Alexandre de Nonneville

Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study

PurposeBenefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1xa0cm 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 chemotherapyxa0±xa0trastuzumab on outcome in this subpopulation.Patients and methodsA total of 356 cases of pT1abN0M0 HER2xa0+xa0breast 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.ResultsA 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 chemotherapyxa0±xa0trastuzumab 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]; pxa0=xa00.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07–0.52]; pxa0=xa00.001). Metastasis-free survival was also increased (HRxa00.25 [0.07–0.86]; pxa0=xa00.018, 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.ConclusionsAdjuvant chemotherapyxa0±xa0trastuzumab 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.

Enhanced recovery after surgery program in Gynaecologic Oncological surgery in a minimally invasive techniques expert center

BackgroundEnhanced 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).MethodsThis 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 (2xa0days), morbidity and readmissions.ResultsExcept 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%; pu2009=u20090.003), 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; pu2009=u20090.002) and proportion of discharged patient at target LOS (45% vs. 24%; pu2009=u20090.002). 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.ConclusionERP 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.

End-of-Life Practices in France under the Claeys-Leonetti Law: Report of Three Cases in the Oncology Unit

On February 2, 2016, the French government enacted the Claeys-Leonetti law introducing the right to deep and continuous sedation and forbade euthanasia for end-of-life patients. This article reports the first descriptions of this kind of intervention at the final stage of life of 3 patients and highlights the need of patient-centered goals and the importance of close collaboration between the patient, family, and medical and paramedical team to achieve a higher quality of final palliative care.

Enhanced recovery after surgery program in older patients undergoing gynaecologic oncological surgery is feasible and safe

BACKGROUNDnEnhanced Recovery After Surgery Programs (ERP) include multimodal approaches of perioperative patients 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.nnnMETHODSnData 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 ≥70u202fyears old compared to younger patients without increasing the proportion of complications and readmission rates. A binary (LOSu202f<u202foru202f≥u202f2u202fdays) 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 ≥70u202fyears old patients.nnnRESULTSnOf a total of 329 patients, 75 were ≥70u202fyears old and 254 were <70. Except a disparity in oncological indications with a higher proportion of endometrial cancer in the ≥70u202fyears old group (56% vs. 27%; pu202f<u202f0.01), there were no differences in patients characteristics and surgical procedures. Ageu202f≥u202f70u202fyears was associated with a longer LOS (means, 3.88 vs. 3.11u202fdays; pu202f=u202f0.024) only in univariate analysis. Considering the logistic regression, age was no longer associated with LOS. Total hysterectomy with pelvic lymphadenectomy and ASA scoreu202f≥u202f3 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 ≥70u202fyears old population, G8 score was not predictive of LOS, morbidities or readmissions.nnnCONCLUSIONnAlthough it is already widely accepted that ERP improves early recovery, our study shows that ERP for patients over 70u202fyears of age undergoing gynaecologic oncological surgery is as safe and feasible as on younger patients.

Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact

BackgroundTumour 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.MethodsPatients 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.ResultsOf 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, pu2009=u20090.010; ERs+/Grade3: HR 1.41, pu2009=u20090.067; ERs−: HR 2.14, pu2009<u20090.0001), endocrine therapy (HR 2.05, pu2009<u20090.0001) and ageu2009<u200940-years old (HR 2.28, pu2009=u20090.005) 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 <u20092-years, in comparison with ≥u20095-years).ConclusionERs/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.

Determinants of favorable or unfavorable opinion about euthanasia in a sample of French cancer patients receiving palliative care

BackgroundOpinion about euthanasia has been explored among the general population and recently in patients receiving palliative care. 96% of the French population declared themselves in favor of euthanasia while less of 50% of palliative care patients are. The aim of the present study was to explore and identify potential determinant factors associated with favorable or unfavorable opinion about euthanasia in a French population of cancer patients receiving palliative care.MethodsWe performed a cross-sectional study among patients in two palliative care units. Eligible patients were identified by the medical staff. Face-to-face interviews were performed by two investigators. Two groups were defined as favorable or unfavorable about euthanasia according to the answer on the specific question about patient opinion on euthanasia. A multivariate analysis including age, belief in God, chemotherapy and gender was built.ResultsSeventy-eight patients were interviewed. Median age was 60.5xa0years (range: 31–87.2). In univariate analysis, patients with a favorable opinion were most often under 60xa0years old (62 versus 38% unfavorable; pu2009=u20090.035), in couple (64 versus 35%; pu2009=u20090.032), didn’t believe in God (72 versus 28% were non-believers; pu2009<u20090.001) and had more frequently an history of chemotherapy treatment (58 versus 42% received at least one cycle of chemotherapy; pu2009=u20090.005). In a multivariate analysis, ageu2009<u2009xa060xa0years, absence of belief in God and an antecedent of chemotherapy were independently associated with a favorable opinion about euthanasia (ORu2009=u20090.237 [0.076–0.746]; pu2009=u20090.014, ORu2009=u20090.143 [0.044–0.469]; pu2009=u20090.001, and ORu2009=u200910.418 [2.093–51.853]; pu2009=u20090.004, respectively).ConclusionWe report here determinants of opinion about euthanasia in palliative care cancer patients. Thus, young patients who do not believe in God and have a history of chemotherapy treatment are more likely to request the discontinuation or restriction of their treatment. A better understanding of these determinants is essential for the development of information and/or interventions tailored to the palliative context.

Safety and efficacy of eribulin for “real-world” older patients with metastatic breast cancer

Breast cancer is the most frequently diagnosed cancer and the leading cause of female cancer-related death worldwide, with amedian age at diagnosis between 60 and 65 years. Nevertheless, numerous studies have shown that older women are often undertreated, leading to higher rates of recurrence and mortality [1]. Patients with metastatic breast cancer (MBC) pre-treated with anthracyclines and taxanes may receive capecitabine, vinorelbine, or eribulin. The latter is one of the few agents to provide a survival gain, albeit small (2.5 months) in a heavily pretreated population of MBC [2]. Despite its extensive use in older patients withMBC, eribulin clinical efficacy and safety in the “real-world” has not been clearly evaluated in this population. Efficacy results obtained in general population cannot be directly extrapolated to older patients without specific evidence. Indeed, this subgroup of patients may have a different pharmacodynamics, pharmacokinetics and safety profiles and therefore treatment benefits might be smaller [3]. Thus, specific exploration of eribulin in the older population is warranted to improve clinical management of this population. The objectives of our study were to evaluate the safety (adverse events incidence, AEs) and efficacy (progression-free survival, PFS) of eribulin in pretreated older patients with MBC.