tbuckley/cabot-search huggingface dataset:
A new prostate cancer biopsy reporting system with prognostic potential.
Authors: Paras Hemant Shah, Carl A. Olsson, David J Paulucci, Matthew Elmasri, Manish Arvind Vira, Oksana Yaskiv, Deepak A. Kapoor
Journal: Journal of Clinical Oncology (2017)

e16572 Background: Presently, prostate biopsy (PBx) results typically report the highest Gleason Grade Group in the PBx as the single metric used to gauge the clinical aggressiveness of tumor and dictate treatment. However, using that single parameter alone limits the clinician by lack of consideration of the entire PBx. Intuitively we presumed that a PBx showing multiple cores of cancer would represent more aggressive disease. Herein, we propose the Weighted Gleason Grade Group (WGGG), a novel scoring system that synthesizes histopathologic data and cancer volume into a single numeric value representing the entire PBx, allowing the urologist to more accurately predict adverse pathologic outcomes of radical prostatectomy (RP). Methods: We studied 246 men who underwent RP after standard multi-core PBx. The highest Gleason score of each PBx was converted to its final GGG. The WGGG was calculated by summing the Gleason score of each positive core and normalized for a 12 core total. RP pathology was studied to determine adverse pathological outcomes, specifically, extraprostatic extension (EPE), positive surgical margins (PSM), seminal vesical invasion (SVI), pathological up-grading and any adverse feature. We then studied the ability of conventional GGG versus WGGG to have ‘predicted’ the risk of these adverse features comparing their respective receiver operating characteristic (ROC) areas under the curve (AUC) for each, as well as any adverse feature. Results: The AUC for the WGGG vs. GGG was significantly higher for predicting EPE (AUC 0.782 vs. 0.697, respectively; z = -3.29; p = .0009), PSM (AUC 0.644 vs. 0.563, respectively; z = -3.00; p = .0027), SVI (AUC 0.829 vs. 0.713, respectively; z = -3.05; p = .0023) and pathologic up-grading (AUC 0.584 vs. 0.349, respectively; z = -3.13; p = .002). Finally, the AUC for any adverse feature was 0.637 for WGGG versus 0.556 for GGG; z = -3.29; p = .001. Conclusions: The WGGG, by providing a metric reflecting the entirety of the PBx, is more informative than conventional single GGG alone in ‘predicting’ adverse pathologic outcomes on radical prostatectomy specimens. We are now studying if % cancer/ PBx core will improve WGGG performance.
Differences in health care costs and utilization: BR vs RCHOP in patients with follicular lymphoma.
Authors: Jifang Zhou, Ashutosh K. Pathak, Danielle M. Brander, Susan Gabriel
Journal: Journal of Clinical Oncology (2017)

e19049 Background: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (iNHL) with an incidence of more than 1500 cases annually and comprising 35% of all iNHL cases in North America. Combination chemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) or bendamustine plus rituximab (BR) are both category 1–approved first-line therapies. This analysis examined differences in healthcare costs and utilization between two cohorts of newly diagnosed FL patients undergoing BR or RCHOP therapy. Methods: Newly diagnosed FL patients from 1/1/2006 to 7/31/2016 treated with first-line RCHOP or BR were identified in the Truven Health MarketScan Research Databases. Inclusion criteria were age ≥18 years and continuous enrollment from 3 months before to 1 month after the index date (eg, first prescription for RCHOP/BR). Healthcare utilization and costs were calculated on a per month basis from the index date to 6 months post-index date. Costs included all payments made by insurance providers except for pharmacy claims. Healthcare utilization variables included number of outpatient visits, emergency room (ER) visits (yes/no), and hospitalizations (yes/no). Logistic regression and general linear models were used to test for differences. Results: Of the 6460 FL patients (male = 55%; mean age = 60.46 years, SD = 12.56) identified, 2360 were in the BR cohort and 4100 patients were in the RCHOP cohort. At baseline, the BR cohort was significantly older; had more comorbid conditions, lower costs, and fewer outpatient visits; and was less likely to have an ER visit or hospitalization relative to RCHOP patients. Over the first 6 months of therapy, controlling for baseline differences, the BR group experienced significantly lower costs and fewer outpatient visits. The BR cohort was also significantly less likely to be admitted to the ER or experience a hospitalization. Conclusions: The results of this analysis suggest that, in general, the healthcare costs and utilization of FL patients receiving BR is significantly lower than for RCHOP patients. These results support the emerging prominence of BR as an effective and safe first-line treatment option for FL patients.
TOMA OS-Seq: An efficient oligo-selective sequencing solution to identify tumor-specific mutations and copy number alterations.
Authors: Yosr Bouhlal, Yannick Pouliot, Jason Stein, Janet Ziegle, Francisco M. De La Vega, Federico Goodsaid, Austin P. So
Journal: Journal of Clinical Oncology (2016)

e23052 Background: Circulating cell-free DNA (cfDNA) in the plasma of cancer patients carries information on tumor burden and can be a valuable tool for the detection and assessment of the disease and the response to therapy. However, technical challenges remain due to the relatively low concentration of cfDNA in the plasma. The majority of existing methods are based on targeted deep sequencing that requires PCR amplification. This can lead to errors and biases specifically when calling copy number alterations and single nucleotide variants. To address these challenges, the TOMA OS-Seq reagents offer an oligo-selective PCR-free sequencing workflow allowing the screening of customized panels of genes known to be associated with the development, progression or treatment of multiple types of cancers. High quality NGS sequencing data can be obtained from low amounts of DNA, - as low as 10ng - purified from plasma, fine needle aspirate and other tissues, in addition to highly degraded archived material (FFPE). The TOMA OS-Seq chemistry represents an extremely effective method to assess the utility of cfDNA as biomarker in cancer patients. Methods: Blood was drawn immediately prior to surgery and solid tumor specimens were obtained from a set of patients with non-metastatic (Stage II/II+) lung and colorectal cancer. DNA was purified from peripheral mononuclear cell (PBMC), plasma and FFPE then processed using TOMA OS-Seq. Targeted sequencing data were generated using appropriate in-house pipelines designed to identify high confidence calls and to evaluate the concordance between tumor, germline and cell-free DNA. Results: Tumor-specific single nucleotide variants (SNP) and copy number alterations (CNA) were identified for each patient highlighting the potential value of TOMA OS-Seq workflow in detecting and monitoring early stage cancer using liquid biopsies. Conclusions: In this study, we demonstrate the capability of TOMA OS-Seq workflow to identify tumor-specific mutations in plasma from early stage cancer patients.
Improving CLL Vγ9Vδ2-T–cell fitness for cellular therapy by ex vivo activation and ibrutinib
Authors: Iris de Weerdt, Tom Hofland, Roeland Lameris, Sanne Endstra, Aldo Jongejan, Perry D. Moerland, Renee C. G. de Bruin, Ester B. M. Remmerswaal, Ineke J. M. ten Berge, Nora Liu, Mario van der Stelt, Laura M. Faber, Mark-David Levin, Eric Eldering, Sanne H. Tonino, Tanja D. de Gruijl, Hans J. van der Vliet, Arnon P. Kater
Journal: Blood (2018)
Enabling a paradigm shift: A preference-tolerant RCT of personalized vs. annual screening for breast cancer.
Authors: Sarah Rosenberg-Wohl, Prihatha Narasimmaraj, Allison S Fiscalini, Karyn DiGiorgio, Lisa Latts, Marcus Thygeson, Martin Eklund, Jason Connor, Kristine Broglio, Jeffrey Tice, MaryBeth Kramer, Andrea LaCroix, Robert A. Hiatt, Barbara A. Parker, Tracy M. Layton, Laura Esserman
Journal: Journal of Clinical Oncology (2016)

e18281 Background: For almost 30 years, annual mammography starting at age 40 has been a cornerstone of the US strategy to reduce breast cancer mortality. The 2009 USPSTF screening guidelines, despite having a sound evidence base, continue to spark debate. Scientific opinion remains divided. Methods: The Wisdom Study (Women Informed to Screen Depending on Measures of Risk) compares annual screening vs. risk-based screening (RBS). In RBS, a comprehensive risk model incorporates high-impact risk factors, including genetic mutations and common genetic variants (SNPs), mammographic density, family history, exposures, and co-morbidities. The goal is to determine if RBS, compared to annual screening, is as safe, is less morbid, enables prevention, and is preferred by women. Results: Funded by the new PCORI initiative ‘Pragmatic Clinical Studies to Evaluate Patient-Centered Outcomes’, the Wisdom Study is designed to determine safety in 5 years, demonstrating that Stage IIB or higher cancers are not increased in RBS. The study has an innovative preference-tolerant design in which participants who are not willing to be randomized to the risk-based or annual arm may join the observational cohort and choose their arm, thus allowing for greater representation and more widely applicable findings. RBS requires payor engagement and is expected to result in cost savings within five years. Since PCORI funds do not cover clinical services, the study has partnered with insurers to cover clinical services associated with the trial. One mechanism for reimbursement is Coverage with Evidence Development (CED). CED accelerates evaluation of value-enhancing clinical innovations to determine if they should be made permanently available to members. Conclusions: By design, the study engages and shares data with multiple stakeholders including participants, investigators, policy makers, technology partners, payors, and scientific granting agencies. Prior to the launch of the study, all stakeholders agree upon, and have access to, metrics for what constitutes the threshold for adoption. Payors will already cover services, so if the threshold for adoption is reached, implementation of RBS can become standard of care immediately. Clinical trial information: NCT02620852.
Pharmacokinetics of cetuximab and tumor uptake of <sup>89</sup>Zr-cetuximab as potential predictive biomarkers for benefit of cetuximab in patients with advanced colorectal cancer.
Authors: Erik Jacobus Van Helden, Catharina Wilhelmina Menke, Eline Boon, Suzanne van Es, Marc C. Huisman, G.a.M.S. van Dongen, Danielle J. Vugts, Derk Jan De Groot, Carla M.L.- Van Herpen, Elisabeth De Vries, Otto S. Hoekstra, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2017)

e15117 Background: One third of patients with RAS wild-type metastatic colorectal cancer (mCRC) do not benefit from anti-EGFR inhibitors. Thus, predictive biomarkers to identify patients with primary resistant mCRC are urgently needed. Methods: Patients with chemotherapy refractory mCRC received 500 mg/m 2 cetuximab 2-weekly (NCT02117466 and NCT01691391). Patients underwent a 89 Zr-cetuximab PET/CT 6 days post-injection after a therapeutic dose of cetuximab. In case of lack of tumor targeting on 89 Zr-cetuximab PET, the cetuximab dose was escalated. Pharmacokinetic (PK) analyses included 89 Zr-cetuximab plasma levels, EGFR saturation in skin, soluble EGFR (sEGFR), and tumor uptake and biodistribution on 89 Zr-cetuximab PET. We defined treatment benefit as response or stable disease (according to RECIST v1.1) at 2 months. Results: Of the 44 patients, median age was 64 years, 25% had a right-sided primary tumor, 5 patients had a BRAF mutated (mt) tumor and 62% had treatment benefit. Cetuximab treatment dose was escalated to maximally 1250 mg/m 2 in 8 patients. Visual and semiquantitative data of 89 Zr-cetuximab uptake in the tumor, biodistribution and plasma activity 6 days post-injection were not correlated with treatment benefit. Although EGFR saturation in skin after 2 cycles cetuximab had a wide range (21 – 98%), saturation did not correlate with treatment benefit. On-treatment levels of sEGFR were higher than baseline (median 4.1 vs 2.0 ng/ml; p &lt; 0.001), but levels and change of sEGFR did not correlate with PK or treatment efficacy. PFS and OS correlated with right-sided mCRC (p &lt; 0.001 and p = 0.002 respectively) and the presence of a BRAF mt (p &lt; 0.001 and p = 0.004 respectively). In a multivariate Cox-regression only BRAF mt remained correlated with PFS and OS (p = 0.003 and p = 0.027). Conclusions: Interpatient variances in PK and tumor uptake of 89 Zr-cetuximab as performed in this setting do not predict treatment benefit of cetuximab in patients with mCRC. In contrast, BRAF status correlated with treatment benefit and warrants further research to confirm the predictive value. Clinical trial information: NCT02117466 and NCT01691391.
Long-term result of out-patient intra-arterial chemotherapy in patients with stage II and III oral cancer.
Authors: Masatoshi Ohmae, Itsuro Kato, Yusei Fujita, Hiroo Tkaoka, Noritoshi Meshii, Ayako Takasu, Mitsuhiro Nakazawa
Journal: Journal of Clinical Oncology (2017)

e17569 Background: We have developed a superselective intra-arterial chemotherapy (iaCT) approach for oral cancer, in which intra-arterial catheter is retrogradely inserted via the superficial temporal artery and/or occipital artery. The extra-arterial portion of catheter is connected to an infusion reservoir implanted subcutaneously around the mastoid process through the subcutaneous tunnel. The catheter and reservoir are completely placed under the skin, so there is little possibility of catheter-related issues such as infection and displacement. Hence, out-patient iaCT (op-iaCT) can be performed. This method has improved ADL of patients without any loss of curative effect and oral function. We reported the usefulness of op-iaCT at the ASCO annual meeting in 2013. We assessed the long-term outcome and survival rate of patients with stage II and III oral cancer who received op-iaCT and survived for at least 5 years. Methods: We have used op-iaCT for 46 patients who had oral cancer, out of which we selected 14 patients with stage II and III oral cancer, and monitored them for more than 5 years. Results: Two patients died owing to distant metastasis, to the brain and liver, and 12 patients were cancer-free. Neck metastases were detected after primary treatment and op-iaCT in 3 patients, who were salvaged by neck dissection. The 5-year survival rate was 86%. Conclusions: Distant and/or regional lymph node metastases were observed in 5 out of 14 patients. The op-iaCT improves quality of life of patients with stage II and III oral cancer, but the metastasis rate is somewhat high. Close observation, intravenous chemotherapy, and /or prophylactic neck dissection should be employed in the op-iaCT approach for oral cancer.
KRAS in non-small cell lung cancer: Single institution experience—What factors are involved?
Authors: Idoroenyi Usua Amanam, Rohan Gupta, Isa Mambetsariev, Marianna Koczywas, Mihaela C. Cristea, Erminia Massarelli, Karen L. Reckamp, Ravi Salgia
Journal: Journal of Clinical Oncology (2017)

11624 Background: Disease heterogeneity with variable molecular mutations is one of the main contributory factors in non-small cell lung cancer (NSCLC). The goal of this study was to better understand the KRAS patients with co-occurring mutations. Methods: We identified 60 patients with a diagnosis of NSCLC and a KRAS mutation in the COH Cancer Registry from 2009 to 2016. Next generation sequencing was performed. Results: Of the 60 patients identified, 42 (70%) were Stage IV at diagnosis, 7 (12%) Stage I and 7 (12%) stage II and 4 (6%) Stage III. 47 (78) patients were smokers. Caucasian was the most common (n = 44, 73%) racial group, followed by Asians (n = 9, 15%), African-Americans (n = 3, 5%), other (n = 3, 5%) and Pacific Islander (n = 1, 1.7%). The average age at diagnosis was 67 (median 69.50) years; 30 patients (50%) were over 70 years, 23 (38%) patients were 51-69 years, and 7 (12%) 50 years or below. Majority of the patients had metastatic disease (n = 52, 87%) with 20% (n = 12) having brain metastasis with average metastatic sites 1.6. An average of 1.97 (range = 0-5) lines of therapy including chemotherapy, biologic agents or immunotherapy were received. 12 (20%) patients received immunotherapy, radiation in 28 (47%) and surgery in 22 (37%) with a median overall survival at 15 months. The most frequent molecular alteration was codon 12 mutation (n = 47, 78%), followed by codon 13 (n = 7, 12%) and codon 61 (n = 6, 10%) mutations. The most common co-occurring mutations in this cohort were TP53 (n = 15, 25%), ATM (n = 9, 15%), LRP1B (n = 9, 15%), ARID1A (n = 8, 13%), STK11 (n = 8, 13%), ARID1B (n = 7, 12%), TERT (n = 7, 12%), EGFR (n = 6, 10%), RBM10 (n = 6, 10%), SPTA1 (n = 6, 10%). We are currently evaluating the relevance of the Circos plot analysis for these mutations, clinical response to immunotherapy and potential biomarkers. Conclusions: KRAS mutations are among the most common molecular alterations identified in NSCLC. Effective treatments targeting KRAS mutations have represented a challenge so far. Understanding the significance of co-mutations and their therapeutic implications, especially in response to immunotherapy and other agents represents an important step to develop better treatment options for KRAS mutated lung cancers.
Impact of MLH1, PMS2, MSH2, and MSH6 alterations on tumor mutation burden (TMB) and PD-L1 expression in 1,057 microsatellite instability-high (MSI-H) tumors.
Authors: Mohamed E. Salem, Axel Grothey, Edward S. Kim, Joanne Xiu, Richard M. Goldberg, Wolfgang Michael Korn, Anthony Frank Shields, Andreas Seeber, Jimmy J. Hwang, Philip Agop Philip, Heinz-Josef Lenz, Derek Raghavan, John Marshall
Journal: Journal of Clinical Oncology (2018)

3572 Background: MSI-H tumors are associated with higher TMB. We examined the yet uncharacterized relationship between TMB and individual MMR gene alterations in MSI-H tumors. Methods: MSI-H was determined by examining altered microsatellite (MS) loci using NextGen sequencing (cutoff: > = 46) on a 592-gene panel. TMB was calculated by enumerating somatic missense mutations. MMR protein expression was evaluated by IHC. ANOVA and chi-square tests were used for comparisons. Results: A total of 1057 MSI-H tumors (283 colorectal cancer [CRC]; 449 endometrial cancer [EC]; and 325 others from 29 cancer types) were examined. High TMB (≥ 17 mutations/megabase [mt/MB]) was seen in 74% of tumors. MSI-H CRC had the highest TMB compared to MSI-H EC and “all others” (mean TMB: 39 vs. 23 vs. 31 mt/MB, respectively; p < 0.0001). There was no difference in TMB between BRAF V600 mutant and wild type MSI-H CRC (38.7 vs. 39 mt/MB). In general the most frequently altered (IHC loss or mutation) MMR genes were MLH1 and PMS2 (72% and 83%, CRC; 90% and 95%, EC). MSH2 and MSH6 were more frequently altered in CRC than EC (21% vs. 5% and 49% vs. 28%, respectively; p < 0.0001). In CRC, MSH2 and MSH6 were more frequently altered in left than right sided MSI-H tumors (45% vs. 12% and 67% vs. 40%; p = 0.01). Overall MSH2 or MSH6 alterations were associated with higher TMB (48.5 and 40 mt/MB, respectively) than MLH1 or PMS2 (27 mt/MB for both); P < 0.0001. Tumors with MSH2/6 co-alterations (4%) had a higher TMB compared to those with MLH1/PMS2 (39%) co-alteration (50 vs. 24 mt/MB; p < 0.0001). PD-L1 overexpression was seen at a higher frequency in tumors with MSH2 (23%) than MSH6 (16%), MLH1 (16%), or PMS (14%); P = 0.01. MSH2/6 alterations in EC were associated with higher MS alterations (MSH2, 88; MSH6, 73; MLH1, 68; PMS2, 68; p < 0.0001), while all genes were equal in CRC. MSH2 alterations were associated with higher frameshift mutation rates in 36 genes in EC, and in different 10 genes in CRC. Conclusions: TMB varies significantly across MSI-H tumors. MSH2/MSH6 alterations were associated with a significantly higher TMB than MLH1/PMS2 across several cancer types. The MS alterations associated with MSH2/6 were tumor-type specific.
Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men
Authors: Mark A. Preston, Travis Gerke, Sigrid V. Carlsson, Lisa Signorello, Daniel D. Sjoberg, Sarah C. Markt, Adam S. Kibel, Quoc-Dien Trinh, Mark Steinwandel, William Blot, Andrew J. Vickers, Hans Lilja, Lorelei A. Mucci, Kathryn M. Wilson
Journal: European Urology (2018)
Meta-analysis of postoperative radiotherapy (PORT) in resectable stage IIIA-N2 non-small cell lung cancer (NSCLC): An update on 3,278 patients.
Authors: Na Li, Xiaoxia Zhu, Yiyi Li, Dianhe Li
Journal: Journal of Clinical Oncology (2016)

8546 Background: In a previous meta-analysis-based modeling study, it was hypothesized that modern PORT may improve both local recurrence (LR) and overall survival (OS) in stage IIIA-N2 NSCLC. There were only four single-arm trials with a total of 357 patients. Since other trials have provided new and controversial data, we performed this updated meta-analysis to test the hypothesis. Methods: A systematic review of Medline, Cochrane and Science Direct up to December 2015 identified publications exploring the efficacy of PORT on OS, disease-free survival (DFS), local recurrence-free survival (LRFS), LR, and distant metastases (DM) in resectable stage IIIA-N2 NSCLC. The hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (95% CI) were calculated for pre-specified endpoints. The fixed- or random-effect models were used. Results: Overall 16 trials comprising 3,278 patients were included. There was a significant benefit in favor of PORT regarding OS (HR 0.73, 95% CI 0.58-0.92, p = 0.008; absolute benefit at 5 years = 8%), DFS (HR 0.70, 95% CI 0.60-0.83, p < 0.0001), LRFS (HR 0.37, 95% CI 0.24-0.58, P < 0.0001). Restriction of the analysis to trials with induction and/or adjuvant chemotherapy (CT) led to similar results. PORT significantly decreased the risk of LR (RR 0.64, 95% CI 0.50-0.82, P = 0.0006) and DM (RR 0.74, 95% CI 0.62-0.88, P = 0.0005), and the absolute risk differences were 13% and 14% respectively. Conclusions: The addition of PORT, with or without CT, significantly improves local control and survival in patients with resectable stage IIIA-N2 NSCLC.
A phase II prospective clinical study of the “sandwich” protocol, VDLP combined with concurrent radiation and cisplatin in newly diagnosed, I/II stage, nasal type, extranodal natural killer/T-cell lymphoma.
Authors: Li Zhang, Ming Jiang, Li Xie, Hong Zhang, Yu Jiang, Weiping Liu, Wenyan Zhang, Rong Tian, Yaotiao Deng, Sha Zhao, Liqun Zou
Journal: Journal of Clinical Oncology (2016)

7553 Background: Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is the second-most common lymphoma in China. However, the standard first-line treatment remains to be studied. In our previous report, the