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Jalid Sehouli - One of the best experts on this subject based on the ideXlab platform.

  • randomized phase iii study to evaluate the impact of secondary cytoreductive surgery in Recurrent Ovarian Cancer final analysis of ago desktop iii engot ov20
    Journal of Clinical Oncology, 2020
    Co-Authors: Andreas Du Bois, Jalid Sehouli, Ignace Vergote, Gwenael Ferron, Alexander Reuss, Werner Meier, Stefano Greggi, Pernille Tina Jensen, Frederic Selle, Frederic Guyon
    Abstract:

    6000Background: The role of secondary cytoreductive surgery in Recurrent Ovarian Cancer (ROC) has been under debate for decades. A recent trial in unselected patients (pts) failed to show an OS ben...

  • quality of life in patients with Recurrent Ovarian Cancer treated with niraparib versus placebo engot ov16 nova results from a double blind phase 3 randomised controlled trial
    Lancet Oncology, 2018
    Co-Authors: Amit Oza, Ursula A. Matulonis, Susana Banerjee, Susanne Malander, Stacie Hudgens, Jalid Sehouli, Giovanni Scambia, Josep M Del Campo, Dominique Bertonrigaud, Jonathan Berek
    Abstract:

    Summary Background Quality of life (QOL) has become an important complementary endpoint in Cancer clinical studies alongside more traditional assessments (eg, tumour response, progression-free survival, overall survival). Niraparib maintenance treatment has been shown to significantly improve progression-free survival in patients with Recurrent Ovarian Cancer. We aimed to assess whether the benefits of extending progression-free survival are offset by treatment-associated toxic effects that affect QOL. Methods The ENGOT-OV16/NOVA trial was a multicentre, double-blind, phase 3, randomised controlled trial done in 107 study sites in the USA, Canada, Europe, and Israel. Patients with Recurrent Ovarian Cancer who were in response to their last platinum-based chemotherapy were randomly assigned (2:1) to receive either niraparib (300 mg once daily) as a maintenance treatment or placebo. Randomisation was stratified based on time to progression after the penultimate platinum-based regimen, previous use of bevacizumab, and best response (complete or partial) to the last platinum-based regimen with permuted-block randomisation (six in each block) using an interactive web response system. The trial enrolled two independent cohorts on the basis of germline BRCA (g BRCA ) mutation status (determined by BRAC Analysis Testing, Myriad Genetics, Salt Lake City, UT, USA). The primary endpoint of the trial was progression-free survival, and has already been reported. In this study, we assessed patient-reported outcomes (PROs) in the intention-to-treat population using the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L). We collected PROs from trial entry every 8 weeks for the first 14 cycles and every 12 weeks thereafter. If a patient discontinued, we collected PROs at discontinuation and during a postprogression visit 8 weeks (plus or minus 2 weeks) later. We assessed the effect of haematological toxic effects on QOL with disutility analyses of the most common grade 3–4 adverse events (thrombocytopenia, anaemia, and neutropenia) using a mixed model with histology, region, previous treatment, age, planned treatment, and baseline score as covariates. This study is registered with ClinicalTrials.gov, number NCT01847274. Findings Between Aug 28, 2013, and June 1, 2015, 553 patients were enrolled and randomly assigned to receive niraparib (n=138 in the g BRCA mut cohort, n=234 in the non-g BRCA mut cohort) or placebo (n=65 in the g BRCA mut cohort, n=116 in the non-g BRCA mut cohort). The mean FOSI score at baseline was similar between the two groups (range between 25·0–25·6 in the two groups). Overall QOL scores remained stable during the treatment and preprogression period in the niraparib group; no significant differences were observed between the niraparib and placebo group, and preprogression EQ-5D-5L scores were similar between the two groups in both cohorts (0·838 [0·0097] in the niraparib group vs 0·834 [0·0173] in the placebo group in the g BRCA mut cohort; and 0·833 [0·0077] in the niraparib group vs 0·815 [0·0122] in the placebo group in the non-g BRCA mut cohort). The most common adverse events reported at screening (baseline) were lack of energy (425 [79%]; 97 [18%] reporting severe lack of energy), pain (236 [44%]), and nausea (118 [22%]). All symptoms, except nausea, either remained stable or improved over time in the niraparib group. The most common grade 3 or 4 toxicities observed in the niraparib group were haematological in nature: thrombocytopenia (124 [34%] of 367 patients), anaemia (93 [25%]), and neutropenia (72 [20%]); disutility analyses showed no significant QOL impairment associated with these toxic effects. Interpretation These PRO data suggest that women who receive niraparib as maintenance treatment for Recurrent Ovarian Cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo. Funding TESARO.

  • the impact of health related quality of life hrqol on short term survival of Recurrent Ovarian Cancer patients analysis of pooled data from the north eastern german society of gynecological oncology noggo meta data base
    Journal of Clinical Oncology, 2018
    Co-Authors: Jalid Sehouli, Radoslav Chekerov, Elena Ioana Braicu, M Keller, G Oskayoezcelik, Rolf Richter
    Abstract:

    5539Background: The goal of this analysis is a predictive score (Recurrent Ovarian Cancer survival score, NOGGO-ROCSurv score) using HRQoL and other risk factors to estimate the risk of 1-year mort...

  • a phase iii open label randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated Recurrent Ovarian Cancer a study of the north eastern german society of gynecological oncology noggo
    Journal of Cancer Research and Clinical Oncology, 2017
    Co-Authors: Jalid Sehouli, O Tome, Desislava Dimitrova, O Camara, I B Runnebaum, Hans Werner Tessen, Beate Rautenberg, Radoslav Chekerov, Mustafa Zelal Muallem, Michael P Lux
    Abstract:

    In Recurrent Ovarian Cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of Recurrent Ovarian Cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

  • impact of secondary cytoreductive surgery on survival in patients with platinum sensitive Recurrent Ovarian Cancer analysis of the calypso trial
    Gynecologic Oncology, 2015
    Co-Authors: Jalid Sehouli, Chee Khoon Lee, Sarah J Lord, Tami Grunewald, Val Gebski, Anneclaire Hardybessard, Kathrine Woie, Mark Heywood, Christian Schauer
    Abstract:

    Abstract Objective The role of secondary cytoreductive surgery (SCR) in platinum-sensitive Recurrent Ovarian Cancer (ROC) remains controversial. The overall survival (OS) benefits for surgery reported in observational studies may be due to the selection of patients with better prognosis. Methods Using data from the CALYPSO trial, OS of patients who had SCR was compared to those treated with chemotherapy alone. Multivariate analyses were performed to adjust for prognostic factors. We also tested for an interaction between baseline prognostic groupings and the benefit of surgery. Results Of the 975 patients randomised in CALYPSO, 19% had SCR and 80% had chemotherapy alone. OS was longer for the SCR group than for chemotherapy alone (median, 49.9 vs. 29.7months; adjusted hazard ratio (HR), 0.68; P =0.004). For patients with SCR, the 3-year OS was 72% for those with no measurable disease, and 28% if residual tumour was larger than 5cm. Patients with good prognostic features benefited the most from SCR (HR 0.43; P P Conclusion SCR was associated with improved OS in platinum-sensitive ROC, particularly in patients with favourable prognostic characteristics. However, these findings may be due to selection bias, and hence randomised trials are still essential.

Dennis S. Chi - One of the best experts on this subject based on the ideXlab platform.

  • secondary cytoreduction and carboplatin hyperthermic intraperitoneal chemotherapy for platinum sensitive Recurrent Ovarian Cancer an msk team ovary phase ii study
    Journal of Clinical Oncology, 2021
    Co-Authors: Oliver Zivanovic, Dennis S. Chi, Qin Zhou, Alexia Iasonos, Jason A Konner, Vicky Makker, Rachel N Grisham, A K Brown, Stacy Nerenstone, John P Diaz
    Abstract:

    PURPOSEThe purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for Recurrent Ovarian Cancer during secondary cytoreductive surgery.MATE...

  • volume based quantitative fdg pet ct metrics and their association with optimal debulking and progression free survival in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery
    European Radiology, 2015
    Co-Authors: H A Vargas, Dennis S. Chi, Irene A Burger, Debra A Goldman, Maura Micco, Ramon E Sosa, Wolfgang A Weber, Hedvig Hricak, Evis Sala
    Abstract:

    Objective Our aim was to evaluate the associations between quantitative 18 F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery.

  • a risk model for secondary cytoreductive surgery in Recurrent Ovarian Cancer an evidence based proposal for patient selection
    Annals of Surgical Oncology, 2012
    Co-Authors: Wen Juan Tian, Jalid Sehouli, Dennis S. Chi, Gennaro Cormio, Claes G Trope, Rong Jiang, Ali Ayhan, Yan Xing, Georg Peter Breitbach, Elena Ioana Braicu
    Abstract:

    To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with Recurrent Ovarian Cancer. Individual data of 1075 patients with Recurrent Ovarian Cancer undergoing SCR from 7 worldwide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] = 1.32, 95% confidence interval [95% CI]: 0.97–1.80), residual disease after primary cytoreduction (OR = 1.69, 95% CI: 1.26–2.27), progression-free interval (OR = 2.27, 95% CI: 1.71–3.01), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 2.23, 95% CI: 1.45–3.44), CA125 (OR = 1.85, 95% CI: 1.41–2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88–4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0–4.7 were categorized as the low-risk group, in which the proportion of complete cytoreduction was 53.4% compared with 20.1% in the high-risk group (OR = 4.55, 95% CI: 3.43–6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiver-operating characteristics for predicting complete SCR was 0.68 (95% CI: 0.60–0.79). This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with Recurrent Ovarian Cancer should have SCR as part of their management.

  • predictors of survival in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort
    British Journal of Cancer, 2011
    Co-Authors: Rongyu Zang, Jalid Sehouli, Dennis S. Chi, Philipp Harter, Gennaro Cormio, Claes G Trope, Rong Jiang, Ali Ayhan, Yan Xing, K Wollschlaeger
    Abstract:

    Predictors of survival in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort

  • Cytoreductive surgery for Recurrent Ovarian Cancer: A meta-analysis
    Gynecologic oncology, 2008
    Co-Authors: Robert E. Bristow, Isha Puri, Dennis S. Chi
    Abstract:

    Abstract Objective To determine the relative effect of multiple prognostic variables on overall post-recurrence survival time among cohorts of patients with Recurrent Ovarian Cancer undergoing cytoreductive surgery. Methods Forty cohorts of patients with Recurrent Ovarian Cancer (2019 patients) meeting study inclusion criteria were identified from the MEDLINE database (1983–2007). Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median post-recurrence survival time of the following variables: year of publication, age, disease-free interval, localized disease, tumor grade and histology, the proportion of patients undergoing complete cytoreductive surgery, requirement for bowel resection, and the sequence of cytoreductive surgery and salvage chemotherapy. Results The mean weighted median disease-free interval prior to cytoreductive surgery was 20.2 months, and the mean weighted median overall post-recurrence survival time was 30.3 months. The weighted mean proportion of patients in each cohort undergoing complete cytoreductive surgery was 52.2%. Median survival improved with increasing year of publication ( p =0.009); however, the only statistically significant clinical variable independently associated with post-recurrence survival time was the proportion of patients undergoing complete cytoreductive surgery ( p =0.019). After controlling for all other factors, each 10% increase in the proportion of patients undergoing complete cytoreductive surgery was associated with a 3.0 month increase in median cohort survival time. Conclusions Among patients undergoing operative intervention for Recurrent Ovarian Cancer, the proportion of patients undergoing complete cytoreductive surgery is independently associated with overall post-recurrence survival time. For this select group of patients, the surgical objective should be resection of all macroscopic disease.

Giovanni Scambia - One of the best experts on this subject based on the ideXlab platform.

  • brca mutation status to personalize management of Recurrent Ovarian Cancer a multicenter study
    Annals of Surgical Oncology, 2018
    Co-Authors: Claudia Marchetti, Angela Musella, Giovanni Scambia, Rossella De Leo, Marco Dindinosante, Ettore Capoluongo, Angelo Minucci, Pierluigi Benedetti Panici, Anna Fagotti
    Abstract:

    The aim of this study was to assess the correlation between BRCA mutation status and disease presentation, treatment strategy, and survival in a multicenter series of Recurrent high-grade serous Ovarian Cancer (HGSOC) women. A consecutive series of Recurrent HGSOC patients with partially or fully platinum-sensitive disease admitted to the Gynecologic Oncology Units of the Catholic University of the Sacred Heart and Sapienza University of Rome. Main eligibility criteria were known BRCA 1/2 germline mutation status and a minimum follow-up period from recurrence of at least 6 months. Overall, 126 patients met the eligibility criteria, of whom 76 (60%) were BRCA wild-type (BRCAwt) and 50 (40%) were BRCA 1/2 germline mutation carriers (BRCAmut). Among the latter, 37 (74%) patients presented with BRCA1 mutation, and 13 (26%) presented with BRCA2. No differences were found regarding patterns of disease presentation between BRCAwt and BRCAmut women. BRCAmut patients had the best post-recurrence survival (PRS) regardless of having received secondary cytoreductive surgery (SCS) or not, with a 5-year PRS of 73% in non-resected women versus 78% in resected women (p = 0.558). Conversely, BRCAwt patients who underwent complete SCS had a significantly longer PRS compared with BRCAwt patients who did not receive surgery (5-year PRS of 54% vs. 42%; p = 0.048). Recurrent Ovarian Cancer BRCAmut patients have the best prognosis regardless of SCS, whereas PRS in BRCAwt women can improve when complete SCS is performed. The identification and incorporation of predictive biomarkers such as BRCA status to tailor the medical and surgical approach is paramount to the success of Recurrent HGSOC treatments.

  • quality of life in patients with Recurrent Ovarian Cancer treated with niraparib versus placebo engot ov16 nova results from a double blind phase 3 randomised controlled trial
    Lancet Oncology, 2018
    Co-Authors: Amit Oza, Ursula A. Matulonis, Susana Banerjee, Susanne Malander, Stacie Hudgens, Jalid Sehouli, Giovanni Scambia, Josep M Del Campo, Dominique Bertonrigaud, Jonathan Berek
    Abstract:

    Summary Background Quality of life (QOL) has become an important complementary endpoint in Cancer clinical studies alongside more traditional assessments (eg, tumour response, progression-free survival, overall survival). Niraparib maintenance treatment has been shown to significantly improve progression-free survival in patients with Recurrent Ovarian Cancer. We aimed to assess whether the benefits of extending progression-free survival are offset by treatment-associated toxic effects that affect QOL. Methods The ENGOT-OV16/NOVA trial was a multicentre, double-blind, phase 3, randomised controlled trial done in 107 study sites in the USA, Canada, Europe, and Israel. Patients with Recurrent Ovarian Cancer who were in response to their last platinum-based chemotherapy were randomly assigned (2:1) to receive either niraparib (300 mg once daily) as a maintenance treatment or placebo. Randomisation was stratified based on time to progression after the penultimate platinum-based regimen, previous use of bevacizumab, and best response (complete or partial) to the last platinum-based regimen with permuted-block randomisation (six in each block) using an interactive web response system. The trial enrolled two independent cohorts on the basis of germline BRCA (g BRCA ) mutation status (determined by BRAC Analysis Testing, Myriad Genetics, Salt Lake City, UT, USA). The primary endpoint of the trial was progression-free survival, and has already been reported. In this study, we assessed patient-reported outcomes (PROs) in the intention-to-treat population using the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L). We collected PROs from trial entry every 8 weeks for the first 14 cycles and every 12 weeks thereafter. If a patient discontinued, we collected PROs at discontinuation and during a postprogression visit 8 weeks (plus or minus 2 weeks) later. We assessed the effect of haematological toxic effects on QOL with disutility analyses of the most common grade 3–4 adverse events (thrombocytopenia, anaemia, and neutropenia) using a mixed model with histology, region, previous treatment, age, planned treatment, and baseline score as covariates. This study is registered with ClinicalTrials.gov, number NCT01847274. Findings Between Aug 28, 2013, and June 1, 2015, 553 patients were enrolled and randomly assigned to receive niraparib (n=138 in the g BRCA mut cohort, n=234 in the non-g BRCA mut cohort) or placebo (n=65 in the g BRCA mut cohort, n=116 in the non-g BRCA mut cohort). The mean FOSI score at baseline was similar between the two groups (range between 25·0–25·6 in the two groups). Overall QOL scores remained stable during the treatment and preprogression period in the niraparib group; no significant differences were observed between the niraparib and placebo group, and preprogression EQ-5D-5L scores were similar between the two groups in both cohorts (0·838 [0·0097] in the niraparib group vs 0·834 [0·0173] in the placebo group in the g BRCA mut cohort; and 0·833 [0·0077] in the niraparib group vs 0·815 [0·0122] in the placebo group in the non-g BRCA mut cohort). The most common adverse events reported at screening (baseline) were lack of energy (425 [79%]; 97 [18%] reporting severe lack of energy), pain (236 [44%]), and nausea (118 [22%]). All symptoms, except nausea, either remained stable or improved over time in the niraparib group. The most common grade 3 or 4 toxicities observed in the niraparib group were haematological in nature: thrombocytopenia (124 [34%] of 367 patients), anaemia (93 [25%]), and neutropenia (72 [20%]); disutility analyses showed no significant QOL impairment associated with these toxic effects. Interpretation These PRO data suggest that women who receive niraparib as maintenance treatment for Recurrent Ovarian Cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo. Funding TESARO.

  • prospective validation study of a predictive score for operability of Recurrent Ovarian Cancer the multicenter intergroup study desktop ii a project of the ago kommission ovar ago study group noggo ago austria and mito
    International Journal of Gynecological Cancer, 2011
    Co-Authors: Philipp Harter, Sven Mahner, Jalid Sehouli, Giovanni Scambia, A Hasenburg, Alexander Reuss, I Vergote, D Cibula, A Reinthaller, A Burges
    Abstract:

    Purpose: The DESKTOP I trial proposed a score for the prediction of complete cytoreduction in Recurrent Ovarian Cancer. Resectability was assumed if 3 factors were present: (1) complete resection at first surgery, (2) good performance status, and (3) absence of ascites. The DESKTOP II trial was planned to verify this hypothesis prospectively in a multicenter setting. Methods: Participating centers prospectively enrolled all consecutive patients with platinum-sensitive first or second relapse. The score was applied to all patients, but centers were free to decide on therapy. All further therapies were documented, and the outcome of patients was analyzed. A 75% complete resection rate in 110 prospectively classified patients had to be achieved to confirm a positive predictive value of 2 or higher of 3 with 95% probability. Results: A total of 516 patients were screened within 19 months; of these, 261 patients (51%) were classified as score positive, and 129 patients with a positive score and first relapse were operated on. The rate of complete resection was 76%, thus confirming the validity of this score regarding positive prediction of complete resectability in 2 or more of 3 patients. Complication rates were moderate including second operations in 11% and perioperative mortality in 0.8%. Conclusions: This score is the first prospectively validated instrument to positively predict surgical outcome in Recurrent Ovarian Cancer. It can aid in the selection of patients who might benefit from secondary cytoreductive surgery and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in Recurrent platinum-sensitive Ovarian Cancer.

  • upper abdominal surgery in advanced and Recurrent Ovarian Cancer role of diaphragmatic surgery
    Gynecologic Oncology, 2010
    Co-Authors: Francesco Fanfani, Anna Fagotti, Giuseppe Vizzielli, Valerio Gallotta, Alfredo Ercoli, Fabio Pacelli, Barbara Costantini, P A Margariti, Giorgia Garganese, Giovanni Scambia
    Abstract:

    Abstract Objective Upper abdominal spread of primary and Recurrent Ovarian Cancer is often considered to be a major obstacle to achieve optimal residual disease at the end of surgery. In this study, we investigate the role of diaphragmatic debulking in the natural history of advanced and Recurrent epithelial Ovarian Cancer patients, and the morbidity of this procedure according to clinico-surgical characteristics. Methods Data from 234 consecutive patients with primary and Recurrent advanced Ovarian Cancer, operated at Catholic University of Rome and Campobasso from January 1, 2005 and December 31, 2008, were retrospectively reviewed. Results Eighty-seven patients (37.2%) underwent a diaphragmatic surgery. Median age was 55 years (range 37–76). Diaphragmatic debulking was performed in 50 out of 120 patients at primary surgery (41.7%), in 16 out of 74 at interval debulking surgery (21.6%) and in 21 out of 40 secondary cytoreductions (52.5%). In the whole study population optimal residual disease at the end of surgery was achieved. The most frequent post-operative complication was pleural effusion, observed in 37 patients (42.5%). Presence of a post-operative pleural effusion was correlated liver mobilization (52.3% vs. 16%; p 5 cm) removal (54.1% vs. 23.5%; p Conclusions Diaphragmatic surgery represents a crucial step in the debulking of advanced and Recurrent Ovarian Cancer patients. Considering the natural history of advanced epithelial Ovarian Cancer and the rate of patients needing diaphragmatic debulking during primary cytoreduction, interval debulking surgery and secondary cytoreduction, this procedure should be present in the surgical repertoire of a gynecologic oncologist.

  • a treatment selection protocol for Recurrent Ovarian Cancer patients the role of fdg pet ct and staging laparoscopy
    Oncology, 2008
    Co-Authors: Anna Fagotti, Francesco Fanfani, Cristiano Rossitto, Domenica Lorusso, A De Gaetano, Alessandro Giordano, Giuseppe Vizzielli, Giovanni Scambia
    Abstract:

    Objective: To investigate the best diagnostic and staging strategy for Recurrent Ovarian Cancer. Methods: The negative predictive value, specificity, positive pre

Philipp Harter - One of the best experts on this subject based on the ideXlab platform.

  • treatment of Recurrent Ovarian Cancer
    Annals of Oncology, 2017
    Co-Authors: Sandro Pignata, Philipp Harter, S C Cecere, A Du Bois, Florian Heitz
    Abstract:

    Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial Ovarian Cancer will develop disease relapse. The same modalities as used primarily are available for treatment of Recurrent Ovarian Cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection. With respect to systemic therapy, tumor histology, BRCA status, the platinum-free interval (PFI) and previous treatment with bevacizumab (anti-VEGF monoclonal antibody) are considered the most important features that influence treatment choice in ROC. In patients with resistant or refractory relapse (PFI   6 months). The integration of surgery, with a 'personalized' approach by the use of antiangiogenic agent and of PARP inhibitors is affecting survival of patients with Recurrent disease and will help epithelial Ovarian Cancer to become a chronic disease.

  • predictors of survival in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort
    British Journal of Cancer, 2011
    Co-Authors: Rongyu Zang, Jalid Sehouli, Dennis S. Chi, Philipp Harter, Gennaro Cormio, Claes G Trope, Rong Jiang, Ali Ayhan, Yan Xing, K Wollschlaeger
    Abstract:

    Predictors of survival in patients with Recurrent Ovarian Cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort

  • clinical trials in Recurrent Ovarian Cancer
    International Journal of Gynecological Cancer, 2011
    Co-Authors: Michael Friedlander, Edward L Trimble, Anna V Tinker, David S Alberts, Elisabeth Avalllundqvist, Mark F Brady, Philipp Harter, Sandro Pignata, Eric Pujadelauraine, Jalid Sehouli
    Abstract:

    The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic Cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined Recurrent Ovarian Cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for Recurrent Ovarian Cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with Recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

  • prospective validation study of a predictive score for operability of Recurrent Ovarian Cancer the multicenter intergroup study desktop ii a project of the ago kommission ovar ago study group noggo ago austria and mito
    International Journal of Gynecological Cancer, 2011
    Co-Authors: Philipp Harter, Sven Mahner, Jalid Sehouli, Giovanni Scambia, A Hasenburg, Alexander Reuss, I Vergote, D Cibula, A Reinthaller, A Burges
    Abstract:

    Purpose: The DESKTOP I trial proposed a score for the prediction of complete cytoreduction in Recurrent Ovarian Cancer. Resectability was assumed if 3 factors were present: (1) complete resection at first surgery, (2) good performance status, and (3) absence of ascites. The DESKTOP II trial was planned to verify this hypothesis prospectively in a multicenter setting. Methods: Participating centers prospectively enrolled all consecutive patients with platinum-sensitive first or second relapse. The score was applied to all patients, but centers were free to decide on therapy. All further therapies were documented, and the outcome of patients was analyzed. A 75% complete resection rate in 110 prospectively classified patients had to be achieved to confirm a positive predictive value of 2 or higher of 3 with 95% probability. Results: A total of 516 patients were screened within 19 months; of these, 261 patients (51%) were classified as score positive, and 129 patients with a positive score and first relapse were operated on. The rate of complete resection was 76%, thus confirming the validity of this score regarding positive prediction of complete resectability in 2 or more of 3 patients. Complication rates were moderate including second operations in 11% and perioperative mortality in 0.8%. Conclusions: This score is the first prospectively validated instrument to positively predict surgical outcome in Recurrent Ovarian Cancer. It can aid in the selection of patients who might benefit from secondary cytoreductive surgery and will be enrolled in the recently started randomized prospective DESKTOP III trial investigating the role of surgery in Recurrent platinum-sensitive Ovarian Cancer.

  • surgery in Recurrent Ovarian Cancer the arbeitsgemeinschaft gynaekologische onkologie ago desktop ovar trial
    Annals of Surgical Oncology, 2006
    Co-Authors: Philipp Harter, Andreas Du Bois, M Hahmann, A Hasenburg, A Burges, Sibylle Loibl, M Gropp, Jens Huober, Daniel Fink, W Schroder
    Abstract:

    The role of cytoreductive surgery in relapsed Ovarian Cancer is not clearly defined. Therefore, patient selection remains arbitrary and depends on the center’s preference rather than on established selection criteria. The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in Recurrent Ovarian Cancer (DESKTOP OVAR) trial was undertaken to form a hypothesis for a panel of criteria for selecting patients who might benefit from surgery in relapsed Ovarian Cancer. The DESKTOP trial was an exploratory study based on data from a retrospective analysis of hospital records. Twenty-five member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee (AGO OC) and AGO-OVAR boards collected data on their patients with cytoreductive surgery for relapsed invasive epithelial Ovarian Cancer performed in 2000–2003. Two hundred and sixty-seven patients were included. Complete resection was associated with significantly longer survival compared with surgery leaving any postoperative residuals [median 45.2 vs. 19.7 months; hazard ratio (HR) 3.71; 95% confidence interval (CI) 2.27–6.05; P 0; P 500 ml (P < .001). A combination of PS, early FIGO stage initially or no residual tumor after first surgery, and absence of ascites could predict complete resection in 79% of patients. Only complete resection was associated with prolonged survival in Recurrent Ovarian Cancer. The identified criteria panel will be verified in a prospective trial (AGO-DESKTOP II) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in Recurrent Ovarian Cancer.

Bradley J Monk - One of the best experts on this subject based on the ideXlab platform.

  • patient counseling and management of symptoms during olaparib therapy for Recurrent Ovarian Cancer
    Oncologist, 2016
    Co-Authors: Kathleen N Moore, Bradley J Monk
    Abstract:

    UNLABELLED : Our primary objective is to review the safety and tolerability profile of olaparib, a novel antiCancer therapy, and to discuss key considerations for symptom management in patients with advanced Ovarian Cancer. Olaparib is the first of a new class of antiCancer therapies, poly (ADP-ribose) polymerase (PARP) inhibitors that target tumors that have deficits in homologous recombination repair (such as BRCA mutations) by a process known as synthetic lethality. Through this process, neither the deficiency in homologous recombination repair nor PARP inhibition alone is cytotoxic, but the combination of these two conditions leads to cell death. In December 2014, olaparib received accelerated approval by the U.S. Food and Drug Administration (FDA) as monotherapy for patients with known or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced Ovarian Cancer who had been treated with at least three lines of chemotherapy. Most adverse events (AEs) reported during olaparib clinical trials conducted in patients with Recurrent Ovarian Cancer and measurable disease were of grade 2 or less severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Fatigue and gastrointestinal AEs are among the most common in Ovarian Cancer clinical trials and can be particularly bothersome to patients. We focus on interventions to address these AEs in patients who are candidates for treatment with olaparib and allow them to remain on therapy for as long as clinically indicated. IMPLICATIONS FOR PRACTICE Olaparib therapy represents a new approach to treating Recurrent Ovarian Cancer. Some associated adverse events can have a substantial effect on quality of life. It is therefore important for patients, caregivers, and health care providers to have realistic expectations and a thorough understanding of the safety and tolerability profile of olaparib to prevent or alleviate key symptoms so that therapy can continue uninterrupted if possible. This report summarizes a practical approach to supportive care for patients receiving olaparib therapy.

  • abstract as27 vtx 2337 a tlr8 agonist plus chemotherapy in Recurrent Ovarian Cancer preclinical and phase 1 data by the gynecologic oncology group
    Clinical Cancer Research, 2015
    Co-Authors: Bradley J Monk, William E Brady, Heather A Lankes, Andrea Facciabene, Kristi Manjarrez, Robert M Hershberg, Paula M Fracasso, Katherine M Bellmcguinn, Joan L Walker, Carolyn K Mccourt
    Abstract:

    Background: Given the absence of clear molecular drivers in high-grade serous Ovarian Cancer, targeting the tumor microenvironment with immunotherapy is an emerging approach. Stimulation of the innate immune system via Toll-like receptors (TLRs) may augment the antitumor activity of cytotoxic chemotherapies, including anthracyclines. VTX-2337 is a potent, small molecule agonist of TLR8 which was previously evaluated as a single agent in patients with advanced Cancer. We report both pre-clinical and clinical data combining VTX-2337 with pegylated liposomal doxorubicin (PLD; Doxil®) chemotherapy in Recurrent Ovarian Cancer. Methods: VTX-2337 was tested in an Ovarian tumor model in immunocompromised mice reconstituted with a human immune system. Additionally, an open-label Phase 1 study of VTX-2337 + PLD in Recurrent platinum-resistant Ovarian Cancer (NCT0129493, n=13) was performed. (The clinical study also evaluated the combination of VTX 2337 + weekly paclitaxel [n=7]; data is not reported herein.) PLD (40 mg/m2) was given on day 1 of a 28 day cycle. Three dose levels of VTX-2337 (2.5, 3.0, 3.5 mg/m2) were sequentially tested and given by SC injection on days 3, 10, and 17 of each treatment cycle. Responses were evaluated using RECIST 1.1. The pharmacokinetics (PK) of VTX-2337 and PLD, and plasma levels of mediators induced by TLR8 activation were assessed. Patients remained on study treatment until disease progression or unacceptable toxicity. Results: In the murine tumor model, the efficacy of the combination of VTX-2337 + PLD was increased compared to that of either agent alone. The development of an adaptive CD8+ T cell response to tumor cells was also enhanced. In humans, treatment with VTX-2337 + PLD increased levels of multiple cytokines and chemokines (G-CSF, MCP-1, MIP-1β, TNFα) consistent with TLR8 stimulation and innate immune activation. The PK of PLD was not affected by VTX-2337. The combination was well tolerated with no dose limiting toxicities and no serious, unexpected treatment-related adverse events (AEs). AEs consisted of those seen with single-agent PLD (Gr 3/4 toxicities; n=6) or VTX-2337 (Gr 1/2 injection site reaction, transient fever, flu-like symptoms; n=13). One subject with non-measurable disease achieved a complete response, 1 subject enrolled based on biochemical evidence of Recurrent disease achieved a complete biochemical response, 7 subjects had stable disease, and 3 subjects had progressive disease. One subject discontinued treatment prematurely and did not undergo tumor response assessment. Overall, subjects treated with the combination of VTX 2337 + PLD experienced a response rate of 15.4% (n=2) and a disease control rate of nearly 70% (n=9; 69.2%). Conclusions: VTX-2337 enhances the therapeutic effects of PLD in a preclinical model of Ovarian Cancer, and the combination is well tolerated in patients. Clinical data and biomarkers consistent with immunostimulation provide rationale for the on-going randomized, placebo-controlled, Phase 2 trial comparing PLD vs PLD + VTX-2337 (GOG-3003; NCT01666444). This trial is fully enrolled. Citation Format: Bradley J. Monk, William E. Brady, Heather A. Lankes, Andrea Facciabene, Kristi L. Manjarrez, Robert M. Hershberg, Paula M. Fracasso, Katherine M. Bell-McGuinn, Joan L. Walker, Carolyn K. McCourt, Carol Aghajanian, George Coukos. VTX-2337, a TLR8 agonist, plus chemotherapy in Recurrent Ovarian Cancer: preclinical and phase 1 data by the gynecologic oncology group [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS27.

  • vtx 2337 a tlr8 agonist plus chemotherapy in Recurrent Ovarian Cancer preclinical and phase i data by the gynecologic oncology group
    Journal of Clinical Oncology, 2013
    Co-Authors: Bradley J Monk, William E Brady, Heather A Lankes, Andrea Facciabene, Kristi Manjarrez, Robert M Hershberg, Paula M Fracasso, Katherine M Bellmcguinn, Joan L Walker, Carolyn K Mccourt
    Abstract:

    3077 Background: Given the absence of clear molecular drivers in high-grade serous Ovarian Cancer, targeting the tumor micro-environment with immunotherapy is an emerging approach. VTX-2337 is a potent, small molecule agonist of TLR8 which stimulates the innate immune response, and was previously evaluated as a single agent in Cancer patients. We report data combining VTX-2337 with chemotherapy in Recurrent Ovarian Cancer. Methods: VTX-2337 was tested in an Ovarian Cancer mouse model with an intact human immune system. Additionally, an open-label phase I study of VTX-2337 + pegylated liposomal doxorubicin (PLD) in Recurrent Ovarian Cancer (NCT01294293, N=13) was performed. PLD (40 mg/m2) was given on day 1 of a 28-day cycle. Three dose levels of VTX-2337 (2.5, 3.0, 3.5 mg/m2, N=13) were serially tested and given by SC injection on days 3, 10, and 17. VTX-2337 (3.0 mg/m2) was also tested with paclitaxel (80 mg/m2; N=7) given on days 1, 8, and 15 of a 28 day cycle. Responses were evaluated using RECIST1.1. ...

  • trabectedin plus pegylated liposomal doxorubicin pld versus pld in Recurrent Ovarian Cancer overall survival analysis
    European Journal of Cancer, 2012
    Co-Authors: Bradley J Monk, Eric Pujadelauraine, Thomas J Herzog, Stanley B Kaye, C N Krasner, Jan B Vermorken, Franco M Muggia, Youn C Park, Trilok V Parekh, Andres Poveda
    Abstract:

    Aim: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in Recurrent Ovarian Cancer (J Clin Oncol 2010;28:3107-14). Methods: Women, stratified by performance status (0-1 versus 2) and platinum sensitivity (platinum-free interval (PFI) <6 versus P6 months), were randomly assigned to receive PLD 30 mg/m 2 IV followed by a 3-h infusion of trabectedin 1.1 mg/m 2 every 3 weeks or PLD 50 mg/m 2 every 4 weeks. The study was powered to show a 33% increase in overall sur- vival (OS) after 520 deaths had occurred. Results: After a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin + PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio (HR) = 0.86; 95% confidence interval (CI): 0.72-1.02; p = 0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD = 13.3 months, trabectedin + PLD = 10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors

  • trabectedin plus pegylated liposomal doxorubicin in Recurrent Ovarian Cancer
    Journal of Clinical Oncology, 2010
    Co-Authors: Bradley J Monk, Eric Pujadelauraine, Thomas J Herzog, Stanley B Kaye, C N Krasner, Jan B Vermorken, Franco M Muggia, Alla Lisyanskaya, A Makhson, Janusz Rolski
    Abstract:

    Purpose The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with Recurrent Ovarian Cancer after failure of first-line, platinum-based chemotherapy. Patients and Methods Women ≥ 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m2 followed by a 3-hour infusion of trabectedin 1.1 mg/m2 every 3 weeks or PLD 50 mg/m2 every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment. Results Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (OR...