tbuckley/cabot-search huggingface dataset:
Association Between Childhood-Onset Epilepsy and Amyloid Burden 5 Decades Later
Authors: Juho Joutsa, Juha O. Rinne, Bruce Hermann, Mira Karrasch, Anu Anttinen, Shlomo Shinnar, Matti Sillanpää
Journal: JAMA Neurology (2017)

The effect of childhood epilepsy on later-life cognitive and brain health is an unclear and little-explored issue.To determine whether adults with a history of childhood-onset epilepsy exhibit increased brain amyloid accumulation, possibly predisposing to accelerated cognitive impairment or even frank cognitive disorders in later life.Forty-one adults from a population-based cohort of individuals with childhood-onset epilepsy in southwestern Finland, together with 46 matched population-based controls, underwent amyloid ligand carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography after long-term prospective follow-up. The PiB uptake was quantified as a region to cerebellar cortex ratio. Tracer uptake was evaluated visually and analyzed voxel by voxel over the entire brain to investigate the spatial distribution of amyloid deposition. The study was conducted from May 2011 to October 2013; data analysis was performed from January 2014 to October 2016.Brain amyloid accumulation.The 41 individuals with epilepsy were originally enrolled in the Turku Adult Childhood Onset Epilepsy study at the mean (SD) age of 5.1 (4.5) years (range, 0-14 years). After a mean 52.5 (4.0) years of follow-up, the participants were evaluated (26 [63%] were women; the mean [SD] age was 56.0 [4.3] years). Nine individuals with childhood-onset epilepsy (22%) and 3 control participants (7%) had a visually abnormal PiB scan showing high cortical uptake in at least 1 of the evaluated brain regions (P = .04). In semiquantitative analyses, there was a significant interaction effect indicating higher prefrontal cortex uptake in apolipoprotein E (APOE) ε4 allele carriers than in noncarriers in participants (mean [SD], 1.66 [0.41] vs 1.43 [0.15]) compared with controls (1.40 [0.26) vs 1.41 [0.12]) (group × APOE interaction, F = 6.8; P = .01). In addition, there was a significant group effect showing higher tracer uptake in participants compared with controls (group effect, F = 8.0; P = .006).Adults with childhood-onset epilepsy, particularly APOE ε4 carriers, have an increased brain amyloid load at late middle age. Thus, epilepsy is linked with a biomarker that might be related to accelerated brain aging and can be considered a neurobiological predisposition to later-life cognitive disorders.
Delayed contrast MRI: A new paradigm in neuro-oncology.
Authors: Yael Mardor, David Guez, David Last, Dianne Daniels, Ouzi Nissim, Yuval Grober, Chen Hoffmann, Galia Tsarfaty, Dvora Nass, Alisa Talianski, Sharona Salomon, Moshe Hadani, Roberto Spiegelmann, Zvi R Cohen, Leor Zach
Journal: Journal of Clinical Oncology (2014)

2063 Background: Conventional MRI is unable to differentiate tumor progression from treatment-induced effects (pseudoprogression/radiation-necrosis) in brain tumor patients, thus significantly impacting patients' management with no current solution. Methods: We have applied a novel MRI-based methodology for high resolution depiction of tumor/non-tumor tissues. This unique model-independent technique is based on robust MRI sequences acquired with a delay, enabling complete separation between tumor (contrast clearance at the delayed time point) and treatment effects (contrast accumulation) with no overlap. 498 treatment response assessment maps were calculated for 149 patients with primary/metastatic brain tumors and 9 with AVM recruited/followed on study. Results: The maps were validated by comparing pre-surgical maps of 51 patients with primary/metastatic brain tumors who underwent surgery with histology, resulting in 100% sensitivity and 94% specificity to active tumor. This validation confirms that contrast clearance in the maps represent morphologically active tumor while contrast accumulation represents non-tumor tissues. Following initial validation, the maps were used for making 231 clinical decisions. In 67 cases the decision was to continue follow-up (no treatment change) and in 164 cases to change treatment (including surgery, chemoradiation, radiation treatments, switch to Avastin, etc). Our data demonstrates the application for management of patients with various types of tumors after various treatments, for depiction of residual tumor post surgery, detection of tumor within hemorrhages and differentiating malignant transformation from treatment effects. Conclusions: Our high resolution, easy to interpret, model-independent maps provide complete/clear differentiation between tumor/non-tumor tissues in patients with brain tumors. The increasing rate in which the maps are being used for clinical decisions making in Israel reflects their added value as an efficient/friendly tool for decision making in neuro-oncology. Excellent agreement between pre-surgical maps and histology suggests that the maps may be further applied for planning high precision procedures such as biopsies, resections, SRS and iMRT.
Advanced pulmonary carcinoid (APC): 20-year experience at Johns Hopkins (JH).
Authors: Patrick M. Forde, Craig M. Hooker, Peter Illei, David S. Ettinger, Charles M. Rudin, Christine L. Hann, Julie R. Brahmer, Ronan Joseph Kelly
Journal: Journal of Clinical Oncology (2013)

7598 Background: APC is a rare thoracic malignancy with limited prognostic data and a perceived lack of treatment options other than surgical resection. This is the largest series of APC patients (pts) ever reported and contains data on locally advanced and metastatic disease. Here we compare clinical outcomes and treatment responses for typical carcinoid (TC) and atypical carcinoid (AC). Methods: This retrospective cohort includes pts referred to JH from 1992 to 2012. Pts were identified using pathology and medical record databases. Information extracted included, pathology, demographics, stage, prior curative resection, time to relapse, chemotherapy/targeted agents and response rate (RR), date of death/last follow-up. Primary outcome was overall survival (OS), defined as time from diagnosis of advanced disease to death from any cause. Secondary endpoint was recurrence-free survival (RFS), defined as time from curative resection to tumor recurrence. OS and RFS were estimated by using the Kaplan-Meier method and log-rank test comparing TC and AC. Results: 49 APC pts (30 female/19 male; 32 AC/17 TC) were identified. 25 pts had relapsed after previous curative resection. Median RFS (n=25), was significantly longer for TC vs. AC (119 months (m) vs. 66 m, p=0.008). Median OS was 85m and significantly longer for TC vs. AC (122m vs. 48m, p=0.009). 39 (80%) pts received systemic therapy for APC. RR to first-line chemotherapy was 22% (5/23) with all 5 (3 AC, 2 TC) responses occurring in pts receiving cisplatin/etoposide. First-line somatostatin therapy was given to 11 pts with 1 partial response (PR) (9%) and 10 pts with stable disease (5 AC, 5 TC) for a median 15m. 5 pts received first-line targeted agents including sunitinib and gefitinib however no responses were seen. 50% (2/4 pts) RR occurred to second-line temozolomide/capecitabine An ongoing PR &gt; 6m to everolimus occurred in a heavily pretreated AC pt. Conclusions: Both AC and TC may recur many years after resection. This study demonstrates significantly poorer survival for AC in advanced disease. Thoracic oncologists perceive APC as resistant to systemic therapy however here we report that both AC and TC may respond to cisplatin/etoposide, temozolomide/capecitabine and mTOR targeted therapy.
Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.
Authors: Jay S. Dalal, Joshua B. Greene, Craig C. Hofmeister, Ann Lau Clark, Joseph Clark
Journal: Journal of Clinical Oncology (2012)

e16027 Background: Platinum-based chemotherapy including cisplatin, 5-fluorouracil (5-FU), and the EGFR-directed monoclonal antibody cetuximab, are active in the treatment of head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis and many have difficulty tolerating cisplatin-based regimens. Oxalipatin, a third-generation platinum derivative, has demonstrated antitumor activity and lacks many of the limiting side effects of cisplatin. We conducted a phase I pilot study to investigate the dose-limitation of oxaliplatin in addition to infusional 5-FU and cetuximab in patients with untreated recurrent or metastatic HNSCC. Methods: The planned dose escalation schedule included: dose level 1: oxaliplatin 100mg/m 2 day 1, 5-FU CIV 750mg/m 2 over 96 hours beginning day 1, and cetuximab 400mg/m 2 cycle 1, day 1 (and 250mg/m 2 weekly thereafter) on a 21-day cycle. Dose level 2: oxaliplatin 130mg/m 2 day 1, 5-FU CIV 1000mg/m 2 over 96 hours beginning day 1 and the same dose and schedule of cetuximab. Results: A total of 10 patients were accrued, consisting of 4 females and 6 males. The first seven were enrolled onto dose level 1 and the following three onto dose level 2. Dose level 1 was tolerated well with acceptable toxicity, including grade 1-2 oral mucositis, grade 1-2 fatigue, grade 1-2 acneiform rash, grade 1 nausea, grade 1-2 anemia and grade 1 transaminitis. All responses observed, (1 MR, 1 PR, 1 CR), were short-lived. Dose level 2 was more toxic than anticipated; 2 of 3 patients experienced grade 4 toxicities (mucositis, diarrhea, acute renal failure) requiring hospitalization with a treatment-related death in one of these patients. The phase I portion of the trial was therefore closed and dose level 1 is considered the maximum tolerated dose. Conclusions: The regimen of oxaliplatin 100mg/m 2 day 1, infusional 5-FU 750mg/m 2 over 96 hours beginning day 1, and cetuximab 400mg/m 2 cycle 1, day 1 (with 250mg/m 2 weekly thereafter), given on a 21-day cycle, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment of unresectable or metastatic HNSCC.
Clinical Efficacy of Bortezomib Based Therapy in Plasma Cell Leukemias.
Authors: Adrian Alegre, B. Aguado, J.J. Lahuerta, C. Cervero, A. Oriol, A. Abella, R. Carrion, R. Renat, J.A. Hernandez-Rivas, J. de la Rubia, M.V. Mateos, R. Garcia-Sanz, R. Rodriguez-Notario, B. Navas, J.M. Fernandez-Rañada, J.F. San Miguel
Journal: Blood (2007)
Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline: A post-hoc analysis of the start study
Authors: H. K. Reddel, W. W. Busse, Søren Pedersen, W. C. Tan, Y. Z. Chen, C. Jorup, D. Lythgoe, P. M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Significance of MRI-assessed tumor response for locally advanced rectal cancer treated with preoperative long-course chemoradiation: Kuwait Cancer Control Center experience.
Authors: Mohamed Salah Fayaz, Gerges Attia Demian, Wael Moftah Fathallah, Heba El-Sayed Eissa, Mustafa El-Sherify, Sadeq Abuzalouf, Thomas George, Suzanne Samir
Journal: Journal of Clinical Oncology (2014)

e14587 Background: To study the predictive and prognostic value of magnetic resonance imaging (MRI)-assessed tumor response after long course neoadjuvant therapy for locally advanced rectal cancer. Methods: This retrospective study included 79 patients who had T3/4 and/or N+ rectal cancer treated by long course neoadjuvant chemoradiation. MRI-detected tumor regression grade (TRG) was assessed in 64 patients. MRI images were reviewed by the study radiologist. Surgical and pathological reports for those operated upon were reviewed. Disease free survival (DFS) was estimated using the Kaplan-Meier method. Progression during therapy, local relapse, metastasis and death resulting from the tumor were classified as events. Statistical significance was calculated using the log-rank test. Results: Eleven patients had complete disappearance of the tumor on MRI (TRG 1). All but one (who chose deferred surgery) had complete pathological response (pCR) with a positive predictive value of nearly 100%. Out of the 20 patients who had MRI-TRG 2, six had pCR. MRI-TRG3, TRG4 and TRG5 were detected in 24, 6, and 3 patients respectively of whom only one patient had pCR. After a median follow-up of 2 years (range 4-62 months), the 2-year DFS was 77%. The MRI-assessed TRG was significant for DFS. The 2-year DFS was 88% for the good responders (MRI-TRG 1 and 2) versus 66% for the poor responders (MRI-TRG 3-5) with a P value of 0.046. Conclusions: MRI assessed complete tumor response (TRG 1) was strongly correlated with pCR thus can be used as a marker to predict absence of viable tumor cells and to choose patients for deferred surgery. Assessment of MRI-TRG can predict the DFS outcome thus poor responders may be offered further treatment options before definitive surgery.
Pazopanib in metastatic renal carcinoma (mRC): Experience of 31 centers in Spain in first, second, third, or subsequent lines in daily clinical practice.
Authors: Angel Rodriguez Sanchez, Rocio García Domínguez, Guillermo De Velasco, Alvaro Pinto, Javier Puente, Gustavo Rubio, Sergio Vazquez-Estevez, Marta Juan, Manuel Constenla, Marta Lopez Brea, Maria Sereno, Javier L. Puertas, Maria Garrido, David Marrupe, Maria L Villalobos, Blanca Cantos, Teresa de Portugal, Rocio Vilchez, Jose-Luis Gonzalez-Larriba, Jose Angel Arranz Arija
Journal: Journal of Clinical Oncology (2013)

e15609 Background: In clinical trials pazopanib (P) was superior to placebo, noninferior to sunitinib, and very well tolerated as 1st-line for mRC, but there is limited information in daily clinical practice. Methods: We retrospectively reviewed 159 patients (p) who received P in in 31 centers in Spain during the first 18 month after P approval, to evaluate the timing of use and its efficacy. Results: Mean age was 66 y, 64.8% were males, 81.1% clear-cell, 12% non-clear cell, and 6.9% unspecified. At diagnosis of mRC 73.6% had nephrectomy, 78.6% and 71.7% of p were of good-intermediate risk (MSKCC and Heng criteria respectively). Metastatic sites were lung (59.7%), lymph nodes (26.4%), bone (22.6%), skin/soft-tissues (17.6%), liver (11.9%), CNS (2.5%), and 31.4% others (adrenal, pancreas, etc.). Median follow-up since diagnosis of mRC was 16 months (m). P was given as 1st systemic treatment in 81 p, (50.9%), as 2nd line in 32 p (20.1%, most after sunitinib, 17 due to intolerance), or as ≥3r line (46 p, 29%). Median follow-up after P was 7 m in 1st line, and 10 m in 2nd or ≥ 3rd line. Toxicity was as expected. No toxic deaths were registered. At the time of analysis, 85 p have discontinued P (progression: 73 p, toxicity: 10 p, other causes: 2 p), and 35 p have died. The table shows time to treatment failure due to progression or toxicity (TTF), and overall survival (OS) since the 1st dose of P. There were statistically significant differences in 1st line TTF and OS between MSKCC subgroups. Conclusions: In p with mRC and good-intermediate prognosis, P appears to be as effective in daily clinical practice as it was in 1st line trials. P also showed efficacy in p with poor risk, in 2nd-line (particularly progression or intolerance to sunitinib), and after 2 or more TKIs. Updated analysis will be available in June 2013. [Table: see text]
IRAP+ endosomes restrict TLR9 activation and signaling
Authors: Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
Journal: Nature Immunology (2017)
Contents, Vol. 45, 1986
Authors: Paul Rodenhauser, H.J. Khamis, Alice Faryna, B. van Houdenhove, Alice Faryna, Paul Rodenhauser, Moshe Torem, Michael Bagby, Adolf-Ernst Meyer, Beate von Holtzapfel, Gerhard Deffner, Klaus Engel, Maggy Klick, F. Wistuba, Graeme J. Taylor, David Ryan
Journal: Psychotherapy and Psychosomatics (1986)
Recent and remote 30-day readmissions among cancer patients: Prevalence and association with overall survival.
Authors: Armin Shahrokni, Larissa K. F. Temple, Sanam Mahmoudzadeh, Jonathan Wills, Kent Sepkowitz, Steven Martin
Journal: Journal of Clinical Oncology (2015)

e17716 Background: 30-day readmission has been shown to be an indicator of poor quality of care. However, it is largely unknown if readmission amongst cancer patients actively receiving treatment is associated with poor quality of care or their prognosis. The overall aim of this study was to assess the association between remote (before one year from death) and recent (within one year from death) 30-day readmission and overall survival of cancer patients. Methods: A retrospective study of patients who had died in 2013 and who were: older than 18, treated for a solid tumor for 1-5 years at a single institution and had been admitted at least once since 2012 is performed. Data on Socio-demographic, Charlson comorbidity index (CCI), cancer (type and stage) and treatment characteristics, acute healthcare utilization were captured. Overall survival (OS) was calculated from the time of the cancer diagnosis till death. Bivariate and multivariate Cox regression analysis were performed. Results: Out of 1697 patients, 560 (33%) and 166 (9.8%) had at least one recent and remote readmission, respectively. In the bivariate analysis, those with at least one recent readmission differed than those with no recent readmission in age (60.09 vs. 64.99, P < .001), Charlson Comorbidity Index (8.85 vs. 9.41, P < .001), receiving chemotherapy (80% vs. 73.1%, P = .002), mean number of remote and recent admissions (0.92 vs. 0.76, P = .024 & 3.66 vs. 1.24, P < .001), and recent total days of stay in hospital (24.76 vs. 9.27, P < .001), however they did not differ in median OS (579 vs. 562 days, P = .45). In the multivariate Cox regression analysis, after adjusting for socio-demographic, CCI, cancer and cancer treatment characteristic, and acute healthcare utilization, remote and recent 30-day readmission remained independent factors associated with worse overall survival (Hazard Ratio = 1.33, 95% CI [1.20-1.47] and 1.07, 95% CI [1.004-1.15]). Conclusions: 30-day readmission is common among cancer patients especially in their final year of life. Those with 30-day readmission occupy hospital beds 3 times more, and could have worse OS than those without 30-day readmission.
Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer. (ISRCTN 12808747) TRAPEZE.
Authors: Nicholas David James, Lazaros Andronis, Ilias Goranitis, Sarah Pirrie, Ann Pope, Darren Barton, Adam Daunton, Duncan McLaren, Joe M. O'Sullivan, Chris Parker, John Staffurth, Andrew Stanley, James Wylie, Sharon Beesley, Alison J. Birtle, Janet Elizabeth Brown, Prabir R Chakraborti, John Martin Russell, Lucinda Billingham
Journal: Journal of Clinical Oncology (2015)

e16108 Background: Bony metastatic CRPC has a poor prognosis and high morbidity. TRAPEZE is a factorial RCT using 3 agents, docetaxel (D), zoledronic acid (ZA) and strontium-89 (Sr89). All have palliative benefits and are used in bony metastatic CRPC to control bone symptoms. This study aims to assess the cost-effectiveness of adding bone-protecting treatments—zoledronic acid (ZA) and strontium-89 (Sr89)—to docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC). Methods: Data on resource use and health outcomes collected prospectively in the TRAPEZE 2x2 factorial trial were used to compare the cost-effectiveness of ZA vs. no ZA, and Sr89 vs. no Sr89. Costs are estimated from the NHS perspective. Outcomes are expressed as quality-adjusted life-years (QALYs) and cost-effectiveness is presented as incremental cost per additional QALY. Results: Based on the availability of generic zoledronic acid, the per-patient cost for ZA was £12,667, £251 (95% CIs: -£1,099 to £1,602) higher than the equivalent value in the no ZA group. Patients in the ZA group experienced on average 0.03 QALYs (95% CIs: -0.07 to 0.13) more than their counterparts in no ZA. The incremental cost-effectiveness ratio (ICER) for this comparison was £8,005. A higher ICER of £42,047 was found when using the price of branded zoledronic acid. Sr89 was associated with a cost of £13,230, £1,365 (95% CIs: -£12 to £2,742) higher than no Sr89. The Sr89 group showed a gain of 0.08 QALYs (95% CIs: -0.02 to 0.18) over no Sr89. The ICER for Sr89 was estimated at £16,884. Conclusions: ZA was associated with a modest additional cost and a slight improvement in QALYs, resulting in an ICER well below the conventional threshold of £20,000 per QALY. Given the availability of generic zoledronic acid at a low cost, ZA appears to be a beneficial option for both CRPC patients and the NHS. Sr89 resulted in an ICER of less than £20,000; nonetheless it is unclear whether findings will prove practice-changing in light of competition from newer radioisotopes. Clinical trial information: 12808747.
Clinical characteristics and molecular profile in patients with non-small cell lung cancer harboring <i>CRKL</i> amplification.
Authors: Hirotsugu Kenmotsu, Masaru Watanebe, Masakuni Serizawa, Mitsuhiro Isaka, Haruyasu Murakami, Tateaki Naito, Tetsuhiko Taira, Hisao Imai, Akira Ono, Tomohiro Maniwa, Shoji Takahashi, Keita Mori, Masahiro Endo, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto, Yasuhiro Koh, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2014)

7567 Background: It has been reported that CRKL amplification, associated with overexpression, has induced cell transformation as well as resistance to EGFR inhibitors. We analyzed CRKLamplification in archived genomic DNA samples from the Shizuoka Lung Cancer Mutation Study. Methods: To identify CRKL amplification, we performed copy number analysis using the real-time PCR system. The standard curve was generated by PCR of serially diluted plasmid clones of CRKL and a reference gene. Triplicate reactions were performed using 2 ng of genomic DNA extracted from surgically resected tissues and tumor biopsies from non-small cell lung cancer (NSCLC) patients. Biopsy samples were obtained from NSCLC patients with EGFR mutations. In surgically resected tissues, TruSeq amplicon cancer panel was used for the detection of somatic mutations in 48 cancer related genes followed by ultra-deep sequencing (Illumina) at an average coverage of approximately 3,400x. ALK, ROS1 and RET translocations and EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications were also detected by multiplex RT-PCR and quantitative PCR, respectively. Results: Between July 2011 and March 2013, 268 NSCLC patients treated with surgical resection, and 40 NSCLC patients with EGFR mutations, were enrolled in this study. Patient characteristics (treated with surgical resection) were as follows: median age (range) 69 (38-92) years; female 35%; never-smoker 27%; histology adenocarcinoma/squamous cell carcinoma/others 74/23/3 %; and differentiation well/moderate/poor 21/53/23 %. We detected CRKL amplification in 7.5% of 268 NSCLC patients treated with surgical resection. Frequencies of CRKL amplification in patients with gene alterations were as follows: 7.5 % of 93 EGFR; none of 38 KRAS, 8.7% of 23 PIK3CA; 8.8% of 91 TP53, none of 4 EML4-ALK, and 50% of 4 KIF5B-RET. 18% of 40 patients with EGFR mutations showed CRKL amplification before EGFR-TKI treatment. Conclusions: CRKL amplification was identified in 7.5% of NSCLC patients. These results suggest that CRKL amplification may be mutually exclusive with mutations in KRAS, and frequently observed in those with KIF5B-RET.