ESTRO 2023 - Abstract Book

S274

Sunday 14 May 2023

ESTRO 2023

Figure 1 Radiotherapy affects HNSCC derived CAFs A) Primary CAFs isolated from 5 HNSCC patients were cultured and subjected to irradiation (0, 2, 6, 10 or 18Gy). Cell growth was monitored with the Incucyte Live-Cell Analysis System. B) Representative fluorescent images of actin (red) and Hoechst (nucleus, blue) of HNSCC patient-derived CAFs, 11 days after irradiation. C) Average cell of 4 HNSCC patient-derived CAFs (CP3, CP7, CP8 and CP9), 11 days after irradiation. D) Representative fluorescent images of 53BP1 (green) and Hoechst (nucleus, blue), 24hrs after irradiation. E) Average number of CP3, CP6, CP7, CP8 and CP9 53BP1 foci 24hr, or F) 6 days after irradiation. G) Representative brightfield image of β - galactosidase staining of HNSCC patient-derived CAFs 11 days after irradiation. H) Average percentage of CP3, CP8 and CP9 b-galactosidase positive cells, 11 days after irradiation.

Symposium: How to optimise radiotherapy and immunotherapy combination

SP-0354 What is the clinical impact so far from IO/radiotherapy combination? P. Bonomo 1 1 Azienda Ospedaliero-Universitaria Careggi, Radiation Oncology, Florence, Italy

Abstract Text After more than a decade from the first revolutionary results of immune checkpoint inhibitors in advanced melanoma and lung cancer, the collective frenzy of oncologists worldwide for the introduction of immunotherapy (IO) into the therapeutic armamentarium of almost any kind of malignant tumors doesn’t seem to stop. Still, relatively few indications in the curative setting have been so far approved based on meaningful advancements of care. In particular, where do we stand in respect to the clinical impact associated with the combination of IO and radiotherapy? Let’s take a step back and go through the available evidence so far, with a focus on randomized phase 2/3 studies. As an introductory note, it is important to remind ourselves that unfortunately in the vast majority of cases we’ve witnessed a jump from preclinical data to large randomized, even registrative sometimes, trials, much like a “leap of faith”. In fact, the exact mechanistic interplay of IO and radiotherapy remains to be fully elucidated. Overall, when looking at the clinical impact of IO/radiotherapy combinations, some lights and shadows can be identified. Within the former, the practice-changing results in unresectable stage III non- small cell lung cancer (Pacific trial) and resected esophageal/gastroesophageal junction cancer (Checkmate 577 trial) highlighted the value of additive – sequential – strategies. Several other promising approaches have been presented in non- small cell lung cancer, as shown by the published Gemstone 301 and Coast studies. Among the shadows, the consistent negative findings of randomized trials in head and neck cancer (Javelin HN-100; Keynote 412; Reach; PembroRad; NRG- HN004) seemed to indicate that a classical “add-on” concurrent approach may not be the way to go, at least when adopting the standard concepts of (chemo) radiation. In addition, the lack of biomarker-driven selection is another caveat to be born in mind. The disappointing head and neck data were backed up by the negative results presented in the context of locally advanced cervical cancer (Calla trial). To summarize, many unknowns remain to be unraveled about IO/radiotherapy combinations: ultimately, their clinical impact in the curative setting across different tumors will need to be re-evaluated again in the near future. For the time being, well designed clinical trials based on sound biological hypotheses should continue to be warranted.