ESTRO 2023

Session Item

Saturday

May 13

09:00 - 10:00

Business Suite 1-2

Palliative radiotherapy & SBRT

Chair: Nicolaus Andratschke, Switzerland

Session Type: Poster Discussion

Track: Clinical

Journey:

Metastases-directed SRT combined with systemic therapy: 2y results of the TOaSTT real-world database

, Switzerland

Presentation Number: PD-0064

Abstract

Abstract Title:

Metastases-directed SRT combined with systemic therapy: 2y results of the TOaSTT real-world database

Authors:

Stephanie Kroeze¹, Jana Schaule², Mathieu Spaas³, Klaus Henning Kahl⁴, Joost JC Verhoeff⁵, Famke L Schneiders⁶, Oliver Blanck⁷, Fabian Lohaus⁸, Susanne Rogers⁹, David Kaul¹⁰, Sergi Benavente¹¹, Stephanie E Combs¹², Georgios Skazikis¹³, Karin Baumann¹⁴, Ilinca Popp¹⁵, Friederike Koppe¹⁶, Hans Geinitz¹⁷, Katrien EA de Jaeger¹⁸, Shankar Siva¹⁹, Susanne Stera²⁰, Andrea Wittig-Sauerwein²¹, Victor Lewitzki²², Franziska Eckert²³, Markus M Schymalla²⁴, Matthias Guckenberger²

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

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Purpose or Objective

Metastases-directed stereotactic radiotherapy (SRT) is frequently performed in patients receiving immunotherapy (IT) or targeted therapy (TT), with different clinical goals like obtaining a durable control of resistant metastases, a prolongation of progression free survival or the prevention of a systemic therapy switch. Due to a lack of prospective data on this topic, our aim was to prospectively collect real-world data and examine the safety and efficacy of metastases-directed SRT combined with targeted therapy or immunotherapy.

Material and Methods

Patients treated with metastases-directed SRT performed concurrent (≤30d) to any type of TT or IT were included in the international multicenter prospective register trial (TOaSTT). Patients received SRT of brain metastases (BM) or extracranial lesions. Overall survival (OS), progression free survival (PFS) and time to discontinuation (TTD) of systemic therapy after SRT were analyzed using Kaplan-Meier survival curves and log rank testing. Treatment-related toxicity was measured using the CTCAE v4.03 criteria.

Results

Data of 1031 SRTs in 479 patients were analyzed. Primary cancer was melanoma (36%), NSCLC (37%), RCC (8%) and breast cancer (6%). ECOG-PS was 0-1 in 92% of patients. SRT of brain or extracranial metastases was performed in 273 and 208 patients, respectively. A median of 1 (range 1-15) lesions was treated with SRT, which was combined with immune checkpoint inhibitors (ICI) (61.4%), TT (29.4%) or antibodies (9%). TT/IT was mostly started before SRT in 69%, with a median of 112 days (range 1-2751) and was interrupted during SRT in 15% of patients, with a median break of 6 (range 1-56) days. Median OS was 24mo (95% CI 20-27mo), PFS 7mo (95% CI 5-9mo) and TTD 22mo (95% CI 19-25mo). 72% of progressing patients received repeat-SRT, radiotherapy or surgery instead of a systemic therapy switch. Severe acute and late SRT-related toxicity occurred in 6.6% and 6.9% of patients, respectively. These included n=5 G5 toxicities, which were all observed in the BRAF/MEKi and aPD-(L)1 group. Most acute severe toxicity was observed in the aPD-(L)1 (6%), aPD-1/aCTLA-4 (9%) and BRAF/MEKi (15%) group, severe late toxicity was most frequently observed in patients receiving concurrent aPD-(L)1 (4.8%), and aEGFR/EGFRi (21%). Overall, there was no significantly increased severe toxicity, whether TT/IT was continued or interrupted during SRT (p=0.098).

Conclusion

This prospectively collected real-world data observed that metastases-directed SRT combined with TT/IT had only short-term effect on the prevention of further distant progression, but enabled a systemic therapy discontinuation for almost one year. Severe SRT-induced toxicity was limited in both intracranial- and extracranial disease. The development of severe toxicity was not significantly influenced by continuation of these targeted agents during SRT.