tbuckley/cabot-search huggingface dataset:
A multicenter observational study of effectiveness and safety of nivolumab in non-small cell lung cancer in real clinical practice.
Authors: Juan Francisco Marín Pozo, Macarena Merino Almazán, Juan Manuel Duarte Pérez, Facundo Alberti Vargas, María Paz Quesada Sanz, Begoña Muros de Fuentes, María Teresa Garrido Martínez, Margarita Garrido Siles, María José Martínez Bautista, Carmen Martínez Díaz, Ana Isabel Gago Sánchez, José Carlos Roldán Morales, Pablo Nieto Guindo, Silvia Maria Artacho Criado, María Dolores Alvarado Fernández, Beatriz Mora Rodríguez, Fátima Artime-Rodríguez-Hermida, Pedro Sánchez Rovira
Journal: Journal of Clinical Oncology (2018)

e21092 Background: Nivolumab is recommended as a standard-of-care treatment in patients (pts) with progression to first-line therapy for non-smal-cell lung cancer (NSCLC). Our objective is to evaluate effectiveness and safety results of Nivolumab in real clinical practice in NSCLC pts. Methods: We designed a multicenter, observational and retrospective study, approved by the National Regulatory Agency and the Institutional Ethical Committee. We included NSCLC pts treated with Nivolumab after primary platinum-based chemotherapy failure, between January 2016 and July 2017 at 14 hospitals from south Spain. The primary endpoint was overall survival (OS) and progression-free survival (PFS). Number of reported treatment-related adverse events (TRAEs) was determined as safety variable. Results were assessed based on tumor histology, ECOG and time from the beginning of primary therapy treatment (TPTT). For the statistical analysis we used Kaplan-Meier method and Cox regression model. Results: 187 pts were enrolled (84% men). Mean age was 64.2 years, 84.1% of pts had ECOG = 0-1 and the remaining ECOG = 2, 54% stage IV. 62.6% of tumors were squamous, being the rest adenocarcinoma histology. At study data cut-off, 60 pts continued on treatment with nivolumab. Mean TPTT was 15.3 months. Median PFS was 4.7 months [95%CI: 3.2-6.2] with a median OS 9.1 months [95%IC: 6.6-11.6]. A statistically significant difference in median of PFS (log rank < 0.0001) and OS (log rank < 0.0001) was observed for ECOG. A minor risk reduction for OS is associated with TPTT (hr = 0.97 [95%IC: 0.95-0.99]), not for PFS. TRAEs of any grade occurred in 67.9% pts, being the most common asthenia (38.5%), dysnea (12.8%) and diarrhea (11.8%). 17.6% pts discontinued or postponed nivolumab because of TRAEs, being pneumonitis (3.7%), asthenia (3.29%), diarrhea, neumonia, cough and dyspnea (2.1% each) the most frequent. Conclusions: This study allows us to confirm that efficacy and safety data obtained in nivolumab clinical trials are comparable to our real population. ECOG = 2 is a poor prognostic factor, so pts with ECOG = 2 might get a minimal benefit from this therapy. The use of nivolumab in this pts type would be questionable.
A nomogram for the prediction of KRAS mutation in colorectal cancer
Authors: W. Xiang, W. Dai, G. Cai
Journal: Annals of Oncology (2018)

Background: KRAS mutation status is crucial in treatment decisions regarding the use of EGFR tyrosine kinase inhibitors in colorectal cancer (CRC). However, genetic testing is not available for some patients, either because tissue is limited and/or tests are not routinely offered. Hence, we aimed to build a nomogram based on clinical factors for the prediction of KRAS mutations in CRC. Methods: Colorectal cancer patients who had their tumors genotyped for KRAS mutation at Fudan University Shanghai Cancer Center (FUSCC) were retrospectively analyzed. Variables of interest were integrated in a multivariate logistic regression model. Results: A total of 759 hospitalized patients were extracted from FUSCC database. KRAS mutation presented in 40.1% (309/759) cases. Multivariate logistic regression suggested that female (OR 1.47, 95%CI 1.06-2.04), mucinous histology (OR 2.04, 95%CI 1.28-3.25), right-sided tumor (OR 1.65, 95%CI 1.13-2.39) and high levels of preoperative CEA (OR 1.45, 95%CI 1.03-2.03), CA19-9 (OR 3.87, 95%CI 2.70-5.53) and albumin/globular protein (OR 2.02, 95%CI 1.33-3.06) were significantly correlated with KRAS mutation status. A nomogram was established and showed considerable discriminating accuracy (AUC 0.744, 95%CI 0.709-0.779) in this cohort. Patients with the highest score had 88.6% chance to bear a KRAS-mutant tumor. Subgroup analysis based on metastasis status revealed a sound applicability of the established nomogram both in metastatic (AUC 0.723, 95%CI 0.666-0.781) and non-metastatic (AUC 0.753, 95%CI 0.707-0.798) CRC. Conclusions: Six simple and easy-to-collect characteristics defined a useful nomogram to predict KRAS status both in metastatic and non-metastatic CRC with great predictive accuracy. Legal entity responsible for the study: Guoxiang Cai. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Biopsy practices for the diagnosis of hepatocellular carcinoma (HCC).
Authors: Alison L Raybould, YunKyung Chang, Alfred S Barritt, Paul H Hayashi, Hanna Kelly Sanoff
Journal: Journal of Clinical Oncology (2017)

e15646 Background: American Association for the Study of Liver Disease (AASLD) guidelines endorse radiographic diagnosis of HCC if key features are present on dynamic contrast-enhanced imaging (arterial hyperenhancement and venous washout) with biopsy for those without these features. As many HCC patients (pts) are diagnosed outside liver transplant centers, we sought to describe the methods of diagnosis of HCC and factors associated with biopsy in routine care in the US. Methods: HCC cases were identified from 2 data sources: SEER-Medicare (M) 2004-2011 and North Carolina Central Cancer Registry (NCCCR) linked to Medicare, Medicaid and private claims 2004-2013. Diagnostic confirmation was identified from registries as pathologic (path) or clinical. Key covariates included age, cancer stage, cause and severity of cirrhosis, and comorbid disease. Specialty consultation, prediagnosis imaging, AFP testing were determined from claims -3 to 0 months from diagnosis. Multivariable logistic regression was used to identify factors associated with path. Results: Path was obtained in a majority of HCC pts: 68% of 10,989 in SEER-M, 72% of 1,809 in NCCCR. In SEER-M, claims for contrasted abdominal CT were more common in those with path than those without (34 vs 30%) but not for MRI (14 vs 14%). Odds of path was higher in pts with contrasted CT (adjusted odds ratio [OR] 1.48, 95% confidence interval [CI] 1.30-1.69) or MRI (OR 1.53, CI 1.31-1.80) vs pts without imaging. In NCCCR, CT (51 vs 41%) and MRI (35 vs 34%) were performed more. Both were associated with increased odds of biopsy vs pts without imaging: contrasted CT scan (OR 1.74, CI 1.22-2.47) or MRI (OR 1.48, CI 1.02-2.13). In neither cohort did ultrasound increase odds of path over no imaging. Pts seen by an oncologist (OR SEER-M 1.66, CI 1.46-1.89) were more likely to have path than pts not seen by oncology. In SEER-M, pts seen at abdominal transplant centers were less likely to have path (OR 0.87, CI 0.77-0.98). Conclusions: Most pts diagnosed with HCC had path confirmation of cancer despite internationally accepted guidelines supporting radiographic diagnosis. The use of biopsy was greater among those with cross-sectional imaging, suggesting this high biopsy rate cannot solely be explained by nondiagnostic imaging.
Progranulin aggravates pulmonary immunopathology during influenza virus infection
Authors: Qin Luo, Xingxing Yan, Hongmei Tu, Yibing Yin, Ju Cao
Journal: Thorax (2018)

Progranulin (PGRN) exerts multiple functions in various inflammatory diseases. However, the role of PGRN in the pathogenesis of virus infection is unknown. Here, we demonstrated that PGRN production was up-regulated in clinical and experimental influenza, which contributed to the deleterious inflammatory response after influenza virus infection in mice. PGRN-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced influx of neutrophils and monocytes/macrophages, release of cytokines and chemokines, and permeability of the alveolar-epithelial barrier without affecting viral clearance. Our findings suggest that PGRN exacerbates pulmonary immunopathology during influenza virus infection.
P01.099 Psychiatric alterations and behavioural changes in brain tumor patients
Authors: A Grisold, A Guekht, R Ruda, S Grisold, W Grisold
Journal: Neuro-Oncology (2018)

Managing patients with brain tumors can involve behavioral and psychiatric phenomena, occurring at different time points. Review of the literature. Five causes were identified. 1. Focal and diffuse brain damage by the tumor Symptoms of anger, loss of emotional control, indifference and changes in behavior and personality appear. The extent to which tumor location impacts on psychopathology is not clear. Clinically, also apathy and loss of executive function can occur. In lesions of the paralimbic structures mood swings are dominant. Neuropsychological symptoms are related to focal pathology. 2. Psychiatric causes Manifestations can present as anxiety, depression, mania and psychosis. Few recent publications are available. It is useful to make a distinction between a,,psychiatric reaction (towards the disease)” and an organic psychosis. 3. Influence of seizures on behavior Brain tumors are one of the main causes of acquired epilepsies and are associated with 3–6% of all new cases of epilepsy. Rapidly growing tumors, as glioblastomas (GBM), are frequently associated with seizures. In patients with primary brain tumors with epilepsy cognitive impairment, abnormal scores in the anxiety scale and depression were noted. Brain tumors can cause status epilepticus, including the non-convulsive type. 4. Tumor treatment Treatment-induced effects may occur at any stage of the disease. Radiation can induce acute, or delayed effects, which are important in low grade glioma (LGG), and less frequent in GBM. Steroids can have psychotropic effects, ranging from unspecific excitatory state, towards psychosis and depression. Also, rapid discontinuation of prolonged steroid therapy causes mood swings. The issue of “chemobrain” has been attracting attention in the treatment of LGG. The clinical correlation is slowing of mentation and cognition and is also termed,,chemofog”. Most antineoplastic drugs used for the treatment of GBM, as temozolomide (TMZ) do not have psychotropic effects. Older drugs as procarbazine can cause psychiatric symptoms. VEGF inhibitors, can induce “posterior reversible encephalopathy syndrome” resulting in mental changes. Benzodiazepines, antidepressants and rarely anti-dementia drugs can cumulate and cause delirium as well as anticonvulsants. 5. Overlap of several causes Practically, often several causes can overlap. The identification of the most prevalent cause is important, followed by symptomatic therapy. Psychiatric alterations can be part of the management of patients with brain tumors. Symptom-oriented treatment of psychiatric manifestations, including psychotherapy, drug treatment and individual care is warranted. Communication with patients, caregivers and the involved health care professionals is essential.
Lack of racial disparity in outcome of African American (AA) and Caucasian patients with symptomatic multiple myeloma (MM) at the Veterans Affairs (VA) hospitals.
Authors: Nathanael Fillmore, Sarvari Yellapragada, Paul S. White, Chizoba Ifeorah, Mahmoud Gaballa, Gustavo Rivero, Saiju Pyarajan, Nhan Do, Mary T. Brophy, Nikhil C. Munshi
Journal: Journal of Clinical Oncology (2018)

8033 Background: Recent studies have identified a significant and increasing disparity in survival amongst AA and Caucasian patients diagnosed with MM in the United States, and a concomitant disparity in access to novel chemotherapy and stem-cell transplant. We sought to investigate whether this disparity holds at the VA, which does not use a fee-for-service model. Methods: We used the VA’s nationwide Corporate Data Warehouse to identify patients diagnosed with MM from 1999 to 2017, as well as their age, race, therapy at induction, and stem-cell transplant status. We compared overall survival between AA and Caucasian using Cox models. We assessed differences in treatment patterns using chi-squared tests. Results: We identified 15,717 patients diagnosed with MM, including 3,254 AA and 8,845 Caucasian patients. The median age at diagnosis was 65.6 years for AA and 70.1 for Caucasian (P<1e-15). As age has a substantial effect on overall survival, we adjusted our survival analysis for age at diagnosis. We found no difference in age-adjusted overall survival between AA and Caucasian, measured by hazard ratio of risk of death among AA relative to Caucasian (HR 0.99, 95% CI 0.94-1.05, P=0.69). However, among patients younger than 65 at diagnosis, we observed a significant decrease in age-adjusted risk of death for AA compared to Caucasian patients (HR 0.86, 95% CI 0.79-0.94, P=0.001). In patients >65 years, survival was similar between the 2 groups. The difference in younger population was not explained by access or utilization of the novel agents. We observed no racial disparity at the VA in the use of novel agents at induction (IMiD or PI), with 82.5% of AA patients and 81.5% of Caucasian patients receiving novel therapy (P=0.21); or in use of stem-cell transplant (10.1% of AA and 9.1% of Caucasian patients; P=0.09). Conclusions: No racial disparity was observed in overall survival or treatment patterns at the VA. Taken with previous research that does show these disparities in other US healthcare systems, this suggests that these disparities may be due primarily to economic factors, including cost of therapy, rather than factors related to disease biology.
Survival of U.S. Medicare patients with multiple myeloma by line of therapy.
Authors: Jay Lin, Melissa Lingohr-Smith, Mohamed Omar, Clara Chen
Journal: Journal of Clinical Oncology (2016)

e18098 Background: Therapies including immunomodulatory drugs (IMiD) and proteasome inhibitors (PI) have improved outcomes of multiple myeloma (MM) during the past decade. However, current real-world data on overall survival (OS) among patients (pts) with MM are limited, particularly by line of therapy (LoT). In this study, OS among Medicare pts with MM from time of diagnosis (Dx) and by treatment (Tx) status was examined. For treated pts, OS was also determined from the time of initiation of each LoT. Methods: A retrospective cohort study was conducted of pts aged 65 years (y) or older with continuous enrollment in Medicare Parts A and B for the 12 months (mo) before the initial Dx of MM in 2007-2011. Pts were selected from the SEER-Medicare linked database and followed until 12/31/2012. Pts with claims for stem cell transplants were excluded. Demographic and clinical characteristics and type of anti-MM Tx received (chemotherapy, PI, IMiD, or steroids) were examined. Descriptive and Kaplan-Meier (KM) statistics were used to analyze OS from the Dx of MM for all pts and separately by receipt of anti-MM Tx. KM analysis was also conducted for each LoT from the Tx start date. Results: 4,985 pts met the selection criteria (Table); 2,369 (48%) received PI and/or IMiD; 637 (13%) received chemotherapy/steroids; for 1,979 pts (40%), no records of drug therapy during the study period were found. Pts who received PI and IMiD were at the lower end of the age range studied, had better socioeconomic status, and had less comorbidity. Median OS for all pts was 29.8 mo; 1-y OS was 69%, 2-y was 56%, and 3-y was 45%. Median OS for pts treated vs not treated with PI and IMiD was 38.8 vs 20.4 mo (p < 0.001). From time of initiation of each LoT, median OS was 29.4 mo for 1L, 23.9 for 2L, and 15.5 for 3L. Conclusions: Despite Tx advances for MM with PI and/or IMiD, more than half of Medicare pts did not receive PI and IMiD. Outcomes for treated and untreated pts remained poor, with less than 50% still alive 3 y after diagnosis or initiation of anti-MM Tx. OS declined with successive LoT. N (%) Median OS (mo) 1-y OS, % 2-y OS, % 3-y OS, % All pts 4,985 29.8 69 56 45 Received PI or IMiD Yes 2,369 (48) 38.8 80 65 52 No 2,616 (52) 20.4 59 47 38 By LoT 1L 3,006 (48) 29.4 72 56 44 2L 829 (17) 23.9 71 50 37 3L 356 (7) 15.5 60 40 25
Validation of the NCI colorectal cancer risk assessment tool in the CSP 380 veterans cohort.
Authors: Laura W. Musselwhite, Thomas S. Redding, Kellie J. Sims, Meghan O'Leary, Elizabeth R. Hauser, Terry Hyslop, David A. Lieberman, Dawn T. Provenzale
Journal: Journal of Clinical Oncology (2017)

e15135 Background: Refining screening to colorectal cancer (CRC) risk may promote screening effectiveness. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool to estimate 5- and 10-year CRC risk in an average-risk Veterans cohort undergoing screening colonoscopy with follow-up. Methods: This was a prospective evaluation of predicted to actual risk of CRC using the NCI CRC Risk Assessment Tool in male Veterans undergoing screening colonoscopy with a median follow-up of 10 years.Family, medical, dietary and physical activity histories were collected at enrollment and used to calculate absolute 5- and 10-year CRC risk, and to compare tertiles of expected to observed CRC risk. Sensitivity analyses were performed. Results: For 2,934 male Veterans with complete data (average age 62.4 years, 15% minorities), 1.3% (N=30) and 1.7% (N=50) were diagnosed with CRC within 5 and 10 years of survey completion. The area under the curve for predicting CRC was 0.69 (95% CI; 0.61-0.78) at 5 years and 0.67 (95% CI, 0.59-0.75) at 10 years. We calculated the sensitivity (0.60, 95% CI; 0.45-0.73), specificity (0.67, 95% CI; 0.65-0.69) positive predictive value (0.031, 95% CI; 0.02-0.04) and negative predictive value (0.99, 95% CI; 0.98-0.99). Conclusions: The NCI CRC Risk Assessment Tool was well-calibrated at 5 years and overestimated CRC risk at 10 years, had modest discriminatory function, and a high NPV in a cohort of ethnically diverse male Veterans. This tool reliably excludes 10-year CRC in low-scoring individuals and may inform patient-provider decision making when the benefit of screening is uncertain. [Table: see text]
Outcomes of video assisted thoracic surgery compared with open thoracotomy in patients with early stage lung cancer.
Authors: Shagufta Shaheen, Brice Jabo, Manmeet Kaur, Maheswari Senthil, Saied Mirshahidi, Salman Zaheer, Hamid R. Mirshahidi
Journal: Journal of Clinical Oncology (2017)

e20061 Background: Video Assisted Thoracic Surgery (VATS) has become the recommended approach for treatment of early stage lung cancer; however, no large randomized clinical trial has been conducted to formally compare VATS to open thoracotomy (OT). The current study sought to assess differences in patients and tumor characteristics for VATS and OT. Additionally, treatment outcomes that included margin status, postoperative length of stay (LOS) and overall survival (OS) were also compared. Methods: A single institution retrospective charts review was conducted for patients diagnosed with stage I-III lung cancer and treated with VATS or OT from May 2005 - May 2015. Patients and tumor characteristics included age at diagnosis, sex, tobacco use, tumor location, stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographic, tumor characteristics and LOS. Multiple logistic and Cox regressions were used to compute relative risk (RR) for positive margins and mortality hazards ratio along with 95 percent confidence interval limits (95%CI), respectively. Results: A total of 232 patients underwent lung resection for cancer diagnosis; VATS n = 99 and OT n = 133. Age at diagnosis, sex, tobacco use, tumor location, and size were not significantly different between the two groups. VATS was more frequently performed for stage I lung cancer compared to OT, p = 0.043. The risk of positive margin RR = 0.49 (95%CI = 0.15, 1.60) and mortality HR = 1.49 (95%CI = 0.90, 2.46) were similar between the two groups. However, the median LOS was significantly shorter (4 days) for VATS than OT (6 days), p = 0.001. Conclusions: Our results show that both short and long-term oncologic outcomes are comparable between VATS and OT. VATS results in shorter LOS and should be considered as the approach of choice for patients undergoing lung resection for cancer. [Table: see text]
Predictors of financial burden at a comprehensive cancer center.
Authors: Sheetal Mehta Kircher, Joshua P Rutsohn, Jessica Lee Yarber, Yanina Guevara, Madison M Lyleroehr, Halla Sayed Nimeiri, Jyoti D. Patel, Mark Agulnik, Mary Frances Mulcahy, Al Bowen Benson, Jonas A. De Souza, Sofia M Garcia
Journal: Journal of Clinical Oncology (2016)

e18263 Background: As the cost of cancer care escalates, patients’ financial concerns are increasingly common and can lead to the inability to afford basic needs such as food and clothes, non-adherence, spending savings, and even bankruptcy. Our objective was to determine predictors of financial burden using validated patient reported measures in outpatient cancer care. Methods: Study participants were patients with gastrointestinal, lung, or sarcoma cancer receiving intravenous chemotherapy who completed measures of financial burden [Comprehensive Score for Financial Toxicity (COST), Personal Finance Well-Being Scale (PFWBS), EORTC QLQ-C30]. A Multivariate Analysis of Variance (MANOVA) was used to examine whether age, gender, comorbidity, race, marital status, employment, income, savings, or insurance type were associated with financial burden. Results: In total, 96 patients completed the baseline survey. The omnibus test indicated that at least one independent variable was associated with COST (p = 0.01), PFWBS (p < 0.0001), and EORTC financial distress (p = 0.03) scores. Marital status (Wilks λ = 0.70, p = 0.002) and income (Wilks λ = .74, p = 0.008) were associated with financial distress. The COST score for incomes of $100,000 or greater were worst than those between $50,000 and $99,999 ( = 8.9, p < 0.0001) and less than $50,000 ( = 7.1, p < 0.0001). The results were similar for PFWBS scores ( = 1.9, p < 0.0001; = 2.2, p < 0.0001, respectively) and EORTC financial distress scores ( = -9.9, p < 0.0001; = -4.6, p < 0.0001, respectively). PFWBS scores and EORTC financial distress scores were statistically significantly worse for separated, divorced, or widowed participants than for married participants ( = -2.3, p < 0.0001; = 24.8, p < 0.0001, respectively). Conclusions: Financial burden is common in cancer patients but not systematically assessed. Our study shows that validated measures, including COST, PFWBS, and EORTC QLQ-C30 can be used feasibly in cancer care. Predictors of burden were consistently found to be marital status and income. Future studies and interventions should focus on potentially vulnerable patients.