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252 Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is platinum-based definitive chemoradiotherapy (dCRT). Previous clinical trials have indicated a clinical complete response (cCR) rate of 11%-25% and median overall survival (OS) of 9-10 months. The cCR rate is strongly correlated with good prognosis, however the predictive factors have not been elucidated. Methods: In this multi-institutional retrospective study, we evaluated the efficacy and safety of dCRT in patients with unresectable locally advanced ESCC. “Unresectable” was defined as the primary lesion (T4b) invading adjacent structures such as the aorta, vertebral body, and trachea, or the regional and/or supraclavicular lymph nodes (LNT4b) invading unresectable adjacent structures. cCR was determined by both computed tomography and endoscopy based on the Response Evaluation Criteria in Solid Tumors (version 1.1) with modifications and Japanese Classification of Esophageal Cancer (11th edition), respectively. Results: A total of 175 patients who started dCRT between January 2013 to March 2020, were included in this study. The overall median age was 68 (31-86). A total of 95 (54%) patients had a performance status of 0. Of these, 124 (71%) patients had T4b and 81 (46%) had LNT4b. The clinically involved site were as follows: thoracic aorta (22%), tracheobronchial tree (73%), and others (14%). The median tumor length was 6 (2-22) cm. 56 (32%) patients were tube-fed owing to obstructive tumors. 165 (96%) patients completed at least one cycle of chemotherapy with 60 Gy of radiation. Further, 84 (48%) patients received consolidation chemotherapy following dCRT. The confirmed cCR rate was 24% (42/175). At a median follow-up interval of 20 months, the 2-year OS and progression-free survival (PFS) rates of cCR cases vs. non-cCR cases were 90% vs. 31% (log-rank p < 0.001) and 59% vs. 2% (log-rank p < 0.001), respectively. Multivariate analysis of the clinicopathological factors contributing to cCR revealed that a tumor length of≥6 cm (OR, 0.4; 95% CI, 0.2–0.9 p = 0.03) was the only a significant predictive factor. The primary adverse events of grade 3 or above were esophagitis (32%), pneumonitis (13%), fistula formation (10%), febrile neutropenia (9%), and dyspnea (6%). Among 22 patients who originally presented with fistula formation, fistula disappeared in 14 (64%), including 3 cCR cases. Two (1%) sudden deaths secondary to severe hemorrhage and suspected aortic fistula were observed during the treatment period. Conclusions: dCRT is feasible for patients with unresectable locally advanced ESCC. The cCR rate of dCRT is consistent with that reported in previous clinical trials, and favorable OS and PFS rates were observed in patients with cCR. Tumor length was observed to be a significant predictive factor of cCR. Research Sponsor: None.

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.

4545 Background: Definitive chemoradiotherapy (dCRT) consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP) with 60 Gy radiotherapy (RT) for clinical (c) Stage II/III esophageal carcinoma (EC) is a standard treatment for patients (pts) refusing surgery (S) in Japan based on the previous trial (JCOG9906). However, poor survival, high incidence of late toxicities, and severe complications of salvage S are problems. We conducted a single-arm confirmatory study of CRT modifications including salvage treatment (ST) to reduce CRT toxicities and facilitate ST to improve survival. We reported the 3-year survival at 2018 ASCO Annual Meeting. We report the final data after 5-year follow-up. Methods: EC pts with cStage II/III (UICC 6th, non-T4), PS 0-1, and age 20-75 years were eligible. Chemotherapy (CT) was CDDP (75 mg/m2 on days 1, 29) and 5-FU (1000 mg/m2/d on days 1-4, 29-32). RT was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Good responders after dCRT received additional 1-2 cycles of CT. For residual or recurrent disease, salvage endoscopic resection (ER) or S was performed based on the prespecified criteria. Planned sample size was 95, with one-sided alpha of 5% and power of 80%, expected and threshold 3-year overall survival (OS) as 55% and 42%. Key secondary endpoint was ST related toxicity. Final analysis was planned after 5-year follow-up for all pts. Results: From 4/2010 to 8/2014, 96 pts were enrolled, two were ineligible and 94 were included in efficacy analysis (cStage IIA/IIB/III, 22/38/34). Complete response was achieved in 55 pts (59%). Salvage ER and S were performed in 5 (5%) and 27 pts (29%). R0 resection of salvage S was achieved in 23 (85%). With a median follow-up of 5.95 years, 3- and 5-year OS was 74.2% (90% CI 65.9-80.8%) and 64.5% (95% CI 53.9-73.3%). 5-year progression-free survival and esophagectomy-free survival were 48.3% (95% CI 37.9-58.0%) and 54.9% (95% CI 44.3-64.4%). 5-year OS after salvage S was 31.0% and hazard ratio of R1-2 to R0 was 5.635 (95% CI: 1.818-17.467). No complications occurred after salvage ER. Five pts (19%) showed ≥ grade 3 operative complications and 1 treatment related death due to bronchus-pulmonary artery fistula occurred after salvage S. Only 9 pts (9.6%) showed grade 3 late toxicities. And no late operative complications more than grade 3 were observed. Conclusions: This combined modality treatment of dCRT with ST showed acceptable toxicities, favorable 5-year survival, and promising esophageal preservation. Clinical trial information: jRCTs031180110 .

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.

104 Background: JCOG0909, a single-arm confirmatory trial of definitive chemoradiotherapy (dCRT) including salvage treatment, demonstrated promising efficacy and safety for cStage II/III (UICC-TNM 6th) esophageal cancer (EC) (Ito Y, ASCO 2018). Radiation (RT) fields included the elective regional lymph node during initial 41.4 Gy, such as bilateral supraclavicular fossae and superior mediastinal lymph nodes for upper thoracic (Ut), and mediastinal and perigastric lymph nodes for middle thoracic (Mt)/lower thoracic (Lt) EC. It is unclear whether the safety and efficacy are associated with the tumor location in patients with cStage II/III EC treated with dCRT. Methods: Patients who were enrolled in JCOG0909 and underwent dCRT were analyzed. Patients were categorized into three groups according to primary tumor location (Ut/Mt/Lt). We compared adverse events during dCRT, complete response (CR) rate, progression-free survival (PFS) and overall survival (OS) among groups. Results: Ninety-four patients (Ut/Mt/Lt: 16/59/19) were analyzed. The proportions of cStage IIA/IIB/III were 31%/44%/25% in Ut group, 20%/42%/37% in Mt group, and 21%/32%/47% in Lt group, respectively. The summary of safety and efficacy was listed in Table 1. Grade 3-4 leukopenia, neutropenia and thrombocytopenia were more frequently observed in Mt and Lt groups than in Ut group. CR rate was 63% in Ut, 63% in Mt, and 42% in Lt, respectively. 3-year PFS in Ut/Mt/Lt was 60%/59%/47% and 3-year OS was 73%/78%/58%, respectively. Conclusions: The RT field by the tumor location might be associated with efficacy and safety of dCRT for cStage II/III esophageal cancer. [Table: see text]

4023Background: For clinical stage I submucosal (cT1b-SM) ESCC, surgery is the standard treatment and CRT is optional. We conducted a single-arm confirmatory study of diagnostic ER plus selective C...

Purpose Most of the esophageal squamous cell carcinomas (ESCCs) and cancers of the head and neck (H&N) region are diagnosed at later stages. To achieve better survival, early detection is necessary. We compared the real-time diagnostic yield of superficial cancer in these regions between conventional white light imaging (WLI) and narrow band imaging (NBI) in high-risk patients. Patients and Methods In a multicenter, prospective, randomized controlled trial, 320 patients with ESCC were randomly assigned to primary WLI followed by NBI (n = 162) or primary NBI followed by WLI (n = 158) in a back-to-back fashion. The primary aim was to compare the real-time detection rates of superficial cancer in the H&N region and the esophagus between WLI and NBI. The secondary aim was to evaluate the diagnostic accuracy of these techniques. Results NBI detected superficial cancer more frequently than did WLI in both the H&N region and the esophagus (100% v 8%, P < .001; 97% v 55%, P < .001, respectively). The sensitivity of NBI for diagnosis of superficial cancer was 100% and 97.2% in the H&N region and the esophagus, respectively. The accuracy of NBI for diagnosis of superficial cancer was 86.7% and 88.9% in these regions, respectively. The sensitivity and accuracy were significantly higher using NBI than WLI in both regions (P < .001 and P = .02 for the H&N region; P < .001 for both measures for the esophagus, respectively). Conclusion NBI could be the standard examination for the early detection of superficial cancer in the H&N region and the esophagus.

4013Background: For clinical(c) stage I submucosal (T1b) thoracic ESCC, surgery with lymph node dissection is the standard treatment. However, pathologic diagnosis after resection sometimes reveals...

207 Background: Local failure is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC), and salvage surgery presents high morbidity and mortality rates. We have introduced photodynamic therapy (PDT) and endoscopic resection (ER) for local failures to develop a less invasive salvage treatment.The aim of this retrospective study was to clarify the long-term outcome of salvage endoscopic treatments (SET). Methods: Between 1998 and 2008, 716 patients with ESCC were treated with definitive CRT in our institution. There were 314 patients with incomplete response and 103 with local recurrence after achieving complete response (CR) once. The indication criteria of SET were as follows: 1) absence of lymph node and distant metastasis and 2) local failures limited within T2. ER was performed for local failures limited to T1b (SM1), and PDT was performed for lesions invading T1b (SM2) or T2, in patients who could not tolerate or who refused surgery. We assessed overall survival (OS), relapse-free survival (RFS), and also prognostic factors. This study was approved by an institutional review board. Results: A total of 164 patients with local failure underwent SET (ER: 58, PDT: 106). The characteristics before CRT were as follows: T1/2/3/4, 44/25/75/20; N0/1, 85/79; stage I/II/III/IV, 35/59/57/13; and those of before SET were as follows: T1/2, 126/38; residue/recurrence, 76/88. ER achieved curative resection in 51 (87.9%), and PDT achieved CR in 61 (57.5%) patients. With a median follow up period of 73 months, the OS and RFS rates at 5 years from SET were 38.6% (95% CI 31.0–46.2) and 28.1% (95% CI 21.0–35.2). Multivariate analysis revealed 2 preferable prognostic factors in common for OS and RFS, N0 before CRT (OS HR: 0.47 [95% CI 0.32–0.69], RFS HR: 0.61 [95%CI 0.43–0.87]) and a period from initiation of CRT to SET longer than 6 months (OS HR: 0.57 [95%CI 0.39–0.84], RFS HR: 0.67 [0.47–0.95]). After 5 years of follow up, 58 patients (35.4%) were alive without any metastasis under esophagus preservation. Conclusions: SET demonstrated a favorable outcome in an analysis of a large number of patients with local failure after definitive CRT for ESCC.

123 Background: We recently reported that porfimer sodium (Photofrin)-based PDT was a less invasive, curative treatment option for carefully selected patients with locally residual EC after CRT (Endoscopy 2011:43:657-63). However, porfimer sodium-based PDT has some problems (long light shielding and skin phototoxicities). Conversely, talaporfin sodium (Laserphyrin)-based PDT using a diode laser system can overcome these problems. Therefore, we conducted a phase I study to establish the recommended dose of laser irradiation and to evaluate safety of talaporfin sodium-based PDT as a salvage treatment after CRT. (UMIN000003970). Methods: We recruited patients with residual or recurrent EC at primary site and who were treated with more than 50 Gy of (chemo)radiotherapy. To determine the dose limiting toxicity (DLT) according to the energy of the diode laser, dose escalation was set at three energy levels (50,75 and 100J/cm2). The DLT was defined as follows; 1) severe pain, 2) ≥ grade 2 CTC-AE fever, 3) esophageal fistulae or stenosis, 4) ≥ grade 3 CTC-AE hemorrhage, and 5) ≥ grade 4 CTC-AE non-hematologic toxicity. Results: Between Oct. 2010 and May 2011, a total of 9 patients (9 men, median age of 72 y-o) were recruited and were treated using up to the third energy level in groups of three individuals. The initial T stage was T1/T2/T3(4/2/3) and recurrent T stage was T1/T2(6/3). None of the patients experienced DLT at all energy levels. A complete response was achieved in 5 of 9 patients (56%). Conclusions: Based on the results of our phase I study, we concluded that irradiation at 100J/cm2 appeared to be a recommended dose for talaporfin sodium-based PDT as a salvage treatment for locally residual esophageal carcinoma after CRT. We are currently running a phase II part of the study to investigate efficacy of salvage talaporfin sodium-based PDT.

4048 Background: Definitive CRT is one of the most common treatment modality for esophageal carcinoma (EC). However, there is only limited data about CRT applied for elderly pts. The aim of this retrospective study was to clarify the feasibility and efficacy of definitive CRT for elderly pts. Methods: Subjects of this study were newly diagnosed thoracic EC between Aug ’92 and Dec ’02, and fulfilled the following criteria; PS ≤ 2, no prior therapy, histologically confirmed SCC, no distant metastatis (M1b) and no serious complication. This analysis compared the efficacy, toxicities and outcome between pts aged ≥ 71 years with those < 70 years. Pts were treated with 5-FU+CDDP+radiotherapy 60Gy (JCO 17, ’99). Results: There were 331 pts who met the recruitment criteria, 58 for ≥ 71 years and 273 for < 70 years. Their characteristics were (≥ 71 vs < 70): male/female: 50/8 vs 232/41, median age (range): 75(71–79) vs 61(39–70), PS 0/1/2: 25/23/0 vs 219/50/4, clinical stage (CS) I/II/III(non T4)/T4 and/or IVA: 8/...