Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study.

BACKGROUND: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer. METHODS: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively. RESULTS: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P < 0.03) and 12 months (P < 0.001) were independent prognostic factors for a shorter recurrence-free interval. CONCLUSIONS: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer. CLINICAL TRIAL REGISTRATION: UMIN000007925.

Tumor Response Predicts Survival Time of Nivolumab Monotherapy for Advanced Gastric Cancer: A Subgroup Analysis of the DELIVER Trial (JACCRO GC-08).

BACKGROUND: This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. PATIENTS AND METHODS: The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. RESULTS: In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (-20%≥DpR; -20%

Long-Term Effects of Oral Nutritional Supplements After Gastrectomy for Gastric Cancer: A Survival Analysis from a Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Weight loss (WL) after gastrectomy for gastric cancer is associated with both decreased compliance with adjuvant chemotherapy and impaired survival. This study examined the effects of administering oral nutritional supplements (ONS) for 3 months after gastrectomy in terms of compliance with adjuvant chemotherapy and survival outcomes. METHODS: This large-scale, multicenter, open-label, randomized controlled trial enrolled 1,003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the control group (n = 503) or ONS group (n = 500). In the ONS group, 400 kcal/day of ONS was recommended in addition to a regular diet for 3 months after gastrectomy. Compliance with adjuvant chemotherapy and survival outcomes were compared between the two groups. RESULTS: Compared with the control group, the ONS group showed significantly decreased WL at 3 months after gastrectomy (8.6 ± 6.1 vs. 7.2 ± 5.7%, respectively, P = 0.0004). The control and ONS groups did not differ regarding the induction rate of adjuvant chemotherapy (84.9 vs. 82.8%, respectively, P = 0.614) or the continuation rate at 3 months postoperatively (75.3 vs. 76.6%, respectively, P = 0.809). Oral nutritional supplements for 3 months showed no survival benefit; the 3- and 5-year overall survival (OS) rates were 91.3% and 87.6% in the control group and 89.6% and 86.4% in the ONS group, respectively, indicating no significant difference (P = 0.548). Subgroup analysis could not detect a population in which ONS administration increased OS. CONCLUSIONS: Administration of ONS for 3 months after gastrectomy was not associated with increased compliance with adjuvant chemotherapy or with improved prognosis.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

BACKGROUND: The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. METHODS: This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70 years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. RESULTS: Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80 years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. CONCLUSION: In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

BACKGROUND: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.

Effects of postoperative oral elemental nutritional supplement on skeletal muscle loss after gastrectomy for gastric cancer.

BACKGROUND: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. METHODS: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. RESULTS: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. CONCLUSION: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. CLINICAL TRIAL REGISTRATION: UMIN000023455.

Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry stomach cancer subcohort.

BACKGROUND: The Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry. METHODS: Stage II-IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled. RESULTS: Of 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 µg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21-2.32; p = 0.002). CONCLUSIONS: VTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy. TRIAL REGISTRATION: UMIN000024942.

Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.

Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction.

BACKGROUND: Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique. CASE PRESENTATION: A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications. CONCLUSION: The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.

Analysis of the risk factors for osteoporosis and its prevalence after gastrectomy for gastric cancer in older patients: a prospective study.

PURPOSE: Osteoporosis leads to fragility fractures and is a major public health problem. We conducted this study to analyze the prevalence of and risk factors for osteoporosis after gastrectomy in older patients. METHODS: This multicenter prospective trial comprised older patients without recurrence of gastric cancer for > 3 years after curative surgery. The prevalence of osteoporosis was identified using the World Health Organization bone mineral density (BMD)-based definition. Univariate and multivariate analyses were performed to identify the risk factors for osteoporosis. RESULTS: BMD values were measured in 267 of the 271 enrolled patients. The prevalence of osteoporosis was 38.2% (men 24.0%; women 60%). Analysis using FRAX® revealed that 51.7% of patients were candidates for pharmacologic therapy. Female sex (odds ratio [OR] 5.16, 95% confidence interval [CI] 2.61-10.2), age (OR 1.06, 95% CI 1.00-1.12), low body mass index (< 19.0 kg/m2) after gastrectomy (OR 5.31, 95% CI 2.79-10.13), and history of fracture (OR 2.06, 95% CI 1.06-4.02) were independently associated with osteoporosis. CONCLUSIONS: The prevalence of osteoporosis in older patients after gastrectomy was 38.2%. Moreover, female sex, age, low body mass index after gastrectomy, and a history of fracture were risk factors significantly associated with osteoporosis. Thus, older patients undergoing gastrectomy should have proactive surveillance and receive treatment for osteoporosis.

[A Case of Locally Advanced Giant Sigmoid Colon Cancer Successfully Treated with Neoadjuvant Chemotherapy].

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

BACKGROUND: We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. METHODS: The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). RESULTS: Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. CONCLUSION: Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).

Prospective Multicenter Interventional Study of Surgical Resection for Liver Metastasis from Gastric Cancer: R0 Resection Rate, and Operative Morbidity and Mortality.

BACKGROUND: The optimal treatment for liver metastasis from gastric cancer (LMGC) remains uncertain. The relevance of surgical resection is controversial. We conducted a prospective multicenter interventional study of surgical resection for LMGC. PATIENTS AND METHODS: Patients with synchronous or metachronous LMGC who were surgically fit were registered. The primary endpoint was 3-year overall survival (OS) of patients who underwent R0 resection. Secondary endpoints were R0 resection rate, operative morbidity and mortality, 3-year recurrence-free survival (RFS) of R0 patients, and OS in all registered patients. RESULTS: Seventy patients were registered from 24 institutions between December 2011 and November 2019 and received preoperative chemotherapy. Three patients were ineligible, and 19 patients discontinued treatment, with disease progression in 12, adverse events in 4, and consent withdrawal in 3 before surgery. Of the 48 patients eventually undergoing surgery, R0 resection of the primary and/or metastatic GC was accomplished in 43 patients, while 1 patient discontinued treatment for positive peritoneal lavage cytology and 4 patients were considered ineligible based on postoperative pathological findings other than GC. The R0 resection rate of all eligible patients was 68.3% [95% confidence interval (CI) 55.3-79.4%, 43/63 patients], while that of all resected patients was 89.6% (95% CI 77.3-96.5%, 43/48 patients). Postoperative complications were identified in 12 out of 43 patients (27.9%), and Clavien-Dindo grade III or higher complications occurred in seven patients (16.3%). No hospital mortality was observed. CONCLUSIONS: R0 resection for LMGC could be performed in approximately two-thirds of all eligible patients, with acceptable surgical morbidity and mortality.

Survival analysis of a prospective multicenter observational study on surgical palliation among patients with malignant bowel obstruction caused by peritoneal dissemination of gastric cancer.

BACKGROUND: Our previous report showed that surgical palliation maintained quality of life (QOL), improved solid food intake, and had an acceptable surgical safety among patients with malignant bowel obstruction (MBO) caused by advanced gastric cancer. This study performed a survival analysis stratified by the patients' QOL to elucidate its impact on survival. METHODS: Patients who underwent resection or bypass of the small intestine/colon or ileostomy/colostomy for bowel obstruction caused by peritoneal dissemination of gastric cancer were included. Validated instruments (EuroQoL-5 Dimensions) were used to assess QOL at baseline and 2 weeks, 1 month, and 3 months following surgical palliation. Postoperative improvement in oral intake was also evaluated using the Gastric Outlet Obstruction Scoring System (GOOSS). Univariate and multivariate survival analyses were performed using baseline characteristics and changes in QOL and GOOSS scores 2 weeks after surgery to determine prognostic factors. RESULTS: We enrolled 60 patients with a median survival time of 6.64 (95% CI 4.76-10.28) months. Patients who received postoperative chemotherapy and had lower baseline C-reactive protein (CRP) levels, higher baseline albumin levels, better baseline EuroQoL-5 Dimensions (EQ-5D) scores, and improved oral intake after palliative surgery exhibited significantly better survival. Multivariate analysis identified postoperative chemotherapy, lower baseline CRP levels, and improved oral intake as independent prognostic factors. CONCLUSIONS: The current study revealed that baseline QOL and postoperative QOL changes did not affect survival. Moreover, improved oral intake, lower baseline CRP levels, and postoperative chemotherapy were significant prognostic factors in patients who underwent palliative surgery for advanced gastric cancer with MBO.

Real-world effectiveness of nivolumab in advanced gastric cancer: the DELIVER trial (JACCRO GC-08).

BACKGROUND: There is no large real-world data regarding efficacy and safety of immunotherapy in gastric cancer (GC). Although some tumors can grow rapidly after immunotherapy, the patient proportions and survival outcomes are unclear in GC. METHODS: A multicenter, prospective observational study was performed to evaluate clinical outcomes including survival time, safety, and tumor behavior of nivolumab treatment for patients with advanced GC. Primary endpoint was overall survival (OS), and secondary endpoints included response rate (RR), disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at first evaluation, and safety. RESULTS: Of 501 enrolled patients, 487 were evaluable (median age 70 years, 71% male, performance status 0/1/2 [42%/44%/14%], 21% HER2-pos, 42% patients with ascites). Median OS was 5.82 months (95% CI 5.29-7.00) with a 1-year survival rate of 30% and median PFS of 1.84 months (95% CI 1.71-1.97). The DCR was 39.4% and the RR was 14.2% (95% CI 10.3-18.8) in 282 patients with measurable lesions. In 219 patients evaluable for TGR, 20.5% were identified as hyperprogressive disease (HPD). OS from the first evaluation of patients with HPD was shorter compared with non-HPD (HR 1.77, 95% CI 1.25-2.51, P = 0.001), but it was not worse than that of patients with progression and non-HPD (HR 1.05, 95% CI 0.72-1.53, P = 0.8). A multivariate analysis revealed the presence of peritoneal metastasis was a prognostic factor for OS and PFS. CONCLUSIONS: Our real-world data demonstrated the comparable survival time to a previous clinical trial and revealed the frequency and prognosis of patients with HPD in advanced GC treated with nivolumab.

Real-world effectiveness of third- or later-line treatment in Japanese patients with HER2-positive, unresectable, recurrent or metastatic gastric cancer: a retrospective observational study.

BACKGROUND: Real-world evidence on the preference for and effectiveness of third- or later-line (3L +) monotherapy for HER2-positive gastric cancer is limited in Japan. This study evaluated the utility of nivolumab, irinotecan, and trifluridine/tipiracil (FTD/TPI) monotherapy as 3L + treatment in Japanese patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer who were previously treated with trastuzumab. METHODS: In this multicenter, retrospective, observational study (20 centers), data of eligible patients were extracted from medical records (September 22, 2017-March 31, 2020), with follow-up until June 30, 2020. Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate (ORR; complete response [CR] + partial response [PR]), and disease control rate (DCR). RESULTS: Of 127 enrolled patients, the overall analysis population comprised 117 patients (median [range] age, 71 [38-89] years). The most commonly prescribed 3L + monotherapy was nivolumab (n = 100), followed by irinotecan (n = 12) and FTD/TPI (n = 5). The median (95% confidence interval [CI]) OS, rwPFS, and TTF were 6.2 (4.5-8.0), 1.9 (1.5-2.3), and 1.8 (1.5-2.2) months, respectively, at median (range) 150 (25-1007) days of follow-up. The ORR (CR + PR) and DCR were 9.0% (1% + 8%) and 32.0%, respectively. Factors such as higher neutrophil-lymphocyte ratio (≥ 2.54), Glasgow prognostic score (≥ 1), Eastern Cooperative Oncology Group performance status (ECOG PS; ≥ 2), and hepatic metastasis significantly impacted OS. CONCLUSIONS: The observed OS in this study for HER2-positive G/GEJ cancer was shorter than that reported previously, suggesting that the effectiveness of nivolumab, irinotecan, or FTD/TPI as 3L + therapy may be limited.

Real-world data on the efficacy and safety of adjuvant chemotherapy in Japanese patients with a high-risk of gastrointestinal stromal tumor recurrence.

BACKGROUND: Complete surgical resection is the only treatment for resectable gastrointestinal stromal tumors (GISTs). Three-year adjuvant chemotherapy (AC) is recommended for patients with high-risk GISTs. However, there are scarce data on this topic in Japan. We aimed to study the efficacy and safety of AC in Japanese patients with high-risk GISTs. METHODS: Patients with high-risk GISTs who received complete resections during 1992-2019 in our hospitals were included in this retrospective study. We evaluated patients' treatments with or without AC, completion rates, adverse events (AEs), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Overall, 89 patients categorized as high risk were enrolled in this study. Fifty-five patients received AC (AC group), and 34 patients did not receive AC (control group). Twenty-three (41.8%) patients experienced Common Terminology Criteria for Adverse Events Grade 2 or higher AEs. At a median follow-up of 61.6 months, 41 (74.5%) patients completed the planned treatment (including six patients with ongoing treatment), whereas 14 (25.4%) patients did not complete the treatment owing to the development of AEs (nine patients), patients' request (three patients), recurrence (one patient), and mutational analysis (one patient). Comparing the data between the treatment and control groups, the RFS rate was significantly better for the AC group (P < 0.001). However, there was no significant difference in the OS rate between the two groups. CONCLUSION: Postoperative AC was well tolerated by Japanese patients at an acceptable rate, and its use may reduce the risk of recurrence in patients with high-risk GISTs.

[A Resected Case of the Pancreatic Tail Cancer with Colonic Obstruction].

A 71-year-old man complained of abdominal pain. He showed fecal occult blood positive and he was referred to our hospital for further examination and treatment. During examinations, he developed colonic obstruction. As a result of examinations, he was diagnosed with pancreatic tail cancer invading to the colon. We underwent distal pancreatectomy, partial colectomy, partial gastrectomy, and left adrenalectomy. Although chylous fistula was observed, he was discharged from hospital 35 days after surgery. He has received adjuvant chemotherapy using S-1, and no recurrence has been observed 4 months after operation.

[A Case Report of Stage â £b Thoracic Esophageal Cancer Responding to Multidisciplinary Treatment].

A 68-year-old man was referred to our hospital because of back pain during swallowing. Upper gastrointestinal endoscopy revealed a lower esophageal type 3 tumor. The patient was diagnosed with esophageal squamous cell carcinoma by the biopsy specimen. CT scan showed thoracic lower esophagus wall thickening, left paracardiac lymph node swelling, and a low-density area in the liver. Therefore, the patient was diagnosed with Stage Ⅳb esophageal cancer. After introducing cisplatin plus 5-FU combination therapy, the liver metastasis disappeared. After 9 chemotherapy courses, the patient received radical chemoradiotherapy. After completing chemoradiotherapy, the patient was followed up without any treatment. After 3 years since the treatment initiation, the patient is surviving without any relapse.