Effectiveness of radiotherapy in delaying treatment changes in primary or secondary immunorefractory oligoprogressive patients: preliminary results from a single-center study

Abstract

Abstract Aims To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). Material and methods Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan–Meier method and long-rank test. Results 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3–4) in patients with innate resistance vs 14 months (range 7–36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7–72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. Conclusion Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance.

Keywords

• Immunotherapy
• Radiotherapy
• Stereotactic radiotherapy
• Lattice radiotherapy
• Immune resistance
• Oligoprogressive