Survival Is Worse in Patients Completing Immunotherapy Prior to SBRT/SRS Compared to Those Receiving It Concurrently or After

PURPOSE/OBJECTIVES: The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies. MATERIALS AND METHODS: This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan–Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis. RESULTS: A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25). CONCLUSIONS: OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB)

Background: Stereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system. Method: This was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not. Results: A total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n = 44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n = 103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p < 0.001). The rate of complication was low and not statistically different between cohorts (p = 0.44). Conclusions: The FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked

Longitudinal monitoring for the emergence of epidermal growth factor C797S resistance mutations in non-small cell lung cancer using blood-based droplet digital PCR

Validation of assays for the C797S mutation as a biomarker for osimertinib resistance is promising in guiding treatment decision-making for multidrug resistant non-small cell lung cancer. A newly developed droplet digital PCR (ddPCR) assay was used to retrospectively evaluate the emergence of the C797S mutation in six remnant plasma samples in this case report. It was found that the detected emergence of C797S clearly correlated with clinical signs of treatment resistance. Had these data been available to aid treatment selection in real time, there would have been hope for recaptured disease response and control instead of treatment cessation. The results of this study show that highly sensitive ddPCR methods can be used for the monitoring of emergent epidermal growth factor somatic variant mutations in circulation

Response criteria in solid tumors (PERCIST/RECIST) and SUVmax in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy

Abstract Background The purpose of this study was to evaluate the prognostic impact of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) and of pre- and post-treatment maximum Standard Uptake Value (SUVmax) in regards to survival and tumor control for patients treated for early-stage non-small cell lung cancer (ES-NSCLC) with stereotactic body radiotherapy (SBRT). Methods This is a retrospective review of patients with ES-NSCLC treated at our institution using SBRT. Lobar, locoregional, and distant failures were evaluated based on PERCIST/RECIST and clinical course. Univariate analysis of the Kaplan-Meier curves for overall survival (OS), progression free survival (PFS), lobar control (LC), locoregional control (LRC), and distant control (DC) was conducted using the log-rank test. Pre- and post-treatment SUVmax were evaluated using cutoffs of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3. ∆SUVmax was also evaluated at various cutoffs. Cox regression analysis was conducted to evaluate survival outcomes based on age, gender, pre-treatment gross tumor volume (GTV), longest tumor dimension on imaging, and Charlson Comorbidity Index (CCI). Results This study included 95 patients (53 female, 42 male), median age 75. Lung SBRT was delivered in 3–5 fractions to a total of 48–60 Gy, with a BEDα/β = 10Gy of at least 100 Gy. Median OS and PFS from the end of SBRT was 15.4 and 11.9 months, respectively. On univariate analysis, PERCIST/RECIST response correlated with PFS (p = 0.039), LC (p = 0.007), and LRC (p = 0.015) but not OS (p = 0.21) or DC (p = 0.94). Pre-treatment SUVmax and post-treatment SUVmax with cutoff values of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3 did not predict for OS, PFS, LC, LRC, or DC. ∆SUVmax did not predict for OS, PFS, LC, LRC, or DC. On multivariate analysis, pre-treatment GTV ≥ 30 cm3 was significantly associated with worse survival outcomes when accounting for other confounding variables. Conclusions PERCIST/RECIST response is associated with improved LC and PFS in patients treated for ES-NSCLC with SBRT. In contrast, pre- and post-treatment SUVmax is not predictive of disease control or survival