Publications by authors named "Fedro Alessandro Peccatori"

38 Publications

Data describing the poor outcome associated with a breast cancer diagnosis in the post-weaning period.

Data Brief 2021 Oct 10;38:107354. Epub 2021 Sep 10.

Department of Oncology, Laboratory of Gynecological Oncology, KU Leuven, Leuven, Belgium.

Postpartum breast cancer (PPBC) - which according to new data, can extend to 5-10 years after the birth - are estimated to represent 35-55% of all cases of breast cancer in women younger than 45 years. Increasing clinical evidence indicates that PPBC represents a high-risk form of breast cancer in young women with an approximately 2-fold increased risk for metastasis and death. Yet, the exact mechanisms that underlay this poor prognosis are incompletely understood and, hence, it is unknown why postpartum breast cancer has an enhanced risk for metastasis or how it should be effectively targeted for improved survival. This article is an accompanying resource of the original article entitled "Breast cancer diagnosed in the post-weaning period is indicative for a poor outcome" and present epidemiological data that compare standard prognostic parameters, first site of metastatic disease and survival and metastatic rates in young women with primary invasive breast cancer diagnosed within two years postpartum (PP-BC), in young women diagnosed during pregnancy (Pr-BC) and nulliparous women (NP-BC). Via an international collaboration of 13 centres participating in the International Network on Cancer, Infertility and Pregnancy (INCIP), retrospective data of 1180 patients with primary invasive breast cancer, aged 25-40 years and diagnosed between January 1995 and December 2017 were collected. In particular, tumour-, patient, and therapy-related characteristics were collected. Furthermore, patient files were reviewed thoroughly to assess, for each parity, if and for how long breastfeeding was given. For PP-BC patients, breastfeeding history was used to differentiate breast cancers identified during lactation (PP-BC) from those diagnosed post-weaning (PP-BC). Primary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, time between cessation of lactation and breast cancer diagnosis and time between breast cancer diagnosis and metastasis or death. Distribution of standard prognostic parameters and first site of distant metastasis among study groups was determined applying fisher's exact, chi-squared, One-Way ANOVA or Kruskal-Wallis tests or logistic regression models, where applicable. The risks for metastasis and death were assessed using Cox proportional hazards models. A subgroup analysis was performed in PP-BC patients that never lactated (PP-BC), lactated ≤3 months (PP-BC) or lactated >3 months (PP-BC).
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http://dx.doi.org/10.1016/j.dib.2021.107354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446787PMC
October 2021

Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting.

BMC Med 2021 09 10;19(1):205. Epub 2021 Sep 10.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

Background: Healthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling and specific expertise.

Main Body: On December 5th-7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to "San Giuseppe Moscati" Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer.

Conclusion: Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted.
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http://dx.doi.org/10.1186/s12916-021-02081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431919PMC
September 2021

"Lights and Shadows": An Interpretative Phenomenological Analysis of the Lived Experience of Being Diagnosed With Breast Cancer During Pregnancy.

Front Psychol 2021 1;12:620353. Epub 2021 Apr 1.

Department of Psychology, Catholic University of the Sacred Heart, Milan, Italy.

Cancer diagnosed during pregnancy is a rare event. The most common type of malignancy diagnosed in pregnant women is breast cancer, whose incidence is expected to raise in the next future due to delayed childbirth, as well as to the increased occurrence of the disease at young age. Pregnant women diagnosed with breast cancer are exposed to multiple sources of stress, which may lead to poorer obstetric outcomes, such as preterm birth and low birth weight. In addition, pregnancy involves physiological changes in the breasts that may blur the signs of cancer, with delayed diagnosis and poor prognosis. However, the lived experience of these women was investigated in very few studies. Given this scenario, we conducted this qualitative study to describe and understand women's subjective experience of being diagnosed with breast cancer during pregnancy. The study was conducted following the principles of Interpretative Phenomenological Analysis. Participants were five women with breast cancer diagnosed during pregnancy, purposefully recruited at a public hospital during medical visits and interviewed at treatment initiation. The interview transcripts were analyzed using thematic analysis. The textual analysis led to the identification of three main themes related to: (1) the emotional storm experienced after cancer diagnosis, and the importance of receiving appropriate information and being focused on treatment decisions; (2) physical changes and comparisons with healthy women, associated with feelings of sadness and inadequacy; (3) being positive, feeling free to disclose all kinds of emotions, religion and spirituality as sources of strength. The paradoxical coexistence of pregnancy and cancer represents a stressful experience for women and their loved ones. Adopting a systemic perspective may be important to understand the effects of such a complex condition, also considering its impact on healthcare workers.
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http://dx.doi.org/10.3389/fpsyg.2021.620353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049111PMC
April 2021

A View from the past into our collective future: the oncofertility consortium vision statement.

J Assist Reprod Genet 2021 Jan 6;38(1):3-15. Epub 2021 Jan 6.

Division of Reproductive Endocrinology & Infertility, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium.

Methods: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process.

Results: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity.

Conclusion: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.
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http://dx.doi.org/10.1007/s10815-020-01983-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786868PMC
January 2021

Synchronous and Metachronous Breast and Ovarian Cancer: Experience From Two Large Cancer Center.

Front Oncol 2020 14;10:608783. Epub 2020 Dec 14.

Istituto Europeo di Oncologia - IRCCS, Milano, Italy.

Purpose: We aimed to evaluate the clinico-pathological characteristics and survival outcomes of patients with synchronous or metachronous breast cancer (BC) and ovarian cancer (OC).

Materials And Methods: Patients with synchronous or metachronous BC and OC were retrospectively identified at two large cancer centers. Clinico-pathological characteristics, and follow-up data were gathered. Patients were classified according to the first cancer diagnosis in the following groups: Breast Cancer , Ovarian Cancer , Synchronous Breast and Ovarian Cancer. Overall survival (OS) was calculated as the time interval between each cancer diagnosis to death or last follow-up.

Results: Overall, 270 patients were included: n = 194 (72%) in group, n = 51 (19%) in , and n = 25 (9%) in was available for 182 (67.4%) patients and 112 (62%) harbored pathogenetic mutations. group included more frequently patients with mutation, triple negative BC phenotype and more aggressive OC features. Median time between the two diagnosis was longer in group group (95 68 months, p = 0.021). A total of 105 OS events occurred, mostly related to OC (70.5%). We observed no differences in terms of OS according to the first cancer diagnosis. Age >50 years and advanced OC stage were negative independent prognostic factors for OS from the first diagnosis.

Conclusions: In this cohort of patients with BC and OC, survival was dominated by OC related mortality. These data may be useful to plan and carry out adequate and timely surveillance programs and preventive measures.
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http://dx.doi.org/10.3389/fonc.2020.608783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768039PMC
December 2020

Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants.

Crit Rev Oncol Hematol 2021 Jan 29;157:103201. Epub 2020 Dec 29.

Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, 16132, Italy; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, 16126, Italy. Electronic address:

The detection of germline BRCA1/2 pathogenic variant has relevant implications for the patients and their family members. Family planning, prophylactic surgery and the possibility of preimplantation genetic testing for monogenic disorders (PGT-M) to avoid transmittance of pathogenic variants to the offspring are relevant topics in this setting. PGT-M is valuable option for BRCA carriers, but it remains a controversial and underdiscussed topic. Although the advances in PGT technologies have improved pregnancy rate, there are still several important challenges associated with its use. The purpose of this review is to report the current evidence on PGT-M for BRCA1/2 carriers, ethical concerns and controversy associated with its use, reproductive implications of BRCA pathogenic variants, underlying areas in which an educational effort would be beneficial as well as possibilities for future research efforts in the field.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103201DOI Listing
January 2021

Seeing beyond COVID-19: understanding the impact of the pandemic on oncology, and the importance of preparedness.

Hist Philos Life Sci 2020 Nov 18;42(4):57. Epub 2020 Nov 18.

European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

The impact of this pandemic is not only through COVID-19 itself: the care for non-COVID-19 related conditions has been dramatically curtailed, shaking entire healthcare services around the world. Amongst the non-COVID-19 related conditions, oncology has been disproportionally affected. We discuss how oncology has changed since the acute phase of the pandemic; its impact on clinicians, trainees, and patients; and offer some medical and historical perspectives to reflect on how this impact could be reduced.
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http://dx.doi.org/10.1007/s40656-020-00351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673241PMC
November 2020

First-in-human pharmacokinetics of tamoxifen and its metabolites in the milk of a lactating mother: a case study.

ESMO Open 2020 10;5(5):e000859

Department of Clinical Science, University of Bergen, Bergen, Norway; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Breast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking.We measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula.Tamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18.This study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (>7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment.
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http://dx.doi.org/10.1136/esmoopen-2020-000859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594360PMC
October 2020

Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity.

Cancers (Basel) 2020 May 18;12(5). Epub 2020 May 18.

Oncology, Rambam Health Care Center, Haifa 3109601, Israel.

Breast cancer is diagnosed in ~0.3% of pregnant women. Studies that have addressed gestational and neonatal outcomes of chemotherapy during pregnancy have demonstrated increased gestational complications including preeclampsia and intrauterine growth retardation. We hypothesized that anthracycline-induced gestational complications could be derived from direct toxicity on the placenta vasculature. Pregnant ICR mice (day E12.5) were treated with doxorubicin (DXR; 8 mg/kg) or saline, while their umbilical cord blood flow was imaged by pulse-wave (PW) Doppler. Mice were euthanized on day E18.5, and their embryos and placentae were collected for further analysis. Unlike control mice, the DXR-treated mice presented an acute change in the umbilical cord's blood flow parameters (velocity time integral and heart rate interval), reduced embryos' weight, reduced placenta efficiency, and modulation in vascular-related pathways of treated placenta proteomics. Apoptosis and proliferation were also enhanced, as demonstrated by TUNEL and proliferating cell nuclear antigen (PCNA) analysis. We further examined the placentae of patients treated with epirubicin (EPI), who had been diagnosed with breast cancer during pregnancy (weeks 27-35). The immunohistochemistry of the EPI-treated human placentae showed enhanced proliferation and apoptosis as compared with matched chemo-naïve placentae, as well as reduced neovascularization (CD34). Our findings suggest that anthracycline-induced vascular insult promotes placental toxicity, and could point to potential agents designated to offset the damage and to reduce gestational complications in pregnant cancer patients.
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http://dx.doi.org/10.3390/cancers12051277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281110PMC
May 2020

Chemotherapy for breast cancer during pregnancy induces vascular alterations and impaired development of placental villi: A preliminary histopathological study.

Eur J Obstet Gynecol Reprod Biol 2020 Jul 29;250:155-161. Epub 2020 Apr 29.

Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.

Objective: To evaluate histological alterations in placentas of women affected by breast cancer and treated with chemotherapy during pregnancy.

Study Design: We retrospectively reviewed histological slides of 23 placentas of patients affected by breast cancer and treated with chemotherapy during pregnancy and 23 control placentas of women without breast cancer and with physiological pregnancies of the same gestational age.

Results: All the patients had breast ductal infiltrating carcinoma, 19 of 23 cases had a G3 cancer. All patients were treated with 2-6 cycles of chemotherapy starting after 16 weeks of gestation, with different protocols. No hypertensive complications and no pre-eclampsia episodes were observed; birth weight was consistent with gestational age in all babies in both group with no uneventful outcomes and no perinatal mortality or fetal malformations. Twenty out of 23 cases (86 %) showed hypoxia-induced villous alterations, including increased syncytial knotting (Tenney-Parker changes), perivillar fibrin deposits, distal villous hypoplasia or accelerated maturation and focal villous chorangiosis. These alterations were found in 19 out of 23 controls (83 %), with no statistically significant difference between the two groups.

Conclusions: These results shows that chemotherapy in the second and third trimester of pregnancy may lead to non-specific alterations in placental vasculature and morphology.
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http://dx.doi.org/10.1016/j.ejogrb.2020.04.012DOI Listing
July 2020

COVID-19: a plea to protect the older population.

Int J Equity Health 2020 05 19;19(1):72. Epub 2020 May 19.

Department of Biomedical and Specialty Surgical Sciences, University of Ferrara (Ferrara) & Civitas Vitae Research Centre (Padova), Ferrara and Padova, Italy.

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http://dx.doi.org/10.1186/s12939-020-01193-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235539PMC
May 2020

Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases.

Breast Care (Basel) 2020 Apr 25;15(2):148-156. Epub 2019 Jul 25.

Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy.

Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation.
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http://dx.doi.org/10.1159/000501473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204783PMC
April 2020

Motherhood during or after breast cancer diagnosis: A qualitative study.

Eur J Cancer Care (Engl) 2020 Mar 6;29(2):e13214. Epub 2020 Jan 6.

Department of Mental Health, ASST Bergamo Est, Seriate, Italy.

Objective: Little is known about the process of becoming a mother in women who experienced a breast cancer diagnosis (BC). In this qualitative study, we investigated maternal representations in pregnant women with experience of BC and those with no oncological history.

Methods: A total of 38 women were recruited, 19 women who experienced a BC diagnosis and 19 who had not. To explore maternal representations, semi-structured interviews were conducted and analysed through thematic analysis.

Results: Four main themes were identified: fears and worries, meaning of motherhood, mother-foetus relationship and partner support. Across themes, differences between primiparous and multiparous are reported. Women with gestational breast cancer (GBC) described fear for their own and their child's survival. Women with previous BC recall contrasting emotions. All women with experience of BC perceived breastfeeding as fundamental and inability to do so provoked worry. Relationship with the partner was considered central, while healthy women were projected towards the future triadic relationship.

Conclusions: Finding a mental space during pregnancy for the representation of the future child could be hard for women with GBC. Dissimilarities in the experience of motherhood in cancer patients provide insight into psychological aspects that should be taken into account in clinical practice.
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http://dx.doi.org/10.1111/ecc.13214DOI Listing
March 2020

Exploring differences in psychological aspects during pregnancy between cancer survivors and women without a history of cancer.

Support Care Cancer 2020 May 28;28(5):2255-2263. Epub 2019 Aug 28.

Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology IRCCS, Milan, Italy.

Young cancer survivors often wish to bear a child after oncological treatments, as they might not have started or completed their families. As young cancer survivors have a higher risk of developing psychological difficulties, this study investigated whether there were significant differences in psychological aspects between pregnant women who received a cancer diagnosis in the past and pregnant women without a history of cancer. A total of 123 pregnant women, of which 36 were cancer survivors and 87 women without a history of cancer, were recruited during their last trimester at different hospitals in Northern Italy. Patients were asked to complete a socio-demographic profile and questionnaires measuring mood states, post-traumatic symptoms, centrality of the pregnancy and cancer event, quality of life, and prenatal attachment. Cancer survivors had significantly higher levels of PTSD symptoms, perceived pregnancy as more central to their identity and life story, perceived lower quality of life and had lower intensity of prenatal attachment compared with the control group. Centrality of the cancer event did not correlate with any psychological variables. Preliminary results suggest that a past cancer diagnosis can influence the mother's psychological functioning and the development of the relationship with their child.
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http://dx.doi.org/10.1007/s00520-019-05048-wDOI Listing
May 2020

Care of adolescents and young adults with cancer in Asia: results of an ESMO/SIOPE/SIOP Asia survey.

ESMO Open 2019 6;4(3):e000467. Epub 2019 Jun 6.

2nd Department of Oncology, Henry Dunant Hospital Center, Athens, Greece.

Background: Adolescents and young adults (AYAs) with cancer require dedicated management encompassing both adult and paediatric cancer services. Following a European survey, the European Society for Medical Oncology, the European Society for Paediatric Oncology and the Asian continental branch of International Society of Paediatric Oncology undertook a similar survey to assess AYA cancer care across Asia.

Methods: A link to the online survey was sent to healthcare professionals (HCPs) in Asia interested in AYA cancer care. Questions covered the demographics and training of HCPs, their understanding of AYA definition, availability and access to specialised AYA services, the support and advice offered during and after treatment, and factors of treatment non-compliance.

Results: We received 268 responses from 22 Asian countries. There was a striking variation in the definition of AYA (median lower age 15 years, median higher age 29 years). The majority of the respondents (78%) did not have access to specialised cancer services and 73% were not aware of any research initiatives for AYA. Over two-thirds (69%) had the option to refer their patients for psychological and/or nutritional support and most advised their patients on a healthy lifestyle. Even so, 46% did not ask about smokeless tobacco habits and only half referred smokers to a smoking cessation service. Furthermore, 29% did not promote human papillomavirus vaccination for girls and 17% did not promote hepatitis B virus vaccination for high-risk individuals. In terms of funding, 69% reported governmental insurance coverage, although 65% reported that patients self-paid, at least partially. Almost half (47%) reported treatment non-compliance or abandonment as an issue, attributed to financial and family problems (72%), loss of follow-up (74%) and seeking of alternative treatments (77%).

Conclusions: Lack of access to and suboptimal delivery of AYA-specialised cancer care services across Asia pose major challenges and require specific interventions.
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http://dx.doi.org/10.1136/esmoopen-2018-000467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555609PMC
June 2019

Current strategies for the targeted treatment of high-grade serous epithelial ovarian cancer and relevance of BRCA mutational status.

J Ovarian Res 2019 Jan 28;12(1). Epub 2019 Jan 28.

Department of Health of Woman and Child, Gynecologic Oncology Unit, Catholic University of Sacred Heart, Largo Agostino Gemelli 8, 00168, Rome, Italy.

Epithelial ovarian cancer is the most lethal gynecologic malignancy. In most women, it is diagnosed at an advanced stage, which largely explains the poor prognosis of this malignancy. Germline mutations of the genes BRCA1 and BRCA2, which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition. BRCA mutations are present in approximately 14% of epithelial ovarian cancers. Somatic BRCA mutations have also been described. Current first-line treatment of high-grade epithelial ovarian cancer includes debulking surgery followed by combination chemotherapy, usually carboplatin and paclitaxel. Ovarian cancer is highly sensitive to chemotherapy, in particular to platinum drugs. Most patient will achieve remission with initial chemotherapy, but most will eventually experience disease recurrence. Targeted therapies, including the anti-angiogenic agent bevacizumab and oral poly (ADP-ribose) polymerase (PARP) inhibitors, have been recently approved for the treatment of ovarian cancer, based on the results from randomized clinical trials showing significant benefits in terms of progression-free survival, with acceptable tolerability and no detrimental effects on quality of life. Olaparib, the first PARP inhibitor to be granted approval, is currently indicated as maintenance monotherapy in ovarian cancer patients with relapsed disease and mutated BRCA who have achieved a complete or partial response to platinum-based chemotherapy. The analysis of BRCA mutational status has, therefore, also become crucial for therapeutic decisions. Such advances are making personalized treatment of ovarian cancer feasible. Here we briefly review treatments for platinum-sensitive, high-grade serous epithelial ovarian cancer that are currently available in Italy, with a focus on targeted therapies and the relevance of BRCA mutational analysis. Based on the evidence and on current guidelines, we propose strategies for the tailored treatment of patients with relapsed ovarian cancer that take into account BRCA mutational status and the treatment received in the first-line setting.
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http://dx.doi.org/10.1186/s13048-019-0484-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348631PMC
January 2019

Fertility preservation in ovarian tumours.

Ecancermedicalscience 2018 6;12:885. Epub 2018 Dec 6.

Department of Gynaecological and Obstetrical Sciences and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy.

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%-14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A-B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life. Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility. We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers.
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http://dx.doi.org/10.3332/ecancer.2018.885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345054PMC
December 2018

Tumor progression and metastatic dissemination in ovarian cancer after dose-dense or conventional paclitaxel and cisplatin plus bevacizumab.

Int J Cancer 2018 11 7;143(9):2187-2199. Epub 2018 Aug 7.

Laboratory of Biology and Treatment of Metastasis, Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short-term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose-dense (with/without DDP) was superior to the conventional scheme in a dose-dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose-dense-high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose-dense-high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule-dose of the treatment and help to explain the unclear benefits after bevacizumab.
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http://dx.doi.org/10.1002/ijc.31596DOI Listing
November 2018

Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences.

Cancer Biol Med 2018 Feb;15(1):6-13

Gynecologic Oncology Department, European Institute of Oncology, Milan 20141, Italy.

Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy (BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842335PMC
February 2018

Fatherhood during dabrafenib and trametinib therapy for metastatic melanoma.

Acta Oncol 2018 08 11;57(8):1131-1133. Epub 2018 Mar 11.

a Melanoma Unit , Istituto Europeo di Oncologia , Milano , Italy.

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http://dx.doi.org/10.1080/0284186X.2018.1449251DOI Listing
August 2018

Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time?

Hum Reprod 2018 02;33(2):181-187

Obstetrics and Gynecology Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 12, 20122 Milan, Italy.

Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted.
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http://dx.doi.org/10.1093/humrep/dex356DOI Listing
February 2018

The care of adolescents and young adults with cancer: results of the ESMO/SIOPE survey.

ESMO Open 2017 8;2(4):e000252. Epub 2017 Sep 8.

Klinikum Stuttgart - Olgahospital, Stuttgart, Germany.

Introduction: Adolescents and young adults (AYA) with cancer require dedicated clinical management and care. Little is known about the training and practice of European healthcare providers in regard to AYA and the availability of specialised services.

Methods: A link to an online survey was sent to members of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE). The link was also sent to ESMO National Representatives and circulated to other European oncology groups. Questions covered the demographics and clinical training of respondents, their definition of AYA, education about AYA cancer, access to specialised clinical and supportive care, research and further education. Data from Europe were analysed by region.

Results: Three hundred tweenty two questionnaires were submitted and we focused on data from the 266 European healthcare professionals. Responses revealed considerable variation both within and between countries in the definition of AYA. Over two-thirds of respondents did not have access to specialised centres for AYA (67%), were not aware of research initiatives focusing on AYA with cancer (69%) and had no access to specialist services for managing the late effects of treatment (67%). The majority of the respondents were able to refer AYA patients to professional psychological support and specialised social workers. However, more than half had no access to an age-specialised nurse or specialised AYA education. Overall, 38% of respondents reported that their AYA patients did not have access to fertility specialists. This figure was 76% in Eastern Europe. Lack of specialised AYA care was particularly evident in Eastern and South-Eastern Europe.

Conclusion: There is important underprovision and inequity of AYA cancer care across Europe. Improving education and research focused on AYA cancer care should be a priority.
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http://dx.doi.org/10.1136/esmoopen-2017-000252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604713PMC
September 2017

Frequency of Pregnancy Related Cancer: A Population Based Linkage Study in Lombardy, Italy.

Int J Gynecol Cancer 2017 03;27(3):613-619

*Department of Obstetrics, Gynecology, and Neonatology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Cà Granda, Ospedale Maggiore Policlinico; †Department of Statistics and Quantitative Methods, Unit of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca; ‡Department of Epidemiology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri"; and §Fertility and Procreation Unit, Division of Gynaecologic Oncology, European Institute of Oncology, Milan, Italy.

Objectives: The aims of this study were to estimate the occurrence of pregnancy-associated cancer overall and by site, to evaluate if the risk increases over time, and to investigate some major determinants.

Methods: This is a population-based linkage study using the regional hospital discharge forms [Scheda di Dimissione Ospedaliera (SDO)] database of Lombardy, Italy, a region with 10 million inhabitants. All resident women with a SDO reporting a birth or abortion between 2001 and 2012 were identified. Pregnancy-associated cancers were defined as a cancer occurring during pregnancy or within 12 months after pregnancy and were identified by selecting all SDOs reporting a first diagnosis of cancer. Risk of developing a pregnancy-related cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. The effect of potential predictors on the risk was estimated using a logistic regression model, and odds ratios (OR) were estimated.

Results: During the period 2001-2012, the risk of pregnancy-related cancer was 122.9 per 100,000 pregnancies. The most common cancers were breast cancer (479 cases, 39.9/100,000 pregnancies), thyroid cancer (186 cases, 15.5/100,000), and lymphomas (157 cases, 13.1/100,000). Skin cancer accounted for 177 cases (14.8/100,000), half of which were melanomas. The risk of developing a pregnancy-related cancer increased significantly with age, from 60 of 100,000 for women less than 30 years old to 265 of 100,000 for women aged more than 40 years. Italian women had a higher risk than foreign ones (OR, 1.6), and the pregnancy outcome was more frequently an abortion (OR, 1.2), whereas no trend in risk was observed with calendar year (P = 0.249).

Conclusions: This study confirms previously reported incidence estimates but does not show increases over time.
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http://dx.doi.org/10.1097/IGC.0000000000000904DOI Listing
March 2017

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

ESMO Open 2016 29;1(5):e000097. Epub 2016 Sep 29.

Department of Breast Tumors , Cancer Institute "Ion Chiricuta" , Cluj-Napoca , Romania.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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http://dx.doi.org/10.1136/esmoopen-2016-000097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070299PMC
September 2016

Fertility-Sparing Options in Young Women with Cervical Cancer.

Curr Treat Options Oncol 2016 Jan;17(1)

European Institute of Oncology "IEO,", Via Giuseppe Ripamonti 435, 20141, Milan, Italy.

Opinion Statement: Cervical cancer (CC) is the fourth most frequent tumor and the fourth most common cause of cancer death among women worldwide. Furthermore, more than 40 % of women with early CC are affected during reproductive age and wish to remain fertile. Thus, many patients demand a more conservative policy for managing these lesions in order to have an uneventful pregnancy in the near future. For this reason, interest in fertility preservation strategies has been increasing, and the number of published studies on this topic has grown significantly. Conization was the first fertility-sparing surgical procedure tested in stage IA1 CC. However, in recent decades, other strategies have been tested, particularly for more advanced tumors. The aim of this review is to analyze the main techniques performed in patients with CC who are eligible for fertility-sparing surgery, with particular attention paid to open questions and controversies.
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http://dx.doi.org/10.1007/s11864-015-0386-9DOI Listing
January 2016

Hematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting.

J Clin Oncol 2016 Feb 30;34(5):501-8. Epub 2015 Nov 30.

Michael Lishner, Meir Medical Center, Kfar Saba, and Tel Aviv University; Irit Avivi, Ichilov Medical Center, Tel Aviv, Israel; Jane F. Apperley, Hammersmith Hospital; Susan Robinson, Guy's and St Thomas' National Health Service Foundation Trust, London; Frank Van den Heuvel, University of Oxford, Oxford, United Kingdom; Andrew M. Evens, Tufts Medical Center, Boston, MA; Monica Fumagalli, University of Milan; Fedro Alessandro Peccatori, European Institute of Oncology, Milan, Italy; Irena Nulman, University of Toronto, and The Hospital for Sick Children, Toronto, Ontario, Canada; Fuat S. Oduncu, University of Munich, Munich, Germany; Kristel Van Calsteren, University Hospital Gasthuisberg; Tineke Vandenbroucke and Frederic Amant, Katholieke Universiteit Leuven; Daan Dierickx, University of Leuven; and Tineke Vandenbroucke, University Hospitals Leuven, Leuven, Belgium.

Purpose: The incidence of hematologic malignancies during pregnancy is 0.02%. However, this figure is increasing, as women delay conception until a later age. Systemic symptoms attributed to the development of a hematologic cancer may overlap with physiologic changes of pregnancy. A favorable prognosis is contingent upon early diagnosis and treatment. Therefore, a high index of suspicion is required by health care providers. Although timely, accurate diagnosis followed by appropriate staging is essential and should not be delayed due to pregnancy, management guidelines are lacking due to insufficient evidence-based research. Consequently, treatment is delayed, posing significant risks to maternal and fetal health, and potential pregnancy termination. This report provides guidelines for clinical management of hematologic cancers during the perinatal period, which were developed by a multidisciplinary team including an experienced hematologist/oncologist, a high-risk obstetrics specialist, a neonatologist, and experienced nurses, social workers, and psychologists.

Methods: These guidelines were developed by experts in the field during the first International Consensus Meeting of Prenatal Hematologic Malignancies, which took place in Leuven, Belgium, on May 23, 2014.

Results And Conclusion: This consensus summary equips health care professionals with novel diagnostic and treatment methodologies that aim for optimal treatment of the mother, while protecting fetal and pediatric health.
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http://dx.doi.org/10.1200/JCO.2015.62.4445DOI Listing
February 2016

Medical treatment of early stage and rare histological variants of epithelial ovarian cancer.

Ecancermedicalscience 2015 22;9:584. Epub 2015 Oct 22.

Academic Division of Gynaecology and Obstetrics, Mauriziano Hospital, University of Turin, Italy.

Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient's performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients' quality of life.
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http://dx.doi.org/10.3332/ecancer.2015.584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631577PMC
November 2015

Attitudes on fertility issues in breast cancer patients: an Italian survey.

Gynecol Endocrinol 2015 Jun 18;31(6):458-64. Epub 2015 May 18.

Department of Gynaecology and Obstetrics, University of Turin , Turin , Italy .

Background: Fertility issues should be discussed with young women before the start of any anticancer treatment. The study is aimed to investigate the attitude on fertility among Italian oncologists and breast surgeons dealing with BCa, and to report the consensus achieved on specific statements.

Methods: One hundred and sixty-two panelists anonymously expressed an opinion through a web-based platform on 19 statements based on the Delphi method.

Results: Ninety-one percent of oncologists considered important to discuss with patients about fertility issues and 83% believed estrogens could stimulate the growth of hidden cancer cells in ER(+) tumors. Difficulties in accessing fertility preservation procedures were mainly due to patients' reluctance, but also to lack of coordination with the assisted reproduction specialists. No full consensus was reached on the prognostic role of pregnancy after BCa. Fifty-four percent of oncologists declared that pregnancy does not affect oncologic prognosis. Treatment with GnRHa during chemotherapy was considered the only mean for preserving ovarian function.

Conclusions: Fertility preservation in BCa patients is a well-accepted practice among Italian oncologists. A poor knowledge of this specific issue emerged from the survey, even if a certain degree of agreement was observed on most fertility-related issues.
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http://dx.doi.org/10.3109/09513590.2014.1003293DOI Listing
June 2015

Difficult choices for young patients with cancer: the supportive role of decisional counseling.

Support Care Cancer 2015 Dec 11;23(12):3555-62. Epub 2015 Apr 11.

Fertility and Procreation in Oncology Unit, European Institute of Oncology, via Ripamonti, 435, 20141, Milan, Italy.

Purpose: The aim of patient decisional support interventions is to promote shared decision making. Many of these interventions are comprehensive of information and guidance. In this pilot study, we evaluate the effects of a decision-making support (decision counseling (DeCo)) on decision making, decisional conflict, and anxiety in cancer patients facing with values-based decisions on fertility and procreation or genetic testing and risk reduction options in oncology.

Methods: DeCo was proposed during the medical consultation. The following questionnaires were administered to 54 patients before the DeCo session and 1 week after it: stage of decision making (SDM), decisional conflict scale (DCS) and subscales ("uncertainty," "informed," "clarity," "support," and "effective decision"), state-trait anxiety inventory. Decision Support Questionnaire and Usefulness of Decision Counseling were created ad hoc for this study. Multivariate logistic models and ANCOVA models were used to investigate the changes of SDM and DCS in association with DeCo.

Results: We found a significant improving in SDM with DeCo (P = 0.01) and a significant reduction in DCS with DeCo (P = 0.007) measured with the Decision Support Questionnaire. In particular, the DCS informed subscale showed a significant decrease in time (P = 0.002).

Conclusion: DeCo is useful to facilitate decision making and reduce decisional conflict. It plays a role in the perception of being informed while not directly providing clinical information. This model of decisional support intervention, in which information is provided only by the clinician and decisional support is focused on personal aspects that influence the decision, could improve shared decision making between patient and clinicians.
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http://dx.doi.org/10.1007/s00520-015-2726-5DOI Listing
December 2015

Risk of thrombosis in women with malignancies undergoing ovarian stimulation for fertility preservation.

Hum Reprod Update 2014 Nov-Dec;20(6):944-51. Epub 2014 Jul 10.

A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Background: Compared with the general population, cancer patients have a higher risk of venous thromboembolism as well as arterial thrombotic events such as stroke, myocardial infarction and peripheral arterial embolism. Therefore a possible concern for women with malignancies undergoing ovarian stimulation for fertility preservation is the increased risk of venous or arterial thrombosis.

Methods: In this article, we revised current available literature on the risk of thrombosis in patients with cancer and in women undergoing ovarian stimulation, with the ultimate aim of drawing some indications for preventive measures.

Results: Unfortunately, there are no specific data on the risk of thrombosis in women with cancer undergoing ovarian stimulation for fertility preservation. However, the literature suggests that the cancer type and stage, surgery, and chemotherapy all influence the risk of venous and, possibly, arterial thrombosis. Reports of cases of ovarian stimulation in women without malignancies have shown that venous thrombosis rarely occurs unless a pregnancy is achieved, while arterial thrombosis can occur in the absence of pregnancy but is usually only associated with ovarian hyperstimulation syndrome (OHSS). OHSS increases the risk of thrombotic events, but only the early form of the syndrome is relevant for women undergoing fertility preservation.

Conclusions: The available evidence on the risks of thrombosis for women undergoing ovarian stimulation for fertility preservation due to a malignancy is reassuring. However the avoidance of the early form of OHSS in women preserving oocytes/embryos due to malignancy is crucial. For these cycles, we advocate the use of a regimen of ovarian stimulation with gonadotrophin releasing hormone (GnRH) antagonists using GnRH agonists to trigger ovulation, an approach that has been shown to markedly reduce the risk of OHSS. Antithrombotic prophylaxis should be administered only to selected subgroups of women such as those with other risk factors or those who do develop early OHSS.
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http://dx.doi.org/10.1093/humupd/dmu035DOI Listing
May 2015
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