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Background: Aggressive angiomyxoma (AA) is a rare, locally aggressive tumor usually arising from pelvis or perineum, with a high local‐recurrence rate after complete surgery. Anecdotal responses to hormone therapy have been reported. In the present study we aimed at studying surgical treatment outcomes and sensitivity to hormone therapy of AA. Materials and Methods: We conducted a multicenter, international retrospective effort including patients with AA treated at three European referral centers (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and the Italian Rare Cancer Network; Centre Léon Bérard, Lyon, France; and Hospital Universitario Virgen del Rocio, Seville, Spain). Results: A total of 36 patients were included. Median follow‐up was 51.3 months. Thirty‐three patients (92%) underwent complete (R0 + R1) surgery, with a local relapse rate of 50% and a median relapse‐free survival of 39 months (95% confidence interval [CI], 27–68.1). Thirteen patients received a first‐line systemic treatment with hormone therapy for locally advanced disease, with an overall response rate of 62% and a median progression‐free survival of 24.6 months (95% CI, 11.0–39.7). In two patients, adding an aromatase inhibitor (AI) on progression to first‐line GnRH agonist (GnRHa) resulted in a new tumor response. Conclusion: Our findings confirm that in AA, surgical local control may be challenging, with a significant rate of local relapse despite complete surgery. Hormone therapy is an active treatment option, with a potential of disease control and of being combined with surgery. The addition of an AI to first‐line GnRHa could be an effective second‐line systemic therapy in premenopausal female patients with AA. Implications for Practice: In this retrospective effort including 36 patients with aggressive angiomyxoma, local relapse rate after complete surgery was 50%, with a median relapse‐free survival of 39 months, confirming that local control is challenging. Overall response rate to first‐line hormone therapy was 62%, with a median progression‐free survival of 24.6 months. Thus, hormone therapy has a potential of disease control and of being combined with surgery. This article reports the results of a study of the natural history of aggressive angiomyxoma, focusing on the disease's sensitivity to hormone therapy and on treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The increasing number of data supporting use of a personalized approach in cancer treatment, is changing the path of patient's management. In the same time, the availability of technologies should allow patients to receive the best test for the specific individual condition. This is theoretically true, when a specific test is designed for the specific disease condition, while it is difficult to implement in the setting of agnostic therapies. Financial sources availability related to the non homogeneous health systems working in the different countries do not allow for an immediate implementation of the technologies and test commercially available. Future perspectives for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. Therefore, the present paper is aimed to both underline a how much important is this new view and also to sensitize the international bodies that supervise health policies at the decision-making level, with the aim of harmonizing cancer treatment pathways in at least all European countries. Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions—notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval—and the role of real-world evidence in the process—and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework—starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients. [ABSTRACT FROM AUTHOR]

Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were ⩾18years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4weeks ago. BI 2536 200–250mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3–4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14–15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. [Copyright &y& Elsevier]

Objective: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies., Methods: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021., Results: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally., Conclusion: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose of Review: Although the survival rate of patients with ovarian cancer (OC) has significantly improved, OC is still one of the most common causes of gynecologic cancer death in women worldwide. The current advances in primary treatment are based on recent regulatory approvals and recurrency of such treatments, challenging the development of a unified approach to care. Herein, we examine how integration of these new approaches is applied to patient's treatment., Recent Findings: We and others have recently reported clinical trials using bevacizumab and/or inhibitors of Poly (ADP-ribose) polymerase (PARP), which have greatly affected the change in first-line treatments for OC. As first-line therapy has evolved, therapeutic agents once designated for recurrent disease are increasingly being incorporated, changing our standard of care following previously indexed trials. Here, we provide an overview of the current treatment for OC patients, and we highlight practice patterns in Europe and in the USA with corresponding opinions on current and future treatments for platinum-sensitive recurrent OC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Rare cancers are defined by an incidence of <6 out of 100 000 cases per year. They are under-represented in clinical research including tumour molecular analysis. The aim of Arcagen is to generate a multinational database integrating clinical and molecular information of patients with rare cancers., Patients and Methods: We present the retrospective feasibility cohort of patients with rare cancers, with previously collected tumour samples available from any stage. Molecular analysis was performed using FoundationOne CDx for all histologies except for sarcoma where FoundationOne Heme was used. Clinical data including demographic data, medical history, malignant history, treatment and survival data were collected., Results: Eighty-seven patients from three centres were screened; molecular data were obtained for 77 patients (41 sarcomas, 9 yolk sac tumours, 14 rare head and neck cancers, 13 thymomas). The median age at the time of diagnosis was 48 (range 28-85). Most patients had reportable genomic alterations (89%). The most common alterations were linked to cell cycle regulation (TP53, RB1, CDKN2A/B deletions and MDM2 amplification). Multiple activating single-nucleotide variants (SNVs) could be detected in the RAS/RAF family. The tumour mutational burden status was globally low across all samples with a median of 3 Muts/MB (range 0-52). Only 4 cases (ie, 4.7% of tumours) had direct actionable mutations for a treatment approved in Europe within the patient's tumour type., Conclusion: The Arcagen project aims to bridge the gap and improve knowledge of the molecular landscape of rare cancers by prospectively recruiting up to 1000 patients., Competing Interests: Competing interests: IR-C has Honoraria (self) from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; honoraria (institution) from GSK, MSD, Roche and BMS; advisory/consulting fees from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; research grant/funding (self) from MSD, Roche and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno and travel support from Roche, AstraZeneca and GSK. JF has Honoraria (self) from BMS, AstraZeneca, Roche, MSD, Merck Sereno; advisory/consulting fees from Servier, BMS, AstraZeneca, Innate Pharma, Roche/Genentech; research grant/funding (self) from AstraZeneca; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno and travel support from BMS, MSD, AstraZeneca. J-YB has research support and honoraria from Roche Genentech. DJ, OH and RE are employees of FMI/Roche and Roche shareholders., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Importance: There is an unmet medical need for the treatment of recurrent ovarian cancer, and new approaches are needed to improve progression-free survival (PFS) and overall survival., Objective: This phase 1/2 study evaluated the activity of alisertib in combination with weekly paclitaxel in patients with breast (phase 1) and ovarian cancer (phase 1 and phase 2)., Design, Setting, and Participants: An open-label phase 1 and randomized phase 2 clinical trial conducted from April 16, 2010, for phase 1 and March 28, 2012, to August 12, 2013, for phase 2 was conducted at 33 sites (United States, France, and Poland). Data are reported from a cutoff date of August 12, 2014, with a median duration of follow-up of 7.2 months in the alisertib plus paclitaxel arm and 4.6 months in the paclitaxel arm. A total of 191 women with advanced breast (phase 1 only) or recurrent ovarian cancer were enrolled, including 142 patients randomized to alisertib plus paclitaxel (n = 73) or paclitaxel alone (n = 69) in the phase 2 study., Interventions: Patients were randomized 1:1 stratified by platinum-free interval (refractory, 0-6 months, 6-12 months) and prior weekly taxane treatment (yes, no) to receive alisertib 40 mg twice per day orally and 3 days on and 4 days off for 3 weeks, plus paclitaxel (60 mg/m2 intravenously, days 1, 8, and 15), or weekly paclitaxel 80 mg/m2 intravenously in 28-day cycles., Main Outcomes and Measures: Primary endpoint was PFS; primary efficacy analysis and safety analysis used modified intention to treat (mITT) population (all randomized patients who received ≥1 dose of study drug)., Results: The median age for the 191 patients enrolled in phase 1 was 59 (range, 29-75) years. The median age for the 142 patients enrolled in phase 2 was 63 (range, 30-81) years for patients receiving alisertib plus paclitaxel and 61 (range, 41-81) years for patients receiving paclitaxel. At data cutoff, 107 (75%) patients had a documented PFS event; 52 (71%) in the alisertib plus paclitaxel arm, and 55 (80%) in the paclitaxel arm. Median PFS was 6.7 months with alisertib plus paclitaxel vs 4.7 months with paclitaxel (HR, 0.75; 80% CI, 0.58-0.96; P = .14; 2-sided P value cutoff = .20 to be considered worthy of further investigation). Drug-related grade 3 or higher adverse events were reported in 63 (86%) vs 14 (20%) patients in the alisertib plus paclitaxel and paclitaxel arms, including 56 (77%) vs 7 (10%) neutropenia, 18 (25%) vs 0 stomatitis, and 10 (14%) vs 2 (3%) anemia; 54 (74%) vs 17 (25%) had adverse events leading to dose reductions. Two patients died during the study (1 in each arm); neither death was considered related to study drug., Conclusions and Relevance: The primary endpoint, PFS, significantly favored alisertib plus paclitaxel over paclitaxel alone. Further investigation is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT01091428.

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Although the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with disease-free survival (DFS) in patients with operable, imatinib-naive GIST., Experimental Design: Clinicopathologic and molecular data from 1,056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months., Results: On testing for potential prognostic parameters, the following were associated with inferior DFS on multivariable Cox model analysis: primary nongastric site, size >10 cm, mitotic index >10 mitoses per 50 high power field, and the KIT exon 9 duplication [hazard ratio (HR), 1.47; 95% confidence interval (CI), 0.9-2.5; P = 0.037] and KIT exon 11 deletions involving codons 557 and/or 558 [KITdel-inc557/558; HR, 1.45; 95% CI, 1.0-2.2; P = 0.004]. Conversely, PDGFRA exon 18 mutations were indicators of better prognosis [HR, 0.23; 95% CI, 0.1-0.6; P = 0.002]. KITdel-inc557/558 were an adverse indicator only in GIST localized in the stomach (P < 0.001) but not in tumors with nongastric origin. In gastric GIST, all other mutations presented remarkably superior 5-year DFS., Conclusions: In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST and should be used for optimizing tailored adjuvant imatinib treatment., (©2014 American Association for Cancer Research.)

Purpose: This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy., Patients and Methods: Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients., Results: Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm., Conclusion: Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.