Timing of Surgery after Neoadjuvant Chemoradiation in Locally Advanced Non–Small Cell Lung Cancer

IntroductionA subset of patients with potentially resectable clinical stage IIIA NSCLC are managed with trimodality therapy. However, little data exist to guide the timing of surgery after neoadjuvant therapy. This study examined whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical resection affects overall survival.MethodsPatients with clinical stage IIIA disease (T1–3 N2) NSCLC who underwent NCRT were identified in the National Cancer Data Base (NCDB) between 2004 and 2012 and categorized on the basis of the interval between chemoradiation and surgery (0 to ≤3, >3 to ≤6, >6 to ≤9, and >9 to ≤12 weeks). Other clinical stages were excluded. The Kaplan-Meier method and log-rank tests were used to compare overall survival rates, and a bootstrapped Cox proportional hazards model was used to determine significant contributors to overall survival.ResultsOf the 1623 patients identified, 7.9% underwent an operation 0 to 3 weeks or less after NCRT, 50.5% underwent an operation greater than 3 and less than or equal to 6 weeks after NCRT, 31.9% underwent an operation greater than 6 and less than or equal to 9 weeks after NCRT, and 9.6% underwent an operation greater than 9 and less than or equal to 12 weeks after NCRT. Multivariate survival analysis demonstrated no significant difference in survival in those who underwent an operation within 6 weeks of NCRT. However, significant drops in overall survival were observed in those who had an operation greater than 6 and less than or equal to 9 weeks after NCRT (hazard ratio = 1.33, 95% confidence interval: 1.01–1.76, p = 0.043) and greater than 9 and less than or equal to 12 weeks after NCRT (hazard ratio = 1.44, 95% confidence interval: 1.04–2.01, p = 0.030).ConclusionsThe findings from this retrospective study suggest that overall survival may be significantly lower in patients with clinical stage IIIA N2 NSCLC who undergo an operation later than 6 weeks after NCRT. These results discourage unnecessary delays in surgery.     

Ablative Therapy for Oligometastatic Non–Small Cell Lung Cancer

The oligometastatic state represents a distinct entity among those with metastatic disease and consists of patients with metastases limited in number and location, representing an intermediate state between locally confined and widely metastatic cancer. Although similar, “oligorecurrence” (limited number of metachronous metastases under conditions of a controlled primary lesion) and “oligoprogressive” (disease progression at a limited number of sites with disease controlled at other disease sites) states are distinct entities. In non–small cell lung cancer (NSCLC), the oligometastatic state is relatively common, with 20% to 50% of patients having oligometastatic disease at diagnosis. This subgroup of patients when receiving ablative therapy, such as surgery or stereotactic body radiation radiotherapy, can obtain markedly long progression-free and overall survival. The role of radical treatment for intracranial oligometastases is well established. Fewer data exist regarding radical treatment of extracranial metastases in lung cancer; however, retrospective series using surgery or stereotactic body radiotherapy for extracranial oligometastatic disease in NSCLC have shown excellent local control, with a suggestion of improvement in progression-free survival. In the present report, we have reviewed the data on the treatment of brain metastases in oligometastatic NSCLC and the results of ablative treatment of extracranial sites. Recently, the first randomized trial comparing ablative treatment versus control in oligometastatic disease was reported, and those data are reviewed in the context of smaller series. Finally, areas of controversy are discussed and a therapeutic approach for patients with oligometastatic disease is proposed.     

Genomic Profiling of Advanced Non–Small Cell Lung Cancer in Community Settings: Gaps and Opportunities

Background

National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non–small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists.

Radiologic Pseudoprogression during Anti–PD-1 Therapy for Advanced Non–Small Cell Lung Cancer

Introduction

Anti–programmed cell death protein 1 (PD-1) therapy can lead to unconventional tumor responses, including radiologic pseudoprogression. Here we have determined the real-world incidence of radiologic pseudoprogression in advanced NSCLC and compared radiologic response criteria for assessment of disease response.

Application of Plasma Genotyping Technologies in Non–Small Cell Lung Cancer: A Practical Review

The rational treatment of metastatic NSCLC hinges on the timely detection of potentially targetable genomic alterations to guide therapy. Recent advances in highly sensitive genotyping technologies have allowed for development of novel plasma genotyping assays that are capable of noninvasively detecting targetable alterations in plasma cell-free DNA without reliance on traditional tissue genotyping. The rapid development of plasma genotyping has led to an explosion in the number of assay platforms available from both commercial and laboratory sources. The sheer number of such platforms has led to confusion among oncologists as to both the test characteristics and limitations of individual plasma genotyping assays and the clinical context in which these tests may be utilized either alone or in combination with traditional tissue genotyping. Reliable data from prospective validation against a tissue genotyping reference standard are available for only a limited number of platforms. Careful retrospective validation of alternative platforms utilizing paired tissue and plasma specimens collected under the auspices of clinical trials represent an alternative but reliable validation strategy. A consistent trend among these well-validated plasma genotyping assays has been the observation of high specificity and positive predictive value and more limited sensitivity. At present, validated assays can be considered actionable in instances in which a targetable genomic alteration is detected or an alternative nontargetable driver mutation is detected and can be used to infer the absence of one of the former.     

Immunological Aspects of Cryoablation of Non–Small Cell Lung Cancer: A Comprehensive Review

In cryoimmunotherapy, target tumors are treated with cryoablation to generate antitumor immune responses. Because immune checkpoint inhibitors have demonstrated that lung cancer can be an immunotherapy-responsive disease, there has been renewed interest in the immunological aspects of cryoablation of lung cancer. Herein, we review preclinical and clinical trials of cryoablation of primary lung tumors. We examine the magnitude of cryoablation-induced antitumor immune responses and the synergy between cryoablation and either other immunotherapies or molecular targeted therapies to improve treatment responses in advanced lung cancer. We further discuss a rationale for the addition of cryoablation to immune checkpoint inhibitors for the treatment of advanced lung cancer, which is currently under clinical investigation.