tbuckley/cabot-search huggingface dataset:
P01.002 Evaluation of 31-P-MR-Spectroscopy in malignant glioma correlated with histopathological results and intraoperative fluorescence
Authors: C F Freyschlag, J Kerschbaumer, R Steiger, D Pinggera, E R Gizewski, C Thomé
Journal: Neuro-Oncology (2018)

The diffuse infiltration of malignant gliomas underlines the necessity for utmost radicality in surgical treatment with respect to functional outcome. According to previous studies, fluorescence techniques and intraoperative imaging facilitate complete or supratotal resection. MR-algorithms may discover areas at high risk by perfusion, diffusion-weighted imaging and spectroscopy. Extensive preoperative investigation with 31-Phosphorus - MR - Spectroscopy (31PMRS) was hypothesized to determine energy-demand and cell-turnover in surrounding tissue in order to unveil information about infiltration into non-contrast enhancing tissue. Patients who underwent surgery for malignant glioma in non-eloquent areas (n=16), were included in this prospective trial. All underwent preoperative standard MRI, with additional whole brain 31PMRS. In all patients, one voxel within the contrast-enhancing tumor (CE+), one voxel at the border (including CE+ areas and surrounding T2-hyperintensive (T2+)) and one distant voxel, purely including T2+ areas (amenable for supratotal resection) were determined by a neuroradiologist. After standardized application of 5-ALA, image guided craniotomy and frameless stereotactic biopsy were performed, followed by microsurgical resection. The metabolites correlated to the contralateral control, histopathology and fluorescence behavior. Biopsies showed tumor cells and fluorescence in all but one tumor (93%), whereas tumor cells were encountered within the infiltration zone in 81% of biopsies with one positive sample without fluorescence. The surrounding tissue included tumor cells in 7 patients, 4 of which were fluorescence negative. Values for resynthesis (CE+/border/T2+: 1,050 ± 0,300/1,029 ± 0,290/1,104 ± 0,277), hydrolysis (0,295 ± 0,241/0,294 ± 0,259/0,332 ± 0,298), energy demand (5,207 ± 13,569/3,938 ± 3,383/3,716 ± 2,004) and membrane turnover (1,367 ± 1,277/1,267 ± 1,092/1,122 ± 0,649) were obtained. Membrane-turnover was significantly higher in CE+, border zone and also in the T2+ areas, when compared to the control (p>0,001; p>0,002). 31PMRS in malignant gliomas provided information on metabolic changes tumor and surrounding edema. There was a evidence of infiltration by tumor cells in biopsies regardless of intraoperative fluorescence.
Estimated glomerular filtration rate: Do we measure the real renal function or are we still groping in the dark?
Authors: Francesco Trevisani, Umberto Capitanio, Alessandro Larcher, Luigi Gianolli, Alessandra Cinque, Arianna Bettiga, Riccardo Vago, Federico Di Marco, Lina Bua, Flaviano Dosio, Roberto Bertini, Andrea Salonia, Alberto Briganti, Natalia Negrin, Anna Gonzales Rinne, Armando Torres, Sergio Luis Lima, Esteban Porrini, Francesco Montorsi
Journal: Journal of Clinical Oncology (2018)

e18809 Background: An accurate assessment of renal function is mandatory in the majority or urological and oncological patients to prevent renal impairment and cancer non-related deaths. Nowadays, the large part of clinicians apply CKD-EPI/MDRD formulas or 24h creatinine clearance to determine the glomerular filtration rate (GFR) for renal surgery (for cancer, donation, etc) and in metastatic patients for establish the right oncological treatment. Unfortunately, estimated GFR (eGFR) displays an error in reflecting real kidney function with measured GFR (mGFR) and this may lead to consequences in the correct evaluations. Methods: A retrospective and prospective study based on 1001 pts composed by 665 pts with uro-oncological cancer (444) or renal functional diseases (221), by 210 pts with non- urological cancer and by 126 pts with nephrological disease was performed in two different centers to compare eGFR formula with renal scintigraphy (N = 1001). The agreement between eGFR and mGFR was evaluated using total deviation index (TDI) and concordance correlation coefficient (CCC). Results: The agreement between formulas and mGFR was poor. The TDI for MDRD was 80% and for CKD-EPI was 74%, indicating that 90% of the estimations for both formulas were included within a margin of error from mGFR of about ± 74 to 80%. CCC for MDRD was 0.73 and for CKD-EPI was 0.77, indicating poor concordance. The population, using eGFR formula (CKD- EPI/MDRD), was composed by 29%-22% of CKD I pts (eGFR > 90 ml/min), 33%-35% CKD II, 15%-19% CKD IIIa, 14%-15% CKD IIIb, 8%-8% CKD IV, 1%-1% CKD V. Using Renal Scintigraphy measurements, we revealed different proportions: 33% CKD I, 30% CKD II, 19% CKD IIIa, 13 % CKD IIIb, 5% CKD IV, 0% CKD V. Moreover, the discrepancy between mGFR with renal scintigraphy and eGFR with formulas was of 30% in CKD I, 54% in CKD II, 63% in CKD IIIa, 62% in CKD IIIb, 63% in CKD IV, 81% in CKD V. Conclusions: Formulas may over or underestimate mGFR in pts, generating false evaluations in the clinical management and drug therapies for oncological, urological and kidney donor patients. We suggest to use mGFR with renal scintigraphy in selected cases when GFR is crucial to determine the surgical/therapeutic approach.
Abstract 18952: Mir-130 Targets Apcdd1 Expression to Inhibit Adipocyte Differentiation: Role in Diet-Induced Obesity
Authors: Ha Won Kim, Kan Hui (Nicole) Yiew, Rod Pellenberg, Tapan K Chatterjee, Yao Liang Tang, Zsolt Bagi, ViJay Patel, David Hui, Neal L Weintraub
Journal: Circulation (2016)

Background: Impaired adipocyte differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to cardiometabolic disease. We recently report...
A randomized, double-blind phase III study of ibrutinib versus placebo in combination with corticosteroids in patients with new onset chronic graft versus host disease.
Authors: David Bernard Miklos, Madan H. Jagasia, Hildegard Greinix, Bor-Sheng Ko, David A. Jacobsohn, Ahmad Mokatrin, Jason Dubovsky, Biljana Horn, Bernhard Hauns, Lori Appel Styles, Mary Flowers
Journal: Journal of Clinical Oncology (2017)

TPS7072 Background: Chronic graft versus host disease (cGVHD) is a common complication of allogeneic stem cell transplantation, with pathophysiology involving alloreactive and dysregulated T and B cells and innate immune populations. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of patients (pts) with CLL/SLL. Ibrutinib recently received breakthrough therapy and orphan drug designation for the treatment of pts with cGVHD who did not respond to one or more lines of systemic therapy. Ibrutinib reduces severity of cGVHD in murine models and recently was shown to achieve an NIH-defined overall response rate of 67% in pts with steroid relapsed/refractory cGVHD (Miklos Blood 2016). Methods: The primary objective of this Phase 3, multicenter, international, randomized, controlled, double-blind study is to evaluate the 24-week response rate of ibrutinib versus placebo in combination with prednisone. Pts with newly diagnosed moderate or severe cGVHD, as per NIH Consensus Development Project Criteria (2014), will be randomized in a 1:1 ratio to receive either oral ibrutinib (arm A) or placebo (arm B) in combination with oral prednisone. Ibrutinib or placebo will be given until unacceptable toxicity, relapse of underlying disease, death, or the need for a new systemic treatment for progressive cGVHD. Eligible study pts (age ≥12 yrs) must require systemic treatment with corticosteroids and have no prior systemic treatment for cGVHD. The primary endpoint is response rate (complete or partial response) at 24 weeks, as per NIH Consensus Development Project Criteria, and must occur in the absence of both new therapy for cGVHD and relapse/return of the underlying disease that was the indication for transplant. Secondary endpoints will assess for additional clinical benefit including corticosteroid dose reduction, improvement of Lee cGVHD Symptom Scale scores, withdrawal of all immunosuppressants, and overall survival. This study is currently enrolling pts. Funding source: Pharmacyclics LLC, an AbbVie Company. Clinical trial information: NCT02959944.
NRG Oncology/NSABP B-31: Stromal tumor infiltrating lymphocytes (sTILs) and outcomes in early-stage HER2-positive breast cancer (BC).
Authors: Rim S. Kim, Nan Song, Patrick G. Gavin, Roberto Salgado, Hanna Bandos, Zuzana Kos, Giuseppe Floris, Gert G. Van den Eynden, Sunil S. Badve, Priya Rastogi, Louis Fehrenbacher, Eleftherios P. Mamounas, Sandra M. Swain, Donald Lawrence Wickerham, Peter C. Lucas, Joseph P. Costantino, Charles E. Geyer, Norman Wolmark, Soonmyung Paik, Katherine L. Pogue-Geile
Journal: Journal of Clinical Oncology (2018)

12010 Background: Stromal tumor infiltrating lymphocytes (sTILs) in HER2-positive and triple-negative breast cancer (BC) are associated with prognosis and treatment response. NSABP B-31 evaluated chemotherapy (C) v C + trastuzumab (CT) for early-stage HER2-positive BC. Methods: Based on International Immuno-Oncology Working Group (IIOWG) guidelines, sTILs were assessed by RSK in 1581/2016 eligible B-31 cases with available slides for H&E review, and as a semi-continuous variable (SCV) in 10% intervals. RSK and five pathologists from the IIOWG reviewed 100 of the cases as a consensus study. sTILs as an SCV and with a predefined lymphocyte-predominant BC (LPBC as > 50% sTILs) were correlated with disease-free survival (DFS), the primary endpoint of B-31. sTILs were also correlated with clinicopathological characteristics, genotyping, intrinsic subtype, gene expression, and mutation profiling. Cox proportional hazard models were used, with p-values < 0.05 considered significant. Results: In both the C and CT arms, increases in sTILs, defined either as a SCV (combined arms HR 0.42, 95% CI 0.27-0.64, p < 0.01) or as LPBC (combined arms HR 0.65, 95% CI 0.49-0.86, p = 0.003), were significantly associated with improved DFS. However, there was no association of sTIL levels with degree of trastuzumab benefit (interaction p = 0.556). ER status by IHC was inversely associated with sTILs (p < 0.01). High sTILs were significantly associated with basal- and HER2- enriched intrinsic subtypes, and the high-benefit group by 8-gene expression model. None of the PIK3CA mutations or genotyping of Fc gamma receptors were associated with sTILs. The mean concordance between RSK and the other pathologists was 90.8%. Conclusions: sTILs were significantly associated with improved DFS in pts with early-stage HER2-positive BC treated with chemotherapy on B-31. However, sTILs were not associated with degree of trastuzumab benefit. sTILs may have utility as a prognostic biomarker to help to define pts with HER2-positive early BC, at low risk for recurrence. Pooled analysis in this clinical context is warranted. SUPPORT: U10CA180868, -180822, UG1-189867, U24-196067, PA DOH; Breast Cancer Research Foundation
A phase 1/2 dose escalation and expansion study of bemcentinib (BGB324), a first-in-class, selective AXL inhibitor, with docetaxel in patients with previously treated non-squamous NSCLC.
Authors: Sawsan Rashdan, Jessica N. Williams, Penny Currykosky, Farjana Fattah, Jonathan Padro, Katarzyna Wnuk-Lipinska, Gro Gausdal, Anthony Brown, David Micklem, Robert J Holt, James Lorens, Murray Yule, David E. Gerber
Journal: Journal of Clinical Oncology (2018)

e21043 Background: AXL is a receptor tyrosine kinase expressed on a variety of tumours as well as innate immune cells. AXL functions to regulate multiple cellular processes including tumour cell survival and proliferation, as well as immunosuppression in the tumour microenvironment. AXL over-expression is an independent negative prognostic factor linked with treatment resistance and poor outcomes in NSCLC. Bemcentinib (BGB324) is a selective orally bioavailable small molecule AXL kinase inhibitor in ph 2 clinical development across multiple cancer indications including combination trials in NSCLC. Preclinically, the combination of bemcentinib with docetaxel was shown to be additive in in vivo models of NSCLC. BGBIL005 is an open-label, investigator-initiated dose escalation and expansion trial designed to assess the safety, tolerability, preliminary efficacy, and biomarkers of bemcentinib in combination with docetaxel in previously treated NSCLC. Methods: Dose escalation of daily bemcentinib in combination with docetaxel (60 or 75 mg/m2 q3wks) followed a standard 3+3 design and was to be performed until the occurrence of Grade 3 or worse non-haematological toxicity or significant hematological toxicity during the first cycle of treatment. Tumor responses were assessed per investigator using RECIST v1.1. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) in patients pre-dose and at C2D1. Results: 11 pts have been treated. The starting dose of 75 mg/m2 docetaxel and 100 mg daily of bemcentinib led to 2 hematological DLTs, thus recruitment is currently ongoing at 60 mg/m2 docetaxel and 100 mg bemcentinib. Confirmed objective responses have been reported at both dose levels. Out of the first 7 pts evaluated, 2 partial responses (29%) were reported as well as 2 stable diseases (29%). Candidate predictive and pharmacodynamic biomarkers have been identified. Conclusions: The combination of bemcentinib and docetaxel is active in the treatment of advanced non-squamous NSCLC. Predictive biomarker candidates will continue to be explored. Clinical trial information: NCT02922777.
Cancer epidemiology in Connecticut prisons.
Authors: Debasmita Saha, Susan Tannenbaum
Journal: Journal of Clinical Oncology (2016)

e18055 Background: In 2013, based on the Bureau of Justice’s latest statistics, 90% of deaths in state prisons were illness-related, 31% of these were due to cancer (CA) followed by heart disease (26%). The demographics of prisoners place them at a higher than ordinary CA risk. The majority of incarcerated cancer patients (ICPs) are young men with viral infections and history of substance abuse. As the University of Connecticut (UCONN Health) is the primary CA care provider for all of CT’s correctional facilities, we aimed to characterize the epidemiology of ICPs in our state. Methods: Based on UCONN’s Tumor Registry, adult ICPs encountered from July 2012 to June 2015 were identified. Demographic and tumor information were collected from UCONN’s electronic medical record and logged in a secure online database (REDCap). Results: 101 ICPs were identified of whom 17 were females. The male: female ratio in ICPs was 1:5, equivalent to the ratio of the general prison population. There were 49 whites, 38 blacks and 15 Hispanics. The average age was 47.6 and the average body mass index was 28. 60 had an ECOG performance status of 0 to 1. 76 were smokers with 35 average pack-years and 57 had a history of illicit drug abuse. Of the 51 with a history of alcohol use, 27 consumed over 7 drinks per week. The prevalence of HIV, hepatitis B and hepatitis C amongst those tested were 38%, 20% and 64% respectively, comprising of 31 patients. 7 had a prior history of CA and 32 had a known first degree relative with CA. Of the 22 with hematological malignancies, 10 had lymphomas. 79 had solid tumors with 7 being non-invasive; gastrointestinal (21) of which 7 were hepatocellular, prostate (11), lung (7), head/neck (7), thyroid (6), breast (4) and sarcoma (4). 25 of the solid CAs presented with stage 3 or 4 diseases and 27 had intermediate to high grade histology. On follow up, 8 ICPs developed a second CA, 50 were released and subsequently lost to follow up. 13 were eventually confirmed dead, 10 of whom were enrolled in hospice. Conclusions: Our country’s correctional facilities contain a significant population with health disparities which may lead to different CA patterns. Understanding the differences in demographics and risk factors in this high risk population will help guide a more directed preventive and treatment strategies.
Challenges of diagnostic concordance of lung cancer cases in Qualified Clinical Data Registry (QCDR) measure collection by CMS in calculating MACRA's rewards and penalties.
Authors: Shawn Dana Glisson, Patricia Anne Goede, Timothy Craig Allen
Journal: Journal of Clinical Oncology (2017)

6604 Background: QCDR was introduced for the Physician Quality Reporting System (PQRS) beginning in 2014. A QCDR is a CMS-approved entity that collects medical and/or clinical data for the purpose of patient and disease tracking to foster improvement in the quality of care provided to patients. Those who satisfactorily participate in PQRS through a QCDR may avoid the 2018 negative payment adjustment -2.0% of total Medicare payments. PQRS #396 is an example of a measurement by which oncologists may be evaluated. A physician’s QCDR score is determined by his/her numerator and denominator per patient based on total data submitted by various healthcare providers. Methods: IRB approval was obtained for a retrospective review of 60 randomly selected NSCLC pathology reports that were diagnosed at UTMB. The Denominator was determined by CMS to be: The patients were between the ages of 18-75; the diagnosis of NSCLC was coded by the appropriate ICD and CPT codes. The Numerator was determined by CMS to be: Pathology reports with a diagnosis that included pT pN for NSCLC with histologic type vs those not documented for medical reasons vs those specimens that were not of lung origin, or were classified as NSCLC-NOS. Results: The study consisted of 60 NSCLC pathology reports of which 2 were determined in retrospect not to have been lung cancer cases. Another 10 were considered to be incomplete. A final 2 were diagnosed as a different histological lung cancer type. As [60 - (2+10+2)]/60 = 76.67%, adherence to the quality standard was less than perfect even though excellent medical care was delivered. This score puts the institution at risk of a 2% Medicare Payment Reduction in 2018 if a majority of other institutions score even slightly higher. Conclusions: Physician remuneration will be reduced by current information submitted to CMS. As the quality scores will be made public, reputations may be negatively impacted. Coding and billing operations may be hindered in their attempt to accurately submit data to CMS. Healthcare Systems may be less inclined to request outside consults (including NGS) that may provide a different diagnosis that could confuse the QCDR.
Influence of chemotherapy combined with radiotherapy on the time-to-development of radiation-induced sarcomas: A multicenter, retrospective analysis.
Authors: Alison Yan Zhang, Ian Robert Judson, Charlotte Benson, Jay Wunder, Isabelle Laure Ray-Coquard, Robert Grimer, Richard Hong Hui Quek, Eva Wong, Aisha Miah, Peter Charles Ferguson, Armelle Dufresne, Jonathan Yi Hui Teh, Martin R. Stockler, Martin HN Tattersall
Journal: Journal of Clinical Oncology (2017)

11046 Background: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present an international multi-centre collaborative study to validate this association. Methods: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between the 1 st January, 2000 to 31 st December, 2014. The primary endpoint was time to development of RIS, defined as the date of diagnosis of the first malignancy to date of the RIS diagnosis. We also assessed the relationship between chemotherapy, patient and cancer characteristics, and time to RIS. Results: We identified 419 patients with RIS, who were predominantly diagnosed with their first malignancy at adulthood. The median interval from the index cancer to development of RIS for the entire cohort was 11 years (range 1-64). Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1·37; 95% CI: 1·08-1·72; P = 0·009). In the multi-variable model, older age (HR 2·11; CI 1·83-2·43; P &lt; 0·001) and chemotherapy for the first malignancy (HR 1·61; CI 1·26-2·05; P &lt; 0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect. Conclusions: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of a RIS. Our data highlights the importance of vigilance in surveillance for RIS after chemotherapy and radiation therapy, particularly in younger patients who also have a longer potential time to develop a second malignancy.
Cold Agglutinins in Mycoplasma Infection—Reply
Authors: Brady Stein, Nicole DeCredico, Luke Hillman
Journal: JAMA (2018)

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