Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Development and validation of a pretreatment nomogram to predict overall survival in gastric cancer.

BACKGROUND: Pretreatment clinical staging is essential to select therapy. However, there have been no published pretreatment gastric cancer nomograms constructed using pretreatment clinical prognostic factors, including in nonresection patients. We aimed to develop a new pretreatment gastric cancer nomogram for individualized prediction of overall survival (OS). METHODS: The nomogram was developed using data of 5231 Japanese gastric cancer patients, and it was created with a Cox regression model. Fifteen clinical variables, which were obtained at pretreatment, were collected and registered. Data of two independent cohorts of patients from Seoul St. Mary's Hospital (1001 patients), and the University of Verona (389 patients) formed the external validation cohorts. The model was validated internally and externally using measures of discrimination (Harrell's C-index), calibration, and decision curve analysis. RESULTS: The developed nomogram showed good discrimination, with a C-index of 0.855; that of the American Joint Committee on Cancer (AJCC) clinical stage was 0.819. In the external validation procedure, the C-indexes were 0.856 (AJCC, 0.795) in the Seoul St. Mary's cohort and 0.714 (AJCC, 0.648) in the University of Verona cohort. The nomogram performed well in the calibration and decision curve analyses when applied to both the internal and external validation cohorts. A stage-specific subset survival analysis of the three risk groups calculated using the nomogram also showed the superiority of nomogram-prediction when compared to AJCC. CONCLUSION: This new pretreatment model accurately predicts OS in gastric cancer and can be used for patient counseling in clinical practice and stratification in clinical trials.

Laparoscopic repair of perforated duodenal ulcers: the simple "one-stitch" suture with omental patch technique.

BACKGROUND: We present, here, the technique and results of our laparoscopic simple "one-stitch" suture with omental patch technique for treating 35 patients with perforated duodenal ulcer. METHODS: The laparoscopic treatment included peritoneal lavage, suture of the perforation without knotting, and then tying the suture over the omentum. Follow-up gastroscopy was performed after an eight-week course of medication with proton-pump inhibitors. RESULTS: Conversion to laparotomy was necessary for two patients, because of a large-sized perforation and the inadequate localization of the perforation site, respectively. The mean operative time was 64 minutes and the mean hospital stay was 6.8 days. Operation-related complications occurred in two patients, including one case of pneumonia and one case of gastric stasis. CONCLUSIONS: This simple "one-stitch" suture with omental patch technique is a safe and easy procedure, and it has an acceptable morbidity rate and a low conversion rate.

Anemia after gastrectomy for early gastric cancer: long-term follow-up observational study.

AIM: To identify the incidence and etiology of anemia after gastrectomy in patients with long-term follow-up after gastrectomy for early gastric cancer. METHODS: The medical records of those patients with early gastric adenocarcinoma who underwent curative gastrectomy between January 2006 and October 2007 were reviewed. Patients with anemia in the preoperative workup, cancer recurrence, undergoing systemic chemotherapy, with other medical conditions that can cause anemia, or treated during follow up with red cell transfusions or supplements for anemia were excluded. Anemia was defined by World Health Organization criteria (Hb < 12 g/dL in women and < 13 g/dL in men). Iron deficiency was defined as serum ferritin < 20 µg/dL. Vitamin B12 deficiency was defined as serum vitamin B12 < 200 pg/mL. Iron deficiency anemia was defined as anemia with concomitant iron deficiency. Anemia from vitamin B12 deficiency was defined as megaloblastic anemia (mean cell volume > 100 fL) with vitamin B12 deficiency. The profile of anemia over 48 mo of follow-up was analyzed. RESULTS: One hundred sixty-one patients with gastrectomy for early gastric cancer were analyzed. The incidence of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo after surgery. The incidence of iron deficiency anemia increased during the follow up and became the major cause of anemia at 48 mo after surgery. Anemia of chronic disease and megaloblastic anemia were uncommon. The incidence of anemia in female patients was significantly higher than in male patients at 12 (40.0% vs 22.0%, P = 0.033), 24 (45.0% vs 25.0%, P = 0.023), 36 (55.0% vs 28.0%, P = 0.004), and 48 mo (52.0% vs 31.0%, P = 0.022) after surgery. Patients with total gastrectomy showed significantly higher incidence of anemia than patients with subtotal gastrectomy at 48 mo after surgery (60.7% vs 31.3%, P = 0.008). The incidence of iron deficiency was significantly higher in female patients than in male patients at 6 (35.4% vs 13.3%, P = 0.002), 12 (45.8% vs 16.8%, P < 0.001), 18 (52.1% vs 22.3%, P < 0.001), 24 (60.4% vs 20.9%, P < 0.001), 36 (62.5% vs 29.2%, P < 0.001), and 48 mo (66.7% vs 34.7%, P = 0.001) after surgery. CONCLUSION: Anemia was frequent after gastrectomy for early gastric cancer, with iron deficiency being the major cause. Evaluation for anemia including iron status should be performed after gastrectomy and appropriate iron replacement should be considered.

The role of surgery in the treatment of recurrent gastric cancer.

BACKGROUND: The purpose of the current study was to determine the role of surgery in the treatment of recurrent gastric cancer. METHODS: Of the 347 patients with recurrent gastric cancer, 61 patients (17.8%) who underwent surgery were evaluated retrospectively. The underlying causes and types of surgery, survival, and postoperative quality of life were analyzed. RESULTS: The most common cause of surgery was intestinal obstruction due to carcinomatosis. Complete resection was possible in 15 patients (24.6 %), including 10 gastric remnant recurrences, and 2 hepatic and 3 ovarian metastases. The survival of patients who had complete resection was significantly longer than the other groups (52.2 months for complete resections, 13.1 months for palliative procedures, and 8.7 months for laparotomy alone, respectively) (P < .05). The median hospital-free survival (HFS) durations were 9.4, 2.9, and 2.2 months for incomplete resection, bypass/enterostomy, and laparotomy only, respectively (P < .05). CONCLUSION: Surgical treatment in recurrent gastric cancer is rarely indicated; however, if complete resection could be accomplished, long-term survival can be expected. Bypass surgery for symptom palliation did not increase the HFS.