Search

Stereotactic body radiotherapy (SBRT) is standard for patients with inoperable early-stage NSCLC and is frequently utilized for pulmonary metastases with limited data. We hypothesized that SBRT for sarcoma pulmonary metastases would achieve high rates of local control with acceptable toxicity and that patients with oligometastatic disease may achieve prolonged survival following SBRT. This IRB-approved retrospective review included patients at our institution treated with SBRT for sarcoma pulmonary metastases. SBRT was delivered in 1 - 8 fractions at the discretion of the treating clinician. Patients were classified as oligometastatic if they had ≤ 3 sites of disease or progression at ≤ 3 sites of metastatic disease. Cumulative incidence of local failure (LF) was calculated using competing risks analysis and compared across groups using Grey's test. LF was defined as progression in the SBRT field on 2 consecutive follow-up scans with LF date backdated to the earliest scan showing progression. We also evaluated toxicity and overall survival from the time of SBRT. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across groups using the Log rank test and Cox proportional hazards regression. Between 2011 and 2021, 69 patients with 101 sarcoma pulmonary metastases were treated with SBRT to a median dose of 48 Gy (range: 25 – 60 Gy) in 4 fractions (range: 1 – 8 fractions). The most common histologies were leiomyosarcoma (n = 20 patients), liposarcoma (n = 8 patients), and osteosarcoma (n = 7 patients). The median follow-up time from SBRT was 26.1 months (95% CI 20.9-34.4) and 19.8 months for patients alive at last follow-up. A total of 35 patients (51%) were oligometastatic. The cumulative incidence of LF at 12 and 24 months was 6% (95% CI 3% to 12%) and 11% (95% CI 6% to 19%), respectively. The cumulative incidence of LF was significantly lower for peripheral compared to central lesions (12-month LF 11.4% vs 0% and 24-month LF 20.7% vs 0%, p = 0.002). OS at 12 and 24 months was 76% (95% CI 66% to 87%) and 52% (95% CI 40% to 67%), respectively. On univariable analysis, OS was significantly higher for patients with oligometastatic disease (12-month OS 85% vs 66%, p < 0.001, HR [95% CI] 0.29 [0.14, 0.59]) and Karnofsky Performance Status ≥ 90 (12-month OS 83 vs 63%, p =.03, HR [95% CI] 0.48 [0.24, 0.93]) but not age, sex, or time between initial pathologic diagnosis and SBRT. Among patients with oligometastatic disease, the median time to next systemic therapy or last follow-up was 10.0 months (range: 1 to 44.4 months). Three patients (4.3%) had grade 2 pneumonitis, and one patient (1.4%) had grade 2 esophagitis. No patients had ≥ grade 3+ toxicity. To the best of our knowledge, this is the largest series of patients treated with SBRT for pulmonary sarcoma metastases. SBRT offers a safe alternative to surgical resection with excellent local control. Minimal toxicity was observed. Patients with oligometastatic disease had prolonged survival after SBRT. [ABSTRACT FROM AUTHOR]

Radiation pneumonitis is an inflammatory process that can lead to substantial morbidity and mortality after thoracic radiotherapy. Though serum biomarkers have been proposed as predictors of radiation pneumonitis, there are no biomarkers that have proven to be clinically useful for monitoring the response of radiation pneumonitis to treatment. We sought to identify serum biomarkers that correlate with pulmonary exacerbations (PEs) from a phase II randomized trial studying the efficacy of nintedanib, a multiple tyrosine kinase inhibitor, plus a prednisone taper compared to placebo plus prednisone taper for the treatment of grade 2 or higher radiation pneumonitis. Blood was drawn from patients with grade 2+ pneumonitis prior to protocol treatment, at 6 and 12 weeks on treatment, and 6 months post-treatment. A panel of 108 biomarkers was evaluated with an immunoassay platform and 42 biomarkers were quantified by ELISA. To find biomarkers of interest, module-trait analysis was used to identify modules that correlated with the total number of PEs. A total of 24 biomarkers including those from the module of interest, targets of nintedanib, and previously reported biomarkers of pneumonitis were selected for individual analysis. Linear regression was used to calculate the slope of each biomarker for each patient over time. Univariable (UVA) associations of biomarker slopes (after transformation to improve convergence) with the total number of PEs were computed using Zero-inflated Poisson regression. The incidence rate ratios (IRR) of pulmonary exacerbations per unit increase in slope of the biomarker with 95% confidence intervals (CI) are reported. Biomarker results from 30 patients were analyzed, of which 19 had calculatable slopes. Of 19 modules identified, one module containing 11 biomarkers was associated with total PEs (p=0.002). On UVA, an increase in the slope of TNFSF12, IL-5, and IP-10 was associated with a statistically significant increase in the incidence of pulmonary exacerbations. An increase in the slope of EGF and a2M was associated with a decreased incidence of PEs. The findings are consistent with the pro- and anti-inflammatory roles of the respective biomarkers and provide insight into the dynamics of circulating biomarkers in active radiation pneumonitis. Additional study is warranted to validate the use of these biomarkers for monitoring treatment response in radiation pneumonitis. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Hydrogel rectal spacer placement (HSP) has been shown to minimize rectal dose during prostate cancer radiotherapy, yet its potential benefit for modulating rectal toxicity could in large part depend upon the quality of prostate-rectal separation achieved from HSP. We therefore developed a practical quality metric to evaluate HSP, validating its association with rectal dose reduction, as well as physician- and patient-reported rectal toxicity using a prospective dataset of men treated with prostate stereotactic body radiotherapy (SBRT).Materials/methods: Using the axial T2-weighted MRI images from a small pilot cohort of men with HSP who had been treated at our institution with prostate SBRT, a hydrogel spacer quality metric was devised from prostate-rectal space thickness (PRST) measurements. A score of 0, 1, or 2 was assigned to a PRST of < 0.3 cm, 0.3-0.9 cm, or ≥1 cm, respectively; an overall spacer quality score (SQS) was computed from individual scores (total of 9) at rectal midline and 1 cm to the right and left, located at the level of the prostate base, midgland, and apex. This quality metric was then applied to MRI simulation scans of 43 men with low/intermediate risk prostate cancer who had been enrolled on a multi-institutional phase II study to assess safety and efficacy of HSP during prostate SBRT. Associations between SQS and rectal dosimetry, late gastrointestinal (GI) toxicity, and EPIC bowel quality of life were quantified in these men treated with 45 Gy in 5 fractions.Results: Among this cohort, the majority had a SQS of 1 (n = 18; 42%) or 2 (n = 18; 42%). SQS was associated with maximum rectal point dose (rectal Dmax; P = 0.001), maximum dose to 1 cc of rectum (D1cc; P = 0.003), and volume of rectum receiving ≥100% of prescription dose (V45; P = 0.03). For those with SQSs of 0, 1 and 2, the median rectal Dmax (cGy) was 4683, 4600, and 3921, respectively. SQS was associated with incidence of late GI toxicity (P = 0.03) and highest late GI toxicity score (P = 0.02). Among the 20 men who developed late GI toxicity, 57%, 67% and 22% with Grade ≥1 had a SQS of 0, 1, and 2, respectively. Men with SQSs of 2 compared to 0-1 had 1.36 times lower odds of an increased rectal Dmax (95% CI: 1.14-1.63); and 1.20 times lower odds of an increased rectal D1cc (95% CI: 1.07-1.34). Men with SQSs of 2 versus 0-1 had 3.30 times lower odds of a higher late GI toxicity score (95% CI: 1.18-9.28). While evidence of a significant difference in baseline EPIC bowel summary score between SQSs was not observed (P = 0.07) as expected, men with SQSs of 2 compared to 0-1 had 3.52 times higher odds (95% CI: 0.91-13.64) of a superior bowel summary score 12 months from prostate SBRT.Conclusion: We developed a reliable, easy to use, and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late GI toxicity in men treated with prostate SBRT. [ABSTRACT FROM AUTHOR]