tbuckley/cabot-search huggingface dataset:
Prevalence of co-morbidities in elderly patients with distant stage neuroendocrine tumors.
Authors: A. Dasari, Chan Shen, Yiyi Chu, Daniel M. Halperin, Ying Xu, Shouhao Zhou, Tina Shih, James C. Yao
Journal: Journal of Clinical Oncology (2017)

e15699 Background: The median age of diagnosis of neuroendocrine tumors (NETs), an indolent tumor characterized by hormone production (carcinoid syndrome, CS) when metastatic is 63 years. Patients (pts) in this age group have multiple co-morbidities. However, their prevalence among elderly pts with metastatic NET is unknown. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify 2,388 elderly patients with distant stage NET (Age: &lt; 70: 631; 70-79: 1200; &gt; 80: 557; Race: white: 83.4%, black: 8.6%) diagnosed between 1/03 and 12/11 identified by ICD-O-3 codes with continuous Medicare Parts A and B enrollment during the one year after NET diagnosis. We examined the prevalence of common co-morbidities in the elderly population: dementia, heart conditions including ischemic heart disease (IHD), hypertension (HTN) &amp; congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, hyperlipidemia, diabetes, arthritis, and two additional relevant comorbidities: osteoporosis (OP) and non-rheumatic tricuspid valve (TV) disorders. Pts were considered to have a condition if they had ≥ 1 inpt or ≥ 2 outpt visits indicative of the condition. We compared the prevalence in the NET group with that in a propensity score matched non-cancer group using chi-square test. Within the NET group, we also examined the association between pt characteristics and the presence of the conditions using a logistic regression model. Results: Compared to the matched non-cancer control group, NET pts were significantly (P &lt; 0.01) more likely to have HTN (74% vs. 66%), OP (14% vs. 11%) &amp; TV disorders (1.72% vs. 0.98%) and less likely to have dementia (7.3% vs 17.4%), IHD (23.2% vs 29%) and diabetes (30.3% vs 33.5%). CS was noted in 25.7% of the NET group and logistic regression showed that these pts with were significantly more likely to have TV disorders (AOR = 2.52, 95% CI: 1.24-5.14) and osteoporosis (AOR: 1.34, 95% CI: 1.01-1.81). Conclusions: This population-based study showed that elderly NET pts have significantly different prevalence of co-morbidities compared to non-cancer controls. The impact of these conditions on survival and therapeutic decisions is being evaluated.
How cancer patients and oncologist assess data-sharing and the risk of re-identification in genomic research? Ethical implications for informed consent and governance.
Authors: Eva Caroline Winkler, Sebastian Schleidgen, Christoph Schickhardt, Christof V. Kalle, Dominik Ose, Alma Husedzinovic
Journal: Journal of Clinical Oncology (2016)

e18186 Background: Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants and revealing personal genomic information rises. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. Methods: We conducted a qualitative focus group study at the National Center for Tumor Diseases (NCT) with five focus groups of cancer patients (n = 16) and two focus groups of oncologists (n = 8). Group discussions were structured and took 75 minutes on average. They were transcribed verbatim, coded and analyzed following qualitative content analysis. Results: Patients and oncologists assessed the informational risks either as minimal or greater than minimal, depending on the context factors of occupational status, age and prognosis of genomic research participants. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational as well as institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. Conclusions: The results suggest 1) comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, 2) establishing independent governance entities in order to minimize the informational risks of genomic research, and 3) policies which offer guidance for physicians and researchers involved in genomic research. Solutions for 1-3 have been implemented at the NCT and will be presented.
Early neutrophil to lymphocyte ratio dynamics to predict progression free survival in patients treated with immune-checkpoint inhibitors.
Authors: Michele Moschetta, Benjamin Kasenda, Gabriel Mak, Mark Voskoboynik, Nataliya Martynyuk, Vincenzo Formica, Saeed Rafii, Hendrik-Tobias Arkenau
Journal: Journal of Clinical Oncology (2016)

e14513 Background: A high neutrophil/lymphocyte ratio (NLR) at baseline has repeatedly been associated with shorter progression free (PFS) and overall survival (OS). We explored whether early changes in NLR can predict PFS to anti-PD1/PDL1 inhibitors in a population of advanced cancer patients (pts) enrolled into Phase-1 (Ph-1) trials. Methods: Pts with various stage IV tumours enrolled into anti-PD1/PDL1 checkpoint inhibitor Ph-1 trials between September 2013 and October 2015 were included in this study. NLR was calculated at baseline and after 2 cycles of treatment. We used Kaplan-Meier estimation and multivariable Cox regression analysis with a random effect for tumour entity (to account for heterogeneity between tumour types) to assess the impact of NLR at baseline and after 2 cycles on PFS. Pts who received less than 2 cycles of treatment were excluded to avoid guarantee time bias. Results: Of 54 pts treated,12 were excluded, as they did not receive 2 full cycles of anti-PD1/PDL1 treatment. In total 42 pts were eligible (median age of 60.2 years, PS 0/1 = 74% / 26%, female = 40.5%). Tumour types were non-small cell lung cancers (n = 11, 26.2%), renal cell (n = 8, 19%), upper gastrointestinal (n = 8, 19%), breast (n = 7, 16.7%), urothelial (n = 4, 9.5%), colorectal (n = 2, 4.8%), ovarian (n = 1, 2.4%), and small bowel cancers (n = 1, 2.4%). Prior to Ph-1 entry pts received a median of 1 treatment line (range 1-6), and presented with a median number of 2 metastatic sites (range 1-4). 62% (n = 26) received an anti-PDL1 monoclonal antibody (MAb), 38% (n = 16) an anti-PD1 MAb. Patients with increasing NLR between baseline and 2 cycles had a significantly shorter PFS (HR 1.56, 95% confidence interval 1.19 – 2.06, p = 0.001). When pts were grouped by tertiles based on NLR variations between baseline and after 2 cycles of treatment a significant differences in PFS can be found (log-rank test P = 0.0261). Conclusions: Early changes in the dynamics of NLR (as continuous variable) may represent a clinical marker of response and may serve as a useful and easy test to select pts most likely to benefit. Currently a validation set in a large population of melanoma and non-small lung cancer pts is ongoing.
Detection of clinically relevant gene fusions in plasma samples of lung cancer patients in routine molecular diagnostics.
Authors: Anna Streubel, Thomas Mairinger, Jens Kollmeier, Susann Stephan-Falkenau, Torsten-Gerriet Blum, Daniel Misch, Anna-Lena Volckmar, Peter Schirmacher, Albrecht Stenzinger, Volker Endris
Journal: Journal of Clinical Oncology (2018)

e24191 Background: Tumor-derived circulating cell-free DNA (ctDNA) has emerged as an important biomarker for non-invasive lung cancer monitoring as well as in defining a molecular tumor profile in patients not suitable for biopsy. Current diagnostic procedures have focused on the detection of EGFR mutations, while identification of drugable targets like EML4-ALK or ROS1 fusions were hampered by the low ctRNA amount in plasma in combination with enzymatic degradation. The analysis of exosomal RNA could be a key issue in completing molecular diagnostic profiling beyond the analysis of cfDNA alone. Hence, the present study analyses several extraction methods and technical parameters to complete liquid biopsy analysis by successful RNA-based detection of fusion genes in addition to cfDNA mutation analysis. Methods: We evaluated different extraction methods with a special focus on exosomal purification in combination with NGS-based multiplex fusion detection panels in a routine diagnostic setting. Plasma samples from patients tested positive for gene rearrangements in tissue were collected before therapy initiation or from cases presenting with resistance during targeted therapy. 40 ml of blood was collected in standard EDTA- and cfDNA-stabilizing tubes. After cfTNA extraction, ultradeep next generation sequencing using AmpliSeq or TagSequencing chemistry was performed. Results: We were able to detect different gene fusions on RNA level from 4 ml plasma of NSCLC patients, including different EML4-ALK variants, FGFR3-TACC fusion or MET Exon 14 skipping events. While sensitivity of fusion detection was highest when applying exosomal RNA extraction, the overall low amount of DNA challenges the detection of classic resistance mutations. Conclusions: In summary, an optimized combination of cfTNA extraction followed by a multiplex NGS-based fusion detection holds promise for sensitive detection of expressed fusion genes in plasma samples.
NanoPac inhalation treatment of NSCLC in a nude rat orthotopic lung cancer model.
Authors: Gere Dizerega, William Johnston, James Verco, Michael Jay Baltezor, Ronald Wolff, Philip Kuehl
Journal: Journal of Clinical Oncology (2018)

8535 Background: NanoPac is sub micronized paclitaxel in stable powder form without coating or carrier agents. In a previous PK study, healthy male rats inhaled a single exposure of nebulized NanoPac (0.37 mg/kg or 1.0 mg/kg) or IV Abraxane (5.0 mg/kg) with a final necropsy time-point at 14 days. T1/2 of NanoPac and Abraxane were 56hrs and 20hrs with drug present at 14 days and not after 3 days, respectively. Tissue examined from the last time point were microscopically indistinguishable from non-treated controls. Methods: 120 nude rats were assigned to 6 groups and intratracheally instilled with Calu-3 lung tumor cells (2x106). Target doses and treatment schedules; Group 1 (Control: untreated), Group 2 (Abraxane: IV 5 mg/kg q1wx3), Group 3 (NanoPac: Inhaled (IH) 0.5 mg/kg q1wx4), Group 4 (NanoPac: IH 1.0 mg/kg q1wx4), Group 5 (NanoPac: IH 0.5 mg/kg q2wx4), Group 6 (NanoPac: IH 1.0 mg/kg q2wx4). Nebulized NanoPac (2µm Mass Median Aerodynamic Diameter) was delivered via nebulization into a nose-only exposure chamber; necropsy occurred (Group 2: 14 days), (Groups 3-6: 1 - 4 days) post final treatment. Histology was performed on sections of left lung stained with H&E from 10 animals in each group and scored using a 4-point grading scale. Results: Average lung/brain weight ratios for Group 2 (2.3) and Groups 3-6 (2.7) indicated a therapeutic effect vs Group 1 (3.2). Lung tumor burden decreased in combined Groups 3-6 as compared to Groups 1 and 2; characterized by the histological measures of tumor mass, primitive tumor cell population and tumor regression. Average primitive tumor cell population was significantly less (p < 0.05) for Groups 3-6 (0.3) compared to Group 1 (0.9) or Group 2 (1.0). Combined NanoPac Groups 3-6 (22/40) exhibited a significant (p < 0.05) incidence of tumor regression compared to Group 1 (0/10) and Group 2 (1/10). Conclusions: NanoPac treatment groups compared to Control and Abraxane groups demonstrated a therapeutic effect as measured by lower lung/brain weight ratio and lower overall lung tumor burden without apparent adverse events. Histological analysis of lung tumor burden treated with NanoPac IH showed a decrease in tumor mass, a decrease in primitive tumor cell population, and an increase in tumor regression.
Abstract 18944: The Mir-33 Locus Coordinately Regulates Macrophage Autophagy
Authors: Mireille Ouimet, Hasini Ediriweera, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Christine Esau, John Pezacki, Ira Tabas, Yves Marcel, Katey Rayner, Kathryn Moore
Journal: Circulation (2016)

Autophagy, which promotes the degradation of cytoplasmic components in lysosomes, is essential for maintaining cellular homeostasis. Defective autophagy in macrophages of the artery wall leads to a...
Prognosis of lung cancer as a second primary malignancy among cancer survivors: A population-based cohort study.
Authors: Lei Deng, Zhengrui Xiao, Changchuan Jiang, Qian Wang, Haiying Cheng, Donghao Lu
Journal: Journal of Clinical Oncology (2018)

e21005 Background: Cancer survivors are at increased risk of developing a second primary malignancy, including lung cancer. However, prognosis of lung cancer as a second primary malignancy (lung-2) remains largely unknown. This study aims to investigate the prognosis of lung-2 in relevant to lung cancer as a first primary malignancy (lung-1). Methods: Lung cancer patients from 1988 to 2014 in the Surveillance, Epidemiology, and End Results program were included. Overall and lung cancer specific mortality are the main outcome. Second primary malignancy was defined according to SEER rules. Results: 679,541 and 85,758 patients were included as lung-1 and lung-2 in this study, respectively. The median time from first primary malignancy to lung-2 diagnosis is 4.3 years. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 was associated with favorable overall (HR 0.97, 95% CI 0.96-0.98) and lung-cancer specific (HR 0.80, 95% CI 0.79-0.80) mortality compared to lung-1. The favorable overall survival of lung-2 was primarily contributed by the decreased risk of overall mortality within first year after cancer diagnosis. The risk of lung cancer specific mortality was reduced within the first 5 years after diagnosis. Conclusions: Lung-2 is not more aggressive compared to lung-1 and is not associated with inferior cancer-specific survival. Table 1 Mortality risk of lung cancer as a second primary malignancy Lung cancer as a first primary Lung cancer as a second primary HR HR (95% CI) Overall mortality Model A* 1.00 0.86 (0.85-0.87) Model B† 1.00 0.97 (0.96-0.98) Lung cancer specific mortality Model A* 1.00 0.70 (0.69-0.70) Model B† 1.00 0.80 (0.79-0.80) HR, hazard ratio; CI, confidence interval* Model A: Adjusted for age and calendar period at diagnosis, sex, race, cohabitation status, and percentile of high-school education, household income in county of residence. †Model B: Adjusted for tumor stage, histology, tumor grade, surgery, radiation therapy, and chemotherapy in addition to what are included in model A.
Risk stratification using patient-reported outcomes (PROs) in patients (pts) with advanced cancer.
Authors: Shiven B. Patel, Ben Haaland, Dominik Ose, Tyler Haydell, Jim Martineau, William A. Dunson, Anna Weinberg Chalmers, Laura Cannon, Betsy Kissell, Neal J. Meropol, Wallace L. Akerley
Journal: Journal of Clinical Oncology (2018)

10101 Background: Performance status is often used to stratify cancer pts for treatment and to guide supportive care resources. This retrospective study was conducted to evaluate whether PROs have prognostic value, independent of physician assessment of functional status. Methods: Pts treated at Huntsman Cancer Institute were assessed using the NCI PROMIS-Ca bank from May 2016. Physical function, fatigue, depression, anxiety, and pain scores were collected via iPad in pts with metastatic NSCLC, CRC, and breast cancer. A single PRO score at the time of metastatic disease for each pt was merged with outcome data using the Flatiron Health database, processed with technology-enabled abstraction and supplemented with third-party death information. Associations between PROs, PROs and overall (OS), and PROs and hospital-free survival (HFS) were assessed. Results: The five PRO domains were interrelated with moderate-strong correlation coefficients (0.40-0.79). Physical function score was worse for NSCLC than both CRC (p < 0.001) and breast cancer (p < 0.001), while both anxiety and depression were worse for NSCLC than CRC (p = 0.003 and p = 0.042, respectively). All individual PRO domains and a summary score were strongly associated with outcomes. Physical function and fatigue provided the greatest discrimination. The correlation of PROs with 12-month survival (table) and HFS were statistically significant. Conclusions: PRO scores, independent of physician interpretation, are prognostic for OS and HFS. These findings have substantial implications for patient care, treatment planning, clinical research, and financial modeling. Kaplan-Meier estimates of 12 month survival by tertile by PRO. Probability of Survival to 12 months Log-rank P-Value Low Tertile Middle Tertile High Tertile Physical Function 0.57 (0.46-0.71) 0.70 (0.61-0.81) 0.83 (0.73-0.94) < 0.001 Pain Interference 0.72 (0.61-0.85) 0.81 (0.72-0.90) 0.54 (0.42-0.68) < 0.001 Fatigue 0.82 (0.72-0.94) 0.69 (0.60-0.79) 0.57 (0.45-0.72) < 0.001 Anxiety 0.73 (0.63-0.86) 0.73 (0.64-0.83) 0.67 (0.56-0.79) 0.014 Depression 0.81 (0.71-0.91) 0.70 (0.60-0.81) 0.62 (0.51-0.75) 0.002 Composite 0.77 (0.66-0.90) 0.75 (0.66-0.86) 0.59 (0.48-0.72) < 0.001
Trial of rucaparib in prostate indications 3 (TRITON3): An international, multicenter, randomized, open-label phase 3 study of rucaparib vs physician’s choice of therapy for patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD).
Authors: Charles J. Ryan, Simon Paul Watkins, Darrin Despain, Chris Alan Karlovich, Andrew Simmons, Anthony A. Golsorkhi, Simon Chowdhury
Journal: Journal of Clinical Oncology (2017)

TPS5087 Background: Pts with mCRPC often initially receive androgen receptor-targeted therapy (eg, abiraterone or enzalutamide), but they almost always progress. Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) have demonstrated clinical activity in pts with mCRPC with a deleterious mutation in a homologous recombination (HR) DNA repair gene; 14 of 16 evaluable pts with mCRPC and a tumor alteration in an HR gene, including BRCA1, BRCA2, and ATM, responded to olaparib (Mateo et al. N Engl J Med. 2015;373:1697-708). The PARP inhibitor rucaparib is approved in the US for treatment of pts with ovarian carcinoma that harbors a deleterious BRCA1 or BRCA2 mutation (germline and/or somatic) who have received ≥2 chemotherapies. These data support investigating rucaparib as a treatment option in pts with mCRPC with HRD. Methods: TRITON3 (NCT02975934)is a phase 3 study evaluating rucaparib (600 mg BID) vs physician’s choice (abiraterone, enzalutamide, or docetaxel) in pts with mCRPC who have a deleterious germline or somatic mutation in BRCA1, BRCA2, or ATM as determined by local and/or central testing. All pts must have progressed on abiraterone or enzalutamide in the mCRPC setting; pts who received prior chemotherapy for mCRPC or PARP inhibitor treatment are excluded. Pts will be randomized 2:1 to rucaparib or physician’s choice of comparator therapy; pts randomized to physician’s choice may cross over to rucaparib on radiographic progression confirmed by independent radiology review (IRR). The primary endpoint is IRR-confirmed radiographic progression-free survival (modified RECIST version 1.1/PCWG3 criteria). Secondary objectives include overall survival, objective response rate, duration of response, clinical benefit rate, pt-reported outcomes, and safety. Pretreatment blood samples will be collected from all pts to enable development of a plasma-based companion diagnostic to identify pts who may benefit from rucaparib treatment. Pts (≈400) will be enrolled at &gt; 100 sites worldwide. Clinical trial information: NCT02975934.
A retrospective study of double-hit lymphomas in elderly patients (&gt; 70 years): Overall outcomes.
Authors: Christie Hancock, Phillip Knouse, Imad Almanaseer, Jacob D. Bitran
Journal: Journal of Clinical Oncology (2018)

e19530 Background: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP. More intensive treatment regimens have been studied, but there is little data on outcomes in elderly patients ( > 70 years) treated with these therapies. We retrospectively studied the efficacy and tolerability of chemotherapy regimens in elderly patients (pts) within the Advocate Healthcare System. Methods: A system-wide search of cases treated from 2012-2017 was completed to identify patients with c-myc with bcl-2 and/or bcl-6 translocations based on FISH. Cases were reviewed for age at diagnosis, stage, LDH, ECOG, details of chemotherapy, grade 3 and 4 toxicities, and responses to therapy. Overall survival (OS) and event-free survival (EFS) were calculated. Results: Twenty pts (11 males, 9 females) with a median age of 77 years (range 70-89 years) were identified. Eight pts received R-EPOCH, 6 received R-CHOP, 1 received bendamustine and rituximab, 1 received the MaGrath regimen, and 1 received cyclophosphamide and rituximab. Three pts were not treated and referred to hospice care. For all patients, the median follow-up was 25 months and the EFS and OS were 32% at 36 months; the median survival was 9 months. For patients treated with R-EPOCH, the EFS was 50% at 24 months. For R-CHOP, EFS was 40% at 24 months. Most common grade 3-4 toxicities were neutropenia, anemia, thrombocytopenia, and infections and were more common in the R-EPOCH group. Three pts died in the R-EPOCH group and 3 died in the R-CHOP group. A total of twelve pts died. Conclusions: Although the numbers are small, elderly pts with DHL can achieve durable EFS and OS that is slightly inferior to younger pts. Our retrospective analysis, given a small sample size, suggests that intensive treatment regimens should be offered to elderly pts with DHL.