tbuckley/cabot-search huggingface dataset:
Evaluation of different treatment strategies between right-sided and left-sided pneumonectomy for stage I-IIIA non-small cell lung cancer patients.
Authors: Ziping Wang, Bo Jia, Qiwen Zheng, Yuyan Wang, Xinmeng Qi
Journal: Journal of Clinical Oncology (2018)

8524 Background: This study aimed to investigate the survival difference between right-sided and left-sided pneumonectomy in stage I-IIIA NSCLC patients, and to further develop the best treatment strategies. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute across 18 cancer registry sites in the United States were used for the present study. To avoid the bias between groups, we used an innovative propensity score matching analysis. Results: Stage I-IIIA NSCLC patients with pneumonectomy from 2004 to 2014 were included in this study. Of all 2,683 patients who received pneumonectomy, Overall survival (OS) (HR = 0.875, 95%CI: 0.793 to 0.967, P = 0.008) and cancer-specific survival (HR = 0.863, 95%CI: 0.771 to 0.965, P = 0.010) were significantly longer with left-sided pneumonectomy over right-sided pneumonectomy. After propensity score matching analysis for 2,050 patients, OS (HR = 0.858, 95%CI: 0.768 to 0.959, P = 0.007) and cancer-specific survival (HR = 0.847, 95%CI: 0.745 to 0.963, P = 0.011) were also significantly superior of left-sided compared with opposite-sided pneumonectomy. After matching procedure, among left-sided pneumonectomy patients, adjuvant therapy significantly prolonged OS (46 versus 30 months, HR = 1.458, 95%CI: 1.239 to 1.715, P < 0.001) and cancer-specific survival (67 versus 51 months, HR = 1.314, 95%CI: 1.093 to 1.579, P = 0.004) while among right-sided pneumonectomy patients, adjuvant therapy was not associated with cancer-specific survival benefit (46 versus 42 months, HR = 1.112, 95%CI: 0.933 to 1.325, P = 0.236). Subgroup analysis showed that adjuvant chemotherapy could significantly improve OS and cancer-specific survival for both sided pneumonectomy patients. But patients with right-sided pneumonectomy who received radiotherapy were associated with worse survival. Conclusions: Right-sided pneumonectomy was associated with worse survival compared with left-sided pneumonectomy. Adjuvant chemotherapy contribute significant benefit to patients who received both sided pneumonectomy, but radiotherapy worsened prognosis for right-sided pneumonectomy.
Assessing the impact of early Medicaid expansion on insurance rates among children with cancer.
Authors: Justin Barnes, Kimberly J. Johnson
Journal: Journal of Clinical Oncology (2018)

e18606 Background: Some evidence suggests that lack of insurance among children with cancer is associated with poorer outcomes and that cancer outcomes are similar among insured children, regardless of whether private or public (i.e. Medicaid). Our objective is to examine 2010-2011 Medicaid expansion related changes on insurance rates and to determine whether the degree of insurance change differs by demographic or socioeconomic factors. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 18 database, we identified children aged 0-14 years diagnosed with a first primary malignancy between 2007-2014. We utilized a quasi-experimental design, comparing Medicaid expansion related changes in insurance rates in the intervention group (cases from early expansion states) to a control group (cases from other states) using difference in differences (DID) analyses applied to linear probability models. Results: We included 18,540 individuals. After early Medicaid expansion, Medicaid enrollment levels rose from 31.9% to 38.3% and from 39.4% to 42% in expansion (EXP) and non-expansion (NEXP) states, respectively. The rate of uninsured decreased from 1.6% to 1.4% in EXP states, while it increased from 1.7% to 2.5% in NEXP states. In DID analyses, we found increases in Medicaid insurance (4.66 Percentage Points [PP], 95% CI = 1.84 to 7.49, p = 0.001) and decreases in the rate of uninsured (-0.88 PP, 95% CI = -1.71 to -0.05, p = 0.037) in EXP relative to NEXP states. We found differing expansion-related changes in Medicaid rates by county poverty level (-3.1 PP, 95% CI = -9.3 to 3.0; 3.3 PP, 95% CI = -2.6 to 9.1; 8.5 PP, 95% CI = 1.9 to 15.0; and 5.6 PP, 95% CI = 0.1 to 11.2 among counties with family poverty rates of < 7.8%, 7.8-10.2%, 10.2-13.7%, and > 13.7%, respectively; p = 0.035). Conclusions: Early Medicaid expansion was associated with increasing the rates of Medicaid insurance and reducing the rates of uninsurance among children with cancer, where the greatest uptake in Medicaid was seen in children residing in counties with higher poverty. Thus, Medicaid expansion may work to improve childhood cancer prognosis and reduce disparities in pediatric cancer outcomes. Further research is needed to evaluate its impact on prognosis.
Race, Ancestry, and Reporting in Medical Journals
Authors: Richard S. Cooper, Girish N. Nadkarni, Gbenga Ogedegbe
Journal: JAMA (2018)

This Viewpoint discusses the appropriateness of documentation of race in the medical history and record, and discusses the challenge of taking the effects of race on patient health seriously without overemphasizing it as an unalterable source of difference at the individual or population level.
Correlation between immune-related adverse events (irAEs) and efficacy in patients with solid tumors treated with immune-checkpoints inhibitors (ICIs).
Authors: Mariona Riudavets, Andrés Barba, Pablo Maroto, IVANA GABRIELA SULLIVAN, Georgia Anguera, David Páez, Luis del Carpio, Ana Callejo, Cintia Gonzalez Blanco, Esther Garcia Planellas, Diego Castillo, Carme Facundo, Idoia Genua, Cristina Martin Lorente, Ana Virgili, Ana Sebio, Oscar Gallego, Antonio Lopez-Pousa, Agust Barnadas, Margarita Majem
Journal: Journal of Clinical Oncology (2018)

3064 Background: ICIs are associated with irAEs. We describe the incidence of irAEs in patients with solid tumors receiving ICIs and its correlation with efficacy. Methods: We retrospectively analyzed all patients with solid tumors receiving ICIs in our center. IrAEs were graded according CTCAE v4.0. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survivals (OS). Analyses were performed using SPSS v24 package. Results: From March 2014 to January 2018, 178 patients received ICIs. Median age was 64.1 [33-88] years, 72% were male. Most frequent tumors were lung (63.5%), bladder (14.6%) and melanoma (11.8%). 96% presented advanced disease. Most common used ICIs were nivolumab (38.2%), pembrolizumab (28.7%) and atezolizumab (17.4%). ICIs were used as monotherapy (74.7%) or in combination with ICI (3.4%), chemotherapy (17.4%) or targeted therapies (4.5%). Median duration of immunotherapy was 6.9 [0.7-46.3] months. 95 (53.4%) patients developed 158 irAEs with a median number per patient of 1.2 [0-4]. Most frequent irAE was rash (24.7%) followed by diarrhea (17.7%), hypothyroidism (9.5%), arthritis (6.9%), hyperthyroidism (3.8%), pneumonitis (3.2%) and mucositis (3.2%). Median time to the onset irAEs was 53.2 [11-490] days. 12 (6.7%) patients presented grade (G) 3-4 irAEs: 5 G-3 diarrhea, 2 G-3-4 liver dysfunction, 1 G-3 pneumonitis, 1 G-3 hypopituitarism, 1 G-3 mucositis, 1 G-3 arthritis and 1 G-3 nephritis. There were 2 (1.1%) treatment-related deaths due to pneumonitis. 21.3% patients required steroids for irAEs management. 8.4% patients discontinued treatment due to irAEs. 73.9% irAEs had improved at the time of analysis. OS was superior in patients with advanced disease experiencing irAEs: 37.3 [95%CI, 19.2-51.4] vs 7.8 [95%CI, 4.9-10.8] months (p < 0.0001). Similarly, PFS was longer: 7.9 [95%CI, 4.4-11.4] vs 2.6 [95%CI, 2.0-3.2] months (p < 0.0001). Conclusions: There was a significant correlation between presence of irAEs and outcomes in patients with advanced solid tumors treated with ICIs.
The effects of the first in class steroid sulfatase inhibitor Irosustat on FLT uptake and Ki67 in estrogen receptor positive early breast cancer: Results of the perioperative IPET study.
Authors: Carlo Palmieri, Richard Szydlo, Marie Miller, Laura Woodley-Barker, Neva Patel, Tara Berwick, Henry Tam, Dimitri Hadjiminas, Jasmin Lee, Abeer Shaaban, Sadie Reed, Hanna Nicholas, Charles Coombes, Laura M. Kenny
Journal: Journal of Clinical Oncology (2016)

e23140 Background: The steroid sulfatase (STS) pathway is involved in oestrogen biosynthesis. Irosustat is a 1st generation, orally active, irreversible STS inhibitor. Changes in the expression of the proliferation marker Ki67 in the context of perioperative studies in estrogen-receptor positive (ER+) early breast cancer (EBC) has been shown to be closely linked with relapse free survival. 3’-deoxy-3’-[18F] fluorothymidine (FLT) is a nucleoside analogue developed as a PET radiotracer for imaging proliferation; FLT uptake has been shown to correlate with tumour cell proliferation. We conducted a perioperative study in ER+ EBC to examine the changes in FLT uptake and Ki67 expression.Our study was designed to test the hypothesis that inhibition of STS with Irosustat for 2 weeks can result in a significant decrease in FLT uptake and therefore, tumour proliferation. Methods: Postmenopausal women with untreated ER+ EBC were recruited, and following a baseline FLT-PET scan received Irosustat (40mg once daily) for at least 2 weeks with a subsequent on treatment FLT-PET scan. The primary endpoint was change in FLT uptake, and other endpoints included safety and tolerability, changes in Ki-67, and expression of intratumoural steroidogenic enzymes and levels of circulating steroid hormone. Results: Between 11/2012 and 11/2014 13 women were recruited, and 10 started Irosustat treatment, followed by a repeat FLT-PET scan (N = 8). The median % changes in SUV and Ki from pre to post treatment were -0.4 (-29.9-48.2) and -7.1 (-62-193), respectively. Defining response as decreases of ≥ 20% in SUV and ≥ 30% in Ki, we observed responses in 1 (12.5% (95%CI 2-47%, p = 0.001)) and 3 (43% (95%CI 16-75%, p = < 0.001) patients respectively. The median % difference in Ki67 from pre to post treatment was 52.3% (p = 0.028). All adverse events were CTCAE Grade ≤ 2, with the most common grade 2 AE being an abnormal ECG. Pharmacodynamic data will be presented. Conclusions: Irosustat treatment resulted in a significant reduction in FLT uptake as well as Ki67, and is well tolerated. These data are the first demonstrating clinical activity of Irosustat in EBC, larger studies are needed. Clinical trial information: NCT01662726.
Palliative treatment of pancreatic adenocarcinoma in a real-world setting.
Authors: Maximilian Kordes, Oscar Malgerud, Masoud Karimi, Jan-Erik Frödin, Maria Gustafsson Liljefors, Matthias Loehr
Journal: Journal of Clinical Oncology (2018)

e16243 Background: Patients with pancreatic adenocarcinoma in routine care are more diverse than in clinical trials. We evaluated first-line palliative treatment in an unselected cohort and examined the efficacy of second-line treatment for which evidence is scarce. Methods: We studied a multiple site, single-institution cohort that started treatment between January 1, 2013 and July 31, 2017. Median survival (OS) and time to treatment failure (TTF) were assessed with Log-rank test and Cox regression. Results: We identified 593 patients. OS, TTF, and hazard ratio for death (HR) according to first-line (A) and second-line (B) treatment are summarized below. Gemcitabine-based first-line followed by 5-FU-based second-line (n = 75; OS 13.1 mo. [11.1-15.1]) was superior to the reverse (n = 26; OS 9.7 mo. [8.5-11]; HR 2.5 [1.4-4.2]). Performance status, diabetes, alcohol abuse, CA 19-9 level and M1-status influenced OS in the Cox model (p < 0.05). In first-line treatment hematological adverse events grade ≥3 (6.5% vs 4.1%) and febrile neutropenia and sepsis (8.5% vs 5.5%) were more common, neuropathy grade ≥3 (1.5% vs 4.1%) increased in second-line. Conclusions: First-line palliative treatment in a real-world setting has outcomes comparable to clinical trials. Gemcitabine and Gemcitabine/nab-Paclitaxel were inferior to other second-line protocols. (A) 1st line GEM GEM/CAP GEM/nPAC FOLFIRINOX 5-FU/OX OTHER BSC Patients – n 185 60 65 29 36 12 206 Median OS – mo 6.7 (5.6-7.8) 10.7 (8-13.4) 9.5 (7.7-11.3) 10 (8.3-11.8) 5.8 (3.5-8.2) 8 (3.5-8.2) 1.8 (1.5-2-2) Median TTF – mo 3.3 (2.9-3.8) 3.7 (2.5-5) 5.1 (4.3-6) 2.9 (1.1-4.7) 2.9 (2.4-3.2) 3.5 (2.1-4.9) – HR 1 0.6 (0.4-0.9) 0.5 (0.4-0.8) 0.7 (0.4-1.1) 1.2 (0.8-1.8) 0.7 (0.3-1.6) 3.2 (2.4-4.3) (B) 2nd line GEM GEM/nPAC 5-FU/OX 5-FU/IRI 5-FU (CAP) OTHER BSC Patients – n 27 22 53 19 13 12 147 Median OS – mo 4 (3.6-4.3) 5.5 (4.0-7) 7.1 (6.3-7.9) 8.2 (6.4-10) 8.4 (0.8-16.1) 4.3 (3.7-4.8) 3.5 (2.9-4.1) Median TTF – mo 3.5 (3.5-3.9) 3.4 (3.5-4.7) 3.2 (3.2-3.9) 2.4 (2.4-2.6) 4 (4-6.3) 4 (4-7.4) – HR 1 0.7 (0.3-1.3) 0.4 (0.3-0.8) 0.3 (0.2-0.7) 0.5 (0.2-1.2) 0.5 (0.2-1.3) 0.9 (0.5-1.4) indicate 95% CI. GEM: Gemcitabine; CAP: Capecitabine; nPAC: nab-Paclitaxel; Ox: Oxaliplatin; IRI: Irinotecan; BSC: Best supportive care
PPARα and Effects of TCE
Authors: James E. Klaunig, Michael A. Babich, Jon C. Cook, Raymond M. David, John G. DeLuca, Richard H. McKee, Jeffrey M. Peters, Ruth A. Roberts, Penelope A. Fenner-Crisp
Journal: Environmental Health Perspectives (2007)

PPARα and Effects of TCEWe would like to offer a different opinion on the ideas presented in the article by Keshava and Caldwell (2006).The authors indicated that their article summarized scientific literature published since an earlier U.S. Environmental Protection Agency (EPA) risk assessment of trichloroethylene (TCE), with an emphasis on the possible role of proliferator-activated receptor α (PPARα) agonism relevant to TCE risk assessment.Interestingly, in the section on recent data on PPARα agonism, Keshava and Caldwell failed to establish any gene expression signature relating TCE and PPARα.Keshava and Caldwell (2006) contended that it is difficult to identify a clear pattern of common gene expression changes for TCE and PPARα agonists in general.However, they did not consider numerous reports and reviews (e.g., Klaunig et al. 2003;Peters et al. 2005) illustrating that there are common and reproducible changes in gene expression associated with PPARα agonists.Further, extensive characterization has definitively demonstrated specific, direct targets of PPARα-retinoid X receptor heterodimers (reviewed by Klaunig et al. 2003).Keshava and Caldwell (2006) also did not discuss the
Treatment outcomes and healthcare resource utilization (HRU) in patients (Pts) with newly diagnosed multiple myeloma (NDMM) with lenalidomide (LEN) only or no maintenance: Connect MM registry.
Authors: Robert M. Rifkin, Sundar Jagannath, Brian G. Durie, Jatin J. Shah, Mohit Narang, Howard R. Terebelo, Cristina Gasparetto, Kathleen Toomey, James W. Hardin, Lynne I. Wagner, Kejal Parikh, Safiya Abouzaid, Shankar Srinivasan, Amani Kitali, Faiza Zafar, Rafat Abonour
Journal: Journal of Clinical Oncology (2017)

e19527 Background: Maintenance therapy (MT) post autologous stem cell transplant (ASCT) improves clinical outcomes in MM, but the effect of continued treatment on HRU is largely unknown. In the Connect MM registry, 1493 NDMM pts are enrolled in cohort 1 (Sept 2009–Dec 2011) in a mostly community setting; of pts receiving MT, 70% received LEN-only MT. The effect of LEN-only vs no MT on progression-free survival (PFS), overall survival (OS) and HRU was evaluated. Methods: Adults with NDMM who completed induction and single ASCT without subsequent consolidation and received LEN-only or no MT were compared. HRU (hospitalization, surgery/procedures, concomitant medications [growth factor, bisphosphonate, neuropathic pain medication]) was assessed from 100 days post-ASCT to end of years 1 and 2. Data cutoff was Jan 7, 2016 (median follow-up of 39.3 mo). Results: 421 pts met the analysis criteria stipulated above. Of these, 180 received LEN-only MT, and 165 did not receive MT. Median age was 60 y (range, 24-78 y); 60% were men; 86%, white. Besides serum creatinine, calculated International Staging System stage, history of monoclonal gammopathy of unknown significance, del(17p), and induction regimen, characteristics were similar across groups. PFS and OS were significantly improved with LEN-only vs no MT (Table). Rate of hospitalization/100 person-years (PY) was similar across groups ( P= NS, all comparisons) at the end of years 1 and 2. Median duration of hospitalization was numerically longer with no MT. Procedures/surgeries and concomitant medication use were similar across both groups at the end of years 1 and 2. Conclusions: For pts with NDMM, LEN-only vs no MT significantly improved survival outcomes without affecting HRU. Clinical trial information: NCT01081028. [Table: see text]
Assessment of conditional survival probability in resected esophageal adenocarcinoma.
Authors: Donna M. Graham, Finian Bannon, Megan Lloyd, Fergus Noble, Rob Walker, Ewen Griffiths, Matthew Bedford, John Whiting, Barbara Nutzinger, Nicola Grehan, Robert O'Neill, Richard Skipworth, Stuart Mercer, John Saunders, Simon L. Parsons, Richard D. Kennedy, Rebecca C. Fitzgerald, Timothy J Underwood, Richard C. Turkington
Journal: Journal of Clinical Oncology (2017)

4030 Background: Prognostication for cancer patients is based upon factors determined at baseline and becomes less relevant over time. Conditional survival (CS) estimates future prognosis based upon survival to a specific time point after treatment. We analyzed CS for patients in the United Kingdom (UK) undergoing surgery and neoadjuvant chemotherapy (NAC) for gastro-esophageal junction (GEJ) or esophageal adenocarcinoma (EAC). Methods: 1409 patients with GEJ/EAC treated with NAC and surgical resection at 7 centers across the UK from 2002-2014 were identified. Clinicopathological and survival data was collected as part of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium. A multivariable Cox survival model was used to analyze the association of factors such as node positivity (N+), lymphovascular invasion (LVI+), tumor differentiation, circumferential resection margin involvement (CRM+) and pathological response by tumor regression grade (TRG ≤2) with risk of relapse (RR) or death from time of surgery. Results: Of 1409 patients, 726 (51.5%) were aged &lt;65 years, and 1195 (84.8%) were male. Hazard ratios (HR) for RR conditional on recurrence-free (RF) years to date are detailed below. N+ was the most robust predictor of relapse and mortality over time. LVI+ and moderate to poor differentiation influenced relapse in the first 2 years whereas CRM+ and TRG≤2 had their greatest effect in the year following surgery. Age, sex, and year of surgery had no association with RR or mortality. Similar patterns were observed for risk of death. Conclusions: CS provides a more dynamic estimate of future RR and survival among patients who have accrued survival time, especially in patients with high-risk features. CRM+ and LVI+ govern early survival events but as time from surgery increases these factors become less relevant. [Table: see text]
Biologic heterogeneity of KRAS-mutated lung adenocarcinomas (K-ADC).
Authors: Tiffany Huynh, Justin F. Gainor, Valentina Nardi, Mari Mino-Kenudson
Journal: Journal of Clinical Oncology (2016)

8532 Background: No effective targeted therapies are currently available for K-ADC. Although the association of PD-L1 expression with KRAS mutations in ADC has been reported suggesting that PD-1/PD-L1 blockade may be a treatment strategy for K-ADC, the majority of K-ADC do not exhibit PD-L1. Furthermore, multiple studies have shown heterogeneity in therapeutic responsiveness and biology in K-ADC. Thus, we evaluated 149 K-ADC with a few biomarkers to classify them into biologically relevant groups. Methods: p53, HNF4a, PD-L1 and CD8 IHC were performed. Nuclear expression of p53 and HNF4a and membranous staining of PD-L1 in the tumor cells were scored in accordance with the published criteria. CD8+ tumor infiltrating lymphocytes (TILs) on > 5% of tumor cells were considered positive. The cohort was classified into p53 abnormal (KP), p53 normal & HNF4a + (KH) and p53 normal & HNF4a - (KN) groups. Clinicopathological and molecular variables, PD-L1 expression, CD8+ TILs and progression free survival (PFS) were compared between the 3 groups. Results: Of the 149 patients (71 stage I, 15 stage II, 20 stage III, and 43 stage IV), 81, 25 and 43 were classified into the KP, KH and KN groups, respectively. The KP group was associated with advanced stage (IV) (43%, p = 0.043 vs. KN), PD-L1 expression (62.5%, p = 0.0002 vs. KH, p = 0.0023 vs. KN) and increased CD8+ TILs (32%, p = 0.0036 vs. KH, p = 0.0015 vs. KN), while the KH group was associated with an invasive mucinous adenocarcinoma (IMA) morphology (48%, p < 0.0001 vs. KP and KN). There was no difference in KRASmutation types between the groups. As for survival, the KN group showed a lower 5-year PFS rate than the KP and KH groups (37%, 48% and 59%, respectively), although it was not significant. Conclusions: K-ADC appear to consist of biologically distinct groups. While those with p53 alterations are more likely to present at an advanced stage, increased PD-L1 expression and CD8+ TILs may make such tumors amenable to PD-1/PD-L1 inhibition. HNF4a + tumors are more likely to exhibit the IMA morphology and follow a more indolent clinical course. Those with neither alteration may have additional abnormalities such as LKB1 loss that has been associated with poor survival in K-ADC. Additional study to evaluate LKB1 expression is underway.
TCT-135 Impact of Clinical Frailty in Patients with Peripheral Artery Disease: from I-PAD Registry
Authors: Tomoaki Mochidome, Takashi Miura, Tamon Kato, Masao Hirabayashi, Daisuke Kashiwagi, Takashi Yanagisawa, Tomoya Hasegawa, Keisuke Machida, Tadamasa Wakabayashi, Naoyuki Abe, Kenichi Karube, Kyuhachi Otagiri, Yoshiteru Okina, Takahiro Kobayashi, Toshio Kasai, Uichi Ikeda
Journal: Journal of the American College of Cardiology (2018)