Natsuko Okita

Everolimus in Neuroendocrine Tumors of the Gastrointestinal Tract and Unknown Primary

Purpose: The RADIANT-4 randomized phase 3 study demonstrated significant prolongation of median progression-free survival (PFS) with everolimus compared to placebo (11.0 [95% CI 9.2-13.3] vs. 3.9 [95% CI 3.6-7.4] months) in patients with advanced, progressive, nonfunctional gastrointestinal (GI) and lung neuroendocrine tumors (NET). This analysis specifically evaluated NET patients with GI and unknown primary origin. Methods: Patients in the RADIANT-4 trial were randomized 2:1 to everolimus 10 mg/day or placebo. The effect of everolimus on PFS was evaluated in patients with NET of the GI tract or unknown primary site. Results: Of the 302 patients enrolled, 175 had GI NET (everolimus, 118; placebo, 57) and 36 had unknown primary (everolimus, 23; placebo, 13). In the GI subset, the median PFS by central review was 13.1 months (95% CI 9.2-17.3) in the everolimus arm versus 5.4 months (95% CI 3.6-9.3) in the placebo arm; the hazard ratio (HR) was 0.56 (95% CI 0.37-0.84). In the unknown primary patients, the median PFS was 13.6 months (95% CI 4.1-not evaluable) for everolimus versus 7.5 months (95% CI 1.9-18.5) for placebo; the HR was 0.60 (95% CI 0.24-1.51). Everolimus efficacy was also demonstrated in both midgut and non-midgut populations; a 40-46% reduction in the risk of progression or death was reported for patients in the combined GI and unknown primary subgroup. Everolimus had a benefit regardless of prior somatostatin analog therapy. Conclusions: Everolimus showed a clinically meaningful PFS benefit in patients with advanced progressive nonfunctional NET of GI and unknown primary, consistent with the overall RADIANT-4 results, providing an effective new standard treatment option in this patient population and filling an unmet treatment need for these patients.

A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma

BackgroundPatients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.MethodsA total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80xa0mg/m2) administered on day 1 and 5-fluorouracil (800xa0mg/m2) administered continuously on days 1–5, every 4xa0weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.ResultsThe median age of the patients was 62 (range 34–84)xa0years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4xa0months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.ConclusionsThe results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.

Clinical outcomes of patients with G1/G2 neuroendocrine tumors arising from foregut or hindgut treated with somatostatin analogs: a retrospective study

SummaryNeuroendocrine tumors (NET) are rare tumors for which somatostatin analogs (SSA) are used not only for symptom control due to a functioning tumor, but also for the disease control of unresectable NET. The efficacy of SSA for midgut NET has been verified by previous studies, but insufficient evidence exists for SSA treatment of NET in the foregut and hindgut (F/H-NET). The aim of this retrospective study was to evaluate the efficacy of SSA for unresectable F/H-NET. Patients with unresectable F/H-NET treated with SSA between February 2011 and August 2017 at our hospital were retrospectively reviewed. Parameters of efficacy were progression-free survival (PFS), overall survival, objective response rate (ORR), and adverse events. Twelve cases with unresectable F/H-NET were extracted from our database. With a median follow-up time of 25.9xa0months, the median PFS was 13.6xa0months. Two- and 3-year survival rates were 87.5 and 62.5%, respectively. The ORR was 8.3%, and the disease control rate was 75%. Serious adverse events were not observed. Subgroup analysis, including G1/G2, and hepatic tumor load, which is the volume of NET liver metastases, did not reveal a difference in PFS. The efficacy and safety of SSA for F/H-NET seemed similar to that found in the PROMID study, highlighting its relevance for the treatment of this disease.

Clinicopathological features and pathological evaluation of preoperative treatment of patients with resectable esophageal carcinosarcoma

BackgroundBecause esophageal carcinosarcoma (ECS) is rare, a treatment strategy similar to that employed in esophageal cancer is usually applied. However, the clinicopathological features and the treatment effects of preoperative chemotherapy or chemoradiotherapy (CT/CRT) are not well known.MethodsWe retrospectively evaluated clinical and pathological characteristics of consecutive patients with pathologically confirmed ECS who underwent esophagectomy from 1996 to 2011 in our institution, and assessed their pathological response to preoperative CT/CRT in surgically resected specimens.ResultsWe identified 19 patients with a final diagnosis of ECS who had then undergone curative surgery. In 6 of these, the preoperative pathological diagnosis by biopsy had been squamous cell carcinoma. In 7 of 13 patients treated by surgery alone, clinical T factors were overdiagnosed compared with pathological findings. Of patients who received preoperative CT (5-fluorouracil plus cisplatin) with (nxa0=xa02) and without (nxa0=xa04) concurrent RT (41.4–50.4xa0Gy), two had a partial response, in three, the disease remained stable, and one patient had progressive disease. Histopathological evaluation showed a limited pathological response in the sarcomatous component. Median overall survival of patients with and without preoperative treatment was 28.0 and 47.2xa0months, respectively [HRxa0=xa01.55 (95% CI 0.36–6.56)], and median relapse free survival was 13.4xa0months versus not achieved [HRxa0=xa02.06 (95% CI 0.54–7.76)].ConclusionThe problems associated with clinical T stage diagnosis as well as the lack of evidence for an effect of preoperative treatment, especially on the sarcomatous component, mean that treatment strategies for ECS should be considered with care.

Esophageal Metastasis from Rectal Cancer Successfully Treated with Fluorouracil-Based Chemotherapy with Bevacizumab: A Case Report and Review of the Literature

Esophageal metastasis from colorectal carcinoma is uncommon, and diagnosis of esophageal metastasis is difficult. We report a case of a 54-year-old woman with postoperative recurrence of rectal cancer metastasizing to the esophagus. She underwent rectectomy and adjuvant chemotherapy with fluorouracil, leucovorin plus oxaliplatin for stage IIIB rectal cancer. Three years later, she presented with dysphagia and cough. Computed tomography showed thickening of the esophagus wall, enlargement of the lymph nodes in the mediastinum and abdomen, and ground-glass opacities in the right lung. Endoscopy revealed a submucosal tumor of the midthoracic esophagus. Histopathological analysis of the tumor biopsy showed infiltration of adenocarcinoma cells into the stroma of the esophagus; tumor cells were positive for caudal type homeobox 2 and negative for thyroid transcription factor 1. A transbronchial biopsy indicated pulmonary lymphangitic carcinomatosis of rectal adenocarcinoma. Based on those findings, she was diagnosed with recurrent rectal cancer. She received fluorouracil-based chemotherapy plus bevacizumab, which ameliorated her symptoms and induced a durable response without severe adverse events. Diagnosis of esophageal metastasis from rectal cancer can thus be made by repeated biopsy. Furthermore, aggressive systemic treatment with fluorouracil-containing chemotherapy and bevacizumab is a treatment option for colorectal cancer patients with esophageal metastasis.

Retrospective comparison of long-term outcomes in patients with stage II/III (UICC-TNM6th) esophageal squamous cell carcinoma treated with 60 Gy or 50.4 Gy of definitive chemoradiotherapy with fluorouracil and platinum.

109 Background: Definitive chemoradiotherapy (dCRT) is one of the treatment options for stage II/III esophageal squamous cell carcinoma (ESCC). RTOG9405 demonstrated that a higher dose of radiation (64.8 Gy) offered no additional survival benefit over the standard dose (50.4 Gy). We compared the long-term outcomes of dCRT with radiation doses of 60 Gy and 50.4 Gy for ESCC. Methods: Selection criteria included thoracic ESCC, stage II/III (non T4), performance status (PS) 0-2, age 20-75 years, adequate organ function and no other active malignancy. We retrospectively analyzed patients who received dCRT as a first-line therapy between Jan. 2000 and Nov. 2011 in our hospital. Group A (n = 180) received 2 cycles of cisplatin (C) (40 mg/m2 on day 1 and 8) with fluorouracil (F) infusion (400 mg/m2/day on day 1-5 and 8-12), or 2 cycles of C (70 mg/m2 on day 1) with F infusion (700 mg/m2/day on day 1-4) repeated every 4 weeks and concurrent radiotherapy at a dose of 60 Gy. Group B (n = 62) received 2 cycles of C (7...