title: Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. A prospective comparison of integrated FDG-PET/contrast-enhanced CT and contrast-enhanced CT for pretreatment imaging of advanced epithelial ovarian cancer. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. A multicentric trial (Olympia-MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer. Whole-body MRI with diffusion-weighted sequence for staging of patients with suspected ovarian cancer: a clinical feasibility study in comparison to CT and FDG-PET/CT Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study. Specialized and high-volume care leads to better outcomes of ovarian cancer treatment in the Netherlands. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome. Thirty-Day Mortality After Primary Cytoreductive Surgery for Advanced Ovarian Cancer in the Elderly Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Gr Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer. 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.
abstract: OBJECTIVE Intraperitoneal ( IP ) chemotherapy prolongs survival in optimally reduced ovarian cancer patients . For patients in whom optimal debulking can not be achieved , one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy . We sought to evaluate overall survival ( OS ) , progression-free survival ( PFS ) , percent of patients optimally debulked and toxicity in patients treated with this strategy . METHODS Women with adenocarcinoma by biopsy or cytology with stage III/IV ( pleural effusions only ) epithelial ovarian , fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous ( IV ) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery ( if > /=50 % decrease in CA125 ) . If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 ( day 1 ) and IP paclitaxel 60 mg/m2 ( day 8) q 28 daysx6 cycles . RESULTS Sixty-two patients were registered . Four were ineligible . Fifty-six were evaluated for neoadjuvant chemotherapy toxicities . One patient died of pneumonia . Five patients had grade 4 toxicity , including neutropenia ( 3 ) , anemia , leukopenia , anorexia , fatigue , muscle weakness , respiratory infection , and cardiac ischemia . Thirty-six patients had debulking surgery . Two had grade 4 hemorrhage . Twenty-six patients received post-cytoreduction chemotherapy . Four had grade 4 neutropenia . At a median follow-up of 21 months , median PFS is 21 months and median OS is 32 months for all 58 patients . PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively . CONCLUSIONS These results compare favorably with other studies of sub-optimally debulked patients BACKGROUND The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian , fallopian tube , or primary peritoneal cancer . We report the long-term follow-up results for survival . METHODS This r and omised controlled trial was done at 85 centres in Japan . Patients with stage II-IV ovarian cancer were r and omly assigned to receive conventional treatment ( carboplatin area under the curve [ AUC ] 6 mg/mL per min and paclitaxel 180 mg/m(2 ) on day 1 ) or dose-dense treatment ( carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 ) . The treatments were repeated every 3 weeks for six cycles ; responding patients had three additional cycles . The r and omisation was done central ly by telephone or fax , stratified by residual disease , stage , and histological type . The primary endpoint was progression-free survival ; overall survival was a secondary endpoint . Long-term information on adverse events was not collected . Efficacy analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 637 patients were enrolled , of whom 631 were analysed ( 312 assigned to the dose-dense regimen , 319 to the conventional regimen ) . Median follow-up was 76·8 months ( IQR 68·9 - 85·6 ) . Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group ( 28·2 months [ 95 % CI 22·3 - 33·8 ] vs 17·5 months [ 15·7 - 21·7 ] ; hazard ratio [ HR ] 0·76 , 95 % CI 0·62 - 0·91 ; p=0·0037 ) . Median overall survival was 100·5 months ( 95 % CI 65·2-∞ ) in the dose-dense treatment group and 62·2 months ( 52·1 - 82·6 ) in the conventional treatment group ( HR 0·79 , 95 % CI 0·63 - 0·99 ; p=0·039 ) . INTERPRETATION Dose-dense treatment offers better survival  than conventional treatment and is a potential new st and ard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer BACKGROUND The international st and ard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy . We aim ed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen . METHODS In this phase 3 , non-inferiority , r and omised , controlled trial ( CHORUS ) undertaken in 87 hospitals in the UK and New Zeal and , we enrolled women with suspected stage III or IV ovarian cancer . We r and omly assigned women ( 1:1 ) either to undergo primary surgery followed by six cycles of chemotherapy , or to three cycles of primary chemotherapy , then surgery , followed by three more cycles of completion chemotherapy . Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2 ) , or an alternative carboplatin combination regimen , or carboplatin monotherapy . We did the r and om assignment by use of a minimisation method with a r and om element , and stratified participants according to the r and omising centre , largest radiological tumour size , clinical stage , and prespecified chemotherapy regimen . Patients and investigators were not masked to group assignment . The primary outcome measure was overall survival . Primary analyses were done in the intention-to-treat population . To establish non-inferiority , the upper bound of a one-sided 90 % CI for the hazard ratio ( HR ) had to be less than 1.18 . This trial is registered , number IS RCT N74802813 , and is closed to new participants . FINDINGS Between March 1 , 2004 , and Aug 30 , 2010 , we r and omly assigned 552 women to treatment . Of the 550 women who were eligible , 276 were assigned to primary surgery and 274 to primary chemotherapy . All were included in the intention-to-treat analysis ; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per- protocol analysis . As of May 31 , 2014 , 451 deaths had occurred : 231 in the primary -surgery group versus 220 in the primary -chemotherapy group . Median overall survival was 22.6 months in the primary -surgery group versus 24.1 months in primary chemotherapy . The HR for death was 0.87 in favour of primary chemotherapy , with the upper bound of the one-sided 90 % CI 0.98 ( 95 % CI 0.72 - 1.05 ) . Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary -surgery group than in the primary -chemotherapy group ( 60 [ 24 % ] of 252 women vs 30 [ 14 % ] of 209 , p=0.0007 , and 14 women [ 6 % ] vs 1 woman [ < 1 % ] , p=0.001 ) . The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups ( 8 women [ 3 % ] in the primary -surgery group vs 14 [ 6 % ] in the primary -chemotherapy group ) . 110 ( 49 % ) of 225 women receiving primary surgery and 102 ( 40 % ) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect ( p=0.0654 ) , mostly uncomplicated neutropenia ( 20 % and 16 % , respectively ) . One fatal toxic effect , neutropenic sepsis , occurred in the primary -chemotherapy group . INTERPRETATION In women with stage III or IV ovarian cancer , survival with primary chemotherapy is non-inferior to primary surgery . In this study population , giving primary chemotherapy before surgery is an acceptable st and ard of care for women with advanced ovarian cancer . FUNDING Cancer Research UK and the Royal College of Obstetricians and Gynaecologists PURPOSE To compare the efficacy and safety of pegylated liposomal doxorubicin ( PLD ) and topotecan in patients with epithelial ovarian carcinoma that recurred after or did n't respond to first-line , platinum-based chemotherapy . PATIENTS AND METHODS Patients with measurable and assessable disease were r and omized to receive either PLD 50 mg/m(2 ) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks . Patients were stratified prospect ively for platinum sensitivity and for the presence or absence of bulky disease . RESULTS A total of 474 patients were treated ( 239 PLD and 235 topotecan ) . They comprised the intent-to-treat population . The overall progression-free survival rates were similar between the two arms ( P = .095 ) . The overall response rates for PLD and topotecan were 19.7 % and 17.0 % , respectively ( P = .390 ) . Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan . Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival ( P = .037 ) , with medians of 28.9 for PLD versus 23.3 weeks for topotecan . For overall survival , PLD was significantly superior to topotecan ( P = .008 ) , with a median of 108 weeks versus 71.1 weeks . The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan ( P = .455 ) . Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification , or growth factor or blood product utilization . CONCLUSION The comparable efficacy , favorable safety profile , and convenient dosing support the role of PLD as a valuable treatment option in this patient population BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer OBJECTIVE The use of tumor debulking surgery in the management of epithelial ovarian cancer ( EOC ) , which is often disseminated in the peritoneal cavity at the time of diagnosis , has a significant impact on prognosis . We compared (18)F-fluorodeoxyglucose ( FDG ) positron emission tomography/contrast-enhanced computed tomography ( PET/CT ) to contrast-enhanced CT for the detection of dissemination into the abdominal cavity preventing successful primary debulking surgery . METHODS Forty-one women with EOC underwent preoperative  whole-body low-dose FDG-PET/CT followed by diagnostic high dose contrast-enhanced CT scan , and the results were compared with systematic ally recorded surgical findings as a reference st and ard . Both site-based and patient-based analyses were conducted . RESULTS FDG-PET/CT was superior to conventional CT for the detection of carcinomatosis in subdiaphragmatic peritoneal surfaces ( p=0.020 ) and in the bowel mesentery ( p=0.001 ) . Patient-based analysis of upper abdominal areas requiring extensive surgical procedures showed no significant differences between the two imaging methods . The sensitivity of PET/CT and CT  was poor in certain areas of the peritoneal cavity ( 64 % vs. 27 % in the small bowel mesentery and 65 % vs. 55 % in the right upper abdomen ) . Extra-abdominal disease spread was detected by PET/CT in 32 patients and by CT in 25 patients . CONCLUSIONS PET/CT was not superior to CT for the detection of intra-abdominal disease spread .  Patients with suspected EOC should be referred for upfront radical surgery regardless of the results of preoperative imaging studies . PET/CT is more effective for the detection of extra-abdominal disease than CT , but the clinical significance of this finding is unclear PURPOSE In r and omized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer . Although in nonr and omized trials , carboplatin and paclitaxel was a less toxic and highly active combination regimen , there remained concern regarding its efficacy in patients with small-volume , resected , stage III disease . Thus , we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population . PATIENTS AND METHODS Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were r and omly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 ( arm I ) , or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours ( arm II ) . RESULTS Seven hundred ninety-two eligible patients were enrolled onto the study . Prognostic factors were similar in the two treatment groups . Gastrointestinal , renal , and metabolic toxicity , as well as grade 4 leukopenia , were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II . Neurologic toxicity was similar in both regimens . Median progression-free survival and overall survival were 19.4 and 48.7 months , respectively , for arm I compared with 20.7 and 57.4 months , respectively , for arm II . The relative risk ( RR ) of progression for the carboplatin plus paclitaxel group was 0.88 ( 95 % confidence interval [ CI ] , 0.75 to 1.03 ) and the RR of death was 0.84 ( 95 % CI , 0.70 to 1.02 ) . CONCLUSION In patients with advanced ovarian cancer , a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity , is easier to administer , and is not inferior , when compared with cisplatin plus paclitaxel OBJECTIVE The objective of the study was to prospect ively evaluate the accuracy of laparoscopy performed in satellite centers ( SCs ) to describe intraabdominal diffusion of advanced ovarian cancer ( AOC ) . STUDY DESIGN Patients with a clinical /radiological suspicion of AOC were included in the protocol . SCs were selected among those surgeons , spending a short intensive training period at the coordinator center ( CC ) to learn the application of staging laparoscopy ( S-LPS ) in AOC . All women underwent  S-LPS at the SCs , and the surgical procedure was recorded and blindly review ed at the CC . Calculating specificity , positive and negative predictive values , and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS . The Cohen 's kappa was used to test the interobserver agreement of each parameter . RESULTS One hundred sixty-eight cases were considered eligible for the study . A per- protocol analysis was performed on 120 cases . The worst laparoscopic assessable feature was mesenteric retraction , whereas the remaining variables ranged from 99.2 % ( peritoneal carcinomatosis ) to 90 % ( bowel infiltration ) . All but 1 SC ( SC number 4 ) reached an accuracy rate of 80 % or greater for both single parameters and overall score . The Cohen 's kappa and the P value for overall predicitive index value were 0.685 and .01 , respectively , but improved to 0.773 and .388 after removing the SC number 4 from the analysis . CONCLUSION S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers Objectives To evaluate whole-body MRI with diffusion-weighted sequence ( WB-DWI/MRI ) for staging and assessing operability compared with CT and FDG-PET/CT in patients with suspected ovarian cancer . Methods Thirty-two patients underwent 3-T WB-DWI/MRI , 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( FDG-PET/CT ) and CT before diagnostic open laparoscopy  ( DOL ) . Imaging findings for tumour characterisation , peritoneal and retroperitoneal staging were correlated with histopathology after DOL and /or open surgery . For distant metastases , FDG-PET/CT or image-guided biopsies were the reference st and ards . For tumour characterisation and peritoneal staging , WB-DWI/MRI was compared with CT and FDG-PET/CT . Interobserver agreement for WB-DWI/MRI was determined . Results WB-DWI/MRI showed 94 % accuracy for primary tumour characterisation compared with 88 % for CT and 94 % for FDG-PET/CT . WB-DWI/MRI showed higher accuracy of 91 % for peritoneal staging compared with CT ( 75 % ) and FDG-PET/CT ( 71 % ) . WB-DWI/MRI and FDG-PET/CT showed higher accuracy of 87 % for detecting retroperitoneal lymphadenopathies compared with CT ( 71 % ) . WB-DWI/MRI showed excellent correlation with FDG-PET/CT ( κ = 1.00 ) for detecting distant metastases compared with CT ( κ = 0.34 ) . Interobserver agreement was moderate to almost perfect ( κ = 0.58–0.91 ) . Conclusions WB-DWI/MRI shows high accuracy for characterising primary tumours , peritoneal and distant staging compared with CT and FDG-PET/CT and may be valuable for assessing operability in ovarian cancer patients .Key Points• Whole-body MRI with diffusion weighting ( WB-DWI/MRI ) helps to assess the operability of suspected ovarian cancer.• Interobserver agreement is good for primary tumour characterisation , peritoneal and distant staging.• WB-DWI/MRI  improves mesenteric/serosal metastatic spread assessment compared with CT and FDG-PET/CT.• Retroperitoneal/cervical-thoracic nodal staging using qualitative DWI criteria was reasonably accurate.• WB-DWI/MRI and FDG-PET/CT showed the highest diagnostic impact for detecting thoracic metastases BACKGROUND A number of elderly cancer patients do not receive st and ard surgery for solid tumors because they are considered unfit for treatment as a consequence of inaccurate estimation of the operative risk . To tailor treatment to onco-geriatric series , oncologists are now beginning to use a comprehensive geriatric assessment ( CGA ) . This study investigates the value of an extended CGA in assessing the suitability of elderly patients for surgical intervention . PATIENTS AND METHODS Preoperative assessment of cancer in the elderly ( PACE ) incorporates vali date d instruments including the CGA , an assessment of fatigue and performance status and an anaesthesiologist 's evaluation of operative risk . An international prospect i ve study was conducted using 460 consecutively recruited elderly cancer patients who received PACE prior to elective surgery .  Mortality , post-operative complications ( morbidity ) and length of hospital stay were recorded up to 30 days after surgery . RESULTS Poor health in relation to disability ( assessed using the instrumental activities of daily living ( IADL ) ) , fatigue and performance status ( PS ) were associated with a 50 % increase in the relative risk of post-operative complications . Multivariate analysis identified moderate/severe fatigue , a dependent IADL and an abnormal PS as the most important independent predictors of post-surgical complications . Disability assessed by activities of daily living ( ADL ) , IADL and PS were associated with an extended hospital stay . CONCLUSION PACE represents a valuable tool in enhancing the decision process concerning the c and idacy of elderly cancer patients for surgical intervention and can reduce inappropriate age-related inequity in access to surgical intervention . It is recommended that PACE be used routinely in surgical practice OBJECTIVE We investigated the influence of hospital and gynecologist level of specialization and volume on surgical results and on survival of ovarian cancer patients . METHODS Data were collected from 1077 ovarian cancer patients treated from 1996 to 2003 in a r and om sample of 18 Dutch hospitals .  Hospitals and gynecologists were classified according to specialization ( general , semi-specialized or specialized ) and by volume ( < or=6 , 7 - 12 , or > 12 cases/year ) . Outcomes were percentage of adequately staged and optimally debulked patients and length of overall survival . Data were analyzed using multivariable logistic regression ( surgical results ) and Cox regression ( survival ) . RESULTS The level of specialization and the volume of hospitals and of gynecologists were strongly related to the proportion of adequately staged patients ( adjusted odds ratio ( OR ) specialized hospitals 3.9 ( 95 % confidence interval ( CI ) 2.0 - 7.6 ) ; specialized gynecologists 9.5 ( 95 % CI 4.7 - 19 ) ) . Patients with stage III disease had a higher chance of optimal debulking when treated in specialized hospitals ( adjusted OR 1.7 ( 95 % CI 1.1 - 2.7 ) ) or by high volume gynecologists ( adjusted OR 2.8 ( 95 % CI 1.4 - 5.7 ) ) . Overall survival was best in patients treated in specialized hospitals and by high-volume gynecologists . CONCLUSION The specialization level of hospitals and the surgical volume of gynecologists positively influence outcomes of surgery and survival . Concentration of ovarian cancer care thus seems warranted OBJECTIVE To establishing whether neoadjuvant chemotherapy ( NACT ) followed by interval debulking surgery ( IDS ) is superior primary debulking surgery ( PDS ) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer ( AEOC ) endowed with high tumour load ( HTL ) . MATERIAL AND METHODS This is a single-Institution , superiority , r and omised phase III trial enrolling supposed AEOC women . Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index ( PI ) of tumour load . All AEOC women with PI≥8 or≤12 ( considered as HTL ) were included . They were r and omly assigned ( 1:1 ratio ) to undergo either PDS followed by systemic adjuvant chemotherapy ( arm A , st and ard ) , or NACT followed by IDS ( NACT/IDS ) ( arm B , experimental ) . Co- primary outcome measures were postoperative complications ( grade d according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system ) and progression free survival ( PFS ) ; secondary outcomes were overall survival , and quality of life ( QoL ) . QoL was assessed using the EORTC QoL question naires . A sample size of 110 patients was required for the analysis of the first co- primary end-point ( major peri-operative morbidity ) whereas recruitment is still on-going to achieve the statistical power on PFS . RESULTS Between October 2011 and November 2014 , we registered 280 AEOC . Of the 110 eligible women , 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery , rates of complete residual disease ( residual tumour=0 cm ) were superimposable between the groups ( 45.5 % versus 57.7 % ; p=0.206 ) . Twenty-nine patients ( 52.7 % ) in arm A experienced early grade III-IV complications versus three patients ( 5.7 % ) in IDS ( p=0.0001 ) . The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage ( 17/55 women ( 30.9 % ) in arm A versus 1/52 ( 1.9 % ) in arm B , p=0.0001 ) . Three grade IV ( 5.4 % ) ( i.e. , two re-operations for postoperative haemorrhage and one septic multi-organ failure ) , and two grade V ( 3.6 % ) ( two deaths for acute cardiopulmonary failure ) early complications were observed in arm A only . Mean QoL scores of several scales/items were shown to ameliorate over time in both arms . Emotional functioning , cognitive functioning , nausea/vomiting , dyspnoea , insomnia and hair loss were statistically and clinical ly better in NACT/IDS compared to PDS arm . CONCLUSIONS Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL . Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL OBJECTIVE : To identify factors associated with increased 30-day mortality after advanced ovarian cancer debulking among elderly women . METHODS : A data base linking Medicare records with the Surveillance , Epidemiology , and End Results ( SEER ) data was used to identify a cohort of 5,475 women aged 65 and older who had primary debulking surgery for stage III or IV epithelial ovarian cancer ( diagnosed 1995–2005 ) . Women were stratified by acuity of hospital admission . Multivariable analysis was performed to identify patient-related and treatment-related variables associated with 30-day mortality . RESULTS : Five thous and four hundred seventy-five women had surgery for advanced ovarian cancer , and the overall 30-day mortality was 8.2 % . Women admitted electively had a 30-day mortality of 5.6 % ( 251 of 4,517 ) , and those admitted emergently had a 30-day mortality of 20.1 % ( 168 of 835 ) . Advancing age , increasing stage , and increasing comorbidity score were all associated with an increase in 30-day mortality ( all P<.05 ) among elective admissions . A group of women at high risk admitted electively included those aged 75 or older with stage IV disease and women aged 75 or older with stage III disease and a comorbidity score of 1 or more . This group had an observed 30-day mortality of 12.7 % ( 95 % confidence interval 10.7%–14.9 % ) . CONCLUSION : Age , cancer stage , and comorbidity scores may be helpful to stratify electively admitted patients based on predicted postoperative mortality . If vali date d in a prospect i ve cohort , then these factors may help identify women who may benefit from alternative treatment strategies . LEVEL OF EVIDENCE : BACKGROUND Intravenous platinum-based chemotherapy is the st and ard primary therapy for advanced ovarian cancer . We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated , stage III , epithelial ovarian cancer . METHODS The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm . Within four weeks after surgery , six courses of intravenous cyclophosphamide ( 600 mg per square meter of body-surface area per course ) plus either intraperitoneal cisplatin ( 100 mg per square meter ) or intravenous cisplatin ( 100 mg per square meter ) were administered at three-week intervals . RESULTS Of 654 r and omized patients , 546 were eligible for the study . The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin ( 49 months ; 95 percent confidence interval , 42 to 56 ) than in the group receiving intravenous cisplatin ( 41 months ; 95 percent confidence interval , 34 to 47 ) . The risk of death was lower in the intraperitoneal group than in the intravenous group ( hazard ratio , 0.76 ; 95 percent confidence interval , 0.61 to 0.96 ; P = 0.02 ) . Moderate-to-severe tinnitus , clinical hearing loss , and neuromuscular toxic effects were significantly more frequent in the intravenous group . CONCLUSIONS As compared with intravenous cisplatin , intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less Three large r and omized clinical trials have shown a survival benefit in women with stage iii epithelial ovarian cancer ( eoc ) who receive intraperitoneal ( IP ) chemotherapy after optimal primary debulking surgery . The most recent Gynecologic Oncology Group study , gog 172 , showed an improvement in median overall survival of approximately 17 months . That result led to a U.S. National Cancer Institute ( nci ) clinical announcement recommending that IP chemotherapy be considered for this group of women with eoc . However , IP chemotherapy is associated with increased toxicity , and rates for completion of treatment are low ( 42 % in gog 172 ) . The optimal IP regimen and duration of treatment has yet to be defined . Women undergoing chemotherapy before optimal debulking surgery were not included in the studies or in the nci clinical announcement . The National Cancer Institute of Canada Clinical Trials Group has developed a protocol for a r and omized phase ii/iii study which will examine whether IP platinum-taxane-based chemotherapy benefits women who have received neoadjuvant chemotherapy before optimal surgical debulking . To address whether the less systemically toxic  carboplatin can be substituted for cisplatin IP , the first phase of the study will have 3 arms : 1 intravenous-only , and 2 IP-containing regimens . At the end of the first stage , and provided that IP therapy is feasible to administer in this patient population , one of the IP regimens , either IP carboplatin or IP cisplatin , will proceed into a phase iii comparison with the intravenous arm . This exciting new study has gathered international support Summary Background The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to st and ard chemotherapy , with the greatest effect in patients at high risk of disease progression . We report the final overall survival results of the trial . Methods ICON7 was an international , phase 3 , open-label , r and omised trial undertaken at 263 centres in 11 countries across Europe , Canada , Australia and New Zeal and . Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease ( International Federation of Gynecology and Obstetrics [ FIGO ] stage I – IIa , grade 3 or clear cell histology ) or more advanced disease ( FIGO stage IIb – IV ) , with an Eastern Cooperative Oncology Group performance status of 0–2 , were enrolled and r and omly assigned in a 1:1 ratio to st and ard chemotherapy ( six 3-weekly cycles of intravenous carboplatin [ AUC 5 or 6 ] and paclitaxel 175 mg/m2 of body surface area ) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks , given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy . R and omisation was done by a minimisation algorithm stratified by FIGO stage , residual disease , interval between surgery and chemotherapy , and Gynecologic Cancer InterGroup group . The primary endpoint was progression-free survival ; the study was also powered to detect a difference in overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N91273375 . Findings Between Dec 18 , 2006 , and Feb 16 , 2009 , 1528 women were enrolled and r and omly assigned to receive chemotherapy ( n=764 ) or chemotherapy plus bevacizumab ( n=764 ) . Median follow-up at the end of the trial on March 31 , 2013 , was 48·9 months ( IQR 26·6–56·2 ) , at which point 714 patients had died ( 352 in the chemotherapy group and 362 in the bevacizumab group ) . Our results showed evidence of non-proportional hazards , so we used the difference in restricted mean survival time as the primary estimate of effect . No overall survival benefit of bevacizumab was recorded ( restricted mean survival time 44·6 months [ 95 % CI 43·2–45·9 ] in the st and ard chemotherapy group vs 45·5 months [ 44·2–46·7 ] in the bevacizumab group ; log-rank p=0·85 ) . In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease , 332 ( 66 % ) died ( 174 in the st and ard chemotherapy group and 158 in the bevacizumab group ) , and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone ( restricted mean survival time 34·5 months [ 95 % CI 32·0–37·0 ] with st and ard chemotherapy vs 39·3 months [ 37·0–41·7 ] with bevacizumab ; log-rank p=0·03 ) . However , in non-high-risk patients , the restricted mean survival time did not differ significantly between the two treatment groups ( 49·7 months [ 95 % CI 48·3–51·1 ] ) in the st and ard chemotherapy group vs 48·4 months [ 47·0–49·9 ] in the bevacizumab group ; p=0·20 ) . An up date d analysis of progression-free survival showed no difference between treatment groups . During extended follow-up , one further treatment-related grade 3 event ( gastrointestinal fistula in a bevacizumab-treated patient ) , three grade 2 treatment-related events ( cardiac failure , sarcoidosis , and foot fracture , all in bevacizumab-treated patients ) , and one grade 1 treatment-related event ( vaginal haemorrhage , in a patient treated with st and ard chemotherapy ) were reported . Interpretation Bevacizumab , added to platinum-based chemotherapy , did not increase overall survival in the study population as a whole . However , an overall survival benefit was recorded in poor-prognosis patients , which is concordant with the progression-free survival results from ICON7 and GOG-218 , and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer . Funding The National Institute for Health Research through the UK National Cancer Research Network , the Medical Research Council , and Roche BACKGROUND Carboplatin plus paclitaxel administered every 3 weeks is st and ard first-line chemotherapy for patients with advanced ovarian cancer . A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial . The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks . METHODS We did a multicentre , r and omised , phase 3 study at 67 institutions in Italy and France . Women with FIGO stage IC-IV ovarian cancer , an ECOG performance status of 2 or lower , and who had never received chemotherapy were r and omly allocated in a 1:1 ratio to receive either carboplatin ( AUC 6 mg/mL per min ) plus paclitaxel ( 175 mg/m(2 ) ) every 3 weeks for six cycles or carboplatin ( AUC 2 mg/mL per min ) plus paclitaxel ( 60 mg/m(2 ) ) every week for 18 weeks . R and omisation was done by computer-based minimisation , stratified by centre , residual disease after surgery , and ECOG performance status . The study was not blinded . Co primary endpoints were progression-free survival and quality of life ( assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [ FACT-O/TOI ] score ) , and analysis was by modified intention to treat . This report presents the final analysis . The study is registered with Clinical Trials.gov , number NCT00660842 . FINDINGS 822 patients were enrolled into the study between Nov 20 , 2008 , and March 1 , 2012 ; 12 withdrew their consent immediately after r and omisation and were excluded , and 810 were eligible for analysis . 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule . After median follow-up of 22·3 months ( IQR 16·2 - 30·9 ) , 449 progression-free survival events were recorded . Median progression-free survival was 17·3 months ( 95 % CI 15·2 - 20·2 ) in patients assigned to treatment every 3 weeks , versus 18·3 months ( 16·8 - 20·9 ) in women allocated to the weekly schedule ( hazard ratio 0·96 , 95 % CI 0·80 - 1·16 ; p=0·66 ) . FACT-O/TOI scores differed significantly between the two schedules ( treatment-by-time interaction p<0·0001 ) ; with treatment every 3 weeks , FACT-O/TOI scores worsened at every cycle ( weeks 1 , 4 , and 7 ) , whereas for the weekly schedule , after transient worsening at week 1 , FACT-O/TOI scores remained stable . Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3 - 4 neutropenia ( 167 [ 42 % ] of 399 patients vs 200 [ 50 % ] of 400 patients ) , febrile neutropenia ( two [ 0·5 % ] vs 11 [ 3 % ] ) , grade 3 - 4 thrombocytopenia ( four [ 1 % ] vs 27 [ 7 % ] ) , and grade 2 or worse neuropathy ( 24 [ 6 % ] vs 68 [ 17 % ] ) . Three deaths during the study were attributed to chemotherapy ; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen . INTERPRETATION A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer . FUNDING None OBJECTIVE Treatment for advanced-stage epithelial ovarian cancer ( AEOC ) includes primary debulking surgery ( PDS ) or neoadjuvant chemotherapy ( NACT ) . A r and omized controlled trial comparing these treatments result ed in comparable overall survival ( OS ) . Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS .  We sought to evaluate the cost implication s of NACT relative to PDS in AEOC patients 65 years old or older . STUDY DESIGN A 5 year Markov model was created . Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel ( CT ) . Arm 2 modeled 3 cycles of CT , followed by interval debulking surgery and then 3 additional cycles of CT . Parameters included OS , surgical complications , probability of treatment initiation , treatment cost , and quality of life ( QOL ) . OS was assumed to be equal based on the findings of the international r and omized control trial . Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates . Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates . Sensitivity analyses were performed . RESULTS Assuming equal survival , NACT produces a cost savings of $ 5616 . If PDS improved median OS by 1.5 months or longer , PDS would be cost effective ( CE ) at a $ 100,000/ quality -adjusted life-year threshold . If PDS improved OS by 3.2 months or longer , it would be CE at a $ 50,000 threshold . The model was robust to variation in costs and complication rates . Moderate decreases in the QOL with NACT would result in PDS being CE . CONCLUSION A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older . Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $ 100,000/ quality -adjusted life-year threshold . Our results support further evaluation of the effects of PDS on OS , QOL and complications in AEOC patients 65 years old or older PURPOSE Conflicting results on prognostic factors for advanced epithelial ovarian cancer ( EOC ) have been reported because of small sample size and heterogeneity of study population . The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC . PATIENTS AND METHODS A retrospective review of demographic , pathologic , treatment , and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel  was conducted . A proportional hazards model was used to assess the association of prognostic factors with progression-free survival ( PFS ) and overall survival ( OS ) . RESULTS Increasing age was associated with increased risks for disease progression ( HR = 1.06 ; 95 % CI , 1.02 to 1.11 for an increase every 10 years ) and death ( HR = 1.12 ; 95 % CI , 1.06 to 1.18 ) . Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas . Patients with performance status ( PS ) 1 or 2 were at an increased risk for recurrence compared with PS 0 ( HR = 1.12 ; 95 % CI , 1.01 to 1.24 ) . Compared with patients with microscopic residual disease , patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence ( HR = 1.96 ; 95 % CI , 1.70 to 2.26 ; and HR = 2.36 ; 95 % CI , 2.04 to 2.73 , respectively ) and death ( HR = 2.11 ; 95 % CI , 1.78 to 2.49 ; P < .001 ; and HR = 2.47 ; 95 % CI , 2.09 to 2.92 , respectively ) . CONCLUSION Age , PS , tumor histology , and residual tumor volume were independent predictors of prognosis in patients with stage III EOC . These data can be used to identify patients with poor prognosis and to design future tailored r and omized clinical trials PURPOSE To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous ( IV ) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin . PATIENTS AND METHODS Patients were r and omized to receive either IV paclitaxel 135 mg/m(2 ) over 24 hours followed by IV cisplatin 75 mg/m(2 ) every 3 weeks for six courses or IV carboplatin ( area under curve 9 ) every 28 days for two courses , then IV paclitaxel 135 mg/m(2 ) over 24 hours followed by intraperitoneal ( IP ) cisplatin 100 mg/m(2 ) every 3 weeks for six courses . RESULTS Of the 523 patients who entered this trial , 462 were determined to be assessable , with prognostic factors well balanced between the treatments . Neutropenia , thrombocytopenia , and gastrointestinal and metabolic toxicities were greater in the experimental arm . As a result , 18 % of the patients received < or = two courses of IP therapy . Progression-free survival was superior for patients r and omized to the experimental treatment arm ( median , 28 v 22 months ; relative risk , 0.78 ; log-rank P = .01 , one-tail ) . There was a borderline improvement in overall survival associated with this regimen ( median , 63 v 52 months ; relative risk , 0.81 ; P = .05 , one-tail ) . CONCLUSION An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a st and ard regimen of IV cisplatin and paclitaxel . Because the improvement in overall survival was of borderline statistical significance and toxicity was greater , the experimental arm is not recommended for routine use . However , the results provide direction for further clinical investigation in small-volume ovarian cancer BACKGROUND Primary debulking surgery before initiation of chemotherapy has been the st and ard of care for patients with advanced ovarian cancer . METHODS We r and omly assigned patients with stage IIIC or IV epithelial ovarian carcinoma , fallopian-tube carcinoma , or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery ( so-called interval debulking surgery ) . RESULTS Of the 670 patients r and omly assigned to a study treatment , 632 ( 94.3 % ) were eligible and started the treatment . The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery ( metastatic lesions that were larger than 5 cm in diameter in 74.5 % of patients and larger than 10 cm in 61.6 % ) . The largest residual tumor was 1 cm or less in diameter in 41.6 % of patients after primary debulking and in 80.6 % of patients after interval debulking . Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking . The hazard ratio for death ( intention-to-treat analysis ) in the group assigned to neoadjuvant chemotherapy followed by interval debulking , as compared with the group assigned to primary debulking surgery followed by chemotherapy , was 0.98 ( 90 % confidence interval [ CI ] , 0.84 to 1.13 ; P=0.01 for noninferiority ) , and the hazard ratio for progressive disease was 1.01 ( 90 % CI , 0.89 to 1.15 ) . Complete resection of all macroscopic disease ( at primary or interval surgery ) was the strongest independent variable in predicting overall survival . CONCLUSIONS Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study . Complete resection of all macroscopic disease , whether performed as primary treatment or after neoadjuvant chemotherapy , remains the objective whenever cytoreductive surgery is performed . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00003636 . BACKGROUND A dose-dense weekly schedule of paclitaxel ( result ing in a greater frequency of drug delivery ) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer . We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab .  METHODS We prospect ively stratified patients according to whether they elected to receive bevacizumab  and then r and omly assigned them to receive either paclitaxel , administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks , plus carboplatin ( dose equivalent to an area under the curve [ AUC ] of 6 ) for six cycles or paclitaxel , administered weekly at a dose of 80 mg per square meter , plus carboplatin ( AUC , 6 ) for six cycles . The primary end point was progression-free survival . RESULTS A total of 692 patients were enrolled , 84 % of whom opted to receive bevacizumab .  In the intention-to-treat analysis , weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks ( 14.7 months and 14.0 months , respectively ; hazard ratio for disease progression or death , 0.89 ; 95 % confidence interval [ CI ] , 0.74 to 1.06 ; P=0.18 ) . Among patients who did not receive bevacizumab  , weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks ( 14.2 vs. 10.3 months ; hazard ratio , 0.62 ; 95 % CI , 0.40 to 0.95 ; P=0.03 ) . However , among patients who received bevacizumab , weekly paclitaxel did not significantly prolong progression-free survival , as compared with paclitaxel administered every 3 weeks ( 14.9 months and 14.7 months , respectively ; hazard ratio , 0.99 ; 95 % CI , 0.83 to 1.20 ; P=0.60 ) . A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab ( P=0.047 ) . Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks ( 36 % vs. 16 % ) , as well as a higher rate of grade 2 to 4 sensory neuropathy ( 26 % vs. 18 % ) ; however , they had a lower rate of grade 3 or 4 neutropenia ( 72 % vs. 83 % ) . CONCLUSIONS Overall , weekly paclitaxel , as compared with paclitaxel administered every 3 weeks , did not prolong progression-free survival  among patients with ovarian cancer . ( Funded by the National Cancer Institute and Genentech ; GOG-0262 Clinical Trials.gov number , NCT01167712 . ) OBJECTIVE To assess the ability of preoperative computed tomography ( CT ) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal ( > 1 cm residual disease ) primary cytoreduction in advanced ovarian , fallopian tube , and peritoneal cancer . METHODS This was a prospect i ve , non-r and omized , multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian , fallopian tube , and peritoneal cancer . A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery , respectively . Four clinical and 20 radiologic criteria were assessed . RESULTS From 7/2001 to 12/2012 , 669 patients were enrolled ; 350 met eligibility criteria . The optimal debulking rate was 75 % . On multivariate analysis , three clinical and six radiologic criteria were significantly associated with suboptimal debulking : age ≥ 60 years ( p=0.01 ) ; CA-125 ≥ 500 U/mL ( p<0.001 ) ; ASA 3 - 4 ( p<0.001 ) ; suprarenal retroperitoneal lymph nodes > 1 cm ( p<0.001 ) ; diffuse small bowel adhesions/thickening ( p<0.001 ) ; and lesions > 1 cm in the small bowel mesentery ( p=0.03 ) , root of the superior mesenteric artery ( p=0.003 ) , perisplenic area ( p<0.001 ) , and lesser sac ( p<0.001 ) . A ' predictive value score ' was assigned for each criterion , and the suboptimal debulking rates of patients who had a total score of 0 , 1 - 2 , 3 - 4 , 5 - 6 , 7 - 8 , and ≥ 9 were 5 % , 10 % , 17 % , 34 % , 52 % , and 74 % , respectively . A prognostic model combining these nine factors had a predictive accuracy of 0.758 . CONCLUSIONS We identified nine criteria associated with suboptimal cytoreduction , and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score . These results may be helpful in pretreatment patient assessment BACKGROUND To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more  from primary surgery or neoadjuvant chemotherapy . METHODS We used data of the European Organisation for Research and Treatment of Cancer ( EORTC ) 55971 trial in which 670 patients were r and omly assigned to primary surgery or neoadjuvant chemotherapy .  The primary outcome was overall survival . Ten baseline clinical and pathological characteristics were selected as potential biomarkers . Using Sub population Treatment Effect Pattern Plots ( STEPP ) , biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection . We also combined selected biomarkers to form a multimarker treatment selection rule . FINDINGS The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment , in terms of five-year survival ( p for interaction : 0.008 and 0.016 , respectively ) . Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours > 45 mm benefited more from neoadjuvant chemotherapy . In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective . We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage , the potential five-year survival rate in the population of treated patients would be 27.3 % ( 95 % confidence interval ( CI ) 21.9 - 33.0 ) , 7.8 % higher than if all were treated with primary surgery , and 5.6 % higher if all were treated with neoadjuvant chemotherapy . INTERPRETATION Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial , we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery , while patients with stage IV disease and large metastatic tumours had higher  survival with neoadjuvant chemotherapy . For patients who did not meet these criteria , both treatment options led to comparable survival rates
target: The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
background: PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .