Evaluation of short versus long course chemotherapy in the neoadjuvant setting in ovarian cancer

Evaluation of short versus long course chemotherapy in the neoadjuvant setting in ovarian cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of short versus long course chemotherapy in the neoadjuvant setting in ovarian cancer Reham Alghandour, Basel Refky, Hasan Elsalman, Doaa Saker, Mohamed Zohdy, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3859807/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: There is a debate about the optimum number of neoadjuvant chemotherapy (NACT) cycles for ovarian cancer and its impact on survival. Objective: This study aimed to assess the optimum number (NACT) cycles that influence the surgical and pathological outcome and its impact on survival. Methods: retrospective cohort study, all patients included were newly diagnosed ovarian cancer who received NACT then underwent interval debulking surgery (IDA), presented to tertiary cancer center from July 2011 to December 2021.patients were classified into two groups according to number of NACT cycles. Group 1; Patients who received ≤ 4 cycles Group 2; Patients who received ≤ 5 cycles. Results: 207 patients were included (130 patients in group 1, 70 patients in group 2). 63.1% of group I were stage III while 51.9% of group II were stage IV. There was no difference between two groups in pathological response to NACT (P = 0.9), or those who underwent optimal cytoreduction (P = 0.8). group 2 received a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value < .001). There were no significant differences between both groups regards overall (OS) or relapse free survivals (RFS) (P = 0.5. 0.1 respectively). Conclusion Receiving more than 4 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery had no impact on achievement of optimal cytoreduction surgery or surgical morbidity and mortality and did not affect relapse free or overall survivals. Ovarian cancer Cytoreduction neoadjuvant chemotherapy serous carcinoma Figures Figure 1 Figure 2 Background Epithelial ovarian neoplasm represents 90% of malignant ovarian neoplasm. It represents the fifth leading cause of cancer mortality in women ( 1 ). Achievement of complete surgical cytoreductive surgery is the corner stone in management of ovarian cancer ( 2 ). Patients presented with early stage are primarily managed by complete debulking surgery followed by adjuvant systemic chemotherapy ( 3 ). However, neoadjuvant chemotherapy followed by interval debulking might be necessary in most cases of advanced ovarian cancer for those the complete cytoreduction cannot be achieved at diagnosis, or those with advanced age, poor performance or comorbidities ( 4 , 5 ). At present there is no consensus about the optimum number of chemotherapy cycles before and after interval debulking surgery ( 6 , 7 ). Hereby, in this study we evaluate the relation between number of neoadjuvant chemotherapy cycles and surgical and pathological outcome and its impact on progression and overall survival. Patients and methods This is a retrospective cohort study, all patients included were newly diagnosed ovarian cancer who received neoadjuvant chemotherapy then underwent interval debulking surgery, presented to the Oncology Center Mansoura University from July 2011 to December 2021. Ethical Approval: Institutional Review Board approval was obtained by the Medical Research Ethics Committee - Institutional Review Board - Mansoura Faculty of Medicine - Mansoura University, (Approval No: R.22.01.1601). All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. Inclusion Criteria: Newly diagnosed patients with advanced epithelial ovarian carcinoma (FIGO stage III-IV) whom complete cytoreduction cannot be achieved. Patients who are not candidate for primary debulking surgery e.g., poor performance, or not fit for surgery due to comorbidities. Patients who received neoadjuvant chemotherapy then underwent interval debulking were included. Exclusion criteria: Patients with early-stage ovarian cancer were candidates for primary cytoreduction. Patients were presented with recurrent disease. Demographics, preoperative, operative, postoperative, pathologic, and oncologic follow-up data were retrieved from a prospectively maintained electronic database. The main outcome of this study is to assess the optimum number of neoadjuvant chemotherapy cycles that influence the surgical and pathological outcome. The secondary outcome is to determine if the number of neoadjuvant chemotherapy cycles could influence the survival of these patients. Statistical analysis: We use the statistical software SPSS (Statistical Package for Social Scientists SPSS 26; Armonk, NY: IBM Corp) for analysis of the study results. Continuous variables will be presented as mean and standard deviation if normally distributed or median and range when non-normally distributed. Independent samples t-test will be used to compare parametric data whereas the Mann-Whitney U test will be used to compare non-parametric data. Categorical data will be compared by Pearson's Chi-square test or Fischer-Exact test when appropriate. A p-value ˂0.05 is considered statistically significant. Results 1.1: Epidemiology 207 patients enrolled. Mean age was 55.9 +/- 9.5 years old. Median BMI 33 (16-62). Only 15 patients (7.2%) had family history of breast/ovarian cancer. 101 (48.8%) has comorbidity with HTN being the commonest followed by DM. The majority were postmenopausal women (76.8%). Abdominal pain was the most common presenting symptom (63.8%) followed by abdominal enlargement (26.1%). Although CT CAP was the main stay investigation in almost all patients (98.6%). MRI pelvis was used in nearly half of them (55.1%). In 57% of patients there was bilateral adnexal masses. There were radiologic peritoneal and omental deposits in 71% and 83.1% of patients respectively. Ascites was present in 90.3% and pleural effusion in 20.3% of patients. 45.4% had enlarged regional LNs. 94.7% were serous carcinoma and 96.7% were high grade. 1.2: Neoadjuvant therapy In 56% the cause of neoadjuvant was irresectable disease at diagnosis. In 95.7% the regimen was Taxan /Carboplatin. However, the number of neoadjuvant cycles varies greatly with 35.3% receiving 3 cycles followed by 27.5% 6 cycles and 26.6% 4 cycles. Most of the patients (83.1%) showed radiologic partial response, followed by 7.2% complete response. 1.3: Surgery and adjuvant treatment: All patients underwent surgery, however 3.4% of patients were closed as debulking was not possible. 70% of the patients underwent optimal cytoreduction (residue <1cm). The surgery was done laparoscopically in only 8.7% of the patients. Lymphadenectomy was done in 49.3% of the patients. 7.3% required GIT resection, 1.4% liver and 1.4% partial bladder resection. 30-day morbidity was 6.8% while mortality was 0.5%. 87.4% of the enrolled patients received adjuvant chemotherapy, in 30.9% this was 3 cycles followed by 2 and 4 in 22.2 % each. 1.4: Relapse/progression: Relapse/progression occurred in 140 (67.6%) of the patients, 43.6% of them was locoregional. 71.4% of relapses were platinum sensitive (occurring >6months of finishing adjuvant platinum-based therapy) and the majority (88.6%) were treated by chemotherapy alone. 1.5: Comparison of 5 cycles: (Table 1) Patients who received less than or equal to 4 cycles were considered as group I (130 patients) and those who received 5 or more cycles were considered as group II (77 patients). Age, Co-morbidity, Menopausal status, peritoneal deposits, omental deposits, ascites, pleural effusion, visceral metastasis, regional and non-regional adenopathy, pathologic subtype, grade, response to neoadjuvant, cytoreduction were not significantly different. However, the clinical FIGO staging was significantly different where the majority (63.1%) of group I were stage III while 51.9% of group II were stage IV (.03). Also, in group I 94.6% received adjuvant chemotherapy in comparison to only 75% in group II (<.001). However, patients who received 5 or more cycles as neoadjuvant were more liable to receive a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value<.001) (Figure 2). 1.6: Outcomes (Table 2) Overall survival was calculated from date of surgery for all patients and was insignificantly different in both groups (.5) (Figure 1A) with 3-year OAS (75% VS 67% in group I and II, respectively). In the other hand, the relapse was calculated only in patients who successfully underwent debulking and was similar (63.1% VS 71.5% in group I and II, respectively (p=.57). Similarly, the difference in the relapse free survival was insignificant (.13) (Figure 1B) with 3-year RFS 20% VS 16%. 1.7: Subgroup analysis according to debulking (Table 3) Both the OAS and the RFS were comparable in both groups in patients who underwent optimal debulking (p=.85 and .3, respectively) as well as in those who underwent suboptimal debulking (p=.65 and .39, respectively). 1.8: Correlation between total number of perioperative chemotherapy and RFS The number of neoadjuvant and adjuvant cycles did not affect the relapse free survival (p=.46) Discussion Highlights of main results No difference regards the radiological, clinal or surgical response when short (4 or less) or long (5 or more) neoadjuvant chemotherapy was received to advanced ovarian cancer patients. No difference in overall or recurrence free survivals when short or long neoadjuvant course were offered for advanced ovarian cancer patients. Results in the context of published literatures Neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has been established as an alternative approach in the treatment of advanced ovarian cancer (8). Although this approach offered better surgical outcomes and less residual disease after surgery, the overall (OS) and progression free survivals (PFS) were non inferior to those who underwent primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy (conventional approach) (9-11). However, pooled analysis reports from EORTC 55971 and CHORUS trials showed NACT (3 cycles NACT followed by ICS) was associated with mild improvement in PFS and OS of patients with more advanced disease (9, 12, 13). It is important to identify the patients who will benefit from NACT based on clinical, radiological, molecular parameters, and laparoscopic scoring models (8). There is a debate in the literature about the optimum numbers of NACT cycles (11). The American Society of Clinical Oncology (ASCO) and Society of Gynecologic Oncology (SGO) guidelines recommend offering 3-4 neoadjuvant platinum based chemotherapy for the patients who are unlikely to achieve primary complete cytoreduction (14), while National Comprehensive Cancer Network (NCCN) recommend offering 3-6 cycles followed by interval debulking for the same category of patients (15). That is why we conducted this study to evaluate the optimum number of neoadjuvant chemotherapy cycles on the response and survival of advanced ovarian cancer patients ineligible for primary cytoreductive surgery. In our study, more than half (56%) of the included (207) patients were irresectable at diagnosis. The recruited patients were categorized in two groups: 130 patients received 4 or less cycles versus 77 patients who received 5-6 NACT cycles. The rationale of extended treatment beyond 4 cycles in 77 patients was to increase the likelihood of achieving optimal cytoreduction after multidisciplinary team discussion, as most of those patients had stable disease after 3-4 cycles of NACT. Notably most of patients of this group had stage IV disease. In their studies, Marchetti et al. and Phillips et al., concluded that the achievement of optimal cytoreduction is the main independent prognostic factor regardless the number of NACT cycles (16, 17). Despite the administration of NACT, optimal cytoreduction achieved in only 70% of all included patients which is comparable to what had been reported in literature (17, 18). In the present study, there was no significant difference in the rate of optimal cytoreduction surgery, pathological nor radiologic response (CR or PR) between those who received 4 or less NACT and those who received 5-6 cycles. This is contradictory to what had been reported by Marchetti et al. In their study they reported a significant increase of complete and partial -responses in patients who received longer NACT treatment (16, 19). Moreover, we did not report any difference between the two groups regarding the surgical approach (laparotomy vs laparoscopy), surgical morbidity and mortality. This could be explained by the heterogeneity of included patients among the two groups and absence of initial baseline homogenous surgical score for all included patients. On other hand, others reported higher incidence of optimal cytoreduction and less surgical morbidity with 6 cycles of NACT (19). Bell et al. found that 6 NACT cycles associated with a 24% lower recurrence risk in patients with serous histology (20) but that was not observed in our study. The increased NACT cycles were not associated with reduction in the recurrence risk or its type (platinum sensitive or resistant). The present study did not observe a significant difference in overall or relapse-free survivals between those who received short or long course NACT. Actually, this point represents an argument in literature (11, 21). Although many studies reported decremental effects on Overall survival with increased number of cycles of NACT (22, 23), others agreed with our finding that there would be no difference in OS with increased number of cycles of NACT (16, 24). Moreover, in a retrospective study conducted in Memorial Sloan Kettering Cancer Center, the longer course of NACT (≥ 5 cycles) had worse PFS and OS even after adjustment for BRCA status and complete gross resection (7). In contrary, Marchetti et al., reported no difference in OS between short or longer course of NACT. Interestingly, in univariate analysis BRCA mutation status was associated with improvement in OS (16). Notably, the presence of residual disease is the most surrogate prognostic factor associated with worse OS regardless the number of NACT cycles (16, 24). Betrian et al. confirmed our results that there was no difference in OS and relapse-free survival regards the number of NACT cycles. After subgroup analysis, poor response to NACT regardless the number was surrogate factor for higher risk of recurrence, as those patients were unlikely to achieve complete cytoreduction due to high peritoneal cancer index (25). Strikingly, the only significant difference between the two studied groups was that patients who received ≥ 5 NACT cycles were more liable to receive a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value<.001). This might be concordant with the NCCN guidelines that recommended that IDS should always be followed by at least 3 cycles of adjuvant chemotherapy regardless of the number of NACT cycles (9). The present study did not demonstrate benefit from prolonging the course of NACT beyond 4 cycles on rate of response or achievement of optimal cytoreduction and did not decrease the risk of relapse. Strength and weakness It is worth mentioning that there are several limitations of our study including the retrospective nature which could have led to selection bias between both groups, absence of unique baseline surgical score, and lack of BRCA mutation status data which might affected the results. Implication for practice and future practice Randomized controlled trials are awaited to still the debate about the optimum number of neoadjuvant chemotherapy cycles to advanced ovarian cancer patients, and implication of baseline surgical scores, with incorporation of molecular background to all included patients. Conclusion Administration more than four cycles of neoadjuvant chemotherapy in ovarian cancer patient had no impact on response, achievement of optimal cytoreduction, surgical approach, morbidity, or mortality, did not reduce the risk of recurrence or improve survival. Further randomized trials are awaited to determine the optimum number of NACT and assess its impact on survival. Declarations Disclosures and funding source: The authors declare no conflict of interest. No funding sources. Ethical Approval: Institutional Review Board approval was obtained. (Approval No: R.22.01.1601), All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments Info rmed Consent: Written informed consent was waived by the Institutional Review Board. Availability of data All data are available upon request. 4. Conflict of Interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. 5 . Funding The authors state that this work has not received any funding. 6. Authors contributions: Hasan Elsalman, Doaa H. Saker, Mohamed Zohdy, Sara Elbaz : were responsible forcollection of data . Reham Alghandour : write the manuscript. Islam Hany : was responsible for statistical analysis Doaa H. Saker, Mohamed Zohdy, Basel Refky: revision and final approval of manuscript Basel Refky: corresponding author 7. Consent for publication : N/A References Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. Brand A, DiSilvestro P, Sehouli J, Berek J. Cytoreductive surgery for ovarian cancer: quality assessment. Ann Oncol. 2017;28:viii25–viii9. Makar AP, Tropé CG, Tummers P, Denys H, Vandecasteele K. Advanced ovarian cancer: primary or interval debulking? Five categories of patients in view of the results of randomized trials and tumor biology: primary debulking surgery and interval debulking surgery for advanced ovarian cancer. Oncologist. 2016;21(6):745. Fagotti A, Ferrandina MG, Vizzielli G, Pasciuto T, Fanfani F, Gallotta V et al. Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int J Gynecol Cancer. 2020;30(11). Van Meurs HS, Tajik P, Hof MH, Vergote I, Kenter GG, Mol BWJ, et al. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Eur J Cancer. 2013;49(15):3191–201. Xu X, Deng F, Lv M, Chen X. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc–IV high-grade serous ovarian cancer. Arch Gynecol Obstet. 2017;295(2):451–8. Liu YL, Zhou QC, Iasonos A, Chi DS, Zivanovic O, Sonoda Y et al. Pre-operative neoadjuvant chemotherapy cycles and survival in newly diagnosed ovarian cancer: what is the optimal number? A Memorial Sloan Kettering Cancer Center Team Ovary study. Int J Gynecol Cancer. 2020;30(12). Patel A, Iyer P, Matsuzaki S, Matsuo K, Sood AK, Fleming ND. Emerging trends in neoadjuvant chemotherapy for ovarian cancer. Cancers. 2021;13(4):626. Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. NCCN guidelines insights: Ovarian cancer, version 1.2019: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2019;17(8):896–909. Melamed A, Rauh-Hain JA, Gockley AA, Nitecki R, Ramirez PT, Hershman DL, et al. Association between overall survival and the tendency for cancer programs to administer neoadjuvant chemotherapy for patients with advanced ovarian cancer. JAMA Oncol. 2021;7(12):1782–90. Quesada S, Thomas QD, Colombo P-E, Fiteni F. Optimal First-Line Medico-Surgical Strategy in Ovarian Cancers. Are We There Yet? Cancers. 2023;15(14):3556. Tajik P, van de Vrie R, Zafarmand MH, Coens C, Buist MR, Vergote I et al. The FIGO stage IVA versus IVB of ovarian cancer: prognostic value and predictive value for neoadjuvant chemotherapy. Int J Gynecol Cancer. 2018;28(3). Vergote I, Coens C, Nankivell M, Kristensen GB, Parmar MK, Ehlen T, et al. Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol. 2018;19(12):1680–7. Vanderpuye VD, Clemenceau JRV, Temin S, Aziz Z, Burke WM, Cevallos NL, et al. Assessment of adult women with ovarian masses and treatment of epithelial ovarian cancer: ASCO resource-stratified guideline. JCO Global Oncol. 2021;7:1032–66. Armstrong DK, Alvarez RD, Backes FJ, Bakkum-Gamez JN, Barroilhet L, Behbakht K, et al. NCCN guidelines® insights: Ovarian cancer, version 3.2022: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2022;20(9):972–80. Marchetti C, Rosati A, De Felice F, Boccia S, Vertechy L, Pavone M, et al. Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis. Gynecol Oncol. 2021;163(1):29–35. Phillips A, Sundar S, Singh K, Nevin J, Elattar A, Kehoe S, et al. Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer. Eur J Surg Oncol. 2018;44(6):760–5. Phillips A, Balega J, Nevin J, Singh K, Elattar A, Kehoe S, et al. Reporting ‘Denominator’data is essential for benchmarking and quality standards in ovarian cancer. Gynecol Oncol. 2017;146(1):94–100. Kumari A, Thakur M, Saha S, Suri V, Prasad G, Patel FD, et al. To compare the optimal cytoreduction rate in advanced epithelial ovarian cancer stage III/IV after 3 versus 6 cycles of neoadjuvant chemotherapy. J Obstet Gynaecol. 2021;41(4):616–20. Bell J, Brady MF, Young RC, Lage J, Walker JL, Look KY, et al. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;102(3):432–9. Nitecki R, Melamed A. Extra cycles of neoadjuvant chemotherapy before interval surgery for ovarian cancer: the more the merrier or too much of a good thing? Int J Gynecol Cancer. 2022;32(8):975–6. Altman AD, McGee J, May T, Lane K, Lu L, Xu W, et al. Neoadjuvant chemotherapy and chemotherapy cycle number: a national multicentre study. Gynecol Oncol. 2017;147(2):257–61. Stoeckle E, Boubli B, Floquet A, Brouste V, Sire M, Croce S, et al. Optimal timing of interval debulking surgery in advanced ovarian cancer: yet to be defined? Eur J Obstet Gynecol Reproductive Biology. 2011;159(2):407–12. Perrone AM, Coada CA, Ravegnini G, De Leo A, Damiano G, De Crescenzo E et al. Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma. Int J Gynecol Cancer. 2023;33(8). Betrian S, Angeles MA, Moreno AG, Cabarrou B, Deslandres M, Ferron G et al. Survival impact of histological response to neoadjuvant chemotherapy according to number of cycles in patients with advanced ovarian cancer. Int J Gynecol Cancer. 2022;32(8). Tables Table 1: Comparison of short course ( 5 cycles) in clinic-epidemiologic parameters. Variable 5 Cycles (77 patients) Significance Age mean +/- SD 55.9 +/- 9.2 55.9 +/- 10.2 .97 Comorbidity No Yes 65 65 41 36 .67 Menopausal status Pre-menopause Post-menopause 31 99 17 60 .86 CA125/CEA ratio 25 6 69 3 36 1 Peritoneal deposits No Yes 39 91 21 56 .75 Omental deposits No Yes 23 107 12 65 .85 Pleural effusion No Yes 106 24 58 19 .29 Regional nodes No Yes 72 58 41 36 .77 Non-regional nodes No Yes 113 16 62 15 .23 Visceral mets No Yes 111 19 62 15 .44 Clinical FIGO I II III IV 3 3 82 42 3 1 33 40 .03 Pathology Serous Mucinous Clear cell Others 121 1 2 6 75 0 0 1 .34 Grade Low High 3 127 1 75 1 Radiologic response to NAC CR PR PD SD 10 107 6 7 5 65 3 4 .98 Type of surgery Optimal Cytoreduction Suboptimal cytoreduction Irresectable 93 33 4 52 22 3 .82 Approach Laparotomy Laparoscopy 119 11 70 7 1 LN surgery No Yes 67 63 38 39 .77 30-day morbidity No Yes 124 6 69 8 .15 Pathologic response No Partial Complete 5 113 8 3 67 4 .96 Adjuvant chemotherapy No Yes 7 123 19 58 <.001 Total number of perioperative chemotherapy median (min-maximum) 6 (3-13) 8 (5-12) <.001 Table 2: Comparison of outcomes short course ( 5 cycles) neoadjuvant chemotherapy. Variable 5 Cycles Significance Relapse No Yes 43 82 18 55 .2 Relapse type Sensitive Resistant Refractory 56 17 9 42 9 4 .57 Site of relapse Locoregional Distant Both 37 23 22 24 16 15 .98 Estimated mean Overall survival (95%CI) 95.4 (86-104.8) 69.3 (60.1-78.6) .5 3-year OAS 75% 67% Median Relapse free survival (95%CI) 17 (11.9-22.1) 15 (11.8-18.1) .13 3-year RFS 20% 16% Table 3: Subgroup analysis of outcomes of short course ( 5 cycles) neoadjuvant chemotherapy in optimal and suboptimal debulking patients. Variable 5 cycles Significance Optimal debulking Estimated mean overall survival (95%CI) 97.7 (87.1-108.3) 74.5 (64.2-84.9) .85 Estimated median relapse free survival (95%CI) 19 (13.2-24.8) 16 (12.4-19.6) .3 Suboptimal debulking Estimated mean overall survival (95%CI) 72.4 (59.3-85.6) 60.5 (44.2-76.8) .65 Estimated median relapse free survival (95%CI) 16 (9.5-22.4) 12 (7-17) .39 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3859807","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272361571,"identity":"02d9bfbd-f8a6-40da-a28e-ef26311551ec","order_by":0,"name":"Reham Alghandour","email":"","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":false,"prefix":"","firstName":"Reham","middleName":"","lastName":"Alghandour","suffix":""},{"id":272361572,"identity":"90141b09-fd6b-487e-8a35-8577ada38fd9","order_by":1,"name":"Basel Refky","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3QIQvCQBTA8SeDszxd3THnZzg5OA3Dz6IIs5jFOBBs2sUvsWQ+uGAZRsuKIojBYJKFgW5gMMhNm+D9y3EcPx7vAEymX0wCKY6G/bxXwk8J0vBrwuSnpJ5Isk8zH/lOnQ4p+F4kLXXWEbrtVVvzWYAiCdocIeCRJEFHR1gMxKmFKic94QKofiRRsDJCs+yOfDW80RTuObFvpcRFIpG5I+EgyGKKtdfuEkOVe7MBOslo7CIb8KUiQiegnk85XLJu014N1zSddL3FZnq8ag3Yr+/FElb+IXryJqtkislkMv1ZDwrBR18kK2xtAAAAAElFTkSuQmCC","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":true,"prefix":"","firstName":"Basel","middleName":"","lastName":"Refky","suffix":""},{"id":272361573,"identity":"3d8cb6b6-3f6f-40af-9fa8-68e2a2344f86","order_by":2,"name":"Hasan Elsalman","email":"","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"","lastName":"Elsalman","suffix":""},{"id":272361574,"identity":"9f52f3c0-4494-4cce-b905-88ffa791f5ba","order_by":3,"name":"Doaa Saker","email":"","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":false,"prefix":"","firstName":"Doaa","middleName":"","lastName":"Saker","suffix":""},{"id":272361575,"identity":"ca652bed-534f-41a8-9b78-5701e5889154","order_by":4,"name":"Mohamed Zohdy","email":"","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Zohdy","suffix":""},{"id":272361576,"identity":"d561d7e8-0c71-497c-ab71-5047fd1cc661","order_by":5,"name":"Sara Elbaz","email":"","orcid":"","institution":"General Surgery Department, Al-Salam Oncology Center","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Elbaz","suffix":""},{"id":272361577,"identity":"f5519bf6-8946-4550-b5fb-28ddf9cf5388","order_by":6,"name":"Islam Hany","email":"","orcid":"","institution":"Oncology Center Mansoura University (OCMU)","correspondingAuthor":false,"prefix":"","firstName":"Islam","middleName":"","lastName":"Hany","suffix":""}],"badges":[],"createdAt":"2024-01-13 10:29:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3859807/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3859807/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51081252,"identity":"925afa19-9972-49f2-852a-6c190195deff","added_by":"auto","created_at":"2024-02-13 19:14:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":86289,"visible":true,"origin":"","legend":"\u003cp\u003eA: Kaplan-Meier curve showing overall survival between short and long course neoadjuvant chemotherapy.\u003c/p\u003e\n\u003cp\u003eFigure 1B: Kaplan-Meier curve showing relapse free survival between short and long course neoadjuvant chemotherapy.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3859807/v1/58a83358250f6da1d4469e55.png"},{"id":51081251,"identity":"95f5bbf8-125b-45c3-b7c7-172565495e5f","added_by":"auto","created_at":"2024-02-13 19:14:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47718,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of distribution of total number of perioperative chemotherapy between both groups.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3859807/v1/dd38a2f697b5f4d4fca141ba.png"},{"id":60503654,"identity":"8746c2be-6547-4d8d-98d4-8936670e0113","added_by":"auto","created_at":"2024-07-17 13:07:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":997908,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3859807/v1/5e32777a-f5a8-4d0f-93e9-172bb9ef730a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of short versus long course chemotherapy in the neoadjuvant setting in ovarian cancer","fulltext":[{"header":"Background","content":"\u003cp\u003eEpithelial ovarian neoplasm represents 90% of malignant ovarian neoplasm. It represents the fifth leading cause of cancer mortality in women (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Achievement of complete surgical cytoreductive surgery is the corner stone in management of ovarian cancer (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Patients presented with early stage are primarily managed by complete debulking surgery followed by adjuvant systemic chemotherapy (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, neoadjuvant chemotherapy followed by interval debulking might be necessary in most cases of advanced ovarian cancer for those the complete cytoreduction cannot be achieved at diagnosis, or those with advanced age, poor performance or comorbidities (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). At present there is no consensus about the optimum number of chemotherapy cycles before and after interval debulking surgery (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Hereby, in this study we evaluate the relation between number of neoadjuvant chemotherapy cycles and surgical and pathological outcome and its impact on progression and overall survival.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eThis is a retrospective cohort study, all patients included were newly diagnosed ovarian cancer who received neoadjuvant chemotherapy then underwent interval debulking surgery, presented to the Oncology Center Mansoura University from July 2011 to December 2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthical Approval:\u003c/u\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board approval was obtained by the Medical Research Ethics Committee - Institutional Review Board - Mansoura Faculty of Medicine - Mansoura University, (Approval No: R.22.01.1601).\u003c/p\u003e\n\u003cp\u003eAll procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eInclusion Criteria:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eNewly diagnosed patients with advanced epithelial ovarian carcinoma (FIGO stage III-IV) whom complete cytoreduction cannot be achieved.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePatients who are not candidate for primary debulking surgery e.g., poor performance, or not fit for surgery due to comorbidities.\u003c/li\u003e\n \u003cli\u003ePatients who received neoadjuvant chemotherapy then underwent interval debulking were included.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eExclusion criteria:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003ePatients with early-stage ovarian cancer were candidates for primary cytoreduction.\u003c/li\u003e\n \u003cli\u003ePatients were presented with recurrent disease.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eDemographics, preoperative, operative, postoperative, pathologic, and oncologic follow-up data were retrieved from a prospectively maintained electronic database.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe main outcome\u003c/strong\u003e of this study is to assess the optimum number of neoadjuvant chemotherapy cycles that influence the surgical and pathological outcome. \u003cstrong\u003eThe secondary outcome\u0026nbsp;\u003c/strong\u003eis to determine if the number of neoadjuvant chemotherapy cycles could influence the survival of these patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStatistical analysis:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe use the statistical software SPSS (Statistical Package for Social Scientists SPSS 26; Armonk, NY: IBM Corp) for analysis of the study results. Continuous variables will be presented as mean and standard deviation if normally distributed or median and range when non-normally distributed. Independent samples t-test will be used to compare parametric data whereas the Mann-Whitney U test will be used to compare non-parametric data. Categorical data will be compared by Pearson\u0026apos;s Chi-square test or Fischer-Exact test when appropriate. A p-value ˂0.05 is considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cu\u003e1.1: Epidemiology\u003c/u\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e207 patients enrolled. Mean age was 55.9 +/- 9.5 years old. Median BMI 33 (16-62). Only 15 patients (7.2%) had family history of breast/ovarian cancer. 101 (48.8%) has comorbidity with HTN being the commonest followed by DM. The majority were postmenopausal women (76.8%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbdominal pain was the most common presenting symptom (63.8%) followed by abdominal enlargement (26.1%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough CT CAP was the main stay investigation in almost all patients (98.6%). MRI pelvis was used in nearly half of them (55.1%). In 57% of patients there was bilateral adnexal masses. There were radiologic peritoneal and omental deposits in 71% and 83.1% of patients respectively. Ascites was present in 90.3% and pleural effusion in 20.3% of patients. 45.4% had enlarged regional LNs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e94.7% were serous carcinoma and 96.7% were high grade. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.2: Neoadjuvant therapy\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eIn 56% the cause of neoadjuvant was irresectable disease at diagnosis. In 95.7% the regimen was Taxan /Carboplatin. However, the number of neoadjuvant cycles varies greatly with 35.3% receiving 3 cycles followed by 27.5% 6 cycles and 26.6% 4 cycles. Most of the patients (83.1%) showed radiologic partial response, followed by 7.2% complete response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.3: Surgery and adjuvant treatment:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent surgery, however 3.4% of patients were closed as debulking was not possible. 70% of the patients underwent optimal cytoreduction (residue \u0026lt;1cm). The surgery was done laparoscopically in only 8.7% of the patients. Lymphadenectomy was done in 49.3% of the patients. 7.3% required GIT resection, 1.4% liver and 1.4% partial bladder resection. 30-day morbidity was 6.8% while mortality was 0.5%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e87.4% of the enrolled patients received adjuvant chemotherapy, in 30.9% this was 3 cycles followed by 2 and 4 in 22.2 % each.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.4: Relapse/progression:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eRelapse/progression occurred in 140 (67.6%) of the patients, 43.6% of them was locoregional. 71.4% of relapses were platinum sensitive (occurring \u0026gt;6months of finishing adjuvant platinum-based therapy) and the majority (88.6%) were treated by chemotherapy alone.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.5: Comparison of \u0026lt; 4 cycles VS \u0026gt; 5 cycles:\u003c/u\u003e (Table 1)\u003c/p\u003e\n\u003cp\u003ePatients who received less than or equal to 4 cycles were considered as group I (130 patients) and those who received 5 or more cycles were considered as group II (77 patients).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAge, Co-morbidity, Menopausal status, peritoneal deposits, omental deposits, ascites, pleural effusion, visceral metastasis, regional and non-regional adenopathy, pathologic subtype, grade, response to neoadjuvant, cytoreduction were not significantly different.\u003c/p\u003e\n\u003cp\u003eHowever, the clinical FIGO staging was significantly different where the majority (63.1%) of group I were stage III while 51.9% of group II were stage IV (.03). Also, in group I 94.6% received adjuvant chemotherapy in comparison to only 75% in group II (\u0026lt;.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, patients who received 5 or more cycles as neoadjuvant were more liable to receive a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value\u0026lt;.001) (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.6: Outcomes (Table 2)\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eOverall survival was calculated from date of surgery for all patients and was insignificantly different in both groups (.5) (Figure 1A) with 3-year OAS (75% VS 67% in group I and II, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the other hand, the relapse was calculated only in patients who successfully underwent debulking and was similar (63.1% VS 71.5% in group I and II, respectively (p=.57). Similarly, the difference in the relapse free survival was insignificant (.13) (Figure 1B) with 3-year RFS 20% VS 16%.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.7: Subgroup analysis according to debulking (Table 3)\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eBoth the OAS and the RFS were comparable in both groups in patients who underwent optimal debulking (p=.85 and .3, respectively) as well as in those who underwent suboptimal debulking (p=.65 and .39, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e1.8: Correlation between total number of perioperative chemotherapy and RFS\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe number of neoadjuvant and adjuvant cycles did not affect the relapse free survival (p=.46)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003eHighlights of main results\u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eNo difference regards the radiological, clinal or surgical response when short (4 or less) or long (5 or more) neoadjuvant chemotherapy was received to advanced ovarian cancer patients.\u003c/li\u003e\n\u003cli\u003eNo difference in overall or recurrence free survivals when short or long neoadjuvant course were offered for advanced ovarian cancer patients.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003eResults in the context of published literatures\u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has been established as an alternative approach in the treatment of advanced ovarian cancer (8). Although this approach offered better surgical outcomes and less residual disease after surgery, the overall (OS) and progression free survivals (PFS) were non inferior to those who underwent primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy (conventional approach) (9-11). However, pooled analysis reports from EORTC 55971 and CHORUS trials showed NACT (3 cycles NACT followed by ICS) was associated with mild improvement in PFS and OS of patients with more advanced disease (9, 12, 13). \u003c/p\u003e\n\u003cp\u003eIt is important to identify the patients who will benefit from NACT based on clinical, radiological, molecular parameters, and laparoscopic scoring models (8). There is a debate in the literature about the optimum numbers of NACT cycles (11). The American Society of Clinical Oncology (ASCO) and Society of Gynecologic Oncology (SGO) guidelines recommend offering 3-4 neoadjuvant platinum based chemotherapy for the patients who are unlikely to achieve primary complete cytoreduction (14), while National Comprehensive Cancer Network (NCCN) recommend offering 3-6 cycles followed by interval debulking for the same category of patients (15). That is why we conducted this study to evaluate the optimum number of neoadjuvant chemotherapy cycles on the response and survival of advanced ovarian cancer patients ineligible for primary cytoreductive surgery.\u003c/p\u003e\n\u003cp\u003eIn our study, more than half (56%) of the included (207) patients were irresectable at diagnosis. The recruited patients were categorized in two groups: 130 patients received 4 or less cycles versus 77 patients who received 5-6 NACT cycles. The rationale of extended treatment beyond 4 cycles in 77 patients was to increase the likelihood of achieving optimal cytoreduction after multidisciplinary team discussion, as most of those patients had stable disease after 3-4 cycles of NACT. Notably most of patients of this group had stage IV disease. In their studies, Marchetti et al. and Phillips et al., concluded that the achievement of optimal cytoreduction is the main independent prognostic factor regardless the number of NACT cycles (16, 17).\u003c/p\u003e\n\u003cp\u003eDespite the administration of NACT, optimal cytoreduction achieved in only 70% of all included patients which is comparable to what had been reported in literature (17, 18). In the present study, there was no significant difference in the rate of optimal cytoreduction surgery, pathological nor radiologic response (CR or PR) between those who received 4 or less NACT and those who received 5-6 cycles. This is contradictory to what had been reported by Marchetti et al. In their study they reported a significant increase of complete and partial -responses in patients who received longer NACT treatment (16, 19).\u003c/p\u003e\n\u003cp\u003eMoreover, we did not report any difference between the two groups regarding the surgical approach (laparotomy vs laparoscopy), surgical morbidity and mortality. This could be explained by the heterogeneity of included patients among the two groups and absence of initial baseline homogenous surgical score for all included patients. On other hand, others reported higher incidence of optimal cytoreduction and less surgical morbidity with 6 cycles of NACT (19). \u003c/p\u003e\n\u003cp\u003eBell et al. found that 6 NACT cycles associated with a 24% lower recurrence risk in patients with serous histology (20) but that was not observed in our study. The increased NACT cycles were not associated with reduction in the recurrence risk or its type (platinum sensitive or resistant).\u003c/p\u003e\n\u003cp\u003eThe present study did not observe a significant difference in overall or relapse-free survivals between those who received short or long course NACT. \u003c/p\u003e\n\u003cp\u003eActually, this point represents an argument in literature (11, 21). Although many studies reported decremental effects on Overall survival with increased number of cycles of NACT (22, 23), others agreed with our finding that there would be no difference in OS with increased number of cycles of NACT (16, 24). \u003c/p\u003e\n\u003cp\u003eMoreover, in a retrospective study conducted in Memorial Sloan Kettering Cancer Center, the longer course of NACT (≥ 5 cycles) had worse PFS and OS even after adjustment for BRCA status and complete gross resection (7). In contrary, Marchetti et al., reported no difference in OS between short or longer course of NACT. Interestingly, in univariate analysis BRCA mutation status was associated with improvement in OS (16). \u003c/p\u003e\n\u003cp\u003eNotably, the presence of residual disease is the most surrogate prognostic factor associated with worse OS regardless the number of NACT cycles (16, 24). Betrian et al. confirmed our results that there was no difference in OS and relapse-free survival regards the number of NACT cycles. After subgroup analysis, poor response to NACT regardless the number was surrogate factor for higher risk of recurrence, as those patients were unlikely to achieve complete cytoreduction due to high peritoneal cancer index (25).\u003c/p\u003e\n\u003cp\u003eStrikingly, the only significant difference between the two studied groups was that patients who received ≥ 5 NACT cycles were more liable to receive a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value\u0026lt;.001). This might be concordant with the NCCN guidelines that recommended that IDS should always be followed by at least 3 cycles of adjuvant chemotherapy regardless of the number of NACT cycles (9). \u003c/p\u003e\n\u003cp\u003eThe present study did not demonstrate benefit from prolonging the course of NACT beyond 4 cycles on rate of response or achievement of optimal cytoreduction and did not decrease the risk of relapse.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003eStrength and weakness \u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is worth mentioning that there are several limitations of our study including the retrospective nature which could have led to selection bias between both groups, absence of unique baseline surgical score, and lack of BRCA mutation status data which might affected the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003eImplication for practice and future practice\u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRandomized controlled trials are awaited to still the debate about the optimum number of neoadjuvant chemotherapy cycles to advanced ovarian cancer patients, and implication of baseline surgical scores, with incorporation of molecular background to all included patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAdministration more than four cycles of neoadjuvant chemotherapy in ovarian cancer patient had no impact on response, achievement of optimal cytoreduction, surgical approach, morbidity, or mortality, did not reduce the risk of recurrence or improve survival. Further randomized trials are awaited to determine the optimum number of NACT and assess its impact on survival.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosures and funding source:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest. No funding sources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board approval was obtained. (Approval No: R.22.01.1601), All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInfo\u003c/strong\u003e\u003cstrong\u003ermed Consent:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was waived by the Institutional Review Board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003cstrong\u003e. \u0026nbsp; \u0026nbsp; \u0026nbsp; Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors state that this work has not received any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6.\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u003cstrong\u003eAuthors contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHasan Elsalman, Doaa H. Saker, Mohamed Zohdy, Sara Elbaz\u003csup\u003e:\u003c/sup\u003e\u003c/strong\u003ewere responsible forcollection of data\u003csup\u003e.\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReham Alghandour\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003ewrite the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIslam Hany\u003csup\u003e:\u003c/sup\u003e\u003c/strong\u003ewas responsible for statistical analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDoaa H. Saker, Mohamed Zohdy, Basel Refky:\u0026nbsp;\u003c/strong\u003erevision and final approval of \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBasel Refky: corresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7. Consent for publication\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003e:\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrand A, DiSilvestro P, Sehouli J, Berek J. Cytoreductive surgery for ovarian cancer: quality assessment. Ann Oncol. 2017;28:viii25\u0026ndash;viii9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakar AP, Trop\u0026eacute; CG, Tummers P, Denys H, Vandecasteele K. Advanced ovarian cancer: primary or interval debulking? Five categories of patients in view of the results of randomized trials and tumor biology: primary debulking surgery and interval debulking surgery for advanced ovarian cancer. Oncologist. 2016;21(6):745.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFagotti A, Ferrandina MG, Vizzielli G, Pasciuto T, Fanfani F, Gallotta V et al. Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int J Gynecol Cancer. 2020;30(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Meurs HS, Tajik P, Hof MH, Vergote I, Kenter GG, Mol BWJ, et al. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Eur J Cancer. 2013;49(15):3191\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu X, Deng F, Lv M, Chen X. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc\u0026ndash;IV high-grade serous ovarian cancer. Arch Gynecol Obstet. 2017;295(2):451\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu YL, Zhou QC, Iasonos A, Chi DS, Zivanovic O, Sonoda Y et al. Pre-operative neoadjuvant chemotherapy cycles and survival in newly diagnosed ovarian cancer: what is the optimal number? A Memorial Sloan Kettering Cancer Center Team Ovary study. Int J Gynecol Cancer. 2020;30(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatel A, Iyer P, Matsuzaki S, Matsuo K, Sood AK, Fleming ND. Emerging trends in neoadjuvant chemotherapy for ovarian cancer. Cancers. 2021;13(4):626.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. NCCN guidelines insights: Ovarian cancer, version 1.2019: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2019;17(8):896\u0026ndash;909.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelamed A, Rauh-Hain JA, Gockley AA, Nitecki R, Ramirez PT, Hershman DL, et al. Association between overall survival and the tendency for cancer programs to administer neoadjuvant chemotherapy for patients with advanced ovarian cancer. JAMA Oncol. 2021;7(12):1782\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuesada S, Thomas QD, Colombo P-E, Fiteni F. Optimal First-Line Medico-Surgical Strategy in Ovarian Cancers. Are We There Yet? Cancers. 2023;15(14):3556.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTajik P, van de Vrie R, Zafarmand MH, Coens C, Buist MR, Vergote I et al. The FIGO stage IVA versus IVB of ovarian cancer: prognostic value and predictive value for neoadjuvant chemotherapy. Int J Gynecol Cancer. 2018;28(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVergote I, Coens C, Nankivell M, Kristensen GB, Parmar MK, Ehlen T, et al. Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol. 2018;19(12):1680\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanderpuye VD, Clemenceau JRV, Temin S, Aziz Z, Burke WM, Cevallos NL, et al. Assessment of adult women with ovarian masses and treatment of epithelial ovarian cancer: ASCO resource-stratified guideline. JCO Global Oncol. 2021;7:1032\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong DK, Alvarez RD, Backes FJ, Bakkum-Gamez JN, Barroilhet L, Behbakht K, et al. NCCN guidelines\u0026reg; insights: Ovarian cancer, version 3.2022: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2022;20(9):972\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchetti C, Rosati A, De Felice F, Boccia S, Vertechy L, Pavone M, et al. Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis. Gynecol Oncol. 2021;163(1):29\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhillips A, Sundar S, Singh K, Nevin J, Elattar A, Kehoe S, et al. Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer. Eur J Surg Oncol. 2018;44(6):760\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhillips A, Balega J, Nevin J, Singh K, Elattar A, Kehoe S, et al. Reporting \u0026lsquo;Denominator\u0026rsquo;data is essential for benchmarking and quality standards in ovarian cancer. Gynecol Oncol. 2017;146(1):94\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumari A, Thakur M, Saha S, Suri V, Prasad G, Patel FD, et al. To compare the optimal cytoreduction rate in advanced epithelial ovarian cancer stage III/IV after 3 versus 6 cycles of neoadjuvant chemotherapy. J Obstet Gynaecol. 2021;41(4):616\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBell J, Brady MF, Young RC, Lage J, Walker JL, Look KY, et al. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;102(3):432\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitecki R, Melamed A. Extra cycles of neoadjuvant chemotherapy before interval surgery for ovarian cancer: the more the merrier or too much of a good thing? Int J Gynecol Cancer. 2022;32(8):975\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAltman AD, McGee J, May T, Lane K, Lu L, Xu W, et al. Neoadjuvant chemotherapy and chemotherapy cycle number: a national multicentre study. Gynecol Oncol. 2017;147(2):257\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStoeckle E, Boubli B, Floquet A, Brouste V, Sire M, Croce S, et al. Optimal timing of interval debulking surgery in advanced ovarian cancer: yet to be defined? Eur J Obstet Gynecol Reproductive Biology. 2011;159(2):407\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerrone AM, Coada CA, Ravegnini G, De Leo A, Damiano G, De Crescenzo E et al. Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma. Int J Gynecol Cancer. 2023;33(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBetrian S, Angeles MA, Moreno AG, Cabarrou B, Deslandres M, Ferron G et al. Survival impact of histological response to neoadjuvant chemotherapy according to number of cycles in patients with advanced ovarian cancer. Int J Gynecol Cancer. 2022;32(8).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Comparison of short course (\u003cu\u003e\u0026lt;\u003c/u\u003e 4 cycles) versus long course (\u003cu\u003e\u0026gt;\u003c/u\u003e 5 cycles) in clinic-epidemiologic parameters.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026lt;\u003c/u\u003e 4 Cycles\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(130 patients)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 5 Cycles\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(77 patients)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge mean +/- SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e55.9 +/- 9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e55.9 +/- 10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMenopausal status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePre-menopause\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePost-menopause\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA125/CEA ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026lt;\u003c/u\u003e25\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeritoneal deposits\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOmental deposits\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePleural effusion\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegional nodes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-regional nodes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisceral mets\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical FIGO\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eII\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIII\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSerous\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMucinous\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eClear cell\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOthers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiologic response to NAC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOptimal Cytoreduction\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSuboptimal cytoreduction\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIrresectable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eApproach\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLaparotomy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLaparoscopy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLN surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e30-day morbidity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathologic response\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePartial\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eComplete\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.807692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal number of perioperative chemotherapy median (min-maximum)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.96153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e6 (3-13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e8 (5-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2: Comparison of outcomes short course (\u003cu\u003e\u0026lt;\u003c/u\u003e 4 cycles) versus long course (\u003cu\u003e\u0026gt;\u003c/u\u003e 5 cycles) neoadjuvant chemotherapy.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026lt;\u003c/u\u003e4 Cycles\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 5 Cycles\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse type\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSensitive\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eResistant\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRefractory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of relapse\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLocoregional\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDistant\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBoth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated mean Overall survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e95.4 (86-104.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e69.3 (60.1-78.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3-year OAS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e67%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian Relapse free survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e17 (11.9-22.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e15 (11.8-18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3-year RFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e16%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3: Subgroup analysis of outcomes of short course (\u003cu\u003e\u0026lt;\u003c/u\u003e 4 cycles) versus long course (\u003cu\u003e\u0026gt;\u003c/u\u003e 5 cycles) neoadjuvant chemotherapy in optimal and suboptimal debulking patients.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.73076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 4 cycles\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt; 5 cycles\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.03846153846154%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOptimal debulking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.73076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated mean overall survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e97.7 (87.1-108.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e74.5 (64.2-84.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.03846153846154%\" valign=\"top\"\u003e\n \u003cp\u003e.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.73076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated median relapse free survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e19 (13.2-24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e16 (12.4-19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.03846153846154%\" valign=\"top\"\u003e\n \u003cp\u003e.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuboptimal debulking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.73076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated mean overall survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e72.4 (59.3-85.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e60.5 (44.2-76.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.03846153846154%\" valign=\"top\"\u003e\n \u003cp\u003e.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.73076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated median relapse free survival (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e16 (9.5-22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.115384615384617%\" valign=\"top\"\u003e\n \u003cp\u003e12 (7-17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.03846153846154%\" valign=\"top\"\u003e\n \u003cp\u003e.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ovarian cancer, Cytoreduction, neoadjuvant chemotherapy, serous carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-3859807/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3859807/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eThere is a debate about the optimum number of neoadjuvant chemotherapy (NACT) cycles for ovarian cancer and its impact on survival.\u003c/p\u003e\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eThis study aimed to assess the optimum number (NACT) cycles that influence the surgical and pathological outcome and its impact on survival.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eretrospective cohort study, all patients included were newly diagnosed ovarian cancer who received NACT then underwent interval debulking surgery (IDA), presented to tertiary cancer center from July 2011 to December 2021.patients were classified into two groups according to number of NACT cycles. Group 1; Patients who received\u0026thinsp;\u0026le;\u0026thinsp;4 cycles Group 2; Patients who received\u0026thinsp;\u0026le;\u0026thinsp;5 cycles.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003e207 patients were included (130 patients in group 1, 70 patients in group 2). 63.1% of group I were stage III while 51.9% of group II were stage IV. There was no difference between two groups in pathological response to NACT (P\u0026thinsp;=\u0026thinsp;0.9), or those who underwent optimal cytoreduction (P\u0026thinsp;=\u0026thinsp;0.8). group 2 received a higher total dose of perioperative chemotherapy (median 8 VS 6 cycles) (P-value\u0026thinsp;\u0026lt;\u0026thinsp;.001). There were no significant differences between both groups regards overall (OS) or relapse free survivals (RFS) (P\u0026thinsp;=\u0026thinsp;0.5. 0.1 respectively).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eReceiving more than 4 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery had no impact on achievement of optimal cytoreduction surgery or surgical morbidity and mortality and did not affect relapse free or overall survivals.\u003c/p\u003e","manuscriptTitle":"Evaluation of short versus long course chemotherapy in the neoadjuvant setting in ovarian cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-13 19:14:48","doi":"10.21203/rs.3.rs-3859807/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a1e23b52-24f4-4435-aa28-ac115ded413f","owner":[],"postedDate":"February 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-17T12:51:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-13 19:14:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3859807","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3859807","identity":"rs-3859807","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}