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Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments.We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated.Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P 0.001).Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at 4 years after ER, careful long-term follow-up examinations are needed.

Background The Cryoballoon focal ablation system (CbFAS) for dysplastic Barrett’s esophagus is simple, time-saving and has high therapeutic efficacy. This study aimed to evaluate the technical feasibility and tissue damage with combination therapy of endoscopic resection (ER) and CbFAS in porcine models. Methods Three pigs (A, B, and C) were included, and all ER procedures were performed by endoscopic mucosal resection using the Cap method (EMR). Combination therapy for each pig was performed as follows: (a) CbFAS was performed for a post-EMR mucosal defect for Pig A; (b) CbFAS for post-EMR scar for Pig B, and (c) EMR for post-CbFAS scar for Pig C. All pigs were euthanized at 32 days after the initial procedure, and the tissue damage was evaluated. Results All endoscopic procedures were followed as scheduled. None of the subjects experienced anorexia, rapid weight loss, bleeding, and perforation during the observation period. They were euthanized at 32 days after the initial endoscopic procedure. On histological assessment, there was little difference between the tissue that was treated with CbFAS alone and that treated with CbFAS in combination with ER. Conclusion Combination therapy with ER and CbFAS can be technically feasible, and its outcome was not significantly different from CbFAS alone in terms of tissue damage.

A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC. This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks. A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1–5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2–3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7–1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD. MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.

Background Improvements in early detection and treatment have resulted in an increasing number of long-term survivors of colorectal cancer (CRC). For the survivors, second primary cancer and recurrence are important issues; however, evidence for an appropriate surveillance strategy remains limited. This study aimed to investigate the frequency and timing of second primary cancer in patients after surgery for exploring an appropriate surveillance strategy by using an integrated analysis of three large-scale randomized controlled trials in Japan. Methods The eligibility criteria of three trials included histologically confirmed CRC and having received surgery. The timing, site and frequency of second primary cancers and recurrence were investigated. Risk factors associated with second primary cancers were also examined. The standardized incidence ratio (SIR) of second primary cancers compared with the national database of the Japan Cancer Registry was estimated. Results A total of 2824 patients were included in this study. The cumulative incidence of second primary cancer increased over time. The SIR of any second primary cancer was 1.07 (95% CI: 0.94–1.21). The SIR for second primary cancers of colon was 1.09 (95% CI: 0.79–1.47). The cumulative incidence of recurrence almost reached plateau at 3 years. Conclusions A common surveillance strategy for the general population can be applied even for curatively resected CRC patients, as the risk of second primary cancers was almost the same as that of the general population.

Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy. Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry. Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naive group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naive patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders. Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.

OBJECTIVES S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC. METHODS We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (

JCOG9801, a randomized phase III trial, reported that vincristine, cyclophosphamide, doxorubicin and prednisone (VCAP); doxorubicin, ranimustine and prednisone (AMP); and vindesine, etoposide, carboplatin and prednisone (VECP) (VCAP-AMP-VECP; mLSG15) showed superior clinical outcomes when compared to cyclophosphamide, doxorubicin, vincristine and prednisone every 2 weeks (CHOP-14; mLSG19) in patients with untreated aggressive adult T-cell leukaemia-lymphoma (ATL). To identify patients who require VCAP-AMP-VECP, we conducted a supplementary analysis of JCOG9801. Overall, 105 patients were included and categorized into low- (n = 44), intermediate- (n = 54) and high-risk (n = 7) groups according to the age-adjusted ATL prognostic index (ATL-PI). We excluded the high-risk group due to small numbers of patients. VCAP-AMP-VECP did not show any superior trend for overall survival (OS) in the low-risk group (hazard ratio: 1·04; 95% confidence interval: 0·54-2·04). Better OS was observed in the intermediate-risk group treated with VCAP-AMP-VECP (hazard ratio: 0·65; 95% confidence interval: 0·36-1·19). In the intermediate-risk group, the VCAP-AMP-VECP arm showed higher complete response rates than the CHOP-14 arm (44·0% vs. 13·8%). The VCAP-AMP-VECP arm in both risk groups exhibited grade 4 thrombocytopenia, while grade 4 neutropenia was only observed in the intermediate-risk group. VCAP-AMP-VECP remains suitable for the intermediate-risk group, whereas its benefits appear modest in the low-risk group.

Background Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. Methods One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. Results GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. Conclusions We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

Background and Aims Lymph node recurrence (LNR) after endoscopic resection (ER) in patients with esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (pMM) without lymphovascular invasion (LVI) has been reported as non-negligible in the ER guidelines for esophageal cancer by the Japan Gastroenterological Endoscopy Society. However, these data were not regarded as high-level evidence because several retrospective case series were tabulated without sufficient long-term follow-up. Hence, this guideline stated that the administration of additional treatment after ER could not be determined for this population. This study aimed to clarify the long-term clinical outcomes after ER of pMM ESCC without LVI. Methods Between January 2009 and November 2017, we enrolled followed-up patients who underwent ER and were pathologically diagnosed with pMM ESCC without LVI without additional treatments. We retrospectively investigated the cumulative recurrence rate and recurrence-free, overall, and disease-specific survival at 5 years after ER. Results Eighty-seven patients were enrolled. During the median follow-up period of 64 months (range: 12–117), 3 patients developed lymph node and/or distant recurrence, and 2 of these cases occurred more than 3 years after ER; all 3 patients died of the primary disease. The 5-year cumulative recurrence rate was 4.3%, and the 5-year recurrence-free, disease-specific, and overall survival rates were 88.8%, 98.2%, and 91.7%, respectively. Conclusions The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

Tumor regression grade of the primary tumor (TRG-PT) and residual lymph node metastasis have been pathologically determined in esophageal squamous cell carcinoma (ESCC) patients who had received neoadjuvant chemotherapy (nCT) followed by surgery; however, TRG of the metastatic tumor involving lymph nodes (LN) has not yet been determined. The aim of the present study was to clarify the impact of TRG on the prognosis of ESCC patients. ESCC patients (n = 110) who had received nCT followed by surgery were enrolled. Dissected LN were classified into 2 categories: plausible positive metastatic LN (pp-MLN) where viable and/or degenerated ESCC cells and/or tissue modifications were observed, and non-metastatic LN (non-MLN) where neither of them was observed. We defined nCT-effective rate (CER) as the ratio of the number of pp-MLN that showed tumor regression to the total number of pp-MLN, and divided CER into low-CER (LCER; ≥0% and

Background and aim Salvage endoscopic resection (ER) is among the curative treatments for superficial local failure after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). The present study aimed to clarify risk factors for recurrence after salvage ER. Methods This study enrolled consecutive ESCC patients treated with salvage ER for local failure after CRT between 1998 and 2013. Recurrences after salvage ER included locoregional recurrences and distant metastases. Multivariate analysis was carried out on clinicopathological parameters to identify risk factors for post-salvage ER recurrence. Results Of the 72 patients enrolled in this study, 37/8/23/4 patients had been staged before CRT as cT1/T2/T3/T4 and 44/28 patients as cN0/N1, respectively, and local failures detected before salvage ER were residual lesions after CRT in 19 and local recurrences in 53 patients. Resected specimens were classified as pT1a (M) in 45 and pT1b (SM) in 27 patients. During the median 45-month follow up (range, 3-175 months) after salvage ER, 27 (38%) patients developed recurrence with a 3-year recurrence-free survival rate of 48.9% (95% confidence interval [CI], 36.5-60.3). Multivariate analysis showed that residual lesions after CRT (HR, 2.55; 95% CI, 1.32-4.94) and lesions with a submucosal tumor (SMT)-like appearance before salvage ER (HR, 2.08; 95% CI, 1.04-4.18) were significantly associated with post-salvage ER recurrence. Conclusions Clinical findings (e.g. residual tumors found immediately after CRT and macroscopic SMT-like appearance before salvage ER) were shown to be significant risk factors for post-salvage ER recurrence.

178 Background: Recently, JCOG0502 trial have shown a comparable efficacy with chemoradiotherapy (CRT) and esophagectomy as standard treatment in patients with clinical stage (cStage) I esophageal squamous cell carcinoma (ESCC), showing the standard treatment option of CRT. However, there is few reports for comparison of clinical outcomes with these treatments in real-world. The aim of this study was to clarify the real-world outcomes in cStage I ESCC who performed with CRT or esophagectomy. Methods: This retrospective study included patients with clinical stage I ESCC who received thoracoscopic or open esophagectomy with three-field lymph node dissection or CRT mainly consisted of 5-fluorouracil and platinum with concurrent radiotherapy (50.4 Gy/28Fr or 60 Gy/30Fr) between 2009 and 2017 at National Cancer Center Hospital East. Survival outcomes were calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: Among a total of 156 patients, 128 were male and median age was 68 years old. 120 and 36 patients underwent esophagectomy and CRT, respectively. ECOG performance status 0/1/2 were 138/12/6 patients. Tumor location was Ut/Mt/Lt in 16/87/53 patients. Clinical tumor depth (MM-SM1/SM2-SM3) were 33/123 patients. Patients’ characteristics were similar among treatment groups, except clinical tumor depth (SM2-3; 84.2% in esophagectomy group vs. 61.1% in CRT group, p = 0.005). All patients underwent radical surgery in esophagectomy group, while three patients (8.3%) in CRT group were received additional esophagectomy or endoscopic resection due to residual disease. With a median follow-up of 72 months, 5-year overall survival (OS) and progression-free survival rate were 81.5%/77.0% in esophagectomy group and 82.6/74.4% in CRT group (p = 0.89 and p = 0.48). In safety profile, grade 3 or higher stenosis was observed in 21.7% of esophagectomy group. There was no treatment-related death in both groups. In subgroup analysis for OS, elderly patients (75 years and older) tended to have better 5-year OS rate in CRT group (76.9% in esophagectomy group vs. 81.8% in CRT group), while younger patients ( < 75 years) showed comparable 5-year OS rate in both groups (82.4% in esophagectomy group vs. 82.9% in CRT group). Conclusions: Real-world data reproduced the results of clinical trial, supporting CRT as one of the standard treatment options in patients with cStage I ESCC.

4565 Background: Esophageal squamous cell carcinoma (ESCC) is associated with synchronous or metachronous cancer at other primary sites. Previous studies have suggested that patients (pts) with ESCC are still at a high risk of second primary malignancies after definitive therapies. In particular, early-stage ESCCs result in good prognosis, which is associated with a higher risk of second primary malignancies. Methods: The JCOG0502 was a phase III trial, which included a randomized and a non-randomized part and compared esophagectomy with definitive chemoradiotherapy in clinical T1bN0 ESCC. We additionally reviewed data of all pts enrolled in the JCOG0502 for second primary malignancies. Lugol-voiding lesions (LVLs) were assessed in the noncancerous esophageal mucosa before the treatments. Results: Among 379 enrolled pts, 213 pts received esophagectomy and the remaining received chemoradiotherapy. Patient characteristics of overall cohort were as follows: male, 85%; median age, 63 (range, 41–75) years; upper- /middle- /lower thoracic esophagus, 11/63/27%; alcohol consumption history, 79%; smoking history, 66%; prevalence of no LVLs/several LVLs/many LVLs/unknown, 45/36/8/11%. With a median follow-up of 7.1 years, a total of 118 second malignancies were observed in 99 pts (26%). Cumulative incidences of second malignancies after 3, 5, 10 years were 9, 15, 36%, respectively. Most common primary tumor sites were head and neck (35%), followed by stomach (20%) and lung (14%). In multivariable analyses, several LVLs [hazard ratio (HR): 2.24, 95% confidential interval (CI): 1.32–3.81, vs. no LVLs] and many LVLs (HR: 2.88, 95% CI: 1.27–6.52, vs. no LVLs) were significantly associated with the development of second malignancies. Regarding the three most common types of cancers, 62 out of the 77 cancers (81%) were diagnosed in clinical stage 0–I. Seventeen pts died due to second primary malignancies. There were 4 and 3 deaths from head and neck and lung cancer, respectively. Whereas, mortality caused by stomach cancer was not observed. Conclusions: In the JCOG0502, the incidence of second malignancies was high, indicating that careful follow-up is required for ESCC pts even after treatment completion. The presence of LVLs in esophagus was identified as an independent predictive factor for second primary malignancies, which may be useful for surveillance strategies. Clinical trial information: UMIN000000551 .

Standard therapy for gastric diffuse large B‐cell lymphoma (DLBCL) is considered to be chemotherapy with or without involved‐field radiation therapy. Although R‐CHOP therapy alone is widely used for DLBCL with gastric lesions (DLBCL‐GL), the outcome and incidence of treatment‐related gastric complications following R‐CHOP are not well known. This study aimed to evaluate the outcome after R‐CHOP therapy in patients with gastric DLBCL including gastric complications and to identify risk factors for the complications. Consecutive patients with newly diagnosed DLBCL‐GL treated with R‐CHOP between 2003 and 2014 were retrospectively evaluated. DLBCL‐GL was defined only when pathologically confirmed in the stomach. Of the 96 patients with DLBCL‐GL, 63 patients were diagnosed with gastric symptoms. Eighty‐eight patients (92%) completed six to eight cycles of R‐CHOP. The complete remission (CR) rate was 86%, and 3‐year and 5‐year overall survival rates were 80% and 73%, respectively. Patients were well stratified according to the Revised International Prognostic Index (R‐IPI). Complication rate was 8% (8/96); seven patients had bleeding and three had stenosis. No patients had gastric perforation. Bleeding occurred during the first cycle of R‐CHOP in five patients (5/7, 71%). Patients with gastric complications had a lower R‐CHOP completion rate (50%, P = 0.001) and a lower CR rate (25%, P

Background and objectives To clarify prognostic factors for the patients with esophageal squamous cell carcinoma (ESCC) through an assessment of surgically resected specimens modified by neoadjuvant chemotherapy (nCT). Methods We retrospectively reviewed the clinicopathological data of 143 consecutive patients with ESCC who underwent nCT followed by surgery between 2008 and 2012 at our institution and conducted survival analysis. The tumor regression grade (TRG) was classified based on the proportion of residual tumor cells in the area where the tumor was thought to have existed before nCT as follows: Grade 0 (no therapeutic effect), Grade 1a (residual tumor cells ≥2/3), Grade 1b (1/3≤ residual tumor cells

Objectives Lymph node metastasis (LNM) in submucosal invasive esophageal squamous cell carcinoma (SM-ESCC) is a prognostic factor. The aim of this study was to identify a histopathologic predictor of LNM in SM-ESCC. Methods In total, 108 patients who underwent an esophagectomy and lymph node dissection without preoperative therapy and who were pathologically diagnosed with SM-ESCC were enrolled in this study. Relationships between several clinicopathologic factors and LNM were examined. Results A multivariate analysis revealed that a tumor size of 35 mm or more (P = .0025), submucosal invasive depth (SID) of 2,000 μm or more (P = .013), and lymphatic infiltration (P < .0001) were significant independent predictors of LNM. In addition, there were significant differences in recurrence-free survival curves between patients with SID less than 2,000 μm or not (P = .029) and tumor size less than 35 mm or not (P = .049). Conclusions This study suggests that SID may predict not only LNM but also poor prognosis.

Background Although several studies suggested that immune checkpoint inhibitors may enhance an efficacy of radiotherapy (RT), it remains unclear in patients (pts) with advanced gastric cancer (AGC). Methods Total 34 AGC pts treated with RT for the primary gastric lesion from April 2013 to March 2019 were analyzed in this study. Pts were divided into two groups according to whether they had received nivolumab before RT or not. Primary tumor responses were assessed according to volumetry on CT scan with tumor response as > 70% decrease in tumor volume. Endoscopic responses were evaluated in pts who underwent endoscopy after RT. Tumor infiltrating lymphocytes (TILs) were also analyzed to examine the tumor microenvironmental immune status in the pts. Results Among 34 pts, 16 pts had received nivolumab before RT. There were no significant differences in baseline characteristics between nivolumab-exposed and nivolumab-naive groups. 70% tumor reductions by RT were observed in 25% (4/16) in nivolumab-exposed group but no patients (0/18) in nivolumab-naive group (P = 0.039). Among pts who received endoscopy after RT, four of seven pts in nivolumab-exposed group experienced partial response, while no response was observed among 10 nivolumab-naive pts (P = 0.015). TILs were evaluated in pts whose tumor samples were available. CD8+ T cells/effector regulatory T cells (eTreg cells) ratio in TILs was markedly increased after nivolumab in pts who achieved response, but not observed in pts who had no tumor reduction. A significant increase of CD8+ T cells/eTreg cells ratio after nivolumab treatment was observed in nivolumab-exposed pts (n = 15), whereas such a tendency was not observed in nivolumab-naive pts (n = 10). Conclusions RT to primary gastric cancer significantly led to tumor response in nivolumab-exposed pts compared with nivolumab-naive pts. Immune profiling suggested that nivolumab might enhance the sensitivity to RT by immunoactivation via increasing CD8+ T cell/eTreg cell ratio.

Background and study aims: One of the major complications after endoscopic resection (ER) for large superficial esophageal squamous cell carcinoma (ESCC) is benign esophageal stricture, which can reduce quality of life even if ESCC achieves a cure without organ resection. Recently, steroid administration has been reported as a prophylactic treatment to prevent esophageal strictures. This retrospective study evaluated the stricture rate according to the different width of mucosal defects due to ER and compared it to that seen with prophylactic steroid administration. Patients and methods: Between June 2007 and December 2013, we enrolled patients with ESCC who had 3/4 or larger circumferential mucosal defects due to ER. In December 2009, steroid injections (triamcinolone acetonide 50 mg) into the ulcer bed due to ER were introduced. Beginning in November 2012, we commenced oral steroid administration (prednisolone 30 mg/day, tapered gradually for 8 weeks) in addition to steroid injection. Patients were classified into 3 groups according to the width of mucosal defect after ER (Group A, ≥ 3/4 and

Introduction The JCOG9801 study, a randomized phase III trial of the Japan Clinical Oncology Group (JCOG), compared CHOP every two weeks (CHOP-14) with VCAP-AMP-VECP (mLSG15) for patients with untreated aggressive adult T-cell leukemia-lymphoma (ATL) [J Clin Oncol 2007;25:5458-64]. Based on a higher complete response (CR) rate and marginally better overall survival (OS), we concluded that mLSG15 could be a sufficiently effective regimen at the expense of higher toxicity profiles. However, there was an insufficient mLSG15 effect among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or those aged ≥56 years, suggesting that mLSG15 is not always a definitive treatment for all patients with aggressive ATL. Thus, identifying patients who should receive mLSG15 is essential. We aimed to conduct a supplementary analysis of patients enrolled in the JCOG9801 study using the ATL prognostic index (ATL-PI) that has been recently advocated for acute- and lymphoma-types of ATL [J Clin Oncol 2012;30:1635-40]. Methods We adopted the "age-adjusted" ATL-PI that was established for ATL patients aged ≤70 years as patients aged between 15 and 69 years were eligible in the JCOG9801 study. Having eliminated "age", this index comprised 4 factors, namely Ann Arbor stage (III or IV), ECOG PS (>1), serum albumin (20,000 U/mL). We excluded patients lacking any factors of the age-adjusted ATL-PI and those with unfavorable chronic type based on the age-adjusted ATL-PI model from patients enrolled in JCOG9801. Subsequently, we categorized the remaining patients into three groups, namely low, intermediate, and high risk, and compared mLSG15 and CHOP-14 in terms of OS, treatment CR rate, and toxicity in each risk group. Results Of 118 enrolled JCOG9801 patients, we included 105 patients in this supplementary analysis based on the above criteria, of which 51 and 54 were treated with mLSG15 and CHOP-14, respectively. According to the age-adjusted ATL-PI, these patients were classified as follows: low (n=44, 41.9%), intermediate (n=54, 51.4%), and high (n=7, 6.7%) risks. Regarding patient characteristics, between the two treatment arms, there were no remarkable differences in age, sex, ECOG PS, ATL subtypes, Ann Arbor stage, presence of B symptoms, presence of bulky mass (≥5 cm), and serum albumin, serum calcium, and sIL-2R levels. The mLSG15 arm included 21 (41.2%), 25 (49.0%), and 5 (9.8%) patients in the low-, intermediate-, and high-risk groups, respectively, whereas the CHOP-14 arm included 23 (42.6%), 29 (53.7%), and 2 (3.7%) patients, respectively. We excluded the high-risk group from our analysis due to the small number of patients. mLSG15 did not show any superior trend for OS compared to CHOP-14 in the low-risk group (hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.491-1.868) (Figure A). In contrast, in the intermediate-risk group, better prognosis for OS was observed with mLSG15 (HR: 1.538; 95% CI: 0.841-2.811) than with CHOP-14 (Figure B). Similarly, the CR rate, including the unconfirmed CR rate, did not differ between both arms of the low-risk group (mLSG15 vs. CHOP-14, 47.6% vs. 43.5%), while in the intermediate-risk group, mLSG15 showed a higher CR rate than CHOP-14 (44.0% vs. 13.8%). Regarding toxicity profiles, grade 4 thrombocytopenia was more frequently observed in the mLSG15 arm of both risk groups than in the CHOP-14 arm (66.7% vs. 4.5% in the low-risk group; 68.0% vs. 24.1% in the intermediate-risk group only). There was a higher incidence of grade 4 neutropenia in the mLSG15 arm than in the CHOP-14 arm (100.0% vs. 75.9%) only in the intermediate-risk group. All three treatment-related deaths were documented in the mLSG15 arm of the intermediate-risk group. Conclusions Given the very poor prognosis of ATL, our findings suggest that despite higher toxicities, mLSG15 is more suitable for the intermediate-risk group of age-adjusted ATL-PI, whereas its benefits appear modest in the low-risk group. This supplementary analysis is exploratory; therefore, a further prospective study of aggressive ATL is necessary to confirm these results. Disclosures Tsukasaki: Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fukushima:NEC corporation: Research Funding. Maruyama:Bristol-Myers Squibb: Honoraria; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; Mundipharma International: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Amgen Astellas BioPharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Nagai:SymBio Pharmaceuticals Limited: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer Yakuhin Ltd.: Research Funding; Abbvie G. K.: Research Funding; Celgene Corporation: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; AstraZeneca plc.: Research Funding; Roche Ltd.: Honoraria; Esai Co., Ltd.: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Sanofi K. K.: Honoraria; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding.

Background: The standard therapy for primary gastric diffuse large B-cell lymphoma (DLBCL) is chemotherapy of R-CHOP with/without involved-field radiation therapy. Although some reports indicated that gastrointestinal complications after chemotherapy for DLBCL occur at a rate of 0-26%, little is known about riskfactors for the complications. In addition, to detect DLBCL in gastric lesion, both of positron emission tomography-computed tomography (PET-CT) and esophagogastroduodenoscopy (EGD) are useful tools. However, there have been few reports comparing them. The aim of this study is to show the outcomes including treatment-related complications in patients with gastric DLBCL and risk factors for the gastric complications. Moreover, we evaluated whether PET-CT is sufficient to detect DLBCL in gastric lesion by comparing with EGD. Patients and methods: This retrospective study included consecutive patients with newly diagnosed DLBCL between October 2003 and July 2014 who underwent EGD and were treated with R-CHOP in our hospital. We classified the patients into three groups. Group A-1: patients who had documented DLBCL in gastric lesion by EGD and underwent PET-CT; group A-2: patients who had documented DLBCL in gastric lesion by EGD and did not underwent PET-CT; group B: patients who had no documented DLBCL in gastric lesion by EGD and underwent PET-CT. Suspected lymphomatous lesions by EGD were biopsied and immunopathologically examined. Gastric DLBCL was defined only when pathologically confirmed. In PET-CT, gastric lesions with SUV max ≥ 5 were considered positive. Outcomes and risk factors for complications among group A were analyzed using the logistic regression model. We evaluated significance of PET-CT and EGD in group A-1 and B by the positive predictive value (PPV) and the negative predictive value (NPV). Results: Among 448 patients diagnosed with DLBCL, 178 patients were enrolled for our study: 55 in group A-1, 28 in group A-2 and 95 in group B. Among 83 patients with gastric DLBCL (group A), the median age was 69 years (range, 29-85). The numbers of patients with clinical stage (Ann Arbor classification) I, II, III, and IV were 27, 18, 5, and 33, respectively. The rate of complete remission was 87%, and the median 3- and 5-year over survival (OS) were 81% and 75%, respectively. The median 3-year OS of patients with very good, good, and poor grade of Revised International Prognostic Index (R-IPI) was 100%, 77%, and 63%, respectively (Figure, p=0.025). Ten patients had gastric complications: 6 with bleeding that needed blood transfusion and 3 with gastrointestinal stenosis defined as ordinary endoscopy could not pass, no patients had gastrointestinal perforation. Most of bleeding (66.7%) occurred during the first cycle of R-CHOP (median, 15 days; range, 1-206). A multivariate analysis showed that low serum albumin (ALB) at diagnosis was an independent risk factor for gastric complications (odds ratio 10.75, p Conclusions: The present study showed that R-IPI was also predictive of survival in gastric DLBCL and low ALB at diagnosis as a significant risk factor for gastric complications following R-CHOP. In addition, our data suggested that PET-CT may be sufficient in the role of detecting gastric lesion of DLBCL because of high PPV and NPV. Disclosures No relevant conflicts of interest to declare.

Background: KRAS exon 2 mutation is a validated biomarker of anti-EGFR antibodies for metastatic colorectal cancer (mCRC) patients. Recently, several reports confirmed that other KRAS (exon 3 or 4) and NRAS mutations are associated with the resistance to anti-EGFR antibodies for mCRC, while impact of BRAF or PIK3CA mutation on efficacy of treatment is still controversial. Methods: We have conducted a prospective, observational study to evaluate the frequencies and clinicopathological features of KRAS, BRAF, NRAS and PIK3CA mutations. These mutations were evaluated by novel research kit to detect 36 mutations in a single reaction. Among patients treated with anti-EGFR antibodies, objective response and progression-free survival (PFS) were also evaluated according to gene status. Results: A total of 265 patients were analyzed until from January 2013 to December 2013. 138 (52.1%) had tumors with no mutation (all wild type), 89 (33.6%) had tumors with mutation in KRAS exon 2, 10 (3.8%) with either KRAS exon 3 or 4, 10 (3.8%) with either NRAS exon 2, 3 or 4, 12 (4.5%) with BRAF codon 600, and 17 (6.4%) with PIK3CA mutations. All mutations except for PIK3CA were mutually exclusive. Rectal primary tumor tended to be more frequently observed in minor RAS mutated tumors rather than RAS wild type (65 vs 46%). BRAF mutated tumors more likely to develop on the right-sided colon (58 vs 20%), and to have the poorly differentiated adenocarcinoma or mucinous histology (33 vs 11%), and peritoneal metastasis (42 vs 17%) in comparison with BRAF wild tumors. Among the 53 patients treated with anti-EGFR therapies, the response rates (15.9 vs 0%) and PFS (5.6 vs 2.3 months) were significantly better in patients with all wild tumors (N = 44) than patients with any of the mutation (N = 9). Conclusions: Minor RAS mutations or BRAF mutations have been observed in KRAS wild type tumor, which associated with some clinicopathological features and resistance to anti-EGFR therapy in our patient cohort.