Yoko Harima

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

Purpose: To evaluate the effectiveness of whole-pelvic hyperthermia (HT) added to standard chemoradiotherapy (CRT) in locally advanced cervical cancer (CC), by investigating the clinical response and survival of patients treated with cisplatin-based CRT vs. CRT with HT (CRT + HT). Materials and methods: This study was conducted at five hospitals in Japan between September 2001 and March 2015 in patients with the International Federation of Gynecology and Obstetrics stage IB (bulky)–IVA CC undergoing definitive CRT. After giving a written informed consent, patients were randomly allocated to two treatment groups: CRT and CRT + HT group. Overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), complete response (CR) rate and tolerability were evaluated. Results: In total, 101 patients were treated. Patient characteristics, total dose of cisplatin and radiotherapy were similar for both groups. Although not statistically significant, the 5-year OS, DFS and LRFS in the CRT + HT group (77.8%, 70.8% and 80.1%, respectively) were better than those in the CRT group (64.8%, 60.6% and 71.0%, respectively). CR was significantly more likely to be achieved in patients in the CRT + HT group than in the CRT group (88% vs. 77.6%; adjusted odds ratio, 3.993; 95% confidence interval, 1.018–15.67; p = .047). CRT + HT was well tolerated and caused no additional acute or long-term toxicity compared with CRT alone. Conclusions: HT combined with CRT improved the CR rate of CRT in patients with locally advanced CC, however, could not improve survival outcomes. Further studies in larger samples are warranted.

Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

In our classic paper, we investigated both the clinical response and survival of patients treated with radiotherapy (RT) or thermoradiotherapy (TRT; RT plus hyperthermia [HT]) for Stage IIIB cervical carcinomas. Our study clearly demonstrated that TRT can result in beneficial effects for complete response and/or local relapse-free survival. To date, six randomized trials including our study have been published on the additive effect of HT in patients with locally advanced cervical cancer. In contrast, the combination of RT and platinum-based chemotherapy (CT) has gained wide acceptance. However, two recent meta-analyses suggested that the impact of adding CT to RT is less obvious in patients with advanced-stage tumors. Conversely, four of six randomized trials comparing the results of RT alone with TRT showed a beneficial effect for the patients with Stage IIIB tumors. From this, the patients with higher stage or bulkier tumors may benefit more from the addition of HT to RT than the addition of CT. To demonstrate the effectiveness of TRT for some cancers, including locally advanced cervical cancer, well designed randomized clinical trials are necessary.

The purpose of this study was to clarify outcome for concurrent chemoradiation (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized retrospective analysis of 226 patients treated with definitive CT-RT or radiotherapy alone (RT alone) in nine institutions between 2001 and 2003. External irradiation consisted of whole pelvic irradiation and pelvic side wall boost irradiation, using a central shield during the latter half of the treatment with the anteroposterior parallel opposing technique. The external beam irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy, platinum based drugs were used alone or in combination with other drugs such as 5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone, respectively. There was no significant difference between CT-RT and RT for overall survival and disease free survival. Univariate analysis suggested that loco-regional control was better with CT-RT, but multivariate analysis could not confirm this finding. Compared to RT alone, CT-RT caused significantly more acute and late complications. Thus, late complication (grade 3-4) free survival rate at 50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window with concomitant radiochemotherapy and HDR brachytherapy may be narrow, necessitating a close control of dose volume parameters and adherence to systems for dose prescription.