tbuckley/cabot-search huggingface dataset:
12 month survival for oncology patients with versus without patient navigation.
Authors: Marc Kowalkowski, Derek Raghavan, Kris Blackley, Victoria Morris, Carol J. Farhangfar
Journal: Journal of Clinical Oncology (2016)

6510 Background: Oncology patient navigation (PN) programs have been developed to improve outcomes and reduce disparities. Few data exist to describe the effect of PN on key clinical outcomes, such as survival. Methods: A nurse-led PN program was initiated at an academic, multi-site community-based cancer institute in Jan 2013. PN comprised regular in-person and virtual interactions and coordination of diagnosis, management and complication follow up. We conducted a retrospective cohort study of adults ( ≥ 18yrs) diagnosed with first primary cancer from Jan 2013-Dec 2014 to assess survival between patients who did and did not receive PN. For adequate numbers of events during available follow up, we analyzed patients diagnosed with any of 8 cancers with poor relative survival, according to American Cancer Society statistics, and with sufficient data for analysis (acute myeloid leukemia, esophagus, liver, lung, myeloma, ovary, pancreas, stomach). Nearest neighbor with caliper propensity score (PS) matching was used to match PN to similar non navigated standard of care (SC) patients. PN were excluded if no similar SC match existed. Electronic medical record and tumor registry data were queried for outcome parameters. Survival was censored at 12 mo for all patients in view of established median survival data. Cox regression was used to evaluate the effect of PN on 12 mo survival. Results: Of 2308 eligible patients (477 PN, 1831 SC), 408 (86%) PN were PS matched to 408 similar SC (816 total) with balanced demographic (age, sex, race, ethnicity, insurance, marital status, employment, rurality) and tumor characteristics (site, stage, grade, vascular invasion, metastases), receipt and nature of treatment, and overall health (comorbidities, inpatient stay 12 mo before diagnosis) between groups. 229 (28%) patients died within 12 mo of diagnosis (PN = 25% SC = 30%; p = 0.13). PN had median 12 mo survival of 355 days compared to 329 days among SC (p = 0.06). Cox regression showed SC had higher odds of death 12 mo from diagnosis (HR = 1.34 95%CI = 1.01-1.78). Conclusions: In a large, diverse PS matched cohort, PN patients had improved 12 mo survival. Further research is needed to confirm long term survival and value proposition benefit and explore subgroup differences.
Impact of skeletal-related events on multiple myeloma treatment.
Authors: Debajyoti Bhowmik, Nianwen Shi, Janna Manjelievskaia, Xue Song, Sarah Vidito, Michele Intorcia
Journal: Journal of Clinical Oncology (2018)

e20009 Background: Skeletal-related events (SREs), sequelae of bone lesions, are common and devastating complications in patients with multiple myeloma (MM).This study assessed the impact of SREs on progress to Next line of anti-MM Therapy (NT), a proxy for disease progression. Methods: In this retrospective cohort study, adults with ≥1 inpatient or ≥2 outpatient MM diagnoses claims between 01/01/2010 and 03/31/2016 were identified from the Truven Health MarketScan Commercial and Medicare databases. The index date was the first anti-MM treatment date post-MM diagnosis. All patients had ≥6-months of continuous enrollment pre- and post-index. SREs were identified during 6 month pre-index period and during first anti-MM treatment post-index. The impact of SREs on progress to NT was assessed, using Cox proportional hazard regression analysis, with occurrence of post-index SREs and renal impairment as time-varying covariates. Results: A total of 5,580 patients met the study criteria, 1,362 (24.4%) of them had SREs pre-index. A total of 1,175 (21.1%) patients experienced SREs during first anti-MM treatment post-index [mean age: 64.3 (±11.8) years, mean Charlson Comorbidity Index score: 3.9 (±2.6), opioid use: 80.4%]. Occurrence of post-index SREs was significantly associated with NT [Hazard ratio (HR): 1.25 {95% confidence interval (CI): 1.13-1.37}] (Table 1). Conclusions: Occurrence of post-index SREs was significantly associated with 25% higher likelihood of progressing to next line of anti-MM therapy, suggesting that SREs may indicate disease worsening in patients with MM. Table 1: Impact of Skeletal-Related Events (SREs) on Progress to Next Line of Therapy in Multiple Myeloma: Cox Proportional Hazard Regression Model Results Patient Characteristics Hazard Ratios (95% Confidence Interval) P-values Post-index SREs 1.25 (1.13-1.37) < 0.0001 Pre-index SREs 0.96 (0.87-1.07) 0.4787 Pre-index Renal impairment 0.83 (0.73-0.95) 0.0050 Post-index Renal Impairment 1.05 (0.95-1.17) 0.3354 Bone lesion 1.14 (1.04-1.25) 0.0066 Hypercalcemia 1.30 (1.15-1.46) < 0.0001 The model was adjusted for age, gender, health plan type, index year, region, comorbidity score, osteoporosis, use of intravenous bisphosphonates, corticosteroids, and opioids
Predictors of post-surgical race-specific prostate cancer progression.
Authors: Jennifer Cullen, Huai-Ching Kuo, Lauren Hurwitz, Inger L. Rosner, Timothy Rebbeck, Anthony Victor D'Amico, Grace L. Lu-Yao
Journal: Journal of Clinical Oncology (2017)

5048 Background: Disparity in prostate cancer (CaP) incidence and mortality for African American (AA) versus Caucasian American (CA) men may reflect tumor biology, comorbidity, treatment, follow-up care, and/or health care access. In a racially diverse cohort of patients undergoing radical prostatectomy (RP), this study examined how race, comorbidity, and PSA doubling time (PSADT) impact CaP progression. Methods: Enrollees in the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1989-2014 who underwent RP within 12 months of CaP diagnosis were eligible. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/mL post-RP. Comorbid conditions included coronary artery disease (CAD), cerebral vascular incident (CVI), Type II diabetes (DB), hypertension (HT), elevated cholesterol (EC), lung disease (COPD), prostatitis (PS), renal insufficiency (RI) and other cancer (OC). Multivariable Cox proportional hazards (PH) analysis was used to examine comorbid conditions (yes vs. no) and PSADT ( &lt; 3, 3-8.9, 9-14.9, and ≥15 mos) to predict BCR, controlling for age at RP, D’Amico risk stratum, pathology features, and adjuvant treatment. Results: A total of 6,785 patients were eligible; 22% AA and 78% CA. Median age and follow-up was 62 and 6.1 years, respectively. Across race, comparable median follow-up time, distributions of pathologic features and adjuvant treatments were observed. However, AA vs. CA patients had greater HT (53 vs. 39% p &lt; 0.0001), DB (17 vs. 7%, p &lt; 0.0001), and RI (3 vs. 1%, p = 0.002). Alternatively, CA vs. AA patients had greater CVD (10 vs. 7%, p = 0.0008) and OC (3 vs. 0.5%, p &lt; 0.0001). Cox PH analysis showed poorer BCR-free survival for AA vs. CA men (HR = 1.28, CI = 1.11, 1.48, p = 0.0009) adjusting for D’Amico risk stratum, pathology, and treatment. PSADT, not comorbidity, was a critical predictor of BCR, with poorest outcome at extremes: HR PSADT &lt; 3 vs. &gt; = 15 months = 41.5, CI = 33.6, 51.3, p &lt; 0.0001). Conclusions: Despite comparable health care access and distribution in clinical risk stratum and pathology features, race persisted in predicting poor CaP outcome. Disparate comorbidity for AA and CA men did not eliminate this difference. PSADT remained the most striking determinant of poor BCR-free survival.
P04.66 Prospects of aptamerotheranostics for glioma
Authors: A M Kopylov, A Novoseltseva, O Antipova, E Savchenko, A Revishchin, E Zavyalova, G Pavlova
Journal: Neuro-Oncology (2018)

Theranostics, also known as personalized medicine, precision medicine, stratified medicine or P4 medicine, is a modern trend in treating diseases. The large part of that is the immunotheranostics, which applies monoclonal antibodies as molecular recognizing elements (MoRE) to interact specifically and block functioning of therapeutically important target. In terms of therapeutic application, being the proteins, antibodies has both advantages and disadvantages: the critical ones are specificity and immunogenisity, respectively. MoRE made of nucleic acids instead of polypeptides is coined as Aptamers. Aptamers are more robust to produce, handle and applied, not mentioning the lack to provoke an immune response. Therefore, some attempts are made to create aptamers to block glioma proliferation. Among them are the following aptamers: for EphB2/3 receptors, for PDGFRβ, to U87-EGFRvIII cells, GBI-10 to tenascin-C, AS1411 to nucleolin, DNA aptamers from whole-cell SELEX. Some applications of aptamers have been developed: surface-immobilized aptamers for cancer cell isolation and cytology, quantum dot-labeled aptamer nanoprobes, aptamer guided gadolinium-loaded liposomes, aptamer functionalization of nanosystems to get through the blood-brain barrier, microRNA-based targeted to eradicate glioblastoma stem-like cells, aptamer conjugated magnetic nanoparticles as nanosurgeons. In this research EGFR has been selected as specific target to explore interaction with aptamers in details for the further possibility to halt proliferation of EGFR positive clones of glioblastoma (GBM). All published aptamer sequences, both DNA and RNA, have been collected and analyzed in terms of possible structures, gaining to find putative scaffold and recognizing parts of aptamers. All promising candidates were checked for affinity to the immobilized extracellular domain of human EGFR protein by surface plasmon resonance, as well as compare with commercial monoclonal antibodies. Derivatives of active aptamers were made to reveal putative scaffold and recognizing domain, and again check the affinity. Studying of interactions of several aptamers with EGFR positive cell lines and clones of surgical samples of GBM were made. A particular aptamer, NA511, has a very promising properties, both structural and functional. It shows distinctive putative structure which is easy to modify; it exhibits affinity similar to commercial antibodies. Therefore, it could be a promising candidate to translate this MoRE for theranostics of GMB. In spite of many aptamers for EGFR had been published till now, most of them do not have an obvious potential for further development. Therefore, a methodology has to be developed yet for translation of the aptamers into the theranostic drugs. The work was supported by Grant RFBR KOMFI 17-00-00162 (K), 17-00-00160.
Can tumor contact length predict extracapsular extension, lymph node involvement, and biochemical recurrence?
Authors: Públio Viana, Thiana Rodrigues, Danilo Pachani, Natally Horvat, Arnaldo Fazoli Carvalho, Giuliano Guglielmetti, Rafael Coelho, Diogo Assed Bastos, William Carlos Nahas
Journal: Journal of Clinical Oncology (2018)

e17016 Background: Prostate cancer (PC) is the cancer most commonly diagnosed in men and the second leading cause of death. Multiparametric magnetic resonance imaging (mpMRI) is the benchmark imaging standard for local staging of PC. Patients with pathological extraprostatic tumor (pEPE) have a worse prognosis than those with confined organ disease with a higher risk of biochemical recurrence (BCR) after radical prostatectomy (RP). These factors, in addition to positive lymph nodes (PLN), are pivotal in the decision-making process regarding treatment. However, the subjective MRI analysis has low sensitivity in the detection of EPE and is plagued by the low interobserver agreement. Tumor contact length (TCL) is an objective parameter of mpMRI defined as the length of prostate cancer in contact with the prostate capsule, which may provide additional information about prostate cancer outcomes. We aimed to evaluate TCL as a predictor of pECE, PLN, and BCR in patients undergoing RP. Methods: We prospectively evaluated 147 consecutive patients who underwent prostate mpMRI followed by radical prostatectomy, from April 2014 to July 2017. TCL was measured using T2-weighted magnetic resonance images. Postoperative prostate-specific antigen (PSA) values were obtained every 3 months in the first year, then biannually and annually thereafter. BCR was defined as PSA≥0.2ng/mL. The exclusion criterion was prior treatment. Results: The median follow-up duration was 14 months, 69/147 (46.9%) patients had pathological ECE, 9/147 (6.1%) had PLN, and 18/147 (12.2%) patients had BCR. TCL values were significantly higher in patients with pathological ECE (17.7 mm vs 10.3 mm, p < 0.001), in patients with PLN (26.5 mm vs 13.0 mm, p = 0.003) and in patients with BCR (18.2 mm vs 13.2 mm, p = 0,049). Using a cut-off of 11.9 mm we found area under curve (AUC) of 0.71 to predict pathological ECE. Using a cut-off of 16.5 mm we found AUC of 0.64 to predict BCR and with a cut-off of 21.7 mm the AUC to predict PLN was 0.79. Conclusions: We prospectively demonstrated in our population that TCL values were significantly higher in patients with pathological ECE, PLN and BCR.
Patient reported outcomes of red blood cell transfusions in an ambulatory oncology population.
Authors: Lawrence David Wagman, Kimberly Moeller, Lillian Jo-ann Chen
Journal: Journal of Clinical Oncology (2016)

e21618 Background: While the standard triggers for transfusion (Tf) in the hospitalized patient are hemoglobin (Hgb) level driven, triggers in the ambulatory oncology population are often symptom based. The symptoms of exercise intolerance (EI), fatigue (F) and shortness of breath (SOB) were identified from hospital quality data. The purpose of this study was to evaluate patient reported symptom (SX) changes following red blood cell (RBC) Tf. Methods: Tf symptom indications were standardized to EI, F, SOB and other SX. Tf orders required a symptom indication(s). Daily Tf rosters were collected. Patients were telephoned and asked to complete a symptom-response survey. Responses were recorded: same, better, or worse. Data collected: # of SX/patient, initial Hgb, days between Tf and survey, cancer diagnosis, # of units Tf, age and gender. Pre and post-Tf responses were calculated. P-values were obtained using binomial distribution, testing that the observed proportion of SX improvement was different from 50%. Results: From 12/2015 to 01/2016, 33 patients underwent 36 Tf episodes (TfE). M:F 11:18. Avg age: 74.5, (50-91). Avg initial Hgb 7.8 (5.3-9.9) Cancer diagnoses included: MDS 18, breast 7, lung 2, ovarian 1, prostate 1, endometrial 1, myeloma 1, lymphoma 1, leukemia 1.33/36( 92%) received 2 units of RBC per TfE. 9/36(25%) were interviewed on post-TfE day 7 (3-14d). Fatigue was the most commonly reported SX in 33 of 36 (92%). When evaluated by TfE: 14/36 (39%) had 1 SX, 13/36 (35%) 2 SX, 9/36 (25%) 3 SX. Conclusions: F, SOB, and total patient reported symptom changes were statistically significant favoring improvement with Tf. The greatest improvement was seen in F, followed by SOB, and then EI. The failure to show a significant difference for EI is likely related to the small sample size. The results of this unique analysis on patient reported symptoms—focused on oncology specific symptoms—can serve as a model for development of guidelines for RBC Tf for the ambulatory oncology population. Patient-reported symptom responses. Total Reported Better (#/%) Same or worse (#/%) Binomial Distribution p-value EI 12 8/66.7 4/33.3 0.93 0.073 Fatigue 33 26/78.8 7/21.2 1.0 > 0.001 SOB 18 13/72.2 5/27.8 0.98 0.015 Total 63 47/74.6 16/25.4 1.0 > 0.001
Predictors of disease progression in smoldering Waldenström macroglobulinemia.
Authors: Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Shaji Kumar, Angela Dispenzieri, Thomas E. Witzig, Martha Lacy, Grzegorz S. Nowakowski, Francis Buadi, David Dingli, Nelson Leung, S. Vincent Rajkumar, Ronald S. Go, Thomas Matthew Habermann, Yi Lin, Taxiarchis Kourelis, Robert A. Kyle, Morie A. Gertz, Prashant Kapoor
Journal: Journal of Clinical Oncology (2018)

7571 Background: There are limited data on predictors of disease progression in patients (pts) with smoldering Waldenström Macroglobulinemia (SWM). We aim to address this issue in a large cohort of SWM with a long follow-up. Methods: Pts with Waldenström Macroglobulinemia (WM) seen at Mayo Clinic, Rochester from 1996-2013 were included. Time-to-progression (TTP) was defined as interval from diagnosis of SWM to initiation of WM-directed therapy per 2002 Consensus criteria or development of light chain amyloidosis (AL) or transformation. Cumulative incidence of progression (CIP) was calculated by competing risk analysis. Median values were chosen as cutoff for dichotomization of continuous variables for univariate analysis (UVA) and multivariate analysis (MVA). Kaplan Meier method was used for time-to-event-analyses. Results: Of 823 WM pts, 143 (17%) had SWM. After a median follow-up of 9.5 years (yrs) [95% CI 8-11.5 yrs], 110 (77 %) pts progressed (107 required therapy for WM, 3 developed AL). CIP was 11%, 37% and 52% at 1, 3 and 5 yrs, respectively. On UVA (Table 1), hemoglobin (Hgb) ≤12.3 g/dL (p = 0.01) and beta-2 microglobulin (β2M) ≥2.7 ug/mL (p = 0.02) were significant predictors of TTP. On MVA, Hgb ≤12.3 g/dL [Risk ratio (RR) 1.9 (95% CI 1.1-3.5); p = 0.02] and β2M ≥2.7 ug/mL [RR 1.95 (95 % CI 1.1-3.6); p = 0.03] remained independent predictors of TTP. A score of 1 was assigned to both, giving a minimum score of 0 and maximum score of 2. The TTP was 9.3 yrs (95% CI 5.6-22.5 yrs), 4.1 yrs (95% CI 2.1-6 yrs) and 2.3 yrs (95% CI 1.5-4.5 yrs) for scores of 0, 1 and 2, respectively (p = 0.004). Conclusions: One-half of pts with SWM progress within five years from diagnosis. Pts with Hgb ≤12.3 g/dL and β2M ≥2.7 ug/mL at diagnosis have the shortest TTP. Impact of baseline characteristics on TTP. Parameter Median (interquartile range) P value (univariate) Age (yrs) 64.3 (59-71.1) 0.76 MYD88L265P mutated (%) 78 0.14 IgM (mg/dL) 2450 (1610-3590) 0.30 Marrow lymphoplasmacytic infiltrate (%) 30 (20-50) 0.88 LDH (U/L) 135 (106-157) 0.71 IgA (mg/dL) 64 (30-125) 0.56 IgG (mg/dL) 664 (486-997) 0.79 Involved/uninvolved serum free light chain ratio 9 (3.4-18.9) 0.07 Hemoglobin (g/dL) 12.3 (11.2-13.3) 0.01 Platelets (109/L) 264 (201-338) 0.52 β2M (ug/mL) 2.7 (2-3.7) 0.02
Testing the impact of adjuvant radiotherapy (aRT) after radical prostatectomy (RP) on overall mortality (OM) in prostate cancer patients with pathologically node positive disease: A nationwide analysis.
Authors: Firas Abdollah, Akshay Sood, Deepansh Dalela, Jacob Keeley, Quoc-Dien Trinh, Shaheen Riadh Alanee, Craig Rogers, James O. Peabody, Mani Menon
Journal: Journal of Clinical Oncology (2018)

5035 Background: Using institutional data, we have previously identified sub-groups of patients with pN1 prostate cancer, who can benefit from aRT plus adjuvant hormonal therapy (aHT) after RP. Our objective is to assess the generalizability of our previous findings using nationwide database. Methods: We identified 4276 patients with pN1 disease, who were treated with RP followed by aHT ± aRT, between 2004 and 2013, within the National Cancer DataBase. We stratified patients into five risk groups using pathological data, and based on previously established criteria - Group 1: men with 1-2 positive nodes and Gleason score (GS) < = 6; Group 2: men with 1-2 positive nodes, GS = 7, and stage < = pT3a with negative surgical margins; Group 3: men with 1-2 positive nodes, GS = 7, and stage > = pT3b or positive surgical margins; Group 4: men with 3-4 positive nodes; and Group 5: men with > 4 positive nodes. Univariable and multivariable analyses tested the relationship between aRT status and OM in each group. Results: Median (interquartile range) age, # of nodes removed, and # of positive nodes were 62 yrs (56-67), 9 nodes (5-15), and 1 node (1-2), respectively. Mean and median follow-up were 53.6, and 49.4 months, respectively. The percentage of men included in Groups 1 to 5 was respectively 0.6%, 14.6%, 60.1%, 14.2%, and 10.4%. On univariable analysis, aRT improved outcomes in Group 3 and Group 4 only. Specifically, in patients treated without aRT vs with aRT, the 5-year OM was 15.2% vs 11.4% (p = .01) in Group3, and 24.7% vs 14.1% (p < .001) in Group 4. In multivariable analysis adjusting to age and comorbidity, aRT decrease OM risk in Group 3 (hazard ratio [HR]: 0.78, p = .01), and Group 4 (HR: 0.37, p < .001), but not in the other groups. Conclusions: We validated our previously published results, and demonstrate that certain sub-groups of patients with pathologically proven node positive prostate cancer can benefit from maximizing local control by adding aRT to RP. Our new findings generalize our results to a nationwide setting, and shows that the beneficial impact of aRT is evident also for OM, which is the most significant endpoint in cancer treatment.
Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study
Authors: Isabel Leiva-Gea, Lidia Sánchez-Alcoholado, Beatriz Martín-Tejedor, Daniel Castellano-Castillo, Isabel Moreno-Indias, Antonio Urda-Cardona, Francisco J. Tinahones, José Carlos Fernández-García, María Isabel Queipo-Ortuño
Journal: Diabetes Care (2018)

OBJECTIVE Type 1 diabetes is associated with compositional differences in gut microbiota. To date, no microbiome studies have been performed in maturity-onset diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of type 1 diabetes, MODY2, and healthy control subjects was compared. RESEARCH DESIGN AND METHODS This was a case-control study in 15 children with type 1 diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and potential factors modifying gut microbiota were controlled. Microbiome composition was determined by 16S rRNA pyrosequencing. RESULTS Compared with healthy control subjects, type 1 diabetes was associated with a significantly lower microbiota diversity, a significantly higher relative abundance of Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira. Children with MODY2 showed a significantly higher Prevotella abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory cytokines and lipopolysaccharides were increased in type 1 diabetes, and gut permeability (determined by zonulin levels) was significantly increased in type 1 diabetes and MODY2. The PICRUSt analysis found an increment of genes related to lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis, arachidonic acid metabolism, antigen processing and presentation, and chemokine signaling pathways in type 1 diabetes. CONCLUSIONS Gut microbiota in type 1 diabetes differs at taxonomic and functional levels not only in comparison with healthy subjects but fundamentally with regard to a model of nonautoimmune diabetes. Future longitudinal studies should be aimed at evaluating if the modulation of gut microbiota in patients with a high risk of type 1 diabetes could modify the natural history of this autoimmune disease.