Stephanie G C Kroeze1, Jana Schaule2, Corinna Fritz3, David Kaul4, Oliver Blanck5, Klaus H Kahl6, Falk Roeder7, Shankar Siva8, Joost J C Verhoeff9, Sonja Adebahr10, Markus M Schymalla11, Markus Glatzer12, Marcella Szuecs13, Michael Geier14, Georgios Skazikis15, Irina Sackerer16, Fabian Lohaus17, Franziska Eckert18, Matthias Guckenberger2. 1. Department of Radiation Oncology, University Hospital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland. Stephanie.kroeze@usz.ch. 2. Department of Radiation Oncology, University Hospital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland. 3. Department of Radiation Oncology, Marienhospital Stuttgart, Böheimstrasse 37, 70199, Stuttgart, Germany. 4. Department of Radiation Oncology, Charité-University Hospital Berlin, Charitestraße 1, 10117, Berlin, Germany. 5. Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Arnold-Heller-Straße 3, Haus 50, 24105, Kiel, Germany. 6. Department of Radiation Oncology, University Clinic Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany. 7. Department of Radiation Oncology, University Hospital Munich, Georgenstraße 5, 80799, Munich, Germany. 8. Department Or Radiation Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, 3000, Australia. 9. Department of Radiation Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. 10. Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany. 11. Department of Radiation Oncology, Philipps-University Marburg, Baldingerstraße, 35043, Marburg, Germany. 12. Department of Radiation Oncology, Saint Gallen Cantonal Hospital, Rorschacher Str. 95/Haus 03, 9007, St. Gallen, Switzerland. 13. Department of Radiation Oncology, University Hospital Rostock, Südring 75, 18059, Rostock, Germany. 14. Department of Radiation Oncology, Ordensklinikum Linz, Fadingerstraße 1, 4020, Linz, Austria. 15. Department of Radiation Oncology, Schwarzwald-Baar Klinikum, Klinikstraße 11, 78050, Villingen-Schwenningen, Germany. 16. Department of Radiation Oncology, Strahlentherapie Freising Und Dachau, Biberstraße 15, 85354, Freising, Germany. 17. Department of Radiation Oncology, University Hospital Dresden, Händelallee 28, 01309, Dresden, Germany. 18. Department of Radiation Oncology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Abstract
BACKGROUND: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients. METHODS: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. RESULTS: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related. CONCLUSIONS: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation. TRIAL REGISTRATION: retrospectively registered.
BACKGROUND: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLCpatients. METHODS: A retrospective multicenter cohort of stage IV NSCLCpatients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. RESULTS:MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPDpatients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related. CONCLUSIONS:Metastases-directed SRT in NSCLCpatients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation. TRIAL REGISTRATION: retrospectively registered.