tbuckley/cabot-search huggingface dataset:
Evaluation of the diagnostic and prognostic performance of the modified G8 screening instrument in oncological patients with age of 60 YEARS or age: Prospective cohort of 889 Brazilian elderly cancer patients.
Authors: Letícia Telles Sales, Jurema Telles O Lima, Mirella Rebello, José Natal Figueiroa, Luiz Claudio Santos Thuler, Anke Bergmann, Flavia Orange, Maria Julia Gonçalves Mello, Davi de brito Camara
Journal: Journal of Clinical Oncology (2019)

e23040 Background: Elderly oncology patients are not often included in studies of new therapeutic guidelines. The modified-G8 is easy to use, has satisfactory accuracy and does not require additional tools. Its value for predicting early death has not been evaluated. Objective: To evaluate accuracy of the modified G8 instrument for prediction of early death (up to 6 months) in elderly Brazilian patients (≥ 60 years). Methods: We used data from a prospective cohort with participants aged 60 years or older and a recent diagnosis of a solid neoplasm, followed in a geriatric oncology outpatient clinic between 2015 and 2017. Sociodemographic, clinical and laboratory data were obtained, along with CGA. From the primary data, we developed a modified-G8 score using 6 as the cut-off point, normal being &lt; 6 and abnormal being ≥ 6. The primary outcome was early death (occurring within up to 6 months) considered the gold standard for the accuracy study of modified-G8 as a predictor of early death. Through bivariate and Cox multivariate analysis, the risk for early death (Hazard Ratio - HR crude and adjusted) was determined. Overall survival was estimated using the Kaplan-Meier method, and the log-Rank test was used for comparisons according to the categorization of the scores. Results: Of the 889 participants included, 537 (60%) had modified G8 scores ≥ 6 (abnormal). The overall mean score was 9.9 ± 8.4; mean age was 72,5 years (range, 60–97 years), 38% were 60 and 70 years of age. Fifty-two percent of the participants were male. The most common tumor sites were prostate (31%) and breast (16%), followed by digestive and gynecological (both with 11%). On analysis of accuracy, we found sensitivity 91.7% (95% CI 86–95.7), specificity 45.7% (95% CI 42.1–49.4), positive predictive value 24.8% (95% CI 21.2–28.6) and negative predictive value 96.6% (95% CI 94.1–98.2), area under the ROC curve 81.7% (95% CI 77.9–85.4). The crude HR for early death among those who had abnormal scores was 8.3 (95% CI 4.6–14.9) and the age-adjusted HR, tumor site and metastatic disease at diagnosis was 4.5 (95% CI 2.5–8.3) times greater and survival was lower (log-rank p 0.001). Conclusions: The modified G8 predicted early death in an elderly population (≥ 60 years) with cancer in a northeastern Brazilian institution. Satisfactory prognostic accuracy was obtained. This instrument could reduce the number of patients who would follow-up with CGA, saving time and resources, and accelerating individualized treatment.
An International Perspective on Drugs for Cancer
Authors: Richard Lehman, Cary P. Gross
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 14144: Adaptive Servo Ventilation Improves Cardiovascular Disability Status and Long-term Prognosis in Heart Failure Patients with Central Sleep Apnea
Authors: Fumihito Nakayama, Hiroyuki Yoshimine, Yoshitaka Harada, Shinji Seto
Journal: Circulation (2010)

Background: About a third of heart failure (HF) patients have Chyene-Stokes Respiration with Central Sleep Apnea (CSR-CSA) and this sleep breathing disorder worsens the cardiovascular disability st...
Pembrolizumab with low dose carboplatin for recurrent platinum resistant ovarian, fallopian tube, and primary peritoneal cancer-interim results.
Authors: John B. Liao, William Rayford Gwin, Renata Urban, Katie Hitchcock-Bernhardt, Andrew L. Coveler, Doreen Higgins, Jennifer S Childs, Hania Shakalia, Sasha E. Stanton, Anna Tinker, Tanya A. Wahl, Richard G. Ancheta, Kathryn F. McGonigle, James Dai, Mary L. Disis, Barbara Ann Goff
Journal: Journal of Clinical Oncology (2019)

5519 Background: Pembrolizumab has shown activity in advanced recurrent ovarian cancer (AOC) with an 8% response rate and median progression-free survival (PFS) of 2.1 months reported in KEYNOTE-100. Because platinum chemotherapies also induce T cell proliferation and enhance tumor cell recognition through PD-1/PD-L, we assessed the safety and activity of pembrolizumab with carboplatin in platinum resistant AOC. Methods: Key eligibility criteria for this Phase 1/2 single arm trial were platinum resistant AOC, fallopian tube, or peritoneal cancer, progression after subsequent systemic therapy, and ECOG PS 0-1. Pembrolizumab 200mg was given on Day 1 and carboplatin AUC 2 on Day 8 and 15 of a 3 week cycle until progression, unacceptable toxicity, or consent withdrawal. Imaging was done before cycles 4 and 8, then every 3 months and unconfirmed objective response assessed by blinded independent review per RECIST 1.1. Adverse events (AEs) were reported per Common Terminology for Adverse Events v5.0. PD-L1 expression was assessed by immunohistochemistry. Results: 27 patients (median age: 64) had received a median of 5 (range: 2-9) prior lines of systemic therapy, which included bevacizumab in 74% of patients. The most common treatment related (TR) AEs were lymphopenia (18%) and anemia (9%). The majority of TR AEs were grade 1 or 2 (93%). 6% of AEs were grade 3 with lymphopenia the most common. Two grade 4 AEs were neutropenia and lymphopenia. Of 23 patients evaluable for best objective response, 13.0% (95% CI, 2.7-33.6) had partial response (PR), 65.2% (95% CI, 42.7-83.6) had stable disease (SD), and 21.7% (95% CI, 7.4-43.7) had progression. 7 of the 23 evaluable patients (30.4%) had archival tumor with modified percent scoring ≥5 for PD-L1 and all achieved PR (3/7, 42.8%) or SD (4/7, 57.2%). Overall median PFS was 4.6 months (95% CI, 2.7-6.2). Rate of PFS at 6 months was 40.4% (95% CI, 25.5-65.5). Median follow-up is 6.2 months and PFS is based on current data, but 8 patients remain on study and estimates will be updated. Conclusions: Pembrolizumab with low dose carboplatin was well tolerated and showed activity in heavily pretreated platinum resistant AOC. Survival and biomarker analyses are ongoing. Clinical trial information: NCT03029598.
Treatment and outcome of elderly patients with PCNSL: A Beaumont experience.
Authors: Yifan Pang, Bolanle Gbadamosi, MD., Saaquib Bakhsh, Susanna S. Gaikazian, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2019)

e23012 Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Prognosis remains poor, and data on clinical characteristics or outcomes are limited, particularly in the elderly. In the literature, age over 50 is a major poor prognostic factor. Herein, we report our experience of PCNSL in elderly patients. Methods: The electronic medical records from 2007 to 2015 of the Beaumont Health System were analyzed. Patients with non-Hodgkin’s Lymphoma (NHL) were reviewed and those with PCNSL were identified. Results: Of the 617 NHL patients, 21 (3.4%) had PCNSL, 12 (57.1%) were male and 17 (81.0%) Caucasian. Median age was 76 (range, 55 to 83), and the majority 18 (85.7%) were above age 65. Deep brain lesions occurred in 11 (52.4%) patients. Eighteen (85.7%) received treatment, including 3/18 (16.7%) with high-dose methotrexate (HD-MTX) only, 5/18 (27.8%) HD-MTX plus rituximab (MR), 2/18 (11.1%) HD-MTX with vincristine and procarbazine, 7/18 (38.9%) MR and other chemotherapy, and 1/18 (5.6%) temozolomide and rituximab. MTX dose ranged from 1.8 to 8 g/m 2 (median, 3.5 g/m 2 ). The number of treatment cycles ranged from 1 to 11 (median, 3). Whole brain radiation was given to 4 (22.2%) patients with refractory disease after systemic chemotherapy. None of the patients received definitive radiation. Overall response rate was 44.4%, including 4/18 (22.2%) CR and 4/18 (22.2%) PR. Median survival was 4.0 months (95% CI, 2.3 to 5.7 months). At the time of data collection (November, 2018), only four patients were alive. Causes of death included disease progression (58.8%), neutropenic sepsis (23.5%), and MTX toxicity, predominantly acute kidney injury and severe gastrointestinal mucositis (17.7%). Age, lesion depth, treatment, and other clinical characteristics did not impact survival (all p &gt; 0.05). Conclusions: Although HD-MTX remained the backbone of therapy for most patients, we observed a heterogeneous treatment pattern in our elderly patient population. More than 50% had primary refractory diseases, while about 40% had treatment related mortality. This study further emphasized the need for more trials enrolling elderly patients with PCNSL, utilizing novel agents, and investigating molecular prognostic markers.
Efficacy and safety of approved first-line tyrosine kinase inhibitor (TKI) treatment in patients with metastatic renal cell carcinoma (mRCC): A network meta-analysis based on phase II/III randomised clinical trials (RCTs).
Authors: Kirsi Manz, Klaus Fenchel, Andreas Eilers, Jon Morgan, Kirsten Wittling, Wolfram CM Dempke
Journal: Journal of Clinical Oncology (2019)

e16074 Background: During the last decade several novel treatment options including TKIs and immune checkpoint inhibitors have been developed for the treatment of mRCC patients. However, results from direct comparisons (head-to-head RCTs) to determine the optimal treatment are lacking for most of these agents. In this network meta-analysis we attempted to indirectly compare efficacy and safety of first-line TKIs in patients with mRCC. Methods: PubMed, Embase, Medline, the Cochrane Central Register of Controlled Trials were searched (English language only). Abstracts of conferences of relevant medical societies were also included from database inception (January 1, 2007) to January 15, 2019. A systematic manual search (including data requests from the publication authors) was also performed. For the purpose of this network meta-analysis only phase II/III RCTs assessing approved first-line TKI therapy for mRCC were analysed. The analysis was done using the software R with the netmeta package. Progression-free survival (PFS) was the primary endpoint; grade 3 and 4 adverse events (AEs) were secondary endpoints. Results: A database search identified 12 studies meeting the eligibility criteria reporting on 4,460 patients. For PFS cabozantinib and sunitinib were found to be superior to sorafenib, however, when compared to tivozanib, PFS did not significantly differ between the TKIs. Furthermore, tivozanib was found to have the highest probability of being the safest drug as first-line treatment in terms of grade 3 and 4 AEs (ranking safety, p score 0.9344). Conclusions: No significant PFS differences for all TKIs currently used for first-line treatment of mRCC have been found when compared with tivozanib. Compared with all approved TKIs tivozanib appears to be the best choice for first-line treatment of these patients because it has demonstrated the most favourable safety profile. These results may provide guidance to oncologists when making treatment decisions for mRCC patients.
Targeting KDM1A with iadademstat in combination with immunotherapy in an <i>in vivo</i> model of melanoma.
Authors: Tamara Maes, Cristina Mascaró, Natalia Sacilotto, Michele MP Lufino, Filippo Ciceri
Journal: Journal of Clinical Oncology (2019)

e14248 Background: By recruiting the immune system against cancer cells, immunotherapy holds promise to achieve long-lasting responses in several malignant conditions. However, a therapeutic response is observed only in a subset of patients. The low mutational burden of “cold” tumors enables them to stay undetected from the host inflammatory response (innate resistance). Also, cancer cells develop a number of coping strategies in response to the selective pressure applied by the treatment with checkpoint inhibitors (recruitment of regulatory cells, defective antigen presentation, immunosuppressant mediators, reduced costimulation, and T cell apoptosis). Hence combinatorial treatments are being considered to tackle the problem of resistances and responsiveness. Iadademstat (ORY-1001) is a selective, orally-available KDM1A inhibitor with low nanomolar potency (Maes et al., 2018). KDM1A is a histone demethylase involved in transcription regulation and key to tumorigenicity in different hematological and solid malignancies. The tolerability and safety of iadademstat has been evaluated in Phase I studies in AML and SCLC and the drug is currently being investigated in combination with SoC in phase II clinical trials in AML and in SCLC. Methods: The combined efficacy of iadademstat administered orally at 10 µg/kg, a dose that does not provoke weight loss or thrombocytopenia, and an anti-Pd1 antibody was evaluated in the mice syngeneic B16F10 melanoma model. Results: Treatment with iadademstat and the checkpoint inhibitor anti-Pd1 monoclonal antibody was well tolerated. By Day 15, treatment with the anti-Pd1 antibody alone or in combo with iadademstat reduced tumor growth by 45% and 65% relative to vehicle controls. Control animals were sacrificed by day 19 due to progression. By day 22, 54% reduction was achieved in the animals treated with the combination compared to the animals treated with the anti-Pd1 antibody alone. Conclusions: This proof-of-concept in vivo experiment highlights the potential of iadademstat in combination with checkpoint inhibitors, prompting further investigation in other oncological indications, characterized by low or no response to the currently approved immune-oncology treatments.
Tumor Mutation Burden—From Hopes to Doubts
Authors: Alfredo Addeo, Giuseppe L. Banna, Glen J. Weiss
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
A phase II trial cohort of nivolumab plus ipilimumab in patients (Pts) with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).
Authors: Vatche Tchekmedyian, Eric Jeffrey Sherman, Lara Dunn, James Vincent Fetten, Loren S. Michel, Anuja Kriplani, Luc Morris, Irina Ostrovnaya, Nora Katabi, Sofia Haque, Crystal Tran, Julian Azar, David G. Pfister, Alan Loh Ho
Journal: Journal of Clinical Oncology (2019)

6084 Background: R/M ACC is a malignant neoplasm most commonly of salivary gland origin with no standard treatment. The impact of combined PD-1/CTLA-4 checkpoint blockade in R/M ACC is unknown. Methods: In a two-stage minimax phase II trial, pts with progressive R/M ACC (non-salivary primaries allowed) were enrolled and treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle = 6 weeks). Imaging, using RECIST v1.1 response assessment, was scheduled to be performed approximately every 12 weeks. The primary endpoint was overall response rate (ORR = complete response [CR]+partial response [PR]) per RECIST v1.1. To detect a difference between an unacceptable ORR of 5% and a desirable ORR of 20% (one-sided type I error of 10%, power of 90%), at least 1 in the first 18 pts required an observed response. At least 4 responses of 32 total pts were needed to meet the primary endpoint. Treatment beyond progression of disease (PD) was allowed at the discretion of the investigator. A second cohort of pts with non-ACC salivary cancer is still accruing for separate analysis. Results: From 6/12/2017-6/20/2018, 32 pts were enrolled and evaluable for the primary endpoint. There was 1 confirmed PR in the first 18 pts, therefore enrollment of the second stage continued. ORR was 6% (2/32). One additional pt had an unconfirmed PR (-31% regression before CNS PD). For best overall response, there were 2 PRs, 15 SD, and 11 PD. Four pts never reached a first disease assessment: 3 due to death from clinical PD and 1 was removed for toxicity. Six pts discontinued the trial for toxicities (Grade 4 (G4) neutropenia/sepsis and G3 adrenal insufficiency (1), G2 hypophysitis (2), G3 arthritis &gt; 7 days (1), G3 colitis (1), and G3 hepatitis/G4 creatinine kinase (CK) elevation (1)). The 2 confirmed PRs consisted of -73.1% and -58.4% regressions, with a duration of therapy of 18.4 and 7.8 months, respectively (treatment ongoing for both). Conclusions: The study did not meet its primary endpoint, though the responses observed were dramatic. Paired biopsy and peripheral blood samples will be analyzed to elucidate insights into mechanisms of response and resistance to dual checkpoint blockade. Clinical trial information: NCT03172624.
Accounting for Height in an Analysis of Body Fat and Breast Cancer Risk—In Reply
Authors: Neil M. Iyengar, Rhonda Arthur, Andrew J. Dannenberg
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Delphi consensus on the follow-up of cancer patients with breakthrough pain under opioid treatment.
Authors: Jose Luis Gonzalez Larriba, Diego Cayuela, Ovidio Fernandez Calvo, Salvador Garcera, Raquel Molina, Juan José Reina-Zoilo, Vicente Guillem, Carlos Camps, Margarita Feyjoo
Journal: Journal of Clinical Oncology (2019)

e23135 Background: Breakthrough cancer pain (BTcP) is one of the most common symptoms related with the disease and its treatment. Its management differs from that of chronic pain but there is not a wide consensus about fundamental aspects of BTcP definition, diagnosis, follow-up, and management. The objective of this study promoted by ECO Foundation, is to reach a consensus on the follow-up of patients with BTcP under opioid treatment. Methods: This work was conducted using a modified Delphi method organized in two rounds and involving a panel of 84 medical oncologists. A questionnaire of 66 items was developed. The items proposed to reach a consensus included the following topics: 1) When to perform the first and subsequent BTcP treatment evaluations; 2) What to assess at the first follow-up visit and how; and 3) What to assess in the following visits and how. Results: After two rounds, a consensus was reached on 80.3% of the items proposed. The main agreements reached include: The first follow-up visit should preferably be face-to-face; increase the number of visits after detecting poor control of BTcP; assess pain control episodes of BTcP in the first and following visits; adjust treatment dose of opioids due to poor control of BTcP; and adopt measures to prevent aberrant opioid-induced behaviors when treating BTcP in patients with cancer. Conclusions: This Delphi consensus highlights the different points of view of medical oncologists regarding the follow-up of patients with BTcP under opioids treatment. Nonetheless, the conclusions reached can facilitate optimizing monitoring of these patients and promote long-term effectiveness of BTcP control.