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.

Evaluation of Auto-Contouring and Dose Distributions for Online Adaptive Radiation Therapy of Patients With Locally Advanced Lung Cancers.

PURPOSE: Retrospective studies were performed to evaluate the accuracy of automatically mapped structures and dosimetric consequences of daily online adaptive radiation therapy (ART) for lung cancer treatments. METHODS AND MATERIALS: Ten patients with locally advanced lung cancer (prescription = 2 Gy × 30) with 297 fractions of treatment were selected for this retrospective study on a research emulator (Ethos, Varian Medical Systems). All adaptive treatments were simulated twice: automatic-ART (A-ART), automatic contours were used without modification, and supervised-ART (S-ART), automatic contours were modified manually by physicians and physicists. Dosimetric results were analyzed by relating supervised scheduled (S-SCH) dose (initial baseline reference plan delivered on daily anatomy and supervised contour correction without any adaptation), A-ART and S-ART to the initial baseline reference dose. RESULTS: Two hundred ninety (of 297) fractions were analyzed. Comparing target volumes between A-ART and S-ART, dice similarity coefficient was 0.93 ± 0.05, mean contour distance was 1.5 ± 1.2 mm, and Hausdorff distance was 4.0 ± 2.3 mm. Analysis of daily results over 290 fractions of treatment showed that average target coverage improved from 0.96 ± 0.04 (S-SCH) to 1.00 ± 0.02 (A-ART) and 1.02 ± 0.04 (S-ART); average upper dose constraint was reduced from 1.01 ± 0.11 (S-SCH) to 0.94 ± 0.10 (A-ART) and 0.93 ± 0.12 (S-ART). A-ART and S-ART improved planning target volume minimum doses by 4.85 ± 3.03 Gy (P = .049) and 4.46 ± 8.99 Gy (P = .058), respectively. Statistical analysis shows that A-ART and S-ART significantly improved cumulative target dose by 0.033 ± 0.087 (P = .002) and 0.032 ± 0.086 (P = .003) and reduced upper constraints by 0.033 ± 0.072 (P < .001) and 0.032 ± 0.072 (P < .001) relative to S-SCH dose results, respectively. CONCLUSIONS: Accuracy of Ethos automatic contouring for lung cancer is considered clinically acceptable. The online adaptive radiation therapy improves target coverage and spares organs-at-risk significantly.

Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort.

PURPOSE: Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. METHODS AND MATERIALS: Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. RESULTS: The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28). CONCLUSIONS: Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.

Influence of rotations on dose distributions in spinal stereotactic body radiotherapy (SBRT).

PURPOSE: To evaluate the impact of rotational setup errors on dose distribution in spinal stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Thirty-nine cone beam computed tomography (CBCT) scans from 16 SBRT treatment courses were analyzed. Alignment (including rotation) to the treatment planning computed tomography was performed, followed by translational alignment that reproduced the actual positioning. The planned fluence was then applied to determine the delivered dose to the targets and organs at risk. RESULTS: The mean planning target volume (PTV) was 71.01 mL (SD +/- 60.05; range, 22.62-250.65 mL). Prescribed dose (to the 62-82% isodose) was 14-30 Gy in one to six fractions. The average rotational displacements were 0.38 +/- 1.21, 1.12 +/- 1.82, and -0.51 +/- 2.0 degrees with maximal rotations of -4.29, 5.76, and -6.64 degrees along the x (pitch), y (yaw), and z (roll) axes, respectively. PTV coverage changed by an average of -0.07 Gy (SD +/- 0.20 Gy) between the rotated and the original plan, representing 0.92% of prescription dose (SD +/- 2.65%). For the spinal cord, planned with 2-mm expansion to create a planning organ at risk volume (PRV), the difference in minimum dose to the upper 10% of the PRV volume was 0.03 +/- 0.3 Gy (maximum, 0.9 Gy). Other organs at risk saw insignificant changes in dose. CONCLUSIONS: PRV expansion generally assures safe treatment delivery in the face of typically encountered rotations. Given the variability of delivered dose within this expansion for certain cases, caution should be taken to properly interpret doses to the cord when considering clinical dose limits.

Intraoperative radiotherapy of soft tissue sarcoma of the extremity.

PURPOSE: Evaluation of treatment outcome after intraoperative radiotherapy (IORT) +/- external-beam irradiation (EBRT) in patients with localized soft tissue sarcoma of the extremity at high risk for local recurrence after limb-sparing surgery. PATIENTS AND METHODS: 28 patients treated between 1989 and 1999 were evaluated retrospectively. Patients presented with locally recurrent (n = 17), T2 (n = 20), high-grade (n = 26), or incompletely resected tumors (n = 11). All patients underwent limbsparing surgery and IORT (median dose of 15 Gy) given either with high-dose-rate brachytherapy or a linear accelerator. 25 patients received additional EBRT with a mean of 50.6 Gy (range: 30.6-60 Gy). The mean follow-up time was 4.3 years (95% confidence interval [CI]: 3.0-5.6 years). RESULTS: The 5-year overall and distant disease-free survival rates were 66% and 54%, respectively. The overall actuarial recurrence rate after 5 years is 16% (95% CI: 1%, 31%). The crude rate after 8 years is 18%. Surgical margin status, primary versus recurrent tumor and tumor stage did not show any statistically significant influence (univariate analysis) on local recurrence rates. Patients with T1 tumors exhibited a borderline significant (p = 0.053) better distant disease-free survival (83%) compared to T2 tumors (43%). Five (24%) grade 3-4 late side effects were observed. CONCLUSION: In patients with high-risk soft tissue sarcomas, IORT +/- EBRT after limb-preserving surgery achieves high local control rates. The risk of normal tissue toxicities is comparable to conventional limb-sparing treatment.