Hyperfractionated radiation therapy plus chemotherapy in locally advanced cervical cancer: results of two phase I dose-escalation Gynecologic Oncology Group trials

OBJECTIVE: The aims of this study were to assess the early and late toxicities of multiple-daily-fraction whole pelvic radiation plus concurrent chemotherapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to determine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix. METHODS: The first study (GOG 8801) of 38 patients utilized hydroxyurea as a single oral dose of 80 mg/kg to a maximum of 6 g at least 2 h prior to a radiation treatment twice every week. In the second study (GOG 8901) of 30 patients, cisplatin and 5-FU were used concomitantly with radiotherapy. Fifty milligrams per square meter of cisplatin was administered on days 1 and 17 of external radiation. 5-FU was given by continuous intravenous infusion at a dose of 1000 mg/m(2)/day for 4 consecutive days on days 2, 3, 4, 5, and 18, 19, 20, and 21 of external radiation therapy. Both studies utilized external radiation given by an accelerated hyperfractionated regimen of 1.2 Gy per fraction, two fractions per day. All patients were treated 5 days per week with a minimum of 4 h between fractions. RESULTS: Acute toxicity was manageable on both protocols but nausea, vomiting, and myelosuppression were more severe with hydroxyurea. Chronic toxicity was primarily enteric and appeared to be dose-related. There was no obvious correlation seen between pelvic failure rates and the radiation dose or between the chemotherapy regimens used. CONCLUSIONS: The defined maximal tolerated dose of whole pelvic radiation was 57.6 Gy in 48 fractions which could be delivered in a hyperfractionated setting with concomitant chemotherapy, followed by brachytherapy. Follow-up is now sufficient that further adverse events should be rare.     

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.     

Phase I trial of concomitant vinorelbine, cisplatin, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies

OBJECTIVE: To determine the maximum tolerated dose (MTD) of vinorelbine in combination with weekly cisplatin and pelvic radiation therapy (RT). METHODS: Eligible patients included those with bulky or locally advanced cervical cancer. Women with other advanced gynecologic malignancies were also eligible. All patients received cisplatin 40 mg/m(-2)/week (maximum dose, 70 mg) during pelvic RT. Vinorelbine was administered on the same day as cisplatin at a starting dose of 10 mg/m(-2)/week and escalated in 5 mg/m(-2)/week increments. Dose-limiting toxicity (DLT) was defined as: grade 3-4 non-hematologic toxicity, grade 4 hematologic toxicity, or any toxicity which required > or =1 week delay in RT or an omission of >1 dose of chemotherapy. RESULTS: Between April 2001 and September 2002, 12 women with pelvic malignancies (11 cervical, 1 recurrent ovarian) were enrolled. Cohorts of 3, 6, and 3 patients were treated at 10, 15, and 20 mg/m(-2)/week dose levels of vinorelbine. At the 20 mg/m2 level, DLT was observed. Two of three patients missed >1 cycle of chemotherapy secondary to predominantly hematologic toxicity. One patient at the 20 mg level developed a creatinine clearance <50 ml/min and missed 1 dose of cisplatin. Another developed transient grade 3 diarrhea. No grade 4 toxicities were observed. CONCLUSIONS: The MTD of vinorelbine in combination with cisplatin and pelvic RT in patients with cervical cancer is 15 mg/m(-2)/week.     

Survival after relapse in patients with endometrial cancer: results from a randomized trial

OBJECTIVE: The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. METHODS: The PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment. RESULTS: The analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group. CONCLUSION: Survival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvic relapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival.     

经腹膜外盆腔淋巴间隙给药对妇科肿瘤患者外周血T细胞亚群及NK细胞的影响

目的:探讨通过盆腔腹膜外淋巴间隙进行肿瘤生物治疗的可行性。方法:妇科恶性肿瘤患者31例随机分白细胞介素2(IL2)组(n=10)、IL2加氟尿嘧啶组(n=11)及氟尿嘧啶组(n=10)。通过经盆腔腹膜外淋巴间隙留置管,分别注射药物IL2、IL2加氟尿嘧啶、氟尿嘧啶,并在注药前后采集患者外周血,用流式细胞仪检测T细胞表面标记、CD25活化标记变化及NK细胞数量,用MTT比色法检测NK细胞杀伤活性。结果:各组治疗后外周血CD3+、CD4+、CD8+,CD25+、NK细胞数量及杀伤活性均比治疗前明显增高(P<0.05)。结论:经盆腔腹膜外淋巴间隙进行生物治疗能有效激活机体全身T细胞反应,促进T细胞增殖和活化,并促进NK细胞增殖和活化。     

Effective palliative radiotherapy for symptomatic recurrent or residual ovarian cancer

OBJECTIVE: To evaluate the efficacy of radiotherapy (RT) for symptomatic recurrent or residual ovarian cancer. METHODS: A review was conducted on patients (pts) treated with palliative RT for symptomatic ovarian cancer at The Ottawa Hospital Regional Cancer Centre between 1990 and 2003. Patient demographics, tumor factors, treatment variables, and clinical outcome were entered into a database. Symptom response was defined as complete (CR), partial (PR), or none. RESULTS: 62 courses of RT were delivered to 53 pts. The symptoms treated were: bleeding (40%), pain (37%), and "others" (23%). The most common dose fractionation scheme was 30 Gy in 10 fractions (f) (range: 5 Gy/1 f to 52.5 Gy/20 f). The overall response rate was 100%, with 68% achieving a CR. The CR rates were 88, 65, and 36% for the symptoms of bleeding, pain, and "others", respectively (P = 0.003). The median duration of response was 4.8 months (range: 1-71 months). In multivariate analysis, the only factors that were found to be significant positive predictors of symptom control were: the symptom bleeding (P = 0.015) and stage III/IV disease at presentation (P = 0.01). The most commonly reported toxicities were grades 1 and 2 nausea/vomiting and diarrhea. There were no grade 3/4 toxicities reported. CONCLUSIONS: Radiotherapy is highly effective in palliating symptomatic ovarian cancer. Excellent results are achieved for patients presenting with bleeding or pain. Symptomatic patients should be strongly considered for palliative radiotherapy. Higher doses of radiotherapy should be considered for those with symptoms other than bleeding or pain and those with longer life expectancies.     

Methods,safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies

Objective

To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies.

Methods

Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45 Gy in 1.8 Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55 Gy in 2.2 Gy fractions (n = 44 sites). An additional sequential boost of 10 Gy in 2 Gy fractions was delivered if deemed appropriate (n = 29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed.

Results

All were treated with a SIB to a dose of 55 Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65 Gy. Median follow-up was 18 months. Rates of acute > grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1–2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1–2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities.

Conclusion

Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity.     

Combined radio-chemotherapy in advanced cervical cancer: a phase-II trial with weekly applied carboplatin, 5-fluorouracil and folinic acid

The 5-year survival of patients with advanced cervical cancer is poor. Major problems are the high frequency of pelvic recurrences and distant metastases. To prevent both, various efforts have been made to combine local radiotherapy with systemic chemotherapy. In this prospective study, 28 previously untreated patients with advanced cervical cancer (FIGO IIB-IVB) were treated with a newly designed therapy consisting of fractionated external beam irradiation (54 Gy) followed by two intracavitary cesium (Cs) applications (2 × 15 Gy), combined with carboplatin (70 mg m⁻²), 5-fluorouracil (5-FU) (400 mg m⁻²) and folinic acid (400 mg m⁻²). Cytotoxic agents were given intravenously on days 1, 8, 15, 22 and 29 as 1-day courses during external irradiation followed by three 3-day courses with carboplatin (100 mg m⁻² i.v. daily), 5-FU (400 mg m⁻² i.v. daily) and folinic acid (400 mg m⁻² i.v. daily) after 8, 12 and 16 weeks of treatment.
Acute toxicities ( WHO grade 2) were leucopenia (27 of 28 patients), diarrhea (23/28), abdominal pain (19/28), nausea (14/28) and skin desquamation (12/28). Clinically diagnosed pelvic response was achieved in 88.5% (23/26) with a complete response of 34.5% (9/26). As yet, 19 of 26 patients (73.1%) are alive and well (persistent complete/partial remission), two patients (7.7%) are alive with local progression, four (15.4%) have died from pelvic and/or distal recurrence and one (3.8%) died some weeks after the start of therapy. The combined modality treatment concept has to be considered for the therapy of advanced cervical cancer and a prospective and randomized trial with a greater number of patients is warranted.     

Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer

OBJECTIVE: Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. METHODS: From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. RESULTS: Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2), 2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% (P value < 0.001), and GI obstruction 0% vs. 7% (P value = 0.08). CONCLUSION: Stage I-II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.     

The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy

PURPOSE: This study was undertaken to evaluate the efficacy of postoperative radiotherapy (post-OP RT) and to investigate the prognostic factors for early-stage cervical cancer patients who were treated by radical surgery, and the pathological findings suggested a relatively high risk of relapse with surgery alone. MATERIALS AND METHODS: From January 1990 to December 1995, 222 patients with stage IB-IIA cervical cancer, treated by radical surgery and a full course of post-OP RT, were included in this study. The indications for post-OP RT were based on pathological findings, including lymph node metastasis, positive surgical margins, parametrial extension, lymphovascular permeation, and invasion of more than two-thirds of the cervical wall thickness. The radiation dose of external beam was 44-45 Gy to the whole pelvis and 50-54 Gy to the true pelvis. One hundred seventy-two patients also received intravaginal brachytherapy as a local boost. The minimal follow-up period was 2 years. RESULTS: The actuarial 5-year overall and disease-specific survival rates for all patients were 76 and 82%, respectively. The tumor control rate within the pelvis reached 94%, and distant metastasis was the major cause of treatment failure. Univariate analysis of clinical and pathological parameters revealed that clinical stage, bulky tumor size, positive lymph nodes, parametrial extension, and histologic type were significant prognostic factors. After multivariate analysis, only positive lymph nodes (P = 0.01), bulky tumor size (P = 0.02), and parametrial extension (P = 0.05) independently influenced the disease-specific survival (DSS). For patients with lymph node metastasis, the number and location of the nodal involvement significantly affected the prognosis. The 5-year DSS for patients with no, one, and more than one lymph node metastasis were 87, 84, and 61% (P = 0.0001), respectively. Patients with upper pelvic lymph node metastasis had a higher incidence of distant metastasis (50% vs 16% in lower pelvic node group, P = 0.03). In the subgroup of single lower pelvic nodal metastasis, the prognosis was similar to that of patients without lymph node involvement (5-year DSS 85% vs 87%, P = 0.71). CONCLUSION: Our results indicate that post-OP RT can achieve very good local control in stage IB-IIA cervical cancer patients whose pathological findings show risk features for relapse after radical surgery. The prognostic factors for treatment failure identified in this study can be used as selection criteria for clinical trials to test the effects of other adjuvant treatments, such as chemotherapy. Patients with a single lower pelvic lymph node metastasis have a relatively good prognosis and may not need adjuvant treatment beyond radiation therapy.     

Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma

OBJECTIVE: To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer. METHODS: Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months). RESULTS: Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT. CONCLUSION: Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients.     

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer

OBJECTIVE: To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. METHODS: From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4-5 weeks), the field was limited to the true pelvis and a further 10-20 Gy delivered in 5-10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50-58 Gy delivered over 5-6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. RESULTS: After 38-119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5-48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. CONCLUSION: This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.     

Incidence and temporal pattern of anorexia, diarrhea, weight loss, and leukopenia in patients with cervical cancer treated with concurrent radiation therapy and weekly cisplatin: comparison with radiation therapy alone

OBJECTIVE: To investigate the temporal patterns of anorexia, diarrhea, weight loss, and leukopenia in chemoradiation therapy (CRT) for cervical cancer compared with radiation therapy (RT) alone. METHODS: Acute toxicities in 43 patients receiving RT alone and 40 patients receiving CRT were retrospectively analyzed. Patients were treated with a combination of external beam irradiation and high-dose rate intracavitary irradiation. Cisplatin was given once a week for 5 weeks concurrently with the external beam irradiation. CRT was divided into low-dose CRT group (cisplatin, 20-30 mg/m(2), n = 16) and high-dose CRT group (cisplatin, 35-40 mg/m(2), n = 24). Toxicities were evaluated before, every week up to 7 weeks during the cycle, and 12 weeks after initial irradiation, according to the National Cancer Institute Common Toxicity Criteria version 2. RESULTS: In the high-dose CRT group, anorexia during the first 5 weeks, leukopenia after 5 weeks, and weight loss after 3 weeks were significantly higher than those in the RT alone group. In the low-dose CRT group, anorexia between 1 and 2 weeks, leukopenia after 5 weeks, and weight loss between 3 and 4 weeks were significantly higher than those in the RT alone group. Diarrhea between 1 and 2 weeks in the high-dose CRT group (P = 0.037, P = 0.025) and between 2 and 3 weeks in the low-dose CRT group (P = 0.015, P = 0.036) was significantly lower compared with RT alone. CONCLUSION: These data can help us understand when patients are likely to develop maximal toxicities and to manage them with optimal timing.     

252Cf中子腔内后装加盆腔外照射治疗子宫颈癌临床分析

目的观察^252Cf腔内后装加盆腔外照射治疗宫颈癌的疗效以及晚期并发症的发生情况,并对治疗方案进行总结。方法选择77例未接受过任何治疗的临床分期为Ⅱa～Ⅳa期的宫颈癌患者作为研究对象,其中Ⅱa期13例,Ⅱb期32例,Ⅲa期18例,Ⅲb期10例,Ⅳa期4例。治疗方案：^252Cf中子腔内后装治疗,宫旁A点剂量为8～11Gy／次,1次／周,共进行4～5次,使宫旁A点累积剂量达36～45Gy;该治疗过程中,间歇穿插前后对穿野全盆腔外照射200cGy／次,4次／周;外照射20—36Gy后,盆腔野中央屏蔽挡铅4cm,继续四野外照射200cGy／次,4次／周,使盆腔外照射总剂量达到45～50Gy左右。总疗程约需5—6周。结果77例患者随访3年,3年局部控制率为94％(72／77);3年总生存率为82％(63／77),其中临床分期Ⅱa期为85％(11／13),Ⅱb期为94％(30／32),Ⅲa期为78％(14／18),Ⅲb期为70％(7／10),Ⅳa期为1／4。放射性膀胱炎发生率为3％,放射性直肠炎发生率为5％。结论^252Cf中子腔内后装加盆腔外照射治疗宫颈癌,患者能较好耐受,且其Ⅱ、Ⅲ期患者的3年生存率较高而并发症发生率较低,具有较好的应用前景。     

Pelvic insufficiency fracture after pelvic irradiation in uterine cervix cancer

OBJECTIVES: Pelvic insufficiency fractures (IF) are well known but uncommon and are frequently misinterpreted sequelae. The clinical features were investigated. METHODS: Four hundred sixty-three patients, who were treated between 1994 and 2000 for uterine cervix cancer, were clinically examined. All patients had been treated with 10 or 15 MV photons, with 50.4-55.8 Gy in 28 fractions with adjuvant intent (n = 235) in addition to high-dose-rate brachytherapy 24 Gy in 6 fractions for curative treatment (n = 228). The median follow-up was 38 months. RESULTS: Eight patients (8/463, 1.7%) developed pelvic IF 7-19 months (median, 12 months) after the treatment. Among these, seven patients (7/228, 3.1%) were treated with curative intent and one (1/235, 0.4%) was treated with adjuvant intent. All patients were postmenopausal and complained of moderate to severe pelvic pain, which resolved after 1-11 months with conservative therapy in all patients. Two of these patients also had radiation proctitis. CONCLUSION: In women who present with pelvic pain after radiotherapy for cervical cancer, bony destruction and fractures may be indicative of a late radiation effect rather than osseous metastasis. IF are more common in the curative treatment group than in the postoperative adjuvant group.     

Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer

BackgroundLimited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT.MethodsA retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded.ResultsPrior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities.ConclusionRe-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.     

妇科恶性肿瘤淋巴结转移的腹膜后与腹腔化学治疗的比较

目的 比较妇科恶性肿瘤患者淋巴结转移的腹膜后化学治疗（化疗）和腹腔化疗的疗效,并进一步评价腹膜后化疗。方法 选择６２例妇科恶性肿瘤患者,手术前分别随机进行腹膜后化疗４３例、腹腔化疗重复给药１１例和腹腔化疗单次注药（５氟嘧啶,５－ＦＵ）８例,采用高效液相色谱侧定法（ＨＰＬＣ）检测淋巴结内－５ＦＵ的浓度。其中１６例腹膜后化疗重复给药患者,比较注药侧与未注药侧淋巴结内５－ＦＵ的浓度。选择腹膜后化疗患者６     

Multivariate analysis of the prognostic factors and outcomes in early cervical cancer patients undergoing radical hysterectomy

OBJECTIVE: This study was performed to identify pathologic and clinical risk factors that best predicted 5-year recurrence-free survival (RFS) among patients with early-stage cervical carcinoma, treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: The records of 197 patients with early-stage invasive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy from 1990 to 1999 were retrospectively reviewed. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial invasion, surgical margin involvement, and pattern of adjuvant therapy were analyzed using univariate and multivariate methods to define those variables that best predicted RFS. RESULTS: Outer 1/3 invasion, LVSI, and LNM were identified as independent poor prognostic factors, which were used to define three prognostic groups: patients (n = 104) with good prognoses (LVSI (-) and LNM (-)), patients (n = 46) with intermediate prognoses (either LVSI (+) without outer 1/3 invasion or LNM (+) without LVSI), and patients (n = 47) with poor prognoses (LVSI (+) patients with outer 1/3 invasion). The estimated 3-year RFS for patients with LVSI and deeply invasive tumors regardless of nodal status and/or nodal metastases receiving adjuvant CT + RT was significantly greater than that for patients who received only adjuvant radiotherapy (80% vs. 49%, P = 0.048 in the group of patients with LVSI and deeply invasive tumors with positive nodes and without positive nodes; 87% vs. 36%, P = 0.013 in the group of patients with LVSI and deeply invasive tumors with positive nodes only). CONCLUSIONS: The multivariate analysis and prognostic grouping system maximally separated patients with early-stage invasive cervical carcinoma into groups with good, intermediate, or poor prognoses, with 3-year RFSs of 90%, 82%, 67%; and 5-year RFSs of 89%, 69%, 43%, respectively. CT + RT played a role in improving RFS among patients with LVSI and deeply invasive tumors and poor prognoses.     

The effect of laparoscopic guidance on gynecologic interstitial brachytherapy

STUDY OBJECTIVE: To compare laparoscopic-assisted interstitial brachytherapy (LAIB) with traditional interstitial brachytherapy (TrIB) in the treatment of gynecologic malignancies. DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: A total of 42 women undergoing interstitial brachytherapy for a gynecologic malignancy. INTERVENTIONS: Interstitial brachytherapy by traditional method versus laparoscopic guidance. MEASUREMENTS AND MAIN RESULTS: In all, 42 women underwent interstitial brachytherapy with a mean follow-up of 24 months. In all, 28 patients underwent TrIB and 14 underwent LAIB. The mean operating department time was 177minutes for LAIB and 91minutes for TrIB (p <.001). No intraoperative complications existed in either group. Of the 14 patients undergoing LAIB, 2 (14%) had carcinomatosis, and the brachytherapy was aborted. Of patients who proceeded with LAIB, 64% had clinically significant pelvic adhesions necessitating lysis of adhesions. Mean radiation doses were similar for both external beam (LAIB = 54Gy, TrIB = 50Gy; p = .12) and brachytherapy (LAIB = 29Gy, TrIB = 30Gy; p = .8). No difference existed in the mean follow-up between groups (p = .7). In regard to long-term grade 3/4 radiation toxicity, 1 (10%) patient undergoing LAIB had a rectovaginal fistula. Six (27%) patients (p = .39; 95% CI 9%-43%) undergoing TrIB experienced high-grade toxicity, including 2 rectovaginal fistulas, 1 rectal stricture, 1 necrotizing fasciitis, 1 urinary incontinence, and 1 soft-tissue necrosis. CONCLUSION: The LAIB procedure appears safe, but substantially increases operating department time. No significant decrease in late high-grade toxicities were detected in comparison with TrIB. The LAIB procedure allows for both lysis of adhesions and identification of unknown carcinomatosis.     

Long-term results of concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after surgery

Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in the pelvis, or pelvis and para-aortic nodes after initial surgery, were treated with concurrent chemo-radiation (CT-RT). The total dose of radiation was tailored to the disease extent. Radiation was delivered to the pelvis and/or pelvis plus para-aortic nodes. Concurrent infusional 5-fluorouracil 1.5 g m-2 day-1 was delivered with bid radiation for one to three courses of 3 or 4 days. In addition, 10 patients received one or two courses of intravenous mitomycin C (Mit C) 6 mg m⁻². Twenty-three of 40 evaluable (58%) had a complete response to CT-RT. Five have subsequently relapsed, two in pelvis alone, one in pelvis and distant sites and two with distant metastases only. Eighteen of 40 (45%) remain alive without disease from 3 to 113 months (median 57 months) after CT-RT. Sustained complete remissions and apparent cure have occured even in poor pronosis patients with pelvic side wall or common iliac nodal diease and those recurrent at short intervals from surgery. Using logistic regression the following varibles were examined for their prognostic significance for pelvic control and survival: Mit C, extent of pelvic diseases number of course of 5-FU, nodal status at original surgery and radiation dose. On multivariate analysis only the number of courses of 5-FU used was predictive of pelvic control and survival. Concurrent 5-FU and radiation is recommended as salvage therapy for patients wth recurrent locoregional cervical cancer.