tbuckley/cabot-search huggingface dataset:
Apparent diffusion coefficient and genetic mutations as effective indexes for radiotherapy time of brain metastases from lung cancer retrospective analysis.
Authors: Ruimei Ren
Journal: Journal of Clinical Oncology (2019)

e20641 Background: The potential value of apparent diffusion coefficient (ADC) before chemoradiotherapy and genetic mutation as monitors for radiotherapy time of lung adenocarcinoma patients with brain metastases were retrospective analysed. Methods: Fifty-seven patients of lung adenocarcinoma with brain metastases were enrolled into the clinical trial. Conventional magnetic resonance imaging (MRI) examination and diffusion weighted imaging (DWI) were performed one week before therapy and after two cycles of chemotherapy or after one month targeted therapy. Symptoms such as headache, nausea, vomiting would be alleviated with mannitol and dexamethasone. Chemotherapy,once every 3 weeks, using in these patients with wild gene included pemetrexed, DDP, bevacizumab (pemetrexed 500mg per square meter ; DDP 75mg per square meter and bevacizumab 15mg per kilogram). 27 Patients with genetic mutations includ ed 1 patient with ALK genetic mutations, 2 patients with T790 genetic mutations, the presence of EGFR mutations was determined by the presence of deletions with exons 19 in 9 patients and 20 in 10 patients and L858R point mutations in exon 21 in 5 patients. Patients with genetic mutations were given targeted drug therapy. After these above treatment, if brain metastasis symptoms persist, brain radiotherapy was performed ahead of schedule. Patients with no obvious symptoms or relieved symptoms after targeted therapy or chemotherapy, two-month review was performed with enhanced MRI, radiotherapy was not added until the lesion no longer continues to shrink. Results: In the cohort of patients with wild gene , when ADC values less than 1.01 in 15 patients, the maximum diameter of tumors were significantly decreased after two treatment cycles, While 14 patients with ADC values greater than 1.01, the maximum diameter of the tumors are no difference after two treatment cycles. After targeted therapy for one month, In patients with ALK and T790 genetic mutations, the maximum diameter of tumors were significantly decreased, while no difference in 18 patients and decreased in 6 patients with presence of EGFR. Conclusions: ADC values and genetic mutation may as effective indexes of radiotherapy time for lung adenocarcinoma patients with brain metastases.
A phase I study of H3B-6527 in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) patients (pts).
Authors: Teresa Macarulla Mercade, Victor Moreno, Binu John, John Charles Morris, Michael B. Sawyer, Wei Peng Yong, Martin Gutierrez, Thomas Benjamin Karasic, Bruno Sangro, Yang Sheng-Shun, Carleen Gentry, Amy Kim, Pavan Kumar, Crystal MacKenzie, Nathalie Rioux, Joanne Schindler, Anand Selvaraj, Richard S. Finn
Journal: Journal of Clinical Oncology (2019)

4095 Background: FGF19 overexpression is hypothesized to hyperactivate FGFR4 and its downstream signaling pathway leading to enhanced tumor growth in HCC/ICC. Targeting FGFR4 may have therapeutic benefit in HCC/ICC with altered FGF19 signaling. A phase 1 study (NCT02834780) was initiated to assess H3B-6527, an investigational highly selective covalent FGFR4 inhibitor. Methods: Adult pts with advanced HCC or ICC, ECOG PS 0-1, well compensated liver function, and who progressed after at least one prior therapy, were administered H3B-6527 orally QD (once daily) on a 21-day cycle following a 3+3 design. Patients in the dose escalation phase were treated regardless of FGF19 status. Adverse events (AEs), pharmacokinetics (PK), and pharmacodynamics (PD) were assessed. Response was determined by RECIST 1.1 or modified RECIST every 6 weeks. Results: As of 06-Jan-2019, 37 pts have been treated with H3B-6527 at doses of 300 to 1400 mg QD (23 pts in escalation; 14 in expansion). In dose escalation, a total of 17 patients with HCC, Child-Pugh A received prior systemic therapy including 100% with prior TKI and 35% with prior IO. 12% had hepatitis B virus and 47% had hepatitis C virus. H3B-6527 plasma levels increased with dose from 300 to 1000 mg QD and plateaued. H3B-6527 was rapidly absorbed with a t max of ~2-3 h and showed a terminal half-life of ~4-5 h, following administration of 1000 mg (fasted). No dose-limiting toxicities or ≥ Grade 3 treatment-related AEs (TRAE) have been observed in escalation. Most common TRAEs (≥ 10%) were diarrhea, nausea, and vomiting. Based on safety, PK, and PD, 1000 mg QD was the recommended phase 2 dose. Durable stable disease and partial responses (PR) have been observed on the once daily fasted schedule; 2 of 17 pts with HCC achieved PRs and an additional 7 with stable disease were on treatment for ≥ 5 months. Conclusions: H3B-6527 is well tolerated and demonstrates early signs of clinical activity. Dose expansion on QD schedule and exploration of BID (twice daily) schedule is ongoing. Clinical trial information: NCT02834780.
Pharmacokinetic (PK) characterization of irinotecan liposome injection in patients (pts) with metastatic breast cancer (mBC).
Authors: Carey K. Anders, Jasgit C Sachdev, Pamela N. Munster, Anna Pedret-Dunn, Fiona Maxwell, Donald W. Northfelt, Hyo S. Han, Cynthia X. Ma
Journal: Journal of Clinical Oncology (2019)

e12003 Background: Irinotecan liposome injection (nal-IRI) uses intraliposomal stabilisation technology to enable high drug load and in-vivo stability. This analysis characterizes the PK profile of nal-IRI in pts with mBC. Methods: The expansion of NCT01770353 enrolled 30 pts with mBC over three cohorts (Cohort 1: ER+ and/or PR+ BC [C-1]; Cohort 2: Triple Negative BC [C-2]; and Cohort 3: BC with active Brain Metastasis [C-3]). Key inclusion criteria: ECOG ≤1; adequate organ function; and &gt;1 and ≤5 prior lines of cytotoxic therapy in metastatic setting. Most pts received nal-IRI 60 mg/m 2 salt-based equivalent (50 mg/m 2 free base equivalent [FBE]) or 80 mg/m 2 (70 mg/m 2 FBE) q2w by iv infusion, based on tolerance; 2 pts were treated at 40 mg/m 2 (35 mg/m 2 FBE). Plasma samples were collected over 360h across cycles 1, 2 &amp;3, and analysed using LC-MS/MS for total irinotecan. Data were analysed by a non-compartmental approach using Phoenix Winnonlin, and were compared with values from studies in other tumor types. Results: 21 patients were evaluable for PK analysis (C-1, n=6; C-2, n=7; and C-3, n=8). No trend for accumulation was observed in cycle 2 or 3, when comparing total irinotecan C max &amp; exposure (area under the curve at 168 h [AUC 168 ]) versus cycle 1. At 40-80 mg/m 2 (35-70 mg/m 2 FBE), C max of irinotecan tended to increase proportionally with total dose, and was comparable to studies in other tumour types (see Table). Among 29 pts who received nal-IRI, partial response (per RECIST) was observed in 10 pts. The most related TEAEs (≥ 25%) were diarrhea, nausea, vomiting, hypokalaemia, decreased appetite and fatigue. Stable disease was observed in 5 pts. Conclusions: PK parameters in patients with mBC were comparable to historical studies in patients with other tumour types. The safety profile of nal-IRI monotherapy appeared consistent with gastrointestinal and blood disorders. [Table: see text]
Understanding differences in total cancer care cost by service site.
Authors: Karen K. Fields, Jason M Burkett, Cindy Terrano, Floyd Dukes, Bharat Gorantla, Marcos Salganicoff, Bharat Rao
Journal: Journal of Clinical Oncology (2019)

e18345 Background: Oncology providers are under mounting pressure to deliver high quality and increasingly complex cancer treatment while simultaneously managing the cost pressures coming from payers and patients alike. Developing an effective strategy to compare costs can be an important tool for assessing and improving performance and cost effectiveness from both a clinical and market competitive standpoint. This comparison can be difficult to achieve in practice, especially between different sites of care and across heterogeneous patient populations. Methods: A large commercial claims dataset with reimbursement data for claims incurred between 2014 and 2017 was used to identify lung cancer patients by site of care. We calculated average annual total cost of care (TCC) for a one year period for patients with a new cancer diagnosis following a one year period of no claims for lung cancer. For study purposes, Moffitt Cancer Center (MCC) was compared to two other peer groups: Large Hospital Systems (LHS) and small hospitals and community-based oncology practices (CBOP). Patients were assigned to each peer group when a majority of claims ( &gt; 70%) were attributed to one of the peer groups. We analyzed overall average annual TCC for all patients and then created a sub-cohort of patients who received surgery within the study period to define early stage patients based on known standard patterns of care for newly diagnosed lung cancer. Results: There were 1249 new lung cancer patients in the study across all three peer groups with an average annual TCC of $134K per patient (range: $110K to $149K). When considering the sub-cohort of early stage patients (n = 396), MCC’s average annual TCC was $124K per patient which was significantly lower than LHS ($152K; p &lt; 0.0499) and CBOP ($167K; p &lt; 0.01). Conclusions: Although claims data generally contain only limited clinical information such as procedures, supplies and diagnosis, this limitation can be address by incorporating known standard of care patterns for cancer treatment to create comparable groups. Using this approach, national claims sets can be leveraged as the basis of a powerful analysis tool for understanding the Total Cost of Cancer care across institutional boundaries while still achieving meaningful comparability of the analyzed patient population.
Air pollution, lung function and COPD: results from the population-based UK Biobank study
Authors: Dany Doiron, Kees de Hoogh, Nicole Probst-Hensch, Isabel Fortier, Yutong Cai, Sara De Matteis, Anna L. Hansell
Journal: European Respiratory Journal (2019)

Ambient air pollution increases the risk of respiratory mortality, but evidence for impacts on lung function and chronic obstructive pulmonary disease (COPD) is less well established. The aim was to evaluate whether ambient air pollution is associated with lung function and COPD, and explore potential vulnerability factors.We used UK Biobank data on 303 887 individuals aged 40-69 years, with complete covariate data and valid lung function measures. Cross-sectional analyses examined associations of land use regression-based estimates of particulate matter (particles with a 50% cut-off aerodynamic diameter of 2.5 and 10 µm: PM2.5 and PM10, respectively; and coarse particles with diameter between 2.5 μm and 10 μm: PMcoarse) and nitrogen dioxide (NO2) concentrations with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), the FEV1/FVC ratio and COPD (FEV1/FVC <lower limit of normal). Effect modification was investigated for sex, age, obesity, smoking status, household income, asthma status and occupations previously linked to COPD.Higher exposures to each pollutant were significantly associated with lower lung function. A 5 µg·m-3 increase in PM2.5 concentration was associated with lower FEV1 (-83.13 mL, 95% CI -92.50- -73.75 mL) and FVC (-62.62 mL, 95% CI -73.91- -51.32 mL). COPD prevalence was associated with higher concentrations of PM2.5 (OR 1.52, 95% CI 1.42-1.62, per 5 µg·m-3), PM10 (OR 1.08, 95% CI 1.00-1.16, per 5 µg·m-3) and NO2 (OR 1.12, 95% CI 1.10-1.14, per 10 µg·m-3), but not with PMcoarse Stronger lung function associations were seen for males, individuals from lower income households, and "at-risk" occupations, and higher COPD associations were seen for obese, lower income, and non-asthmatic participants.Ambient air pollution was associated with lower lung function and increased COPD prevalence in this large study.
Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell–Derived Endothelial Cells
Authors: Won Hee Lee, Sang-Ging Ong, Yang Zhou, Lei Tian, Hye Ryeong Bae, Natalie Baker, Adam Whitlatch, Leila Mohammadi, Hongchao Guo, Kari C. Nadeau, Matthew L. Springer, Suzaynn F. Schick, Aruni Bhatnagar, Joseph C. Wu
Journal: Journal of the American College of Cardiology (2019)
Does ethnicity affect the relationship between body mass index (BMI) and overall survival (OS) in non-small cell lung cancer (NSCLC)? A pooled analysis of 17,326 International Lung Cancer Consortium (ILCCO) patients (pts).
Authors: Aline Fusco Fares, Daniel Shepshelovich, Lin Lu, M. Catherine Brown, Ping Yang, Jie Zhang, Brid M Ryan, David C. Christiani, Ann Schwartz, Chu Chen, Garcia Adonina, Matthew B. Schabath, Kouya Shiraishi, Teare Down, Loic Le Marchand, Zhang Zuo-Feng, Hermann Brenner, Wei Xu, Rayjean J Hung, Geoffrey Liu
Journal: Journal of Clinical Oncology (2019)

1562 Background: In Caucasian-predominant populations, overweight or obese NSCLC pts (BMI≥25-kg/m2) have better prognosis while underweight (BMI≤18.5-kg/m2) pts have a worse prognosis. A large pooled sample allowed us to evaluate the role of ethnicity in this BMI-NSCLC OS relationship. Methods: Using individual data, survival analysis was performed on 15 ILCCO studies, assessing the interactions between ethnicity and BMI on overall survival (OS). Adjusted Hazard Ratios (aHR) from Cox models and adjusted penalized smoothing spline plots were generated. Results: Among 13416 (77%) Caucasian, 2975 (17%) Asian, and 935 (5%) Black NSCLC pts analyzed, we confirmed that for all pts, being underweight at NSCLC diagnosis was associated with worse OS (aHR=1.68, CI 1.5-1.8, p&lt;0.001), while overweight/obese pts had improved survival (aHR 0.89, CI 0.8-0.9, p&lt;0.001), when compared to pts with normal BMI. In general, Black pts had poorer OS than Caucasian pts (aHR 1.26 CI 1.1-1.4, p&lt;0.001). However, the BMI-OS relationship differed according to ethnicity (BMI-ethnicity interaction, p=0.009): Caucasian underweight pts had poorer OS (aHR 1.67, CI 1.5-1.8, P&lt;0.001) while overweight/obese pts had improved OS (aHR 0.89, CI 0.8-0.9, P&lt;0.001). In Asian pts, these two associations were aHR 1.15, CI 0.8-1.5, P=0.33, and aHR 0.91, CI 0.7-1.1, P=0.32, respectively. In Black pts, these two associations were aHR 1.06, CI 0.7-1.5, p=0.73 and 0.75, CI 0.6-0.8 p&lt;0.001, respectively. For overweight/obese patients, as BMI rises from 25-kg/m2 through 45-kg/m2, the prognosis worsens for Caucasian pts, remains stable for Asian pts, but improves for Black pts. Conclusions: InCaucasian pts, being underweight had a greater negative impact on OS than for Asian or Black pts, while being obese had a greater beneficial impact in Blacks than in other ethnic groups. These ethnic differences likely reflect genetically-informed muscle/adipose tissue distributions, where Black pts may have less sarcopenic obesity than other ethnicities. In future prognostic studies, BMI relationships must account for ethnic differences.
Competing causes of death in patients with neuroendocrine tumor.
Authors: Soon Khai Low, Bao Long Hoang Trong, Nourelhoda Sami Bahaie, Dimitrios Giannis, Gehad Mohamed Tawfik, Shin Yin Lee, Nguyen Tien Huy
Journal: Journal of Clinical Oncology (2019)

e23009 Background: Increasing survival of patients with neuroendocrine tumors (NETs) may be associated with higher risk of mortality due to causes other than the primary NET, namely the competing causes of death (CCD). Therefore, our study focused on comprehensively investigating the magnitude of the CCD on the overall NET mortality and the associated demographic, clinicopathologic and treatment factors using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with histologically confirmed primary NET diagnosed from 1973 through 2015 were identified using the SEER-9 registries for subsequent data collection and analysis. CCD were stratified and analyzed using standardized mortality ratios (SMRs) as measures of the relative risks of mortality for NET patients in comparison to the general population in the US adjusted by age, sex and race over the same time period. Competing risk regression analysis was performed using Fine and Gray multivariate regression model. Results: A total of 29,981 NET patients were included, 5481 (42.5%) of which deceased due to CCD. Overall SMR attributed to CCD was 2.50 [95% Confidence interval (CI): 2.43–2.56]. The SMR of non-cancer CCD was 2.65 (95% CI:2.58–2.73) and that of SPN was 1.91 (95% CI:1.79–2.04). Heart diseases and other cardiovascular diseases accounted for approximately half of all non-cancer CCD. SPN mortality accounted for 16.1% of CCD, with lung and bronchus cancer being the most prevalent. Stratification by the year of diagnosis revealed a drastic rise in CCD was observed in the last decade between 2005 and 2015, during which the SMR peaked. Advanced age, black race, small intestinal and gastric NETs, and cancer-directed surgery were significantly associated with an increased risk of CCD (p&lt;0.001). Interestingly, female sex, pancreatic NETs, recto-anal NETs, NETs of unknown primary site, race other than white and black, distant and regional spread, chemotherapy and radiotherapy were significantly associated with a decrease in the incidence of CCD. Conclusions: CCD play an increasingly significant role in NET mortality in recent years, especially for those with higher risk of CCD. Further prospective studies are needed to evaluate the association of NETs with these CCD.
A phase 1/2 study of osimertinib and bevacizumab as initial treatment for patients with metastatic EGFR-mutant lung cancers.
Authors: Helena Alexandra Yu, Rachel Kim, Alex Makhnin, Linda Su Hyun Ahn, Ai Ni, Sara A. Hayes, Robert J. Young, Gregory J. Riely, Mark G. Kris
Journal: Journal of Clinical Oncology (2019)

9086 Background: Osimertinib (osi) demonstrated improved progression-free survival (PFS) over erlotinib as initial treatment (trmt) for EGFR-mutant (EGFR+) lung cancers. The addition of bevacizumab (bev) to erlotinib as initial trmt resulted in improved PFS compared to erlotinib alone (16 vs 10 months, HR 0.41). The phase 1 study of osi and bev confirmed the ability to combine osi and bev at full doses. Methods: The phase 2 study is assessing safety and efficacy of the combination. The primary endpoint is PFS at 12 months; secondary endpoints include overall response (ORR), overall survival (OS), and CNS PFS. All pts had interval CNS as well as systemic imaging. Pre-treatment and post-progression (PD) tumor tissue and interval plasma samples are being collected to identify mechanisms of resistance (MOR) and for biomarker assessment. Results: From Nov 2016 to May 2018, 49 pts were enrolled, including 6 pts from the phase 1. Median age: 60; Women 69%; Never-smokers 65%. 13 pts had CNS metastases (9 untreated, 5 measurable) prior to study initiation. 49 pts are eligible for response; 34/49 pts had a confirmed partial response (PR)(ORR 69%). PFS at 12 months is 0.70 (95% CI: 0.57-0.84), with 8/49 pts on study without PD for less than 12 months. All pts with measurable CNS disease had a PR in the CNS; PD in the CNS was uncommon (17%). 24 pts remain on study without PD; 2 are being treated beyond PD. Reasons for study discontinuation include PD (n = 16), resection of all sites of disease (n = 3), withdrawal of consent (n = 3), unrelated death (n = 2), toxicity (n = 1). The most frequent trtmt-related adverse events (any grade) were thrombocytopenia (61%), diarrhea (57%), hypertension (55%), and rash (47%). 24% required a dose reduction of osi, 18% discontinued bev and median doses of bev was 17. 9 pts have paired pre-trtmt and post-progression tissue biopsies; MOR identified include squamous cell (n = 2) and small cell (n = 1) transformation, PTEN loss, and CCNE amplification. Conclusions: Combination osi and bev was well-tolerated and efficacy to date supports further evaluation. Results of secondary endpoints including PFS, mechanisms of resistance, cfDNA data are forthcoming. A randomized study of osi compared to osi and bev is planned (EA5182). Supported by AstraZeneca Clinical trial information: NCT02803203.
Impact of cisplatin-related adverse health outcomes (AHOs) on employment outcomes and self-reported health (SRH) among testicular cancer survivors (TCS).
Authors: Sarah L. Kerns, Chunkit Fung, Sophie D. Fossa, Paul C Dinh, Patrick O. Monahan, Howard D. Sesso, Robert D. Frisina, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Neil E. Martin, Robert A Huddart, Christian K. Kollmannsberger, Deepak M. Sahasrabudhe, Shirin Ardeshirrouhanifard, Lawrence H. Einhorn, Lois B. Travis
Journal: Journal of Clinical Oncology (2019)

e16058 Background: We aim to provide new information on cisplatin-related AHOs and employment status in TCS and evaluate impact on SRH. Methods: 1,815 TCS ³1 year post-chemotherapy underwent physical exam, audiometry, renal function evaluation, and completed questionnaires. Therapy data were obtained from medical records. A cumulative burden of morbidity score (CBM Pt ) assessed the number and severity of platinum-related AHOs (peripheral sensory neuropathy (PSN), hearing loss, tinnitus, and renal function) with grading per CTCAE v4.03. Multivariable regression assessed relations between CBM Pt score, individual AHOs and employment status as well as SRH, adjusting for sociodemographic/clinical factors. Unemployment in TCS was compared with subjects in the Behavioral Risk Factor Surveillance System (BRFSS) of similar age/race/ethnicity. Results: Almost 1 in 10 TCS were either on disability leave (2.4%) or unemployed (6.8%) at a median age of 37 yr (median follow-up: 4 yr). TCS with tinnitus (OR = 3.1, grade 3 vs. 0, P = 0.04), renal dysfunction (OR = 13.5, grade 3 vs. 0, P = 0.01), or pain (OR = 7.2 and 40.9, grade 2 or 3 vs. 0, respectively; P &lt; 0.001 each) had significantly greater odds of disability leave vs. full-time employment after adjusting for sociodemographic/clinical factors; pain was strongly correlated with PSN (Pearson r 2 = 0.40; P &lt; 0.001). CBM Pt score was associated with disability leave (OR = 1.5, P = 0.04), but not with unemployment. A significantly higher percentage of TCS were unemployed vs. BRFSS norms (e.g. 3.6% of TCS age 35-39 vs. 2.0% in BRFSS). PSN (OR = 2.2, grade 3 vs. 0, P = 0.02), self-reported hearing loss (OR = 1.8, grade 2/3 vs. 0, P = 0.04), and pain (OR = 2.8 and 8.5, grade 2 or 3 vs. 0, respectively; P &lt; 0.01 each) were each associated with increased odds of unemployment vs. full-time employment. Cisplatin-related AHOs and pain were associated with significantly worse SRH (P &lt; 0.05). Conclusions: Our findings have new, important implications regarding productivity loss and socioeconomic costs in TCS. Survivorship care strategies should include inquiries about employment status, and every effort made to assist affected TCS in returning to the work force.