tbuckley/cabot-search huggingface dataset:
Risk prediction of anthracycline-related cardiomyopathy (AC) in childhood cancer survivors (CCS): A COG-ALTE03N1 and CCSS report.
Authors: Xuexia Wang, Yanjun Chen, Lindsey Hageman, Purnima Singh, Wendy Landier, Javier G. Blanco, Douglas S. Hawkins, A. Kim Ritchey, Jill P. Ginsberg, Naomi J. Winick, Yadav Sapkota, Yutaka Yasui, Lindsay M. Morton, Gregory T. Armstrong, Kevin C. Oeffinger, Melissa M. Hudson, Eric Jessen Chow, Leslie L. Robison, Mary V. Relling, Smita Bhatia
Journal: Journal of Clinical Oncology (2019)

10015 Background: CCS treated with anthracyclines are at risk for AC. While risk increases with dose, significant inter-patient variability in AC risk suggests a role for genetic predisposition in moderating the risk and provides an opportunity to identify patients at high or low risk. Methods: We curated candidate single nucleotide polymorphisms (SNPs) associated with AC from previous publications and used these to develop a risk prediction model, drawing upon COG-ALTE03N1 (CCS with AC [155 cases] matched with CCS without AC [256 controls]). Final Model (clinical + genetic) was obtained using backward variable selection guided by effect on area under receiver operating characteristic curve (AUC). Bootstrapping corrected for optimism of AUC. Regression coefficient estimates from Final Model were used to calculate risk scores, which were used to create risk groups. We validated the model in an independent sample from CCSS (229 cases; 5,360 controls). Results: Previously-published SNPs (rs1786814 [ CELF4], rs11864374 [ ABCC1], rs1800566 [ NQO1], rs4673 [ CYBA], rs2232228 [ HAS3]) were verified in COG-ALTE03N1 and were included, along with GxE interaction of rs1786814, rs4673, rs2232228 in a Final Model containing age at cancer, sex, race, cumulative anthracyclines (mg/m 2 ), chest radiation, diabetes, hypertension, dyslipidemia. This yielded an optimism-corrected AUC = 0.8138, which was superior ( P= 0.0002) to the Clinical Model (corrected AUC = 0.7677). The sensitivity/specificity of the prediction model were 73.7%/ 81.3%. The prediction model was successfully replicated in CCSS (Final Model performed significantly better than the Clinical Model, P= 0.02). Conclusions: It is possible to identify CCS at high or low risk for AC on the basis of genetic and clinical information. This information can be used to inform interventions in CCS. [Table: see text]
Real-time detection of patient-reported outcomes (PRO) through an app: A Brazilian experience.
Authors: Alessandra Menezes Morelle, Geraldine Eltz de Lima, Nathalia D'Agustini, Fernando Castilho Venero, Carlos H. Barrios
Journal: Journal of Clinical Oncology (2019)

e23059 Background: patient-reported outcomes (PRO) data are critical for informing patient-centered care and have been shown to enhance our ability to communicate with patients and to control their symptoms. Evidence suggests that patient active participation in symptom reporting and prompt attention to management may have a positive and measurable impact in survival. However, PRO data are not commonly collected in routine cancer care due to challenges – cost, technological rigidity of existing electronic health records and misalignment of stakeholders’ incentives. Methods: in an effort to bridge the unmet needs of PRO collection and integration into routine cancer care, we developed a symptom monitoring and management system that was launched as a free mobile app in August, 2018. Tummi app is designed for reporting 28 symptoms based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Symptoms are reported in a 3-point scale (mild, moderate, severe) and patient reported an overall well-being scale represented by emojis. Tummi has the ability to record symptoms, summarize the reporting in physical printout, and automatically store and analyze the input symptoms into graphical interpretations. Results: since august 2018, 1292 patients downloaded and enjoyed the app. Of these, 240 recorded spontaneously their diagnosis. The most common side effect registered was fatigue followed by back pain. Regarding general well-being reports, male patients (25.68%) and female patients (74.32%) totaled 3771 records. Of these, on 50.22% of the time the patients were well, while in 40.17% they were average and in 9.59% they felt bad when made the report. Conclusions: there is an opportunity to better deliver our care for cancer patients, empowering them through collecting their own data. Tummi proved to be doable and understandable for patients’ language in Brazil.
Correlating the effects of VeriStrat result, anti-PD1 therapy, and neutrophil-to-lymphocyte ratio (NLR) on progression-free survival (PFS) in patients with stage IV non-small cell lung cancer (NSCLC).
Authors: Megan Randall, Sanjib Basu, Marta Batus, Jeffrey Allen Borgia, Philip D. Bonomi, Mary J. Fidler
Journal: Journal of Clinical Oncology (2019)

e20660 Background: Biodesix VeriStrat (VS) is a mass spectrometry assay found to be prognostic in previously treated and front-line NSCLC patients. A label assigns a “good” or “poor” result and is believed to in part represent host inflammatory reaction to tumor. This study looks to correlate VS good (VS-G) or poor (VS-P) label with the neutrophil to lymphocyte ratio (NLR) and outcomes in front-line NSCLC patients who were screened for actionable mutations as part of a companion diagnostic. Methods: Retrospective chart review was conducted of 76 patients with advanced NSCLC who had pretreatment VS testing. Included patients had at least 3-month follow up. Chi squared analysis was used to correlate VS label with patient characteristics and Cox proportional hazards was used to correlate PFS with VS label, NLR and other baseline characteristics in patients receiving anti-PD1 targeted therapy as part of their first treatment. Results: Median PFS was 6.31 months (follow up range 3-17 months). Of 76 tested patients, 23 never received treatment and 47 received anti-PD1 therapy. 51 had VS-G and 23 had VS-P (2 indeterminate). Using two standard NLR cutoffs of 3.5 and 5, 29 and 47, and 42 and 34 had values above and below the cutoff, respectively. VS-G vs VS-P correlated with performance status (PS) as well as NLR at both cut points and on a continuous scale. (P = 0.031, 0.043, 0.045, and 0.056 respectively, VS-G correlating with good PS and low NLR). There was no correlation with PDL1 or body mass index. On multivariate analysis VS label and NLR were also associated with PFS and OS (P = &lt; 0.001 and P = 0.046). Among a subset of 47 patients treated with ICIs, VS-G and NLR &lt; 5 were associated with longer PFS (P = 0.010 and 0.010) though PDL1 result was not. Conclusions: This is the first description of the performance of the VS mass spectrometry assay in front-line patients whose regimen included an anti-PD1 agent. The VS label was able to predict for PFS in this patient population despite relatively short follow up. VS-G label also correlated with low NLR by multiple methods analyzed. Further evaluation of the impact of cytotoxic chemotherapy to anti-PD1 is warranted.
Treatment monitoring of immunotherapy and targeted therapy using FET PET in patients with melanoma and lung cancer brain metastases: Initial experiences.
Authors: Norbert Galldiks, Diana S.Y. Abdulla, Matthias Scheffler, Viola Schweinsberg, Max Schlaak, Nicole Kreuzberg, Jennifer Landsberg, Philipp Lohmann, Garry Ceccon, Jan-Michael Werner, Eren Celik, Maximilian I. Ruge, Martin Kocher, Simone Marnitz, Gereon R. Fink, Karl-Josef Langen, Juergen Wolf, Cornelia Mauch
Journal: Journal of Clinical Oncology (2019)

e13525 Background: Due to the lack of specificity of contrast-enhanced (CE) MRI, the differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (IT) or targeted therapy (TT) may be challenging, especially when IT or TT is applied in combination with radiotherapy (RT). Similarly, for response assessment of RT plus IT or targeted therapy (TT), the use of CE MRI alone may also be difficult. For problem solving, the integration of advanced imaging methods may add valuable information. Here, we evaluated the value of amino acid PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) in comparison to CE MRI for these important clinical situations in patients with brain metastases (BM) secondary to malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Methods: From 2015-2018, we retrospectively identified 31 patients with 74 BM secondary to MM (n = 20 with 42 BM) and NSCLC (n = 11 with 32 BM) who underwent 52 FET PET scans during the course of disease. All patients had RT prior to IT or TT initiation (61%) or RT concurrent to IT or TT (39%). In 13 patients, FET PET was performed for treatment response assessment of IT or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET PET was used for the differentiation of progression from PsP related to RT plus IT or TT. In all BM, metabolic activity on FET PET was evaluated by calculation of tumor/brain ratios. FET PET imaging findings were compared to CE MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. Results: In 4 of 13 patients (31%), FET PET provided additional information for treatment response evaluation beyond the information provided by CE MRI alone. Furthermore, responding patients on FET PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE MRI findings suggesting progression, FET PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. Conclusions: FET PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with IT or TT.
Biomarker predictors of outcome from a randomized trial of nivolumab +/- stereotactic body radiotherapy (SBRT) in metastatic (M1) head and neck squamous cell carcinoma (HNSCC).
Authors: Sean Matthew McBride, Nancy Y. Lee, David G. Pfister, Eric Jeffrey Sherman, C. Jillian Tsai, Jahan Aghalar, Juliana Eng, Wanqing Iris Zhi, Daniel Curtis McFarland, Loren S. Michel, Lara Dunn, Alan Loh Ho, Nadeem Riaz
Journal: Journal of Clinical Oncology (2019)

6063 Background: A minority of patients with M1 HNSCC respond to the anti-programmed death (PD-1) monoclonal antibody, Nivolumab (Nivo). We sought to determine biomarker predictors of outcome to Nivo in M1 HNSCC. Methods: Patients with M1 HNSCC were randomized (n = 60) with stratification by virus status (EBV/HPV+ vs not) to either Nivo alone or Nivo+SBRT to a single lesion. The primary end-point was objective response rate (ORR) in non-irradiated lesions with overall survival (OS) as a secondary end-point. PD-L1 staining in ≥ 1% of tumor cells was regarded as positive. Tumor mutation burden (TMB) was determined using a next generation sequencing assay (MSK IMPACT). Predictive model selection was done to minimize the Akaike Information Criterion (AIC). Results: There was no difference in ORR comparing the two treatment arms (p = 0.86). On univariate analysis, virus status trended towards predicting both ORR (Positive 41.9% vs Negative 20.7%, (p = 0.14)) and OS (1-yr OS for Positive, 65.9% vs 1-yr OS for Negative 40.6%, p = 0.08). In the sub-group of patients for whom PDL1 staining was available (n = 56), there was a trend towards association with ORR: PDL1+ 50% vs PDL1- 23.5% (p = 0.08). PDL1+ patients demonstrated significantly longer OS (1-yr OS 63% vs 47%, p = 0.02). There was no association between virus status and PDL1 staining. IMPACT data was available in 46 patients. TMB was significantly higher in virus negative (mean 8.1 mut/mB) vs. virus positive (mean 4.6 mut/mB) (p = 0.01); TMB was similar comparing PDL1+ to PDL1- (p = 0.47). TMB was higher in responders than non-responders (p = 0.02); TMB was significantly higher in virus positive responders (p = 0.01) and trended towards being higher in virus negative responders (p = 0.10). A model to predict ORR that included PDL1, virus status, and TMB minimized AIC with a C-index of 0.72. A model to predict OS that included PDL1 and virus status minimized AIC with a C-index of 0.62. Conclusions: A multi-variate model including viral status, PDL1 status, and TMB predicts well response to Nivolumab in M1 HNSCC. A model containing PDL1 and virus had moderate predictive value for OS. Clinical trial information: NCT02684253.
SP0109 HOT: DIAGNOSIS AND TREATMENT OF INFECTION RELATED ARTHRITIDES
Authors: Robert Schoen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Management of infectious arthritis has evolved because of empiric knowledge, clinical studies, and emerging pathogens. For patients with bacterial arthritis, organism specific, effective anti-microbial therapy is essential, but assessment of co-morbidities, adequate joint drainage, and supportive care are also required. For patients with infectious arthritis an acute intervention is usually necessary, since delay in diagnosis often leads to unsatisfactory outcome. In some situations, the distinction between infection and a post-infectious inflammatory process may be challenging. <h3>Objectives:</h3> The goal of this lecture is to review management of septic arthritis in native joints. In addition, I will discuss Lyme arthritis and chronic chikungunya arthritis as examples of the broadening spectrum of infectious arthritis. <h3>Methods:</h3> This lecture will rely on my clinical experience and a Pubmed literature search. <h3>Results:</h3> In this HOT lecture, I will provide practical, up to date information about the diagnosis and management of septic (bacterial) arthritis of native joints. I will discuss longstanding treatment paradigms, as well as advances in management and areas of uncertainty. I will then consider two emerging infections, Lyme arthritis and chronic chikungunya arthritis, that illustrate the changing spectrum of infectious arthritis. <h3>Conclusion:</h3> It is the intention of this lecture to assist rheumatologists in management of patients across the spectrum of infectious arthritis. Accurate diagnosis and treatment are often challenging, but critical to satisfactory patient outcome. <h3>References:</h3> [1] Ross JJ: Septic arthritis of native joints. Infect Dis Clin North Am 2017; 31: 203-218. [2] Schoen RT: Musculoskeletal manifestations of Lyme disease. In: Basow DS (ed): UptoDate 2019. Waltham, MA. [3] Kennedy Amaral Pereira J, Schoen RT: Management of chikungunya arthritis. Clin Rheumatol 2017; 36: 2179-2186. <h3>Disclosure of Interests:</h3> None declared
Characterization of genomic alterations in Chinese LCNEC and SCLC via comprehensive genomic profiling.
Authors: Lin Wu, Liming Cao, Likun Chen, Bo Zhu, Xiaohua HU, Lin Gen, Yingcheng Lin, Sheng Zhang, Cheng Huang, Wenying Peng, Meilin Jiang, Xinru Mao, Tengfei Zhang, Junyi Ye, Lu Zhang
Journal: Journal of Clinical Oncology (2019)

1575 Background: LCNEC and SCLC are aggressive neuroendocrine carcinomas with overlap in clinical, histopathologic, morphologic and genomic features. Differential molecular features between the two subtypes have not been well elucidated, contributing the uncertainty for optimal clinical strategy for each subtype. Here we interrogated the genomic characteristics in LCNEC as compared to SCLC along with their histologically related subtypes: carcinoids and atypical carcinoids via comprehensive genomic profiling. Methods: FFPE samples from 31 LCNECs, 35 SCLCs, 14 carcinoids and 22 atypical carcinoids were sequenced in a CLIA-certified sequencing laboratory using 520-cancer-related gene panel, with an average sequencing depth of 1385×. Results: Comparative mutational analysis revealed that both LCNEC and SCLC sub-cohorts displayed higher rate of TP53 alterations than that of carcinoid (p &lt; 0.001, p &lt; 0.001). SCLC patients harbored more RB1 and PIK3CA mutations than LCNECs (p &lt; 0.001, p = 0.014) and carcinoids (p &lt; 0.001, p = 0.018). In addition, mutation frequencies of LRP1B, FAT1, PRKDC, NOTCH1, SPTA1, EPHA3 and KEAP1 in SCLC were significantly higher than that in carcinoid. Mutations in TP53 and RB1 occurred concurrently in 83% (29/35) SCLC patients, whereas in only 32.3% (10/31) LCNECs. We further investigated the distribution of mutations across KEGG pathways and found that mutation frequencies in both HIF-1 and Notch signaling pathways were lower in LCNEC than SCLC (p = 0.032, p = 0.025). Copy number variation (CNV) analysis revealed that LCNEC and SCLC had comparable CNVs which were significantly higher than carcinoid (p &lt; 0.001, p &lt; 0.001) and atypical carcinoid (p = 0.010, p = 0.028). TMB analysis also revealed a comparable TMB status of LCNEC (12.7/Mb) and SCLC (11.9/Mb), and relatively lower TMB in both carcinoid (2.4/Mb, p &lt; 0.001, p &lt; 0.001) and atypical carcinoid (5.6/Mb, p = 0.003, p = 0.009) than LCNEC and SCLC. Conclusions: We demonstrated the differential genomic characteristics in the four subtypes of neuroendocrine carcinomas. Compared with SCLC, LCNEC has lower mutation frequencies in RB1, PIK3CA, as well as HIF-1 and Notch signaling pathways. In addition, LCNEC and SCLC had comparable CNV and TMB status, which significantly higher than that of carcinoids and atypical carcinoid.
Mutational profiles and amplifications on circulating tumor DNA testing in patients with young-onset colorectal cancer.
Authors: Saivaishnavi Kamatham, Dorin Colibaseanu, Amit Merchea, Faisal Shahjehan, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2019)

e15067 Background: There has been a concerning rise of colorectal cancer (CRC) in young individuals (&lt;50 years). There appears to be a preponderance of left-sided tumors and rectal cancers, however, the etiology and biology is not entirely known. Our aim was to describe the results of circulating tumor DNA based (ctDNA) testing in young-onset CRC. Methods: We studied the results of 186 patients with CRC who had ctDNA testing, of whom 41 (22%) had young-onset CRC from January 2017 to January 2019 at Mayo Clinic, Florida. They were categorized based on their age at diagnosis. Results: The age distribution and the aberrations seen are summarized in the table. 25 (61%) were left sided, 9 (22%) were right sided, 7 (17%) were rectal tumors. ctDNA testing was able to identify mutations in 4 (9.8%) patients with BRAFV600E, 8 (19.5%) with RAS and categorized 29 (70.7%) as RAS/RAF wild-type. Furthermore, amplifications were detected in MYC 6 (14.6%) , MET 3 (7.3%) and ERBB2 1 (2.4%). 3(7.3%) were MSI-High and there were 4 individuals with BRCA1/2 noted on ctDNA testing. Conclusions: ctDNA testing for young onset CRC is feasible and identifies a spectrum of clinically meaningful and actionable aberrations. These can further be of use to evaluate treatment response, progression or help in selection of clinical trials. [Table: see text]
Distance from the anal verge as an indirect measure to predict response to anti-EGFR therapy in left side metastatic colon cancer.
Authors: Daniela Pezzutti DOMINGUES Armentano, Mariana Ribeiro Monteiro, Raphael Araujo, Renata Arakelian, Paula Freire Cardoso, Jessica Tsukamoto, Raphael Brandao Moreira, Fernando Picon
Journal: Journal of Clinical Oncology (2019)

e15153 Background: Right and left sided colon cancers (RC, LC) differ with respect to biology and response to therapy. Several retrospective analyses have assessed the clinical effect of epidermal growth fator receptor (EGFR) targeted agents in patients with metastatic CRC (mCRC) according to the primary tumor location. Differentiating only right from left. But can in the LC responses differ according to the distance from the anal verge (DAV)? Methods: Exploratory retrospective analyses was planned to evaluate if LC responses differ according to the DAV. LC was defined as tumors originating anywhere from the distal rectum to the left colic flexure (splenic flexure). DAV was describe in cm measured by previous to surgery or treatment, colonoscopy, CT or MRI. Patients were divided for analysis purposes in two groups: Group A (tumors above 12cm from de anal verge), Group B (tumors below 12cm from the anal verge). Results: We retrospectively evaluated 29 patients with left metastatic colorectal cancer treated with anti-EGFR therapy as part of their treatment at the Paulistano Hospital -São Paulo from 2011 to 2018. Median population age 51.8 years (48.5-62.3). Median DAV 14.5 (4.6-25 cm). Median follow-up 12.8 months. No significant difference on stable and partial response rate was detected (Group A 43.7% vs Gropup B 56.3%), p=0.211. Long-rank test with a median pFS 8,5 meses and a PFS at 6 months of 66.7 vs 78,8 (Group A and Group B respectively ), p=0.901. Two-year OS was 58.4 % in Group A and 100% in Group B, p=0.17. Conclusions: Although no significant diferences were detected, responses rates were numerically higher in patients with tumors located below 12 cm from the anal verge. Further studies are needed to evaluate the association between response and DAV.
Clinicopathological and prognostic significance of microsatellit instability (MSI) status and PDl-1 expression in Turkish patients with gastric cancer.
Authors: Ibrahim Yildiz, Seyma Bahsi, Sibel Erdamar, Suha Goksel, Gokhan Demir, Ozlem Er, Bilgi Baca, Tayfun Karahasanoglu, Ismail Hamzaoglu, Ali Arican, Leyla Ozer, Mustafa Bozkurt, Cihan Uras, Taner Korkmaz, Umit Ince
Journal: Journal of Clinical Oncology (2019)

e15538 Background: The aim of this study was to evaluate the prognostic role of microsatellite instability (MSI) status and PD-L1 expression in surgically resected gastric cancer and the relationship of these parameters with clinicopathological features. Methods: Eighty six gastric cancer patients which had curative surgical resection at Acibadem Atakent and Maslak Hospitals between 2010 and 2017 were analysed. Tumor samples were evaluated with MSI and PD-L1 antibodies by immunohistochemical (IHC) methods. PD-L1 IHC scoring was performed using the combined positive score (CPS). Survival analysis was accomplished using the Kaplan-Meier method. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival. Results: The rate of PD-L1 expression in tumor cells was 34.9% (n = 30) and the frequency of PD-L1 expression in immune cells with CPS (≥1%) was 57% (n = 49). MSI-H was detected in 11.6%(n = 10), and more observed in PD-L1 positive cases (p = 0.021). MSI-H status was significantly correlated with older age, increased tumor size, presence of PD-L1 expression, and adenocarcinoma subtype. PD-L1 expression was associated with lymph node metastasis, adenocarcinoma subtype, microsatellite instability, presence of preoperative treatment and improved response to preoperative chemotherapy. In our study, the impact of MSI status on survival was not demonstrated, but PD-L1 expression positivity(≥1%) in both tumor cells (15.7 vs 53.4 months, p = 0.008)and in immune cells (20.4 vs NR; p = 0.027) was associated with short overall survival. PD -L1 expression in tumor cells was an independent prognostic factor for overall survival in multivariate analysis (HR: 2.28, p = 0.047). Conclusions: PD-L1 expression was related to a poor prognosis in patients with gastric cancer and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.