Variability In Treatment Modalities Research Articles

P06.04 Tertiary center experience in the treatment of intracranial germinoma

Abstract BACKGROUND Intracranial germinoma is a rare malignant neoplasm, accounting for approximately two-thirds of central nervous system germ cell tumors, which occurs in the suprasellar region, pineal gland, or basal nuclei in children and young adolescents. Due to the rare occurrence, there is relatively high variability in treatment modalities. This article aims to assess the symptoms, and treatment outcomes of radiotherapy and chemotherapy for intracranial germinoma, based on tertiary center experience. METHODS The study includes retrospectively gathered data from 35 consecutive patients treated for intracranial germinoma between 1999–2020 at a single institution. The statistical analysis used basic statistical tools and the Kaplan-Meier method. RESULTS The median age at diagnosis was 17 years (IQR 14–22), 85.7% of the patients were male. The majority of the patients had histopathological confirmation of the diagnosis (88.5%), 76% of which were non-secreting germinomas. The primary tumor was most frequently localized in the area of the pineal gland (34.3%), followed by bifocal (25.7%), suprasellar (17.1%), and basal germinoma (8.6%). The remaining patients had disseminated disease (14.3%). The most common symptoms at the onset of the disease were headache (54.3%), visual impairment (45.7%), vomiting (25.7%), polydipsia (22.9%), weight loss (17.1%), or minor neurological deficits (11.4%). As much as 54.3% of the patients presented with neuroendocrine disorders at diagnosis, and 42.9% of the patients presented radiological symptoms of hydrocephalus. Each patient received radiotherapy, which was preceded by chemotherapy in 77.1%, and surgery in 31.4% of the cases. The majority of the patients received radiotherapy to the ventricular system (51.4%), craniospinal irradiation (34.3%), or whole-brain radiotherapy (8.6%) followed by a focal boost in 88%. The remaining patient was treated with focal radiotherapy only. The 5- and 10-year overall survival rate was found to be 97% and 87% respectively, including two patients who died despite disease control (pulmonary and ventricular embolism). The 5-year progression-free survival was 83%. CONCLUSIONS Despite variability in treatment methods, there is a relatively high cure and survival rate in patients with intracranial germinoma. However, the rare occurrence of the disease seems to negatively impact the diagnostic process. The tumor is often diagnosed at an advanced stage, presenting significant, often irreversible symptoms.

20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions.

STUDY QUESTIONHow has the performance of the European regional register of the European IVF-monitoring Consortium (EIM)/European Society of Human Reproduction and Embryology (ESHRE) evolved from 1997 to 2016, as compared to the register of the Centres for Disease Control and Prevention (CDC) of the USA and the Australia and New Zealand Assisted Reproduction Database (ANZARD)?SUMMARY ANSWERIt was found that coherent and analogous changes are recorded in the three regional registers over time, with a different intensity and pace, that new technologies are taken up with considerable delay and that incidental complications and adverse events are only recorded sporadically.WHAT IS KNOWN ALREADYEuropean data on ART have been collected since 1997 by EIM. Data collection on ART in Europe is particularly difficult due to its fragmented political and legal landscape. In 1997, approximately 78.1% of all known institutions offering ART services in 23 European countries submitted data and in 2016 this number rose to 91.8% in 40 countries.STUDY DESIGN, SIZE, DURATIONWe compared the changes in European ART data as published in the EIM reports (2001–2020) with those of the USA, as published by CDC, and with those of Australia and New Zealand, as published by ANZARD.PARTICIPANTS/MATERIALS, SETTING, METHODSWe performed a retrospective analysis of the published EIM data sets spanning the 20 years observance period from 1997 to 2016, together with the published data sets of the USA as well as of Australia and New Zealand. By comparing the data sets in these three large registers, we analysed differences in the completeness of the recordings together with differences in the time intervals on the occurrence of important trends in each of them. Effects of suspected over- and under-reporting were also compared between the three registers. X2 log-rank analysis was used to assess differences in the data sets.MAIN RESULTS AND THE ROLE OF CHANCEDuring the period 1997–2016, the numbers of recorded ART treatments increased considerably (5.3-fold in Europe, 4.6-fold in the USA, 3.0-fold in Australia and New Zealand), while the number of registered treatment modalities rose from 3 to 7 in Europe, from 4 to 10 in the USA and from 5 to 8 in Australia and New Zealand, as published by EIM, CDC and ANZARD, respectively. The uptake of new treatment modalities over time has been very different in the three registers. There is a considerable degree of underreporting of the number of initiated treatment cycles in Europe. The relationship between IVF and ICSI and between fresh and thawing cycles evolved similarly in the three geographical areas. The freeze-all strategy is increasingly being adopted by all areas, but in Europe with much delay. Fewer cycles with the transfer of two or more embryos were reported in all three geographical areas. The delivery rate per embryo transfer in thawing cycles bypassed that in fresh cycles in the USA in 2012, in Australia and New Zealand in 2013, but not yet in Europe. As a result of these changing approaches, fewer multiple deliveries have been reported. Since 2012, the most documented adverse event of ART in all three registers has been premature birth (<37 weeks). Some adverse events, such as maternal death, ovarian hyperstimulation syndrome, haemorrhage and infections, were only recorded by EIM and ANZARD.LIMITATIONS, REASONS FOR CAUTIONThe methods of data collection and reporting were very different among European countries, but also among the three registers. The better the legal background on ART surveillance, the more complete are the data sets. Until the legal obligation to report is installed in all European countries together with an appropriate quality control of the submitted data the reported numbers and incidences should be interpreted with caution.WIDER IMPLICATIONS OF THE FINDINGSThe growing number of reported treatments in ART, the higher variability in treatment modalities and the rising contribution to the birth rates over the last 20 years point towards the increasing impact of ART. High levels of completeness in data reporting have been reached, but inconsistencies and inaccuracies still remain and need to be identified and quantified. The current trend towards a higher diversity in treatment modalities and the rising impact of cryostorage, resulting in improved safety during and after ART treatment, require changes in the organization of surveillance in ART. The present comparison must stimulate all stakeholders in ART to optimize surveillance and data quality assurance in ART.STUDY FUNDING/COMPETING INTEREST(S)This study has no external funding and all costs are covered by ESHRE. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

ART in Europe, 2015: results generated from European registries by ESHRE.

STUDY QUESTIONWhat are the European trends and developments in ART and IUI in 2015 as compared to previous years?SUMMARY ANSWERThe 19th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe, and this increase, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries all point towards the increasing impact of ART on European society.WHAT IS KNOWN ALREADYSince 1997, the ART data generated by national registries have been collected, analysed and reported in 18 manuscripts published in Human Reproduction.STUDY DESIGN, SIZE, DURATIONCollection of European data by the European IVF-Monitoring Consortium (EIM) for ESHRE. The data for treatments performed between 1 January and 31 December 2015 in 38 European countries were provided by national registries or on a voluntary basis by clinics or professional societies.PARTICIPANTS/MATERIALS, SETTINGS, METHODSFrom 1343 institutions in 38 countries offering ART services a total of 849 811 treatment cycles, involving 155 960 with IVF, 385676 with ICSI, 218098 with frozen embryo replacement (FER), 21 041 with preimplantation genetic testing (PGT), 64 477 with egg donation (ED), 265 with IVM and 4294 with FOR were recorded. European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1352 institutions offering IUI in 25 countries and 21 countries, respectively. A total of 139 050 treatments with IUI-H and 49 001 treatments with IUI-D were included.MAIN RESULTS AND THE ROLE OF CHANCEIn 18 countries (14 in 2014) with a population of approximately 286 million inhabitants, in which all institutions contributed to their respective national registers, a total of 409 771 treatment cycles were performed, corresponding to 1432 cycles per million inhabitants (range: 727–3068 per million). After IVF the clinical pregnancy rates (PRs) per aspiration and per transfer were slightly lower in 2015 as compared to 2014, at 28.5 and 34.6% versus 29.9 and 35.8%, respectively. After ICSI, the corresponding PR achieved per aspiration and per transfer in 2015 were also slightly lower than those achieved in 2014 (26.2 and 33.2% versus 28.4 and 35.0%, respectively). On the other hand, after FER with own embryos the PR per thawing continued to rise from 27.6% in 2014 to 29.2% in 2015. After ED a slightly lower PR per embryo transfer was achieved: 49.6% per fresh transfer (50.3% in 2014) and 43.4% for FOR (48.7% in 2014). The delivery rates (DRs) after IUI remained stable at 7.8% after IUI-H (8.5% in 2014) and at 12.0% after IUI-D (11.6% in 2014). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 37.7, 53.9, 7.9 and in 0.5% of all treatments, respectively (corresponding to 34.9, 54.5, 9.9 and in 0.7% in 2014). This evolution towards the transfer of fewer embryos in both IVF and ICSI resulted in a proportion of singleton, twin and triplet DR of 83.1, 16.5 and 0.4%, respectively (compared to 82.5, 17.0 and 0.5%, respectively, in 2014). Treatments with FER in 2015 resulted in twin and triplet DR of 12.3 and 0.3%, respectively (versus 12.4 and 0.3% in 2014). Twin and triplet delivery rates after IUI-H were 8.9 and 0.5%, respectively (in 2014: 9.5 and 0.3%), and 7.3 and 0.6% after IUI-D (in 2014: 7.7 and 0.3%).LIMITATIONS, REASONS FOR CAUTIONThe methods of data collection and reporting vary among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution.WIDER IMPLICATIONS OF THE FINDINGSThe 19th EIM report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART worldwide, detailed information about ongoing developments in the field is provided.STUDY FUNDING/COMPETING INTEREST(S)The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE).

What are the European trends and developments in ART and IUI in 2014 as compared to previous years? The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant.

Pegvisomant monotherapy is effective and safe in treatment of acromegaly. However, some clinicians combine pegvisomant with somatostatin analogues (SSA) or dopamine agonist (DA). In this analysis of ACROSTUDY, a long-term non-interventional study, the use of combination regimens was evaluated. Based on their baseline treatment, 2043 patients were retrospectively categorized as: long-acting SSA combined with pegvisomant, ‘Combo SSA’ 768 patients (38%); DA combined with pegvisomant, ‘Combo DA’ 123 (6%); pegvisomant monotherapy, ‘Peg mono’ 1128 (55%). Treatment patterns changed over the 10-year period, with recent patients more likely to receive any combination (20% in 2003 vs 54% in 2012). Combo SSA use varied widely among countries from 22% to 78%. Exposure periods of the three treatment modalities were defined from pegvisomant start until the last visit in ACROSTUDY; patients could switch treatment categories. At year 4, IGF-I was normal in 62% of Combo SSA, 63% of Combo DA and 65% of Peg mono groups. Pegvisomant was initiated as daily injections in 94% of patients in the Peg mono group, 66% of Combo SSA and 91% of Combo DA patients. During 6169 years of treatment exposure, 3424 adverse events (AEs) were reported in 946 (51%) patients, of which 617 (18%) were serious and 401 (12%) were considered treatment related. The reported incidence of serious AEs and treatment-related non-serious AEs were similar among the three treatment modalities. This analysis describes real-world clinical care and shows favorable efficacy and safety for Peg mono and combinations. Novel findings include an increased use of combination therapy over time and variability in treatment modalities between countries.

OR Practice—Modeling Potential Demand for Supply-Constrained Drugs: A New Hemophilia Drug at Bayer Biological Products

This paper describes the evolution and application of a novel approach for forecasting drug demand in markets where supply limitations have significantly curtailed sales volumes and thus reduced the usefulness of conventional sales-based forecasting methods. This occurs frequently with biological (biotech) drugs. We use methods from decision analysis to explicitly model the variability in epidemiological data together with the variability in treatment modalities to estimate latent therapeutic demand (LTD)—the underlying demand that captures how physicians would prescribe treatment and how patients would comply if ample supplies of drugs were available and affordable. Our approach evolved from efforts to help Bayer Biological Products with strategic decisions regarding its drug for treating hemophilia A, the future of which had been clouded for several years, primarily due to a lack of confidence in demand estimates. Use of the LTD model resulted in a better understanding of the therapeutic needs of the global hemophilia community and helped Bayer make good decisions. We believe this approach is widely applicable to forecasting potential demand for supply-constrained as well as brand-new drugs, and thus can be very useful in helping both drug manufacturers and health-care agencies worldwide to ensure adequate supplies of critical drugs.

Papillary Lesions of the Breast

Papillary lesions of the breast include a variety of benign, atypical, and malignant lesions whose hallmark is the formation of either papillary tufts composed only of epithelium, or true papillary structures with fibrovascular support and epithelium. The precise diagnosis has significance because of the variability in treatment modalities. This article attempts to describe the basic features seen in papillary-type lesions and their correlation with imaging studies.

Race and gender influences on the survival of patients with mouth cancer

Previous studies have shown that race and gender are important correlates of survival among patients with cancer of certain sites. Since race and gender influence the stage of disease at diagnosis and the choice of therapy it has been argued that survival differentials may not be real but instead, they represent secondary associations with clinical variables. Therefore, verification of the true prognostic effects of race and gender requires proper controlling for potential confounders, such as stage and treatment. We have studied the 15-year survival experience of a hospital-based cohort of 4527 patients diagnosed with cancer of the mouth over a 28-year period in Brazil. Race and gender were strong predictors of stage and treatment. The odds ratios for no treatment were 1.35 (95% confidence limits [CL]: 1.09, 1.66) for females and 1.63 (CL: 1.29, 2.06) for non-white patients even after adjustment by stage, presumably a key criterion to define treatment. Survival differentials were found for lip cancer, with respect to race, and for cancers of the gum, floor of mouth, and other oral subsites, with respect to gender. Non-whites experienced 2.1 times the risk of lip cancer recurrence (CL: 1.20, 3.61) and 2.3 times the risk of dying from it (CL: 1.29, 4.09) as compared to whites. However, controlling for stage and treatment modality variables by proportional hazards regression reduced the same risk ratios to 1.01 (CL: 0.57, 1.78) and 1.17 (CL: 0.65, 2.13), respectively. The survival advantage experienced by females (17% lower risk of recurrences and 29% lower risk of cancer deaths) regarding other oral sites was independent from the effect of clinical factors.