Motoo Nomura

Comparison between surgery and definitive chemoradiotherapy for patients with resectable esophageal squamous cell carcinoma: a propensity score analysis

PurposeOur intent was to compare survival following neoadjuvant chemotherapy followed by surgery versus chemoradiotherapy (CRT) among patients with potentially resectable esophageal squamous cell carcinoma.MethodsInformation about 406 consecutive esophageal cancer patients with resectable disease who underwent surgery with neoadjuvant chemotherapy consisting of cisplatin plus 5-fluorouracil or who underwent definitive CRT was reviewed. The survival outcomes were analyzed using the Kaplan–Meier method and propensity score-adjusted Cox proportional hazards models. Relevant variables were included in the propensity score model.ResultsOverall, 206 patients planned to undergo surgery (S group) and 200 patients planned to undergo CRT (CRT group). In the unadjusted situation, progression-free survival and overall survival did not differ statistically between the groups. After matching, both survival outcomes were better in the S group compared to the CRT group. Subanalysis showed both survival outcomes were better in the S group for patients with only stage III disease. However, survival outcomes for stages I, II, and IV were not significantly different between treatment groups.ConclusionsAmong patients with resectable disease, survival outcomes in the S group were favored over those of the CRT group. These results indicate that different therapeutic strategies should be used for stage III esophageal cancer than for other stages.

Comparison between neoadjuvant chemotherapy followed by surgery and definitive chemoradiotherapy for overall survival in patients with clinical Stage II/III esophageal squamous cell carcinoma (JCOG1406-A)

Background Neoadjuvant chemotherapy followed by surgery (NAC-S) represents the standard treatment for patients with Stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. Chemoradiotherapy (CRT) is performed in patients who refuse or have contraindications to surgery. However, randomized clinical trials that compare NAC-S with CRT have not been conducted. The aim of this study was to explore subgroups of patients undergoing CRT to identify those with survival outcomes potentially equivalent to NAC-S. Methods Pooled data from two clinical trials in patients with Stage II/III ESCC, the JCOG9907 trial and the JCOG9906 trial were used. JCOG9907 demonstrated that NAC-S resulted in superior overall survival (OS) compared with surgery followed by adjuvant chemotherapy. JCOG9906 was a single-arm trial that explored the efficacy and safety of CRT. The eligibility criteria in the two trials were almost identical. Subgroup analyses of clinical data (serum albumin, cT, cN, cstage and tumor location) were conducted with Cox proportional hazards regression models for patients assigned to receive NAC-S in JCOG9907 and patients in JCOG9906. Results The analysis comprised 163 patients from JCOG9907 in NAC-S arm (NAC-S group) and 73 patients from JCOG9906 who received CRT (CRT group). Baseline characteristics were similar between the two groups. OS was better in the NAC-S group than the CRT group (adjusted hazard ratio 1.72; 95% confidence interval 1.19-2.50). All subgroups in the NAC-S group had longer OS compared with those in the CRT group. Conclusions OS was superior after NAC-S rather than CRT. None of the CRT subgroups had similar OS to the NAC-S groups.

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

Dear Editor, Effective immune checkpoint blockades have improved the overall survival of patients with metastatic melanoma. The monoclonal antibody nivolumab blocks programmed death-1 (PD-1), an inhibitory immune checkpoint receptor expressed on activated T cells. The conventional dermoscopic analysis of tumor lesions, which is based on the recognition of specific criteria, is available as a non-invasive diagnostic technique for melanoma. Although various dermoscopic patterns of melanoma have been reported, the dermoscopic patterns of residual melanoma after treatment with nivolumab have not yet been described. A 66-year-old Japanese woman was referred to our hospital for treatment of malignant melanoma on her left chest and metastases in the small intestine (Fig. 1a). Dermoscopic analysis of the skin lesion showed a blue-whitish veil, irregular streaks, scar-like depigmentation and an atypical pigment network (Fig. 1b). Histological analysis of the skin biopsy revealed a nest of neoplastic cells with melanin in the basal layer (Fig. 1c). Extensive regression was visible in the middle of the lesion (Fig. 1a). Positron emission computerized tomography (PET/CT) conducted at a previous hospital showed metastases in the pelvic peritoneum, abdominal lymph nodes, left axillary lymph nodes, left cervical lymph nodes and left erector muscle of the spine. We commenced treatment with nivolumab (2 mg/ kg) every 3 weeks. After two courses of nivolumab, the tumor in the small intestine, the only measurable lesion, had reduced in size by more than 30% compared with baseline. After eight courses of nivolumab, we found that the macule on her left chest had grown pale and a depigmented spot appeared. (Fig. 1d) Dermoscopic analysis showed sporadic and closely spaced peppering inside the depigmented area (Fig. 1e). To

Readministration of Nivolumab after Persistent Immune-related Colitis in a Patient with Recurrent Melanoma

Nivolumab shows promising efficacy against metastatic melanoma. However, immune-related adverse events are of great concern. We herein report a case of persistent colitis that developed during nivolumab monotherapy and nivolumab readministration. An 82-year-old Japanese woman with recurrent melanoma developed Grade 3 colitis after 6 cycles of nivolumab. She was treated with corticosteroid for 28 days. Follow-up by computed tomography and colonoscopy after corticosteroid treatment revealed persistent pancolitis. Her symptoms ameliorated spontaneously in two months. Given the amelioration, nivolumab was restarted and resulted in the maintenance of stable disease for 21 months without recurrence of colitis. Even in cases of persistent colitis over several months, nivolumab readministration should be considered.

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab

BackgroundThe objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab.Patients and methodsA retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields. The target lesions ratio (the sum of the diameters of the target lesions inside the irradiated fields/all target lesions) was also assessed.ResultsAmong the patients, seven received ipilimumab and radiotherapy (Ipi-RT), six received nivolumab and radiotherapy (Nivo-RT), and three sequentially received Ipi-RT and Nivo-RT. The overall response rate (all patients regardless of inside or outside radiation fields) was 30%. The response rate inside the radiation fields was 68.8% for all patients combined. The response rates of Ipi-RT and Nivo-RT inside the radiation fields were 37.5 and 100% (P = 0.03), respectively. Grade 3 adverse events were observed in three patients treated with Ipi-RT. The target lesions ratio was a predictive marker of disease control rate among patients treated with Nivo-RT.ConclusionsThis study showed that concurrent immunoradiotherapy is an option for patients with metastatic melanoma after progression on nivolumab.

The Neuropathology of Drug Addictions and Substance Misuse: Assays for Fentanyl

Abstract Based on the evaluation of drug monitoring, various assays have always been discussed to perform the screening methods of central nervous system agents in biological samples. However, until now, the drug monitoring of central nervous system agents would be minor concepts compared to the medical strategies of conventional therapeutic drug monitoring (TDM) such as antibiotic, anticancer pharmaceuticals, cardiac antiarrhythmic drugs, and other related peripheral systems. Today, analytical advancements for narcotic analgesic agents are a major topic in modern neuropathology of drug addictions and substance misuse, as demonstrated by the growing advances in the various fields that have been defined as a discipline based on the forensic pathology and TDM study domains through applied analytical chemistry. In this chapter, this basic picture of fentanyl is described, which includes the historic background and application based on previous reports.

633PCOMPARISON OF SURGERY WITH DEFINITIVE CHEMORADIOTHERAPY FOR POTENTIALLY RESECTABLE ESOPHAGEAL CANCER: A PROPENSITY-SCORE ANALYSIS

ABSTRACT Aim: To compare the survival by surgery (S group) to that by definitive chemoradiotherapy (CRT: R group) among patients with potentially resectable esophageal squamous cell carcinoma. Methods: From January 2003 to June 2012, 564 consecutive patients were reviewed. Overall survival (OS) was analyzed using Kaplan-Meier method and propensity-score adjusted Cox proportional hazard models. The variables included in propensity score model were age, gender, performance status (PS), histologic grade, primary cancer site, cT, cN, cM, serum albumin, and year of treatment (3 groups). Results: Three hundreds forty-two patients was in S group and 222 patients was in R group. Of the S group, 243 had preoperative chemotherapy, 37 had postoperative chemotherapy, and 62 had no adjuvant therapy. All values in patient characteristics were significantly different between S and R groups except for gender (age ≥ 65 years, 42% vs. 58%; gender male, 85% vs. 88%; Cancer site Ut/Mt/Lt, 14/49/37% vs. 14/60/27%; PS 0/1, 28/72% vs. 37/63%; cT stage 1/2/3, 19/13/68% vs. 40/9/51%; cN stage 0/1/2/3, 22/57/21/0% vs. 36/41/22/1%; cStage 1/2/3/4, 10/29/51/9% vs. 27/23/36/14%). In both unadjusted and adjusted analysis, there were no significant differences in survival of patients with cT1 and cT2 stages individually between S and R groups (cT1, unadjusted hazard radio (uHR) 1.9, p = 0.15; adjusted hazard radio (aHR) 1.5, p = 0.38. cT2, uHR2.1, p = 0.20; aHR1.8, p = 0.39). The R group was associated with worse OS compared to S group in those with cT3 stage (uHR1.9, p = 0.001; aHR1.8, p = 0.003). While OS benefit of S group was detected for cStage III patients (uHR2.2, p Conclusions: Our study indicated CRT is comparable survival to surgery based therapy for patients with esophageal squamous cell carcinoma except for patients with cT3 or cStage III. Disclosure: All authors have declared no conflicts of interest.