Phase I trial of apatinib and paclitaxel+oxaliplatin+5-FU/levoleucovorin for treatment-naïve advanced gastric cancer.

Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment-naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional "3 + 3" study design. Among 21 treated patients, one experienced a dose-limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3-4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand-foot syndrome (14.3%). Median progression-free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first-line treatment for AGC in a larger study.

Prognostic Factors and Outcomes in Elderly Esophagectomy Patients with Esophageal Cancer.

BACKGROUND: Choosing the appropriate treatment for elderly patients with esophageal cancer remains a contentious issue. While surgery is still a valid option, we aimed to identify predictors and outcomes in elderly esophagectomy patients with esophageal cancer. PATIENTS AND METHODS: We analyzed characteristics, surgical outcomes, survival rates, cause-specific mortality, and recurrence in 120 patients with stage I-IV esophageal cancer. Univariate and multivariate analyses were used to identify risk factors for event-free survival (EFS) and overall survival (OS). RESULTS: The median follow-up period was 31 months, with 5-year overall survival (OS) and event-free survival (EFS) rates standing at 45.2% and 41.5%, respectively. Notably, lower body mass index (BMI ≤ 22 kg/m2) and reduced preoperative albumin levels (pre-ALB < 40 g/L) led to a significant decrease in OS rates. Postoperative pulmonary complications resulted in higher in-hospital and 90-day mortality rates. After about 31 months post-surgery, the rate of cancer-specific deaths stabilized. The most common sites for distant metastasis were the lungs, supraclavicular lymph nodes, liver, and bone. The study identified lower BMI, lower pre-ALB levels, and postoperative pulmonary complications as independent risk factors for poorer EFS and OS outcomes. CONCLUSIONS: Esophagectomy remains a safe and feasible treatment for elderly patients, though the prevention of postoperative pulmonary infection is crucial. Factors such as lower BMI, lower pre-ALB levels, advanced tumor stage, postoperative pulmonary complications, and certain treatment modalities significantly influence the outcomes in elderly esophagectomy patients. These findings provide critical insights into the characteristics and outcomes of this patient population.

High-dose chemotherapy sensitizes locally advanced esophageal squamous cell carcinoma to PD-1 blockade for a higher pathological complete response rate and survival.

BACKGROUND: PD-1 inhibitor and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). The present study aimed to evaluate the efficacy of PD-1 inhibitors plus different dose intensity neoadjuvant chemotherapy in the treatment of locally advanced ESCC. METHODS: Patients with locally advanced but resectable thoracic ESCC, staged as T3 or T4a, N0-3, and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes), were enrolled in this study. The eligible patients received tislelizumab plus different dose intensity chemotherapy for a 21-day cycle with repeated 2-4 cycles before surgery. The primary endpoints are pathological complete response (pCR) and major pathological response (MPR), and the secondary endpoints are objective response rate (ORR), disease control rate (DCR), and disease-free survival (DFS). RESULTS: From November 2019 to February 2022, 122 cases received at least two cycles neoadjuvant chemoimmunotherapy and were evaluated by imaging examination. Subsequently, 99 patients underwent surgery and were evaluated by pathological evaluation. According to chemotherapy dose intensity, the patients were divided into three cohorts: cohort 1 (<80% dose intensity), cohort 2 (80-90% dose intensity), cohort 3 (90-100% dose intensity). All surgery patients underwent minimally invasive esophagectomy (MIE). The average pCR was identified in 22.22%; 16% had pCR in cohort 1, 17.65% had pCR in cohort 2, and 30.00% had pCR in cohort 3. MPR was observed in 9 (36.00%) patients in cohort 1, 18 (52.94%) patients in cohort 2, 22 (55.00%) patients in cohort 3. In univariable and multivariable analysis, dose intensity was significantly associated with MPR (p = 0.048) in patients who underwent esophagectomy. For surviving patients, the median follow-up was 13.76 months after esophagectomy. Compared to cohort 1, cohorts 2 and 3 had better DFS (p = 0.056). In addition, the prognosis of patients with MPR was better than that of patients without MPR (p = 0.014). CONCLUSIONS: The robust antitumor activity of neoadjuvant chemoimmunotherapy for locally advanced but resectable thoracic ESCC was confirmed. More than 80% of chemotherapy dose intensity combined with immunotherapy resulted in a high pCR rate and prolonged DFS.

Glucose-6-phosphate dehydrogenase promotes the proliferation and migration of lung adenocarcinoma cells via the STAT3 signaling pathway.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, and the leading cause of cancer-related deaths worldwide. G6PD has been reported to enhance the progression of various tumors by regulating the intracellular redox state and mediating nucleic acid synthesis. However, the biological role and molecular mechanism of G6PD in LUAD remain largely unknown. In this study, we found that G6PD was significantly upregulated in LUAD specimens and cell lines, and that the high levels of G6PD expression were closely associated with a poor prognosis for LUAD patients. Moreover, we found that G6PD significantly promoted the proliferation and migration of LUAD cells in vitro, and overexpression of G6PD also play a role of facilitating tumorigenesis in in vivo experiments. Mechanistically, the STAT3 signaling pathway was significantly activated by G6PD-mediated LUAD progression. Overall, our results suggest that G6PD could serve as a novel prognostic marker and therapeutic target for treating LUAD.

Erratum: RPL35 promotes neuroblastoma progression via the enhanced aerobic glycolysis.

[This corrects the article on p. 5701 in vol. 11, PMID: 34873488.].

RPL35 promotes neuroblastoma progression via the enhanced aerobic glycolysis.

Neuroblastoma (NB) is an rare type of tumor that almost affects children age 5 or younger due to its rapid proliferation ability. The overall survival rate of patients with advanced NB is not satisfactory. Ribosomal proteins (RPs) play a critical role in the development and progress of cancer. However, the contribution of RPL35 in NB has not been proven. In this study, we reveal that RPL35 is upregulated in NB tissues and the upregulation of RPL35 promotes proliferation and migration of NB while RPL35 knockdown significantly restrained the proliferation of NB cells. In terms of mechanism, glycolysis was decreased and the mitochondrial respiration was increased with knockdown of RPL35 in NB cells, indicating that RPL35 function as a positive regulator in aerobic glycolysis. Importantly, our data indicated that RPL35 deficiency decreased HIF1α expression both in mRNA and protein levels. Western blot analysis showed that RPL35 knockdown has a negative regulatory effect on the ERK pathway, and RPL35 modulated aerobic glycolysis in part through its regulation of the RPL35/ERK/HIF1α axis. Overall, RPL35 functions as a positive regulator of aerobic glycolysis, and the RPL35/ERK/HIF1α axis could be a potential therapeutic target for the therapy of NB.

Safety of subxiphoid uniportal video-assisted thoracoscopic surgery for anterior mediastinal tumour in obese patients.

INTRODUCTION: Subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) has been gradually applied for the treatment of anterior mediastinal tumour (AMT). However, whether obesity is a risk factor for subxiphoid uniportal VATS for AMT is still unknown. AIM: To explore the safety and short-term outcome of subxiphoid uniportal VATS for AMT in obese patients. MATERIAL AND METHODS: The clinical data of 142 patients who received VATS via subxiphoid approach for AMT were analysed. According to body mass index (BMI), the patients were divided into an obese group (BMI ≥ 28 kg/m2) and a non-obese group (BMI < 28 kg/m2). Then, the clinical and surgical characteristics between the obese group and the non-obese group were analysed to explore the effect of obesity on VATS for AMT. The pain scores were evaluated by the Numeric Rating Scale. RESULTS: The operative time and tracheal intubation time using subxiphoid uniportal VATS for AMT in the obese group were longer than that in the non-obese group (p < 0.05). However, there was no obvious difference in intraoperative blood loss, chest tube drainage time, chest tube drainage volume, and length of hospital stay between the obese group and the non-obese group (p > 0.05). Moreover, there was also no significant difference in postoperative complications, including pulmonary complications, wound infection, arrhythmia, and pulmonary leak, between the obese group and the non-obese group. In addition, the pain scores in the obese group were similar to those in the non-obese group. CONCLUSIONS: Although obesity might prolong operative time of subxiphoid uniportal VAST for AMT, it does not increase the rate of postoperative complications. An experienced centre can properly conduct VAST via subxiphoid approach when treating AMT in obese patients.

A pathological complete response to neoadjuvant chemotherapy and immunotherapy in a non-small cell lung cancer patient.

Lung cancer is the leading cause of cancer-related mortality worldwide. Patients with locally advanced non-small cell lung cancer (NSCLC) have lower overall survival. Studies have shown that some patients with unresectable stage III NSCLC develop disease progression after initial chemoradiotherapy, and new treatment is needed to improve the prognosis of these patients. The rapid development of therapy has greatly changed and continued to renew the treatment strategy of advanced NSCLC. However, the clinical treatment for patients with the wild-type gene remains problematic, and chemotherapy with platinum are not yet considered satisfactory. Herein, we are reporting a case of a patient with wild-type gene mutation locally advanced NSCLC who was treated with neoadjuvant therapy by using combined targeted anti-PD-1 immunotherapy and chemotherapy. The percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) was 90% or greater. After receiving all three cycles of treatment, the patient underwent video-assisted right upper lung lobectomy and wedge resection plus radical mediastinal lymph node dissection. Pathological section samples showed a pathological complete response. This experience has led us to believe that the subgroup of patients with unresectable advanced NSCLC may benefit from this strategy and may have an opportunity for radical surgery.