| Cervical cancer is the third most common cancer for women in the world. Either radiation therapy (RT) or radical hysterectomy and pelvic lymph node dissection is primary therapy for International Federation of Gynecology and Obstetrics stage IAto stage IIA cervical carcinoma. Certain clinicopathologic findings have been previously identified as risk factors for recurrence in patients with cervical cancer who undergo radical surgery as their primary treatment. Common iliac node (CIN) and/or a para-aortic node (PAN) metastasis represents the most significant negative prognostic factor. It has been suggested that patients undergo extended-field radiation therapy (EFRT). The use of concurrent cisplaton-based chemotherapy and postoperative conventional EFRT significantly produce high rates of toxicity. In the current study, we retrospectively evaluated the treatment outcomes and toxicity in patients with cervical cancer with a pathologically confirmed positive CIN or PAN who underwent radical hysterectomy with pelvic lymph node dissection and para-aortic lymph node sampling and received postoperative extended-field IMRT (EF-IMRT) with concurrent chemotherapy. We began by exploring the feasibility of reducing ovarian toxicity and evaluated the variation of ovarian function in patients with ovarian transposition. Objective:Retrospectively, to assess the toxicity of delivering postoperative EF-IMRT and concurrent cisplatin chemotherapy for patients with cervical cancer with a pathologically confirmed positive common iliac node and/or a para-aortic node.Method:Each patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. A planning CT scan of each patient was obtained following administration of oralandi.v..A clinical target volume (CTV) was contoured consisting of the upper vagina, parametria, and presacral and pelvic lymph node regions (obturator; common, internal, and external iliac nodal regions; presacral region) and para-aortic regions. The cklinical target volume was expanded by 0.8-1.0cm to create a planning target volume (PTV) in all directions. The small bowl, rectum,bladde,pelvic bone marrow, femur heads, kidneys and spinal cord were delineated as risk organs for each patients.7-field,6-MV, coplanar EF-IMRT plans were generated for all patients. Dose constrain is V45<50%　for rectum, V45<50% for bladder, V35<45%　for small bowel (the high dose was38.5Gy), V25<33%　for kidney, Dlcc<40Gy for spinal cord, V30<30%　for liver, V20<80% and V35<45% for bone marrow, V7<50%for ovarian。All patients received docetaxel at 75 mg/m2 followed by cisplatin at a dose of 75 mg/m2, both drugs on day one, during the course of external beam radiotherapy. Two course of chemotherapy were administered at 3-week interval during radiotherapy. After RT completion, all patients were evaluated by a radiation oncologist and gynecologic oncologist after 1 month, followed by evaluations at 3-month intervals for 2 years and then every 6 months thereafter. Radiological studies and blood chemistries were ordered at the discretion of the treating oncologists. Ovarian function was evaluated by the presence or absence of postmenopausal symptoms and by the measurement of follicle-stimulating hormone (FSH) and estrogen levels. We checked the FSH levels frequently when patients returned for cancer status follow-up during the 3-month and 6-month intervals.Transient ovarian failure may last for a long time, and we defined ovarian failure as two elevated (>40 U/L) FSH levels measured at least 3-6 months apart, over 2 years of follow-up after the completion of cancer treatment. Survival was measured from the date of diagnosis to the date of death or to the date of the most recent follow-up. Time to recurrence was measured from the date of diagnosis to the date of the first failure. Acute toxicities, measured from the initiation of treatment to 90 days after completion, were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 (CTCAE 3.0). Late toxicities, experienced more than 90 days after completion of therapy, were graded according to the Radiation Therapy Oncology Group (RTOG) late toxicity scale. Toxicities are reported as counts with percentages.Results:Fifty-eight patients were treated with postoperative EF-IMRT and concurrent cisplatinchemotherapy.27 patients (46%) had stage IB disease,19 (32%) had stage ⅡA disease, and 12 (22%) had stage ⅡB disease. The median age was 48 (range,27-72). The median follow-up was 34 months (rang,5-76). Eighteen patients (31%) had recurrence. The region of recurrencewas in-field in 2 patients (3.4%) and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal, genitourinary, and hematologic toxicity occurred in 2,1, and 11patients, respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen patients experienced ovarian transposition during radical surgery procedure. Ovaries were transposed as high or as laterally as possible, with metallic clips applied to each transposed ovary, which were subsequently identified by CT simulation localization. The mean ovarian dose was 2.5-3.4 Gy. Ten patients (77%) maintained ovarian function. Three patients, aged 43, 44, and 48, were classified as having ovarian failure. Their serum levels of FSH and luteinizing hormone rose progressively, and their serum estradiol levels declined over 4 weeks after radiation. The lengths of time when their FSH levels were first elevated to more than 40 U/L were 96,101, and 127 days after treatment, respectively. Forty-one patients (71%) were alive at the last follow-up. The 3-year DFS and the OS rates for the entire cohort were 66% and 71.5%, respectivelyConclusion:Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition. |
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