Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear.
In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent ...GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed.
Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0-1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2-3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001).
PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC.
UMIN000032164.
Background
Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), ...we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer.
Methods
Patients aged 20–75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS).
Results
Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% 95% confidence interval (CI) 54.1–69.6 in Arm A and 60.9% (95% CI 52.7–68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI 0.679–1.236).
Conclusions
For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.
Background
Malnutrition is an independent risk factor for postoperative mortality and morbidity in major gastrointestinal surgery. The aim of this study was to investigate the prevalence of ...malnutrition and identify the optimal preoperative nutritional support for preventing postoperative surgical site infections (SSIs) in malnourished gastric cancer patients undergoing gastrectomy.
Methods
We analyzed 800 patients with gastric cancer who underwent gastrectomy. Nutritional risk factors included weight loss >10 % within 6 months, body mass index <18.5 kg/m
2
, Subjective Global Assessment Grade C, and serum albumin <3.0 g/dl. Adequate energy intake was defined as receiving ≥25 kcal/kg ideal body weight per day. Optimal nutritional support was examined in terms of both duration and calorie intake.
Results
Overall, 152 patients (19.0 %) were classified as malnourished. The incidence of SSIs was significantly higher in malnourished patients than in well-nourished patients (35.5 vs. 14.0 %;
p
< 0.0001). The incidence of SSIs in malnourished patients was significantly lower in the well-supported group receiving adequate energy support for at least 10 days than in the poorly-supported group, which received inadequate or no energy support or adequate energy support for <10 days (17.0 vs. 45.4 %;
p
= 0.0006). In multivariate analysis, well-managed nutritional support was identified as an independent factor associated with fewer SSIs (odds ratio 0.14; 95 % confidence interval 0.05–0.37;
p
= 0.0002).
Conclusions
Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.
We established a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer. Twenty-two gastric cancer patients aged 65 years or older with a diagnosis ...of sarcopenia according to the algorithm proposed by the European Working Group on Sarcopenia in Older People received our preoperative program. The median duration of the program participation was 16 days. Total calorie and protein intakes were significantly higher after the program than before 29.4 ± 6.9 kcal/kg ideal body weight (IBW) vs 27.3 ± 5.6 kcal/kg IBW,
p
= 0.049, and 1.3 ± 0.4 g/kg IBW vs 1.1 ± 0.3 g/kg IBW,
p
= 0.0019, respectively. Handgrip strength significantly increased after the program (21.2 ± 5.2 kg vs 20.0 ± 5.3 kg,
p
= 0.022). Likewise, gait speed and skeletal muscle mass index increased, although the differences did not reach statistical significance. Four patients became nonsarcopenic after the program. Postoperative complications were observed in three patients (13.6%); however, none of these complications were severe (Clavien-Dindo grade III or lower). A preoperative exercise and nutritional support program has the potential to reduce sarcopenia and improve postoperative outcome in elderly sarcopenic patients with gastric cancer.
Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the ...prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study.
Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC.
330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %.
Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.
Background & Aims Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this ...process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. Methods We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1–9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. Results Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C ( P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C ( P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C ( P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25–0.91; P = .025), whereas smoking abstinence did not. Conclusions Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
Background
Body weight loss (BWL) after gastrectomy is associated with not only a deteriorated quality of life but also a poor prognosis. Oral nutritional supplements (ONS) may be used to minimize ...BWL, which is observed in the first 3 months after gastrectomy and becomes stable thereafter, although the results of several randomized trials remain controversial.
Methods
We performed a multicenter, open-label randomized controlled trial including 1003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the ONS group or the control group. In the former, 400 ml (400 kcal) per day for 12 weeks as enteral nutrition was planned, and the actual intake amount was recorded daily by patients themselves. The primary endpoint was BWL 1 year after gastrectomy.
Results
BWL data were available in 880 patients (ONS 437, control 443). BWL at 3 months was significantly lower in the ONS group than in the control group (7.1 ± 5.6% and 8.5 ± 5.8%,
p
= 0.0011). However, the difference gradually declined after 6 months and was not significant 1 year after surgery (9.3 ± 8.2% and 9.8 ± 8.7%,
p
= 0.37). In the ONS group, 50.4% of patients took more than 200 ml/day of ONS (average 301 ml) and showed significantly less BWL (8.2 ± 7.2%) at 1 year than the control (
p
= 0.0204).
Conclusion
The administration of ONS for 12 weeks after gastrectomy did not improve BWL at 1 year. However, the improvement in BWL remained until 1 year after surgery in patients who took more than 200 kcal/day of ONS.
Background
The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection.
Methods
In this six-institution, matched-cohort study, ...2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns.
Results
Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (
p
= 0.0078), 41.0% (
p
= 0.0297), and 55.3% (
p
= 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (
p
= 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (
p
= 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (
p
= 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (
p
= 0.0183).
Conclusions
Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.
Background
Malignancy is a secondary cause of sarcopenia, which is associated with impaired cancer treatment outcomes. The aim of this study was to investigate the prevalence of preoperative ...sarcopenia among elderly gastric cancer patients undergoing gastrectomy and the differences in preoperative dietary intake and postoperative complications between sarcopenic and non-sarcopenic patients.
Methods
Ninety-nine patients over 65 years of age who underwent gastrectomy for gastric cancer were analyzed. All patients underwent gait and handgrip strength testing, and whole-body skeletal muscle mass was measured using a bioimpedance analysis technique based on the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for the evaluation of sarcopenia before surgery. Preoperative dietary intake was assessed using a food frequency questionnaire.
Results
Of these patients, 21 (21.2 %) were diagnosed with sarcopenia. Sarcopenic patients consumed fewer calories and less protein preoperatively (23.9 vs. 27.8 kcal/kg ideal weight/day and 0.86 vs. 1.04 g/kg ideal weight/day;
P
= 0.001 and 0.0005, respectively). Although the overall incidence of postoperative complications was similar in the two groups (57.1 % vs. 35.9 %;
P
= 0.08), the incidence of severe (Clavien–Dindo grade ≥ IIIa) complications was significantly higher in the sarcopenic group than in the non-sarcopenic group (28.6 % vs. 9.0 %;
P
= 0.029). In the multivariate analysis, sarcopenia alone was identified as a risk factor for severe postoperative complications (odds ratio, 4.76; 95 % confidence interval, 1.03–24.30;
P
= 0.046).
Conclusions
Preoperative sarcopenia as defined by the EWGSOP algorithm is a risk factor for severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.
Background
Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality ...of life (QOL), but few prospective studies on palliative surgery in this patient population have been published.
Patients and methods
We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D™) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications.
Results
Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D™ utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of ≥ grade III according to the Clavien–Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients).
Conclusions
In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.
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