bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between immunoglobulin dose and incidence of severe and serious infections in secondary immunodeficiencies.
Authors: Ehlers Hans-Ulrich , Otremba Burkhard Joerg , Plath Margarete , Slawik Hans R. , Innig Georg , Pfruender Dietmar 
Published: September 2018

e21686 Background: In an interim analysis of an ongoing multicenter observational study on the efficacy and safety of the polyvalent i.v. immunoglobulin product (IVIG) Privigen, we investigated a possible correlation between the two mostly used treatment regimens in Germany - 10 g or 20 g once a month - and the incidence of severe and serious infections in secondary immunodeficiencies (SID). Methods: All patients fulfilling the following criteria were included in this analysis: 1) SID; 2) observation period ≥120 d; 3) ≥6 Privigen infusions; 4) stable dosing, defined as identical doses from the 2nd up to the last administration (a differing loading or test dose at baseline was accepted); 5) a series of at least 4 consecutive dosing intervals each with a duration of at least 21 d and not more than 35 d (any time during the observation period); 6) no other IVIG indication than SID. The cut-off date was Dec. 19, 2016. Results: 835 patients (454 m, 381 f; average 68 years, 76 kg) in 112 centers fulfilled the above criteria. The most frequent underlying diseases were CLL (n = 422), myeloma (175) and NHL (182). The mean observation period was 20.5 mo; the median dosing interval was 28 d. Most patients had a stable Privigen dosing of either 10 g (n = 575; 69%) or 20 g (n = 192; 23%); 68 patients (8%) received other dosages. In order to reduce potential confounding effects of varying dosing intervals, only intervals ( = cycles) complying with the following "steady-state rules" were included in the analysis: 1) duration 21-35 d; 2) each of the 3 preceding intervals also 21-35 d long. 7,858 out of 15,687 treatment cycles (50%, all dosages) complied with these rules and were evaluated for severe and serious infections (acc. to FDA criteria). With the 10 g regimen, 34 severe or serious infections occurred in 5,306 evaluable treatment cycles, while with the 20 g regimen, it was only 2 in 1,851 (p = 0.003). This corresponds to rates of 8.3 vs. 1.4 severe/serious infections per 100 patient years (about half of them pneumonias). There was no increase of reported adverse reactions with the higher dose. Conclusions: With a monthly dose of only 10 g IVIG compared with 20 g, adult SID patients have a considerably higher risk of severe and serious infections.
The effect of clinical outcome on patient's perception of physician compassion: A randomized clinical trial (RCT).
Authors: Tanco Kimberson , Azhar Ahsan , Rhondali Wadih , Rodriguez-Nunez Alfredo , Liu Diane D , Wu Jimin , Baile Walter F. , Bruera Eduardo 
Published: September 2018

e21694 Background: We previously found in a RCT video study that patients perceived a physician delivering a more optimistic message as more compassionate and professional. The primary objective of this study was to determine if the clinical outcome modifies the patient’s perception of physician compassion. Methods: 128 patients were randomized to observe a standardized video depicting a physician discussing treatment information (more optimistic [MO] vs. less optimistic message [LO]) with a patient with advanced cancer followed by a vignette depicting the clinical outcome of the patient who continued to decline and now under hospice care. Both physicians displayed identical number of empathetic statements (5) and posture. Surveys were completed after the video and repeated after the vignette including the Physician Compassion Questionnaire (0 = best, 50 = worst). Actors and patients were blinded to the purpose of the study. Investigators were blinded to the video observed by the patient. Results: No significant difference was found in change in compassion scores between [p = 0.40] and within each group (MO vs. LO) after the vignette and video [mean difference(SD): MO 1.7(8.74) p = 0.47 vs LO 0.89(10.24) p = 0.12]. There was a significant decrease of impression of the physician within each group [mean difference(SD): MO -0.79(1.62) p < 0.0001 vs LO -1.17(1.91) p < 0.0001]. There was a significant decrease in total professionalism score within each group [mean difference(SD): MO -0.88(2.25) p = 0.0022 vs LO -0.76(2.22) p = 0.0094]. Overall patient preference decreased for the MO group for the physician being their own physician [mean difference(SD) -0.29(0.77) p = 0.0049] and to recommend the physician to their family [mean difference(SD) -0.29(0.71) p = 0.0009]. Conclusions: The perception of physician compassion was not affected by the actual outcome of the patient. However, the physician was considered less professional. Furthermore, there was also worse preference for the more optimistic physician as physician for self and family after the poor outcome (vignette). More research is necessary to understand the association of clinical outcome and patient perception of physician attributes. Clinical trial information: NCT02498899.
Evaluation of the nutritional status in children with acute lymphoblastic leukemia and its effect on the outcome of induction in a developing country.
Authors: Khalid Arifa ,   Syed Nasir Bukhari, Alia Ahmed, Mahwish Faizan, Safia Khan
Published: September 2018

e22004 Background: Acute Lymphoblastic Leukemia (ALL) is the most frequently occurring cancer among the children and adolescents. Cure rate is improved up to 90% with early diagnosis and better supportive care. Under nutrition among pediatric acute leukemia patients is more in developing countries 60% as compared to 10% in developed countries. The poor nutritional status is found to be associated with poor outcome. Therefore, optimum nutritional support can play a vital role in the outcome of induction. Methods: The population of research was newly diagnosed patients of ALL, reported from June 2016 to January 2017, in the Pediatric Hematology & Oncology Department of Children’s Hospital, Lahore. A sample of 151 patients of Acute Lymphoblastic Leukemia was analyzed prospectively. The study subjects were stratified into undernourished & well nourished based on the Z-score for weight for age.The data was collected irrespective of any discrimination based on demographic factors. and the following characters were recorded in both the groups: Mid treatment & end of treatment bone marrow response, culture proved infection, duration of hospital stay & outcome. Results: Among the 151 patients of ALL 80.1 % (n = 121) were Pre-B and 19.8% (n = 30) were Pre-T .Male to female ratio was 1.5:1. Malnutrition was established in 98 (64.9%) patients on the bases of Z-score. The undernourished group had significantly increased rate of culture proven sepsis (11% vs. 2%) respectively and required longer duration of hospital stay (p < 0.001).Rapid early response was observed in 21.8% malnourished and 32.8% well-nourished patients. End of treatment complete response was recorded in 63% vs. 69.1% respectively with significant p value. Expiry was observed in 9.1% malnourished patients. Conclusions: On the basis of this study it is concluded that the nutritional status at the initial presentation had a significant impact on the induction outcome. The undernourished patients of ALL are more prone to infections, requiring longer duration of hospital stay. Therefore, optimum nutritional support to such patients can help to decrease the chances of infections & ultimately improve the outcome.
Pediatric cancer registry Turkey: 2009-2016 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yesilipek Akif 
Published: September 2018

e22015 Background: Each year 300.000 new cancer cases are expected in children & adolescents aged 0-19 years at global level. Although the long term survival rates have been improved to 85% in high income countries it is lower than this LMICs. Pediatric registries are essential for planning, evaluation, comparison for pediatric cancer care. This study focuses to pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association established a WEB based cancer registry in Turkey in 2002. The registry information for 2002-2008 was presented earlier. This study, now, is including the distribution of pediatric cancer registry for the years of 2009-2016. International Childhood Classification System was used in classification. Basic demographic findings, ICD-O-3 morphology & topography codes were recorded for each cases. Results: During the 8 years from 2009 to 2016, 13123 pediatric cancer cases were recorded. For all cases, median age was 6.5 year (0–17; M/F 7356/5759, 3 hermaphrodite). Age distribution was 0–4 yrs, 41.3%; 5–9 yrs, 24.3%; 10–14 yrs , 23.2%; 15–19 yrs, 11.0%. 7 cases older than were registered (%0.1). The distribution of tumor types were [number of cases, percentage of total, median age years, M/F]: Leukemia (3751, 28.6%, 5.5, 2148/1603); Lymphoma and other RES tumors (2381, 18.1%, 9.5, 1613/763); CNS [brain & spinal] (1672, 12.7% , 7.13, 908/764); Symphatetic system (1053, 8.0% , 2.42, 550/503); Retinoblastoma (339, 2.6%, 1.33, 188/151); Renal (675, 5.1%, 3.33, 314/361); Liver (217, 1.7% , 1.75, 116/101); Malignant bone (892, 6.8 %, 12.55, 486/406); Soft tissue sarcomas (868, 6.6% , 7.21, 518/350); Germ cell (818, 6.2%, 7.58, 292/523); Carcinoma and other malignant epithelial (391, 3.0% , 13.60, 191/200); Other/non-specific malignant (66, 0.5%, 6.54, 32/34) tumors. Five year survival rate was found as 69.5 %. Conclusions: This registry since 2002 became a critical source for health care professionals in Turkey. Survival rates for children increased from 65% to 70% based on the latest information from this study. This is compatible with Turkey’s development level as an upper middle income country. This data also allows us to use the registry information at national and international studies.
Relationship between inhibin B, puberty, and secondary sex characteristics in childhood cancer survivors.
Authors: Unal Emel Cabi , Simsek Gulsum KADIOGLU , Tacyildiz Nurdan , Dincaslan Handan , Yavuz Gulsan , Siklar Zeynep , Berberoglu Merih 
Published: September 2018

e22018 Background: Prognosis in childhood cancer improved with intensive tx regimens, improved survival,concerns&issues related to QOL become crucial point of interest. Methods: Gonadal functions were studied in 33M,22F survivors of childhood cancers treated w gonadotoxic chemotherapy,with HL,NHL, ALL,Osteosarcoma,Rhabdomyosarcoma. All event-free survivors for > 1year, postpubertal, > 15 years of age at the time of study, 8 pts received abdominal RT,9 pts had prophylactic cranial RT. Patients answered a questionnaire concerning sexual functions,underwent a comprehensive physical examination, clinical evaluation of pubertal development, secondary sex characteristics,menstrual history, measurement of FSH, LH,sex steroids, inhibinB, compared w age-matched controls. Results: All patients had normal pubertal development for age,Females showed no significant differences in secondary sex characteristics, than controls &the progression of puberty, adult-type hair growth in males were significantly late (P:0.002) than controls, low levels of testosterone were found in all.Pubertal development normal in female patients, w elevated FSH than control.(P:0.025)FSH levels in males didn't differ,inhibinB levels were significantly lower than control.(P:0.022).We couldn't demonstrate significant association with age at dx,time elapsed after tx,dx type,gonadotoxic agent.. Conclusions: Our study showed tx of childhood cancer could lead to gonadal toxicity.Our study investigating relationship between puberty,secondary sex characteristics,inhibinB in early postpubertal stage. Findings suggest that, even in the presence of gonadal toxicity, in females, secondary sex characteristics&puberty weren't affected.Inhibin B as a marker for gonadal toxicity is not superior to FSH. In fact that, we found a decrease in InhibinB as the only marker of gonadal dysfunction in males.With normal pubertal development &FSH levels in postpubertal males,low detection of inhibinB can be used as an early,sensitive marker for gonadal toxicity.Late adult-type hair growth with low testosterone demonstrating chemotherapy-induced testicular damage. Clinical trial information: BAP-2734.
Cross sectional survey of male adolescent and young adult (AYA) childhood cancer survivors regarding fertility.
Authors: Harrison Douglas James , Welch Jennifer JG , Matook Katherine , Schwartz Cindy L. 
Published: September 2018

e22019 Background: 30% of male cancer patients receive gonadotoxic therapy that results in infertility. Research exploring male cancer survivors’ attitudes regarding risk of infertility has focused on adults. To understand how AYA survivors perceive their risk of fertility, a cross sectional survey was conducted of male AYA survivors of pediatric cancer. Methods: After IRB approval, the home institution’s database was queried to identify subjects. Eligibility criteria included male survivors between the ages of 15-25 years who had completed treatment in the last 5 years. A self-report survey was designed to assess perspectives of male survivors of pediatric cancer on survivorship with a focus on fertility. Descriptive analysis was performed for all demographic variables collected. To identify whether there was an association between specific demographic variables on survivors’ perspectives regarding their fertility, Fisher’s Exact Test was used (cut-off p-value: 0.05). Results: 33 patients enrolled. Two were deemed ineligible (n = 31). Median age was 20 yrs. Disease and treatment demographics encompassed a wide range of diagnoses and therapy. Subjects were evenly divided as to whether they expected difficulty siring a successful pregnancy. No demographic variable was significantly associated with survivors’ belief that they would have difficulty. A majority recalled being informed during treatment that they may have difficulty siring a pregnancy and having been offered sperm cryopreservation. Of the 22 patients who did not participate in cryopreservation, 12 reported they would have done so to protect their fertility; one would not. Subjects were split as to whether they would have waited to start treatment to allow for cryopreservation. Conclusions: Male survivors of pediatric malignancy are concerned with their future fertility and are informed regarding their risk. Male patients should be counseled regarding their fertility risk and options for fertility preservation. [Table: see text]
Areas for quality improvement in pediatric supportive oncology services.
Authors: Reichek Jennifer , Weldon Christine B. , Ganesan Rani , Suh Eugene , Dighe Dipti , Trosman Julia Rachel , Choi Daniel K. , Berardi Rosa , Sanford Stacy D. , Downing Kim , Owen Erika D , Kim Molly , Boss Kathleen , Kniola Allison , Newmark Monica , Pillay Smiley Natasha , Brown Melanie 
Published: September 2018

e22022 Background: In 2013, the Institute of Medicine report recommended that supportive oncology services be initiated at time of diagnosis. Providers of pediatric cancer care in the Chicagoland community, supported by The Coleman Foundation, sought to define areas for quality improvement of supportive oncology delivery to children. Methods: Focus groups and surveys with clinicians providing pediatric cancer care and supportive services at 14 sites were used to prioritize areas needing improvement. Results: 100% (14/14) of sites participated. Of the eligible sites, 6 were pediatric cancer treatment sites and 8 cancer care community organizations. Sites demonstrated consistent agreement for 8 of the 12 areas of focus for improvement. Over 50% of sites reported areas of focus (table) as important or very important. Conclusions: Sites identified the need for quality improvement in delivery of psychosocial, survivorship and palliative care for pediatric cancer patients. Survey results demonstrate a need for collaboration and efforts to guide care delivery improvement across sites. [Table: see text]
Next generation sequencing (NGS) in wild type GISTs.
Authors: Qiu Haibo , Zhuang Wei , Wu Ting , Huang Min , Zhou Zhiwei , Wang Xueding 
Published: September 2018

e22507 Background: The majority driven mutation of GIST are located in KIT and PDGFRA. A proportion of the remaining 10% of GIST without KIT or PDGFRA mutations called wild type GIST (wt-GIST). It is poor response to imatinib, sunitinib or regorafenib in these wt-GIST patients. It is lack of precise drug target of wt-GIST. We analyzed next generation exome sequencing (NGS) results in wt-GISTs. Methods: Whole exome sequencing was performed on freezing tumor tissue and peripheral blood DNA with 100X sequencing depth. The low frequency somatic mutation was confirmed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and Sanger sequencing. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: A total of 11 wt-GIST samples were analyzed. ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) was mutated in one CD117 negative patients with 5.3% mutation frequency of c. 364G > A (p. A122T). Sanger sequencing couldn’t found the ROS1 mutated in tumor tissue. But this low frequency somatic mutation was verified by MALDI-TOF. Conclusions: This is the first report showed a new ROS1 somatic mutation in wt-GIST. Our results indicated that ROS1 could be a new possible driven mutation in wt-GIST. ROS1 rearrangement have been described in a subset of non-small-cell lung cancers (NSCLC). Crizotinib shows a potent curative effect in ROS1 rearrangement NSCLC. Therefore, crizotinib might be an appropriate drug to GIST patients with mutated ROS1.
Clinical evidence from two phase 3 trials supporting statistical adjustment methods to assess confounding impact of treatment crossover on overall survival (OS).
Authors: Kappeler Christian , Wagner Andrea , Kalmus Joachim , Brose Marcia S. , Schlumberger Martin , Demetri George D. 
Published: September 2018

e22509 Background: In controlled trials that allow patients to crossover from placebo (PBO) to active treatment (ACT) after progression, OS in PBO patients is confounded by ACT. Statistical methods to adjust OS for crossover rely on an assumption of common treatment effect (i.e. PBO to ACT crossover after progression has the same impact as ACT started at randomization). This exploratory analysis of two phase 3 trials (PBO-controlled and allowing crossover) with regorafenib in GIST and sorafenib in thyroid cancer provides evidence to support this assumption. Methods: Target lesions were assessed at baseline and at regular intervals post baseline. Progression-free survival (PFS) was assessed during double-blind (DB) treatment and secondary PFS (SPFS) in PBO patients during open-label (OL) treatment. Changes in target lesion diameter over time were estimated by a parametric model. Early tumor growth rate (TGR), defined as percent change from baseline/month in the sum of target lesion diameters, was calculated as the model curve slope at earliest time on the TGR curve. Results: SPFS during OL in PBO patients is closer to DB PFS in ACT patients than to DB PFS in PBO patients (Table). Early TGR during OL in PBO patients is closer to DB early TGR in ACT patients than to DB early TGR in PBO patients. Conclusions: Currently available statistical methods to adjust for the impact of treatment crossover are supported by clinical results from two independent randomized, controlled phase 3 studies. These results provide validity to crossover correction analyses. Clinical trial information: NCT01271712; NCT00984282. [Table: see text]
Clinicopathological features and prognosis of primary GISTs with tumor rupture in the real world.
Authors: Nishida Toshirou , Cho Haruhiko , Masuzawa Toru , Chiguchi Gaku , Tsujinaka Toshimasa , Hirota Seiichi 
Published: September 2018

e22510 Background: Ruptured GIST has poor prognosis and patients (pts) with ruptured GISTs are recommended for imatinib adjuvant therapy, however, their clinicopathological features and the prognosis in the era of imatinib are unknown. Using data obtained from two different registry studies in Japan, we examined ruptured GIST patients in clinical practice. Methods: The study cohort registered 665 pts (339 male and 326 female; median age 66 yrs) with histologically-proven primary GISTs who underwent R0 or R1 surgery between 2003 and 2007. The validation cohort included 172 pts (100 and 72; median age 62.5) between 2000 and 2014. Pathological Dx was done with H&E, KIT- and DOG1-IHC. Results: Disease located in the stomach (n = 506), small intestine (n = 119), large intestine (n = 26), or others (n = 14) in the study cohort and it was 120, 37, 14 or 2 in the validation, respectively. Median tumor size was 4.0 and 5.0 cm, median mitosis 2.6 and 5.0 /50HPF, and tumor rupture was seen in 21 pts (3.2%) and 5 pts (2.9%) in the study and validation cohorts, respectively. Rupture occurred preoperatively in 12 pts and intraoperatively in 9 of the study cohort. Ruptured GISTs showed high mitotic activities (median mitosis 13.0 vs 2.5 /50HPF; P < 0.0001), larger tumor (median size 9.6 vs 4.0 cm; P = 0.0008), and were more symptomatic than non-ruptured in the study cohort. Ruptured GIST pts had more frequent relapses (P < 0.0001) and showed shorter RFS (estimated RFS = 2.4 yrs; P < 0.0001) than non-ruptured (8.4 yrs). There were no difference in age, gender, location, surgical approach, cell type, preoperative and postoperative imatinib use between two groups.These results were confirmed in the validation cohort. Ruptured GISTs showed more frequnent relapses in the peritoneum. Multivariate analysis indicated that location (HR = 1.6), size (1.07), mitosis (1.01), and rupture (4.5) were independent prognostic factors of RFS. Rupture was not always prognostic for OS, and age (1.03), gender (2.3), and mitosis (1.01) were independent prognostic factors of OS. Conclusions: Ruptured GISTs were symptomatic larger tumors with high mitotic activity and showed frequent relapses, however, it was not independently prognostic for OS in the era of imatinib.
Primary pulmonary sarcomas: The results of surgical treatment.
Authors: Golota Janusz , Rucinska Monika , Osowiecka Karolina , Orlowski Tadeusz 
Published: September 2018

e22540 Background: Primary pulmonary sarcomas (PPS) are the very rare cancer type (0.01% - 0.4% of all malignant tumours of the lung). PPS can derive from stromal elements of the bronchial wall, blood vessels and connective tissue steep of lung parenchyma. The aim of the study was evaluation of PPS patients’ outcome. Methods: The analysis included 23 patients (11 males, 12 females) age 28-70 years (median 49.6 years) with PPS treated surgically in the Department of Surgery, Institute of Lung Diseases and Tuberculosis in Warsaw from 1994 to 2009. Results: There were 3 leiomyosarcomas (13%), 3 hemangiopericitomas (13%), 3 MFH (13%), 3 malignant peripheral nerve sheath tumours (13%), 3 PNET (13%), 2 fibrosarcomas (8.8%), 2 liposarcomas (8.8%), 2 sarcomas synoviale (8.8%), 1 angiosarcomas (4.3%), 1 chondrosarcomas (4.3%) (according to the 3rd edition of the WHO Classification of Tumours of Soft Tissue and Bones). There were performed 5 pneumonectomies (21.7%), 5 lobectomys (21.7%), 5 wedge resection (21.7%), 6 exploratory thoracotomys (26.1%), 2 stent inserts (8.8%). In the case of 15 patients (65%) were performed operation R0. Adjuvant therapy was used in 7 patients (30%), 3 patients (13%) received chemotherapy, 2 patients (13%) radiotherapy and 1 patient (4%) chemo-radiotherapy. Palliative chemotherapy and or radiotherapy were given to 6 patients (26%). Median overall survival (OS) was 22 months (5- and 10-years OS was 26% and 17%, respectively) and depended on sex (p = 0.006), tumor size (p = 0.02), operation R0 (p = 0.07). Conclusions: Surgery, especially operation R0, is the most effective treatment method of PPS. Subsequent studies on larger groups are necessary.