TY - JOUR
T1 - Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy
T2 - efficacy and safety reporting from the 'TOaSTT' database
AU - Kroeze, Stephanie G C
AU - Schaule, Jana
AU - Fritz, Corinna
AU - Kaul, David
AU - Blanck, Oliver
AU - Kahl, Klaus H
AU - Roeder, Falk
AU - Siva, Shankar
AU - Verhoeff, Joost J C
AU - Adebahr, Sonja
AU - Schymalla, Markus M
AU - Glatzer, Markus
AU - Szuecs, Marcella
AU - Geier, Michael
AU - Skazikis, Georgios
AU - Sackerer, Irina
AU - Lohaus, Fabian
AU - Eckert, Franziska
AU - Guckenberger, Matthias
N1 - Funding Information:
This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication.
Funding Information:
SA is supported by the German Cancer Consortium (DKTK), M Geier received a speaker fee from Roche and a speaker fee from Bristol-Myers-Squibb. SS is supported by a National Health and Medical Research Council (NHMRC) fellowship, and Cancer Council Victoria (CCV) Colebatch Fellowship. MS received a speaker fee from Merck Serono, AstraZeneca and Pierre Fabre. SK received a speaker fee from AstraZeneca.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Funding Information:
This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication.
Funding Information:
SA is supported by the German Cancer Consortium (DKTK), M Geier received a speaker fee from Roche and a speaker fee from Bristol-Myers-Squibb. SS is supported by a National Health and Medical Research Council (NHMRC) fellowship, and Cancer Council Victoria (CCV) Colebatch Fellowship. MS received a speaker fee from Merck Serono, AstraZeneca and Pierre Fabre. SK received a speaker fee from AstraZeneca.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Concurrent
KW - Immunotherapy
KW - NSCLC
KW - Oligometastases
KW - Radiotherapy
KW - Stereotactic
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85098801252&partnerID=8YFLogxK
U2 - 10.1186/s13014-020-01730-0
DO - 10.1186/s13014-020-01730-0
M3 - Article
C2 - 33407611
SN - 1748-717X
VL - 16
JO - Radiation Oncology [E]
JF - Radiation Oncology [E]
IS - 1
M1 - 4
ER -