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4011Background: Trastuzumab (Tmab) is a key drug for HER2-positive breast and gastric or gastro-esophageal junction (G/GEJ) cancer. While continuous use of Tmab beyond progression (TBP) showed a be...

4036Background: RAM (a human IgG1 antibody against vascular endothelial growth factor receptor-2) plus paclitaxel has been found to improve overall survival compared with paclitaxel alone as second...

4029Background: WJOG7112G study, comparing paclitaxel plus trastuzumab (PT; n = 44) with paclitaxel alone (P; n = 45), did not demonstrate survival benefit of trastuzumab continuation beyond progre...

To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy.Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed.Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade 2 RP (p0.01). The incidences of grade 2 RP were 13%, 33%, and 78% in patients with V20s of 24%, 25-36%, and 37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis.DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.

699 Background: Plasma levels of VEGF-A short isoforms (VEGF-A110 and -A121) measured by immunological multiparametric chip technique (IMPACT) were reported to be associated with clinical benefits from bevacizumab (BV) in advanced gastric and pancreatic cancer but not in metastatic colorectal cancer (mCRC). Negative results in mCRC studies might be caused by different sample handling: citrate instead of EDTA and repetition of freeze/thaw. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). A median value of pVEGF-A was used as a cut-off point to categorize patients (pts) into the low and high pVEGF-A groups. Progression free survival (PFS) and overall survival (OS) between the low and high pVEGF-A groups were compared, using Cox proportional hazards model. We hypothesized that BV-containing treatment extend shorter PFS of pts with high pVEGF-A to that with low pVEGF-A, and estimated a threshold hazard ratio (HR) between them as below 1.15. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0] and response rate was 64.6 % [range, 53.3-74.9]. pVEGF-A was measured in 97 pts and the median value was 36.8 pg/ml [range, 6.5- 262.2]. The hazard ratios of PFS and OS between the high and low pVEGF-A groups were 1.23 [95%CI, 0.76-1.97, p = 0.40] and 2.47 [95%CI, 1.14-5.36, p = 0.02], respectively. Conclusions: mCRC pts with high pVEGF-A showed shorter PFS than those with low pVEGF-A beyond the predefined threshold (HR 1.15) in BV-containing chemotherapy, suggesting that pVEGF-A could not be a predictive marker for BV efficacy. Clinical trial information: UMIN000012442.

670 Background: Bevacizumab (BV)-containing chemotherapy has been established as the standard first-line treatment for metastatic colorectal cancer (mCRC). However, no biomarkers have been established to predict the clinical benefit of BV for patients (pts) with mCRC. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). Median values of pICAM-1 and pIL-8 were used as cut-off points to categorize pts into the low and high groups. Progression free survival (PFS) and overall survival (OS) were compared between two groups, using Cox proportional hazards model. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0]. Response rate was 64.6 % [53.3-74.9]. pICAM-1 and pIL-8 were measured in 99 pts and the median values were 190.0 ng/ml [range, 58.0- 1080.1] and 311.5 pg/ml [range, 83.2-4541.4], respectively. The hazard ratios of PFS and OS between the high and low pICAM-1 groups were 2.08 [95%CI, 1.28-3.40, p = 0.003] and 2.04 [0.92-4.50, p = 0.079], respectively. The hazard ratios of PFS and OS between the high and low pIL-8 groups were 1.63 [95%CI, 1.00-2.65, p = 0.048] and 3.42[1.57-7.44, p = 0.002], respectively. Conclusions: High pICAM-1 and pIL-8 were associated with short PFS and OS of mCRC pts treated with BV-containing chemotherapy, suggesting that pICAM-1 and pIL-8 could be predictive markers for prognosis of mCRC treated with BV. Clinical trial information: UMIN000012442.

121 Background: The standard 1st-line chemotherapy for AGC pts with SPM has not been established. F alone is generally used for their treatment because of difficulty of hydration for dosing of cisplatin (CDDP) in pts with massive ascites, and has shown limited efficacy. It is unclear whether a combination of F and P (CDDP or oxaliplatin): FP improves their clinical outcome. We therefore investigated the efficacy and safety of FP in comparison with F alone. Methods: This retrospective study comprised of AGC pts with SPM and HER2 negative or unknown tumors who received FP or F as 1st-line chemotherapy between Jul 2010 and Sep 2016 at 6 institutions in Japan. SPM was defined as having massive ascites and/or inadequate oral intake requiring intravenous nutrition support. Overall survival (OS), progression-free survival (PFS), response rate of ascites, improvement rate of oral intake, and safety were compared between two treatment groups. Results: A total of 129 pts (64 in FP group, 65 in F group) were included. Patient characteristics (FP vs F) were as follows: median age, 62 vs 67; PS 0/1/2/3/4 (%), 6/64/25/3/2 vs 8/42/42/8/0; massive ascites/inadequate oral intake/both (%), 61/25/14 vs 35/29/35; number of metastatic sites 1-2/3-5 (%), 77/23 vs 78/22; median serum albumin level (g/ml), 3.1 vs 3.1. OS was significantly longer in FP group than F group (median, 9.0 vs 5.0 months; HR 0.56, 95%CI 0.39-0.82; log-rank p < 0.01); it remained significant upon multivariate analysis adjusting for prognostic variables (HR 0.48, 95% CI 0.32-0.73, p < 0.01). Pts in FP group had significantly better PFS in both uni- and multivariate analyses (median, 4.3 vs 2.3 months; HR 0.44, p < 0.01 and HR 0.40, p < 0.01, respectively). Response rate of ascites (51% vs 17%) and improvement rate of oral intake (64% vs 43%) also were better in FP group (p < 0.01 and p = 0.09, respectively). Toxicities were tolerable in both groups, but grade ≥3 neutropenia was more frequent in FP group (36% vs 11%). Conclusions: FP showed significantly better efficacy than F alone, and it could be a promising option as 1st-line treatment for AGC pts with SPM.

Although triweekly administration of paclitaxel is approved for gastric cancer in Japan, currently, the drug is often delivered with a weekly schedule because of the equivalent efficacy and lesser toxicity of this dosing schedule as compared with the triweekly administration schedule. Weekly administration of paclitaxel as second-line or first-line chemotherapy for gastric cancer has been reported to yield a response rate of about 20%. Because there has been no report of the efficacy of weekly paclitaxel in the third-line setting, this retrospective study investigated the efficacy and toxicities of weekly paclitaxel used in the third-line setting for the treatment of gastric cancer refractory to all three key drugs, fluorouracil, irinotecan, and cisplatin, used in clinical practice.In 85 patients with advanced or recurrent histologically confirmed gastric adenocarcinoma who had failed to respond to prior chemotherapy regimens containing fluorouracil, irinotecan, and cisplatin, paclitaxel (80 mg/m(2)) was administered weekly, three times, for 3 weeks out of 4.The median number of courses was 3 (range, 1-38). The overall response rate was 23.2% (19/82) in the patients with measurable lesions, and ascites disappeared in 15 of 48 patients (31.3%). Progression-free survival was 105 days and the median survival time was 201 days from the initiation of paclitaxel administration. Grade 3 or 4 leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 25 (29%), 25 (29%), 37 (44%), and 3 (4%) patients. Other, nonhematological, toxicities were nausea, vomiting, anorexia, sensory neuropathy, fatigue, and febrile neutropenia.Weekly paclitaxel administration shows activity against advanced gastric cancer also in the third-line setting.

Although peritoneal dissemination of gastric cancer is common and often causes deterioration of the patient's condition and quality of life (QOL), these patients are usually excluded from clinical trials. We retrospectively investigated the clinical benefit and toxicity of sequential methotrexate and 5-fluorouracil (MTX/5FU) therapy for patients with peritoneal dissemination.The subjects were 31 patients with severe peritoneal dissemination of gastric cancer who were treated with MTX/5FU. The treatment schedule comprised weekly administration of MTX (100 mg/m(2)) followed by 5FU (600 mg/m(2)). Leucovorin (10 mg/m(2)) was administered six times, every 6 h, starting 24 h after MTX administration.The median survival time was 255 days, and the median progression-free survival was 127 days. Of the 21 patients with measurable lesions, 4 (19%) patients achieved a partial response. Ascites volume decreased markedly in 14 (54%) of the 26 patients with ascites. Seventeen patients had adequate oral intake, but the other 14 patients had required nutritional support before treatment. The median dripinfusion free survival was 100 days in the former 17 patients, and oral intake improved in 3 (21%) of the latter 14 patients. Grade 3 or 4 neutropenia was observed in 26% of the patients and anemia was observed in 45%. The grade 3 nonhematological toxicities were vomiting (6%) and fatigue (10%). Early death, within 30 days of the last administration of MTX/5FU, occurred due to disease progression in 2 patients, but there were no treatment-related deaths.MTX/5FU chemotherapy may be effective in treating peritoneal dissemination of gastric cancer and might improve the patient's condition in terms of reducing ascites and improving oral intake.

We retrospectively reviewed to investigate the efficacy and toxicity of monotherapy with S-1 in patients with advanced or recurrent gastric cancer after failure of first-line chemotherapy. Twenty-one patients were evaluated. The median number of treatment cycles was 2 (range 1-19). There were no cases showing either complete or partial response, and 10 patients (47.6%) showed stable disease. The median progression-free survival was 89 days. Sixteen patients (76%) received third-line chemotherapy. The median survival time was 271 days after the initiation of S-1, with a 1-year survival rate of 32%. Hematological toxicities were Grade 4 anemia (9.5%), Grade 3 or 4 neutropenia (9.5%) and leukopenia (4.7%). As for non-hematological toxicities, Grade 3 or 4 diarrhea and anorexia were noted in 9.5% and 14.2% of the patients, respectively. S-1 was found to show no efficacy and cannot be recommended for second-line chemotherapy against gastric cancer.

Many studies of concurrent chemoradiation therapy with 5-fluorouracil (5-FU) for locally advanced pancreatic cancer have been reported with a median survival time of approximately 10 months. Recently, gemcitabine (GEM) has been administered immediately after chemoradiation. The clinical outcome of chemoradiation therapy in conjunction with 5-FU and second-line chemotherapy with GEM after disease progression has not been clarified.Patients with locally advanced pancreatic cancer were treated with concurrent radiation therapy (1.8 Gy/fraction; total dose, 50.4 Gy) with 5-FU (200 mg/m(2) every day) until disease progression, followed by GEM (1000 mg/m(2), days 1, 8, 15, and every 4 weeks) as second-line therapy.Of the 18 patients with locally advanced pancreatic cancer who received chemoradiation therapy with 5-FU, there were three partial responses, giving a response rate of 17%. The median time to progression was 170 days. The median survival time was 443 days. During chemoradiation therapy, the incidences of grade 3 or 4 anorexia, nausea, mucositis, and gastric ulcer were 33%, 22%, 17%, and 17%, respectively. Sixteen patients received second-line chemotherapy with GEM, of whom one patient had a partial response. The median time to progression from the initiation of GEM was 113 days, and median overall survival time was 231 days. Major toxicities were hematological toxicities: grade 3 or 4 leukopenia in 75% and anemia in 31%.The treatment strategy with concurrent chemoradiation and maintenance chemotherapy with 5-FU followed by second-line chemotherapy with GEM may be an option for locally advanced pancreatic cancer.

Objective: In patients with metastatic colorectal cancer (mCRC), several prognostic factors such as performance status (PS), number of metastatic sites, carcinoembryonic antigen (CEA), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported. The objective of this study was to clarify the prognostic impact of Baseline Sum of Longest Diameter (BSLD) of target lesions by Response Evaluation Criteria in Solid Tumor (RECIST) in patients with mCRC. Methods: The subjects of this study were consecutive 103 patients with mCRC who had been received the first line systemic chemotherapy between September 2002 and March 2005. Results: The chemotherapy regimens included leucovorin-modulated 5-fluorouracil (5-FU) (n ¼ 27) and 5-FU plus irinotecan (n ¼ 76). The median overall survival time was 547 days. The median BSLD was 14.3 cm (range, 1.1‐54.7). In univariate analysis, identified prognostic variables on survival were PS (0, 1 versus 2), number of metastatic sites (1 versus .1), peritoneal dissemination (þ versus 2), pleural effusion (PE) and/or ascites, white blood cell (� versus ,10 000/mm 3 ), ALP (� versus ,300 IU), LDH (� versus ,300 IU), CEA (� versus ,5 ng/ml), chemotherapy regimen, presence of liver metastasis, and BSLD. In multivariate analysis with covariates of the above significant factors, BSLD (� versus ,10 cm) (HR 0.431, 95% CI 0.237‐0.785, P ¼ 0.0059), PS (HR 0.248, 95% CI 0.107‐0.577, P ¼ 0.0012), PE and/or ascites (HR 0.402, 95% CI 0.228‐0.708, P ¼ 0.0016) were independent prognostic factors. Conclusion: BSLD of target lesions by RECIST representing tumor volume might be an independent prognostic factor of patients with mCRC after systemic chemotherapy.

In Japan, chemotherapeutic agents that have been approved for the treatment of esophageal cancer include cisplatin, nedaplatin, 5-fluorouracil, vindesine, and docetaxel. We retrospectively investigated the efficacy and toxicity of a combination of nedaplatin plus vindesine, or docetaxel alone, for patients with unresectable or recurrent squamous cell carcinoma of the esophagus refractory to prior chemotherapy with 5-fluorouracil plus platinum.Nedaplatin was administered at 90 mg/m(2) intravenously on day 1, and vindesine was administered at 3 mg/m(2) intravenously on days 1 and 8 every 28 days. Docetaxel 60 mg/m(2) or 70 mg/m(2) was administered intravenously every 21 days. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 24 patients treated with nedaplatin plus vindesine and 28 patients treated with docetaxel.In patients treated with nedaplatin plus vindesine, the response rate of the 13 patients with measurable lesions was 8% (1/13), the median progression-free survival time was 1.8 months, and the median survival time was 5.5 months. In patients treated with docetaxel, the response rate of the 17 patients with measurable lesions was 18% (3/17), the median progression-free survival time was 2.1 months, and the median survival time was 5.1 months. The most frequent toxicity was neutropenia (grade 4; 13% in the group with nedaplatin plus vindesine and 50% in the docetaxel group), and febrile neutropenia (grade 3; 4% and 18%, respectively).The efficacy of the two regimens for unresectable or recurrent squamous cell carcinoma of the esophagus refractory to chemotherapy with 5-fluorouracil plus platinum was unsatisfactory. New, more effective therapies are needed.

A 78-year-old man presented with a chief complaint of dysphagia. He was diagnosed with an esophageal squamous cell carcinoma and referred to our hospital. A type 3 tumor was identified in the lower thoracic esophagus on endoscopy. A CT scan revealed lymph node metastases at the No. 3 station. The clinical stage of the tumor was T3N1M0, Stage III. The patient was treated with neoadjuvant chemotherapy consisting of2 courses of5 -FU and nedaplatin. He had a partial response and underwent a radical esophagectomy. Histopathological examination revealed a complete response of the primary lesion and viable cancer cells in only one lymph node at the No. 3 station. No adjuvant chemotherapy was administered. Three months after the operation, recurrences in the upper abdominal multiple para-aortic lymph nodes were detected. Although he was treated with chemotherapy, he died 7 months after the operation. Even after a complete response of the primary lesion was achieved using neoadjuvant chemotherapy, esophageal cancer with lymph node metastasis has the potential for an early recurrence. Therefore, we should consider adjuvant therapy in such cases.

Objective There is little information about the patterns of care for elderly esophageal squamous cell carcinoma patients, and a standardized strategy has not been established. Therefore, we conducted a questionnaire survey about the patterns of care for these patients. Methods On September 2014, the questionnaires were sent to all 43 institutions of the Japan Esophageal Oncology Group, which comprised five parts: (i) definition of 'elderly' (age, method), (ii) basic treatment strategy according to stage and elderly status (fit/vulnerable/frail), (iii) patterns of care in each stage, (iv) considerations about conducting future clinical trials and (v) other information about geriatric oncology concerning esophageal squamous cell carcinoma. Results All answers were obtained by January 2015. Nearly half institutions (47%) considered the chronological definition of elderly to be over 80 years old. Among 43 institutions, 36 (84%) reported that the type of comorbidity and performance status were important factors for decision-making; no institution selected geriatric scale as an indicator. The most selected treatment strategy in fit healthy elderly patients was the same as the standard treatment of non-elderly patients. Radiation alone was considered the main treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Most of the institutions answered that clinical trials for the elderly are warranted. Most institutions (70%) chose Stage II/III (non-T4) esophageal squamous cell carcinoma as an important investigational target. Conclusions Fit healthy elderly were considered the same as non-elderly patients, although there are no established treatment selection criteria. Radiation alone plays most important role in the treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Stage II/III (non-T4) disease is attractive and warranted for future investigations.

Summary Background Although leucovorin enhances the efficacy of fluorouracil, the anti-tumour activity of S-1 and leucovorin and their combination with oxaliplatin for patients with advanced gastric cancer is unknown. We compared the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy for advanced gastric cancer. Methods In this multicentre, randomised, open-label, phase 2 trial, we recruited chemotherapy-naive patients with unresectable or recurrent gastric cancer with measurable lesions aged 20 years or older from 25 general hospitals and specialist centres in Japan. Patients were randomly assigned (1:1:1) centrally to receive S-1 plus leucovorin (S-1 40–60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S-1 plus leucovorin and oxaliplatin (S-1 plus leucovorin and intravenous oxaliplatin 85 mg/m 2 on day 1, every 2 weeks), or S-1 plus cisplatin (S-1 40–60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m 2 on day 8, every 5 weeks). Randomisation was done with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors. The primary endpoint was independently reviewed overall response in the full analysis set. This trial is registered with Japic CTI, number 111635. Findings Between Oct 20, 2011, and Dec 17, 2012, we enrolled and randomly assigned 145 patients: 49 patients were assigned to S-1 plus leucovorin, 47 to S-1 plus leucovorin and oxaliplatin, and 49 to S-1 plus cisplatin. An objective response assessed by the independent review committee was achieved in 20 (43% [95% CI 28·3–57·8]) of the 47 patients in the S-1 plus leucovorin group, 31 (66% [50·7–79·1]) of the 47 patients in the S-1 plus leucovorin and oxaliplatin group, and 22 (46% [31·4–60·8]) of the 48 patients in the S-1 plus cisplatin group (Fisher's exact test, p=0·84 for S-1 plus leucovorin vs S-1 plus cisplatin, p=0·063 for S-1 plus leucovorin and oxaliplatin vs S-1 plus cisplatin, and p=0·038 for S-1 plus leucovorin and oxaliplatin vs S-1 plus leucovorin). The most common grade 3–4 adverse events were neutropenia (three [6%] of 48 patients in the S-1 plus leucovorin group vs 12 [26%] of 47 patients in the S-1 plus leucovorin and oxaliplatin group vs 17 [35%] of 49 patients in the S-1 plus cisplatin group), decreased appetite (six [13%] vs 14 [30%] vs 12 [24%]), anaemia (five [10%] vs seven [15%] vs 13 [27%]), and hyponatraemia (two [4%] vs two [4%] vs nine [18%]). Interpretation S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable toxic effects for patients with advanced gastric cancer. A phase 3 trial comparing S-1 plus leucovorin and oxaliplatin with S-1 plus cisplatin is underway. Funding Taiho Pharmaceutical.

Although both the response rate and survival time of patients with metastatic or recurrent gastric cancer have improved through the development of new anti-cancer agents, it is still difficult to achieve a complete response(CR)of a tumor. Compared to the best supportive care alone, second-line chemotherapy can prolong survival after the failure of first-line therapy in patients who otherwise are in good health. In the WJOG4407 trial, which compared irinotecan and paclitaxel as secondary chemotherapies, there was no difference in response rate or survival time. A large proportion of these patients could undergo third-line chemotherapy, and paclitaxel is currently used as a control in many secondary chemotherapy trials. The molecularly targeted agents ramucirumab and apatinib have been shown to have high efficacy in phase III trials. Ramucirumab will be approved for medical insurance reimbursement next year in Japan, and its combination with paclitaxel is considered the standard treatment for this malignancy.

Purpose: A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy. Experimental Design: Biopsy specimens from 51 patients with esophageal cancer (T2-3, any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated. Results: The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome. Conclusion: Computer-assisted tumor microvessel analysis is a powerful tool in predicting the outcome for patients with esophageal cancer treated with chemoradiotherapy because intraobserver and interobserver variability is minimized.

Paclitaxel scheduled every 3 weeks has shown a response rate of approximately 20% for gastric cancer, with modest hematological toxicity. Weekly administration of paclitaxel in patients with breast or ovarian cancer has shown equivalent efficacy and milder toxicity compared with an every-3 week schedule. We investigated, retrospectively, the antitumor effects and toxicity profiles of weekly paclitaxel for patients with metastatic or recurrent gastric cancer in clinical practice.In 38 patients who had metastatic or recurrent histologically confirmed gastric cancer and a history of one prior chemotherapy regimen, other than paclitaxel or docetaxel, paclitaxel (8 mg/m2) was administered weekly, three times every 4 weeks, with short-term premedication.All 38 patients had had prior chemotherapy that included 5-fluorouracil, the fluoropyrimidine anticancer drug S-1, or cisplatin. The median number of courses in the present regimen was 6 (range, 1-44+). Dose intensity was 5mg/m2 per week, corresponding to 92% of the planned dose (6 mg/m2 per week). The overall response rate was 24% (6/25) in measurable lesions, and pleural effusion and ascites disappeared in 2 of 7 patients (29%) and in 3 of 21 patients (14%), respectively. Median survival time was 151 days from the commencement of this treatment, with a median follow-up period of 260 days. Grade 3 or 4 leukopenia and neutropenia were observed in 11 (29%) and 12 (32%) patients, respectively. Seven patients (18%) died within 30 days of the last administration of paclitaxel.Weekly paclitaxel seems to be active as second-line chemotherapy against metastatic and recurrent gastric cancer. Further study is needed to confirm the efficacy and safety of weekly paclitaxel.

Background RAS (KRAS and NRAS) testing is required to predict anti-epidermal growth factor receptor (EGFR) treatment efficacy in metastatic colorectal cancer (CRC). Although direct sequencing (DS) with manual microdissection (MMD) is widely used, a diagnostic kit providing rapid detections of RAS mutations would be clinically beneficial. We evaluated the MEBGENTM RASKET KIT (RASKET KIT), a multiplex assay using PCR-reverse sequence specific oligonucleotide and xMAP® technology to concurrently detect exon 2, 3, and 4 RAS mutations in a short turnaround time (4.5 h/96-specimens). Methods Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 308 consenting patients with histologically-confirmed CRC at six hospitals in Japan. For the RASKET KIT, we used only 50–100 ng DNA from each FFPE specimen not processed by MMD. The primary endpoint was the concordance rate between RAS mutations identified with the RASKET KIT and two reference assays (DS with MMD and TheraScreen® K-RAS Mutation Kit). As the secondary endpoints, we evaluated the concordance rate between DS and the RASKET KIT for RAS mutations in the wild-type KRAS exon 2 population and the genotyping performance of the RASKET KIT compared with DS. Findings Among 307 analyzable specimens, the reference assays detected 140 (45.6%, 140/307) RAS mutations: 111 KRAS exon 2 and 29 other (minor) RAS mutations. The RASKET KIT detected 143 (46.6%, 143/307) mutations: 114 KRAS exon 2 and 29 minor RAS mutations. The between-method concordance rate was 96.7% (297/307) (95% CI: 94.1–98.4%). Minor RAS mutations were detected in 15.7% (30/191) of the wild-type KRAS exon 2 population (n = 191); the concordance rate was 98.4% (188/191) (95% CI: 95.5–99.7%). The concordance rate of RAS genotyping was 100% (139/139) (95% CI: 97–100%). Interpretation The RASKET KIT provides rapid and precise detections of RAS mutations and consequently, quicker and more effective anti-EGFR therapy for CRC (Study ID: UMIN000011784). Funding Medical & Biological Laboratories Co., Ltd. (MBL). MBL had roles in study design, data collection, data analysis, and writing of the report for the study., Highlights • We performed clinical evaluation of MEBGEN RASKET KIT to detect RAS mutations. • MEBGEN RASKET KIT detects 48 RAS mutations in a single well. • The overall agreement between MEBGEN RASKET KIT and the gold standard methods was 96.7%. • MEBGEN RASKET KIT provides RAS testing of 96 samples simultaneously. • Results are obtained within 4.5 h per batch using MEBGEN RASKET KIT.

A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC] classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU; 400 mg/m(2) by continuous infusion; days 1-5 and 8-12) and cisplatin (40 mg/m(2) by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1-5, 8-12, and 15-19; total, 30 Gy per course) with the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m(2); days 1-5) and cisplatin (80 mg/m(2); day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient received second-line chemotherapy with irinotecan (150 mg/m(2); every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine (1000 mg/m(2) weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy using paclitaxel (80 mg/m(2); weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung may be applicable for these carcinomas of the esophagus.

Patients with squamous cell carcinoma of the head and neck have a high prevalence of second primary esophageal squamous cell carcinomas. This study assessed the risk of developing second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck based on multiplicity of Lugol-voiding lesions observed by chromoendoscopy and patient characteristics.Three hundred eighty-nine patients with newly diagnosed squamous cell carcinoma of the head and neck were divided into 4 groups: no Lugol-voiding lesions; several (/=10) small Lugol-voiding lesions; many (10) small Lugol-voiding lesions; and many irregularly shaped, multiform Lugol-voiding lesions. Relative risk for the development of synchronous second primary esophageal squamous cell carcinomas was investigated by using univariate and multivariate analysis. Metachronous second primary esophageal squamous cell carcinomas was also studied among 227 patients followed more than 1 year after initial examination.Fifty-four (14%) of the 389 patients were found to have synchronous second primary esophageal squamous cell carcinomas. In particular, 55% of the patients with many irregular-shaped multiform Lugol-voiding lesions had synchronous second primary esophageal squamous cell carcinomas. Univariate analysis showed that the presence of many irregular-shaped multiform Lugol-voiding lesions, drinking habit, male gender, and smoking were significant risk factors for the development of synchronous second primary esophageal squamous cell carcinomas. Multivariate analysis also revealed that many irregular-shaped multiform Lugol-voiding lesions (odds ratio: 21.4; p0.001) and drinking habit (odds ratio: 3.3; p0.02) were independent risk factors. During follow-up, 7 patients (3%) had metachronous second primary esophageal squamous cell carcinomas; 6 had many irregular-shaped multiform Lugol-voiding lesions and the seventh had many small Lugol-voiding lesions in the background mucosa.The presence of numerous irregular-shaped multiform Lugol-voiding lesions was closely associated with second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck. This might be explained by the concept of "field cancerization." Ingestion of alcohol may play an important role in the occurrence of this phenomenon.

We report a case of carcinoma in a hyperplastic polyp in a 78-year-old female that was diagnosed before resection using a magnifying colonoscope. The patient presented with fecal occult blood and underwent total colonoscopy, which revealed a 12-mm sessile polyp in the cecum. When seen in magnified view, an irregularly shaped pit was evident at the center of the polyp that was distinct from the asteroid-type pits observed over most of the lesion. We diagnosed this lesion as a hyperplastic polyp with a carcinoma component. The patient underwent endoscopic mucosal resection, and histologic section revealed a well-differentiated intramucosal adenocarcinoma in the hyperplastic polyp. Hyperplastic polyps of the colon are regarded as benign, nonneoplastic lesions. Few have reported carcinomas in or with hyperplastic polyps, and most of those were diagnosed after resection and histologic investigation. The literature suggests a precise observation and consideration of resection for large solitary hyperplastic polyps in the right side of the colon, because the risk of malignancy is high. Magnifying colonoscopy is helpful for observing the surface in detail and for correctly diagnosing and managing the lesion.

4041 Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. Methods: This study is ongoing with 20 major cancer centers. Patients with aNon-CRC, who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to whether genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of advanced gastric cancer (aGC) cohort. Results: As of October 31st in 2016, a total of 565 aGC samples were analyzed. The sequence with the OCP was successfully performed in 425 (75.2%). Out of 475 patients except for the 90 patients in which precise data is not collected, the proportion of histology type is followed; intestinal type 44.6%, diffuse type 54.5%, other 0.6%, unknown 0.2%. Out of 406 samples of which results were available, the frequently detected mutations were TP53 (47.8%), PIK3CA (8.6%), KRAS (5.4%), SMAD4 (4.9%), TET2 (4.4%), APC (3.9%), ERBB2 (3.7%) and CNVs were ERBB2 (10.8%), CCNE1 (9.4%), KRAS (3.7%), ZNF217 (3.2%), FGFR2 (2.7%), and MET (2.5%). FGFR3-TACC3 fusion, WIPF2- ERBB2 fusion and EGFR vIII were detected in 2, 1, and 2 cases, respectively. Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aGC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.

Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm).

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737.

Background. Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. Methods. This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10 mg/m2 was administered six times, every 6 h, starting 24 h after MTX administration. Results. Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. Conclusions. This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer.

A 58-year-old man was diagnosed to have an esophageal adenocarcinoma arising in Barrett's esophagus by screening examination at the previous hospital. Endoscopically, a slightly reddish elevated lesion with a central depressed component was detected in the Barrett's epithelium. Endoscopic ultrasonography showed the thickness of the second layer of the esophagus and no enlarged lymph node. Histological examination of a biopsy specimen revealed well or moderately differentiated adenocarcinoma. From these findings, the lesion was diagnosed as a mucosal esophageal cancer, type IIa + IIc, arising in Barrett's esophagus. As he refused operation, the lesion was resected endoscopically with his informed consent. Histologically, the resected specimens showed moderately differentiated adenocarcinoma arising in Barrett's esophagus. The adenocarcinoma had invaded the superficial muscularis mucosa, but was limited to the deep one with no vessel invasion. Barrett's esophagus often has a double muscularis mucosa. Connective tissues containing vascular and lymphatic vessels exist between them. However, one consideration is whether the existence of vessels between the double muscularis mucosa and the presence of vessel invasion are risk factors for metastasis. In order for a definitive indication for endoscopic mucosal resection, the frequency of lymph node and distant metastasis in cases of early Barrett's cancer needs to be investigated.

BACKGROUND: Patients with bone metastasis of gastric cancer occasionally experience disseminated intravascular coagulation (DIC), with a very poor prognosis.METHODS: We treated 18 gastric cancer patients with bone metastasis with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU therapy). The treatment schedule comprised weekly administration of methotrexate (MTX; 100 mg/m(2), i.v. bolus) followed by 5-fluorouracil (5-FU; 600 mg/m(2), i.v. bolus) after an interval of 3 h. Calcium leucovorin (10 mg/m(2), p.o. or i.v.) was administered six times, every 6 h starting 24 h after the administration of MTX.RESULTS: In 11 patients with measurable metastatic lesions, the response rate was 64% (7/11). Nine patients (50%) had DIC before the initiation of chemotherapy, and 8 of them (89%) recovered from it. Two of these 9 patients (22%) survived for more than 1 year. The median survival times for all patients and for the 9 with DIC were 186 and 113 days, respectively. Grade 4 leukopenia was observed in 3 patients (17%). No treatment-related deaths occurred.CONCLUSION: Sequential MTX/5-FU therapy may have palliative potential and may be a feasible treatment for gastric cancer patients with bone metastasis with or without DIC.

Background: This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). Methods: Ninety patients were randomised to a standard dose of wPTX (80 mg m−2) or an escalated dose of wPTX (80–120 mg m−2) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8. Results: The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34). Conclusion: Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P

Objective Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. We evaluated the efficacy and toxicity of radiotherapy at a dose of 50.4 Gy concurrent with chemotherapy for Stage II-III esophageal cancer. Methods Esophageal cancer patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) were eligible. Radiotherapy was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Concurrent chemotherapy comprised two courses of 5-fluorouracil (1000 mg/m(2)/day) on days 1-4 and 2-h infusion of cisplatin (75 mg/m(2)) on Day 1; this was repeated every 4 weeks. Two courses of 5-fluorouracil with cisplatin were added. Results Fifty-one patients were enrolled in the study from June 2006 to May 2008. The characteristics of the 51 patients enrolled were as follows: median age 64 years; male/female, 45/6; performance status 0/1, 32/19 patients; Stage IIA/IIB/III, 9/20/22 patients, respectively. A complete response was achieved in 36 patients (70.6%). The 1- and 3-year overall survival rate was 88.2 and 63.8%, respectively. The median 1- and 3-year progression-free survival rate was 66.7% (80% CI: 57-74%) and 56.6% (80% CI: 47.1-64.9%), respectively. Acute toxicities included Grade 3/4 anorexia (45%), esophagitis (35%) and febrile neutropenia (20%). Eight patients (15.6%) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery. Conclusion Chemoradiation therapy at a dose of 50.4 Gy with elective nodal irradiation is promising with a manageable tolerability profile in esophageal cancer patients.

S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients.In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate.Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36-86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0-27.4 months), respectively (P = 0.064). Progression-free survival was significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression.No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.

4021Background: This multicenter phase II trial assessed the safety and efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (IC) and subsequent conversion surgery (...

e15521Background: AGC and chemotherapy are associated with a high incidence of VTE. Risk factors of VTE in AGC pts receiving chemotherapy, and prognostic impact of VTE on their survival are not wel...

4058Background: We conduct the nationwide cancer genome screening project in Japan since 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), ca...

Background: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. Methods: TAS-102 was administered twice daily on days 1–5 and days 8–12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. Results: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m−2 per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m−2. α, α, α-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m−2 per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m−2 per day was the recommended dose for phase II studies. Conclusions: TAS-102 at 70 mg m−2 per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer.

Objective: Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Methods: Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Results: Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade � 3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease � 24 weeks, 7 had stable disease � 16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. Conclusions: The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Background. Oral intake of many patients with locally advanced head and neck cancer (LAHNC) decrease during chemoradiotherapy (CRT). Although prophylactic percutaneous endoscopic gastrostomy (PEG) is recommended, not a few patients complete CRT without using PEG tube. Patients and Methods. The subjects were patients with LAHNC who received CRT. We retrospectively investigated the incidence and duration of nutritional support during and after CRT, and predicting factors of nutritional support. For patients who required nutritional support, we also checked the day of initiation and the duration of nutritional support. Results. Of 53 patients, 29 patients (55%) required nutritional support during and/or after CRT. While no clear relation between requirement of nutritional support and variables including age, T stage, N stage, clinical stage and chemotherapy regimen, there could be some relationships between tumor primary sites and the requirement and duration of nutritional support. 17 (77%) of 22 patients with oropharynx cancer(OP) required nutritional support and prolonged for 4.4 months, and 11 (46%) of 24 patients with hypopharynx cancer(HP) required nutritional support and prolonged for 21.9 months. Conclusion. Nutritional support is indicated many HNC patients treated with CRT and primary sites may have some relation to its indication and duration.

OBJECTIVES In western countries, 7% to 10% of patients with pancreatic cancer (PC) have a familial predisposition to their disease. The aim of this study was to determine the familial susceptibility to PC in Japan. METHODS Five hundred seventy-seven patients with PC and 577 age- and gender-matched controls were analyzed for cancer history in their first-degree relative(s) (FDRs) and demographic factors. RESULTS The patients with PC were more likely to have an FDR with PC (6.9%) than the controls (2.9%; odds ratio [OR], 2.5; P = 0.02). Three patients (0.5%), but none of the controls, had a family history of PC in multiple FDRs. Smoking, especially current smoking (OR, 1.5; P = 0.005), and diabetes mellitus (OR: 1.7, P = 0.001) were also associated with PC. The odds increased up to 10-fold if the patients were positive for these 3 factors. The patients with familial PC were more likely to be current smokers (40%) and to have diabetes mellitus (32.5%) than the sporadic cases (30.1% and 20.1%; OR, 1.6 and 1.9). CONCLUSIONS A family history of PC is a risk of PC in Japan (6.9%) as is a personal history of diabetes and smoking. It is prudent to inform the kindred of patients with familiar PC of the risk of smoking and to follow carefully if they develop diabetes.

Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC.We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups.The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively.Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.