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Background and aim Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of trophoblastic tissue. Since GTD and its malignant sequel gestational trophoblastic neoplasia (GTN) are rare diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. Methods Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid trophoblastic tumours and follow-up. Results Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. Conclusions Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.

Febrile neutropenia (FN) is an inflammatory response causing fever that may develop during cancer therapy-induced neutropenia. FN may herald life-threatening infectious complications and should therefore be considered a medical emergency. Patients presenting with FN are routinely subjected to careful history taking and physical examination including X-rays and microbiological evaluations. Nevertheless, an infection is documented clinically in only 20–30% of cases, whereas a causative microbial pathogen is not identified in over 70% of FN cases. The oral cavity is generally only visually inspected. Although it is recognized that ulcerative oral mucositis may be involved in the development of FN, the contribution of infections of the periodontium, the dentition, and salivary glands may be underestimated. These infections can be easily overlooked, as symptoms and signs of inflammation may be limited or absent during neutropenia. This narrative review is aimed to inform the clinician on the potential role of the oral cavity as a potential source in the development of FN. Areas for future research directed to advancing optimal management strategies are discussed.

Based on the principles of biomedical ethics, the authors conducted a survey focusing on the ethical aspects of, didactic benefits of and possible alternatives to live surgery events. This work provides an investigation of the ethics of live surgery events in an interdisciplinary and multicentre setting. Critical ethical concerns regarding the justification of such events are highlighted through evaluation of attendees and surgeons.

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.

Introduction/Background Clear cell carcinoma (CCC) is a rare subtype of ovarian and endometrial cancer. It carries a poor prognosis and response to chemotherapy in recurrent disease is low. As angiogenesis pathways are activated in CCC, we performed a trial comparing nintedanib (BIBF1120), an orally available, triple kinase inhibitor targeting VEGFR, PDGFR and FGFR with physician’s choice of chemotherapy. As the first randomised trial in relapsed CCC, it gives important information on the efficacy and toxicity of both nintedanib and chemotherapy. Here we report the ovarian cancer (OC) results. Methodology This was an international, multi-centre, randomised, open label phase II, 3 outcome design. Patients were randomised to nintedanib 200 mg PO twice daily or chemotherapy (paclitaxel (80 mg/m2 IV Day 1,8,15), pegylated liposomal doxorubicin (40 mg/m2 IV) or topotecan (4 mg/m2 IV Day 1,8,15) every 28 days). Treatment was given until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS) in the ovarian cohort. Secondary objectives included overall survival (OS), response rate (RR), disease control rate (DCR) and patient reported outcomes. With 90 OC patients, the study was powered to detect an improvement in median PFS from 3 to 5 months (HR=0.6) with >90% power, 20% 1-sided significance. A statistically significant PFS difference at the 1-sided 10% level (Nintedanib superior) would give a clear signal that a phase III study is warranted. A statistically significant result at the 1-sided 20% level would require other supportive evidence. EudraCT Ref:2013-002109-73. ISRCTN No:ISRCTN50772895. Results 91 OC patients were included in the analysis. Median age was 54 years. Median number of previous lines was 2. After a median follow up of 20.7 months the median PFS was 2.3 months with nintedanib and 1.9 months with chemotherapy (hazard ratio=0.79, 80% CI=(0.58,1.06), p(1-sided)=0.1521. Median OS was 9.0 and 4.9 months, respectively. Difference in OS estimates at 6 and 12 months were 19.7% and 8.9% demonstrating non-proportional hazards. RR was 2.1% and 0%, and DCR at 16 weeks was 23.4% and 9.1% (odds ratio=5.81, 80%CI=(1.79,18.89), p(1-sided)=0.0276) with nintedanib and chemotherapy, respectively. Conclusion The study failed to demonstrate sufficient activity of nintedanib as a monotherapy to support a phase III trial. However, the benefit in PFS, DCR and OS suggests it may be interesting to combine nintedanib with other agents in OCCC. Chemotherapy is ineffective and the outcomes for women with OCCC are extremely poor confirming the need for continued research into novel targets and therapies. Translational research is on-going (figures 1 and 2). Disclosures The study was funded by an educational grant from Boehringer Ingelheim and supported by Cancer Research UK Grant ref: C8361/A15600. Author disclosures Rosalind Glasspool: Grant funding for clinical trials from Boehringer Ingelheim, Lilly/Ignyta and Clovis. Consultancy fees, travel support and/or speaker fees for AstraZeneca, GSK/Tesaro, Clovis, Immunogen and Sotio. Site PI for studies sponsored by AstraZeneca, GSK/Tesaro, Clovis, Immunogen, Lilly and Pfizer. Samantha Hinsley: none. Jonathan Ledermann: Advisory Board and Lecture fees from AstraZeneca, Pfizer, Clovis Oncology, MSD/Merck, Eisai, Artios Pharma, GSK and grant funding from AstraZeneca and MSD/Merck. IDMC fees from Regeneron. Iain McNeish: Advisory Board fees from AstraZeneca, Clovis Oncology, Tesaro/GSK, Roche, Scancell and Carrick Therapeutics. Institutional grant funding from AstraZeneca. Jerome Alexandre: Grant funding from Janssen, MSD. Consultancy fees, travel support and/or speaker fees for AstraZeneca, GSK/Tesaro, MSD, Eisai, Novartis, Pharmamar. Site PI for studies sponsored by AstraZeneca, GSK/Tesaro, MSD, Agenus, Merck Serono, Seattle Genetics Anneke Westermann: none. Claire Lawless: none Nelleke Ottevanger: none Mansoor Raza Mirza: Personal Financial Interests: AstraZeneca, Biocad, Clovis Oncology, Geneos, Genmab, Karyopharm Therapeutics, merck, msd, Oncology Centre, Pfizer, Roche, SeatleGenetics, Sera Prognostics, Sotio, Tesaro-GSK, ZaiLab. Institutional financial interests (study grants): AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Pfizer, Tesaro-GSK Isabelle Ray-Coquard: 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.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

Adult hepatoblastoma (AHB) is a rare liver tumor with a poor prognosis in adolescents and adults. This contrasts with hepatoblastoma in children and is not fully understood. Here we describe two adolescents with AHB who were treated in our hospital. Adolescents are likely to receive less intensive chemotherapy protocols and are treated in hospitals with less experience in pediatric oncology, resulting in poor outcome. More research is necessary for optimal treatment of AHB in adolescents. Adolescents with AHB should be referred to hospitals experienced in pediatric oncology and receive intensive chemotherapy, followed by hemihepatectomy.

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.

Contains fulltext : 229154.pdf (Publisher’s version ) (Closed access) Cisplatin is the first choice treatment in mediastinal germ cell tumors. However, concerns regarding increased toxicity of cisplatin hamper its administration in patients with impaired renal function. We describe a 42-year-old man with chronic kidney disease stage 4 who was diagnosed with a mediastinal germ cell tumor and metastases in lung and brain. Treatment with cisplatin-etoposide was considered essential for a chance of cure. In order to administer the full cisplatin dose, 4-hour hemodialysis sessions were performed after each cisplatin infusion. During treatment cycle 3, 4 and 5, total and unbound plasma platinum concentrations were measured. Trough concentrations and half-life were at the higher end of the range of those observed in patients with adequate renal function who received the same dose of cisplatin. Hemodialysis aided platinum clearance, although our patient was also able to clear some platinum by his own renal function. With this full dose treatment, our patient obtained a favorable tumor response, with a strong decrease of beta-human chorionic gonadotropin and tumor size. The side effects experienced by our patient were serious, although not worse than what could be expected with this type of treatment. His renal function remained stable during the treatment period.

5519 Background: Lower responses to chemotherapy and the unique molecular profile of LGSO led to the adoption of MEK-inhibitors for this disease. Updated analysis from the MILO/ENGOT-ov11 phase III study of binimetinib vs PCC in recurrent LGSOC showed response rate of 24% in those treated with binimetinib (JCO, 2020; NCT01849874). Here we present results of the post-hoc tumor tissue biomarker analysis performed with MILO/ENGOT-ov11. Methods: Mutational/copy number analysis was performed via Foundation Medicine on archival tissue obtained prior to randomization. Unbiased univariate analysis was used to test association between mutation status and outcomes in binimetinib and PCC treated patients. Outcomes examined were progression free survival (PFS), binary response by local RECIST 1.1 (complete or partial response [CR/PR] vs. stable [SD] or progressive disease [PD]), and ordinal response. Kaplan-Meier was used to estimate PFS. Cox regression, binary logistic regression, and ordinal logistic regression were used to examine relationship between mutation status and outcomes. Results: MILO/ENGOT-OV11 enrolled 341 patients from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or PCC. Based on January 1, 2020 data cut-off the data is as-is, amongst those patients treated with binimetinib with molecular results available, PFS data is available for 144 and response rate (RR) data for 135. There were 47 mutations detected in ≥5% of patients, most commonly KRAS (33%). Patients harboring a KRAS mutation had 3.4 times the odds of responding to treatment with binimetinib as patients without KRAS mutation (95% CI 1.57,7.67; p-value 0.002). There was no difference in effect of KRAS G12V mutation vs other KRAS mutation on PFS (PFS HR 1.06; 95% CI:0.53, 2.12; p value 0.9). In the 135 patients with binimetinib RR data, other MAPK mutations were identified as follows; NRAS in 11(8.1%), BRAFV600E in 8(5.9%), RAF1 in 2 (1.5%), NF1 in 7 (5.2%). In patients with MAPK mutation (as defined above) the RR was 41% vs 13% in those without MAPK mutation. PFS was significantly better in patients treated with binimetinib harboring MAPK mutation vs those without (HR 0.5; 95% CI 0.31, 0.79; p = 0.003). In patients treated with PCC there was a nonsignificant trend towards improved PFS in those with MAPK mutation vs those without (HR 0.82; 95% CI 0.43,1.59; p = 0.6). A test for interaction between treatment and MAPK pathway was not significant by Cox regression model (p = 0.32). Conclusions: While this hypothesis generating analysis is limited by multiple testing, higher response rates and longer PFS were seen in those patients with LGSOC treated with binimetinib who harbored MAPK mutations, most commonly in KRAS. Somatic tumor testing should be routinely performed in patients with recurrent LGSOC to aid in clinical decision making. Clinical trial information: NCT01849874.

Introduction. Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. Patients and Methods. From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. Results. Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993–1998 to 12.8% in 2009–2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. Discussion. Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment.

Autosomal-dominant hypertension and brachydactyly syndrome (HTNB; Bilginturan syndrome) is known to cause stroke before age 50 when untreated. We report a novel PDE3A gene mutation in a mother and daughter affected with dominant brachydactyly of the hands and feet, a short stature, and hypertension. The hypertension was medically responsive to anti-hypertensive treatment. The 3-bp deletion in the PDE3A gene presented de novo in the mother. Here, we expand the list of PDE3A mutations identified in Bilginturan syndrome and emphasize the importance of standardized genetic testing of HTNB patients to improve diagnostics at an early age. We recommend extended phenotyping in patients with brachydactyly, a short stature or hypertension in clinical practice.

ObjectivesThe Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management.MethodsPublished articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made.ResultsThe approach to management of uterine and ovarian leiomyosarcoma management is reviewed.ConclusionsUterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management.

High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth.Disease is usually advanced with approximately 70% of the patients staged III to IV according to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingo-oophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings.

Endometrial stromal sarcoma (ESS) accounts for approximately 20% of all uterine sarcomas and presents, at a mean age, around 50 years of age. Half of the patients are premenopausal. ESS often manifests as an endometrial polyp and 60% of cases present with FIGO stage I disease. The natural history is one of slow growing indolent disease. Typical microscopic findings include a uniform population of endometrial stromal-type cells invading the myometrium and myometrial vessels. Imaging studies cannot reliably diagnose ESS preoperatively, so surgical resection for a presumed fibroid is a common scenario. Hysterectomy is the cornerstone of treatment for localized ESS, but morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome. Leaving the ovaries in situ does not worsen survival and this is of importance especially for young women. The data support the current practice to administer adjuvant hormonal treatment, although several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Repeat surgery for recurrent disease that is indolent and hormone sensitive appears to be an acceptable approach. Systemic treatment for recurrent disease is mainly hormonal.

SummaryEvent-related potentials (ERP) are regarded as age dependent. However, it is not known whether this is an intrinsic property of ERP or an extrinsic factor. We designed a setting in which ERP were evoked using a modified oddball paradigm with highly differentiable and detectable target and non-target stimuli. A total of 98 probands were enrolled in this study. We evaluated the latency and amplitude of the P3 component of visually evoked ERP. The mean P3 latency was 294 ± 28 ms and was not related to age (r = –0.089; p = 0.382; Spearman-rank-correlation). The P3 amplitude was related to age in the total sample (r = –0.323; p = 0.001; Spearmanrank-correlation) but not in the probands under the age of 60 years. There were no significant differences regarding sex. Our findings suggest that ERP are not age dependent if highly differentiable and detectable stimuli are used. This should be considered when normal values of ERP are created for clinical use.

Background Combined radiotherapy and hyperthermia is a well-established alternative to chemoradiotherapy for advanced stage cervical cancer patients with a contraindication for chemotherapy. Pre-clinical evidence suggests that the radiosensitizing effect of hyperthermia decreases substantially for time intervals between radiotherapy and hyperthermia as short as 1–2 h, but clinical evidence is limited. The purpose of this study is to determine the effect of the time interval between external beam radiotherapy (EBRT) and same-day hyperthermia on in-field recurrence rate, overall survival and late toxicity in women with advanced stage cervical cancer. Methods Patients with advanced stage cervical cancer who underwent a full-course of curative daily EBRT and (4–5) weekly hyperthermia sessions between 1999 and 2014 were included for retrospective analysis. The mean time interval between EBRT fractions and same-day hyperthermia was calculated for each patient; the median thereof was used to divide the cohort in a ‘short’ and ‘long’ time-interval group. Kaplan-Meier analysis and stepwise Cox regression were used to compare the in-field recurrence and overall survival. Finally, high-grade (≥3) late toxicity was compared across time-interval groups. DNA repair suppression is an important hyperthermia mechanism, DNA damage repair kinetics were therefore studied in patient biopsies to support clinical findings. Results Included were 58 patients. The 3-year in field recurrence rate was 18% and 53% in the short (≤79.2 min) and long (>79.2 min) time-interval group, respectively (p = 0.021); the 5-year overall survival was 52% and 17% respectively (p = 0.015). Differences between time-interval groups remained significant for both in-field recurrence (HR = 7.7, p = 0.007) and overall survival (HR = 2.3, p = 0.012) in multivariable Cox regression. No difference in toxicity was observed (p = 1.00), with only 6 and 5 events in the short and long group, respectively. The majority of DNA damage was repaired within 2 h, potentially explaining a reduced effectiveness of hyperthermia for long time intervals. Conclusions A short time interval between EBRT and hyperthermia is associated with a lower risk of in-field recurrence and a better overall survival. There was no evidence for difference in late toxicity.

Background: In anthracycline-pretreated metastatic breast cancer (MBC) patients, it is unknown whether weekly single-agent docetaxel is preferable to 3-weekly docetaxel regarding its toxicity and efficacy profile.Patients and methods: In this multicenter, randomised, open-label phase III trial, 162 patients were randomised to weekly docetaxel (group A) or 3-weekly docetaxel (group B). The primary end-point was tolerability; secondary end-points were efficacy and quality of life (QoL).Results: Group A (weekly docetaxel, n = 79) experienced less haematological toxicity, with just 1.3% versus 16.9% febrile neutropenia in group B (3-weekly docetaxel, n = 77) (p = 0.001). Not this difference, but fatigue and general malaise foremost led to more patient withdrawals in group A (24 versus 12 patients, p = 0.032), less patients completing treatment (29 versus 43 patients, p = 0.014) and reduced dose-intensity (15.6 versus 26 mg/m(2)/week, 58% versus 70% of projected dose, p = 0.017). As a result, 3-weekly docetaxel was related to better overall survival in multivariate analysis (hazard ratio 0.70, p = 0.036), although in univariate analysis efficacy was similar in both groups. Reported QoL was similar in both groups, but less effective treatment with more general toxicity led to less completed QoL forms in group A (65.4% versus 50%, p = 0.049).Conclusion: Weekly docetaxel is less well tolerated than a 3-weekly schedule, due to more non-haematological toxicity, despite less febrile neutropenia. Also, no efficacy benefits can be demonstrated for weekly docetaxel, which may even be inferior based on multivariate analysis. Therefore, a 3-weekly schedule should be preferred in the setting of MBC. (C) 2011 Elsevier Ltd. All rights reserved.

International audience; In this study, we describe the incidence, treatment, and outcome of breast cancer (BC) during the period 1994-2003 in the South-American country of Surinam and compare these with those of BC in the Netherlands. Pathology reports and hospital charts from all BC cases diagnosed between 1994 and 2004 were retrieved from Surinam's single pathology laboratory and its five hospitals. Data on demographics, tumor characteristics, treatment, and follow-up were gathered. We compared our data to BC statistics of first generation immigrants from Surinam to the Netherlands. 421 patients were diagnosed with BC during the study period. The age-adjusted incidence rate was 26 per 100,000 compared to 65/100,000 in first generation Surinamese women in the Netherlands. The majority had a fairly advanced stage at presentation, with 60% of tumors larger than 2 cm, and 41.6% with lymph node involvement. Because of the absence of radiotherapy facilities, local treatment in most patients was radical mastectomy. Adjuvant hormonal therapy (51.6%) was administered more frequently than adjuvant chemotherapy (20.3%). A significant number of patients were lost to follow-up, resulting in a median follow-up duration of only 23 months. The 5-year overall survival was 79%. BC incidence in Surinam is low compared to that in the western world, but the advanced stage at diagnosis, the low utilization of systemic adjuvant therapy, and the inadequate follow-up may lead to poor outcomes. A number of steps are underway to improve the level of cancer care in Surinam.

Background. Because gestational trophoblastic disease (GTD) is highly sensitive to chemotherapy, life-threatening hemorrhage from metastases can occur especially early after starting therapy. Cases. Two cases of post-term choriocarcinoma with liver metastases complicated by profuse life-threatening hemorrhage are reported. Emergency treatment with transcatheter angiographic embolization of the hepatic artery was performed to control bleeding. Discussion. Although embolization of the iliac vessels for gynecologic malignancies, including GTD, have been described, this is the first time that embolization of the hepatic artery to control bleeding from liver metastases in GTD is reported. The use and indications for embolization are expanding, and also in acute hemorrhagic complications in GTD, this intervention should be considered. (c) 2005 Elsevier Inc. All rights reserved

BACKGROUND. Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma. METHODS. Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and brachytherapy were administered for a biologically effective dose ! 86.7 gray. At least 4 courses of weekly cisplatin (40 mg/m 2 ) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy. RESULTS. Sixty-eight patients with a median age of 45 years were enrolled. Fulldose radiotherapy was delivered to all patients according to plan. At least 4 courses of chemotherapy were received by 97% of patients, and at least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to that described for chemoradiotherapy alone, and the median total treatment time was 45 days. Complete remission was achieved by 61 patients (90%). After a median follow-up of 538 days, 74% of patients remained alive without signs of recurrence, and the overall survival rate was 84%. CONCLUSIONS. The combination of full-dose radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a multicenter international setting among patients with advanced cervical carcinoma. A Phase III study comparing this novel triplet with standard chemoradiation, designed to show at least a 15% improvement in overall survival, has been launched. Cancer 2005;104:763‐70. © 2005 American Cancer Society.

Objective. Hyperthermia enhances carboplatin cytotoxicity preclinically, and clinical studies have shown radiant heat Whole Body Hyperthermia (WBH) to be safe. In this study, the efficacy and toxicity of the combination of 41.8degreesC WBH and carboplatin in recurrent and/or metastatic cervical cancer were explored. Methods. Recurrent and/or metastatic cervical cancer patients were treated with 41.8degreesC WBH and concurrent carboplatin, cycled every 28 days (max. 6 cycles). Results. Twenty-one of 25 participants were evaluable for response: one complete remission, six partial responses, stable disease in nine patients and progression in five, leading to a response rate of 33%. Three of four evaluable chemotherapy pre-treated patients progressed, while this was seen in only 2 of 17 chemotberapy-naive patients. The median survival is 7.8 months (range 1.3 to 43+) and no patients were lost to follow up. Grades 3/4 toxicities were common: leukopenia in 35%, thrombopenia in 61% and anemia in 22% of all treatments. Excessive, partly reversible renal toxicity was seen in two patients (grades 3 and 4). Conclusion. The efficacy of WBH and carboplatin in recurrent and/or metastatic cervical cancer seems comparable to that of other palliative chemotherapy regimens in this disease. The considerable toxicity, though largely manageable, includes unexpected and severe unacceptable renal toxicity. This regimen seems less suitable for palliative care. (C) 2004 Elsevier Inc. All rights reserved

Although complete debulking surgery for epithelial ovarian cancer (EOC) is more often achieved with interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT), randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS). We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1998 and 2010 in three Dutch referral gynaecological oncology centres were included. The prognostic value of residual disease after surgery for disease specific survival was assessed using Cox-regression analyses. In total, 462 patients underwent NACT-IDS and 227 PDS. Macroscopic residual disease after debulking surgery was an independent prognostic factor for survival in both treatment modalities. Yet, residual tumour less than one centimetre at IDS was associated with a survival benefit of five months compared to leaving residual tumour more than one centimetre, whereas this benefit was not seen after PDS. Leaving residual tumour at IDS is a poor prognostic sign as it is after PDS. The specific prognostic value of residual tumour seems to depend on the clinical setting, as minimal instead of gross residual tumour is associated with improved survival after IDS, but not after PDS.

Objective. The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy.Methods. Between 1970 and 2007, 292 patients received adjuvant radiotherapy after a radical hysterectomy with pelvic lymphadenectomy for early stage cervical carcinoma. All patients received pelvic radiotherapy (40 Gy-46 Gy in 1.8 Gy-2 Gy/fraction). Vaginal vault brachytherapy boost (10-14 Gy) was increasingly used for patients with high-risk factors, and since 1993 systematically applied in patients with at least 2 of the 3 risk factors: adenocarcinoma, nodal involvement and parametrial invasion. Cisplatin-based chemotherapy was introduced in this group of patients from 2000.Results. The 5-year cumulative risk of local recurrence (CRLR) was 13% (95%CI 9%-17%), resulting in an overall 5-year survival (OS) of 78% (95%CI 83%-73%). Since 1970, the OR for the 5-year locoregional recurrence risk (LRR) decreased from 2.5 to 1.15 (linear-OR = -0.02/year). The OR for the 5-year mortality risk reduced from 2.2 in 1970 to 1.0 in 2007 (linear-OR = -0.03/year). The largest risk reductions were observed before 1990 with a minor rise after 2002. The risk of severe late toxicity reduced from 1.8% to 1.5% (linear-OR = -0.03/year). The addition of concomitant adjuvant chemotherapy since 2000 may have benefited a subgroup of patients with squamous cell carcinoma, but not the patients with adenocarcinoma, and after introduction of chemotherapy the risk of severe late toxicity tripled from 2% to 7%.Conclusion. Since 1970, tumour recurrence risk and mortality have decreased, as radiation dose increased. The potential benefit of concomitant adjuvant chemotherapy could not be demonstrated in this nonrandomized study. (C) 2014 Elsevier Inc. All rights reserved.

Purpose: Bioactive lipids have been causally linked to intraabdominal malignancies such as ovarian cancer. In advanced tumors confined to the peritoneal cavity, inhibition of lipid growth factors present in ascites might induce tumor remissions. The systemic toxicity of the growth factor inhibitor suramin has so far hampered its use in standard oncologic practice, but this could be alleviated by intraperitoneal administration. In this study the feasibility, toxicity and pharmacokinetics of intraperitoneal suramin administration are described. Methods: Patients with histologically verified cancer confined to the abdominal cavity, for which no effective therapy was available, were treated with intraperitoneal suramin through a Tenckhoff catheter. Patients with ascites were treated with low-volume continuous i.p. infusions of 500 mg/24 h, and patients without ascites were treated with intermittent large-volume i.p. infusions of 1000 mg three times a week. Regular pharmacokinetic sampling of plasma and ascites fluid was carried out. Patients were treated for 6 weeks or until development of progressive disease or until plasma suramin levels exceeded 250 mg/l. Results: Nine patients were treated in ten periods, three with intermittent i.p. suramin, and seven with continuous i.p. suramin, for a median of 28.5 days (16–42 days), with a median suramin dose of 12 g (range 9–21 g ). Treatment was discontinued because of high systemic suramin levels in three patients (all in the intermittent schedule), progressive disease (five patients) or completion of planned treatment (one patient). Toxicity was mild, without any of the systemic side effects commonly associated with suramin. Intraperitoneal suramin levels were consistently higher than plasma levels in all patients, but this effect was most marked in the continuous infusion schedule. Conclusions: Intraperitoneal suramin infusion in patients with advanced peritoneal cancers is feasible and well-tolerated. Continuous low volume i.p. infusion in patients with ascites confers the largest pharmacokinetic advantage.

Summary Background Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (SIP) are bioactive phospholipids with mitogenic and growth factor-like activities that act via specific cell-surface receptors present in many normal and transformed cell types. LPA has recently been implicated as a growth factor present in ascites of ovarian cancer patients. The presence of LPA-like activity and the hypothesis that levels of this bioactivity in effusions of ovarian cancer patients are higher than those in effusions of other cancer patients was studied. Materials and methods A neurite retraction bioassay in a neuroblastoma cell line previously developed for in vitro detection of LPA activity on cell lines was employed and bioactivity was expressed in virtual LPA-equivalent levels. LPA-equivalent levels were tested in effusions of 62 patients with a range of malignancies, including 13 ovarian cancer patients. Biochemical and clinical parameters were evaluated for correlations with LPA-equivalent levels. Results Average LPA-equivalent levels were 50.2 μm (range 5.4–200) for all patients, and 94.5 μm (range 15–200) for ovarian cancer patients (P = 0.004). There were no additional independent significant correlations between LPA-equivalent levels in effusions and a range of other biochemical and clinical characteristics. Conclusion These data suggest a role for LPA-like lipids in the peritoneal spread of ovarian cancer and possibly that of other predominantly intraperitoneal malignancies.

ObjectivePatients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT.MethodsAll consecutive chemotherapy-naive patients in 3 referral hospitals who were treated with chemotherapy for residual or recurrent GCT between 1968 and 2011 were included. Main outcome was the response according to Response Evaluation Criteria in Solid Tumor criteria. A literature search in MEDLINE through PubMed was performed, from inception to August 19, 2013.ResultsTwenty-seven patients with a GCT who received chemotherapy were identified. Eighteen patients were not evaluable because they had either no measurable disease, or no imaging was performed before and after chemotherapy. One of the 9 evaluable patients (11%) had a complete response, and 1 patient (11%) had a partial response, resulting in a response rate of 22% (95% confidence interval, 0%–49%). Seven patients (78%) had stable disease (range, 2–50 months), and none had progressive disease. Fifteen studies that assessed response rates to chemotherapy on measurable disease in a total of 224 patients showed a response rate of 50% (95% confidence interval, 44%–57%). Strict criteria of response, however, were not uniformly applied in the majority of these published series.ConclusionsIn the present study, we present only a moderate beneficial effect of chemotherapy in patients with irresectable GCT with measurable disease. Comparison with previous studies is hampered by a lack of standardized response evaluation in the majority of studies. Given the toxicity of platinum-based chemotherapy, administering this treatment should be a well-considered decision.

Background: Concomitant hyperthermia has been shown to improve response rate after cisplatin in recurrent cervical cancer in previously irradiated patients. It is unclear whether similar response rates can be obtained in patients with a recurrence after previous platinum-containing chemoradiation. Objective: This study aimed to evaluate the outcome of cisplatin-based chemotherapy with concurrent hyperthermia in patients with recurrent cervical cancer after radiotherapy and cisplatin. Methods: Patients with recurrent cervical cancer after cisplatin-based chemoradiation or neoadjuvant chemotherapy followed by surgery and radiotherapy who were treated with concurrent platinum-based chemotherapy and hyperthermia were eligible for this retrospective analysis. All patients received six or eight weekly platinum-based chemotherapy cycles in combination with six or eight weekly hyperthermia sessions. The time-to-event variables were estimated using Kaplan-Meier analysis. P-values less than 0.05 were considered significant. Results: All 38 evaluable patients were selected from the hyperthermia database in the Academic Medical Centre (Amsterdam) and the Erasmus Medical Centre (Rotterdam). Mean age at relapse was 45.7 years (range 27-74). Median time to recurrence after first-line treatment was 15 months. A total of 27 patients had a local and/or regional recurrence; 11 had disease beyond the pelvis. All planned courses of cisplatin chemotherapy and hyperthermia were administered in 17/38 patients. Median follow-up was 6.5 months. One patient died during treatment; response rate was 4/37 (14%), with one complete response. Overall survival was 23% at 12 months and 4% at 24 months. The incidence of grade 3-4 haematological complications did not exceed 10%. Conclusion: In this retrospective study, concurrent cisplatin and hyperthermia after first-line cisplatin-containing chemoradiation showed poor response and survival. We do not recommend this treatment for recurrence of locally advanced cervical cancer.

Item does not contain fulltext Primary intracranial germ-cell tumors are rare tumors primarily of adolescence, and literature on this disease in adults is scarce. The available evidence on intracranial germ-cell tumors is reviewed with a focus on adult patients whenever possible, and used to make suggestions for diagnosis and treatment. Diagnostic and treatment algorithms were developed to provide an evidence-based backbone to base treatment on in adult patients with a (suspected) primary intracranial germ-cell tumor.

PURPOSE To determine the feasibility and safety of multiple, closely timed courses of high-dose cyclophosphamide, thiotepa, and carboplatin (CTC) with peripheral-blood progenitor-cell transplantation (PBPCT). PATIENTS AND METHODS Forty-eight patients with advanced cancer were scheduled to undergo either two or three courses of CTC with PBPCT. All PBPCs were harvested before high-dose therapy began. Full-dose CTC courses incorporated cyclophosphamide (6,000 mg/m2), thiotepa (480 mg/m2), and carboplatin (1,600 mg/m2) divided over days -6, -5, -4, and -3. Tiny CTC courses (tCTC) contained 67% of the doses of each of these agents. Second or third courses of CTC or tCTC began on day 28. RESULTS A sufficient number of PBPC could be harvested from all but two patients. Thirty-five first full-dose courses of CTC were given, 28 second courses, and 10 third courses. Second courses could be given on time and at full dose in 80% of the patients, but there was one toxic death from venoocclusive disease (VOD). Only four of 12 patients scheduled to receive three courses of full-dose CTC could be treated at the time and dose planned. There were three toxic deaths: one of VOD, one of sepsis, and one of hemolytic uremic syndrome (HUS). Eight patients were scheduled to receive three courses of tCTC. Eight first, seven second, and six third courses were given. One of the third courses had to be delayed and one had to be reduced in dose. CONCLUSION A sufficient number of PBPCs for two or three transplantations can be harvested from most patients without much difficulty before high-dose therapy. Two full-dose CTC courses or three tCTC courses can be given safely and with acceptable toxicity at 5-week intervals. Organ toxicity rather than bone marrow toxicity has become dose-limiting for alkylating agents.

Contains fulltext : 118179.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cisplatin-based chemotherapy (etoposide 100mg/m(2) days 1-5, methotrexate 300mg/m(2) day 1, cyclophosphamide 600mg/m(2) day 1, actinomycin D 0.6mg/m(2) day 2 and cisplatin 60mg/m(2) day 4, EMACP) was compared to EMA/CO (etoposide 100mg/m(2) days 1-2, methotrexate 300mg/m(2) day 1 and actinomycin D 0.5mg i.v. bolus day 1 and 0.5mg/m(2) day 2, alternating with cyclophosphamide 600mg/m(2) day 8 and vincristine 1mg/m(2) day 8) for the treatment of high-risk gestational trophoblastic neoplasia (GTN). PATIENTS AND METHODS: In the Netherlands, 83 patients were treated with EMACP and 103 patients with EMA/CO. Outcome measures were remission rate, median number of courses to achieve normal human chorionic gonadotrophin (hCG) concentrations, toxicity, recurrent disease rate and disease specific survival. RESULTS: Remission rates were similar (EMACP 91.6%, EMA/CO 85.4%). The median number of courses of EMA/CO to reach hCG normalisation for single-agent resistant disease and primary high-risk disease was three and five courses, respectively, compared to 1.5 (p=0.001) and three (p

e17023Background: Standard treatment of locally advanced cervical carcinoma consists of concurrent radiotherapy (including brachytherapy) and chemotherapy (weekly cisplatin 40 mg/m2), or chemoradio...

TPS5603Background: Clear-cell carcinoma (CCC) is an uncommon histotype of ovarian and a rare histotype of endometrial cancer. Prognosis for recurrent disease is poor and response rates to standard ...

This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC

In this study, we report coexpression of proteinase-activated receptor (PAR)-1- and PAR-3-type thrombin receptors in primary cultures obtained from surgically resected specimens of renal cell carcinomas (RCCs). Receptor expression on RNA level was evaluated by using the RT-PCR technique. Results demonstrated the presence of mRNA encoding PAR-1 and PAR-3, but mRNA encoding PAR-4 could not be found in human RCC cells. The expression of PAR-1 and PAR-3 on protein level was investigated with confocal laser fluorescence and freeze-fracture electron microscopy. Both thrombin receptor types were localized on the cell membrane but were also found on intracellular compartments of RCC cells. On the outer cell membrane, clustering of PAR-1 and PAR-3 molecules was partly observed. This is the first study demonstrating presence of both PAR-1 and PAR-3 in human carcinoma cells.

Summary Background After high-dose chemotherapy with autologous stem-cell support long hospital stays in the aplastic phase are expensive, lead to increased risk of hospital infections and to increasing pressure on available hospital beds. We developed a home care regimen that allows patients to be at home for most of the aplastic period, without daily hospital visits. Patients and methods Between October 1995 and December 1997, transfer of supportive care to the home setting took place in three phases for patients undergoing high-dose chemotherapy with stem-cell transplant for malignant lym-phoma (one course of BEAM), breast cancer or germ-cell cancer (three courses of tCTC). In the inpatient cohort, the supportive care designed for at home use was administered in the hospital until neutrophile recovery to 0.5 x 109/l. In the second, outpatient cohort, patients were discharged the day after stem-cell reinfusion but the supportive care was delivered daily in hospital. The third, home care cohort, consisted of patients who were discharged the day after stemcell reinfusion, after which specialized home care professionals delivered all supportive care including transfusions and parenteral antibiotics at home, with once weekly check-up in hospital by the transplant physician. Results Forty-two patients were treated with 81 cycles of high-dose chemotherapy (11, 18 and 13 patients and 17, 40 and 24 courses in the inpatient, outpatient and home care cohorts respectively). Inpatients were hospitalized in the aplastic phase for a median of 14 days. Patients in the outpatient cohort were at home in the aplastic phase for a median of six days (with a median of six days in hospital), and in the home care cohort for a median of 10 days (with a median of 1.5 days in hospital). Unscheduled readmissions and hospital visits were frequent in the outpatient and home care cohorts, mostly due to fever, central indwelling catheter malfunctioning or chemotherapy-related toxicity. However, patients could usually be discharged again after observation and treatment. No infectious deaths or unexpected emergencies occurred in the outpatient or home care cohort. Neither was there any suggestion of an increased number of fevers, infections, or other complications. Conclusions At home management in the aplastic phase after high-dose chemotherapy and stemcell transplant by community-based professionals is feasible without signs of increased toxicity or infections.

e16547 Background: MA can compromise QoL in pts with OC. The safety and efficacy of catumaxomab in pts with MA due to EpCAM+ carcinomas where standard therapy was not available, not effective or no longer feasible was confirmed in a phase III trial comparing a 3-h intraperitoneal (i.p.) infusion with and without prednisolone premedication (Sehouli, ASCO 2012). Pts with OC who received subsequent CTX after treatment with catumaxomab (post-catumaxomab CTX) were analysed separately. Methods: OC pts in both treatment arms were pooled. The efficacy parameters time to next puncture (TTPu), puncture-free survival (PuFS) and OS were evaluated in relation to post-catumaxomab CTX. Results: 42/109 (39%) pts with MA due to OC received post-catumaxomab CTX, which included a platinum-containing regimen in 19 pts (17%). 21/109 (19%) received >1 post-catumaxomab CTX regimen. Pts with any post-catumaxomab CTX compared with those without CTX had significantly prolonged OS (median 273 vs 81 d, HR 0.24, p1 post-catumaxomab CTX compared with 1 post-catumaxomab CTX had significantly prolonged OS (480 vs 167 d, HR 0.20, p < 0.0001). The difference between the groups with 1 and >1 post-catumaxomab CTX in PuFS (153 vs 123 d, HR 0.64, p = 0.1804) and TTPu (153 vs 169 d, HR 1.52, p = 0.3600) was not significant. Pts who received platinum-containing post-catumaxomab CTX had significantly prolonged OS compared with those who received post-catumaxomab CTX without platinum (462 vs 169 d, HR 0.32, p = 0.0026). The difference between the groups with and without platinum in PuFS (153 vs 123 d, HR 0.76, p = 0.4448) and TTPu (153 vs 229 d, HR 1.68, p = 0.2373) was not significant. Conclusions: The data indicate that pts with MA due to OC who are able to receive CTX after catumaxomab treatment have significantly prolonged survival compared with pts who could not receive CTX. Further trials have been initiated to identify the best patient population to receive i.p. catumaxomab followed by subsequent CTX.

e13095^ Background: Malignant Ascites (MA) is associated with a poor prognosis and limited palliative treatment options. To demonstrate the value of a new treatment the assessment of quality of life (QoL) is of particular importance. Following the demonstration of catumaxomab’s potential to stabilize QoL and prolong the time to first deterioration of QoL, results from CASIMAS give evidence that the QoL of patients remains unaffected during catumaxomab treatment Methods: In a two-arm, open-label, multicentre phase II/III study 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts) QoL was measured using the EQ-5D visual analogue scale (EQ-VAS). The EQ-VAS reports the respondent’s self-rated health on a vertical scale where the endpoints are labelled “Best imaginable health state” (100) and “Worst imaginable health state” (0). This information is used as a quantitative measure of health outcome. Patients were asked to complete EQ-VAS during the treatment period (d 0, 3 and 10) and follow-up (d8, 28). Descriptive analyses were performed according to EQ-5D User Guide (Version 4.0). Additionally ascites related symptoms were measured with a disease specific FACIT patient questionnaire. Results: For the pooled population (catumaxomab plus prednisolone and catumaxomab alone) longitudinal analysis of the EQ-VAS showed no relevant changes in mean score during the treatment period of catumaxomab (d0: 51.5; d3: 50.9; d10: 51.0) and compared to screening (52.7). An increase in mean values was observed in the follow-up period (d8: 53.9, d28: 57.1). Descriptive comparison of both treatment groups revealed no major differences in QoL and ascites related symptoms during the treatment and follow-up period, indicating that prednisolone has no impact on patient`s self-rated health. Conclusions: This analysis shows that QoL as measured by EQ-VAS remains unaltered during the treatment with catumaxomab and improves after the treatment period. The improvement is plausible due to the prolonged-puncture-free survival and is consistent with previous observations of QoL changes during and after intraperitoneal treatment with catumaxomab.

Background: Premature infants need iron supplementation. Their enteral iron absorption varies, but to some degree it seems that they can adapt their absorption to their iron needs. Individualized iron supplementation is difficult, as most laboratory parameters have limitations. Hepcidin is a newly described peptide hormone, which regulates iron homeostasis. Aim: To evaluate whether serum hepcidin concentrations (Hep(S)) correlate with parameters of iron metabolism, erythropoiesis and urinary hepcidin concentrations (Hep(U)). Patients and Methods: 31 patients (23 - 32 weeks gestational age at birth) with clinical indication for blood transfusion. Prior to transfusion serum and urine were collected to determine hepcidine with ELISA. Furthermore, blood count and iron parameters were determined. Results: Hep(S) pre-transfusion was 52.4 (28.7-87.9) ng/ml, the two highest values (530 and 472.1 ng/ml) were measured in patients with suspected sepsis and candida infection, respectively. Log(Hep(S)) and Log (Hep(U)) correlated strongly (r=0.751, p< 0.0001). Log (Hep(S)) correlated with Log (Ferritin) (r=0.57, p=< 0.001), reticulocyte hemoglobin (r=0.569, p=< 0.001) and sTfR/logFerritin ratio (r=-0.48, p=< 0.01). Infants with lower hemoglobin concentrations (< 8g/dl vs. ≥8g/dl) and higher reticulocyte counts (≥100000/µl vs. < 100000/µl) had lower hepcidin concentrations: 29.47 (8,65-34,54) ng/ml vs 64.44 (45.98-118.07) ng/ml, p=< 0.05 and 45.47 (14.55-61.70) ng/ml vs 83.02 (50.50-217.43) ng/ml, p=< 0.01. Conclusion: This is the first report on hepcidin in premature infants. In this small group of sick premature infants factors other than iron status also had an impact on hepcidin concentration. Further evaluation on the use of urinary hepcidin for non-invasive monitoring in preterm infants appears justified.