tbuckley/cabot-search huggingface dataset:
FOLFIRINOX (F-NOX) followed by individualized radiation for borderline-resectable pancreatic cancer (BRPC): Toxicity, R0 resection, and interim survival data from a prospective phase II study.
Authors: Janet E. Murphy, Jennifer Yon-Li Wo, David P. Ryan, Wenqing Jiang, Beow Y. Yeap, Lorraine C. Drapek, Lawrence Scott Blaszkowsky, Eunice Lee Kwak, Jill N. Allen, Jeffrey W. Clark, Jason Edward Faris, Andrew X. Zhu, Lipika Goyal, Harvey J. Mamon, Brian M. Wolpin, Keith D Lillemoe, Thomas F. DeLaney, Carlos Fernandez-del Castillo, Cristina Ferrone, Theodore S. Hong
Journal: Journal of Clinical Oncology (2017)

4113 Background: F-NOX is increasingly utilized in BRPC as neoadjuvant therapy. However, prospective data remains limited; the largest series is a 22 patient (pt) cooperative group trial (Alliance A021101), in which 14 pts had R0 resection. In this study, we evaluate neoadjuvant F-NOX followed by individualized chemoradiation (CRT) for BRPC. Methods: Pts ECOG PS 0-1 with biopsy-proven BRPC defined by NCCN criteria were enrolled in a single institution, NCI-sponsored phase II study (NCT01591733). Pts received F-NOX for 8 cycles. If after chemotherapy the tumor was radiographically resectable, pts received short course CRT in 5 (protons 25 GyE) or 10 fractions (photons 30 Gy) with capecitabine 825 mg/m2 bid. If the tumor was still abutting vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. Primary endpoint was R0 resection rate. Results: 50 pts were enrolled from 8/2012 to 8/2016. Two pts were ineligible (lung metastasis, negative biopsy); 48 pts were evaluable. Median age was 62y (46-74). Median tumor size was 37 mm (21-56). Thirty-six pts (75%) had pancreatic head tumors. Median follow up was 18.2 months among 31 patients still alive. Of the evaluable pts, 40 (83%) completed therapy. Reasons for not completing therapy include pt withdrawal (3), physician decision (3), unacceptable toxicity (1) and progression (1). Grade 3 or greater toxicity occurred in 48% of pts, but no individual grade 3 toxicity exceeded 15%. Twenty-seven pts (56%) had short course CRT, while 13 pts (27%) had long course CRT. Twenty-nine pts were resected; R0 resection was achieved in 28/29 (96.5%). R0 resection rate among all evaluable pts was 58.3%. Median PFS among all evaluable pts was was 14.7 months; mOS was 37.7 months, with 1y OS 79.5% and 2y OS 59.3%. Among resected patients, mOS has not been reached. 1y PFS was 78.1% and 2y PFS 55.4%; 1y OS was 92.6% and 2y OS was 80.6%. Conclusions: Preoperative F-NOX followed by individualized chemoradiation in BRPC results in high R0 resection rates as well as prolonged mPFS and mOS in this large prospective cohort. Clinical trial information: NCT01591733.
Emergency department diagnosis of gynecologic malignancy versus office diagnosis and association with overall survival in a low-income, racially diverse patient population.
Authors: Jenna Zechmeister Marcus, Deborah Rosenbaum, Jennifer Jorgensen, Gregory M. Gressel, Bruce D. Rapkin, Marina I. Frimer, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2018)

e17571 Background: Twenty to fifty percent of patients with breast, colon and lung cancers are diagnosed in the emergency department globally. The objective of our study was to characterize the association of clinical risk factors, treatment patterns and outcomes with the diagnosis of a gynecologic malignancy in the emergency room compared to the outpatient ambulatory clinic. Methods: After institutional review board approval, women diagnosed with gynecologic malignancies were identified from the Montefiore Medical Center tumor registry between 2009-2015. Data were collected by retrospective chart review including demographics, co-morbidities, histopathological characteristics, treatments, and outcomes. Household incomes were assigned using geocoding and publically available census data. Multivariable logistic regression modeling and Cox proportional hazards survival analyses were performed utilizing Stata 14.2. Results: Of the 241 women with gynecologic malignancies, 62 (25%) were diagnosed in the emergency department. When compared to diagnoses in the ambulatory setting, emergency room cancer diagnoses were associated with lower median income ($35,117 vs. $45,185, p < 0.001), stage IV disease (OR 4.99, 95% CI 2.20- 11.31), lower likelihood of primary surgical management (OR 0.23, 95% CI 0.12-0.43) and Charlson Co-morbidity Index greater than or equal to 2 (OR 3.25, 95% CI 1.46- 7.21). Overall survival was worse for women diagnosed in the emergency department (log rank test p < 0.001). Cox- proportional hazards modeling demonstrated that diagnosis in the emergency department was associated with an increased hazard of death (HR 2.42, 95% CI 1.37-4.28), along with age and stage III/IV disease, adjusting for other covariates. Conclusions: Among a racially diverse population, diagnosis in the emergency department was associated with lower income and advanced stage diagnoses. Adjusting for other clinical risk factors, women diagnosed in the emergency department were less likely to undergo primary surgery and had significantly decreased overall survival.
The prognostic value of serum IL-6 and YKL-40 in patients with metastatic colorectal cancer.
Authors: Benny Vittrup Jensen, Mathias Holsey Gramkow, Camilla Stedstrup Mosgaard, Christian Dehlendorff, Per Pfeiffer, Camilla Qvortrup, Mette K. N. Yilmaz, Finn Ole Larsen, Stig Egil Bojesen, Jakob Hagen Vasehus Schou, Mogens Karsbol Boisen, Dorte Nielsen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2017)

e15060 Background: The prognostic value of serum IL-6, YKL-40 and CEA before first (1) and third line therapy (3LT) in metastatic colorectal cancer (mCRC) is lacking and was evaluated in this study. Methods: From 2004 to 2015 serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 years (range 33-87) and male/female ratio 243(59%)/172(41%). Serum IL-6 (R&amp;D, UK) and YKL-40 (Quidel, USA) were determined by ELISA. Progression-free (PFS) and overall survival (OS), crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated with Cox regression analysis. CEA, IL-6 and YKL-40 were included as log 2 -transformed continuous variables with mutual adjustment between CEA, IL-6 and YKL-40, primary tumor location, sex and age. Results: In 3LT IL-6, YKL-40 and CEA levels were higher (P &lt; 0.001) than in 1LT (IL-6: 9.5 pg/ml [IQR4.2-18.5] vs. 4.6 [2.5-10.5]; YKL-40: 140 ng/ml [77-272] vs. 101 [62-172]; and CEA: 59 ug/l [14-288] vs. 23[5.8-153]). In 3LT univariate analysis showed that increased levels of IL-6, YKL-40 and CEA were associated with shorter PFS (IL-6: HR = 1.19, 95% CI 1.07-1.31, P &lt; 0.01; YKL-40: HR = 1.13, 1.04-1.24, P = 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT only high IL-6 was associated with shorter PFS (HR = 1.09, 1.01-1.17, P = 0.03). In a multivariate analysis only high IL-6 was significantly associated with shorter PFS in 3LT (HR = 1.15, 1.03-1.29, P &lt; 0.01) and none of the biomarkers in 1LT. In 3LT univariate analysis showed that increased levels of all 3 biomarkers were associated with a shorter OS (IL-6: HR = 1.36, 1.23-1.51, P &lt; 0.01; YKL-40: HR = 1.21, 1.10-1.33, P &lt; 0.01; CEA: HR = 1.11, 1.06-1.16, P &lt; 0.01). In 1LT high levels of IL-6 (HR = 1.17, 1.08-1.27, P &lt; 0.01) and YKL-40 (HR = 1.18, 1.00-1.38, P = 0.05), but not CEA, were associated with short OS. In 3LT the multivariate analysis showed that both higher IL-6 (HR = 1.34, 1.20-1.50, P &lt; 0.01) and CEA (HR = 1.09, 1.03-1.14, P &lt; 0.01), but not YKL-40 were significantly associated with a shorter OS. In 1LT only higher IL-6 was associated with a shorter OS (HR = 1.19, 1.08-1.31, P &lt; 0.01) Conclusions: Serum IL-6 and YKL-40 may be useful prognostic biomarkers in combination with CEA in patients with mCRC
In-hospital outcomes of tumor lysis syndrome: A population-based study using the National Inpatient Sample (NIS).
Authors: Urshila Durani, Ronald S. Go
Journal: Journal of Clinical Oncology (2016)

6582 Background: The epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We use the NIS to study outcomes and predictors of mortality in hospitalized patients with TLS. Methods: Years 2010-2013 of the NIS, a nationally representative weighted sample of all US hospital discharges, were queried for patients with TLS (ICD-9 code 277.88). Baseline characteristics and outcomes were analyzed. A multivariable logistic regression analysis was performed to identify predictors of mortality. Results: 30,864 patients had a discharge diagnosis of TLS. The median age was 62 years (IQR 47-72); 37% were female and 70% were white. The most common malignancies were non-Hodgkin lymphoma (32%), acute myeloid leukemia (20%), solid tumor (16%) and acute lymphocytic leukemia (13%). Co-existing renal failure (17%), diabetes mellitus (16%), hypertension (43%), and coagulopathy (38%) were common. The median length of stay was 10 days (IQR 5-21). 43% (95% CI 42-44) of patients developed at least one serious complication and 22% (21-23) died during hospitalization. Rates of complications were: sepsis 22% (21-23), dialysis 15% (14-16), ARDS 23% (22-24), mechanical ventilation 16% (15-17), GI hemorrhage 6% (5-7), cerebral hemorrhage 2% (2-3), seizures 1% (0.6-1), and cardiac arrest 2% (2-3). Significant independent predictors of mortality were older age, solid tumor, seizure, cardiac dysrhythmia, coagulopathy, and liver disease (Table). Conclusions: In the US many patients with TLS develop life-threatening complications and a quarter die during hospitalization. As more cancer treatments become available, strategies to improve the supportive care of patients with TLS should be a priority. Predictors of in-hospital mortality Odds Ratio P-value Age 1.02 0.00 Primary payor - - Private Ref - Medicaid 1.11 0.32 Medicare 0.84 0.04 Self-pay/other 1.22 0.12 Comorbidities - - Hypertension 0.70 < 0.01 Coagulopathy 1.61 < 0.01 Liver disease 1.74 < 0.01 Renal failure 1.05 0.56 Chronic lung disease 1.06 0.52 Congestive heart failure 1.12 0.24 Underlying malignancy - - Solid tumor 1.36 < 0.01 Non-Hodgkin’s lymphoma 0.80 0.01 ALL 0.47 < 0.01 AML 1.21 0.05 CLL 0.61 < 0.01 Seizures 2.60 0.01 Dysrhythmias 1.73 < 0.01
Spatially resolved profiling of colorectal cancer lipid biochemistry via DESI imaging mass spectrometry to reveal morphology-dependent alterations in fatty acid metabolism.
Authors: Reza Mirnezami, Kirill Veselkov, Nicole Strittmatter, Robert D Goldin, James M Kinross, Justin Stebbing, Elaine Holmes, Ara W. Darzi, Jeremy K Nicholson, Zoltan Takats
Journal: Journal of Clinical Oncology (2016)

e15104 Background: Lipid metabolic alterations are recognised as potential oncogenic triggers that promote malignant transformation. Here we performed spatially-resolved profiling of lipid signatures in colorectal cancer (CRC) tissue and matched healthy mucosa using desorption electrospray ionisation imaging mass spectrometry (DESI-MSI). The objectives of this study were to comprehensively define the CRC ‘lipidome’ and to assess lipid signatures in discrete histological regions-of-interest, specifically morphologically bland peri-tumoural epithelium (PT-e) and tumour stroma (T-s). Methods: Fresh frozen tissue sections from 42 patients with confirmed CRC were subjected to negative-ion mode DESI-MSI analysis. Mass spectra in the 200-1000 m/zrange were collated from CRC epithelium (CRC-e), PT-e, T-s and healthy tumour-remote epithelium (TR-e). Spectral signatures were subjected to multivariate analysis using a recursive maximum margin criterion (RMMC) algorithm operating in MATLAB. Results: Increased levels of long/very-long chain fatty acids (LCFA/VLCFA) were seen in CRC-e compared with TR-e(AUC = 0.99). Correspondingly, increased expression of lipogenic and elongase enzymes was found on IHC. Transmission electron microscopy was performed to evaluate peroxisomal distribution and morphology in CRC-e, as these organelles metabolise LCFA/VLCFA through β-oxidation, to negligibly low levels, in healthy cells. No discernible difference in peroxisomal distribution, abundance or structure was found between CRC-e and TR-e. PT-e demonstrated a lipid expression pattern almost identical to that of CRC-e, and markedly different from TR-e (AUC = 0.89). Conclusions: A shift towards increased LCFA/VLCFA production may be an important metabolic trait in CRC facilitated through upregulation of de novo lipogenesis and fatty acid elongation and concurrent impairment of peroxisomal β-oxidation. This phenotype was also observed in morphologically bland PT-e, suggesting that enhanced de novo LCFA/VLCFA biosynthesis and impaired peroxisomal function may represent important steps in peri-tumoural field cancerisation.
Concordance of DNA mismatch repair deficient (dMMR)/microsatellite instability (MSI) assessment by local and central testing in patients with metastatic CRC (mCRC) receiving nivolumab (nivo) in CheckMate 142 study.
Authors: Scott Kopetz, Sara Lonardi, Raymond S. McDermott, Massimo Aglietta, Alain Hendlisz, Michael Morse, Joseph W. Leach, Bart Neyns, Emily Chan, Franklin Chen, Ka Yeung Mark Wong, James J. Lee, Pilar Garcia-Alfonso, Andrew G Hill, Heinz-Josef Lenz, Jayesh Desai, Rebecca Anne Moss, Z. Alexander Cao, Michael J. Overman, Thierry Andre
Journal: Journal of Clinical Oncology (2017)

3548 Background: MMR or MSI testing is recommended for mCRC pts and is often done locally by IHC or PCR testing, respectively (NCCN V1.2017) Nivo, a fully human anti-PD-1 mAb, demonstrated durable responses and a 12-mo OS rate of 73.8% in pts with mCRC locally assessed for dMMR/MSI-H status in the CheckMate 142 study (NCT02060188; Overman M, et al. 2017). Here we describe the results of local and central testing with respect to MMR/MSI status and clinical outcomes in the CheckMate 142 study. Methods: MMR/MSI status was assessed locally on archival tumor using IHC/PCR at screening and confirmed centrally by PCR (modified Bethesda panel) testing of tumor biopsy at enrollment. dMMR was defined by IHC as a loss of expression in ≥1 mismatch repair proteins. Stable microsatellite (MSS), low MSI (MSI-L), and high MSI (MSI-H), were defined as instability in 0, 1, or ≥2 markers, respectively. Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg Q2W. Results: 74 pts were dMMR/MSI-H by local testing. Of these pts, 53 (72%) were centrally confirmed as MSI-H, 7 pts had insufficient tissue sample for PCR testing, and 14 pts had a central test that did not match local test results. Of the 14 pts, 3 pts with a clinical history of LS were identified locally as dMMR but centrally as MSS (Table). INV-reported ORR was 31.1% in 74 pts locally determined as dMMR/MSI-H, 35.8% in 53 pts locally and centrally confirmed as MSI-H, and 21.4% in 14 pts not centrally confirmed as MSI-H. Conclusions: The similar clinical activity between pts locally confirmed as MSI-H and pts who were centrally confirmed as MSI-H suggest local testing is appropriate for identifying the dMMR/MSI-H pts who may benefit from nivo monotherapy. Clinical trial information: NCT02060188. [Table: see text]
Clinical genomic testing of anaplastic thyroid carcinoma (ATC) and need for integration into future prospective clinical trials.
Authors: Vlad Sandulache, Michelle D. Williams, Stephen Yenzen Lai, Charles Lu, William N. William, Naifa Lamki Busaidy, Maria E. Cabanillas
Journal: Journal of Clinical Oncology (2016)

6085 Background: ATC is an aggressive disease requiring rapid diagnosis. Targeted therapeutics provide ATC patients (pts) with previously unavailable treatment options. Development of high throughput next generation sequencing (NGS) platforms provides clinicians with the ability to characterize the genomic background of ATC. In ATC, a rapid, blood based test is ideal for several reasons: Lack of available tumor; Expedited results allowing for expanded treatment options; Enhanced enrollment in clinical trials. Methods: We evaluated consecutive ATC pts treated at MD Anderson between 8/2015 and 12/2015. All pts underwent genomic profiling of tumor and cell free circulating DNA (cfDNA, blood based) using NGS. Results: 14 patients were included. The most commonly mutated genes noted on both platforms were BRAF (7/14) and TP53 (11/14). Concordance between tumor and cfDNA data was high for BRAF, PIK3CA, NRAS and moderate for TP53 (Table). Twelve of 14 pts were slated for treatment, one pt elected hospice and another was observed following outside treatment. Seven pts were initiated on targeted therapy or immunotherapy based in part on tumor genomic data. Mean time to results was 13.6 days with blood-based method vs. 16.8 days with tumor-based method. Conclusions: This is one of the largest cohorts of ATC pts who have undergone blood and tumor based genomic profiling. Based on these data, we recommend utilization of both tumor based and cfDNA analysis in order to maximize sensitivity for putative targets. Integration of cfDNA in clinical trials is recommended, as turn-around time is somewhat shorter than that for tissue based testing. Genetic alterations identified in ATC patients. Genetic alteration TP53 BRAF Other Tissue based testing N=9 (R196, R282W, R175H, E258*, E258K, T170M, M246I, R248Q, Y220C) N=7 (BRAFV600E) N=10 PIK3CA (H1047R, E524K, H1047R, E542K) NRAS, HRAS, CDKN2A, SMARCB1, PTEN, TERT Blood based testing N=11 (R282W, H193R, R267W, R175H, R273S, A189D, M246I, Q192*, P27T, G266R, R248Q) N=5 (BRAFV600E) N=22 PIK3CA (H1047R, E524K, H1047R, E542K) NRAS,BRCA2, AR, PDGFRA, JAK2, CDK4, MAP2K2, PTEN, EGFR, CCNE1, APC, SMO, CCND2, BRCA1, TERT, MET (2)
Preliminary results of the first-in-human, dose-finding PROCLAIM-CX-072 trial of the PD-L1 Probody therapeutic CX-072 as monotherapy in patients (pts) with advanced solid tumors.
Authors: Karen A. Autio, Hendrik-Tobias Arkenau, Bert H. O'Neil, Johanna C. Bendell, Anthony El-Khoueiry, James Strauss, Amy Weise, Nataliya Volodymyrivna Uboha, Naiyer A. Rizvi, Beiyao Zheng, Luc Desnoyers, Mark Stroh, Lori Carman, Rachel W. Humphrey, Matthias Will, Valentina Boni, Alexander I. Spira, Aung Naing
Journal: Journal of Clinical Oncology (2018)

3071 Background: In single-agent trials, antibodies (Abs) targeting programmed cell death ligand 1 (PD-L1) improve survival in many cancers but are associated with immune-related toxicities (most commonly in skin, thyroid, liver, and lung), particularly when administered with other anticancer agents in combination. CX-072 is an anti–PD-L1 Probody therapeutic designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Preclinically, Probody therapeutics exhibited anticancer activity of the parent Ab but reduced toxicities in models of autoimmunity. Methods: This part (A) of the ongoing phase 1-2 PROCLAIM-CX-072 study (Probody Clinical Assessment In Man; NCT03013491) is evaluating CX-072 as monotherapy in a dose escalation cohort in pts with advanced, heavily pretreated solid tumors. Eligible pts include those who are PD-1, PD-L1, and CTLA-4 inhibitor naive, with immunotherapy (IMT) unavailable as a standard of care (SOC) for their disease. CX-072 is given every 14 days in cohorts of doses ranging from 0.03-30 mg/kg IV. Results: Escalation is complete (n=22). Median age is 65 years (range, 32-81); pts had 6 (range, 1-13) prior anticancer treatments. One DLT was observed (grade 3 febrile neutropenia; 3 mg/kg); MTD was not reached. Grade 3-4 treatment-related events were observed in 2 pts: febrile neutropenia/thrombocytopenia (3 mg/kg) and elevated AST/ALT (30 mg/kg). Across all dose levels, best response based on change in target lesions from baseline in 17 evaluable pts included 2 PR (thymoma and PD-L1-negative TNBC), 11 SD, and 4 PD. Target lesions decreased from baseline in 7/17 pts (41%) evaluable as per RECIST v1.1. Target lesions decreased from baseline at dose levels ≥3 mg/kg in 5/8 pts (63%). Conclusions: Preliminary data for CX-072 in heavily pretreated pts with IMT-naive solid tumors where checkpoint blockade is unavailable as SOC for their disease show a manageable safety profile with signals of antitumor activity. These data warrant further exploration of CX-072 as monotherapy and in combination with other checkpoint inhibitors or targeted therapies. Clinical trial information: NCT03013491.
An assessment of the prevalence and incidence of comorbidities among patients with metastatic colorectal cancer in the United States using SEER-Medicare data.
Authors: Kimberly Lowe, Quan Doan, Michelle L. Gleeson, Michael Anthony Kelsh, Gerry C. Bohac, Mark D. Danese
Journal: Journal of Clinical Oncology (2016)

e15082 Background: Understanding the burden of comorbidities in patients with metastatic colorectal cancer (mCRC) may aid in determining the best course of care for patients and improve patient management following treatment. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data, we identified 7,502 patients diagnosed with mCRC from 2007-2011. A cohort of 7,502 cancer-free individuals was frequency-matched by Medicare enrollment year and county of residence. Subjects were ≥ 66 years-old at the time of mCRC diagnosis (defined as the index date) to allow for ≥ 1 full year of Medicare coverage. Prevalence (%) of comorbidities prior to diagnosis and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis were estimated for 55 comorbidities. Rates in cancer-free individuals were standardized to the age, gender, and race distribution of cancer patients. Results: The prevalence (95 % confidence interval [CI]) of most comorbid conditions was modestly higher in patients with mCRC versus the cancer-free individuals. Examples include: hypertension 59.66 (58.57-60.76) vs. 46.36 (45.23-47.49), infectious disease 34.42 (33.36-35.48) vs. 24.65 (23.67-25.62), and anemia 28.42 (27.42-29.42) vs. 13.58 (12.81-14.36). The 3-month incidence (95% CI) of most comorbid conditions was also higher in the cancer patients than the cancer-free individuals. Examples include: gastric perforation 1881.47 (1802.18-1960.76) vs. 12.69 (7.51-17.88), electrolyte disorder 1685.38 (1609.83-1760.92) vs. 51.33 (40.22-62.44), and anemia 1638.86 (1557.61-1720.11) vs. 32.69 (23.89-41.49). Conclusions: The potential reasons for the higher prevalence and incidence of comorbidities among mCRC patients than cancer-free individuals include: increased diagnostic testing, physician visits, and reporting of morbidities that occurs with the diagnosis of cancer, as well as the effects of cancer and its treatment.