Sinoatrial Node Dose Is Associated With Worse Survival in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Cancers.

PURPOSE: Our purpose was to evaluate the clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing stereotactic body radiation therapy (SBRT) for central non-small cell lung cancer (NSCLC) tumors. METHODS AND MATERIALS: A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located thoracic tumors from February 2007 to December 2021 was performed. The SAN and AVN were contoured in accordance with a published contouring atlas, and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and overall survival. RESULTS: Among 93 eligible patients, the median age was 72.5 years (IQR, 66.6-78.3), and median follow-up was 32.4 months (IQR, 13.0-49.6). The median SAN Dmax and Dmean were 95 cGy (range, 9-5394) and 58 cGy (range, 7-3168), respectively. The median AVN Dmax and Dmean were 45 cGy (range, 4-2121) and 34 cGy (range, 3-1667), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1309 and 836 cGy, respectively. No associations between AVN parameters and survival outcomes were identified. Upon multivariate Cox regression, the SAN Dmax cutoff (hazard ratio [HR], 2.03 [1.09-3.79]; P = .026) and SAN Dmean cutoff (HR, 2.22 [1.20-4.12]; P = .011) were significantly associated with overall survival. For noncancer-associated survival, the SAN Dmax cutoff trended toward significance (HR, 2.02 [0.89-4.57]; P = .092), and the SAN Dmean cutoff remained significantly associated (HR, 2.34 [1.05-5.18]; P = .037). CONCLUSIONS: For patients undergoing SBRT for NSCLC, SAN Dmax and Dmean were significantly associated with worse overall survival using cut-off values of 1309 and 836 cGy, respectively. Further studies examining the effect of SAN irradiation during SBRT are warranted.

Long-Term Survival and Failure Outcomes of Single-Fraction Stereotactic Body Radiation Therapy in Early Stage NSCLC.

Introduction: This study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. Methods: A single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. Results: Among 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70-81 y) and median follow-up time was 27.2 months (IQR: 14.25-44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4-2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6-50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. Conclusions: Consistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.

Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC.

BACKGROUND: The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. METHODS: A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan-Meier plotting, Fine-Gray competing risk MVA, and propensity score matching were performed. RESULTS: A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74-1.46) or PFS (aHR of 1.05, 95% CI of 0.76-1.45). On Fine-Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. CONCLUSION: The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy.

BACKGROUND: The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS: A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.

Brachial Plexopathy After Single-Fraction Stereotactic Body Radiation Therapy in Apical Lung Tumors.

PURPOSE: The objective of this study was to evaluate the incidence of brachial plexus injury (BPI) after single-fraction stereotactic body radiation therapy (SBRT) to apical lung tumors. METHODS AND MATERIALS: A retrospective cohort analysis was performed of all patients treated with single-fraction lung SBRT at our institution from 2007 to 2022. Apical tumors were identified as those with an epicenter located above the arch of the aorta. Dosimetric analysis of dose to the brachial plexus (BP) was done using both the subclavian vessel (SCV) surrogate structure and anatomic BP. BPI was assessed per Common Terminology Criteria for Adverse Events, version 4.0, as regional paresthesia, marked discomfort and muscle weakness, and limited movement of the arm or hand. RESULTS: A total of 45 patients met inclusion criteria with median follow-up of 21 months. There were 9 patients who exceeded the BP dose constraint using the SCV or anatomic BP volume. Only 1 patient (2.2%) developed grade 2 BPI, occurring 7 months after SBRT. Dose to the anatomic BP for the affected patient was 26.39 Gy. For the entire cohort, the median SCV and anatomic maximum BP doses were 8.44 and 7.14 Gy, respectively. CONCLUSIONS: There is considerable variability in dose delivered to the BP after SBRT to apical lung tumors. BPI after single-fraction SBRT to apical tumors is rare and rates are comparable with those reported with multifraction regimens.

Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer.

PURPOSE: RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials. METHODS AND MATERIALS: Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival. RESULTS: Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02). CONCLUSIONS: Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.

Treatment of locally advanced unresectable pancreatic cancer: a 10-year experience.

PURPOSE: We retrospectively analyzed the results of patients with locally advanced unresectable pancreatic cancer (LAPC) treated with either chemoradiation (CRT) or chemotherapy alone over the past decade. METHODS AND MATERIALS: Between December 1998 and October 2009, 116 patients with LAPC were treated at our institution. Eighty-four patients received concurrent chemoradiation [RT (+) group], primarily 5-flourouracil based (70%). Thirty-two patients received chemotherapy alone [RT (-) group], the majority gemcitabine based (78%). Progression-free survival (PFS) and overall survival (OS) were calculated from date of diagnosis to date of first recurrence and to date of death or last follow-up, respectively. Univariate statistical analysis was used to determine significant prognostic factors for overall survival. RESULTS: Median patient age was 67 years. Sixty patients were female (52%). Median follow-up was 11 months (range, 1.6-59.4 months). The RT (+) group received a median radiation dose of 50.4 Gy, was more likely to present with ECOG 0-1 performance status, and experienced less grade 3-4 toxicity. PFS was 10.9 versus 9.1 months (P=0.748) and median survival was 12.5 versus 9.1 months (P=0.998) for the RT (+) and RT (-) groups respectively (P=0.748). On univariate analysis, patients who experienced grade 3-4 toxicity had worse overall survival than those who did not (P=0.02). CONCLUSIONS: Optimal management for LAPC continues to evolve. Patients who developed treatment-related grade 3-4 toxicity have a poorer prognosis. Survival rates were not statistically significant between chemotherapy and chemoradiotherapy groups.