Minig L.,Valencian Institute of Oncology |
Achilarre M.T.,Italian National Cancer Institute |
Garbi A.,Italian National Cancer Institute |
Zanagnolo V.,Italian National Cancer Institute
International Journal of Gynecological Cancer | Year: 2017
Robotic-assisted surgery is a technological advancement derived from conventional laparoscopy, which facilitates the application of minimally invasive techniques for complex operations in the field of gynecological oncology. However, its introduction in gynecological cancer has been scarce in most hospitals worldwide. Most publications on robotic surgery are still retrospective or descriptive in nature. Some studies compare robotic-assisted laparoscopy with open procedures, which is a questionable analysis, because the advantages of minimally invasive surgery have been already well established. Robotic surgery should be directly compared with conventional laparoscopy to determine whether its additional direct and indirect costs are in accordance with some improvements within patient clinical outcomes. On the other hand, the role of robotic-assisted surgery in allowing more patients to receive the benefits of the minimally invasive approach should also be considered. The objective of this article was, therefore, to review the literature regarding the role of conventional and robotic-assisted laparoscopy to treat women with gynecologic cancer. Copyright © 2017 by IGCS and ESGO.
Minig L.,Valencian Institute of Oncology |
Minig L.,University of San Pablo - CEU |
Chuang L.,Mount Sinai School of Medicine |
Patrono M.G.,University of San Pablo - CEU |
Cardenas-Rebollo J.M.,University of San Pablo - CEU
Journal of Minimally Invasive Gynecology | Year: 2015
Study Objective: To compare the surgical outcome and short-term postoperative complications in premenopausal women who had undergone hysterectomies for benign indication with or without prophylactic bilateral salpingectomy. Design: A cohort of consecutive women who had undergone hysterectomy plus bilateral salpingectomy between May 2012 and July 2014 (group A) were compared with the same number of consecutive premenopausal patients who had undergone simple hysterectomy operated on before May 2012 (group B). Inclusion criteria included premenopausal women and benign indication for surgery (Canadian Task Force classification III). Setting: tertiary care hospital. Intervention: Salpingectomy versus no salpingectomy at the time of benign hysterectomy. Measurements and Main Results: A total of 97 and 71 patients were included in groups A and B, respectively. No differences between the 2 groups were observed regarding patient characteristics. The average operative time, estimated blood loss, uterine size, and intraoperative complications were similar between groups. The mean (standard deviation) length of hospitalization time was 43.7 (22.4) hours in group A and 53.9 (83.5) hours in group B (p = .008). There were no significant differences in terms of the incidence of postoperative complications, emergency visits after readmission, and hospital readmission between both groups of patients. Conclusion: Prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women is safe and feasible and does not worsen surgical outcomes or the incidence of intraoperative and postoperative complications. © 2015 AAGL.
Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: Outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial
Poveda A.,Valencian Institute of Oncology |
Vergote I.,University Hospital |
Tjulandin S.,Russian Cancer Research Center |
Kong B.,Shandong University |
And 9 more authors.
Annals of Oncology | Year: 2011
Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear. Patients and methods: Within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup. Results: Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months). Conclusion: This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months). © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: A randomised, phase 3, non-inferiority trial
Strnad V.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Ott O.J.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Hildebrandt G.,University of Leipzig |
Hildebrandt G.,University of Rostock |
And 30 more authors.
The Lancet | Year: 2016
Background In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. Methods We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. Findings Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). Interpretation The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. Funding German Cancer Aid. © 2016 Elsevier Ltd.
Martin M.,Gregorio Maranon University General Hospital |
Brase J.C.,Sividon Diagnostics |
Calvo L.,University of La Coruña |
Krappmann K.,Sividon Diagnostics |
And 14 more authors.
Breast Cancer Research | Year: 2014
Introduction: EndoPredict (EP) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) who are being treated with adjuvant endocrine therapy. Herein we report the prospective-retrospective clinical validation of EP in the node-positive, chemotherapy-treated, ER+/HER2- BC patients in the GEICAM 9906 trial. Methods: The patients (N = 1,246) were treated either with six cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if they had hormone receptor-positive disease. The patients were assigned to EP risk categories (low or high) according to prespecified cutoff levels. The primary endpoint in the clinical validation of EP was distant metastasis-free survival (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and multivariate analysis was performed using Cox regression. Results: The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2- tumors from the 800 available samples in the GEICAM 9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as low risk. MFS was 93% in the low-risk group and 70% in the high-risk group (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this ER+/HER2- cohort, EP results are an independent prognostic parameter after adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and progesterone receptor (PR) status and proliferation index (Ki67). Using the predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk group, who had excellent outcomes and no distant recurrence events (absolute risk reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were no statistically significant differences in MFS between treatment arms (FEC vs FEC-P) in either the high- or low-risk groups. The interaction test results between the chemotherapy arm and the EP score were not significant. Conclusions: EP is an independent prognostic parameter in node-positive, ER+/HER2- BC patients treated with adjuvant chemotherapy followed by hormone therapy. EP did not predict a greater efficacy of FEC-P compared to FEC alone. © 2014 Martín et al.; licensee BioMed Central Ltd.
PubMed | Parc Tauli Health Corporation, Reina Sofia Hospital Complex, University of Barcelona, Valencian Institute of Oncology and 13 more.
Type: Journal Article | Journal: The oncologist | Year: 2016
In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.
GEC-ESTRO multicenter phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patient compliance
PubMed | Clemenshospital, Valencian Institute of Oncology, University of Bern, Centrum Onkologii Instytut im Marii Sklodowskej and 14 more.
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2016
To compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer.Between April 2004 and July 2009, 1328 patients with UICC stage 0-IIA breast cancer were randomized to receive WBI with 50Gy and a boost of 10Gy or APBI with either 32.0Gy/8 fractions, or 30.1Gy/7 fractions (HDR-brachytherapy), or 50Gy/0.60-0.80Gy per pulse (PDR-brachytherapy). This report focuses on early side-effects and patient compliance observed in 1186 analyzable patients. ClinicalTrials.gov identifier: NCT00402519.Patient compliance was excellent in both arms. Both WBI and APBI were well tolerated with moderate early side-effects. No grade 4 toxicity had been observed. Grade 3 side effects were exclusively seen for early skin toxicity (radiation dermatitis) with 7% vs. 0.2% (p<0.0001), and breast infection with 0% vs. 0.2% (p=n.s.) for patients treated with WBI and APBI. The incidence of grades 1-2 early side effects for WBI and APBI was 86% vs. 21% (p<0.0001) for skin toxicity, 2% vs. 20% (p<0.0001) for mild hematoma, and 2% vs. 5% (p=0.01) for mild breast infection rates, respectively. No differences had been found regarding grades 1-2 early breast pain (26% vs. 29%, p=0.23).APBI with interstitial multicatheter brachytherapy was tolerated very well and dramatically reduced early skin toxicity in comparison to standard WBI.
Monk B.J.,Creighton University |
Kaye S.B.,Foundation Medicine |
Poveda A.,Valencian Institute of Oncology |
Herzog T.J.,Columbia University |
And 6 more authors.
Gynecologic Oncology | Year: 2014
Objective This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC). Patients and methods Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results A statistically significant correlation between high levels of nibrin and lower ORR (P = 0.03), shorter PFS (P = 0.007) and shorter OS (P = 0.01) was observed. After stratification, in patients with platinum-sensitive disease treated with the combination of trabectedin plus PLD, high levels of nibrin correlated with lower ORR (P = 0.01) and shorter PFS (P = 0.02). A better clinical outcome (ORR, PFS and OS) was also associated to low levels of CHK2 in trabectedin plus PLD treated patients. No correlations were found in PLD-treated patients. According to the results of a multivariate analysis, there was a statistically significant correlation between high nibrin (P = 0.001) and low BRCA2 levels (P = 0.03) and a worse PFS, and between high nibrin levels and a worse OS (P = 0.006). Conclusion Our results indicate that high nibrin expression seems to be associated with a worse clinical outcome in serous ROC, particularly in patients treated with the combination trabectedin plus PLD. Prospective studies to determine clinical usefulness of nibrin as a possible biomarker in other series of patients with ROC are warranted. © 2013 Elsevier Inc.
Fernandez-Martos C.,Valencian Institute of Oncology |
Garcia-Albeniz X.,Harvard University |
Pericay C.,Parc Tauli Hospital |
Maurel J.,Clinic Hospital |
And 11 more authors.
Annals of Oncology | Year: 2015
Background: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. Patients and methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). Results: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. Conclusion: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Lago V.,University of Toledo |
Minig L.,Valencian Institute of Oncology |
Fotopoulou C.,Imperial College London
International Journal of Gynecological Cancer | Year: 2016
Objectives This study aimed to determine the incidence of lymph node (LN) metastases in presumed stage I-II low-grade epithelial ovarian cancer (EOC). Methods Eligible studies were identified from MEDLINE and EMBASE (time frame, 2015-1975), that analyzed patients with clinical or radiologic presumed early-stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as part of their surgical staging. The number and site of dissected and involved LNs and the correlation with overall outcome are analyzed. The term low grade and also the older term well differentiated were used. Results Thirteen of 978 identified studies were selected, and 13 of 75 studies were identified as eligible. A total of 1403 patients were analyzed in these 13 retrospective studies. The final International Federation of Gynecology and Obstetrics staging after completed surgical staging was I to II in 912 patients (65%). A total of 338 patients (24%) had grade 1 tumors whereas 473 patients (34%) had grade 2, and 502 patients (36%) had grade 3 tumors. Systematic lymphadenectomy was performed in 1159 patients (83%), whereof 1142 (82%) were pelvic and para-aortic LN dissections. In 185 patients (13%), an upstaging from an apparent clinical stage I-II to IIIC occurred because of LN involvement: 64 (35%) of the patients had only pelvic LNs metastases, 69 (37%) had only para-aortic LNs metastasis, and 51 (28%) had both a pelvic and para-aortic LN involvement. When analyzing only the patients with low-grade (grade 1 as the old classification) presumed early-stage disease (n = 273), only 8 patients (2.9%; range, 0-6.2) were identified with LNs metastases present. Conclusions The incidence of occult LN metastases in apparent early-stage low-grade EOC is 2.9% in a metaanalysis of retrospective studies. Future larger-scale prospectively assessed studies with established surgical quality of the LN dissection are warranted to establish the true incidence of LN metastasis in presumed early low-grade disease. Copyright © 2016 by IGCS and ESGO.