427Letters to the Editor

Anti-angiogenic therapy in ovarian cancer; what is the bestpopulation?

To the Editor

With regard to the comments by Kichenadasse et al:

1. Our understanding of the impact of anti-angiogenic strategies inovarian cancer is rapidly evolving. Recent subset analysis of ICON 7data indicates that the addition of Bevacizumab seems to impactboth PFS and OS endpoints to the greatest degree in the advancedstage residual disease population with much less effect in earlystage or no residual disease patients [1]. The report on the OCEANStrial shows a tremendous impact on PFS (HR 0.48) with the use ofBevacizumab in a high risk recurrent disease population [2]. Boththese reports combined with the negative results of the currenttrial may indeed indicate that anti-angiogenic strategies are moreapplicable to advanced disease populations.

2. Interesting questions regarding the prevalence of clear cellhistology in the current trial are raised as well. The most likelyexplanation is a changing and improving histologic classification ofovarian cancers over the past several decades. Histologic re-reviewof many of the very early studies in ovarian cancer run by the GOGrevealed a substantial number of borderline tumors and mucinoustumors not likely of ovarian origin. Pathology review in morerecent GOG trials has recognized these factors and these morerigorous criteria for calling a tumor a true early stage ovariancancer probably account for the differences that are pointed out.Corroborating evidence is found in trials for advanced disease suchas GOG 182 and GOG 218 where the prevalence of clear cell cancerremains very low and consistent with trials run in previousdecades [3,4]. The potential for contamination by borderline andnon-ovarian mucinous tumors is much less likely in the advanceddisease population and probably represents a better place toidentify any likely change in prevalence of tumor types over time.

Conflict of interest statementNo conflict of interest.

References

[1] Kristensen G, Perren T, Qian W, et al. Result of interim analysis of overall survival inthe GCIG ICON7 phase III randomized trial of bevacizumab in women with newlydiagnosed ovarian cancer. J Clin Oncol 2011;29 (suppl; abstr LBA5006).

[2] Aghajanian C, Finkler NJ, Rutherford T, et al. OCEANS: a randomized, double-blinded,placebo-controlled phase III trial of chemotherapy with or without bevacizumab(BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primaryperitoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 2011;29 (suppl; abstrLBA5007).

[3] Bookman M, Brady M, McGuire W, et al. Evaluation of new platinum-basedtreatment regimens in advanced-stage ovarian cancer: a phase III trial of theGynecologic Cancer Intergroup. J Clin Oncol 2009;27:1419–25.

[4] Burger RA, Brady MF, Bookman MA, et al. Phase III trial of bevacizumab (BEV) in theprimary treatment of advanced epithelial ovarian cancer (EOC), primary peritonealcancer (PPC) or fallopian tube cancer (FTC): a Gynecologic Oncology Group study. J ClinOncol 2010;28(18S):946s (ASCO Abstract LBA#1).

Robert S. MannelDepartment of Obstetrics and Gynecology,

University of Oklahoma Health Sciences Center,PO Box 26901, Oklahoma City, OK 73126, USA

Fax: +1 405 271 8017.

The effect of operative hysteroscopy conducted before progestintreatment in early stage endometrial cancer from the view offertility

To the Editor

A pilot study by Laurelli et al. evaluated the safety and theeffectiveness of combined operative hysteroscopy (HSC) and progestintherapy as a conservative treatment for FIGO stage IA (intramucous),grade 1, endometrioid adenocarcinoma (AC) of the endometrium[1]. The results showed that the combined therapy had a high rate oflong lasting complete remission (CR) with only one (7%) case ofrecurrent AC which was restricted to the endometrium. A high rate ofcure without progression is an important prerequisite of fertility-sparing treatment.

A recent multicenter prospective study with dilation andcurettage followed by progestin (MPA 600 mg daily for 26 weeks)presented relatively worse outcomes with 67% of CR rate and 47% ofrecurrence rate in patients with AC or atypical endometrial hyperplasia[2]. A substantial portion of patients with non-response or relapse waspathologically upstaged after definitive surgery.

The researchers of this pilot study resected the endometriallesion and a layer of the myometrium below using a cutting loopelectrode and they suggested a possible role of operative HSCwhich could contribute to an accuracy of pathologic diagnosisand clinical staging. However, destruction of the basal layer ofthe endometrium should be determined with caution, which isoften followed by the subsequent replacement of the endometriallining with fibrosis [3]. A prospective study detected a frequencyof 31% of Asherman's syndrome after hysteroscopic resectionof solitary fibroids [4]. Intrauterine adhesion causes infertility,repeated pregnancy loss, and other obstetric complications.The electric damage of the myometrium during hysteroscopicmetroplasty can cause a rare but fatal obstetric outcome, uterinerupture [5].

This research reported that only three patients out of 14 attemptedto conceive and one delivered a term baby because of low desire forchildbearing. One of the aims of conservative treatment is to preservefertility and then to have live births. We think that more followingobstetric outcomes of this protocol can potentiate the role of operativehysteroscopy in a conservative treatment and the effects of trauma tothe uterine wall on future pregnancy should be fully discussed beforefurther validation study.

Conflict of interest statementThe authors declare that there are no conflicts of interest.

References

[1] Laurelli G, Di Vagno G, Scaffa C, Losito S, Del Giudice M, Greggi S. Conservativetreatment of early endometrial cancer: preliminary results of a pilot study. GynecolOncol 2011;120:43–6.

[2] Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, et al. Multicenterphase II study of fertility-sparing treatment with medroxyprogesterone acetate forendometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol2007;25:2798–803.doi:10.1016/j.ygyno.2011.07.095

428 Letters to the Editor

[3] Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome-one century later.Fertil Steril 2008;89:759–79.

[4] Taskin O, Onoglu A, Inal M, Turan E, Sadik S, Vardar E, et al. Long-termhistopathologic and morphologic changes after thermal endometrial ablation.J Am Assoc Gynecol Laparosc 2002;9:186–90.

[5] Sentilhes L, Sergent F, Roman H, Verspyck E, Marpeau L. Late complicationsof operative hysteroscopy: predicting patients at risk of uterine ruptureduring subsequent pregnancy. Eur J Obstet Gynecol Reprod Biol 2005;120:134–8.

Hyun ParkDepartment of Obstetrics and Gynecology, Bundang CHA Medical Center,

CHA university, Seongnam, Gyunggi-do, Republic of Korea

Seok Ju Seong⁎Bo Sung Yoon

Department of Obstetrics and Gynecology, Gangnam CHAMedical Center,CHA university, Seoul, Republic of Korea

⁎Corresponding author. Department of Obstetrics and Gynecology,Gangnam CHA Medical Center, CHA University, 650-9, Yoksam-dong,

Gangnam-gu, Seoul 135-913, Republic of Korea.Fax: +82 2 558 1112.

E-mail address: sjseongcheil@yahoo.co.kr (S. J. Seong).

5 January 2011

doi:10.1016/j.ygyno.2011.01.012