Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan / 부인종양

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer / 부인종양

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.

The relationship between positive peritoneal cytology and the prognosis of patients with FIGO stage I/II uterine cervical cancer / 부인종양

OBJECTIVE: The purpose of this study was to assess whether peritoneal cytology has prognostic significance in uterine cervical cancer. METHODS: Peritoneal cytology was obtained in 228 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics [FIGO] stages IB1-IIB) between October 2002 and August 2010. All patients were negative for intraperitoneal disease at the time of their radical hysterectomy. The pathological features and clinical prognosis of cases of positive peritoneal cytology were examined retrospectively. RESULTS: Peritoneal cytology was positive in 9 patients (3.9%). Of these patients, 3/139 (2.2%) had squamous cell carcinoma and 6/89 (6.7%) had adenocarcinoma or adenosquamous carcinoma. One of the 3 patients with squamous cell carcinoma who had positive cytology had a recurrence at the vaginal stump 21 months after radical hysterectomy. All of the 6 patients with adenocarcinoma or adenosquamous carcinoma had disease recurrence during the follow-up period: 3 with peritoneal dissemination and 2 with lymph node metastases. There were significant differences in recurrence-free survival and overall survival between the peritoneal cytology-negative and cytology-positive groups (log-rank p<0.001). Multivariate analysis of prognosis in cervical cancer revealed that peritoneal cytology (p=0.029) and histological type (p=0.004) were independent prognostic factors. CONCLUSION: Positive peritoneal cytology may be associated with a poor prognosis in adenocarcinoma or adenosquamous carcinoma of the uterine cervix. Therefore, the results of peritoneal cytology must be considered in postoperative treatment planning.

Clinical research of olanzapine for prevention of chemotherapy-induced nausea and vomiting resistant to standard antiemetic treatment for highly emetogenic chemotherapy

<b>Purpose</b>: Olanzapine has antiemetic activity for chemotherapy-induced nausea and vomiting (CINV). The purpose of this retrospective study is to evaluate the efficacy of olanzapine for prevention of CINV in patients with severe nausea resistant to standard antiemetic regimen for highly emetogenic chemotherapy (HEC). <b>Methods</b>: Olanzapine was administered in twenty gynecological cancer patients receiving HEC. They had grade 3 nausea (CTCAE ver.4.0) for the acute (24 hours postchemotherapy) and/or delayed (24-120 hours postchemotherapy) period despite the combined use of 5-HT3 receptor antagonist, NK-1 receptor antagonist, and dexamethasone. Oral olanzapine (5 mg/day) was administered on day -1 prior to chemotherapy and continued for 7 days in combination with standard antiemetic regimen. The nausea control rate (grade 0-1) with olanzapine were evaluated. <b>Results</b>: The nausea control rate improved from 30% to 95% for the acute period, 0% to 95% for the delayed period, and 0% to 90% for the overall period. In each period, the nausea control rate improved significantly (<i>p</i>≤0.001). Grade 0-1 sleepiness was observed but there were no grade 3 or 4 toxicities. Conclusion: In this study, olanzapine combined with the standard antiemetic regimen had good antiemetic activity at both acute and delayed period in most of chemotherapy-naive patients receiving HEC. The efficacy of olanzapine suggested additional improvement in the control of severe CINV resistant to standard antiemetic regimen for HEC.