tbuckley/cabot-search huggingface dataset:
Population-based patterns of palliative systemic therapy use in elderly patients with metastatic colorectal cancer (mCRC).
Authors: Matthew Chan, Gillian Gresham, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

9547 Background: Elderly cancer patients are consistently under-represented in clinical trials, which may lead to under-treatment. Our aims were to 1) determine the impact of advanced age on use of palliative systemic therapy in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: All patients diagnosed with mCRC from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada were reviewed. Summary statistics were used to describe treatment patterns between elderly patients (EP; &gt;/=70 years) and young patients (YP; &lt;70 years). Cox regression models that adjusted for age and confounders were used to determine the effect of systemic therapy on overall survival (OS). Results: We identified 1,013 patients: median age was 67 years (range 23-93); 42% were elderly and 58% were young; 57% were men; and 66% had ECOG 0/1. Compared to YP, fewer EP were offered systemic therapy (46 vs 76%, p&lt;0.001). Among those treated, EP were less likely than YP to be given combination chemotherapy (47 vs 81%, p&lt;0.001) and bevacizumab (19 vs 47%, p&lt;0.001). Most common reasons for no treatment were similar in EP and YP: patient choice (32% for both), poor ECOG (18% of EP and 16% of YP), and significant comorbidities (11% for both). Advanced age alone was also cited as a reason among EP (7%) for not receiving therapy. In the subset that was treated, risk of adverse events (24 vs 14%, p=0.24) and early treatment discontinuations (14 vs 13%, p=0.88) were comparable between EP and YP, respectively. Receipt of systemic therapy was associated with improved OS in both the elderly (HR for death 0.45, 95% CI 0.37-0.56, p&lt;0.001) and the young (HR for death 0.43, 95% CI 0.35-0.53, p&lt;0.001), regardless of age (p interaction of age and treatment &gt;0.05). Conclusions: In this population-based cohort of mCRC, EP were more likely to receive no treatment, monotherapy rather than combination therapy, or a regimen without bevacizumab. In carefully selected EP, however, it appears that rate of adverse events, frequency of early treatment discontinuations, and magnitude of survival benefit from systemic therapy were comparable to YP.
Expression of mTOR in diffuse large B-cell lymphoma.
Authors: Srivalli Gopaluni, Neerja Vajpayee, Nancy Newman, Charu Thakral, Juhi Husain, Ajeet Gajra
Journal: Journal of Clinical Oncology (2012)

e18535 Background: The mammalian target of rapamycin (mTOR) pathway mediates protein synthesis, cell growth and survival of normal and malignant cells. This pathway is constitutively activated in several B-cell lymphomas. We studied immunohistochemical expression of mTOR, phosphorylated mTOR (pmTOR) and bcl-2 in 55 cases of diffuse large B-cell lymphomas (DLBCL) and their association with established prognostic factors as well as treatment outcomes in a retrospective single instituition study. Methods: After IRB review, 55 cases of DLBCL were identified. Immunostains for mTOR, pmTOR and bcl-2 were performed and their expression correlated with clinical and survival data. Associations of demographic (age and gender), clinical (stage, IPI score) and chemotherapy (RCHOP or other) with marker expression as well as association with recurrence and survival were studied using chi square and t-test for univariate analysis and logistic regression for multivariate evaluation. Results: Of the 55 patients, 44% were &gt; age 65, 65% were males and 65% had advanced stage (III or IV) disease. High IPI scores were noted in 42% and 87% received the RCHOP regimen.On univariate analysis, high mTOR expression was associated with male gender (85% vs. 46%, p&lt;0.01), high IPI score (67% vs. 18%, p, 0.001) and higher mean age (66 vs. 53 years, p &lt; 0.001). With high mTOR expression a trend towards higher stage ( 78% vs 54% p=0.08) and likelihood of poor overall survival (defined as survival &lt;3 years; 41% vs 18% p =0.08) was noted. Further, on univariate analysis bcl-2 expression was associated with higher risk of recurrence (35% vs.11%, p 0.05) whereas no association with clinical factors or outcomes was noted with pMTOR expression. On multivariate analysis the only parameter found to be significant was IPI [0R 11.6 95% CI 1.4-100]. Conclusions: High mTOR expression is associated with gender, age, IPI and showed a trend towards advanced stage and shorter survival. This target needs to be investigated prospectively in DLBCL as a prognostic factor and predictive marker. Given the availability of several mTOR inhibitors, the natural history of patients with poor risk DLBCL(high IPI) with high expression of mTOR may be favorably altered.
Recent Trends in Adherence of Physical Activity and Sedentary Behavior—We Need to Move More and Sit Less
Authors: Katrina L. Piercy
Journal: JAMA Network Open (2019)

Yang Du, MD, MS; Buyun Liu, MD, PhD; Yangbo Sun, MD, PhD; Linda G. Snetselaar, PhD; Robert B. Wallace, MD; Wei Bao, MD, PhD
Serum HER2 in the context of circulating tumor cells in patients with metastatic breast cancer.
Authors: Volkmar Mueller, Sabine Riethdorf, Brigitte Kathrin Rack, Wolfgang Janni, Peter A. Fasching, Erich Solomayer, Bahriye Aktas, Sabine Kasimir-Bauer, Klaus Pantel, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2012)

10599 Background: Circulating tumor cells (CTC) reflect an aggressive tumor behavior by hematogenous tumor cell dissemination. Overexpression of HER2 in breast cancer (BC) is associated with increased angiogenesis and therefore potentially linked to increased hematogenous tumor cell spread. The aim of the analysis was to investigate whether concentrations of serum HER2 (sHER2) deliver prognostic information in the context of CTC detection in metastatic BC patients. Methods: Blood was obtained in a prospective multicenter setting from 254 patients with metastatic BC at the time of disease progression. sHER2 was determined using a commercial ELISA-kit (Wilex). CTC were detected with the CellSearch system (Veridex). Patients received systemic treatment according to national and international guidelines including HER2-targeted treatment. Results: Five or more CTC were detected in 122 of 245 evaluable patients (49.8%).119 of 251 (47%) metastatic patients had serum sHER2 levels above 15ng/mL. Median PFS was 9.2 months (95%-CI: 9.9 – 13.0 mths) with elevated sHER2 versus 11.4 mths (9.9 – 13.0 mths) with non-elevated levels (p=0.07). OS was 17.4 mths (14.6 – 20.3 mths) vs. 26.5 mths (23.1-29.8 mths; p&lt;0.01). In patients with 5 or more CTC, serum levels were above the cut-off for sHER2 in 61% vs. 33% in those with less than 5 CTC (p&lt; 0.01). Patients with elevated sHER and 5 or more CTC hat a PFS of 9.1 mths (7.2 – 11.1 mths) and a OS of 14.5 mths (11.8 – 17.2 mths), those with non-elevated sHER2 and less than 5 CTC a PFS of 12.1 (10.1 – 14.1 mths) and a OS of 29.5 month (25.4 – 33.6 mths) (p=0.15 for PFS and p&lt; 0.01 for OS). Including sHER2, CTC and established prognostic factors in the multivariate analysis, the presence of CTC, line of therapy, ER and HER2 status of the primary tumor remained independent predictors of OS. Conclusions: Elevated serum levels of sHER2 are associated with the presence of CTC and indicate poor clinical outcome. However, sHER2 has no independent prognostic value when presence of CTC were taken into account.
Subcutaneous omacetaxine mepesuccinate in patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) resistant/intolerant to two or three approved tyrosine-kinase inhibitors (TKIs).
Authors: Franck E. Nicolini, Jeffrey Howard Lipton, Hagop Kantarjian, Meir Wetzler, Luke Paul Akard, Michele Baccarani, Adam Craig, Nisha Nanda, Peter D. Brown, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6513 Background: Omacetaxine mepesuccinate (“omacetaxine”) is a first-in-class, reversible, transient inhibitor of protein elongation that facilitates tumor cell death without depending on BCR-ABL signaling. Clinical activity was shown in two phase 2, open-label, multicenter studies in treatment-resistant CML. Methods: A subset from the phase 2 studies included patients in CP or AP who were resistant/intolerant to ≥2 approved TKIs. Omacetaxine 1.25 mg/m 2 was given SC twice daily: ≤14 consecutive days/28-day cycle for induction, ≤7 days/cycle as maintenance. Secondary results were calculated for responses by number of prior TKIs. Results: Of 122 patients (median age, 60 years), 62 had received 2 TKIs (100% imatinib; 76% dasatinib; 24% nilotinib) and 60 had received all 3 approved TKIs. Prior non-TKI therapies (eg, 52% hydroxyurea, 34% interferon) were common. Of 45 CP patients in the 2 TKI group, 12 (27%) had major cytogenetic response (MCyR; median duration of 17.7 mo), and of 36 in the 3 TKI group, 4 (11%) had MCyR (median duration not reached). Of 17 AP patients in the 2 TKI group, 6 (35%) had major hematologic response (MaHR; median duration, 13.4 mo), and of 24 in the 3 TKI group, 5 (21%) had MaHR (median duration, 6.4 mo). Median months of survival in the 2 and 3 TKI groups were 30.1 and not reached for CP and 12.0 and 24.6 for AP. Treatment-related grade 3/4 adverse events (AEs) occurred in 52 (84%) patients in the 2 TKI group and 42 (70%) in the 3 TKI group (most common: thrombocytopenia [71%, 48%]). Fifteen (24%) and 16 (27%) had an AE leading to discontinuation, primarily disease progression. There were 20 deaths (primarily disease progression), 11 in the 2 TKI group and 9 in the 3 TKI group; 4 were considered related to treatment (sepsis in 2, pancytopenia, febrile neutropenia). Conclusions: In patients with heavily pretreated CML, response to omacetaxine therapy occurred whether they had received 2 or 3 prior TKIs. The drug was well tolerated. Tolerability was similar across the TKI groups in both CP and AP patients. Support: Teva Pharmaceutical Industries Ltd.
Clinical implication of PET/CT and skeletal bone survey in evaluation of multiple myeloma and related monoclonal disorders.
Authors: Muhammad Jawad Popalzai, Homam Alkaied, Maryah Mansoor, Arnold Brenner, Qun Dai
Journal: Journal of Clinical Oncology (2012)

e18574 Background: Whole body skeletal x-ray is considered a gold standard for detecting bone lesions in patients with plasma cell disorders. PET/CT has been increasingly used but its role is yet to be defined. We conducted this study to compare the role of these two imaging modalities in evaluation of plasma cell disorders. Methods: This is single institution, retrospective study to evaluate the role of skeletal survey and PET/CT in patients with multiple myeloma, smoldering myeloma and MGUS. Patients’ records, imaging reports and subsequent management plan were reviewed and compared. Results: A total of 16 patients were reviewed. Among them, 11 patients had multiple myeloma, 2 had smoldering myeloma, and 3 had MGUS. 7/11 patients with multiple myeloma had concordant findings on skeletal survey and PET. 3 of these patients had negative skeletal surveys but had positive finding on PET/CT. PET/CT also identified plasmacytomas in 2 patients. In 2 patients with smoldering myeloma, both skeletal survey and PET/CT were negative. 2/3 patients with MGUS had lytic lesions on skeletal surveys which were not revealed by subsequent PET/CT’s. Both patients were observed without treatment and at 2 years follow up did not show disease progression. Conclusions: Our retrospective analysis showed that skeletal survey is still important for base-line evaluation of bone lesions in multiple myeloma and related monoclonal disorders. PET/CT is more sensitive for detection of bone lesions and can also detect extraosseous lesions such as plasmacytomas. Using tumor metabolic activity, PET/CT may improve diagnostic accuracy and is complementary to conventional skeletal survey. [Table: see text]
CD97 is a critical regulator of acute myeloid leukemia stem cell function
Authors: Gaëlle H. Martin, Nainita Roy, Sohini Chakraborty, Alexis Desrichard, Stephen S. Chung, Carolien M. Woolthuis, Wenhuo Hu, Iryna Berezniuk, Francine E. Garrett-Bakelman, Jörg Hamann, Sean M. Devlin, Timothy A. Chan, Christopher Y. Park
Journal: The Journal of Experimental Medicine (2019)

Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSCs) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G protein–coupled receptors (GPCRs), as a frequently up-regulated antigen on AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. These phenotypes are due to CD97’s ability to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML.
Comparison of 11C-Choline and 11C-Methionine PET/CT in Multiple Myeloma
Authors: Constantin Lapa, Malte Kircher, Matteo Da Via, Martin Schreder, Leo Rasche, K. Martin Kortüm, Hermann Einsele, Andreas K. Buck, Heribert Hänscheid, Samuel Samnick
Journal: Clinical Nuclear Medicine (2019)

Purpose PET/CT with both 11 C-choline and 11 C-methionine has recently been reported to offer advantages over 18 F-FDG for imaging in multiple myeloma (MM). The aim of this study was to directly compare the diagnostic performance of both non-FDG radiotracers in MM patients. Methods Nineteen patients with a history of MM (n = 18) or solitary bone plasmacytoma (n = 1) underwent both 11 C-choline and 11 C-methionine PET/CT for diagnostic imaging. In this retrospective analysis, scans were compared on a patient and on a lesion basis. In 12 patients, respective tracer uptake in the iliac crest was correlated with the extent of malignant bone marrow plasma cell infiltration. Results 11 C-methionine detected more intramedullary MM lesions in 8 (42.1%) of 19 patients. In the remainder (11/19 [57.9%]), both 11 C-choline and 11 C-methionine provided equal results. 11 C-methionine demonstrated higher lesion-to-muscle ratios ( P = 0.0001). In the 12 patients in whom a recent bone marrow biopsy was available, SUVmean as well as SUVmax correlated significantly with the degree of malignant plasma cell infiltration for both 11 C-methionine (SUVmean: r = 0.85, P &lt; 0.001; SUVmax: r = 0.82, P = 0.001) and 11 C-choline (SUVmean: r = 0.72, P &lt; 0.008; SUVmax: r = 0.73; P = 0.006). Conclusions Our data suggest that 11 C-methionine PET/CT might be more sensitive than 11 C-choline PET/CT for the detection of active MM lesions.
Sociodemographic disparities in treatment receipt for prostate cancer: A population-based study.
Authors: Marianna De Camargo Cancela, Linda Sharp, Maria Kelly, Harry Comber
Journal: Journal of Clinical Oncology (2012)

e16514 Background: Prostate cancer (PC) treatment remains controversial. Little is known about how this controversy plays out in routine clinical practice. Most studies of treatment patterns are from the US, specialist centres, and/or involve selected patients. In a national, population-based analysis, using linked cancer registration and hospital in-patient data, we investigated associations between socio-demographic and clinical factors and PC treatment in Ireland. Methods: PC cases (ICD10 C61) diagnosed 2002-2008, and with a hospital in-patient episode within one year of diagnosis (n=9658) were included. Comorbidity (assessed by Charlson and Elixhauser indices) was determined from diagnoses on hospital episodes. Multinomial logistic regression was used to investigate associations between age, marital status, smoking status, area of residence, deprivation category, comorbidity, diagnosis period, stage and Gleason score, and receipt of different treatment modalities. Results: Age was a significant determinant of treatment receipt, after adjusting for socio-demographic and clinical factors. Compared to younger men, men aged ≥70 were significantly less likely to undergo radical prostatectomy (RP), and significantly more likely to be treated by TURPS, androgen deprivation therapy (ADT) or radiotherapy with ADT. Within the 40-69 age-group, likelihood of RP decreased with increasing age. After adjusting for age and other factors, presence of comorbidities, overall, had a moderate impact on treatment receipt. Some conditions had a stronger effect (e.g. congestive heart failure). There were strong variations in treatment by area of residence, which persisted after adjustment for age, comorbidity and other factors. Conclusions: These results suggest socio-demographic factors, including patient age and area of residence, strongly influence PC treatment. Strategies to reduce these disparities have potential to improve PC survival and mortality in the population.
Immunotherapy in small-cell lung cancer: from molecular promises to clinical challenges
Authors: A. Pavan, I. Attili, G. Pasello, V. Guarneri, P. F. Conte, L. Bonanno
Journal: Journal for ImmunoTherapy of Cancer (2019)

Management of small cell lung cancer (SCLC) has not changed over the last decades. In more recent years, alterations of DNA repair machinery and other molecular pathways have been identified in SCLC and preclinical data suggest that dysregulation of these pathways might offer new therapeutic opportunities. While immune checkpoint inhibitors (ICIs) have had a major impact on the clinical outcome of several solid tumors, including non-small cell lung cancer, the potential role of ICIs is currently under investigation in SCLC and some promising data are available. However, several clinical and biological hurdles have to be overcome and predictive markers are still eagerly needed. Knowledge of molecular pathways specifically involved in SCLC growth and treatment resistance is essential for a more rational planning of new combinations including ICIs. The present manuscript summarizes the current clinical evidence on immunotherapy in SCLC, describes the molecular bases underlying treatment resistance and discusses the potentialities and the rationale of different therapeutic combinations.
Hormone receptor-dependent regulation of ABAT and beta-alanine metabolism in breast cancer.
Authors: Jan Budczies, Scarlet F. Brockmoeller, Berit Mueller, Manfred Dietel, Oliver Fiehn, Carsten Denkert
Journal: Journal of Clinical Oncology (2013)

11112 Background: Recently, we identified beta-alanine as biomarker for breast cancer using GC-MS based metabolomics. Beta-alanine is increased in breast cancer compared to normal tissues and in the more aggressive ER- subtype compared to ER+ breast cancer. Beta-alanine is a substrate of 4-aminobutyrate aminotransferase (ABAT), can be catabolised to malonate semialdehyde and used for reduction of NAD and acetylation of coenzyme A. The aim of the current study is to analyze ABAT protein and RNA expression in a large cohort of breast cancers. Methods: The specificity of a polyclonal antibody against ABAT was validated using siRNA in MFC7 cells. A cohort of 164 paraffin-embedded breast cancer tissues from the METAcancer biobank was investgated by immunohistochemistry. Tumor cells were evaluated separately for staining intensity (low, moderate or high) and percentage of stained cells. A cohort of 156 METAcancer samples was investigated for gene expression using whole genome DASL. Results: ABAT protein intensity correlated strongly with estrogen receptor (ER) status (p &lt; 0.001), but not with HER2 status. In particular, the ABAT protein was highly expressed in 41% of the ER+ tissues, but only in 2% of the ER- tissues. Further, ABAT intensity correlated strongly with tumor grade (p &lt; 0.001). ABAT intensity did not correlate with tumor stage or nodal status. Explorative evaluation of ABAT protein in normal cells revealed weak expression in some of the ducts and negative expression in adipose cells. ABAT protein and RNA expression strongly correlated in the subcohort investigated by DASL. Analysis of a large external data set (publicly available at www.kmplot.com) showed that low ABAT expression is associated with an unfavorable prognosis of breast cancer. Both, ABAT protein and RNA expression, showed a strong negative correlation with beta-alanine abundance. Conclusions: We reported on changes in beta-alanine metabolism that occur between the molecular subtypes of breast cancer and normal breast tissue. High expression of ABAT in ER+ breast cancer is compatible with catabolic use of beta-alanine. Differently, beta-alanine might be preferable used anabolic in ER- breast cancer, possibly for the synthesis of carnosine.
Assignment of virus and antimicrobial resistance genes to microbial hosts in a complex microbial community by combined long-read assembly and proximity ligation
Authors: Derek M. Bickhart, Mick Watson, Sergey Koren, Kevin Panke-Buisse, Laura M. Cersosimo, Maximilian O. Press, Curtis P. Van Tassell, Jo Ann S. Van Kessel, Bradd J. Haley, Seon Woo Kim, Cheryl Heiner, Garret Suen, Kiranmayee Bakshy, Ivan Liachko, Shawn T. Sullivan, Phillip R. Myer, Jay Ghurye, Mihai Pop, Paul J. Weimer, Adam M. Phillippy, Timothy P. L. Smith
Journal: Genome biology (2019)

We describe a method that adds long-read sequencing to a mix of technologies used to assemble a highly complex cattle rumen microbial community, and provide a comparison to short read-based methods. Long-read alignments and Hi-C linkage between contigs support the identification of 188 novel virus-host associations and the determination of phage life cycle states in the rumen microbial community. The long-read assembly also identifies 94 antimicrobial resistance genes, compared to only seven alleles in the short-read assembly. We demonstrate novel techniques that work synergistically to improve characterization of biological features in a highly complex rumen microbial community.
An Observational, Non-Interventional, Multicentre Study of Immune Thrombocytopenia: The Africa Middle East and Asian Immune Thrombocytopenia Registry
Authors: Faisal Alsayegh, Mohammed Qari, Mervat Matar, Yasser Wali, Muhammad Kanani, Ali Al Madhani, Ibrahim Al Hijji, Doaa El Demerdash, Mahmoud Abbas
Journal: Blood (2017)