tbuckley/cabot-search huggingface dataset:
Are the gene expression profiles of Hispanic patients with lung cancer living in the US different from Hispanics living abroad?
Authors: Luis E. Raez, Edgardo S. Santos, Jennifer Mourafetis, Alice Yeonkyung Kim, Brian Hunis, Candice Sareli, Evelio Velis, Lilibeth del Carmen Castillero, Robert A. Hirsch, Neil Abrahams
Journal: Journal of Clinical Oncology (2016)

e18059 Background: The frequency of epidermal growth factor receptor mutations (EGFR) in lung cancer tumors in Latin-America (LATAM) is higher than the US. We believe that the frequency of EGFR and other molecular markers (MM) in Hispanic (H) patients (pts) living in the US does not follow that pattern and it’s similar between H and non-Hispanic Whites (NHW). Methods: To identify EGFR and other MM (ALK, RET, ROS-1, KRAS, c-Met and BRAF), next generation sequencing (NGS) and FISH were done in tumors of pts with NSCLC at Memorial Cancer Institute and Lynn Cancer Center in Florida. All MM were not available for all pts. Pts were divided by ethnicity. Chi-square and Fisher’s Exact tests were used to assess associations between GEP and ethnicity. All summary statistics on time-to-event variables were calculated according to the Kaplan-Meier method and were compared by means of the log-rank test. Adjusted hazard ratios and 95% confidence intervals were reported based on the results of a multivariate Cox regression model for overall survival. Results: MM were requested for 492 pts and tumor samples were sufficient in 436 (88%). Of these pts: 25% were H, 61% women, 34% non-smokers and 93% had adenocarcinomas. EGFR were seen in 22% of the tumors [76 % in exons 19&21 and 13% in exons 18&20]. There was an increase in exon 19 in H vs. NHW (82% vs. 45% of “good” EGFRs) (p < 0.05). ALK 5%, RET 4%, ROS-1 8%, c-MET 31%, KRAS 30%, and BRAF 5%. There was no significant association between H vs. NHW with any MM. There were no differences in survival between H and NHW as well as differences in survival between H and NHW for any MM. Conclusions: The incidence of MM in H living in the US is lower than the one reported in LATAM and it’s similar to the NHW. There are no differences between H and NHW leaving in the US in the frequencies of MM presentations and survival. In our pts, EGFR exon 19 is more common in H than NHW. EGFR&ROS-1 frequency in NHW is higher than the US average. Molecular Marker Frequency % in HIS pts % in NHW pts # Tumors tested EGFR 22% 25% 21% 380 ALK 5% 4.6% 5.2% 339 ROS-1 8% 3% 9% 180 KRAS 30% 27% 31% 258 c-MET 31% 27% 32% 165 BRAF 5% 9.5% 3.5% 156 RET 4% 0% 6% 122
Cyclophosphamide (Cy) pharmacogenetics (PGx) in allogeneic stem cell transplant (SCT) patients (pts) receiving Cy, fludarabine, total body irradiation and post-transplant Cy (FluCyTBI-postCy).
Authors: Jai Narendra Patel, Qing Zhang, Issam Hamadeh, Nury Steuerwald, Alicia Hamilton, Jonathan Michael Gerber, Michael Richard Grunwald, Lawrence Druhan, Jiaxian He, Belinda Rene Avalos, Edward Alan Copelan
Journal: Journal of Clinical Oncology (2018)

7058 Background: Cy is the backbone for many SCT conditioning regimens and is used post-SCT to prevent graft vs. host disease (GVHD). It has been proposed that genetic polymorphisms impact Cy exposure and clinical outcomes; however, no PGx studies have been performed in pts receiving FluCyTBI-postCy. Methods: Germline DNA from SCT pts receiving FluCyTBI-postCy was genotyped using a custom Ion AmpliSeq™ PGx Panel for polymorphisms in: ALDH1A1 (*2), ALDH3A1 (Pro329Ala), GSTA1 (135T > C), GSTM1 (null), GSTP1 (Ile105Val, Ala114Val), CYP2B6 (*2, *4, *5, *6, *18, *22), CYP2C8 (*2, *3), CYP2C9 (*2, *3, *8, *11), CYP2C19 (*2, *3, *17), CYP3A4 (*1B, *22), and CYP3A5 (*3, *6, *7). Phenotypes (poor [PM], intermediate [IM], normal [NM], and rapid metabolizers [RM]) were inferred based on literature. Cy 14.5 mg/kg IV was given on days -6 & -5 pre-SCT, and 50 mg/kg on days +3 & +4 post-SCT. Univariate logistic regression was used to investigate the association between polymorphisms and any grade cardiotoxicity, hemorrhage cystitis [HC], liver toxicity, and/or acute GVHD up to day +100. Univariate Cox proportional hazards regression was used to investigate the association between polymorphisms and overall [OS] & progression-free survival [PFS]. Results: In 59 evaluable pts, the median age was 57 (24-77), 61% were male, 73% received haploidentical SCT and 27% matched related donor SCT. The table summarizes significant findings (P < 0.05). Conclusions: Several genes involved in the activation (CYPs) and inactivation (ALDHs & GSTs) of Cy and its metabolites were associated with SCT outcomes and toxicities. Prospective studies exploring the combined effects of these genes on outcomes are needed to validate findings. Phenotype Gene HR/OR 95% CI P-value OS ALDH3A1 IM v PM 0.22 0.06-0.82 0.024 CYP3A5 NM v PM 5.67 1.20-26.7 0.028 CYP3A4 NM v IM RM v IM 0.17 0.22 0.05-0.63 0.05-0.92 0.008 0.038 PFS CYP3A4 NM v IM RM v IM 0.14 0.18 0.04-0.45 0.05-0.66 0.001 0.009 CYP2C8 NM v IM 0.48 0.24-0.97 0.039 Cardiotox GSTP1 IM v PM NM v PM 0.19 0.09 0.04-0.82 0.01-0.45 0.031 0.007 HC ALDH1A1 NM v IM 0.09 0.004-0.65 0.036 Liver tox CYP2C8 NM v IM 0.23 0.05-0.83 0.038
Trends in Visits to Acute Care Venues for Treatment of Low-Acuity Conditions in the United States From 2008 to 2015
Authors: Sabrina J. Poon, Jeremiah D. Schuur, Ateev Mehrotra
Journal: JAMA Internal Medicine (2018)

Over the past 2 decades, a variety of new care options have emerged for acute care, including urgent care centers, retail clinics, and telemedicine. Trends in the utilization of these newer care venues and the emergency department (ED) have not been characterized.To describe trends in visits to different acute care venues, including urgent care centers, retail clinics, telemedicine, and EDs, with a focus on visits for treatment of low-acuity conditions.This cohort study used deidentified health plan claims data from Aetna, a large, national, commercial health plan, from January 1, 2008, to December 31, 2015, with approximately 20 million insured members per study year. Descriptive analysis was performed for health plan members younger than 65 years. Data analysis was performed from December 28, 2016, to February 20, 2018.Utilization, inflation-adjusted price, and spending associated with visits for treatment of low-acuity conditions. Low-acuity conditions were identified using diagnosis codes and included acute respiratory infections, urinary tract infections, rashes, and musculoskeletal strains.This study included 20.6 million acute care visits for treatment of low-acuity conditions over the 8-year period. Visits to the ED for the treatment of low-acuity conditions decreased by 36% (from 89 visits per 1000 members in 2008 to 57 visits per 1000 members in 2015), whereas use of non-ED venues increased by 140% (from 54 visits per 1000 members in 2008 to 131 visits per 1000 members in 2015). There was an increase in visits to all non-ED venues: urgent care centers (119% increase, from 47 visits per 1000 members in 2008 to 103 visits per 1000 members in 2015), retail clinics (214% increase, from 7 visits per 1000 members in 2008 to 22 visits per 1000 members in 2015), and telemedicine (from 0 visits in 2008 to 6 visits per 1000 members in 2015). Utilization and spending per person per year for low-acuity conditions had net increases of 31% (from 143 visits per 1000 members in 2008 to 188 visits per 1000 members in 2015) and 14% ($70 per member in 2008 to $80 per member in 2015), respectively. The increase in spending was primarily driven by a 79% increase in price per ED visit for treatment of low-acuity conditions (from $914 per visit in 2008 to $1637 per visit in 2015).From 2008 to 2015, total acute care utilization for the treatment of low-acuity conditions and associated spending per member increased, and utilization of non-ED acute care venues increased rapidly. These findings suggest that patients are more likely to visit urgent care centers than EDs for the treatment of low-acuity conditions.
Prognostic signatures of oligometastasis in colorectal cancer liver metastasis.
Authors: Sajid A. Khan, Philip Paty, Zhaoshi Zeng, Jun Lu
Journal: Journal of Clinical Oncology (2017)

3588 Background: Knowledge of molecular differences between limited metastasis (oligometastasis) and widespread metastases may provide biomarkers for selection of patients who will benefit from curative metastasis resection and provide useful prognostic information. In this study, we detect messenger RNA expressional patterns in patients with colorectal cancer liver metastasis (CRCLM) and identify networks of coding and noncoding RNAs corresponding to oligometastatic phenotype. Methods: RNA was prepared from frozen tumor tissue of 55 patients with CRCLM patients treated with liver resection and/or biopsy of their metastatic tumors with greater than 15 years of follow-up. Survival was calculated and stratified according to risk of recurrence. Cases were subject to RNA-Sequencing experiments with paired end sequencing. Results: RNA analysis with TopHat and Cuffdiff found significant differences in transcript expression according to recurrence for 667 genes (P &lt; 0.05). Of these transcripts, 166 had a greater than 2-fold gene expression between groups when comparing mean Fragments Per Kilobase of transcript per Million mapped reads (FPKM) (P &lt; 0.05). Unsupervised hierarchical clustering revealed distinct genomic patterns based on clinical outcome. A supervised gene expression analysis revealed a differential expression of genes in the Homeobox ( HOX) family (P &lt; 0.05). Overexpression of individual members of the HOX gene family are associated with prognosis. Upregulation of the HOXD11 gene was associated with cure in 60% of cases while downregulation was associated with 5-year overall survivals of 16% (P = 0.023). Furthermore, when clusters of HOX family members were compared, we found that expression correlated with survival, underlining the importance of this gene family in oligometastasis biology. A high ratio of the HOXD cluster to HOXA cluster was associated with a long recurrence free survival (P = 0.002). Conclusions: Common genomic signatures characterize patients with liver oligometastasis from primary colorectal cancer. The HOX gene family strongly correlates with prognosis and represents a unique molecular subtype of patients. Further mechanistic studies of the HOX gene family in metastases are underway.
A longitudinal assessment to evaluate the impact of higher body mass index on cancer-related fatigue in breast cancer patients receiving chemotherapy.
Authors: Julia Ellen Inglis, Michelle Christine Janelsins, Eva Culakova, Javier Bautista, Karen Michelle Mustian, Po-Ju Lin, Ian Kleckner, Luke Joseph Peppone
Journal: Journal of Clinical Oncology (2018)

10061 Background: Obesity and weight gain post-chemotherapy leads to increases in all-cause mortality, inflammation, and decreased quality of life but little is known about how obesity contributes to cancer-related fatigue (CRF). Inflammation is also associated with cancer-related fatigue (CRF). We conducted a secondary analysis of a large prospective, nationwide study to assess the impact of obesity on CRF levels in breast cancer patients. Methods: Female breast cancer patients (N = 565, aged 53±10.61) completed the multidimensional fatigue symptom inventory (MFSI) and the symptom inventory (SI) to measure CRF symptoms at baseline pre-chemotherapy (T1), post-chemotherapy (T2), and six months post-chemotherapy (T3) as part of a longitudinal study for cognitive impairment. Height and weight were collected at T1 and subjects were categorized based on BMI: Obese (OB: ≥30.0 kg/m2; n = 294), overweight (OV: 25.0-29.9 kg/m2; n = 146) and normal weight (NW: 18.5-24.9 kg/m2; n = 125). Multivariate regression models were used to evaluate the relationship of obesity level to CRF over time controlling for age, race, radiation history, hormonal therapy, cancer stage, exercise level and KPS score. Results: At T1, the obese had significantly higher CRF symptoms than normal weight subjects for both the MFSI (OB = 11.4 vs NW = 8.1; p = 0.03) and SI (OB = 3.5 vs NW = 2.9; p = 0.02). Significantly higher SI fatigue scores persisted at T2 for the obese (OB = 4.4 vs NW = 3.8; p = 0.02) with a trend towards significance for the overweight (OV = 4.4 vs NW = 3.8; p = 0.08) group. At T3, obese subjects still had significantly higher SI fatigue scores (OB = 3.8 vs NW = 3.2; p = 0.03). Over the course of the study, obese subjects maintained higher MFSI subscale scores for General, Mental, and Emotional subscales (p < 0.05). Conclusions: This nationwide multicenter study is one of the first to directly tie obesity to fatigue from pre-chemotherapy through six months post-chemotherapy. Recommendations for weight loss or weight maintenance should be considered to prevent CRF in obese breast cancer patients before and after chemotherapy. Funding: NCI UGCA189961, R25 CA102618
Effect of Mobile Device–Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain
Authors: Richard L. Kravitz, Christopher H. Schmid, Maria Marois, Barth Wilsey, Deborah Ward, Ron D. Hays, Naihua Duan, Youdan Wang, Scott MacDonald, Anthony Jerant, Joseph L. Servadio, David Haddad, Ida Sim
Journal: JAMA Internal Medicine (2018)

Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice. To determine whether patients randomized to participate in an n-of-1 trial supported by a mobile health (mHealth) app would experience less pain and improved global health, adherence, satisfaction, and shared decision making compared with patients assigned to usual care. This randomized clinical trial compared participation in an individualized, mHealth-supported n-of-1 trial vs usual care. The participating 215 patients had CMSP for at least 6 weeks, had a smartphone or tablet with a data plan, were enrolled in northern California from July 2014 through July 2016, and were followed for up to 1 year by 48 clinicians in academic, community, Veterans Affairs, and military settings. Intervention patients met with their clinicians and used a desktop interface to select treatments and trial parameters for an n-of-1 trial comparing 2 pain-management regimens. The mHealth app provided reminders to take designated treatments on assigned days and to upload responses to daily questions on pain and treatment-associated adverse effects. Control patients received care as usual. The primary outcome was change in the PROMIS (Patient-Reported Outcomes Measurement Information System) pain-related interference 8-item short-form scale (full scale range, 41-78) from baseline to 6 months. Secondary outcomes included patient-reported pain intensity, overall health, analgesic adherence, trust in clinician, satisfaction with care, medication-related shared decision making, and, for the n-of-1 group only, participant engagement and experience. Among 215 patients (108 randomized to the n-of-1 intervention and 107 to control), 102 (47%) were women, and the mean (SD) age was 55.5 (11.1) years. At the 6-month follow-up, pain interference was reduced in both groups, though there was no difference between the intervention and control groups (-1.36 points; 95% CI, -2.91 to 0.19 points; P = .09). There were no advantages in secondary outcomes for intervention patients vs control patients except for higher medication-related shared decision making at 6 months (between-group difference, 11.9 points; 95% CI, 2.6-21.2 points; P = .01). Among patients assigned to the n-of-1 group, 88% (n = 86) affirmed that the mHealth app could help people like them manage their pain. In this population of patients with CMSP, mHealth-supported n-of-1 trials were feasible and associated with a satisfactory user experience, but n-of-1 trial participation did not significantly improve pain interference at 6 months vs usual care. ClinicalTrials.gov identifier: NCT02116621.
Association of CYP17A1 single nucleotide polymorphism (SNP) with response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ben Yiming Zhang, Moritz Binder, Brian Addis Costello, Fernando Quevedo, Manish Kohli
Journal: Journal of Clinical Oncology (2016)

e16603 Background: Abiraterone acetate (AA) is a potent inhibitor of enzymes encoded by CYP17A1 and HSD3β2 in the sex steroid synthesis pathway in the testis, adrenal glands, and prostate cancer cells. While AA has been shown to prolong survival in patients with mCRPC, it is crucial to identify predictive biomarkers for this drug. Therefore, we set out to investigate the associations between polymorphisms in CYP17A1 and HSD3β2 and outcomes to AA treatment. Methods: Germline DNA was extracted from peripheral blood mononuclear cells of mCRPC patients. CYP17A1 and HSD3β2 genes were tagged using SNPs from HapMap with minor allele frequency (MAF) of > 5% (4 SNPs for CYP17A1, 2 for HSD3β2). Genotyping was carried out on the MassARRAY iPLEX platform. The clinical outcomes of interest included PSA response after initiation of AA therapy (defined as ≥ 50% decrease in PSA), time to PSA progression (defined as > 25% increase in PSA on two consecutive tests at least two weeks apart), and time to change of treatment because of disease progression on AA. Logistic and Cox regression models were used to assess the associations with response and time to event, respectively. The overall adjusted α-level after correcting for multiple testing was 0.010. Effect measures were expressed as odds or hazard ratio per minor allele. Results: Eighty-eight mCRPC patients undergoing treatment with AA were genotyped. The median age at initiation of AA was 73 years (range 54-90). Bone and soft tissue metastases were present in 85% and 50% of the men, respectively. Sixty-five percent (57/88) of patients had received docetaxel prior to AA. An association of rs2486758 in CYP17A1 (MAF = 0.22) was observed with PSA response (OR 0.22, 95% CI 0.07-0.63, p = 0.005; 17% with ≥ 1 minor allele vs. 50% in wild type), time to PSA progression (HR 2.23, 95% CI 1.39-3.56, p < 0.001), and time to treatment change (HR 2.14, 95% CI 1.34-3.42, p = 0.002). No SNP in HSD3β2 was associated with the outcomes of interest. Conclusions: We discovered a strong association between genetic variations in a common CYP17A1 SNP with AA efficacy in mCRPC. These promising results warrant validation in a larger independent cohort.
ADXS11-001 immunotherapy in squamous or non-squamous persistent/recurrent metastatic cervical cancer: Results from stage I of the phase II GOG/NRG0265 study.
Authors: Warner King Huh, Don S. Dizon, Matthew A. Powell, Charles A. Leath, Lisa Michelle Landrum, Edward Tanner, Robert Higgins, Stefanie M. Ueda, Michael T. McHale, Bradley J. Monk, Carol Aghajanian
Journal: Journal of Clinical Oncology (2016)

5516 Background: There is no approved treatment with a survival benefit for persistent/recurrent metastatic cervical cancer (PRmCC) patients (pts) who have progressed after ≥ 1 line of systemic-dose chemotherapy (sdCTx), and historical 12-mo overall survival (OS) in this population has never exceeded 30%. ADXS11-001 is a live attenuated Listeria monocytogenes (Lm)-listeriolysin O immunotherapy bioengineered to secrete an HPV16-E7 fusion protein targeting HPV-transformed cells (eg, cervical cancer), inducing antitumor T-cell immunity and breaking immune tolerance in the tumor microenvironment. GOG/NRG-0265 is an ongoing study of ≥ 2nd-line ADXS11-001 in pts with PRmCC. This analysis presents Stage 1 safety and OS data. Methods: This is a single-arm, 2-stage phase II study (NCT01266460; target n = 27 for Stage 1). Eligible pts ( ≥ 18 yr) have ≥ 1 prior line of sdCTx (bevacizumab permitted), measurable disease (RECIST v1.1), squamous/non-squamous PRmCC not amenable to curative therapy, and GOG PS of 0/1. Pts receive ADXS11-001 1 x 109CFU on day 1 and q28 days for 3 doses. Co-primary endpoints are the tolerability/safety of ADXS11-001 and 12-mo OS rate. Secondary endpoints are PFS, OS, and objective response (OR). Conditional power ≥ 20% based on 12-mo OS in historical controls (24.5% after adjustment for age, race, and PS) is required to open Stage 2. Results: In total, 29 pts enrolled; 26 were treated. Median age was 46.5 yr, 62% had GOG PS 0, 62% received ≥ 2 prior lines of sdCTx, and 31% received bevacizumab. All pts experienced ≥ 1 AE: 91% were grade 1–2; 38% were drug related, with nausea, vomiting, chills, fatigue, and fever most common. Stage 1 12-mo OS rate was 38.5% (n = 10). Median PFS was 3.1 mo (95% CI: 2.8–3.7) and median OS was 7.7 mo (95% CI: 3.9–12.4). Preliminary assessment of OR includes 1 unconfirmed PR and 9 SD. Post-hoc analysis of the 18/26 pts (69%) who received all 3 per-protocol doses of ADXS11-001 showed a median OS > 1 yr (12.1 [95% CI: 6.8–NR] mo), and 12-mo OS rate of 55.6%. Conclusions: ADXS11-001 is well tolerated, and the 38.5% 12-mo OS rate suggests that it is active in PRmCC. Stage 2 is now enrolling and has been amended to allow for continuous cycles of Tx. Clinical trial information: NCT01266460.
Multicenter, randomized phase II trial of physical activity (PA), metformin (Met), or the combination on metabolic biomarkers in stage I-III colorectal (CRC) and breast cancer (BC) survivors.
Authors: Jeffrey A. Meyerhardt, Melinda L Irwin, Lee Jones, Sui Zhang, Nancy Campbell, Justin C. Brown, Michael N. Pollak, Alexandra Sorrentino, Brenda Cartmel, Maura Harrigan, Miranda West, Sara M. Tolaney, Rachel Lynn Yung, Eric P. Winer, Kimmie Ng, Thomas Adam Abrams, Charles S. Fuchs, Tara Beth Sanft, Pamela Douglas, Jennifer A. Ligibel
Journal: Journal of Clinical Oncology (2017)

10059 Background: Observational data demonstrate an inverse relationship between PA and Met to disease outcomes in CRC &amp; BC pts. A mechanism that these could impact cancer recurrence and mortality is hypothesized to involve insulin and related growth factors. We investigated the effects of PA, Met or the combination on metabolic biomarkers in CRC &amp; BC pts. Methods: In a phase 2 RCT, stage I-III CRC &amp; BC survivors at least 2 months from completing standard therapy (excluding hormone rx or trastuzumab) were randomized to PA, Met, PA + Met or control. Major eligibility included absence of recurrence or diabetes (glucose &lt; 160 (random) or &lt; 126 (fasting) mg/dl) and exercising &lt; 120 min/wk. The PA intervention consisted of supervised aerobic training at least 2 x /wk. Metformin dosing was 850 mg 1x/day titrated to 850 mg 2x/day after 2 wks if tolerated. Interventions were 12 weeks in duration. Fasting bloods at baseline &amp; 12 wks were analyzed for insulin (1 o endpoint), leptin, IGF1, IGFBP1 &amp; IGFBP3. Results: 139 pts were enrolled: 62% BC/38% CRC; 83% female; median BMI 28.3; median 2 yrs from dx; median age 56 (range 34-79). 107 pts completed assigned therapy. Pts in PA and PA + Met arms increased PA by 166 and 140 min/wk vs 30 min/wk in controls (both P&lt;0.0001). Pts in the Met and PA + Met arms lost weight vs controls (-1.41 and -0.91 kg vs + 1.97 kg, both P &lt;0.0001). Both interventions had impact on metabolic biomarkers (Table). Conclusions: PA and Met both led to significant changes in insulin and other biomarkers in CRC &amp; BC survivors with potential synergistic effect on leptin with dual intervention. Clinical trial information: NCT01340300. [Table: see text]