tbuckley/cabot-search huggingface dataset:
A phase 2 trial of ABVD followed by brentuximab vedotin consolidation in limited stage non-bulky Hodgkin lymphoma.
Authors: Steven I. Park, Oludamilola A. Olajide, Nishitha M. Reddy, L. Elizabeth Budde, Nilanjan Ghosh, Kristy L. Richards, Allison Mary Deal, Jeanne F. Noe, Thomas C. Shea, Stephen Maxted Ansell
Journal: Journal of Clinical Oncology (2016)

7508 Background: The current standard for limited stage Hodgkin lymphoma (HL) is chemotherapy with or without radiation therapy. Given the unclear overall survival advantage and the long-term side effects associated with consolidative radiation, the use of this modality remains controversial in the treatment of HL. Brentuximab vedotin (BV) has emerged as one of the most active therapeutic agents in HL. We hypothesize that BV may be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage HL. Methods: In this phase 2 multicenter study, patients with previously untreated limited stage non-bulky HL received ABVD followed by BV (NCT01578967). The primary objective was to estimate the proportion of patients who achieve PET-negative disease (Deauville score ≤ 2) after ABVD followed by BV consolidation. Patients received 2 to 6 cycles of ABVD based on their baseline risk factors and the interim PET scan result. Approximately 6 weeks after the induction therapy, 1.8 mg/kg of BV was given every 3 weeks for 6 cycles. Results: Forty one patients were enrolled from April 2012 through December 2015. Out of 40 evaluable patients, the median age was 29 years (range 19 – 67), and 46% presented with unfavorable disease. Over 90% of patients received ≤ 4 cycles of ABVD, and one patient received radiation due to disease progression. Grade ≥ 3 toxicities associated with BV included neutropenia in 3 patients and peripheral neuropathy and rash in 1 patient each. There was one death due to sepsis and hepatic failure, a very rare but known complication of BV, and all reported ≥ grade 4 toxicities were associated with this event. After 2 cycles of ABVD, 72% of patients achieved PET-negative disease, and 90% of patients were PET-negative after the completion of BV. The estimated one-year progression free and overall survival rates are 91% and 96%, respectively, with a median follow up of 12 months. Conclusions: BV demonstrates promising safety and clinical activity following ABVD. BV consolidation may obviate the need for radiation therapy and achieve similar survival outcomes in the majority of patients with limited stage non-bulky HL. Clinical trial information: NCT01578967.
Atrial fibrillation and mortality in advanced lung cancer patients.
Authors: Shashank Jain, Yulanka Castro, Njambi Mathenge, Eman Rashed, Natalija Odanovic, Edward Rojas, Riju Banerjee, Monali Patel, Ahmad Al Turk, Elena Dolmatova, Kasra Moazzami, Shanti Srinivas, Steve Tsai, Victor Tsu-Shih Chang
Journal: Journal of Clinical Oncology (2016)

e23205 Background: The incidence of atrial fibrillation (AF) and cancer are rising as the population ages. An increased risk of new-onset AF has been reported after lung and esophageal cancer surgery, but the effect of AF on the natural history of pts with lung cancer is unknown. We hypothesized that AF affects mortality in lung cancer pts. Methods: We evaluated a retrospective convenience sample of 228 pts diagnosed with stage III/IV lung cancer at a VA medical center from 1997-2011. Baseline demographics and clinical characteristics (including stage and histological type), comorbid conditions, presence of atrial fibrillation and survival data were abstracted. Complete data was available for 218 patients. Summary statistics and Cox survival analyses were performed with SPSS v20. Results: Of 218 pts, 32 (15%) were stage IIIa, 46 (21%) IIIb and 139 (64%) IV; 48 pts (22%) had small cell lung cancer. Eleven pts (5%) had baseline AF and 23 (10%) developed AF after diagnosis. Pts with baseline AF were older than those with new-onset AF and without AF (mean (±SD) age: 72.9 ± 10.7 vs 69.5 ± 8.1 vs 65.9 ± 9.5 years, respectively; p = 0.001). Pts with AF had significantly higher prevalence of hypertension (82.4 vs 58.4% p = 0.009), coronary artery disease (41.2 vs 15.1% p < 0.00) and chronic obstructive pulmonary disease (50 vs 27.1% p = 0.009). New-onset AF was independently associated with higher incidence of heart failure, compared to pts without AF (34.8 vs 6.6%, p = 0.008). Pts with baseline AF had a shorter overall median survival compared to those without baseline AF (2.6 months 95% CI: 1.9 to 3.4 vs 7.4 months 95% CI: 6.3 to 8.4, p = 0.103). In multivariate survival analyses, after adjusting for age and stage, pats with lung cancer and baseline AF had an increased risk of 1-year mortality (HR: 2.91, 95% CI: 1.25 to 6.76, p = 0.013). Conclusions: AF may alter survival in lung cancer. These findings should be confirmed in a larger sample and in other populations.
Higher dairy intake is linked to lower risk of cardiovascular disease and death, finds study
Authors: Susan Mayor
Journal: BMJ (2018)

People who consume more than two servings of dairy products each day have lower rates of cardiovascular disease and mortality than those with lower intakes, a global observational study has reported.1

“Our findings support that consumption of dairy products might be beneficial for mortality and cardiovascular disease, especially in low and middle income countries where dairy consumption is much lower than in North America or Europe,” said lead author Mahshid Dehghan, from McMaster University, Hamilton, Canada.

Dietary guidelines currently recommend restricting consumption of whole fat dairy products because they contain saturated fats that are presumed to adversely affect lipid levels and increase cardiovascular risk. There is, however, limited evidence for this and the recommendation fails …
Chronic pain and disability in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Cynthia Karlson, Nicole M Alberts, Wei Liu, Tara M. Brinkman, Robert Annett, Daniel A. Mulrooney, Fiona Schulte, Wendy Leisenring, Todd M. Gibson, Rebecca M. Howell, Deokumar Srivastava, Kevin C. Oeffinger, Gregory T. Armstrong, Lonnie K. Zeltzer, Kevin R. Krull
Journal: Journal of Clinical Oncology (2018)

10568 Background: Chronic pain has not been well characterized in survivors of pediatric cancer. The current study is the first to examine prevalence and predictors of chronic pain and pain-related disability in this population. Methods: Participants included 10,012 adult survivors (48.7% female; median age 31 years; M time since diagnosis 15.3 years) from the CCSS. Participants completed the Short-Form 36 and Brief Symptom Inventory-18 on two occasions between 2002 and 2011. Chronic pain was defined as self-report of moderate to severe pain at both time points. Pain-related disability was defined as pain that interferes with normal work at either time point. Covariates included sex, age, time since diagnosis, treatment, and grade 3-4 chronic health conditions. Multinomial logistic regression estimated relative risk (RR) and 95% confidence intervals (CI) for predictors. Structural equation models examined associations between pain, depression, anxiety, and vitality. Results: 29% of survivors reported moderate to severe pain at either time point, 32% reported moderate to severe pain-related disability, and 10% reported chronic pain. Compared to survivors of leukemia, survivors of sarcoma (RR 1.33, CI 1.32-1.34) and solid tumors (RR 1.04, CI 1.03-1.06) reported more chronic pain. Survivors with a history of amputation (RR 1.54, CI 1.52-1.56) and, in separate models, those with chronic health conditions (RR 1.57, CI 1.56-1.59) were more likely to report chronic pain. Survivors with symptoms of depression (RR 1.11; CI 1.09-1.12) and anxiety (RR 1.25; CI 1.24-1.27) were also more likely to report chronic pain. Similar patterns were observed for pain-related disability. Controlling for demographics, treatment, and chronic health conditions, vitality mediated the effects of depression and anxiety on chronic pain (RMSEA 0.011) and pain-related disability (RMSEA 0.000). Conclusions: Adult survivors of childhood cancer experience chronic pain and pain-related disability that is associated with amputation, chronic health conditions, depression, anxiety, and poor vitality. Increased screening and comprehensive treatment of pain is warranted, particularly for these risk factors.
Abstract 14260: Mid-Life Vitamin D Levels Are Not Associated With 20-Year Cognitive Decline in Whites and Blacks: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Andrea L Schneider, Di Zhao, Pamela L Lutsey, Rebecca F Gottesman, A. R Sharrett, Alvaro Alonso, Myron Gross, David Knopman, Thomas H Mosley, Elizabeth Selvin, Erin D Michos
Journal: Circulation (2016)

Introduction: Prior studies, largely limited by short follow-up and the possibility of reverse causation, suggest that low vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is associated with cognitive decline. Less is known about the long-term associations of mid-life 25(OH)D levels with change in cognition among whites and blacks. Hypothesis: We hypothesized that lower 25(OH)D would not be associated with greater decline in cognitive function over 20 years compared to higher 25(OH)D. Methods: We conducted prospective (1990-1992 through 2011-2013) analyses of 13,044 ARIC participants with measured cognition and 25(OH)D at baseline. 25(OH)D was categorized as <20 ng/ml (deficient) versus ≥20 ng/ml. Cognition was measured by 3 tests at up to 3 time points (Delayed Word Recall, Digit Symbol Substitution, Word Fluency); these 3 tests were combined into global cognitive Z scores. Multiple imputation by chained equations were used to impute missing covariates and follow-up cognition data. Linear mixed-effe...
Prevalence and estimated trend in chemotherapy use near death from population-based studies on cancer patients: A systematic review and meta-analysis.
Authors: Pei-Chun Chou, Chen Hsiu Chen, Tsang-Wu Liu, Siew Tzuh Tang
Journal: Journal of Clinical Oncology (2017)

6590 Background: Chemotherapy (CMT) use near death, based on US national guidelines, is an indicator of aggressive treatment and poor quality of end-of-life (EOL) care. US law also decreased Medicare payments for outpatient CMT since 2005-2006. To evaluate the impact of US payment reform and guidelines on CMT use at EOL, we estimated and compared the overall prevalence of CMT use at EOL in the US and other countries as well as before and after 2007 in the US. Methods: Six databases were systematically searched to January 2017 for population-based studies of CMT use at EOL for patients in all cancer groups. Two reviewers independently extracted data.Overall CMT use prevalence was pooled by a random-effects model. Differences in prevalence of CMT use were compared by meta-regression between subgroups (US vs non-US countries; before and after 2007 in the US). Results: We identified 9 and 7 articles from the US and non-US countries, respectively. CMT was provided to 28.9% [95% confidence interval (CI) 26.2%-31.8%], 23.2% [95% CI 21.7%- 24.8%], 10.0% [95% CI 8.5%-11.8%], and 4.5% [95% CI 3.9%- 5.2%] of cancer patients in their last 6, 3, and 1 months as well as 14 days of life, respectively. CMT use in the last 6 months was more common in the US than in non-US countries (32.4% vs. 26.2%, p = 0.015) but similar to that of other countries in the last month (9.3% vs.11.2%, p = 0.179) and last 14 days (4.6% vs.5.6%, p = 0.683) of life. Prevalence of CMT use in the last 14 days of life in the US did not differ significantly before and after 2007 (5.1% vs. 5.2%, p = 0.967). Conclusions: Many cancer patients worldwide receive CMT at EOL, and the prevalence of CMT use in US patients’ last 14 days of life was virtually unchanged over time. Effective interventions should be developed and provided to offset the trend of continuing CMT use at EOL.
P01.083 Expression and prognostic value of the immune checkpoint molecule galectin-9 in glioblastomas
Authors: S Andersen, A M Knudsen, R H Dahlrot, M D Sørensen, B W Kristensen
Journal: Neuro-Oncology (2018)

Glioblastomas are highly malignant with a median survival time below15 months. Immunotherapy has shown promising results in different types of cancer, and novel therapies targeting PD-1/PD-L1 signalling have been approved for treatment of patients with melanoma and lung cancer. Galectin-9, a checkpoint molecule, may be a potential therapeutic target. Galectin-9 and its receptor, TIM-3, are involved in cancer cell aggregation, induced T-cell apoptosis, and tumor progression. Previous studies indicate that galectin-9 may be expressed in high-grade gliomas. The aim of this study was to investigate the expression and prognostic value of galectin-9 in glioblastomas. Tissue from 166 glioblastoma patients from the Region of Southern Denmark glioma cohort was included. The tissue sections were immunohistochemically stained with anti-galectin 9 antibody. Image analysis and area fraction quantification of the stainings were performed using the image analysis software, Visiopharm. Galectin-9 was highly expressed in most glioblastomas, especially in cells with microglial and macrophage morphology, but some glioblastomas had a very limited expression. The mean positive area fraction was 0.06 (range 0.01–0.32). When dichotomized at the median no difference in the median overall survival was observed. Galectin-9 was not associated with overall survival (HR= 0.97, p=0.8) in multivariate analysis including age, performance status, post-surgical treatment and MGMT status. The galectin-9 protein was expressed in most glioblastomas. Targeting of galectin-9 may therefore be of potential value in most glioblastoma patients in order to obtain immune-mediated anticancer effects.Galectin-9 expression was not associated with patient survival. Potential co-localization of alectin-9 and its receptor TIM-3 will be investigated in our future work, as will the correlation with PD-L1 expression, to discover potential strategies for combination treatment.
P03 Histological Subtype of Lung Adenocarcinoma and Programmed Death Ligand 1 (PD-L1) Expression in Tumor Cells
Authors: O. Arrieta, G. Cruz-Rico, A. Avilés-Salas, X. Popa-Navarro, K.Y. Flores-Vélez, L. Ramírez-Tirado, E. Vergara, F. Barrón, L.A. Cabrera-Miranda
Journal: Journal of Thoracic Oncology (2018)
Meeting the needs of women at high risk for breast cancer: Facilitated group visits.
Authors: Kathryn Trotter, Jennifer K Plichta
Journal: Journal of Clinical Oncology (2018)

e18508 Background: Women with an increased risk of breast cancer are often anxious about their risk and need additional counseling related to risk assessment, breast surveillance, and risk-lowering interventions. Methods: In conjunction with their follow-up visits, women in the high-risk breast clinic were invited to attend monthly one-hour lunchtime breast education sessions. . Bringing a friend or family member was encouraged. The sessions were facilitated by the breast surgery NP and breast surgeon who manage the clinic. The structure of the session included check-in with a self-assessment tool, which ranked topics of interest, followed by an ice breaker activity. A variety of education methods were used ranging from myth busters Q&A, standing continuum of risk factors, and connect with someone with a matching nutrition card. Guest experts also presented to focus on topics, such as genetics, nutrition, breast imaging, breast reconstruction, and exercise impact on cancer risk. At the end of each session, a patient satisfaction survey was conducted. Results: Women were overwhelmingly pleased with the series. The eleven survey questions were analyzed and questions 1-9 were categorized into four sections: Healthcare Professionals (Q1, Q2), Environment (Q5, Q6, Q8), Participant Understanding (Q3, Q4, Q7), and Return Rate (Q9). Of the completed surveys (N = 58), the mean satisfaction rating was calculated for each category, which was based on a scale of 1-5 with 1 = strongly agree and 5 = strongly disagree. The results showed that the Healthcare Professionals category had the highest satisfaction (mean 1.095), followed closely by Environment (mean 1.167), then Participant Understanding (1.175), and Return Rate (1.287). The satisfaction scores were supported by the qualitative data recorded from Q10 and Q11. All comments were positive statements, such as: “extremely helpful!”, “very informative!”, and “great session!”. Topics requested included nutrition, exercise, risk assessment, conducting personal tests, and genetics. Conclusions: Facilitated group sessions were received well by women in the high-risk breast clinic. This may serve as a new model for patient care and education for women with in an increased risk of breast cancer.
Long term follow-up (FU) of lenalidomide plus R-CHOP therapy in patients with newly diagnosed diffuse large b-cell lymphoma (DLBCL): Combined analysis from two phase 2 trials.
Authors: Alessia Castellino, Betsy LaPlant, Levi Pederson, Annalisa Chiappella, Gianluca Gaidano, William R Macon, Alessandra Tucci, Rebecca L. King, Angela Giovanna Congiu, Thomas E. Witzig, Umberto Vitolo, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2018)

7562 Background: The combination of lenalidomide (Len) with Rituximab-CHOP (R2CHOP21) has been shown to be safe and effective. These early results [Nowakowski et al. JCO 2014, Vitolo et al. Lancet Oncol 2014] led to two randomized trials. However, durability of response and safety have not been reported. Here, we present the long-term FU in de novo DLBCL patients (pts) who received R2CHOP21 in two independent phase 2 studies. Methods: We included newly diagnosed DLBCL pts enrolled in two R2CHOP21 phase 2 trials, conducted by Mayo Clinic (MC) and Italian Lymphoma Foundation (FIL). All pts received R-CHOP21 plus Len at 25 mg/d for 10 days/cycle and 15 mg/d for 14 days/cycle in MC and FIL trial respectively. We analyzed the long term FU outcome in terms of progression-free survival (PFS), time to progression (TTP), overall survival (OS) and the cumulative incidence of late toxicities and second tumors. Results: 108 DLBCL pts (59 MC, 49 FIL) were included. Main characteristics were: median age 69 years (y) (25 (23%) ≥ 75 y), stage 3-4 in 94 (87.0%) and International Prognostic Index (IPI) ≥ 3 in 60 (55.6%). At a median FU of 5.1 y, 5y PFS was 65.4%, 5y TTP 69.9% and 5y OS 77.4%. In total, 31 pts have relapsed, with only 4 cases occurring beyond 3y and only 2 CNS relapses. 5y PFS in germinal center (GCB) lymphomas vs non-GCB was 55.8% vs 65.7%, 5y TTP 62.3 vs 68.0 and 5y OS 71.7% vs 75.3% respectively. Only 4 pts had grade (gr) 4-5 late toxicities (1 gr 5 sepsis and 3 gr 4 neutropenia). Milder toxicities were infections (N 5 (4.6%), only 1 gr 3), thrombosis (N 1, gr 2) and persistent neuropathy (N 3, gr 1-2). Second neoplasia were 8 (6.4%): 1 acute myeloid leukemia, 2 second lymphoma (T-cell) and 5 other solid tumors. Conclusions: Long term FU shows that R2CHOP21 efficacy was maintained with high rate of PFS, TTP and OS, considering high risk features of patients included. The addition of len to RCHOP appears to mitigate the negative prognostic impact of non-GCB phenotype. The incidence of second tumors was low and no new worrisome safety signals were seen. This long -term analysis will aid interpretation of early results from randomized clinical trials, expected to be reported in near future.
Transcriptional analysis of immune genes in Epstein-Barr virus-associated gastric cancer and association with clinical outcomes.
Authors: Raghav Sundar, Aditi Qamra, Angie Lay Keng Tan, Shenli Zhang, Cedric Chuan Young Ng, Bin Tean Teh, Jeeyun Lee, Kyoung-Mee Kim, Patrick Tan
Journal: Journal of Clinical Oncology (2018)

e16024 Background: Anti-PD-1 immune checkpoint inhibitors have recently been approved in the treatment of advanced gastric cancer. Epstein-Barr virus associated gastric cancer (EBVaGC) has traditionally been associated with high expression of PD-L1 and immune cell infiltration. Correlations between PD-L1 and other immune-related gene (IRG) expression in EBVaGC has not been previously described. We conducted a study of transcriptomic expression of PD-L1 and other IRGs related to intra-tumoral cytolytic activity, cytokines and immune checkpoints in EBVaGC. Methods: EBVaGC samples were obtained from gastric cancer patients undergoing primary tumor resection at Samsung Medical Centre, South Korea, from 1996 to 2011 who consented to research use of their tissue samples. For controls, EBV-negative samples from the previously reported Asian Cancer Research Group (EBVnegACRG) cohort were used. Transcriptomic expression was measured using the NanoString platform on formalin-fixed paraffin embedded gastric cancer samples. EBV status was determined using EBV-encoded RNA in situ hybridization. Samples with PD-L1 expression greater than the 35th percentile were defined as PD-L1high and the remaining as PD-L1low. Disease-free survival (DFS) was calculated from the time of surgery to the time of disease progression or death. Results: We identified 72 cases of EBVaGC and 193 EBV-negative ACRG samples as controls. EBVaGC showed higher expression of all queried IRGs compared to EBVnegACRG samples (p < 0.01). EBVaGC had significantly higher PD-L1 expression (p < 0.001) compared to EBVnegACRG samples. PD-L1low EBVaGC samples (n = 25, 35%) had consistently decreased expression of all other IRGs including markers of cytolytic activity such as CD8A, GZMA and PRF1 and other immune checkpoints such as PD-1 (p < 0.001). PD-L1low EBVaGC samples were also associated with worse DFS (HR = 4.78, p = 0.039) compared to PD-L1high EBVaGC samples. Conclusions: A substantial proportion of EBVaGC do not express high levels of PD-L1 and other IRGs. EBVaGCs with lower transcriptomic expression of PD-L1 tend to have a poorer prognosis through low expression of other IRGs.