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

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

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

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

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

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

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

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

Pulmonary metastasectomy for recurrent metastatic ovarian cancer.

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

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Development and Validation of a New Integrative Score Based on Various Systemic Inflammatory and Nutritional Indicators in Predicting Prognosis in Patients With Resectable Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Recent studies revealed that various inflammatory and nutritional indexes were associated with prognosis in esophageal cancer (EC). However, these studies only evaluated one or two indexes, and the prognostic value of these indexes individually or in combination is unclear. This study aimed to construct an integrative score based on various inflammatory and nutritional indexes for prognosis in resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 421 consecutive patients were randomly divided into either a training or validation cohort at a ratio of 7:3 for retrospective analysis. Using logic regression analyses, independent risk factors from peripheral blood indexes were screened to construct an integrative score. The associations regarding the integrative score, clinical characteristics, cancer-specific survival (CSS), and overall survival (OS) were analyzed. RESULTS: Out of 20 indexes, hemoglobin (HB), C-reactive protein to albumin ratio (CAR), and platelet to lymphocyte ratio (PLR) were independent risk factors based on logical regression analyses. Then, an integrative score with the optimal cut-off value of .67 was established according to the Combination Of HB, CAR, and PLR (COHCP). The area under the curve (AUC) indicated higher predictive ability of COHCP on prognosis than other indicators. Multivariate analyses revealed that COHCP serves as an independent prognostic score. Patients with COHCP low group (≤.67) had better 5-year CSS (57.3% vs 13.5%, P < .001) and OS (51.1% vs 12.3%, P < .001) than those with high group, respectively. Finally, the nomogram based on COHCP was established and validated regarding CSS and OS, which can accurately and effectively predict individual survival in resected ESCC. CONCLUSION: The COHCP was a novel, simple, and useful predictor in resectable ESCC. The COHCP-based nomogram may accurately and effectively predict survival.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Long-term outcomes and prognostic factor analysis of resected Siewert type II adenocarcinoma of esophagogastric junction in China: a seven-year study.

BACKGROUND: The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) has significantly increased over the past two decades. Surgery remains the only curative treatment. However, there are currently few studies on Chinese AEG patients. The purpose of this study was to retrospectively analyze the survival and prognostic factors of AEG patients in our center. METHODS: Between January 2008 and September 2014, 249 AEG patients who underwent radical resection were enrolled in this retrospective study, including 196 males and 53 females, with a median age of 64 (range 31-82). Prognostic factors were assessed with the log-rank test and Cox univariate and multivariate analyses. RESULTS: The 5-year survival rate of all patients was 49%. The median survival time of all enrolled patients was 70.1 months. Pathological type, intraoperative blood transfusion, tumor size, adjuvant chemotherapy, duration of hospital stay, serum CA199, CA125, CA242 and CEA, pTNM stage, lymphovascular or perineural invasion, and the ratio of positive to negative lymph nodes (PNLNR) were significantly associated with overall survival when analyzed in univariate analysis. CONCLUSIONS: Our study found that adjuvant chemotherapy, PNLNR, intraoperative blood transfusion, tumor size, perineural invasion, serum CEA, and duration of hospital stay after surgery had significance in multivariate analysis and were independent risk factors for survival.

Prognostic and predictive significance of tumor length in patients with esophageal squamous cell carcinoma undergoing radical resection.

BACKGROUND: The objective of this study was to investigate the prognostic and predictive significance of tumor length in patients with esophageal squamous cell carcinoma undergoing radical resection. METHODS: Tumor length and other clinicopathological variables were retrospectively evaluated in 1435 patients with squamous cell carcinoma treated with radical resection between 2003 and 2010. Tumor length was analyzed as categorical and continuous variable. Associations with overall survival were assessed with Cox proportional hazards models. Model-based nomograms were constructed. Predictive accuracy was measured with C-index. Decision curve analysis was used to evaluate clinical usefulness of prediction models. RESULTS: Both categorically and continuously coded tumor length were independent prognostic factors in multivariable analysis. Adding categorically and continuously coded tumor length to TNM staging model increased predictive accuracy by 0.2 and 0.4 % respectively. Decision curve analysis revealed that the models built by the addition of categorically or continuously coded tumor length did not perform better than TNM staging model. CONCLUSIONS: Tumor length is an independent prognostic factor in patients with esophageal squamous cell carcinoma treated with radical resection. It increases predictive accuracy of TNM staging system for overall survival in these patients. But it does not increase clinical usefulness of TNM staging system as a prediction model.

Preoperative platelet lymphocyte ratio (PLR) is superior to neutrophil lymphocyte ratio (NLR) as a predictive factor in patients with esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various cancers. The aim of this study was to determinate the prognostic value of the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Preoperative NLR and PLR were evaluated in 483 patients undergoing esophagectomy for ESCC from January 2005 to December 2008. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC) curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. RESULTS: High preoperative NLR (≥3.5 versus < 3.5, P = 0.039) and PLR (≥150 versus < 150, P < 0.001) were significantly associated with poor overall survival in multivariate analysis. However, our study demonstrated a better discrimination for the PLR in terms of hazard ratio(HR) than the NLR (HR = 1.840 versus HR = 1.339). Patients with NLR ≥3.5 had significantly poorer overall survival compared to NLR <3.5 (35.4% versus 57.7%, P < 0.001). Patients with PLR ≥150 also had significantly poorer overall survival compared to patients with PLR <150 (32.7% versus 63.5%, P < 0.001). The area under the curve (AUC) was 0.658 (95% confidence interval (CI): 0.610 to 0.706, P < 0.001) for NLR and 0.708 (95% CI: 0.662 to 0.754, P < 0.001) for PLR, indicating that PLR was superior to NLR as a predictive factor in ESCC. CONCLUSIONS: Preoperative NLR and PLR were significant predictors of overall survival in patients with ESCC. However, PLR is superior to NLR as a predictive factor in patients with ESCC.

Does recurrent laryngeal nerve lymph node metastasis really affect the prognosis in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus?

BACKGROUND: Recurrent laryngeal nerve (RLN) lymph node metastasis used to be shown a predictor for poor prognosis in esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prognostic impact of RLN node metastasis and the number of metastatic lymph nodes in node-positive patients with squamous cell carcinoma of middle thoracic esophagus. METHODS: A cohort of 235 patients who underwent curative surgery for squamous cell carcinoma of middle thoracic esophagus was investigated. The prognostic impact was evaluated by univariate and multivariate analyses. RESULTS: Lymph node metastasis was found in 133 patients. Among them, 81 had metastatic RLN nodes, and 52 had at least one positive node but no RLN nodal involvement. The most significant difference in survival was detected between patients with metastatic lymph nodes below and above a cutoff value of six (P < 0.001). Multivariate analysis revealed that the number of metastatic lymph nodes was a significant factor associated with overall survival (P < 0.001), but RLN lymph node metastasis was not (P = 0.865). CONCLUSIONS: RLN Lymph node metastasis is not, but the number of metastatic nodes is a prognostic predictor in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus.

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

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

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

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

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

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

Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial.

We conducted a proof-of-concept, phase 2 trial to assess neoadjuvant SHR-1701 with or without chemotherapy, followed by surgery or radiotherapy, and then consolidation SHR-1701 in unresectable stage III non-small-cell lung cancer (NSCLC). In the primary cohort of patients receiving neoadjuvant combination therapy (n = 97), both primary endpoints were met, with a post-induction objective response rate of 58% (95% confidence interval [CI] 47-68) and an 18-month event-free survival (EFS) rate of 56.6% (95% CI 45.2-66.5). Overall, 27 (25%) patients underwent surgery; all achieved R0 resection. Among them, 12 (44%) major pathological responses and seven (26%) pathological complete responses were recorded. The 18-month EFS rate was 74.1% (95% CI 53.2-86.7) in surgical patients and 57.3% (43.0-69.3) in radiotherapy-treated patients. Neoadjuvant SHR-1701 with chemotherapy, followed by surgery or radiotherapy, showed promising efficacy with a tolerable safety profile in unresectable stage III NSCLC. Surgical conversion was feasible in a notable proportion of patients and associated with better survival outcomes.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .