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Minimally invasive interval debulking surgery in ovarian neoplasm (MISSION trialeNCT02324595): a feasibility study Salvatore Gueli Alletti, MD; Carolina Bottoni, MD; Francesco Fanfani, MD; Valerio Gallotta, MD; Vito Chiantera, MD; Barbara Costantini, MD; Francesco Cosentino, MD; Alfredo Ercoli, PhD; Giovanni Scambia, MD; Anna Fagotti, PhD

BACKGROUND: Laparoscopy has acquired an increasing role in the management of ovarian cancer. Laparoscopic cytoreduction could represent a new frontier for selected patients after neoadjuvant chemotherapy (NACT). OBJECTIVE: We sought to assess feasibility and early complication rate of minimally invasive (MI) interval debulking surgery (IDS) in stage III-IV epithelial ovarian cancer (EOC) patients after NACT. STUDY DESIGN: This is a phase II multicentric study in advanced EOC cases with clinical complete response after NACT, according to Gynecologic Cancer Intergroup and Response Evaluation Criteria In Solid Tumors criteria. Institutional review board approval was obtained and all patients signed written informed consent to be included in the protocol. The study was registered in clinicaltrials.gov (NCT02324595) and was named “MISSION” trial. For patients meeting inclusion criteria, surgical procedures started with diagnostic laparoscopy to confirm preoperative findings and assess surgical complexity. MI-IDS included hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, peritonectomy, and bowel resection. Pelvic and/or aortic lymphadenectomy was not considered as standard procedure in these cases. Intraoperative and postoperative outcomes, time to restart chemotherapy, survival rate, and quality of life data were registered. RESULTS: From December 2013 through February 2015, of 184 advanced EOC patients considered eligible for IDS, 52 (28.2%) met inclusion criteria and were enrolled in the study. For 22 (12%) of them, standard laparotomic approach was preferred because of intraoperative surgeon evaluation. Thirty (16.3%) patients received the planned treatment

Introduction Primary debulking surgery with optimal cytoreduction followed by platinumbased chemotherapy is the current firstline treatment in patients with advanced ovarian cancer.1 However, current guidelines suggest neoadjuvant

Cite this article as: Gueli Alletti S, Bottoni C, Fanfani F, et al. Minimally invasive interval debulking surgery in ovarian neoplasm (MISSION trialeNCT02324595): a feasibility study. Am J Obstet Gynecol 2016;214: 503.e1-6. 0002-9378/$36.00 ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2015.10.922

of MI-IDS. Median age was 61 (range 39-81) years and median body mass index was 24 (range 20-31) kg/m2. Median numbers of NACT cycles was 4 (range 3-7). Median operative time was 285 (range 124-418) minutes and median estimated blood loss was 100 (range 50-200) mL. Surgical procedures included 28 (93.3%) hysterectomy and bilateral salpingooophorectomy, 29 (96.6%) omentectomy, 2 (6.6%) appendectomy, 11 (36.6%) regional peritonectomy, and 1 (3.4%) bowel resection. A residual tumor of 0 cm was reached in 29 (96.6%) patients and 0.5 cm in only 1 (3.4%) case. The vast majority of patients were discharged on postoperative day 2 (range 2-3). No early postoperative complications were registered. Median time to restart chemotherapy was 20 (10-30) days and all patients successfully completed the cycles. Histological findings showed 3 (10%) complete response, 9 (30%) microscopic residual disease, and 18 (60%) evidence of macroscopic residual disease. With a median follow-up of 10.5 month, 5 peritoneal and 2 lymph nodal recurrences were observed. Psychometric test revealed moderate discomfort in the vast majority of patients (66.7%). All patients are still alive. CONCLUSION: Invasive-IDS in patients with clinically complete response to NACT seems to be feasible and safe in terms of perioperative outcomes, psycho-oncological impact, and survival rate. The equivalence between MI surgery and laparotomy needs to be confirmed with a longer follow-up and a larger number of patients. Key words: advanced ovarian cancer, interval debulking surgery,

laparoscopic cytoreduction, minimally invasive surgery, neoadjuvant chemotherapy, quality of life

chemotherapy (NACT) followed by interval debulking surgery (IDS) in specific cases to reduce tumor size and increase chances of optimal cytoreduction. The objective of IDS is to remove as much disease as possible, to improve potential response to subsequent chemotherapy.2 Some randomized controlled trial studies have demonstrated that patients with optimal cytoreduction after NACT have approximately the same survival rate as patients optimally cytoreduced at primary debulking surgery.2,3 In the last decade, we have observed an evolution in the management of ovarian cancer thanks to the introduction of minimally invasive (MI) surgery

(MIS), improvement of technological supports, and development of new chemotherapeutic strategies. In this context, an increasingly important role has been attributed to laparoscopy in both apparent early-stage and advanced epithelial ovarian cancer (AEOC).4,5 In fact, laparoscopic procedures needed to completely stage early epithelial ovarian cancer (EOC), including complete omentectomy and paraaortic lymphadenectomy as well as total abdominal hysterectomy-bilateral salpingo-oophorectomy (BSO) and peritoneal biopsies, have been shown to be as effective as standard laparotomy.5 Moreover, MIS allows performance of

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complex procedures at the level of the upper and lower abdomen, in case of single recurrence in ovarian cancer patients.6 Since 2006, laparoscopy has been introduced in AEOC management to identify patients deemed unresectable at primary surgery, obtaining a histological diagnosis and avoiding a large explorative laparotomy with subsequent delayed start of NACT.4 Subsequently, laparoscopy has been shown to be a valid technique to recognize partial responders to NACT to submit to IDS or to shift to a second-line therapy.7 The primary objective of this study was to assess feasibility of total laparoscopic/robotic interval cytoreduction in patients with AEOC and clinical complete response to NACT. Secondary objectives were assessing perioperative outcomes, survival, and quality of life.

Materials and Methods This is a multicentric phase II clinical trial, with the aim of assessing feasibility of MI-IDS (either by laparoscopy or robotics) after NACT in patients affected by AEOC (International Federation of Gynaecology and Obstetrics [FIGO] stage IIIC and IV). Inclusion criteria were the following: age >18 years, histologically proven EOC, clinical complete response after NACT, and Eastern Cooperative Oncology Group (ECOG) performance status <2. Women with American Society of Anesthesiologists (ASA) score IIIIV and body mass index (BMI) >40 kg/ m2 were excluded. Clinical response was assessed according to Gynecologic Cancer Intergroup (GCIG)8 and Response Evaluation Criteria In Solid Tumors (RECIST)9 criteria. Completeness of response according to 1 of the 2 criteria was sufficient to include the patient in the protocol. Institutional review board approval was obtained and all patients signed written informed consent to be included in the protocol. The study was registered in clinicaltrials.gov (NCT02324595) and was named “MISSION” trial. For each patient, preoperative data (type and number of cycles of NACT,

prechemotherapy/postchemotherapy CA125 serum levels, and computed tomography [CT] scan results) were collected to evaluate eligibility to a MI approach. Perioperative outcomes (operative time, estimated blood loss, conversion to laparotomy, surgical procedures, residual tumor size, ileus, hospital discharge, days needed to restart chemotherapy, and histological findings) were registered. Early postoperative complications were registered according to the Memorial Sloan Kettering Cancer Center grading system.10 Data regarding prognosis, recurrence rate, pattern of recurrence, and progression-free survival were also analyzed. All patients were administered a psychometric test, General Well-Being Schedule (GWBS), to evaluate quality of life after surgery.

(Intuitive Surgical, Sunnyvale, CA) was used in standard surgical setting. Cytoreduction consisted in total/ radical hysterectomy, BSO, omentectomy, and pelvic or upper peritonectomy. Traditionally, we do not perform systematic pelvic and aortic lymphadenectomy, in absence of residual disease at this level, detectable at radiological imaging and/or macroscopically.11 Additional abdominal procedures (eg, anterior rectal resection) were performed if needed. In cases of increased surgical complexity additional trocars were placed in the right or left subcostal spaces. Advanced multifunctional instruments were used to optimize advanced surgical procedures in terms of efficacy, safety, and operative time. At the end of surgery, residual tumor was registered.

Follow-up Study design Patients meeting inclusion/exclusion criteria were selected to enter into the MISSION trial. All surgical procedures started with a staging laparoscopy (S-LPS) through open access at the umbilicus or Palmer point, according to surgeon’s preference and patient’s previous laparotomies. The objective of diagnostic laparoscopy was to assess preoperative findings and to consider complexity and safety of surgery in terms of technical and oncological principles. In case of evidence of partial response, surgical approach was chosen at the surgeon’s discretion. Eligible patients were submitted to MI-IDS, either by laparoscopy or robotics, to remove all macroscopic lesions. In case of increased surgical risk or technical impossibility the case was registered as laparotomic conversion.

Surgical procedures A careful exploration of the peritoneal cavity was the first surgical step. A 10-mm, flexible-tip, HD 3dimensional video-laparoscope (Olympus, Hamburg, Germany) was used to explore all peritoneal recesses. In eligible patients, for laparoscopic approach three 5-mm trocars were placed in standard position for pelvic surgery, instead for robotic procedures da Vinci Xi platform

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In accordance with National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology,1 follow-up consisted of gynecological examination, abdominal and pelvic ultrasonography, CA-125 serum levels every 3 months, and chest and abdomen CT scan every 6 months for the first 2 years. In case of increased CA-125 serum levels and/ or suspicious CT scan findings, a fluorodeoxyglucose-positron emission tomography/CT scan was requested to confirm recurrence.

The GWBS The GWBS is a psychometric test to assess the state of general well-being of the patient. This test evaluates the subjective well-being and the level of concern over the last month. The scale determines how the person feels about her inner state rather than the outer; the 6 dimensions investigated are anxiety, depression, general health, well-being positive, self-control, and vitality. The 3 scores are: severe discomfort (range 0-60), moderate discomfort (range 61-72), and wellness (range 73-110). A psycho-oncologist administered the test within 30 days after surgery.

Results From December 2013 through February 2015, 184 AEOC patients submitted to

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FIGURE 1

TABLE 1

STARD flow diagram

Patient’s characteristics

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Variable

No. (%)a

All cases

30

Median age, y (range)

61 (39e81)

Median BMI (range)

24 (20e31)

Previous laparotomies

11 (36.6)

ASA score -I

0

- II

30 (100)

PS ECOG AEOC, advanced epithelial ovarian cancer; cCR, clinical complete response; cPR, clinical partial response; IDS, interval debulking surgery; pts, patients; S-LPS, staging laparoscopy. Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

-0

27 (90)

-1

3 (10)

Histotype (WHO) - High-grade serous

NACT were considered eligible for IDS at the Division of Gynecologic Oncology at the Catholic University of the Sacred Heart of Rome; Division of Minimally Invasive Gynecology at the University of Perugia; “Giovanni Paolo II” Foundation of Campobasso; and Policlinic of Abano Terme, Padua. Among them, 102 (55.5%) women showed clinical stable/ partial response, and were not eligible for the study. Eighty-two (44.5%) patients showed clinical complete response, but only 52 (28.2%) met inclusion criteria and were enrolled in the study. The remaining 30 (16.3%) cases were excluded for BMI >40 kg/m2 and/or ASA III-IV. Fifty-two women received S-LPS. For 22 (12%) of them, standard laparotomic approach was preferred because of intraoperative surgeon evaluation (3 for the presence of extended adhesions, and 19 for evidence of partial macroscopic response, the laparoscopic management of which would make the surgical procedure unsafe, either from a technical or oncological point of view): among them, optimal cytoreduction was reached in 95.4%. Finally, 30 women received the planned treatment of MI-IDS. The STARD flow diagram of the study is shown in Figure 1. Patients’ characteristics are shown in Table 1. Median patient age was 61 (range 39-81) years and median BMI was 24 (range 20-31) kg/m2. Eleven

29 (96.6)

- Endometrioid

1 (3.4)

FIGO stage at diagnosis - IIIC

29 (96.6)

- IV

1 (3.4)

RECIST response - Complete

6 (20)

- Partial

24 (80)

GCIG response - Complete

27 (90)

- Partial

3 (10)

Median CA-125 serum level (range) at IDS, UI/mL Median no. of NACT cycles (range)

32.5 (3.2e64.3) 4 (3e7)

Type of chemotherapy - Carboplatin-paclitaxel every 21 d

18 (60)

- Carboplatin-paclitaxel-bevacizumab

8 (26.6)

- Carboplatin-paclitaxel weekly

2 (6.6)

- Carboplatin-paclitaxel-gencitabine

1 (3.4)

- Carboplatin weekly

1 (3.4)

BMI, body mass index; FIGO, International Federation of Gynaecology and Obstetrics; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; WHO, World Health Organization. a Unless otherwise noted. Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

(36.6%) patients received previous laparotomy. The majority of the patients (96.6%) presented with highgrade serous histotype and FIGO stage IIIC at diagnosis. Median number of NACT cycles was 4 (range 3-7). Patients enrolled in the trial were not selected on type or on number of NACT cycles; type of chemotherapy

is detailed in Table 1. According to GCIG and RECIST criteria, patients showed 27 (90%) serological and 6 (20%) radiological complete responses to NACT. Median CA-125 serum level at MI-IDS was 35.2 (3.2-64.3) UI/mL. Twenty-six (86.6%) patients were submitted to laparoscopic surgery and 4 (13.3%) to robotic surgery. In the

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TABLE 2

TABLE 3

Surgical data

Histological findings No. (%)a

Variable All cases

30

Type of surgery

Variable - Complete response

3 (10)

- Microscopic disease

9 (30) 18 (60)

- Radical hysterectomy  BSO

28 (93.3)

- Omentectomy

29 (96.6)

- Macroscopic disease

- Appendectomy

2 (6.6)

Site of microscopic disease

- Regional peritonectomy - Bowel resection

11 (36.6)

- Uterus

0 (0)

1 (3.4)

- Adnexa

6 (20)

- Omentum

3 (10)

- Peritoneum

1 (3.3)

- Bowel

0 (0)

RT, cm 0

29 (96.6)

<1

No. (%)

Histological findings

1 (3.4)

Median OT, min (range)

285 (124e418)

Median EBL, mL (range)

100 (50e200)

Site of macroscopic disease - Uterus

2 (6.6)

Median length of stay, d (range)

2 (2e3)

- Annexes

Early postoperative complications per MSKCC

0

- Omentum

6 (20)

- Peritoneum

8 (26.6)

- Bowel

1 (3.3)

Median TTC, d (range)

20 (10e30)

BSO, bilateral salpingo-oophorectomy; EBL, estimated blood loss; MSKCC, Memorial Sloan Kettering Cancer Center; OT, operative time; RT, residual tumor; TTC, time to restart chemotherapy after surgery. a

Unless otherwise noted. Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

latter, the primary approach was always S-LPS. Median operative time was 285 (range 124-418) minutes and median estimated blood loss was 100 (range 50-200) mL. Surgical procedures included 28 (93.3%) hysterectomy and BSO, 29 (96.6%) omentectomy, 2 (6.6%) appendectomy, 11 (36.6%) regional peritonectomy, and 1 (3.4%) bowel resection. Residual tumor was 0 in 29 (96.6%) patients and 0.5 cm in 1 (3.4%) case at the level of the diaphragm. In 2 cases mini-laparotomy was performed: 1 to complete specimen removal in a patient without uterus and 1 to perform bowel anastomosis. The vast majority of patients (27 of 30, 90%) were discharged on postoperative day 2 (range 2-3). No early postoperative complications were registered. Median time to restart chemotherapy after surgery was 20 days (range 10-30), and all patients successfully completed adjuvant chemotherapy (Table 2). Histological findings showed only 3 (10%) pathological complete responses. Microscopic residual disease was found in 10 (33.3%) patients (6 [20%] in the

adnexa; 3 [10%] in the omentum; and 1 [3.3%] in the peritoneum). Macroscopic disease was found in 18 (60%) patients (2 [6.6%] on uterus, 17 [56.6%] on the adnexa, 6 [20%] on the omentum, 8 [26.6%] on the peritoneum, and 1 [3.3%] on the bowel) (Table 3). With a median follow-up of 10.5 (range 6-18) months, median PFS was not reached. Seven (23.3%) recurrences were observed. Among them, 5 (16.6%) were intraperitoneal and 2 (6.6%) were lymph nodal. All patients are still alive. As far as the psychometric test is concerned, the scores (mean  SD) highlighted a moderate discomfort in the majority of patients (20 of 30, 66.7%) whereas severe distress and positive wellbeing were observed in 7 (23.3%) and 3 (10%) patients, respectively (Figure 3).

Comment This study demonstrates that MI-IDS is a feasible and safe approach in patients with clinical complete response after NACT. In fact, all surgical procedures required for complete cytoreduction

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17 (56.6)

Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

were carried out with no conversion to standard laparotomy or intraoperative and early postoperative complications. The presence of an experienced surgical equipe in advanced laparoscopy, supported by a forefront technology, has led to this result (Figure 2). Feasibility rate of 36.5% (30 of 82 women with clinically complete response) is the result of very strict inclusion criteria adopted in this first experience, such as low BMI and good ASA score. This approach could allow the surgeon to test MI-IDS in a selected population, in terms of surgical complexity and perioperative outcomes. Based on these promising results, it is conceivable that a prospective multicenter trial, with larger embraced criteria, including partial responders, obese women, and use of new robotic platforms (da Vinci Xi), could offer benefits of MIS to a larger population. In this context, previous laparotomy (36.6%) was not considered an absolute limit to MI-IDS. We report also a median time to start chemotherapy of 20 (range 10-30) days,

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FIGURE 2

General well-being schedule

Qol, quality of life. Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

due to the choice of prudent waiting for adequate postoperative recovery. Considering that this interval has been reported as an important disease prognostic factor,12 and that it might be shorter, it represents another potential advantage of MI-IDS over laparotomy. Regarding quality of life, we report moderate distress (66.7%), which is coherent with women’s oncological experience and goes beyond the surgical approach. A high level of satisfaction was informally recorded for our patients, in line with the fact that a scarless surgery may help to avoid an unnecessary mark of a difficult history,13 and reduce postoperative pain. However, only a

FIGURE 3

Radicality in upper abdominal district: surgical finding after radical omentectomy

Panoramic view of left hypogastric region after radical laparoscopic omentectomy. Gueli Alletti et al. The MISSION trial. Am J Obstet Gynecol 2016.

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comparison with standard laparotomic approach will definitively clarify any advantage of MI-IDS over laparotomy in this field. To our knowledge there are only 2 recently published studies suggesting feasibility and oncological safety of MI-IDS in a small and retrospective series of cases. More in depth, Favero et al14 reported on a small sample of patients treated by MI-IDS compared to a control group undergoing standard laparotomy. They concluded that laparoscopic IDS is feasible in selected patients, but with less satisfying oncological outcomes. The authors hypothesize that this results can be ascribed to a more favorable environment for tumor cell implantation in laparoscopic procedures; in fact, increased abdominal pressure with decreased intraabdominal temperature could determine a considerable attenuation of the inflammatory response of peritoneal surface.14 More recently, Corrado et al15 published a retrospective series of 30 patients treated with a MI cytoreductive surgery after 3 cycles of NACT. The authors concluded that MIIDS is feasible when performed by a skilled surgeon and may decrease the impact of aggressive surgery on highmorbidity patients.15 The strength of our study is in the prospective design, suggesting the real impact of such an approach in clinical practice, in terms of both feasibility and safety. Survival remains the main issue to assess the value of MI-IDS. Although median follow-up is too short to drive definitive conclusions, median PFS reported in this study is consistent with data recently shown by randomized controlled trials in the same subset of patients.16,17 Looking more in depth to the type of recurrences observed, 2 of them have been exclusively retroperitoneal. Since lymphadenectomy at the time of IDS is never performed in case of negative radiological investigation11 in our centers, it is conceivable that this type of recurrence has not been influenced by the surgical approach. Regarding peritoneal recurrences, which are the real challenge in ovarian cancer patients, the equivalence between MIS and laparotomy needs to be confirmed

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with a longer follow-up and a larger number of patients.18 To this purpose, a prospective clinical trial is now starting to definitively assess the prognostic impact and the psycho-oncological outcome of such an approach. n References 1. NCCN Clinical Practice Guidelines in Oncology. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. Version 1.2015. Available at: http://www.nccn. org/professionals/physician_gls/f_guidelines.asp. Accessed February 16, 2016. 2. Fanfani F, Ferrandina G, Corrado G, et al. Impact of interval debulking surgery on clinical outcome in primary unresectable FIGO stage IIIC ovarian cancer patients. Oncology 2003;65: 316-22. 3. Rutten MJ, van de Vrie R, Bruining A, et al. Predicting surgical outcome in patients with International Federation of Gynecology and Obstetrics stage III or IV ovarian cancer using computed tomography: a systematic review of prediction models. Int J Gynecol Cancer 2015;25:407-15. 4. Fagotti A, Ferrandina G, Fanfani F, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol 2008;199:642.e1-6. 5. Gallotta V, Ghezzi F, Vizza E, et al. Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multiinstitutional series. Gynecol Oncol 2014;135: 428-34. 6. Nezhat FR, Denoble SM, Cho JE, et al. Safety and efficacy of video laparoscopic surgical debulking of recurrent ovarian, fallopian tube and primary peritoneal cancers. JSLS 2012;16: 511-8. 7. Fagotti A, Fanfani F, Vizzielli G, et al. Should laparoscopy be included in the work-up of advanced ovarian cancer patients attempting interval debulking surgery? Gynecol Oncol 2010;116:72-7. 8. Alexandre J, Brown C, Coeffic D, et al. CA-125 can be part of the tumor evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial. Br J Cancer 2012;106: 633-7. 9. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 10. Strong VE, Selby LV, Sovel M, et al. Development and assessment of Memorial Sloan Kettering Cancer Center’s Surgical Secondary Events grading system. Ann Surg Oncol 2015;22:1061-7. 11. Fagotti A, De Iaco P, Fanfani F, et al. Systematic pelvic and aortic lymphadenectomy in advanced ovarian cancer patients at the time of interval debulking surgery: a double-institution case-control study. Ann Surg Oncol 2012;19: 3522-7.

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12. Mahner S, Eulenburg C, Staehle A, et al. Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: analysis of prospective randomized phase III trials. Eur J Cancer 2013;49:142-9. 13. Yuen PM, Yu KM, Yip SK, et al. A randomized prospective study of laparoscopy and laparotomy in the management of benign ovarian masses. Am J Obstet Gynecol 1997;177:109-14. 14. Favero G, Macerox N, Pfiffer T, et al. Oncologic concerns regarding laparoscopic cytoreductive surgery in patients with advanced ovarian cancer submitted to neoadjuvant chemotherapy. Oncology 2015;89: 159-66. 15. Corrado G, Mancini E, Cutillo G, et al. Laparoscopic debulking surgery in the management of advanced ovarian cancer after

neoadjuvant chemotherapy. Int J Gynecol Cancer 2015;25:1253-7. 16. Cornelis S, Van Calster B, Amant F, Leunen K, Van Der Zee AG, Vergote I. Role of neoadjuvant chemotherapy in the management of stage IIIC-IV ovarian cancer: survey results from the members of the European Society of Gynecological Oncology. Int J Gynecol Cancer 2012;22:407-16. 17. Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomized, controlled, noninferiority trial. Lancet 2015;386:249-57. 18. Usami T, Kato K, Taniguchi T, et al. Recurrence patterns of advanced ovarian, fallopian tube, and peritoneal cancers after complete cytoreduction during interval debulking surgery. Int J Gynecol Cancer 2014;24:991-6.

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Author and article information From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome (Drs Gueli Alletti, Bottoni, Gallotta, Costantini, Cosentino, and Scambia); Department of Medicine and Aging Sciences, University “G.D’Annunzio” of Chieti-Pescara, Chieti (Dr Fanfani); Division of Gynecologic Oncology, “Giovanni Paolo II,” Department of Obstetrics and Gynecology, University of Molise, Campobasso (Dr Chiantera); Department of Gynecology, Policlinic of Abano Terme, Abano Terme, Padua (Dr Ercoli); and Minimally Invasive Gynecology, St Maria Hospital, University of Perugia, Terni (Dr Fagotti), Italy. Received Aug. 11, 2015; revised Oct. 23, 2015; accepted Oct. 27, 2015. The authors report no conflict of interest. Corresponding author: Salvatore Gueli Alletti, MD. [email protected]