tbuckley/cabot-search huggingface dataset:
A single center experience with next generation sequencing (NGS) for the care of advanced non-small-cell lung cancer (NSCLC).
Authors: Deepa Rangachari, Paul A VanderLaan, Xiuning Le, Erik Folch, Michael S Kent, Sidharta P Gangadharan, Adnan Majid, Richard L. Haspel, Loren Joseph, Mark Huberman, Daniel Botelho Costa
Journal: Journal of Clinical Oncology (2015)

e19109 Background: Tumor genotyping using single gene assays (SGAs) is a standard approach in advanced NSCLC. We evaluated how therapeutic decision-making was altered by the introduction of NGS into routine practice. Methods: Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution. Results: 82 tumors were genotyped: 75 by SGAs, 7 by NGS alone. SGAs identified 10 EGFR-mutated, 3 ALK-rearranged, and 21 KRAS-mutated tumors. Sequential testing with SGAs followed by NGS was more common for patients with EGFR/ALK/KRAS-negative tumors (22/29 or 75.9%) and adenocarcinomas (ACs) (21/22 or 95.5%); most EGFR/ALK/KRAS-negative tumors were sent for NGS (21/35 or 60%). Of 17 ACs, 10 harbored abnormalities in a known driver oncogene (1-EGFR, 2-ERBB2, 1-ROS1, 1-RET, 2-MET, 2-KRAS and 1-MAP2K1). Primary NGS was used mainly in squamous cell cancers (SCCAs) (6/7 or 85.7%). In 7 SCCAs, 1 sample had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). NGS was successful in 24/29 (82.7%) tumors. There was a trend toward increased assay failure in those samples undergoing sequential SGAs followed by NGS as compared to primary NGS alone. All patients with EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. Clinical decisions were impacted by NGS results in 8/17 (47.0%) ACs (trial consideration in 6, off-label TKI use in 2). Therapeutic decisions were influenced by NGS results in 0/7 SCCAs. Actionable therapeutic targets were significantly more frequent in patients with a ≤ 15 pack-year tobacco history vs. those with > 15 pack-years of tobacco use (17/27 or 62.9% vs. 3/42 or 7.1%, respectively; p < 0.0001). Conclusions: Targeted NGS can identify a significant number of driver events in lung ACs—particularly in never/light smokers—for which targeted therapies are available or in development. However, for SCCAs, NGS results are less likely to alter standard practice, barring participation in biomarker-driven studies. Future research into the cost effectiveness and optimal use of NGS in NSCLC is warranted.
Final results of a phase I trial of fasting prior to platinum-based chemotherapy.
Authors: David I. Quinn, Susan G. Groshen, Manali Shah, Denice D Tsao-Wei, Agustin A. Garcia, Huyen Pham, Yvonne Gail Lin, Charlean Ketchens, Kristy Massopust, Min Wei, Valter Longo, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2013)

9632 Background: Fasting confers dramatic protection against chemotherapy toxicity in mice (PNAS 2008). We studied safety and feasibility of escalated fasting duration prior to platinum doublet chemotherapy in cancer patients (pts). Insulin, glucose, ketones and insulin-like growth factor (IGF) were measured as potential biomarkers of the fasting state. Methods: 3 fasting cohorts were evaluated: 24, 48 and 72 hours (hr) (48 pre/24 post chemotherapy). Subjects recorded all calories consumed during the fast period. Feasibility was defined as 4/6 subjects in each cohort consuming &lt; 200 kCal/24 hr without excess fasting toxicity (using CTCAE v4.0). Results: Primary cancer: Urothelial 5, breast 5, ovarian 7, uterine 1, NSCLC 1. Regimens: gemcitabine+ cisplatin 6, docetaxel + carboplatin (C) + trastuzumab 5, C + paclitaxel 8. Median age: 61y (31-73). 4/6 pts, 5/7 pts and 4/6 pts in the 24, 48 and 72 hr groups were fasting compliant &lt;200 kCal/24 hr with no significant toxicities. Median weight change was 0 after 1 cycle of fasting (-3.8% to +3.1%); 1 pt failed to regain 25% of lost weight prior to second cycle and per protocol did not fast again. Reasons for failure included forgetting and inability to maintain fast. Worst symptoms during the 48 and 72 hr fast: grade 1 hypoglycemia and hyponatremia; grade 2 headache, fatigue and dizziness; there were no grade 3 or 4 fasting-related toxicities. After fasting, insulin levels fell by medians of 69% in 24hr pts and 60% in 48hr pts (p=0.014). Median IGF1 levels Δ by -18.3% (p=0.012), interestingly 3 pts who fasted 72 hr had further Δ -19% to -59% from 48 to 72 hr. Conclusions: Fasting for up to 72 hr around chemotherapy is safe and feasible for cancer pts and resulted in significant decline in insulin and IGF1 levels. The randomized phase II portion of the trial commenced with 72 hr fast, seeking to delineate insulin and IGF1 as potential biomarkers of chemotherapy toxicity reduction. Clinical trial information: NCT00936364.
Recurrent Tongue Masses in a Young Boy
Authors: Michael W. Chan, Priya Gopwani
Journal: JAMA Pediatrics (2017)

A 7-year-old healthy boy had recurrent painless tongue masses since birth that would resolve spontaneously over the course of days to weeks. The lesions were usually white and the size of a pinhead, and located on the anterior portion of the tongue. What is your diagnosis?
The Prescriptions I Write
Authors: Norah Neylon
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Gene expression changes linked to efficacy in human tumor xenografts treated with the CDK4/6 inhibitor PD0332991
Authors: Seth Sadis, Xianxian Zheng, Mary Anne Meade, Clarence Lewis, Mark Molloy, Laura Fleischer, Steven J. Madore, Li Xi, Megan Robinson, Eric Kaldjian, William Elliot, Wilbur R. Leopold, David W. Fry
Journal: Cancer Research (2004)

4755   Phosphorylation of the retinoblastoma protein (Rb) by cyclin dependent kinases 4 and 6 (CDK4/6) is typically required for human cancer cell proliferation. PD0332991 is a potent, selective, and orally bioavailable inhibitor of CDK4/6. In human tumor xenografts, PD0332991 caused significant reductions in tumor mass and/or growth delay in several xenograft models but had less effect in others despite effectively blocking Rb phosphorylation in all models. To investigate differences in sensitivity to PD0332991, we characterized gene expression in human tumor cell cultures and xenografts treated with PD0332991 using Affymetrix GeneChip (HU133A) technology. Three human xenograft tumors were chosen that varied in response to PD0332991: Colo205 (tumor regression), MDAMB435 (tumor stasis), and SW620 (slight tumor growth delay). There was an apparent association between the extent of gene modulation (both in number of genes and in magnitude of response for individual genes) and the sensitivity to tumor growth delay of the xenograft model. Indeed, the capacity of PD0332991 to modulate gene expression as determined by number of gene changes (≥2-fold,  p ≤0.05) was correlated with objective measures of tumor growth delay across the 3 xenograft models and 3 dose levels, suggesting that efficacy is mechanistically linked to the ability of PD0332991 to alter gene expression. The physiological roles of genes regulated by PD0332991 were characterized using Gene Ontology annotation. In both MDAMB435 cell cultures and the 3 xenograft models, PD0332991 primarily downregulated genes associated with DNA replication and repair, cell cycle, signal transduction, and mitosis. Many genes modulated by PD0332991 have been previously characterized as being transcriptionally activated by E2F transcription factors. Gene changes shared between models were identified. This gene cohort was similar to the previously described proliferation gene signature noted in several cancer types and may be an appropriate efficacy related clinical biomarker for PD0332991. Changes in gene expression were confirmed for selected markers using RT-PCR, ELISA, and western blotting. The results suggest that PD0332991, by selectively blocking Rb phosphorylation, causes transcriptional down-regulation of genes required for cancer cell proliferation. Differences in sensitivity to PD0332991 may be due to factors that associate with hypophosphorylated Rb to regulate transcription.
Association outcome with genes involved in immune response and checkpoints in patients with resected colorectal liver metastases.
Authors: Stefan Stremitzer, Wu Zhang, Dongyun Yang, Yan Ning, Sebastian Stintzing, Ana Sebio, Yu Sunakawa, Shinichi Yamauchi, Satoshi Matsusaka, Rita Elie El-Khoueiry, Judith Stift, Friedrich Wrba, Thomas Gruenberger, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

3563 Background: In patients with colorectal liver metastases (CLM), liver resection offers the chance of cure and long-term survival. The liver is a highly immunogenic organ harboring approximately 80% of the body’s tissue macrophages. Emerging data demonstrate a critical role of an immune response for cancer treatment. In this study we investigated genetic variations within genes involved in immune response and checkpoints and their association with recurrence and outcome in patients with CLM. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected bevacizumab-pretreated CLM from 149 patients [median age 62 years (range 30-80), 58.4% male, median follow-up 3.9 years (range 0.02-7.7)]. Single nucleotide polymorphisms (SNP) in nine genes associated with immune surveillance and checkpoints (CCL2, CCR2, LAG3, CD73, PDCD1, PDL1, IDO1, CTLA4, CD24) were analyzed by direct Sanger DNA sequencing and evaluated for association with response, recurrence-free survival (RFS) and overall survival (OS). Results: In univariate analysis, rs3739319 (IDO1) and rs8734 (CD24) showed a significant difference in three-year OS rate [(G/G or G/A 75%, A/A 49%; HR (95% CI) 2.52 (1.33, 4.80), P=0.007) and (G/G 63%, G/A or A/A 76%; HR (95% CI) 0.53 (0.28, 0.97), P=0.042), respectively]. In multivariate analysis adjusted for age, number of metastases, size of metastases and time since diagnosis of colorectal cancer, rs3739319 remained significant (HR (95% CI) 2.04 (1.03, 4.03), P=0.040). Recursive partitioning analyses revealed that rs8734 and rs3739319 were the dominant SNPs predicting histological response and OS, respectively. Conclusions: Our data suggest that gene variations within genes involved in immune response and checkpoints are associated with outcome in patients with resected CLM. These data might lead to improved treatment strategies modulating anti-tumor immune response by targeting novel immune checkpoints.
Cancer patients' answers to surveys: Incorporation into the electronic health record (EHR) can decrease manual data entry and increase patient-centered information.
Authors: Katy E. French, Thomas W. Feeley, Tayab A. Andrabi, Alexis B. Guzman, John D. Calhoun
Journal: Journal of Clinical Oncology (2017)

130 Background: Delivery of value-based cancer care has centered on the use of EHR’s and how these applications can document health information, including patient reported outcomes (PRO’s), (1-4). Survey information must be incorporated into the medical record with minimal staff intervention. Our institution, and many cancer centers are currently using “EPIC” as their EHR platform. Although this is a data driven platform, and data can be extracted and reported as desired, certain things need to be done prior to going live in order to ensure this occurs. Surveys must be built using standardized “smart data elements” (SDE’s). If patient data is gathered, but not integrated correctly into the EHR, one will find themselves manually entering data. The goal is to allow patients to answer questions about their health history 1 time, validate answers, incorporate into the EHR, and report data. Methods: We engaged our technology team prior to “go-live” to build patient survey questionnaires. 40 survey questions, were mapped to 72 specific EHR/“EPIC” SDE’s. The SDE’s included cancer diagnoses and past medical history. Patients received and completed the electronic survey via the patient portal. Clinic providers validated patient answers from the surveys and the information was incorporated into the EHR. Results: Patient entered survey data collected, documented, and reported within the EHR. Decreased data entry by providers, efficiently incorporating the patient cancer diagnosis and medical history into the EHR. Data collected for review/reporting/research as needed. Conclusions: EHR’s can gather specific/discrete patient data to benefit both patients and providers. Cancer patients can participate in providing health information easily incorporated and documented by the provider. Data can be updated as needed, and used for patient reported outcomes (PRO’s) and other research endeavors. EHR’s should enhance care by allowing providers to spend more face to face time with patients and providing data that is most important to patients from which they may make informed decisions about their health care.
Direct‐acting antivirals during or after immunochemotherapy in hepatitis C virus–positive diffuse large B‐cell lymphomas
Authors: Michele Merli, Marco Frigeni, Manuel Gotti, Paolo Grossi, Raffaele Bruno, Francesco Passamonti, Luca Arcaini
Journal: Hepatology (2017)

Merli, Michele; Frigeni, Marco; Gotti, Manuel; Grossi, Paolo; Bruno, Raffaele; Passamonti, Francesco; Arcaini, Luca Author Information
Effect of seedling age and spacing schedule on the productivity and quality traits of rice under system of rice intensification (SRI)
Authors: K. Kanaka Durga, P. Sambasiva Rao, K. Raju
Journal: Journal of Clinical Oncology (2015)

Studies on the effects of seedling age and spacing schedule on the productivity and quality traits of rice adopted under system of rice intensification (SRI) was taken up at Seed Research and Technology Centre, Rajendranagar, Hyderabad during kharif, 2008 and 2009 using popular rice cultivar, Swarna (MTU 7029). 16 days seedlings planted at 20 × 20 cm, 12 days / 20 × 20 cm (56.2 q/ha) and 14 days / 20 × 20 cm (53.4 q/ha), 12 days / 25 × 25 cm (52.2 q/ha) and 12 days / 30 × 30 cm (51.2 q/ha) were found superior for grain yield and were significantly different from the rest of the treatments. Of all the five treatments, 12 days aged seedlings besides recording highest grain yield were also found superior for spikelet fertility and ear bearing tillers per hill. Further, 12 days old seedlings planted at 25 × 25 cm recorded 100% germination with longer seedlings and high seedling vigour Index I.

	 

	Key words: Seedling age, spacing schedule, system of rice intensification (SRI), grain yield.
Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.
Authors: Angela Di Giannatale, Kieran Mc Hugh, Nathalie Dias, Annick Devos, Birgit Geoerger, Tim Jaspan, Raphael Calmon, Frederic Courbon, Katty Malekzadeh, Isabelle Aerts, Arnauld Verschuur, Michela Casanova, Fanny Fouyssac, Herve Rubie, Nadege Corradini, Yves Perel, Michel Zwaan, Riccardo Riccardi, Marie-Cécile Le Deley, Huib Caron
Journal: Journal of Clinical Oncology (2012)

9517 Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.
Primary retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ-cell tumor (NSGCT): Impact of trends in patient selection on retroperitoneal pathology and outcome
Authors: A. J. Stephenson, G. J. Bosl, R. J. Motzer, D. F. Bajorin, J. P. Stasi, J. Sheinfeld
Journal: Journal of Clinical Oncology (2004)

4523 Background: Elevated pre-RPLND serum tumor markers (STM) is prognostic for relapse for clinical stage (CS) IS and pathologic stage (PS) N1 patients, and for persistence of disease for PS N2–3 patients. Since 1999, we have recommended that patients with elevated STM and/or CS IIB receive induction chemotherapy. We examined the impact of these selection criteria on outcome after primary RPLND. Methods: Since 1989, 453 patients with NSGCT have undergone primary RPLND (345 pre-1999, 108 post-1999). Data was obtained from a prospective database. A level of AFP or BhCG that was elevated and not declining according to half-life pre-RPLND was considered elevated. The median follow-up was 68 and 25 months for patients treated pre- and post-1999, respectively. Results: Pre-1999, 28 (8%) patients had elevated STM and 23 (7%) had CS IIB. Post-1999, all patients had normal STM and 1 (1%) had CS IIB. Patients treated since 1999 trended toward a lower rate of PS II (44% pre- vs. 33% post-1999, P=0.06). Among patients with PS II, those treated since 1999 were more likely to have low-volume (PN1) retroperitoneal disease at RPLND (64% vs. 40%, P=0.01), even when excluding patients with elevated STM and CS IIB (63% vs. 52%, P=0.02). Patients treated since 1999 have had lower rates of relapse after RPLND (4-year relapse-free survival 97% vs. 90%, P=0.04), even when excluding those receiving adjuvant chemotherapy (96% vs. 88%, P=0.049). In multivariate analysis, elevated STM (P=0.001) was the only significant pre-RPLND predictor of relapse when accounting for the use of adjuvant chemotherapy. Although not statistically significant, embryonal carcinoma predominance (P=0.06), treatment year (P=0.07) and clinical stage (P=0.09) may also be important predictors of relapse. Conclusions: As a result of excluding patients with elevated STM and/or CS IIB, proportionately more PS II patients have low-volume retroperitoneal disease and are likely to be cured by RPLND alone. Patients treated since 1999 may have a favorable prognosis independent of STM status and clinical stage. No significant financial relationships to disclose.
Risk factors for adverse outcomes in solid tumor interhospital transfer patients.
Authors: Christopher Wee, Leticia Varella, Lisa A. Rybicki, James Stevenson
Journal: Journal of Clinical Oncology (2017)

191 Background: We previously reported that inter-hospital transfer patients to our institution’s oncology service experienced higher mortality and increased length of stay (LOS) compared to other origins of admission. We sought to identify risk factors for adverse outcomes in this hospital transfer population. Methods: We reviewed all inter-hospital transfers from Jan-June 2016 to the Cleveland Clinic’s solid tumor oncology service. Patient characteristics, including age, albumin, and case severity indices (mortality and severity risk scores and AP-DRG), as well as encounter characteristics, including admitting provider (house staff or hospitalist), admission time (8AM-5PM or evening), admission day (weekday or weekend), and time between transfer acceptance and admission were recorded. Adverse events examined included activation of adult medical emergency team (AMET), ICU transfer, LOS, in-hospital mortality, and 30-day readmission. Associations of patient and encounter characteristics with adverse events were assessed using Wilcoxon and Fisher’s exact tests. Results: Fifty-three transfer admissions were identified. Patients had a median age of 67 years and 58.5% were male. House staff admitted the majority of patients (81.1%) and most occurred after hours (62.3%). Age, admission time and day, and type of admitting physician were not associated with adverse events. There was a significant association between higher AP-DRG and mortality/severity risk scores with ICU transfers, AMET activations, and mortality. Patients who experienced any adverse events on average had a lower mean albumin than those who did not (2.3 vs 3.0 g/dL p=0.006). LOS and readmission were not significantly associated with any patient or encounter characteristics. Conclusions: Burden of disease as measured by mortality/severity risk and AP-DRG as well as lower albumin levels are associated with adverse events in solid tumor inter-hospital transfer patients, while encounter characteristics do not predict for poorer outcomes. This population should be targeted for improvements in communication and handoffs at the time of transfer, as well as early involvement of palliative care providers.