Abstract

Evert S.M. van Aken¹, Yvette M. van der Linden², Corrie A.M. Marijnen^1,2, Johannes V. van Thienen³, Adrianus J. de Langen⁴, Monique C. de Jong¹

¹The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Department of Radiation Oncology, Amsterdam, The Netherlands; ²Leiden University Medical Center, Department of Radiation Oncology, Leiden, The Netherlands; ³The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam, The Netherlands; ⁴The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Department of Thoracic Oncology, Amsterdam, The Netherlands

With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the overall survival of advanced cancer patients has vastly improved for many tumor types. Although it is unclear whether hypofractionated radiotherapy combined with these drugs is safe, patients are increasingly referred. No international guidelines or consensus exist on whether or how to combine these drugs with radiotherapy. Therefore, the purpose of this study was to investigate the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.

A survey was sent to all 21 Dutch radiotherapy institutions via the Dutch Society for Radiotherapy and Oncology (NVRO). Dedicated radiation oncologists (ROs), medical oncologists (MOs) and pulmonologists (Ps) were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, encountered clinical difficulties and (factors influencing) treatment decisions.

The survey was filled out by 54 respondents from 19 different institutes (27 ROs, 10 MOs and 17 Ps). The median annual number of patients per RO referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of ROs state that they have sufficient information (resources) for adequate treatment decision making. Just 31% of all respondents (strongly) agree that there is sufficient knowledge within their institute regarding this topic. A multidisciplinary protocol is rarely available (17%) and the application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varies widely. ROs, MOs and Ps have different opinions about the toxicity of drug-radiotherapy combinations and the risk of tumor flare upon temporary drug discontinuation (Fig. 1).

Radiotherapy referral during targeted drugs or immunotherapy occurs regularly in clinical practice. There is no consensus amongst involved medical specialties on toxicity and whether to combine or discontinue systemic treatment. An urgent need for multidisciplinary, evidence-based guidelines for the optimal management of these patients exists. It is necessary to perform clinical studies examining the safety of these combined treatments and to incorporate radiotherapy into phase I-III clinical trials for new targeted drugs and immunotherapy.