tbuckley/cabot-search huggingface dataset:
Subependymal giant cell astrocytoma in pediatric patients with tuberous sclerosis complex treated with mTOR inhibitors: One center experience.
Authors: Alma Edith Benito, Farina Esther Arreguin, Blanca Olivia Almazan, Eduardo Jorge BaÃ Âos, Beatriz Mariana Navarro, Jose de Jesus Figueroa Carbajal
Journal: Journal of Clinical Oncology (2016)

e22001 Background: Tuberous sclerosis complex (TSC) is an autosomal dominant, genetic disorder caused by mutations in TSC1 or TSC2, causing subependymal giant cell astrocytomas (SEGA) in 5%–20% of patients with TSC. SEGA are slow-growing tumors that typically develop near the foramen of Monro. ² ³ Standard treatment has been surgical resection, although complications include intraventricular hemorrhage, hydrocephalus, cognitiveimpairment, and inevitable recurrence if gross total resection is not achieved. ⁴ ⁵ Everolimus inhibits mTOR complex 1, correcting the specific molecular defect causing the tuberous sclerosis complex. ⁸ Methods: We report a cohort of three pediatric cases with tuberous sclerosis complex as follows:CASE 1. Female teenager aged 17, diagnosed at 3 years of age with tuberous sclerosis complex, with seizures and facial angiofibromas. At 17 it is detected by neuroimaging studies ventricular subependymal Astrocytoma. She was treated with everolimus.After six months of treatment, the patient showed clinical and radiological response to treatment.CASE 2: Male patient, 10 years old, who started at 5 years of age with the presence of facial angiofibromas, being addressed and diagnosed with tuberous sclerosis complex. At 10 years of age cardiac rhabdomyomas and subependymal astrocytoma diagnosed in both ventricles. He began treatment with everolimus.Case 3: Male patient, 10 years old, diagnosed at 8 months of age with tuberous sclerosis complex, at age 10 had seizures and data intracranial hypertension requiuiring referral peritoneal ventricle, underwent neurosurgery, removing 80% astrocytoma, however presented subsequent tumor recurrence so he started treatment with mTOR inhibitor showing good response at eight months of treatment. Results: All 3 cases presented clinical and radiolog showed a decreasednumber of convulsive events, decrease in the amount of facial angiofibromas and thereby noticeably improved their quality of life. Conclusions: The use of m-TOR inhibitors, everolimus is safe and effective in pediatric patients with giant cell subependymal astrocytoma associated to tuberous sclerosis complex.
BTC1.03 Investigating the causal relevance of hypothesized risk factors for glioma using population level genetic data.
Authors: A E Howell, J Zheng, S Tsavachidis, R Wootton, C Relton, R Martin, M M Bondy, P Haycock, K M Kurian
Journal: Neuro-Oncology (2018)

Gliomas are a group of primary brain tumours, the most common and aggressive subtype of which is glioblastoma (GBM). GBM has a median survival of just 15 months after diagnosis. Only previous exposure to ionizing radiation and certain inherited genetic syndromes are accepted risk factors for glioma: the majority of cases are thought to occur spontaneously.Observational studies have described associations between several risk factors and glioma, but studies are often conflicting and whether these associations reflect true casual relationships is unclear because observational studies are prone to confounding, measurement error and reverse causation. Mendelian randomization (MR) is an approach to causal analysis that utilises genetic variants robustly associated with risk factors of interest as instrumental variables to determine whether the associations between the trait of interest and disease are causal. We aimed to investigate the causal relevance of hypothesized risk factors for glioma incidence. Hypothesized risk factors for glioma were first identified from published literature by conducting a search of PubMed. We employed two-sample MR using summary results from genome-wide association studies (GWAS) to index 24 potential risk factors that were investigated in relation to GWAS data 4572 glioma cases and 3286 controls. The outcome data coincided with the SNPs used for exposures in the analysis. We determined the odds ratio (OR) for each risk factor with glioma using the inverse variance weighted (IVW) method. To evaluate the robustness of our results and to ensure the MR assumptions were not violated by the presence of directional pleiotropy we performed weighted median, weighted mode and MR-Egger regression. The MR analysis suggested a causal association between a genetically predicted increase in telomere length and an increase in glioma risk by IVW (OR per standard deviation [SD] increase: OR:4.46, CI:2.28–8.73), by weighted median (OR:2.74, CI:1.37–5.50), MR Egger (OR:5.77, CI:0.16–200.19) and weighted mode (OR:2.56, CI:1.28–5.11). There was no strong indication that this result could be a result of pleiotropy. An inverse association between height and glioma risk was observed by IVW (OR per SD increase in height (OR:0.82 CI:0.73–0.92), weighted median (OR:0.74, CI:0.61–0.89), MR Egger (OR:0.59, CI:0.41–0.83) and weighted mode (OR:0.57, CI:0.36–0.88). For all other risk factors evaluated, we found no evidence for a causal association with glioma. These results confirm previous evidence that genetically predicted increase in telomere length, increases the risk of glioma. Our results may provide novel evidence that height is associated with a decreased risk of glioma.
Patterns of osteoporosis (OP) in survivors of colorectal cancer (CRC) enrolled on SWOG trials.
Authors: Afsaneh Barzi, Dawn L. Hershman, Cathee Till, Heinz-Josef Lenz, Howard S. Hochster, Joseph M. Unger
Journal: Journal of Clinical Oncology (2017)

10056 Background: There are currently 1.5 million CRC survivors in US and this number will continue to rise with advancements in treatment. The risk of OP in CRC survivors has not been well described. Methods: We used data from 3 SWOG CRC treatment trials, all of which were phase III and had long term follow-up. Enrollees were linked to Medicare claim files for identification of OP and fractures using HCPCS and ICD9 codes. First, we compared patterns of osteoperosis and fracture risk by sex in colorectal cancer patients. To assess whether patterns of fracture risk by sex differed between patients with vs. without colorectal cancer, we compared the difference in fracture risk by sex in colorectal cancer patients to the difference in fracture risk by sex in the general U.S. population, using data from the National Health Interview Survey (NHIS) and the National Hospital Discharge Survey (NHDS). Finally, we assessed whether absolute estimates of osteoperosis and fracture risk differed between men with colorectal cancer and men without colorectal cancer. Comparison data for men without colorectal cancer were obtained from the placebo arm of the Prostate Cancer Prevention trial (PCPT). Results: We linked 1233 CRC cases with Medicare claims. The median age at CRC diagnosis was marginally higher for women (65 vs 64 ys, p = 0.03). 47% of females, 15% of men with CRC, and 19% of men without CRC had a OP diagnosis. The female to male ratio of osteoporotic fracture in general U.S. population was 1.67, while the same ratio in CRC survivors was 2.84, an increase of 70% (p-value &lt; 0.001). Conclusions: Our study indicates that the risk disparity for OP fracture for females is much greater in CRC survivors than in the general U.S. population. This may be due to more OP diagnoses for female CRC survivors, but not for male CRC survivors.
Abstract 18859: Blockade of Exosome Generation With GW4869 Reduce Cardiac Dysfunction After Myocardial Infarction
Authors: Vanessa Biemmi, Giuseppina Milano, Elisabetta Cervio, Nicolò Pernigoni, Tiziano Moccetti, Giuseppe Vassalli, Lucio Barile
Journal: Circulation (2016)

Introduction: Myocardial infarction induces severe inflammatory responses that lead to progressive heart failure. It also has been reported that large amounts of circulating pro-inflammatory cytoki...
Quality of life in low-risk prostate cancer treated with surgery, external beam radiotherapy, and brachytherapy: A prospective, multicentric cohort study.
Authors: Almudena Cascales, Maria Colmenero, Alfredo Rodriguez, Pilar Samper, Jeanette Valero, Carmen Gonzalez Sansegundo, Jose Andres Cabrera, Francisco Gomez-Veiga, Maria Luz Couselo, Borja Garcia Gomez, Alberto Hernando Arteche, Jose Ponce Diaz-Reixa, Carmen Rubio, Maite Rodriguez Cabrera, Cristina Martin-Arriscado, David Lora, Maria Angeles Cabeza Rodriguez
Journal: Journal of Clinical Oncology (2016)

e16592 Background: Low Risk Prostate Cancer (LR PCa) can be treated with Surgery (Sx), External Beam Radiotherapy (RT) or Brachytherapy (BT) with similar oncologic results. Quality of life (QoL) changes secondary to treatment (tt) are measurable with tests. We aim to quantify QoL in Low Risk PCa treated with Sx, BT or RT over time, and to compare the validity of EORTC-QLQ-C30/PR25 and CAVIPRES tests against the gold standard (EPIC). Methods: Prospective, multicentric cohort study of 3 non-randomized interventions (Sx, BT, RT) evaluating QoL in LR PCa patients (pts) not receiving hormonal tt. EPIC, EORTC QLQ C30 (C30), EORTC QLQ PR 25 (PR 25) and CAVIPRES tests made at 0, 1, 3, 6, 12 and 24 months (m) after tt. Planned size per arm was 133 pts to get accuracy on EPIC but recruitment was unachieved. Median values evaluated on each measure. Differences assessed using the repeated measure's ANOVA. Test items followed a scale of 100 (0 = poor, 100 = the best QoL). Results: 73 pts recruited (2011 – 2014), 2-year follow-up. 10 pts had Sx, 45 BT and 18 RT. EPIC median score for Sx on urinary (UF)/ bowel (BF)/sexual (SF) function at 0, 1, 3, 6, 12 and 24 m was: 96/100/73, 59/98/24, 71/100/30, 91/100/21, 87/98/31, 95/100/31. For BT was 100/100/74, 85/96/67, 90/96/65, 96/96/65, 100/99/65, 100/100/60 respectively. For RT 90/97/54, 85/93/47, 92/97/52, 98/98/56, 95/98/52, 96/97/43. Statistically significant differences (SSD) found between the 3 groups on UF at all measurements (p < 0.02), and SF at 1 m (p < 0.01). C30 had SSD at 1m in social function and constipation (p < 0.05). PR25 had SSD on UF at 0 m, SF at 3 and 12 m (p < 0.05). CAVIPRES test had SSD on SF at 1 m (p < 0.001). Conclusions: UF was the most affected item, worse in Sx, better in BT, improving with time. SF had SSD after 1 m, mainly on Sx pts. At 12m most of the items improved, yet SF remained affected on Sx pts. C30 showed social function and constipation changes, whereas PR 25 just found UF differences in certain periods. CAVIPRES had SF differences at 1 m. More recruitment would allow to compare more in detail the accuracy of the tests. As active surveillance is now a possibility in LR PCa, further trials testing QoL with this approach are needed.
Characteristics and predictors of pain in patients with newly diagnosed and relapsed acute leukemia (AL).
Authors: Adir Shaulov, Gary Rodin, Anne Rydall, Gordana Popovic, Aaron David Schimmer, Lisa W Le, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2017)

e21633 Background: AL is a hematopoietic stem cell malignancy associated with substantial morbidity and mortality. The prevalence, correlates and causes for pain in this population have not been well studied. We present the results of a large cross-sectional study of pain in individuals with AL. Methods: Patients with newly-diagnosed or recently-relapsed AL admitted to a large tertiary cancer center completed the Memorial Symptom Assessment Scale (MSAS, which has subscales of prevalence, severity, frequency and distress, with ratings of 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). Demographic information, and disease and treatment variables were recorded. Two raters completed chart reviews in duplicate (with discussion of discordant results) for patients with severe pain (MSAS severity ≥3/4) to assess the site of pain. Results: A total of 362 patients were recruited from January 2008 to October 2013: 249 (68.8%) with AML, 80 (22.1%) ALL and 33 (9.1%) APL. Of these, 326 (90.1%) were newly diagnosed and 36 (9.9%) had relapsed disease; 346 (95.6%) were treated with (re)induction chemotherapy. Of 360 who completed the MSAS, pain was reported in 174 (48.3%), of whom 34.4% scored ≥3/4 on severity, 43.1% on frequency, and 44.3% on distress related to the pain. On multivariable analysis, patients reporting pain were more likely to be younger (OR 0.98 old vs young, p &lt; 0.001), and to have ALL (OR 0.57 AML vs ALL, p &lt; 0.05); duration of illness, gender, education, income and treatment intensity were not associated with pain. Pain was correlated with difficulty sleeping, worrying, difficulty concentrating, and feeling sad, nervous or irritable (all p &lt; 0.001). Of the 60 patients reporting severe pain (≥3/4), its site was identified in 53 (88.3%). The most common sites were oropharynx (29.7%), head (18.9%), abdomen (14.9%) and musculoskeletal (12.2%). Only 1.1% (4/362) of the cohort was referred to the palliative care/symptom control team over the month prior to or following assessment. Conclusions: Pain is a frequent and distressing symptom in patients with newly diagnosed or relapsed AL. Further research is needed to assess the efficacy of supportive care interventions in this population.
Molecular pathogenesis of disease progression in MLL-rearranged AML
Authors: Shinichi Kotani, Akinori Yoda, Ayana Kon, Keisuke Kataoka, Yotaro Ochi, Yusuke Shiozawa, Cassandra Hirsch, June Takeda, Hiroo Ueno, Tetsuichi Yoshizato, Kenichi Yoshida, Masahiro M. Nakagawa, Yasuhito Nannya, Nobuyuki Kakiuchi, Takuji Yamauchi, Kosuke Aoki, Yuichi Shiraishi, Satoru Miyano, Takahiro Maeda, Jaroslaw P. Maciejewski, Akifumi Takaori-Kondo, Seishi Ogawa, Hideki Makishima
Journal: Leukemia (2018)

Leukemic relapse is frequently accompanied by progressively aggressive clinical course. To understand the molecular mechanism of leukemic relapse, MLL/AF9-transformed mouse leukemia cells were serially transplanted in C57BL/6 mice (N = 96) by mimicking repeated recurrences, where mutations were monitored by exome sequencing (N = 42). The onset of leukemia was progressively promoted with advanced transplants, during which increasing numbers of somatic mutations were acquired (P < 0.005). Among these, mutations in Ptpn11 (p.G60R) and Braf (p.V637E) corresponded to those identified in human MLL-AML, while recurrent mutations affecting Msn (p.R295C) were observed only in mouse but not in human MLL-AML. Another mutated gene of interest was Gnb2 which was reported to be recurrently mutated in various hematological neoplasms. Gnb2 mutations (p.G77R) were significantly increased in clone size (P = 0.007) and associated with earlier leukemia onset (P = 0.011). GNB2 transcripts were significantly upregulated in human MLL-AML compared to MLL-negative AML (P < 0.05), which was supported by significantly increased Gnb2 transcript induced by MLL/AF9 overexpression (P < 0.001). In in vivo model, both mutation and overexpression of GNB2 caused leukemogenesis, and downregulation of GNB2 expression reduced proliferative potential and survival benefit, suggesting a driver role of GNB2. In conclusion, alterations of driver genes over time may play an important role in the progression of MLL-AML.
Impact of adherence to pomalidomide on medication adherence in pre-existing chronic conditions in patients with multiple myeloma.
Authors: Justin Gatwood, Ankur Dashputre, Katie S Gatwood
Journal: Journal of Clinical Oncology (2018)

e20010 Background: Oral oncolytics have increased survival in patients with multiple myeloma (MM) but the extent to which initiating these medications impacts adherence to medications for pre-existing chronic conditions is unknown. Methods: This was a retrospective cohort analysis of the MarketScan®Commercial Claims and Medicare Databases for years 2013-2015. Adult patients (≥18 years) were included if they had an ICD-9/10 diagnosis code for MM (203.xx/C90.XX), ≥ 2 pomalidomide claims, continuous eligibility 12 months prior to and 6-months after pomalidomide initiation, and no evidence of HIV. Evidence of diabetes, hypertension, and/or hyperlipidemia was determined by ICD9/ICD10 diagnosis codes and confirmed by filling ≥ 2 medications for one or more of these conditions in the 6 months prior to pomalidomide initiation. Adherence was measured using proportion of days covered (PDC) in the 6 months before and after pomalidomide initiation and PDC ≥ 80% was considered adherent. Repeated measures ANOVA assessed the impact of pomalidomide use on changes in chronic medication adherence. Logistic regression assessed the association of prior chronic medication adherence with pomalidomide adherence. Results: A total of 357 patients were identified. Mean age was 63.4 (± 10.9 years), a majority were male (58%), and 112 patients had at least one of the target chronic conditions. Small changes in mean PDC were observed for hypertension (93.9% vs 93.0%), hyperlipidemia (96.0% vs 92.4%), and diabetes (92.1% vs 89.2%). Repeated measures ANOVA revealed a non-significant impact of pomalidomide adherence on changes in adherence to hypertension (p = 0.16), hyperlipidemia (p = 0.63), and diabetes (p = 0.79) medications. The odds of adhering to antihypertensive medications was not impacted by level of pomalidomide adherence (OR: 1.02; 95% CI: 0.34-3.08). Conclusions: Initiation of pomalidomide appears to not impact use of existing medications for chronic conditions, at least in the short-run. Assessment of long-term pomalidomide should be considered that investigates whether patients remain adherent to both oral oncolytic and chronic disease medications.
Identifying advanced cancer patients readiness for goals of care conversations.
Authors: Cardinale B. Smith, Shelli Feder, Jenny J Lin, Nina A. Bickell, Dena Schulman-Green
Journal: Journal of Clinical Oncology (2016)

e18213 Background: Goals of care (GoC) conversations reduce healthcare utilization & improve quality of care, yet only 37% of advanced cancer patients report having them, often at the end of life. Identifying patient readiness to have these conversations is critical & remains largely unexplored. We sought to describe patients’ cues of readiness to engage in GoC conversations as perceived by patients & oncologists to inform a communication training intervention. Methods: We conducted semi-structured interviews at academic, community, municipal & rural hospitals (n = 4) in New York & Connecticut among advanced cancer patients (n = 19) & oncologists (n = 17). Interviews were audiotaped & transcribed. Three coders developed a code key & independently coded transcripts. Codes were compared & discrepancies resolved. We analyzed data using interpretive description. Results: Oncologists were 65% male with a mean age of 45 years. Sixty-nine percent were White, 23% Asian, & 8% Hispanic. Mean number of years in practice was 19 & 59% reported training in GoC. Among patients, 63% were female, mean age of 58 years. A third were White, 42% Black, 16% Hispanic, 5% Asian & 5% other. Readiness indicators identified by patients were asking questions about prognosis/disease status, emotional responsiveness (less emotive indicating readiness), active participation/listening, & the oncologist-patient relationship (quality & length). A patient summarized, “That's not an easy thing to judge, but you (oncologist) could tell. You could see how upset they are. You could see if they're responding to you. If you say something or you ask a question or whatever & by their response you could tell they are listening. They are participating…” Oncologists similarly identified information-seeking & emotional response as cues of readiness. Additional cues were non-verbal cues, practice experience & asking indirect questions. An oncologist stated, “Just the way he asked the question… I can’t tell you exactly how I know.” Conclusions: Patients identified concrete ways to establish GoC conversation readiness while oncologists report relying on non-tangible cues. Enabling oncologists to directly assess patient readiness may facilitate increased rates of GoC conversations. Clinical trial information: NCT02374255.
Randomized phase II trial comparing 4 doublets as a front-line treatment in Asian patients with recurrent/metastatic gastric cancer.
Authors: Hongjae Chon, Chan Kim, Minkyu Jung, Seungtaek Lim, Joo Hoon Kim, Ji Soo Park, Hyo Song Kim, Seung Hoon Beom, Hyun Cheol Chung, Sun Young Rha
Journal: Journal of Clinical Oncology (2016)

4063 Background: Despite a large number of randomized trials, there is no global consensus as to the standard regimen for front-line chemotherapy of recurrent/metastatic gastric cancer. We conducted a randomized phase II study to compare 4 doublet regimens, S-1 and cisplatin (SP); FOLFOX; docetaxel and 5-FU (DF); and paclitaxel and 5-FU (TF), for their therapeutic efficacy and safety as a first line treatment. Methods: Patients with no prior chemotherapy for recurrent/metastatic gastric adenocarcinoma were enrolled and randomized evenly to each regimen. The primary endpoint was progression free survival (PFS), and secondary endpoints were overall survival (OS), response rate (RR), and safety profile. Analysis was performed by intention to treat. Results: A total of 177 patients were enrolled from MAR 2010 to MAY 2015. Four treatment arms were well-balanced: median age 57, male 69.5%, and ECOG performance 0/1/2 = 61/37/2%. At data cutoff (DEC 31, 2015), median PFS were 8.6 (3.5-13.7) months for SP, 5.8 (2.9-8.7) months for FOLFOX, 6.8 (2.4-11.2) months for DF, and 4.6 months for TF (3.6-5.6) (p = 0.054). Median OS were 14.7 months for SP, 11.3 months for FOLFOX, 11.7 months for DF, and 10.7 months for TF (p = 0.208), and RR were 17.8% for SP, 21% for FOLFOX, 16% for DF, and 33% for TF). In terms of platinum- and taxane-based regimens, the PFS and OS did not differ significantly (PFS: 7.2 vs. 5.7 months; p = 0.207, OS: 13.3 vs. 11.7 months; p = 0.701). Toxicity was generally well tolerated, with grade 3-4 neutropenia observed in 33.3% of SP, 9.3% of TF, 55.6% of DF, and 45.5% of FOLFOX arm, while febrile neutropenia was observed in only 1 patient in SP arm and 2 patients in DF arm. There was no treatment-related mortality. Conclusions: Although none of the 4 regimens revealed significant superiority over others in the treatment of recurrent/metastatic gastric cancer, SP regimen showed a tendency of increased PFS and OS compared with other regimens. Clinical trial information: NCT01283204.
TCT-252 A Prospective, Multi Center Pilot Study Evaluating Plaque Photoablation Using the Novel Non-Guidewire Based RA-308 Excimer Laser in Subjects with Symptomatic Infrainguinal Lower Extremity Vascular Occlusions
Authors: Ehtisham Mahmud, Mitul Patel, Raghotham Patlola
Journal: Journal of the American College of Cardiology (2018)