台灣婦癌醫學會 Taiwan Association of Gynecologic Oncologists

                                                        本期編輯 陳子健 醫師   

壹、 會務報告

一、近期學會活動

二、南區婦癌學術研討會圓滿閉幕

感謝周振陽大夫與鄭雅敏大夫的鼎力支持，以及演講者們的精心準備，使得2/14 於成大所舉辦的南區婦癌學術研討會能順利進行，並且讓與會者獲益匪淺。

三、第六屆第五次理監事聯席會議報告

秘書長報告：

一、會員：郭宗正，編號：152，來函自98年起申請退 會。

      二、97年度「專科醫師甄審」報告：兩會共5人參加筆試，3人通過；5人參加口試，1人通過（廖正義醫師）。

三、第十四屆台灣癌症聯合學術年會將於今年5月2、3日在國防醫學中心舉辦，本學會邀請兩位國外的演講者，一位是從M.D. Anderson 的Dr. Kavanagh；另一位是UCSF的Dr. Chan；另外年會壁報論文截稿日期為2/15，請各位踴躍投稿多多參與。

      四、行政院國家科學委員會行文「總統科學獎」，如有推薦人選請各位理監事向學會提出。

    各委員會工作報告：

      一、教育委員會（周振陽醫師）：

1、「婦癌專科醫師訓練辦法及資格審核要點」請大家看看是否有需要再修改的地方。

2、建議教育委員會委員分成三組（排除自己訓練的學生），審查準會員的口頭及書面報告，以決定是否可予通過或要補充資料。

3、對以往曾報考過「專科醫師甄審」之準會員，仍需每年繳交兩次書面報告（但不需口頭報告），經由教育委員會認定通過，始得報考專科醫師甄審。

二、學術研究委員會（張廷彰醫師）「學術研究委員案」：

1、現以三大婦科癌症為主題， Cervical Cancer推派賴瓊慧醫師擔任召集人；Endometrial Cancer推派顏明賢醫師擔任召集人；Ovarian Cancer推派周振陽醫師擔任召集人；DSMC推派陳祈安醫師擔任召集人。

2、三月份開始每個星期一晚上6：00∼9：00召開一個主題，提供交通費及餐點。試行2個月再來檢討後續作法。

捌、討論事項

提案1：97年度工作報告、決算收支表、資產負債表、現金出納表、基金收支表、財產目錄及工作人員待遇表討論案。（秘書處）

決議：通過。

提案2：98年度工作計畫、收支預算表討論案。（秘書處）

決議：通過。

提案3：第十四屆台灣癌症聯合學術年會第一次籌備會議中提案：「建議往後台灣癌症聯合學術年會能配合在ASCO之後的七月舉辦」，若有過半數學會同意，可在2010年開始實施。（秘書處）

決議：因適逢暑假期間比較不容易邀請到國外的講者，本國會員的出席率也可能會比較低，而且為颱風季節，因此表決不同意延後。

提案4：97年報考專科醫師甄審之準會員，有兩位筆試未通過，四位口試未通過，今年（98）是否還需要口頭報告及繳交書面報告？（秘書處）

決議：今年（98）以前有報考專科醫師甄審的人，不需要再口頭報告，但書面報告仍須繳交（因會有新的病例）。

提案5：部分準會員在97年11月口頭報告過，今年（98）是否還要再口頭報告？（秘書處）

決議：請該組教育委員會來審核認定是否符合報考的資格。

提案6：本會與中華民國婦癌醫學會兩會會員資格互相承認討論案

決議：暫時先成立兩會共同秘書辦事處，兩會同步工作，後續進程仍待討論。

四、學會網站誠徵衛教文章

歡迎各位會員踴躍賜稿，以充實學會的網站內容。來稿請e-mail至tago.gyn@gmail.com

貳、 會員動態及意見與回應

(歡迎提供會員動態、意見，以及衛教文章（學會E-mail address: tago.gyn@gmail.com)

参、 前月文獻選錄

Ca-Cancer J Clin

Ref 1: Lymphedema 之處置

N Engl J Med

Ref 2: Surgical safety checklist 有助於減少mortality & morbidity

Lancet

Ref 3: 不贊成對於early endometrial cancer施行lymphadenectomy的另一 

       篇大作

Ref 4: 不贊成為intermediate- or high-risk early endometrial cancer 進

       行external beam irradiation

J Natl Cancer Inst

Ref 5: 測HPV type 18 DNA load 沒什麼用

Ref 6: 以HPV 作initial cervical screening的strategy 最好

J Clin Oncol

Ref 7: ASCO guidelines for chemotherapy and radiotherapy protectants

Lancet Oncol

Ref 8:  Livial 還是會增加breast cancer 的 recurrence

Cancer

Ref 9:  GOG 的ovarian cancer pretreatment CA125 研究

Br J Cancer

  Ref 10:  carboplatin + paclitaxel 處理carcinoma of unknown primary

Gynecol Oncol

Ref 11: 關於卵巢癌 secondary cytoreduction 之meta-analysis

Ref 12: PET 有助於找出salvageable asymptomatic recurrent cervical

        cancer

Ref 13: Cochrane review: interval debulking 有效嗎?

  Ref 14: GOG cervical cancer CCRT with cisplatin-paclitaxel

Ref 15: Carboplatin + Lipo dox for platinum-sensitive recurrent ovarian

        cancer 之台灣經驗

Obstet Gynecol

Ref 16: NIH 發表CIN2常會自行regress

Ref 17: early ovarian cancer在手術中弄破, 其實是會影響預後的

Am J Obstet Gynecol

Ref 18: Laparoscopic staging 於early ovarian cancer

Br J Obstet Gynaecol

Ref 19: Early endometrial cancer 或 atypical complex hyperplasia 之

        保守處置

Ref 1: CA Cancer J Clin. 2009 Jan-Feb;59(1):8-24.

Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment.
Lawenda BD, Mondry TE, Johnstone PA.
Radiation Oncology, Naval Medical Center, San Diego, CA, 92134, USA. brian.lawenda@med.navy.mil
The primary goals of oncologic therapy are the compassionate care of cancer patients, eradication of disease, and palliation of symptoms. Advances in various targeted therapies such as highly conformal and image-guided radiotherapy techniques, sentinel lymph node dissection, and molecularly targeted agents hold the promise of allowing those goals to be reached with fewer treatment-related complications. Unfortunately, certain side effects remain problematic due to the inability to completely avoid injuring normal tissues. Lymphedema, a chronic condition that occurs as a result of the body's inability to drain lymph fluid from the tissues, is a common treatment-related side effect experienced by cancer patients. In this review, many of the important aspects of lymphedema with which clinicians who treat cancer patients should be familiar are outlined, including the anatomy, pathophysiology, diagnosis, and management of this condition. The authors also identify some of the resources available both to cancer patients with lymphedema and to the clinicians who treat them. It is hoped that this review will convey the importance of the early identification and management of this incurable disorder because this is essential to minimizing its complications.

Ref 2:  N Engl J Med. 2009 Jan 29;360(5):491-9.

A surgical safety checklist to reduce morbidity and mortality in a global population.
Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AH, Dellinger EP, Herbosa T, Joseph S, Kibatala PL, Lapitan MC, Merry AF, Moorthy K, Reznick RK, Taylor B, Gawande AA; Safe Surgery Saves Lives Study Group.Collaborators (47)

Harvard School of Public Health, Massachusetts General Hospital, Boston, USA.
BACKGROUND: Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery. METHODS: Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation. RESULTS: The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001). CONCLUSIONS: Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals.

Ref 3:    Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.
Lancet. 2009 Jan 10;373(9658):125-36.
ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK.Collaborators (180) BACKGROUND: Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. METHODS: From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. FINDINGS: After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). INTERPRETATION: Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.

Ref 4:  Lancet. 2009 Jan 10;373(9658):137-46.

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.
ASTEC/EN.5 Study Group, Blake P, Swart AM, Orton J, Kitchener H, Whelan T, Lukka H, Eisenhauer E, Bacon M, Tu D, Parmar MK, Amos C, Murray C, Qian W.Collaborators (158)

BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Ref 5:  J Natl Cancer Inst. 2009 Feb 4;101(3):153-61.
Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3.
Xi LF, Koutsky LA, Castle PE, Wheeler CM, Galloway DA, Mao C, Ho J, Kiviat NB.
Department of Pathology, School of Medicine, University of Washington, 1914 North 34th St, Suite 300, Seattle, WA 98103, USA. longfu@u.washington.edu
BACKGROUND: The clinical relevance of the amount of human papillomavirus type 18 (HPV18) DNA in cervical tissue (ie, HPV18 DNA load) is unknown. METHODS: Study subjects were 303 women who were HPV18 positive at enrollment into the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. HPV18 DNA load, expressed as copies of HPV18 per nanogram of cellular DNA, at enrollment was quantitatively measured. Subjects were followed up semiannually for a period of 2 years for detection of cervical intraepithelial neoplasia 2-3 (CIN2-3). A linear regression model was used to examine associations of CIN2-3 with HPV18 DNA load. All statistical tests were two-sided. RESULTS: CIN2-3 was confirmed in 92 of 303 (30.4%) HPV18-positive women. Among women without CIN2-3, HPV18 DNA load was positively associated with increasing severity of cervical cytology at enrollment (Ptrend < .001). However, among those with CIN2-3, HPV18 DNA load was not associated with severity of cervical cytology at enrollment (Ptrend = .33). The ratios of geometric means of HPV18 DNA load at enrollment among women with CIN2-3, relative to those without, were 6.06 (95% confidence interval [CI] = 0.31 to 117.92) for those with normal cytology at enrollment, 0.50 (95% CI = 0.10 to 2.44) for those with ASC-US, 0.11 (95% CI = 0.03 to 0.46) for those with LSIL, and 0.07 (95% CI = 0.01 to 0.80) for those with high-grade squamous intraepithelial lesion (HSIL). After adjusting for age and coinfection with other high-risk HPVs, a statistically significant association of lower HPV18 DNA load with CIN2-3 was observed among women with LSIL or HSIL at enrollment (P = .02). Within the 2-year period, HPV18 DNA load was unrelated to the timing of CIN2-3 diagnosis. Overall results were similar when the outcome was CIN3. CONCLUSIONS: HPV18 DNA load was higher for women with LSIL or HSIL at enrollment with no evidence of CIN2-3 during the 2-year follow-up period than it was for women with CIN2-3. Thus, testing for high levels of HPV18 DNA does not appear to be clinically useful.

Ref 6: J Natl Cancer Inst. 2009 Jan 21;101(2):88-99.

Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
Naucler P, Ryd W, Törnberg S, Strand A, Wadell G, Elfgren K, Rådberg T, Strander B, Forslund O, Hansson BG, Hagmar B, Johansson B, Rylander E, Dillner J.
Department of Medical Microbiology, Lund University, Malmö University Hospital, Malmö, Sweden.
BACKGROUND: Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective. METHODS: We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. RESULTS: Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests). CONCLUSIONS: Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

Ref 7: J Clin Oncol. 2009 Jan 1;27(1):127-45.

American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants.
Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, Cohen GI, Emami B, Gradishar WJ, Mitchell RB, Thigpen JT, Trotti A 3rd, von Hoff D, Schuchter LM.
Memorial Sloan-Kettering Cancer Center, New York, NY, USA. guidelines@asco.org
PURPOSE: To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer. METHODS: An update committee reviewed literature published since the last guideline update in 2002. RESULTS: Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002. RECOMMENDATIONS: Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m(2) doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy-associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.

Ref 8  Lancet Oncol. 2009 Feb;10(2):135-46.

Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.
Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Yip CH, Egberts J, Mol-Arts M, Mulder R, van Os S, Beckmann MW; LIBERATE Study Group.Collaborators (296)

Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, Netherlands. kenemans@vumc.nl

BACKGROUND: Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints. METHODS: Between July 11, 2002, and Dec 20, 2004, women surgically treated for a histologically confirmed breast cancer (T(1-3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of four. The primary endpoint was breast-cancer recurrence, including contralateral breast cancer, and was analysed in the intention-to-treat (ITT) and per-protocol populations; the margin for non-inferiority was set as a hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number NCT00408863. FINDINGS: Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1 years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098 (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254 [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor symptoms and bone-mineral density improved significantly with tibolone, compared with placebo. INTERPRETATION: Tibolone increases the risk of recurrence in breast cancer patients, while relieving vasomotor symptoms and preventing bone loss.

Ref 9: Cancer. 2009 Jan 20;115(5):1028-1035.

The prognostic value of pretreatment CA 125 in patients with advanced ovarian carcinoma : a Gynecologic Oncology Group study.
Zorn KK, Tian C, McGuire WP, Hoskins WJ, Markman M, Muggia FM, Rose PG, Ozols RF, Spriggs D, Armstrong DK.
Division of Gynecologic Oncology, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
BACKGROUND:: The objective of the current study was to determine the prognostic significance of a pretreatment serum CA 125 level in patients with advanced epithelial ovarian carcinoma (EOC) who received treatment with a standard chemotherapy regimen. METHODS:: Patients with International Federation of Gynecology and Obstetrics stage III/IV ovarian carcinoma who were on 1 of 7 Gynecologic Oncology Group (GOG) phase 3 trials and received treatment with a standard regimen of intravenous cisplatin and paclitaxel were included. A Cox regression model was used to assess the impact of CA 125 levels drawn before the initiation of chemotherapy on progression-free survival (PFS) both overall and by subgroup, including surgical debulking status, disease stage, and histologic subtype. RESULTS:: In total, 1299 patients who were on the cisplatin/paclitaxel arms of the GOG trials were eligible. The median CA 125 level was 246 U/mL. Only 7.6% of patients had a normal CA 125 level (Shorter PFS was observed with increasing CA 125 and persisted in multivariate analysis. Overall and in the serous subgroup, a 1-fold increase in CA 125 level was associated with a 7% increase in the hazard of disease progression (P < .001). This association was even more pronounced in patients who had stage III disease that was debulked to microscopic disease (15%; P = .003) and in patients who had endometrioid tumors (17%; P = .001). CONCLUSIONS:: A normal CA 125 level in the setting of advanced EOC was rare even after surgical debulking. The pretreatment CA 125 level was an independent predictor of PFS in patients with advanced EOC who received a standard chemotherapy regimen, particularly in the setting of disease that was debulked to a microscopic residual and in the serous or endometrioid subtypes.

Ref 10 Br J Cancer. 2009 Jan 13;100(1):44-9.

Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial.
Huebner G, Link H, Kohne CH, Stahl M, Kretzschmar A, Steinbach S, Folprecht G, Bernhard H, Al-Batran SE, Schoffski P, Burkart C, Kullmann F, Otremba B, Menges M, Hoffmann M, Kaiser U, Aldaoud A, Jahn A; German CUP Study Group.
Westpfalz-Klinikum, Hellmut-Hartert-Str 1, 67655 Kaiserslautern, Germany. lghuebner@web.de
Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary (CUP), yielding response rates of 30% and median overall survival of 9-11 months in selected patients. Yet these combinations have not been subject to a randomised trial to overcome selection bias, a major problem in CUP. We randomised 92 patients to either paclitaxel/carboplatin (arm A) or the non-platinum non-taxane regimen gemcitabine/vinorelbine (arm B). The primary endpoint was rate of practicability as defined: application of >or=2 cycles of therapy (1) with a maximal delay of 1 week (2) and survival of >or=8 months (3). Practicability was shown in 52.4% (95% CI 36-68%) in arm A and in 42.2% (95% CI 28-58%) in arm B, respectively. The median overall survival, 1-year survival -rate and response rate of patients treated in arm A was 11.0 months, 38, and 23.8%, arm B 7.0 months, 29, and 20%. In conclusion, the paclitaxel/carboplatin regimen showed clinically meaningful activity in this randomised trial

Ref 11. 關於卵巢癌 secondary cytoreduction 之meta-analysis

Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis.
Gynecol Oncol. 2009 Jan;112(1):265-74.
Bristow RE, Puri I, Chi DS.
Department of Gynecology, The Kelly Gynecologic Oncology Service, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. rbristo@jhmi.edu
OBJECTIVE: To determine the relative effect of multiple prognostic variables on overall post-recurrence survival time among cohorts of patients with recurrent ovarian cancer undergoing cytoreductive surgery. METHODS: Forty cohorts of patients with recurrent ovarian cancer (2019 patients) meeting study inclusion criteria were identified from the MEDLINE database (1983-2007). Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median post-recurrence survival time of the following variables: year of publication, age, disease-free interval, localized disease, tumor grade and histology, the proportion of patients undergoing complete cytoreductive surgery, requirement for bowel resection, and the sequence of cytoreductive surgery and salvage chemotherapy. RESULTS: The mean weighted median disease-free interval prior to cytoreductive surgery was 20.2 months, and the mean weighted median overall post-recurrence survival time was 30.3 months. The weighted mean proportion of patients in each cohort undergoing complete cytoreductive surgery was 52.2%. Median survival improved with increasing year of publication (p=0.009); however, the only statistically significant clinical variable independently associated with post-recurrence survival time was the proportion of patients undergoing complete cytoreductive surgery (p=0.019). After controlling for all other factors, each 10% increase in the proportion of patients undergoing complete cytoreductive surgery was associated with a 3.0 month increase in median cohort survival time. CONCLUSIONS: Among patients undergoing operative intervention for recurrent ovarian cancer, the proportion of patients undergoing complete cytoreductive surgery is independently associated with overall post-recurrence survival time. For this select group of patients, the surgical objective should be resection of all macroscopic disease.

Ref 12.  Surveillance FDG-PET detection of asymptomatic recurrences in patients with cervical cancer.
Brooks RA, Rader JS, Dehdashti F, Mutch DG, Powell MA, Thaker PH, Siegel BA, Grigsby PW.
Gynecol Oncol. 2009 Jan;112(1):104-9.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.
OBJECTIVES: To evaluate survival after detection of recurrent cervical cancer by FDG-PET in symptomatic versus asymptomatic patients. METHODS: This is a prospective registry study of 103 patients treated with definitive chemoradiation for advanced cervical cancer who demonstrated no abnormal FDG uptake (a complete metabolic response, CMR) on their 3-month posttherapy FDG-PET. Their median age was 48 years (range 26-84). The clinical stages were Ib in 38, IIa in 1, IIb in 39, and IIIb in 25. All patients underwent subsequent surveillance FDG-PET. Patients were grouped according to symptom status at the time of the surveillance FDG-PET. Recurrence sites and survival data were analyzed. RESULTS: The median time from the 3-month posttherapy FDG-PET to the first surveillance FDG-PET was 13 months. 25 patients (25/103; 24%) were symptomatic at the time of surveillance FDG-PET and 21 of these had FDG-PET findings indicative of recurrence. 78 patients (78/103; 76%) were asymptomatic and 9 of these had tumor recurrence detected by PET. All recurrences were confirmed by biopsy or radiologic progression. The recurrences in the 21 symptomatic patients were loco regional in 4 and distant in 17. The 9 asymptomatic patients had isolated loco regional disease in 8 and distant disease in 1. All patients received treatment for recurrence. The three-year cause-specific survival for symptomatic recurrences was 19% versus 59% for asymptomatic recurrences (p=0.09). CONCLUSIONS: Surveillance FDG-PET can detect asymptomatic recurrent disease that is potentially amenable to salvage therapy. Prospective investigation of surveillance PET is warranted.

Ref 13. Gynecol Oncol. 2009 Jan;112(1):257-64.

Interval debulking surgery for advanced epithelial ovarian cancer: a Cochrane systematic review.
Tangjitgamol S, Manusirivithaya S, Laopaiboon M, Lumbiganon P.
Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Dusit District, Bangkok, Thailand.
OBJECTIVES: To assess the effectiveness of interval debulking surgery (IDS) for patients with advanced stage epithelial ovarian cancer (EOC). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, EMBASE, and reference lists for randomized controlled trials (RCTs) of advanced stage EOC. The trials had to report survival of women who had primary surgery and had IDS performed between cycles of chemotherapy comparing to survival of women who had conventional treatment (primary debulking surgery and adjuvant chemotherapy). Two review authors independently assessed trial quality and extracted data. Meta-analysis of overall survival (OS) and progression-free survival (PFS) was performed using fixed effects models. RESULTS: Three RCTs, involving 853 women of whom 781 were evaluated, met the inclusion criteria. OSs were substantial heterogeneity between trials (I(2)=58%). Subgroup analysis in two trials, wherein the primary surgery was not performed by the gynecologic oncologists, or was less extensive, showed benefit of IDS: hazard ratio=0.7 (95% confidence interval [CI]: 0.5 to 0.9, I(2)=0%). Substantial heterogeneity between two trials for PFS evaluating 702 women was also shown (I(2)=75%). Toxic reactions to chemotherapy were similar in both arms (RR=1.3, 95% CI: 0.4 to 3.6). Only one trial reported quality of life, which was generally similar in both treatment arms. CONCLUSIONS: Our review could not conclude whether IDS would improve the survival of women with advanced EOC compared with conventional treatment. IDS appeared to yield benefit only in the patients whose primary surgery was not performed by expert surgeons.

Ref 14. Gynecol Oncol. 2009 Jan;112(1):78-84.

A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: a Gynecologic Oncology Group study.
Walker JL, Morrison A, DiSilvestro P, von Gruenigen VE; Gynecologic Oncology Group.
Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City, OK 73190, USA. joan-walker@ouhsc.edu
OBJECTIVES: To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with extended field irradiation in women with cervical cancer metastatic to the para-aortic nodes. METHODS: Patients with carcinoma of the cervix and histologically documented para-aortic node metastases were eligible for this phase I/II trial. Chemotherapy agents were administered weekly concurrent with extended field radiation with escalating doses of paclitaxel from 30-50 mg/m(2) in each of three cohorts of three patients each. A phase II cohort was then evaluated at the selected maximum tolerated dose (MTD). RESULTS: The MTD was determined to be cisplatin 40 mg/m(2) (maximum dose of 70 mg) and paclitaxel 40 mg/m(2) administered weekly for six cycles concurrent with extended field radiation therapy. There were 19 evaluable patients for the phase II analysis of toxicity and efficacy. Grade three and four gastrointestinal toxicity was seen in 6 and neutropenia in 7. Radiation therapy was successfully completed in 36.8% of patients at eight weeks and in 68.4% of patients at nine weeks, with a median time to completion was 56 days. A total of 27 evaluable patients were enrolled, twelve are dead (mean survival of those deceased is 25 months), and 15 (56%) are alive, and have been followed for a mean of 48 months (range 25-68; median of 46 months). CONCLUSIONS: Paclitaxel and cisplatin combination chemotherapy concurrent with extended field pelvic para-aortic irradiation can be administered at the described MTD and shows a higher than previously reported disease-free survival in relation to historical data. The 56% survival to date, and 50% estimated 48 month survival, warrants validation in a larger prospective cohort. Central radiation dose reduction is being considered in the next trial to decrease late toxicity of regimen.

Ref 15. Gynecol Oncol. 2009 Jan;112(1):35-9.

Phase II trial of carboplatin and distearoylphosphatidylcholine pegylated liposomal doxorubicin (Lipo-Dox) in recurrent platinum-sensitive ovarian cancer following front-line therapy with paclitaxel and platinum.
Hsiao SM, Chen CA, Lin HH, Hsieh CY, Wei LH.
Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, Pan-Chiao, Taipei, Taiwan.
OBJECTIVE: To evaluate the effectiveness and toxicity of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer. METHODS: A phase II study of carboplatin/DPLD treatment for platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer was initiated in July 2002. As of March 2008, a total of 32 patients were enrolled. RESULTS: Of the 32 patients, one achieved a complete response; 19 (59%) achieved a partial response. The overall objective response rate was 62% (95% confidence interval [CI], 45%-80%). The median progression-free survival and overall survival for all 32 patients was 9.1 months (95% CI, 6.4-10.4 months) and 27.9 months (95% CI, 13.9-38.6 months), respectively. Toxicity was tolerable. The most common grade 3 or 4 toxicities were anemia (n=3) and nausea/vomiting (n=3). Grade 3/4 leukopenia (n=2), grade 3/4 thrombocytopenia (n=2) and grade 4 hepatitis (n=1) occurred in five patients. CONCLUSION: Carboplatin/DPLD appears to be an effective regimen with low toxicity for treatment of patients with platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer

Ref 16. Obstet Gynecol. 2009 Jan;113(1):18-25.

Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2.
Castle PE, Schiffman M, Wheeler CM, Solomon D.
Divisions of Cancer Epidemiology and Genetics, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. castlep@mail.nih.gov
OBJECTIVE: To estimate the fraction of cervical intraepithelial neoplasia 2 (CIN 2) that might regress if untreated using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS). METHODS: We compared the cumulative occurrence of CIN 2 (n=397) and CIN 3 or more severe (n=542) diagnosed by the Pathology Quality Control Group in three trial arms-immediate colposcopy, human papillomavirus (HPV) triage, and conservative management-over the 2-year duration of the ALTS trial. A nonparametric test of trend was used to test for differences in the number of CIN 2 cases relative to number of CIN 3 or more severe cases across study arms with an increasing percentage of women referred to colposcopy at baseline. RESULTS: There were no significant differences in the cumulative 2-year cumulative CIN 3 or more severe diagnoses by study arm (10.9%, conservative management; 10.3%, HPV; 10.9%, immediate colposcopy) (Ptrend=.8), but there was a significant increase in CIN 2 diagnoses (5.8%, conservative management; 7.8%, HPV triage; 9.9%, immediate colposcopy) (Ptrend<.001) in the study arms, with increasing number of women referred to colposcopy at baseline. The relative differences in cumulative CIN 2 by study arm among women who tested HPV-16 positive at baseline were less pronounced (Ptrend=.1) than women who tested positive for other high-risk-HPV genotypes (Ptrend=.01). CONCLUSION: There was evidence that approximately 40% of undiagnosed CIN 2 will regress over 2 years, but CIN 2 caused by HPV-16 may be less likely to regress than CIN 2 caused by other high-risk-HPV genotypes.

Ref 17. Obstet Gynecol. 2009 Jan;113(1):11-7.

Influence of intraoperative capsule rupture on outcomes in stage I epithelial ovarian cancer.
Bakkum-Gamez JN, Richardson DL, Seamon LG, Aletti GD, Powless CA, Keeney GL, O'Malley DM, Cliby WA.
Division of Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota, USA. bakkum.jamie@mayo.edu
OBJECTIVE: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer. METHODS: All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and chi test were used for statistical analyses. RESULTS: There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture. CONCLUSION: In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative.

Ref 18. Am J Obstet Gynecol. 2009 Jan;200(1):83.e1-6.

Laparoscopic management of early ovarian and fallopian tube cancers: surgical and survival outcome.
Nezhat FR, Ezzati M, Chuang L, Shamshirsaz AA, Rahaman J, Gretz H.
Division of Gynecologic Oncology, Minimally Invasive Surgery and Gynecologic Robotics, Department of Obstetrics and Gynecology, St Luke's-Roosevelt Hospital Center, New York, NY 10019, USA. fnezhat@chpnet.org
OBJECTIVE: To evaluate the role of laparoscopy for staging of early ovarian cancers. STUDY DESIGN: Case series conducted at the University Hospital with 36 patients who had presumed early-stage adnexal cancers. Laparoscopic staging/restaging was performed. RESULTS: Cases included 20 invasive epithelial tumors, 11 borderline tumors, and 5 nonepithelial tumors. Mean number of peritoneal biopsies, paraaortic nodes, and pelvic nodes were 6, 12.23, and 14.84, respectively. Eighty-three percent of the patients had laparoscopic omentectomy. On final pathology, 7 patients were upstaged. Postoperative complications included 1 small bowel obstruction, 2 pelvic lymphoceles, and 1 lymphocele cyst. Mean duration of follow-up is 55.9 months. Three patients had recurrences. All patients are alive without evidence of the disease. CONCLUSION: This represents 1 of the largest series and longest follow-ups of laparoscopic staging for early-stage adnexal tumors. Laparoscopic staging of these cancers appears to be feasible and comprehensive without compromising survival when performed by gynecologic oncologists experienced with advanced laparoscopy.

Ref 19.  BJOG. 2009 Jan;116(1):114-8.

Fertility-sparing treatment in young women with endometrial cancer or atypical complex hyperplasia: a prospective single-institution experience of 21 cases.
Signorelli M, Caspani G, Bonazzi C, Chiappa V, Perego P, Mangioni C.
Department of Obstetrics and Gynecology, San Gerardo Hospital, Monza, University of Milan-Bicocca, Milan, Italy. maurosignorelli@inwind.it
We conducted a prospective study of conservative treatment in 21 young nulliparous women with grade (G)1 endometrial cancer stage IA (11) or atypical complex hyperplasia (10). All were treated with a low-dose cyclic natural progestin therapy (200 mg/day from day 14-25) and encouraged to attempt pregnancy immediately. No adverse therapy-related effects were recorded. Overall response rate to progestin therapy was 57%. Nine women conceived (43%). There were 13 pregnancies, of which 13 were spontaneous and 8 were in women with persistent disease or partial response to hormonal treatment. Three additional complete responses were observed after delivery. Only women with known primary infertility or severe polycystic ovary syndrome showed inadequate pregnancy rate. Fifteen women underwent definitive surgery after enrolment (median 27 months, range 3-56 months). All 21 women are alive and disease free after a median follow up of 98 months.

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