Predictive factor of distant recurrence in locally advanced squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy.

OBJECTIVE: To identify prognostic factors in patients with locally advanced squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy (CCRT). METHODS: We analyzed 108 patients with FIGO stage Ib2-IVa carcinoma of the cervix treated with CCRT between 1996 and 2003 at the University of the Ryukyus Hospital. Patients with a local tumor size of 4cm or more in diameter or lymph node enlargement were treated with CCRT. Disease-free survival (DFS) was estimated by the Kaplan-Meier method. The log-rank test was used to test differences in survival. Fisher's exact test was used for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. RESULTS: The median age and the median follow-up were 50 years (range: 25-70 years) and 48 months (range: 4-102 months), respectively. The 4-year distant DFS of all patients were 83%. Thirty-two of 108 patients were diagnosed with recurrence. Twenty patients had distant failure, of which 17 had only distant metastasis, three patients both distant and loco-regional recurrence, and the remaining 12 patients recurred loco-regionally. Positive serum squamous cell carcinoma antigen (SCC) immediately after CCRT was an independent predictive factor for distant recurrence on multivariate analysis. The 4-year distant DFS of these patients was 62.5%, which was significantly worse than 89.2% in patients with negative serum SCC level (p=0.003). It should be noted that the distant metastasis occurred within 6 months in six of the nine patients. CONCLUSION: Positive serum SCC immediately after the treatment was a predictive factor for distant recurrence. New strategies should be considered to control distant recurrence in this group of patients.

Treatment and prognosis of brain metastases from gynecological cancers.

Brain metastases from gynecological cancers were retrospectively investigated in 18 patients who were treated between 1985 and 2006. Six patients received surgical resection followed by radiotherapy, and 12 patients received only radiotherapy. The median survival for all patients was 4.1 months (range 0.7-48.2 months), and the actuarial survival rates were 11% at both 12 months and 24 months. Univariate analysis showed that treatment modality, extracranial disease status, total radiation dose, number of brain metastases, and Karnofsky performance status (KPS) all had statistically significant impacts on survival. Two patients survived for more than 2 years, and both had single brain metastasis, inactive extracranial disease, 90-100% KPS, and were treated with surgical resection followed by radiotherapy. Improvements in neurological symptoms were observed in 10 of the 12 patients treated with palliative radiotherapy, with median duration of 3.1 months (range 1.5-4.5 months). The prognoses for patients with brain metastases from gynecological cancers were generally poor, although selected patients may survive longer with intensive brain tumor treatment. Palliative radiotherapy was effective in improving the quality of the remaining life for patients with unfavorable prognoses.

Radiation enterocolitis requiring surgery in patients with gynecological malignancies.

PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact on the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.

Postoperative whole abdominal radiotherapy in clear cell adenocarcinoma of the ovary.

OBJECTIVES: The aim of this study was to clarify the efficacy of postoperative whole abdominal radiotherapy (WAR) for ovarian clear cell adenocarcinoma (OCCA). METHODS: Between 1996 and 2004, 16 patients with OCCA underwent initial debulking surgery and received postoperative WAR. Indications for WAR were as follows: OCCA, International Federation of Gynaecology and Obstetrics (FIGO) stage Ic-III, no macroscopic residual disease in the upper abdomen and residual disease in the pelvic cavity < or = 2 cm. The planned WAR comprised external beam radiotherapy (EBRT) to the entire abdominal cavity with 22.0-24.0 Gy/22-24 fractions followed by EBRT to the pelvis with 23.4-21.6 Gy/12-13 fractions. Overall survival (OS) and disease-free survival (DFS) were compared with 12 historical control (HC) patients treated with initial debulking surgery followed by platinum-based chemotherapy. RESULTS: The FIGO stage in the WAR group was stage Ic in 11 patients, stage II in 3, and stage III in 2. Fifteen of the 16 patients (94%) completed the planned WAR. Two patients developed radiation enterocolitis and required bowel surgery. Five-year OS and DFS in the WAR/HC group were 81.8%/33.3% and 81.2%/25.0% (p=0.031 and p=0.006), respectively. CONCLUSIONS: This study suggests that postoperative WAR may be effective in selected patients with OCCA. Prospective randomized trials should be considered to assess postoperative WAR for OCCA.

Epstein-Barr virus (EBV)-related oral squamous cell carcinoma in Okinawa, a subtropical island, in southern Japan--simultaneously infected with human papillomavirus (HPV).

Up to now, many authors have reported on the EBV infection and its carcinogenic importance in undifferentiated nasopharyngeal carcinoma (WHO classification, type III), but the infection of the virus in well differentiated oral squamous cell carcinoma has not been well described. We introduce the EBV-related well differentiated oral squamous cell carcinomas in Okinawa, a subtropical island in the southernmost part of Japan. This study aimed to clarify the pathogenesis of this malignancy in this area by carrying out analysis of the histology and the Epstein-Barr (EBV) and human papillomavirus (HPV) infection. In the Department of Oral Surgery, Ryukyu University Hospital Okinawa, 188 cases of oral malignant tumours were encountered from 1996 to 2000. The histopathological examination and the sequence analysis of LMP-1 carboxy terminal region and EBNA2 region of EBV were carried out, as were the analysis of virus subtypes, A and B, BamHI-F and f, and C and D. Additionally, HPV infection in the squamous cell carcinomas were demonstrated using E6 and E7 region primer sets by PCR method. In Okinawa, 94% (177/188) of the cases were squamous cell carcinomas. A surprisingly large number of EBV (72%) and HPV (78%) infections in the oral squamous cell carcinomas were demonstrated. EBV type B virus infection was found in 36% of EBV-related oral squamous cell carcinoma in Okinawa, but in only 2-5% of the mainland cases. In both regions the incidence of the BamHI- f variant infection was very low. The infected virus in 79 out of 80 (39 Okinawan and 41 mainland) cases was BamHI- F type. In Okinawa, the numbers of C and D variants were almost equal, whereas in the mainland the D variant was rare. Further, a 30 bp deletion in LMP-1 gene was frequently demonstrated in Okinawan and mainland cases of type A virus, but not in type B virus. Lastly, single nucleotide mutations in EBNA2 region of type A virus when compared with B95-8 strain were demonstrated in Okinawan cases. The prognosis for (mostly EBV/HPV infected) squamous cell carcinomas in Okinawa was better than that in the mainland where most cases were negative for EBV and/or HPV.