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.

Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy for uterine cervical cancer.

OBJECTIVE: We retrospectively reviewed our experience with concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) to assess its feasibility and efficacy in the treatment of patients with uterine cervical cancer. METHODS: Forty patients with uterine cervical squamous cell carcinoma treated with CCRT using HDR-ICBT were analyzed. The median cervical tumor size assessed by MRI was 63 mm (range: 40-86 mm). Eighteen patients (45%) had enlarged pelvic nodes on MRI (> or =10 mm). Cisplatin (20 mg/m2/day) was concurrently administered with radiotherapy for 5 days at 21-day intervals for a median of three courses (range: 1-5 courses). Thirty-eight (95%) patients received whole pelvic external beam radiotherapy (EBRT) with 40 Gy/20 fractions followed by HDR-ICBT with 18 Gy/3 fractions to point A. Subsequently, additional pelvic EBRT with 10 Gy/5 fractions was delivered with a midline block. The cumulative biological effective dose (BED) at point A of this schedule was 77 Gy10. The median follow-up period for all 40 patients was 37 months (range: 8-71 months). RESULTS: Grade 3/4 leukopenia was the most common acute side effect (83%). The actuarial 3-year pelvic control rate, disease-free survival rate, and overall survival rate were 91%, 67%, and 79%, respectively. Eight (20%) patients suffered late gastrointestinal complications (all grades). No patient suffered radiation cystitis (all grades). Only one patient experienced grade 3 complication (enterocolitis). The actuarial 3-year late complication rate (all grades) was 9% for proctitis and 15% for enterocolitis. CONCLUSION: This preliminary study suggests that CCRT using HDR-ICBT is feasible and efficacious for patients with locoregionally advanced uterine cervical cancer.

Persistence of human papillomavirus infection as a predictor for recurrence in carcinoma of the cervix after radiotherapy.

OBJECTIVE: This study was undertaken to examine a possible correlation between clearance or persistence of human papillomavirus (HPV) infection and radiation response in carcinoma of the cervix. STUDY DESIGN: We reviewed 97 patients with HPV-positive cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IB-IVA) treated with radiotherapy. Examination of HPV DNA was performed by the polymerase chain reaction-based assay. RESULTS: Cervical HPV DNA cleared in 42 patients (43.3%) and persisted in 55 patients (56.7%) at the end of irradiation. All of 42 HPV-cleared patients (100.0%) and 50 of 55 HPV-persistent patients (90.9%) had complete response. Of 92 patients with complete response, 20 (21.7%) had local recurrence develop. The recurrence rate was significantly higher in HPV-persisted patients (34.0%) than in HPV-cleared patients (7.1%) ( P = .0016). Univariate analysis demonstrated the significant differences for both 5-year local disease-free survival (LDFS) and overall survival (OAS) between HPV-cleared and HPV-persisted groups. Multivariate analysis showed that persistence of HPV DNA was the most powerful independent predictor for LDFS and OAS compared with other prognostic factors, such as FIGO stage or node swelling. CONCLUSION: In HPV-positive cervical carcinoma, persistence of HPV DNA in the cervix at the end of irradiation was highly predictive of LDFS and OAS.

Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule.

PURPOSE: To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. METHODS: Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. RESULTS: The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). CONCLUSIONS: In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.

Management of invasive carcinoma of the uterine cervix associated with pregnancy: outcome of intentional delay in treatment.

OBJECTIVE: To investigate patients with invasive cervical carcinoma associated with pregnancy, with special reference to the maternal and neonatal outcomes after planned treatment delay to improve fetal maturity. METHODS: The medical records of 28 patients with invasive cervical carcinoma diagnosed during pregnancy or within 1 month after pregnancy were retrospectively reviewed. RESULTS: Twenty-two patients (79%) had Stage I disease and 6 (21%) had Stage II or III disease. Tumor histology revealed squamous cell carcinoma in 27 cases and adenocarcinoma in 1. Twenty cases were diagnosed before 22 weeks gestation, 4 between 22 and 36 weeks, 1 after 36 weeks gestation, and 3 were diagnosed postpartum. In the immediate treatment group (n = 16), the diseases were Stage IA in 3 cases, IB in 7, and II or III in 6. In 11 patients, hysterectomy was performed after therapeutic abortion or with fetus in situ. In 2 patients, cesarean section was followed by hysterectomy or radiotherapy. Three patients diagnosed postpartum were treated with either hysterectomy or radiotherapy. Fifteen patients were free of disease during the follow-up of 27 to 114 months. In the delayed treatment group (n = 12), the diseases were Stage IA1 in 8 cases, IA2 in 1, IB1 in 2, and IB2 in 1 case. In 8 patients with Stage IA1 tumor, the treatment was deferred until term with a delay of 6 to 25 weeks, and hysterectomy or therapeutic conization was performed after delivery. In 4 patients with Stage IA2, IB1 or IB2 tumor, the treatment was postponed until after 30 weeks gestation with a delay of 6 to 15 weeks. No disease progression was documented. Cesarean delivery was followed by hysterectomy in these patients. All patients were free from disease during the follow-up of 70 to 156 months and their babies were well with no sequelae. CONCLUSION: Delay in treatment to allow for fetal maturity is safe in patients with early Stage I cervical carcinoma associated with pregnancy.

High dose-rate intracavitary brachytherapy for carcinoma in situ of the vagina occurring after hysterectomy: a rational prescription of radiation dose.

OBJECTIVE: Our purpose was to profile patients who were treated with high dose-rate intracavitary brachytherapy for carcinoma in situ of the vagina that occurred after hysterectomy, with special reference to a rational prescription of radiation dose. STUDY DESIGN: We reviewed 13 patients who were treated for posthysterectomy carcinoma in situ of the vagina by the brachytherapy as the sole treatment. The brachytherapy was delivered by a remote-controlled afterloading intracavitary radiation system. RESULTS: The mean age of the patients was 62 years. The total dose of absorbed radiation was 36 and 30 Gy that was prescribed at 1.0-cm depth to the vaginal surface in 3 cases and at 40 and 30 Gy that was prescribed at 0.5-cm depth in 10 cases. All patients had vaginal mucosal radiation changes of mild to moderate grade. Three cases that were irradiated to a total dose of 30 Gy at 1.0-cm depth had rectal bleeding and/or macroscopic hematuria. Complaints regarding sexual functioning were not found in this retrospective analysis. All patients remain free of disease after a median follow-up period of 127 months. CONCLUSION: High dose-rate brachytherapy with a dose prescription at 0.5-cm depth can yield a promising rate of tumor control, with lower associated morbidity than that with a dose prescription at 1.0-cm depth in the treatment of posthysterectomy carcinoma in situ of the vagina.