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%

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.

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.

BACKGROUND: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. METHODS: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. RESULTS: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters. CONCLUSIONS: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. TRIAL REGISTRATION: UMIN000040462.

Effect of the number of cycles of docetaxel + S-1 therapy on long-term survival in adjuvant chemotherapy for stage III gastric cancer. A pooled analysis of the OGSG0604 and OGSG1002 trials.

BACKGROUND: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. RESULTS: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5-90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. CONCLUSION: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. TRIAL REGISTRATION: Registration number: UMIN00000714 and UMIN000004440.

[A Case of Laparoscopic Uterine and Vaginal Resection for Local Recurrence after Abdominoperineal Resection for Anal Canal Cancer].

The patient was an 80s woman. She visited our hospital with chief complaint of melena, and further evaluation revealed anal canal cancer. We performed robot-assisted abdominoperineal resection(D3 lymphadenectomy)and lateral lymph node dissection. The pathological diagnosis was anal canal cancer, muc>por1>tub2, T3N1bM0, pStage Ⅲb. One year after the surgery, she had a mass in the soft tissue of perineum on CT scan and PET-CT showed abnormal accumulation, which was diagnosed as local recurrence. At the same time, she also had a mass with abnormal accumulation in ascending colon, and it was diagnosed as ascending colon cancer. In both cases, we judged radical resection was possible, and the policy of surgery was decided. First, laparoscopic ileocecal resection was performed. The local recurrence lesion became a mass, invading the soft tissue of the perineum, the posterior wall of the vagina, and the cervix. So, we performed laparoscopic excision of local recurrent region together with the uterus and the posterior wall of the vagina. Based on the result of pathological examination, the patient was diagnosed with ascending colon cancer(tub1, pT1bN1aM0, pStage Ⅲa), and recurrence of anal canal cancer. The postoperative course is good and there are no signs of recurrence for 6 months after the operation.

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).

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.

[A Case of Robotic-Assisted Total Pelvic Exenteration for Locally Advanced Rectal Cancer Invading the Prostate].

The patient was a 60s man, whose chief complaint of melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Rb)invading the prostate with obturator lymph node metastasis. The clinical diagnosis was T4b (prostate)N3M0, Stage Ⅲc. He was administered 4 courses of CAPOX plus bevacizumab. After chemotherapy the primary tumor and lymph nodes showed PR, the diagnosis of ycT4bN1bM0, Stage Ⅲc. We performed robot-assisted total pelvic exenteration. He has been cancer-free for 5 months.

[A Case of Laparoscopic Total Pelvic Exenteration for Sigmoid Colon Cancer Using Infrared Illumination System (IRIS)].

The patient was 80s woman, whose chief complaint of fever and abdominal pain. She visited our hospital, and further evaluation revealed sigmoid colon cancer invading the uterus and abdominal wall. The pooling of pus in the uterus was formed and we diagnosed as pyometra. The clinical diagnosis was T4b(uterus, abdominal wall)N0M0, cStage Ⅱc. We performed laparoscopic sigmoidectomy, uterus and bilateral ovaries. We report a case in which the intraoperative infrared illumination system(IRIS)was used to support the identification of the ureter by near-infrared light and total pelvic exenteration could be safely performed.

[A Case of Early Appendiceal Adenocarcinoma Coexisting with High-Grade Appendiceal Mucinous Neoplasm].

We report a case of a female in her fifties with early appendiceal adenocarcinoma coexisting with high-grade appendiceal mucinous neoplasm(HAMN)with a review of the literature. The patient presented to our hospital because of an enlarged appendix noted by contrast-enhanced CT performed for hematuria. Contrast-enhanced CT showed that the appendix had swollen to 10 mm and mucus had accumulated inside, which had no evidence of obvious malignancy. She was followed up on CT once a year. Four years after her first visit, she underwent laparoscopic appendectomy for a definitive diagnosis. There were no adhesions or inflammation in her abdominal cavity, and the appendix root was dissected with an automatic anastomosis device. Her resected specimen macroscopically showed mild wall thickening, but no obvious neoplastic lesion. Pathological examination revealed that in many areas centered on the tip of the appendix, highly columnar atypical epithelium with enhanced mucus production was densely proliferated in the form of glandular tubular and papillary. The nuclei of the proliferating epithelium were large and the fission image was conspicuous, but they remained in the mucosa. Pathological examination diagnosed as HAMN according to the WHO classification. The atypical epithelium in a small area at the tip was particularly strong in nuclear atypia, and showed a strong positive diffusely in p53, which was an image of well-differentiated tubular adenocarcinoma. The pathological diagnosis was V, Type 0-Ⅱb, 2 mm, tub1 in HAMN, pTis, Ly0, V0, Pn0, pPM0, pDM0, pRM0, R0. Six months have passed since the operation, but no recurrence has been observed.

A phase II study of S-1 therapy for patients with advanced and recurrent esophageal cancer resistant or intolerable to fluorouracil, platinum, and taxane therapy (OGSG 1404).

BACKGROUND: Fluorouracil (FU), platinum (PT), and taxane (TAX) therapy was the standard chemotherapy for esophageal squamous cell carcinoma (ESCC) before the era of anti-programmed death-1 antibodies. The aim of this phase II trial was to evaluate the efficacy and safety of S-1 monotherapy for patients with recurrent or metastatic (R/M) ESCC resistant or intolerable to FU, PT, and TAX therapy. METHODS: Eligible patients had R/M ESCC; no prior S-1 use; were intolerant or refractory to prior FU, PT, and TAX therapy; aged ≧ 20 years; and Eastern Cooperative Oncology Group performance status 0 or 1. S-1 was administered orally from days 1 to 28, every 6 weeks until disease progression. The primary endpoint was the disease control rate (DCR) for each patient, assessed by Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were overall survival, progression-free survival, time to treatment failure, response rate, and toxicity. RESULTS: Between October 2015 and December 2017, 17 patients were recruited, and the trial was terminated because of slow accrual. The DCR was 46.7%. The response rate was 13.3%. The median progression-free survival was 2.0 months. The median time to treatment failure was 1.9 months. The median overall survival was 8.4 months, and the 1 year overall survival rate was 30.5%. CONCLUSIONS: Although this trial closed early because of slow accrual, we observed modest clinical activity with S-1 in patients with R/M ESCC who could not tolerate or whose tumors were refractory to FU, PT, and TAX therapy.

Docetaxel plus S-1 versus cisplatin plus S-1 in unresectable gastric cancer without measurable lesions: a randomized phase II trial (HERBIS-3).

BACKGROUND: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. METHODS: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80-120 mg on days 1-14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80-120 mg on days 1-21, every 5 weeks). The primary endpoint was overall survival (OS). RESULTS: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2-49) with DS and 5.5 (range 1-10) with CS. There were no treatment-related deaths. The most common grade 3-4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337-1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). CONCLUSIONS: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.

Oral nutritional supplements versus a regular diet alone for body weight loss after gastrectomy: a phase 3, multicenter, open-label randomized controlled trial.

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.

Randomized phase II study of CPT-11 versus PTX versus each combination chemotherapy with S-1 for advanced gastric cancer that is refractory to S-1 or S-1 plus CDDP: OGSG0701.

BACKGROUND: To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin (SP). METHODS: Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m2, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m2, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m2, days 1, 15, S-1; 80 mg/m2, days 1-21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m2, day1, 8, S-1; 80 mg/m2, days 1-14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety. RESULTS: From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months, p = 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups. CONCLUSIONS: There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy.

[A Case of Giant Intestinal GIST That Was Resected Just after TAE].

A 42-year-old woman visited our hospital complaining of fever and diarrhea. She had abdominal swelling and muscular defense. CT revealed a lobulated tumor occupying the lower abdomen. The tumor contained solid and cystic areas. The main artery vascularizing the tumor was the ileocecal artery, so we considered the tumor to be derived from the intestine or mesentery. We anticipated massive bleeding due to resection, and immediately after the embolization of the artery just before the operation. A vascular bundle from the terminal ileum and mesentery was found on the dorsal side of the tumor, and an outflow from the inferior mesenteric vein was also observed. We ligated each vessel and performed ileocecal resection. The operation lasted 4 hours and 18 minutes, with an estimated blood loss of 2,585 mL, requiring the transfusion of 6 units of concentrated red blood cells. According to histopathological findings, tumor cells with spindle-shaped to ellipsoidal nuclei proliferated in bundles and intricately, and immunostaining was positive for c-kit and DOG-1. We identified the tumor as high-risk GIST. The clinical course after the operation was uneventful. She continued to take imatinib for 3 years and is currently alive and without recurrence for 6 years after the operation.

Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer.

BACKGROUND: Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. METHODS: 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. RESULTS: 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). CONCLUSIONS: PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. CLINICAL TRIAL REGISTRATION: UMIN000032164.

A Phase II Study of Perioperative Capecitabine plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

LESSONS LEARNED: Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result. Perioperative CapeOx therapy showed good feasibility. Further studies with larger sample size are required to validate this novel approach. BACKGROUND: D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. METHODS: The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). RESULTS: Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4-68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3-4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). CONCLUSION: Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.