Three years follow-up of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer.

Neoadjuvant chemoimmunotherapy plays a crucial role in resectable non-small cell lung cancer (NSCLC). Neoadjuvant chemotherapy before sleeve lobectomy was safe and feasible, but the impact of neoadjuvant chemoimmunotherapy before sleeve lobectomy was unclear. In our retrospective study, patients diagnosed as stage IIB to IIIB resectable NSCLC between December 1, 2018 and December 1, 2020 in the Department of Thoracic Surgery, Zhejiang Cancer Hospital were collected. We analyzed the efficacy and safety of neoadjuvant chemoimmunotherapy for resectable NSCLC patients and analyzed the impact of different types of surgery on postoperative complications, surgical difficulty, and long-term survival. In total, 56 patients were included in this retrospective study. With a median follow-up of 35 months, 1-year EFS, 2-year EFS, and 3-year EFS were 87.5%, 80.4%, and 76.7%, respectively. 1-year OS, 2-year OS, and 3-year OS were 96.4%, 91.1%, and 85.6%. respectively. Both median EFS and OS were not reached. The percentage of patients with pCR was 51.8%. 48 (85.7%) patients had nodal downstaging and primary tumor downstaging. In 40 (61.4%) patients occurred neoadjuvant chemoimmunotherapy-related adverse events (AEs), most of them of Grade 1 and 2. Postoperative complications occurred in 19 (33.9%) patients. Subgroup analysis showed that sleeve lobectomy was related to better survival and had no impact on operation duration, hospital stay, intraoperative blood loss, and postoperative complications. Neoadjuvant chemoimmunotherapy led to a high pCR rate, favorable 3-year survival rate, and acceptable AEs. Sleeve lobectomy was safe and related to better survival.

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.

Influence of body mass index on the long-term outcomes of patients with esophageal squamous cell carcinoma who underwent esophagectomy as a primary treatment: A 10-year medical experience.

We explored the influence of body mass index (BMI) on long-term outcomes in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy as a primary treatment. BMI is a risk factor for development of esophageal cancer. However, the details of the relationship between BMI and cancer prognosis remains unclear. Patients who underwent esophagectomy as an initial treatment in 2000 to 2009 period were included. The patients were divided into 3 groups according to Asian-specific BMI cut-offs. The associations between BMI and long-term outcomes were explored. This study included 1082 ESCC patients between 2000 and 2009; all the patients underwent esophagectomy. The median overall survival (OS) of the BMI <18.5, 18.5 ≤ BMI <23, and BMI ≥23 kg/m groups were 21, 24, and 29.5 months, respectively; they differed significantly (P = 0.005). The 5-year survival rates of the 3 groups were 24.6%, 30.4%, and 35.3%, respectively. Multivariate analysis showed that lower BMI was an independent risk factor for a shorter OS (18.5 ≤ BMI <23 kg/m vs. BMI ≥23 kg/m, hazard ratio [HR] = 1.18; 95% confidence interval [CI] = 1.00-1.40, P = 0.054, BMI <18.5 kg/m vs. BMI ≥23 kg/m, HR = 1.38; 95% CI = 1.09-1.75, P = 0.007). The better OS of the BMI ≥23 kg/m patients remained statistically significant in never-smoking patients (P < 0.05). In conclusion, patients with BMIs ≥23 kg/m experienced better OS, and multivariate analysis further indicated that BMI ≥23 kg/m was an independent predictor of survival. When stratified by smoking status, BMI ≥23 kg/m was still a factor in better OS among never smokers.

Elevated levels of preoperative circulating CD44⁺ lymphocytes and neutrophils predict poor survival for non-small cell lung cancer patients.

BACKGROUND: Certain circulating cells have been shown to predict the clinical outcome of several cancers. The objective of this study was to identify clinical, hematological and immunological predictors of prognosis in non-small cell lung cancer (NSCLC) patients. METHODS: A retrospective study on a prevalent cohort of 225 NSCLC patients hospitalized at the Zhejiang Province Cancer Hospital (ZPCH) was conducted from August 1, 2006 to April 15, 2008. Circulating lymphocytes were measured by flow cytometry. WBC count and classification in peripheral blood were measured with a Coulter counter. We calculated the proportion of patients surviving after first hospital admission and hazard ratios (HR) using the Cox proportional hazards model. RESULTS: Elevated levels of preoperative circulating CD44(+) lymphocytes, WBCs and neutrophils indicated low cumulative survival. Clinical stage (HR: 2.292; 95% confidence interval (CI): 1.34-3.91, P=0.002), neutrophils (HR: 1.877; 95% CI: 1.34-2.62, P<0.001) and CD44(+) lymphocytes (HR: 1.018; 95% CI: 1.00-1.03, P=0.002) are independent predictors of survival in NSCLC patients, respectively. Elevated levels of CD44(+) lymphocytes and neutrophils correlated with distant metastasis and prognosis in NSCLC patients with stage III/IV, respectively. CONCLUSIONS: CD44(+) lymphocytes along with neutrophils could serve as an independent prognostic marker for NSCLC patients.

Apoptosis induction of ZBB-006, a novel synthetic diterpenoid, in the human hepatocellular carcinoma cell line HepG2 in vitro and in vivo.

Diterpenes, present in many medicinal plants, have been the focus of continuous studies for the development of new anticancer agents. ZBB-006 is a new synthetic diterpenoid derivative which exhibited significant anti-proliferation activity against various cancer cell lines in our previous study. Here, we investigated the antitumor effect of ZBB-006 and its potential mechanisms in the human hepatocellular carcinoma cell line HepG2, both in vitro and in vivo. We found that oral administration of ZBB-006 effectively suppressed the growth of HepG2 xenograft tumor in nude mice without body weight decline as compared with the control group. Meanwhile, the growth inhibitory effect of ZBB-006 on HepG2 cells was observed with MTT assay. Apoptosis induced by ZBB-006 in HepG2 cells was evidenced by DAPI staining and Annexin V/PI double staining assay. ZBB-006 also dissipated the mitochondrial membrane potential (ΔΨm) apparently as revealed by JC-1 staining. Furthermore, the cleavage of PARP, activation of caspase-3 and caspase-9 but not caspase-8 was demonstrated by western blot assay both in vitro and in vivo. Additionally, the proapoptotic protein Bax was markedly elevated, while the antiapoptotic protein Bcl-2 was downregulated. Collectively, our data indicated that ZBB-006 exerted a strong antitumor effect on HepG2 cells by initiating the mitochondrial-dependent apoptosis, and it has potential to be explored as a new promising therapeutic agent against human hepatoma.