tbuckley/cabot-search huggingface dataset:
First-line FOLFIRI and bevacizumab in patients with advanced colorectal cancer prospectively stratified according to serum LDH: Final results of the Italian Research Group for Digestive Tract Cancer (GISCAD) CENTRAL (ColorEctalvastiNTRiAlLdh) and SENTRAL (Serum angiogenesis-cENTRAL) analysis.
Authors: Mario Scartozzi, Riccardo Giampieri, Bruno Daniele, Daris Ferrari, Sara Lonardi, Alberto Zaniboni, Luigi Cavanna, Gerardo Rosati, Nicoletta Pella, M. Giulia Zampino, Pietro Sozzi, Laura Casula, Lorena Cozzi, Domenico Germano, Marco Puzzoni, Cristian Loretelli, Vittorina Zagonel, Roberto Labianca, Luciano Frontini, Stefano Cascinu
Journal: Journal of Clinical Oncology (2016)

e15116 Background: Previous findings suggested that bevacizumab might improve clinical outcome in colorectal cancer patients with high basal LDH levels. We conducted a prospective trial to ascertain whether bevacizumab and FOLFIRI had an improved clinical activity in high LDH serum levels patients. A pre-planned analysis (SENTRAL) was conducted to identify changes in circulating pro-angiogenic factors during treatment. Methods: Primary end-point of the study was response rate (RR), according to previous findings required sample size was set at 75 patients and LDH cut-off was set at 1.2 LDH UNL. Secondary end-points were overall survival (OS), progression free survival (PFS) and changes in circulating pro-angiogenic factors (HGF, SDF-1, PLGF, FGF-2, MCP-3, IL-8). Assessment of circulating factors was performed before start of treatment and at each cycle until treatment discontinuation. Results: Eighty-one patients were enrolled in the study, 47% of the patients showed high LDH levels, whereas 43% had low LDH levels. The RR in the high LDH level group was 39% vs. 31% in the low LDH levels stratum. Median PFS for patients showing an increase in FGF-2 levels, from basal levels to first-radiological evaluation was 15.8 months vs. 6.9 months for patients demonstrating a decrease in FGF-2 levels (HR:0.37, 95%CI:0.17-0.78, p = 0.0101). We also observed a trend towards improved overall survival for patients showing an increase in FGF-2 levels (not reached vs. 15.1 months, HR: 0.36, 95%CI:0.12-1.09, p = 0.10). No further differences were identified in the remaining proangiogenic factors examined. Conclusions: The CENTRAL trial failed to demonstrate that high LDH levels are related to improved RR in patients receiving first-line FOLFIRI+Bevacizumab. The improved clinical outcome for patients showing an increase in FGF-2 might be a result of an efficient angiogenic blockade. We can in fact hypothesise that in presence of an effective anti-angiogenic activity, mechanisms of escape involving FGF-2 are activated.
Abstract 13160: Low-intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Contractile Cardiac Function in Pressure-Overloaded Hearts in Mice
Authors: Tsuyoshi Ogata, Kenta Ito, Tomohiko Shindo, Kazuaki Hatanaka, Kumiko Eguchi, Ryo Kurosawa, Yuta Kagaya, Hiroaki Shimokawa
Journal: Circulation (2016)

Introduction: Chronic pressure overload causes relative ischemia with resultant left ventricular (LV) dysfunction. Because the number of patients with chronic heart failure of ischemic origin is increasing worldwide, development of novel therapeutic strategies for those patients are needed. We have previously demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. We also have recently reported that the LIPUS ameliorates post-MI LV remodeling in a mouse model of acute myocardial infarction (AMI). In the present study, we thus examined whether LIPUS also ameliorates contractile cardiac function in pressure-overloaded hearts in mice. Methods and Results: Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. The heart was treated with either placebo or LIPUS three times in the first week after TAC and was subsequently repeated once a week for 8 weeks. At 8 weeks, LV fractional shortening (LVFS) was significantly depressed in the placebo group, which was significantly ameliorated in the LIPUS group (36.2±3.8 vs. 30.4±0.5%, P&lt;0.05). Capillary density in the LV was significantly higher in the LIPUS group than in placebo group (4229±455 vs. 3243±143 /mm 2 , P&lt;0.05). Perivascular fibrosis was attenuated in the LIPUS group compared with the placebo group (P&lt;0.05). The mRNA expression of BNP and Collagen III (Iα) was lower in the LIPUS group than in the placebo group (both P&lt;0.05). Western blot analysis revealed that VEGF, eNOS and Hif-1α were significantly up-regulated in the LIPUS group (all P&lt;0.05 vs. placebo). Akt was also significantly activated in the LIPUS group (P&lt;0.05 vs. placebo). No adverse effect related to LIPUS therapy was noted. Conclusions: These results indicate that the LIPUS therapy ameliorates contractile cardiac function in pressure overload-induced cardiac dysfunction, for which enhanced myocardial angiogenesis may be involved. Thus, the LIPUS therapy may be a promising, non-invasive therapeutic strategy for the treatment of cardiac dysfunction due to pressure overload.
Nivolumab (Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with &lt;1% tumor PD-L1 expression: Results from CheckMate 227.
Authors: Hossein Borghaei, Matthew David Hellmann, Luis G. Paz-Ares, Suresh S. Ramalingam, Martin Reck, Kenneth John O'Byrne, Prabhu Bhagavatheeswaran, Faith Ellen Nathan, Julie R. Brahmer
Journal: Journal of Clinical Oncology (2018)

9001 Background: CheckMate 227 (NCT02477826), a phase 3 study of 1L nivo + ipilimumab (ipi), nivo, or nivo + chemo vs chemo in advanced NSCLC, met its co-primary endpoint of prolonged progression-free survival (PFS) with nivo + ipi vs chemo in patients (pts) with tumor mutational burden ≥10 mutations/Mb. Identifying effective tx for pts without known predictive biomarkers remains an unmet need. Prior studies suggest addition of chemo to anti–PD-(L)1 tx can improve outcomes in an unselected pt population, although benefit is most pronounced in pts with higher tumor PD-L1 expression. We report results for nivo + chemo vs chemo in pts with < 1% tumor PD-L1 expression. Methods: Pts (n = 550) with chemo-naive, stage IV/recurrent NSCLC, no known sensitizing EGFR/ALK mutations, and < 1% tumor PD-L1 expression were stratified by tumor histology and randomized 1:1:1 to nivo 3 mg/kg Q2W + ipi 1 mg/kg Q6W, nivo 360 mg Q3W + chemo, or chemo (optional pemetrexed maintenance after chemo for nonsquamous [non-SQ] NSCLC). Pts were treated up to 2 yr. A descriptive analysis was performed for the secondary endpoint of PFS for nivo + chemo vs chemo in pts with < 1% tumor PD-L1 expression. No alpha was allocated for this analysis. Results: Baseline characteristics were balanced between nivo + chemo (n = 177) and chemo (n = 186) arms. PFS was improved with nivo + chemo vs chemo (HR = 0.74 [95% CI: 0.58, 0.94]; minimum follow-up 11.2 mo; descriptive comparison). PFS benefit with nivo + chemo was observed across most subgroups. Among histologic subgroups, benefit was more pronounced in non-SQ (HR = 0.68) relative to SQ NSCLC (HR = 0.92). Rates of any grade tx-related adverse events leading to discontinuation were 13% with nivo + chemo and 14% with chemo. Conclusions: 1L nivo + chemo improved PFS vs chemo in pts with advanced NSCLC and < 1% tumor PD-L1 expression, and was well tolerated. Results are encouraging in this analysis, which includes only pts with < 1% PD-L1. CheckMate 227 Part 2 (ongoing) is evaluating nivo + chemo vs chemo irrespective of PD-L1 expression and will further inform benefit from this combination across different subgroups of NSCLC. Clinical trial information: NCT02477826.
Emergency department (ED) presenting symptom clusters for chemotherapy patients.
Authors: Robert Michael Daly, Kevin Nicholas, Dmitriy Gorenshteyn, Stefania Sokolowski, Lior Gazit, Lynn Adams, Jennie Matays, Lauren L. Katzen, Ophelia O. Chiu, Han Xiao, Rori Salvaggio, Abigail Baldwin, Kimberly Chow, Mikel Ross, Kenneth K. Ng, Alice Zervoudakis, Wendy Perchick, Diane Lauren Reidy, Brett A Simon, Isaac Wagner
Journal: Journal of Clinical Oncology (2018)

e18509 Background: The Centers for Medicare and Medicaid Services (CMS) has identified inappropriate management of chemotherapy side effects as a significant gap in the care of cancer patients and has proposed to measure cancer hospitals’ performance based on the frequency of ED visits for these conditions: anemia, dehydration, diarrhea, emesis, nausea, neutropenia, fever, pain, pneumonia, and sepsis. Guidelines to manage chemotherapy-related symptoms are limited as they do not address the co-occurring nature of these conditions. Methods: We identified patients at a cancer hospital who had an ED visit for a CMS-defined preventable symptom within 30 days of chemotherapy in 2016. Co-occurrence of symptoms was measured using a Jaccard index. We then used a network community detection algorithm to define symptom clusters based on a random walk process. We next expanded our cohort to include a larger subset of potentially preventable symptoms to enable greater understanding of the symptomatology of chemotherapy patients. A potentially preventable symptom was defined as “a symptom that could be managed safely in the outpatient setting if identified early and managed proactively.” The same methodology was then applied to understand co-occurrence. Results: There were 9,900 ED presentations among active chemotherapy patients of which 6,800 had primary diagnoses that met CMS criteria. For the CMS cohort, the network analysis identified two distinct symptom clusters for pain/nausea/emesis/diarrhea/dehydration and fever/neutropenia/pneumonia/sepsis/anemia and the Jaccard index was strongest for pain co-occurring with nausea and emesis and for fever co-occurring with neutropenia. The expanded cohort included 80 symptoms and network analysis identified five distinct symptom clusters centered around fever, fatigue, nausea, dyspnea, and pain. The Jaccard index was strongest for fever co-occurring with neutropenia and abdominal pain co-occurring with nausea and emesis. Conclusions: Uncontrolled symptoms during treatment are associated with patient and caregiver distress, treatment delays, and unplanned acute care. There is a need for improved decision support tools that recognize the complexity of symptom co-occurrence.
Abstract 19639: Reducing Educational Barriers to Address Cpr Training Disparities in a Large Us Urban Community
Authors: Kelsey Sheak, Laura Hatchman, Jenelle Dunstan, Helene Lynch, Carlos Huerta, Marion Leary, Benjamin S Abella
Journal: Circulation (2015)

Background: Bystander CPR (BCPR) is a crucial therapy for cardiac arrest, yet less than 30%of victims receive it in most communities. Previous research has shown that BCPR training rates vary significantly according to community socioeconomicstatus (SES), with black or Hispanic individuals and those with low medianhousehold incomes being statistically less likely to have CPR training. We sought to test whether a community-based mobile layperson training approach that removed both cost and transportation barriers would target these disparities. Objective: To characterize the impact of our mobile layperson training intervention in a low-SES population through descriptive statistics and choropleth mapping of CPR training activity and associated SES. Design/Methods: A survey study of subjects trained through the mobile training intervention between 03/2013 and 03/2015 in which subjects’ demographics, prior CPR training status, and residential location were collected and analyzed. Subjects’ neighborhood SES at the block group level was ascertained using 2010 United States Census data. Results: Of 5789 subjects trained, 70% completed a demographic survey. 65% were female, 32% identified as white-Hispanic, 43% as black non-Hispanic, and 17% as white non-Hispanic. Of those &gt; 18 years of age, 71% did not complete college. 65% reported never having received CPR training. Attached figure represents the census block groups of the City of Hartford by those trained by the mobile project (A) and associated SES (B). The census block groups with &gt; 90 individuals trained were of low SES. Conclusion: A CPR training approach without transportation or cost barriers was successful in reaching a population of low-SES trainees with little previous exposure to CPR education. This approach holds promise as a scalable method to address SES disparities in BCPR provision.
Clinical characteristics and survival of lung cancer patients according to insurance status prior to and post implementation of the Affordable Care Act.
Authors: Adriana Reis Brandao Matutino, Allan Andresson Lima Pereira, Elizabeth Kornaga, Gilberto Lopes, D. Gwyn Bebb, Sunil Verma
Journal: Journal of Clinical Oncology (2018)

e18607 Background: Insurance status affects cancer stage at diagnosis, access to treatment and survival in the US. The Affordable Care Act (ACA) was implemented to expand access to health care. The aim of this study was to determine the association of insurance status with clinical characteristics, access to surgical treatment and survival among lung cancer pts pre and post-ACA. Methods: US SEER data was obtained for 18 to 64yo pts diagnosed with lung cancer from 2007 to 2012. Pts ≥65yo were excluded due to unreliable insurance status classification. To account for the introduction of the ACA in the US in 2010, data was analyzed by years 2007-2009 vs 2010-2012. OS was evaluated over a period of 26m and the 50th percentile was estimated. Pearson’s χ2 was used to assess significance of associations with insurance status and diagnosis year, and unadjusted associations were compared using the log-rank test. HRs were estimated using Cox proportional hazards model. Results: 84,549 pts were included. Median age was 58y. Black pts were more represented in the Medicaid (23.1%) and uninsured (21.1%) groups compared to the insured group (12.9%, P < 0.001). Insured pts were less likely to present with distant disease (50.4%) and more likely to receive surgery (27.7%) than pts in the Medicaid (55.3%; 16.7%) or uninsured groups (61.9%; 13.7%; P < 0.001). Median OS was longer in the insured (16m; p < 0.001) compared with uninsured (9m) or Medicaid (10m) groups. In an adjusted Cox regression, pts in the Medicaid and uninsured groups had worse OS relative to the insured group [HR = 1.28 (95%CI: 1.25-1.31); HR = 1.25 (95%CI: 1.22-1.30); P < 0.001]. When the groups pre and post-ACA were compared, the percentage of Medicaid pts increased in the post-ACA vs pre-ACA years (21.7 vs 18.7%; p < 0.0001) and median OS showed a significant improvement in the post-ACA-years (14m) than in the pre-ACA years (13m; p = 0.0002). Conclusions: Among lung cancer pts, those in the Medicaid or uninsured groups were more likely to present with advanced disease, less likely to receive cancer-directed surgery and had worse OS. The number of Medicaid pts increased and survival rates in all insurance groups improved in the years post-ACA.
Use of next-generation sequencing (NGS) panels to predict recurrence in low-grade, early-stage endometrioid endometrial carcinoma.
Authors: Katherine Kurnit, Bryan Fellman, Diana L Urbauer, Gordon B. Mills, Russell Broaddus
Journal: Journal of Clinical Oncology (2016)

5580 Background: Predicting recurrence in low grade, early stage endometrial cancer (EC) is both difficult and important, as recurrence outside the pelvis is typically incurable. We sought to determine whether somatic mutations from NGS panels could help identify at-risk patients. Methods: This was a single-institution, retrospective cohort study of 342 patients. Clinical data were obtained by review of the electronic medical record. Low grade, early stage EC was defined as FIGO grade 1 or 2 endometrioid histology with stage I or II (EC confined to the uterus) at the time of hysterectomy. Molecular testing was performed using NGS panels of 46 or 50 genes (clinical assay) or 200 genes (research assay). Univariate, multivariate, and Kaplan-Meier statistical analyses were performed to identify variables that were associated with recurrence-free survival (RFS). Results: In the cohort, 72% of patients had endometrioid histology. The most frequent mutations in these tumors were PTEN, PIK3CA, ARID1A, CTNNB1, and KRAS. Among 137 patients with low grade, early stage endometrioid EC, CTNNB1 mutation and TP53 mutation were significantly associated with decreased RFS. On multivariate analysis, CTNNB1 mutation, TP53 mutation, and age were the only significant predictors of worse RFS. Multivariate analysis using a combination of CTNNB1 mutation or TP53 mutation showed a hazards ratio of 4.65 for the combined mutation group in low grade, early stage endometrioid tumors (Table 1). Only one patient in the low grade, early stage group had a mutation in both TP53 and CTNNB1. Conclusions: CTNNB1 and TP53 mutations in low grade, early stage, endometrioid EC predicted a subset of patients with worse RFS in a multivariate model. This information could be incorporated into updated adjuvant treatment strategies. Multivariate model of RFS. Hazard Ratio 95% Confidence Interval p-value Age at diagnosis 1.05 1.02-1.08 0.001 BMI 0.99 0.95-1.02 0.42 Deep invasion ( ≥ 50%) 1.24 0.59-2.60 0.56 LVSI 1.46 0.71-3.01 0.31 Adjuvant treatment 0.89 0.43-1.84 0.75 Mutations PTEN 0.94 0.49-1.80 0.85 KRAS 1.47 0.66-3.28 0.35 PIK3CA 0.96 0.50-1.83 0.89 CTNNB1 or TP53 4.65 2.33-9.30 < 0.001
Association of decreased tumor DAB2IP and high-risk prostate cancer-specific survival.
Authors: Corbin Jacobs, Vasu Tumati, Payal Kapur, Raquibul Hannan, Jer-Tsong Hsieh, Dong W. Kim, Debabrata Saha
Journal: Journal of Clinical Oncology (2016)

e16553 Background: Our pilot study, which analyzed DAB2IP expression in 46 patients' biopsies and had short follow up, showed that DAB2IP reduction correlates with worse outcome in patients with high-risk prostate cancer treated with radiation therapy and androgen deprivation. With longer follow up and increased sample size, we hypothesized that pretreatment tumor status of DAB2IP would also predict worse prostate cancer-specific survival (PCSS). Methods: Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. PCSS was defined as death due to prostate cancer, radiation toxicity, or unknown cause with distant metastasis or castration resistance. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Results: 79 patients with NCCN-defined high-risk prostate cancer treated with radiotherapy from 2005-2012 at our institution were evaluated. 28% (22/79) of pretreatment biopsies revealed DAB2IP-reduction while 72% (57/79) retained DAB2IP expression. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients with reduced DAB2IP were statistically more likely to have higher T stage (p = 0.0149), pretreatment PSA (p = 0.0379), and Gleason scores (p = 0.0048). Patients with reduced DAB2IP also demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4-year: 34% vs. 92%; p < 0.0001), CRFS (4-year: 58% vs. 96%; p = 0.0039), DMFS (4-year: 58% vs. 100%; p = 0.0006), and PCSS (5-year: 83% vs. 100%; p = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in the multivariable analysis. Conclusions: This study suggests that about one-fourth of men with high-risk prostate cancer have decreased DAB2IP tumor expression. This subpopulation with reduced DAB2IP has a suboptimal response and worse PCSS following radiation therapy and androgen deprivation. Further study into improving treatment response and survival in this subpopulation is warranted.
Association of body mass index (BMI) with overall survival (OS) in metastatic melanoma (MM) patients (pts) treated with combined anti-CTLA4 + anti-PD1.
Authors: Jennifer Leigh McQuade, Allison Betof Warner, Minmin Li, Jeewon Chon, Lauren Elaine Haydu, Carrie Daniel-MacDougall, Kenneth R. Hess, Douglas Buckner Johnson, Alexander M. Menzies, Michael A. Davies, Alexander Noor Shoushtari
Journal: Journal of Clinical Oncology (2018)

9562 Background: Obesity has recently been associated with improved outcomes in male, but not female, MM pts treated with single-agent anti-CTLA4 and with single-agent anti-PD1 immunotherapy. However, the association between BMI, sex, and outcomes in MM pts treated with combined anti-CTLA4 + anti-PD1 is unknown. Methods: We examined the association of WHO BMI category at treatment initiation with outcomes in an international, multi-institutional cohort of MM pts treated with anti-CTLA4 + anti-PD1. Kaplan-Meier analysis was used to estimate progression free survival (PFS) and OS. Associations between BMI, PFS, and OS were assessed in Cox proportional hazard models adjusted for age, sex, AJCC 8 stage, LDH, and performance status. Results: The cohort included 413 pts from 4 institutions. Median age was 57; 67% were male, 56% had ECOG PS > 0, 31% had elevated LDH, 46% had BRAFV600 mutation. Clinical stage was 9% III, 12% M1a, 20% M1b, 40% M1c, 19% M1d. 75% of pts were overweight/obese (BMI≥25), including 83% of males and 58% of females. In multivariable (MV) models, BMI was not associated with PFS (BMI≥25 vs. BMI < 25 HR 1.0, 95% CI 0.7-1.4) or OS (HR 1.0, 95% CI 0.6-1.7) in the full cohort. On sex-stratified MV analysis, BMI≥25 was associated with shorter OS in females (HR 2.6, 95% CI 1.1-5.8); no significant association was detected in males (BMI≥25 vs. BMI < 25 HR 0.7, 95% CI 0.4-1.3; pinteraction= 0.03). BMI was not associated with PFS in either sex. Pts with higher BMI were more likely to have immune related adverse events (irAEs) leading to treatment discontinuation (p = 0.03); this association did not differ by sex. Conclusions: Higher BMI is associated with shorter OS in female MM pts treated with combined anti-CTLA4 + anti-PD1 immunotherapy. There was a significant interaction between BMI and sex, consistent with analyses of other cohorts. However, unlike observations in cohorts of MM pts treated with anti-PD1 or anti-CTLA alone, higher BMI was not associated with improved PFS or OS in males with combined anti-PD1 + anti-CTLA4. Rates of irAEs were higher in patients with higher BMI. Further studies should examine the basis for the observed associations.