Clinical significance of geriatric nutritional risk index in esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy.

OBJECTIVE: The geriatric nutritional risk index (GNRI) is a novel nutrition-related indicator designed to predict the risk of clinical outcomes in various cancers. The clinical significance of risk assessment, therapeutic response, and prognostic prediction of GNRI in esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunochemotherapy (NICT), a hot point of treatment these days, have not been documented in any research. METHODS: Two hundred and twenty-four cases with ESCC who underwent radical resection after NICT were retrospectively recruited. Using the calculation formula of GNRI (1.489 × albumin (g/L) + 41.7 × current weight/ideal weight), the cases were split into two cohorts. Analysis was done on the connections between GNRI and clinical outcomes, such as clinical features, postoperative complications, and pathological complete response (pCR). Prognostic factors of overall survival (OS) and disease-free survival (DFS) were also performed. RESULTS: Patients were then categorized as low (n = 139) or high (n = 85) group based on the threshold. After radical surgery, 67 patients achieved pCR (29.9%). Higher pCR rates were attained by patients in the high GNRI group (41.2% vs. 23.0%, P = 0.004). Lower GNRI patients experienced a considerably higher severe morbidity (36.7% vs. 23.5%, P = 0.040), particularly in the case of respiratory complications (28.8% vs. 14.1%, P = 0.012). Compared to high GNRI patients, lower GNRI cases had inferior 3-year OS (68.5% vs. 87.3%, P = 0.003) and DFS (64.8% vs. 81.5%, P = 0.002). It was also discovered that GNRI was a significant independent variable of both DFS [hazard ratios (HR) = 0.436, P = 0.009] and OS (HR = 0.294, P = 0.012). CONCLUSION: The GNRI, based on nutrition-related indicators, was independently related to postoperative complications, pCR prediction, and prognostication in ESCC receiving NICT.

Clinical significance of preoperative CALLY index for prognostication in patients with esophageal squamous cell carcinoma undergoing surgery.

The C-reactive protein-albumin-lymphocyte (CALLY) index has been identified as a useful and sensitive predictive tool for stratification in cancers. This investigation aimed to validate the prognostic ability of CALLY in esophageal squamous cell carcinoma (ESCC). Clinical characteristics of 318 patients with ESCC who underwent radical excision were gathered and analyzed retrospectively. A restricted cubic spline (RCS) model was used to determine an ideal threshold of CALLY due to the non-linear relation. To investigate the predictors, Cox hazard regression analysis was used. The recursive partitioning analysis (RPA), a method of risk categorization, was also developed for prognostic prediction. The receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were used to distinguish from the traditional TNM stage. Patients were compared by groups according to the optimal threshold of CALLY index, which was depicted by the non-linear relation between the cancer-specific survival (CSS) and CALLY index (P < 0.0001). Compared to those with high CALLY index, patients with low CALLY index experienced significantly worse 5-year CSS (21.8% vs. 62.6%, P < 0.001). At different TNM stages, patients with high CALLY index also had better 5-year CSS (I: P = 0.029; II: P < 0.001; III: P < 0.001) in subgroup analyses. The hazard ratio for CSS was 0.368 and CALLY index was an independent predictive factor (P < 0.001). Using TNM stage and CALLY-based RPA algorithms, a new staging was created. The RPA model considerably outperformed the TNM classification for prognostication using ROC (P < 0.001). The DCA also demonstrated that the new model outperformed the TNM stage with significantly improved accuracy for CSS. The prognostic value of CALLY in ESCC undergoing radical resection was initially determined in this study. CALLY was substantially related to prognosis and might be utilized in conjunction with TNM to evaluate ESCC prior to surgery.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Serum Protein Fishing for Machine Learning-Boosted Diagnostic Classification of Small Nodules of Lung.

Diagnosis of benign and malignant small nodules of the lung remains an unmet clinical problem which is leading to serious false positive diagnosis and overtreatment. Here, we developed a serum protein fishing-based spectral library (ProteoFish) for data independent acquisition analysis and a machine learning-boosted protein panel for diagnosis of early Non-Small Cell Lung Cancer (NSCLC) and classification of benign and malignant small nodules. We established an extensive NSCLC protein bank consisting of 297 clinical subjects. After testing 5 feature extraction algorithms and six machine learning models, the Lasso algorithm for a 15-key protein panel selection and Random Forest was chosen for diagnostic classification. Our random forest classifier achieved 91.38% accuracy in benign and malignant small nodule diagnosis, which is superior to the existing clinical assays. By integrating with machine learning, the 15-key protein panel may provide insights to multiplexed protein biomarker fishing from serum for facile cancer screening and tackling the current clinical challenge in prospective diagnostic classification of small nodules of the lung.

Pretreatment Pan-Immune-Inflammation Value (PIV) in Predicting Therapeutic Response and Clinical Outcomes of Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma.

PURPOSE: The pan-immune-inflammation value (PIV), which reflects the balance between the host immune and inflammatory status, is a readily available index for evaluating cancer outcomes. Until now, however, no study has demonstrated the clinical response of PIV to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study included 218 patients with ESCC who underwent NICT. The relationship between PIV and therapeutic response (pathological complete response [PCR]) and clinical outcomes (overall survival [OS] and disease-free survival [DFS]) was examined. Cox proportional, hazard-regression analyses and the Kaplan-Meier method were used for survival analyses. Recursive partitioning analysis (RPA) was used to establish a novel risk stratification model. RESULTS: Sixty-six patients (30.3%) achieved PCR after NICT. Using PCR as the endpoint of interest, patients were compared in groups based on the optimal threshold. PIV was closely related to PCR (odds ratio [OR] 0.311, 95% confidence interval [CI] 0.140-0.690, P = 0.004). Compared with patients in the low PIV cohort, patients with high PIV had worse 3-year OS (58.7% vs. 83.6%, P < 0.001) and DFS (51.9% vs. 79.1%, P < 0.001). PIV was an independent predictor of OS (hazard ratio [HR] 2.364, 95% CI 1.183-4.724, P = 0.015) and DFS (HR 1.729, 95% CI 1.026-2.913, P = 0.040). Three risk groups with varied DFS and OS were staged by using an RPA method, and the prognostication accuracy was considerably improved. CONCLUSIONS: Pretreatment PIV can predict the therapeutic efficacy of NICT for ESCC. Because of better prognostic stratification, pretreatment PIV is a novel, sensitive, and effective indicator in ESCC receiving NICT. The prognostic results of PIV need to be verified in additional prospective studies.

Enhanced efficacy of a novel aspirator in uniportal video-assisted thoracoscopic mediastinal lymph node dissection: a non-randomized prospective clinical trial.

Background: Video-assisted thoracoscopic surgery (VATS) is the standard approach in early-stage non-small cell lung cancer (NSCLC) and surgical aspirators play a crucial role. Traditional aspirators lack the ability to pull and lift tissue and cannot achieve optimal exposure. Therefore, we designed a new surgical aspirator that combined the function of thoracoscopic forceps. In this study, we aimed to validate the efficacy and safety of this new surgical aspirator. Methods: We performed a prospective non-randomized intervention trial and enrolled 504 consecutive patients scheduled for uniportal VATS in early NSCLC requiring mediastinal lymph node dissection. A novel aspirator we developed with a clamping function via a front pliers-like structure was implemented in intervention group, whereas traditional aspirator was used in control group. Time spent for nodal dissection in No. 2/4R and No. 7R/L (No. 7 lymph nodes resected through right or left side) lymph nodes and perioperative adverse events related to lymph node dissection were recorded. Mann-Whitey U test was applied to analyze sex and pathological type, an independent-samples t-test was applied to analyze surgery time and age. Results: In total, 250 of enrolled patients were allocated into traditional aspirator group and 254 of them were allocated into new aspirator group. Surgeons spent 544.71±120.80 (range, 332-917, median 541) seconds dissecting No. 2/4R lymph nodes with traditional aspirators and 507.54±100.00 (range, 348-702, median 520) seconds dissecting with new aspirators (P=0.008). The traditional aspirator group had an average surgery time of 507.11±104.61 (range, 310-785, median 510) seconds for No. 7R lymph nodes and 608.47±128.50 (range, 397-919, median 606) seconds for No. 7L lymph nodes, while that in the new aspirator group was 465.09±94.94 (range, 271-744, median 476) seconds (P=0.001) and 549.39±102.11 (range, 368-782, median 538) seconds (P<0.001). The new aspirator showed an efficacy advantage in mediastinal lymph node dissection in VATS, without additional risk. Conclusions: This is the first report about a new suction device combining the functions of both traditional surgical aspirators and forceps, which can effectively shorten the time of mediastinal lymph node dissection and improve the efficiency of thoracoscopic surgery without increasing lymph node dissection-related adverse events.

A novel immune-nutritional score predicts response to neoadjuvant immunochemotherapy after minimally invasive esophagectomy for esophageal squamous cell carcinoma.

Background: The role of neoadjuvant immunochemotherapy (NICT) has gradually attracted attention in recent years. To date, sensitive and reliable blood indicators to forecast the therapeutic response are still lacking. This study aimed to conduct a novel predictive score based on a variety of peripheral hematological immune-nutritional indicators to predict the therapeutic response in esophageal squamous cell carcinoma (ESCC) receiving NICT. Methods: There were 206 ESCC patients receiving NICT retrospectively recruited. With pathological complete response (pCR) as the dependent variable, independent risk variables of various peripheral blood immune-nutritional indexes were screened by logistic regression analyses to establish an integrative score. Results: By logical regression analyses, lymphocyte to monocyte ratio (LMR) and body mass index (BMI) were independent risk factors among all immune-nutritional indices. Then, an integrative score named BMI-LMR score (BLS) was established. Compared with BMI or LMR, BLS was related to complications, especially for respiratory complication (P=0.012) and vocal cord paralysis (P=0.021). Among all patients, 61 patients (29.6%) achieved pCR after NICT. BLS was significantly related to pCR [odds ratio (OR)=0.269, P<0.001)]. Patients in high BLS cohort demonstrated higher 3-year overall survival (OS) (89.9% vs. 67.9%, P=0.001) and disease-free survival (DFS) (81.2% vs. 62.1%, P=0.001). BLS served as an independent factor of DFS [hazard ratio (HR) =2.044, P =0.020) and OS (HR =2.960, P =0.019). Conclusion: The BLS, based on immune-nutritional indicators of BMI and LMR, employed as a straightforward, accurate, and useful indicator of pCR and prognostic prediction in ESCC patients undergoing NICT.

Pulmonary metastasectomy for recurrent metastatic ovarian cancer.

AIM: The prognosis of patients with ovarian cancer with lung metastasis is poor; data on pulmonary metastasectomy for such patients are lacking. This study aimed to determine the safety and feasibility of pulmonary resection as part of cytoreductive surgery for recurrent metastatic ovarian cancer. METHODS: Medical records of patients with ovarian cancer, who underwent pulmonary resection for lung metastasis in our hospital from April 2012 to February 2022, were retrospectively reviewed. RESULTS: Ten patients were included (median age, 53 years). Five patients had metastatic disease limited to the lungs. Additional surgeries included diaphragm resection, partial hepatectomy, para-aortic lymph node dissection, and cytoreduction. We achieved complete cytoreduction for all patients without severe complications, and the 30-day mortality was zero. After a median follow-up of 23 months, four of the patients experienced recurrence. One patient recurred 9 months after the operation and was lost to follow-up at 17 months, two died at 68 and 26 months respectively, one is alive with disease (23 months), and six are alive without recurrence, among whom two have survived for 56 and 124 months. CONCLUSIONS: Pulmonary resection for recurrent metastatic ovarian cancer seems safe and feasible, with long-term survival observed in certain patients. Pulmonary metastasectomy can be performed as part of the debulking surgery for selected patients with relapsed metastatic ovarian cancer. Both the patient lost to follow-up and the one who died at 26 months, had two lung metastatic nodules and did not receive postoperative chemotherapy, which might have led to relatively poor prognosis.

Clinical utility of preoperative pan-immune-inflammation value (PIV) for prognostication in patients with esophageal squamous cell carcinoma.

BACKGROUND: Several researches have shown that pan-immune-inflammation value (PIV) is related to cancer prognosis in recent years. In esophageal squamous cell carcinoma (ESCC), nevertheless, the prognostic impact of PIV remains unclear. The present study sought to investigate the prognostic impact of preoperative PIV in ESCC with radical resection. METHODS: The data of 294 ESCC patients who received radical resection were retrospectively analyzed. Based on analyzing the non-linear relationship between PIV and cancer-specific survival (CSS), the optimal cutoff value for PIV was calculated by the restricted cubic spline (RCS) model. Cox proportional hazards regression was carried out to identify the prognostic factors. A risk stratification model was established by recursive partitioning analysis (RPA). The performance of the RPA-based model was assessed by the decision curve analysis (DCA) and receiver operating characteristic (ROC). RESULTS: The RCS visualized the non-linear relationship between PIV and CSS (P < 0.0001). Then patients were then divided into high and low groups based on the optimal threshold of 308.2. The 5-year CSS (17.7 % vs. 48.3 %, P < 0.001) was significantly worse in patients with high PIV than those in the low group. Subgroup analyses confirmed that patients with low PIV also achieved better 5-year survival at different pathological tumor node metastasis (pTNM) stages (pTNM I: P = 0.022; pTNM II: P = 0.001; pTNM III: P = 0.011). PIV served as an independent prognostic factor of CSS (hazard ratio = 1.983, P < 0.001). A new staging involving three risk groups with significantly different CSS was developed using RPA algorithms based on pTNM and PIV. Compared with the pTNM classification, the RPA-based model exhibited significantly superior performance for prognostication. CONCLUSION: The present study confirmed the prognostic impact of PIV in ESCC who treated with radical resection. PIV was associated with the tumor stage and prognosis, which might be useful in the preoperative assessment of ESCC.

Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation.

OBJECTIVE: This study aimed to build radiomic feature-based machine learning models to predict pathological clinical response (pCR) of neoadjuvant chemoradiation therapy (nCRT) for esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 112 ESCC patients who underwent nCRT followed by surgical treatment from January 2008 to December 2018 were recruited. According to pCR status (no visible cancer cells in primary cancer lesion), patients were categorized into primary cancer lesion pCR (ppCR) group (N = 65) and non-ppCR group (N = 47). Patients were also categorized into total pCR (tpCR) group (N = 48) and non-tpCR group (N = 64) according to tpCR status (no visible cancer cells in primary cancer lesion or lymph nodes). Radiomic features of pretreatment CT images were extracted, feature selection was performed, machine learning models were trained to predict ppCR and tpCR, respectively. RESULTS: A total of 620 radiomic features were extracted. For ppCR prediction models, radiomic model had an area under the curve (AUC) of 0.817 (95% CI: 0.732-0.896) in the testing set; and the combination model that included rad-score and clinical features had a great predicting performance, with an AUC of 0.891 (95% CI: 0.823-0.950) in the testing set. For tpCR prediction models, radiomic model had an AUC of 0.713 (95% CI: 0.613-0.808) in the testing set; and the combination model also had a great predicting performance, with an AUC of 0.814 (95% CI: 0.728-0.881) in the testing set. CONCLUSION: This study built machine learning models for predicting ppCR and tpCR of ESCC patients with favorable predicting performance respectively, which aided treatment plan optimization. CLINICAL RELEVANCE STATEMENT: This study significantly improved the predictive value of machine learning models based on radiomic features to accurately predict response to therapy of esophageal squamous cell carcinoma patients after neoadjuvant chemoradiation therapy, providing guidance for further treatment. KEY POINTS: • Combination model that included rad-score and clinical features had a great predicting performance. • Primary tumor pCR predicting models exhibit better predicting performance compared to corresponding total pCR predicting models.

Comprehensive nutritional index predicts clinical outcomes for esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy.

OBJECTIVE: No study has reported the clinical outcomes of comprehensive nutritional index (CNI) in esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy combined with chemotherapy (nICT). METHODS: This retrospective study involved 233 ESCC patients who underwent nICT. Principal component analysis was performed to establish the CNI based on 5 indexes including body mass index, usual body weight percentage, total lymphocyte count, albumin and hemoglobin. The relationships between the CNI and therapeutic response, postoperative complications and prognosis were analyzed. RESULTS: One hundred and forty-nine and 84 patients were assigned to the high and low CNI group, respectively. The incidences of respiratory complications (33.3% vs. 18.8%, P = 0.013) and vocal cord paralysis (17.9% vs. 8.1%, P = 0.025) in low CNI were significantly higher than those in high group, respectively. Seventy (30.0%) patients achieved pathological complete response (pCR). High CNI patients achieved a better pCR rate than those with low CNI (41.6% vs. 9.5%, P < 0.001). The CNI served as an independent pCR predictor [odds ratio (OR) = 0.167, 95% confidence interval (CI) = 0.074-0.377, P < 0.001)]. High CNI patients had better 3-year disease-free survival (DFS) (85.4% vs. 52.6%, P < 0.001) and overall survival (OS) (85.5% vs. 64.5%, P < 0.001) than those with low CNI, respectively. The CNI served as an independent prognostic score regarding DFS [hazard ratio (HR) = 3.878, 95% CI = 2.214-6.792, P < 0.001)] and OS (HR = 4.386, 95% CI = 2.006-9.590, P < 0.001). CONCLUSION: Based on nutrition-related indicators, the pretreatment CNI serves as a sensitive and effective predictor of therapeutic response, postoperative complications and prognosis in ESCC receiving nICT.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.

PURPOSE: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. METHODS AND MATERIALS: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. RESULTS: Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples. CONCLUSIONS: nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.

Surgical selection and regional lymph node dissection for stage I second primary lung cancer patients following surgery for stage I first primary lung cancer.

Introduction: Studies investigating surgery for second primary non-small cell lung cancer (SP) patients are rare. The aim of this study was to explore the effects of surgical methods and regional lymph node (LN) dissection on lung cancer-specific mortality (LCSM) in stage I SP patients following surgery for stage I first primary non-small cell lung cancer (FP). Methods: Data on patients diagnosed with stage I SP after surgery for stage I FP were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative incidence function (CIF) curves, a competing risk model and propensity score matching (PSM) were adopted to compare the LCSM among different subgroups (including surgery and regional LN dissection). Results: A total of 238 stage I SP patients were extracted from the SEER database. Overall, the 5-year LCSM rate was 29.8% (CI: 23.1%-36.5%) for the whole cohort. Both before and after PSM, lobectomy had a similar LCSM incidence as sublobectomy, and ≥4 regional LN dissections had a significantly lower LCSM incidence than 1~3 regional LN dissections.In addition, patients who underwent 1~3 regional LN dissections had a comparable incidence of LCSM to those without LN dissections. Discussion: Stage I SP patients tended to gain more survival benefits when surgeons dissect ≥4 regional LNs. Allowing for the comparable LCSM incidence of sublobectomy to lobectomy, sublobectomy may be a reasonable choice for thoracic surgeons when performing surgery for these patients.

Neoadjuvant Camrelizumab for Non-Small Cell Lung Cancer: A Retrospective Multicenter, Real-World Study (CTONG2004).

BACKGROUND: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. METHODS: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. RESULTS: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1-6). The median interval from the last dose to surgery was 33 days (range 13-102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5-1200 mL), and the median operative time was 3.0 h (range 1.5-6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4-85.0%), and the disease control rate was 93.8% (95% CI 86.9-97.7%). Twenty-six patients (27.1%, 95% CI 18.5-37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. CONCLUSION: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted.

Neoadjuvant therapy with immunoagent (nivolumab) or placebo plus chemotherapy followed by surgery and adjuvant treatment in subjects with resectable esophageal squamous cell carcinoma: study protocol of a randomized, multicenter, double blind, phase II trial (NATION-2203 trial).

Background: Neoadjuvant chemotherapy (nCT) has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to nCT may improve oncologic outcome and survival. However, high-level evidence of neoadjuvant immunotherapy (nIT) combined with nCT in locally advanced resectable ESCC patients are still lacking. Hence, we describe this randomized controlled trial in order to assess the efficacy and safety of neoadjuvant nivolumab in combination with chemotherapy for locally advanced (stage II-III) ESCC patients. Methods: This prospective, randomized, multicenter phase II trial aims to enroll 90 locally advanced (stage II-III) ESCC patients who will undergo nivolumab or placebo plus chemotherapy followed by surgery. Patients will be 2:1 randomized to nivolumab/chemo and placebo/chemo group by method of stratified randomization. In both arms, patients who have not achieved complete pathological complete response (pCR) will be administered with adjuvant nivolumab for up to 1 year. The primary endpoint is pCR rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events (AEs). The safety will be evaluated by AEs, grading by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 classifications. The double-blind will be maintained between subjects and investigators until the final unblinding process. Discussion: This protocol has been reviewed and approved by the Ethics Committee of Zhongshan Hospital (B2022-004R). This is the first prospective, multicenter, randomized controlled trial to compare the combination of immunotherapy and chemotherapy with standard chemotherapy in neoadjuvant treatment for ESCC, also to explore whether adjuvant immunotherapy offers additional benefit in non-pCR patients after nCT with/without immunotherapy and R0 resection. We hypothesize that the pCR rate, R0 resection rate, EFS and OS of the study group (nivolumab/chemo) is significantly better than those of control group. Registration: ClinicalTrial.gov: NCT05213312.

Effectiveness and safety of camrelizumab in inoperable or advanced non-small cell lung cancer patients: a multicenter real-world retrospective observational study (CTONG2004-ADV).

Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.

Prediction of pathologic complete response prediction in patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant immunochemotherapy: A real-world study.

As an emerging hotspot for patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC), neoadjuvant immunochemotherapy (nICT) is safe and feasible. Pathological complete response (pCR) is considered to be an important therapeutic effect of neoadjuvant therapy. However, few studies have explored pCR predictors for nICT in LA-ESCC. The purpose of this study was to predict pCR after nICT in LA-ESCC by pretreatment clinical characteristics and hematological indexes. The primary endpoint was to explore the impacts on the predictors for pCR prediction. Clinical characteristics and hematological indexes including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), prognostic nutritional index (PNI) and platelet lymphocyte ratio (PLR) were conducted. A total of 150 LA-ESCC patients were enrolled in the current study. There were 14 (9.3%) female and 136 (90.7%) male patients. Fifty-two patients achieved pCR (34.7%). A higher pCR rate was found in low-NLR group (43.7% vs. 26.6%, P=0.028) and high-LMR group (43.8% vs. 21.3%, P=0.004), respectively. Differentiation [odds ratio (OR) =0.464, 95% confidence interval (CI)=0.259-0.830, P=0.010], LMR (OR=0.309, 95% CI=0.132-0.707, P=0.007) and cTNM (OR=0.225, 95% CI=0.115-0.441, P<0.001) were independent predictors for pCR. The nomogram for pCR prediction based on LMR, differentiation and cTNM stage had good discrimination performance and calibration coordination (C-index=0.779). The results of our study are of great significance for designing therapeutic strategies. Nomogram based on LMR, differentiation and cTNM may accurately and effectively predict pCR.