Single-port video-assisted thoracoscopic sleeve lobectomy after neoadjuvant immunochemotherapy: a case report.

Background: The morbidity and mortality of lung cancer have always ranked first among malignant tumors (MTs). Previous studies have shown that neoadjuvant chemotherapy can improve the 5-year survival rate of patients with non-small cell lung cancer (NSCLC), but the benefit is limited. Studies have proven that neoadjuvant immunotherapy combined with chemotherapy has unique advantages in prolonging patient survival, reducing distant recurrence, and inducing antitumor immunity. However, its impact remains to be more comprehensively investigated. Case Description: A 59-year-old male who was admitted to the hospital with a primary complaint of repeated cough and expectoration for 6 months. Preoperative assessment showed right upper lung squamous cell carcinoma with multiple hilar and mediastinal lymph node metastasis, and the clinical stage was cT2aN2M0 stage (IIIA). After three cycles of pembrolizumab + carboplatin + paclitaxel therapy were administered, the reexamination of the tumor was evaluated as partial response (PR), and a sleeve lobectomy of the right upper lung was performed under single-port thoracoscopic surgery. The operation proceeded smoothly without conversion to thoracotomy, and R0 resection was successfully achieved. Postoperative pathological stage was ypT1bN0M0 stage IA, and postoperative pathological remission was evaluated as major pathological response (MPR). After the operation, three cycles of immunotherapy combined with chemotherapy were completed, which was followed by maintenance therapy with pembrolizumab monotherapy for 1 year, and no signs of tumor recurrence and metastasis have been found in follow-up thus far. Conclusions: Through this case, we believe that for locally advanced NSCLC sleeve lobectomy after neoadjuvant therapy may be a safe and feasible treatment option, can avoid pneumonectomy, protect the lung function of patients, and still ensure the R0 resection rate. Moreover, it may does not significantly increase the difficulty of surgical operation or reduce safety. However, further research is needed to confirm our conclusion. And then, neoadjuvant therapy in the perioperative period may induce a series of side effects or adverse reactions, and thus greater attention should be paid to its timely management.

The efficacy of neoadjuvant immunotherapy combined with chemotherapy in resectable stage II-IV non-small cell lung cancer: a preliminary study.

Background: Lung cancer is currently the world's leading malignancy in terms of morbidity and mortality. Neoadjuvant therapy is widely used in clinic to improve R0 resection rates and long-term survival after surgery, and patients with locally resectable non-small cell lung cancer (NSCLC) may benefit from neoadjuvant therapy. Methods: Data from 78 patients with stage II to IV NSCLC who had received neoadjuvant immunotherapy combined with chemotherapy from January 2019 to May 2022 were collected. The patients were categorized into groups based on their eligibility for posttreatment surgery, the level of pathological remission, and receipt of adjuvant therapy. The progression-free survival (PFS) and survival rates of patients in each group were compared. Efforts were made to identify the factors that influence patients' prognoses. Results: The incidence of adverse events in patients who received neoadjuvant immunotherapy combined with chemotherapy was 19%. The proportion of patients receiving neoadjuvant immunotherapy and chemotherapy undergoing surgery was 83.33%, and the rate of R0 resection was 64.10%. The pathological complete response (pCR) and major pathological response (MPR) rates were 26.25% and 21.87%, respectively. Patients who received adjuvant therapy were less likely to experience recurrent metastases than were those who did not receive adjuvant therapy (χ2=7.183; P=0.007<0.05). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy has a low incidence of adverse events in resectable stage II-IV NSCLC, does not significantly increase the difficulty of surgery, and provides greater benefit in terms of PFS for patients who receive operation and adjuvant therapy.

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC.

Outcome improvement in patients with driver-gene-negative advanced non-small cell lung cancer (NSCLC) has been significantly enhanced through targeting the immune system, specifically the PD-L1/PD-1 axis. Nevertheless, only a subset of patients with advanced NSCLC may derive benefits from immuno-monotherapy or immunotherapy combined with chemotherapy. Hence, in order to identify patients who will gain the maximum advantage from immunotherapy, it is crucial to investigate predictive biomarkers. This review provides a summary of the currently identified biomarkers associated with the extent of benefit from immuno-monotherapy or immunotherapy combined with chemotherapy in patients with advanced NSCLC. These biomarkers can be categorized into three groups: tumor-related, tumor-microenvironment-related, and host-factor-related.Tumor-related factors include PD-L1 expression, tumor mutational burden and specific genetic mutations, while tumor-microenvironment-related factors include extracellular vesicles and T-cell receptors, and host-related factors include systemic inflammation, circulating fatty acid profile, and the microbiome.

Cost-effectiveness of the combination of immunotherapy and chemotherapy for extensive-stage small-cell lung cancer: a systematic review.

BACKGROUND: The combination of immunotherapy and chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC) was primarily carried out with a combination of immune checkpoint inhibitors (ICIs) and platinum-etoposide (EP). It is likely to be more effective in treating ES-SCLC than EP alone, but could result in high healthcare costs. The study aimed to investigate the cost-effectiveness of this combination therapy for ES-SCLC. METHODS: We searched literature from the following databases: PubMed, Embase, Cochrane Library, and Web of Science for studies on cost-effectiveness of immunotherapy combined with chemotherapy for ES-SCLC. The literature search period was up to April 20, 2023. The quality of the studies was evaluated using the Cochrane Collaboration's tool and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: A total of 16 eligible studies were included in the review. All studies met CHEERS recommendations, and all randomized controlled trials (RCTs) in these studies were rated as having low risk of bias using the Cochrane Collaboration's tool. The treatment regimens compared were ICIs plus EP or EP alone. All studies mainly used incremental quality-adjusted life year and incremental cost-effectiveness ratio as outcomes. Most ICIs plus EP treatment regimens were not cost-effective based on corresponding willingness-to-pay thresholds. CONCLUSIONS: Adebrelimab plus EP and serplulimab plus EP were probably cost-effective for ES-SCLC in China, and serplulimab plus EP was probably cost-effective for ES-SCLC in the U.S. Lowering the price of ICIs and selecting ES-SCLC patients who were sensitive to ICIs could improve the cost-effectiveness of the ICIs-combined treatment.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

A propensity score-matched analysis of neoadjuvant chemoimmunotherapy versus surgery alone for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the safety, efficacy, and oncologic outcomes of neoadjuvant immunotherapy combined with chemotherapy (NICT) group and surgery alone group in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A series of 232 consecutive patients who underwent surgery with or without NICT from June 2019 to August 2022 were evaluated. We performed propensity score matching between the NICT and surgery alone groups on the basis of estimated propensity scores for each patient. RESULTS: After propensity score matching, data of 137 patients with clinical stages II-IV ESCC, including 85 receiving surgery alone and 52 receiving NICT, were analyzed. Compared with the surgery alone group (301.7 ± 94.4 min), the operation time was significantly longer in the NICT group (333.4 ± 79.7 min). However, there was no significant difference between the two groups in the postoperative complications, intraoperative blood loss, thoracic fluid volume, chest tube duration, lengths of intensive care unit stay and postoperative hospitalization. Additionally, 90-day mortality rate and 30-day readmission were similar in both groups. CONCLUSIONS: Overall, NICT followed by esophagectomy appears to be safe and feasible for locally advanced ESCC. However, further multicenter prospective clinical trials are needed to validate our results.

Classification of Tumor Immune Microenvironment According to Programmed Death-Ligand 1 Expression and Immune Infiltration Predicts Response to Immunotherapy Plus Chemotherapy in Advanced Patients With NSCLC.

INTRODUCTION: According to mechanisms of adaptive immune resistance, tumor immune microenvironment (TIME) is classified into four types: (1) programmed death-ligand 1 (PD-L1)-negative and tumor-infiltrating lymphocyte (TIL)-negative (type I); (2) PD-L1-positive and TIL-positive (type II); (3) PD-L1-negative and TIL-positive (type III); and (4) PD-L1-positive and TIL-negative (type IV). However, the relationship between the TIME classification model and immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced NSCLC. METHODS: On the basis of RNA-sequencing and immunohistochemistry data from the ORIENT-11 study, we optimized the TIME classification model and evaluated its predictive value for the efficacy of immunotherapy plus chemotherapy. RESULTS: PD-L1 mRNA expression and immune score calculated by the ESTIMATE method were the strongest predictors for the efficacy of immunotherapy plus chemotherapy. Therefore, they were determined as the optimized definition of the TIME classification system. When compared between combination therapy and chemotherapy alone, only the type II subpopulation with high immune score and high PD-L1 mRNA expression was significantly associated with improved progression-free survival (PFS) (hazard ratio = 0.12, 95% confidence interval: 0.06-0.25, p < 0.001) and overall survival (hazard ratio = 0.27, 95% confidence interval: 0.13-0.55, p < 0.001). In the combination group, the type II subpopulation had a much longer survival time, not even reaching the median PFS or overall survival, but the other three subpopulations were susceptible to having similar PFS. In the chemotherapy group, there was no marked association between survival outcomes and TIME subtypes. CONCLUSIONS: Only patients with both high PD-L1 expression and high immune infiltration could benefit from chemotherapy plus immunotherapy in first-line treatment of advanced NSCLC. For patients lacking either PD-L1 expression or immune infiltration, chemotherapy alone might be a better treatment option to avoid unnecessary toxicities and financial burdens.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Prognostic value of metabolic parameters of 18F-FDG PET/CT in advanced non-small cell lung cancer treated with first-line immunotherapy combined with chemotherapy / 中华放射医学与防护杂志

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.