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Introduction: Predicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy. Methods: We retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model's performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort. Results: We enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil–Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram's superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model. Conclusion: The nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods: A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results: Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% (p < 0.001), and the 2-year PFS was 77.7% vs. 23.5% (p < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS (HR 6.258, 95% CI 1.798–21.778; p = 0.004) and PFS (HR 3.431, 95% CI 1.341–8.780; p = 0.010), but not ypN. Conclusions: LNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT. [ABSTRACT FROM AUTHOR]

Background: In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods: This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results: After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P < 0.001) and favorable tumor regression grade (TRG), as well as reduced ypT stages and less perineural and angioinvasion, despite comparable ypN stages. Despite the improvement in complete pathological response (pCR) in the nCRT group, the 3-year disease-free survival (DFS) and overall survival (OS) rates did not significantly differ between the groups (DFS: 58.32% vs 56.16%, P = 0.67; OS: 69.96% vs 71.99%, P = 0.99). Crucially, The nICT group showed a lower incidence of grade 3 and 4 adverse events in Leukopenia (2.8% vs 29%; P < 0.001) and Neutropenia (2.8% vs 24%; P < 0.001) during neoadjuvant treatment, comparing with nCRT group. Conclusions: Our preliminary findings suggest that nICT followed by surgery offers comparable survival rates to nCRT, despite being less effective in pathologic outcomes. Nonetheless, nICT is a safe and feasible strategy for locally advanced ESCC, warranting further exploration to understand its impact on long-term survival. [ABSTRACT FROM AUTHOR]

Abstract Objective The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Abstract Background In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P

Abstract Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC.

Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. Methods: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. Results: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P= 0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P= 0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P= 0.143). Conclusions: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC. Trial registration: Clinical Trials.gov. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (ESCA) is one of the most common tumors in the world, and treatment using neoadjuvant therapy (NT) based on radiotherapy and/or chemotherapy has still unsatisfactory results. Neoadjuvant immunochemotherapy (NICT) has also become an effective treatment strategy nowadays. However, its impact on the tumor microenvironment (TME) and regulatory mechanisms on T cells and NK cells needs to be further elucidated. Methods: A total of 279 cases of ESCA who underwent surgery alone [nonneoadjuvant therapy (NONE)], neoadjuvant chemotherapy (NCT), and NICT were collected, and their therapeutic effect and survival period were compared. Further, RNA sequencing combined with biological information was used to analyze the expression of immune-related genes. Immunohistochemistry, immunofluorescence, and quantitative real-time PCR (qRT-PCR) were used to verify the activation and infiltration status of CD8+ T and CD16+ NK cells, as well as the function and regulatory pathway of killing tumor cells. Results: Patients with ESCA in the NICT group showed better clinical response, median survival, and 2-year survival rates (p < 0.05) compared with the NCT group. Our RNA sequencing data revealed that NICT could promote the expression of immune-related genes. The infiltration and activation of immune cells centered with CD8+ T cells were significantly enhanced. CD8+ T cells activated by PD-1 inhibitors secreted more IFN-γ and cytotoxic effector factor cells through the transcription factor of EOMES and TBX21. At the same time, activated CD8+ T cells mediated the CD16+ NK cell activation and secreted more IFN-γ to kill ESCA cells. In addition, the immunofluorescence co-staining results showed that more CD276+ tumor cells and CD16+ NK cells were existed in pre-NCT and pre-NICT group. However, CD276+ tumor cells were reduced significantly in the post-NICT group, while they still appeared in the post-NCT group, which means that CD16+ NK cells can recognize and kill CD276+ tumor cells after immune checkpoint blocker (ICB) treatment. Conclusion: NICT can improve the therapeutic effect and survival period of resectable ESCA patients. NICT could promote the expression of immunerelated genes and activate CD8+ T and CD16+ NK cells to secrete more IFN-γ to kill ESCA cells. It provides a theoretical basis and clinical evidence for its potential as an NT strategy in ESCA. [ABSTRACT FROM AUTHOR]

Background: To investigate the relationship between the Scottish inflammatory prognostic score (SIPS), treatment-related adverse events (TRAEs), and prognostication in patients with neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESCC). Methods: A retrospective investigation was carried out on 208 ESCC patients treated with NICT. The relationships between the SIPS, TRAEs, and prognosis [disease-free survival (DFS) and overall survival (OS)] were analyzed. Results: The patients, comprising 62 (29.8%) cases of SIPS0, 103 (49.5%) cases of SIPS1, and 43 (20.7%) cases of SIPS2, were categorized into three groups based on SIPS. Among patients with SIPS2, the oldest age (P=0.006), lowest BMI (P=0.001), longest tumor length (P=0.001), most advanced ypT stage (P=0.014), and ypN stage (P<0.001) were identified. Pathological complete response (PCR) rates showed statistically significant variations between the three groups (SIPS0: 45.2%, SIPS1: 27.2%, SIPS2: 16.3%, P=0.004). All TRAEs were found in 63.9% (133 cases) of the cases, with serious TRAEs (grade 3-4) accounting for 13.9% (29 cases). TRAEs themselves were not linked with SIPS (P=0.668), while serious TRAEs had a significant correlation with SIPS (P=0.002). Multivariate logistic analysis showed that SIPS2 seemed to confer serious TRAEs [odds radio (OR)=4.044; 95% CI: 1.395-11.722; P=0.010]. For patients classified as SIPS0, 1, or 2, the 3-year DFS was 83.9%, 58.3%, and 39.5% (P<0.001). The 3-year OS for those with SIPS0, 1, or 2 was 88.7%, 72.8%, and 53.5%, respectively (P<0.001). SIPS was substantially correlated with DFS (but not with OS) and could be utilized as an independent predictor [SIPS2: hazard ratio (HR)=3.743, 95% CI: 1.770-7.914, P=0.001; SIPS1: HR=2.303, 95% CI: 1.149-4.616, P=0.019]. Conclusion: The SIPS is associated with serious TRAEs and can be used as a predictor of serious TRAEs in ESCC receiving NICT. SIPS may be employed for pretreatment assessment since it was found to be substantially correlated with DFS. [ABSTRACT FROM AUTHOR]

IntroductionPredicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy.MethodsWe retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model’s performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort.ResultsWe enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil–Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram’s superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model.ConclusionThe nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients.

Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC. Methods 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathological response rate, incidence of adverse events, and quality of life were compared between the two groups. Results There were no statistically significant differences in clinical baseline data between the two groups (P>0.05). Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group (P=0.002). There were no significant differences in surgical time, intraoperative blood loss, number of dissected lymph nodes, duration of chest tube placement, postoperative hospital stay, and R0 resection rate between the two groups (P>0.05). The overall incidence of postoperative complications was 31.25% in the nICT group and 22.64% in the surgery alone group, with no statistically significant difference (P=0.380). In the nICT group, the objective response rate (ORR) was 84.38%, with 5 cases of complete response (CR)(15.63%), 22 cases of partial response (PR)(68.75%), 15 cases of pathological response rate (pCR)(46.88%), and 11 cases of major pathological reaponse (MPR) (34.38%). During nICT treatment, 12 cases (37.50%) experienced grade 3 treatment-related adverse events, no death induced by adverse events or immune related adverse events. Moreover, the symptoms of the patients were improved after nICT treatment. Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC, with manageable treatment-related adverse events. It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

Wenbin Zou,1,&ast; Wan Kuang,2,&ast; Chun Cai,1 Yan Qian1 1Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Qian, Tongji Hospital, Tongji Medical College, 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province, 430000, People’s Republic of China, Tel +86-27-83665211, Email qianyan@tjh.tjmu.edu.cnBackground & Aims: The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy.Methods: Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications.Results: Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group.Conclusion: The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.Keywords: prognostic nutritional index, neoadjuvant immunochemotherapy, postoperative complications, esophageal squamous cell carcinoma

Abstract Objective The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. Methods This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). Results Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. Conclusions The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

Abstract Background Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition. Case description In this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen. Conclusions We have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC.

Abstract Background To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. Methods We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). Results We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819–0.928) and 0.772 (95% CI: 0.699–0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P

Objectives: To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image. Methods: This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Results: In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686. Conclusion: The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management. [ABSTRACT FROM AUTHOR]

Objective: This study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment. Methods: This retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model. Results: The PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4 + LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8 +, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92). Conclusion: NICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. Methods: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). Results: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. Conclusions: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. Methods: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). Results: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171–0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145–0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. Conclusion: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety. [ABSTRACT FROM AUTHOR]

Background: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. Methods: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). Results: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819–0.928) and 0.772 (95% CI: 0.699–0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896–0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models. Conclusions: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have shown that programmed cell death-1 (PD-1) inhibitors can activate T cells and inhibit cancer growth. Therefore, the use of a PD-1 inhibitor plus chemotherapy as neoadjuvant chemotherapy for locally advanced esophageal cancer is worth further exploration. Methods: Patients with locally advanced esophageal squamous cell carcinoma were enrolled in this study to receive two cycles of a preoperative combination of toripalimab, paclitaxel, and cisplatin. Efficacy was evaluated after two treatment cycles. The patients' postoperative pathological staging was analyzed and compared. Surgery was performed within 42 days of the start date of the last chemotherapy cycle. Results: Neoadjuvant immunochemotherapy achieved a high pathologic complete response (pCR) rate (29.0%), major pathological response rate (41.9%), and objective response rate (80.6%) and demonstrated statistically significant downstaging after neoadjuvant therapy (P <.05) with manageable treatment-related adverse effects. No significant association was found between PD-L1 level and pCR (P =.365). In addition, R0 resection was achieved in all 31 (100%) patients during surgery. For all the included patients, the one-year progression-free survival rate was 87.1% (95% CI: 75.3%-98.9%), the one-year overall survival (OS) rate was 96.8% (95% CI: 79.8%-95.9%), and the two-year OS rate was 83.9% (95% CI: 71.6%-92.2%). Conclusions: Our findings indicate that this combination may be a potential neoadjuvant therapy regimen in this setting. [ABSTRACT FROM AUTHOR]

Background: There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. Methods: This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. Results: From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). Conclusions: Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival. [ABSTRACT FROM AUTHOR]

Introduction: For locally advanced, inoperable esophageal cancer, concurrent chemoradiotherapy (CCRT) becomes the norm. Combining immunotherapy with radiotherapy has been shown to improve efficacy. Circulating tumor DNA (ctDNA) is a strong predictor of effectiveness and tumor recurrence and is indicative of minimal residual disease (MRD). Patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC) are enrolled in the ECMRD-001 trial to evaluate changes in MRD status before and after CCRT combined with immunotherapy and adjuvant immunotherapy following neoadjuvant immunochemotherapy. Methods and analysis: The ECMRD-001 trial is a prospective cohort study. Eligible patients will receive radical concurrent chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy, followed by adjuvant immunotherapy for at least one year. Follow-up will be up to three years. MRD-related blood and tissue samples and T-cell immunohistobank related blood and tissue samples collected before, during and after treatment and follow-up will be grouped into sample collection time points. The relationship between MRD status at different time points and treatment efficacy is the primary outcome. Correlation between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence are the secondary outcomes. Examination of ctDNA mutations is the exploratory outcome. Discussion: ctDNA-based MRD may be a potential predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients. Elevated ctDNA-MRD may predict tumor recurrence earlier than imaging. ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment should be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Wen-Yu Zhai,1,2,&ast; Fang-Fang Duan,3,&ast; Yao-Bin Lin,1,2,&ast; Yong-Bin Lin,1,2 Ze-Rui Zhao,1,2 Jun-Ye Wang,1,2 Bing-Yu Rao,1,2 Lie Zheng,4 Hao Long1,2 1Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Medical oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Medical Imaging Division, Department of Medical Imaging and Interventional Radiology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Long, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, and Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email longhao@sysucc.org.cn Lie Zheng, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, and Medical Imaging Division, Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhenglie@sysucc.org.cnBackground: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients’ selection.Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan–Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR.Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response.Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.Keywords: non-small-cell lung cancer, pan-immune-inflammatory value, neoadjuvant immunochemotherapy, pathological complete response, survival benefits

The lymph node ratio (LNR) is regarded as a prognostic indicator in esophageal cancer (EC), but its applicability to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC) remains unexplored. This retrospective study, conducted between 2019 and 2021, analyzed ESCC patients who underwent radical esophagectomy following NICT. Patients were divided into two groups based on their LNR values according to the X-tile software: Low-LNR group (LNR 0-10%) and High-LNR group (LNR 10-100%). The association between LNR and clinical outcomes in ESCC after NICT were analyzed. A total of 212 ESCC patients who underwent surgery after NICT were included in this study, among which, 169 (79.7%) and 43 (20.3%) cases were allocated to the Low- and High-LNR groups, respectively. Pathologic complete response (PCR) was observed in 28.3% (60/212) of the overall cohort. Patients in the Low-LNR group demonstrated a significantly improved 3-year overall survival (OS) (81.7% vs 55.3%; P < 0.001) and disease-free survival (DFS) (79.9% vs 37.4%; P < 0.001). These findings were consistent among those with non-PCR (3-year DFS was 73.7% vs 37.4%; P < 0.001, and the 3-year OS was 78.9% vs 55.3%; P < 0.001, respectively). High LNR was associated with a 4.013-fold increased risk of relapse and a 7.026-fold elevated risk of death. Compared to the post-neoadjuvant therapy pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for DFS and OS. To the best of our knowledge, this study is the first to investigate the prognostic value of LNR in ESCC after NICT, suggesting that LNR may serve as a viable alternative to the ypN stage for prognostication in ESCC patients treated with NICT.

Background: Neoadjuvant immunochemotherapy may benefit patients with non-small cell lung cancer (NSCLC), but its impact requires further investigation. Methods: A meta-analysis was conducted. PubMed, Embase, Web of Science, and the Cochrane Library were searched. The study was registered in PROSPERO (registration no. CRD42022360893). Results: 60 studies of 3,632 patients were included. Comparing with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy showed higher pCR (RR: 4.71, 95% CI: 3.69, 6.02), MPR (RR, 3.20, 95% CI: 2.75, 3.74), and ORR (RR, 1.46, 95% CI: 1.21, 1.77), fewer surgical complications (RR: 0.67, 95%CI: 0.48, 0.94), higher R0 resection rate (RR: 1.06, 95%CI: 1.03, 1.10, I² = 52%), and longer 1-year and 2-year OS, without affecting TRAEs. For neoadjuvant immunochemotherapy in NSCLC, the pooled pCR rate was 0.35 (95% CI: 0.31, 0.39), MPR was 0.59 (95% CI: 0.54, 0.63), and ORR was 0.71 (95% CI: 0.66, 0.76). The pooled incidence of all grade TRAEswas 0.70 (95% CI: 0.60, 0.81), and that of >= grade 3 TRAEs was 0.24 (95% CI: 0.16, 0.32). The surgical complications rate was 0.13 (95% CI: 0.07, 0.18) and R0 resection rate was 0.98 (95% CI: 0.96, 0.99). The pooled 1-year OS was 0.97 (95%CI: 0.96, 0.99), and 2-year OS was 0.89 (95%CI: 0.83, 0.94). Patients with squamous cell carcinoma, stage III or higher PD-L1 performed better. Notably, no significant differences were observed in pCR, MPR, and ORR between 2 or more treatment cycles. Pembrolizumab-, or toripalimab-based neoadjuvant immunochemotherapy demonstrated superior efficacy and tolerable toxicity. Conclusion: According to our analysis, reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC were demonstrated. [ABSTRACT FROM AUTHOR]

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in the treatment landscape of non-small cell lung cancer (NSCLC). Despite the promising long-term survival outcomes and optimization of pathological complete response (cPR) demonstrated by various studies such as Impower010 and Checkmate-816, the effectiveness of neoadjuvant immunotherapy in advanced resectable NSCLC remains a subject of debate. Although previous research has explored the connection between the efficacy of neoadjuvant therapy and surgical-related safety, limited studies have specifically investigated the surgical-related safety of neoadjuvant immunotherapy. Therefore, our study aims to assess the efficacy and surgical-related safety of neoadjuvant immunotherapy in advanced resectable non-small cell lung cancer.MethodWe conducted a retrospective study on a cohort of 93 patients with stage IIIA-IIIC NSCLC who underwent neoadjuvant therapy and surgical resection. Among them, 53 patients received neoadjuvant immunotherapy, 18 patients underwent neoadjuvant chemotherapy while the remaining 22 underwent neoadjuvant targeted therapy. The patients were separated into further groups according to their pathological type. Data analyses were performed using Mann-Whitney U test, chi-square test.ResultsAll patients were categorized into six distinct groups. Notably, the neoadjuvant immunotherapy squamous carcinoma group exhibited a favorable edge over the neoadjuvant targeted squamous carcinoma group concerning the duration of drainage tube indwelling and the extent of lymph node dissection. Furthermore, the neoadjuvant immunotherapy adenocarcinoma group outperformed neoadjuvant targeted therapy adenocarcinoma counterpart in terms of achieving complete pathological response (cPR). Simultaneously, the neoadjuvant immunotherapy adenocarcinoma group surpassed the neoadjuvant chemotherapy adenocarcinoma group in the incidence of hydrothorax. Nevertheless, no statistically significant disparities were noted between the neoadjuvant immunotherapy squamous carcinoma group and the neoadjuvant chemotherapy carcinoma group.ConclusionRegarding surgical outcomes, neoadjuvant immunotherapy conferred notable advantages compared to conventional neoadjuvant chemotherapy and neoadjuvant targeted therapy for patients diagnosed with adenocarcinoma. In the case of squamous carcinoma, neoadjuvant immunotherapy exhibited superiority over neoadjuvant targeted therapy, although additional evidence is required to conclusively establish its precedence over neoadjuvant chemotherapy.

Simple Summary: Neoadjuvant immunochemotherapy (NICT) has demonstrated impressive short-term efficacy, with over half of patients experiencing significant tumor shrinkage and achieving major pathological responses (MPR). These findings highlight the pressing need for further investigation into strategies for organ preservation and radiotherapy adjustments in patients who achieve MPR. Our objective was to utilize non-invasive and accessible clinical assessments to predict pathological response before surgery. By employing enhanced CT scans, esophagograms, and esophagoscopy before and after neoadjuvant treatment, we collected objective and quantitative parameters that reflected the dynamic shrinkage of tumors. Subsequently, we constructed prediction models for pathological response using multivariate logistic regression based on those dynamic parameters. These models accurately predicted pathologic complete response (pCR) (AUC 0.879) and MPR (AUC 0.912) of the primary tumor after neoadjuvant immunochemotherapy. This advancement may significantly aid informed decision-making in patient management. To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy. [ABSTRACT FROM AUTHOR]

Background: Locally advanced oral squamous cell carcinoma (LAOSCC) is associated with a high rate of recurrence and poor survival. Given the recent successes of neoadjuvant immunochemotherapy (NAICT) in solid tumors, it is promising to use this treatment modality to achieve a better pathological response and improve the survival of LAOSCC, and clinical evidence is needed to assess its safety and efficacy. Patients and Methods: A prospective trial of NAICT with toripalimab (PD-1 inhibitor) and albumin paclitaxel/cisplatin (TTP) was conducted in patients with clinical stage III and IVA OSCC. Intravenous albumin paclitaxel (260 mg/m²), cisplatin (75 mg/m²), and toripalimab (240 mg) were given in sequence on day 1 of each 21 day cycle for two cycles, followed by radical surgery and risk-adapted adjuvant (chemo)radiotherapy. The primary endpoints were safety and major pathological response (MPR). Targeted next generation sequencing and multiplex immunofluorescence were performed to assess clinical molecular characteristics and the tumor immune microenvironment in the pre-NAICT and post-NAICT tumor samples. Results: Twenty patients were enrolled. NAICT was well-tolerated with a low incidence of grades 3-4 adverse events in three patients. The completion rates of NAICT and subsequent R0 resection were 100%. The MPR rate was 60%, including a 30% pathological complete response. MPR was achieved in all four patients with a combined positive score of PD-L1> 10. The density of tertiary lymphatic structure in post-NAICT tumor samples predicted the pathological response to NAICT. During the median 23- month follow-up, the disease-free survival was 90%, and the overall survival was 95%. Conclusions: NAICT with the TTP protocol in LAOSCC is feasible and well tolerated, with a promising MPR and no obstruction on subsequent surgery. This trial is supportive of further randomized trials using NAICT in LAOSCC. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant immunochemotherapy has been increasingly applied to treat non-small cell lung cancer (NSCLC). However, the comparison between robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the feasibility and oncological efficacy following neoadjuvant immunochemotherapy is scarce. This study aims to assess the superiorities of RATS over (VATS) concerning short-term outcomes in treating NSCLC patients with neoadjuvant immunochemotherapy. Methods: NSCLC patients receiving RATS or VATS lobectomy following neoadjuvant immunochemotherapy at Shanghai Chest Hospital from 2019 to 2022 were retrospectively identified. Baseline clinical characteristics, perioperative outcomes, and survival profiles were analyzed. Results: Forty-six NSCLC patients with neoadjuvant immunochemotherapy were included and divided into the RATS (n=15) and VATS (n=31) groups. The baseline clinical characteristics and induction-related adverse events were comparable between the two groups (all p>0.050). The 30-day mortality in the RATS and VATS groups were 0% and 3.23%, respectively (p=1.000). Patients undergoing RATS were associated with reduced surgical-related intensive unit care (ICU) stay than those receiving VATS (0.0 [0.0-0.0] vs. 0.0 [0.0-1.0] days, p=0.026). Moreover, RATS assessed more N1 LNs (6.27 ± 1.94 vs 4.90 ± 1.92, p=0.042) and LN stations (3.07 ± 1.03 vs 2.52 ± 0.57, p=0.038) compared with VATS. By comparison, no difference was found in surgical outcomes, pathological results, and postoperative complications between the RATS and VATS groups (all p>0.050). Finally, RATS and VATS achieved comparable one-year recurrence-free survival (82.96% vs. 85.23%, p=0.821) and the timing of central nervous system, LN, and bone recurrences (all p>0.050). Conclusion: RATS is safe and feasible for NSCLC patients with neoadjuvant immunochemotherapy, reducing surgical-related ICU stay, assessing increased N1 LNs and stations, and achieving similar survival profiles to VATS. [ABSTRACT FROM AUTHOR]

Background: Recently, the use of immunochemotherapy in the treatment of advanced gastric cancer (GC) has been increasing and programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy has become the firstline treatment for advanced GC. However, few studies with small sample sizes have examined this treatment regimen to assess its effectiveness and safety in the neoadjuvant treatment phase of resectable local advanced GC. Materials and methods: Herein, we systematically searched PubMed, Cochrane CENTRAL, and Web of Science for clinical trials on neoadjuvant immunochemotherapy (nICT) in advanced GC. The primary outcomes were effectiveness [evaluated by major pathological response (MPR) and pathological complete response (pCR)] and safety [assessed by grade 3–4 treatment-related adverse events (TRAEs) and postoperative complications]. A meta-analysis of non-comparative binary results was performed to aggregate the primary outcomes. Direct comparative analysis was used to compare pooled results of neoadjuvant chemotherapy (nCT) with nICT. The outcomes emerged as risk ratios (RR). Results: Five articles with 206 patients were included, and all of them were from the Chinese population. The pooled pCR and MPR rates were 26.5% (95% CI: 21.3%–33.3%) and 49.0% (95% CI: 42.3%–55.9%), while grade 3–4 TRAEs and post-operative complication rates were 20.0% (95% CI: 9.1%–39.8%) and 30.1% (95% CI: 23.1%–37.9%), respectively. Direct comparison showed that with the exception of grade 3–4 TRAEs and postoperative complications, all outcomes including pCR, MPR, and R0 resection rate favoured nICT to nCT.Conclusion: nICT is a promising strategy for use as an advisable neoadjuvant treatment for patients with advanced GC in Chinese population. However, more phase III randomized controlled trials (RCTs) will be required to further consolidate the efficacy and safety of this regimen. [ABSTRACT FROM AUTHOR]

Background and purpose: Unnecessary surgery can be avoided, and more appropriate treatment plans can be developed for patients if the efficacy of neoadjuvant immunochemotherapy for esophageal cancer (EC) can be predicted before surgery. The purpose of this study was to evaluate the ability of machine learning models based on delta features of immunochemotherapy CT images to predict the efficacy of neoadjuvant immunochemotherapy in patients with esophageal squamous cell carcinoma (ESCC) compared with machine learning models based solely on postimmunochemotherapy CT images. Materials and methods: A total of 95 patients were enrolled in our study and randomly divided into a training group (n = 66) and test group (n = 29). We extracted preimmunochemotherapy radiomics features from preimmunochemotherapy enhanced CT images in the preimmunochemotherapy group (pregroup) and postimmunochemotherapy radiomics features from postimmunochemotherapy enhanced CT images in the postimmunochemotherapy group (postgroup). We then subtracted the preimmunochemotherapy features from the postim munochemotherapy features and obtained a series of new radiomics features that were included in the delta group. The reduction and screening of radiomics features were carried out by using the Mann-Whitney U test and LASSO regression. Five pairwise machine learning models were established, the performance of which was evaluated by receiver operating characteristic (ROC) curve and decision curve analyses. Results: The radiomics signature of the postgroup was composed of 6 radiomics features; that of the delta-group was composed of 8 radiomics features. The area under the ROC curve (AUC) of the machine learning model with the best efficacy was 0.824 (0.706-0.917) in the postgroup and 0.848 (0.765-0.917) in the delta group. The decision curve showed that our machine learning models had good predictive performance. The delta group performed better than the postgroup for each corresponding machine learning model. Conclusion: We established machine learning models that have good predictive efficacy and can provide certain reference values for clinical treatment decisionmaking. Our machine learning models based on delta imaging features performed better than those based on single time-stage postimmunochemotherapy imaging features. [ABSTRACT FROM AUTHOR]

Background: Studying the application of neoadjuvant immunochemotherapy (NICT) in the real world and evaluating its effectiveness and safety in comparison with neoadjuvant chemotherapy (NCT) are critically important. Methods: This study included the II-IIIB stage non-small cell lung cancer (NSCLC) patients receiving NCT with or without PD-1 inhibitors and undergoing surgery after neoadjuvant treatments between January 2019 to August 2022. The clinical characteristics and treatment outcomes were retrospectively reviewed and analyzed. Results: A total of 66 patients receiving NICT and 101 patients receiving NCT were included in this study. As compared to NCT, NICT showed similar safety while not increasing the surgical difficulty. The ORR in the NICT and NCT groups was 74.2% and 53.5%, respectively, P = 0.009. A total of 44 patients (66.7%) in the NICT group and 21 patients (20.8%) in the NCT group showed major pathology response (MPR) (P <0.001). The pathology complete response (pCR) rate was also significantly higher in NICT group than that in NCT group (45.5% vs. 10.9%, P <0.001). After Propensity Score Matching (PSM), 42 pairs of patients were included in the analysis. The results showed no significant difference in the ORR between the two groups (52.3% vs. 43.2%, P = 0.118), and the proportions of MPR (76.2%) and pCR (50.0%) in NICT group were significantly higher than those of MPR (11.9%) and pCR (4.7%) in the NCT group (P <0.001). The patients with driver mutations might also benefit from NICT. Conclusions: As compared to NCT, the NICT could significantly increase the proportions of patients with pCR and MPR without increasing the operationrelated bleeding and operation time. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare short and mid-term outcomes in esophageal squamous cell carcinoma (ESCC) patients undergoing open or minimally invasive McKeown esophagectomy (MIE) after neoadjuvant PD-1 inhibitor plus chemotherapy. Methods: Patients with locally advanced ESCC underwent open or minimally invasive McKeown esophagectomy after neoadjuvant PD-1 inhibitor plus chemotherapy were retrospectively included from June 2019 to June 2021. The baseline characteristics, pathological data, short-and mid-term outcomes were collected and compared based on the surgical approach. Results: A total of 35 patients were included in the study. An open procedure was performed for 13 patients (37.1%), and 22 (62.9%) patients underwent MIE after neoadjuvant therapy. Compared with open group, MIE group had shorter operative times (350.8± 117.8 vs. 277.9 ± 30.2 min, P = 0.009). The total number of resected lymph nodes was not significantly different, but more left recurrent laryngeal lymph nodes were harvested from the Open group (2.6 ± 3.2 vs. 0.9 ± 1.7, P = 0.047). The median follow-up time was 1.42 years (range, 0.35-2.59 years) from the first day of treatment. Three patients (8.6%) died during follow-up, one in the open surgery group and two in the MIE group. There were six (17.1%) patients developed recurrence, three in each group. The 2-year cumulative survival rates were 92.3 ± 7.4% and 89.5 ± 7.1% for the open and MIE groups, respectively. Overall survival was not different between the two surgical approaches. Conclusions: MIE might be safe and feasible for patients with locally advanced ESCC undergoing neoadjuvant PD-1 inhibitor plus chemotherapy. [ABSTRACT FROM AUTHOR]

Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches.

IntroductionThe treatment response to neoadjuvant immunochemotherapy varies among patients with potentially resectable non-small cell lung cancers (NSCLC) and may have severe immune-related adverse effects. We are currently unable to accurately predict therapeutic response. We aimed to develop a radiomics-based nomogram to predict a major pathological response (MPR) of potentially resectable NSCLC to neoadjuvant immunochemotherapy using pretreatment computed tomography (CT) images and clinical characteristics.MethodsA total of 89 eligible participants were included and randomly divided into training (N=64) and validation (N=25) sets. Radiomic features were extracted from tumor volumes of interest in pretreatment CT images. Following data dimension reduction, feature selection, and radiomic signature building, a radiomics-clinical combined nomogram was developed using logistic regression analysis.ResultsThe radiomics-clinical combined model achieved excellent discriminative performance, with AUCs of 0.84 (95% CI, 0.74-0.93) and 0.81(95% CI, 0.63-0.98) and accuracies of 80% and 80% in the training and validation sets, respectively. Decision curves analysis (DCA) indicated that the radiomics-clinical combined nomogram was clinically valuable.DiscussionThe constructed nomogram was able to predict MPR to neoadjuvant immunochemotherapy with a high degree of accuracy and robustness, suggesting that it is a convenient tool for assisting with the individualized management of patients with potentially resectable NSCLC.

ObjectivesNeoadjuvant immunochemotherapy (nICT) has been confirmed with promising pathological complete response (pCR) among locally advanced esophageal squamous cell carcinoma (ESCC). However, there were still no reliable and accurate predictors to predict the treatment response. This study aimed to explore the predictive value of inflammatory and nutritional parameters.MethodsPatients with ESCC who underwent radical surgery after nICT between January 2020 and April 2022 were included in the study. First, the least absolute shrinkage and selection operator regression (LASSO) logistic regression analysis was used to screen independent inflammatory and nutritional parameters. Secondly, univariate and multivariate logistic regression were used to screen and predict independent risk factors for pCR. Thirdly, a nomogram was constructed based on the independent predictive factors, and 30% of the included population was randomly selected as the validation cohort. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model.ResultsA total of 97 ESCC patients were screened for analysis, with 20 patients with pCR (20.32%). Only the systemic immune-inflammation index (SII) was screened after LASSO-logistic regression when λ was 0.06. The cut-off value of SII was 921.80 with an area under curve (AUC) value of 0.62. We defined SII > 921.80 as high SII and SII ≦ 921.80 as low SII. Further, the univariate and multivariate analysis further determined SII(OR = 3.94, 95%CI:1.26–12.42, P = 0.02) and clinical stage(OR = 0.35, 95%CI:0.12–0.98, P = 0.05) were independent predictive factors of pCR. One novel nomogram was established with an AUC value of 0.72 in the training cohort and 0.82 in the validation cohort. The Brier score of the calibration curve was 0.13. The calibration curve showed good agreement between the predicted results and the actual results in both the training cohort and the validation cohort. Compared with the clinical stage, the DCA confirmed a better clinical value of the nomogram model in both the training cohort and the validation cohort.ConclusionsHigh pretreatment SII and early clinical stage were independently associated with pCR among ESCC receiving nICT. We further established and validated one novel nomogram model to effectively predict pCR among ESCC after nICT.

Objectives: The efficacy and safety of neoadjuvant immunochemotherapy (nICT) are widely explored in locally advanced esophageal squamous cell carcinoma (ESCC). Whether the “wait-and-see” strategy is applicable in ESCC after nICT is still lacking a theoretical basis. This study aimed to preliminarily explore the distribution of residual tumors and the regression pattern of ESCC after nICT. Methods: Patients undergoing radical esophagectomy after nICT in Fujian Medical University Union Hospital between January 2020 and March 2022 were identified. The resection specimens were re-evaluated by one experienced pathologist. The pathological response was assessed by tumor regression grade (TRG) (modified Ryan scheme). The TRG grade was divided into grades 0 (pathological complete response), 1, 2, and 3. The pathological stage was evaluated in the Eighth Edition AJCC. In the non-pCR group, the residual model was divided into four types: Type I, regression towards the lumen; type II, regression towards the invasive front; type III, concentric regression; and type IV, scattered regression. Results: A total of 95 consecutive patients were included for analysis. Seventysix (80.0%) of 95 patients were in non-pCR (pathological complete response), and nine patients (9/76, 11.84%) had isolated residual tumors in lymph nodes. There was no significant difference in baseline characteristics between the pCR group and the non-pCR group (p > 0.05). The overall distribution of TRG for all esophageal wall layers was TRG 0 = 28 (28/95, 29.5%), TRG 1 = 17 (17/95, 17.9%), TRG 2 = 18 (18.9%, 18/95), and TRG 3 = 32 (32/95, 33.7%). In 67 patients with residual tumors in the esophageal wall (TRG ≧11), 63 (63/67, 94.0%) had residual tumor cells in the mucosa and/or submucosa, and four had isolated residual tumors in the muscle layer (4/67, 6.0%). Further analysis showed eight (8/67, 11.9%) patients with submucosal involvement but without mucosal involvement. The distribution of regression patterns was type I (n = 35, 52.2%), type II (n = 3, 4.5%), type III (n = 8, 11.9%), and type IV (n = 21, 31.3%). Conclusions: The mucosa and/or submucosa are frequently involved in residual malignancy, and the frequent regression models are regression toward the lumen and random regression. There is an opportunity to carefully test the residual tumors in a subgroup of the population with ESCC following nICT. However, some patients had residual tumors only in the muscle layer or lymph nodes. The clinical application of the wait-and-see strategy in ESCC after nICT should be explored using an appropriate evaluation protocol. [ABSTRACT FROM AUTHOR]

Background: The controlling nutritional status (CONUT) score, as an immune-nutritional index, has been reported to be related to prognosis in several cancers. Neoadjuvant immunochemotherapy (nICT) is an emerging pattern for cancer treatment in recent years. However, the usefulness of CONUT in esophageal squamous cell carcinoma (ESCC) with nICT has not been reported so far. This study attempted to clarify the usefulness of CONUT in predicting disease-free survival (DFS) in ESCC with nICT. Methods: Two hundred sixteen ESCC patients receiving nICT between 2019 and 2021 were retrospectively enrolled. Based on CONUT, the patients were divided into two groups: low groups (score ≤ 2) and high (score ≥ 3) groups. The relationships between CONUT and clinical characteristics were estimated. Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs) were also performed to evaluate the prognostic factors of DFS. Results: Fifty-nine (27.3%) patients achieved pathologic complete response (pCR), and 30 (13.9%) cases had a recurrence. There were 150 cases (69.4%) in low CONUT group and 66 cases (30.6%) in high CONUT group, respectively. The results revealed that vessel invasion (P = 0.037), postoperative pneumonia (P = 0.001), advanced ypT stage (P = 0.011), cTNM stage (P = 0.007), and ypTNM stage (P < 0.001) were significantly related to patients with a high CONUT score. A high pCR rate was found in patients with a low CONUT score (33.3% vs. 13.6%, P = 0.003), and a high recurrence rate was found in patients with a high CONUT score (24.2% vs. 9.3%, P = 0.004), respectively. Patients with a low CONUT score had a better 1-year DFS than those with a high CONUT score (90.7% vs. 75.8%, P = 0.004). Multivariate analyses indicated that the pretreatment CONUT score was an independent predictor regarding DFS (HR = 2.221, 95% CI: 1.067--4.625, P = 0.033). Conclusion: A better response and a lower recurrence were found in ESCC patients with a lower pretreatment CONUT. As a useful index for immune-nutritional status, the CONUT might be a reliable prognostic indicator in ESCC patients with nICT. [ABSTRACT FROM AUTHOR]

Objectives: Neoadjuvant immunochemotherapy (nICT) is a novel pattern for locally advanced esophageal squamous cell carcinoma (ESCC), and the time to surgery (TTS) is recommended as 4-6 weeks. However, there were some patients with prolonged TTS(> 6 weeks). This study aimed to explore whether prolonged TTS (> 6 weeks) would affect the outcomes. Methods: Patients diagnosed with locally advanced ESCC between January 2020 and March 2022 and undergoing esophagectomy following nICT were identified based on a prospectively collected database. Primary outcome measures were pathological complete response (pCR) and disease-free survival (DFS), and the secondary outcomes were 30-day postoperative mortality and morbidity, surgical time, postoperative hospital stay, and hospital expense. Results: Total of 95 patients were included for analysis, with 52 patients in the standard TTS group and 43 patients in the prolonged TTS group. The clinical and demographic characteristics of the two groups were comparable. The prolonged group had a median 18 days longer TTS(P<0.001). The pCR rate was 23.08% (12/52) in the standard group and 16.28% (7/43) in the prolonged group (P=0.41). Multivariate regression analysis further indicated that TTS wasn't an independent factor in predicting pCR (P=0.41). The median follow-up time was 10.5 months in the standard TTS group and 11.2 months in the prolonged TTS group. A total of five recurrences occurred with two events in the standard TTS group and three events in the prolonged TTS group, and no significant difference was observed in DFS(P=0.60). Both groups were comparable in postoperative hospital stays, total hospital stay, hospital expenses, and comprehensive complications index (CCI). The complications and major complications were also similar in both groups. Spearman test further indicated that there was no linear correlation among TTS with hospital expenses, postoperative hospital stays, hospital stay, CCI index, lymph nodes moved number, or surgical time, with a p-value of 0.48, 0.63, 0.80, 0.92, 0.09, 0.38 respectively. Conclusions: Based on present evidence, TTS after completion of nICT is not of major importance concerning pathological response, disease-free survival, and short-term postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objective: There is currently no consensus over whether neoadjuvant immunochemotherapy is more effective in young patients than in elderly patients with IIA-IIIB non-small-cell lung cancer (NSCLC). In this study, we compare the efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA-IIIB NSCLC., Methods: This retrospective study consecutively included IIA-IIIB NSCLC patients who received 2-4 cycles preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2022. The 1:1 propensity score match analysis was conducted to balance the confounding factors between the young patient group (< 65 years old) and elderly patient group (≥ 65 years old). The follow-up period would not end until at least 1 year after surgery or patient's decision to abandon treatment. The primary endpoint was pathological response, while the secondary endpoints were objective response rate (ORR), adverse events (AEs), disease-free survival (DFS) and overall survival (OS)., Results: A total of 179 patients were included in our study: <65 years group (71 patients) and ≥ 65 years group (108 patients). After a 1:1 propensity score matching,132 patients (66 pairs) were analyzed to compare the efficacy and safety between the two groups. The ORR in the young patient group and elderly patient group was 72.7% and 71.2% (P = 1.000), respectively. The incidence of grade 3-4 AEs in the elderly patient group was similar to the young patient group (13.6% vs. 16.7%, P = 0.627). About 62.1% (41/66) in the young patient group and 54.5% (36/66) in the elderly patient group eventually underwent surgery. The rate of major pathological response (MPR) in the young patient group and elderly patient group was 68.3% and 55.6% (P = 0.903), respectively. The rate of pathological complete response (pCR) in the young patient group was significantly higher than that in the elderly patient group (46.3% vs. 22.2%, P = 0.027). The median DFS in the young patient group was not reached and 32.2 months in the elderly patient group (P = 0.071). The 1-year DFS rate, 2-year DFS rate and 3-year DFS rate in the young patient group were 90.2%, 85.4% and 80.5%, with that in the elderly patient group 86.1%, 69.4% and 66.7%. The median OS in the young patient group was 42.4 months and not reached in the elderly patient group (P = 0.067). The 1-year OS rate, 2-year OS rate and 3-year OS rate in the young patient group were 97.6%, 90.2% and 90.2%, with that in the elderly patient group 88.9%, 80.6% and 72.2%., Conclusions: For IIA-IIIB NSCLC, neoadjuvant immunochemotherapy in young patients can produce a higher percentage of patients with a pCR than in elderly patients. However, the survival benefits and incidence of AEs are similar in young and elderly patients., Competing Interests: Declarations. Ethical approval: This trial was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (2021 IIT No. 844), and done in accordance with the Declaration of Helsinki (as revised in 2013) and Good Clinical Practice Guidelines. Written informed consent was obtained from patients so that we could acquire and use required information from their medical record in our hospital. Conflict of interest: The authors have no conflicts of interest to declare., (© 2024. The Author(s).)

Background: We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728)., Methods: Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr +/- , for Br-ESCC., Findings: Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr + resection, and 38.9% (7/18) were classified as Rbr - resection. With a median postoperative follow-up of 17.9 months, 4 patients out of 11 who underwent Rbr + resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr - resection experienced local recurrence., Conclusions: Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr + resection leads to a higher rate of local recurrence in patients with Br-ESCC., Funding: This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A series of randomized controlled trials (RCTs) have demonstrated the promising prospect of immunotherapy in operable non-small cell lung cancer (NSCLC) and further changed the clinical practice. However, current studies still yet to answer which immunotherapy mode is the optimal strategy, and there is currently a lack of direct comparison between neoadjuvant immunochemotherapy and perioperative immunotherapy ("sandwich mode", including neoadjuvant immunochemotherapy and adjuvant immunotherapy). Thus, we conducted a network meta-analysis (NMA) to evaluate the efficacy between neoadjuvant immunochemotherapy and perioperative immunotherapy., Methods: We performed a Bayesian NMA (PROSPERO registration number: CRD42024495955) by retrieving relevant eligible studies from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences until December 31, 2023. Phase II or III RCTs that evaluated the efficacy of different strategies of immunotherapy in operable NSCLC, including neoadjuvant immunochemotherapy and perioperative immunotherapy ("sandwich mode"), were retrieved for analysis. The patients were grouped into neoadjuvant chemotherapy alone (arm A), neoadjuvant immunotherapy plus chemotherapy (arm B); neoadjuvant immunotherapy plus chemotherapy followed by surgery and adjuvant immunotherapy (arm C), respectively. The endpoint was event-free survival (EFS) in different subgroups., Results: Seven studies of 2,934 patients were selected for this NMA finally. Compared with neoadjuvant chemotherapy, both neoadjuvant immunochemotherapy [hazard ratio (HR) 0.61, 95% confidence interval (CI): 0.36-0.98] and perioperative immunotherapy (HR 0.56, 95% CI: 0.42-0.71) significantly improved the EFS in intention-to-treat population, but there was no statistical difference between these two treatments (HR 1.1, 95% CI: 0.62-1.9). There was no statistical difference between perioperative immunotherapy and neoadjuvant immunochemotherapy in all subgroup analysis of EFS. However, in patients with non-squamous disease, programmed cell death-ligand 1 (PD-L1) expression more than 50%, or stage III disease, both neoadjuvant immunotherapy [(HR 0.50, 95% CI: 0.26-0.97), (HR 0.24, 95% CI: 0.061-0.96), (HR 0.50, 95% CI: 0.39-0.63)] and perioperative immunotherapy [(HR 0.64, 95% CI: 0.46-0.87), (HR 0.40, 95% CI: 0.21-0.71), (HR 0.54, 95% CI: 0.34-0.85)] improved EFS significantly compared with neoadjuvant chemotherapy., Conclusions: Both neoadjuvant immunochemotherapy and perioperative immunotherapy significantly increased EFS compared with neoadjuvant chemotherapy. There is no evidence that perioperative immunotherapy is better than neoadjuvant immunochemotherapy in EFS. Patients with non-squamous disease, PD-L1 expression more than 50%, or stage III disease can try the neoadjuvant immunochemotherapy mode., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-287/coif). All authors report that this study was supported by the Youth Project of the Natural Science Foundation of Guangdong Province (No. 2022A1515110399), and the National Key R&D Program of China (No. 2022YFE0133100). The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: There is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: This is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St. II-IVA) who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2021. In this study, patients were planned to receive 2-4 cycles of chemoimmunotherapy. In this secondary analysis, patients who received three to four cycles of neoadjuvant immunochemotherapy were compared to those receiving two cycles in terms of safety and oncologic outcomes. The follow-up duration required for inclusion was at least one year following surgery, or until the patient died or independently elected to cease treatment if less than one year., Results: Our study identified a total of 142 participants, who were categorized into two groups based on the number of neoadjuvant treatment cycles: the two cycles group (2 cycles) (n=65) and the three to four cycles group (3-4 cycles) (n=77). Regarding the rate of major pathologic response (MPR), the rates for the 3-4 cycles and 2 cycles groups were 22.1% and 20.0%, respectively, although this difference was not statistically significant (P=0.25). Similarly, the rate of pathologic complete remission (pCR) was higher in the 3-4 cycles group at 14.3% compared to 7.7% in the 2 cycles group, but the difference did not reach statistical significance (P=0.07). However, the incidence of adverse events (AEs) classified as grade 3 or 4 was significantly higher in the 3-4 cycles group than in the 2 cycles group (36.4% vs. 18.5%; P=0.02). The median disease-free survival (DFS) for the 3-4 cycles group was 30.8 months [95% confidence interval (CI): not reached to not reached] and was not reached in the 2 cycles group (hazard ratio 2.35, 95% CI: 1.134-4.86; P=0.02). The 2 cycles group did not reach the median overall survival (OS) (hazard ratio 2.47, 95% CI: 1.08-5.53; P=0.045), with that in the 3-4 cycles group 34.9 months (95% CI: 24.5 to not reached). Interestingly, the survival outcomes were more favorable in the 2 cycles group for certain subgroups of patients: those who were male, those with a history of smoking, those with a history of drinking, and those who did not achieve MPR., Conclusions: Two cycles of neoadjuvant immunochemotherapy can be considered in locally advanced ESCC at high risk of developing toxicity with 3-4 cycles with similar oncologic outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1365/coif). J.M.P. received honoraria from ASTELLAS and J&J Worldwide, and payment for participation in Advisory Board from Ferranova, and serves as the Chair of the Florida Chapter of the American College of Surgeons (FCACS) Surgical Education Committee. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Neoadjuvant immunochemotherapy (nICT) has emerged as a popular treatment approach for advanced gastric cancer (AGC) in clinical practice worldwide. However, the response of AGC patients to nICT displays significant heterogeneity, and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes., Aim: To establish a radiomic model to predict the response of AGC patients to nICT., Methods: Patients with AGC who received nICT ( n = 60) were randomly assigned to a training cohort ( n = 42) or a test cohort ( n = 18). Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT. An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature. The performance of all the models was assessed through receiver operating characteristic curve analysis, decision curve analysis (DCA) and the Hosmer-Lemeshow goodness-of-fit test., Results: The radiomic nomogram could accurately predict the response of AGC patients to nICT. In the test cohort, the area under curve was 0.893, with a 95% confidence interval of 0.803-0.991. DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models., Conclusion: A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC. This tool can assist clinicians in treatment-related decision-making., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)