Rectal bleeding and its management after irradiation for uterine cervical cancer

PURPOSE: To present an evaluation of the risk factors of radiation-induced rectal bleeding and discuss its optimal management in patients with cancer of the cervix. METHODS AND MATERIALS: A total of 213 patients treated with radiotherapy (RT) alone were included. All patients underwent external beam radiotherapy with high-dose-rate brachytherapy. The rectal dose was calculated by both the International Commission on Radiation Units and Measurements (ICRU) Report 38 guidelines and the anterior rectal wall point on radiographs. Rectal bleeding was scored using the late effects normal tissue-subjective, objective, management, and analytic criteria. RESULTS: The incidence was 12.7% (27 of 213; Grade 1 in 9, Grade 2 in 16, and Grade 3 in 2). Most (92.6%) developed rectal bleeding within 2 years after RT completion (median 16 months). In univariate analysis, three significant factors were found: ICRU cumulative rectal biologically equivalent dose (CRBED) >100 Gy (19.7% vs. 4.2%), external beam RT dose to the parametrium >55 Gy (22.1% vs. 5.1%), and advanced stage (III-IV; 31.8% vs. 10.5%). In multivariate analysis, the ICRU-CRBED was the only significant factor. Six patients with Grade 1 bleeding experienced immediate relief with sucralfate enema for 1 month. For Grade 2 bleeding, sucralfate enema and/or coagulation were effective. Grade 3 bleeding lasted for 1 year despite frequent transfusions and coagulation. CONCLUSION: Grade 2 and 3 rectal bleeding occurred in 8.5% of patients. The most significant risk factor was the ICRU-CRBED. Prompt treatment with a combination of sucralfate enema and coagulation was effective in controlling Grade 1 and 2 rectal bleeding without the development of fistula or stricture.     

Results of combined therapy of irradiation and bleomycin suppository for advanced uterine cervical cancer

Efficacy, survival rats and adverse effects of the combined therapy of irradiation with intravaginal bleomycin suppositories were analyzed and discussed in 49 patients with uterine cervical cancer. The results were as follows: Histological examination of biopsy specimens from the uterine cervix taken just after the completion of this treatment showed favorable control over the primary lesions. However, the efficacy of the bleomycin suppositories was too mild to form a basis for treatment without intracavitary irradiation. Because of the low concentration of bleomycin in serum after suppository administration, it is thought that bleomycin would have little effect on distant metastases. Survival rates in stage III patients were 83% at 12 months, 77% at 24 months and 70% at 36 months. These were superior to those for irradiation alone. The major adverse effect of bleomycin suppositories was fever, reduction of the bleomycin dose in each suppository but controlled this to some extent Lung fibrosis or severe damage to the liver, kidney and bone marrow were not found.     

The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone

Background  

The aim of our study was to investigate and evaluate the prognostic value of and correlations between preclinical and clinical factors such as the stage of the disease, blood Hb level before treatment, size of cervix and lymph nodes evaluated by CT, age, dose of irradiation and duration of radiotherapy related to overall survival, disease-free survival, local control and metastases-free survival in cervical cancer patients receiving radiotherapy alone.     

HIV and uterine cervical cancer

There is an increased risk in patients infected with the human immunodeficiency virus (HIV) to he also infected with the human papillomavirus (HPV). Type of HPV is the same in patients infected -or not- by the HIV (in patients with the same criteria of HIV infection). However, there is a higher rate of persistent HPV infections in HIV+ patients, especially with oncogenic virus subtypes. Persistence of high-risk virus is necessary for the development of dysplasic lesions: therefore, there is a higher incidence of cervical intra-epithelial neoplasias (CIN) and cervical cancers in HIV+ patients. In 1993, the Centers of Disease Control (CDC) designated invasive cervical carcinoma as a defining condition of AIDS. After conservative treatment in CIN, the recurrence rate is higher, together with a high rate of positive margins. It may he of some interest to perform a medical treatment, in association with the dysplasia surgical procedure. Invasive cancers have a worse pronostic than in HIV- patients, due to the specific aggressiveness of cervical carcinomas in seropositive patients. Standard treatment consists in surgery and radiotherapy with or without cisplatin chemotherapy, depending on the stage. This treatment is modulated according to CD4 rate. Antiviral treatment and infectious prophylaxis have to be reinforced. A special care will be required for radiotherapy technical execution and clinical (digestive) and hematological follow-up through out the treatment.     

18F-FDG PET/CT在宫颈癌初诊及随访监测中的价值

目的:探讨18F氟脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射断层显像术(positron-emission tomography,PET)/计算机体层摄影术(computed tomography,CT)在宫颈癌初诊及随访监测中的价值。方法:回顾性分析72例宫颈病变患者的18F-FDGPET/CT检查结果及其他临床相关资料。43例初诊疑似宫颈癌的初诊患者行18F-FDGPET/CT检查用于诊断分期和术前评估,29例既往接受过手术、化疗和(或)放疗的宫颈癌患者行18F-FDGPET/CT检查用于随访监测有无肿瘤复发或转移。结果:初诊组43例患者中,18F-FDGPET/CT诊断宫颈癌的敏感度、特异度和准确度分别为83.8%、50.0%和79.1%;31例宫颈癌患者中,淋巴结转移率为38.7%(12/31)。随访监测组29例患者中,11例患者有肿瘤复发、残余和转移,18F-FDGPET/CT诊断的敏感度、特异度和准确度分别为100%、77.8%和86.2%;45.5%(5/11)被检出有小淋巴结转移灶,63.6%(7/11)被检出有远处转移。结论:18F-FDGPET/CT用于宫颈癌初诊及随访监测具有较高的敏感度和特异度,有助于进行准确的临床分期,并及时发现肿瘤的复发、残余和远处转移。     

Prognostic factors of uterine cervical cancer

The large majority of gynecologic malignancies are comprised of uterine cervical cancer, endometrial cancer and ovarian cancer. Prognostic factors for each disease are based on various clinical pathological features, including clinical stage, tumor size, and lymph node metastatis for uterine cervical cancer. In addition to these factors, recent studies have investigated the role of various molecules including tumor markers and Hb level, apoptosis-related molecules as well as various genetic abnormalities as prognostic factor or indicators for uterine cervical cancer. This molecular background of uterine cervical cancer will shape future directions in the increasingly individualized basis of treatment.     

Immunologic treatments for precancerous lesions and uterine cervical cancer

Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem.     

Postmenopausal estradiol-progestagen therapy and risk for uterine cervical cancer

The aim of this study was to evaluate the association of postmenopausal estradiol-progestagen therapy (EPT) with the risk for precancerous lesions, squamous cell carcinoma and adenocarcinoma of the uterine cervix. All Finnish women who had used EPT in 1994-2008 for at least 6 months (n = 243,857) at the age of 50 years or more were identified from the national Medical Reimbursement Registry and linked to the Finnish Cancer Registry. The incidence of cervical precancerous or cancerous lesions among EPT users was compared to that in the background population. There were 210 EPT users with squamous lesions (178 with precancerous and 32 with cancer) and 79 EPT users with glandular lesions (14 precancerous and 65 adenocarcinomas). The ever use of EPT did not associate with the incidence of precancerous lesions, but the risk for squamous cell carcinoma decreased (standardized incidence ratio 0.41; 95% confidence interval 0.28-0.58) and that for adenocarcinoma increased (1.31; 1.01-1.67). After the use of EPT for 5 years, the risk for squamous cell carcinoma decreased (0.34; 0.16-0.65), and the risk for adenocarcinomas increased (1.83; 1.24-2.59). The prolonged use of EPT is associated with the occurrence of cervical malignancies. If the association would be a causal one, the use for 5+ years among 10,000 women followed for 10 years would mean about two to three fewer cases of cervical squamous cell carcinoma but about two extra cases with adenocarcinoma.     

复发性子宫颈癌调强放射治疗的临床观察

目的探讨调强放射治疗（IMRT）治疗复发性宫颈癌的近期疗效及并发症的发生情况。方法回顾性分析38例盆腔复发和腹膜后淋巴结转移的宫颈癌患者采用IMRT放疗的临床资料,其中复发前接受单纯手术20例、单纯放疗8例、手术后辅助放疗者10例,采用6my—X线5～9野照射,曾经接受放疗的患者给予处方剂量95％PTV50GY,无放疗史患者给予处方剂量95％PTV70GY,分割2GY／次,每周5次,共25～35次完成,放疗后3个月评估疗效,并将曾经接受放疗的患者（18例）与单纯手术患者（20例）进行对比,观察两组患者的近期疗效和放疗并发症的发生情况。结果下肢水肿、腰腿疼痛症状缓解率100％,肾盂积水缓解率75％（9／12）,3个月疗效评估：完全缓解率65．8％（25／38）,部分缓解率13．1％（5／38）,稳定率10．5％（4／38）,进展率10．5％（4／38）,有效率78．9％（30／38）。曾经接受根治性放疗和术后放疗与单纯手术比较有效率分别为61％（11／18）（P=0．016）和95％（19／20）,近期毒副作用主要为骨髓抑制,≥Ⅲ度31．6％（12／38）,胃肠道和泌尿系反应均为I～Ⅱ度。结论IMRT放疗治疗复发性宫颈癌,能很好地缓解症状,近期疗效高,对于复发性宫颈癌IMRT放疗是一种有效的方法。     

Clinical results of transcatheter arterial infusion for uterine cervical cancer

The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. Two or three sessions of transcatheter arterial infusion therapy were performed for 68 patients with primary uterine cervical cancer. The number of patients with stage I, II, III, or IV disease were 13, 22, 24, and 9, respectively. Patients with squamous cell carcinoma comprised 3, 17, 17, and 5 of the respective groups, and the patients with stage I and II disease had either adenocarcinoma or adenosquamous carcinoma, or bulky tumor (>4 cm). The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Fifty-eight of the 68 patients (85%) received a radical hysterectomy after transcatheter arterial infusion: 12 of 13 with stage I disease, 21 of 22 with stage II disease, 20 of 24 with stage III disease, and five of nine with stage IV disease. Two patients with stage III disease received radical radiotherapy. The other eight patients (one with stage I disease, one with stage II disease, two with stage III disease, and four with stage IV disease) did not receive an operation after transcatheter arterial infusion because they had distant metastases at the time of operation. Thirty-two of 58 patients (56%) received postoperative radiotherapy. The complete histologic response rates (no active cancer cells) after transcatheter arterial infusion were: 2 of 12 patients with stage I disease, 3 of 21 patients with stage II disease, 5 of 20 patients with stage III disease, and one of five patients with stage IV disease. Tumors with squamous cell carcinoma disappeared at a significantly better rate (10/36, 28%) than did tumors with adenocarcinoma or adenosquamous cell carcinoma (1/22, 5%; p < 0.05). The overall 5-year survival rates of the patients with stages I, II, and III disease were 92.3%, 62.2%, and 71%, respectively. The 5-year survival rates of the patients who underwent surgery with stage I, II, and III disease were 100%, 66.3%, and 71.5%, respectively. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. Transcatheter arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.     

早期宫颈癌术后辅助治疗的研究进展

早期宫颈癌的治疗首选根治性手术,术后存在危险因素的患者需给予放化疗。目前宫颈癌辅助治疗主要依据NCCN推荐的宫颈癌治疗指南,术后存在任何一项高危因素（淋巴结转移、阴道切缘阳性和宫旁浸润）,推荐给予含顺铂同步放化疗;而对于无高危因素,但存在中危因素、符合Sedlis标准的宫颈癌患者,建议术后补充盆腔外照射±含顺铂同期化疗。但是目前早期宫颈癌术后危险因素的评估、辅助治疗的指征以及方式仍存在争议,本文重点阐述早期宫颈癌术后存在危险因素患者辅助治疗的研究进展。     

High dose-rate brachytherapy for elderly patients with uterine cervical cancer

BACKGROUND: The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix. METHODS: From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively. RESULTS: The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34). CONCLUSION: Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.     

宫颈癌术后骨髓保护调强放疗研究

Objective: The aim of this study was to compare bone marrow-sparing intensity-modulated radiotherapy (IMRT) with IMRT without entering pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods: For a cohort of 10 patients, bone marrow-sparing IMRT and routine IMRT planning were designed. The prescribed dose was 45 Gy/1.8 Gy/25f, 95% of the planning target volume received this dose. Doses were computed with a commercially available treatment planning system (...     

Treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy

Objective

To evaluate treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy (POEFRT) with or without chemotherapy.

Methods

Between 1983 and 2006, 35 patients with a pathologically confirmed positive para-aortic node (PAN) or common iliac node (CIN) who underwent a radical hysterectomy with bilateral pelvic lymph node dissection and PAN dissection received POEFRT with (N=23) or without (N=12) chemotherapy. Prognostic factors such as age, stage, size, parametrium invasion, lymphovascular space invasion, nodal station, depth of stromal invasion and use of chemotherapy were analyzed.

Results

With a median follow-up of 44 months, the 5-year overall survival (OS), disease-free survival (DFS), distant failure-free survival (DFFS) and loco-regional failure-free survival rates were 51%, 51%, 59% and 93%, respectively. The use of chemotherapy significantly improved the 5-year OS rate (61% vs. 48%, p=0.004), the 5-year DFS rate (54% vs. 38%, p=0.004) and the 5-year DFFS rate (57% vs. 48%, p=0.009). PAN involvement resulted in a compromised 5-year DFS rate (42% vs. 73%, p=0.002) and 5-year DFFS rate (47% vs. 82%, p=0.004) as compared to CIN involvement. Grade 3 or higher hematological toxicity was observed more frequently in patients who received POEFRT combined with chemotherapy as compared to patients who received POEFRT alone (52% vs. 17%, p=0.04).

Conclusion

The use of POEFRT resulted in an excellent loco-regional control rate. The addition of chemotherapy may improve outcome in patients who have received POEFRT, but with higher manageable toxicity.     

Treatment of cervical carcinoma by total hysterectomy and postoperative external irradiation

The survival rates of 36 patients with early cervical carcinoma who had undergone total hysterectomy and bilateral salpingoophorectomy (THBSO) were compared to the survival rates of 41 patients who were subjected to the radical operation. As an integral part of their therapy both groups postoperatively received adequate doses of external beam supervoltage irradiation. Satisfactory results were obtained in both groups of patients. According to these results THBSO followed by postoperative radiotherapy is adequate treatment for early cervical carcinoma. In comparison to the radical operation or curietherapy alone this type of treatment has the advantage of requiring less surgical or radiotherapeutic expertise; it probably is associated with less morbidity.