tbuckley/cabot-search huggingface dataset:
Predicting the outcome of percutaneous biopsy in renal neoplasms using a CAD algorithm to derive peak lesion enhancement on four-phase CT.
Authors: Heidi Coy, Michael Douek, Jonathan Young, Matthew S. Brown, Jonathan Goldin, James Sayre, Steven Raman
Journal: Journal of Clinical Oncology (2016)

e16067 Background: The incidence of renal cell carcinoma has steadily increased, in part due the increased number of incidentally detected renal neoplasms on imaging. Although a small renal mass can have imaging features of a typical clear cell renal cell carcinoma (ccRCC), up to 30% of these are found to be benign after surgery. Most commonly oncocytoma (O) and fat-poor angiomyolipoma (AML). Discrimination between ccRCC, and O or AML on imaging would preclude the need for biopsy, and could alter management between surgery and ablation, or active surveillance and no further evaluation. The purpose of our study is to predict the probability of a lesion being ccRCC vs. O or AML from relative lesion-to cortex enhancement (RE) on four-phase MDCT derived from Computer Aided Diagnostic (CAD) algorithm. Methods: With IRB approval for this HIPAA-compliant retrospective study, we queried our pathology and imaging databases to obtain a cohort of percutaneously biopsied renal lesions with preoperative MDCT using a four-phase renal mass protocol (unenhanced, corticomedullary, nephrographic, and excretory). A whole lesion 3D contour was obtained in all phases. The CAD algorithm determined a 0.5cm diameter region of interest (ROI) of peak lesion enhancement ≤ 300HU within the 3D lesion contour. A 0.5cm ROI was placed in uninvolved renal cortex. RE was calculated as: (lesion CAD ROI-cortex ROI)/ (cortex ROI)* 100%). A model was derived using logistical regression with CAD derived RE from all four phases of the ccRCC and the benign lesions (O and AML) as input. Discrimination was evaluated using receiver operator characteristic (ROC) curves. Results: 46 patients (78% men, 20% women) with 57 unique renal masses (29 (51%) clear cell RCC, 19 (33%) Oncocytoma, 8 (14%) lipid-poor angiomyolipoma) were analyzed. Mean lesion size in ccRCC = 2.3cm (range 0.8-6.4), O = 2.6cm (range 1.0-4.7), and AML = 1.8cm (range 0.7-3.6). The model demonstrated discriminatory power in predicting ccRCC from benign lesions with an area under the curve of 0.858 (0.756-0.961 95% CI). Conclusions: CAD derived relative lesion to cortex attenuation can aid the clinician in discrimination of ccRCC from benign subtypes.
Risk factors associated with ifosfamide (IFOS)-induced encephalopathy in patients (pts) with metastatic (Met) sarcoma (Sarc).
Authors: Adebayo Ogunniyi, Anjali Varma Desai, Troy Z Horvat, Li-Xuan Qin, Ping Chi, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2017)

e22518 Background: IFOS is commonly used in the treatment of met sarc. IFOS has been reported to cause encephalopathy in 5 - 30% of pts. Potential risk factors for IFOS-induced encephalopathy (IIE) include female gender, older age, route of administration of IFOS, low serum albumin, existence of pelvic disease and renal failure. Unfortunately, the majority of the data surrounding potential risk factors is from heterogeneous cohorts. Methods: The purpose of this single-center retrospective analysis was to identify risk factors for developing IIE in a homogenous cohort of met sarc pts treated at MSKCC between 1/2010 and 5/2015. Logistic regression was used to examine the univariate effect of baseline and treatment variables. Variables significant at the 0.05 level were entered into a multivariate model. Results: A total of 328 met sarc pts with a median age of 51 years were analyzed. Thirty-four pts (10%) developed IIE. Of those 34 pts, 88% developed encephalopathy with the first or second cycle of IFOS. Age at the time of treatment (p = 0.0037), low serum albumin (p &lt; 0.0001), increased serum alkaline phosphatase (p = 0.0022), liver met disease (p = 0.0011) and more than 3 met sites at time of IFOS dose (p = 0.0008) were all identified as risk factors by univariate analysis. Only low serum albumin (p &lt; 0.0001, odds ratio = 0.33) and more than 3 met sites at time of IFOS dose (p = 0.0068, odds ratio = 2.47) maintained statistical significance after multivariate analysis. Conclusions: To our knowledge, this is the largest retrospective analysis of risk factors for IIE in the met sarc population. This analysis identified low serum albumin and more than 3 met sites at time of IFOS as predictors of IIE. Our data would suggest that clinicians considering the option of IFOS in met sarc pts should give particular attention to these predictive risk factors when making their treatment decisions.
Use of next generation sequencing and quantitative mass spectrometry to determine HER2 status.
Authors: Pedram Razavi, Fabiola Cecchi, Dara S. Ross, Sumit Middha, Ahmet Zehir, Maria E. Arcila, Todd A. Hembrough, Michael F. Berger, Maurizio Scaltriti
Journal: Journal of Clinical Oncology (2016)

e23237 Background: Traditional methods for HER2 assessment such as IHC and FISH are semi-quantitative and often limited by reproducibility issues. This may be a problem in tumors with borderline HER2 expression. We propose that selected reaction monitoring mass spectrometry (SRM-MS) and next generation sequencing (NGS) can be utilized to assess HER2 status. Methods: HER2 status was determined as per ASCO/CAP 2013 guidelines. SRM-MS was utilized to quantify HER2 protein levels in FFPE tissue blocks and a value ≥ 740 amol/μg was considered as positive. The same samples were analyzed using a capture-based NGS assay (MSK-IMPACT) to exome sequence 410 cancer-related genes. The Spearman rank correlation coefficient was calculated to assess the relationship between HER2 protein level by SRM-MS and HER2 gene fold change (FC) by NGS. Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 FC predictive of HER2 status by IHC/FISH and SRM-MS. Results: A total of 26 cases tested by IHC/FISH were selected and subjected to NGS and SRM-MS analysis. HER2 FC by NGS was highly correlated with HER2 protein level by SRM-MS (Spearman ρ = 0.94, P < .0001). In the ROC analysis, an NGS amplification FC threshold of 2 showed 92% agreement with HER2 protein level by SRM-MS (24/26 cases, Specificity = 100%, P < .0001). This threshold showed an agreement of 85% with HER2 status per IHC/FISH. One discordant case was IHC 3+ with low expression of HER2 per SRM-MS and no amplification by NGS (FC = 1.6). The other three discordant cases had IHC 2+ with borderline FISH (ratio 2.1-2.2), relatively low expression of HER2 by SRM-MS (422-953 amol/μg) and NGS amplification levels below our arbitrary threshold (FC: 1.5-1.8). We are expanding the analysis to include more HER2 equivocal cases to assess the discriminatory value of NGS and SRM-MS. Conclusions: Capture exome sequencing of a limited number of genes is becoming the gold standard to guide targeted therapy against oncogene-driven tumors. Given that this technique also allows the assessment of HER2 gene copy number, we posit that together with SRM-MS HER2 quantification it could be used to define the HER2 status of samples with borderline IHC/FISH and, ultimately, substitute these traditional techniques.
Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women
Authors: Qing Liu, Alice H Lichtenstein, Nirupa R Matthan, Simin Liu, Matthew A Allison, Barbara V Howard, Lisa W Martin, Carolina Valdiviezo, JoAnn E Manson, Charles B Eaton
Journal: Circulation (2016)

Introduction: Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index (LI, defined as the sum of the products between FA percentage and melting points (°C) of each FA, divided by the total percentage of FAs) is a novel index that captures the overall FA profile and reflects lipoprotein fluidity. Limited studies have evaluated the relationship between plasma LI and CHD risk, and none has assessed this association among postmenopausal women. Hypothesis: Higher plasma LI is associated with increased CHD risk among postmenopausal women. Methods: In a nested case-control study in Women’s Health Initiative Observational Study, we measured levels of plasma phospholipid FAs, expressed as molar percentage (mol%), in 1214 matched CHD cases (including myocardial infarction and coronary death) and controls. Multivariate conditional logistic regression was used to calculate ORs for CHD risk between each quartiles (based on controls) of LI after adjusting for confounders. Results: The mean age of the women was 67.8±6.8 years, average BMI was 27.6±6.0, 89.5% were White, 6.6% were current smokers, 41.2% were hypertensive, and 15.2% had dyslipidemia. The median plasma LI among cases and controls were 22.5 and 22.1, respectively. Palmitic acid (16:0) and stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), and docosahexaenoic acid (22:6) were the most common saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs, respectively. The association between quartiles of LI and CHD risk are shown in Table below. After multivariate adjustment in the parsimonious model, plasma LI was significantly associated with an increased risk of CHD: OR=1.61 (95% CI 1.25-2.07, P for trend&lt;0.01) comparing extreme quartiles. This association was attenuated to 1.57 (1.22 - 2.03, P for trend&lt;0.01) in the fully adjusted model. Conclusion: Our study indicated that higher plasma LI, which represents lower FA fluidity, was associated with higher risk of CHD among postmenopausal women.
Updated efficacy data and MRD analysis according to risk status in newly diagnosed myeloma patients treated with carfilzomib + lenalidomide or cyclophosphamide (FORTE trial).
Authors: Francesca Maria Gay, Robin Foà, Pellegrino Musto, Chiara Cerrato, Barbara Gamberi, Elena Zamagni, Angelo D. Palmas, Antonio Spadano, Paola Omedè, Tommaso Caravita, Nicola Giuliani, Stelvio Ballanti, Francesca Patriarca, Rossella Troia, Massimo Gentile, Giovanni Desabbata, Letizia Canepa, Antonio Palumbo, Michele Cavo, Mario Boccadoro
Journal: Journal of Clinical Oncology (2018)

8009 Background: Carf plus Len-Dex (KRd) or Cyclo-Dex (KCd) is effective in NDMM. Treatment of high-risk pts is an unmet medical need. Methods: NDMM pts ≤65 yrs were randomized (1:1:1; stratification ISS and age) to ARM A: 4 28-day induction cycles with KCd (Carf: 20/36 mg/m2 IV days 1,2,8,9,15,16; Cyclo: 300 mg/m2 days 1,8,15; Dex: 20 mg days 1,2,8,9,15,16) followed by MEL200-ASCT and consolidation with 4 KCd; ARM B: 4 28-day cycles with KRd (Carf: 20/36 mg/m2 IV days 1,2,8,9,15,16; Len: 25 mg days 1-21; Dex: 20 mg days 1,2,8,9,15,16) followed by MEL200-ASCT and 4 KRd; ARM C: 12 KRd cycles. Primary endpoint was VGPR rate with KRd vs KCd induction. For this analysis, the 2 KRd arms were pooled (2:1), as treatment was the same until that point. Enrollment was completed in March, 2017; data cut-off was November 30, 2017. Results: 474 pts were randomized (KRd, n = 315; KCd, n = 159). Pts characteristics were well balanced: 49% of KRd pts vs 49% of KCd pts had ISS Stage 2-3 at baseline, 31% vs 35% had high-risk chromosomal abnormalities [del17 and/or t(4;14) and/or t(14;16) by FISH], 68% vs 74% had Revised ISS Stage 2-3. Rates of sCR/CR (14% vs 3%; P = 0.0004), ≥nCR (33% vs 21%; P = 0.0106) and ≥VGPR (75% vs 60%; P = 0.0017) were significantly higher with KRd vs KCd. The advantage of KRd was consistent in all subgroups; ≥VGPR, ≥nCR in high-risk pts treated with KRd were comparable to the overall population. MRD evaluation (8 color second generation flow cytometry, sensitivity 10-5) was available in a subset of pts: 144 KRd and 56 KCd. Rate of MRD negativity in evaluable pts was 56% with KRd vs 29% with KCd (P = 0.008). MRD negativity in high-risk pts treated with KRd was comparable to the overall population (Table). Treatment was well tolerated, as previously shown (Gay F ASCO 2017). Conclusions: KRd induction significantly improved sCR/CR, ≥nCR, ≥VGPR rates and MRD negativity vs KCd with similar efficacy in high-risk pts. Clinical trial information: NCT02203643. All pts HIGH RISK by FISH ISS 2-3 Revised ISS 2-3 KCd KRd KCd KRd KCd KRd KCd KRd Response N = 159 N = 315 N = 43 N = 79 N = 69 N = 143 N = 91 N = 173 ≥nCR 21% 33% 12% 30% 16% 31% 13% 29% ≥VGPR 60% 75% 63% 71% 58% 78% 59% 76% MRD N = 56 N = 144 N = 14 N = 38 N = 36 N = 73 N = 39 N = 88 MRD negative 29% 56% 36% 61% 31% 58% 26% 56%
Etoposide and cisplatin (EP) for metastatic good-risk germ cell tumors (GCTs): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience in 944 patients (pts).
Authors: Samuel Funt, Deaglan Joseph McHugh, Stephanie Tsai, Devon O'Donnell, Andrea Knezevic, Sujata Patil, Deborah Silber, Victor E. Reuter, Joel Sheinfeld, Brett Stewart Carver, Maryann Carousso, Robert J. Motzer, Dean F. Bajorin, George J. Bosl, Darren R. Feldman
Journal: Journal of Clinical Oncology (2018)

4550 Background: Standard of care for pts with metastatic, good-risk GCTs consists of either 3 cycles of bleomycin, etoposide, and cisplatin (BEPx3) or 4 cycles of EP (EPx4). EPx4 avoids both pulmonary and vascular bleomycin toxicity. Methods: 944 pts with good-risk GCTs (LDH modified to < 3 x upper limit of normal) were treated with EPx4 at MSKCC from1982 to 2015. EP consisted of cisplatin 20mg/m2 and etoposide 100mg/m2 on days 1 to 5 at 21-day intervals. Response, post-EP surgical findings, and survival were obtained for 655 pts treated from 2000 to 2015 and compared with the same outcomes plus updated follow-up for 289 pts treated from 1982 to 2002 previously reported by Kondagunta et al. (JCO, 2005). Results: Of the recent 655 pts, median age was 33 (range, 15-77), nonseminoma comprised 65%, seminomas 35%, AFP elevated in 27%, HCG 53%, and LDH 31% with 7.6% of nonseminoma with LDH 1.5 - 3 times upper limit of normal. 97% pts completed 4 cycles of EP. Of 655 pts, 313 underwent post-EP retroperitoneal lymph node dissection (RPLND): 59.1% necrosis or fibrotic debris, 38.0% pure teratoma, 2.6% viable, non-teratomatous GCT, 1 patient unclassified. Febrile neutropenia and thromboembolic events occurred in 15.9% and 8.9%, respectively. In the combined group of 944 pts, 927 (98.2%) achieved a favorable response (CR or PR-negative markers); there was 1 treatment-related death. With median follow up for the combined 944 pt group of 6.8 years, five-year PFS and OS rates were 93.4% and 97.9%, respectively. Outcomes summarized in the table. Conclusions: In the largest series of good-risk pts treated with EPx4 ever reported, our results confirm that this regimen is highly effective and well-tolerated. EPx4 remains a standard treatment option for good-risk GCT and remains the preferred regimen at MSKCC. JCO 2005 Current Updated Total (%) Number of Pts 289 655 944 Favorable Response (%) 282 (98) 645 (98) 927 (98) Viable, non-teratomatous GCT at Post-EP Surgery (%)* 11/134 (8) 8/313 (3) 19/447 (4) Relapse (%) 18 (6)^ 26 (4) 44 (5) Died of Disease (%) 10 (3)^ 4 (1) 14 (2) *JCO 2005 includes any post-EP surgery. Current limited to RPLND.^1 pt relapsed and died of disease post-publication
TCT-243 Are Percutaneous Patent Foramen Ovale Closure Devices effective? A Comprehensive Meta-Analysis Assessing their Long Term Outcomes
Authors: Armaghan Soomro, Abdullah Bin Munir, Emad Barsoum, Ruben Kandov, Chad Kliger, Roman Royzman, Srinivas Duvvuri, Stavros Snyder, None James Malpeso, James Lafferty, Donald McCord, Perwaiz Meraj, Cindy Grines
Journal: Journal of the American College of Cardiology (2018)
Head and neck squamous cell carcinoma organoids as a platform for personalized medicine
Authors: E. Driehuis, S. Kolders, L. Devriese, S. Willems, H. Clevers, R. de Bree, E. de Ruiter
Journal: Annals of Oncology (2018)

Background: Organoids are 3D structures that recapitulate morphological, functional and genetic characteristics of the tissue of origin. Grown as organoids, primary cells can be kept in culture long-term without the requirement for immortalization or genetic alterations. In this study, we report the establishment of organoids derived of Head and Neck Squamous Cell Carcinomas (HNSCCs), which are tumors that arise from the squamous epithelium lining the oral cavity, pharynx and larynx. Overall five-year survival of patients diagnosed with this tumor is poor, and although many of the mutations detected in these tumors are therapeutically targetable, introduction of these treatment into the clinic has failed. Methods: Organoids are established from HNSCC biopsies or surgical resections. Subsequently, the organoids are characterized using histology and DNA and RNA sequencing. In vitro, organoids are tested for sensitivity to a range of drugs. Results: Here we report the establishment of organoids derived of HNSCCs. These structures seem to recapitulate genetic and histological features of the tumors of which they are derived. Upon drug exposure in vitro, these organoids show differential responses to different therapies, including cisplatin, carboplatin and the anti-EGFR antibody cetuximab, which are currently used in the clinic. Our data suggests that this system might have the potential to guide personalized therapy in the future. To validate these findings, we are currently setting up a study to test the predictive potential of patient-derived organoid lines for the first line treatment of HNSCC patients. We will expose tumor-derived organoids to these therapies. Retrospectively, organoid responses will be compared to patient response. The results of this study will show if, in this patient group, organoids can serve as a tool to guide therapy choice. Conclusions: This work suggests that HNSCC-derived organoids might have the potential to predict patient response, a hypothesis we will hope to validate by the study described above. Retrospectively, we will correlation patient outcome to in vitro organoid response. This will help us determine the potential of this system to predict therapy response of patients with HNSCC. Legal entity responsible for the study: Hans Clevers research group, Hubrecht Institute. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Afatinib in combination with pembrolizumab in patients (pts) with stage IIIB/IV squamous cell carcinoma (SCC) of the lung.
Authors: Benjamin Philip Levy, Luis G. Paz-Ares, Jaafar Bennouna, Enriqueta Felip, Delvys Rodríguez Abreu, Dolores Isla, Fabrice Barlesi, Olivier Molinier, Jeannick Madelaine, Clarisse Audigier-Valette, Sang-We Kim, Mustafa Ozguroglu, Mustafa Erman, Firas Benyamine Badin, Tarek Mekhail, Ronald J. Scheff, Jonathan W. Riess
Journal: Journal of Clinical Oncology (2018)

TPS9117 Background: Afatinib and pembrolizumab have demonstrated improvements in the outcomes of pts with SCC of the lung and are approved as monotherapy. Afatinib is a selective and irreversible ErbB family blocker with activity against all homo- and heterodimers formed by ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4. Pembrolizumab is a humanized IgG4 monoclonal antibody with potent receptor-blocking activity for PD-1. Given the efficacy of these agents as monotherapy in chemo-refractory lung SCC, concurrent inhibition of PD-1 and EGFR pathways represents a promising approach to improve clinical outcomes in lung SCC. Methods: Study 1200.283 (NCT03157089; LUX-Lung IO/Keynote 497) is a phase II, single-arm study (n = 50–62). Eligible pts have stage IIIB/IV lung SCC, progressed during/after first-line platinum-based chemotherapy, and have an ECOG PS 0/1. Prior immune checkpoint inhibitor or EGFR targeted therapy are prohibited. A safety run-in will be performed in 12 pts, using afatinib (starting dose 40 mg/day, with potential dose de-escalation to 30 mg) with pembrolizumab (200 mg every 3 weeks) to assess the safety and confirm the recommended Phase II dose (RP2D) based on dose limiting toxicities observed during the first cycle. In the main trial, afatinib at the RP2D, in combination with pembrolizumab, may be continued for a maximum of 35 cycles. In case of toxicity, afatinib dose reduction to 30/20 mg will be permitted. Primary endpoint is objective response (OR; complete response [CR] or partial response [PR] [RECIST v1.1]). Further endpoints include disease control (CR, PR, stable disease), duration of OR, PFS, OS, and pharmacokinetics. All pts will provide a fresh or archived tumor tissue sample to measure PD-L1 expression and mRNA expression of genes involved in the immune system. Exploratory biomarkers include the evaluation of immune status by determination of tumor infiltrating cells (e.g. CD8+ cells) or TH1-type cytokines, and blood biomarkers related to the emergence of resistance at progression. This study is conducted in the US, Spain, France, Turkey, and Korea. As of January 2018, enrollment in the safety run-in is complete (n = 12). Clinical trial information: NCT03157089.
Advancing Age and Comorbidity in a US Insured Population‐Based Cohort of Patients With Chronic Hepatitis B
Authors: Mindie H. Nguyen, Joseph K. Lim, A. Burak Ozbay, Jeremy Fraysse, Iris Liou, Nicole Meyer, Geoffrey Dusheiko, Stuart C. Gordon
Journal: Hepatology (2018)

Chronic hepatitis B (CHB) comorbidity data are limited. Using insurance claims databases, our aims were to determine the prevalence and incidence of nonliver comorbidities in CHB patients over time and the predictors of select comorbidities in CHB patients. Patients were adults with continuous coverage (commercial/Medicare or Medicaid) 6 months prior to and after the first CHB diagnosis and matched non-CHB patients. Deyo-Charlson Comorbidity Index (DCCI) and comorbidities were analyzed (cardiovascular disease [CVD], carcinoma, diabetes mellitus [DM], obesity, hypertension [HTN], hyperlipidemia, alcohol use, renal impairment, chronic kidney disease [CKD], and osteoporosis/fracture [OF]). The study population included 44,026 CHB cases and 121,568 matched controls. CHB patient mean age increased from 48.1 ± 11.9 years in 2006 to 51.8 ± 12.4 years in 2015 for commercial/Medicare and from 44.1 ± 11.1 years to 50.2 ± 10.2 years for Medicaid (P < 0.001 for both). The Medicaid CHB cohort was the sickest (DCCI, 2.6, P < 0.001). The commercial/Medicare 2006 CKD prevalence rate was 36.1/1,000 in CHB patients and 10.2/1,000 in controls, increasing to 97.6 and 38.8 in 2015, respectively. The 2006 CKD incidence (per 1,000 person-years) was 10.3 and 4.8 and 15.2 and 11.3 by 2015, respectively (P < 0.05 for all). The strongest predictors for CKD were DM (hazard ratio [HR], 2.48), HTN (HR, 3.29), and CVD (HR, 2.61) (all P < 0.0001). Similar prevalence and incidence changes were observed for OF. The strongest predictors for OF were female gender (HR, 2.22), alcohol use (HR, 2.02), and viral coinfection (HR, 1.37) (all P < 0.0001). Conclusion: Insured CHB patients were older, had more comorbidities, and experienced higher incidence and prevalence of CKD and OF than controls.