National Cancer Institute®
Last Modified: January 1, 2002
UI - 10791373
AU - van der Zee J; Gonzalez Gonzalez D; van Rhoon GC; van Dijk JD; van
TI - Putten WL; Hart AA Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.
SO - Lancet 2000 Apr 1;355(9210):1119-25
AD - Subdivision of Hyperthermia, Academic Medical Centre, Amsterdam, The Netherlands. firstname.lastname@example.org
BACKGROUND: Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy. METHODS: The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat. FINDINGS: Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up. INTERPRETATION: Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.
UI - 11148562
AU - Adachi S; Ogasawara T; Wakimoto E; Tsuji Y; Takemura T; Koyama K;
TI - Takayasu Y; Inoue J; Nakao N Phase I/II study of intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical carcinoma.
SO - Cancer 2001 Jan 1;91(1):74-9
AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya City, Hyogo, Japan. email@example.com
BACKGROUND: Nedaplatin, a platinum analog with less renal toxicity and similar efficacy for cervical carcinoma, recently has been shown to have a synergistic effect on cervical carcinoma lines in combination with cisplatin. To determine the clinical efficacy of this combination in patients with cervical carcinoma, the authors conducted a Phase I/II study of intravenous nedaplatin and intraarterial cisplatin combined with transcatheter arterial embolization (TAE). METHODS: Eligibility criteria were as follows: cervical carcinoma (Stages IB2-IV; International Federation of Gynecology and Obstetrics), 16-70 years of age, performance status between 0 and 2, and adequate bone marrow, renal, and hepatic function. Nedaplatin (40-70 mg/m2) was administered intravenously on Day 1 followed by intraarterial administration of cisplatin (70 mg/m2) on Day 3 via both uterine arteries by using the Seldinger method. This then was followed by TAE. This course of treatment was repeated every 3 weeks for 3 cycles. RESULTS: Patient data were as follows: age 37-68 (median, 55 years) and Stages IB2:4, IIA:3, IIB:2, IIIA:1, IIIB:3, IVA:2 carcinoma. The response to therapy was defined by magnetic resonance imaging as follows: partial response in 60% (9 of 15) of patients, complete response in 40% (6 of 15) of patients, and an overall response rate of 100% (95% confidence interval, 78-100%). Myelosuppression was manageable. Grade 3/4 renal toxicity was observed in 2 patients who received 70 mg/m2 of nedaplatin. Thirteen patients received radical hysterectomy, 1 patient received lymph node sampling, and 11 patients received adjuvant radiotherapy or chemotherapy. CONCLUSIONS: The maximum tolerable dose was 70 mg/m2 nedaplatin, and the dose-limiting toxicity was renal toxicity. The recommended dose was 60 mg/m2 nedaplatin intravenously followed by 70 mg/m2 cisplatin intraarterially. Intravenous nedaplatin followed by intraarterial cisplatin with TAE appears to be very effective for locally advanced cervical carcinoma. Copyright 2001 American Cancer Society.
UI - 11148563
AU - Ishikawa H; Mitsuhashi N; Sakurai H; Maebayashi K; Niibe H
TI - The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone.
SO - Cancer 2001 Jan 1;91(1):80-9
AD - Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Gunma, Japan. firstname.lastname@example.org
BACKGROUND: It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy. METHODS: Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received radiation therapy alone were reviewed. The combination of external beam irradiation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedded tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCR-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 status, and other parameters on clinical outcome were investigated by univariate analysis. RESULTS: HPV-DNA was detected in 40 patients (76.9%), and 14 patients (26.9%) had mutations of the p53 gene in the study. There was a significant correlation between the existence of HPV and p53 status (P < 0.001). Mutations of the p53 gene were detected in 6 of 12 patients (50%) who had local recurrent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achieved local control. The p53 mutation had a significant correlations with local tumor recurrence. Furthermore, p53 status caused statistical significant differences in the curves of the recurrence free survival rate and local control rate as determined by the log rank test (P = 0.02 and P = 0.03, respectively). Conversely, no obvious correlation with any clinical outcome for patients with cervical carcinoma was found concerning HPV infection. CONCLUSIONS: It is possible that the p53 gene may be used as a predictive factor in radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix. Copyright 2001 American Cancer Society.
UI - 11467376
AU - Lee CT; Ng SH; Ko SF; Wan YL; Liu JW; Chen JB
TI - Culture-negative tuberculous enterovesical fistula mimicking late urological complications after radiotherapy.
SO - Int J Tuberc Lung Dis 2001 Jul;5(7):687
UI - 11487720
AU - Hirashima Y; Kobayashi H; Nishiguchi T; Miura K; Kanayama N
TI - A case of glassy cell carcinoma of the uterine cervix effectively responding to chemotherapy with paclitaxel and carboplatin.
SO - Anticancer Drugs 2001 Aug;12(7):627-30
AD - Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka, 431-3192, Japan. email@example.com
Glassy cell carcinoma (GCC) of the uterine cervix is a highly malignant tumor and has a poor prognosis. As yet, no effective systemic chemotherapy to this tumor has been reported. Here we describe a case of recurrent GCC that responded to paclitaxel and carboplatin combination treatment. The patient, a 32-year-old woman, with clinical staging FIGO IB1 disease had a radical hysterectomy and postoperative radiotherapy. Three months after initial treatment, she had a relapse as peritoneal dissemination, which was confirmed in the second surgery (adnectomy) and which did not respond to platinum-based conventional chemotherapy (cisplatin, adriamycin, cyclophosphamide and carboplatin, etoposide). The recurrent peritoneal tumors responded well to paclitaxel and carboplatin combination treatment. An elevated serum concentration of carcinoembryonic antigen (672 ng/ml) was reduced to 14.4 ng/ml by six such courses. Peritoneal histopathology confirmed a complete response in the third surgery (ileostomy) for adhesive ileus by the radiotherapy. This is the first report of effective systemic chemotherapy with paclitaxel and carboplatin to recurrent GCC of the uterine cervix.
UI - 11504285
AU - Grigsby PW
TI - Cervical cancer: combined modality therapy.
SO - Cancer J 2001 Jul-Aug;7 Suppl 1():S47-50
AD - Mallinckrodt Institute of Radiology, Washington University Medical Center, St Louis, Missouri 63110, USA.
Prospective, randomized studies conducted over the past 10 years have changed the management of patients with advanced cervical cancer. The reviewed studies evaluated the use of surgery, irradiation, and chemotherapy in patients with various stages of cervical carcinoma in the absence and presence of high-risk factors for recurrence. A study by the Radiation Therapy Oncology Group (RTOG) compared pelvic with pelvic plus prophylactic para-aortic irradiation in patients with stages IB (> 4 cm), IIA, and IIB cervical cancer. The 10-year survival advantage was 11% for patients treated with prophylactic para-aortic irradiation. A follow-up study compared pelvic plus prophylactic para-aortic irradiation and brachytherapy with pelvic irradiation, brachytherapy, and chemotherapy with cisplatin and 5-FU in patients with IB-to IVA-stage cervical cancer. Overall and disease-free survivals were significantly improved in patients receiving chemotherapy. In patients with a prevalence of stage IIB and III, the Gynecologic Oncology Group (GOG) demonstrated that treatment with hydroxyurea alone was inferior to cisplatin or cisplatin, 5-FU, and hydroxy-urea in patients treated concurrently with pelvic irradiation and brachytherapy, and the GOG adopted irradiation and weekly cisplatin as standard therapy. Further GOG studies suggest that irradiation and weekly cisplatin chemotherapy without hysterectomy is the optimal treatment for patients with stage IB cervical cancer. High-risk factors for recurrence include tumor size, depth of tumor invasion, lymphovascular space involvement, and lymph node involvement. Prospective, randomized studies conducted by the GOG evaluated the effectiveness of various treatments in patients with high-risk factors. In one study that did not use chemotherapy, the recurrence-free interval was about 10% better for stage IB patients receiving postoperative irradiation after radical hysterectomy and pelvic lymphadenectomy compared with those who received no further therapy. Patients with Stages IB and IIA disease who, following radical hysterectomy and lymph node dissection, are identified as having positive pelvic lymph nodes and positive parametrial involvement, are at higher risk for recurrence and death than the high-risk group described above. An intergroup study conducted by the GOG, RTOG, and Southwest Oncology Group compared postoperative pelvic irradiation alone with postoperative pelvic irradiation plus concurrent chemotherapy in this group of patients. Overall and progression-free survivals were superior for patients receiving chemotherapy, and their greatest survival occurred in patients who received 3 or 4 chemotherapy cycles compared with 1 or 2 cycles or no chemotherapy. These findings are summarized with respect to their implications fortreatment of patients with advanced cervical cancer.
UI - 11549857
AU - Aoki Y; Watanabe M; Sasaki M; Sato T; Kase H; Aida H; Kurata H; Tanaka K
TI - Prognostic factors and failure pattern in lymph node-negative stage IB and II cervical carcinoma treated with radical hysterectomy and postoperative irradiation.
SO - Gynecol Obstet Invest 2001;52(1):13-7
AD - Department of Obstetrics and Gynecology, Niigata University Faculty of Medicine, Niigata, Japan. firstname.lastname@example.org
The aim was to determine the prognostic factors and recurrence pattern in stages IB and II cervical carcinoma patients with negative pelvic lymph nodes. 224 patients with stages IB and II cervical carcinoma underwent radical hysterectomy (RH) from 1982 through 1995. Of 161 patients with negative lymph nodes, 65 patients received postoperative irradiation (RT) and 96 patients were given no further therapy according to surgical pathological findings. The overall 5-year disease-free survival was 94.1%. Two of 96 RH patients (2%) and 10 of 65 RH + RT patients (15%) had recurrence in pelvic and distant sites almost equally. Multivariate analysis revealed deep cervical invasion as the only independent prognostic factor. The 5-year disease-free survival was 98.8% for patients with shallow invasion and 85.8% for patients with deep invasion (p < 0.0001). It is worthwhile to develop new strategies for the lymph node-negative patients with deep stromal invasion. Copyright 2001 S. Karger AG, Basel
UI - 11563873
AU - Stern PL; Faulkner R; Veranes EC; Davidson EJ
TI - The role of human papillomavirus vaccines in cervical neoplasia.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Oct;15(5):783-99
AD - Immunology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, UK.
Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.
UI - 11574761
AU - Krauss T; Huschmand Nia A; Viereck V; Emons G
TI - New developments in the treatment of cervical cancer.
SO - Onkologie 2001 Aug;24(4):340-5
AD - Klinik fur Gynakologie und Geburtshilfe, Georg-August-Universitat, Gottingen.
Cervical cancer is world-wide the second most frequent cancer found in women and represents 12% of all female malignancies. In fact, it is the most common female cancer in developing countries. There is now sufficient evidence to recommend that women with locally advanced cervical cancer confined to the pelvis receive concurrent pelvic radiation and chemotherapy. New surgical techniques such as laparoscopically assisted radical vaginal hysterectomy and trachelectomy (a fertility-preserving radical operation technique) are being established and have to be evaluated for their long-term safety. Causal treatment by developing multivalent antiviral drugs and vaccines is no longer a pure theoretical approach. Despite these improvements, the early diagnosis by colposcopy and gynaecological cytology remains the safest method to ensure early treatment avoiding death of cervical cancer. Copyright 2001 S. Karger GmbH, Freiburg
UI - 11578733
AU - Olszewska AM; Saarnak AE; de Boer RW; van Bunningen BN; Steggerda MJ
TI - Comparison of dose-volume histograms and dose-wall histograms of the rectum of patients treated with intracavitary brachytherapy.
SO - Radiother Oncol 2001 Oct;61(1):83-5
AD - Medical Physics Department, M. Sklodowska-Curie Memorial Cancer Center, W.K. Roentgen 5, 02-781, Warsaw, Poland.
The correlation between dose values from dose-volume histograms (DVHs) and dose values from dose-wall histograms (DWHs) of the rectum tissue of patient with uterine cervix cancer was determined. The minimum dose in 2 cm3 in the high-dose region of the DVH is a good estimate of the dose in the rectum wall.
UI - 11588128
AU - Keefe KA; Schell MJ; Brewer C; McHale M; Brewster W; Chapman JA; Rose
TI - GS; McMeeken DS; Lagerberg W; Peng YM; Wilczynski SP; Anton-Culver H; Meyskens FL; Berman ML A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia.
SO - Cancer Epidemiol Biomarkers Prev 2001 Oct;10(10):1029-35
AD - Division of Gynecologic Oncology, and Chao Family Comprehensive Cancer Center, University of California, Irvine, Medical Center, Orange, California 92868, USA.
To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.
UI - 11605045
AU - Ishiko O; Sumi T; Yoshida H; Matsumoto Y; Honda K; Deguchi M; Yamada R;
TI - Ogita S Association between overexpression of cyclooxygenase-2 and suppression of apoptosis in advanced cancer of the uterine cervix after cyclic balloon-occluded arterial infusion.
SO - Oncol Rep 2001 Nov-Dec;8(6):1259-63
AD - Department of Obstetrics and Gynecology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. email@example.com
Recent advances in cancer chemotherapy have drawn the attention of investigators to the usefulness of chemotherapy for cancer of the uterine cervix in general, and we ourselves have previously reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI), which enabled treatment by hysterectomy in patients with advanced cervical cancer. Nevertheless, there have been some patients in whom CDDP therapy by BOAI was ineffective, and hysterectomy was impracticable. In the present study we investigated the expression of cyclooxygenase-2 (COX-2) in these cases in an attempt to identify the cause of the lack of efficacy. The subjects of the study were 38 women with advanced cervical cancer classified as FIGO (International Federation of Gynecology and Obstetrics) stage III or higher who were admitted to the Department of Gynecology of Osaka City University Medical School Hospital between July expression of COX-2, angiogenic factors, and cancer cell apoptosis, before and after BOAI were examined, and survival rates were compared. The 18 patients in whom BOAI was ineffective showed significantly higher expression of COX-2 after BOAI, and cancer cell apoptosis was inhibited. The 5-year survival rate of these patients was 16.8%, as opposed to 54.1% in the 20 patients in whom BOAI was effective. These results suggest that overexpression of COX-2 inhibits cancer cell apoptosis and adversely influences the prognosis.
UI - 11606081
AU - Aoki Y; Tomita M; Sato T; Watanabe M; Kase H; Fujita K; Kurata H; Tanaka
TI - K Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix.
SO - Gynecol Oncol 2001 Nov;83(2):263-7
AD - Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi dori, Niigata, 951-8510, Japan. firstname.lastname@example.org
OBJECTIVE: To evaluate the response rate and toxicity and to improve survival, neoadjuvant chemotherapy (NAC) was utilized in patients younger than 50 years with locally advanced cervical squamous cell carcinoma. METHODS: Twenty-one patients were treated with preoperative NAC. Eligibility included patients with previously untreated stage IB or IIA with deep stromal invasion assessed by magnetic resonance imaging or bulky tumor or IIB squamous cell carcinoma who were younger than 50 years. The NAC consisted of cisplatin (60 mg/m(2)) on day 1, vinblastine (4 mg/m(2)/day) on days 1 and 2, and peplomycin (10 mg/day) on days 1, 8, and 15 (PVP). Treatment was repeated every 3 weeks for a total of two cycles. All 21 patients underwent radical hysterectomy following NAC. Postoperative radiotherapy was given to 18 patients. We used 21 patients who underwent radical hysterectomy and postoperative radiation therapy as a nonrandomized control group. RESULTS: The response rate for NAC was 86% (18/21). Two patients required discontinuation of PVP treatment after one administration because of grade 4 neutropenia and thrombocytopenia, and decreased carbon monoxide diffusion capacity, respectively. In the NAC group, stromal invasion was significantly reduced (P = 0.0103), and the incidence of lymph node metastasis was decreased. No patients had positive parametrial and vaginal margins. The overall 5-year survival rate was 84.0% in the NAC group, which was significantly better than that in the control group (58.9%) (P = 0.0434). CONCLUSIONS: NAC for younger patients with locally advanced cervical carcinoma is thought to be safe, well tolerated, effective, and useful for increasing operability, decreasing pathological risk factors, and improving survival. Copyright 2001 Academic Press.
UI - 11606083
AU - Ghosh K; Padilla LA; Murray KP; Downs LS; Carson LF; Dusenbery KE
TI - Using a belly board device to reduce the small bowel volume within pelvic radiation fields in women with postoperatively treated cervical carcinoma.
SO - Gynecol Oncol 2001 Nov;83(2):271-5
AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Minnesota Medical Center, Minneapolis, USA.
ObJECTIVE: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique. METHODS: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1). RESULTS: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date. CONCLUSIONS: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity. Copyright 2001 Academic Press.
UI - 11606092
AU - Scambia G; Ferrandina G; Distefano M; Fagotti A; Manfredi R; Zannoni GF;
TI - Mancuso S Is there a place for a less extensive radical surgery in locally advanced cervical cancer patients?
SO - Gynecol Oncol 2001 Nov;83(2):319-24
AD - Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, 00168, Italy. email@example.com
OBJECTIVE: The aim of this study was to assess the association among the pathological status of different lymph node groups and parametrium in a single institutional population of 103 locally advanced cervical cancer (LACC) cases who underwent surgery after a neoadjuvant approach. A series of 29 early cervical cancer patients was also included in the analysis. METHODS: Eighty-two LACC patients with documented clinical response to neoadjuvant treatment and 29 early stage cases underwent radical surgery. The operative technique consisted of a type II-V radical hysterectomy and systematic pelvic lymphadenectomy (median number of lymph nodes removed 46; range 5-140). Sixty-four cases were submitted to para-aortic lymphadenectomy up to the level of the inferior mesenteric artery (median number of lymph nodes removed 13; range 1-37). RESULTS: Two subgroups of lymph nodes were defined: lower pelvic lymph nodes (LPN), including obturator and external iliac nodes, and upper pelvic nodes (UPN) including common iliac, presacral, and internal iliac nodes. Metastatic UPN involvement showed a strict association with LPN involvement: in LACC cases, 6 of 7 (86%) positive UPN cases had tumor disease at the LPN level. The single positive UPN case with negative LPN was intraoperatively identified by palpation and frozen section. Similarly, in early cervical cancer patients, 100% of positive UPN cases showed metastatic involvement at the LPN level. Sixty-three of 70 (90%) LACC patients with negative histological parametrium had negative LPN. Among 12 cases with metastatic involvement of parametrium, 5 cases (41.7%) had positive LPN. In early stage cervical cancer, 23 of 27 (85%) cases with negative parametrium showed no lymph nodal involvement. Intraoperative palpation of the parametrium could identify all cases with parametrial involvement not predicted by LPN status. CONCLUSIONS: These data offer the basis for tailoring the extent of radical surgery in LACC patients, through the selection of those lymph node stations likely to provide reliable information on the pathological status of UPN and parametrium. Copyright 2001 Academic Press.
UI - 11606099
AU - Huh WK; Gomez-Navarro J; Arafat WO; Xiang J; Mahasreshti PJ; Alvarez RD;
TI - Barnes MN; Curiel DT Bax-induced apoptosis as a novel gene therapy approach for carcinoma of the cervix.
SO - Gynecol Oncol 2001 Nov;83(2):370-7
AD - Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 35249, USA. firstname.lastname@example.org
OBJECTIVE: The transfer of tumor suppressor genes has been shown to revert the malignant phenotype. In this regard, bax is a pro-apoptotic molecule that also functions as a tumor suppressor. The purpose of this study was to evaluate bax as a gene therapeutic in the context of cervical cancer. METHODS: Efficiency of viral transduction in cervical cancer cell lines and primary cervical cancer cells was evaluated with an adenoviral vector encoding green fluorescent protein and luciferase, respectively. We generated a recombinant adenoviral vector that encodes the bax gene under inducible conditions. To this end, expression of this pro-apoptotic gene was controlled by a Cre-LoxP system. Following infection with the recombinant bax adenovirus, the viability of cervical cancer cell lines and primary cervical cancer cells was evaluated using crystal violet staining and FACS analysis. Apoptotic cell death was monitored using annexin V staining. RESULTS: High levels of viral infection were observed in all cervical cancer cell lines (>85%) and primary cervical cancer cells. Significant cytotoxicity was seen in all cervical cancer cells lines and, more importantly, patient-derived primary cervical cancer cells. Moreover, bax-mediated cell death occurred via an apoptotic pathway. CONCLUSIONS: Our results indicate that a bax recombinant adenoviral vector causes cell death mediated via an apoptotic pathway in multiple cervical cancer cell lines and primary cervical cancer cells. These data suggest that bax may be a candidate for human gene therapy in the setting of cervical carcinoma. Copyright 2001 Academic Press.
UI - 11678487
AU - Rock CL; Moskowitz A; Huizar B; Saenz CC; Clark JT; Daly TL; Chin H;
TI - Behling C; Ruffin MT 4th High vegetable and fruit diet intervention in premenopausal women with cervical intraepithelial neoplasia.
SO - J Am Diet Assoc 2001 Oct;101(10):1167-74
AD - Department of Family and Preventive Medicine, University of California, San Diego, La Jolla 92093-0901, USA. email@example.com
OBJECTIVE: To examine whether diet intervention can promote increased vegetable and fruit intake, as reflected in increased plasma carotenoid and decreased plasma total homocysteine concentrations, in premenopausal women with cervical intraepithelial neoplasia, a precancerous condition. DESIGN: Randomized controlled diet intervention study. SUBJECTS: Fifty-three free-living premenopausal women who had been diagnosed with cervical intraepithelial neoplasia, were randomly assigned to an intervention (n = 27) or a control (n = 26) group. INTERVENTION: Individualized dietary counseling to increase vegetable and fruit intake. MAIN OUTCOME MEASURES: Diet was assessed by food frequency questionnaire. Plasma carotenoids and total homocysteine were measured at enrollment and at 6 months follow up. ANALYSIS: Associations between baseline plasma concentrations of carotenoids and homocysteine and influencing factors were examined with multiple regression analysis. Repeated measures analysis of variance was used to test for group by time effects in these plasma concentrations. Plasma carotenoids at baseline and 6 months in the study groups, and differences in homocysteine concentrations from baseline to 6 months, were compared with independent sample t tests. RESULTS: Repeated measures analysis of variance showed significant group by time effects (P<.01) in plasma carotenoid and homocysteine concentrations. In the intervention group, total plasma carotenoids increased by an average of 91%, from 2.04+/-0.13 (mean+/-standard error of the mean) to 3.90+/-0.56 micromol/L and plasma total homocysteine was reduced by 11%, from 9.01+/-0.40 to 8.10+/-0.44 micromol/L (P<.003). Neither changed significantly in the control group. APPLICATIONS: Individualized dietary counseling can effectively promote increased vegetable and fruit intake in premenopausal women. This dietary pattern may reduce risk for cancer and other chronic diseases and also promote an improvement in folate status.
UI - 11697325
AU - Ryu S; Stein JP; Chung CT; Lee YJ; Kim JH
TI - Enhanced apoptosis and radiosensitization by combined 13-cis-retinoic acid and interferon-alpha2a; role of RAR-beta gene.
SO - Int J Radiat Oncol Biol Phys 2001 Nov 1;51(3):785-90
AD - Department of Radiation Oncology, SUNY Health Science Center, Syracuse, USA. firstname.lastname@example.org
PURPOSE: Combined use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFNalpha) induced significant radiosensitization in human cervical cancer ME-180 cell line, whereas it failed to achieve similar radiation enhancement in HeLa cells. The differential radiosensitization could be from the difference of retinoic acid receptor (RAR) expression because RAR-beta was highly expressed in ME-180 cells in contrast to the HeLa cells where RAR-beta was not detectable. We examined the role of this gene in mediating radiosensitization by cRA and IFNalpha, and explored the mechanism of radiation-induced cell killing. METHODS AND MATERIALS: Human cervical cancer cell lines, ME-180 and HeLa, were treated with cRA and IFNalpha followed by radiation. Apoptosis and radiosensitization were quantitated by TUNEL assay (in situ DNA nick end labeling) and colony-forming ability of surviving cells. The cells were transfected with bcl-2 gene and RAR-beta gene to test the role of these genes in mediating radiosensitization and apoptosis. RESULTS: Synergistic radiosensitization and apoptosis was observed by combined use of cRA and IFNalpha with radiation in ME-180 cells which express high level of RAR-beta mRNA, whereas these were not seen in HeLa cells where RAR-beta mRNA is not detectable. Both radiosensitization and apoptosis were abolished by bcl-2 gene in ME-180 cells. RAR-beta gene transfection induced similar radiation enhancement and apoptosis in HeLa cells. CONCLUSION: Apoptosis and radiation response were enhanced in the cells with high level of RAR-beta mRNA expression. The RAR-beta gene appears to mediate the radiation-induced apoptosis by cRA and IFNalpha. These findings indicate that presence of RAR-beta in the cancer cells could be exploited for patient selection in using these drugs for apoptosis and radiosensitization.
UI - 11689597
AU - Kim WC; Kim GE; Suh CO; Loh JJ
TI - High versus low dose rate intracavitary irradiation for adenocarcinoma of the uterine cervix.
SO - Jpn J Clin Oncol 2001 Sep;31(9):432-7
AD - Department of Radiation Oncology, Inha University, College of Medicine, Inchon, Korea. email@example.com
BACKGROUND: Traditionally, low dose rate (LDR) brachytherapy has been used as a standard modality in the treatment of patients with carcinoma of the uterine cervix. The purpose of this work was to evaluate the effects of high dose rate (HDR) brachytherapy on patients with adenocarcinoma of the uterine cervix and to compare them with the 1992, 104 patients suffering from adenocarcinoma of the uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University. LDR brachytherapy was carried out on 34 patients and HDR brachytherapy on 70 patients. In the LDR group, eight patients were in stage IB, six in IIA, 12 in IIB, three in IIIA and five in IIIB. External radiation therapy was delivered with 10 MV X-rays, 2 Gy fraction per day, total dose of whole pelvis 36-52 Gy (median 46 Gy). LDR radium intracavitary irradiation was performed with a Henschke applicator, 37-59 Gy targeted at point A (median 43 Gy). In the HDR group, there were 16 patients in stage IB, six in IIA, 32 in IIB and 16 in IIIB. The total whole pelvis dose of external radiation was 40-50 Gy (median 44 Gy), daily 1.8-2.0 Gy. HDR Co-60 intracavitary irradiation was performed with a remotely controlled after-loading system (RALS), 30-48 Gy (median 39 Gy) targeted at point A, three times per week, 3 Gy per fraction. RESULTS: The 5-year overall survival rate in the LDR group was 72.9, 61.9 and 35.7% in stage I, II and III, respectively and the corresponding figures for HDR were 87.1, 58.3 and 43.8% (p > 0.05). There was no statistical difference between the HDR group and the LDR group in terms of the 5-year overall survival rate from adenocarcinoma of the uterine cervix. There was a late complication rate of 12% in the LDR group and 27% in the HDR group. The incidence of late complications in stages II and III was higher in the HDR group than in the LDR group (31.6 vs 16.7% in stage II, 37.3% vs 12.5% in stage III, p > 0.05). No prognostic factors were evident in the comparison between the two groups. CONCLUSION: There was no difference in terms of 5-year survival rate in the patients with adenocarcinoma of the uterine cervix between those treated with HDR and those treated with LDR brachytherapy. Even though late complication rates were higher in the HDR group, most of them were classified as grade I. This retrospective study suggests that HDR brachytherapy may be able to replace LDR brachytherapy in the treatment of adenocarcinoma of the uterine cervix.
UI - 11680016
AU - Budrukkar AN; Shrivastava SK; Jalali R; Agarwal JP; Deshpande DD; Nehru
TI - RM; Dinshaw KA Transperineal low-dose rate iridium-192 interstitial brachytherapy in cervical carcinoma stage IIB.
SO - Strahlenther Onkol 2001 Oct;177(10):517-24
AD - Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India.
PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.
UI - 11683043
AU - Xiang W; Weingandt H; Liessmann F; Klein S; Stepp H; Baumgartner R;
TI - Hillemanns P Photodynamic effects induced by aminolevulinic acid esters on human cervical carcinoma cells in culture.
SO - Photochem Photobiol 2001 Oct;74(4):617-23
AD - Department of Obstetrics and Gynecology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Fluorescence diagnosis and photodynamic therapy using 5-aminolevulinic acid (ALA) provide new methods for the detection and treatment of cervical cancer and especially its precursors. However, these techniques are restricted by the rate of uptake of the hydrophilic ALA, its poor diffusion through the bilayer of biological membranes or both. In this study we evaluated the effect of some esterified ALA derivatives on the induction of the endogenous photosensitizer, protoporphyrin IX (PpIX), and the photodamage in cultured human cervical cells (C33-A and CaSki). The kinetics of PpIX accumulation showed that ALA esters, especially the ALA-hexylester (h-ALA), induced significantly faster PpIX formation than ALA at the same concentration (0.5 mM). The PpIX induction showed a dose-dependent characteristic. The highest PpIX values could be achieved by an up to 1.3-13-fold lower concentration of ALA esters than with ALA. Using the Annexin V assay, apoptosis was found to be induced rapidly after irradiation in both ALA- and ALA esters-treated cells. On measuring mitochondrial activity, the incubation with h-ALA induced a more pronounced photodamage. The results indicate that improved or at least comparable photodynamic effects can be achieved by using remarkably lower doses of ALA esters.
UI - 11682933
AU - Chirenje ZM; Rusakaniko S; Akino V; Mlingo M
TI - A review of cervical cancer patients presenting in Harare and Parirenyatwa Hospitals in 1998.
SO - Cent Afr J Med 2000 Oct;46(10):264-7<