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Session Item

Monday
August 30
16:45 - 17:45
Room 1
Proffered papers 37: Immuno and targeted agents
Emmanouil Fokas, Germany;
Matthias Guckenberger, Switzerland
Proffered papers
Clinical
16:55 - 17:05
Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
Stephanie Kroeze, Switzerland
OC-0626

Abstract

Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
Authors:

Stephanie Kroeze1, Jana Schaule1, Mathieu Spaas2, Klaus H Kahl3, Joost JC Verhoeff4, Famke L Schneiders5, Oliver Blanck6, Fabian Lohaus7, Susanne Rogers8, David Kaul9, Sergi Benavente10, Stephanie E Combs11, Georgios Skazikis12, Karin Baumann13, Ilinca Popp14, Friederike Koppe15, Hans Geinitz16, Katrien EA de Jaeger17, Shankar Siva18, Susanne Stera19, Andrea Wittig-Sauerwein20, Victor Lewitzki21, Franziska Eckert22, Markus M Schymalla23, Matthias Guckenberger24

1University Hospital Zürich, Radiation Oncology, Zürich, Switzerland; 2Ghent University Hospital, Radiation Oncology, Ghent, Belgium; 3Universitätsklinikum Augsburg, Radiation Oncology, Augsburg, Germany; 4University Medical Center Utrecht, Radiation Oncology, Utrecht, The Netherlands; 5Amsterdam Univerisity Medical Center, Radiation Oncology, Amsterdam, The Netherlands; 6University Medical Center Schleswig-Holstein, Radiation Oncology, Kiel, Germany; 7Technische Universität Dresden, Radiation Oncology, Dresden, Germany; 8Kantonsspital Aarau , Radiation Oncology Center KSA-KSB, Aarau, Switzerland; 9Charité-University Hospital Berlin, Radiation Oncology, Berlin, Germany; 10Vall d'Hebron University Hospital, Radiation Oncology, Barcelona, Spain; 11Technical University Munich, Radiation Oncology, Munich, Germany; 12Schwarzwald-Baar Klinikum, Radiation Oncology, Villingen-Schwenningen, Germany; 13Klinikum Stuttgart, Radiation Oncology, Stuttgart, Germany; 14University of Freiburg, Radiation Oncology, Freiburg, Germany; 15Instituut Verbeeten, Radiation Oncology, Tilburg, The Netherlands; 16Ordensklinikum Linz, Radiation Oncology, Linz, Austria; 17Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands; 18Peter MacCallum Cancer Centre, Radiation Oncology, Melbourne, Australia; 19University Hospital Frankfurt, Frankfurt, Frankfurt, Germany; 20University Hospital Jena, Radiation Oncology, Jena, Germany; 21University Hospital Würzburg, Radiation Oncology, Würzburg, Germany; 22University Hospital Tübingen, Radiation Oncology, Tübingen, Germany; 23Philipps-University Marburg, Radiation Oncology, Marburg, Germany; 24Univerisity Hospital Zürich, Radiation Oncology, Zürich, Switzerland

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Purpose or Objective

Stereotactic radiotherapy (SRT) is increasingly performed in patients receiving targeted therapy (TT) and/or immunotherapy (IT) to obtain a durable local control and possibly improve prognosis or prolong the time to systemic therapy switch. However, knowledge on the safety of this approach remains limited. The aim of this study was to prospectively collect real-life data and examine the safety of SRT combined with targeted therapy or immunotherapy in metastatic cancer patients. 

Material and Methods

Metastatic cancer patients receiving SRT concurrent (≤30d) to any type of TT or IT were included in this international multicenter prospective register database (TOaSTT). Patients received SRT of brain metastases (BM) or extracranial lesions. Treatment-related toxicity was measured using the CTCAE v4.03 criteria. The primary endpoint of this study was severe acute (≤3 months) and late (>3 months) toxicity within one year following SRT. 

Results

Between July 2017 and August 2019, 1031 SRTs were performed in 479 patients from 27 centers. Patients were followed up for a minimum of 12 months. Most frequent histologies were NSCLC (37%), melanoma (36%), RCC (8%) and breast cancer (6%). Median age was 62 (range 26-88) years, ECOG-PS was 0-1 in 92% of patients. SRT of brain or extracranial metastases was performed in 273 and 208 patients, respectively. Median GTV volume was 2.1cc (range 0.1-54) for BM and 9.9cc (range 0.1-267) for extracranial lesions. The median prescribed dose was 20 Gy in 1 fraction for BM and 30Gy in 5 fractions for extracranial lesions. A median of 1 (range 1-15) lesions were treated simultaneously. SRT was combined with immune checkpoint inhibitors (ICI) (51%), ICI combined with targeted agents (TT) (10.4%), TT (29.4%) or antibodies (9%). TT/IT was started before SRT in 69%, with a median of 112 days (range 1-2751), 31% of patients started TT/IT concurrent with SRT, a median of 10 (range 1-30) days after SRT. TT was interrupted during SRT in 15% of patients, with a median break of 6 (range 1-56) days. Any grade acute and late SRT-related toxicity occurred in 50% and 44% of patients, respectively. Severe acute toxicity occurred in 6.6% of BM-SRT patients, including n=3 G5 toxicities. After extracranial SRT, severe acute toxicity was observed in 4.3% patients, with no G5 observed. Severe late toxicity was observed in 8.2% BM-SRT patients and 3.4% extracranial SRT patients. There was no significant difference in severe toxicity whether TT/IT was interrupted or not (p=0.373 acute toxicity, p=0.216 for late toxicity).

Conclusion

This real-life database is the first to prospectively report the risk of toxicity of combined SRT and targeted therapy or immunotherapy in metastatic cancer patients. Overall, severe toxicity was observed in <10% of the patients treated for brain and extracranial metastases. There was no increased toxicity when TT/IT was not interrupted during SRT.