tbuckley/cabot-search huggingface dataset:
Implementing universal genetic counseling (GC) and multigene germline testing (MGT) for pancreatic cancer (PC) patients (pts).
Authors: Matthew B. Yurgelun, Anu B. Chittenden, Chinedu I. Ukaegbu, Tara G. Dhingra, Shraddha Gaonkar, Jiliane Sotelo, Douglas Adam Rubinson, Nadine Jackson McCleary, Thomas E. Clancy, Thomas Adam Abrams, James M. Cleary, Audrey P. Madigan, Lauren K. Brais, Kimberly Perez, Brian M. Wolpin, Sapna Syngal
Journal: Journal of Clinical Oncology (2018)

1512 Background: MGT will identify cancer susceptibility gene variants in 4-10% of unselected PC pts. Such data have prompted calls for universal GC and MGT of all PC pts, but the real-world benefits and barriers to implementing such systematic testing are unknown. This study’s aim was to study the implementation of universal hereditary cancer risk assessment for all PC pts seen in an academic oncology practice. Methods: All gastrointestinal medical oncologists at the Dana-Farber Cancer Institute (DFCI) were recommended to refer all PC pts for GC and MGT beginning 12/2016. A special referral sheet was placed in new PC pt charts to remind providers and streamline GC referral workflows. Clinical and germline data were collected on a consecutive cohort of PC pts undergoing GC and MGT from 3/1/2017-1/31/2018. Results: Over the 11-month study period, 443 (43.9/month) PC pts were seen for medical oncology new patient visits at DFCI, 114 (10.4/month) were referred for GC, and 92 (8.4/month) eligible PC pts underwent GC and consented to MGT and study enrollment. Among the 92 participants, median time from first DFCI appointment to GC was 44 days (IQR 23-142 days), 33 (35.9%) underwent MGT within 30 days of their first DFCI appointment, and 4 (4.3%) died within 30 days of receiving MGT results. 8/92 (8.7%; 95% CI 2.9-14.5%) were found to carry germline mutations (2 BRCA1, 2 BRCA2, 1 ATM and PALB2, 1 NBN, 1 PMS2, 1 STK11) on MGT. There were no significant differences in patient age, sex, race, personal cancer history, family history of PC, or family history of other cancers between mutation carriers and non-carriers. 4/8 (50%) carriers received targeted therapy (eg, PARP inhibitors) based on MGT results (2 remain on 1st line chemotherapy; 2 died without undergoing targeted therapy) and 5/8 (63%) have family members who are actively pursuing cascade testing for the identified mutation. Conclusions: Clinical implementation of universal GC/MGT in PC pts is potentially feasible and results in the detection of mutations that are actionable for PC pts and their at-risk family members. In spite of streamlined workflows, lack of oncologist referral is a critical barrier to the real-world efficacy of universal GC/MGT in PC. Clinical trial information: NCT03060720.
Posttraumatic Stress Disorder in Primary Care Practice
Authors: Matthew J. Friedman
Journal: JAMA Internal Medicine (2018)

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
Clinical trials: A key tool in improving breast cancer survival in Nigeria.
Authors: Omolara A. Fatiregun, Olufunmilayo I. Olopade, Abiodun Popoola
Journal: Journal of Clinical Oncology (2017)

e18198 Background: Clinical trials has continued to sharpen the treatment guidelines in managing breast cancer in the United States. The trends in breast cancer management in developed countries and the shifts in treatment paradigms have impacted on breast cancer diagnosis from an incurable entity in the early 1900s’ to the situation today where most women are diagnosed in early stage and cured while advanced staged women are living with the disease for several years. Clinical research in breast cancer is in its infancy stage in Nigeria. There is an urgent need for more clinical trials in Nigeria geared towards developing treatment algorithms in a bid to increase survival in Breast cancer patients. Methods: A systematic review of all research published on breast cancer since 1963 till 2017 in Nigeria .We reviewed all articles found on PubMed and Google scholar search engines by searching “ Breast cancer in Nigeria”. Using the PRISMA and NIH guidelines, we reviewed classified them based on their study designs into different levels of evidence. Information extracted from studies include, year of publications, study designs and level of evidence. Studies selected were group into seven levels of evidence .Meta-analysis was not considered in the review due to vary study designs and difficulty n pooling then together. Results: Out of 430 published articles cited relating to Breast cancer, only 282 articles where eligible for the systematic review. 56.4%(159) of studies done on breast were cross sectional studies, followed by case – control studies 11.7% (33), then case reports &amp; series 10.4%(29) ,2.8%(8) , only 1.1% (3)of studies cited were clinical trials registered on Clinical Trials.gov on breast cancer treatment. On Levels of Evidence, Level 6 accounted for 54.9 %( 155) followed by Level 7, 18.1 %( 51), level 1, 2, 3 were 0%, 1.1%, 8.9%.Conclusions: A vast majority of research done on Breast Cancer done in the Country are still at the Levels 4, 6 and 7 of Evidence. Clinical trials in Breast cancer treatment are rare in Nigeria, they however provide Level 1, 2 or 3 evidence which helps to develop treatment protocols for Breast cancer Treatment in Nigeria. , it is pertinent to develop more clinical trials so as to improve quality of care and life in breast cancer patients.
Abstract 18713: Quantification of Cortical Recovery After Cardiac Arrest With Continuous Somatosensory Evoked Potentials
Authors: Nicole L Werner, Joshua Mergos, Liqun Sun, Trevor Tooley, Fares Alghanem, Nick Chulski, Christy Villa, William Stacey, Robert H Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2015)

Objective: Reliable early prognostication of neurologic recovery in comatose cardiac arrest (CA) survivors remains a major clinical challenge. We hypothesized that continuous somatosensory evoked potentials (SSEP) in the immediate post-CA period could enable early quantification of cortical recovery. Methods: Pigs were instrumented for hemodynamic and SSEP monitoring. For SSEP, stimulation was applied to the right median nerve and electrodes in the brachial plexus and scalp acquired recordings. The primary cortical signal was the N20. Animals were then subjected to ventricular fibrillation CA that was left untreated for up to 4 minutes and followed by advanced cardiac life support until return of spontaneous circulation (ROSC). SSEP monitoring started before CA and continued after ROSC until SSEPs were unchanged for 60 minutes. Results: Six experiments were performed. In all animals, peripheral, subcortical, and cortical SSEPs were acquired prior to CA, demonstrating morphology similar to that of humans. Cortical potentials completely disappeared during CA. Average arrest duration was 6.9 ± 3.0 min. After ROSC, the N20 signal returned but with variable recovery rate and amplitude. The final N20 amplitude inversely trended with total duration of arrest (Figure 1). The N20 amplitude recovery over time took a logarithmic shape and ranged from 5 to 180 minutes to reach maximum (Figure 2). Conclusions: Continuous SSEP monitoring allows for quantification of cortical recovery within hours of short duration CA in a porcine model. The maximum N20 amplitude and rate of increase may be useful tools for quantifying recovery of cortical function in comatose cardiac arrest survivors.
Nodal staging of high-risk cutaneous squamous cell carcinoma
Authors: Matthew Fox, Marc Brown, Nicholas Golda, Dori Goldberg, Christopher Miller, Melissa Pugliano-Mauro, Chrysalyne Schmults, Thuzar Shin, Thomas Stasko, Yaohui G. Xu, Kishwer Nehal
Journal: Journal of the American Academy of Dermatology (2018)
Dianhydrogalactitol in bevacizumab-refractory GBM: Further analysis of a phase 1-2 trial.
Authors: Kent C. Shih, Manish R. Patel, Nicholas A. Butowski, Gerald Steven Falchook, Sani Haider Kizilbash, Suzanne Fields Jones, Jeffrey A. Bacha, Dennis Brown, Richard Stephen Schwartz, Sarath Kanekal, John C.I. Constant, Howard A. Burris
Journal: Journal of Clinical Oncology (2018)

2061 Background: Dianhydrogalactitol (VAL-083) is a first-in-class DNA-targeting agent with anticancer activity established in prior NCI-sponsored trials. We have previously reported results of DLM-10-001 (NCT01478178), a multicenter Phase 1-2 trial of VAL-083 in bevacizumab refractory GBM (BEV-rGBM), with median overall survival (mOS) of 8.35mo from BEV failure and an observed dose response. Here, we report further analysis of OS in DLM-10-001 from the start of treatment for patients (pts) receiving a clinically active dose of VAL-083 compared to pts receiving an inactive dose of the agent and two derived controls of historical and recent electronic medical records (EMR) data. Methods: 45 BEV-rGBM pts were enrolled across 10 cohorts at doses ranging from 1.5mg/m2 to 50mg/m2. Pts received VAL-083 IV on days 1, 2, 3 of a 21-day cycle. MTD was established at 40mg/m2/day. A clinically active dose of VAL-083 was determined at or below MTD based on PK data and in vitro studies against GBM cell-lines included pts from 20, 30 & 40 mg/m2 dose cohorts. OS in DLM-10-001 was calculated from the 1st dose of VAL-083. DLM-10-001 trial data are also compared to historical publications of BEV-rGBM, and recent EMR for BEV-rGBM pts receiving salvage therapy with TMZ, CCNU or carboplatin. mOS and hazard ratios (HR) were estimated by Kaplan-Meier and nominal p-values to compare survival curves by log-rank test (MedCalc Software v18). Results: OS for BEV-rGBM pts treated with a clinically active dose of VAL-083 (mOS = 7.9mo, 95% CI = 3.1-9.6mo) was superior to OS for pts receiving an inactive dose of VAL-083 (mOS = 2.9, HR = 0.341, p = 0.003); historical publications (mOS = 2.8mo, HR = 0.362, p = 0.0005); and EMR data (mOS = 2.9mo, HR = 0.399, p = .011). There was no statistical difference between the control groups. Pts receiving a clinically active dose of VAL-083 demonstrated an OS benefit compared to an aggregate of the controls (mOS = 2.9mo, HR = 0.395, p = .0003). Conclusions: The results suggest a statistically significant and meaningful OS benefit for BEV-rGBM pts treated with a clinically active dose of VAL-083. While small sample size and retrospective nature of the analyses is limiting, the results warrant further exploration via a randomized trial. Clinical trial information: NCT01478178.
Temporal trends in late-onset morbidity and mortality after medulloblastoma diagnosed across three decades: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Ralph Salloum, Yan Chen, Yutaka Yasui, Roger Packer, Wendy M. Leisenring, Elizabeth M. Wells, Allison A. King, Rebecca M. Howell, Todd M. Gibson, Kevin R. Krull, Leslie L. Robison, Kevin C. Oeffinger, Maryam Fouladi, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2017)

10516 Background: Therapy for medulloblastoma and primitive neuroectodermal tumor has evolved from surgery and adjuvant radiotherapy to risk-adapted multimodal regimens. The impact of these changes in treatment on long-term outcomes remains unknown. Methods: Cumulative incidence of late mortality ( &gt; 5 years from diagnosis), subsequent malignant neoplasms (SMN), chronic health conditions and psychosocial functioning were evaluated among 5-year survivors in CCSS diagnosed between 1970 and 1999. Survivors were stratified according to treatment decade (1970s, 1980s, 1990s) and treatment exposure (surgery + craniospinal irradiation [CSI] ≥30 Gy, no chemotherapy; surgery + CSI ≥30 Gy + chemotherapy [high-risk therapy], surgery + CSI ˂30 Gy + chemotherapy [standard-risk therapy]). Rate ratios (RRs), odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for long-term outcomes among treatment eras and exposure groups using multivariable piecewise-exponential models. Results: Among 1,380 eligible survivors (median [range] age 29 [6-20] years; 21.4 [5-44] years from diagnosis), the 15-year cumulative incidence of all-cause (21.9% 1970s vs. 12.8% 1990s; p = 0.003) and recurrence-related (16.2% vs 9.6%, p = 0.03) late mortality decreased with no reduction in mortality attributable to late effects of therapy including SMN. Among 959 participants, the incidence of SMN did not decrease by era or by treatment group. However, survivors treated in the 1990s had an increased cumulative incidence of severe, life-threatening and fatal health conditions (16.9% 1970s vs 25.4% 1990s; p = 0.03), and were more likely to develop multiple severe or life-threatening health conditions, RR = 2.98 (95% CI, 1.10-8.07). Survivors of standard-risk therapy were less likely to use special education services than high-risk therapy patients, OR = 0.51 (95% CI, 0.33-0.78). Conclusions: Historical changes in therapy have improved 5-year survival, reduced risk of late mortality due to disease recurrence, and reduced special education utilization, at the cost of increased risk for multiple, severe and life-threatening chronic health conditions.
Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms
Authors: Kuan-Pin Su, Ping-Tao Tseng, Pao-Yen Lin, Ryo Okubo, Tien-Yu Chen, Yen-Wen Chen, Yutaka J. Matsuoka
Journal: JAMA Network Open (2018)

Importance No systematic review or meta-analysis has assessed the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) for anxiety. Objective To evaluate the association of anxiety symptoms with omega-3 PUFA treatment compared with controls in varied populations. Data Sources PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases were searched up to March 4, 2018. Study Selection A search was performed of clinical trials assessing the anxiolytic effect of omega-3 PUFAs in humans, in either placebo-controlled or non–placebo-controlled designs. Of 104 selected articles, 19 entered the final data extraction stage. Data Extraction and Measures Two authors independently extracted the data according to a predetermined list of interests. A random-effects model meta-analysis was performed and this study was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Main Outcomes and Measures Changes in the severity of anxiety symptoms after omega-3 PUFA treatment. Results In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g , 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (&amp;amp;lt;2000 mg/d). Conclusions and Relevance This review indicates that omega-3 PUFAs might help to reduce the symptoms of clinical anxiety. Further well-designed studies are needed in populations in whom anxiety is the main symptom.
Palbociclib (P) in patients (Pts) with pancreatic cancer (PC) and gallbladder or bile duct cancer (GBC) with <i>CDKN2A</i> alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Tareq Al Baghdadi, Susan Halabi, Elizabeth Garrett-Mayer, Pam K. Mangat, Eugene R Ahn, Vaibhav Sahai, Ricardo H. Alvarez, Edward S. Kim, Kathleen J Yost, Kuo Guo, Andrew Lawrence Rygiel, Kaitlyn R. Antonelli, Nicole L. Butler, Suanna S. Bruinooge, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2018)

2532 Background: The TAPUR Study is a phase II multi‐basket study that evaluates the anti‐tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations known to be drug targets. Results in two cohorts of PC and GBC pts each with CDKN2A loss or mutation treated with P are reported. Methods: Simon’s optimal two stage design was used to test the null hypothesis of 15% response rate versus the alternative of 35%. Power and alpha were set at 85% and 10%, respectively. Response was assessed per RECIST v1.1. This design requires 10 pts in stage 1 and if < 2 pts have objective response (OR) or stable disease (SD) at 16‐weeks (wks), the cohort is closed. Secondary endpoints are progression‐free survival (PFS), overall survival (OS) and safety. Genomic testing was performed using commercially available tests selected by clinical sites. Treatment was determined according to protocol matching rules based on pre‐defined genomic inclusion criteria. Results: Twelve pts were enrolled in the PC cohort from July 2016 to April 2017, but 2 were subsequently found to be ineligible due to minor deviations from inclusion criteria. Ten pts were enrolled in the GBC cohort from August 2016 to November 2017. All pts are included in the data analysis for demographics, safety, PFS and OS (Table 1). No ORs or SD at 16 wks were observed in the PC or GBC pts and both cohorts were therefore closed. The most common toxicity from P was thrombocytopenia. Conclusions: Monotherapy with P does not have clinical activity in PC or GBC pts with CDKN2A loss or mutation. Toxicity is similar to previous experience with P. These pts should be offered other treatments, including clinical trials. Clinical trial information: NCT02693535.Baseline demographics, clinical characteristics and outcomes by cohort. Palbociclib targeting CDKN2A Tumor Type PC (N = 12) GBC (N = 10) Median age, yrs (range) 62 (52, 70) 63 (54, 81) Male% 67 50 ECOG Performance Status, % 25 10 0 1 67 60 2 8 30 Median PFS, wks (90% CI) 7.2 (4.0, 8.0) 7.4 (4.0, 8.4) Median OS, wks (90% CI) 12.4 (4.7, 23.1) 11.9 (5.1, 14.0) Drug‐related AEs, grades 3‐4 (% of pts) 8 40
Efficacy of incomplete metastasectomy with targeted therapy in patients with metastatic renal cell carcinoma.
Authors: Rashida Orlova, Pavel Borisov, Petr A Karlov, Michail Shkolnik
Journal: Journal of Clinical Oncology (2016)

e16117 Background: Complete metastasectomy in patients with potentially surgically resectable metastases have an important role in the management of metastatic renal cell carcinoma (mRCC).Clinical benefits of incomplete metastasectomy (iME) can be assessed in the era of targeted therapy. The aim of present retrospective study was to evaluate the preliminary efficacy of iME and following targeted therapy. Methods: Data was collected from single center for patients with clear cell mRCC and metastases at presentation treated surgically with following therapy or medical treatment alone from 2008-2015. Resection of metastases was incomplete (patients had at least 1 but not all metastases resected). All patients had prior nephrectomy. Kaplan Meier analysis was used to estimate progression-free (PFS) and overall (OS) survival. Results: Median follow-up was 31.2 months (3–82). In total, 47 of 147 patients (32.0%) received iME with systemic therapy, and 100 (68.0%) patients were treated with systemic therapy alone. These treatments included sunitinib (n = 53), bevacizumab+IFN (n = 11), pazopanib (n = 21), sorafenib (n = 73), axitinib (n = 11), everolimus (n = 22), and immunotherapy (n = 56). 80 (54.4%) patients received more than 2 treatment lines. Most common metastatic sites were lungs (70%) and bones (28%). MSKCC prognosis and ECOG PS did not differed between patients who did and did not undergo iME (P > 0.05). The use of systemic treatment was associated with a trend of improvement in survival in patients who underwent iME, with a median OS of 46 months compared with 31 months in group of patients with unresected metastases (P = 0.09). iME significantly increased PFS in first-line therapy (P = 0.018), and did not cause a significant impacton PFS in second- or third- lines (P > 0.1). Conclusions: The current results supposed that incomplete resection of RCC metastases may be associated with increased efficacy of first-line targeted therapy and long-term survival of selected mRCC patients. Prospective trials are needed to better establish the role of iME in this group of patients.
The relationship between Ki-67 index and prognosis for patients with well-differentiation gastric NETs.
Authors: Ivan N. Peregorodiev, Vahan Yurikovich Bokhian, Vera V. Delektorskaya, Peter Arkhiri, Andrey Ryabov, Ivan S. Stilidi
Journal: Journal of Clinical Oncology (2018)

e16160 Background: Given the wide range of the index of cell proliferation activity of well-differentiated NETs (from 1% to 20%), clinical and prognostic heterogeneity of this group of patients, we analysed the proliferation activity of tumor cells to determine the correlation of the Ki-67 index and prognosis. Considering the literature review, which indicate that for the patients with pancreatic NETs the threshold value of Ki-67 in 5% more accurately correlates with the prognosis and course of disease, we assessed the overall five-year survival for the patients with stomach NETs with the thresholds of Ki-67 from 2 to 5%. Methods: The prognostic role of Ki-67 index was studied in 36 patients with stomach NETs undergoing surgical treatment in the open or laparoscopic approach in the National Medical Research Center of Oncology named after N. N. Blokhin from 2001 to 2015. The Morphological study of material was conducted in accordance with WHO Classification of Tumours of the Digestive System 2010. Results: The research showed that in group of patients with index of proliferative activity 5% and less, five-year survival rate was 91.6%. When the Ki-67 index ranged from 6% to 20% five-year survival rate was 60.4% (p = 0.02). The overall five-year survival rate was analyzed for the patients with well-differentiated NETs of the stomach (Grade I and Grade II). The survival difference is not statistically significant: with an index of proliferative activity of up to 2% five-year survival amounted to 87.5%, more than 2% - 77,7% (p = 0,74). The survival difference was not statistically significant when comparing the threshold level of Ki-67 in 3 and 4%. Conclusions: Consequently, the statistically significant prognostic factor for the NETs of the stomach Grade I/Grade II is the level of the Ki-67 index greater than 5% (overall 5-year survival rate of 50.4% vs 90.9%, p = 0.02)