Lung Cancer Resection after Immunochemotherapy Versus Chemotherapy in Oligometastatic Nonsmall Cell Lung Cancer.

BACKGROUND: Neoadjuvant immunochemotherapy is currently being tested in pivotal trials for stage I to III nonsmall cell lung cancer (NSCLC). The impact of immunochemotherapy in patients with oligometastatic disease (OMD) remains undefined. This study aimed to compare the outcomes of radical treatment after the neoadjuvant course of immunochemotherapy versus chemotherapy. METHODS: We retrospectively analyzed patients with OMD who were treated with immunochemotherapy or chemotherapy combined with local ablation of metastases and radical primary tumor resection between 2017 and 2021. Group A included eight patients with immunochemotherapy; Group B included seven patients with chemotherapy. Descriptive statistical analysis included the characteristics of the patients, tumors, and outcomes. RESULTS: There was no difference in postoperative morbidity rates between the groups (p = 0.626). The 30-day mortality in both groups was 0%. The median overall survival for Group A was not reached, with a median follow-up time of 25 (range: 13-35) months; the median overall survival for Group B was 26 (range: 5-53) months. In Group A, all patients remained alive; in contrast, in Group B, four patients died (p = 0.026). There was no local thoracic recurrence in either group. In Group B, the recurrent disease was identified significantly more often (12.5 vs. 85.75%; p = 0.009). The rates of complete and major pathologic response were 37.5 and 0% in Group A and 42.85 and 14.25% in Group B, respectively. CONCLUSION: Despite the small patient number and short-term results, the progression-free and overall survival in patients with OMD after local therapy for metastases and primary tumor resection following a neoadjuvant course of immunochemotherapy might be promising compared with chemotherapy.

Functional and clinical characterization of the putative tumor suppressor WWOX in non-small cell lung cancer.

INTRODUCTION: The oxidoreductase WWOX was initially described as a putative tumor suppressor in breast cancer. Non-small cell lung cancers (NSCLCs) frequently show aberrant WWOX expression. Herein, we characterized WWOX at a functional level in preclinical NSCLC models and in primary NSCLC biopsies. METHODS: The human wild-type (wt) WWOX complementary DNA and a mutant WWOX with structurally disrupted short-chain dehydrogenase/reductase domain were conditionally expressed at physiological levels in several human NSCLC models. Resulting transgenic cell populations were analyzed with respect to clonogenic survival and apoptosis sensitivity in vitro and tumor growth in immune-deficient mice. Tissue microarrays prepared from surgically resected primary human NSCLC tumors were studied to correlate intratumoral WWOX expression with patient outcomes. RESULTS: Conditional expression of wt WWOX, but not mutant WWOX, suppressed clonogenic survival of NSCLC cells in vitro and tumor growth in vivo. In addition, preserved intratumoral WWOX expression was associated with improved outcome in a cohort of 85 patients with surgically resected NSCLC. Unexpectedly, wt WWOX failed to sensitize NSCLC cells to various apoptotic stimuli but robustly protected against apoptosis induced by inhibitors of growth factor signal transduction. CONCLUSIONS: WWOX acts as a tumor suppressor in human NSCLC models in a short-chain dehydrogenase/reductase domain-dependent manner. This activity is independent of sensitization to apoptotic cell death. WWOX expression as detected by immunohistochemistry may be a prognostic biomarker in surgically resected, early-stage NSCLC.