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Preserving the colon while preventing colorectal cancer is challenging in patients with familial adenomatous polyposis. Although prophylactic colectomy is the current standard of care, some patients with familial adenomatous polyposis may wish to postpone colectomy as long as polyposis can be managed by endoscopic resection. This study examined our endoscopic management and prognostic results for patients with familial adenomatous polyposis who refused to undergo colectomy. We retrospectively analyzed the data of 12 patients with familial adenomatous polyposis treated at our hospital between January 1995 and December 2020. All patients opted to postpone prophylactic colectomy although they had significant polyp burdens and underwent endoscopic management, in which colorectal polyps sized 5 mm were thoroughly resected during baseline colonoscopies and subsequently, newly arising colorectal polyps sized 5 mm were periodically resected during surveillance colonoscopies. Patients (median age, 33 years) were followed up for a median of 5.2 years. The median number of colonoscopies and resected lesions per patient was 2 and 14 at baseline as well as, 9 and 32 during surveillance, respectively. The interval between colonoscopies was 1.0 and 7.0 months for baseline and surveillance, respectively. The colons of all 12 patients were preserved, and no invasive colorectal cancer developed. In 10 patients, 35 cases of high-grade dysplasia were observed and managed by endoscopic resection. Repeated endoscopic resection of colorectal polyps sized 5 mm with appropriate surveillance may be an alternative form of endoscopic management for patients with familial adenomatous polyposis wishing to postpone colectomy.

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 Salvage endoscopic resection is recommended when the local recurrence at primary site after chemoradiotherapy for esophageal squamous cell carcinoma is localized and superficial. This retrospective study aimed to comparatively analyse the short-term outcomes and local control of salvage endoscopic submucosal dissection versus salvage endoscopic mucosal resection for local recurrence after chemoradiotherapy or radiotherapy. Methods A total of 96 patients who underwent initial salvage endoscopic resection for cT1N0M0 local recurrence after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma between December 1998 and August 2019 patients were assigned to either the salvage endoscopic submucosal dissection (40 patients; 40 lesions) or salvage endoscopic mucosal resection (56 patients; 56 lesions) group. We evaluated the en bloc and R0 resection rates, severe adverse events and local failure rate after salvage endoscopic resection. Multivariate analysis was conducted to identify risk factors of local failure after salvage endoscopic resection. Results The en bloc resection rate was significantly higher in the salvage endoscopic submucosal dissection group than in the salvage endoscopic mucosal resection group (95% versus 63%; P Conclusions Salvage endoscopic submucosal dissection is the effective treatment for local recurrence based on the short-term outcomes and local efficacy.

Recently, the JCOG0502 has shown a comparable efficacy of chemoradiotherapy and esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma. However, few studies have compared the clinical outcomes of these treatments in esophageal squamous cell carcinoma patients (including elderly patients) based on real-world data.This retrospective study determined real-world outcomes in patients who underwent chemoradiotherapy or esophagectomy, including those with clinical T1N0M0 esophageal squamous cell carcinoma, between 2009 and 2017 at the National Cancer Center Hospital East.Among a total of 156 patients, 120 and 36 patients underwent esophagectomy and chemoradiotherapy, respectively; 138, 12 and 6 patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively; and 33 and 123 patients had clinical tumor depth MM-SM1 and SM2-SM3, respectively. In a median follow-up of 72 months, 5-year progression-free survival and overall survival were respectively 77.0% and 81.5% in the esophagectomy group and 74.4% and 82.6% in the chemoradiotherapy group (P = 0.48 and, P = 0.89). Moreover, no treatment-related death was detected in both groups. In elderly patients (75 years or older), 5-year progression-free survival and overall survival were not significantly different between esophagectomy and chemoradiotherapy groups (5-year progression-free survival: 72.3% vs. 81.8%, P = 0.38; 5-year overall survival: 76.9% vs. 81.8%, P = 0.59).This real-world study confirms the results of a previous clinical trial, and the present findings support chemoradiotherapy as one of the standard treatment options in patients of all ages with clinical T1N0M0 esophageal squamous cell carcinoma.

Objectives Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. Methods Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. Results A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of Conclusions This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.

There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607).The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with 2 cm in size, or UL-positive with ≤ 3 cm; (4) age 20-75 years. The difficult case was defined as ESD taking ≥ 120 min, piecemeal resection, and/or developing perforation during procedure.Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14-462) min, and it was ≥ 120 min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120 min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with 5 cm (vs. UL-negative with ≤ 3 cm, odds ratio, 24.993; 95% CI 6.130-101.897, p 0.0001) had the largest odds ratio and followed by UL-negative with 3-5 cm upper or middle portion of stomach and age ≤ 60 years were significantly associated with difficulty.UL-negative lesion with 3 cm, upper or middle portion of stomach and age ≤ 60 years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

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.

A randomized phase III trial was initiated in Japan in August 2019 to confirm the superiority of preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy compared to the standard treatment, i.e. surgery plus adjuvant chemotherapy, for locally recurrent rectal cancer in local relapse-free survival. In all, 110 patients from 43 Japanese institutions will be recruited over a period of 6 years. Eligible patients would be registered and randomly assigned to each group with an allocation ratio of 1:1. The primary endpoint is local relapse-free survival. The secondary endpoints are overall survival, relapse-free survival, proportion of local relapse, proportion of distant relapse, proportion of patients with pathological R0 resection, response rate of preoperative chemoradiotherapy (preoperative chemoradiotherapy arm), pathological complete response rate (preoperative chemoradiotherapy arm), proportion of patients who completed the protocol treatment, incidence of adverse events (adverse reactions) and quality of life after surgery. This trial has been registered at the Japan Registry of Clinical Trial: jRCTs031190076 [https://jrct.niph.go.jp/latest-detail/jRCTs031190076] and ClinicalTrials.gov: NCT04288999 [https://clinicaltrials.gov/ct2/show/NCT04288999].

A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with >90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].

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.

TPS257 Background:Parallel-group controlled trial of esophagectomy versus chemoradiotherapy (JCOG0502) showed chemoradiotherapy (CRT) is considered as a standard treatment option for clinical-T1bN0M0 esophageal squamous cell carcinoma (ESCC) with organ preservation. However, locoregional recurrence after CRT occurs in 20% of patients and requires salvage treatment including salvage surgery, chemo(radio)therapy, and endoscopic resection. Salvage treatments can cause complications and treatment-related death. CRT with elective nodal irradiation (ENI) have been reported to reduce the locoregional recurrence of esophageal cancer. We conduct the clinical trial to evaluate the efficacy of modified CRT with ENI compared with CRT without ENI for the patients with cTbN0M0 ESCC. The primary purpose of this study is to investigate whether modified CRT with ENI reduces the locoregional recurrence that cannot be completely resected by salvage endoscopic resection and preserve esophagus without compromising overall survival. Methods:Eligibility criteria include the followings; thoracic ESCC, adenosquamous, or basaloid cell carcinoma with clinical-T1bN0M0, age 20 or older, performance status 0 or 1, adequate organ function, and patient who do not have a preference to receive a surgical resection as an initial therapy. Patients are randomly assigned to following two arms using the minimization method with a random component to balance institution, tumor length (≤4cm versus > 4cm), and age (≤65 years old versus > 65 years old). Patients in arm A receive CRT consisted of CDDP (70 mg/m2/day, days 1 and 29) and 5-FU (700 mg/m2/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (60 Gy/30 fr without ENI). Patients in arm B receive CRT consisted of CDDP (75 mg/m2/day, days 1 and 29) and 5-FU (1000 mg/m2/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (50.4 Gy/ 28 fr with ENI of 41.4 Gy/23 fr). Primary endpoint is major progression-free survival (MPFS), defined as the time from randomization to the date of death or disease progression except achieving curative resection by salvage endoscopic resection. We assumed 5-year MPFS with arm A to be 70% and expected a 10% improvement for arm B. The planned sample size was calculated as a total of 280 patients (140 patients per arm) with a one-sided alpha of 5%, power of 70%, an accrual period of 4 years, and a follow-up period of 5 years. This trial was activated in July 2020. The study was also registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCTs031200067. Clinical trial information: jRCTs031200067.

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 .

TPS457 Background: Near Infrared Photoimmunotherapy (NIR-PIT) is a newly developed, molecular targeted cancer therapy based on conjugating a near infrared silica-phthalocyanine dye to a monoclonal antibody, which result in necrotic cell death of targeted cancer cell immediately after exposure to near infrared light. Phase IIa trial of NIR-PIT with RM-1929 (anti-EGFR antibody cetuximab conjugated to IRDye 700DX) showed a 43% objective response rate (ORR) for recurrent head and neck squamous cell carcinoma (Cognetti DM, et al.ASCO 2019 abstr 6014). Meanwhile, PD-1 blockade reverses adaptive immune resistance, resulting in activation of tumor infiltrating lymphocyte after NIR-PIT in syngeneic mouse models (Nagaya T, et al. Cancer immunology research. 2019). The objective of this study is to investigate the safety and efficacy of the NIR-PIT using ASP-1929 (analogous to RM-1929) in combination with nivolumab for advanced gastric or esophageal cancer. Methods: The study is an open-label, single-arm, single-center, Phase Ib clinical trial. Eligible patients are with unresectable esophagogastric squamous cell carcinoma or EGFR positive adenocarcinoma after standard chemotherapy. Dose escalation cohort is designed to determine the recommended dose of laser irradiation energy density in a “3+3” design (50, 75, and 100 J/cm2). Nivolumab of 240 mg on Day 1 and ASP-1929 of 640 mg/m2 on Day 8 is administered, and laser irradiation is performed under endoscopy using the laser PIT unit on Day 9. In expansion cohort, approximately 20 patients will be enrolled. The primary endpoint is proportion of incidence of dose-limiting toxicity, and the secondary endpoints are proportion of incidence of adverse events, ORR, local complete response rate, progression-free survival (PFS), local PFS, overall survival, and proportion of incidence of device malfunction. We also investigate several biomarkers using pre- and post-treatment biopsied samples. First patient will be enrolled in December 2019. Clinical trial information: JapicCTI-194969.

TPS263 Background: Local recurrence is one of the most common forms of recurrence after curative resection for primary rectal cancer. Surgical resection is recommended for locally recurrent rectal cancer (LRRC) to achieve radical cure if the tumor is judged as resectable with negative margins. However, a high local re-recurrent risk after surgery is a major problem due to the difficulty of re-resection and the serious symptoms, such as pain or fistula, resulting from re-recurrence. Preoperative chemoradiotherapy (preCRT) is expected to improve local control after radical surgery for radiation naïve LRRC; however, high frequency of surgical complications after preCRT cannot be ignored. Due to the refractory nature and rarity of LRRC, the true impact of preCRT on oncological and surgical outcomes has not been clarified by clinical trials. The purpose of this study is to confirm the superiority of preCRT followed by surgery plus adjuvant chemotherapy over surgery plus adjuvant chemotherapy alone, in terms of local relapse-free survival for resectable LRRC. Methods: Eligibility criteria include resectable LRRC without distant metastasis, no prior pelvic irradiation, no prior surgery for LRRC, aged 20-80 years, and sufficient organ function. Eligible patients are randomized into the surgery and adjuvant chemotherapy (arm A) or preCRT followed by surgery and adjuvant chemotherapy (arm B). PreCRT consists of the standard dose of capecitabine and radiotherapy (50.4Gy). Adjuvant chemotherapy consists of mFOLFOX6, CAPOX, capecitabine, or 5FU+l-LV. The primary endpoint is local relapse-free survival (LRFS), and the secondary endpoints include overall survival, relapse-free survival, %R0 resection, incidence of adverse events, and quality of life after surgery. The 3-year LRFS of arm A is assumed to be 60% with a 13% increase expected in arm B. The sample size was calculated as 106 (53 per arm) with a one-sided alpha of 10%, power of 70%, and accrual period of 6 years. This trial was initiated on 19 August 2019. Clinical trial information: jRCTs031190076.

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.

301 Background: S-1 is an oral agent consisting of a mixture of tegafur which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyrimidine (DHP) and potassium oxonate. Serum concentration of 5-FU increases in case of renal dysfunction due to decrease of DHP excretion into urine. The aim of this study was to evaluate the influence of renal function to the efficacy and safety of S-1 with concurrent radiotherapy (RT) for locally advanced pancreatic cancer (LAPC). Methods: This study was an integrated exploratory analysis of JCOG1106 and LAPC- S1RT, in which pts with LAPC received RT (50.4Gy/28 fr over 5.5 weeks) and concurrent S-1 (40 mg/m2/dose, bid. on the day of irradiation). Eligibility criteria for this study were pts who received both irradiation and S-1 at least once without induction chemotherapy, and who had creatinine clearance (CCr) ≥ 50 ml/min at the time of registration. We assigned pts into high (≥ 80 ml/min) and low (< 80 ml/min) CCr groups. The primary endpoint was the incidence of ≥ Grade 3 adverse reactions (ARs). Secondary endpoints were the incidence of ≥ Grade 2 gastrointestinal ARs (GI-ARs) defined as anorexia, nausea, vomiting, diarrhea and mucositis oral, relative dose intensity of S-1, CA19-9 response, progression-free survival, and overall survival. Results: Fifty and 59 pts were included in this study from JCOG1106 and LAPC-S1RT, respectively. Median age was 65 years old (range: 31–80), and 57 pts were male. Median CCr was 80.4 ml/min. High CCr group included 57 pts and the median was 97.5 ml/min (range 80.0–194.6), and low CCr group included 52 pts and the median was 64.4 ml/min (range 50.0–78.3). Low CCr group tended to have more ≥ Grade 3 ARs and ≥ Grade 2 GI-ARs compared to high CCr group (30.8% vs. 15.8% and 51.9% vs. 36.8%). However, no evident tendencies were observed in other secondary endpoints. Multivariable analysis showed risk ratio of low CCr group for ≥ G3 ARs was 1.493 [95% CI: 0.710–3.145], although risk ratio of females was 2.486 [95% CI: 1.043–5.924]. Conclusions: Our study indicated that renal dysfunction may increase adverse reactions in the treatment of S-1 with concurrent RT for LAPC, and we should pay attention to renal function and consider for dose reduction.

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.

Background The incidence rate has been increasing for superficial head and neck squamous cell carcinoma (HNSCC) discovered through surveillance endoscopic study using narrow band imaging (NBI), a procedure mainly used for high-risk patients with esophageal squamous cell carcinoma (ESCC). However, there are few reports on the natural history of superficial HNSCC. The aim of this retrospective study was to investigate the natural history of superficial HNSCC. Methods From January 2007 to December 2012, 535 consecutive histologically confirmed superficial HNSCCs at the oropharynx, hypopharynx, or larynx in 319 patients were detected by endoscopic surveillance examination by using NBI. Of those, 20 untreated and observed lesions fulfilled the eligibility criteria and were analyzed in this study. Results Twenty lesions from 17 patients were analyzed. All patients were men ranging from 52 to 86 years of age, with a median age of 69 years. The median endoscopic follow-up period was 20 months (range, 6–71); 17 lesions progressed in size. In this study, four patients died; the causes of death were synchronous ESCC, synchronous HNSCC, acute myocardial infarction, and unknown causes. No patient died from progression of superficial HNSCC. Conclusions Most superficial HNSCC has the potential to change progressively. Therefore, superficial HNSCC should be detected at an early stage and be treated less invasively, such as with endoscopic resection or partial resection.