SP-035: Deformable image registration - Commissioning and QA – Challenges
Radiotherapy and Oncology · 2019
ESTRO meets Asia 2019 S15 delivery.Immunotherapy, and in particular immunecheckpoint inhibitors targeting the PD-1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings of several trials in metastatic disease (1, 2).Radiation therapy combined with immunotherapy represent a new therapeutic opportunity, given the role of RT in reversing immunosuppressive barriers within the tumour microenvironment (3).The growing enthusiasm for immune-oncology and its possible applications in radiation oncology led to a remarkable expansion of pre-clinical and clinical studies testing various combinations of immunotherapeutic agents and radiation.Stage III unresectable NSCLC is an interesting setting for the combined use of chemo-radiation and immunotherapy, also considering the multiple experimental evidences in favor of a synergistic effect between radiation and immune checkpoint inhibitors, with the potential of enhancing immuno-modulating effects and overcoming resistance.Antonia et al, in PACIFIC trial (PD-L1 inhibitor Durvalumab vs placebo, unresectable stage III NSCLC who did not progress following concurrent platinum-based chemo-radiotherapy) showed a major improvement in 2year PFS (primary endpoint), especially when Durvalumab was administered within 2 weeks from end of RT (HR0.39 vs HR 0.63) (4).This finding suggests some positive effect of chemoradiotherapy on the efficacy of durvalumab.In the updated analysis, the PFS benefit has translated to a significant prolongation in OS, with a 24-month OS rate of 66.3% in the treatment group, compared with 55.6% in the placebo group (p =0.0025) (5).Based on these results, Durvalumab was approved for the treatment of patients with unresectable stage III NSCLC whose disease had not progressed after platinum-based CT-RT.In the PACIFIC trial post-hoc analysis, this survival benefit was prominent in the PD-L1-positive subgroup of patients (PD-L1 expression ≥1%), but no survival benefit was evident in the PD-L1-negative subgroup (PD-L1 expression <1%), suggesting that PD-L1 expression levels would probably be necessary to stratify patients (6).Even the use of Pembrolizumab (anti-PD-1 agent) is under investigation in a series of trials, while due to results of a phase I trial , criteria were met for advancement to part II of the study where Atezolizumab (another anti PD-L1 antibody) would be added to CT-RT followed by consolidation Atezolizumab, Carboplatin, and Paclitaxel.(7) Regarding the optimal timing when combining immunotherapy and CT-RT, considering the possibility to improve this synergism even further, more evidence is awaited from several ongoing trials.( 2)