tbuckley/cabot-search huggingface dataset:
Importance of pharmacist intervention in preventing adverse drug events after chemotherapy infusion.
Authors: Nathalia Gambôa, João Raphael Maia
Journal: Journal of Clinical Oncology (2017)

e18256 Background: The importance of monitoring Adverse Drug Reactions (ADRs) is undeniable, because it may limit the therapy and lead to stop a cancer treatment. Early identification and appropriate clinical management, prior to after chemotherapy, may mitigate or reverse undesirable effects. Effective Pharmacovigilance occurs through active participation and assertive communication among health professionals. In this context, the present work is aimed at quantifying Pharmaceutical Interventions after ADR and its impact on therapy. Methods: The data collection was done by analysis of the Nursing Evolutions on the ADR presented during infusion. After identifying them, the Clinical Pharmacist investigates and suggests interventions in a pre-chemotherapy scheme to the Oncologist, if pertinent. Work performed between April 2016 and January 2017, at a private Oncology Clinic in Rio de Janeiro, Brazil. Results: During the period, 60 pharmaceutical interventions were performed on prescriptions of patients who presented adverse drug reactions. Of these, 40 patients (67%) did not present the same reaction again and 20 patients (33%) presented it again, despite the change in pre-chemotherapy. The most common reactions were hypersensitivity (47%) and abdominal colic (43%). The most commonly prescribed drugs were hydrocortisone (22%), diphenhydramine (25%) and atropine (40%). Conclusions: These findings reaffirm pharmacovigilance as an important multidisciplinary instrument to promote the safe use of drugs, the efficacy of cancer treatment and the improve of quality of life in cancer patients. This importance is strengthened in the oncology clinic, in which patients are more likely to present possible ADR due to the frequent use of multidrug therapy.
Prediction of clinical outcomes for early gastric cancer using radiomic signatures derived from the quantitative texture analysis of conventional CT scans and machine learning.
Authors: Jacob G Woolsey, Julio C Cárdenas-Rodríguez, Jeeyun Lee, Andre Burkett, Ronald Lee Korn
Journal: Journal of Clinical Oncology (2018)

e16091 Background: Gastric cancer recurrence is a major problem despite advances in treatment regimens. Current predictors of recurrence include age and nodal involvement but suffer from poor sensitivity and specificity. To date, the incorporation of radiographic features into predictive models of recurrence has not been commonly pursued. In this pilot study, we demonstrate that a powerful predictive model for tumor recurrence can be identified by combining radiomic signatures derived from quantitative texture analysis (QTA) of the in situ gastric tumor and normal liver parenchymal tissue when used alone or combined with clinical outcomes using machine learning techniques. Methods: Regions of interest (ROI) were posited on gastric lesions and liver parenchymal tissue using QTA platform TexRad. A 6x6 matrix of texture features (mean, SD, MPP, entropy, skewness, and kurtosis) using 6 spatial scale filter levels (SSF 0, 2-6) was determined for each ROI. QTA data was aligned with 6 clinical features (age, stage, pathologic node, nodal stage, lymphovascular and perineural invasion). Two ML algorithms, random forest classification (RFC) and logistic regression (LR), randomly selected 80% of subject data to train a model, reserving 20% as a validation set on which to predict recurrence at the 2-year landmark. Model performance was evaluated by imposing two metrics on these out-of-sample predictions: area under the ROC curve (AUC) and Cohen’s kappa (κ). Results: The optimal performing model for gastric recurrence relied on both QTA and clinical features. The RFC model at SSF 4 had an AUC = 0.90 and κ = 0.75, with the most significant features being age, skewness, and SD. When using liver parenchyma best performance occurred with the RFC model at SSF 6 using QTA features only (AUC = 0.88 and κ = 0.78). The top 3 features were SD, entropy, and skewness. Conclusions: This retrospective evaluation using ML algorithms highlights the potential value of using imaging derived texture features to predict recurrence at 2 years. If validated, imaging features may be used in combination with clinical information to better identify patients at risk for early recurrence.
Incidence and risk of second primary malignancy after an index potentially-human papillomavirus-associated cancer.
Authors: Eric Adjei Boakye, Paula Buchanan, Leslie J. Hinyard, Nosayaba Osazuwa-Peters, Matthew C Simpson, Mario Schootman, Jay F Piccirillo
Journal: Journal of Clinical Oncology (2018)

1593 Background: Approximately 39,000 HPV-associated cancers are diagnosed annually in the US. Oncogenic HPV-infections are associated with virtually all cases of cervical, 95% of anal, 73% of oropharyngeal, 65% of vaginal, 50% of vulvar, and 35% of penile cancers. Cancer survivors are at increased risk of a second primary malignancy (SPM). We assessed the risk of developing a SPM after an index potentially-HPV-associated cancer (P-HPV-AC). Methods: This was population-based cohort study of patients with P-HPV-AC in the Surveillance, Epidemiology, and End Results registry (2000-2014). Only patients with invasive P-HPV-AC [cervical, vagina, vulva, penile, anal canal, and oropharynx] per International Classification of Diseases for Oncology, 3rd edition, were included. SPM was defined as the first subsequent primary cancer occurring at least 2 months after first cancer diagnosis. Excess SPM risk was quantified using standardized incidence ratios (SIRs) stratify by gender. Results: A total of 100,960 patients with an index P-HPV-AC were identified, and 7.37% developed a SPM overall. In all P-HPV-AC patients, the overall SIR was 1.72 (95% CI: 1.68–1.76). All index P-HPV-AC sites presented with a statistically significant increase in the risk of SPM. Among males, the greatest increase in risk of SPM was observed among patients diagnosed with an index P-HPV-AC oropharynx (SIR = 1.83; 95% CI, 1.76–1.90). Among females, the greatest increase in risk of SPM was observed among patients diagnosed with an index P-HPV-AC oropharynx (SIR = 2.47; 95% CI, 2.29–2.65, Table). Conclusions: HPV cancer survivors experience significantly excess risk of SPM; thereby calling for a more effective program for surveillance of patients with HPV-associated cancers. Cancers Observed SIR Rate 95% CI Overall All potentially-HPV-associated cancers 7,447 1.72 1.68 – 1.76 Male and female Oropharynx (head and neck) 3,240 1.91 1.84 – 1.98 Anal 1,131 1.52 1.43 – 1.61 Male Oropharynx (head and neck) 2,672 1.83 1.76 – 1.90 Anal 453 1.48 1.35 – 1.62 Penile 251 1.41 1.24 – 1.59 Female Oropharynx (head and neck) 568 2.42 2.22 – 2.62 Anal 678 1.55 1.44 – 1.67 Cervical 2,017 1.51 1.44 – 1.58 Vulvar 618 2.33 2.15 – 2.52 Vaginal 190 1.78 1.54 – 2.06
Phase I study combining olaparib and tremelimumab for the treatment of women with BRCA-deficient recurrent ovarian cancer.
Authors: Sarah Foster Adams, Olivier Rixe, Ji-Hyun Lee, Dennis J. McCance, Sheri Westgate, Steven C. Eberhardt, Teresa Rutledge, Carolyn Muller
Journal: Journal of Clinical Oncology (2017)

e17052 Background: With evidence that BRCA dysfunction is associated with increased T cell recruitment to tumor sites, and that PARP-inhibition may increase the immunogenicity of tumor cells, we evaluated the combination of a PARP-inhibitor and CTLA4 immune checkpoint antibody in BRCA1- ovarian cancer models. Our results demonstrated significant therapeutic synergy and durable treatment responses in preclinical studies. Based on this, a Phase I study was conducted to assess the tolerability of this regimen in women with BRCA mutation-associated recurrent ovarian cancer. Methods: Eligibility criteria included a documented BRCA1 or BRCA2 germline mutations and a diagnosis of recurrent ovarian, tubal, or primary peritoneal cancer with measurable disease. Both platinum-sensitive and platinum resistant patients were eligible. Patients with prior exposure to PARP-inhibitors or to immune therapy with the exception of CTLA4 antibodies were also eligible. Exclusion criteria included current use of anti-inflammatory agents or a prior history of autoimmune disease. Treatment consisted of Olaparib at 300mg twice daily, as well as monthly infusions of Tremelimumab at a dose of 10mg/kg, with plans for a dose reduction if toxicity was encountered. Patients completing two full treatment cycles were evaluated for evidence of toxicity, particularly immune-related adverse events, to define a dose for Phase II testing. Results: Three women were treated at the starting dose of 300mg BID of Olaparib and 10mg/kg monthly of Tremelimumab for two cycles without evidence of any dose-limiting toxicities or grade 3 adverse events. All patients experienced grade 1 and 2 toxicities, including immune related toxicities consistent with prior studies of immune checkpoint inhibitors. All three patients showed evidence of treatment response by cycle 3 based on CA125 levels and a decrease in tumor size on CT scans. Conclusions: The combination of PARP-inhibition and CTLA-4 blockade is tolerable in heavily pre-treated women with recurrent BRCA-associated ovarian cancer. Preliminary results also demonstrate evidence of therapeutic effect, supporting ongoing evaluation of this regimen in Phase II trials. Clinical trial information: NCT02571725.
Response of tumor-induced osteomalacia (TIO) to the FGFR inhibitor BGJ398.
Authors: Carole Brennan Miller, Clemens Bergwitz, Jenny Blau, Alison Boyce, Rachel I Gafni, Lori Guthrie, Georgios Z Papadakis, Flora Miranda, Eric Daniel Slosberg, Diana Graus-Porter, Christine Hopmann, Erica Glass, Randi Isaacs, Michael T. Collins
Journal: Journal of Clinical Oncology (2016)

e22500 Background: TIO is a paraneoplastic syndrome characterized by bone pain, muscle weakness, and fractures. Symptoms are due to renal phosphate wasting, resulting in hypophosphatemia and osteomalacia. TIO is caused by ectopic production of the phosphate- and vit D-regulating hormone, FGF23, usually by mixed tissue mesenchymal tumors. Evidence suggest a role for FGFR signaling in FGF23 regulation and TIO tumorigenesis, with a recent finding of a fibronectin 1(FN1)/FGFR1 gene fusion in TIO tumors that generates a FN/FGFR chimeric protein with active FGFR signaling. BGJ398 is a selective pan-FGFR inhibitor which has anti-tumor activity in FGFR-driven tumors and inhibits the phosphaturic effects of FGF23 in preclinical models, suggesting a role for BGJ398 in treating TIO. Methods: We have treated two patients (pts) with BGJ398 on an IRB-approved phase 2 trial (BGJ398 Signature Trial; NCT02160041) . Pt 1 has a rare form of TIO with widely metastatic disease where a FGFR rearrangement was identified. Pt 2 has symptomatic metabolic manifestations of the disease but no identifiable tumor. Pt 1 has received 9 cycles(125 mg po daily for 21 days every 28 days) and pt 2 is in the first cycle. Results: In pt 1, treatment resulted in disappearance of FDG activity with a 43.9% decrease in total Metabolic Tumor Volume after one cycle with progressive shrinkage(confirmed PR) and calcification of metastases on CT scan. Plasma FGF23 levels declined from 100-fold above normal to near normal and phosphorus levels normalized on BJG398. Comparison of pre- and post-treatment biopsies of a metastatic lesion revealed mature lamellar bone, suggesting tumor differentiation and osseous metaplasia. In pt 2, FGF23 levels that were 3 times normal became undetectable and serum phosphate normalized by day 8 of BJG398. Side effects were grade 1/2 and included stomatitis,hand-foot syndrome, diarrhea, anemia, corneal ulcer and serous retinopathy. Conclusions: BGJ398 is tumoricidal to phosphaturic mesenchymal tumors in TIO and leads to terminal differentiation of tumor cells. In TIO, FGF23 production is FGFR-dependent and normalizes with FGFR inhibition. Further investigation of BGJ398 for the treatment of TIO is warranted. Clinical trial information: NCT02160041.
Effect of PET-CT on disease recurrence and its management in patients with potentially resectable colorectal cancer liver metastases. The long-term results of a randomized controlled trial (PET-CT Imaging prior to liver resection for colorectal adenocarcinoma metastases).
Authors: Pablo Emilio Serrano Aybar, Chu-Shu Gu, Mohamed Husien, Diederick Jalink, Guillaume Martel, Melanie E. Tsang, Julie I. Hallet, Steven Gallinger, Anne Ritter, Vivian McAlister, Nathalie Sela, Hannah Solomon, Kaitlyn Beyfuss, Christine Li, Erika Lee, Carol-Anne Moulton, Mark Norman Levine
Journal: Journal of Clinical Oncology (2018)

3527 Background: The PETCAM randomized trial evaluated the effect of preoperative PET-CT (vs. no PET-CT) on surgical management in patients with colorectal cancer liver metastases. This trial resulted in 8% change in surgical management, including a higher proportion of major liver resections in the PET-CT arm. This study is the long-term follow up of the PETCAM trial and aims to compare the disease-free (DFS), overall survival (OS), and long-term clinical course of enrolled patients. Methods: Recruitment to the trial occurred between 2005-2010, with last follow-up in 2013. Data on recurrence, management and mortality from 2013-2017 was collected retrospectively. Cox proportional Hazard Models were used to calculate risk for recurrence and death. OS was calculated with Kaplan-Meir method and compared with log-rank test. Results: At 5 years, 172/404 (43%) patients were alive. There were no differences in DFS (HR: 1.13, 95%CI: 0.89-1.43) or OS (HR: 1.02, 95%CI: 0.78-1.32) between groups. Median DFS was 17 months, 95%CI: 14-19. Risks factors for recurrence were: extrahepatic disease, liver tumour size, nodal stage and disease-free duration. Median OS was 51 months, 95%CI: 44-64. During the follow-up period, 264/368, 72% patients recurred, mostly lung (51%) and liver (41%); 120/264 (46%) received chemotherapy and 112/264, 42% were re-resected, with a recurrence of 72% (81/112). Median OS following first recurrence was 28 months, 95%CI: 24-31. Most important risks factors for death following recurrence are node-positive disease, more than one recurrence site and disease-free duration < 5 months. Conclusions: PET-CT did not improve DFS or OS. Recurrence following liver resection is common. Prognosis following recurrence is worse compared to first recurrence. Patients with high risk factors should not undergo surgical resection. Clinical trial information: NCT00265356.
TCT-256 Impact of Coronary Artery Tortuosity on PCI Outcomes: An Individual Patient-Data Pooled Analysis From 6 Randomized Controlled Trials
Authors: Maayan Konigstein, Bjorn Redfors, Ori Ben-Yehuda, Mahesh Madhavan, Thomas McAndrew, Zixuan Zhang, David Kandzari, James B. Hermiller, Ziad Ali, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Access to smoking cessation resources for cancer patients across Canada and systemic barriers to implementing change in systems process.
Authors: Michelle Halligan, Deb Keen, Caitlyn Timmings, Graham W. Warren
Journal: Journal of Clinical Oncology (2018)

e18539 Background: Though smoking by cancer patients and survivors causes adverse cancer treatment outcomes, most cancer patients do not receive evidence-based treatment for smoking cessation. The purpose of this study was to evaluate practice patterns and barriers across all provinces and territories within Canada. Methods: Beginning in 2017, the Canadian Partnership Against Cancer (CPAC) convened initiatives to assess smoking cessation resources for cancer patients across all provinces and territories in Canada using the Pan-Canadian Tobacco Cessation and Cancer Care Network (Network). Key strategic meetings were held to assess access and barriers by Network members including representatives from governmental departments responsible for tobacco control, public health, indigenous health authorities, patient and family advisors, and cancer care executives from each province or territory. Results: Existing smoking cessation resources were available to cancer patients in 56% (70/125) of cancer care settings across Canada. Most jurisdictions used an ask-advise-refer (AAR) model with approximately half of jurisdictions using telephone, text, or online counseling, and a minority (5) using internal or external smoking cessation services. Few jurisdictions offered free pharmacotherapy (5) or support to family members (4). The dominant reported barrier to adoption was a need for culture change (77% or provinces and territories) followed by access to free or low-cost pharmacotherapy (52%). Competing priorities in cancer care (28%), limited use of electronic information systems (28%), and lack of quality indicators/accreditation standards (15%) were perceived as barriers less frequently. Development of a pan-Canadian vision and framework including cost considerations were reported as opportunities to support accelerated uptake of smoking cessation with cancer systems. Conclusions: Addressing barriers and providing a pan-Canadian framework are opportunities to promote widespread implementation of evidence-based smoking cessation for cancer patients. Continued Network collaboration will facilitate real-time assessment of practice change and adoption.
Differences in relapse-free survival (RFS) and survival after relapse (SAR) in right (R) versus left (L) stage I-III colon cancer (CCa).
Authors: Hagen F. Kennecke, Caroline Speers, Janine Marie Davies, Winson Y. Cheung, Richard M. Lee-Ying
Journal: Journal of Clinical Oncology (2016)

3578 Background: Genomic analyses describe significant differences between R and L sided CCa. Four distinct Consensus Molecular Subtypes (CMS1-4) have recently been described: CMS1 is predominantly R, stage II and appears to do well in early stages, but has inferior SAR. CMS2 is predominantly L and has a more favorable SAR. We hypothesize that RFS and SAR outcomes are different in R versus L CCa. Methods: Patients diagnosed with stage I-III CCa were identified from the BC Cancer Agency GI Cancers Outcomes Unit. Disease location, demographic, pathologic, treatment, recurrence and mortality information was prospectively collected. R included cecal to transverse tumors; L included splenic flexure to sigmoid tumors. Kaplan Meier survival analysis was performed by stage and stratified by use of adjuvant chemotherapy. RFS was measured from date of surgery until recurrence and censored at death or last follow-up. SAR was measured from relapse, until death or last follow-up. Cox-proportional hazard models were used to control for baseline clinicopathologic characteristics. Results: Of 5378 patients with stage I-III CCa, 46% were R and 54% L. The median age was 67. Compared to L, R sided was significantly associated with females (52 vs 43%), grade 3 (23 vs 10%), stage II (39 vs 35%), > 12 lymph nodes sampled (60 vs 45%) and no adjuvant chemotherapy (54 vs 47%). 5Y survival outcomes and hazard ratios (HR) are listed. In multivariate analysis, R was associated with superior RFS for only stage II disease, while L experienced better SAR overall and in stages II and III. Conclusions: R vs L sided CCa has a prognostic impact in both early stage and relapsed disease, independent of adjuvant therapy. Until better molecular classification is available, R versus L CCa may be a meaningful reflection of molecular subtypes and represent relevant stratification and prognostic factors. 5Y RFS (%) HR (95% CI) N R L p-value R vs L p-value Any Stage 5378 75 73 0.093 1.1 (1.0-1.2) 0.322 II 1946 85 78 < 0.001 1.3 (1.1-1.7) 0.007 III 2840 64 66 0.245 1.0 (0.8-1.1) 0.598 5Y SAR (%) HR (95% CI) Any Relapse 1452 7 15 < 0.001 0.8 (0.7-0.9) < 0.001 Relapsed II 631 11 21 < 0.001 0.7 (0.6-0.9) 0.009 Relapsed III 821 5 12 < 0.001 0.8 (0.7-0.9) < 0.001
Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial
Authors: Gary T Ferguson, Klaus F Rabe, Fernando J Martinez, Leonardo M Fabbri, Chen Wang, Masakazu Ichinose, Eric Bourne, Shaila Ballal, Patrick Darken, Kiernan DeAngelis, Magnus Aurivillius, Paul Dorinsky, Colin Reisner
Journal: The Lancet Respiratory Medicine (2018)
Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark
Authors: Julie C Antvorskov, Thorhallur I Halldorsson, Knud Josefsen, Jannet Svensson, Charlotta Granström, Bart O Roep, Trine H Olesen, Laufey Hrolfsdottir, Karsten Buschard, Sjudur F Olsen
Journal: BMJ (2018)

Abstract Objective To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. Design National prospective cohort study. Setting National health information registries in Denmark. Participants Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, Main outcome measures Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants’ children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes. Results The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v &lt;7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)). Conclusions High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.