tbuckley/cabot-search huggingface dataset:
Association of bone mineral density with incidental renal stone in long-term survivors of childhood acute lymphoblastic leukemia.
Authors: Prasad Laxman Gawade, Kirsten K. Ness, Shelly Sharma, Zhenghong Li, Deo Kumar Srivastava, Sheri L. Spunt, Kerri Nottage, Melissa M. Hudson, Sue Kaste
Journal: Journal of Clinical Oncology (2012)

9527 Background: With 5-year survival of childhood acute lymphoblastic leukemia (ALL) now exceeding 90%, long term morbidities are of growing concern. Both low bone mineral density (BMD) and renal dysfunction have been reported in ALL survivors. Our objective was to evaluate the association between low BMD and incidental renal stones, a known predictor of renal dysfunction. Methods: Adult participants who were 10+ year survivors of childhood ALL and members of St. Jude Lifetime Cohort study were recruited between 12/2007 and 3/2011. During their risk-based medical evaluations they underwent quantitative computed tomography (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists’ review of axial QCT source images. Demographic information was abstracted from responses to health surveys and dietary intake from a Block food frequency questionnaire. Association between BMD and renal stones was evaluated in a multivariable logistic regression model. Confounding variables were selected using directed acyclic graphs and change in effect estimates strategy. Results: At a median of 26.1 years from diagnosis, BMD Z score of &gt; 1 standard deviation (SD) was detected in 77/662 (11.6%) and renal stones in 73/662 (11%) participants. In a multivariable model adjusted for age, dietary vitamin D and renal radiation, when compared to BMD Z score &gt; 1 SD, the risk of renal stones increased with a decrease in BMD Z-score; 1 to 0 SD (Odds Ratio (OR), 1.93; 95% confidence interval (CI), 0.69 to 5.41), 0 to -1 SD (OR, 1.46; 95% CI, 0.52 to 4.05), -1 to -2 SD (OR, 2.72; 95% CI, 0.81 to 6.41), and ≤ -2 SD (OR, 4.96; 95% CI, 1.43 to 17.13). Older age (45-54 vs.18-24 y; OR, 3.66; 95% CI, 1.10 to 12.15), renal radiation (OR, 1.97; 95% CI, 0.59 to 6.50) and &gt; 141.5 IU intake of vitamin D (OR, 1.65; 95% CI, 0.98 to 2.77) were also associated with renal stone formation. Conclusions: Our results not only help us recognize survivors at risk, but also informs radiologists to be vigilant of incidental renal stones among older ALL survivors with low BMD.
Comparing outcomes data from dedicated oncology-subspecialist hospitalists to those from a traditional care model on an inpatient oncology service.
Authors: Kristina Fanucci, Andrew Chung Yang, Steven E. Reinert, Rabin Niroula
Journal: Journal of Clinical Oncology (2019)

11538 Background: Changes in the complexity and delivery of health care and efforts to contain rising costs gave rise to the hospitalist model of care delivery in the 1990s. More recently some hospitals have begun using the hospitalist model on inpatient oncology floors. Oncology patients are a unique population who require high rates of hospitalization for problems arising from their progressive disease burden and side effects of cancer-directed therapy and have high rates of 30 day readmissions (30DR), an important quality metric. The majority of studies in this area have shown similar outcomes comparing care given by internal medicine hospitalists working full time on an inpatient oncology service compared to multiple oncologists working in rotating shifts on the same inpatient oncology service (Traditional). A new care model using dedicated hematology/oncology subspecialist hospitalists (H-O) to care for patients admitted to the oncology service has been implemented at our academic medical center. Methods: We conducted a retrospective chart review to identify patients with a cancer diagnosis admitted to the oncology service over a six year period. 7/1/2012-6/30/2015 marked the Traditional care model and 7/1/2015-7/1/2018 the H-O model. We compared 30DR, discharge to hospice, length of stay (LOS), and inpatient mortality between these two groups. Results: We identified a total of 3778 patients admitted to the oncology service over this six year period—1932 patients admitted to the Traditional service and 1846 patients admitted to the H-O service. There was a significant difference in 30DR between the Traditional v. H-O service (36.7% v. 29.5%, χ 2 = 21.1, p &lt; 0.00001) and discharge to hospice (7.6% v. 12.9%, χ 2 = 29.0, p &lt; 0.0000001). There was no significant difference in LOS between the Traditional and H-O services (6.40 days v. 6.03 days, p = 0.122) or in-hospital mortality (2.6% v. 1.9%, χ 2 = 2.16, p = 0.14). Conclusions: The shift to dedicated hospitalist-oncologists caring for patients on the inpatient oncology service significantly decreased 30DR at our institution. There were also significantly more patients transferred to hospice care. We found no significant difference between the two groups in LOS or inpatient mortality. This care model may help reduce the cost of caring for oncology patients by decreasing 30DR.
P14.115 A Neurologist’s Foray into Gamma Knife: Lessons Learned from the first 100 cases:
Authors: G H J Stevens, S T Chao, E S Murphy, J H Suh, J Yu, G Neyman
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Gamma Knife Radiosurgery typically involves a neurosurgeon, radiation oncologist and physicist. Neurologists performing Gamma Knife provides a potential paradigm shift. METHODS The first 100 Gamma Knife procedures were completed on an Elekta Perfexion or ICON system between October 2015 and August 2018. Head frames were placed by the treating neurologist who also completed the contouring and targeting. The Radiation Oncologist defined the prescription dose and verified the plan, along with the physicist. RESULTS Of the first 100 cases completed by the treating neurologist, 52 were females and 48 males. The average age was 61.4 years. There were 64 metastatic cases, 25 meningiomas, 8 gliomas, 2 hemangioblastoma and 1 pituitary adenoma. There were 245 individual lesions targeted. No frame related placement complications occurred. Five large metastasis were treated as a staged procedure 1 month apart. A bolus was used on 4 occasions for lesions invading the skull. Secondary to large bifrontal craniotomies, cheek posts were used on 2 occasions, and 3 posts were used in 5 cases secondary to large unilateral frontal craniotomies. Four cases were completed under general anesthesia. In one patient with a very large head, the frame would not fit and was deconstructed, placed around the neck, reconstructed with pins placed in the cheeks. 64 of the treated patients are still alive. CONCLUSION While unconventional, neurologists can function as a surgical surrogate to treat intracranial neoplasms with Gamma Knife. This offers unique advantages, especially in regards to continuity of care as many of these patients had been followed and will continue to follow with neurology. With the advent of the ICON frameless based system, concerns about frame placement also become less of an issue and more facile for neurologists to perform these procedures.
Temporal Trends and Contemporary Use of Insulin Pump Therapy and Glucose Monitoring Among Children, Adolescents, and Adults With Type 1 Diabetes Between 1995 and 2017
Authors: Louisa van den Boom, Beate Karges, Marie Auzanneau, Birgit Rami-Merhar, Eggert Lilienthal, Simone von Sengbusch, Nicolin Datz, Carmen Schröder, Thomas Kapellen, Markus Laimer, Sebastian M. Schmid, Heiko Müller, Johannes Wolf, Reinhard W. Holl
Journal: Diabetes Care (2019)

OBJECTIVE To investigate temporal trends and contemporary use of insulin pump therapy and glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS In a population-based study, we analyzed the use of insulin pump therapy, continuous glucose monitoring (CGM), and self-monitoring of blood glucose (SMBG) from 1995 to 2017 in patients with type 1 diabetes identified from the Diabetes Prospective Follow-up (DPV) database in Germany and Austria. Patients were stratified by age, sex, migration background, and country. RESULTS Among 96,547 patients with type 1 diabetes (median age 17.9 years, 53% males), the percentage using insulin pump therapy increased from 1% in 1995 to 53% in 2017, with the highest rates in the youngest patients (92% in preschoolers, 74% in children, 56% in adolescents aged &amp;lt;15 years, 46% in adolescents aged ≥15 years, 37% in adults). The percentage of patients using CGM increased from 3% in 2006 to 38% in 2017, with the highest rates in the youngest patients (58%, 52%, 45%, 33%, and 15% of respective age-groups). Daily SMBG frequencies increased from 1995 to 2016 and decreased afterward, most prominently in the youngest patients. Between 2015 and 2017, pump therapy was more frequently used in female versus male adolescents and adults (all P &amp;lt; 0.001), while no sex differences were observed for pump use in children &amp;lt;10 years (all P = 1.0) and for CGM use in all age-groups (all P = 1.0). CONCLUSIONS Since 1995, insulin pump use has continuously increased, and insulin pump therapy is now standard in patients aged &amp;lt;15 years. CGM use sharply rose in recent years, particularly in young children.
Updated Analyses of the International, Open-Label, Randomized, Phase 3 Alcanza Study: Longer-Term Evidence for Superiority of Brentuximab Vedotin Versus Methotrexate or Bexarotene for CD30-Positive Cutaneous T-Cell Lymphoma (CTCL)
Authors: Steven M. Horwitz, Julia J. Scarisbrick, Reinhard Dummer, Madeleine Duvic, Youn H. Kim, Jan Walewski, Sean Whittaker, Pietro Quaglino, Pier Luigi Zinzani, Pascal Wolter, Herbert Eradat, Jose A. Sanches, Pablo L. Ortiz-Romero, Oleg E. Akilov, Judith Trotman, Kerry Taylor, Stephane Dalle, Michael Weichenthal, David C. Fisher, Rudolf Stadler, Tatyana A Feldman, Timothy M. Kuzel, Alejandro A. Gru, Yinghui Wang, Maria Corinna Palanca-Wessels, Hui-Min Lin, Yi Liu, Meredith Little, H. Miles Prince
Journal: Blood (2017)
Revascularization in Patients With Spontaneous Coronary Artery Dissection and ST-Segment Elevation Myocardial Infarction
Authors: Angie S. Lobo, Stephanie M. Cantu, Scott W. Sharkey, Elizabeth Z. Grey, Katelyn Storey, Dawn Witt, Gretchen Benson, Ross F. Garberich, Yasuhiko Kubota, C. Noel Bairey Merz, Timothy D. Henry
Journal: Journal of the American College of Cardiology (2019)
Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure
Authors: Benedikt Schrage, Alicia Uijl, Lina Benson, Dirk Westermann, Marcus Ståhlberg, Davide Stolfo, Ulf Dahlström, Cecilia Linde, Frieder Braunschweig, Gianluigi Savarese
Journal: Circulation (2019)

Most randomized trials on implantable cardioverter-defibrillator (ICD) use for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction enrolled patients >20 years ago. We investigated the association between ICD use and all-cause mortality in a contemporary heart failure with reduced ejection fraction cohort and examined relevant subgroups.Patients from the Swedish Heart Failure Registry fulfilling the European Society of Cardiology criteria for primary-prevention ICD were included. The association between ICD use and 1-year and 5-year all-cause and cardiovascular (CV) mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort and in prespecified subgroups.Of 16 702 eligible patients, only 1599 (10%) had an ICD. After matching, 1305 ICD recipients were compared with 1305 nonrecipients. ICD use was associated with a reduction in all-cause mortality risk within 1 year (hazard ratio, 0.73 [95% CI, 0.60-0.90]) and 5 years (hazard ratio, 0.88 [95% CI, 0.78-0.99]). Results were consistent in all subgroups including patients with versus without ischemic heart disease, men versus women, those aged <75 versus ≥75 years, those with earlier versus later enrollment in the Swedish heart failure registry, and patients with versus without cardiac resynchronization therapy.In a contemporary heart failure with reduced ejection fraction population, ICD for primary prevention was underused, although it was associated with reduced short- and long-term all-cause mortality. This association was consistent across all the investigated subgroups. These results call for better implementation of ICD therapy.
Exploration of tumor genetic alterations and associations with clinical outcomes: Retrospective genomic analysis of archived liposarcoma (LPS) and leiomyosarcoma (LMS) samples from phase III trial of trabectedin (T) versus dacarbazine (D).
Authors: Shibu Thomas, Shilpy Joshi, Dong Shen, Roland Elmar Knoblauch, Michael Gormley, George C. Wang, Deborah S. Ricci, Clifford Motley, Robert G. Maki, Margaret von Mehren, Shreyaskumar Patel, George D. Demetri
Journal: Journal of Clinical Oncology (2019)

11019 Background: To explore tumor genomic associations with response/resistance as potential predictive or prognostic biomarkers for T and D in metastatic LMS and LPS tumor samples. Methods: Genomic alterations [single nucleotide variants (SNVs) or gene copy number variations (CNVs)] were identified using whole exome sequencing (WES) of archived tumor samples from NCT01343277. Association of tumor-subtype or genetic alterations with clinical outcomes including maximum tumor volume reduction (MTVR), overall survival (OS), progression free survival (PFS) and treatment cycles received was assessed using multivariate Cox proportional hazard models. Results: A total of 178 uterine LMS (uLMS), 121 non-uterine LMS (non-uLMS), 60 de-differentiated LPS (ddLPS), 40 myxoid LPS (mLPS) and 14 pleomorphic LPS (pLPS) tumors underwent WES. Homozygous deletions (HD) were observed at relatively high frequency in 4 genes -AC092821.1 (36.4%), LCE3B (35.4%), LCE3C (32.1%), HEATR4 (24.4%) across all sarcoma subtypes. These genes are involved in cell proliferation, innate immune response and differentiation. HD in any of these genes was associated with improved OS in the T treatment arm. Tumors with MDM2 amplifications showed worse clinical outcome in the T treatment arm in terms of PFS and OS consistent with T-mediated induction of p-53 dependent apoptosis (Table). Conclusions: HD in any of 4 genes was associated with longer OS in patients treated with T. This molecular signature, which covers 40% of total sarcoma and 0.4% of overall solid tumors population, warrants further prospective validation. Novel genetic alterations and clinical associations. [Table: see text]
Malaria eradication within a generation: ambitious, achievable, and necessary
Authors: Richard G A Feachem, Ingrid Chen, Omar Akbari, Amelia Bertozzi-Villa, Samir Bhatt, Fred Binka, Maciej F Boni, Caroline Buckee, Joseph Dieleman, Arjen Dondorp, Alex Eapen, Neelam Sekhri Feachem, Scott Filler, Peter Gething, Roly Gosling, Annie Haakenstad, Kelly Harvard, Arian Hatefi, Dean Jamison, Kate E Jones, Corine Karema, Richard Nchabi Kamwi, Altaf Lal, Erika Larson, Margaret Lees, Neil F Lobo, Angela E Micah, Bruno Moonen, Gretchen Newby, Xiao Ning, Muhammad Pate, Martha Quiñones, Michelle Roh, Ben Rolfe, Dennis Shanks, Balbir Singh, Kenneth Staley, James Tulloch, Jennifer Wegbreit, Hyun Ju Woo, Winnie Mpanju-Shumbusho
Journal: The Lancet (2019)
Screening Mammography Outcomes: Risk of Breast Cancer and Mortality by Comorbidity Score and Age
Authors: Joshua Demb, Linn Abraham, Diana L Miglioretti, Brian L Sprague, Ellen S O’Meara, Shailesh Advani, Louise M Henderson, Tracy Onega, Diana S M Buist, John T Schousboe, Louise C Walter, Karla Kerlikowske, Dejana Braithwaite
Journal: JNCI Journal of the National Cancer Institute (2019)

Potential benefits of screening mammography among women ages 75 years and older remain unclear.We evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999-2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years.During median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66-74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75-84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85-94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66-74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75-84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66-74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75-84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%).Cumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening.
OS6.5 ERGO2: A prospective randomized trial of a 9-day schedule of calorically restricted ketogenic diet and fasting or standard diet in addition to re-irradiation for malignant glioma
Authors: M Voss, M Wagner, N von Mettenheim, P N Harter, K Wenger, K Franz, J Bojunga, R Gerlach, M Glatzel, F Paulsen, E Hattingen, O Baehr, M W Ronellenfitsch, E Fokas, D Imhoff, J P Steinbach, C Rödel, J Rieger
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ketogenic diet (KD) and fasting have anticancer effects in tumor models, possibly due to a differential stress response with sensitization of tumor cells and protection of normal tissue. We therefore set up ERGO2 (NCT01754350), the first randomized clinical trial of calorically-restricted KD and intermittent fasting (KD-IF) in addition to re-irradiation for recurrent malignant gliomas. MATERIAL AND METHODS Patients were randomized 1:1 to re-irradiation combined with either calorically unrestricted diet (standard diet, SD) or KD-IF. The KD-IF schedule included 3 days of KD (21–23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. The primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary endpoints were PFS, local control, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS 50 patients were included. Four patients quit the trial before treatment and three patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6, and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1±1.8 kg. No severe adverse events attributable to the diet occurred. There was no difference in PFS6 between the two groups (KD-IF: 20%, SD: 16%). Similarly, no difference in PFS, local PFS6 and OS were observable. Explorative analysis revealed that among patients of the KD-IF group, those who achieved ketosis of at least 1.5 mmol/l had significantly longer PFS compared to those with lesser or no ketosis. CONCLUSION KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioblastoma. However, the short schedule reported here failed to increase the efficacy of re-irradiation.
P13.03 Identification of novel gene fusions in glioblastomas with chromothripsis
Authors: F Ah-Pine, D Casas, B Boisselier, P Guardiola, P Menei, E Garcion, A Rousseau
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Genomic rearrangements are thought to occur in a stepwise manner during cancer development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome (chr) rearrangements in a one-step catastrophic event termed chromothripsis (CT). In this scenario, the chr shatters into tens to hundreds of pieces, some of which are then stitched together in a mosaic patchwork of genomic fragments. Such random stitching may give rise to fusion genes with oncogenic potential. CT has not been thoroughly studied in diffuse gliomas, such as glioblastomas (GB). The aim of the project was to detect CT in GB and identify novel fusion genes in CT regions. Those genes are potential therapeutic targets. MATERIAL AND METHODS 170 de novo IDH wild-type GB were screened for CT patterns using whole genome SNP arrays. RNA sequencing was performed in 52 cases with CT features to identify novel fusion genes within the rearranged genomic regions. Expression levels of transcripts were measured using FPKM (fragments per kilobase of exon per million fragments mapped) normalization method. Candidate fusion genes were validated by RT-PCR followed by Sanger sequencing. RESULTS Out of 66 GB with CT patterns (66/170, 38.8%), 40 cases (out of 52 RNA-sequenced cases, 77%) harbored at least one fusion gene within CT regions, which were mostly detected on chr 7, 9, and 12. Overall, 137 candidate fusion genes were identified, 26 of which with a predicted open reading frame. Twelve out of 26 fusions were validated by RT-PCR followed by Sanger sequencing (validation of the remaining fusions is ongoing). The fusions involved either well-known key oncogenes such as EGFR, MDM2, and MET or potential oncogenes (CPM, PPM1H, SEPT14, SEC61G) with a yet-to-discover role in GB pathogenesis. GB with CT on chr 12 (11/66, 16.7%) showed a distinct transcript expression profile at the locus 12q13-15, particularly in the vicinity of MDM2 and CDK4 genes. In our cohort, this so-called “multi-aberration region” recurrently harbored gene fusions, involving, among others, CPM (12q15). CPM, encoding an extracellular membrane-bound carboxypeptidase, is recurrently amplified in liposarcoma and is a potential oncogene involved in the EGFR signaling pathway. Three cases (3/26, 11.5%) harboring an in-frame gene fusion involving CPM showed higher levels of CPM transcripts and did not exhibit any EGFR amplification. Gene fusions involving CPM might constitute an alternative mechanism of EGFR pathway activation in de novo IDH wild-type GB. CONCLUSION The occurrence of CT points to underlying gene fusions in IDH wild-type GB. Such fusions may drive tumorigenesis and represent promising therapeutic targets. We identified CPM as a recurrent fusion partner and a potential alternative mechanism of EGFR signaling pathway activation in de novo IDH wild-type GB.
Current Management of Symptomatic Pericardial Effusions in Cancer Patients
Authors: Audrey Besnard, MD, François Raoux, MD, Nizar Khelil, MD, Jean-Luc Monin, MD, PhD, Jean Pierre Saal, MD, Aurelie Veugeois, MD, Kostantinos Zannis, MD, Mathieu Debauchez, MD, Christophe Caussin, MD, Nicolas Amabile, MD, PhD
Journal: JACC CardioOncology (2019)

Neoplasia and hematologic malignant diseases are common causes of acute pericardial effusion. The presence of malignant pericardial effusion (MPE) is associated with poor prognosis in these patients, with a shortened survival median time. The best management for symptomatic MPE (surgical drainage