tbuckley/cabot-search huggingface dataset:
Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof-of-Concept Study in Patients
Authors: Ashok J. Theruvath, Hossein Nejadnik, Anne M. Muehe, Felix Gassert, Norman J. Lacayo, Stuart B. Goodman, Heike E. Daldrup-Link
Journal: Clinical Cancer Research (2018)

Osteonecrosis is a devastating complication of high-dose corticosteroid therapy in patients with cancer. Core decompression for prevention of bone collapse has been recently combined with the delivery of autologous concentrated bone marrow aspirates. The purpose of our study was to develop an imaging test for the detection of transplanted bone marrow cells in osteonecrosis lesions.In a prospective proof-of-concept clinical trial (NCT02893293), we performed serial MRI studies of nine hip joints of 7 patients with osteonecrosis before and after core decompression. Twenty-four to 48 hours prior to the surgery, we injected ferumoxytol nanoparticles intravenously to label cells in normal bone marrow with iron oxides. During the surgery, iron-labeled bone marrow cells were aspirated from the iliac crest, concentrated, and then injected into the decompression track. Following surgery, patients received follow-up MRI up to 6 months after bone marrow cell transplantation.Iron-labeled cells could be detected in the access canal by a dark (negative) signal on T2-weighted MR images. T2* relaxation times of iron-labeled cell transplants were significantly lower compared with unlabeled cell transplants of control patients who were not injected with ferumoxytol (P = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different (P = 1), suggesting that the added ferumoxytol administration did not negatively affect bone repair.This immediately clinically applicable imaging test could become a powerful new tool to monitor the effect of therapeutic cells on bone repair outcomes after corticosteroid-induced osteonecrosis.
Insurance status and survival among prostate cancer patients: A population-based study.
Authors: Grace L. Lu-Yao, Jianming He, William Kevin Kelly, David J. Delgado, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2017)

e16563 Background: This population-based study assesses the relationship between insurance status and survival outcomes among men with prostate cancer diagnosed before 65 years of age. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 114,871 prostate cancer patients diagnosed before age 65 in 2007-2013. Insurance type was classified as uninsured, Medicaid, and other (including private insurance and coverage from the military or veterans affairs). Disease risk group was based on the NCCN criteria. We used multivariable Cox proportional hazards models to estimate the relative risks of all-cause mortality and prostate cancer specific mortality (PCSM), adjusted by age, race, marital status, region, diagnosis period, and primary treatment. Results: Compared with patients with other insurance, Medicaid and uninsured patients experienced 103% and 41% higher all-cause mortality. The corresponding increase for PCSM were 61% and 32%. Medicaid patients experienced 44% (HR=1.44, 95% 1.25-1.65) higher all-cause mortality than uninsured patients. Table 1 provides data stratified by risk status at diagnosis. Conclusions: Uninsured and Medicaid patients experienced higher PCSM and all-cause mortality compared to other insured patients across all disease severity. Medicaid patients experienced worse all-cause mortality compared with uninsured patients. Further studies are warranted to investigate factors related to poor survival outcomes among uninsured and Medicaid patients. [Table: see text]
Removing financial incentives for GPs led to decline in performance, finds study
Authors: Susan Mayor
Journal: BMJ (2018)

The removal of financial incentives is associated with an immediate decline in general practices’ performance on quality indicators, an analysis of electronic medical records for one third of GP practices in England has shown.1

Reductions were greatest for indicators related to giving health advice but also affected clinical activities, with a nearly 20% reduction in cholesterol testing in patients with a stroke or transient ischaemic attack (TIA) in the first year after payments through the Quality and Outcomes Framework (QOF) stopped.

“Removal of financial incentives was associated with an immediate decline in performance on quality measures,” said the study authors. The study was led by Bruce Guthrie, from the University of Dundee, working with researchers from the National Institute for Health and …
Real world outcomes of metastatic pancreatic cancer (mPC) patients (pts) treated with liposomal irinotecan (nal-IRI) in the US.
Authors: Afsaneh Barzi, Rebecca Miksad, Andy Surinach, Frank A. Corvino, Siqi Wang, Aracelis Z. Torres, Khalid Kevin Mamlouk, Sonia J. Pulgar, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2018)

e16229 Background: The NAPOLI-1 study, a randomized phase 3 study in patients with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in overall survival (OS), progression-free survival (PFS), and objective response rate with nal-IRI + folinic acid/ leucovorin (5-FU/LV) vs. 5-FU/LV. In this analysis, we describe real world characteristics and outcomes of mPDAC pts treated with nal-IRI in the US. Methods: This retrospective observational study utilized data from Flatiron Health’s longitudinal database derived from electronic health records data from over 265 diverse cancer clinics. Patient characteristics, OS, time-to-treatment failure (TTF), and adverse events (AEs) abstracted from structured lab data were assessed in adult pts diagnosed with mPDAC who received nal-IRI treatment between November 18, 2015 and August 31, 2017. Results: Of the 257 mPDAC pts treated with nal-IRI, 51% were male, 28% had a pancreatectomy, and median age was 67 (IQR: 61-74). Among pts with an ECOG score recorded at nal-IRI initiation (n=189), 20% had an ECOG of 2 or greater. Following diagnosis of metastatic or recurrent disease, 57% of pts received nal-IRI in the first or second line, and 43% in third line or later. Median OS was 5.59 months [95% CI 4.83,7.33] for pts receiving nal-IRI as the first or second treatment (n=145) and 4.11 months [95% CI 3.38, 4.9] for those receiving it in third or later lines (n=112), respectively. TTF was 2.33 [1.64, 3.02] for those treated in first or second line, and 1.64 [1.38, 1.87] for those in third line or later. Among pts for whom reasons for discontinuation were available(n=186), disease progression (57%), disease-related symptoms (17%), and treatment toxicity (14%) were reported most often. Structured AEs were generally consistent with those reported in NAPOLI-1. Conclusions: In this real world US population with older median age and poorer performance status, median OS, TTF, and structured AEs were similar to those reported in NAPOLI-1. As would be expected, pts receiving nal-IRI treatment in earlier lines had a higher median OS.
Sexual Risk Behavior Differences Among Sexual Minority High School Students — United States, 2015 and 2017
Authors: Catherine N. Rasberry, Richard Lowry, Michelle Johns, Leah Robin, Richard Dunville, Sanjana Pampati, Patricia J. Dittus, Alexandra Balaji
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Sexual minority youths (i.e., those identifying as gay, lesbian, bisexual, or another nonheterosexual identity or reporting same-sex attraction or sexual partners) are at higher risk than youths who are not sexual minority youth (nonsexual minority youth) for negative health behaviors and outcomes, including human immunodeficiency virus (HIV) infection, other sexually transmitted diseases (STDs), pregnancy (1),* and related sexual risk behaviors (2). Less is known about sexual risk behavior differences between sexual minority youth subgroups. This is the first analysis of subgroup differences among sexual minority youths using nationally representative Youth Risk Behavior Survey (YRBS) data. CDC analyzed pooled data from the 2015 and 2017 cycles of the national YRBS, a cross-sectional, school-based survey assessing health behaviors among U.S. students in grades 9-12. Analyses examined differences in eight sexual risk behaviors between subgroups of sexual minority youths and nonsexual minority youths, as well as within sexual minority youths. Logistic regression models controlling for race/ethnicity and grade found that bisexual females and "not sure" males reported higher prevalences for many behaviors than did heterosexual students. For behavior-based subgroups, the largest number of differences were seen between students who had sexual contact with both sexes compared with students with only opposite-sex sexual contact. Findings highlight subgroup differences within sexual minority youths that could inform interventions to promote healthy behavior.
Systematic reviews and meta-analyses in geriatric oncology.
Authors: Marek S. Poniewierski, Gary H. Lyman
Journal: Journal of Clinical Oncology (2017)

e21517 Background: Cancer incidence for most malignancies increases with age with the majority diagnosed after age 65. Aging is also associated with an increasing number of major comorbidities and greater risk and consequences of treatment-related complications. Geriatric Oncology has emerged as a subdiscipline within oncology focused on clinical management and research related to the elderly. Methods: A comprehensive search of the English language literature between 1990-2016 was undertaken for systematic reviews or meta-analyses (SRMAs) related to geriatric oncology. Titles, abstracts and full text manuscripts when needed were reviewed. 1,088 potentially eligible records were identified including 703 not limited to elderly patients, 89 not cancer studies and 236 not SRMAs. Results:More than half of 61 eligible studies were published in the last five years including systematic reviews in 42 (69%), meta-analyses in 42 (69%) and both in 23 (40%). Studies came from Europe (30), US (14), Canada (9), Asia (7) and South America (1) with elderly age cutoffs ranging from &gt; 60 to &gt; 80. While 17 reviews included multiple cancer types, 44 were limited to lung cancer (9), colorectal cancer (8), breast cancer (7), multiple myeloma (5) and lymphoma (4). Research focus was survivorship or end-of-life (41), treatment (24), geriatric assessment (11) and supportive care (8). Studies were limited to randomized controlled trials (37), non-RCTs (9) and both (16). The primary outcome was overall survival (39), progression free or relapse-free survival (15), response or recurrence (11), treatment-related toxicity (21) and geriatric assessment or frailty (9). More than half of SRMAs included &lt; 10 studies while 20% included &gt; 30 with the number of subjects in included trials ranging from 153 to &gt; 15,000. Conclusions: The development of Geriatric Oncology has spanned nearly three decades. While a strong evidence base of published research including rigorous SRMAs in Geriatric Oncology has only emerged over the past decade, steady growth across a range of topics and outcomes relevant to cancer in the elderly is apparent.
Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type.
Authors: Zoran Gatalica, Anatole Ghazalpour, Daniel Holterman, Nianqing Xiao, Peggy Overberg, Inga Rose, Gargi Dan Basu, Daniel D. Von Hoff, Omid Hamid
Journal: Journal of Clinical Oncology (2014)

e22091 Background: PD-1 activation by ligands (PD-L1 and PD-L2) inhibits T-cell activation and facilitates cancer progression. Trials exploring interruption of PD-1/PD-L1 signaling showed benefit in several cancer types, but the complexity of PD-L1 expression and patterns of PD-1 tumor infiltrating lymphocytes (TIL) make development of the predictive biomarker challenging. We analyzed distribution of PD-1+ lymphocytes and PD-L1 expressing tumor cells in common cancer types and their association with other cancer characteristics. Methods: 339 carcinomas (lung, breast, prostate, colon, ovary, endometrium, kidney, liver, bladder, pancreas) and 24 melanomas were profiled (Caris Life Sciences) using immunohistochemistry, in-situ hybridization and next generation sequencing (Illumina TruSeq panel). Results: PD-1+ lymphocytes are consistently identified in reactive, peri-tumoral lymphoid follicles, but intra-tumoral PD-1+ lymphocytes in direct cell-to-cell contact with cancer cells were less common (e.g. 50% of breast cancers, 58% melanomas and 75% of NSCLC). PD-L1 was consistently detected in tumor microenvironment (endothelium, macrophages, myofibroblasts), but specific cancer cells’ expression of PD-L1 was less common (e.g. 43% BrCA, 52% NSCLC, 21% sporadic CRC), except in melanomas which were PD-L1+ in 92% of cases. Intra-tumoral PD-1+ TILs and PD-L1+ cancer cells were co-present in 58% melanomas, 44% NSCLC, 28% breast carcinomas and 8% CRC. Triple-negative breast cancers (TNBC) were frequently PD-L1 positive (59% all TNBC and 100% in metaplastic TNBC). In NSCLC, PD-1+/PD-L1+ tumors were mostly seen in the absence of targetable genetic abnormality (i.e. EGFR, ALK and ROS1 negative). Conclusions: The study provides useful guidance for evaluation of PD-1 and PD-L1 as potential biomarkers for clinical trials as well as their frequency distribution in different types of malignancies. Not all patients respond to immunotherapy and intratumoral PD-1+ TILs and cancer specific PD-L1 expression may be required for the potential benefit to immune checkpoint inhibition therapy.
A phase I/II trial of ketoconazole + calcitriol [1,25(OH)2D3] in castration-resistant prostate cancer.
Authors: Donald L. Trump, William E. Brady, Jeanny B. Aragon-Ching, Roberto Pili, Ellis Glenn Levine, Saby George, Candace S. Johnson
Journal: Journal of Clinical Oncology (2016)

5065 Background: Considerable evidence indicates that exposure of tumor cells to high concentrations of 1,25(OH)2 vitamin D3 [1,25D3] in vitro can suppress in vivo tumor growth. Several studies have shown that administration of very high doses of 1,25D3 is safe, particularly with intermittent administration. Another way to achieve high intracellular concentrations of 1,25D3 is to combine it with an inhibitor of 1,25D3 breakdown. Ketoconazole is a non-specific inhibitor of CYP enzymes, including the dominant 1,25D3 catabolic enzyme, CYP24A1. We have shown that KETO + 1,25D3 are synergistic. (Muindi JR, et al Endocrinology 2010. 151:4301). A phase I/II trial in men with CRPC was conducted with 2 objectives: (1) to determine the maximum tolerated dose (MTD) of 1,25D3 + “high dose” KETO (400mg TID) (2) to conduct a 2 stage, phase II trial of 1,25D3 + KETO in men with CRPC. Pharmacokinetics of 1,25D3 were determined in 8 patients before and after 2 weeks of ketoconazole therapy in phase II. Methods: 6 CRPC patients entered the phase I portion and 37 patients in phase II. Results: Phase I: At dose level 2 of the 1,25D3 escalation (15mcg QDX3, weekly), limiting toxicity (grade 3) was seen in 3/3 patients[hypercalcemia{1},hyperkalemia{1} & dysphagia/elevated serum calcium{1}]. Dose level 1 (10mcg po QDX3 weekly) was employed for the phase II portion of this trial. The phase II 2 stage design had a stopping rule at 17 patients, if < 2 had a complete or partial PSA response. 7/17 patients met the criteria for response so the trial continued to enroll. For administrative reasons, the trial was interrupted when a total of 37 patients were accrued; 25 patients were evaluable for response. Complete or partial PSA response was seen in 15 patients (60%). Since 15 responses were seen with accrual of 25 evaluable patients, the trial was closed, and judged “positive”. Toxicities in phase II were primarily those associated with high dose ketoconazole administration (GI). No hypercalcemia was seen. Serum pharmocokinetics of 1,25D3 were not changed by co-administration with KETO. Conclusions: KETO(400mg TID) +1,25D3 (10mcgQDX3, weekly) is an active, reasonably tolerated regimen, deserving further evaluation. (supported by 5R01 CA067267-19) Clinical trial information: NCT00536991.
Remote access thyroid surgery for thyroid tumor: Initial institutional experience more than 100 surgeries from India.
Authors: Gyan Chand, Saroj Kant Mishra
Journal: Journal of Clinical Oncology (2018)

e18113 TITLE: Remote Access Thyroid Surgery for thyroid tumor: Initial Institutional Experience more than 100 surgeries from India ABSTRACT: Background: Endoscopic thyroidectomy allows surgeons to remove a thyroid tumor from remote site and provide excellent cosmetic outcome. The aim of study to evaluate the completeness surgery through Axillary and Breast Approach (ABA) & Bilateral Axillary and Breast Approach (BABA). Methods: 110 cases of endoscopic thyroid surgery were performed via ABA and BABA between Jan 2014 till Dec 2017. 46- ABA, 50- BABA and 06- TOVA. The variables studied were mean age, duration of goiter, functionality & fine needle aspiration cytology, mean size & weight of gland, hospital stay, final histopathology, complications and cosmetic outcome. Results: M:F= 1:5, Mean age 33.25 years ( 16-70 years), mean duration of goiter 32.33 months (<1month to 40 years); 88.64% euthyroid; FNAC reveled 70.45% colloid nodule, 13.63% follicular lesion, 2.27% PTC , 1.14% metastatic FTC , 7.95% not available . 92% operated successfully and 08% converted to open due to suspicious of malignancy in BABA and hemorrhage in ABA. Mean tumor size was 6.125 cm (BABA), 4.21cm (ABA) 4.17cm (TOVA) & mean weight was 54.19gm (BABA), 17.15gm (ABA), 11.58gm (TOVA). Mean operating time BABA was 3hrs 56 minutes(TT) and 2 hrs 43 minutes (HT); TOVA 2hrs 05 min (HT); ABA 2 hrs 20 min (HT) & 4 hrs 03 min (TT). Final histopathology - 57.96 % colloid Nodules, 13.60% Follicular adenoma, 25% thyroid carcinoma. 10.27% develop temporary voice change. 09.09% patients of TT develop temporary hypocalcaemia and managed with oral calcium & vit D, however 02 patients required intravenous calcium. The cosmetic outcome was excellent during 06 month follow-up in all the group. Conclusions: We believe that endoscopic thyroidectomy through ABA, BABA & TOVA have role in the treatment of thyroid tumor; however BABA endoscopic thyroid surgery approach is more appropriate for the large goiters.
Neuroendocrine carcinoma of luminal gastrointestinal tract.
Authors: Mahvish Muzaffar, Abdul Rafeh Naqash, Paul R. Walker, Charles Knupp, Darla K. Liles
Journal: Journal of Clinical Oncology (2018)

e16186 Background: Neuroendocrine Carcinoma(NEC)of gastrointestinal tract is very rare and an aggressive variant of neuroendocrine tumor. The purpose of this study was to assess the disease characteristics and outcome of luminal gastrointestinal tract NEC. Methods: Surveillance, Epidemiology, and End Results Program database was searched to identify patients diagnosed between 1990–2014 with neuroendocrine carcinoma with primary site labelled as stomach, small intestine, colon, rectum and anus. Kaplan‐Meier curves estimated disease specific survival (DSS) and overall survival (OS) and multivariate Cox models were utilized to analyze variables. Results: This study included 2074 patients with NEC of stomach, small intestine, colon and anorectum. The mean age was 66.69 yrs,55% of patients were male,81% were white and colon was the most common site. Around 50% patient had distant metastasis at diagnosis and 67% of patients were diagnosed between 2002-2014. A multivariate Cox model revealed factors associated with poor outcome include advanced stage (HR 2.9, p < 0.0001), site of primary disease with colon associated with poor outcome (HR 1.34, p = 0.0002), year of diagnosis before 2001 (HR 1.21, p = 0.003) and older age > 65yrs (HR 1.37, p = < 0.0001). Race did not show any influence on outcome (p = 0.35) in the overall cohort. The site-specific analysis revealed some variability, advanced stage had poor outcome irrespective of primary site, female sex was associated with better outcome only in colon and anorectal NEC, and black race was associated with poor outcome in colon NEC only. Conclusions: There is paucity of data regarding NEC of GI tract and our knowledge regarding outcome is often extrapolated from pulmonary NEC. We noted variation in demographics and outcomes based on primary site. NEC of colon was associated with poor outcome, and stage was an independent prognostic factor across all sites. Variable Median Survival(mo.) P value Age < 65 9 < .0001 ≥65 6 Sex < .0001 Male 7 Female 10 Primary Site 0.0003 Stomach 9 Small intestine 15 Colon 7 Anorectum 9 Summary Stage < .0001 Localized 40 Regional 15 Distant 4 Unknown 6
Dynamic monitoring of driver gene mutation profiles in plasma cfDNA using an 85 gene panel for postoperative prognosis in colorectal cancer.
Authors: Tanxiao Huang, Ligang Xia, Mingyan Xu, Yuanyuan Liu, Xiaoni Zhang, Charles E. Melançon, Mengyuan Liu, Jeremy Edwards, Shifu Chen
Journal: Journal of Clinical Oncology (2018)

e15536 Background: Postoperative monitoring of patients with colorectal cancer (CRC) requires sensitive biomarkers associated with response to therapy following surgery. Identifying molecular residual disease (MRD) using ctDNA after treatment of CRC could facilitate early intervention and precision adjuvant therapies. Methods: The present study enrolled 30 patients with CRC. All patients underwent surgery; and a number of patients underwent postoperative chemotherapy. Tumor tissues and serial blood samples were collected from each patient; and somatic mutations from each sample were identified using next-generation sequencing. Results: The mutational landscape and mutational dynamics were analyzed for each patient. These results were compared with changes in CEA levels. In 83% (25/30) of patients, at least 1 of the variants detected in tumor tissue was also detected in plasma. The majority of actionable mutations detected in tissue were also detected in plasma. A number of driver genes were selected, including TP53, APC, PIK3CA and KRAS, to monitor the postoperative outcome of the 30 CRC patients. Driver mutations were detected in the preoperative plasma of 25 patients; and marked decreases in postoperative plasma mutation levels compared to preoperative levels were observed. In 5 patients, driver mutations were not detected in either preoperative or postoperative plasma. In the 2 patients with metastatic CRC, the ctDNA level increased significantly; however no marked changes in CEA level were observed. Conclusions: The results of ctDNA analysis correlate well with the presence or absence of tumors in preoperative and postoperative patients with CRC; and shows promise for identifying residual/recurrent disease earlier. In summary, ctDNA analysis is a highly sensitive and specific method for predicting postoperative outcome in patients with CRC.