tbuckley/cabot-search huggingface dataset:
Prospective study of the financial burden of cancer clinical trial patients referred to a cancer care equity program (CCEP).
Authors: Emily Poles, Ryan David Nipp, Elyse R. Park, Bruce Allan Chabner, Beverly Moy
Journal: Journal of Clinical Oncology (2016)

e18056 Background: Clinical trials (CTs) often represent the best option for patients (pts) with cancer, yet the financial burden (FB) of CT pts is understudied. We sought to assess the FB of CT pts and describe associated demographic and clinical characteristics. Methods: From 7/2015-1/2016, we enrolled CT pts who expressed interest in the CCEP, a program that funds travel and lodging expenses for CT pts. We assessed FB (COST measure [scored 0-44], cost-motivated behaviors [scored yes/no], degree of FB [scored none-catastrophic]) and distress (NCCN Distress Thermometer [DT] scored 1-10). By June 2016, we anticipate reporting results for 75 pts. We compared differences between groups using descriptive statistics. Results: We have enrolled 40 of 55 (73%) eligible pts (median age=52 years; 25 (62.5%) female; 30 (75%) on phase I CTs). Most had incomes <$60k (55%). COST (median=31) and DT (median=7) scores were high in our cohort. Most (87%) reported concerns about costs of travel for CTs. Most (60%) reported significant/catastrophic FB related to the costs of their cancer care, with lower income pts reporting greater FB (trend test, p=0.02). Pts with significant/catastrophic FB were more likely than pts with less FB to report problems paying medical bills (63% vs 27%), spending >10% of income on health care (54% vs 13%) and concerns about costs of travel for CTs (96% vs 71%) (all p<0.05). Pts reporting concerns about costs of travel for CTs had higher median COST (33 vs 23, p=0.08) and DT (7 vs 2, p=0.04) scores than pts without travel concerns. Conclusions: CT pts are at risk for having high FB and distress. Most pts in our study reported concerns about costs of travel for CTs and, correspondingly, pts with travel concerns had higher FB and distress scores. Our results underscore the need for targeted interventions to reduce the FB and distress experienced by CT pts. Cost-motivated behaviors (n=40) % Took smaller dose than prescribed 10 Did not fill prescription 13 Purchased cheaper medicine 30 Forgone medical care 15 Took money from savings 88 Sold possessions 28 Borrowed money 43 Took on credit card debt 50 Thought about bankruptcy 8 Filed for bankruptcy 3 Spent >10% of income on health care 40 Problems paying medical bills 50
Characteristics and outcomes of primary plasma cell leukemia in the era of novel agents: Single center experience.
Authors: Iman Aboudalle, Maliha Khan, Lei Feng, Sheeba K. Thomas, Elisabet Esteve Manasanch, Krina K. Patel, L Jeffrey Medeiros, Rohtesh Mehta, Qaiser Bashir, Muzaffar H. Qazilbash, Robert Z. Orlowski, Donna M. Weber, Shimin Hu, Hans Chulhee Lee
Journal: Journal of Clinical Oncology (2018)

8054 Background: Plasma cell leukemia (PCL) is a rare and aggressive disease characterized by a clonal proliferation of plasma cells in bone marrow and blood. PCL can present as de novo disease without underlying multiple myeloma. The purpose of this study is to describe the clinical characteristics and outcomes of primary (p) PCL in the era of novel agents. Methods: This is a retrospective study of patients (pts) with pPCL treated at The University of Texas MDACC from 01/1998-12/2017. The Kaplan Meier method was used to estimate progression free survival (PFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards models were used to evaluate the associations between a continuous variable and important prognostic covariates, respectively, with time to event endpoints. Results: We identified 77 pts with pPCL as defined by International Myeloma Working Group (IMWG) criteria. 64 (83%) pts were treated with immunomodulatory drugs (IMiD) and/or proteasome inhibitors (PI) during induction. Overall response rate was 70% (45 pts) by IMWG response criteria in pts treated with novel agents. 30 pts received consolidation with autologous stem cell transplantation (ASCT). For all pts, median PFS was 11.1 months (mos) (95% CI: 8.6-14.8), with 8 pts presenting with leptomeningeal disease at the time of relapse. Median OS (mOS) from the time of diagnosis was 19.1 mos (95% CI: 15.3-26.1) with a median follow-up of 20 mos. The mOS for pts receiving ASCT was 33.6 mos (95% CI: 22.6-40.2). Pts who underwent ASCT had significantly prolonged mOS (HR=0.2, 95% CI: 0.11-0.45; p<0.0001) on multivariate analysis. The main cause of death was disease progression in 84% of pts. Conclusions: pPCL prognosis can be improved with the incorporation of novel agents and early consolidation with ASCT. Baseline characteristics. No. of pts 77 Median age in years (range) 58 (31-85) Sex, M/F 46/31 Extramedullary disease, N (%) 15 (23) R-ISS, N (%) I 2 (3) II 28 (36) III 27 (35) Unknown 20 (26) Del 17p, N (%) Yes 19 (25%) No 27 (35%) Unknown 31 (40%) Induction treatment, N=72 N (%) Chemotherapy 8 (11) IMiD Doublet 4 (6) IMiD-Chemotherapy 1 (1) PI Doublet 5 (7) PI-Chemotherapy 25 (35) PI-IMiD Triplet 21 (29) PI-IMiD-Chemotherapy 8 (11)
Using real world data (RWD) analytics to drive operational efficiencies in basket trials.
Authors: Stelios Tzellos, Jamie Adams, Anika Arora, Steffen Brehmer, Niranjan Grandhi, Bhavani Krishnan, Nobumasa Kawasaki, Sriram Lakshmi Narayanan, Cathy Bismark-Pettit, Joaquin Palancar, Thomas Séjourné, Jeffrey Stewart, Brian Todd, Jeffrey Hodge
Journal: Journal of Clinical Oncology (2018)

e14517 Background: Many basket trials in immunotherapy and targeted therapy utilize Simon two-stage design, independently in each basket. Each basket represents a different indication with its own futility criteria, effectively rendering the trial overall as a series of independent phase II clinical trials. To minimize operational challenges, we wanted to evaluate the potential of utilizing data analytics to develop a site network that will allow operational efficiencies by identifying overlap among tumor types across sites in the same country. Methods: RWD were used to characterize US and European hospitals treating a range of specific solid tumors. Dependent on country, diagnosis, drug prescriptions, procedure, and claims data were analyzed to identify hospitals that could support a basket trial design. For example, in the case study presented for France, ICD-10 diagnosis and CCAM procedure codes were used to determine a network of sites treating all solid tumors of interest. A similar methodology was employed to categorize hospitals treating hematological malignancies, including non-Hodgkin lymphoma (NHL). Results: Sites in France were ranked based on total patient count for the tumor types below. A similar analysis has been done for NHL subtypes and for other countries (US and UK). Conclusions: In France, RWD identified site networks for complex basket trials. These insights can create operational efficiencies during the site ID/feasibility process. This process can be replicated, depending on the type of RWD assets, in other countries leading to the development of a global site network. Site Esophageal STS NSCLC Melanoma Mesothelioma Cervical Prostate RCC Bladder 1 138 131 1191 367 43 43 568 204 384 2 54 109 589 800 29 79 734 261 323 3 86 160 1062 441 62 300 409 227 90 4 112 46 1338 149 48 55 343 139 270 5 119 124 749 10 31 106 633 308 412
Role of cerebrospinal fluid (CSF) in the pathogenesis and treatment of patients with brain metastases.
Authors: Ayesha Ali, Tao Ouyang, Thamburaj Krishnamoorthy, Dawit Gebremichael Aregawi, Brad Zacharia, Michael J. Glantz
Journal: Journal of Clinical Oncology (2018)

e14006 Background: The assumption that metastases reach the brain by hematogenous spread informs concepts of pathogenesis and therapy in ways that may be incorrect. We suggest that the initial site of most CNS metastasis may be the CSF, that tumor cells then reach the brain parenchyma, possibly by way of the choroid plexus, that intraventricular (IT) chemotherapy can be expected to reach most brain metastases, and that such therapy may be effective. Methods: Two neuro-radiologists independently assessed whether brain metastases were adjacent to a CSF space in 108 consecutive patients using pre-treatment MRI scans. CSF was examined for malignant cells in 66 consecutive patients with brain metastases. We contoured the normal brain MRIs of 3 individuals to calculate the percentage of brain within 5 mm of a CSF space. Finally, we queried an international neoplastic meningitis registry for patients with both brain metastases and neoplastic meningitis to see whether we could document responses of brain metastases to IT chemotherapy alone Results: Mean age of the 108 patients was 63.8 (SD 13); 53 were male; 76 had lung cancer, 11 melanoma, 5 breast, 6 renal, and 4 colorectal cancer. The mean number of metastases was 4.16 (SD 4.89), and 87% of metastases touched a CSF space. In 65% of patients, all metastases touched a CSF space. In our consecutive series of patients, 44% (10/23) with one, 46% (5/11) with two, 63% (5/8) with three, and 71% (17/24) with more than three metastases had malignant cells in the CSF (R2= 0.93, p = 0.037). In three patients (25, 57, and 67 years old), at least 48%, 75%, and 70% of all brain tissue lay within 5 mm of a CSF space. In 4 of 6 patients with both brain and CSF metastases who received only IT chemotherapy, a measurable reduction in the size of at least some metastases was documented Conclusions: Our data suggest that brain metastases may access the CNS through the CSF rather than the bloodstream, and further suggest the need to look prospectively at whether the CSF should be monitored in all patients at risk for brain metastases; whether the CSF acts as a reservoir and protected site for tumor cells during systemic therapy; and whether true cures for patients with brain metastases require treatment of the CSF space
Prostitution is a symptom of structural inequalities
Authors: Fabienne El-Khoury Lesueur
Journal: BMJ (2018)

Behaviours do not exist in a vacuum. Structural inequalities influence many health determinants and behaviours, with social gradients affecting factors ranging from self esteem to smoking, bad diet, and cancer.123 Examining any outcome while disregarding the structure of the society that shapes it is nonsensical.

Prostitution is at the intersection of many structural inequalities …
Randomized phase II study of preoperative chemoradiotherapy (CRT)+/- Panitumumab (P) followed by consolidation chemotherapy (C) in potentially operable locally advanced (stage IIIa, N2+) non-small cell lung cancer (LANSCLC): Nrg oncology/RTOG 0839.
Authors: Martin J. Edelman, Chen Hu, Quynh-Thu Le, Jessica Donington, Warren D. D'Souza, Adam Dicker, Billy W. Loo, Elizabeth Gore, Gregory M.M. Videtic, Nathaniel R. Evans, Joseph Leach, Maximilian Diehn, Steven J. Feigenberg, Yuhchyau Chen, Jeffrey D Bradley
Journal: Journal of Clinical Oncology (2016)

8510 Background: Multimodality therapy has curative potential in LANSCLC. Mediastinal nodal sterilization (MNS) after induction CRT can serve as an intermediate marker for efficacy. RTOG 0229 demonstrated the feasibility and efficacy of combining full dose XRT (61.2GY) with C followed by resection and C. Based upon that experience and evidence that EGFR antibodies are radiosensitizing, we explored adding P to CRT followed by resection and C in LANSCLC with a primary endpoint of MNS. Methods: Resectable LANSCLC pts were eligible if deemed suitable for trimodality therapy prior to treatment. Surgeons were required to demonstrate expertise after CRT and adhere to specific management guidelines. Induction C consisted of weekly CBDCA (AUC = 2.0) and paclitaxel (50 mg/m2). Concurrent RT: 60 Gy delivered in 30 2.0 Gy fractions. There was a 2:1 randomization in favor of P at 2.5 mg/kg weekly x 6. Mediastinum was pathologically reassessed prior to or at the time of resection. Consolidation C was CBDCA AUC = 6, paclitaxel 200 mg/m2q 21d x 2. The study was designed to detect an improvement in MNS from 52% to 72%. Using a 0.15 1-sided type 1 error and 80% power, 97 patients were needed. Results: The study was opened 11/2010 and closed 8/2015 by the Data Monitoring Committee after 71 pts were accrued for futility and excessive toxicity in the P arm. 61 pts were eligible. Demographics (see table). 19 pts (86%) on CRT and 30 pts (77%) on CRT +P underwent surgery. Toxicity: 3 (13.6%) grade 4 AEs and 0 (0%) grade 5 AEs on CRT vs. 6 (15.4%) grade 4 AEs and 3 (7.7%) grade 5 AEs on CRT+P (all postoperative). MNS rates were 68.2% (95% CI 45.1%, 86.1%) and 48.7% (95% CI 32.4%, 65.2%), for CRT and CRT +P, respectively (p = .96). Conclusions: The addition of P to CRT did not improve MNS. There was an unexpectedly high mortality rate on the P arm, though the relationship to P is unclear. The control arm had outcomes similar to RTOG 0229. Clinical trial information: NCT00979212.Characteristic CXRT (n = 22) % CXRT + P (n = 39) % Age (median,years) 61 61 Sex (M/F) 59/41 46/54 Race (C/AA/other) 96/0/4 90/5/5 PS 0/1 73/27 74/26 IMRT 50 51 IGRT 41 36 Squamous/nonsquamous/NOS 36/59/5 18/77/5
Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatectomy or liver transplantation.
Authors: Hidetoshi Nitta, Marc Antoine Allard, Mylene Sebagh, Gabriella Pittau, Oriana Ciacio, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Catherine Guettier, Didier Samuel, Hideo Baba, Rene Adam
Journal: Journal of Clinical Oncology (2017)

4079 Background: Microvascular invasion (MVI) is the strongest prognostic factor following surgery of hepatocellular carcinoma (HCC). However, it is usually not available on the preoperative setting. A predictive model of MVI in patients scheduled for hepatic resection (HR) or liver transplantation (LT) would thus help guiding treatment strategy. The aim of this study was to develop a predictive model for MVI of HCC before either HR or LT. Methods: HCC patients who consecutively performed HR or LT from January 1994 to June 2016 at a single institution were subdivided into a training and validation cohort. Risk factors for MVI in the training cohort were used to develop a predictive model for MVI, to be validated in the validation cohort. The outcomes of the HR and LT patients with high or low MVI probability based on the model, were compared using propensity score matching (PSM). Cut-off values for continuous factors were determined based on ROC curve analysis. Results: A total of 910 patients (425 HR, 485 LT) were included in the training (n = 637) and validation (n = 273) cohorts. In the training cohort, multivariate analysis demonstrated that alpha-fetoprotein ≥100ng/ml ( p &lt; 0.0001), largest tumor size ≥40mm ( p = 0.0002), non-boundary HCC type on contrast-enhanced CT ( p = 0.001), neutrophils-to-lymphocytes ratio ≥3.2 ( p = 0.002), aspartate aminotransferase ≥62U/l ( p = 0.02) were independently associated with MVI. Combinations of these 5 factors varied the MVI probability from 15.5% to 91.1%. This predictive model achieved a good c-index of 0.76 in the validation cohort. In PSM (109 HR, 109 LT), there was no difference in survival between HR and LT patients among the high MVI probability (≥50%) patients, (5y-OS; 46.3% vs 42.2%, p = 0.77, 5y-RFS; 54.0% vs 28.8%, p = 0.21). Among the low probability ( &lt; 50%), survival was significantly decreased following HR compared with LT (5y-OS; 54.1% vs 78.8%, p = 0.007, 5y-RFS; 17.3% vs 86.1%, p&lt; 0.0001). Conclusions: This model developed from preoperative data allows reliable prediction of MVI, and may thus help with preoperative decisions about the suitability of HR or LT in patients with HCC.
The impact of chronic hepatitis C virus infection on survival in oropharyngeal cancer patients.
Authors: Minas P. Economides, Erich M. Sturgis, Moran Amit, Jeff Hosry, Parag Mahale, Ying Jiang, Harrys A. Torres
Journal: Journal of Clinical Oncology (2017)

e17556 Background: An association between Hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported; however, the clinical significance of this epidemiological finding remains unknown. We therefore analyzed the oncologic outcomes of HCV-infected patients (pts) with OPCs. Methods: In this retrospective cohort study, all pts with OPCs seen at MD Anderson (1/2004-12/2015) were reviewed. HCV infection was defined as detectable HCV RNA in serum. Risk of 5-year (yr) overall survival (OS) and progression-free survival (PFS) was compared between HCV-infected (HCV+) and uninfected (HCV-) pts. OPCs that were positive for p16 by immunohistochemistry were considered HPV-related. Antiviral therapy (AVT) included either interferon (IFN)-based or IFN-free regimens. Multivariate cox proportional hazards model was used to identify independent predictors of mortality. Results: We studied 161 pts. Most of the pts were white (141; 88%), male (132; 82%) and had tumor stage 3 or 4 (147; 92%). The OPC involved tonsils (83; 52%), base of tongue (67; 42%) or soft palate (11; 7%). The median follow-up time after OPC diagnosis was 3 yrs (range: 1-13 yrs). HCV+ (n = 25) and HCV- pts (n = 136) were comparable in regards to smoking and alcohol status. In univariate analysis, HCV+ pts had more OPC progression after 1 st line cancer treatment (48% vs 20.6% in HCV-, P = .0009) and were more likely to relapse (26% vs 5% in HCV-, P = .02). In multivariate analysis, HCV was associated with increased all-cause mortality [hazard ratio (HR): 2.15, 95% confidence intervals (CI): 1.08-6.85; P = .02] and risk of OPC progression [HR: 5.42, 95% CI: 2.64-11.14; P = .0008] independent of age and cirrhosis status. In HPV+ OPCs (n = 86), HCV + and HCV- pts did not have significant difference in mortality [HR: 2.03, 95% CI: 0.82-4.98; P = .12]. AVT was administered after OPC diagnosis in 8 of the 25 HCV+ pts (32%), with 6 of them receiving IFN-free AVT. HCV+ pts that received AVT had better 5 yr OS (median of 5.2 vs 2.3 yrs, P = .005) and PFS (median of 3.1 vs 0.7 yrs, P = .007) than the ones who did not. Conclusions: HCV seems to affect the oncologic outcomes of pts with OPCs and treating this infection might be beneficial. HCV screening and treatment should be considered in such pts.
Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.
Authors: Marco Giallombardo, Jorge Jorge Chacartegui, Pablo Reclusa, Jan P. Van Meerbeeck, Riccardo Alessandro, Marc Peeters, Patrick Pauwels, Christian Diego Rolfo
Journal: Journal of Clinical Oncology (2016)

e23035 Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid biopsy is a promising one. Exosomes are the latest discovered component, containing reliable tumor informations. We performed a follow-up analysis of selected micro-RNAs (miRNAs), EGFR mutation related , in exosomes isolated from plasma of metastatic NSCLC EGFR mutated pts receiving osimertinib, in order to evaluate their potential prognostic biomarker features Methods: After ethical committee approval, for institutional study, 1 ml plasma sample of 2 EGFR positive NSCLC pts were used as exosome source for each follow-up time point during osimertinib treatment within a PK study (NCT02157883). Exosome were isolated through commercial-kit or sucrose density-gradient ultracentrifugation. After exosome characterization by Western-Blot, Transmission and Scanning Electron Microscopy, a panel of selected miRNAs (has-miR-30b-5p, 30c-5p, 221-3p, 222-3p), related to EGFR status, was analyzed. Real-Time PCR was used for miRNAs analysis and mir-1228-3p was selected as stable endogenous control. Time point before treatment was used as baseline and data were processed according to the formula 2-ΔΔct Results: Exosomes analysis is feasible in a routine clinical screening in NSCLC patients as a liquid biopsy tool. An upregulation of plasma exosomal oncomiRs (hsa-miR-221-3p/222-3p), during the first month of treatment, could predict a good clinical outcome in NSCLC patients. However, the trial was PK only and no efficacy data was collected as trial data Conclusions: A routinely non-invasive follow up of NSCLC patients during TKI treatment seems to be possible via exosomes analysis. The study of selected plasma exosomal miRNAs, related to EGFR status, could follow the disease progression during the treatment. The upregulation of oncomiRs (hsa-miR-221-3p/222-3p), correlated to a good clinical outcome, could be related to a selective exosomal disposal of oncomiRs during osimertinib treatment. Further analysis are ongoing to support these hypothesis
Clinical, pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer: A multicenter experience in Madrid.
Authors: Maria Sereno, Sandra Falagan, Juan Moreno-Rubio, Rosa Maria Alvarez Alvarez, Maria Eugenia Olmedo Garcia, Xabier Mielgo, Fatima Navarro Expósito, Ricardo Ramos, Ana Belen Enguita Valls, Sagrario Garcia, Amparo Benito, Maria Cebollero, Isabel Alemany, Carolina Castillo, Enrique Casado, Santiago Ponce Aix
Journal: Journal of Clinical Oncology (2018)

e21128 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but there are other factors whose influence on the evolution of these patients is uncertain. Recently, different drugs targeted against EGFR, ALK and ROS 1 reach OS longer than 2 years in a limited number of patients (less than 20%). Immunotherapy in NSCLC has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we have focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 8 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological and immunological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months) from same centers. We used a NGS method of RNA-seq technology with the idea of identify differentiating profiles of gene expression between the two opposite populations with a later confirmation by RT-PCR in the rest of the tissue samples and liquid biopsy. Results: We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 overexpressed and 42 under-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this profile belong to different families and cellular pathways: Secretin receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca bindings protein channel and Toll like Receptor family. A further confirmation of this profile is carrying on by RT-PCR in the rest of the samples and liquid biopsy from the rest of the patients included in the study. Conclusions: We present the first data from a genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA profile