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Although systemic therapy has recently made strides, the 5-year survival rate of mRCC patients is still low — around 10%. Through the abscopal effect, SBRT can improve the antitumor immunity of PD-1 immune checkpoint inhibition (ICI) in metastatic RCC. OmRCC patients have a low tumor load and a favorable prognosis, so more active treatment strategies are needed. It might work even better when all lesions of omRCC are controlled by SBRT. The study aims to evaluate whether the antitumour immunity can be enhanced by combination of ICI and all-lesion SBRT for omRCC.
Patients with progression disease after ≤ 2 prior anti-angiogenic therapies and with ≤ 5 lesions located in ≤ 3 non-brain metastatic sites may all suitable for SBRT are included. Tislelizumab was given as 200 mg in intravenously on day 1, Q3W, until PD or unacceptable toxicity. Hypofractionated radiation at a dose and schedule of 5-8 Gy×3-10 fractions were performed according to lesion site, size and organs at risk individually. SBRT of first lesion were applied after 7 days from the first infusion of Tislelizumab. SBRT of other lesions were performed sequentially during the intervals of Tislelizumab. The primary objective is Objective Response Rate (ORR) according to RECIST v1.1. Secondary endpoints are progression free survival (PFS), overall survival (OS) and safety profile. An exploratory project also identifies molecular basis of synergistic effect of SBRT and immunotherapy, potential mechanisms of ICI resistance.
Fifteen patients were enrolled from May 2021 to May 2022. Totally 36 lesions were radiated, including 10 lung lesions (63 Gy/9 fractions), 10 bone lesions (24-40 Gy/5-8 fractions), 7 lymph nodes (30-50 Gy/6-10 fractions), 4 kidney lesions (40 Gy/5 fractions), and 5 other lesions. ORR were 33.3% for patients (CR=0, PR=5, SD=7, PD=2, not evaluable=1) and 27.8% for lesions (CR=2, PR=8, SD=11, PD=3, not evaluable=12). The most common treatment-related toxicities include fatigue (20%), hypothyroidism (20%), and pneumonia (13.3%), all with G1-2. One patient suffered G3 treatment-related hematologic toxicity. There were no treatment related deaths. Median PFS and OS were not reached.Conclusions:The combination of all-lesion SBRT with ICI is feasible and associated with an accepted safety profile. Encouraging antitumor activity was observed warranting further investigations. Clinical trial information: ChiECRCT20210046.