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.

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%

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.

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.

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.

Clinical Significance of Increased Skeletal Muscle Mass During Nab-Paclitaxel Plus Gemcitabine Treatment in Patients With Advanced Pancreatic Cancer.

OBJECTIVES: The clinical significance of increased skeletal muscle mass during nab-paclitaxel plus gemcitabine (AG) treatment in patients with advanced pancreatic cancer (APC) remains unknown. Therefore, we retrospectively investigated the characteristics of patients after AG treatment to evaluate the clinical significance of increased skeletal muscle mass during treatment. METHODS: From January 2015 to August 2021, 67 patients with APC received AG as first-line chemotherapy at Higashiosaka City Medical Center. Of these patients, 39 received second-line (2L) chemotherapy after AG therapy, and 28 received best supportive care. Patients' characteristics at the end of AG treatment were compared retrospectively between these 2 groups, and the relevant factors at the end of first-line treatment for 2L chemotherapy induction were analyzed. RESULTS: A performance status of 0 to 1 and increased skeletal muscle mass during AG therapy were independently associated with 2L chemotherapy induction in multivariate analysis. A high relative dose intensity (≥50%) in the first 8 weeks of AG treatment was more frequently found in patients with increased skeletal muscle mass during treatment ( P = 0.037). CONCLUSIONS: Increased skeletal muscle mass during AG treatment might contribute to the higher prevalence of 2L chemotherapy induction in patients with APC.

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.

Soluble programmed cell death ligand 1 predicts prognosis for gastric cancer patients treated with nivolumab: Blood-based biomarker analysis for the DELIVER trial.

BACKGROUND: The clinical value of soluble forms of programmed cell death-1 (sPD-1), PD ligand 1 (sPD-L1) and cytotoxic T lymphocyte-associated protein-4 (sCTLA-4) for gastric cancer (GC) patients treated with nivolumab monotherapy has remained unknown. METHODS: Blood samples collected before nivolumab treatment from 439 GC patients enrolled in the DELIVER (Japan Clinical Cancer Research Organisation GC-08) trial were analysed for sPD-1, sPD-L1 and sCTLA-4. Corresponding baseline clinical data were also retrieved. RESULTS: Higher plasma levels of sPD-1 (hazard ratio [HR] = 1.27, p = 0.020), sPD-L1 (HR = 1.86, p < 0.001) and sCTLA-4 (HR = 1.33, p = 0.008) were significantly associated with shorter overall survival (OS), whereas only higher sPD-L1 levels was significantly associated with shorter progression-free survival (HR = 1.30, p = 0.008). The sPD-L1 concentration was significantly associated with the Glasgow prognostic score (GPS) (p < 0.001), but both sPD-L1 (HR = 1.67, p < 0.001) and GPS (HR = 1.39, p = 0.009 for GPS 0 versus 1; HR = 1.95, p < 0.001 for GPS 0 versus 2) were independently associated with OS. Patients with a GPS of 0 and low sPD-L1 thus showed the longest OS (median, 12.0 months) and those with a GPS of 2 and high sPD-L1 showed the shortest OS (median, 3.1 months), yielding a HR of 3.69 (p < 0.001). CONCLUSION: Baseline sPD-L1 levels have the potential to predict survival for advanced GC patients treated with nivolumab, with the prognostic accuracy of sPD-L1 being improved by its combination with GPS.

[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.

Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer.

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.

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.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

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).

[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.

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 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.

[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.

Effects of an oral elemental nutritional supplement in gastric cancer patients with adjuvant S-1 chemotherapy after gastrectomy: A multicenter, open-label, single-arm, prospective phase II study (OGSG1108).

AIM: Post-surgical weight loss influences chemotherapy compliance and may be a risk factor for survival. Intake of an oral elemental nutritional supplement (OENS) can reduce weight loss after gastric cancer (GC) surgery. We assessed whether therapy completion levels would increase in patients receiving postoperative adjuvant chemotherapy in combination with an OENS. METHODS: This was a multicenter, open-label, single-arm, phase II study in GC patients who underwent curative total or distal gastrectomy (TG/DG) and received adjuvant S-1 chemotherapy. The primary endpoint was the S-1 completion rate for 1 year with a relative performance (RP) value of ≥70%; secondary endpoints included factors affecting the completion rate of S-1, RP value after eight S-1 courses, S-1 and OENS persistence rates, nutritional index, OENS compliance, and safety. RESULTS: In 71 efficacy-evaluable patients, the S-1 completion rate was 69.0% (TG, 68.0%; DG, 69.6%) and the RP value was 87.5 (TG, 89.1; DG, 87.5). Over eight treatment courses, median persistence rates were 89.0% for S-1 and 93.8% for the OENS. The mean OENS compliance was 81.8% at the fourth S-1 course and 52.9% at the eighth course. The incidence of Grade 3 or 4 adverse events was 27.2%, most commonly neutropenia (12.3%). CONCLUSIONS: The completion rate of S-1 for 1 year in patients who could take the OENS exceeded the pre-defined threshold level. Randomized controlled trials are warranted to confirm the role of OENS in adjuvant chemotherapy.