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Introduction/BackgroundIn this retrospective study, we investigated the ovarian function of 69 premenopausal patients with hormone-receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer receiving tamoxifen with a focus on the management and survival of patients with ovarian cyst formation.Methodology69 premenopausal women treated with tamoxifen for early primary HER2- negative breast cancer - referred to the gynaecology ultrasound department of the university hospitals of Leuven between 2003 and 2018 - were selected. Patients that received chemotherapy, adjuvant radiotherapy or ovarian suppression were excluded. Oncological data, gynaecological ultrasound reports, details on menstruation pattern during tamoxifen and hormonal blood tests were obtained from patient records.ResultsIn total, 31 patients developed a cyst during tamoxifen treatment. Median age at diagnosis of breast cancer was 47 years (37–53) and younger patients were more likely to develop ovarian cysts (p<0.002). Median interval between initiation of tamoxifen and detection of ovarian cysts was 10 months (1–59). Median size of ovarian cysts was 47 mm (30–96). Most patients (20/31) were followed conservatively, with spontaneous regression of the cysts. In 4/31 patients regression occurred after interruption of tamoxifen or additional ovarian suppression. Surgery was performed in 7/31 patients for large symptomatic cysts or torsion. Bleeding pattern changed in 55 out of 68 of the patients (one patient was excluded because of hysterectomy), most frequently oligomenorrhea or amenorrhea. 13/49 available records of the patients had high oestradiol levels (>400 pg/ml) while treated with tamoxifen. Survival of all patients was excellent; with a median follow-up of 73 months no events occurred.ConclusionWe reported that the administration of tamoxifen in premenopausal women is associated with ovarian cyst formation and high estradiol levels. Ovarian cysts mostly can be managed conservatively. In this series, the impact of tamoxifen on ovarian function does not appear to affect survival.DisclosureNothing to disclose.

Introduction/Background*Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases.MethodologyUsing a large data set of 88,294 NIPT performed in our University Hospital Leuven, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumour biopsy.Result(s)*Fifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, a novel multidisciplinary care path for efficient clinical management of these cases was presented.Conclusion*The here presented approach for analysing NIPT results has an unparalleled high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the novel care model that we presented here.These findings have now been accepted for publication in eClinicalMedicine (online journal of The Lancet group), showing the importance of these data.

Introduction/BackgroundThe purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management.MethodologyClinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis.ResultsThe median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy.In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations.Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers.ConclusionSurvival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important.DisclosureThis project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.Abstract P95 Figure 1Distribution of birth weight expressed in customised percentile for gestational age (n=117)Abstract P95 Figure 2Progression-free (A) and overall (B) survival of early stage HL during pregnancy

Introduction/BackgroundThe International Network of Cancer, Infertility and Pregnancy was launched in order to register women of reproductive age with a cancer diagnosis. Over the years, the project has expanded with currently 2653 cases registered by 114 centres and an annual registration rate of 150 patients. The expected rising numbers of cancer diagnosis during pregnancy as a result of an increased age at first childbirth and the possibility of early cancer detection by the non-invasive prenatal testing calls for an ongoing evaluation of clinical practice. Moreover, women might become pregnant while exposed to new target therapies that are being introduced into oncological practice.MethodologyThe INCIP database consists of a secured on-line registration tool. Oncological, obstetric and neonatal data are registered by members. Annual scientific meetings give updates on the ongoing research projects.ResultsMost patients were registered in Belgium, the Netherlands, Italy and USA and one third of participating centres are non-European. Currently 2059 patients with a cancer diagnosis or treatment during pregnancy are registered, 395 women that received fertility preservation and 199 patients with a postnatal cancer diagnosis (figure 1). Breast cancer, lymphoma and cervical cancer are the most frequent registered cancer types and the majority of patients (67%) received antenatal cancer treatment (figure 2). Most women delivered a live born baby (88%), however 47% delivered preterm and 80% of preterm deliveries were medically induced. One-fifth of neonates (21%) were small for gestational age. Congenital malformations were reported in 3% of live births.Abstract – Figure 1Registered cases by INCIPAbstract – Figure 2Management of cancer during pregnancy according to trimester of diagnosisConclusionCancer occurring in women endangers obstetrical and neonatal outcome and potentially future fertility. The INCIP registry is open for further collection of data since for such a relatively rare situation, only a large scale project will provide better insights on maternal and foetal risks assessment, which is essential for optimal patient counselling and care.DisclosureThe INCIP network would not be able to operate without the ongoing support of ESGO. Furthermore the project is supported by the Research Foundation—Flanders (FWO) in Belgium (grant no G070514N) and the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. There are no conflicting interests to declare.

Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the following indications: recent chemotherapy induced febrile neutropenia (5; 12%), dose dense chemotherapy (28, 67%), poly chemotherapy (7, 17%), or prevention of neutropenia at delivery (2; 5%). Among 24 women receiving dose dense chemotherapy, three (13%) patients recovered from asymptomatic neutropenia within 5 days. One patient developed pancytopenia following polychemotherapy after which the pregnancy was complicated by chorioamnionitis and intrauterine death. Nineteen singleton livebirths (49%) were born preterm. Sixteen neonates (41%) were admitted to the Neonatal Intensive care Unit (NICU). No neonatal neutropenia occurred. Two neonates had congenital malformations. Out of 21 children in follow-up, there were four children with a motor development delay and two premature infants had a delay in cognitive development. In conclusion, the rate of maternal and neonatal complications are similar to those described in (pregnant) women treated with chemotherapy. Due to small numbers and limited follow-up, rare or delayed effects among offspring exposed to G-CSF in utero cannot be ruled out yet.

The cleaning of daguerreotypes is a process that must remove tarnish layers and debris without altering the optical properties of the daguerreotype. This means that (1) the polished silver layer substrate must not be etched or pitted and (2) the image particles must not be altered or damaged. Electro cleaning is the only known method of cleaning gilded daguerreotypes; however, it is not suitable for the treatment of ungilded and coloured daguerreotypes. This article describes a new laser method for cleaning daguerreotypes. A model is developed for the cleaning process and testing procedures are discussed. This method permits (1) the cleaning of gilded and ungilded plates, (2) local treatment and (3) removal of tarnish without immersion in solvents and chemicals. /// Le nettoyage des daguerréotypes est un procédé qui doit permettre d'éliminer les couches ternies et les résidus sans altérer les propriétés optiques de l'œuvre. Ce qui signifie (1) que le substrat, constitué par une couche d'argent poli ne doit pas être gravé ni percé et (2) que les fragments d'image ne doivent pas être altérés ou endommagés. Le nettoyage electrolytique est la seule méthode connue pour nettoyer des daguerréotypes virés à l'or; néanmoins, elle n'est pas applicable pour ceux qui ne le sont pas dorés ou pour les plaques colorées. Cet article présente une nouvelle méthode de nettoyage au laser des daguerréotypes. On y présente un protocole pour le procédé de nettoyage, ainsi qu'une réflexion s.ur les procédures de test. Cette méthode permet (1) le nettoyage de plaque virées à l'or ou non, (2) un traitement ponctuel et (3) l'élimination de dégradations sans immersion dans des solvants ou des produits chimiques. /// Bei der Reinigung von Daguerrotypien müssen Verfärbungen und Ablagerungen entfernt werden ohne dabei die optischen Eigenschaften der Daguerrotypie zu beeinträchtigen. Das bedeutet, daß (1) die Silberschicht nicht angetastet werden darf und daß (2) die Bildpunkte nicht verändert oder gar beschädigt werden dürfen. Die elektrolytische Reinigung war bisher die einzig bekannte Methode zur Reinigung von vergoldeten Daguerrotypien. Dieses Verfahren ist jedoch ungeeignet für nicht vergoldete und farbige Daguerrotypien. Eine neuer Weg ist die Reinigung mit Hilfe der Lasertechnik. Die Autoren entwickeln ein Modell zur Beurteilung des Reinigungsvorganges und beschreiben die durchgeführten Tests. Die neue Methode gestattet (1) die Reinigung vergoldeter ebenso wie nicht vergoldeter Fotoplatten; ebenfalls möglich ist (2) die lokale Begrenzung einer Maßnahme und (3) die Beseitigung von Verfärbungen ohne Verwendung von Tauchbädern. /// La limpieza de daguerrotipos es un proceso que ha de eliminar capas de oxidación y suciedad sin alterar las propiedades ópticas del propio daguerrotipo. Esto significa que (1) la capa de plata subyacente pulimentada no ha de sufrir marcas ni daños de ningun tipo, y (2) las partículas de la imágen no han de ser alteradas o afectadas. La limpieza por medios eléctricos es el único método conocido de limpieza de daguerrotipos dorados; sin embargo, no es aplicable para el tratamiento de daguerrotipos coloreados o no-dorados. En este artículo se describe un nuevo método basado en el láser para la limpieza de estos objetos. Se desarrolla un modelo para los procesos de limpieza y se discuten procedimientos de prueba. Este método permite: (1) la limpieza de placas doradas y no-doradas, (2) el tratamiento local y (3) la eliminación del óxido sin inmersión en disolventes o productos químicos.