Cryotherapy for nodal metastasis in NSCLC with acquired resistance to immunotherapy

Abstract

Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwent two lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes.

Clinical pattern of failure after a durable response to immune checkpoint inhibitors in non-small cell lung cancer patients

“…Gettinger et al reported that 11 NSCLC patients continued immunotherapy beyond AR 13 . Adam LC et al reported an AR case of successful local control with cryotherapy combined with immunotherapy beyond progression 23 . Further analysis will help to define the clinical benefit for NSCLC patients with a durable response treated with ICI beyond progression.…”

<p>Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC</p>

“…3 In order to prevent NSCLC metastasis to prolong the survival of patients, several approaches have been proposed, such as traditional Chinese medicine therapy, the development of new compounds, chemo-immunotherapy, etc. [4][5][6] Among them, the chemo-immunotherapy combinations will become the first-line treatment for NSCLC, which significantly improved the progression-free survival (PFS) and overall survival (OS) rates of these patients. First-line chemoimmunotherapy combinations are starting to and will certainly revolutionize the current paradigm of metastatic NSCLC treatment because of their superior performance in PFS and OS, compared to the based chemotherapy.…”

Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression

“…The excellent response to PD-1 blockade despite negative PD-L1 status could be due to numerous mechanisms. Cryoablation has been suggested to sensitize tumors to immunotherapy [ 7 , 8 ]. In one proposed mechanism, tumor antigens released after cryoablation are taken up by antigen-presenting cells, which mature and induce tumor-specific T-cell activation and proliferation [ 9 ].…”