tbuckley/cabot-search huggingface dataset:
P01.079 Determining the content validity of measures of basic and instrumental activities of daily living (ADL) in patients with brain tumours, a systematic review.
Authors: Q Oort, M Taphoorn, S Sikkes, B Uitdehaag, J Reijneveld, L Dirven
Journal: Neuro-Oncology (2018)

Brain tumour patients may experience impairments in everyday functioning due to both physical and cognitive symptoms. Measures of everyday functioning may therefore be relevant for brain tumour patients in both clinical trials and practice. Everyday functioning can be assessed using activity of daily living (ADL) outcome measures. There are two categories of ADL: basic activities of daily living (BADL; e.g. washing and dressing) and instrumental activities of daily living (IADL; e.g. shopping or cooking). The aim of this systematic review was to identify outcome measures containing items on BADL and/or IADL that currently are used in studies with brain tumour patients, and to assess the content validity of these instruments. Several electronic databases (i.e. PubMed, Embase, Cochrane, PsycINFO and CINAHL) were searched up to April 2017 to identify studies with brain tumour patients that used outcome measures with ADL items. Articles were selected based on predetermined in- and exclusion criteria. The literature search identified 31 unique outcome measures containing items on BADL and/or IADL. There were 22 (71%) outcome measures containing BADL items and 29 (94%) outcome measures containing IADL items. More than half (65%) of the outcome measures contained both BADL and IADL items. The number of BADL items in each questionnaire ranged from 0% to 83%, and from 0% to 100% for IADL items. Only two outcome measures were specifically developed to measure BADL (Barthel Index and Katz-ADL), and two specifically for IADL (Lawton-Brody IADL and preliminary IADL-brain tumour). However, these instruments have not (yet) been validated in brain tumour patients. Currently, there is a lack of suitable options to sufficiently measure BADL and/or IADL in brain tumour patients. Validation of currently existing BADL and IADL measures in brain tumor patients seems necessary, or the development of new tools.
Hepatic injury after treatment for childhood cancer: A report from the St. Jude Lifetime Cohort study.
Authors: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Deokumar Srivastava, Mary V. Relling, Carrie R Howell, Kirsten K. Ness, Sue C. Kaste, William Greene, Israel Fernandez-Pineda, Ching-Hon Pui, Sima Jeha, Michael William Bishop, Wayne Lee Furman, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2017)

10567 Background: We assessed hepatic injury (HI) in a large cohort of childhood cancer survivors (CCS). Methods: We measured aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 2751 SJLIFE CCS ( &gt; 10 years (yrs) post-diagnosis, age ≥18 yrs), and graded using the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Multivariable log binomial regression was used to estimate associations between demographic and clinical factors and grades 1–4 ALT and AST. Variables with a p &lt; 0.1 were examined in multivariable models. Results: 1339 (48.7%) CCS were female. 2271 (82.6%) were non-Hispanic white (NHW). Median age at diagnosis - 7.4 yrs, median age at evaluation - 31.4 yrs, and median time from diagnosis to evaluation - 23.2 yrs. 177 (6.4%) had grades 1-4 AST (grade 1 = 164, grade 2 = 9, grade 3 = 4), and 421 (15.3%) had grades 1-4 ALT (grade 1 = 394, grade 2 = 18, grade 3 = 8). The multivariable results are shown in the table below. Conclusions: Male gender, obesity, hepatitis C virus infection, and treatment with busulfan are risk factors for increased AST and ALT. V10 is an additional risk factor for increased ALT. These results may guide future treatment designs and lifestyle interventions. [Table: see text]
Abstract 20134: Can Cryoballoon Ablation Isolate the Left Atrial Posterior Wall Including the Pulmonary Veins for Paroxysmal Atrial Fibrillation?
Authors: Yoshimasa Murakami
Journal: Circulation (2016)

Introduction: Pulmonary vein (PV) isolation with cryoballoon ablation (CRA) has been introduced and proven useful for curing atrial fibrillation (AF). Isolating the left atrial posterior wall (LAPW...
Effect of expanded genomic testing in lung adenocarcinoma (LUCA) on survival benefit: The Lung Cancer Mutation Consortium II (LCMC II) experience.
Authors: Dara Aisner, Lynette M. Sholl, Lynne D Berry, Eric B. Haura, Suresh S. Ramalingam, Bonnie S. Glisson, Mark A. Socinski, Saiama Naheed Waqar, Edward B. Garon, Jeremy Paul Cetnar, Katerina A Politi, Joan Schiller, Michael R. Rossi, Heidi Chen, John D. Minna, Ignacio Ivan Wistuba, Bruce E. Johnson, Mark G. Kris, Paul A. Bunn, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2016)

11510 Background: EGFR mutation (MT) and ALK rearrangement (RR) testing is standard of care for advanced stage LUCA due to effective targeted therapies. Testing for additional driver alterations in LUCA is not yet accepted as standard of care. We sought to examine the frequency and clinical impact of testing a broader set of alterations in a multi-institutional setting. Methods: 16 institutions participated in LCMC II. Enrollment required stage IV, centrally confirmed LUCA; PS 0-2; available tumor tissue, and consent. 1315 patients (pts) were enrolled between May 2012 and November 2015. All testing was performed in CLIA certified laboratories with a minimum panel of 97 alleles in 8 genes (AKT1, BRAF, EGFR, ERBB2, KRAS, MEK1, NRAS, PIK3CA), plus evaluation for ALK, ROS1, RET RRs and MET amplification (AMP), and MET and PTEN expression (EXP) by IHC. 12 sites utilized next generation sequencing (NGS) for analysis of all or some cases, and additional mutational data, including for TP53 and PTEN, was provided as available. Therapies were provided as standard of care and via clinical trials. Results: 980 pts were eligible and molecular data was obtained from 919 eligible pts (94%). 529 (53.9%) had genetic alteration(s) detected: EGFR (16%), KRAS (27%), ALK (4%), ROS1 (2%), RET (2%), BRAF (4%) ERBB2 (2%), and MET AMP by FISH or NGS (5%), with co-occurring drivers (most commonly MET AMP) in 2%. MET EXP and PTEN loss by IHC was observed in 59% and 15% of cases, respectively. 127 pts received targeted therapies. A 'targetable' cohort consisting of alterations in EGFR/BRAF(V600E)/ERBB2/ALK/ROS1/RET/MET and with clinical follow-up (n=187) showed a survival benefit when targeted therapy was used (n=113) versus not (n=74) (median survival 2.8 vs. 1.5 years, p=0.039). One or more alterations in TP53, PIK3CA, and/or PTENwere identified in a subset of tumors from the targeted cohort (complete data available on 78, of which 29 (37%) were positive), which showed a trend as a negative prognostic factor, with further analysis of these and other genes, including IHC analysis, ongoing. Conclusions: Expanded tumor mutational analysis combined with targeted therapy in LUCA provides potential for patient benefit.
A phase I/II study of fosbretabulin in combination with everolimus in neuroendocrine tumors that have progressed after at least one prior regimen for metastatic disease.
Authors: Aman Chauhan, Susanne Arnold, Stacey A. Slone, Heather Flynn, Heidi Weiss, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2018)

TPS4148 Background: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are rare tumors. Recent SEER database analysis shows consistent surge in the incidence of GEPNETs. Due to indolent nature of GEPNETs the prevalence of disease far exceeds the incidence. Treatment options for metastatic progressive neuroendocrine tumors are expanding. Fosbretabulin is a synthetic, water-soluble, phosphorylated prodrug of the natural product Combretastatin A4 (CA4P), which was originally isolated from the bark of the South African bush willow, Combretum caffrum. Fosbretabulin is the lead compound in a class of agents termed vascular disrupting agents (VDAs) and has shown activity as single agent in ovarian cancers and GEPNETs. Rationale: The vasoconstrictive effect of fosbretabulin is potent, though short-lived (4-8 hours), with no cumulative adverse effect. Everolimus inhibits angiogenesis, slows tumor growth and has a prolonged half-life (30 hours). Combining these two agents with distinctly different mechanisms of action may improve tumor control without additional toxicities, and has the potential of reducing drug resistance. Methods: This is an investigator initiated, single center, open label, phase I/II study involving gastroenteropancreatic neuroendocrine tumors, consisting of a dose escalation Part A followed by an expansion cohort Part B. Primary Objective is to establish the maximum tolerated dose of the combination of everolimus and fosbretabulin in neuroendocrine tumors that have progressed after at least one prior regimen for metastatic disease. Secondary Objectives include evaluation of safety profile of the combination and to observe and record anti-tumor activity. Patients will be treated with daily oral everolimus. Fosbretabulin will be administered IV either q3 weekly or q weekly based on partial order continuous reassessment model (PO CRM). Clinical trial information: NCT03014297.
A phase II study of subcutaneous bevacizumab for recurrent glioblastoma: Roadblocks and promises.
Authors: Joseph Quillin, William L. Read
Journal: Journal of Clinical Oncology (2018)

e14089 Background: Bevacizumab is a VEGF inhibitor currently utilized in its intravenous formulation to treat recurrent glioblastoma. Bevacizumab has been demonstrated to slow tumor growth and prolong progression free survival. Monoclonal antibodies are effective in both subcutaneous (subq) and IV formulations. Providing drugs for subq self-administration, akin to insulin or heparin, not only empowers the patient to treat their disease conveniently at home, but also diminishes the burden placed upon their support system. Methods: Eligible patients had a history of high grade glioma with either radiographic tumor progression or pseudoprogression that required high dose steroid administration. Because bevacizumab is indicated in recurrent GBM, we intended to bill insurance for the drug but not for its administration, which would be done by the patient. The primary endpoint was radiographic response. Responders would continue 3 week cycles of treatment until there was progression, toxicity, or lack of benefit. Results: 3 patients were enrolled in this study over 2 years. Patient 1 demonstrated no radiographic response after 3 weeks and was then changed to IV bevacizumab, which also produced no response. Patient 2 demonstrated tumor progression at a separate region outside the initial XRT field after 3 weeks. They had simultaneous regression of contrast enhancement in the original radiation field. Both of these changes persisted after switch to IV bevacizumab. Patient 3 had a good radiographic response and was maintained on subq therapy for 23 weeks. Logistical problems were encountered in billing insurance for bevacizumab not given intravenously requiring us to take them off study despite continuing to do well. Conclusions: This is the first phase II trial of subcutaneous bevacizumab for recurrent GBM. Administration through the subcutaneous route was well-tolerated and convenient for patients. One patient had an excellent and sustained radiographic response. Unfortunately, we could not unbundle the insurance charge for drug from the charge for IV administration. This logistical challenge necessitated study closure.
Similar T-cell repertoires of tumor infiltrating lymphocytes and Crohn’s-like lymphoid reaction in colorectal cancer.
Authors: Asaf Maoz, Joel K Greenson, Marilena Melas, Ryan O Emerson, Marissa Vignali, Harlan Robins, Chenxu Qu, Stephanie Schmit, Mila Pinchev, Kevin J McDonnell, Gad Rennert, Stephen B. Gruber
Journal: Journal of Clinical Oncology (2017)

e15133 Background: Tumor infiltrating lymphocytes (TILs) and Crohn’s-like Lymphoid Reaction (CLR) are independently associated with improved survival in colorectal cancer (CRC). Whereas TILs are localized within tumors, CLR are extra-tumoral lymphocytic aggregates. The origins and relationships of the T-cell repertoire of TILs and the T cells within CLR of the colorectal cancer tumor microenvironment are unknown. Methods: Expert pathology review identified and circled areas of invasive adenocarcinoma and areas containing CLR from 13 CRC patients for macrodissection from formalin fixed paraffin embedded (FFPE) slides. DNA was extracted from matched tumor and CLR areas for multiplex PCR sequencing of the CDR3 region of the T-cell receptor beta chain (TCRβ), using the immunoSEQ platform. This approach permits 1) estimating the T-cell content of each sample, 2) measuring the clonality of the T-cell repertoire as a measure of diversity, and 3) quantifying the overlap and similarity of T-cell repertoires across samples. Results: The T-cell content (Spearman’s r s = 0.56, p = 0.046) and clonality (Spearman’s r s = 0.66, p = 0.014) were highly correlated among matched tumor and CLR samples. The ten most frequently identified TIL clones were found at similar frequencies in matched CLR enriched tissues. Comparisons of all the clones detected in tumor and matched CLR tissue demonstrated substantial similarity of these immune repertoires, with an average of 186 shared clones between samples. This degree of similarity was significantly greater than published reports of the similarity of the T-cell repertoire of colorectal tumors and adjacent normal tissue (p = 1.1e-5). Conclusions: The T-cell repertoire of CLR is highly similar to the tumor infiltrating T-cell repertoire, providing supporting evidence for the hypothesis that tumor-specific antigen presentation and lymphocyte maturation occur within CLR.
Ten years survival of differentiated thyroid cancer patients treatment without radio-iodine therapy.
Authors: Aynur Oktamovna Kenjaeva, Dauren Galimuli Adilbay, Galim Adilbayev, Damir Bekputin
Journal: Journal of Clinical Oncology (2018)

e18092 Background: Radioiodine treatment recommended by different guidelines to most of the patients with intermediate risk and all patients with high risk differentiated thyroid cancer. The objective is to analyze the outcome of thyroid cancer patient’s treatment without using radioiodine therapy independent of the risk stratification. Methods: It is a retrospective case review study of patients treated in a tertiary cancer center in Almaty, Kazakhstan in 2005-2007. Totally 155 patients included in the study with papillary and follicular thyroid cancer, without receiving radioiodine treatment. Results: Out of 155 patients, 133 were female, 21 male. Mean age was 46.7 years(standard deviation 16.2) with the youngest girl at eight and oldest patient at 79. One hundred forty-two patients have had a thyroidectomy and 12 lobectomy+isthmusectomy. Forty-nine patients along with thyroidectomy had lateral compartment neck dissection either on one side or both sides of the neck. Thirty-one deaths occurred during this 10-12 years period; all other patients are life by 10th January 2018. Overall ten years survival for all risk groups is – 80.5%. High-risk group had low levels of survival in both MSKCC and ATA risk stratification systems. Overall survival for high-risk group was from 11.1% to 21.0% depending on stratification system. Most of intermediate risk group patients did quite well even without radio-iodine therapy, ten years OS reaching 90.0%. Conclusions: This study gives additional evidence to fine-tune the indications to radioiodine therapy. Several papers are showing that a subgroup of intermediate risk patients can be treated safely with surgery alone, we believe that this approach must be studied in prospective studies.
Specific adaptive immune pattern induced by NBTXR3 exposed to radiation therapy in soft tissue sarcoma (STS) patients.
Authors: Jerome Galon, Marick Laé, Zsuzsanna Papai, Philippe Rochaix, Laszlo Csaba Mangel, Bernhard Mlecnik, Fabienne Hermitte, Zoltan Sapi, Martine Delannes, Tamas Tornoczky, Anne Vincent-Salomon, Sylvie Bonvalot
Journal: Journal of Clinical Oncology (2017)

e14615 Background: NBTXR3 are functionalized hafnium oxide nanoparticles, undergoing seven clinical trials for enhancing radiation therapy (RT). The high electron density of the nanoparticles, when exposed to radiotherapy (NBTXR3 + RT), allow absorption/deposition of a high radiation dose within the cancer cells to physically kill the cells, and possibly improve outcome. Besides, NBTXR3 + RT has shown subsequent ability to enhance immunogenic cell death and immune response in preclinics. We hypothesized that NBTXR3 + RT could trigger an enhanced immune response when compared to RT in patients with STS. Methods: Tumor tissues pre- (biopsy) and/or post-treatment (resection) were collected from patients (pts) with locally advanced STS, who received either NBTXR3 as intratumor injection and RT (14 pts) or RT (12 pts), as preoperative treatment (NCT02379845). Immunohistochemistry and Digital Pathology for immune biomarkers and for Immunoscore (CD3/CD8) were analyzed. Gene expression profiling and pre-optimized immune-gene signatures called Immunosign were also used. Results: A significant increase of T cells (CD3+, CD8+) and a marked increase of CD103+ immune cell infiltration post- vs pre-treatment were observed for NBTXR3 + RT ( P&lt; 0.01), while no differences were seen for RT. Post-treatment, an increased Immunoscore (CD3 + CD8 cell densities) was observed for NBTXR3 + RT compared to RT (P &lt; 0.07). Consistently, the up-regulation of pan immune genes expression and specifically expression of adaptive immunity genes between pre- and post-treatment, was pronounced for NBTXR3 + RT when compared to RT. Functional analysis of genes up-regulated in NBTXR3 + RT showed an enrichment of cytokine activity (IL7, IFNA, IL16, IL11, IFNG), adaptive immunity (RAG1, GZMA, TAP1, TAP2, TBX21, STAT4, IFNG, LCK, LTK, CD37, CD22) and T cell receptor signaling pathway (CD28, CTLA4, CD274, BTLA, TIGIT, CD40LG, CD5, CD3E, ZAP70). Conclusions: NBTXR3 + RT induces a specific adaptive immune pattern. As such, it may contribute to convert “cold” tumor into “hot” tumor and be effectively combined with immunotherapeutic agents across oncology. These data warrant more tissue samples evaluation to reinforce these findings.
Prognostic role of neutrophil-to-lymphocyte ratio (NLR) dynamics during first-line FOLFOXIRI in advanced pancreatic cancer (aPC).
Authors: Irene Pecora, Gianna Musettini, Silvia Catanese, Caterina Vivaldi, Giulia Pasquini, Chiara Caparello, Monica Lencioni, Alfredo Falcone, Lorenzo Fornaro, Enrico Vasile
Journal: Journal of Clinical Oncology (2017)

e15754 Background: Elevated pre-treatment NLR is a well-known poor prognostic factor in several tumours, including aPC. However, the role of NLR changes during first-line chemotherapy is less investigated. Methods: We retrospectively evaluated aPC patients (pts) treated with FOLFOXIRI (infusional 5-fluorouracil, oxaliplatin, irinotecan). NLR was calculated before the first (NLR-0) and the fourth (NLR-3) cycle, high NLR being defined as &gt; 4. We evaluated the correlation between NLR change and overall survival (OS), progression-free survival (PFS), response rate (RR) and disease-control-rate (DCR). Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Multivariate analysis was performed by Cox proportional hazards model. Results: Ninety-four pts were evaluable. Median age was 62 years; at diagnosis, 38 (40.4%) pts had unresectable stage III and 56 (59.6%) had stage IV disease. In the overall population, median PFS (mPFS) and OS (mOS) were 8.0 and 12.9 months, respectively. NLR-0 was significantly associated with poor prognosis: among the 12 pts with NLR-0 &gt; 4 mOS was 5.1 months compared with 13.5 months for the 82 pts with NLR-0 ≤4 (p &lt; 0.001). As regards NLR dynamics, NLR-3 remained high or was increased (H/I) in 5 pts (5.3%) while was stably low or decreased (L/D) in 89 pts (94.7%). mOS was 5.1 months (95%CI 0.4-9.8) in H/I and 13.5 months (95%CI 10.9-16.1) in L/D (p &lt; 0.001) pts. The same association was found for PFS, with 4.7 (95%CI 2.1-7.3) vs 8.3 months (95%CI 6.2-10.4, p = 0.004), respectively, but not for RR and DCR. At multivariate analysis, NLR change was confirmed as independent predictor of OS (HR 6.854, 95%CI 2.109-22.269, p = 0.001) and, when added to performance status, liver metastases and NLR-0, allowed a better risk stratification in good (no negative factors), intermediate (1-2 factors) and poor (3-4 factors) risk groups, with mOS of 18.0, 10.0 and 5.1 months, respectively (p = 0.012). Conclusions: Not only NLR-0, but also changes after 3 cycles of first-line FOLFOXIRI could predict OS in aPC pts. Early variations in NLR might be a cheap, reproducible and useful factor to predict prognosis and to better refine treatment strategy.
Refining the sensitivity of plasma cell-free DNA (cfDNA) genotyping by controlling for plasma tumor content.
Authors: Catherine Meador, Yuebi Hu, James Chih-Hsin Yang, Tony Mok, Gianluca Laus, Tina Hovey, Kenneth S. Thress, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2018)

9071 Background: Plasma cfDNA genotyping has been widely adopted for NSCLC diagnosis due to its convenience and high positive predictive value. However, limited assay sensitivity means negative plasma genotyping requires reflex tumor testing. We hypothesized that quantification of plasma tumor content could be used to aid interpretation of results. Methods: EGFR T790M plasma genotyping results were studied from patients (pts) with pretreated EGFR mutation-positive (EGFRm) advanced NSCLC and confirmed tumor T790M from two multicenter trials (AURA, AURA3). Quantitative plasma genotyping was performed for AURA using BEAMing (Sysmex) and for AURA3 using next-generation sequencing (NGS, Guardant) and droplet digital PCR (ddPCR, Biodesix). Using EGFR Ex19del/L858R allele frequency (driver AF) as an adequacy assessment, T790M sensitivity was studied across a range of plasma tumor content. Results: Overall T790M sensitivity from AURA was 70%, but 96% (95/99) in pts with detected driver AF > 0.5% and 39% (15/38) in pts with detected driver AF ≤0.5% (Table). In AURA3, T790M sensitivity with NGS (66%) and ddPCR (61%) increased to 97% for both methods (173/178 and 112/115) in pts with detected driver AF > 1% (Table). Combining AURA and AURA3 data (BEAMing and NGS), T790M false negative rate was 48% (54/112) with detected driver AF ≤1%, and 3% (9/265) with detected driver AF > 1%. Conclusions: In pts with pretreated EGFRm NSCLC and T790M-negative plasma genotyping, high driver AF suggests a low likelihood of missed T790M, but missed T790M is common in pts with low driver AF. While a negative plasma result should trigger reflex tumor testing, these emerging data may inform the decision to proceed with tumor biopsy, especially in high-risk pts. Investigations are planned to study whether cfDNA adequacy assessments are broadly applicable in pts with NSCLC undergoing plasma testing. Clinical trial information: NCT01802632; NCT02151981.Sensitivity Driver AF, % Negative ≤0.5 0.5 to ≤1 1 to ≤5 5 to ≤10 > 10 AURA BEAMing 111/158 (70%) 1/21 (5%) 15/38 (39%) 12/12 (100%) 23/25 (92%) 11/11 (100%) 49/51 (96%) AURA3 NGS207/ 316 (66%) 3/76 (4%) 15/39 (38%) 16/23 (70%) 54/58 (93%) 30/30 (100%) 89/90 (99%) AURA3 ddPCR 126/205 (61%) 3/48 (6%) 6/26 (23%) 5/16 (31%) 27/30 (90%) 15/15 (100%) 70/70 (100%)