PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer.

Background: Chemoresistance is a significant factor contributing to tumor recurrence and treatment failure in non-small cell lung cancer (NSCLC). The phosphofructokinase, platelet (PFKP) is highly expressed in NSCLC and is associated with a poor prognosis. Exploring the molecular mechanism and identifying effective strategies to overcome chemoresistance will have important clinical significance in improving the diagnosis and treatment of NSCLC. Methods: The correlation between PFKP and cisplatin resistance in NSCLC patients was assessed by organoids and immunohistochemistry. The impact of PFKP on the prognosis of NSCLC patients was analyzed using The Cancer Genome Atlas (TCGA) database. In NSCLC cell lines, the expression of PFKP was modulated using lentivirus, and cisplatin sensitivity was assessed by flow cytometry. Subsequently, the therapeutic effect of cisplatin was tested in BALB/c nude mice implanted subcutaneously with tumor cells. We performed luciferase assay and immunohistochemistry (IHC) to investigate the correlation between PFKP and ABCC2 (ATP-binding cassette sub-family C member 2). Results: Overexpression of PFKP was correlated with poorer survival rates in NSCLC patients who received platinum-based chemotherapy. Using NSCLC organoid, we found that the expression of PFKP was elevated in cisplatin (CDDP)-resistant patients with NSCLC. Overexpression of PFKP decreased the sensitivity of NSCLC cells to CDDP, while genetic inhibition of PFKP enhanced CDDP sensitivity both in vitro and in vivo. Furthermore, we found that PFKP upregulated ABCC2 by increasing the levels of phosphorylation of IκBα and nuclear p65 NF-κB subunit protein. Conclusions: PFKP can regulate the expression of ABCC2 through the activation of NF-κB, which in turn promotes chemoresistance in NSCLC. PFKP has the potential to be a personalized therapeutic target for NSCLC patients with chemoresistance.

Deep learning-based solid component measuring enabled interpretable prediction of tumor invasiveness for lung adenocarcinoma.

BACKGROUND: The nature of the solid component of subsolid nodules (SSNs) can indicate tumor pathological invasiveness. However, preoperative solid component assessment still lacks a reference standard. METHODS: In this retrospective study, an AI algorithm was proposed for measuring the solid components ratio in SSNs, which was used to assess the diameter ratio (1D), area ratio (2D), and volume ratio (3D). The radiologist measured each SSN's consolidation to tumor ratio (CTR) twice, four weeks apart. The area under the receiver-operating characteristic (ROC) curve (AUC) was calculated for each method used to discriminate an Invasive Adenocarcinoma (IA) from a non-IA. The AUC and the time cost of each measurement were compared. Furthermore, we examined the consistency of measurements made by the radiologist on two separate occasions. RESULTS: A total of 379 patients (the primary dataset n = 278, the validation dataset n = 101) were included. In the primary dataset, compared to the manual approach (AUC: 0.697), the AI algorithm (AUC: 0.811) had better predictive performance (P =.0027) in measuring solid components ratio in 3D. Algorithm measurement in 3D had an AUC no inferior to 1D (AUC: 0.806) and 2D (AUC: 0.796). In the validation dataset, the AI 3D method also achieved superior diagnostic performance compared to the radiologist (AUC: 0.803 vs 0.682, P =.046). The two measurements of the CTR in the primary dataset, taken 4 weeks apart, have 7.9 % cases in poor consistency. The measurement time cost by the radiologist is about 60 times that of the AI algorithm (P <.001). CONCLUSION: The 3D measurement of solid components using AI, is an effective and objective approach to predict the pathological invasiveness of SSNs. It can be a preoperative interpretable indicator of pathological invasiveness in patients with lung adenocarcinoma.

PD-1/PD-L1 based immunochemotherapy versus chemotherapy alone for advanced esophageal squamous cell carcinoma: A meta-analysis focus on PD-L1 expression level.

BACKGROUND: Immunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC). AIMS: We aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD-1/PD-L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD-L1 expression level. METHODS AND RESULTS: Five randomized controlled trials comparing PD-1/PD-L1 based immunochemotherapy with chemotherapy alone for advanced ESCC were included. We extracted efficacy data (objective response rate [ORR], disease control rate [DCR], overall survival [OS] rate, progression-free survival [PFS] rate) and safety data (treatment-related adverse events, treatment-related mortality) and performed meta-analyses. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long-term survival advantage (OS: hazard ratio [HR] = 0.68, 95% confidence intervals [CI] 0.61-0.75; PFS: HR = 0.62, 95% CI 0.55, 0.70, respectively). Even with PD-L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage (OS: HR = 0.65, 95% CI 0.46-0.93; PFS: HR = 0.56, 95% CI 0.46-0.69, respectively). However, for PD-L1 combined positive score (CPS) < 1, the survival advantage of immunochemotherapy was not significant (OS: HR = 0.89, 95% CI 0.42-1.90; PFS: HR = 0.71, 95% CI 0.47-1.08, respectively). The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment-related mortality (odds ratio = 1.11, 95% CI 0.67-1.83). CONCLUSION: In this study, treatment-related mortality was similar between immunochemotherapy and chemotherapy. PD-1/PD-L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS <1, the survival advantage of immunochemotherapy was not significant compared with chemotherapy.

Camrelizumab Plus Carboplatin and Pemetrexed as First-Line Treatment for Advanced Nonsquamous NSCLC: Extended Follow-Up of CameL Phase 3 Trial.

INTRODUCTION: In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stages IIIB to IV nonsquamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization. METHODS: Eligible patients were randomized 1:1 to 4 to 6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n = 205 and 207, respectively). Total camrelizumab exposure was up to 2 years. RESULTS: As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio = 0.72 [95% confidence interval: 0.57-0.92]). In the chemotherapy-alone group, 95 patients (45.9%) crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio = 0.55 [95% confidence interval: 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%), and 93.9% (31 of 33) of the patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab. CONCLUSIONS: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity and remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced nonsquamous NSCLC.

Survival Outcomes of Sublobectomy and Lobectomy in Elderly Patients with Peripheral Solid-Dominant Non-small Cell Lung Cancer.

BACKGROUND: According to the JCOG0802 study, there were many non-cancer-related deaths in the lobectomy group. Meanwhile, the median age of the enrolled patients in the JCOG0802 study was 67 years old. Whether this difference in perioperative outcomes and survival outcomes is related to age remains unknown. We aim to investigate whether the sublobectomy was comparable to lobectomy in elderly (≥ 75 years old) patients with peripheral solid-dominant [50% ≤ consolidation tumor ratio (CTR) ≤ 1] and diameter ≤ 2 cm non-small cell lung cancer (NSCLC). METHODS: We retrospectively included 10,830 patients who underwent surgery treatment at two large-volume medical centers, Taizhou Hospital of Zhejiang Province and Shanghai Chest Hospital, from January 2016 to January 2018. Of these, 164 patients aged ≥ 75 years, tumor ≤ 2 cm, and 50% ≤ CTR ≤ 1 who received lobectomy or sublobectomy were included in our study. The perioperative outcomes, survival analyses, analysis of death patterns, tumor recurrence patterns, and Cox regression analyses were performed. RESULTS: On perioperative outcomes, sublobectomy was associated with a shorter operation time (p < 0.001), and in terms of survival outcomes, the 5-year overall survival (OS, p = 0.85) and 5-year disease-free surivial (DFS, p = 0.58) did not differ significantly between the two groups. The Cox regression analyses showed that CTR value, visceral pleural infiltration, and smoking were independent risk factors for worse OS. Furthermore, tumor recurrence pattern and death patterns between the two groups did not differ significantly. CONCLUSIONS: Sublobectomy could achieve superior perioperative outcomes and equivalent oncological efficacy in comparison with lobectomy in elderly patients (≥ 75 years old) with peripheral solid-dominant and diameter ≤ 2 cm NSCLC.

Minigene Assay as an Effective Molecular Diagnostic Strategy in Determining the Pathogenicity of Noncanonical Splice-Site Variants in FLCN.

Primary spontaneous pneumothorax (PSP) or pulmonary cyst is one of the manifestations of Birt-Hogg-Dubé syndrome, which is caused by pathogenic variants in FLCN gene. Genetic testing in patients with PSP identifies a certain number of missense or intronic variants. These variants are usually considered as variants of uncertain significance, whose functional interpretations pose a challenge in clinical genetics. To improve recognition of pathogenic splice-altering variants in FLCN gene, computational tools are used to prioritize potential splice-altering variants and then a hybrid minigene assay is performed to verify the RNA splicing pattern. Herein, variants in FLCN exon 11 and its flanking sequence are focused. Eight variants detected in 11 patients with PSP are evaluated, and six variants are prioritized by in silico tools as potential splice-altering variants of uncertain significance. Four variants (c.1177-5_1177-3delCTC, c.1292_1300+4del, c.1300+4C>T, and c.1300+5G>A) are demonstrated by minigene assay to alter RNA splicing of FLCN, and the last three of them are novel. RT-PCR of patient-derived RNA gives consistent results. Genotype-phenotype correlation analysis in patients with PSP with these variants demonstrates good concordance. Our results underline the importance of RNA analysis, which could provide molecular evidence for pathogenicity of a variant, and provide essential information for the clinical interpretation of variants. Combining the clinical information, a definitive diagnosis could be made.

Lymph Node Ratio Improves Prediction of Overall Survival in Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy: A National Cancer Database Analysis.

OBJECTIVE: This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer. BACKGROUND: A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy. METHODS: Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index ( C -index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial. RESULTS: Both ypN ( P <0.001) and r-ypN ( P <0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C -index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C -index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C -index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort. CONCLUSIONS: LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.

Impact of Lymph Node Dissection on Survival After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

OBJECTIVE: To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). SUMMARY OF BACKGROUND DATA: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. METHODS: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group. RESULTS: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20. CONCLUSIONS: Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local diseasecontrol. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010.

OBJECTIVES: The prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis. METHODS: The phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy. RESULTS: In total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence. CONCLUSIONS: Prerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.

Factors influencing surgical choice and anxiety in patients with pulmonary nodules smaller than 8 mm.

Background: The detection of pulmonary nodules significantly impacts the lives and mental health of patients. Although the 2020 National Comprehensive Cancer Network (NCCN) guidelines recommend scheduled surveillance for nodules ≤8 mm, patients often opt to have their nodules surgically removed. Methods: A cross-sectional questionnaire was administered to patients with small pulmonary nodules who presented to a local grade 3 hospital with small pulmonary nodules and decided to receive surgery versus prescribed monitoring. The questionnaire included four aspects: (I) patient characteristics; (II) nodule-specific knowledge; (III) doctor-patient communication; and (IV) nodular-specific distress. Nodular-specific distress was measured by the Impact of Event Scale-Revised (IES-R). Results: A total of 234 (69%) patients responded to the survey and were included in the final analysis. Poor performance in activities of daily living (ADLs), the presence of solid nodules, multifocal disease, and a family history of lung cancer were significantly associated with reported anxiety. Most notably, facilitating patient choice for surgery was the computed tomography (CT) scan results, with reference to lung nodule size and number of nodules, where concerns related to lung nodule, cancer risk, and fear of surgery or death had a significant psychological impact on patients. Conclusions: In this cohort of patients who elected to have their small pulmonary nodules surgically removed, we identified key factors underlying their anxiety toward guideline recommended surveillance. Our findings will be useful for clinicians when discussing treatment options with their patients.

The role of ferroptosis in esophageal cancer.

Esophageal cancer is one of the most common cancers with high mortality rate around the world. Although the treatment strategy of this disease has made great progress, the prognosis of advanced patients is not ideal. Ferroptosis, a novel regulatory cell death model, that is different from traditional apoptosis and characterized by increased Fenton reaction mediated by intracellular free iron and lipid peroxidation of cell membrane. Ferroptosis has been proved to be closely linked to a variety of diseases, especially cancer. This review aims to summarize the core mechanism of ferroptosis in esophageal cancer, the regulation of ferroptosis signaling pathway and its current application. At the same time, we emphasize the potential and prospect of ferroptosis in the treatment of esophageal cancer. Collectively, targeting ferroptosis pathway may provide new insights into the diagnosis, treatment and prognosis of esophageal cancer.

Lymph node micrometastasis in non-small cell lung cancer.

Lung cancer has some of the highest morbidity and mortality rates of all cancers, and an important risk factor for mortality in patients with lung cancer is tumor metastasis. Even if a tumor is completely removed at an early stage of the disease, quite a number of patients still have the risk of recurrence. With the advent of molecular diagnostic and therapeutics, more and more studies have found that a poor prognosis may be related to lymph node micrometastasis. However, clinicians still find that predicting the prognosis and choosing the type of surgery and postoperative adjuvant chemotherapy are still challenging. Thus, this article reviews the current research status of lymph node micrometastasis in non-small cell lung cancer, envision to provide some updates and insights in this area.

(Neo)adjuvant Chemoradiotherapy is Beneficial to the Long-term Survival of Locally Advanced Esophageal Squamous Cell Carcinoma: A Network Meta-analysis.

PURPOSE: To determine the most effective and safest treatment mode for locally advanced resectable esophageal squamous cell carcinoma through a network meta-analysis. METHOD: A Bayesian model was used for a network meta-analysis comparing the efficacy and safety of surgery alone, neoadjuvant therapy, and adjuvant therapy. RESULTS: Thirty clinical studies, including thirty-one articles, 4866 patients, were analyzed. Overall survival rate: Adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy were significantly advantageous over surgery alone [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.93; HR 0.75, 95%CI 0.65-0.86]. There was no statistically significant difference between adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy [HR 0.97, 95%CI 0.75-1.28]. Disease-free survival rate: Compared with surgery alone, neoadjuvant chemoradiotherapy had significant benefits [HR 0.65, 95%CI 0.53-0.78]; adjuvant chemoradiotherapy had similar, but not significant benefits [HR 0.7, 0.95%CI 0.45-1.06]. The difference between neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy was also not statistically significant [HR 0.94, 0.95%CI 0.61-1.43]. Surgery after neoadjuvant chemoradiotherapy: The R0 resection rate was significantly improved [relative risk (RR) 0.25, 95%CI 0.07-0.86], but the overall postoperative morbidity rate and 30-day postoperative mortality rate tended to increase [RR 1.27, 95%CI 0.8-2.01; RR 1.59, 95%CI 0.7-3.22]. Neither neoadjuvant chemotherapy nor neoadjuvant radiotherapy significantly altered the surgical safety or R0 resection rate. CONCLUSION: Both neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy appear to be the best supplements to surgery for locally advanced resectable esophageal squamous cell carcinoma.

Spontaneous versus mechanical ventilation during video-assisted thoracoscopic surgery for spontaneous pneumothorax: A randomized trial.

OBJECTIVE: Spontaneous ventilation video-assisted thoracic surgery (SV-VATS) is reported to have superior or equal efficacy on postoperative recovery to mechanical ventilation VATS (MV-VATS). However, perioperative safety of the SV-VATS blebectomy is not entirely demonstrated. METHODS: We performed a noninferiority, randomized controlled trial (No. NCT03016858) for primary spontaneous pneumothorax patients aged 16 to 50 years undergoing a SV-VATS and the MV-VATS procedure. The trial was conducted at 10 centers in China from April 2017 to January 2019. The primary outcome was the comparison of intra- and postoperative complications between SV-VATS and MV-VATS procedures. Secondary outcomes included total analgesia dose, change of vital sign during surgery, procedural duration, recovery time, postoperative visual analog pain scores, and hospitalization length. RESULTS: In this study, 335 patients were included. There was no significant difference between the SV-VATS group and the MV-VATS group in the intra- and postoperative complication rates (17.90% vs 22.09%; relative risk, 0.81; 95% confidence interval, 0.52-1.26; P = .346). The SV-VATS group was associated with significantly decreased total dose of intraoperative opioid agents; that is, sufentanil (11.37 µg vs 20.92 µg; P < .001) and remifentanil (269.78 µg vs 404.96 µg; P < .001). The SV-VATS procedure was also associated with shorter extubation time (12.28 minutes vs 17.30 minutes; P < .001), postanesthesia care unit recovery time (25.43 minutes vs 30.67 minutes; P = .02) and food intake time (346.07 minute vs 404.02 minutes; P = .002). Moreover, the SV-VATS procedure deceased the anesthesia cost compared with the MV-VATS ($297.81 vs $399.81; P < .001). CONCLUSIONS: SV-VATS was shown to be noninferior to MV-VATS in term of complication rate and in selected patients undergoing blebectomy for primary spontaneous pneumothorax.

Neoadjuvant chemoradiotherapy, chemotherapy, and radiotherapy do not significantly increase the incidence of anastomotic leakage after esophageal cancer surgery: a meta-analysis.

This study investigated whether neoadjuvant therapies, such as neoadjuvant chemoradiotherapy (NCRT), neoadjuvant chemotherapy (NCT), and neoadjuvant radiotherapy (NRT), would affect the incidence of anastomotic leakage (AL) after esophageal cancer surgery. Published randomized controlled trials were reviewed, and the incidence of AL after esophageal cancer was statistically analyzed in each study. Meta-analysis was performed using Revman and Stata software. A total of 17 randomized controlled trials with 2874 patients were reviewed showing that, in general, preoperative neoadjuvant therapies were not significant risk factors for AL after esophageal cancer surgery (relative risk [RR] = 0.82, 95% CI = 0.64-1.04). NCRT and NRT did not significantly increase the risk of postoperative AL in patients with esophageal cancer (RR = 0.81, 95% CI = 0.63-1.05; RR = 0.64, 95% CI = 0.14-2.97, respectively). Moreover, NCT has no significant correlation with the occurrence of AL (RR = 1.01, 95% CI = 0.57-1.80). NCRT, NCT, and NRT do not significantly increase the incidence of gastroesophageal AL after esophageal cancer surgery.

Pathological complete response after neoadjuvant treatment determines survival in esophageal squamous cell carcinoma patients (NEOCRTEC5010).

BACKGROUND: Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. METHODS: All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. RESULTS: Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. CONCLUSIONS: pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

The role of ferroptosis in lung cancer.

Lung cancer is one of the most common cancers in the world. Although medical treatment has made impressive progress in recent years, it is still one of the leading causes of cancer-related deaths in men and women. Ferroptosis is a type of non-apoptotic cell death modality, usually characterized by iron-dependent lipid peroxidation, rather than caspase-induced protein cleavage. Excessive or lack of ferroptosis is associated with a variety of diseases, including cancer and ischaemia-reperfusion injury. Recent preclinical evidence suggests that targeting ferroptotic pathway is a potential strategy for the treatment of lung cancer. In this review, we summarize the core mechanism and regulatory network of ferroptosis in lung cancer cells, and highlight ferroptosis induction-related tumor therapies. The reviewed information may provide new insights for targeted lung cancer therapy.

A narrative review of primary research endpoints of neoadjuvant therapy for lung cancer: past, present and future.

OBJECTIVE: This review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer. BACKGROUND: Neoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research. METHODS: Therefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov. CONCLUSIONS: Pathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods. KEYWORDS: Neoadjuvant therapy; resectable lung cancer; clinical research endpoint; pathological response.