. Race was not significantly associated with RT treatment approach, use of concurrent chemotherapy, or the dose to the planning target volume (PTV) or organs at risk including the heart and lungs. However, there was increased patient-reported general pain in African-American patients (compared with White patients) at several time points including pre-RT (22% (vs 15%), P=0.02) and at the end of RT (30% (vs 17%), P=0.001). African-American patients were significantly less likely to have provider-reported grade 2+ radiation pneumonitis (odds ratio (OR) 0.36, P=0.03), despite similar levels of patient-reported respiratory toxicities such as cough and shortness of breath and even after controlling for known patient and treatment-related factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race categories. Conclusions: In this large multi-institutional observational study, we reassuringly found no evidence of differences in radiation treatment or chemotherapy approaches by race, in contrast to historical differences by race in surgical care that led to worse survival and outcomes in minority race patients. However, we did unexpectedly find that African-American race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis despite similar patient-reported toxicities of shortness of breath and cough. There are several possibilities for this finding including that pneumonitis is a multifactorial diagnosis that relies on clinical as well as radiologic information and clinical information alone may be insufficient. The Spearman correlation analysis also revealed stronger correlations between patient- and provider-reported toxicities in White patients compared with African-American patients, particularly for trouble swallowing/esophagitis. These findings together for pneumonitis and esophagitis discouragingly suggest possible under-recognition of symptoms in black patients. Further investigation is now warranted to better understand how these findings impact the care of racially diverse lung cancer patients

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

Racial Differences in Treatments and Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Thoracic Radiation Therapy

PURPOSE: Historical racial disparities in lung cancer surgery rates resulted in lower survival in Black patients. Our objective was to examine racial differences in thoracic radiation treatments and toxicities in patients with non-small-cell lung cancer. METHODS AND MATERIALS: A large institutional review board-approved statewide patient-level database of patients with stage II-III non-small-cell lung cancer who received definitive thoracic radiation from March 2012 to November 2019 was analyzed to assess associations between race and other variables. Race (White or Black) was defined by patient self-report. Provider-reported toxicity was defined by Common Terminology Criteria for Adverse Events version 4.0. Patient-reported toxicity was determined by the Functional Assessment of Cancer Therapy-Lung quality-of-life instrument. Univariable and multivariable regression models were fitted to assess relationships between race and variables of interest. Spearman rank-correlation coefficients were calculated between provider-reported toxicity and similar patient-reported outcomes. RESULTS: One thousand four hundred forty-one patients from 24 institutions with mean age 68 years (range, 38-94 years) were evaluated. Race was not significantly associated with radiation or chemotherapy approach. There was significantly increased patient-reported general pain in Black patients at the preradiation and end-of-radiation time points. Black patients were significantly less likely to have provider-reported grade 2+ pneumonitis (odds ratio 0.36, P = .03), even after controlling for known patient and treatment factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race groups except for a stronger correlation between patient- and provider-reported esophagitis in White patients. CONCLUSION: In this large multi-institutional study, we found no evidence of racial differences in radiation treatment or chemotherapy approaches. We did, however, unexpectedly find that Black race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis. The stronger correlation between patient- and provider-reported esophagitis and swallowing symptoms for White patients also suggests possible under-recognition of symptoms in Black patients. Further research is needed to study the implications for Black patients

Racial Differences in Treatments and Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Thoracic Radiation Therapy

PURPOSE: Historical racial disparities in lung cancer surgery rates resulted in lower survival in Black patients. Our objective was to examine racial differences in thoracic radiation treatments and toxicities in patients with non-small-cell lung cancer. METHODS AND MATERIALS: A large institutional review board-approved statewide patient-level database of patients with stage II-III non-small-cell lung cancer who received definitive thoracic radiation from March 2012 to November 2019 was analyzed to assess associations between race and other variables. Race (White or Black) was defined by patient self-report. Provider-reported toxicity was defined by Common Terminology Criteria for Adverse Events version 4.0. Patient-reported toxicity was determined by the Functional Assessment of Cancer Therapy-Lung quality-of-life instrument. Univariable and multivariable regression models were fitted to assess relationships between race and variables of interest. Spearman rank-correlation coefficients were calculated between provider-reported toxicity and similar patient-reported outcomes. RESULTS: One thousand four hundred forty-one patients from 24 institutions with mean age 68 years (range, 38-94 years) were evaluated. Race was not significantly associated with radiation or chemotherapy approach. There was significantly increased patient-reported general pain in Black patients at the preradiation and end-of-radiation time points. Black patients were significantly less likely to have provider-reported grade 2+ pneumonitis (odds ratio 0.36, P = .03), even after controlling for known patient and treatment factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race groups except for a stronger correlation between patient- and provider-reported esophagitis in White patients. CONCLUSION: In this large multi-institutional study, we found no evidence of racial differences in radiation treatment or chemotherapy approaches. We did, however, unexpectedly find that Black race was associated with lower odds of provider-reported grade 2+ radiation pneumonitis. The stronger correlation between patient- and provider-reported esophagitis and swallowing symptoms for White patients also suggests possible under-recognition of symptoms in Black patients. Further research is needed to study the implications for Black patients

Predictors of Pneumonitis After Conventionally Fractionated Radiotherapy for Locally Advanced Lung Cancer

PURPOSE: Multiple factors influence the risk of developing pneumonitis after radiation therapy (RT) for lung cancer, but few resources exist to guide clinicians in predicting risk in an individual patient treated with modern techniques. We analyzed toxicity data from a state-wide consortium to develop an integrated pneumonitis risk model. METHODS AND MATERIALS: All patients (N = 1302) received conventionally fractionated RT for stage II-III non-small cell lung cancer between April 2012 and July 2019. Pneumonitis occurring within 6 months of treatment was graded by local practitioners and collected prospectively from 27 academic and community clinics participating in a state-wide quality consortium. Pneumonitis was modeled as either grade ≥2 (G2+) or grade ≥3 (G3+). Logistic regression models were fit to quantify univariable associations with dose and clinical factors, and stepwise Akaike information criterion-based modeling was used to build multivariable prediction models. RESULTS: The overall rate of pneumonitis of any grade in the six months following RT was 16% (208 cases). 7% (94 cases) were G2+ and \u3c1% (11 cases) were G3+. Adjusting for incomplete follow-up, estimated rates for G2+ and G3+ were 14% and 2%, respectively. In univariate analyses, gEUD, V5, V10, V20, V30, and Mean Lung Dose (MLD) were positively associated with G2+ pneumonitis risk, while current smoking status was associated with lower odds of pneumonitis. G2+ pneumonitis risk of ≥22% was independently predicted by MLD of ≥20 Gy, V20 of ≥35%, and V5 of ≥75%. In multivariate analyses, the lung V5 metric remained a significant predictor of G2+ pneumonitis even when controlling for MLD, despite their close correlation. For G3+ pneumonitis, MLD and V20 were statistically significant predictors. Number of comorbidities was an independent predictor of G3+, but not G2+ pneumonitis. CONCLUSIONS: We present an analysis of pneumonitis risk after definitive RT for lung cancer using a large, prospective dataset. We incorporate comorbidity burden, smoking status, and dosimetric parameters in an integrated risk model. These data may guide clinicians in assessing pneumonitis risk in individual patients

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