tbuckley/cabot-search huggingface dataset:
Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy
Authors: Christopher Strouse, Ashutosh Mangalam, Jun Zhang
Journal: Gut Microbes (2018)

The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.
Pilot and definitive randomised double-blind placebo-controlled trials evaluating an oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting (CINV).
Authors: Antony Mersiades, Annette Tognela, Paul Haber, Martin R. Stockler, Nicholas Lintzeris, Iain McGregor, Ian Olver, David J Allsop, Craig Gedye, Adrienne Kirby, Rachael L Morton, Anh T Tran, Karen P. Briscoe, Peter Fox, Stephen John Clarke, Morteza Aghmesheh, Nicole Wong, Anna Walsh, Carmel Hahn, Peter S. Grimison
Journal: Journal of Clinical Oncology (2018)

TPS10128 Background: Up to half of patients receiving chemotherapy of moderate or high emetic risk experience CINV despite optimal anti-emetic prophylaxis. Limited evidence suggests cannabinoid medicine in the form of tetrahydrocannabinol (THC) may reduce CINV, and addition of cannabidiol (CBD) may improve efficacy and tolerance. The aim of this multi-centre, randomised, placebo-controlled, phase II/III trial is to determine efficacy and cost-effectiveness of the addition of an oral cannabinoid-rich THC/CBD cannabis extract for control of CINV. Methods: Target population is adult patients experiencing CINV during moderate and highly emetogenic chemotherapy regimens despite appropriate anti-emetic therapy, who are scheduled to receive at least 2 more consecutive cycles (A, B and, where applicable, C). Treatment consists of oral THC 2.5mg/CBD 2.5mg (Tilray TN-TC11M) capsules or placebo TDS days -1 to 5, in addition to guideline-consistent anti-emetics, including rescue medications. Patients will start with 1 tablet PO TDS and can dose-titrate to a maximum of 4 tables PO TDS based on nausea control and side-effects. In the pilot trial (N = 80), subjects are randomised for cycle A, cross-over for cycle B, and nominate preferred treatment for cycle C (if applicable). The planned definitive trial (N = 250) will randomise subjects to investigational product or placebo for cycles A, B and C in a parallel design. The primary end-point is the proportion of patients gaining a complete response (no emesis and no use of rescue medications) (0 – 120h), with additional end-points of (i) complete response, (ii) no emesis, (iii) no significant nausea and (iv) no use of rescue medication during the a) acute, b) delayed, and c) overall phases of cycle A, B and C, (iv) adverse events, (v) quality of life, and (vi) cost-effectiveness. As of 12/02/2018, 41 of 80 patients have been recruited to the pilot study, with expected recruitment completion in 2nd quarter 2018. Funding: NSW Department of Health. Acknowledgements: Trial participants, investigators and research staff. Drug supply by Tilray. ACTRN: 12616001036404 Clinical trial information: 12616001036404.
The negative association between Charlson Comorbidity Index and TNM stage at diagnosis in non-small cell lung cancer.
Authors: James X Zhang, Jianfeng Meng, Yonglin Pu
Journal: Journal of Clinical Oncology (2018)

e21118 Background: It is unclear how comorbidities are associated with the stage of non-small cell lung cancer (NSCLC) at cancer diagnosis. We aimed to evaluate the association between Charlson Comorbidity Index (CCI) and TNM stage at diagnosis among a large sample of NSCLC patients. Methods: From the database of our institutional Cancer Center Cancer Registry, we found 2,510 patients with NSCLC who were diagnosed and treated at our institution from 2004 to 2014. The patients were enrolled based on the following inclusion criteria: 1) had undergone a baseline FDG PET/CT, 2) had no evidence of brain metastasis, and 3) did not have concurrent diagnosis or a history of other primary cancer. A total of 949 patients were enrolled and used for this retrospective study. 19 comorbidities at the baseline defined by the Charlson, et al., were used to determine the CCI. Overall survival (OS) was determined from the FDG PET date to the death from any cause. Other factors included age, gender, race, and smoking history, NSCLC clinical staging at diagnosis (7th edition). Multivariate regression analyses were performed to determine the association between the CCI and TNM stages, adjusting for age, gender, race and smoking history. Results: Among the 949 incident NSCLC patients, 429 (45%) were male, 452 (48%) were black, with a mean age of 67 (s.d. 11), and median survival of 24 months (interquartile range 10-55 months). The number of patients with TNM stage for IA, IB, IIA, IIB, IIIA, IIIB, and IV were 171 (18%), 103 (11%), 67 (7%), 40 (4%), 164 (17%), 107 (11%), and 297 (31%), respectively. Three hundred fifty-three (37%) patients had no comorbidity at the baseline, 251 (26%) patient with CCI of 1, 171 (18%) of patients with CCI of 2, and 99 (10%) with CCI of 3, and 75 (8%) patients with CCI of 4 or higher. Controlling for age, gender, race, and smoking history, the adjusted parameter estimate of CCI is -0.20 (95% CI: -0.30, -0.10, p = 0.01). Conclusions: Higher value of CCI is negatively associated with an advanced cancer stage at diagnosis, suggesting healthier adults being less likely to receive an early diagnosis of NSCLC.
Utility of comprehensive genomic profiling (CGP) for personal cancer vaccine development via neoantigen analysis.
Authors: Dana Vuzman, Shermin Pei, Angeliki Pantazi, Jennifer E. Ring, Meaghan Russell, Dilhan Weeraratne, Maria Lvova, Stephen Lyle, Julie Y Tse
Journal: Journal of Clinical Oncology (2018)

3100 Background: Cancer vaccines against neoantigens have shown promise in treating advanced stage cancers [1,2]. Typically, detection of somatic mutations underlying neoantigen expression is done using WES, a cost and time-ineffective platform for routine clinical use. Here, we assess the feasibility of a large NGS panel for use in cancer vaccine development through discovery of somatic mutations and prediction of neoantigen load. Methods: Various patient tumor samples with a range of mutational loads [n = 30; mean: 84 mutations, range: 34-248] were profiled using CANCERPLEX, a 435-gene panel for identifying clinically-relevant genomic alterations in cancer [3]. For each mutation, all possible 9- and 10-mer peptides were enumerated. For mutations that result in novel open reading frames (neoORF), peptides overlapping the entire neoORF were considered. The 28 most frequent HLA-A and HLA-B alleles in the Caucasian, African, and Asian populations were used. Peptides were computationally evaluated for binding to HLA using the NetMHCpan-3.0 algorithm [4]. For each neoantigen, the rank relative to the collective mutant and wildtype 9- or 10-mers was determined. Neoantigens were classified as strong binders if rankmutant/rankwt ≥ 0.5. For each HLA allele, the neoantigen load was calculated as the number of strong binders per given allele. Results: The number of neoantigens was significantly correlated with mutational load. The neoantigen load was dependent on the HLA allele binding partner, with HLA alleles B07:02, A33:03, A30:01, and B42:01 predicted to have higher binding affinity. This allele dependent distribution suggests that certain HLA alleles are better binding partners for potential neoantigens or preferential for certain peptide. Conclusions: The high number of neoantigens identified suggests that CGP is a feasible alternative to WES for cancer vaccine development. CANCERPLEX accurately detects somatic mutations [3] thus enabling prediction of tumor neoantigens, an emerging biomarker in immune-oncology [5]. Future studies incorporating HLA transcription testing with CGP are warranted to further establish the platform for cancer vaccine development.
P01.063 Influence of Pregnancy on Glioma Patients
Authors: M Forster, P Baumgarten, F Gessler, G Maurer, C Senft, E Hattingen, V Seifert, P Harter, K Franz
Journal: Neuro-Oncology (2018)

Data about the influence of pregnancy on progression free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation. The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed. Results were compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection and tumor location. Tumor pathology was astrocytoma in 9 patients, oligodendroglioma in 6 patients and ependymoma in 3 patients. Time interval between tumor resection and delivery was 5.3 ± 4.4 years, and all newborns were healthy after uneventful deliveries. Tumor progression was diagnosed during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these patients underwent second surgery after delivery, whereas resection of recurrent tumor was performed in two women before pregnancy. Among nulliparous patients 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with children and patients without children (6.0 ± 4.2 vs. 7.5 ± 3.2 years; p=0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients. Pregnancy has neither a positive nor a negative influence on the clinical course of glioma patients. Likewise, glioma has no impact on delivered children’s health.
AB0525 Identification of effective parameters informing the selection of intravenous cyclophosphamide versus mycophenolate mofetil for induction therapy for lupus nephritis
Authors: N. Mino, H. Yamashita, K. Motomura, M. Nakahara, K. Suga, A. Yashima, Y. Takahashi, H. Kaneko
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The 2012 EULAR recommendations gave equal weight to intravenous cyclophosphamide (IVCY) and mycophenolate mofetil (MMF) as the induction therapy for class III/IV lupus nephritis (LN). However, there are no effective parameters that could inform the choice the induction therapy (IVCY or MMF) in individual cases. <h3>Objectives</h3> This study examined the patient characteristics that determine the most appropriate treatment for LN: IVCY or MMF. <h3>Methods</h3> We retrospectively examined 29 patients with LN who received induction therapy with IVCY (n=16) or MMF (n=13) between January 1994 and December 2015. Their baseline characteristics and the complete response (CR) rate at week 24 were analysed. CR was defined as a urine protein:creatinine ratio &lt;0.5 g/gCre with normal urine sediment. <h3>Results</h3> At baseline, the time since diagnosis of systemic lupus erythematosus (SLE) was longer in the IVCY group than the MMF group (4.8±6.4 <i>vs.</i> 1.3±2.5 years, p=0.06) and the IVCY group had more frequent flares (1.9±2.4 <i>vs.</i> 0.7±1.1 times, p=0.08); however, the differences were not significant. Moreover, there was no difference in age, sex, complement levels, anti-dsDNA antibody titers, anti-Sm/RNP antibody positivity rates, proteinuria, or rate of abnormality in urine sediment at baseline between the two groups. CR was achieved at week 24 in 11/16 patients (69%) in the IVCY group and 9/13 patients (69%) in the MMF group. Considering the 20 patients who achieved CR at week 24, univariate analyses revealed that in addition to a longer time since diagnosis of SLE (4.5±6.6 <i>vs.</i> 1.0±1.7 years, p=0.12) and more frequent flares (1.9±2.8 <i>vs.</i> 0.6±1.0 times, p=0.16), the anti-RNP antibody positivity rate was higher (OR 8.15; p=0.07) in the IVCY group. Furthermore, the positivity rate of anti-RNP antibody differed significantly (OR 12.9; p=0.03) in the multivariate analysis. <h3>Conclusions</h3> Although IVCY and MMF are equivalent treatment options for LN, IVCY might be more effective for patients with anti-RNP antibody. <h3>Reference</h3> [1] George K, Bertsias, et al. Annals of the Rheumatic Diseases2012;71:1771–1782. <h3>Disclosure of Interest</h3> None declared
Abstract 18519: Is Amplitude Spectrum Area (AMSA) Affected by Various Depth and Rate of Chest Compressions
Authors: Bjarne Madsen Hardig, Jonas Carlson, Trygve Sjöberg, Stig Steen, Pyotr Platonov
Journal: Circulation (2016)

Introduction: Amplitude Spectrum Area (AMSA) is a proposed ECG-based indicator of ventricular activity during ventricular fibrillation (VF), which has demonstrated its value for prediction of effec...
Are patients with high-risk polycythemia vera (PV) receiving cytoreductive medications? A retrospective analysis of real-world data.
Authors: Dilan Paranagama, Jingbo Yu, Philomena Colucci, Kristin Evans, Machaon Bonafede, Shreekant Parasuraman
Journal: Journal of Clinical Oncology (2017)

e18031 Background: Risk-adapted therapy in PV is aimed at preventing thrombotic events (TE). Under current treatment recommendations (including European LeukemiaNet), high-risk patients (age ≥ 60 y and/or history of TE) should be managed with cytoreductive medications in addition to phlebotomy and low-dose aspirin. The objective of this study was to describe cytoreductive medication usage in patients with high-risk PV. Methods: Retrospective claims from the Truven Health MarketScan Database were analyzed. Inclusion criteria were ≥ 2 non-diagnostic claims for PV &gt;30 days apart, age ≥ 18 y, continuous enrollment during pre-index (1/1/2012–12/31/2012), and continuous enrollment through or death during the study period (1/1/2013–12/31/2014). Patients with claims for myelodysplastic syndrome, myelofibrosis, acute myelogenous leukemia, or secondary polycythemia were excluded. Descriptive statistics were used. Results: The study included 2856 patients. Mean (SD) age was 62.5 (13.5) y, 65.9% of patients were male, and 63.8% were high-risk. Comorbid conditions of interest were reported more frequently in high-risk patients than low-risk patients: hypertension (65.0% vs 43.1%), diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). In low- and high-risk patients, the most commonly used cytoreductive medications were hydroxyurea (93.6%), anagrelide (7.6%), and interferon (2.4%). Low-risk patients received cytoreductive medications less often than high-risk patients (Table). However, only 42% of the high-risk patients received treatment with a cytoreductive medication by the end of the study. Conclusions: Despite higher cardiovascular risk and treatment recommendations, less than half of the high-risk PV patients received cytoreductive medications. Furthermore, less than a third of younger patients with a prior TE received cytoreductive medications. [Table: see text]
A first in human study using photodynamic therapy with Redaporfin in advanced head and neck cancer.
Authors: Julio Oliveira, Eurico Monteiro, Juliana Santos, Jose Dinis Silva, Luis Almeida, Lúcio Lara Santos
Journal: Journal of Clinical Oncology (2017)

e14056 Background: Photodynamic therapy (PDT) may be an appealing approach when head and neck cancer (HNC) patients (pts) develop locoregional standard treatment failure. Currently available systemic photosensitizers (PST) present several limitations, such as longstanding photosensitivity. Redaporfin is a new PST specifically designed to achieve improved efficacy and safety over existing options. Methods: This phase I/IIa clinical trial had the objective to determined Redaporfin tolerability, anti-tumor effect and pharmacokinetics (PK). “Dose-finding phase”: each patient was submitted to a single-ascending dose of Redaporfin, administered by iv infusion, lasting 10-20 minutes, in ≥ 21 days interval; drug was titrated up to a dose that, in combination with a laser light of 50 J/cm 2 at 749±3 nm, was safe and caused tumor necrosis (“effective dose”) in a spot of 1.0 cm of diameter of tumor surface. “Final PDT session”: all accessible tumor was treated with the individual effective dose. Results: Thirteen pts (10 men, 3 women; median age 62 yrs; range 35-80) with advanced HNC in symptomatic treatment were submitted to Redaporfin doses: 0.05 mg/kg (n = 6), 0.1 mg/kg (n = 4), 0.25 mg/kg (n = 2), 0.5 mg/kg (n = 4), 0.75 mg/kg (n = 6) and 1.0 mg (n = 1). Treatment-related adverse events (TRAE): 2 pts had grade (G) 3 photosensitivity reaction (PR) after accidental exposure to intense sun-light (0.75 mg/Kg dose); G≤2 TRAEs in 7 pts (G2 infusion-related reactions in 2 pts and PR in 2 pts). Photodynamic effect was observed in all subjects at doses ≥ 0.5 mg/kg and was dose-dependent; 0.75 mg/kg dose caused necrosis in 1 cm diameter target spot deeper than 5 mm. The patient submitted to final PDT session achieved complete tumor necrosis of treated area. PK showed to be linear; drug was eliminated from the body in a relatively fast manner (half-life of 19 hrs following Redaporfin 0.75mg/Kg). Reported data allowed to conclude phase I part of the trial; next steps of clinical development were authorized. Conclusions: Redaporfin effective dose was established at 0.75 mg/Kg. PDT with Redaporfin revealed anti-tumor effect and was safe in patients with advanced HNC. Further research with this promising compound is ongoing. Clinical trial information: NCT02070432.
A proportional comparison of cancer burden and patient advocacy organization (PAO) funding by histology demonstrates many underfunded histologies.
Authors: Suneel Deepak Kamath, Sheetal Mehta Kircher, Al Bowen Benson
Journal: Journal of Clinical Oncology (2018)

6606 Background: PAOs in oncology are vital in funding research for rare cancers, young investigators and innovative projects, but some histologies may be underfunded relative to their burden. This study examined the alignment of cancer burden by histology with PAO funding for each histology to raise awareness of areas of unmet need. Methods: The GuideStar database was used to find all cancer PAOs with > $5 million (M) in annual revenue (AR) using NTEE codes and 165 cancer-related search terms. Care delivery PAOs were excluded. PAOs were classified by the histology they support. AR was obtained from IRS Form 990s for each PAO. Total annual revenue (TAR) per histology was calculated by adding ARs for each PAO in that histology. Cancer burden based on annual incidence, deaths and person-years of life lost (PYLL) was obtained from SEER data. Comparison of TAR with incidence, deaths and PYLL of each histology was done using descriptive statistics. Results: 125 PAOs with TAR of $6.4 billion were included. 64 (51%) were histology agnostic. Cancers with the most PAOs were pediatric (14, 11%), breast (13, 10%), leukemia (4, 3%) and lung (4, 3%). There were no PAOs with AR > $5 M for esophageal, gastric, kidney or bladder cancers. Histology-agnostic PAOs had $5 billion (78%) of TAR. Cancers with largest TARs were breast ($460M, 7%), pediatric ($207M, 3%), leukemia ($201M, 3%) and lymphoma ($145M, 2%). The ratios of TAR by histology vs. incidence, deaths and PYLL are shown in Table 1. PAOs in pediatric cancer, breast cancer, leukemia and lymphoma had the highest ratios in all 3 metrics. Colon, liver and uterine cancer PAOs had the lowest ratios. Conclusions: Cancer PAOs generate substantial AR that complements government research funding. Cancer PAOs overall can be better funded, especially PAOs in GI, GU and gynecologic cancers to drive research and awareness. Breast Colon Uterine Leukemia Liver Lymphoma Lung Melanoma Ovary Pancreas Pediatric Prostate TAR (millions $) 460 18 5 201 6 145 92 14 23 58 207 76 TAR/Incidence ($) 1804 133 87 3241 115 1802 412 160 1012 1087 13,586 472 TAR/Deaths ($) 11,207 359 490 8219 185 6840 588 1433 1614 1354 115,901 2847 TAR/PYLL ($) 595 23 33 547 15 476 39 87 91 100 2255 278
Physicians’ documented performance of shared decision-making with chronic lymphocytic leukemia patients.
Authors: Anthony R. Mato, Matthew Steven Davids, Jeffrey D Carter, Laurence Greene, Tamar Sapir
Journal: Journal of Clinical Oncology (2018)

e18786 Background: With expanding treatment options for chronic lymphocytic leukemia (CLL), shared decision-making (SDM) is essential for high-quality care. In a quality improvement program, we evaluated physicians’ chart-documented performance of key SDM practices with CLL patients. Methods: Participants were 15 oncologists in 2 community health systems. In 150 consecutive charts of CLL patients, we used directed content analysis of progress notes to assess performance rates for 6 SDM subskills adapted from validated instruments. Chi-square tests were performed to compare frequencies of documented SDM practices for patients grouped by age ( < 65 vs ≥65 years), sex, B symptoms ( < 2 vs ≥2), comorbidities ( < 2 vs ≥2), and stage (Rai 0-4). Results: Patients’ median age was 73 years, 47% were female, and 64% had received CLL treatment. For the 6 SDM practices, documented physician performance ranged from 46% to 69% (Table). For a small number of SDM practices, significantly higher rates were observed for males vs females and for patients with more B symptoms. No patient factors, including age and disease or treatment status, consistently distinguished documented SDM practices. Conclusions: These findings apply to identifying areas for improvement in performing and documenting SDM practices for CLL patients. The findings may also inform initiatives for adapting electronic medical records to add structured fields for SDM. Table. Documented Performance of SDM Practices SDM Practice % Documented Charts (n = 150) Provide patient/caregiver with treatment options 58 Explain treatment benefits and risks 59 Check for understanding of options 61 Explore patient/caregiver concerns and fears 69 Solicit questions about options 68 Arrange to review treatment decisions 46 SDM Practice by Sex Provide patient/caregiver with treatment options Males: 66% Females: 49% p= .04 Arrange to review treatment decision Males: 52% Females: 38% P <.01 SDM Practice by # of B Symptoms Provide patient/caregiver with treatment options ≥2: 65% < 2: 49% p= .05 Explain treatment benefits and risks ≥2: 67% < 2: 49% p= .02