Zervixkarzinom

Kernaussagen

In den letzen Jahren hat sich das Spektrum der Therapie- und Präventionsmöglichkeiten beim Zervixkarzinom deutlich erweitert.

Seit Kurzem stehen für die primäre Prävention 2 Impfstoffe zur Verfügung. Die Impfung ist am effektivsten für junge Frauen ohne HPV-Infektion, d. h. vor dem ersten Sexualkontakt.

Die Stadieneinteilung des Zervixkarzinoms erfolgt bei den sichtbaren Läsionen entsprechend der FIGO bis heute rein klinisch, wobei der wichtigste Prognosefaktor, der Lymphknotenstatus, nicht abgebildet wird. CT und MRT haben eine unzureichende Aussagekraft in der Beurteilung pelviner und paraaortaler Lymphknoten.

Nur ein chirurgisches Staging, insbesondere als laparoskopischer Eingriff, erlaubt eine exakte Stadieneinteilung, auch wenn bisher keine valide randomisierte Studie den Überlebensvorteil einer Therapiemodifikation nach chirurgischer Stadieneinteilung bewiesen hat.

Die operative Therapie des primären Zervixkarzinoms umfasst, je nach Tumorstadium, die Konisation und einfache Hysterektomie, das chirurgische Staging, die Trachelektomie als fertilitätserhaltende Operation, die radikale Hysterektomie mit ihren verschiedenen Zugangswegen und Modifikationen sowie die exenterative Chirurgie. Bei fortgeschrittenem Tumor (ab FIGO II B) und bei Befall der pelvinen und / oder paraaortalen Lymphknoten ist die primäre Radiochemotherapie der Standard. Kombinationen aus radikaler Hysterektomie und Radiochemotherapie verdoppeln das Risiko höhergradiger Spättoxizität, ohne die onkologischen Ergebnisse zu verbessern, und sollten deshalb vermieden werden. Das operative Staging erlaubt eine sichere Patientenselektion für die operative Therapie oder die primäre Radiochemotherapie.

Einen Sonderfall stellt die Therapie im Stadium IV A. Es existiert keine Standardtherapie. Der Einsatz der exenterativen Chirurgie bzw. der Radiochemotherapie sollte interdisziplinär diskutiert und kritisch gegeneinander abgewogen werden. Insbesondere für Patientinnen ohne Fernmetastasen, bei denen eine R0-Resektion möglich erscheint, ist die Exenteration eine valide Alternative zur Radiochemotherapie.

In der metastasierten, rezidivierten Situation dient die systemische Therapie der Symptomverbesserung, der Verbesserung der Lebensqualität und der Verlängerung des Überlebens. Die aktuelle Phase-III-Studie der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) vergleicht die Kombination aus Paclitaxel / Topotecan gegen Cisplatin / Topotecan beim rezidivierten oder persistierenden Zervixkarzinom.

Ein interdisziplinäres Team und eine vertrauensvolle Zusammenarbeit sind beste Voraussetzungen für die optimale Therapie der Patientinnen. Das Zervixzentrum der Charité bietet allen niedergelassenen und den in der Klinik tätigen Kolleginnen und Kollegen die Möglichkeit, Patientinnen in der interdisziplinären Konferenz via Internet vorzustellen, um therapeutische Konzepte abzustimmen bzw. Zweitmeinungen einzuholen.

Wir stehen unter der Website https://tumorzentrum-cbf-ssl.charite.de/ für die wöchentliche Konferenz bzw. über die Website des Zervixzentrums http://cervixcentrum.charite.de/ zur Verfügung.

Publication History

Publication Date:
07 October 2008 (online)

• Literatur

• 1 Parkin DM, Bray F, Ferlay J. et al Global cancer statistics, 2002.. CA Cancer J Clin 2005; 55: 74-108
• 2 Robert-Koch-Institut, Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V.. Hrsg Krebs in Deutschland 2003–2004. Häufigkeiten und Trends.. 6. überarb. Aufl. Berlin; 2008
• 3 Statistisches Bundesamt. Gesundheitsberichterstattung, Todesursachenstatistik.. www.gbe-bund.de, Abfrage: 18.7.2008
• 4 zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application.. Nat Rev Cancer 2002; 2: 342-350
• 5 Walboomers JM, Jacobs MV, Manos MM. et al Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.. J Pathol 1999; 189: 12-12
• 6 Munoz N, Bosch FX, de Sanjose S. et al Epidemiologic classification of human papillomavirus types associated with cervical cancer.. N Engl J Med 2003; 348: 518-527
• 7 Clifford GM, Smith JS, Plummer M. et al Human papillomavirus types in invasive cervical cancer worldwide: a metaanalysis.. Br J Cancer 2003; 88: 63-73
• 8 Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections.. J Clin Virol 2005; 32: S16-S24
• 9 Villa LL, Costa RL, Petta CA. et al Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised doubleblind placebo-controlled multicentre phase II efficacy trial.. Lancet Oncol 2005; 6: 271-278
• 10 Villa LL, Costa RL, Petta CA. et al High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6 / 11 / 16 / 18 L1 virus-like particle vaccine through 5 years of follow-up.. Br J Cancer 2006; 95: 1459-1466
• 11 Garland SM, Hernandez-Avila M, Wheeler CM. et al for the Females United to Unilaterally Reduce Endo / Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.. N Engl J Med 2007; 356: 1928-1943
• 12 FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions.. N Engl J Med 2007; 356: 1915-1927
• 13 Fachinformation Gardasil.. Merck C., inc., Whitehouse station, NJ 08889, USA; 2006
• 14 Harper DM, Franco EL, Wheeler C. et al Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.. Lancet 2004; 364: 1757-1765
• 15 Harper DM, Franco EL, Wheeler CM. et al Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial.. Lancet 2006; 367: 1247-1255
• 16 Wheeler CM, Teixeira J, Romanowski B. et al High and sustained HPV-16 and 18 antibody levels through 6.4 years in women vaccinated with Cervarix™ (GSK HPV-16 / 18 AS04 vaccine). ESPID (European Society for Paediatric Infectious Diseases. Graz, Austria: May 13–17; 2008)
• 17 Press release EMEA: statement on the safety of Gardasil.. London: January 24; 2008 (www.emea.europa.eu/humandocs/PDFs/EPAR/gardasil/Gardasil_press_release.pdf
• 18 Villa LL, Ault KA, Giuliano AR. et al Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18.. Vaccine 2006; 24: 5571-5583
• 19 Carter JJ, Koutsky LA, Hughes JP. et al Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection.. J Infect Dis 2000; 181: 1911-1919
• 20 Viscidi RP, Schiffman M, Hildesheim A. et al Seroreactivity to human papillomavirus (HPV) types 16, 18, or 31, and risk of subsequent HPV infection: results from a populationbased study in Costa Rica.. Cancer Epidemiol Biomarkers Prev 2004; 13: 324-327
• 21 Gall SA, Teixeira J, Wheeler CM. et al Substantial impact on precancerous lesions and HPV infections through 5.5 years in women vaccinated with the HPV-16 / 18 L1 VLP AS04 candidate vaccine. Presented at American Association for Cancer Research (AACR). Los Angeles, CA, USA: April 14–18; 2007
• 22 Paavonen J, Jenkins D, Bosch FX. et al HPV PATRICIA study group. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial.. Lancet 2007; 369: 2161-2170 Erratum in: Lancet 2007; 370: 1414
• 23 Brown D. HPV Type 6 / 11 / 16 / 18 vaccine: first analysis of cross-protection against persistent infection, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS) caused by oncogenic HPV types in addition to 16 / 18. Presented at: 47^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, IL, USA: 17–20 September; 2007
• 24 Robert-Koch-Institut. Mitteilung der Ständigen Impfkommission (STIKO) am Robert-Koch-Institut: Impfung gegen humane Papillomaviren (HPV) für Mädchen von 12 bis 17 Jahren – Empfehlung und Begründung.. Epidemiologisches Bulletin 2007; 12: 97-103
• 25 Pathirana D. für das HPV Management Forum. S3-Leitfür das HPV Management Forumlinie zur Impfprävention HPV-assoziierter Neoplasien.. Chemotherapie Journal 2008; 17: 120-171
• 26 Luna J, Saah A, Hood S. et al Safety, efficacy, and immunogenicity of quadrivalent HPV vaccine (Gardasil) in women aged 24–45.. 24^th International Papillomavirus Congress: Beijing, China: November 3–9; 2007
• 27 Schwarz TF, Dubin G. the HPV Vaccine Study Investigators for Adult Women. Human papillomavirus (HPV) 16 / 18 L1 AS04 virus-like particle (VLP) cervical cancer vaccine is immunogenic and well-tolerated 18 months after vaccination in women up to age 55 years (Abstract 3007).. J Clin Oncol 2007 2007; 25 ASCO Annual Meeting Proceedings Part I
• 28 Wright TCJr, Huh WK, Monk BJ. et al Age considerations when vaccinating against HPV.. Gynecol Oncol 2008; 109: 40-47
• 29 Gross G. Für das Deutsche HPV-Management-Forum Wer sollte wann, wo und wie geimpft werden? Antworten des HPV-Management-Forums auf viel diskutierte Fragen, die mit Einführung von zwei unterschiedlichen HPV-Impfstoffen zur Prävention des Zervixkarzinoms und der Condylomata acuminata in Zusammenhang stehen.. Dtsch Ärzteblatt 2006; 103: 3384-3388
• 30 Schneider A, Schwarz TF, Hammerschmidt T. et al Einfluss einer Impfung gegen humane Papillomviren auf die Inzidenz und Mortalität von Zervixkarzinom in Deutschland.. Med Klin 2007; 102: 515-523
• 31 Altenhofen L. 2005 Hochrechnung zur Akzeptanz von Gesundheitsuntersuchungen und Krebsfrüherkennungsuntersuchungen bei gesetzlich Versicherten.. Berlin: Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik Deutschland
• 32 Peto J, Gilham C, Fletcher O. et al The cervical cancer epidemic that screening has prevented in the UK.. Lancet 2004; 364: 249-956
• 33 Kaufmann AM, Schneider A. Therapeutic human papillomavirus vaccination.. Therapy 2008; 5: 339-348
• 34 Hertel H, Köhler C, Elhawary T. et al Laparoscopic staging compared with imaging techniques in the staging of advanced cervical cancer.. Gynecol Oncol 2002; 87: 46-52
• 35 Hricak H, Gatsonis C, Coakley FV. et al Early invasive cervical cancer: CT and MR imaging in preoperative evaluation – ACRIN / GOG comparative study of diagnostic performance and interobserver variability.. Radiology 2007; 245: 491-498
• 36 Sironi S, Buda A, Picchio M. et al Lymph node metastasis in patients with clinical early-stage cervical cancer: detection with integrated FDG- PET / CT.. Radiology 2006; 238: 272-279
• 37 Yildirim Y, Sehirali S, Avci ME. et al Integrated PET / CT for the evaluation of para-aortic nodal metastasis in locally advanced cervical cancer patients with negative conventional CT findings.. Gynecol Oncol 2008; 108: 154-159
• 38 Loft A, Berthelsen AK, Roed H. et al The diagnostic value of PET / CT scanning in patients with cervical cancer: a prospective study.. Gynecol Oncol 2007; 106: 29-34
• 39 Choi HJ, Roh JW, Seo SS. et al Comparison of the accuracy of magnetic resonance imaging and positron emission tomography / computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma: a prospective study.. Cancer 2006; 106: 914-922
• 40 Fagotti A, Fanfani F, Longo R. et al Which role for pretreatment laparoscopic staging?. Gynecol Oncol 2007; 107: 101-105
• 41 Ayhan A, Al RA, Baykal C. et al A comparison of prognoses of FIGO stage I B adenocarcinoma and squamous cell carcinoma.. Int J Gynecol Cancer 2004; 14: 279-285
• 42 Singh N, Arif S. Histopathologic parameters of prognosis in cervical cancer–a review.. Int J Gynecol Cancer 2004; 14: 741-750
• 43 Creasman WT, Kohler MF. Is lymph vascular space involvement an independent prognostic factor in early cervical cancer?. Gynecol Oncol 2004; 92: 525-529
• 44 Lai CH, Huang KG, Hong JH. et al Randomized trial of surgical staging (extraperitoneal or laparoscopic) versus clinical staging in locally advanced cervical cancer.. Gynecol Oncol 2003; 89: 160-167
• 45 Vidauretta J, Bermudez A, di Oaola G. et al Laparoscopic staging in locally advanced cervical carcinoma: a new possible philosophy?. Gynecol Oncol 1999; 75: 366-371
• 46 Marnitz S, Köhler C, Roth C. et al Stage-adjusted chemoradiation in cervical cancer after transperitoneal laparoscopic staging.. Strahlenther Onkol 2007; 183: 473-478
• 47 Leblanc E, Narducci F, Frumovitz M. et al Therapeutic value of pretherapeutic extraperitoneal laparoscopic staging of locally advanced cervical carcinoma.. Gynecol Oncol 2007; 105: 304-311
• 48 Tillmanns T, Lowe MP. Safety, feasibility and costs of outpatient laparoscopic extraperitoneal aortic nodal dissection for locally advanced cervical carcinoma.. Gynecol Oncol 2007; 106: 370-374
• 49 Marnitz S, Köhler C, Roth C. et al Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer?. Gynecol Oncol 2005; 99: 536-544
• 50 Hertel H, Köhler C, Grund D. et al Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: prospective multicenter study of 100 patients with early cervical cancer.. Gynecol Oncol 2006; 103: 506-511
• 51 Plante M, Renaud MC, Francois H. et al Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature.. Gynecol Oncol 2004; 94: 614-623
• 52 Shepherd JH, Spencer C, Herod J. et al Radical vaginal trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer – cumulative pregnancy rate in a series of 123 women.. Brit J Obstet Gynaecol 2006; 113: 719-724
• 53 Marchiole P, Benchaib M, Buenerd A. et al Oncological safety of laparoscopic-assisted vaginal radical trachelectomy (LARVT or Dargent's operation): a comparative study with laparoscopic-assisted vaginal radical hysterectomy.. Gynecol Oncol 2007; 106: 132-141
• 54 Dursun P, LeBlanc E, Nogueira MC. Radical vaginal trachelectomy (Dargent's operation): a critical review of the literature.. Eur J S. 2007; 33: 933-941
• 55 Shepherd JH, Ind T, Tozer A. Fertility preservation surgery for early stage cervical cancer: lessons learned.. Gynecol Oncol 2008; 108: 63-63
• 56 Wright JD, Grigsby PW, Brooks R. et al Utility of parametrectomy for early stage cervical cancer treated with radical hysterectomy.. Cancer 2007; 110: 1281-1286
• 57 Stegemann M, Louwen M, van der Velden J. et al The incidence of parametrial tumor involvement in selected patients with early cervix cancer is too low to justify parametrectomy.. Gynecol Oncol 2007; 105: 475-480
• 58 Rob L, Charvat M, Robova H. et al Less radical fertility-sparing surgery than radical trachelectomy in early cervical cancer.. Int J Gynecol Cancer 2007; 17: 304-310
• 59 Altgassen C, Altgassen C, Hertel H. et al Multicenter validitation study of the sentinel lymph node concept in cervical cancer: AGO study group.. J Clin Oncol 2008; 26: 2943-2951
• 60 Wertheim E. The extended abdominal operation for carcinoma uteri.. Am J Obstet Gynecol 1912; 6: 169-232
• 61 Schauta F. Die erweiterte vaginale Totaloperation des Uterus beim Collumkarzinom.. Wien J Safar 1908
• 62 Piver MS, Rutledge F, Smith JP. Five classes of extended hysterectomy for women with cervical cancer.. Obstet Gynecol 1974; 44: 265-272
• 63 Querleu D, Morrow CP. Classification of radical hysterectomy.. Lancet Oncol 2008; 9: 297-303
• 64 Hertel H, Schneider A, Altgassen C, Hillemanns P. Zervixkarzinom.. Gynäkologe 2008; 41: 355-360
• 65 Zakashansky K, Bradley WH, Nezhat FR. New techniques in radical hysterectomy.. Curr Opinion Obstet Gynecol 2008; 20: 14-19
• 66 Höckel M. Totale mesometriale Resektion.. Gynäkologe 2008; 41: 361-368
• 67 Yabuki Y, Asamoto A, Hoshiba T. et al Radical hysterectomy: an anatomic evaluation of parametrial dissection.. Gynecol Oncol 2000; 77: 155-163
• 68 Frumovitz M, dos Reis R, Sun CC. et al Comparison of total laparoscopic radical hysterectomy and abdominal radical hysterectomy for patients with early-stage cervical cancer.. Obstet Gynecol 2007; 110: 96-102
• 69 Ghezzi F, Cromi A, Ciravolo G. et al Surgicopathologic outcome of laparoscopic versus open radical hysterectomy.. Gynecol Oncol 2007; 106: 502-506
• 70 Li G, Yan X, Shang H. et al A comparison of laparoscopic radical hysterectomy and pelvic lymphadenectomy and laparotomy in the treatment of I b–II a cervical cancer.. Gynecol Oncol 2007; 105: 176-180
• 71 Steed H, Rosen B, Murphy J. et al A comparison of laparoscopic-assisted radical vaginal hysterectomy and radical abdominal hysterectomy in the treatment of cervical cancer.. Gynecol Oncol 2004; 93: 588-593
• 72 Uccella S, Laterza R, Ciravolo G. et al A comparison of urinary complications following total laparoscopic radical hysterectomy and laparoscopic pelvic lymphadenectomy to open abdominal surgery.. Gynecol Oncol 2007; 107: 47-149
• 73 Boggess J. Robotic surgery in gynecologic oncology: evolution of a new surgical paradigm.. J Robotic Surg 2007; 1: 31-37
• 74 Köhler C, Tozzi R, Possover M. et al Explorative laparoscopy prior to exenterative surgery.. Gynecol Oncol 2002; 86: 311-315
• 75 Marnitz S, Köhler C, Müller M. et al Indications for primary and secondary exenterations in patients with cervical cancer.. Gynecol Oncol 2006; 103: 1023-1030
• 76 Marnitz S, Dowdy S, Lanowska M. et al Exenterations 60 years after first description – results of a survey among US and German gynecologic oncology centres.. Int J Gynecol Oncol 2008; [submitted]
• 77 Whitney CW, Sause W, Bundy BN. et al Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage II B–IV A carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.. J Clin Oncol 1999; 17: 1339-1348
• 78 Rose PG, Bundy BN, Watkins EB. et al Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.. N Engl J Med 1999; 340: 1144-1153
• 79 Stehman FB, Bundy BN, Kucera PR. et al Hydroxyurea, 5-fluorouracil infusion, and cisplatin adjunct to radiation therapy in cervical carcinoma: a phase I–II trial of the Gynecologic Oncology Group.. Gynecol Oncol 1997; 66: 262-267
• 80 Pearcey R, Brundage M, Drouin P. et al Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.. J Clin Oncol 2002; 20: 966-972
• 81 Morris M, Eifel PJ, Lu J. et al Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.. N Engl J Med. 1999; 340: 1137-1143
• 82 Stehman FB, Ali S, Keys HM. et al Radiation therapy with or without weekly cisplatin for bulky stage 1 B cervical carcinoma: follow-up of a Gynecologic Oncology Group trial.. Am J Obstet Gynecol 2007; 197: 503-506
• 83 Green J, Kirwan J, Tierney J. et al Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.. Cochrane Database Syst Rev 2005; 3: CD002225-CD002225
• 84 Keys HM, Bundy BN, Stehman FB. et al Gynecologic Oncology Group. Radiation therapy with and without extrafascial hysterectomy for bulky stage I B cervical carcinoma: a randomized trial of the Gynecologic Oncology Group.. Gynecol Oncol 2003; 89: 343-353
• 85 Rose PG, Ali S, Watkins E. et al Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study.. J Clin Oncol 2007; 25: 2804-2810
• 86 Therapieempfehlungen des National Cancer Institut zum Zervixkarzinom.. www.cancer.gov
• 87 Pötter R, Dimopoulos J, Georg P. et al Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer.. Radiother Oncol 2007; 83: 148-155
• 88 Moore KN, Gold MA, McMeekin DS. et al Vesicovaginal fistula formation in patients with Stage IV A cervial cancer.. Gyn Oncol 2007; 106: 498-501
• 89 Rotman M, Pajak TF, Choi K. et al Prophylactic extendedfield irradiation of para-aortic lymph nodes in stages II B and bulky I B and II A cervical carcinomas. Ten-year treatment results of RTOG 79–20.. J Amer Med Assoc 1995; 274: 387-393
• 90 Haie C, Pejovic MH, Gerbaulet A. et al Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group.. Radiother Oncol 1988; 11: 101-112
• 91 Small WJr, Winter K, Levenback C. et al Extended-field irradiation and intracavitary brachytherapy combined with cisplatin chemotherapy for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of ARM 1 of RTOG 0116.. Int J Radiat Oncol Biol Phys 2007; 68: 1081-1087
• 92 Perez CA, Grigsby PW, Chao KS. et al Tumor size, irradiation dose, and long-term outcome of carcinoma of uterine cervix.. Int J Radiat Oncol Biol Phys 1998; 41: 307-317
• 93 Eifel PJ, Thoms WW, Smith TL. et al The relationship between brachytherapy dose and outcome in patients with bulky endocervical tumors treated with radiation alone.. Int J Radiat Oncol Biol Phys 1994; 28: 113-118
• 94 Lanciano RM, Won M, Coia LR. et al Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: a final report of the 1973 and 1978 patterns of care studies.. Int J Radiat Oncol Biol Phys 1991; 20: 667-676
• 95 Girinsky T, Rey A, Roche B. et al Overall treatment time in advanced cervical carcinomas: a critical parameter in treatment outcome.. Int J Radiat Oncol Biol Phys 1993; 27: 1051-1056
• 96 Fyles A, Keane TJ, Barton M. et al The effect of treatment duration in the local control of cervix cancer.. Radiother Oncol 1992; 25: 273-279
• 97 Lanciano RM, Pajak TF, Martz K. et al The influence of treatment time on outcome for squamous cell cancer of the uterine cervix treated with radiation: a patternsof-care study.. Int J Radiat Oncol Biol Phys 1993; 25: 391-397
• 98 Petereit DG, Sarkaria JN, Chappell R. et al The adverse effect of treatment prolongation in cervical carcinoma.. Int J Radiat Oncol Biol Phys 1995; 32: 1301-1307
• 99 Chen MF, Tseng CJ, Tseng CC. et al Clinical outcome in posthysterectomy cervical cancer patients treated with concurrent Cisplatin and intensity-modulated pelvic radiotherapy: comparison with conventional radiotherapy.. Int J Radiat Oncol Biol Phys 2007; 67: 1438-1444
• 100 Beriwal S, Gan GN, Heron DE. et al Early clinical outcome with concurrent chemotherapy and extended-field, intensity-modulated radiotherapy for cervical cancer.. Int J Radiat Oncol Biol Phys 2007; 68: 166-171
• 101 Salama JK, Mundt AJ, Roeske J. et al Preliminary outcome and toxicity report of extended-field, intensitymodulated radiation therapy for gynecologic malignancies.. Int J Radiat Oncol Biol Phys 2006; 65: 1170-1176
• 102 Huang KG, Lee CL, Tsai CS. et al A new approach for laparoscopic ovarian transposition before pelvic irradiation.. Gynecol Oncol 2007; 105: 234-237
• 103 Toki N, Tsukamoto N, Kaku T. et al Microscopic ovarian metastasis of the uterine cervical cancer.. Gynecol Oncol 1991; 41: 46-51
• 104 Yamamoto R, Okamoto K, Yukiharu T. et al A study of risk factors for ovarian metastases in stage I b–III b cervical carcinoma and analysis of ovarian function after a transposition.. Gynecol Oncol 2001; 82: 312-316
• 105 Veerasarn V, Lorvidhaya V, Kamnerdsupaphon P. et al A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results.. Gynecol Oncol 2007; 104: 15-23
• 106 Kim YS, Shin SS, Nam JH. et al Prospective randomized comparison of monthly fluorouracil and cisplatin versus weekly cisplatin concurrent with pelvic radiotherapy and high-dose rate brachytherapy for locally advanced cervical cancer.. Gynecol Oncol 2008; 108: 195-200
• 107 Kirwan JM, Symonds P, Green JA. et al A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer.. Radiother Oncol 2003; 68: 217-226
• 108 Matthews KS, Rocconi RP, Straughn JM. Complete uterine necrosis following chemoradiation for advanced cervical cancer: a case report.. Gynecol Oncol 2007; 106: 265-267
• 109 Marnitz S, Köhler C, Füller J. et al Uterus necrosis after radiochemotherapy in two patients with advanced cervical cancer.. Strahlenther Onkol 2006; 182: 45-51
• 110 Lerouge D, Touboul E, Lefranc JP. et al Preoperative concurrent radiation therapy and chemotherapy for operable bulky carcinomas of uterine cervix stages I B2, II A, and II B with proximal parametrial invasion.. Cancer Radiother 2004; 8: 168-177
• 111 Modarress M, Maghami FQ, Golnavaz M. et al Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage I B–II B bulky cervical cancer and with tumor diameter greater than 4 cm.. Int J Gynecol Cancer 2005; 15: 483-488
• 112 Petsuksiri J, Chansilpa Y, Therasakvichya S. et al Treatment options in bulky stage I B cervical carcinoma.. Int J Gynecol Cancer 2008; in press
• 113 Darus CJ, Callahan MB, Nguyen QN. et al Chemoradiation with and without adjuvant extrafascial hysterectomy for I B2 cervical carcinoma.. Int J Gynecol Cancer 2007; [E-pub ahead of print]
• 114 Bonomi P, Blessing JA, Stehman FB. et al Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study.. J Clin Oncol 1985; 3: 1079-1085
• 115 Thiepgen T. The role of chemotherapy in the management of carcinoma of the cervix.. Cancer J 2003; 9: 425-425
• 116 McGuire WP, Blessing JA, Moore D. et al Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study.. J Clin Oncol 1996; 14: 792-795
• 117 Morris M, Brader KR, Levenback C. et al Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix.. J Clin Oncol 1998; 16: 1094-1098
• 118 Muderspach LI, Blessing JA, Levenback C. et al A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study.. Gynecol Oncol 2001; 81: 213-215
• 119 Brader KR, Morris M, Levenback C. et al Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design.. J Clin Oncol 1998; 16: 1879-1884
• 120 Omura GA, Blessing JA, Vaccarello L. et al Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study.. J Clin Oncol 1997; 15: 165-171
• 121 Moore DH, Blessing JA, McQuellon RP. et al Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.. J Clin Oncol 2004; 22: 3113-3119
• 122 Long HJ, Bundy BN, Grendys EC. et al Gynecologic Oncology Group study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group study.. J Clin Oncol 2005; 23: 4626-4633
• 123 Monk BJ, Huang HQ, Cella D. et al Gynecologic Oncology Group study. Quality of life outcomes from a randomized phase III trial of cisplatin with or without topotecan in advanced carcinoma of the cervix: a Gynecologic Oncology Group study.. J Clin Oncol 2005; 23: 4617-4625
• 124 Monk BJ, Sill M, McMeekin DS. et al A randomized phase III trial of four cisplatin containing doublet combinations in stage IV B, recurrent or persistent cervical cancer: a Gynecologic Oncology Group (GOG) study.. J Clin Oncol 2008; 26 (suppl): 5504-5504
• 125 Landoni F, Maneo A, Colombo A. et al Randomised study of radical surgery versus radiotherapy for stage I b–II a cervical cancer.. Lancet 1997; 350: 535-540