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Background Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. Materials and Methods Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. Results Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%–41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. Conclusion Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.

The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.

BACKGROUND Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the ‘VELOUR’ trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment. AIM To determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings. METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor location, RAS and RAF status, metastatic sites, number of previous treatment cycles, therapeutic response, adverse events, duration of previous AI treatment, and survival time. The end points were time to AFL treatment failure (aTTF) and median survival time post-AFL (aMST). Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting, which was defined as the days since the end of second-line therapy. RESULTS All 41 patients who received AFL + FOLFIRI for advanced CRC had metastatic or unresectable cancer. Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting. The patient characteristics were similar in the two groups, except for two factors. The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients (144 d vs 323 d, P = 0.006). In the second-line and salvage therapy groups, the objective response rates were 11% and 0%, respectively (P = 0.50), and the disease control rates were 53% and 50%, respectively (P = 1.00). In the second-line and salvage therapy groups, the aTTF (123 d vs 71 d, respectively), aMST (673 d vs 396 d, respectively), and incidence of adverse events of grade 3 [8 (36%) vs 9 (47%)] were not significantly different between the two groups. CONCLUSION AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignant tumor. It is a refractory tumor and the median overall survival is very short. We report two autopsy cases of DSRCT, both of which were already advanced and metastasized at the first medical examination. Both cases showed typical DSRCT findings in terms of localization of the lesions, histopathology and genetics, but the rate of disease progression was quite different. Survival after initial symptoms in Case 1 was only 12 months. On the other hand, survival after primary hospitalization in Case 2 was 42 months. The Case 2 patient initially received chemotherapy for advanced pancreatic carcinoma, because a nodule of the pancreatic tail was found on computed tomography (CT) scan. After chemotherapy, tumor regression was observed on CT scan. It is thus implied that adoption of the regimen for pancreatic carcinoma might have been one of reasons of the long survival in Case 2.

348 Background: CapeOX is a standard regimen for treating advanced gastric cancer (AGC). However, limited data are available for its use in the elderly patients. Geriatric assessment (GA) assessment is also considered important other than the age. Therefore, we conducted a multicenter, single-arm, phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in elderly patients. We performed GA assessments using the G8, and the MINI-COG. Methods: The inclusion criteria were: HER2-negative or unknown status, age 70 years or older, PS 0 or 1, no history of chemotherapy or radiotherapy, and an evaluable lesion based on the RECIST v1.1 guidelines. The initial treatment plan consisted of capecitabine (1,000 mg/m2, b.i.d., on days 1–14), and oxaliplatin (130 mg/m2, on day 1) every three weeks. After the initial feasibility assessment, the treatment plan was modified and consisted of capecitabine (750 mg/m2, b.i.d., on days 1–14) and oxaliplatin (100 mg/m2, on day 1) every three weeks. The primary endpoint was overall survival (OS). G8 assessments were performed before the beginning of the treatment, every three months after the start of the treatment, and at the end of the treatment. MINI-COG assessments were performed before the beginning of the treatment, and at the end of the treatment. Results: Between November 2016 and June 2020, 108 patients were enrolled, out of which 104 were evaluated. Thirty-nine patients received the initial treatment whereas sixty-five patients received the modified treatment. The primary endpoint was met. The median OS, progression-free survival (PFS), and time-to-treatment failure (TTF) were 12.9 (95% CI: 11.7–14.8), 5.8 (95% CI: 5.1–7.1), and 4.3 (95% CI: 3.9–5.7) months, respectively, for all patients. The median OS, PFS, and TTF for the initial treatment plan were 13.4 (95% CI: 9.6–16.0), 5.8 (95% CI: 4.1–7.9), and 5.3 (95% CI: 3.5–7.3) months, respectively, and for the modified treatment plan were 12.8 (95% CI: 11.3–15.3), 5.7 (95% CI: 4.4–7.0), and 4.2 (95% CI: 3.7–5.7) months, respectively. The most common grade 3/4 toxicities in the initial treatment plan patients were neutropenia (17.9%), anemia (12.8%), thrombocytopenia (12.8%), anorexia (10.3%), and nausea (10.3%) and in the modified treatment plan patients were (13.8%) and anorexia (12.3%). Mean G8 score was 11.4 before the treatment, 13.4 during the treatment and 11.6 at the end of the treatment. Mean MINI-COG score was 4.0 before the treatment, and 4.1 at the end of the treatment and the positive screen for dementia was 13.5% before the treatment and 11.4% at the end of the treatment. Conclusions: Our results show that the modified treatment plan is favorable for the elderly patients with gastric cancer based on the OS and the toxicities. Clinical trial information: 000022450 .

253 Background: The peritoneal dissemination is one of the metastatic forms of gastrointestinal cancer and has a poor prognosis. It has been reported that the presence of CA125 in mesothelial cells lining the peritoneum is involved in the elevation of CA125 due to peritoneal dissemination and inflammation of cancerous ascites, and CA125 may be a useful predictor of peritoneal dissemination in gastrointestinal cancer. It has also been reported that CA125 correlates with ascites volume and prognosis. However, there are no reports evaluating the clinical significance of CA125 in the later line of metastatic colorectal cancer (mCRC). Therefore, we conducted a multicenter retrospective study. Methods: We retrospectively analyzed the clinical data of 121 patients who received trifluridine/tipiracil (FTD/TPI) or Regorafenib from January 2012 to May 2018 in 10 centers and had the result of serum CA125 just before the treatment. Patients who had received either FTD/TPI or Regorafenib were excluded. In this study, the levels of ascites were classified as follows: "none" as undetectable by computed tomography scanning, "mild" as confined to the pelvic cavity or upper abdomen, "severe" as continuous from the pelvic cavity to the upper abdomen, and "moderate" as between "mild" and "severe". RECIST ver.1.1 was used for analysis of tumor response. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 75 patients in the baseline CA125 normal group (group N) and 46 patients in the high group (group H). ECOG PS tended to be worse in group H than in group N (ECOG PS (0/1/2) 26/43/6 and 9/28/9 in N and H groups, p=0.076). There were significantly more patients with ascites in group H than in group N (Yes/No 7/68 and 26/20 in N and H groups, p

BackgroundAlthough an initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at a high risk of bleeding.MethodsIn this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. ResultsOf the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who had experienced MB and CRNMB recovered.ConclusionsThe risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.

DNA methylation status correlates with clinical outcomes of anti-epidermal growth factor receptor (EGFR) treatment. There is a strong need to develop a simple assay for measuring DNA methylation status for the clinical application of drug selection based on it. In this study, we collected data from 186 patients with metastatic colorectal cancer (mCRC) who had previously received anti-EGFR treatment. We modified MethyLite to develop a novel assay to classify patients as having highly methylated colorectal cancer (HMCC) or low-methylated colorectal cancer (LMCC) based on the methylation status of 16 CpG sites of tumor-derived genomic DNA in the development cohort (n = 30). Clinical outcomes were then compared between the HMCC and LMCC groups in the validation cohort (n = 156). The results showed that HMCC had a significantly worse response rate (4.2% vs 33.3%; P = .004), progression-free survival (median: 2.5 vs 6.6 mo, P .001, hazard ratio [HR] = 0.22), and overall survival (median: 5.6 vs 15.5 mo, P .001, HR = 0.23) than did LMCC in patients with RAS wild-type mCRC who were refractory or intolerable to oxaliplatin- and irinotecan-based chemotherapy (n = 101). The DNA methylation status was an independent predictive factor and a more accurate biomarker than was the primary site of anti-EGFR treatment. In conclusion, our novel DNA methylation measurement assay based on MethyLight was simple and useful, suggesting its implementation as a complementary diagnostic tool in a clinical setting.

Background Adolescent idiopathic scoliosis (AIS) is a potentially progressive deformity, and early detection is crucial for timely intervention. However, the methods and criteria justifying screening for pediatric scoliosis remain controversial. We have, therefore, independently developed a Digital Moiré (DM) as a tool for scoliosis screening. The purpose of this study was to assess the usefulness of DM for scoliosis screening. Methods From March 2016 to March 2017, 126 patients (18 boys, 108 girls, mean age: 13.2 ± 2.2 years) with AIS underwent radiographic imaging of their whole spine. We tested the accuracy and reliability of DM by categorizing the examination results as Class 0 (no abnormality), Class 1 (return visit in one year), and Class 2 (further examination needed) and determined the distribution of the population by Cobb angle. The intra/inter-rater reliability and receiver operating characteristic (ROC) analyses were used to categorize the patients with positive findings into Class 1 or 2. Results Regarding the population distribution per Cobb angle in each of the distributions, 11 patients (8.7%) were Class 0, of which nine and two patients had Cobb angle ≤ 10 ° and > 10 °, respectively. There were 20 (15.9% ) Class 1 cases, of which 17 and three had Cobb angle ≤ 10 ° and > 10 °, respectively. Of the 95 (75.4%) Class 2 cases, five and 90 had a Cobb angle of ≤ 10 ° and > 10 °, respectively. The receiver operating characteristic (ROC) analysis of patients with positive findings showed that the area under the curve (AUC), sensitivity, specificity, and false-positive rate were 0.76, 0.98, 0.53, and 0.47, respectively, when predicting Cobb angle > 10°. Intra-rater and inter-rater reliability were 0.73 and 0.70, respectively. Conclusions This study demonstrated the usefulness of DM for determining whether a child with AIS requires a follow-up observation such as radiograph. Our findings suggest that the novel DM shows high accuracy and reliability for scoliosis screening.

TPS4152 Background: Paclitaxel and ramucirumab combination therapy had become a standard regimen in the second-line treatment of advanced gastric cancer, since RAINBOW trial showed paclitaxel and ramucirumab combination therapy increased overall survival compared with paclitaxel monotherapy. However, the incidence of neuropathy in paclitaxel and ramucirumab combination therapy has been reported 70.6% and 38.3% in Japanese and western patients, and the toxicity sometimes disturbs treatment continuation. Whereas docetaxel monotherapy used to be one of standard second-line treatment of advanced gastric cancer as well as paclitaxel monotherapy because the phase III trial, COUGAR-2 showed clinical benefit of docetaxel monotherapy. In addition, the combination therapy of docetaxel and ramucirumab was reported to cause neuropathy at an incidence of 21.3% in patients with lung cancer. Based on these results, we hypothesized that the combination therapy of docetaxel and ramucirumab for patients with gastric cancer could be as effective as the paclitaxel and ramucirumab combination therapy and could reduce the incidence of neuropathy. Therefore, we planned to develop new combination chemotherapy with docetaxel and ramucirumab for advanced gastric cancer. Methods: To evaluate efficacy and safety of docetaxel and ramucirumab combination therapy, HGCSG1903 study started as a multicenter, non-randomized, single arm, prospective, phase II study in November 2020. The patients with metastatic gastric adenocarcinoma that were refractory or intolerant to initial chemotherapy are eligible. Docetaxel and ramucirumab combination therapy is administered as follows; an intravenous infusion of docetaxel at 60 mg/m2 on day 1, an intravenous infusion of ramucirumab at 8 mg/kg on day 1 and day 15 of each 4-week cycle is performed. The therapy is repeated until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint is response rate, and the secondary endpoints are overall survival, progression-free survival, safety, and dose intensity for each drug. The response rate is calculated based on the RECIST version 1.1 criteria. Adverse events are evaluated using the CTCAE v5.0 criteria. A hypothesis test of binary probability was performed, with condition that threshold of response rate was set to 10.7% of docetaxel monotherapy in phase III trial and the expected response rate was set to 27.9% of paclitaxel and ramucirumab combination therapy in RAINBOW trial. A minimum number of cases that achieved a detection power of 80% at a one-sided significance level of 5% was calculated to be 32 cases. In anticipation of dropouts, the total number of registration cases was set to 35. Sixteen institutions are participated, and the registration period is 2 years. This study is registered with Japan Registry of Clinical Trials (jRCTs011200010). Clinical trial information: jRCTs011200010.

217 Background: Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody. The RAINBOW trial showed RAM plus paclitaxel (PTX) increased overall survival (OS) compared with PTX alone for advanced gastric cancer (AGC) in second-line treatment. WJOG 4007 trial demonstrated equivalent efficacy between irinotecan (IRI) and PTX. We conducted this trial to examine the efficacy and safety of RAM plus IRI combination therapy in the second-line treatment for AGC. Methods: This non-randomized, single arm, phase 2 trial was carried out at 22 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM 8 mg/kg and IRI 150 mg/m2 combination therapy administered every two weeks were continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint was progression-free survival (PFS) rate at six-month, the target was set as 16% with an expected threshold of 39%. A total of 35 cases are planned for registration. The secondary endpoints were OS, PFS, response rate (RR) and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011180029. Results: Between Jan 2018 and Sept 2019, 35 patients were enrolled. Median age was 70 (range, 47-80); female/male were 10/25; ECOG PS 0/1, 22/13. PFS rate at six months was 26.5% (95%C.I., 13.2-41.8%, p = 0.1353). Median PFS and OS were 4.2 (95%C.I., 2.5-5.4 months) and 9.6 months (95%C.I., 6.5-16.6 months), respectively. RR was 26% and disease control rate was 85%. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), febrile neutropenia (11%), diarrhea (9%), hypertension (9%), proteinuria (9%), hypokalemia (9%), hypoalbuminemia (9%), thrombocytopenia (6%), and hyponatremia (6%). No death and new safety signals with a causal relation to study treatment were observed. Conclusions: Although the primary endpoint was not achieved statistically, the results are clinically encouraging, especially take into account that more elderly patients enrolled in this trial. The combination of RAM plus IRI has anti-cancer activity and manageable safety profile in second-line treatment for patients with AGC. Clinical trial information: jRCTs011180029.

Immune checkpoint inhibitors may have different clinical effects compared with conventional anticancer drugs. An 85-year-old male received chemotherapy for recurrent gastric cancer. As liver metastasis progressed, nivolumab was introduced as a fourth line treatment. Progression of liver metastasis in size was observed in CT after 3 courses of nivolumab therapy. Nivolumab treatment was discontinued, because the general condition of the patient also worsened. However, his general condition improved as hepatobiliary enzyme levels, inflammatory response, and tumor markers improved. Liver metastasis was shrinking on the image, so we resumed nivolumab therapy. To the authors' knowledge, this is the first case of pseudoprogression undergoing immunotherapy for gastric cancer. In this case, the antitumor effect was exhibited in a delayed manner and the tumor shrinkage was obtained.

A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.

Background The regimens of nab-P+GEM have become available for advanced pancreatic cancer, especially metastatic disease. However, there are not enough data of nab-P+GEM for LAPC. Methods This is a retrospective multiple institutes cohort study using medical records of LAPC patients who received nab-P+GEM between January 2015 and September 2017. We have surveyed their characteristics and treatment outcomes. Results The number of relevant patients was 48 at 11 institutes. Median age was 68 years old, male/female : 22/26, ECOG PS 0/1/2 : 33/13/2, primary site; head/body/tail : 28/18/2. Relative dose intensity was nab-P; 0.588 (0.065-1.012) and GEM; 0.656 (0.368-1.012). Response rate was 27.0% and Disease control rate was 94.6% among patients who had target lesion. Median progression-free survival was 9.4 months (95% CI, 5.4 – 13.4) and median overall survival was 19.6 months (95% CI, 13.9 – 24.3). The most common adverse event of grade 3 or higher was neutropenia (61.7%). Febrile neutropenia was 8.3%. Conclusions It seemed that nab-P+GEM was effective for patients with LAPC. Prospective and further investigation in more cases is expected. Legal entity responsible for the study Hokkaido Gastrointestinal Cancer Study Group. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Anti-EGFR antibody is one of the options for treatment of RAS wild-type metastatic colorectal cancer (mCRC), especially when the primary tumor site locates in the left sided large intestine. We have shown that methylation status evaluated by genome-wide DNA methylation test correlates with clinical outcomes of anti-EGFR treatment in RAS wild-type mCRC. Here, we report about the development of novel in vitro diagnostics (IVD) based on DNA methylation status of selected CpG sites. Method We retrospectively collected KRAS wild-type mCRC cases who received anti-EGFR treatment in salvage line. DNA methylation status was measured for 16 CpG sites by our novel IVD using real-time PCR method for each case. Based on DNA methylation status, they were classified into 2 groups. Highly-methylated colorectal cancer (HMCC) was defined when 8 or more sites among 16 sites were methylated and low-methylated colorectal cancer (LMCC) was classified when it was less than 8 sites. We compared the clinical outcomes between the 2 groups, and the predictive accuracy of the DNA methylation status by the new diagnostic method was examined. Results A total of 83 cases were collected, with 20 cases classified as HMCC and 63 cases classified as LMCC. The response rate of the anti-EGFR treatment was 5.0% (1/20 cases) in HMCC and 30.2% (19/63 cases) in LMCC, respectively (p = 0.032). The median progression-free survival were 2.8 months and 5.3 months, respectively (p Conclusion DNA methylation status of the 16 CpG sites measured by our novel IVD was significantly correlated with the therapeutic effect of anti-EGFR treatment for KRAS wild-type mCRC. Currently, extended analysis is in progress using the data of more than 200 cases. We will report the results including the analysis of RAS status and primary tumor site.

TPS183 Background: As second-line chemotherapy for gastric cancer, a survival benefit has been shown in several clinical trials. Irinotecan and taxanes are recommended as second-line regimen. However, therapeutic outcomes have remained unsatisfactory and more effective treatment are expected. Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody that prevents ligand binding of VEGF-A, VEGF-C, and VEGF-D and the receptor-mediated pathway activation in endothelial cells, subsequently inhibiting neovascularization. In the REGARD study, RAM monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma improved median overall survival (mOS) compared with placebo. Moreover, in the RAINBOW study, RAM plus paclitaxel (PTX) versus placebo plus PTX, mOS showed significantly longer in RAM plus PTX group than in placebo plus PTX group. In contrast, there are no data on the efficacy of RAM and irinotecan in the second-line treatment for gastric cancer. The WJOG 4007 study demonstrated an equivalent efficacy between irinotecan and PTX. In this study, we propose to examine the efficacy of RAM plus irinotecan. Methods: This study is carried out as a multicenter, non-randomized, single arm, prospective, phase II study. The patients with metastatic or advanced gastric cancer that is refractory or intolerance to primary chemotherapy are eligible for this study. RAM and irinotecan combination therapy is administered every two weeks, which is continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint is progression-free survival rate at six months, and the secondary endpoints are OS, progression-free survival, response rate, safety, and dose intensity for each drug. A total of 35 cases areplanned for registration. This study is registered with the University Hospital Medical Information Network. Clinical trial information: UMIN000030372.

Glioblastoma (GBM) is the most lethal and aggressive adult brain tumor, requiring the development of efficacious therapeutics. Towards this goal, we screened five genetically distinct patient-derived brain-tumor initiating cell lines (BTIC) with a unique collection of small molecule epigenetic modulators from the Structural Genomics Consortium (SGC). We identified multiple hits that inhibited the growth of BTICs in vitro, and further evaluated the therapeutic potential of EZH2 and HDAC inhibitors due to the high relevance of these targets for GBM. We found that the novel SAM-competitive EZH2 inhibitor UNC1999 exhibited low micromolar cytotoxicity in vitro on a diverse collection of BTIC lines, synergized with dexamethasone (DEX) and suppressed tumor growth in vivo in combination with DEX. In addition, a unique brain-penetrant class I HDAC inhibitor exhibited cytotoxicity in vitro on a panel of BTIC lines and extended survival in combination with TMZ in an orthotopic BTIC model in vivo. Finally, a combination of EZH2 and HDAC inhibitors demonstrated synergy in vitro by augmenting apoptosis and increasing DNA damage. Our findings identify key epigenetic modulators in GBM that regulate BTIC growth and survival and highlight promising combination therapies.

We report the case of a patient with advanced colon cancer receiving oxaliplatin-based chemotherapy that was able to continue systemic chemotherapy by performing mild partial splenic embolization (PSE) for thrombocytopenia caused by splenomegaly due to oxaliplatin. Mild PSE may be useful for thrombocytopenia due to splenomegaly in cancer patients because it provides more treatment opportunities.

Background: The prognosis of advanced gastrointestinal cancer, especially in patients with poor performance status (PS), is generally dismal. Patients with PS 3–4 are almost ineligible for participation in clinical studies. Patients and Methods: From June 2000 to February 2007, 116 patients with poor PS (PS 3 = 73 and PS 4 = 43) were treated with chemotherapy. Retrospective analysis was performed. Results: Of the 107 patients with at least one measurable lesion, a partial response was obtained in 15 patients (14.0%). Of 65 patients with ascites and/or pleural effusion, 12 patients achieved decreased fluid accumulation. A decline in tumor markers was observed in 30 patients. As a result, 38 patients (32.7%) achieved tumor response, a decrease in fluid accumulation or a decline in tumor markers (responders), which resulted in a survival benefit compared to the other 78 patients without effect (6.9 vs. 2.2 months, p < 0.001). PS improvement was seen in 16 patients (13.8%). Conclusions: The results suggest that chemotherapy may be beneficial in gastrointestinal cancer patients with poor PS, as demonstrated by a certain degree of improvement in PS and survival in responders. Further study is required to confirm the benefit of chemotherapy in this patient population.

Objective: The aim of this study was to evaluate the efficacy and safety of a combination regimen using irinotecan plus S-1 in patients with metastatic pancreatic cancer. Methods: Based on the results of our previous phase I/II study in patients with gastric and colorectal cancer, we initiated a regimen with irinotecan at 100 mg/m2 on days 1 and 15 and S-1 at 80 mg/m2 starting at day 1 for 14 consecutive days, followed by a 14-day rest period. This treatment was repeated every 28 days. Results: From November 2003 to December 2006, a total of 16 patients were enrolled. All patients presented with metastatic disease. Six patients had received prior gemcitabine. The median number of treatment cycles was 4 (range 1–16) and the response rate was 43.7% (95% confidence interval 19.5–68.1). The median time to progression was 4.9 months, and the median survival time was 11.3 months. Grade 3–4 neutropenia developed in 5 of 16 patients and grade 3 diarrhea in 1 patient. Conclusions: The combination of irinotecan and S-1 is feasible and promising for pancreatic cancer. Further evaluation of this combination chemotherapy is required.

778 Background: The CORRECT trial revealed the safety and efficacy of regorafenib (REG) for patients (pts) with colorectal cancer including Japanese. REG was approved in Japan in March 2013. However, there are few studies exploring the efficacy and safety of REG in a large number of patients, particularly in daily practice. Methods: We analyzed 173 pts who received REG from May 2013 in the multi-institutional retrospective study (HGCSG1401). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients’ characteristics were as follows; male/female 98/75, median age 66 (range 29-87), ECOG PS (0/1/2/3) 58/96/18/1, KRAS Exon2 wild/mutant 98/74 (1 patient ; KRAS Exon2 status was not tested). The initial starting dose was 160 mg (n = 145, 83.8%), 120mg (n = 22, 12.7%), and 80mg (n = 6, 3.5%) respectively. Dose reductions were required in 73 pts (42.2%); 38 pts (22.0%) discontinued therapy due to AEs. The common ≥ grade 3 AEs ( ≥ 15%) were palmar-plantar erythrodysesthesia syndrome (n = 48; 27.7%), hypertension (n = 34; 19.7%), proteinuria (n = 24; 19.2%) and AST increased (n = 24; 13.9%). RR and disease control rate (DCR) were 1.3% and 29.6%, respectively. Median PFS and median survival time (MST) were 2.1 and 6.3 months. In an analysis on relationship between ECOG PS (PS 0-1 vs. PS 2-3) and efficacy, median PFS was 2.3 vs. 1.2 months (HR 3.598, p < 0.001), and MST was 7.0 vs. 2.1 months (HR 4.751, p < 0.001). Conclusions: The efficacy of REG in pts with PS 0–1 was similar to the previous report; however, REG was not effective in patients with PS 2–3. In adverse events, hypertension and liver dysfunction were expressed more frequently than previously reported. We will continue the analysis of the factors associated with liver dysfunction and prognostic/predictive factors.

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF)in patients with advanced gastric cancer with gastrointestinal stenosis in clinical practice.In the chemotherapy-naïve patients who had metastatic or recurrent histologically confirmed gastric cancer, docetaxel(40mg/m2), levofolinate(200mg/m / / / 2), fluorouracil(400mg/m2)on day 1, fluorouracil 1,000 mg/m2d-2 days intravenous continuous in fusion beginning on day 1, and cisplatin(40mg/m2)on day 3 was administered every 2 weeks.Six patients received mDCF therapy. In 5 patients with measurable disease, the overall response rate was 86%. Median progression-free survival was 310 days and median overall survival was 599 days. Symptom improvement after the first cycle of mDCF was obtained in all patients. Grade 3 or 4 leukopenia and neutropenia were observed in 2(33%)and 6(100%)patients, respectively. There were no treatment-related deaths.mDCF seems to be active against metastatic and recurrent gastric cancer with gastrointestinal stenosis. Further study is needed to confirm the efficacy and safety of mDCF regimen.

A 42-year-old man was found to have an adenocarcinoma arising from ectopic gastric mucosa in Meckel's diverticulum, as diagnosed with surgical pathology. Recurrence was recognized with massive ascites at 1 year and 6 months after surgery. Chemotherapy in the first and second lines was not effective. In the third line of chemotherapy, pemetrexed and carboplatin were both administered and this resulted in a good response for massive ascites. This palliative therapy was effective and safe.

Background Japanese surgeons have to macroscopically assess nodal metastasis from colon cancer according to the general rules established in Japan. Adjuvant therapy is sometimes started after macroscopic assessment of nodal metastasis. Macroscopic assessment, however, is difficult in many cases.

A case of rectal cancer with an extramural growth is presented. A 50-year-old woman complained of severe constipation. A pelvic tumor which was 10 cm in diameter and compressed the rectum, was pointed out by digital examination, Barium enema, and CT examination. The tumor was hypervascular and fed by the superior rectal artery. With a diagnosis of rectal leiomyosarcoma, a laparotomy was performed. The tumor invaded the rectum, uterus, left ovary, left ureter, and pelvic wall. The resection of the tumor including affected organs, sigmoido-proctostomy, and left uretero-cutaneostomy were performed. Microscopically, the tumor was poorly differentiated adenocarcinoma which partially contained adeno-squamous cell carcinoma. Though the origin of the tumor was thought to be either the rectum or ovary, the tumor was finally diagnosed as rectal cancer with an extramural growth based on imaging findings including angiography. The extramural growth is rare in rectal cancers.

進行大腸癌330例を対象に, 原発巣にどのような組織型が混在した場合にリンパ節転移頻度が高いのかを求め, また, 組織型個々のリンパ節転移頻度を原発巣でのその組織型の多寡に応じて求めることから, 組織型の混在がリンパ節転移頻度に及ぼす影響を解析した. 組織型の組み合わせ別リンパ節転移頻度は, 従組織型として低分化腺癌が混在した場合にのみ, 組織多様性のない癌より有意に高率だった (73%vs. 48%; p

大腸他臓器重複癌例 (重複例) のhigh risk例を同定し, 早期発見早期治療を行って治療成績を向上させるために, 当科の重複例からその特徴を検討した.重複例は626例中106例 (17%) だった.重複例の臨床的因子を非重複例と, また癌重複時期の違いで比較検討した結果, 性差や大腸癌診断時年齢, 癌家族歴に差を認めたが, high risk例選定に有用な特徴は得られなかった.重複する癌の検討では, 胃癌が最も多く, ついで子宮癌であり, その多くが放射線治療後に大腸癌を重複した例であることから子宮癌放射線治療例は癌重複のhigh risk例と考えられた.重複例の転帰は同時性例では進行度の高い一方の癌によって, 異時性例では第2癌によって規定されることから, 治療成績向上のためには胃癌を含めた第2, 第3癌の同時性, 異時性の存在を念頭において検査, 治療することが重要である.