Innovative ablation techniques have gained momentum in the last decade in order to offer alternative approaches to patients not amenable to conventional surgery. Cryoablation, a procedure by which tumor cell death is induced through cycles of freezing and thawing, represents such a pioneering technique.~The procedure involves the insertion of a cryoprobe in the tumor bed with subsequent application of very low temperatures leading to cell necrosis and tumor antigens release. In the absence of significant heat-related denaturation seen in other ablative therapy techniques (microwave, radio frequency, steam, HIFU, etc.) and as intracellular content remains in circulation following cryo-activation, it is hypothesized that such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region.~This phenomenon would be reminiscent of the abscopal effect, a reaction mediated by locoregional radiotherapy exposure with the potential to trigger a systemic immune response prompting metastatic disease regression. While such immune activation would in itself be insufficient to eradicate tumor cells at distant sites, the addition of immunotherapy through checkpoint inhibition in the advanced setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses in patients with NSCLC.~A phase I/II clinical trial will be conducted in order to evaluate the safety and efficacy of cryo-activation therapy in patients with previously untreated advanced NSCLC amenable to anti-PD-1 monotherapy (i.e. PD-L1 ≥50%).
Cryo-activation involves the insertion of a cryoprobe in the tumor bed with subsequent cell necrosis and tumor antigens release. Such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region. The addition of cryo-activation to immune-checkpoint blockers (ICB) in the advanced NSCLC setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses