Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

[Diagnosis, treatment and prognosis of neuroendocrine carcinoma of the colorectum].

OBJECTIVE: To investigate the diagnosis, treatment and prognosis of colorectal neuroendocrine carcinoma. METHODS: Clinical data of 39 patients with colorectal neuroendocrine carcinoma from Jan 1995 to Jan 2010 were analyzed retrospectively and the related literatures were reviewed. RESULTS: There were 27 males and 12 females. No patients presented endocrinal dysfunction symptoms. Fourteen patients were diagnosed as neuroendocrine cancer by preoperative pathological examination. All the patients received postoperative adjuvant chemotherapy including cis-platinum and etoposide. Twenty-two patients underwent curative resection, while 14 underwent palliative resection and 3 underwent biopsy alone. Of the 36 surgical resection specimens, vascular invasion was found in 27 patients (75.0%) and regional lymph node metastasis was found in 29 patients (80.6%). Length of follow-up ranged from 4 to 67 months. The 1-year, 3-year and 5-year survival rates were 48.2%, 16.5% and 6.8%, respectively. Statistically significant differences in survival were observed and associated with tumor staging, vascular invasion and surgery type (P<0.05), but not related to gender, age, tumor location, or diameter (P>0.05). CONCLUSIONS: Clinical symptoms and signs of colorectal neuroendocrine carcinoma are nonspecific with poor prognosis. Tumor staging, vascular invasion and surgical type have potential impact on survival.