tbuckley/cabot-search huggingface dataset:
Prognostic impact of pre-treatment cytogenetics in adult acute lymphoblastic leukemia (ALL).
Authors: Ghayas C. Issa, Hagop M. Kantarjian, Cameron C. Yin, Farhad Ravandi, Guillermo Garcia-Manero, Deborah A. Thomas, Jorge E. Cortes, Nicholas James Short, Koji Sasaki, Wei Qiao, Koichi Takahashi, Sherry Pierce, Srdan Verstovsek, Tapan M. Kadia, Gautam Borthakur, Susan Mary O'Brien, Elias Jabbour
Journal: Journal of Clinical Oncology (2016)

7038 Background: Reports on the prognostic impact of cytogenetics in adult ALL have been inconsistent. While some studies report that low hypodiploidy (Ho) and complex karyotype (Cx) are adverse prognostic factors, more recent studies in patients (pts) receiving pediatric-inspired regimens have failed to confirm these findings. Methods: Between 2000 and 2015, 442 pts with Philadelphia negative (Ph-) ALL with pre-treatment cytogenetics were identified. 330 (75%) pts were treated with hyper-CVAD-based regimens, 98 (22%) with augmented-BFM. Cx was defined as ≥ 5 chromosomal (ch) abnormalities (excluding established translocations) given that there was no difference in survival between pts with 3-4 ch abnormalities and pts in the diploid (Dp) group (p= 0.51). Based on the choromosome number, pts were categorized as low hypodiploidy (Ho; 30-39 ch)/near triploidy (Tr; 60-78 ch) (analyzed together), high hyperdiploidy (HeH; 51-65 ch), and tetraploidy (Tt; ≥ 80 ch). Results: Median age was 40 years (13-86). 191 pts (43%) were Dp, 32 (7%) were Cx, 29 (6%) were Ho-Tr, 25 (5%) were HeH, 6 (1%) were Tt, and 28 (5%) pts had MLL rearrangement (MLL). Baseline characteristics were mostly similar among the groups. However, pts with Ho-Tr and Tt were significantly older than Dp pts (median age 62 and 68 vs. 39; p = 0.0001 and p = 0.0003, respectively), and pts with Ho-Tr had a lower platelet count than Dp pts (median platelets 25 vs. 45, p = 0.0008). 5-year OS rates are listed in the Table. Pts with MLL, Ho-Tr and Cx had significantly worse OS than did pts with Dp; in contrast, there was a trend towards longer OS for HeH pts. In a multivariate analysis, Cx was the only cytogenetic group predictive for survival and was the strongest predictor when compared to Dp with a HR of 2.8 (95% CI 1.6-4.7, p < 0.01). Other independent factors identified included age, WBC, albumin and performance status. OS among all cytogenetic groups was similar whether pts were treated with hyper-CVAD or augmented-BFM. Conclusions: In this cohort of adult Ph- ALL pts receiving two different types of treatment, complex karyotype was the only cytogenetic risk group independently prognostic for OS. OS. % 5-year 95% CI P Dp 53 46-61 - HeH 72 55-94 0.13 MLL 26 12-58 < 0.01 Ho-Tr 37 20-69 0.01 Cx 29 15-54 < 0.01
Cctg BL12: Randomized phase II trial comparing nab-paclitaxel (Nab-P) to paclitaxel (P) in patients (pts) with advanced urothelial cancer progressing on or after a platinum containing regimen (NCT02033993).
Authors: Srikala S. Sridhar, Normand Blais, Ben Tran, M. Neil Reaume, Scott A. North, Martin R. Stockler, Kim N. Chi, Neil Eric Fleshner, Geoffrey Liu, John W Robinson, Som Mukherjee, Yasmin Rahim, Eric Winquist, Christopher M. Booth, Nghia Trung Nguyen, Emma Kate Beardsley, Nimira S. Alimohamed, Gail T McDonald, Keyue Ding, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2018)

4505 Background: Nab-P has shown promising activity as second line treatment of advanced urothelial cancer post platinum (Ko YJ, Lancet Oncol 2013) and may be more active and less toxic compared to P. Methods: Canadian Cancer Trials Group led a multicentre randomized phase II trial comparing Nab-P 260mg/m2 IV q21 days to P 175mg/m2 IV q21 days in pts with advanced urothelial cancer progressing after one line of platinum-based therapy. The primary endpoint was progression free survival (PFS); secondary endpoints included overall survival (OS), response rate (RR), adverse events (AEs) using CTC AE V4.03 and QOL (EORTC-C15-PAL, FACT-Taxane). A sample size of 199 pts was selected to detect target PFS HR of 0.67 using a 1-sided 5% level test with 81% power. Stratification factors included ECOG, liver mets, LN only mets, Hb level and ≤6mo from last platinum regimen. Results: 199 pts from Canada and Australia were enrolled from 2014-2017 with median age 67y, including 72% males, 30% liver mets, 84% ECOG 0/1 and 55% ≤6mo from last platinum therapy. Relative dose intensity ≥90% was 78% for Nab-P vs 67% for P. With median follow up 16.4mo, median PFS for Nab-P was 3.4mo vs 3.0mo for P (HR 0.92, 90%CI 0.68-1.23, p = 0.31); median OS for Nab-P was 7.5mo vs 8.8mo for P (HR 0.95, 90%CI 0.70- 1.30, p = 0.40). RR were similar, Nab-P 21% vs P 23% (p = 0.97). Rate of Grade(Gr)3+ all causality AEs was 67% for Nab-P vs 46% for P (p = 0.009); peripheral sensory neuropathy was 74% (Gr3+ 7%) for Nab-P vs 66% (Gr3+ 3%) for P (p = 0.27 (all grades), 0.33(Grd3+)). There were no significant differences in mean scores in any domain of QOL between Nab-P and P. Conclusions: Nab-P has similar efficacy and QOL compared to P as second line therapy in advanced urothelial cancer. Gr3+ all causality AEs were higher in the Nab-P arm. Clinical trial information: NCT02033993.
Lifestyle and periodontitis: The emergence of personalized periodontics
Authors: P. Mark Bartold
Journal: Periodontology 2000 (2018)

Abstract Personalized medicine is a medical model that involves the tailoring of healthcare ‐ with medical decisions, practices, and/or products being customized to an individual patient. In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, molecular, physiologic, or cellular analyses. With the advent of major advances in periodontal medicine, including genomic discoveries and greater understanding of the multifactorial nature of periodontitis, it seems that the time is ripe to use personalized medicine as a model for personalized periodontics. This volume of Periodontology 2000 explores how new advances in our understanding of periodontitis within a medical model can evolve into new treatment strategies tailor‐made for individual patients and not merely based on wholesale treatment paradigms.
Correlation of hypomagnesemia from cetuximab with survival in metastatic squamous cell cancer of the head and neck (SCCHN).
Authors: Sabarish Ram Ayyappan, Panayiotis Savvides, Dhivya Prabhakar, Pingfu Fu, Michael K. Gibson, Neelesh Sharma
Journal: Journal of Clinical Oncology (2016)

6041 Background: Cetuximab (C) improves survival and response rate in metastatic SCCHN. It also causes hypomagnesemia by renal electrolyte wasting. We evaluated incidence of hypomagnesemia and correlated this with clinical outcomes. Methods: This is a retrospective study of 46 patients with metastatic SCCHN treated with C alone or in combination with chemotherapy from 2003 – 2014. Patients received IV magnesium (Mg) supplementation on the day of infusion as per protocol. Clinical experimental variables: mg at baseline, on day 1 of each cycle and post therapy. Co-variates included age, sex, stage, skin toxicity, number of C infusions and concurrent chemotherapy. The predictive value of serum mg change on progression free survival (PFS) and overall survival (OS) was evaluated using the Kaplan-Meier method and Cox models. Results: Twenty six (57 %) patients developed hypomagnesemia that required replacement therapy. Fifty-four % had a 20% or greater change from baseline levels and nine patients (20%) developed grade 2-4 hypomagnesemia. Median time to first low mg was 39 days (3, 595). By univariate analysis, > 20% drop of mg was associated with better PFS (p = 0.02). By univariate Cox regression, % change of Mg, number of C infusions and time-to-lowest mg were significantly associated with PFS. There was an association between skin rash and drop of mg [ > 20% drop in 63.6 % with skin rash vs 30.8% without (p = 0.044)]. Median PFS was 4.1 months (95% CI- 2.7-6.4) and median OS was 9.4 months (95% CI- 6.6- 11.2). In the multivariate Cox proportional hazards analysis, age, percentage change of mg and skin rash were independently associated with OS and PFS (table 1). Conclusions: The incidence of C induced hypomagnesemia was 57% . Change in mg correlated with PFS and OS. Akin to skin rash, hypomagnesemia as a marker of outcome in SCCHN warrants further study. Multivariate analysis of covariates with PFS and OS. Factor OS PFS HR 95% C.I p-value HR 95% C.I p-value Age (per year increase) 1.07 1.01-1.14 0.026 1.07 1.02-1.14 0.011 % Change of magnesium 0.12 0.02-0.89 0.038 0.03 0.003-0.21 0.0007 Skin toxicity (Yes vs. no) 0.18 0.08-0.44 0.0001 0.19 0.08-0.44 < 0.0001
Molecular genetic testing patterns for patients with newly diagnosed acute myeloid leukemia (AML) enrolled in the CONNECT MDS/AML disease registry.
Authors: Daniel Aaron Pollyea, Tracy George, Kathryn M Foucar, Harry Paul Erba, Michael A. Thompson, Mehrdad Abedi, Gail J. Roboz, Danny Landau, John M. Pagel, Karen Seiter, Christopher R. Cogle, Melissa Nifenecker, Arlene S. Swern, Pavel Kiselev, Mary M. Sugrue
Journal: Journal of Clinical Oncology (2017)

7022 Background: Recurrent mutations in AML-associated genes have prognostic value and may help guide treatment decisions. Molecular genetic testing patterns for AML in clinical practice are largely unknown. Previously the CONNECT MDS/AML Disease Registry (George et al. ASH 2016. Abstract 3548) showed suboptimal adherence to WHO 2008 recommendations for AML in a cohort of newly diagnosed (ND) AML patients (pts) in clinical practice. Here we report a detailed analysis of patterns of molecular genetic testing in pts with ND AML in community and academic settings. Methods: The CONNECT MDS/AML Disease Registry (NCT01688011) is a US prospective, observational cohort study of pts with ND AML (≥55 years) or MDS. Enrollment is ongoing. All clinical decisions are made by study clinicians. The current analysis evaluated the percentage of pts with AML with molecular genetic testing recommended by NCCN guidelines ( NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, DNMT3A, and KIT). Chi-square tests evaluated effects of several variables on likelihood of molecular genetic testing. Results: Between 12 Dec 2013, and 8 Dec 2016 (data cutoff), 259 AML pts were enrolled at 86 sites. Molecular genetic testing was reported in 67% (173/259) of pts. Likelihood of testing varied, respectively, for academic vs community sites (76% [70/92] vs 62% [103/167], P= .018), normal vs abnormal karyotype (77% [79/103] vs 59% [79/133], P= .006), age &lt; 65 vs ≥65 (83% [65/78] vs 60% [108/181], P= .0003), and Medicare vs other insurance (61% [83/137] vs 74% [90/122], P= .025). In pts with molecular genetic testing (n = 173), the mutations tested varied substantially. All of the NCCN-recommended molecular genetic tests were reported in 9% (15/173) of pts, including 8% (6/79) of those with normal karyotype. Of the 7 NCCN-recommended tests, NPM1 (77%) and FLT3-ITD (76%) were most often reported and DNM T3A least often (16%). Conclusions: Early data from the CONNECT MDS/AML Disease Registry reveal that despite molecular testing reported in 67% of ND AML pts, a majority do not receive guideline-recommended testing. This prospective registry is uniquely positioned to capture changes in testing patterns as guidelines are established.
Choroid plexus tumors of the central nervous system: Searching for therapy targets with comprehensive genomic profiling.
Authors: Robert John Corona, Shakti H. Ramkissoon, Julia Andrea Elvin, James Suh, Jo-Anne Vergilio, Eric Allan Severson, Sugganth Daniel, Jonathan Keith Killian, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Glenn Jay Lesser, Paul D. Aridgides, Vincent A. Miller, Laurie M. Gay, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2018)

e14084 Background: Choroid plexus tumors (CPT) include papilloma (CPP), atypical papilloma (ACPP) and carcinoma (CPC) types. We hypothesized that comprehensive genomic profiling (CGP) could uncover potential new routes for treatment for relapsed and recurrent disease. Methods: Hybrid capture-based CGP was performed on DNA from 27 refractory FFPE CPT and analyzed for all classes of genomic alterations (GA), including base substitutions, insertions and deletions, gene fusions and copy number changes. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was calculated by principal components analysis of optimal homopolymer regions. Results: Clinically relevant GA in CPT were relatively rare, but included MET, EGFR, KIT and PTEN in less than 20% of sequenced CPT. The CPP group had a low KI67 index, few alterations per tumor (0.7), and were absent oncogene (OG) and tumor suppressor (TS) GA, or TMB. However, TERT mutations were detected, suggesting methylation silencing events. The ACPP group had an intermediate Ki67 index, 1.5 GA/tumor with intermediate frequencies of OG activation and TS loss, 27% TERT GA, but low TMB. The CPC group featured significantly higher Ki67 indices, more GA per tumor (2.67), 0% TERT GA, intermediate OG activation but high TS loss (75%, including 45% with TP53 GA), but 0 cases with high TMB. No CPT was MSI High. Conclusions: Although CGP can identify differences in GA in the 3 groups of refractory CPT, only a minority of CPT harbor potentially targetable GA that could potentially impact clinical outcome. CGP in the three groups reflects the contrasting histologic appearances of the low-, intermediate- and high-grade features in the three tumor types. Given the low TMB, absence of MSI High status and low frequencies of single gene predictors of efficacy (PRMB1, BRAF, MET), opportunities for immunotherapies for the CPT patients appear limited. CPP Atypical CPP CPC Cases 3 11 12 Median Age (years) 34 13 51 Gender M 66% M 55% M 50% Epithelial Marker 100% 83% 91% Mean KI-67 Index 2% 8% 30% GA/tumor 0.7 1.5 2.67 Oncogene Activation 0% 27% 25% Tumor Suppressor Gene Loss 0% 18% 75% TP53 0% 0% 45% TERT 33% 27% 0% MSI High 0% 0% 0% TMB ≥20 mut/Mb 0% 0% 0%
Uterus Transplantation: Response to Open Peer Commentaries on the Ethics of Using Deceased Versus Living Donors
Authors: Bethany Bruno, Kavita Shah Arora
Journal: The American Journal of Bioethics (2018)

We thank the commentators for their thoughtful responses. The breadth of thematic material in the responses is a testament to the complexity of the evolving science and bioethical conversation. Fur...
Venous thromboembolism incidence in radiation oncology: Retrospective trial.
Authors: Mikhail A Cherkashin, Natalia A Berezina
Journal: Journal of Clinical Oncology (2017)

e18289 Background: Venous thromboembolism (VTE) prevention in oncology patients during external beam radiation therapy (RT) in outpatient setting is the challenging question. We performed analysis of our own data. The aim of study is the clear assessment of VTE incidence in these patients Methods: In retrospective analysis 5134 patients' medical records were included (2612 with RT and 2522 with chemotherapy). Inclusion criteria were: RT in outpatient setting and chemotherapy in outpatient setting. Exclusion criteria: combined radiochemotherapy, hospitalzation, central venous catheter, palliative treatment. 487 patients were selected for the final analysis and stratified in 3 groups: group I (n = 165) 3D-conformal RT for brain tumors or brain metastasis; group II (n = 158) RT for body tumors (abdominal, retroabdominal, pelvic, chest, breast); group III (n = 164) was control –brain and body tumors on chemotherapy. Mean fraction numbers were 25 (11 - 32), mean total dose – 52 Gy (22 - 66). VTE assessment based on clinical data, ultrasound examination (US) and chest CT. Statistical analysis was performed by OpenEpi, Version 3 software pack. Results: Deep vein thrombosis (DVT) was detected in 10 cases (6.06%) in group I, 4 cases in group II and 4 case in control group. VTE patients has a different tumors (astrocytomas, brain trunk tumors, skull basis cancer, rectal cancer, breast cancer). 3 patients were available for long-term outcomes assessment (12 months after radiation therapy). During 1-year period we haven’t detected thrombosis recurrence. One patient on 11th follow-up month was exposed with repeated course of RT without any complications. The difference between VTE incidence for group I and group III characterized by statistical significance (p = 0.018). Risk difference for these groups was 5% (p &lt; 0.05). Conclusions: Based on study results we suggest that external beam radiation therapy is potentially an independent risk factor for VTE development even in outpatient settings. High degree of clinical suspicion and aggressive diagnostic work-up in case of suspicion is necessary. In our opinion low molecular weight heparins prevention should be considered at least during active radiation therapy.
Comparison of patient reported symptom burden in patients with ovarian cancer undergoing primary vs. interval tumor reductive surgery.
Authors: Larissa Meyer, Qiuling Shi, Maria Iniesta, Melinda Harris, Charlotte C. Sun, Javier Lasala, Shelley Wang, Alpa Manchandia Nick, Karen H. Lu, Pedro T Ramirez
Journal: Journal of Clinical Oncology (2017)

5557 Background: Patient-reported outcomes (PROs) are important in comparative effectiveness research. We compared symptom burden and functional recovery in pts undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS). Methods: Perioperative PROs were measured for women with ovarian cancer undergoing PCS or ICS using the MD Anderson Symptom Inventory- Ovarian Cancer, a 27-item validated tool which was administered preoperatively, daily in hospital, and at least weekly for 8 weeks post-op. Mixed-effect modeling was performed. Results: 108 pts (45 PCS, 63 ICS) participated. There was no difference in median age, Charlson comorbidity index, ASA status, history of chronic opioid use, length of stay or readmission rate. At pre-op baseline assessment, the mean pain score was higher in the PCS group (3.8 vs. 1.8, p = .0005). ICS pts had a lower median surgical complexity score (4.0 vs. 2.0, p = .03), and shorter median surgical time (260 min vs. 223 min, p = .05). During hospitalization, pts undergoing PCS reported significantly more bloating, urinary urgency, distress, sadness and mood disturbance. Women who received NACT had a significantly higher symptom burden of neuropathy, leg cramps and memory disturbances. There was no difference in pain, fatigue, drowsiness, nausea, or emesis within the first 5 days postoperatively. While there was no significant differences in the physical interference composite score, (walking, work, activity), those who underwent ICS had improved affective interference scores (mood, relations, enjoyment of life). Conclusions: Within an ERAS program, there were few significant differences in surgery related symptoms related to physical recovery between pts undergoing PCS or ICS. The differences in overall symptom burden suggest that disease related symptoms (pain, bloating, urinary urgency) and emotional symptoms may be related to recent diagnosis and higher tumor burden in pts undergoing PCS while the increased numbness, leg cramps and memory issues reflect chemo-related effects in the ICS cohort.
Expansion of HER2-CAR T cells after lymphodepletion and clinical responses in patients with advanced sarcoma.
Authors: Meenakshi Hegde, Christopher C. DeRenzo, Huimin Zhang, Melinda Mata, Claudia Gerken, Ankita Shree, Zhongzhen Yi, Vita Brawley, Olga Dakhova, Meng-Fen Wu, Hao Liu, John Hicks, Bambi Grilley, Adrian P. Gee, Cliona M. Rooney, Malcolm K. Brenner, Helen E. Heslop, Winfried Wels, Stephen Gottschalk, Nabil M. Ahmed
Journal: Journal of Clinical Oncology (2017)

10508 Background: Outcome for patients with advanced sarcoma is extremely poor and treatment options are limited. Encouragingly, in our phase 1 dose-escalation trial (Ahmed et al, JCO 2015), systemic administration of up to 1x10 8 /m 2 autologous HER2-CAR T cells in patient with HER2+ sarcoma was safe. While T cells did not expand, 4/19 evaluable patients are alive 37-61 months post infusion without evidence of disease. The goal of this study was to evaluate if lympohodepleting chemotherapy can safely induce the expansion of HER2-CAR T cells. Methods: In a phase 1 clinical study, NCT00902044, we administered 1x10 8 /m 2 autologous HER2-CAR (with a CD28.zeta signaling domain) T cells to patients with refractory/metastatic HER2+ sarcoma after lymphodepletion. Results: Six patients with refractory/metastatic HER2+ sarcoma (4 osteosarcoma, 1 rhabdomyosarcoma, 1 synovial sarcoma) with a median age of 16 (range: 4 to 55) received up to 3 infusions of 1x10 8 cells/m 2 CAR T cells after lymphodepletion with either fludarabine (Flu; n = 3) or Flu and cyclophosphamide (Flu/Cy; n = 3). Flu and Flu/Cy induced lymphopenia with an absolute lymphocyte count (ALC) of &lt; 100/ml at the day of the T-cell infusion. Only Flu/Cy induced neutropenia (absolute neutrophil count [ANC] &lt; 500/ml) for up to 14 days. 4/6 patients developed grade 1-2 cytokine release syndrome (CRS) within 24 hours of CAR T-cell infusion that resolved completely with supportive care within 3 days of onset. T cells expanded in 5/6 patients (median 89-fold (range: 41 to 2,893) with a median peak expansion on day 7 (range: 5 to 28). CAR T cells could be detected by qPCR in 6/6 patients at 6 weeks post infusion. One patient with rhabdomyosarcoma metastatic to the bone marrow had a complete responses (CR), 2 had stable disease (SD), and 3 had progressive disease (PD). Two patients are alive with a median overall survival of 14.2 months. Conclusions: Infusion of autologous HER2-CAR T cells after lymphodepletion is safe, and can be associated with objective clinical benefit in patients with advanced HER2+ sarcoma. These findings warrant further evaluation in a phase 2b study as a single agent or in combination with other approaches. Clinical trial information: NCT00902044.