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Aim: CIL has been reported to be predictive of better survival in some studies with various malignant tumors especially in metastatic setting. However, the relationship between CIL and survival in pre-Cx for the patients (pts) with ESCC has not been well discussed. We analyzed the association of CIL with overall survival (OS) using the data of JCOG9907 in which pre-Cx showed survival advantage over postoperative chemotherapy in stage II/III ESCC. Methods: Pre-Cx consisted of two courses of 5-FU (800mg/m2 day1-5) and cisplatin (80mg/m2 day1) repeated every 3 weeks. Among the pts assigned to pre-Cx arm in JCOG9907, we analyzed the pts who underwent surgery and also whose leucocytes were measured as scheduled. They were divided into two groups: group A, those who experienced Gr. 2-4 leucopenia at least once during pre-Cx; group B, those with Gr.0-1. The association of CIL with OS, progression-free survival (PFS) was analyzed with multivariate analyses using Cox proportional hazard model. Results: A total of 152 out of 164 pts who assigned to pre-Cx arm were included in this analysis, where 52 pts were classified into group A and 100 pts to group B. There were no remarkable differences between group A and B in their background except for age and sex. 3-year OS for group A were inferior to group B (48.1% vs 73.9%; hazard ratio (HR) = 1.94, p = 0.0074). As for 3-year PFS, similar tendency was observed (44.2% vs 55.8%; HR = 1.38, p = 0.16). There was no difference of frequency of postoperative infectious complications between the two groups. As is shown in the table, multivariate analysis identified CIL had inferior tendency to survival (HR = 1.54, p = 0.10). Multivariate analysis of OS Factors category HR 95% CI p-value Leucocyte Gr. 2-4 (vs. 0-1) 1.54 0.93-2.55 0.10 CT T3 (vs. T1-2) 2.70 1.26-5.78 0.010 Albumin >4.0 g/dL (vs. 0.44 0.26-0.73 0.0016 Dose of chemotherapy Actual /planned dose >90% (vs. 0.52 0.29-0.94 0.030 Pathological response Gr. 2-3 (vs. 0-1) 0.37 0.15-0.94 0.037 Conclusions: CIL was reported to be a positive prognostic factor, but was shown to be a negative prognostic factor in this study. The meaning of CIL should be discussed further. Disclosure: All authors have declared no conflicts of interest.

Background Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment of stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of two courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes (LNs) and regional LNs. Esophagectomy with extensive lymphadenectomy (≥D2) was carried out 42–56 days after NeoCRT. The primary end point was the completion rate of NeoCRT and R0 resection. Results Thirty-three patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. The completion rate of protocol treatment was 93.5% (29/31). During CRT, the most common grade 3 or 4 toxic effects were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), hyponatremia (16%). One treatment-related death was observed. The incidence of operative morbidity was similar to that in previous studies but incidence of anastomotic leakage was observed more frequently (27%). According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 42% (13/31). Conclusions NeoCRT was tolerable and active. The randomized, controlled trial compared with neoadjuvant chemotherapy is needed and we plan it.

Background Preoperative chemoradiotherapy (PCRT) was one of the standard care for resectable esophageal cancer. Because there is tendency of high morbidity at surgery after PCRT, risk benefit balance for PCRT should be considered.Predictive marker which can select the patients who have more benefit for PCRT is needed. Methods To identify a biomarker to predict efficacy of preoperative PCRT for esophageal cancer, expression profiles of serum proteins were determined. The expression levels of 84 serum proteins in 37 patients (7 responders to PCRT and 30 poor-responders) weremeasured. Responders were defined as the patients whom two third or more cancer was pathologically degenerated at the time of operation. The usefulness of biomarkers was validated with two independent retrospective cohorts (PCRT and preoperative chemotherapy (PCT) by cisplatin and 5-FU) and two phase II clinical cohorts (PCRT and PCT with docetaxel, cisplatin and 5-FU) (n = 187). Results In a discovery cohort, the expression levels of six proteins [macrophage inflammatory protein beta 1 (MIP1B), soluble interleukin 6 receptor (sIL6R), macrophage inflammatory protein alpha1 (MIP1A), insulin, interferon alpha 2 (IFNA2) and matrix metalloproteinase 3 (MMP3)] were significantly different between responders and poor-responders to PCRT. The most predictive factor for survival was soluble interleukin 6 receptor (sIL6R) (p = 0.008, log-rank test); sIL6R in poor-responders was higher than in responders (p = 0.005, Student's t-test). The increases of sIL6R in poor-responder who underwent PCRT were confirmed in a etrospective cohort (n = 38), and a phase II clinical trial (n = 26). However, sIL6R levels of patients who underwent PCT only in a retrospective cohort (cisplatin and 5FU n = 100) and a phase II clinical trial (docetaxel, cisplatin and 5FU, n = 23) were not significantly different. Conclusion Serum sIL6R have a potential to be a predictive biomarker for PCRT in esophageal cancer patients, not for preoperative chemotherapy. Disclosure All authors have declared no conflicts of interest.