tbuckley/cabot-search huggingface dataset:
Final results from the dose-escalation stage of a phase 1/2 trial of TPI 287, a brain penetrable microtubule inhibitor, plus bevacizumab in patients with recurrent glioblastoma.
Authors: Samuel Aaron Goldlust, Louis B. Nabors, Nimish Mohile, Tara L. Benkers, Sigmund H. Hsu, Sandra Silberman, Samuel Singer, Mayank Rao, Lori Cappello, George Farmer
Journal: Journal of Clinical Oncology (2017)

2021 Background: Microtubule inhibitors, including taxanes, are active in preclinical models of glioblastoma (GBM), however, clinical benefit is hampered by poor blood-brain barrier (BBB) accumulation. TPI 287, a third-generation taxane designed to evade P-glycoprotein mediated efflux, readily penetrates the BBB and overcomes this limitation. CB-017 is a multi-center phase 1/2 trial designed to determine the optimal dose of TPI 287 and potential efficacy in patients treated with this drug plus bevacizumab (BEV) for treatment of recurrent GBM. Final results of the dose escalation Phase 1 stage of this trial are reported. Methods: GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. BEV was administered at 10 mg/kg every 2 weeks and TPI 287 every 3 weeks via IV infusion. MRIs were obtained every six weeks with response assessed via RANO criteria. TPI 287 dose escalation was based on a traditional 3+3 design. Results: Twenty-four patients were enrolled in 7 TPI 287 dose-escalation cohorts (140-220 mg/m2) from 6 U.S. centers. Twenty and 23 patients were evaluable for response and survival, respectively. Median follow-up was 28 months. Results are shown in the table below. Of the 9 patients from which biomarker data was available, tumors from 8 patients (89%) harbored an unmethylated MGMT promoter, an established negative prognostic indicator for survival. No DLTs were reported and myelosuppression (n=3) was the only drug-related grade 3/4 adverse event. Conclusions: TPI 287 in combination with BEV is safe and well tolerated at doses up to 220 mg/m2. Final survival results from the Phase 1 portion of this study compare favorably with historical controls and support further investigation of TPI 287 plus BEV for treatment of recurrent GBM. Clinical trial information: NCT01933815. [Table: see text]
Epidemiological profile of adolescent and young adults (AYA) with cancer: A decade long experience of a tertiary care centre from South India.
Authors: Jayanthi Srirambhatla, Radhika Parimkayala, Sudha Sinha, Meher Lakshmi Konatam
Journal: Journal of Clinical Oncology (2016)

e13102 Background: Cancers in Adolescent and young adults is a variegated group with special needs which is an orphaned subject. Methods: to study the epidemiological profile of cancers in adolescent and young adults (15-29yrs) attending MNJ Institute of Oncology, Regional cancer centre (MNJ IO RCC) located in Hyderabad ,India. A retrospective analysis of records of all patients of 15-29 years attending our institute from 2004-2014 was done. Epidemiological data was captured and analysed for the type of cancer, age/sex distribution year wise by descriptive analysis Results: MNJ IO RCC has a total enrolment of 8322 -10192 new cases of cancers every year. Cancers in AYA account for 8.9% of total new cases. Majority of the cases occured in 25-29 year age group. The male to female ratio was 1.1:0.9. There is a steady increase in the number of cases from 2004 (n = 697) to 2014 (n = 917). The introduction of cashless government health scheme has resulted in increasing utilisation of services. The top five most common cancers in males are leukemia/ lymphoma, head and neck, digestive system, skeletal system, male genital tract cancers (testicular). Among the females leukemia/lymphoma, female genital tract, endocrine system (thyroid ),breast and digestive cancers are the top five cancers noted. Conclusions: Cancers in AYA is increasing. Leukemia /lymphoma constitute the most common cancer. Increasing incidence of head and neck cancers reflects the effect on environment and lifestyle.
Letter to the Editor re: ‘Long‐term complications of Stevens–Johnson syndrome/toxic epidermal necrolysis ( <scp>SJS</scp> / <scp>TEN</scp> ): the spectrum of chronic problems in patients who survive an episode of <scp>SJS</scp> / <scp>TEN</scp> necessitates multidisciplinary follow‐up’
Authors: C. Olteanu, N. Shear, R. Hashimoto, R. P. Dodiuk‐Gad
Journal: British Journal of Dermatology (2017)

We read with great interest, the review paper by Lee et al. on the long term complications of Stevens-Johnson syndrome and toxic epidermal necrolysis. We would like to congratulate the authors on this important and excellent overview. This review demonstrated that SJS/TEN has a severe, chronic phase with major physical morbidities. We wish to raise awareness to the major emotional complications among survivors; as was found in our study published in the British Journal of Dermatology by Dodiuk-Gad et al.

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Abstract 13500: Gender Comorbidities and Outcome Disparities in Transcatheter Aortic Valve Replacement. A Novel Gender Gap?
Authors: Marco A Magalhaes, Sa`ar Minha, Israel M Barbash, Salem Badr, Joshua P Loh, Omar Alfazir, Lakshmana K Pendyala, Itsik Ben-Dor, Hironori Kitabata, Hideaki Ota, Rebecca Torguson, Fang Chen, Petros Okubagzi, William O Suddath, Kenneth M Kent, Lowell F Satler, Augusto D Pichard, Ron Waksman
Journal: Circulation (2013)

Background: Although female gender comprises the majority of patients referred to transcatheter aortic valve replacement (TAVR), few studies have systematically analyzed the gender comorbidities co...
Do patients with reflux follow doctors advice? – A long term study of patients proton pump inhibitor usage following endoscopy
Authors: A Murdock, GB Turner, TCK Tham
Journal: Endoscopy (2005)

Aims: For patients with simple reflux symptoms endoscopy is recommended to evaluate the degree of oesophagitis and plan long term medical therapy. There are few studies evaluating whether patients follow this advice post endoscopy.
Incidental lung cancers and positive CT images in HIV-infected individuals: results from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study
Authors: Andreas Ronit, T Kristensen, Ditte M. Klitbo, Marco Gelpi, Anna Kalhauge, T Benfield, Jan Gerstoft, Jens D. Lundgren, Jorgen Vestbo, Klaus Kofoed, S Nielsen
Journal: European Respiratory Journal (2016)
Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: 5-year outcomes of NSABP protocol B-41.
Authors: Andre Robidoux, Gong Tang, Priya Rastogi, Charles E. Geyer, Catherine A. Azar, James Norman Atkins, Louis Fehrenbacher, Harry Douglas Bear, Luis Baez-Diaz, Shakir Sarwar, Richard G. Margolese, William Blair Farrar, Adam M. Brufsky, Henry R. Shibata, Hanna Bandos, Soonmyung Paik, Joseph P. Costantino, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2016)

501 Background: The primary aim of this randomized trial of neoadjuvant therapy in operable, HER2-positive breast cancer (BC) was to determine the effect on pathologic complete response (pCR) rates of substituting lapatinib (L) for trastuzumab (T) in combination with weekly paclitaxel (WP) following AC as well as adding L to T with WP following AC. Previously reported results showed pCR breast 52.5% for AC→WP+T, 53.2% for AC→WP+L, and 62% for AC→WP+TL. Planned secondary endpoints included 5-year recurrence-free interval (RFI) and overall survival (OS) and are reported here. Methods: All patients received standard AC q3wks x 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15 q28 days x 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, all patients received T to complete 52 wks of HER2-targeted therapy. 529 pts were randomized and 522 had follow-up. Median follow-up for this analysis was 5 years. Results: Five-year RFI was 84.3% for AC→WP+T, vs 78.6% for AC→WP+L (p=0.14: HR, 1.27; 95% CI, 0.74-2.20), and 90% for AC→WP+TL (p=0.33: HR, 0.66; 0.34-1.25). Five-year OS was 94.5% for AC→WP+T, vs 89.4% for AC→WP+L (p=0.11: HR, 1.52; 0.69-3.35), and 95.7% for AC→WP+TL (p=0.55: HR, 0.63; 0.24-1.67). Long-term outcomes correlated with pCR status. The HR for RFI (pCR breast vs non-pCR) was 0.45 (0.28-0.73; p=0.0009) for the entire study population, 0.64 (0.33-1.25; p=0.19) in the estrogen receptor (ER)-positive cohort, and 0.24 (0.12-0.49; p<0.0001) in the ER-negative cohort. The HR for OS was 0.28 (0.13-0.60; p=0.0004), 0.43 (0.11-1.65; p=0.20), and 0.16 (0.06-0.39; p<0.0001), respectively. Conclusions: Results of 5-year outcomes (RFI and OS) were consistent with previously reported findings regarding pCR status. While pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes and the improvement was more remarkable in the ER-negative subset. Support: GlaxoSmithKline Clinical trial information: NCT00486668.
Use of a marketing plan for recruitment to a lung cancer screening study.
Authors: John R. Goffin, Gregory Russell Pond, Alain Tremblay, Michael R. Johnston, Glenwood D. Goss, Garth Andrew Nicholas, Simon Martel, Rick Bhatia, Geoffrey Liu, Heidi Roberts, Martin Tammemagi, Sukhinder Atkar-Khattra, Ming Sound Tsao, Stephen C. Lam, Janice Rudkowski
Journal: Journal of Clinical Oncology (2017)

1548 Background: Recruitment to clinic trials is typically poor. Among barriers to recruitment may be the limited knowledge of trialists with respect to marketing techniques. Improvements in marketing could decrease recruitment time and shorten the time to access new interventions. We hypothesized that a marketing plan would improve recruitment to a lung cancer screening study. Methods: The Pan-Canadian Early Detection of Lung Cancer Trial recruited subjects from 8 centres to a screening study of low-dose CT scan and autofluorescence bronchoscopy. Recruitment processes were undertaken independently at each centre. One centre (M) used marketing expertise and a marketing plan, including surveying study candidates for motivators, resulting in specific newsprint advertisements. Screened trial candidates provided demographic and tobacco use data and indicated how they had heard about the study (bus, friend/family, MD, mail, newsprint, radio, TV, other). No site paid for radio or TV time. We used regression analyses to assess whether newsprint advertisements were more effective for recruitment at site M compared with all other sites. Results: From 2008 to 2010, 7059 candidates contacted all centres for eligibility screening, including 779 at centre M. Overall, 50.2% were female; median age was 59 yrs. Compared with other centres, candidates at centre M had less education (p &lt; 0.001), a higher median 3-year lung cancer risk (2.3 vs 2.0%, p &lt; 0.001), but were more likely to have learned of the study by newsprint (58.8 vs 53.3%, chi-squared p = 0.004), and were more likely to be recruited (44.0 vs 34.9%, p &lt; 0.001). It was more likely that newsprint was the driver for screening contact among candidates with higher education level (OR 1.05/level), higher age (OR 1.03 / yr) and contact at site M (OR 1.31) (all &lt; 0.001). Recruitment after eligibility screening was higher when newsprint was the driver for contact on univariable but not multivariable analysis. Conclusions: The effectiveness of newsprint advertising in motivating study contact may be improved by the formal use of marketing expertise. Newsprint advertising may improve the likelihood of recruitment after study screening, possibly through improved initial self-screening by the candidate. Clinical trial information: NCT00751660.
Covered Cheatham-Platinum Stents for Aortic Coarctation
Authors: Aphrodite Tzifa, Peter Ewert, Grazyna Brzezinska-Rajszys, Bjoern Peters, Maria Zubrzycka, Eric Rosenthal, Felix Berger, Shakeel A. Qureshi
Journal: Journal of the American College of Cardiology (2006)
Global epidemiology of nonalcoholic fatty liver disease: Meta‐analytic assessment of prevalence, incidence, and outcomes
Authors: A. Lonardo, C.D. Byrne, S.H. Caldwell, H. Cortez‐Pinto, G. Targher
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Caldwell received grants from Gilead, Genfit, NGM, Immuron, Galmed, Taiwan, and Conatus. Author names in bold designate shared co‐first authorship. To the Editor: We appreciated Dr. Younossi and colleagues' meta‐analysis of the global prevalence, incidence, progression, and outcomes of nonalcoholic fatty liver disease (NAFLD).1 We believe that the topic is important, and we appreciate the opportunity to offer some comment and perspective on the concepts implicit in this work. Rather than being exclusively considered as always "the hepatic manifestation of the metabolic syndrome," it is conceivable that NAFLD should actually be considered a precursor of the metabolic syndrome.2 Strong evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidemia, and increases the risk of incident metabolic syndrome.3 Perhaps more importantly, the authors found that NAFLD was associated with liver‐related mortality but not with cardiovascular disease (CVD) mortality.1 To date, clear evidence indicates that CVD is the leading cause of death among NAFLD patients.3 Convincing evidence also substantiates a link between NAFLD and functional and structural cardiac abnormalities.3 Thus, we wonder whether the criteria adopted by the authors for selecting the studies (e.g., exclusion of studies including only patients with obesity or diabetes) may have led to underestimating the impact of NAFLD on overall and CVD mortality. In this regard, it is unclear why the authors included the same population‐based cohort of individuals, i.e., the Third National Health and Nutrition Examination Survey cohort, many times in their meta‐analysis (see supplementary table H). By using different selection criteria, other investigators concluded that NAFLD was associated with increased all‐cause and CVD mortality.4 These nuances of interpretation of the literature belie the complexity of modifiers of the NAFLD phenotype, such as genotype, lipid metabolism, inflammation, insulin resistance, and fibrosis, and whether NAFLD influences CVD risk, diabetes risk, or risk of other extrahepatic complications linked with NAFLD, such as chronic renal disease.2 We appreciate the authors' call for more liberal NAFLD screening policies. Based on recent analyses of epidemiological modifiers of NAFLD and preliminary cost‐utility analyses, we reached similar conclusions. Individuals belonging to NAFLD high‐risk groups warrant screening for fatty liver disease.5
Are we still adjusting to multigene panel testing? An NCI-designated cancer center's 2-year experience.
Authors: Chethan Ramamurthy, Mark A. Hitrik, Lyudmila DeMora, Andrea Forman, Kim Rainey, Michelle Savage, Susan Montgomery, Agnes Masny, Sharon Schwartz, Michael J. Hall, Mary Beryl Daly, Elias Obeid
Journal: Journal of Clinical Oncology (2017)

1585 Background: Genetic testing for hereditary cancer predisposition has rapidly changed over the past few years with the introduction of multigene panel testing. Multigene testing has evolved from disease-agnostic comprehensive (C) panels alone to include disease-specific but expanded (DSE) panels as well as guideline-based (GB) panels. We analyzed trends in utilization of genetic testing over a two-year period in one NCI-designated Cancer Center, hypothesizing that over time genetic testing usage would trend toward more disease-specific panels. Methods: We conducted a retrospective analysis of our program’s database for all germline genetic tests ordered from 9/1/2013 to 8/31/2015 (n = 619; 246 in year 1, and 373 in year 2). Tests were categorized into three groups based on specificity: GB (range: 2-12 genes tested), DSE (12-35 genes tested), and C (28-80 genes tested). The Chi-square test was used to analyze test types ordered in year 1 (9/1/2013-8/31/2014) and year 2 (9/1/2014 – 8/31/2015) and the proportions of resulting mutation types. Results: A total of 604 germline genetic tests met the inclusion criteria: 39 GB (20 year 1, 19 year 2), 171 DSE (43 year 1, 128 year 2), and 394 C (180 year 1, 214 year 2). Compared to year 1, a larger proportion of DSE tests (35% v. 18%, p &lt; 0.001), and a smaller proportion of C tests (59% v. 74%, p &lt; 0.001) and GB tests (5% vs. 8%, p = 0.146) were ordered. DSE panels revealed a pathogenic variant (PV) at a rate of 16% and a variant of unknown significance (VUS) at a rate of 24%. C tests revealed a PV and VUS at rates of 14% and 29%, respectively. GB tests revealed a PV and VUS at rates of 21% and 18%, respectively. No statistically significant differences in detection rates of mutation types (PV or VUS) were found between GB, DSE, or C tests. Conclusions: The rates of PV detection were not significantly different between test types, but the profile of tests ordered changed over time to favor DSE panels. Exploration of factors contributing to changing trends in genetic testing are warranted as counselors and clinicians adapt to the quickly expanding number of genes associated with hereditary cancer risks, many of them moderate-risk, and the evolving landscape of multigene panel testing.
Phase I study of ABBV-399, a c-Met antibody-drug conjugate (ADC), as monotherapy and in combination with erlotinib in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Eric Angevin, John H. Strickler, Colin D. Weekes, Rebecca Suk Heist, Daniel Morgensztern, John J. Nemunaitis, Xiaolin Fan, Juliette Beaulieu, Monica Motwani, Daniel E. Afar, Louie Naumovski, Karen Kelly
Journal: Journal of Clinical Oncology (2017)

2509 Background: The c-Met receptor is overexpressed in ~50% of pts with NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data demonstrate that ABBV-399 can deliver a potent cytotoxin directly to c-Met+ tumor cells. Methods: ABBV-399 was administered at doses ranging from 2.4 to 3.0 mg/kg (dose expansion and combination cohorts at 2.7 mg/kg) once every 21 days to 29 pts with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) NSCLC both as monotherapy (ABBV-399/monoT; 16 pts) and in combination with oral erlotinib 150 mg daily (ABBV-399/ERL; 13 pts) (NCT02099058). c-Met overexpression was assessed by IHC utilizing the SP44 antibody (Ventana; Tucson, AZ, USA). Results: As of January 9, 2017, 16 pts with c-Met+ NSCLC received ≥1 dose of ABBV-399/monoT. Monotherapy treatment-related adverse events (TRAEs) occurring in ≥10% of pts (all dose levels and all grades) were fatigue (43.8%), nausea (37.5%), neuropathy (25.0%), vomiting (18.8%), and anemia, constipation, and diarrhea (12.5% each). Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC pts had a confirmed partial response (PR) with duration of response (DOR) 3, 4.5, and 10+ months. At week 12, 6 of 16 pts (37.5%) had disease control. TRAEs in ABBV-399/ERL occurring in ≥10% of pts (all grades) were neuropathy (30.8%), and acneiform rash, diarrhea, fatigue, nausea, and dry skin (15.4% each). Four of 13 (31%) evaluable ABBV-399/ERL–treated c-Met+ pts had a PR (3 confirmed, 1 unconfirmed) with DOR 1+, 2.7, 5.3+, and 11+ months. Three of the 4 pts with PR had EGFR-mutated tumor and recently progressed on TKI. At week 12, 8 of 13 pts (61.5%) had disease control. There were no treatment-related deaths as monotherapy or in combination with erlotinib. Responses were seen in both squamous and non-squamous histology. Conclusions: ABBV-399 is well tolerated at 2.7 mg/kg once every 21 days and has demonstrated antitumor activity in pts with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated efficacy/safety data and MET gene status will be presented. Clinical trial information: NCT02099058.
Breast cancer metastases to cerebellum.
Authors: Zorica Tomasevic, Zoran M. Tomasevic, Zeljko Kovac, Zorka Milovanovic
Journal: Journal of Clinical Oncology (2014)

e11600 Background: According to scarce literature data, approximately 10% of breast cancer (BC) patients develop metastases to cerebellum. However, details about patient characteristics, time to metastases development or molecular subtypes of BC that metastasize to this part of brain are not available. Methods: The aim of this study is to define the percentage of BC cerebellar metastases from a prospective single center data base. Molecular BC characteristics, time to development, brain directed treatment and survival after cerebellar metastases were also analyzed. Results: From January 2007 to December 2013, 242 BC patients with brain metastases are registered. Eighteen patient (18/242;7,4%) had cerebellar metastases. Median age in this subgroup was 43,5 (range 29-63) years. Histology of the primary BC was: ductal carcinoma (66,6%), lobular carcinoma (27,7%) and was not specified in 1 patient (5,5%). Her2 3+ was confirmed in 13/18 (72,2%). Estrogen/progesterone receptors were negative in 50% of primary BC. Median time from BC diagnosis was 23 months (range 1-42). Cerebellar metastases were first metastatic site in 11/18 patients (61%) and 8/11 (73%) had Her2 3+BC. All patients have been treated with WBRT. Neurosurgery was performed in 11 (61%) patients with solitary lesion. Survival after cerebellar metastases was median 13 months (range 2-84+). Conclusions: Amongst 242 BC patients with brain metastases, 18 (7,4%) had cerebellar metastases. In that subgroup, Her2 over-expression was higher than expected (13/18;72,2%). Compared to all Her2 3+BC (73/242;30%) from our data base, cerebellar metastases were diagnosed in 17,8% (13/73), and only in 3% (5/169) of patients with Her2 negative BC. Majority (11/18; 61%), developed cerebellar metastases as a resectable, first metastatic site, and 73% (8/11) of these patients had Her2 3+ BC, treated with trastuzumab. Our results suggest that Her2 3+ BC has a greater propensity to metastasize to cerebellum than Her2 negative BC.