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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Cervical Cancer - January 2002
National Cancer Institute®
Last Modified: January 1, 2002
Table of Contents
1
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. zee@hyph.azr.nl
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.
2
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. adachi@hyo-med.ac.jp
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.
3
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. hisikawa@med.gunma-u.ac.jp
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.
4
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
5
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.
hirame@hama-med.ac.jp
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.
6
UI - 11527305
AU - Jones B
TI -
Outcomes of cervix cancer treatments in 1993.
SO - Clin Oncol (R Coll Radiol) 2001;13(3):237-8
7
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.
8
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. yoichi@med.niigata-u.ac.jp
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
9
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.
10
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
11
UI - 11686113
AU - Simpson L
TI -
One on one. Leatrice Simpson. Interview by Enid Vazquez.
SO - Posit Aware 2001 May-Jun;12(3):24
12
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.
13
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.
14
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. ishikoo@msic.med.osaka-cu.ac.jp
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.
15
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. yoichi@med.niigataa-u.ac.jp
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.
16
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.
17
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. giovanni.scambia@libero.it
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.
18
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. whuh@uab.edu
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.
19
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. clrock@ucsd.edu
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.
20
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. sryu1@hfhs.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.
21
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. cancer@inha.ac.kr
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.
22
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.
23
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.
24
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<
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