Toxicity and efficacy of combined stereotactic radiotherapy (SRT) and systemic targeted or immunotherapy (TOaSTT)

Study PI (Switzerland):

Prof. Dr. Matthias Guckenberger
University Hospital Zurich
Matthias.Guckenberger@usz.ch

Dr. Stephanie Kroeze, MD PhD
University Hospital Zurich
Stephanie.Kroeze@usz.ch

Study PI (Germany):

Prof. Dr. Anca Grosu
Universitätsklinikum Freiburg
anca.grosu@uniklinik-freiburg.de

Study design:

● multi-center, international retrospective study, followed by a
● multi-center prospective registry study

Study objective:

● To evaluate the safety of combined SRT and systemic targeted therapy or immunotherapy.
● To analyze efficacy and survival of combined SRT and systemic targeted therapy or immunotherapy.

Project status:

  • Study closed
  • Final analysis pending
  • 1 systematic review and multiple manuscripts published

Retrospective part:

● Data collection succesfully closed 01.07.2018
● 3 Abstracts accepted for oral presentations at the ESTRO 2019
● Several papers in preparation

Prospective part:

● Ethics approval obtained in Switzerland
● Data collection started in January 2017 and is ongoing
● The study is open to all interested institutions:
● Detailed information is provided here (SBRT_registry_info)

Major findings and results:

Kroeze SGC, Fritz C, Schaule J, et al (2021) Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis. Cancers (Basel) 13(19):4780.
https://pubmed.ncbi.nlm.nih.gov/34638265/

Kroeze SGC, Schaule J, Fritz C, et al (2021) Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database. Radiat Oncol 16(1):4.
https://pubmed.ncbi.nlm.nih.gov/33407611/

Kroeze SGC, Fritz C, Schaule J, et al (2020) Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma. BJU Int 127(6):703-711.
www.pubmed.ncbi.nlm.nih.gov/33113260/

  • 53 patients with metastatic renal cell carcinoma and 128 SRT treatments concurrently receiving targeted therapy or immunotherapy were retrospectively assessed for overall survival, progression-free survival, local metastasis control, time to systemic therapy, and toxicity
  • Median follow-up 12 months, 1 - 5 (median 1) metastatic lesions per patient treated with SRT, median biologically equivalent dose 65 Gy
  • 1-y-OS: 71%, 1-y-PFS: 25%, 1-y- LC: 75%
  • Oligometastatic disease state (≤ 5 syn.- or metachronous metastases) and performance status were independent prognostic factors for OS and PFS in multivariate analysis
  • No excess toxicity was recorded for combination treatment of SRT and targeted therapy or immunotherapy (G3 acute: 2 patients, G1 late: 1 patient, no G4 or G5)

Schaule J, Kroeze SGC, Blanck O, et al (2020) Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy. Radiat Oncol 15:135.
www.pubmed.ncbi.nlm.nih.gov/32487100/

  • 110 melanoma patients with a median of 2 brain metastases were assessed retrospectively (international “TOaSTT” database) for prognostic factors of overall survival
  • All patients had stereotactic radiotherapy to brain metastases and concurrent targeted therapy or immunotherapy
  • Median follow-up 8 months, median overall survival 8.4 months
  • The previously established molecular graded prognostic assessment model (molGPA) was not associated with overall survival. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous), and systemic therapy with concurrent targeted therapy vs. immunotherapy were significantly associated with overall survival in multivariate analysis
  • A new score for predicting survival in this context is proposed: VTS score (volume-timing-systemic therapy score)

Kroeze SGC, Fritz C, Basler L, et al (2019) Combination of stereotactic radiotherapy and targeted therapy: Patterns-of-care survey among German-speaking countries. Strahlenther Onkol 195(3):199-206.
https://pubmed.ncbi.nlm.nih.gov/30737541/

  • A survey on treatment practice of combined SRT and targeted- or immunotherapies was collected in 19 German-, 1 Austrian and 7 Swiss radiation oncology clinics.
  • SRT and targeted therapy or immunotherapy are given concurrently in 52% of clinics.
  • The majority of clinics pause targeted therapy or immunotherapy 1 week before and after SRT, irrespective of the type of systemic therapy given.

Kroeze SGC, Fritz C, Hoyer M, et al (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapies or immunotherapy: a systematic review. Cancer Treat Rev 53:25-3
https://pubmed.ncbi.nlm.nih.gov/28056412/

  • Data on toxicity of 49 published original articles evaluating concurrent treatment with stereotactic radiotherapy (SRT) and targeted therapy or immunotherapy up to april 2016 were collected.
  • Cranial SRT was mostly well tolerated when combined with the majority of immuno- or targeted therapies.
  • Increased toxicity was observed when cranial SRT was combined with BRAF inhibitors
  • For extra-cranial SRT, available toxicity information is more limited and needs to be evaluated separately for all combinations of drugs and treatment sites.

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