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ObjectiveWe sought to evaluate the impact of chemotherapy response score according to the number of cycles of neoadjuvant chemotherapy, on disease-free survival and overall survival, in patients with advanced epithelial ovarian cancer ineligible for primary debulking surgery.MethodsThis multicenter retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV epithelial ovarian cancer who underwent 3–4 or 6 cycles of a platinum and taxane-based neoadjuvant chemotherapy, followed by complete cytoreduction surgery (CC-0) or cytoreduction to minimal residual disease (CC-1), between January 2008 and December 2015, in four institutions. Disease-free survival and overall survival were assessed according to the histological response to chemotherapy defined by the validated chemotherapy response score.ResultsA total of 365 patients were included: 219 (60.0%) received 3–4 cycles of neoadjuvant chemotherapy, and 146 (40.0%) had 6 cycles of neoadjuvant chemotherapy before cytoreductive surgery. There were no significant differences in early relapses, disease-free survival, and overall survival according to the number of neoadjuvant chemotherapy cycles. However, regardless of the number cycles of neoadjuvant chemotherapy, persistent extensive histological disease (chemotherapy response score 1–2) was significantly associated with a higher peritoneal cancer index, minimal residual disease (CC-1), and early relapses. Median disease-free survival in patients with complete or near-complete response (score 3) was 28.3 months (95% CI 21.6 to 36.8), whereas it was 16.3 months in patients with chemotherapy response score 1–2 (95% CI 14.7 to 18.0, pConclusionIn our cohort, the number of neoadjuvant chemotherapy cycles was not associated with disease-free survival or overall survival. Chemotherapy response score 3 improved oncological outcome regardless of the number of neoadjuvant chemotherapy cycles.

To ensure patient care in an oncological fertility preservation (FP) programme, specialists must provide technology that best suits the patients’ clinical conditions. In vitro oocyte maturation (IVM) and ovarian tissue cryopreservation (OTC) are possible fertility preservation treatments for women in need of urgent oncological treatment. IVM consists of the retrieval of immature oocytes from small antral follicles, with no or minimal ovarian stimulation by gonadotropins. Therefore, IVM has become a pertinent option for fertility preservation, especially for cases whereby ovarian stimulation is unfeasible or contra-indicated. Existing data on immature oocytes, retrieved transvaginally (OPU-IVM) or extracted from ovarian tissue ‘ex vivo’ (OTO-IVM), are still limited on technical consistency, efficacy, and safety. The present retrospective cohort study includes 89 women undergoing fertility preservation using IVM methodologies and 26 women undergoing ovarian stimulation (OS) in concomitant period. In total, 533 immature oocytes were collected from IVM patients, achieving a maturation rate of 57% and 70% in OTO-IVM and 73% and 82% in OPU-IVM at 24 h and 48 h in culture, respectively. The observed high maturation rates might be due to the use of patients’ serum in its innate status, i.e., without heat-inactivation. This permitted 7.6 ± 5.7 and 4.6 ± 4.9 oocytes to be vitrified in OTO-IVM and OPU-IVM, respectively, compared to 6.8 ± 4.6 from OS patients. Regarding OS patients, two of them underwent embryo transfer following the insemination of warmed oocytes after complete remission, resulting in a single live birth from one patient. Upon follow-up of two OTO-IVM patients after the termination of their oncological treatment, a total of 11 warmed oocytes lead to a transfer of a single embryo, but pregnancy was not achieved. From OPU-IVM, six embryos were transferred in three patients 4.25 years after oocyte vitrification, leading to the live birth of a healthy boy. The present case of live birth is among the first cases reported so far and supports the notion that IVM might be a relevant and safe FP option for cancer patients when oocyte preservation is required but ovarian stimulation is contra-indicated.

Introduction: To use positron emission tomography coupled with computed tomography (18FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all 18FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox9s proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUVmax were significantly associated with OS (p

Neuroendocrine tumors (NET) develop from the diffuse endocrine system. These are rare tumors that can affect diverse organs. We present here the case of a 42-year-old female patient in whom a NET of the breast was discovered that was likely not of mammary origin. The main challenge was finding the primary tumor using immunohistochemistry and specific medical imaging modalities for NET. The primary tumor was localized at the last ileal loop upstream of the Bauhin valve thanks to the use of 18F-DOPA-PET. Ileocaecal resection by laparoscopy was performed. A WHO grade 2 NET of the ileum measuring 2.2 cm × 1.5 cm was found that infiltrated the submucosa with six metastatic lymph nodes of the eight removed (6N+/8). This unusual clinical case is the first one of a digestive NET of the ileum-caecal junction by mammary metastasis.

International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.

In this phase I trial, 42 women with metastatic breast cancer were treated with a fixed dose of epirubicin (75 mg/m2) and escalating doses of ixabepilone (25, 30, and 35 mg/m2). The maximum-tolerated dose of ixabepilone in combination with epirubicin was 30 mg/m2 (the recommended dose for phase II evaluation), and the dose-limiting toxicity dose was 35 mg/m2 with grade 4 neutropenia.The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLT), pharmacokinetics, and the recommended phase II dose for ixabepilone in combination with epirubicin in women with metastatic breast cancer.Patients ≥18 years old with an histologically or cytologically confirmed diagnosis of invasive breast cancer and clinical evidence of locally recurrent or metastatic disease were enrolled and treated with a fixed dose of epirubicin (75 mg/m(2)) and escalating doses of ixabepilone (25, 30, and 35 mg/m(2)).Forty-two women were treated at 3 different dose levels of ixabepilone: 25 (n = 6), 30 (n = 30), and 35 mg/m(2) (n = 6) in combination with 75 mg/m(2) epirubicin. The MTD of ixabepilone in combination with epirubicin 75 mg/m(2) was 30 mg/m(2), and the DLT dose was 35 mg/m(2) with grade 4 neutropenia. Grade 3/4 neutropenia was the most frequent moderate-to-severe adverse event and was manageable and reversible. No deaths were reported. Objective responses were achieved in 18 of 32 patients with measurable disease (56% [90% CI, 40%-71%]) and in 9 of 22 evaluable patients treated at the MTD (41% [90% CI, 23%-61%]). Ixabepilone clearance and the epirubicin pharmacokinetic profile were similar across ixabepilone dose levels.The combination of ixabepilone and epirubicin was clinically active. The recommended dose for evaluation in phase II is epirubicin 75 mg/m(2), followed by ixabepilone 30 mg/m(2) every 3 weeks.

We retrospectively studied the therapeutic significance of extended-field radiotherapy combined with concurrent platinum-based chemotherapy for the management of cervical carcinoma with paraaortic spread. Treatment response and survival outcomes were evaluated. One hundred and fifteen women were retrospectively studied. Radiological staging was conducted in 101 (87.8%) patients and paraaortic lymphadenectomy in 78 (67.8%). Patterns of treatment comprised chemoradiation therapy (100%), intracavitary brachytherapy (81.7%), completion surgery (60%) and neoadjuvant chemotherapy (4.3%). Four-year overall and disease-free survivals were 32.7% and 28.8%, respectively. Progression and relapse mostly involved the locoregional area and distant organs, rather than the paraaortic area. Advanced FIGO stage at baseline was the most significant prognostic factor (HR=3.02, p=0.01). Despite systematic extended-field chemoradiation therapy, paraaortic involvement in cervical cancer is associated with poor survival outcomes. The patterns of progression and recurrence suggest the existence of occult metastatic disease at presentation. Additional systemic treatment might thus be beneficial.

Background Pazopanib is a multi-targeted tyrosine kinase inhibitor shown to be clinically active in the treatment of various cancer types. This study aimed to evaluate the maximum tolerated regimen (MTR), safety, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab in adult patients with relapsed or refractory metastatic colorectal cancer (mCRC). Patients and methods This was a Phase I, 3 + 3 design, open-label, dose-escalation study (NCT0050943; VEG108925) conducted in sequential cohorts to determine the MTR of pazopanib and irinotecan administered with cetuximab. Twenty-five patients received treatment in three dosing cohorts and were evaluated for safety and tolerability of the combination and pharmacokinetics of individual drugs. Results The MTR was determined to be 400 mg pazopanib per day orally in combination with 150 mg/m2 irinotecan biweekly and 250 mg/m2 cetuximab weekly by infusion. Neutropenia was the main dose-limiting toxicity. Pharmacokinetic results suggested that the overall systemic exposure to SN-38, the active metabolite of irinotecan, was affected by pazopanib to a greater extent than was the systemic exposure to irinotecan itself. Conclusions This study provided evidence for the manageable safety profile and feasibility of using the novel triplet combination of pazopanib, irinotecan, and cetuximab in patients with refractory mCRC. Further large-scale Phase II studies are warranted.

OBJECTIVE: Mutations in the ligand-binding domain of the human androgen receptor (AR) figure among the ways used by prostate adenocarcinoma (PCa) cells to escape androgen dependence. These mutations may broaden the specificity and/or affinity of the AR to other hormones, resulting in inappropriate receptor activation and thus affecting the PCa response to physiological stimuli and hormonal therapies. DESIGN: In order to clarify the impact of these mutations on disease progression and treatment, we have developed a yeast-based functional assay that allows the detection of mutant ARs and the analysis of their transactivation capacities in response to different ligands. METHODS: AR cDNA was directly cloned into an expression vector in a yeast strain that carries a reporter gene (ADE2) linked to an androgen-dependent promoter. The expression of the ADE2 gene and consequently the yeast cell growth in a selective medium depleted in adenine depends on the specificity of the AR for the ligand added to the medium. RESULTS: By analysing the transactivation capacities of different AR molecules in response to a broad range of steroid and non-steroid ligands, we have demonstrated that this assay can discriminate among wild-type AR, T877A, C685Y and L701H mutant ARs and that at least 1% of mutant ARs could be detected when mutant and wild-type ARs were mixed at the cDNA level. CONCLUSIONS: The data presented here show that this simple AR assay is convenient for the routine detection of mutant ARs in PCa and is also suitable to evaluate the antagonist activities of anti-androgen molecules.