tbuckley/cabot-search huggingface dataset:
Correlation between genetic mutation state and cancer-associated thrombosis in advanced cancer patients.
Authors: Da Jiang, Xue Zhang, Jing Zuo, Yu Su, Ying Li, Yapei Zhang
Journal: Journal of Clinical Oncology (2018)

e13524 Background: To investigate the correlation between genetic mutation state and cancer-associated thrombosis in advanced cancer patients. Methods: 133 cases of advanced cancer patients were divided into mutation group and non-mutation group according to their genetic states. Venous Doppler ultrasound examination was performed to determine the incidence of thrombosis. Incidence of thrombosis was compared between 2 groups. Genetic mutation rate was calculated in thrombosis patients. Risk factors for thrombosis were analyzed in 2 groups. Sensitivity and specificity were compared using Khorana risk assessment model. Low-risk subgroups/middle-risk subgroups/high-risk subgroups were determined by Khorana risk assessment model in mutation/non-mutation group. Incidence of thrombosis were compared between corresponding subgroups (low-risk to low-risk, middle-risk to middle-risk, high-risk to high-risk). Results:Genetic mutation rate was 75.2% in all patients. Thrombosis rate was 13.53% in all patients. Genetic mutation rate in thrombosis patients was 88.89%. 2. Thrombosis rates in mutation/non-mutation group were 16.0% and 6.1%, respectively (P = 0.2490). 3. The thrombosis rates in EGFR, ALK, TP53, Her-2, KRAS, PIK3CA, T790M gene mutation were 27.8%, 5.6%, 33.3%, 5.6%, 11.1%, 0, 5.6%, respectively (P = 0.248,0.873,0.804,1.000,0.959,0.469,1.000). 4. Sensitivity and specificity in mutation group were 16.8% and 60.0% in Khorana risk assessment model. In non-mutation group those were 6.9% and 100.0%, respectively. AUC for 2 groups ROC were 0.571 and 0419, respectively (P > 0.05). 5. Thrombosis rates for each corresponding subgroups were 33.3% vs 0% (mutation low-risk subgroup vs non-mutation low-risk subgroup), 10.7% vs 7.1% (mutation middle-risk subgroup vs non-mutation middle-risk subgroup) and 57.1% vs 0% (mutation high-risk subgroup vs non-mutation high-risk subgroup). P values were 0.497, 0.940, 1, separately. Conclusions: There is no correlation between genetic mutation state and cancer-associated thrombosis in advanced cancer patients.
Beyond BRCA1/2: Clinician-reported utility 3 years post panel testing.
Authors: Edward D. Esplin, Anu B. Chittenden, Jill Stopfer, Katherine Schneider, Rosalba Sacca, Samantha Stickevers, Lindsay Kipnis, Diane R. Koeller, Shraddha Gaonkar, Jilliane Sotelo, Whitney Espinel, Marjan Champine, Judith Westman, Pamela Brock, Kate P. Shane-Carson, Rachel Pearlman, Robert Pilarski, Kevin Sweet, Joanne M. Jeter, Heather Hampel
Journal: Journal of Clinical Oncology (2018)

e18705 Background: Germline testing guidelines are centered on BRCA1 and BRCA2 despite clear medical management recommendations in several other high and moderate penetrance genes. Clinician utilization of findings in these genes is not well studied. We report results from a multisite clinical utility study in breast cancer patients with pathogenic/likely pathogenic (P/LP) variants in cancer risk genes beyond BRCA1/2. Methods: We retrospectively examined 2,184 patients undergoing multigene testing. Clinicians completed case report forms (CRF) describing genetic test result based clinical actions for patients with P/LP findings in a non-BRCA1/2 cancer risk gene. De-identified CRFs were returned for 104 patients. Results: In 80% of cases, clinicians reported that counseling and/or clinical management recommendations were changed for the patient and/or patient’s family members based on the genetic test findings, with 57% (60/104) of patients receiving result-based recommendations. Changes in clinical management were made for over 60% of patients with P/LP variants in both high-risk genes (APC, CDH1, MSH2, MSH6, PALB2, PTEN, TP53 ) and moderate-risk genes (ATM, CHEK2, RAD51C). For example, 70% of patients in this study were potentially eligible for an actively enrolling PARP inhibitor trial based on their BRCA wild-type status and their germline mutation beyond BRCA, one of whom was already enrolled based on her germline RAD51C mutation status (NCT02401347). Conclusions: This study provides evidence that P/LP variants in cancer genes beyond BRCA1/2 changed clinical management for a majority of patients, and have already impacted patients’ health outcomes. P/LP findings in genes beyond BRCA1/2 have clinical utility in patient care consistent with established management guidelines, however, insurance does not always cover testing for these genes. More research is needed to understand barriers to patients following through on germline genetic result based medical management recommendations.
Phase II trial of sorafenib combined with on-demand transarterial chemoembolization for advanced stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C): STAB study.
Authors: Yozo Sato, Hideyuki Nishiofuku, Taku Yasumoto, Atsuhiro Nakatsuka, Kunihiro Matsuo, Yoshihisa Kodama, Daisuke Abo, Hironao Okubo, Haruyuki Takaki, Yoshitaka Inaba, Koichiro Yamakado, Shozo Hirota
Journal: Journal of Clinical Oncology (2017)

e15648 Background: Sorafenib has been acknowledged as a standard treatment for advanced stage hepatocellular carcinoma (HCC). This study was conducted to evaluate the safety and efficacy of combination therapy of sorafenib and on-demand transarterial chemoembolization (TACE) for advanced stage HCC. Methods: Inclusion criteria were advanced stage HCC (Barcelona Clinic Liver Cancer stage C), a systemic chemotherapy native status, an Eastern Cooperative Oncology Group performance status 0–1, and a Child-Pugh grade-A. Sorafenib therapy (800 mg daily) was started 4–28 days after TACE. On-demand TACE was allowed. The primary endpoint was the completion rate of protocol treatment, which was defined as sorafenib administration at least for 2 months from initial TACE. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Results: From July 2013 to September 2015, a total of 32 patients were registered from 9 institutions, but one patient was excluded because his tumor turned out to be combined hepatocellular carcinoma and cholangiocarcinoma. The protocol treatment was completed in 28 of 31 enrolled patients (90.3%, 28/31). The median treatment duration was 7.0 months (range 0.5–30) with the median number of TACE was 1 (range 1–4) and the median sorafenib dosage of 400 mg daily (range 154-800). The ORR and DCR were 77% and 90%, respectively. Median OS and PFS were 17.3 months [95% confidence interval (CI), 11.9–22.6] and 5.4 months (95% CI, 4.6–6.2), respectively. The most common grade-3 or -4 adverse events were increased aspartate aminotransferase (55%, 17/31), increased alanine aminotransferase (45% 14/31), and hypertension (23%, 7/31). Conclusions: Combination therapy of sorafenib and on-demand TACE was well tolerated and safe. Furthermore, this combination treatment may provide a survival benefit to patients with advanced stage HCC. Clinical trial information: UMIN000014213.
Use of acute-devoted departments (ADD) in cancer patients at the end of life in an Italian homogeneous area: Preliminary data.
Authors: Ilaria Panzini, Elisabetta Fabbri, Marco Maltoni, Chiara Cherubini, Davide Gallegati, Oriana Nanni, Ilaria Massa, Lucia Rossi, Lorenzo Gianni, Davide Tassinari
Journal: Journal of Clinical Oncology (2016)

e18180 Background: To assess the attitude of using ADD in the clinical assistance of cancer patients at the end of life in an homogeneous area of the north-east of Italy. Methods: The records of all cancer patients that deceased in 2 different district of Romagna (an homogeneous area of the north-east of Italy) in 2013 were reviewed. For all the patients were reported name, sex, age in 2013, kind of disease date and place of death, use of hospice or ADD in the last 30 days of life. Primary aim of the trial was to assess the number of patients admitted in ADD in the last 30 days of life; secondary end points were the differences in the different districts of the Area, the use of hospice care in the last 30 days of life, the number of patients dead in ADD or Hospice. The results are the preliminary phase of an integrated process of audit in the area on the effectiveness of the integration between oncology and palliative care and the comprehensive quality of care in favor of patients with advanced cancer. Results: The 2 district of Romagna accounted 727196 inhabitants and 2260 deaths for cancer in 2013. The 2 districts refer to 2 oncologic departments and 2 hospices with home care services, with a partial integration between the 2 services. In the 2 districts there were respectively 335199 and 391997 inhabitants, and 967 and 1293 deaths for cancer in 2013. The main data of our research are reported in the table. Conclusions: Our data confirm the trend for cancer patients of using ADD or Emergency Rooms in the last part of life, reducing the comprehensive quality of the care and increasing the costs of the assistance. A clinical audit is probably needed to assess the critical aspects of the assistance to improve the quality of this phase of oncologic care. Center Patients admitted in ADD (%) Patients admitted in Emergency Rooms (%) Mean Stay in ADD (days) Patients deceased in ADD (%) Patients admitted in hospice care (%) District 1 549 (56.77) 559 (57.81) 12 395 (40.85) 155 (16.03) District 2 649 (50.19) 690 (53.36) 10 467 (36.11) Not Available Total 1198 (53) 1249 (55.26) 11 862 (38.14) Not Available
Quality-adjusted time without symptoms or toxicity (Q-TWiST): Analysis of cabozantinib (Cabo) vs sunitinib (Sun) in patients with advanced renal cell carcinoma (aRCC) of intermediate or poor risk (Alliance A031203).
Authors: Ronald C. Chen, Marion Feuilly, Jie Meng, Johanna Lister, Florence Marteau, Michael J. Morris, Daniel J. George, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

4556 Background: CABOSUN (NCT01835158), a randomized, open-label phase II trial, demonstrated significant improvement in progression-free survival with Cabo (8.6 months) versus Sun (5.3) months) in the first-line treatment of patients with intermediate- or poor-risk clear cell aRCC. To evaluate the overall treatment difference, we conducted a post hoc analysis using a quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) methodology. Methods: Each patient's overall survival was partitioned into 3 mutually exclusive health states: time with grade 3/4 toxicity (TOX) before progression; time without symptoms of disease progression or grade 3/4 toxicity (TWiST); and time after progression or relapse (REL). Time spent in each state was weighted by a health-state utility associated with that state and summed to calculate Q-TWiST. A threshold utility analysis was used, applying utilities across a range of 0 (death) to 1 (perfect health). Results: The analysis period was 650 days (d) (median survival follow-up period). Mean time spent with TWiST was 121 d (95% confidence interval, 43–199) longer for Cabo compared with Sun. Mean time spent with TOX was 8 d longer for Cabo; mean time spent with REL was 104 d shorter for Cabo. In the threshold utility analysis, the difference in Q-TWiST ranged from 129 d (TOX = 1, REL = 0) to 17 d (TOX = 0, REL = 1) in favor of Cabo across all utility combinations. When considering relative utility weights consistent with those observed in aRCC patients (TOX = 0.5, REL = 0.5), the difference in Q-TWiST was 73 d in favor of Cabo. Conclusions: Treatment with Cabo was associated with longer Q-TWiST compared with Sun, primarily due to longer time without symptoms of disease or grade 3/4 toxicities. This analysis, which accounts for disease control efficacy, treatment toxicity and health-related quality of life, provides clinicians with a measure of Cabo and Sun treatment differences on the quality of survival to help with clinical decision-making. Support for CaboSun: U10CA180821, U10CA180882; funding for present study: Ipsen. Clinical trial information: NCT01835158.
1p19q codeletion and RET rearrangements in small cell lung cancer.
Authors: Hongyang Lu, Jing Qin, Haimiao Xu, Na Han, Fajun Xie, Yun Fan, Weimin Mao
Journal: Journal of Clinical Oncology (2016)

e20102 Background: The prognosis of SCLC is very poor, despite trends toward modest improvement in survival. No targeted agents have been approved for small-cell lung cancer (SCLC) patients to date, and chemotherapy is also the cornerstone of the treatment. A lot of researches were focus on precision medicine to improve prognosis of SCLC. Precise molecular diagnosis is the basis of precision treatment, and it is important to know the molecular characteristic of SCLC such as 1p19q codeletion and RET rearrangements. Temozolomide can be recommended for relapse SCLC and its therapeutic effect is related to 1p19q codeletion in anaplastic oligodendroglial tumors. NSCLC patients with RET rearrangements may be effective to cabozantinib.The purpose of this study is to know 1p19q codeletion and RET rearrangements in SCLC. Methods: 32 SCLC resected specimens were retrospectively collected in Zhejiang Cancer Hospital, China, between 2008 and 2014. Fluorescence in situ hybridization (FISH) was used to detect 1p19q codeletion and RET rearrangement. Results: Of the 32 examined SCLC specimens, 1p deletion was detected in eleven patients, 19q deletion was 6 patients, and only 3 patients were found with be1p19q codeletion and none patients were RET rearrangements. Three patients with 1p19q codeletion were follow-up for 58, 50, and 30 months respectively and are all alive now. Conclusions: RET rearrangements may be not an ideal molecular target. 1p19q codeletion is promising in SCLC, and it may suggest a good prognosis.
Prognostic factors for survival in locally advanced NSCLC treated with concurrent chemo- radiation: An institutional analysis.
Authors: Sowmini Medavaram, Amna Falak Sher, Barbara Nemesure, Roger Keresztes
Journal: Journal of Clinical Oncology (2018)

e20512 Title: Prognostic factors for survival in locally advanced NSCLC treated with concurrent chemoradiation (CRT): An institutional analysis Background: CRT is the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Analysis of prognostic factors in NSCLC has defined patient subsets with varying survival .There is limited data about these factors in patients treated with CRT. The purpose of this study is to explore factors predictive of survival in this patient population. Methods: In this retrospective study, data from patients with locally advanced NSCLC, treated with CRT at Stony Brook University Hospital from 2007 to 2015 were collected. Age, gender, histology, TNM stage and number of positive lymph node stations (PLNS) were evaluated as independent prognostic factors.3-year Kaplan-Meier survival curves were generated and log rank tests were used to evaluate the difference in survival between groups. Results: 134 patients were included in the study. 3-year overall survival (OS) was 24.6 %, which was comparable to estimates published in literature. Advanced stage and number of nodal stations significantly affected OS. 3-year OS for stage II, III and IV patients was 42.9%, 25.5 % and 0% (p = 0.006), respectively. Patients with less than 3 PLNS had improved OS outcomes compared to those with 3 or more PLNS (29.7% vs 18.3%, p = 0.019). Age, gender and histology did not significantly affect survival. Conclusions: TNM stage and number of PLNS have the greatest impact on survival in locally advanced NSCLC patients treated with CRT. Our study suggests that these factors should be included in risk stratification models in this patient population. 3-Yr OS in Locally advanced NSCLC treated with CRT Variables No. of patients 3-Yr OS % P value Age (yrs) < 65 57 17.5 0.234 65+ 77 29.9 Gender Male 66 24.2 0.761 Female 68 25.0 Stage* II 7 42.9 0.006 III 110 25.5 IV 12 0.0 Nodal Stations < 3 74 29.7 0.019 3+ 60 18.3 Histology Squamous 58 22.4 0.76 Non squamous 76 26.3 Total 134 24.6 *5 patients were missing information on stage
Intensive first line FIr-C/FOx-C association of triplet chemotherapy plus cetuximab in <i>RAS</i> wild-type metastatic colorectal cancer patients: Preliminary phase II data and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers.
Authors: Gemma Bruera, Silvia Massacese, Francesco Pepe, Umberto Malapelle, Antonella Dal Mas, Eugenio Ciacco, Giuseppe Calvisi, Paolo Marchetti, Giancarlo Troncone, Maurizio Simmaco, Enrico Ricevuto
Journal: Journal of Clinical Oncology (2018)

e15517 Background: Intensive triplet chemotherapy/bevacizumab significantly increased MCRC outcome. Phase II study investigated safety/activity of FIr-C/FOx-C triplet/cetuximab (CET) in first-line RAS wild-type and prediction of individual limiting toxicity syndromes (LTS) by pharmacogenomic biomarkers. Methods: Simon two-step design: p0 70%, p1 85%, power 80%, α5%, β20%; projected ORR I step 14/19. FIr-C/FOx-C: 5-fluorouracil (5-FU) 12h-timed-flat-infusion 900 mg/m2 d1-2,8-9,15-16,22-23; irinotecan (CPT-11) 160 mg/m2 d1,15, oxaliplatin 80 mg/m2 d8,22; CET 400 then 250 mg/m2 d1,8,15,22; every 28d. Toxicity, individual LTS evaluated, compared by chi-square test; activity/efficacy by log-rank. 5-FU/CPT-11 pharmacogenomic biomarkers, 5-FU degradation rate (5-FUDR), SNPs ABCB1, CYP3A4, DYPD, UGT1A1 evaluated in patients with LTS and at recommended dose. Results: Enrolled: 29 patients < 75 years, primary/intermediate CIRS; from 04/2014 KRAS/NRAS wild-type; median age 59; 7 young-elderly (yE) 24%; 7 liver-limited (L-L) 24%. Recommended CPT-11/5-FU 120/750 mg/m2. Primary endpoint met: OR 14/18 78% as-treated, confirmed in preliminary phase II 17/23 74% intent-to-treat. Liver metastasectomies 14%, 57% L-L. At median follow-up 18 months, PFS 12, OS 23 months. At recommended doses, received DI > 80%; G3-4 toxicities: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%; LTS 19 (65.5%), 83% yE. LTS prevalently multiple (ms) vs single site (59 vs 7% p 0.006). Reduced FUDR 56%, SNPs CYP3A4 22%, UGT1A1 71%, > 2 positive pharmacogenomics biomarkers 78% prevalently in patients with gastrointestinal LTS. Conclusions: Intensive first-line FIr-C/FOx-C at recommended doses is tolerable, highly effective in RAS wild-type. Reduced FUDR, CYP3A4, UGT1A1 SNPs may predict individual LTS-ms to select fit patients. Prospective studies personalized by toxicity biomarkers will confirm efficacy. Clinical trial information: Numero EudraCT 2009-016793-32.
Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Signe Holst Søegaard, Klaus Rostgaard, Kristin Skogstrand, Joseph Leo Wiemels, Kjeld Schmiegelow, Henrik Hjalgrim
Journal: Cancer Research (2018)

Abstract It has been proposed that children with acute lymphoblastic leukemia (ALL) are born with a dysregulated immune function that together with postnatal environmental exposures causes childhood ALL. Despite its importance for the understanding of ALL etiology, this hypothesis has been inadequately explored. In a population-based case–control study, we measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with Danish nationwide registers, we also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL. Children who developed B-cell precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6 receptor (sIL6R) α, TGFβ1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared with matched controls. Concentrations of IL10 were below the detection level for both patients and controls. Birth order (IL18 and CRP), gestational age (sIL6Rα, TGFβ1, and CRP), and sex (sIL6Rα, IL8, and CRP), but not maternal age, infections during pregnancy, birth weight nor mode of delivery were significantly associated with the neonatal concentrations of inflammatory markers. Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function. Significance: Children who develop acute lymphoblastic leukemia are immunologically distinct at birth and could potentially react abnormally to infections in early childhood. Cancer Res; 78(18); 5458–63. ©2018 AACR.
TCT-729 Procedural Outcomes of Percutaneous Coronary Interventions for Chronic Total Occlusions via the Radial Approach: Insight from an International CTO Registry
Authors: Peter Tajti, Dimitri Karmpaliotis, Khaldoon Alaswad, Farouc Amin Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Philip Dattilo, Catalin Toma, A.J. Conrad Smith, Barry Uretsky, Oleg Krestyaninov, Dmitrii Khelimskii, Elizabeth Holper, R. Michael Wyman, David Kandzari, Santiago Garcia, Michail Koutouzis, Ioannis Tsiafoutis, Wissam Jaber, Habib Samady, Jeffrey W. Moses, Nicholas Lembo, Manish Parikh, Ajay Jayant Kirtane, Ziad Ali, Darshan Doshi, Iosif Xenogiannis, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
Clinical and pathological features of solid pseudopapillary neoplasm (SPN) of the pancreas: A retrospective review of cases at Mayo Clinic.
Authors: Cristobal T. Sanhueza, Zhaohui Jin, Thomas C. Smyrk, Mindy L. Hartgers, Steven R. Alberts, Amit Mahipal
Journal: Journal of Clinical Oncology (2017)

e15757 Background: SPN is a rare neoplasia of the pancreas, defined by the World Health Organization (WHO) as an epithelial low-grade malignant neoplasm, with a high-grade malignant transformation potential. Literature in this subject is scarce and limited only to small retrospective series. Methods: This is a retrospective study aiming to characterize patients with the diagnosis of SPN at Mayo Clinic between 1992 and 2016. Demographics, clinical and pathological features, recurrence rate and overall survival were recorded. Malignant SPN was defined as per the WHO 2010 classification (Perineural invasion, angioinvasion or deep tissue invasion) and compared to Benign SPN. Results: 44 patients with SPN were identified. 39 patients (88.6%) were female. Median age at diagnosis was 27.5 (Range: 13-64). The most frequent presentation was abdominal pain (52.6%), whereas 36.8% were diagnosed based on incidental imaging findings. Majority (60.4%) of the tumors were located at the pancreatic tail, and 48.5% were solid-cystic lesions. Vascular and lymph node involvement were infrequent. 15 cases (30.23%) were classified as malignant. Tumor size was associated with malignant behavior (Table). Three patients had a metastatic presentation. All but 1 patient were treated with surgery. R1 resection was more frequent in malignant SPN, and 2 patients experienced disease recurrence. Two Stage IV patients were treated with surgery and experienced long term survival, one of them without evidence of disease. There was only 1 death recorded. Conclusions: SNP presents predominantly on young women. The prognosis is excellent even in presence of malignant features, and a complete surgery remains as the main treatment. [Table: see text]