tbuckley/cabot-search huggingface dataset:
Comparisons of palliative care utilization in metastatic cancer patients between multi-payer non-universal health care and single-payer universal health care systems.
Authors: Raymond Nienchen Kuo, C. Jillian Tsai
Journal: Journal of Clinical Oncology (2018)

10110 Background: Previous studies reported that private insurance was associated with receiving recommended care and better outcomes. However, it is unclear whether insurance type is associated with the utilization of palliative care among metastatic cancer patients who survived for less than 6 months following diagnosis. This study compares the utilization of palliative care among patients in the U.S. and patients in Taiwan. Methods: Analysis was conducted using data for the period 2010 – 2013 obtained from the U.S. National Cancer Database and Taiwan Cancer Registry. This study include patients newly diagnosed with metastatic (M1) breast, colorectal, lung, and prostate cancers and who died within six months after diagnosis. Logistic regression models were used to compare the odds of receiving palliative care under different health insurance schemes. Results: This study included 70,084 U.S. patients (49,374 lung, 13,591 colorectal, 4,837 breast, 2,285 prostate) and 8,882 Taiwanese patients (6,131 lung, 2,188 colorectal, 255 breast, 308 prostate). Among these cases, 18,458 patients in the U.S. (26.3%) and 5,338 patients in Taiwan (60.1%) received palliative care before dying. In the U.S., breast, colorectal, and lung cancer patients covered by private health insurance were more likely to utilize palliative care (17.6% - 31.1%), than were patients covered by public health insurance (16.0% - 28.7%). Multivariate logistic regression analysis revealed that after controlling for demographic factors, disease severity and treatment type, there were no differences in the administration of palliative care among patients covered by private health insurance and those covered by public health insurance. Conclusions: This study revealed that there were no differences in the administration of palliative care among patients covered by private health insurance and those covered by public health insurance. Nonetheless, Taiwanese patients were more likely to undergo palliative care than were patients in the U.S. This implies that the lower cost and more comprehensive benefit scheme may improve access to palliative care.
MANAGEMENT AND CLINICAL OUTCOME OF PATIENTS WITH ACUTE CORONARY SYNDROME CAUSED BY PLAQUE RUPTURE AND PLAQUE EROSION: AN INTRAVASCULAR OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Haibo Jia, Harold Dauerman, Catalin Toma, Habib Samady, Stephen Lee, Rocco Vergallo, Sining Hu, Jinwei Tian, Tsunenari Soeda, Zhao Wang, Hang Lee, Iris McNulty, Bo Yu, Shiro Uemura, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2014)
Exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26).
Authors: Gilles Crehange, Aurelie Bertaut, Didier Peiffert, Elisabeth Le Prise, Pierre-Luc Etienne, Emmanuel Rio, Renata Pereira, Georges Noel, Karen Benezery, Franck Bonnetain, Jean Francois Seitz
Journal: Journal of Clinical Oncology (2017)

4037 Background: In esophageal cancer (EC), 20 to 45% of patients suffer from local failure after 50Gy concomitant chemoradiation (cCRT). Improvements in staging together with target definitions led us to test dose escalation in the modern era of new technologies. Methods: Patients were randomly assigned cCRT to 40Gy elective nodal irradiation with either a 10Gy boost (Arm A) or 26Gy boost (Arm B) combined with FOLFOX-4. The primary endpoint of this phase II was acute toxicity according to the NCIC-CTCAE (version 4.0). Quality of life according to the EORTC QLQ-C30 and OG25 was a secondary endpoint. All analyses were performed in intent-to-treat. Results: 160 patients were randomized between Jun 2011 and Feb 2016: 81 patients in arm A and 79 patients in arm B. The mean age at diagnosis was 61.9 (7.9) years and 62.1 (7.8) years, respectively. Seventy patients in each arm had squamous cell carcinoma (86.4% in arm A and 88.6% in arm B) and 59 patients (72.8%) and 58 patients (73.4%) had stage III disease in arms A and B, respectively. IMRT was performed in 57 (70.4%) and 55 (69.6%) patients in arms A and B. The rates of grade ≥3 (G3+) non-hematological toxicity were not significantly different between arms A and B (76.5% vs 86.0%, p = 0.12). The rates of G3+ hematological toxicity were not significantly different between arms A and B (82.7% vs 88.6%, p = 0.29). The rates of G3+ non-hematological toxicity were not significantly different between patients treated with 3DRT (83.3%) and IMRT (81.3%) (p = 0.77). The mean global health scores at baseline and 3 months were 63.9 (sd = 21.4) vs 69.6 (sd = 23.1) in arm A (p = 0.10) and 65.27 (sd = 19.54) vs 58.8 (sd = 19.9) in arm B (p = 0.16). The presence of dysphagia was neither significantly different between arm A (89.23%) and arm B (86.21%) (p = 0.61) at baseline nor at 3 months (77.78% vs 86.84%, p = 0.29). Odynophagia was present at baseline in 78.46% in arm A and 75.86% in arm B (p = 0.73) while the rates observed at 3 months were 68.18% and 73.68%, respectively (p = 0.59). Conclusions: Dose escalated cCRT in patients with EC is feasible with no increased acute toxicity and no deterioration of QOL. A phase III trial is on-going to conclusively address the issue of local control with cCRT. Clinical trial information: NCT01348217.
OP0284 Muc5b promoter variant rs35705950 is a risk factor for rheumatoid arthritis – interstitial lung disease
Authors: P.-A. Juge, J.S. Lee, E. Ebstein, H. Furukawa, E. Dobrinskikh, S. Gazal, C. Kannengiesser, S. Ottaviani, N. Tsuchiya, S. Oka, S. Tohma, J. Rojas-Serrano, M.-I. Gonzalez-Perez, M. Mejia, I. Buendia-Roldan, R. Falfan-Valencia, E. Manali, S.A. Papiris, T. Karageorgas, D. Boumpas, K. Antoniou, C. Van Moorsel, J. van der Vis, Y. de Man, J. Grutters, Y. Wang, R. Borie, L. Wemeau-Stervinou, B. Wallaert, R.-M. Flipo, H. Nunes, D. Valeyre, N. Saidenberg, S. Marchand-Adam, K. Deane, A. Walts, T. Fingerlin, E. Matteson, T. Niewold, D. Assayag, A. Gross, P. Wolters, M. Schwarz, M. Holers, J. Solomon, T. Doyle, M.-P. Debray, C. Boileau, B. Crestani, D. Schwartz, P. Dieudé
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) share phenotypic similarities. The gain-of-function <i>MUC5B</i> promoter variant rs35705950 is the strongest risk factor for development of IPF <h3>Objectives</h3> We hypothesised that rs35705950 would also contribute to the risk of ILD in RA patients. <h3>Methods</h3> Using a French discovery population and multi-ethnic validation populations from 6 different countries, we tested the association of the <i>MUC5B</i> promoter variant in RA-ILD (n=620), RA without ILD (n=614), and unaffected controls (n=5448). <h3>Results</h3> The discovery population revealed an association of the <i>MUC5B</i> promoter variant with RA-ILD when compared to unaffected controls (OR<sub>adj</sub>=3.8 95% CI: 2.8 to 5.2; p=9.7x10–1<sup>7</sup>) (figure 1A). Similar to the discovery cohort, the <i>MUC5B</i> promoter variant was significantly over-represented among the cases of RA-ILD in the multi-ethnic study cohorts when compared to unaffected controls (OR<i><sub>adj</sub></i>=5.5 95% CI: 4.2 to 7.2; p=4.7x10–3<sup>5</sup>) (figure 1A), and when the discovery population and the multi-ethnic cohorts were combined (OR<i><sub>combined</sub></i>=4.7 95% CI: 3.9 to 5.8; p=1.3x10–4<sup>9</sup>) (figure 1A). Additionally, the <i>MUC5B</i> promoter variant was found to increase the risk of ILD among patients with RA (OR<i><sub>combined</sub></i>=3.1 95% CI: 1.8 to 5.4; p=7.4x10–5), however, no statistical association with the <i>MUC5B</i> promoter variant was observed for RA without ILD (figure 1B). The association of the <i>MUC5B</i> promoter variant with RA-ILD increased significantly when restricted to the usual interstitial pneumonia (UIP) by high-resolution computed tomography (OR<i><sub>combined</sub></i>=6.1 95% CI: 2.9 to 13.1; p=2.5x10–6) (figure 1C). Immunohistochemical and <i>in-situ</i> hybridization analysis of RA-ILD lung tissue demonstrated expression of <i>MUC5B</i> by type 2 alveolar epithelial cells undergoing endoplasmic reticulum stress. <h3>Conclusions</h3> Our findings demonstrate that <i>MUC5B</i> promoter variant rs35705950 is a risk factor for RA-ILD specifically associated with radiologic evidence of UIP. <h3>Disclosure of Interest</h3> None declared
Associations of medication measures and geriatric impairments with chemotherapy dose intensity in older adults with advanced cancer: A University of Rochester NCI Community Oncology Research Program study.
Authors: Mostafa R. Mohamed, Supriya Gupta Mohile, Huiwen Xu, Asad Arastu, Spencer Obrecht, Kah Poh Loh, Ronald John Maggiore, Eva Culakova, Holly Michelle Holmes, Ginah Nightingale, Bryan Faller, Tony Philip, Adedayo A. Onitilo, Erika E. Ramsdale
Journal: Journal of Clinical Oncology (2018)

e22034 Background: Older patients (pts) with cancer have more chemotherapy (chemo) toxicities leading to dose modifications. Few studies have evaluated the association of concomitant medications (meds) and geriatric impairments with chemo dosing. This study examines the associations of medication measures [polypharmacy (PP), potentially inappropriate medications (PIM) and potential drug interactions (PDI)] and Geriatric Assessment (GA) impairments with relative dose intensity (RDI) of chemo in older adults with advanced cancer. Methods: A secondary analysis was conducted on the control arm of an ongoing prospective randomized study enrolling pts > 70 with advanced cancers on chemo. PP was defined as concurrent use of ≥5 meds at baseline. PIMs were categorized using 2012 Beers criteria and Screening Tool of Older Person’s Prescriptions (STOPP). PDI were reviewed using Lexi-Interact® Online with category D and X as major PDI. Pts underwent a GA at baseline evaluating PP, cognition, nutrition, physical function, comorbidities, mood, and social support. A score of 1 was given to an impaired domain (except for PP and comorbidity) and total score was generated. RDI was a ratio of received to standard dose of chemo for the first 3 months of therapy ( < 65 vs. ≥65%). Bivariate and multivariate logistic regressions analyses were performed controlling for covariates at P < 0.1. Results: Among 60 pts (mean age 77, 57% males, 87% stage IV, 33% had upfront dose reduction), mean number of meds was 8 (range 0-24). Mean number of GA impairment was 3. The prevalence of med measures was as follows: PP (83%), PIM by Beers (55%), PIM by STOPP (58%), major PDI not involving chemo (55%), and major PDI involving chemo (15%). 29% had RDI < 65%. Multivariate analysis showed that higher GA impairment score was associated with RDI < 65% (OR 0.52, P = 0.038). No med measures were associated with RDI < 65%. Conclusions: Older pts with cancer have high prevalence of PP/PIM/PDI, but these were not associated with lower dose intensity. Higher GA impairment score was associated with lower RDI reflecting the importance of GA in predicting chemo tolerance.
P04.91 ABC-drug efflux transporters at the blood-brain barrier limit the efficacy of treatment against primary and secondary brain tumors
Authors: O van Tellingen, M C de Gooijer, L C M Buil, L Fan, N A de Vries, E M Kemper, C Citirikkaya, J H Beijnen
Journal: Neuro-Oncology (2018)

ABCB1 (P-glycoprotein; Pgp) and ABCG2 (Breast Cancer Resistance Protein; BCRP) are drug efflux transporters that are abundantly expressed at the blood-brain barrier (BBB). They limit the brain penetration of numerous compounds including many anticancer agents and protect the brain from drug induced toxicities. In primary as well as in metastatic brain tumors, the BBB is often disrupted. But does this imply that anticancer agents will be able to readily reach the tumor and elicit an antitumor response? Materials and Methods: We tested a series of primary and metastatic brain tumor models, including primary human glioma stem cell (GSC) line models, DIPGs, metastases models of different origins (breast, skin) as well as inducible genetically engineered mouse models of glioblastoma (GBM). Transplantable tumors were implanted into ABCB1/ABCG2 proficient (wildtype; WT) or deficient (knockout; KO) recipient animals and/or we used elacridar, a dual pump inhibitor to block their function. We characterized these models for leakiness of the BBB using contrast-enhanced MRI, fluorescent dyes and 14C-labeled amino isobutyric acid. We have stained tissue specimens by IHC for ABCB1 and ABCG2. We have determined drug levels in brain and brain tumors and we have performed efficacy experiments with cytotoxic drugs or relevant targeted agents. Leakiness of the BBB in primary brain tumor models varies from extensive (U87) to almost absent (GBM8, DIPG). In all models, the tumor vasculature expresses ABCG2 and ABCB1 with intensities usually higher than in normal brain capillaries. Drug levels in non-leaky tumors (e.g. GBM8) are similar as in normal brain. Although the drug levels are higher in leakier tumors (several models, including metastatic models), the levels further increase when the same tumors grow in ABCG2/ABCB1 KO mice and/or in WT mice when treated in combination with elacridar. This was even the case in very leaky GBM tumors such as U87. Only in very leaky metastatic tumors (e.g. Mel57 with ectopic overexpression of VEGF) the ABC transporters did not reduce treatment efficacy. Leakiness of the BBB in tumors does not imply good accessibility of drugs to brain tumors. Although therapeutics can exert a response against brain tumors, their efficacy is limited by the ABC transporters even when tumors clearly enhance on MRI scans.
Reasons for the cold immune microenvironment of neuroendocrine tumors.
Authors: Lotte D de Hosson, Grietje Bouma, Gursah Kats-Ugurlu, Marian Bulthuis, Elisabeth G.E. de Vries, Martijn Van Faassen, Ido P Kema, Anna Maria Elisabeth Walenkamp
Journal: Journal of Clinical Oncology (2018)

e15142 Background: Tumors can escape the immune system by expressing programmed death-ligand-1 (PD-L1) which allows them to bind to PD-1 on T-cells and thereby to avoid recognition by the immune system. PD-L1 and PD-1 inhibitors have antitumor activity across numerous tumor types. In addition, T-cells, indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) play a role in immune suppression. However, there is limited knowledge of interaction of neuroendocrine tumor (NETs) with their immune microenvironment and the role of immunotherapy in patients with NET. Therefore, this study aimed to investigate the immune microenvironment of serotonin-producing (SP) and non-serotonin producing NETs (NSP-NETs). Methods: Tumor tissues of 51 patients with NETs grade 1 or 2, collected before start of systemic treatment, were selected. 5-Hydroxyindolacetic acid (5-HIAA) in 24-h urine and/or platelet serotonin were measured by liquid chromatography in combination with isotope dilution mass spectrometry to analyze the serotonin production by the NET. Immunohistochemical analyses were performed for PD-L1, T-cells, IDO and TDO. Additionally, stroma cells were stained with α-SMA. Results: Tumors of 33 patients with SP-NET and 18 patients with NSP-NETs were studied. PD-L1 expression was < 1% in tumor cells and T-cells. T-cells, were present in 33% of evaluable NETs, varying between 1-10% T-cells per high power field. IDO was expressed in 55% of SP-NETs and 22% of NSP-NETs (p = 0.039). TDO staining was prominent in stroma in 44% of NETs with or without concomitant positive TDO staining in tumor cells in 37% of evaluable NETs. TDO was expressed in stromal cells in 89% of SP-NETs and 22% NSP-NETs (p = 0.001). α-SMA positive stroma cells were identified as cancer associated fibroblasts (CAFs). Conclusions: NETs lack pre-existing immunity as they do not express PDL-1 expression in tumor- or T-cells, and there are only few tumor infiltrating T-cells. We found IDO and TDO expression in tumor cells and TDO expression in stromal cells (CAFs), especially in SP-NETs. These two mechanisms can be responsible for the cold immune microenvironment in NETs, which can be further explored to enhance anti-tumor immunity and clinical responses.
A high-risk genetic profile for premature menopause (PM) in childhood cancer survivors (CCS) exposed to gonadotoxic therapy: A report from the St. Jude Lifetime Cohort (SJLIFE) and Childhood Cancer Survivor Study (CCSS).
Authors: Russell J Brooke, Wassim Chemaitilly, Carmen Louise Wilson, Matthew J. Krasin, Zhenghong Li, Cindy Im, Lindsay M. Morton, Gang Wu, Zhaoming Wang, Wenan Chen, Rebecca M. Howell, Gregory T. Armstrong, Smita Bhatia, Stephen J. Chanock, Jinghui Zhang, Daniel M. Green, Charles A. Sklar, Melissa M. Hudson, Leslie L. Robison, Yutaka Yasui
Journal: Journal of Clinical Oncology (2017)

10502 Background: CCS are at increased risk of therapy-related PM but contribution of genetic factors is unknown. Methods: Using Affymetrix 6.0 SNP array, treatment exposures [cumulative alkylating agents (AA), ovarian radiotherapy (RT) dose] and clinically-assessed PM status (menopause &lt; 40 years), a genome-wide association analysis was conducted using logistic regression in SJLIFE. A cluster of most statistically significant SNPs on chr4 was further examined, stratifying by ovarian RT and AA. Replication was performed using self-reported PM in CCSS. Results: PM was diagnosed in 30 of 805 SJLIFE female survivors. A loci of 13 SNPs in 4 linkage disequilibrium blocks (mean r 2 = 0.51) in the upstream regulatory region of Neuropeptide Receptor 2 ( NPY2R) was identified with a minimum p-value of 3.3x10 -7 (all &lt;10 -5 ). ENCODE gene expression, motifs, and chromatin remodeling data suggest these SNPs alter transcription factor binding sites, potentially disrupting neuroendocrine events necessary for ovulation. Among CCS exposed to ovarian RT, homozygous carriers of a risk profile (RP) defined by 4 of the 13 SNPs, found in over half of the survivors with clinically-diagnosed PM and 1 in 7 in the general population, significantly increased PM risk (odds ratio (OR) 25.8, p=5.4x10 -5 ) (Table). This finding was replicated using self-reported PM status of 1644 survivors in CCSS (OR 4.2, p=4.6x10 -4 ). Prediction of clinically-diagnosed PM (in the SJLIFE discovery cohort) improved by adding the RP to the model with age and treatment (area under ROC curve 0.84 vs. 0.93, p=0.011). Conclusions: The common RP is associated with PM risk in pediatric cancer survivors and may have potential for clinical application. [Table: see text]
Significance of Prognostic Nutritional Index in post-surgical outcomes after surgical management in gastric cancer patients.
Authors: Marytere Herrera, Nora Sobrevilla-Moreno, IVAN LYRA-GONZALEZ, German Calderillo, Consuelo Diaz, Erika Ruiz Garcia
Journal: Journal of Clinical Oncology (2017)

e15535 Background: Preoperative nutritional status in gastric cancer patients is not only correlated with postoperative complications, also, prognostic nutritional index or Onodera´s nutritional index (PNI) may relate with overall survival (OS) after gastrectomy. There is no available data of preoperative nutritional status in Mexican population. We decide to explore these variables and analyze its impact in outcomes reported in our population. Methods: This is a retrospective included a total of 91 patients patients with locally advanced gastric cancer confirmed by laparoscopy treated in the National Cancer Institute in México between January 2010 and June 2016. The PNI level was determined according the following formula: 10 x serum albumin (g/dl) + 0.005 x total lymphocyte count (per mm3). The optimal cutoff value of PNI in our population was set at 38.7 according the median, we stratified patients in high (PNI &gt; 38.7) or low (PNI &lt; 38.7) nutritional status, clinicopathologic features were compared. Results: We analyzed 91 patients, the mean patients age was 58, 61.5% were man, the 51.6% went to total gastrectomy with D2 dissection, 56% were pathologic stage III and 61.5% of the patients received adjuvant chemotherapy. The patients with high nutritional status had a OS of 46 months vs patients with low nutritional status with 25 months (p = 0.009). Patients with body mass index (BMI) &gt; 23 had a OS of 41 months vs patients with BMI &lt; 23 with 19 months of OS (p = 0.001), finally the patients with albumin &gt; 3.75 had a 39 months of OS vs 23 months with albumin &lt; 3.75 (p = 0.011) Conclusions: The low PNI group had worse OS than the high PNI group (46 months vs 25 months, p = 0.009). Preoperative is a simple and useful marker to predict overall survival in patients with locally advanced gastric cancer
Evaluation of disease-free survival as an intermediate metric for overall survival in localized renal cell carcinoma: A trial-level meta-analysis.
Authors: Lauren Christine Harshman, Wanling Xie, Raphael Brandao Moreira, Dominick Bosse, Gustavo Ruiz Ares, Christopher Sweeney, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

4585 Background: Adjuvant trials aim to integrate systemic therapy earlier to increase cure rates over surgery alone. Overall survival (OS) is a critical endpoint for these studies but requires long durations to events and significant patient resources. We explored the potential use of disease-free survival (DFS) as an intermediate readout for OS in the adjuvant setting for localized renal cell carcinoma (RCC). Methods: We performed a systematic literature review following the PRISMA guidelines. Inclusion criteria required randomized controlled trials (RCT) for adjuvant systemic therapy in localized RCC, which reported on both DFS and OS. Data on hazard ratio (HR) and 5-year event-free rate from Kaplan-Meier estimates were extracted. We performed a trial level meta-analysis and correlated these estimates for OS and DFS, weighted by the number of DFS events. R-square &gt; 0.7 would indicate a strong correlation and potential for surrogacy. Results: Thirteen RCTs encompassing 6,473 patients treated with various forms of systemic therapy were eligible for the analyses. Minimum follow-up was 40 months. There was a moderate correlation between 5-year DFS and 5-year OS rates (R-square = 0.49, 95% CI:0.15-0.68) and between treatment effects as measured by DFS and OS hazard ratios (R-square = 0.44, 95% CI:0.00-0.69). Conclusions: Across trials of adjuvant systemic therapy for localized RCC, we observed a moderate correlation between 5-year DFS and OS rates and between treatment effects (HRs) on these endpoints. Further granularity may be achieved using individual patient data to assess different and earlier time points for surrogacy than are commonly reported. [Table: see text]