tbuckley/cabot-search huggingface dataset:
The rates of ABO, Rh, and Kell antigens in children with cancer.
Authors: Andrey A. Maslov, Nailya Guskova, Ekaterina Guskova, Kristina Avanesova, Svetlana V. Belgova, Ekaterina Gornostaeva, Irina V. Tselishcheva, Viktoria Zakharchenko, Izabella Torpudzhyan, Aliya K. Donskaya, Marina A. Gusareva, Svetlana V. Abakumova, Nadezhda Golomeeva, Anastasia Nozdricheva
Journal: Journal of Clinical Oncology (2017)

e22007 Background: The purpose of the study was to analyze phenotypic characteristics of red blood cells by the AVBO, Rh and Kell systems in children with cancer. Methods: ABO and Rh blood groups were determined and erythrocyte antigens (D, С, с, С w , Е, е, К, k) were typed (AutoVue Innova, USA) in blood samples of 114 children with solid tumors. Results: ABO blood groups distribution was as follows: A(II) &gt; O(I) &gt; B(III) &gt; AB(IV) with A(II) prevalence. Rh(D)-positive phenotype was observed in 82 (71.9%) patients of 114: 47 (57.3%) boys and 35 (42.6%) girls. 32 (28.1%) patients of 114 were Rh(D)-negative: 15 (46.8%) boys and 17 (53.1%) girls. Only 8 (7%) children were Kell-positive, which was similar to the antigen prevalence in European population. 4 erythrocyte phenotypes were the most frequent in Rh(D)-positive patients: СсDееK− (34.1%), ССDееK− (22.0%), ccDEeK− (13.4%) and СсDЕеK− (11.0%). I.e., more than a half of children with oncopathologies (56.1%) had Kell-negative phenotypes, СсDееK− and ССDееK−. 86.4% of Rh(D)-positive patients had homozygous combinations of Rhesus antigens causing transfusion reactions - СС, сc, ЕЕ and ее. 18 (22.0%) of Rh(D)-positive patients were homozygous for the C antigen and 64 (78.0%), i.e. every third patient, had the c antigen. Children with the C antigen may be sensitized to the c antigen through blood transfusion with subsequent development of hemolytic complications. The K (Cellano) antigen was found in all children, and 93% of them had kk phenotype and 7% - Kk. The С w (Willis) antigen was revealed only in 5 (6.0%) Rh(D)-positive patients with rare phenotypes - C w CceeK-, C w ccEeK-, C w CcEEK-, C w CcEeK-. Matching a donor for patients with one of these phenotypes could pose a problem. Conclusions: Studying phenotypic characteristics of red blood cells is necessary for providing a successful blood transfusion, especially in children Kell-positive for the K antigen, in children homozygous for the C antigen with ССDееК- phenotype and in children with the С w antigen and С w СсееК-, С w ссЕеК-, С w СсЕЕК- and С w СсЕеК- phenotypes.
Comparative efficacy and acceptability of first-line single-agent chemotherapy in metastatic breast cancer.
Authors: Ying Wang, Yunfang Yu, Qiyun Ou, Quanlong Gao, Tuping Fu, Dagui Lin, Herui Yao
Journal: Journal of Clinical Oncology (2018)

e13082 Background: The relative clinical outcomes associated with recommended first-line single-agent chemotherapy in metastatic breast cancer (MBC) is not clearly established. We aimed to comprehensively investigate the efficacy and safety of first-line single-agent chemotherapy in MBC patients. Methods: We searched for randomized clinical trials (RCTs) investigating randomized controlled trials (RCTs) that compared single-agent chemotherapy drugs containing: capecitabine, carboplatin, docetaxel, doxorubicin, epirubicin, gemcitabine, ixabepilone, liposomal-doxorubicin, mitozantrone, nanoparticle albumin-bound paclitaxel, paclitaxel or vinorelbine in MBC. Efficacy and toxicity were integrated by network meta-analyses. The PROSPERO registry number is CRD42018081185. Results: A total of 4,068 patients from 16 RCTs were included. Combining direct and indirect effects showed that different monotherapy regimens shared equivalent effect on overall survival and progression-free survival. However, compared with gemcitabine, doxorubicin (relative risk [RR] 2.8, 95% confidence interval [CI] 1.2 to 6.6), epirubicin (RR 2.5, 95% CI 1.2 to 5.1), nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (RR 3.6, 95% CI 1.2 to 11.0) achieved with higher overall response rate (ORR). The nab-paclitaxel showed increased ORR versus paclitaxel (RR 2.0, 95% CI 1.1 to 3.7). Patients treated with doxorubicin had significantly superior ORR than those treated with mitozantrone (RR 2.0, 95% CI 1.1 to 4.0). In grade 3 to 4 toxicity, increased nausea/vomiting was found for capecitabine. Alopecia was found higher in anthracyclines, but lower in liposomal-doxorubicin. Nab-paclitaxel has the lower odds of diarrhea, and lower odds of stomatitis was found for mitozantrone. Conclusions: This study indicated that there was no significant survival difference of first-line single-agent chemotherapy drugs in MBC, although significant difference was found in ORR. We should consider the balance between response rate, survival and acceptability of single-agent chemotherapy during the clinical practice.
Baseline characteristics in the international, open-label, early-access program of trifluridine/tipiracil in previously treated metastatic colorectal cancer (phase IIIb).
Authors: Timothy Jay Price, Julien Taieb, Alfredo Falcone, Jean Francois Seitz, Lucjan Wyrwicz, Martin Becquart, Shanti Moreno, Nadjat Mounedji, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2018)

761 Background: In the phase 3 RECOURSE trial, trifluridine/tipiracil (FTD/TPI, also known as TAS-102) significantly improved overall and progression-free survival versus placebo in patients (pts) with metastatic colorectal cancer (mCRC) progressing after all available standard therapies (Mayer et al. N Engl J Med 2015;372:1909-19). FTD/TPI is approved after regorafenib in the same setting for management of previously treated mCRC patients. A phase 3b early-access program (EAP) is ongoing to provide access to FTD/TPI for mCRC pts with similar eligibility criteria to assess safety profiles in real-world setting (EudraCT Number: 2016‐002311‐18). First pt was enrolled in Oct 2016. We describe the characteristics of pts included up to 7 March 2017. Methods: Eligible pts had histologically confirmed mCRC previously treated with, or not considered candidates for, available therapies. Other inclusion criteria include Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1. Pts planned to receive FTD/TPI (35 mg/m2 bid) orally on days 1–5 and 8–12 of each 28-day cycle. Results: A total of 298 pts from 7 countries had received at least 1 dose of treatment. Median age was 65 years (range 28–87); 65% were male; 98% were Caucasian (n = 264 out of 269). Among 271 pts, 40% and 60% had respectively ECOG PS 0 and 1 at baseline except 1 pt with PS 2. Primary site of disease was colon (55%, of which 27% right-sided and 61% left-sided); 33% have rectum as primary site; and not specified in 12%,52% had synchronous disease at diagnosis. Median time from initial diagnosis was 37 months (range 6–302) and from first metastasis was 32 months (range 1–180). 59% had RAS mutation (n = 164 out of 279). More than 95% received fluoropyrimidine and/or oxaliplatin and/or irinotecan, while 82%, 39% and 37% received anti-VEGF, anti-EGFR and regorafenib prior to study enroll, respectively. Conclusions: Analysis of the baseline characteristics shows a heavily pretreated mCRC population still seeking additional anti-cancer therapy. Optimal treatment sequencing in 3rd line is not yet established. Preliminary safety and efficacy results are anticipated in 2018. Clinical trial information: 2016-002311-18.
Efficiency and toxicity of mifamurtid in childhood osteosarcoma.
Authors: Nurdan Tacyildiz, Sonay incesoy Ozdemir, Emel Cabi Unal, Handan Dincaslan, Gulsan Yavuz, Fikret Asarcikli, Gulsah Tanyildiz, Yusuf Yildiz
Journal: Journal of Clinical Oncology (2017)

e22010 Background: There are only few data concerning efficiency and toxicity of mifamurtide in children with osteosarcoma (OS). The aim of this study was to evaluate efficiency and side effects of mifamurtide in childhood OS. Methods: We retrospectively analyzed the data of 18 patients with OS and who received mifamurtide between January 2012 and December 2016. Four hundred seventy seven doses of 2 mg/m 2 intravenous mifamurtide, along with paracetamol premedication were given in 15 patients with primary non-metastatic OS after complete surgical resection and 3 patients with progressive OS. Results: There were 11 males and 7 females, and the median age was 14 years (ranged, 9-18). The median follow-up time was 20 months (ranged, 7-51). The metaphyseal plates around the knee was the most frequent disease location with 94.4%. The median necrosis percentage was 94 (range, 35-100). All patients received Euromos protocol. The most common side effects were chills and fever (17/18). These reactions were observed in 4 patients during every administration, in only one patient at last administration and in the remaining 12 patients during first or first two administration. Headache, myalgia and arthralgia were observed in 2 patients during every infusion. In another one case, headache was observed during only first two infusions and he also hearing loss was developed (could be related CisPlatin) Back pain was observed in two patient during first infusion but one them suffered with severe back pain after few doses and stoped Mifamurtid. . Grade 3-4 neutropenia, trombocytopenia, abnormal liver enzymes and abnormal BUN and creatinin levels were not observed in patients who received mifamurtide alone after completion of chemotherapy. Of the 15 patients with primary non-metastatic OS treated with the addition of mifamurtide to chemotherapy, 13 showed complet remission for median 24 months (ranged,16-36) and 2 patients are still under treatment with complet remission. Of the 3 patients with progressive disease, 2 died and 1 had progressive disease for 51 months. Conclusions: Mifamurtide therapy is safe and well tolerated in childhood OS. Chills and fever were the major side effects, These events were transient and often no longer observed in subsequent administrations.
Association of high tumor mutation (TMB) with DNA damage repair (DDR) alterations and better prognosis in ovarian cancer.
Authors: Wenjuan Tian, Boer Shan, Yuzi Zhang, Yulan Ren, Shanhui Liang, Jing Zhao, Xiaochen Zhao, Dongxian Peng, Shangli Cai, Huaying Wang
Journal: Journal of Clinical Oncology (2018)

5512 Background: Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased tumor mutation burden (TMB) in multiple types of cancers. But the prognostic value of TMB and association between DDR and TMB in ovarian cancer is still unclear. Methods: Whole-exome sequencing data of 434 ovarian tumors from The Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 93 ovarian tumors from 3D Medicines were analyzed to explore the association between 21 cancer-related DDR genes and TMB, defined as number of somatic non-synonymous mutations. We also performed analysis of clinical data from TCGA to identify the impact of TMB on ovarian cancer prognosis. Results: 27.4% of ovarian tumors in TCGA and 40.9% in 3D Med harbored at least one DDR alteration. The most frequently mutated genes were POLE (21%), BRCA1 (5.1%), BRCA2 (4.1%), ATM (3.0%), FANCA (2.5%), PALB2 (2.3%), FANCD2 (2.1%), and ATR (2.1%) in TCGA, and BRCA1 (12.9%), BRCA2 (10.8%), ATM (5.4%), RAD51 (3.2%), BRIP1 (3.2%), FANCD2 (3.2%), and PALB2 (3.2%) in 3D Med. Any DDR alteration was significantly associated with higher TMB in both TCGA (P < 0.00) and 3D Med (P = 0.021). Any two DDR gene alterations were associated with even much higher degree of TMB in both TCGA (P < 0.00) and 3D Med (P = 0.03) compared with DDR wild type. Co-mutated TP53 and any DDR significantly associated with higher TMB in both TCGA (P < 0.00) and 3D Med (P = 0.02). Prognosis analysis was performed on patients from TCGA. High TMB (cut off as median) was associated with significantly longer DFS (16.4m vs. 14.1m, HR 0.83, P = 0.04) and OS (41.0m vs. 32.1m, HR 0.77, P < 0.00). Moreover, median PFS for patients with and without DDR alterations was 19.2m and 16.7m (P = 0.07). Median OS was 54.6m and 41.5m respectively (P = 0.02). Conclusions: DDR deficiency is prevalent in ovarian cancer and associated with higher TMB. High TMB was associated with more favorable DFS and OS in ovarian cancer patients. Our results suggest that DDR gene alterations may correlated with anti-tumor immunity in forms of increased TMB, which is known to increase the neoantigen load of tumors. This may assist with the selection of ovarian cancer patients likely to benefit from immunotherapy.
Abstract 16723: Rates of Interventions Post Coarctation Repair in Neonates Versus Infants: Does Age Matter?
Authors: Rinske IJsselhof, Hua Liu, Frank Pigula, John Mayer, Pedro del Nido, Meena Nathan
Journal: Circulation (2016)

Introduction: Conflicting reports exist about the timing of coarctation (CoA) repair and rate of subsequent interventions on the CoA site and other left sided structures (LSS). Hypothesis: There wi...
P01.164 Cognitive and neuropsychological outcome after awake surgery for left frontal and left temporal tumor resection
Authors: F Kilinc, A Noack, I Lortz, V Seifert, M Behrens, M Forster
Journal: Neuro-Oncology (2018)

Surgery of brain tumors aims, in general, at complete tumor resection. However, persuing this aim, neuropsychological deficits cannot be considered all the time. Due to its importance regarding quality of life and further professional ability, we analysed the influence of left frontal and left temporal brain tumor surgery on patients′ neuro-cognitive performance. Neuropsychological evaluation was performed pre-operatively in 33 patients who underwent awake surgery for brain tumors in the left inferior frontal gyrus (IFG), the left anterior frontal lobe (ATL) or the left supramarginal gyrus (SMG). Twelve of these patients underwent additional postoperative neuropsychological examination. Evaluation focused on aspects of language, attention, execution as well as working, verbal and visual memory. Results were analysed descriptive. While first testing was carried out in all patients within 1 month before awake surgery, postoperative evaluation was realized in 12 patients 6.47 ± 3.07 months after surgery. Defining test performances within the 25th and the 75th percentile as normal, patients with tumors involving the IFG or SMG showed unimpaired. However, in patients suffering from lesions involving the ATL, reduced verbal memory and impaired interference ability was noted preoperatively, recovering to normal after surgery. Thus, removal by awake surgery of lesions involving the IFG, SMG or ATL did not result in long-term neuropsychological impairments. Our results underline the importance of considering cognitive outcome by evaluating neuropsychological deficits in brain tumor patients.
Pancreatic exocrine insufficiency (PEI) secondary to chronic use of long-acting (LA) somatostatin analogues (SSA) in pts with neuroendocrine tumors (NETs): Pooled analysis (USA and UK).
Authors: Wasif M. Saif, Angela Lamarca, Valerie Relias, Melissa H Smith, Jorge Barriuso, Christina Nuttall, Alicia Romano, Lynne McCallum, Wasat Mansoor, Mairead Geraldine McNamara, Richard Hubner, Juan W. Valle
Journal: Journal of Clinical Oncology (2018)

e16166 Background: SSAs are the most common treatment for well-differentiated NETs. Side effects include biliary and GI disorders, injection-site pain and hyperglycemia. There is often misdiagnosis or delayed diagnosis of PEI pts receiving SSAs, as confused with disease progression or SSA failure. This is the largest study to describe the incidence of PEI secondary to SAAs in NET. Methods: A total 160 pts treated with SSAs for NETs were identified. Data including demographics, pathology, stage, pharmacy records (dose/duration of long and short-acting SSAs, use of antidiarrheal, pancreatic enzyme replacement therapy (PERT), proton pump inhibitors (PPI) or H2-Receptor antagonist (H2RA) was collected. Laboratory data include chromogranin A (CgA), 5-HIAA in urine (110) and serum (50), quantitative fecal fat test (QFFT) or fecal elastase (FE-1). PEI was defined by a FE-1 below 200 μg/g or QFFT > 21gm/72hr. Results: Of 160 pts, 134 received Octreotide and 26 Lanreotide. Of these, 23 also received short-acting SSA for worsening diarrhea, 96 had intensification of antidiarrheals and 1 got telotristat. A nutritionist and/or gastroenterologist evaluated 79 pts. In pts with worsening diarrhea despite stable or improved CgA/5-HIAA, QFFT was performed in 47 pts and FE-1 in 50 pts. FE-1 confirmed PEI in 8, QFFT in 19, 27 based on clinical diagnosis, and 16 had sample error or refusal. CTCAE v4.0 grades (G) of PEI in these pts were: G2 (69%), G3 (22%) and G4 (9%). Median time to development of PEI was 12 months (range 3 - 32). Except 1 pt (religious), 53 received PERT either with concomitant PPI (50) and 2 H2RA. Response was evaluable in 110 pts; 78% had PEI improved within 4-8 weeks. 2 pts were non-compliant and another 3 had motility disorders. Conclusions: SSA-induced PEI occurs in 34% of pts. This is the largest study addressing this under-diagnosed but relevant complication of SSAs. SSAs may inhibit secretion and release of amylase, trypsin, lipase, secretin, CCK, motilin, bile acid leading to PEI. Clinicians should actively identify and treat this toxicity to improve diarrhea and weight loss in these pts.
Prognostic value of cell-free DNA in patients with oropharyngeal cancers.
Authors: Julia Beck, Margret Rave-Fraenk, Kirsten Bornemann-Kolatzki, Markus Schirmer, Michael Oellerich, Howard Urnovitz, Ekkehard SchÃ¼tz, Martin Canis
Journal: Journal of Clinical Oncology (2016)

e17511 Background: Tumor derived plasma cell-free DNA (TcfDNA) is described as biomarker to monitor tumor burden in cancer. Large somatic genome aberrations are hallmarks of malignancies and detectable in cfDNA. However, levels of TcfDNA are variable according to cancer types. We obtained copy-number instability (CNI) scores of cfDNA in treatment-naïve head and neck cancers before and after therapy. Methods: In a blinded study, plasma cfDNA from 21 cancer (13 hypopharyngeal, 8 laryngeal) patients were investigated before therapy (3 surgery alone and 18 followed by platinum-based chemoradiotherapy with total radiation doses of 64Gy) together with 4 non-malignant controls. Samples during treatment were obtained for five patients. Plasma cfDNA was subjected to whole genome sequencing (Illumina NextSeq500). Copy-numbers in 5.5Mbp (HG19) windows with coverage of 24,000-fold per bin were transformed into log2 ratios and converted into Z-values vs. a reference population. Values reaching the critical distance to zero were used to calculate a general CNI-score. Results: CNIs above the 97.5thpercentile (Score: 30) of the reference population were detected in 18 (Score: 41-3880) of 21 pre-surgical samples and none in the benign run controls. Significant differences in CNIs were detected, stratified by nodal stages < N2 (mean: 172, SE: 70, n = 7) versus ≥ N2 (mean: 882, SE: 362, n = 12, p = 0.05). In contrast, no significant differences were observed for primary tumor stage ( ≤ T2 vs. > T2). Rapid decreases of CNIs immediately after surgery were seen in 5|5 patients with close follow-up to 10% of baseline values. One patient, not falling below 30 after surgery with subsequently rising CNIs was suffering a relapse thereafter. Complete remission of one tumor (initial CNI = 41) was reflected by a CNI of ≤ 6 after surgery and during 3 months follow-up. Conclusions: Even small sized head and neck tumors are detectable by cfDNA analyses if nodal stages are higher, therefore CNI-scores also might be of prognostic value. If CNIs stay elevated or rise during follow up, a relapse must be suspected. Overall cfDNA shows an unexpectedly high sensitivity in such cancers and might be a valuable addition to patient risk stratification and monitoring.
Metastatic colorectal cancer (mCRC) and micro-satellite instability.
Authors: Timothy Jay Price, Christos Stelios Karapetis, Joanne Young, Cynthia Piantadosi, Amitesh Chandra Roy, Rob Padbury, Guy Maddern, David Roder, Amanda Rose Townsend
Journal: Journal of Clinical Oncology (2018)

e15510 Background: Microsatellite instability (MSI) has been associated with better survival outcomes in early stage CRC. In mCRC MSI is a smaller subgroup (3-5%). There is evolving evidence that treatment pathways should include anti-PD-1 antibodies. We undertook an analysis to explore the relevance of MSI status. Methods: SA mCRC registry data were analysed to assess patient characteristics and survival outcomes comparing patients with MSI or microsatellite stable (MSS) disease. K-M survival analysis was used to assess OS. Cox-regression analysis was undertaken to assess prognostic factors Results: Of 4359 patients registered on the data base, 598 (14%) had been tested and 62 (10.1%) of these patients had demonstrable MSI. Patient characteristics and outcomes are summarized in table. There are statistically higher rates of right sided primary, poorly differentiated pathology and BRAF mutation in MSI group associated with a trend to reduced survival. Chemotherapy and biological received MSI v MSS was as follows; 5FU 31% v 25%, 5FU/irinotecan 17% v 12%, 5FU/oxaliplatin 52% v 58%, bevacizumab 31% v 42%, anti-EGFR 0 v 4.6%. Independent predictors of survival were chemotherapy and BRAF mutation, but not MSI. Conclusions: The patient characteristics of MSI mCRC are in keeping with those previously reported although potential biases inherent in the selection of patients for MSI testing may have exaggerated the MSI rate. MSI in this population based registry is associated with lower survival although it is not statistically an independent prognostic factor. The number of patients with MSI/MSS status available will likely increase over time, and an updated analysis is planned. MSI N = 62 MSS N = 536 p-value Median Age (years) 69.1 (range 27-95) 63.9 (20-93) 0.028 Female gender 48% 39% 0.17 Synchronous 56.5% 66% 0.14 Right side primary 59.7% 29.3% < 0.001 Histology poorly differentiated 50% 31% 0.002 KRAS MT 20% 38% 0.1 BRAF MT 42% 11% < 0.001 Chemotherapy Ø 2 lines 46% 17% 73.4% 30% < 0.001 Liver surgery 11.2% 18.5% 0.16 mOS all (months) 9.5 (95% CI 2.1-16.8) 21.3 (95% CI 23.0-29.2 0.052 3 year 18% 23% 0.35 mOS chemotherapy (months) 16.3 (95% CI 0.0-33.0) 26 (95% CI 23.0-29.2) 0.39