NCI CANCERLIT^® Search: Therapy of Cervical Cancer - September 2001

Imprima English

Ultima Vez Modificado: 1 de noviembre del 2001

Late radiation effects to the rectum and bladder in gynecologic cancer patients: the comparison of LENT/SOMA and RTOG/EORTC late-effects scoring systems.
Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.
High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications.
Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis.
Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papillomavirus oncogene expression.
Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38.
Set-up verification of cervix cancer patients treated with long treatment fields; implications of a non-rigid bony anatomy.
Comments on "Chemoradiation for carcinoma of the cervix: advances and opportunities" by Patricia Eifel (Radiat. Res. 154, 229-236, 2000).
Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy.
Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.
Chemotherapy in the treatment of locally advanced cervical cancer during pregnancy.
Radical hysterectomy for early stage cervical cancer and resulting morbidity.
Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation and subsequent pregnancy in the treatment of early invasive cervical cancer.
Ovarian function after radical hysterectomy with ovarian preservation for cervical cancer.
Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer.
Intraoperative electron beam radiotherapy during radical surgery for locally advanced and recurrent cervical cancer.
Impact of hemoglobin levels before and during concurrent chemoradiotherapy on the response of treatment in patients with cervical carcinoma: preliminary results.
Optimizing radiation treatment for cervical cancer.
Postradiation sarcomas of the pelvis after treatment for uterine cervical cancer: review of the CT and MR findings of five cases.
[The association of radiation-induced apoptosis with radiosensitivity of cervical carcinoma]
Lymphocyte radiosensitivity is a significant prognostic factor for morbidity in carcinoma of the cervix.
Image-based dose planning of intracavitary brachytherapy: registration of serial-imaging studies using deformable anatomic templates.
Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer receiving pelvic and para-aortic irradiation.
Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study.
Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects.

CancerMail from the National Cancer Institute

1
UI - 21376163
AU - Anacak Y; Yalman D; Ozsaran Z; Haydaroglu A
TI - Late radiation effects to the rectum and bladder in gynecologic cancer patients: the comparison of LENT/SOMA and RTOG/EORTC late-effects scoring systems.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1107-12
AD - Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey. yanacak@hotmail.com
PURPOSE: To test the correlation of LENT/SOMA and RTOG/EORTC late-effect scales for rectum and bladder, 116 cases with gynecologic malignancies that were treated with radiotherapy were assessed with both scales. METHODS AND MATERIALS: All cases had been treated at least 6 months before the date of assessment with external beam radiotherapy (50--54 Gy to midline) and 1--2 fractions of HDR brachytherapy (2 x 8.5 Gy to point-A for 32 inoperable cases; 1 x 9.25 Gy to 5--9 mm from the ovoid surface for 84 postoperative cases). The patients were questioned with both scales, and the correlation between the two scales was analyzed by Spearman's rho (rank correlation) test. RESULTS: There were 64 cases with uterine cervix carcinoma and 52 cases with endometrium carcinoma, The overall (external + brachy) doses to ICRU points were 57.8 +/- 3.8 Gy for rectum and 59.3 +/- 4.9 Gy for bladder. The statistical analysis of LENT/SOMA and RTOG/EORTC scales revealed a very good correlation for rectum (r = 0.81; p < 0.01) and a good correlation for bladder (r = 0.72; p < 0.01). CONCLUSION: The LENT/SOMA system is a further step on the reporting of late radiation effects. Some modifications will improve its precision, and multicentric randomized studies are needed to test its validity.

2
UI - 21376164
AU - Buffa FM; Davidson SE; Hunter RD; Nahum AE; West CM
TI - Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1113-22
AD - Department of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, London, England, UK. fbuffa@icr.ac.uk
PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

3
UI - 21376165
AU - Ferrigno R; dos Santos Novaes PE; Pellizzon AC; Maia MA; Fogarolli RC; Gentil AC; Salvajoli JV
TI - High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1123-35
AD - Department of Radiation Oncology, Hospital do Cancer A.C. Camargo, Sao Paulo, Brazil. rferrigno@uol.com.br
PURPOSE: This retrospective analysis aims to report results of patients with cervix cancer treated by external beam radiotherapy (EBR) and high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: From September 1992 to December 1996, 138 patients with FIGO Stages II and III and mean age of 56 years were treated. Median EBR to the whole pelvis was 45 Gy in 25 fractions. Parametrial boost was performed in 93% of patients, with a median dose of 14.4 Gy. Brachytherapy with HDR was performed during EBR or following its completion with a dose of 24 Gy in four weekly fractions of 6 Gy to point A. Median overall treatment time was of 60 days. Patient age, tumor stage, and overall treatment time were variables analyzed for survival and local control. Cumulative biologic effective dose (BED) at rectal and bladder reference points were correlated with late complications in these organs and dose of EBR at parametrium was correlated with small bowel complications. RESULTS: Median follow-up time was 38 months. Overall survival, disease-free survival, and local control at 5 years was 53.7%, 52.7%, and 62%, respectively. By multivariate and univariate analysis, overall treatment time up to 50 days was the only statistically significant adverse variable for overall survival (p = 0.003) and actuarial local control (p = 0.008). The 5-year actuarial incidence of rectal, bladder, and small bowel late complications was 16%, 11%, and 14%, respectively. Patients treated with cumulative BED at rectum points above 110 Gy(3) and at bladder point above 125 Gy(3) had a higher but not statistically significant 5-year actuarial rate of complications at these organs (18% vs. 12%, p = 0.49 and 17% vs. 9%, p = 0.20, respectively). Patients who received parametrial doses larger than 59 Gy had a higher 5-year actuarial rate of complications in the small bowel; however, this was not statistically significant (19% vs. 10%, p = 0.260). CONCLUSION: This series suggests that 45 Gy to the whole pelvis combined with four fractions of 6 Gy to point A with HDR brachytherapy is an effective and safe fractionation schedule in the treatment of Stages II and III cervix cancer if realized up to 50 days. To decrease the small bowel complications, we decreased the superior border of the parametrial fields to the S2-S3 level and the total dose to 54 Gy.

4
UI - 21376166
AU - Sakurai H; Mitsuhashi N; Takahashi M; Akimoto T; Muramatsu H; Ishikawa H; Imai R; Yamakawa M; Hasegawa M; Niibe H
TI - Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1136-44
AD - Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Gunma, Japan. hsakurai@med.gunma-u.ac.jp
PURPOSE: A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed. MATERIALS AND METHODS: Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy. RESULTS: A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease. CONCLUSION: Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.

5
UI - 21412293
AU - Finzer P; Kuntzen C; Soto U; zur Hausen H; Rosl F
TI - Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papillomavirus oncogene expression.
SO - Oncogene 2001 Aug 9;20(35):4768-76
AD - Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung Tumorvirus-Immunologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Histone deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A arrest human papillomavirus (HPV)-positive carcinoma cells in G1 to S transition of the cell cycle, which is paralleled by an up-regulation of the cyclin-dependent kinase inhibitors (CKIs) p21CIP1 and p27KIP1 as well as the complete loss of cdk2 activity. Although HPV expression was hitherto thought to be required to maintain a proliferative phenotype of these cells, cdk2 suppression is achieved even in the presence of ongoing viral transcription. While CKIs normally cannot exert their cdk2-inhibitory function in the presence of the viral oncoprotein E7, co-immunoprecipitation experiments revealed that E7 binding is prevented. Increase of p27KIP1 correlates with down-regulation of p45SKP2, a component of the ubiquitin-protein ligase SCF(SKP2) controlling the half-life of regulatory proteins during the cell cycle. HDAC inhibition also triggered an E7-dependent degradation of pRb, while the levels of E2F remained unaffected. The presence of free intracellular E2F and the concomitant up-regulation of CKIs during G1 arrest results in a 'conflicting growth situation', which finally renders the cells to undergo apoptosis. These data provide novel molecular insights into how the transforming potential of HPV can be bypassed and open new therapeutical perspectives for the treatment of cervical cancer.

6
UI - 21304137
AU - Datta NR; Kumar S; Das KJ; Pandey CM; Halder S; Ayyagari S
TI - Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38.
SO - Radiother Oncol 2001 Jul;60(1):15-24
AD - Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
PURPOSE: This paper examines the extent of variation in the applicator geometry during multiple high dose rate (HDR) intracavitary brachytherapy (ICBT) applications and its impact on reporting as per ICRU report 38. MATERIALS AND METHODS: Eighty orthogonal radiographs from 20 consecutive patients of carcinoma cervix (FIGO stages, IIA-IIIB) having four HDR ICBT applications of 6 Gy each at weekly intervals following teletherapy were evaluated. The applicator consisted of a flexible intrauterine tandem (IUT) independent of the ovoid assembly. The applicator geometry was evaluated in terms of: alpha angle, beta angle, intrauterine length (IUTL), interovoid (IOV), os to right ovoid (ORT) and os to left ovoid (OLT) distances along with vertical (VDL) and anteroposterior displacements (ADL) of the os with respect to the ovoids. The Cartesian co-ordinates (X, Y, and Z) of the IUT tip, centre of both ovoids and os were also measured. Doses to right point A (ARD), left point A (ALD), along with a reference volume of 6 Gy for ICRU height (IRH), width (IRW), thickness (IRT) and volume (IRV) were estimated for each application. RESULTS: Highly significant differences (P<0.001) between four insertions in any given patient across 20 patients for alpha angle, beta angle, IUTL, IOV, ORT, VDL, co-ordinates of the IUT, ovoids and os were observed, except for ADL (P=0.041) and OLT (P=0.247). As a consequence, variations were observed in ARD (P=0.027), ALD (P=0.017); IRH, IRW, IRT and IRV (all P<0.001). Applicator factors which influenced the various dose specification parameters were: beta angle and ORT for both ARD and ALD; UTLN, VDL and ORT for IRH; UTLN and IOV for IRW; UTLN for IRT and VDL for the 6 Gy IRV. CONCLUSIONS: A significant variation of the applicator geometry and its movement was observed in patients undergoing multiple HDR ICBT. This could have implications for reporting dose and volume specifications as required by ICRU report 38.

7
UI - 21304138
AU - Quint S; de Boer HC; van Sornsen de Koste JR; Heijmen BJ; Olofsen-van Acht MJ
TI - Set-up verification of cervix cancer patients treated with long treatment fields; implications of a non-rigid bony anatomy.
SO - Radiother Oncol 2001 Jul;60(1):25-9
AD - Department of Radiation Oncology, Daniel den Hoed Cancer Center, Dijkzigt Hospital, University Hospital Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
BACKGROUND AND PURPOSE: For cervix cancer patients, treatment fields may extend up to vertebra L1. In clinical practice, set-up verification is based on measured displacements of the pelvic rim as visible in the caudal part of the treatment fields. The implications of this procedure for the positions of bony structures in the cranial part of the fields were investigated. MATERIALS AND METHODS: Twelve patients had four repeat simulator sessions. Both during treatment simulation (the reference) and the repeat sessions, anterior radiographs were acquired covering the whole treatment field. The films were used to investigate differences between the cranial and the caudal parts of the treatment field in day-to-day bony anatomy displacements. RESULTS: Both in the transversal and the longitudinal directions, these differences were significant (3.5 mm, 1 SD). Indications were found that large differences in the cranio-caudal direction may be correlated with (non-rigid) internal pelvic rim rotations around a lateral axis. In the longitudinal direction, the position of L1 correlated much better with the position of vertebra S1 than with the position of the pelvic rim, which is usually used for set-up verification. CONCLUSIONS: Due to the non-rigid bony anatomy of the studied patients, the usual set-up verification and correction procedure can result in set-up errors of 10 mm and more for structures in the cranial part of the treatment field, even in the case of a perfect set-up of the pelvic rim. Possibly, other patient set-up and immobilization procedures may result in a better day-to-day reproducibility of the 3D bony anatomy shape. (Remaining) Differences in anatomy position changes between the caudal and cranial field ends may be accounted for by using non-uniform clinical target volume-to-planning target volume margins, or by an adapted patient set-up verification and correction protocol.

8
UI - 21342550
AU - van der Zee J; Burger CW; Koper PC
TI - Comments on "Chemoradiation for carcinoma of the cervix: advances and opportunities" by Patricia Eifel (Radiat. Res. 154, 229-236, 2000).
SO - Radiat Res 2001 Aug;156(2):221-2

9
UI - 21423692
AU - Santoso JT; Hannigan EV; Levine L; Solanki DR; Mathru M
TI - Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy.
SO - Gynecol Oncol 2001 Aug;82(2):252-6
AD - Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA. santoso@1331union.com
OBJECTIVE: The goal of this study was to evaluate the safety of hemodilution on global and splanchnic perfusion and blood coagulation during radical hysterectomy. METHODS: A pulmonary artery catheter and a gastric tonometry catheter were placed in 16 patients with cervical carcinoma. Global perfusion indices, splanchnic perfusion index, and coagulation tests were obtained. Blood was removed to achieve a hemoglobin measurement of 8-9 9 g/dL. Three more measurements were repeated after hemodilution, at the end of surgery, and after the retransfusion of blood. Analysis of variance was used to determine statistical significance. RESULTS: Sixteen patients with cervical carcinoma had 1.0 +/- 0.3 L (mean +/- SD) of blood removed and had a blood loss of 0.8 +/- 0.7 L. Hemodiluted preoperative hemoglobin was 8.7 +/- 1 g/dL. All of the global perfusion indices, except for arterial pH and oxygen consumption, decreased after hemodilution and recovered with the retransfusion of blood (P < or = 0.004). Splanchnic perfusion and coagulation tests were unchanged (P > or = 0.1). Major complication was pulmonary edema in one patient. CONCLUSION: Hemodilution during radical hysterectomy, in this select group of patients, does not appear to compromise tissue perfusion or coagulation. Copyright 2001 Academic Press.

10
UI - 21423706
AU - Mundt AJ; Rotmensch J; Waggoner SE; Yamada D; Langhauser C; Fleming GF
TI - Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.
SO - Gynecol Oncol 2001 Aug;82(2):333-7
AD - Department of Radiation and Cellular Oncology, Section of Gynecologic Oncology, Chicago, Illinois 60637, USA. mundt@rover.uchicago.edu
OBJECTIVE: The aim of this study was to determine the feasibility and toxicity of concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in patients with advanced cervical cancer and other pelvic malignancies. METHODS: Eligible patients included those with large or locally advanced cervical cancer. In addition, patients with other advanced gynecologic malignancies were eligible. In part I, vinorelbine was administered as a single agent during pelvic RT at a starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5 mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20 mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week. RESULTS: Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium, 2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity. In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia, with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1 week in 2 of 6 patients (33%). CONCLUSIONS: Concomitant pelvic RT and vinorelbine with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to this combination is associated with significant hematologic toxicity and is thus not a feasible approach. Copyright 2001 Academic Press.

11
UI - 21423726
AU - Rose PG
TI - Chemotherapy in the treatment of locally advanced cervical cancer during pregnancy.
SO - Gynecol Oncol 2001 Aug;82(2):409-10

12
UI - 21423729
AU - Barton DP; Butler-Manuel S; Buttery LD; A'Hern R; Polak JM
TI - Radical hysterectomy for early stage cervical cancer and resulting morbidity.
SO - Gynecol Oncol 2001 Aug;82(2):410-1

13
UI - 21409725
AU - Rodriguez M; Guimares O; Rose PG
TI - Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation and subsequent pregnancy in the treatment of early invasive cervical cancer.
SO - Am J Obstet Gynecol 2001 Aug;185(2):370-4
AD - University Hospital of Cleveland, Case Western Reserve University, Ireland Comprehensive Cancer Center, USA.
BACKGROUND: Recently, pregnancies in patients after radical vaginal trachelectomy and laparoscopic pelvic lymphadenectomy have been reported. Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation has been previously described; however, subsequent outcome and pregnancy has not. METHODS: Three patients with cervical carcinoma, 1 with stage IA1 with lymph-vascular space invasion and 2 with stage IA2, were treated with radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation. RESULTS: All patients underwent the planned procedure with no significant intraoperative or postoperative complications. All patients had return to normal menstrual function. One patient had a successful pregnancy delivered at 39 weeks by cesarean section and is now subsequently pregnant with a second pregnancy. CONCLUSION: Radical abdominal trachelectomy is a technically feasible operation that uses operative techniques familiar to the American-trained gynecologic oncologist and results in wider parametrial resection than radical vaginal trachelectomy. In young patients desiring to retain fertility, successful pregnancies after radical abdominal trachelectomy are possible. Intraoperative and postoperative complications are likely to be lower with an abdominal versus a vaginal approach. Long-term survival of patients treated with radical trachelectomy for early invasive cervical cancer are yet to be determined.

14
UI - 21254124
AU - Ishii K; Aoki Y; Takakuwa K; Tanaka K
TI - Ovarian function after radical hysterectomy with ovarian preservation for cervical cancer.
SO - J Reprod Med 2001 Apr;46(4):347-52
AD - Department of Obstetrics and Gynecology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan. keisui28@med.niigata-u.ac.jp
OBJECTIVE: To investigate the function of preserved ovaries following radical hysterectomy in premenopausal women with cervical carcinoma and to attempt to identify clinical factors influencing ovarian function. STUDY DESIGN: Between 1991 and 1998, 33 premenopausal patients with International Federation of Gynecology and Obstetrics stage IB and II cervical cancer underwent radical hysterectomy with ovarian preservation, including lateral ovarian transposition in 20 patients. In 12 cases of squamous cell carcinoma with deep stromal invasion or a suspicious, positive node, neoadjuvant chemotherapy was performed. Postoperative whole pelvic radiotherapy was administered to 11 patients. Ovarian function was evaluated by serum FSH level during the follow-up period, 12 months to 9 years. RESULTS: Fifteen of 33 patients became climacteric after treatment. Ten of 12 patients over 40 years old became climacteric, as did 5 of 21 under 39 (P = .0013). Using multiple regression analysis, a significant correlation between ovarian dysfunction and age (under 40) was observed (P = .0286). No ovarian recurrence or symptomatic ovarian cyst was observed in preserved ovaries during the study period. CONCLUSION: Ovarian preservation is safe in patients under 40 years old undergoing radical hysterectomy even if they received additional treatment, such as neoadjuvant chemotherapy or postoperative radiotherapy with ovarian transposition.

15
UI - 21411780
AU - Wagenaar HC; Trimbos JB; Postema S; Anastasopoulou A; van der Geest RJ; Reiber JH; Kenter GG; Peters AA; Pattynama PM
TI - Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer.
SO - Gynecol Oncol 2001 Sep;82(3):474-82
AD - Department of Gynecology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
OBJECTIVE: The aim of this study was to evaluate the predictive value of pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor diameter and volume with regard to recurrent disease. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 126 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T(2)-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a combined approach based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and lymph-node involvement) were associated and linked to patient outcome. RESULTS: MRI-based tumor diameter correlated strongly with histological tumor invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume on MRI was significantly associated only with tumor invasion depth into adjacent tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived tumor diameter and volume and clinical FIGO stage are associated with progression-free survival. Correlation analysis showed a strong association between MRI-derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1 versus Ib2) cervical tumors (r = 46.7%, P < 0.01). CONCLUSION: Tumor diameter and volume, determined by pretreatment MRI examinations, predict progression-free survival for patients with invasive cervical carcinoma. This study demonstrates the value of MRI as an adjunct to clinical evaluation of invasive cervical cancer, providing more complete assessment of morphological risk factors important in patient prognosis and treatment planning. Copyright 2001 Academic Press.

16
UI - 21411789
AU - Martinez-Monge R; Jurado M; Aristu JJ; Moreno M; Cambeiro M; Perez-Ochoa A; Lopez-Garcia G; Alcazar JL
TI - Intraoperative electron beam radiotherapy during radical surgery for locally advanced and recurrent cervical cancer.
SO - Gynecol Oncol 2001 Sep;82(3):538-43
AD - Department of Oncology, Clinica Universitaria, Univeridad de Navarra, 31080 Pamplona, Spain. rmartinezm@unav.es
OBJECTIVE: The goal of this study was to determine the toxicity patterns and clinical usefulness of intraoperative electron beam radiotherapy (IOERT) in patients with unfavorable-outcome cervical cancer. METHODS: From January 1986 to June 1999, 67 patients (36 recurrent, 31 primary disease) were treated with IOERT. Previously unirradiated patients received preoperative chemoradiation to 45 Gy with cisplatin 20 mg/m(2) and 5-fluorouracil 1000 mg/m(2). IOERT median dose was 12 Gy for primary disease (range: 10-25) and 15 Gy for recurrent disease (range: 10-20). RESULTS: The 10-year control rate within the area treated with IOERT ("in-field" (IF)) for the entire group was 69.4, with 92.8 and 46.4% 10-year IF control rates for the primary and recurrent patients, respectively. IF control rate correlated with involvement of the parametrial margin (P = 0.001), amount of residual disease (P = 0.001), and pelvic lymph node involvement (P = 0.032). The overall incidence of toxic events that might be attributable to IOERT was 14.9%. Chronic pain was observed in 8 of 67 evaluable patients (11.9%) and motor neuropathy of the lower extremity in one patient (3.2%). CONCLUSIONS: IOERT is a valuable boosting technique in the management of advanced but resectable cervical cancer. Patients, especially recurrent cases, with positive lymph nodes, parametrial involvement, and/or incomplete resections have poor local control rates despite IOERT at the doses used in this study. Copyright 2001 Academic Press.

17
UI - 21433652
AU - Obermair A; Cheuk R; Horwood K; Janda M; Bachtiary B; Schwanzelberger B; Stoiber A; Nicklin JL; Perrin LC; Crandon AJ
TI - Impact of hemoglobin levels before and during concurrent chemoradiotherapy on the response of treatment in patients with cervical carcinoma: preliminary results.
SO - Cancer 2001 Aug 15;92(4):903-8
AD - Queensland Center for Gynecological Cancer, Royal Women's Hospital, Brisbane, Queensland 4029, Australia. a_obermair@hotmail.com
BACKGROUND: In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma. METHODS: The authors collected data on hemoglobin (Hb) levels before and during treatment from 57 patients with cervical carcinoma. The stage of disease ranged between Stage IB and Stage IVA. All patients were treated with concurrent chemoradiation. Response to chemoradiation was evaluated by univariate and multivariate analyses. RESULTS: The mean Hb level at the time of presentation was 12.9 +/- 1.6 g/dL in patients with a complete clinical response (CCR) and 12.1 +/- 1.4 g/dL in those with persistent disease (P = 0.126). In patients with a CCR, the mean nadir Hb level was 11.1 +/- 1.3 g/dL, and in patients with treatment failure, it was 9.8 +/- 1.8 g/dL (P = 0.008). A univariate logistic regression model demonstrated that the nadir Hb level was the most predictive factor for treatment failure (relative risk, 1.92; P = 0.015) followed by disease stage (relative risk, 0.51; P = 0.074). In a multivariate model, the nadir Hb level remained the only prognostically relevant factor predicting the response to chemoradiation. Only patients with nadir Hb values > 11 g/dL throughout chemoradiation had a more than 90% chance of achieving a CCR. CONCLUSIONS: In patients undergoing chemoradiation for cervical carcinoma, the nadir Hb level is highly predictive of response to treatment, whereas the Hb level at the time of presentation is prognostically not significant. Copyright 2001 American Cancer Society.

18
UI - 21434980
AU - Lanciano R
TI - Optimizing radiation treatment for cervical cancer.
SO - Surg Clin North Am 2001 Aug;81(4):859-70
AD - Department of Radiation Oncology, Delaware County Memorial Hospital, Drexel Hill, Pennsylvania 19026, USA.
The technical and radiobiological improvements in the science of radiotherapy, coupled with the use of cisplatin-containing regimens concurrent with radiation therapy, have improved dramatically the cure rate and quality of Life for cervical cancer survivors. Further research is necessary to understand the complex dose distribution of external beam and intracavitary radiation and their relationship to tumor control and complications. With the use of CT-compatible applicators for intracavitary radiation, CT simulation and three-dimensional treatment planning for EBRT, the radiation oncology community should meet this challenge.

19
UI - 21257102
AU - Nakanishi K; Yoshikawa H; Ueda T; Araki N; Tanaka H; Aozasa K; Nakamura H
TI - Postradiation sarcomas of the pelvis after treatment for uterine cervical cancer: review of the CT and MR findings of five cases.
SO - Skeletal Radiol 2001 Mar;30(3):132-7
AD - Department of Radiology, Osaka Seamen's Insurance Hospital, 1-8-30, Chikko, Minato-ku, Osaka 552-0021, Japan.
OBJECTIVE: To characterize the radiologic features of postradiation sarcomas arising in the pelvic bones following treatment for uterine cervical carcinoma. DESIGN AND PATIENTS: Five patients who developed postradiation sarcomas in the pelvic bones following radiation therapy for carcinoma of the uterine cervix within the irradiated field were evaluated. Pelvic radiographs, computed tomography (CT) and magnetic resonance (MR) imaging were undertaken in all patients. Histologic confirmation of the tumor type was obtained. RESULTS: Three patients whose tumors were characterized as an osteosarcoma, an angiosarcoma and a malignant fibrous histiocytoma (MFH) showed a large round or oval mass mainly in the sacroiliac joint which extended into the posterior gluteal soft tissues. In a fourth patient an osteosarcoma developed in the central ilium extending widely into the soft tissues both anteriorly and posteriorly, with calcified areas within the extraosseous mass. The fifth patient had a MFH which showed osteolytic destruction of the cortex of the acetabulum, and minimal soft tissue extension. There were no specific features or signal intensity changes on MR imaging to differentiate these cases from primary sarcomas. CONCLUSION: Postradiation sarcoma must be considered in patients with uterine carcinoma when a soft tissue mass is seen in the previously irradiated field, especially if the mass is posterior to the sacroiliac joint and the latent period is more than 5 years.

20
UI - 21373310
AU - Zhang M; Cai S; Shi D
TI - [The association of radiation-induced apoptosis with radiosensitivity of cervical carcinoma]
SO - Zhonghua Fu Chan Ke Za Zhi 1999 Dec;34(12):729-31
AD - Cancer Hospital Affiliated of Shanghai Medical University, Shanghai 200032.
OBJECTIVE: To study the relationship between apoptosis, radiation-induced apoptosis and radiosensitivity of cervical carcinoma and find new markers for predicting radiosensitivity. METHODS: TdT-mediated bio-dUTP nick end labeling (TUNEL) method was used to check apoptosis cells. The association of radiation-induced apoptosis with tumor volume shrinkage, radiation damage grade and local control rate was analysed. RESULTS: There was no relationship between apoptosis before radiation and tumor volume shrinkage(P > 0.05); Radiation-induced apoptosis had a significant association with tumor volume shrinkage (P < 0.01); In patients with radiation-induced apoptosis 10 or more, the grade of radiation damage IIb-III accounted for 76% (13/17), while for less than 10, it was 39% (5/13, P < 0.05); After 6 months of radiotherapy, local control rate was 88% (15/17) in the former, 69% (9/13) in the latter, respectively (P > 0.05). CONCLUSION: Radiation-induced apoptosis has some reference value for predicting radiosensitivity of cervical carcinoma.

21
UI - 21407942
AU - West CM; Davidson SE; Elyan SA; Valentine H; Roberts SA; Swindell R; Hunter RD
TI - Lymphocyte radiosensitivity is a significant prognostic factor for morbidity in carcinoma of the cervix.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):10-5
AD - CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, United Kingdom. cwest@picr.man.ac.uk
PURPOSE: To study the relationship between pretreatment peripheral blood lymphocyte radiosensitivity and morbidity following radiation therapy. METHODS AND MATERIALS: A prospective study was carried out in which patients with carcinoma of the cervix underwent radiation therapy. Intrinsic radiosensitivity was measured on pretreatment peripheral blood lymphocytes, using a limiting dilution clonogenic assay. Late morbidity was assessed using the Franco-Italian glossary. Results were correlated in an actuarial analysis. RESULTS: There were no correlations between the measured lymphocyte radiosensitivity (SF2) and colony-forming efficiency, patient age, tumor grade, or disease stage. For 83 patients, lymphocyte SF2 was a significant prognostic factor for the probability of developing both any (p = 0.002) and Grade 3 (p = 0.026) morbidity. In 174 patients, stage showed borderline significance as a prognostic factor for morbidity (p = 0.056). However, the type of treatment (intracavitary alone, intracavitary plus parametrial irradiation, single insertion plus whole-pelvis irradiation) was significantly associated with the probability of developing late complications (p = 0.013). There was a weak significant inverse correlation between lymphocyte SF2 and grade of morbidity (r = -0.34, p = 0.002). CONCLUSION: These data highlight the importance of normal cell radiosensitivity as a factor determining radiation therapy response. They also show that peripheral blood lymphocyte SF2 is a highly significant prognostic factor for the probability of developing late radiation morbidity, and that carcinoma of the cervix is a good model for testing radiobiologic principles in the clinic.

22
UI - 21407970
AU - Christensen GE; Carlson B; Chao KS; Yin P; Grigsby PW; Nguyen K; Dempsey JF; Lerma FA; Bae KT; Vannier MW; Williamson JF
TI - Image-based dose planning of intracavitary brachytherapy: registration of serial-imaging studies using deformable anatomic templates.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):227-43
AD - Department of Electrical Engineering, University of Iowa, Iowa City, IA, USA.
Purpose: To demonstrate that high-dimensional voxel-to-voxel transformations, derived from continuum mechanics models of the underlying pelvic tissues, can be used to register computed tomography (CT) serial examinations into a single anatomic frame of reference for cumulative dose calculations.Methods and Materials: Three patients with locally advanced cervix cancer were treated with CT-compatible intracavitary (ICT) applicators. Each patient underwent five volumetric CT examinations: before initiating treatment, and immediately before and after the first and second ICT insertions, respectively. Each serial examination was rigidly registered to the patient's first ICT examination by aligning the bony anatomy. Detailed nonrigid alignment for organs (or targets) of interest was subsequently achieved by deforming the CT exams as a viscous-fluid, described by the Navier-Stokes equation, until the coincidence with the corresponding targets on CT image was maximized. In cases where ICT insertion induced very large and topologically complex rearrangements of pelvic organs, e.g., extreme uterine canal reorientation following tandem insertion, a viscous-fluid-landmark transformation was used to produce an initial registration.Results: For all three patients, reasonable registrations for organs (or targets) of interest were achieved. Fluid-landmark initialization was required in 4 of the 11 registrations. Relative to the best rigid bony landmark alignment, the viscous-fluid registration resulted in average soft-tissue displacements from 2.8 to 28.1 mm, and improved organ coincidence from the range of 5.2% to 72.2% to the range of 90.6% to 100%. Compared to the viscous-fluid transformation, global registration of bony anatomy mismatched 5% or more of the contoured organ volumes by 15-25 mm.Conclusion: Pelvic soft-tissue structures undergo large deformations and displacements during the external-beam and multiple-ICT course of radiation therapy for locally advanced cervix cancer. These changes cannot be modeled by the conventional rigid landmark transformation method. In the current study, we found that the deformable anatomic template registration method, based on continuum-mechanics models of deformation, successfully described these large anatomic shape changes before and after ICT. These promising modeling results indicate that realistic registration of the cumulative dose distribution to the organs (or targets) of interest for radiation therapy of cervical cancers is achievable.

23
UI - 21407973
AU - Portelance L; Chao KS; Grigsby PW; Bennet H; Low D
TI - Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer receiving pelvic and para-aortic irradiation.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):261-6
AD - Department of Radiology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, MO 63110, USA.
PURPOSE: The emergent use of combined modality approach (chemotherapy and radiation therapy) for the treatment of patients with cervical cancer is associated with significant gastrointestinal and genitourinary toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the target structures while sparing the normal organs and could also allow for dose escalation to grossly enlarged metastatic lymph node in pelvic or para-aortic area without increasing gastrointestinal/genitourinary complications. We conducted a dosimetric analysis to determine if IMRT can meet these objectives in the treatment of cervical cancer. METHODS AND MATERIALS: Computed tomography scan studies of 10 patients with cervical cancer were retrieved and used as anatomic references for planning. Upon the completion of target and critical structure delineation, the imaging and contour data were transferred to both an IMRT planning system (Corvus, Nomos) and a three-dimensional planning system (Focus, CMS) on which IMRT as well as conventional planning with two- and four-field techniques were derived. Treatment planning was done on these two systems with uniform prescription, 45 Gy in 25 fractions to the uterus, the cervix, and the pelvic and para-aortic lymph nodes. Normalization was done to all IMRT plans to obtain a full coverage of the cervix with the 95% isodose curve. Dose-volume histograms were obtained for all the plans. A Student's t test was performed to compute the statistical significance. RESULTS: The volume of small bowel receiving the prescribed dose (45 Gy) with IMRT technique was as follows: four fields, 11.01 +/- 5.67%; seven fields, 15.05 +/- 6.76%; and nine fields, 13.56 +/- 5.30%. These were all significantly better than with two-field (35.58 +/- 13.84%) and four-field (34.24 +/- 17.82%) conventional techniques (p < 0.05). The fraction of rectal volume receiving a dose greater than the prescribed dose was as follows: four fields, 8.55 +/- 4.64%; seven fields, 6.37 +/- 5.19%; nine fields, 3.34 +/- 3.0%; in contrast to 84.01 +/- 18.37% with two-field and 46.37 +/- 24.97% with four-field conventional technique (p < 0.001). The fractional volume of bladder receiving the prescribed dose and higher was as follows: four fields, 30.29 +/- 4.64%; seven fields, 31.66 +/- 8.26%; and nine fields, 26.91 +/- 5.57%. It was significantly worse with the two-field (92.89 +/- 35.26%) and with the four-field (60.48 +/- 31.80%) techniques (p < 0.05). CONCLUSION: In this dosimetric study, we demonstrated that with similar target coverage, normal tissue sparing is superior with IMRT in the treatment of cervical cancer.

24
UI - 21419029
AU - Wagenaar HC; Pecorelli S; Mangioni C; van der Burg ME; Rotmensz N; Anastasopoulou A; Zola P; Veenhof CH; Lacave AJ; Neijt JP; van Oosterom AT; Einhorn N; Vermorken JB
TI - Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research and Treatment of Cancer (EORTC) Gynecological Cancer Group study.
SO - Eur J Cancer 2001 Sep;37(13):1624-8
AD - Department of Gynaecology, Leiden University Medical Center, Department of Gynaecology, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. wagenaari@hotmail.com
The aim of this study was to investigate the tumour response rate and toxicity of a combination chemotherapy consisting of mitomycin-C and cisplatin in patients with disseminated squamous-cell carcinoma of the uterine cervix. Chemotherapy consisted of mitomycin, 6 mg/m(2) intravenously (i.v.), and cisplatin, 50 mg/m(2) given i.v., both administered on day 1 of each cycle. The regimen was repeated at 4-weekly intervals. Mitomycin-C/cisplatin were used to treat 33 evaluable patients aged 29-67 years (median: 50 years). All patients except 1 had previously been treated with either surgery, radiation or both. At the initiation of chemotherapy, 8 patients had loco-regional and disseminated disease and 25 women had only distant metastases. The overall response rate was 42% (95% confidence interval (CI): 26-61%). Five complete and nine partial responses were observed with a median duration of response of 7.9 months (95% CI: 3.7-23.5 months). 9 patients had stable disease and 10 developed progressive disease during mitomycin-C/cisplatin-treatment. World Health Organization (WHO) grade III/IV side-effects were documented in 15 women, of whom 10 had gastro-intestinal toxicity, 3 had haematological toxicity, 1 had alopecia and 1 developed an allergic reaction to cisplatin. There were neither drug-related deaths nor severe or irreversible renal or hepatic dysfunction or peripheral neuropathy. The median progression-free survival was 5.0 months (95% CI: 3.6-6.2 months) for all patients and 10.5 months (95% CI: 6.2-15.2 months) for the responders. The median overall survival was 11.2 months (95% CI: 6.5-18.4 months).The mitomycin-C/cisplatin combination showed antitumour activity in the treatment of advanced or recurrent squamous-cell carcinoma of the uterine cervix. The regimen was well tolerated and could be administered on an outpatient basis.

25
UI - 21445774
AU - Dale PS; Tamhankar CP; George D; Daftary GV
TI - Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects.
SO - Cancer Chemother Pharmacol 2001 Jul;47 Suppl():S29-34
AD - Nargis Dutt Memorial Cancer Hospital, Maharashtra, India.
PURPOSE: The use of additional therapy with an oral enzyme preparation containing trypsin, chymotrypsin and papain has been suggested for the reduction of toxicity due to radiation therapy. This study was conducted to test the efficacy and tolerability of this enzyme combination in preventing or reducing the acute side effects of radiation therapy in patients with locally advanced cervical cancer. METHODS: A prospective, randomised, open, clinical trial was carried out on 120 patients (aged 24-85 years) with locally advanced, biopsy-proven carcinomas of the uterine cervix (stages IIa, lIb or IIIb). Patients received 50 Gy of external radiation therapy over a period of 5 weeks, followed by intracavitary brachytherapy (20-30 Gy). Patients assigned to the test group (60 patients) received additional treatment with enzymes. Patients were evaluated at weekly intervals for acute radiation therapy-related side effects, according to the RTOG/EORTC grading criteria, and then after the end of radiation therapy for another 8 weeks. Occurrence of adverse events, if any, was also recorded. RESULTS: The study revealed that the maximum extent of acute radiation side effects was reduced in the enzyme group: skin reactions (mean: 0.97 vs 1.68 in the control group, P < 0.001), vaginal mucosal reactions (0.55 vs 0.85, P = 0.10), genitourinary symptoms (0.93 vs 1.38, P < 0.001) and gastrointestinal reactions (1.12 vs 1.30, P = 0.12). The sum-scores during treatment, expressed as area under the curve, were significantly less in the enzyme treated patients. In the follow-up visits all observed side effects of radiation therapy were of lower intensity in the enzyme group than in the control group. CONCLUSIONS: In patients with locally advanced cancer of the uterine cervix, oral enzyme therapy was found to be effective in significantly reducing radiation therapy-related side effects such as genitourinary symptoms, subcutaneous changes and reactions of the vaginal mucosa.