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Background: Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points., Methods: Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes., Results: Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years)., Conclusion: ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.

Background: Enhanced Recovery After Surgery Programs (ERP) include multimodal approaches of perioperative patient's clinical pathways designed to achieve early recovery after surgery and a decreased length of hospital stay (LOS). By allowing patients to return rapidly to their everyday surroundings, older patients are those who could take the greatest benefit from ERP. This is the first study to date to assess feasibility and safety of ERP on older patients undergoing gynaecologic oncological surgery., Methods: Data were prospectively collected between December 2015 and September 2017 at the Institut Paoli-Calmettes, a French comprehensive cancer centre. All the patients included in the study were referred for hysterectomy and/or pelvic or para-aortic lymphadenectomy for gynaecological cancer. The primary objective was to achieve similar LOS in patients ≥70 years old compared to younger patients without increasing the proportion of complications and readmission rates. A binary (LOS < or ≥ 2 days) logistic regression was built, including age, Charlson score, BMI, ASA score, oncological indication, surgical procedures and surgical approaches. G8 score was estimated for all the ≥70 years old patients., Results: Of a total of 329 patients, 75 were ≥70 years old and 254 were <70. Except a disparity in oncological indications with a higher proportion of endometrial cancer in the ≥70 years old group (56% vs. 27%; p < 0.01), there were no differences in patient's characteristics and surgical procedures. Age ≥ 70 years was associated with a longer LOS (means, 3.88 vs. 3.11 days; p = 0.024) only in univariate analysis. Considering the logistic regression, age was no longer associated with LOS. Total hysterectomy with pelvic lymphadenectomy and ASA score ≥ 3 were independently associated with longer LOS while mini-invasive techniques were associated with a shorter LOS. Morbidities and readmissions occurred respectively in 23% and 8% of the total population without any difference between the two groups. In the ≥70 years old population, G8 score was not predictive of LOS, morbidities or readmissions., Conclusion: Although it is already widely accepted that ERP improves early recovery, our study shows that ERP for patients over 70 years of age undergoing gynaecologic oncological surgery is as safe and feasible as on younger patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to report a 30-year experience of PE for gynecologic malignancies in a cancer center., Materials and Methods: A retrospective study was conducted at Institut Paoli-Calmette including patients who underwent PE for gynecologic malignancies. Four periods were evaluated: P1 before 1992, P2 between 1993 and 1999, P3 between 2000 and 2006 and P4 after 2006. The study evaluated the number of PE performed during each period, the type of PE, its level, indication, location of the primary tumor, patient age, previous radiotherapy ≥45 Gy, the rate of "curative" PE and exenteration-related reconstructive techniques. 90-day post-operative mortality and morbidity using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03 were reported., Results: 277 PE were performed. The number of PE performed for recurrences rose during the study period (p = 0.042), PE performed for central tumors increased during P3 (64.4%) and P4 (67.4%) (p < 0.0001) and administration of radiotherapy ≥45 Gy was more frequent (p < 0.0001). The rate of "curative" PE increased (p < 0.0001). In multivariate analysis, "curative" PE were correlated with PE type, central locations and study period. Pelvic filling was progressively more frequently performed (p = 0.002). 90-day complication rate was 56.3%. In multivariate analysis there was a significant difference in distribution of CTCAE grade 3-4-5 morbidity depending on the period. Overall survival (OS) improved during the 2 last periods (p = 0.008)., Conclusion: A better selection of eligible patients for PE, namely through improvement in imaging techniques, has enabled to raise the rate of curative PE., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Three randomized trials have concluded at non inferiority of omission of complementary axillary lymph node dissection (cALND) for patients with involved sentinel node (SN). However, we can outline strong limitations of these trials to validate this attitude with a high scientific level. We designed the SERC randomized trial ( ClinicalTrials.gov , number NCT01717131) to compare outcomes in patients with SN involvement treated with ALND or no further axillary treatment. The aim of this study was to analyze results of the first 1000 patients included., Methods: SERC trial is a multicenter non-inferiority phase 3 trial. Multivariate logistic regression analysis was used to identify independent factors associated with adjuvant chemotherapy administration and non-sentinel node (NSN) involvement., Results: Of the 963 patients included in the analysis set, 478 were randomized to receive cALND and 485 SLNB alone. All patient demographics and tumor characteristics were balanced between the two arms. SN ITC was present in 6.3% patients (57/903), micro metastases in 33.0% (298), macro metastases in 60.7% (548) and 289 (34.2%) were non eligible to Z0011 trial criteria. Whole breast or chest wall irradiation was delivered in 95.9% (896/934) of patients, adjuvant chemotherapy in 69.5% (644/926), endocrine therapy in 89.6% (673/751) and the proportions were similar in the two arms. The overall rate of positive NSN was 19% (84/442) for patients with cALND. Crude rates of positive NSN according to SN status were 4.5% for ITC (1/22), 9.5% for micro metastases (13/137), 23.9% for macro metastases (61/255) and were respectively 29.36% (64/218), 9.33% (7/75) and 7.94% (10/126) when chemotherapy was administered after cALND, before cALND and for patients without chemotherapy., Conclusion: The main objective of SERC trial is to demonstrate non inferiority of cALND omission. A strong interaction between timing of cALND and chemotherapy with positive NSN rate was observed., Trial Registration: This study is registered with ClinicalTrials.gov , number NCT01717131 October 19, 2012.

Over the past 20 years, feasibility of laparoscopic approaches has been validated in gynecologic surgery. This procedure has specific challenges due its longer learning curve and the limits imposed by the technique. For the surgical treatment of recurrent pelvic cancers or locally advanced tumors, open surgery remains the gold standard for most surgical teams. Robotic assistance could be an interesting alternative. The aim of this study is to present our department's robotic surgical procedures in this specific field and show its feasibility and reproducibility on several patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The spread of systematic screening and the emergence of oncoplastic techniques allow more breast conservative treatment associating lumpectomy and external beam radiation therapy. In order to furthermore facilitate the patient's treatment, intraoperative radiation therapy (IORT) has been developed. The oncological safety of this technique has been studied, and is considered acceptable. Many questions remain unsolved in regard of the toxicity of this procedure as well as the patient's selection criteria. In this study, we present the first results and complications rate of patients treated by IORT in a single French institution. Between 2012 and 2015, all patients with breast cancer treated in a one-step procedure associating lumpectomy and IORT were retrospectively included in a monocentric cohort. Acute and long-term toxicities were evaluated using CTCAE v4.0 classification. 280 breast cancers were treated using IORT procedure. Additional external beam radiation therapy was requested for 45.7% patients. The acute complications rate was 14.6%, with 5 surgical revisions needed (1.78%). With a median follow up of 911 days, the long-term grade-3 toxicity rate was 1.1%. The only risk factor for local fibrosis was external beam radiation therapy (EBRT) (OR = 1.99; IC95 [1.05-3.81], P = 0.036). Three patients (1.07%) were diagnosed with local recurrence. The results from this cohort confirm the low complication and recurrence rate of IORT procedure. A good selection of patients is necessary in order to lower the EBRT rate and allow therapeutic de-escalation. The classification of tumors into IHC subsets seems a good selection gate. Intraoperative radiation therapy appears to have a low toxicity rate with an acceptable local recurrence risk, and should therefore be considered as an option in the treatment of early breast cancer., (© 2018 Wiley Periodicals, Inc.)

Background: Pelvic exenteration remains one of the most mutilating procedures, with important postoperative morbidity, an altered body image, and long-term physical and psychosocial concerns. This study aimed to assess quality of life (QOL) during the first year after pelvic exenteration for gynecologic malignancy performed with curative intent., Methods: A French multicentric prospective study was performed by including patients who underwent pelvic exenteration. Quality of life by measurement of functional and symptom scales was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires before surgery, at baseline, and 1, 3, 6, and 12 months after the procedure., Results: The study enrolled 97 patients. Quality of life including physical, personal, fatigue, and anorexia reported in the QLQ-C30 was significantly reduced 1 month postoperatively and improved at least to baseline level 1 year after the procedure. Body image also was significantly reduced 1 month postoperatively. Global health, emotional, dyspnea, and anorexia items were significantly improved 1 year after surgery compared with baseline values. Unlike younger patients, elderly patients did not regain physical and social activities after pelvic exenteration., Conclusions: Therapeutic decision on performing a pelvic exenteration can have a severe and permanent impact on all aspects of patients' QOL. Deterioration of QOL was most significant during the first 3 months after surgery. Elderly patients were the only group of patients with permanent decreased physical and social function. Preoperative evaluation and postoperative follow-up evaluation should include health-related QOL instruments, counseling by a multidisciplinary team to cover all aspects concerning stoma care, sexual function, and long-term concerns after surgery.

Background: Enhanced Recovery After Surgery Programs (ERP) includes multimodal approaches of perioperative patient's clinical pathways designed to achieve early recovery after surgery and a decreased length of hospital stay (LOS)., Methods: This observational study evaluated the implementation of ERP in gynaecologic oncological surgery in a minimally invasive techniques (MIT) expert center with more than 85% of procedures done with MIT. We compared a prospective cohort of 100 patients involved in ERP between December 2015 and June 2016 to a 100 patients control group, without ERP, previously managed in the same center between April 2015 and November 2015. All the included patients were referred for hysterectomy and/or pelvic or para-aortic lymphadenectomy for gynaecological cancer. The primary objective was to achieve a significant decrease of median LOS in the ERP group. Secondary objectives were decreases in proportion of patients achieving target LOS (2 days), morbidity and readmissions., Results: Except a disparity in oncological indications with a higher proportion of endometrial cancer in the group with ERP vs. the group without ERP (42% vs. 22%; p = 0.003), there were no differences in patient's characteristics and surgical procedures. ERP were associated with decreases of median LOS (2.5 [0 to 11] days vs. 3 [1 to 14] days; p = 0.002) and proportion of discharged patient at target LOS (45% vs. 24%; p = 0.002). Morbidities occurred in 25% and 26% in the groups with and without ERP and readmission rates were respectively of 6% and 8%, without any significant difference., Conclusion: ERP in gynaecologic oncological surgery is associated with a decrease of LOS without increases of morbidity or readmission rates, even in a center with a high proportion of MIT. Although it is already widely accepted that MIT improves early recovery, our study shows that the addition of ERP's clinical pathways improve surgical outcomes and patient care management.

Intravenous leiomyomatosis has an unusual growth pattern characterized by proliferation of smooth muscle in uterine and systemic veins. Although histologically benign, this condition could eventually have a clinically aggressive course. At an early stage, the disease is often misdiagnosed on preoperative imaging because of its low prevalence, non-specific initial clinical manifestation, and poorly known radiological characteristics. An early, accurate diagnosis is needed for appropriate surgical management that could result in a good prognosis, reducing the risk of recurrence and morbidity. Magnetic resonance imaging is a particularly valuable technique for assessing intravenous leiomyomatosis preoperatively.

Aim: To assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement., Materials and Methods: We retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980-1999, 2000-2005 and 2006-2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group., Results: More than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT., Conclusion: We failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN)., Materials and Methods: A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN., Results: 12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors >20 and < 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p < 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073)., Conclusion: The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose To evaluate the association between dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging with pathologic complete response after preoperative combined chemotherapy and radiation therapy for cervical carcinoma and evaluate the risk of local recurrence. Materials and Methods The institutional ethics committee approved the study and waived the requirement to obtain informed consent. The study comprised 52 patients with locally advanced carcinoma, treated first with combined chemotherapy and radiation therapy, who underwent MR imaging before final surgery between June 2011 and July 2015. Three radiologists evaluated conventional, DW, and DCE MR images to identify a complete response. The standard of reference was surgical-pathologic findings. Results An initial increase in signal intensity on DCE MR images that was greater in the cervical lesion than in the myometrium was defined as time-signal intensity curve type B and showed a significant association with incomplete response (P = .0004). DCE MR imaging parameters (ie, maximum slope enhancement, area under the gadolinium concentration-time curve during the first 90 seconds after gadolinium injection [AUGC90], and volume transfer constant [K trans ]) and a low signal intensity on apparent diffusion coefficient (ADC) maps were significantly associated with an incomplete response (P = .027, P = .041, P = .037, and P = .032, respectively). A mean ADC of 0.0014 m 2 /sec or less (hazard ratio [HR] = 8.3), low ADC signal intensity (HR = 7.3), high signal intensity at DW imaging (HR = 7.1), and time-signal intensity curve type B (HR = 4.3) were associated with earlier recurrence (P < .05). Excellent agreement between readers was found for time-signal intensity curve analysis (κ > 0.9) and the following parameters: AUGC90, K trans , and maximum slope enhancement (intraclass correlation coefficient, >0.9). Conclusion DCE MR imaging parameters, especially the time-signal intensity curve, and DW imaging are associated with complete response and incomplete response and could potentially help oncologists with management decisions. Moreover, DCE and DW MR imaging could help oncologists accentuate the follow-up for patients with a high risk of local recurrence to assess for recurrence. © RSNA, 2017 Online supplemental material is available for this article.

Introduction: The aim of this study was to examine changes in therapeutic practices for early breast cancer T0-2 N0 managed by upfront surgery and SLNB., Population: Between 1999 and 2012, 15.508 patients were treated. Four periods were determined: 1999-2003, 2004-2006, 2007-2009 and > 2009. Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1-2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+)., Methods: Rates of axillary lymph node dissection (ALND), adjuvant chemotherapy ± trastuzumab, endocrine treatment, mastectomy and post mastectomy radiotherapy (PMRT) were analyzed according to treatment periods with univariate and multivariate analysis. Overall and disease-free survivals were analyzed according to treatment periods adjusted for HR and then for tumor subtypes., Results: Rates of ALND, adjuvant chemotherapy and endocrine treatment varied significantly according to treatment periods, for HR positive and negative tumors. ALND rate decreased for all tumor subtypes with a decrease of adjuvant chemotherapy rate for Luminal A tumors and an increase for Luminal B Her2+ and Her2-tumors. Endocrine treatment rate decreased for Luminal A and increased for Luminal B Her2+ tumors. In multivariate analysis, these modifications with time remained significant. Mastectomy and PMRT rates increased. In multivariate analysis, overall and disease-free survivals increased during successive periods., Conclusion: A global therapeutic de-escalation in ALND and adjuvant systemic treatment, combined with an actual escalation in some specific subsets was demonstrated, but without negative impact on survival., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: To compare survival outcomes after mastectomy (Mt) and lumpectomy plus interstitial brachytherapy (LpIB) in the treatment of breast cancer local recurrence (LR) occurring after conservative surgery., Methods: Medical records of patients treated for an isolated LR from January 1, 1981 to December 31, 2009 were reviewed. To overcome the bias due to the fact that treatment choice (Mt or LpIB) was based on prognostic factors with LpIB proposed preferentially to women with good prognosis, Mt and LpIB populations were matched and compared with regard to overall survival (OS) and metastasis free survival (MFS)., Results: Among 348 patients analyzed, 66.7% underwent Mt, 17.8% LpIB and 15.5% Lp alone. After a median follow-up of 73.3 months, 65 patients had died (42/232 Mt, 8/62 LpIB, 15/54 Lp). Before matching, OS and MFS at 5 years were significantly better in the LpIB compared to the Mt group, due to significantly more frequent poor prognostic factors in the latter (p = 0,07 and p = 0,09 respectively, log-rank significance limit of 10%). After matching, the benefits of LpIB disappeared since MFS and OS rates were not significantly different in both groups (p = 0.68 and 0.88 respectively). After LpIB, the second LR rate was 17% at 5 years and 30% at 10 years., Conclusion: A second conservative breast cancer treatment associating lumpectomy and interstitial brachytherapy is possible for selected patients with LR, without decrease in neither OS nor MFS compared to mastectomy., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Inflammatory breast cancer (IBC) is a very aggressive form of breast cancer, as compared to locally advanced breast cancer (LABC). Neoadjuvant chemotherapy followed by surgery is the standard treatment in both cases. Whether IBC is less chemosensitive than LABC remains unclear. We retrospectively compared the rate of pathological complete response (pCR) to neoadjuvant chemotherapy in IBC and LABC., Methods: Patients with IBC or LABC treated with neoadjuvant anthracycline-based chemotherapy followed by surgery were selected from our institutional database. The primary endpoint was the pCR rate, defined as absence of invasive tumor in breast and axillary lymph nodes., Results: A total of 450 patients were included, 144 with IBC and 306 with LABC. The pCR rate was similar between the two groups, in the whole population (31%) and in each molecular subtype separately. Univariate analyses for pCR in IBC and LABC separately identified the same predictive variables, except the pathological type that was associated with pCR in LABC only, but not in IBC. IBC patients displayed shorter 5-year metastasis-free survival and overall survival than LABC patients in the whole population (57% and 69% versus74% and 88% respectively), and in each molecular subtype separately. The IBC phenotype was an independent prognostic feature. Similarly, IBC patients displayed shorter 5-year loco-regional relapse-free survival than LABC patients (86% versus 95%)., Conclusions: Similar pCR rates to chemotherapy were found in IBC and LABC, suggesting that IBC is not less chemosensitive than LABC. Survival was shorter in IBC, suggesting that the corresponding poorer prognosis is more due to a higher metastatic risk and/or other feature(s) than to a lesser chemosensitivity., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Context: Even if neoadjuvant chemotherapy (NACT) and oncoplastic techniques have increased the breast conserving surgery rate, mastectomy is still a standard for multifocal or extensive breast cancers (BC). In the prospect of increasing breast reconstruction, an alternative therapeutic protocol was developed combining NACT with neoadjuvant radiation therapy (NART), followed by mastectomy with immediate breast reconstruction (IBR). The oncological safety of this therapeutic plan still needs further exploration. We assessed pathological complete response (pCR) as a surrogate endpoint for disease free survival., Methods: Between 2010 and 2016, 103 patients undergoing mastectomy after NACT and NART were recruited. After CT and RT were administrated, a completion mastectomy with IBR by latissimus dorsi flap was achieved 6 to 8 weeks later. pCR was defined by the absence of residual invasive disease in both nodes and breast. Histologic response was analyzed for each immunohistochemical subset., Results: pCR was obtained for 53.4% of the patients. This pCR rate was higher in hormonal receptor negative (HER2 and triple negative) patients when compared to luminal tumours (69.7% vs 45.7%, p=0.023)., Discussion: The pCR rate found in this study is higher than those published in studies analyzing NACT (12.5%-27.1%). This can be explained by the combination of anthracycline and taxane, the use of trastuzumab when HER2 was overexpressed but also by RT associated to NACT., Conclusion: Inverting the sequence protocol for BC, requiring both CT and RT, allows more IBR without diminishing pCR and should therefore be considered as an acceptable therapeutic option., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Studies evaluating chemotherapy high dose chemotherapy with autologous haematopoietic stem cell transplantation (HDC-ACSH) in the treatment of metastatic (MBC), locally advanced (LABC) and inflammatory (IBC) breast cancer have in common lack of biomarker information, in particular the HER2 status., Patients and Methods: All consecutive female patients treated for breast cancer with HDC and AHSCT at Institut Paoli Calmettes between 2003 and 2012 were included. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: luminal, (HR+/HER2-), HER2 (HER2+, any HR) and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the IHC subtypes., Results: Three hundred and seventy-seven patients were included. For MBC, the TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95 % CI 11.76-44.4) compared to 44.64 months (95 % CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (P<0.01). For IBC, HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89 % (95 % CI 64-97) compared to 57 % (95 % CI 33-76) for the TN subgroup (HR 5.38, 95 % CI 1.14-25.44; P=0.034). For CSLA, luminal subgroup appeared to have the best prognosis with a 5-year OS of 92 % (95 % CI 71-98) against 75 % (95 % CI 46-90) for HER 2 subtype and 70 % (95 %CI 97-88) for TN subtype (P=0.301)., Conclusion: The HDC-ACSH does not change the prognosis value of IHC subtype in breast cancer patients., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation., Patients and Methods: A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade., Results: A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors., Conclusions: Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

Objective: This study aims to evaluate the different surgical approaches, perioperative morbidity and surgical staging according to age in patients with endometrial cancer., Methods: Multicentre retrospective study. Cancer characteristics and perioperative data were collected for patients surgically treated for endometrial cancer. The patients were divided into 2 groups according to their age: younger or older than 75 years., Results: Surgery was performed on 270 women <75 years old and on 74 ≥ 75 years old. Minimally invasive surgery was performed less often in the elderly compared with their younger counterparts (58.2% vs. 74.8%; p = 0.006). Independently of the surgical approach, the rate of pelvic and para-aortic lymphadenectomy was lower in women older than 75 years old than their younger counterparts (52.7% vs. 74.8%; p < 0.001; 8.1% vs. 21.8%; p = 0.007 respectively). According to the guidelines, more frequent surgical understaging was seen in the elderly compared with the younger (37% vs. 15.2%; p = 0.002). In the comparison of complications for each surgical approach, there was no statistical difference in the ≥75-year-old age group in terms of intra- or postoperative complications between the laparotomy, laparoscopy or robotic surgery group. We found a shorter length of hospital stay for the women who underwent laparoscopy or robotic surgery compared with laparotomy (p < 0.0001)., Conclusion: Elderly women with endometrial cancer are often surgically understaged whereas there is no evidence of greater perioperative complications than for their younger counterparts. They should benefit from minimally invasive surgery and optimal surgical staging to the same extent as younger women., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The aim of this study is to analyze the feasibility of ambulatory hospitalization or 24hours hospitalization for breast cancer treatment by mastectomy, as well as the satisfaction and the preferences of patients with regard to these ways of hospitalization., Methods: This observational retrospective study listed the patients operated for breast cancer who had required a mastectomy at the institute Paoli-Calmettes between the 1st of January 2013 and June 30th, 2015. A questionnaire of satisfaction was proposed to the patients regarding their mode of hospitalization., Results: One hundred and thirteen patients were included among which 29 were in the ambulatory group and 84 in the 24hours hospitalization group. The complications were represented by the rate of hematomas (3.5 %), which required a surgical resumption for two of the patients in the 24hours hospitalization group and for one patient in the ambulatory group (P=0.75). Patient's satisfaction rate was globally high: 72.7 % regardless of the mode of hospitalization (P=0.064)., Conclusion: The realization of mastectomy in ambulatory hospitalization seems feasible when the organization in pre- and postoperative is anticipated with a high degree of satisfaction of the patients. The psychological impact of this radical surgery seems to be a factor to be taken into account and requires a meticulous selection of the patients., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Advanced minimal access surgical training is an important component of training in gynecological oncology (GO). Europe-wide data on this topic are lacking. We present data on availability and trainee experience of advanced laparoscopic surgical (ALS) and robotic surgical (RS) training in GO across Europe., Method: A prospective web-based anonymized survey of European GO trainees was sent to the European Network of Young Gynaecological Oncologists members/trainees. It included sociodemographic information and specific questions pertaining to training experience or satisfaction in laparoscopic and robotic surgery. χ test was used for evaluating categorical variables and Mann-Whitney/Kruskal-Wallis (nonparametric) tests for continuous variables between 2 and more independent groups., Results: A total of 113 GO trainees from 29 countries responded. The mean (standard deviation) age was 35.2 (6.1) years, 59.3% were men, 40.7% were women, and 46% were in accredited training posts. The ALS and RS training was offered in only 43% and 23% of institutes respectively, and 54% and 23% of trainees had undergone some form of formal or informal training in ALS and RS respectively. A total of 62.4% felt that RS should be a formal component of GO training programs. A total of 61% and 35% planned to go outside their institute for ALS or RS training respectively. Trainees rating (1-5 scale) of their open surgery and ALS or RS skills (3.3/2.6/1.9) and training experience (3.5/2.8/2.1), respectively, were higher for open surgery than ALS or RS (P < 0.0005). Accredited posts were more likely than nonaccredited posts to offer ALS training (60%/31%, P = 0.002), formal training schedules (27.9%/4.4%, P = 0.003), and use of logbooks (46%/23%, P = 0.035)., Conclusions: Training and experience in ALS and RS are poorly rated by GO trainees across Europe, and only few centers offer this. There is an urgent need to expand and harmonize training opportunities for ALS and RS. Most trainees want RS included as a formal component of their training.

Aim: To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma., Methods: Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented., Results: In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached., Conclusion: The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population., Results: Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC., Methods: aBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX., Conclusions: Precision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases.

Background: To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate., Methods: This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008., Results: Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial's eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different., Conclusions: Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.

Objective: Carry out a preliminary study comparing postoperative pain and intraoperative and postoperative complications between micro-laparoscopy and laparoscopic monotrocart non-oncological adnexal surgery., Methods: All patients should benefit from a benign adnexal surgery were included prospectively from February to May 2014. The insufflation pressure, infiltration of trocar holes with a local anesthetic, postoperative analgesics were prescribed standardized. Operative and postoperative complications, type and length of hospital stay as well as EVA and analgesic consumption were recorded., Results: Nine patients were included in monotrocart group versus 7 in the micro-laparoscopy group. There were no differences in operative and postoperative complications, the type and length of hospital stay, as well as cosmetics satisfaction. However, there was a significant difference in the VAS to D2 (2.15 vs. 4.08, P=0.04) and analgesic consumption at D0 (P=0.04), D1 (P=0.04), D2 (P=0.02) and D3 (P=0.01), for the benefit of micro-laparoscopy., Discussion and Conclusion: Despite an enrollment of patients low, micro-laparoscopy appears to have a significant advantage over the monotrocart laparoscopy for postoperative pain in benign adnexal surgery., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion., Methods: A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts., Findings: Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36-4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74-2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46-5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90-2.73)., Interpretation: A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Triple-negative breast cancers (TNBCs) are the most deadly form of breast cancer (BC) subtypes. Axillary lymph node involvement (ALNI) has been described to be prognostic in BC taken as a whole, but its prognostic value in each subtype is unclear. We explored the prognostic impact of ALNI and especially of small size axillary metastases in early TNBCs., Methods: We analysed in this multicentre study all patients treated for early TNBC in 12 French cancer centres. We explored the correlation between clinicopathological data and ALNI, with a specific focus on the dichotomisation between macrometastases and occult metastases, which is defined as the presence of isolated tumour cells or micrometastases. The prognostic value of ALNI both in terms of disease-free survival (DFS) and overall survival (OS) was also explored., Results: We included 1237 TNBC patients. Five-year DFS and OS were 83.7% and 88.5%, respectively. The identified independent prognostic features for DFS were tumour size >20 mm (hazard ratio (HR)=1.86; 95% CI: 1.11-3.10, P=0.018), lymphovascular invasion (HR=1.69; 95% CI: 1.21-2.34, P=0.002) and ALNI both in case of macrometastases (HR=1.97; 95% CI: 1.38-2.81, P<0.0001) and occult metastases (HR=1.72; 95% CI: 1.1-2.71, P=0.019). DFS and OS were similar between tumours with occult metastases and macrometastases. Tumours presenting at least two pejorative features (out of ALNI, lymphovascular invasion and large tumour size) displayed a significantly poorer DFS in both the training set and validation set, independently of chemotherapy administration. Tumours with no more than one of the above-cited pejorative features had a 5-year OS of ⩾90% vs 70% for other cases (P<0.0001)., Conclusions: Axillary lymph node involvement is a key prognostic feature for early TNBC when isolated tumour cells were identified in lymph nodes. This impact is independent of chemotherapy use.

Purpose: Studies examining high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC-AHSCT) strategies in inflammatory breast cancer (IBC), showed encouraging results in terms of disease-free survival (DFS), and overall survival (OS). The lack of data regarding HER2 status in all of these studies prevented any prognostic analysis involving breast cancer subtypes. Methods: All consecutive female patients treated for IBC with HDC and AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. Since 2005, trastuzumab was included in initial treatment. Patient, tumor and treatment characteristics were collected. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: Luminal, (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The main objective was the analysis of OS according to the IHC subtypes. Results: Sixty-seven patients were included. Eleven patients received trastuzumab. Median follow up was 80.04 months (95% CI 73.2-88.08). Five-year OS and DFS for the whole population patients were 74% (95% CI 61-83) and 65 % (95% CI 52-75), respectively. OS differed across subtypes (p=0.057) : HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89% (95% CI 64-97) compared to 57% (95% CI 33-76) for the TN subgroup (HR 5.38, 95% CI 1.14-25.44; p=0.034). Conclusions: In IBC patients receiving HDC-AHSCT, OS favorably compares with data available in the literature on similar groups of patients. TN patients carried the least favourable OS and HER2 patients, half of them also receiving trastuzumab, had the best outcome. These findings provide additional information and options for patients with IBC and who could potentially benefit of HDC-AHSCT., Competing Interests: The authors have declared that no competing interest exists.

Purpose: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications., Methods: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected., Results: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01)., Conclusion: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

Purpose: We aimed to investigate the safety, adequacy and oncological outcomes of laparoscopic surgery (LS) and robot-assisted laparoscopic (RALS) approach for the treatment of early-stage ovarian cancer., Methods: We performed a multicentric, retrospective cohort study, enrolling patients affected by early-stage ovarian cancer who underwent laparoscopic management for early-stage ovarian cancer between 2006 and 2014. Surgical, pathologic and oncologic outcome data were analyzed to compare LS and RALS performances for early-stage ovarian cancer management., Results: 39 patients underwent laparoscopic staging for presumed stage I ovarian cancer: 23 underwent LS and 16 underwent RALS. The mean operative time was 281 ± 81 min (LS 288 ± 88 min; RALS 270 ± 72 min; p = 0.49). No conversion to laparotomy occurred, and one patient had intraoperative hemorrhage requiring blood transfusion. Four patients (10.2 %) experienced postoperative complications of grade 3 according to the Clavien-Dindo classification. The median hospital stay was 3 days (1-15); the differences were not statistically significant between two groups [LS = 4 (1-15); RALS = 3 (1-7); p = 0.43]. During a mean follow-up period of 19.4 months, tumor recurrence occurred in 3 patients: 2 (8.7 %) in the LS group and 1 (6.25 %) in the RALS group. Overall survival and disease-free survival for the entire cohort were 97.4 and 92.3 %, respectively., Conclusions: LS and RALS seem to be adequate and feasible for the treatment of early-stage ovarian cancer in terms of the surgical outcomes and oncological safety. Furthermore, in our experience, perioperative outcomes are comparable between LS and RALS making them an acceptable approach in selected patients.

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

Purpose: We retrospectively studied the different strategies of para-aortic (PA) staging of patients with PA involvement in locally advanced cervical cancer as conducted in eight centers in France and their impact upon survival and management., Methods: All patients enrolled in this multicenter study presented with cervical cancer with PA involvement. The diagnosis of PA spread was based on imaging assessment of the PA area and/or pathological examination of harvested PA lymph nodes when staging lymphadenectomy was performed. Imaging modalities comprised positron emission tomography (PET), magnetic resonance imaging and/or computed tomography. Survival outcomes were evaluated retrospectively., Results: One hundred and fifteen women were retrospectively studied. Radiological staging was conducted in 101 (87.8 %) patients. PET was performed in 66 patients (57.4 %). Its FN rate was 22.7 % (15/66) and its sensitivity 77.3 %. Para-aortic lymphadenectomy was conducted in a large proportion of patients (67.8 %). Its indications were not restricted to negative radiological workup. The lymphadenectomy rate was significantly higher in patients with earlier stages (p = 0.02) and lower tumor volume (p = 0.01). Treatment consisted of chemoradiation therapy with extended-field radiotherapy in all patients, followed by intracavitary brachytherapy in 94 cases (81.7 %) and completion surgery in 69 cases (60 %). Patients without para-aortic metastasis on radiological examination were more likely to receive all treatment modalities (p = 0.04)., Conclusion: Despite established recommendations, our results point out the tremendous heterogeneity regarding para-aortic assessment. These differences in management are perhaps related to a recommended therapeutic strategy that does not appear to improve the poor prognosis associated with PA involvement.

Background: The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival., Patients and Methods: From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established., Results: Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p < 0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p < 0.0001), age >50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size >20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017)., Conclusions: Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A meta-analysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists.

The advent of sentinel lymph-node technique has led to a shift in lymph-node staging, due to the emergence of new entities namely micrometastases (pN1mi) and isolated tumor cells [pN0(i+)]. The prognostic significance of this low positivity in axillary lymph nodes is currently debated, as is, therefore its management. This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting, discussing the locoregional treatment in pN0(i+) and pN1mi patients (completion axillary dissection, axillary irradiation with or without regional nodes irradiation, or observation), according to systemic treatment, with the goal to help physicians in their daily practice.

Introduction: The objective of this study was to evaluate the outcome of patients affected with different subtypes of metastatic breast cancer (MBC) following treatment with high-dose chemotherapy (HDC) and autologous haematopoietic progenitor cell transplantation (AHSCT)., Methods: All consecutive female patients treated for MBC with HDC and AHSCT at the Institut Paoli-Calmettes between 2003 and 2012 were included. Patient, tumour and treatment characteristics were collected. Patients were categorised in three subtypes based on hormonal receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of the primary tumour: luminal (L), (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the immunohistochemical (IHC) subtypes., Results: A total of 235 patients were included, median age was 46 (range 21-62). Median follow up was 53.28 months (95% confidence interval [CI] 45.12-57.6). The TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95% CI 11.76-44.4) compared to 44.64 months (95% CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (p < 0.01). In the multivariate analysis, the TN subtype retained an independent poor prognosis value compared to the luminal subtype, with a hazard ratio of 2.03 (95% CI 1.26-3.29, p = 0.037)., Conclusion: HDC-AHSCT does not change the prognostic value of IHC subtypes in MBC patients. OS favourably compares with data available in the literature on similar groups of patients. These findings provide additional information and options for patients with MBC and who could potentially benefit of HDC-AHSCT., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Two options are possible for the management of early stage cervical cancer, without lymph node involvement: radical surgery or brachytherapy followed by surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) of early stage cervical cancers managed by uterovaginale brachytherapy followed by extrafasciale hysterectomy (group 1) or by radical hysterectomy alone (group 2). The secondary objectives were to compare the morbidity of these two different approaches and to evaluate the parametrial involvement rate in patients managed by radical hysterectomy., Materials and Methods: It is a retrospective and collaborative study between the Paoli Calmettes Institute (Marseille) and the Oscar Lambret Center (Lille) from 2001 to 2013, in patients with tumors FIGO stages IA1, IA2, IB1 and IIA less than 2 cm of diameter, without pelvic lymph node involvement., Results: One hundred and fifty-one patients were included (74 in group 1 and 77 in group 2). The demographic characteristics of the two groups were comparable. OS and DFS were respectively 92.3% versus 100% (p = 0.046) and 92.3% and 98.7% (p = 0.18). Complication rates were 12.2% and 44.2%, respectively (p < 0.0001). In group 2, the parametrial invasion rate in this study was 1.30%., Conclusion: In our study, the two strategies are comparable in terms of DFS. Complications seem more frequent in the group 2, but more severe in the group 1. Finally, the low rate of parametrial invasion in group 2 confirms the interest of a less radical surgical treatment in these stages with good prognosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations., Methods: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis., Results: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS., Conclusions: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Background: We are reporting the preliminary multicentric experience in extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy (EPLRL) in gynecologic oncology., Materials and Methods: Two teams from the cancer centers performed EPLRL in 37 patients with gynecologic cancer., Results: There were 30 patients with cervical cancer, 6 with endometrial cancer, and 1 with adnexal cancer. The skin-to-skin operative time, mean lymph node count, and estimated blood loss were 221 (±61) minutes, 18.7 (±11), and 105 (±134) mL.There was no conversion to laparotomy, one laparoscopic conversion for hemorrhage lateral to the inferior mesenteric artery, and one use of hemostatic matrix for an injury to the left gonadal artery (2 nontransfused patients). The proportion of patients who reported postoperative complications was 32.5% (12/37): 7 with lymphocysts with computed tomographic scan drainage (19%), 3 with leg dysesthesia (left genitofemoral nerve), 1 with leg lymphedema, and 1 with lateral aortic hematoma not requiring a transfusion or return to the operating room., Conclusion: The EPLRL technique is feasible and efficient but with a high rate of symptomatic lymphocyst. A marsupialization could be useful to decrease the risk of lymphocyst.

Objective: Robotic surgical techniques are known to be expensive, but they can decrease the cost of hospitalization and improve patients' outcomes. The aim of this study was to compare the costs and clinical outcomes of conventional laparoscopy vs robotic-assisted laparoscopy in the gynecologic oncologic indications., Methods: Between 2007 and 2010, 312 patients referred for gynecologic oncologic indications (endometrial and cervical cancer), including 226 who underwent conventional laparoscopy and 80 who underwent robot-assisted laparoscopy, were included in this prospective multicenter study. The direct costs, operating theater costs, and hospital costs were calculated for both surgical strategies using the microcosting method., Results: Based on an average number of 165 surgical cases performed per year with the robot, the total extra cost of using the robot was €1456 per intervention. The robot-specific costs amounted to €2213 per intervention, and the cost of the robot-specific surgical supplies was €957 per intervention. The cost of the surgical supplies specifically required by conventional laparoscopy amounted to €1432, which is significantly higher than that of the robotic supplies (P < 0.001). Hospital costs were lower in the case of the robotic strategy (€2380 vs €2841, P < 0.001) because these patients spent less time in intensive care (0.38 vs 0.85 days). Operating theater costs were higher in the case of the robotic strategy (€1490 vs €1311, P = 0.0004) because the procedure takes longer to perform (4.98 hours vs 4.38 hours)., Conclusions: The main driver of additional costs is the fixed cost of the robot, which is not compensated by the lower hospital room costs. The robot would be more cost-effective if robotic interventions were performed on a larger number of patients per year or if the purchase price of the robot was reduced. A shorter learning curve would also no doubt decrease the operating theater costs, resulting in financial benefits to society.

Objectives: Ovarian cancer is the leading cause of mortality by gynecologic cancers in Western countries. Many publications have suggested that age may be an independent prognostic factor in ovarian carcinoma. There are only few data concerning the impact of treatments and geriatric features within the elderly population., Methods/materials: We collected data of older (≥ 70 years old) patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. First we described usual clinical and pathological features for these patients, as well as their outcome. We compared these parameters with that of young (<70 years old) patients treated during the same period. We then observed geriatric features in our set: Eastern Cooperative Oncology Group performance status, number of medications, Charlson index, body mass index, hemoglobin, and glomerular filtration rate. We finally looked for prognostic factors specific of the elderly population., Results: One hundred nine elderly patients were identified and compared with 488 younger cases. There was no difference concerning clinicopathologic data. Surgery was more frequently complete in young women (58% vs 41.7%), and older patients received less chemotherapy courses and less taxanes (38.4% vs 67.1%). Young patients had a longer overall survival (median, 65.2 vs 26.2 months, P = 8.5E-10, log-rank test). Multivariate analyses confirmed that age was an independent prognostic factor and that within the elderly set the International Federation of Gynecology and Obstetrics stage, surgery results, number of chemotherapy cycles administered and performance status had a significant prognostic value. No clear correlation could be observed between geriatric characteristics and treatments administration., Conclusions: Ovarian cancer prognosis is poorer for older women, but they are more frequently suboptimally treated. No correlation could be observed between geriatric factors and surgery or chemotherapy achievement. Treatment decision should be based on objective geriatric assessment in order to improve outcome in this population.

Sentinel node biopsy without complementary axillary lymph node dissection was validated for T1-2 N0 unifocal breast cancer without previous treatment since several years. In the situation of multifocal multicentric breast tumors, this procedure was considered as a contraindication. The aim of this work was to analyse literature results to determine if sentinel lymph node biopsy can be considered as a valid option without complementary axillary lymph node dissection for negative sentinel lymph node., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to evaluate perioperative outcomes of robotic-assisted laparoscopic para-aortic lymphadenectomy (PAL) in patients with gynecologic cancers during the learning phases of robotic surgery programs and to compare results of extraperitoneal versus transperitoneal approaches of PAL., Materials and Methods: This study is a retrospective multicentric study of patients who underwent robotically assisted laparoscopic PAL (N = 487). Eleven European centers and 1 US center participated in the study. Abstracted data included age, body mass index, indication, type of surgical approach (transperitoneal or extraperitoneal), associated surgical procedures, operative time, estimated blood loss, lymph node count, hospital length of stay (LOS), and complications. Para-aortic lymphadenectomy was performed by an extraperitoneal approach in 58 cases (12%) and transperitoneal in 429 cases (88%)., Results: The mean (SD) para-aortic lymph node count was 12.6 (8.1), operative time was 217 (85) minutes, estimated blood loss was 105 (110) mL, and LOS was 2.8 (3.2) days. Four (0.8%) conversions to open and 2 (0.4%) conversions to laparoscopy were described. There were 32 lymphocysts (6.6%), 3 deep venous thromboses (0.6%), and 10 transfusions (2.1%). For transperitoneal approach, the average number of lymph nodes removed was higher in isolated PAL group than the hysterectomy combined group (report node counts 95% confidence interval, -7.29 to -3.52, P = 1.5 × 10⁻⁶). For isolated PAL, the LOS was shorter in the extraperitoneal group than in the transperitoneal group (report data 95% CI, -1.35 to -0.35, P = 0.001)., Conclusions: Robotic-assisted PAL seems safe and feasible. More lymph nodes were removed during an isolated transperitoneal PAL dissection compared with a combined procedure with hysterectomy. Extraperitoneal approach seems attractive relative to transperitoneal dissection, but the superiority of one or the other way is not demonstrated by our study.

Objective: The objective of this study was to demonstrate that robotically assisted laparoscopy for aortic lymph node dissection was improved when double docking (DD) of the Da Vinci system is used for combined surgical procedures [defined by the combination of a pelvic procedure and a para-aortic lymphadenectomy (PAL)]., Methods: From February 2007 to February 2013, 41 patients underwent combined procedures including PAL up to the left renal vein in 2 cancer centers. We used 2 different approaches as follows: a single docking (SD) of the Da Vinci system (transperitoneal PAL and pelvic surgery) during the first period (22 patients) and a DD during the second period (19 patients). We recorded retrospectively the lymph node count (main criteria), operative time, estimated blood loss, hospital stay, and postoperative complications., Results: We observed a statistical difference between SD and DD concerning aortic lymph node count (5.86 vs 10.89, P < 0.005). Operative time is longer in the DD group (326.1 vs 239.4 minutes, P < 0.05). No difference was observed concerning estimated blood loss. Hospital stay was longer in the DD group (4.9 vs 3.2 days, P < 0.05). Only 1 conversion to open was described in the SD group., Conclusions: In our experience of robotically assisted laparoscopy, when PAL is combined to a pelvic procedure, the use of a DD seems to improve aortic lymph node count.Despite a longer operative time compared to SD, DD seems to be a good solution to combine the advantages of robotic assistance to our quality criteria of aortic dissection., Synopsis: We compare 2 techniques to realize robotic assisted para-aortic lymphadenectomy combined with pelvic procedure. Double docking seems to improve histological results compared to single docking.

Background: We wished to estimate the proportion of patients with breast cancer eligible for an exclusive targeted intraoperative radiotherapy (TARGIT) and to evaluate their survival without local recurrence., Methods: We undertook a retrospective study examining two cohorts. The first cohort was multicentric (G3S) and contained 7580 patients. The second cohort was monocentric (cohort 2) comprising 4445 patients. All patients underwent conservative surgery followed by external radiotherapy for invasive breast cancer (T0-T3, N0-N1) between 1980 and 2005. Within each cohort, two groups were isolated according to the inclusion criteria of the TARGIT A study (T group) and RIOP trial (R group).In the multicentric cohort (G3S) eligible patients for TARGIT A and RIOP trials were T1E and R1E subgroups, respectively. In cohort number 2, the corresponding subgroups were T2E and R2E. Similarly, non-eligible patients were T1nE, R1nE and T2nE, and R2nE.The eligible groups in the TARGIT A study that were not eligible in the RIOP trial (TE-RE) were also studied. The proportion of patients eligible for TARGIT was calculated according to the criteria of each study. A comparison was made of the 5-year survival without local or locoregional recurrence between the TE versus TnE, RE versus RnE, and RE versus (TE-RE) groups., Results: In G3S and cohort 2, the proportion of patients eligible for TARGIT was, respectively, 53.2% and 33.9% according the criteria of the TARGIT A study, and 21% and 8% according the criteria of the RIOP trial. Survival without five-year locoregional recurrence was significantly different between T1E and T1nE groups (97.6% versus 97% [log rank=0.009]), R1E and R1nE groups (98% versus 97.1% [log rank=0.011]), T2E and T2nE groups (96.6% versus 93.1% [log rank<0. 0001]) and R2E and R2nE groups (98.6% versus 94% [log rank=0.001]). In both cohorts, no significant difference was found between RE and (TE-RE) groups., Conclusions: Almost 50% of T0-2 N0 patients could be eligible for TARGIT.

Objectives: Ovarian cancers are usually diagnosed at an advanced stage. The extent of the disease before surgery partly determines the ability to perform a complete cytoreduction. The peritoneal cancer index (PCI) is used to evaluate peritoneal carcinomatosis and has been validated in ovarian cancer and correlated with resectability. The aim of our study was to assess the feasibility of single-port laparoscopy (SPL) for suspicion of advanced ovarian cancer and to describe the ability to calculate the PCI score at the time of laparoscopy., Study Design: Between February 2011 and January 2013, 33 patients underwent SPL for suspected advanced ovarian cancer. Individual records for all patients were prospectively reviewed and analyzed. For each patient, we determined the PCI score., Results: 33 patients underwent initial SPL, 85% had increased carcinological markers and 67% a radiological suspicion of peritoneal carcinomatosis. The median operative time was 90min. During SPL, 76% of patients underwent ascites evacuation; all patients had peritoneal cytology and peritoneal biopsies. Only 3 patients experienced perioperative complications. Two open conversions were recorded. Quotation of the PCI score was possible for all patients. Eighteen patients (55%) had a PCI score below 10; one had a maximal PCI score of 39. The PCI score was null for 9 patients. Non-browsing areas marked 8 procedures., Conclusions: SPL appeared to be feasible, with satisfying immediate results and postoperative outcome, compared to conventional laparoscopy. It allowed a satisfying exploration of the abdomino-pelvic cavity and a good description of peritoneal carcinomatosis with only a few non-browsing PCI areas., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)