tbuckley/cabot-search huggingface dataset:
Prognostic impact of aberrant t/NK cell marker expression in AML.
Authors: Abhijit Balkrishna Saste, Rohit Gulati, Philip Kuriakose, Kedar Inamdar, Kristin Karner, John Carey, Madhu Menon
Journal: Journal of Clinical Oncology (2016)

e18502 Background: Aberrant expression of NK and T cell antigens (NK/T) in AML blasts is well known.However,their influence on EFS(after standard first line AML induction) & OS has not been well studied.We conducted such an analysis in AML with normal cytogenetics.We also studied the prognostic significance of NK/T expression in FLT3 & NPM1 negative cases. Methods: A retrospective analysis of 266 cases of AML over 10 years was conducted. Flow cytometry done at the time of initial diagnosis was available for 201 of the 266 cases.NK/T cell markers such as CD2,CD3,CD5,CD7 & CD56,available in 83 cases,were analyzed.NK/T positivity threshold was set at > 20% of the gated blast population. EFS and OS were compared between NK/T+ and NK/T- groups using log-rank tests/Kaplan-Meier curves.FLT3 and NPM1 proportions in NK/T+ and NK/T- cases were compared using Fisher’s exact test. Results: NK/T+ and NK/T- frequencies were 46% (38/83) and 54% (45/83) respectively. Amongst NK/T+ cases CD56 (67%) was the most commonly expressed marker and
Correlating wearable activity monitor data with PROMIS detected distress and physical functioning in advanced cancer patients.
Authors: Arvind Manohar Shinde, Gillian K. Gresham, Andrew Eugene Hendifar, Quanlin Li, Brennan Spiegel, Bj Rimel, Christine S. Walsh, Richard Tuli, Steven Piantadosi, Robert A. Figlin
Journal: Journal of Clinical Oncology (2017)

e21689 Background: Patients with advanced cancer experience significant distress. Timely identification and treatment of distress can improve outcomes and quality of life. Domains of distress (i.e. pain, fatigue, physical function) can be assessed using patient reported outcome (PRO) questionnaires. However, PROs can be burdensome to patients, particularly when performed serially. Given the relationship between physical activity and sleep with domains of distress, wearable activity monitors may assist in the real-time detection of distress in advanced cancer patients. Methods: We conducted a prospective, observational study at Cedars-Sinai Medical Center and enrolled patients with measurable stage 3+ cancer, ≥18yr, English speaking, ambulatory, with a smartphone, and prognosis of &gt; 3 months. Patients wore a Fitbit Charge HR continuously through 3 consecutive clinic visits, and completed NIH PROMIS tools (Physical Function, Pain, Sleep, Fatigue, and Emotional Distress) during visits. Fitbits recorded average daily step counts, stairs climbed, and sleep time. We conducted regression analyses that adjusted for baseline confounding variables and accounted for correlated responses. Results: 35 patients (Mean age 62; 53% males; 82% GI cancers) were evaluated. Patients had ECOG PS of 0 (20%), 1 (40%), 2 (23%), and 3(17%). The table below displays regression coefficients for steps, floors, and sleep in each PROMIS distress domain. Conclusions: There is a significant association between steps and floors climbed with multiple domains of distress and physical functioning. The lack of association between total sleep time and these PROs, may suggest that other metrics of sleep quality (i.e. awakenings), may be more relevant. These findings support further exploration of wearable data as a continuously monitored PRO surrogate in advanced cancer patients; wearable data should be further validated for use in both clinical and therapeutic trial settings. Clinical trial information: NCT02659358. [Table: see text]
Neutrophil count and efficacy of chemoradiation in patients with locally advanced unresectable pancreatic carcinoma: An ancillary study of in the LAP 07 trial.
Authors: Antoine Schernberg, Dewi Vernerey, David Goldstein, Jean Luc Van Laethem, Bengt Glimelius, Paul Van Houtte, Franck Bonnetain, Christophe Louvet, Pascal Hammel, Florence Huguet
Journal: Journal of Clinical Oncology (2017)

4120 Background: Predictive biomarkers of Overall Survival (OS) and Progression Free Survival (PFS) in locally advanced pancreatic cancer (LAPC) pts are mandatory. Baseline leukocyte, neutrophil and monocyte counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts. Efficacy of chemoradiation (CRT) depending on neutrophil count was retrospectively analyzed in the largest Phase III cohort of LAPC. Methods: The international multicenter randomized LAP07 phase III trial (NCT00634725) has recruited 442 LAPC pts. We have studied the predictive and prognostic value of systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil count &gt; 7 G/L at first randomization) or (ii)increased absolute neutrophil count (IANC) after induction chemotherapy vs baseline. Univariate and multivariate Cox analysis evaluated the benefit of CRT for OS, PFS and Local Control (LC) in pts without systemic inflammation. Results: Patients with baseline neutrophilia (11%) had a worse OS (median 8.9 vs 13.3 months, p = 0.01). At 2nd randomization, 9% and 29% pts had baseline neutrophilia or IANC, respectively. Both neutrophilia (median OS 10.6 vs 16.1 months, p = 0.03) and IANC (median OS 14.6 vs 17.4 months, p = 0.02) predicted poor OS. Systemic inflammation predicted local resistance to CRT (p = 0.02, interaction = 0.015). After excluding pts with systemic inflammation, 1-year local control was 80% in CRT vs 54% in chemotherapy arms (p &lt; 0.001). Pts without systemic inflammation in CRT arm had improved PFS vs chemotherapy arm (median 10.3 vs 8.3 months, p = 0.04). In multivariate analysis in this population, CRT increased PFS (HR = 0.66, 95%CI: 0.45 - 0.97, p = 0.03), after adjusting on age, tumor size, pain at enrollment, albumin, and CA 19.9 according to PROLAP nomogram parameters. Conclusions: In LAPC pts with tumor controlled after induction chemotherapy, systemic inflammation may help to better predict those who will benefit from CRT. This result may impact clinical management and the design of future clinical trials for LAPC. An external validation with a cohort from the ARCAD pancreas meta-analysis is under consideration. Clinical trial information: NCT00634725.
Impact of NET MDT on overall survival within NETwerk, a collaborative ENETS Center of Excellence.
Authors: Timon Vandamme, Lesley De Backer, Marc Simoens, Pascale Abrams, Ann Driessen, Bart Op de Beeck, Wim Demey, Tim Rondou, Marijke Ulenaers, Geert Roeyen, Willem Lybaert, Marc Peeters
Journal: Journal of Clinical Oncology (2018)

e18861 Background: Since January 2016, patients with neuroendocrine tumors of 9 hospitals in the Antwerp-Waasland region in Belgium, are jointly discussed during NET specific multidisciplinary tumor boards (NET MDT), additionally to a local MDT. This network (NETwerk), obtained the certificate of ENETS Centre of Excellence in 2017. The aim is to report NET MDT impact on treatment decision and 5-year overall survival outcome of NET cases, treated within NETwerk and diagnosed between January 2011 and February 2018. Methods: All patients, discussed on the NET MDT, were prospectively included in the NETwerk database. Patient recruitment occurs by treating physician or by pathologist referral. Treatment decision data, date of diagnosis, age at diagnosis, sex, tumor grade (WHO 2010) and date of death were collected. Overall survival rates were calculated at 3 and 5 years using Kaplan Meier statistics. Results: In 41 NET MDTs, 280 patients were discussed (table). For 80% of the NET cases, treatment plans were the same in local and NET MDT. In 20% of the cases, the NET MDT advised additional therapeutic and diagnostic interventions compared to the local MDT. In metastatic diseases, 5-year survival rate was 34.9%. For pancreatic NETs, the 5-year survival rate was 63.8% while patients with small intestine NETs had a 5-year-survival rate of 77.9%. According to tumor grade, 5-year survival of grade 1 and grade 2 tumors was 80.7% and 67.3% respectively. For grade 3 tumors, no patients survived up to 5 years. In this grade 3 group, 3-year survival rate was only 43.2%. Conclusions: The implementation of the joint NET MDT, leads to more specialized disease management. Patients within NETwerk have a good prognosis, even in metastatic setting, conforming the relative indolent course of NETs. Our cohort contains a large proportion of WHO grade 3 NETs. These grade 3 tumors only have limited survival, demonstrating the need for new treatment strategies. Patients characteristics (n = 280) Median age at diagnosis 64 years Sex (female) 43.5% Primary - Pancreas 22.8% - Small intestine 17.1% - Appendix 11.7% - Rectum 16.7% - Colon 5.0% - Lung 7.5% - Unknown 7.8% - Other 11.0% WHO grade - Grade 1 44.6% - Grade 2 23.9% - Grade 3 23.2% - Unknown 8.2% Metastases at diagnosis 18.2%
Role of ofatumumab (OFA) maintenance treatment in relapsed chronic lymphocytic leukemia (CLL): Final analysis of PROLONG study.
Authors: Marinus Van Oers, Lukas Smolej, Mario Petrini, Fritz Offner, Sebastian Grosicki, Mark-David Levin, Jaclyn Davis, Tommaso Stefanelli, Hiya Banerjee, Petra Hoever, Christian Geisler
Journal: Journal of Clinical Oncology (2018)

7517 Background: An interim analysis of the PROLONG phase 3 study in patients (pts) with CLL showed a significant increase in progression free survival (PFS) with OFA maintenance without unexpected side effects (van Oers, et al, 2015). Here, we present the final analysis of the study. Methods: Pts in complete or partial remission after 2nd or 3rd line treatment for CLL were randomized 1:1 to OFA (300 mg followed 1 week later by 1000 mg every 8 weeks for up to 2 years) or to observation (Obs) arm. The primary endpoint was investigator-assessed PFS. Secondary endpoints included time to next treatment (TTNT), overall survival (OS), and safety. Results: Overall, 480 pts were randomized to either OFA arm or Obs arm. Baseline characteristics were similar between the 2 arms. Median duration of OFA treatment was 608 days. Median follow-up was 40.89 months (mo). Median PFS was 34.17 mo for OFA (95% confidence interval [CI]: 29.70, 38.01) and 16.89 mo (95% CI: 12.98, 20.37) for Obs (Hazard ratio [HR] = 0.55; 95% CI: 0.43, 0.70; P < 0.0001) arm. Median TTNT was 37.36 mo (95% CI: 30.55, 42.61) for OFA and 27.56 mo (95% CI: 23.52, 32.62) for Obs (HR = 0.72; 95% CI: 0.57, 0.91; P < 0.0044). The OS data although not yet mature, do not show a difference (HR = 0.99; 95% CI: 0.72, 1.37). Death rate was similar in both the arms (32% in OFA vs. 29% in Obs). Adverse events (AEs) were reported in 92% of pts in OFA arm vs. 82% in Obs arm; 62% of pts in OFA arm had ≥grade 3 AEs vs. 51% in Obs arm. Serious AEs (SAEs) were reported in 48% of pts in OFA vs. 46% in the Obs arm. Most common ( > 5% of all pts) ≥grade 3 AEs were neutropenia (OFA: 23% vs Obs: 10%), pneumonia (OFA: 13% vs Obs: 12%), febrile neutropenia (OFA: 6% vs Obs: 4%), and pyrexia (OFA: 5% vs Obs: 2%). Due to AEs, 12% of pts discontinued OFA permanently. Up to 60 days after the last treatment, there were 5 SAEs leading to death in the OFA arm vs 7 in the Obs arm; none were considered to be related to the study drug. Conclusions: This final analysis confirmed the results of the interim analysis, the treatment effect of maintenance OFA was maintained with more mature data. A significant clinical benefit was observed in pts with relapsed CLL after OFA maintenance. Treatment was well tolerated without unexpected toxicities. Clinical trial information: NCT01039376.
Elevated plasma levels of hTERT mRNA and DNA in patients with gastric cancer in Northwest of Iran
Authors: S.S. Hosseini-Asl, H. Akhavan
Journal: Annals of Oncology (2018)

Background: Gastric cancer (GC) as the fourth common cancer over the world and responsible for the second cause of cancer-related deaths, has high incidence rate in Iran and especially in its North-Western province, Ardabil. In this study, the circulating hTERT mRNA and DNA were studied in patients affected with GC in Ardabil. Methods: Using conventional PCR and RT-PCR, Q-PCR and Q-RT-PCR, evaluating the circulating hTERT nucleic acids in the plasma samples of the 100 GC cases and the same number of sex-, age-, and residence place adjusted healthy volunteers, as the control group has been done. Results: The circulating hTERT mRNA level in patients was higher (40X) than the controls. In the case of circulating DNA, cases had higher difference (65X). These findings have been evaluated as significant difference. There were no significant relationships between hTERT level and age groups or adenocarcinoma type among cases. Conclusions: The elevated hTERT mRNA/ DNA plasma level among patients indicates the accuracy of the proposed subjects. However, performing cohort studies on circulating hTERT mRNA is advised. Legal entity responsible for the study: Ardabil University of Medical Sciences. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Comparing the prevalence of non-AIDS defining cancers by HIV status in the Ohio Medicaid population.
Authors: Siran M. Koroukian, Suparna Navale, Nicholas K Schiltz, Gregory Cooper, Li Li
Journal: Journal of Clinical Oncology (2018)

1567 Background: Persons living with human immunodeficiency virus (PLWHV) are over-represented in low income and minority populations. This makes Medicaid data particularly relevant for evaluating cancer care needs and outcomes among PLWHV. As a first step, we compare the prevalence of non-AIDS defining cancers (NADCs) between PLWHV and their non-HIV counterparts, hypothesizing that, adjusting for age, race, and sex, PLWHV are more likely than others to have been diagnosed with NADCs. Methods: This is a cross-sectional of Medicaid beneficiaries 18-64 years of age, using the 2012 Ohio Medicaid Analytic eXtract (MAX) file. Demographics included age, race (White, Black, and Other), and sex (male, female). We identified HIV status, as well as cancer for the different anatomic sites based on ICD-9 diagnosis codes documented in inpatient and outpatient claims data. We conducted descriptive analysis, and multivariable logistic regression analysis to evaluate the association between HIV status and NADCs after adjusting for age, race and sex. Given that a large percentage of Medicaid beneficiaries are enrolled in Medicaid for only part of the year, we also adjusted for the length of enrollment in Medicaid in our multivariable analysis. Results: Our study population included 1,061,471 individuals; 0.28% were PLWHV. Men and Blacks represented 55.2% and 58.9% of PLWHV, respectively, compared with 35.7% and 28.5% of their non-HIV counterparts. Adjusting for age, race, and sex, the two NADCs with which PLWHV were significantly more likely to have been diagnosed were rectal cancer (adjusted odds ratio: 4.03 (95% confidence interval: 2.31 - 7.03)), and anal cancer (34.19 (21.82-53.57)). Conclusions: For some cancers, the burden is significantly higher in PLWHV than among others. The higher prevalence of rectal and anal cancer highlights the importance of cancer prevention through screening and safe sex practice.
The Mitral Annulus Disjunction Arrhythmic Syndrome
Authors: Lars A. Dejgaard, Eystein T. Skjølsvik, Øyvind H. Lie, Margareth Ribe, Mathis K. Stokke, Finn Hegbom, Esther S. Scheirlynck, Erik Gjertsen, Kristoffer Andresen, Thomas M. Helle-Valle, Einar Hopp, Thor Edvardsen, Kristina H. Haugaa
Journal: Journal of the American College of Cardiology (2018)

Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral valve leaflet hinge point. MAD has been associated with mitral valve prolapse (MVP) and sudden cardiac death.The purpose of this study was to describe the clinical presentation, MAD morphology, association with MVP, and ventricular arrhythmias in patients with MAD.The authors clinically examined patients with MAD. By echocardiography, the authors assessed the presence of MVP and measured MAD distance in parasternal long axis. Using cardiac magnetic resonance (CMR), the authors assessed circumferential MAD in the annular plane, longitudinal MAD distance, and myocardial fibrosis. Aborted cardiac arrest and sustained ventricular tachycardia were defined as severe arrhythmic events.The authors included 116 patients with MAD (age 49 ± 15 years; 60% female). Palpitations were the most common symptom (71%). Severe arrhythmic events occurred in 14 (12%) patients. Longitudinal MAD distance measured by CMR was 3.0 mm (interquartile range [IQR]: 0 to 7.0 mm) and circumferential MAD was 150° (IQR: 90° to 210°). Patients with severe arrhythmic events were younger (age 37 ± 13 years vs. 51 ± 14 years; p = 0.001), had lower ejection fraction (51 ± 5% vs. 57 ± 7%; p = 0.002) and had more frequently papillary muscle fibrosis (4 [36%] vs. 6 [9%]; p = 0.03). MVP was evident in 90 (78%) patients and was not associated with ventricular arrhythmia.Ventricular arrhythmias were frequent in patients with MAD. A total of 26 (22%) patients with MAD did not have MVP, and MVP was not associated with arrhythmic events, indicating MAD itself as an arrhythmogenic entity. MAD was detected around a large part of the mitral annulus circumference and was interspersed with normal tissue.
Phosphorylation of AKT kinase substrates to predict response to the AKT inhibitor MK2206 in the I-SPY 2 trial in both HER2- and HER2+ patients.
Authors: Julia Dianne Wulfkuhle, Denise M Wolf, Christina Yau, Rosa Isela Gallagher, Lamorna Brown Swigart, Gillian L. Hirst, Laura Esserman, Donald A. Berry, Laura van 't Veer, Emanuel Petricoin
Journal: Journal of Clinical Oncology (2018)

12099 Background: In the I-SPY 2 TRIAL, the allosteric AKT inhibitor MK2206 was available to all HR/HER2 subtypes and graduated in the HR-/HER2+ signature. Qualifying biomarker analysis was performed on 26 proteins/phosphoproteins in the HER-AKT-mTOR pathway to identify candidate proteins correlated with pCR in the HER2+ and HER2- populations treated with MK2206. We postulated that response to MK2206 could be predicted by the relative level of phosphorylation of AKT kinase substrates. Methods: Of 151 patients in the MK2206 and control arms, 138 patients (MK2206: 87, controls: 51) had RPPA and pCR data. Data for 26 (phospho-) proteins involved in HER-AKT-mTOR signaling were assessed for association between biomarker and response in the MK2206 and control arms alone (likelihood ratio test), and relative performance between arms (biomarker x treatment interaction) using a logistic model. Analysis was also performed adjusting for HR/HER2 status. Markers were analyzed individually; p-values are descriptive and were not corrected for multiple comparisons. Results: In the HER2+ cohort, phosphorylation of the AKT kinase substrates mTOR S2448 (p = 0.004), GSK3 S21/9 (p = 0.009), FOXO1 S256 (p = 0.007), FOXO1 T24/FOXO3a T32 (p = 0.026), S6RP S240/S244 (p = 0.036), Tuberin/TSC1 Y1571 (p = 0.043) and eIF4G S1108 (p = 0.047) were associated with response. FOXO1 S256 also had a significant interaction with treatment in logistic model testing. In the HER2- population, AKT S473 (p = 0.012), AKT T308 (p = 0.011), Estrogen Receptor alpha (p = 0.013), mTOR (p = 0.04), NFkB S536 (p = 0.017) and Tuberin/TSC2 Y1571 (p = 0.03) were negatively associated with MK2206 response. FOXO S253 (p = 0.031) and ERBB2 Y877 (p = 0.02) were both positively associated with response and had a significant interaction with treatment in this cohort. Conclusions: While our sample size is too small to draw definitive conclusions, our results suggest that the measurement of AKT kinase substrate phosphoproteins could be predictive of MK2206 clinical activity in both HER2+ and HER2- tumors regardless of HR status. These results will need to be validated in independent study sets in order to judge the significance of these initial findings. Clinical trial information: NCT01042379.
Improving diagnostic and prognostic accuracy of myeloid neoplasms (MNs) by next generation sequencing.
Authors: Candice Schwartz, Jason Nathaniel Macklis, Lela Buckingham, Jamile M. Shammo
Journal: Journal of Clinical Oncology (2017)

e18567 Background: Molecular aberrations in MNs have been well described. Driver mutations such as JAK2, MPL, and CALR, are pathognomonic for MNs, whereas other somatic mutations are less specific but have prognostic significance. Multi-gene panel testing for known somatic mutations has been utilized for diagnostic and prognostic purposes, and testing for somatic mutations to identify clonal hematopoiesis has been adopted by the WHO 2016 classification of myeloid malignancies. We sought to assess the impact of testing for somatic mutations by NGS on diagnosis and management of pts with MNs. Methods: We employed a myeloid panel (MP) of 40 commonly mutated genes involving RNA splicing, chromatin remodeling, and signaling pathways. Testing was performed on ptswho presented to the clinic between 2/2015 and 12/2016. Initial diagnosis and rationale for testing (diagnostic or prognostic) were recorded. We then determined whether the MP resulted in a change in diagnosis, prognosis, or management. Results: 55 pts with a known or suspected MN had a MP performed.Diagnoses at presentation were: MDS (27), MF (8), MPN-U (8), MDS/MPN (4), multiple diagnoses (2), and no definitive diagnosis of MN (6). 87% (48/55) of pts had at least one somatic mutation.In 13 pts (23.6%) the MP led to a definitive diagnosis or a change in diagnosis. For example, 2 pts initially diagnosed with MPN-U were diagnosed with CNL after detection of CSF3R mutation. All 4 pts initially diagnosed with MDS with fibrosis were subsequently diagnosed with primary myelofibrosis; 3 had a MPL mutation and 1 had a CALR mutation. Management was altered in 12 pts (21.8%) and prognosis was changed in 11 pts (20.0%). For example, 2 pts were treated with a JAK-2 inhibitor and 2 pts with low risk MDS were referred for transplant evaluation due to the presence of a TP53mutation. Conclusions: Our study confirms that panel testing meaningfully improves diagnostic accuracy and provides prognostic value. In total, the MP resulted in a change in diagnosis, prognosis, or management in 43.6% (24/55) of cases. Confirmation of these observations merits prospective evaluation for a larger number of pts.