tbuckley/cabot-search huggingface dataset:
Comparison of Taqman low density array (TLDA) five-gene assay for tumor cells in bone marrow and blood with histologic bone marrow examination and imaging for disease assessment and outcome in patients with recurrent/refractory neuroblastoma (NBL): A new approaches to neuroblastoma therapy (NANT) study.
Authors: Araz Marachelian, Judith Villablanca, Shahab Asgharzadeh, Wei Yao Liu, Betty Liu, Sabrina Young, Brian D. Weiss, Howard M. Katzenstein, Susan Lerner Cohn, Sylvain Baruchel, Clare Twist, Meaghan Granger, Katherine K. Matthay, Jemily Malvar, Richard Sposto, Robert Seeger
Journal: Journal of Clinical Oncology (2013)

10039 Background: Accurate quantification of tumor burden in NBL patients is needed to define homogenous populations for therapy and establish response criteria that predict outcome. The 5-gene TLDA assay was developed for quantification of NBL cells in bone marrow (BM) and blood (BLD). Methods: Expression of CHGA, DCX, DDC, PHOX2B, and TH (NBL genes) was quantified with TLDA and reported as the geometric mean cycle threshold for the 5 genes (DGS=detection gene score; inversely related to tumor content, 40=negative). Sixty-three patients with recurrent/refractory NBL had TLDA performed on 107 BM and 99 BLD samples (66 paired) at 140 time points. Based on central review of reports, tumor longest diameter (LD) on CT/MRI (n=118), and number of 123 I-MIBG avid sites (n=120) were recorded. Percentage of tumor cells in BM was from institutional reports of bilateral BM aspirates/biopsies (n=109). Overall response was assessed per NANT Response Criteria. Spearman rank correlation was performed. Results:TLDA detected tumor cells in 62/99(63%) BLD (average DGS=37.45) and 91/107(85%) BM samples (average DGS=33.42). 39/91(42%) with positive BM TLDA were negative by morphology. BLD and BM TLDA were correlated r = 0.6540, p&lt; 0.0001 with stronger correlation with lower BM DGS scores. The BM and BLD DGS correlated with % BM involvement (BM r= -0.63, p&lt;0.0001; BLD r= -0.35, p=0.0023) and number of MIBG sites (BM r=-0.34, p=0.001, BLD r=-0.51 p&lt;0.0001) but not LD. Number of MIBG sites was also correlated with % BM involvement (r= 0.45, p&lt;0.001) and LD (r= 0.28, p=0.0039). Analysis of 43 BM pairs demonstrated decreasing DGS correlated with overall progressive disease (r= 0.39, p=0.01). Conclusions: This TLDA assay detects NBL cells in both BM and BLD at high rates, and frequently detects tumor cells when BM morphology is negative. Quantification of tumor with DGS correlates with % BM involvement and number MIBG sites. TLDA may provide an additional parameter to delineate response in NBL. Clinical trial information: NCT01587300.
Extended neoadjuvant chemotherapy (CT) in borderline resectable pancreas cancer (BRPC).
Authors: J Bart Rose, Flavio G. Rocha, Bruce S. Lin, Adnan Alseidi, Thomas A. Biehl, Ravi Moonka, John A. Ryan, L. William Traverso, Scott Helton, Vincent J. Picozzi
Journal: Journal of Clinical Oncology (2013)

4043 Background: The optimal surgical (S) approach to BRPC is unknown. We evaluated an approach to BPRC using extended course chemotherapy (CT) without routine neoadjuvant chemoradiation (CRT). Clinical outcomes were evaluated on an "intent to treat" basis. Methods: Patients (pts) were identified from a prospectively-maintained database started in 2008. Pts required 1) Dx BRPC with non-tail primary per radiographic staging using AHPBA/NCCN guidelines 2) No prior therapy (Rx) 3) Negative staging/exploratory laparoscopy prior to S 4) All cancer Rx at VMMC prior to S. Pts received gemcitabine/docetaxel (G/D) as initial CT. Pts with systemic progression/comorbid complication prior to 24 wks were not offered local Rx; pts with localized cancer at 24 wks judged likely to achieve R0 resection were offered S; all other pts were offered fluoropyrimidine-based CRT. Results: Of 76 identified pts (median age 66), 12 (16%) are on initial CT and not fully evaluable. G/D as sole CT achieved 24 wk disease control in 46/64 (72%) pts and &gt;50% decline in baseline CA 19.9 in 39/55 pts (71%). 53/64 fully evaluable pts (83%) completed 24 wks CT, 11/64 pts (17%) did not (4 systemic progression, 3 Rx- related, 4 intercurrent illness). 50/53 pts attempted local Rx (40 S, 10 CRT, 2 unfit, 1 refused). 30/40 pts (75%) had successful S (all R0), 10/40 pts (25%) had inoperable disease (4 local-subsequently received CRT, 6 systemic). 23/30 pts (77%) have received some form Rx post R0 resection. With median f/o of 20 mo, 23/44 (52%), 17/30 (57%), and 6/14 (43%) receiving any local Rx, S, and CRT-only remain progression free. 13/30 S pts recurred, 3 local (10%) and 10 systemic (33%). 1-yr, 2-yr, 3-yr, and median overall survivals (OS) for fully evaluable pts respectively are 82%, 50%, 36%, and 27 mo. Median OS for pts receiving CT-only (20 pts), CT+CRT (14 pts), and R0 pts are 12 mo, 17 mo, and &gt;20 mo, respectively. 25/30 R0 pts remain alive (range 6-54 mo). Conclusions: 1) Extended neoadjuvant CT without routine neoadjuvant CRT is a feasible approach to BRPC. 2) G/D has significant activity in BRPC. 3) Pretreatment surgical staging combined with the above Rx yields a high probability of R0 resection. 4) OS for both resected and non-resected pt was superior to usual literature comparators.
Addressing tobacco use at NCI designated cancer centers: Online resources available for patients.
Authors: Eric K. Singhi, Alix W. Pommerenke, Sarah Mushtaq, Kenneth Michael Cummings, James Roger Marshall, Anthony Alberg, Graham Walter Warren
Journal: Journal of Clinical Oncology (2015)

e12566 Background: Tobacco is the single largest preventable cancer risk factor, and continued tobacco use by cancer patients causes adverse treatment outcomes. The purpose of this study was to evaluate online patient resources provided by NCI designated cancer centers (NDCCs) about the adverse health effects of tobacco use and available tobacco cessation programs. Methods: A survey instrument was created to uniformly evaluate user accessibility to online information about tobacco use and cessation at NDCCs. The survey of NDCC websites for the 61 NDCCs that offer clinical care for patients was completed in the fall of 2014. Results: Of 61 centers, 18% provided information on tobacco use or cessation on the homepage and 95% had information on one or more embedded pages. When applicable, information was available on ≥ 74% patient information, research information, or disease-specific pages in contrast to only ≤ 23% of education and outreach pages. On disease-specific pages, tobacco information was almost solely limited to thoracic cancers (44 of 47). When using a center-specific search engine, 28% of NDCCs had no information on tobacco or cessation within the top 20 search results. When tobacco cessation program information was available (n = 43), 51% presented a clinical program only, 16% presented a research program only, and 33% presented both. Referrals to other online resources were provided by 44% of NDCCs. The overall adverse health effects of smoking were discussed by 48%, and 36% addressed the health benefits of quitting, but only 10% specifically discussed the health effects of smoking in cancer patients. Cessation tips and medications were provided by 28-34% of NDCCs, but only 13% discussed medication dose, duration, contraindications or side effects. Contact information for a tobacco cessation program was provided by 52%. Information on e-cigarettes was provided by 8% of NDCCs. Conclusions: Many NDCCs provide at least cursory online information on tobacco use and cessation, but the fact that few detail the effects of tobacco in cancer patients and only one-half provide contact information for cessation support highlights the need to improve NDCC efforts to more thoroughly address this critical cancer care topic.
CAD-based discrimination of clear cell renal cell carcinoma from RCC subtypes and benign small renal masses at multidector CT.
Authors: Heidi Coy, Jonathan Young, Michael Douek, Moe Moe Ko, War War Ko, Pechin Lo, Matthew S. Brown, Jonathan Goldin, Steven Raman
Journal: Journal of Clinical Oncology (2015)

e15616 Background: Currently, all solid enhancing non-fatty renal neoplasms are presumed to be malignant. Up to 70% of renal neoplasms are found incidentally at imaging, and up to 30% of these lesions are benign. Clear cell renal cell carcinoma (RCC) has the highest incidence and the highest metastatic potential. Therefore, it is of great clinical value to differentiate renal masses at imaging, as each has a different prognosis. The purpose of our study was to evaluate the performance of a novel computer aided diagnostic (CAD) algorithm to derive relative attenuation (RE) in renal lesions scanned on four-phase MDCT to distinguish clear cell RCC from other solid renal masses (SRM). Methods: With IRB approval and HIPAA compliance, a cohort of histologically proven SRM preoperatively scanned on MDCT with a four phase renal mass protocol (unenhanced (U), corticomedullary (C), nephrographic (N), excretory (E)) was contoured in each phase using proprietary software. A CAD algorithm derived a 0.5 cm diameter region of peak enhancement within the 3D lesion contour and RE was calculated from cortex enhancement (lesion CAD-cortex ROI)/cortex ROI)* 100%). A genitourinary radiologist approved all contours. A paired t-test was used to compare RE of clear cell RCC (ccRCC) to the other RCC subtypes and benign SRM with p < 0.05. Results: 223 lesions (105 ccRCC, 41 oncocytoma (O), 14 lipid-poor angiomyolipoma (AML), 45 papillary RCC (pRCC), 18 chromophobe RCC (chRCC)) in 206 consecutive subjects underwent volumetric CAD analysis. On C phase, ccRCC had a significantly higher RE compared to O ( p < 0.0001), AML ( p < 0.0001), pRCC (p < 0.0001), and chRCC (p = p = 0.003). The N phase had a significantly higher RE of the ccRCC compared to the O ( p = 0.018), AML ( p < 0.0001), pRCC (p < 0.0001), and chRCC (p < 0.0001). The E phase had a significantly higher RE of the ccRCC compared to the O ( p = 0.003), AML ( p < 0.0001), pRCC (p < 0.0001), and chRCC ( p < 0.0001). Conclusions: A CAD algorthim to determine renal lesion enhancement compared to normal renal cortex can be used as a noninvasive means on four phase MDCT in preoperative clinical decision making of renal neoplasms to determine which patients require watchful waiting, biopsy, or surgery.
Volumetric tumor growth in advanced NSCLC patients (pts) with <i>EGFR</i> mutations during EGFR-TKI therapy: Developing criteria to define slow progression.
Authors: Mizuki Nishino, Suzanne Eleanor Dahlberg, Stephanie Cardarella, David Michael Jackman, Michael S. Rabin, Nikhil H. Ramaiya, Hiroto Hatabu, Pasi Antero Janne, Bruce E. Johnson
Journal: Journal of Clinical Oncology (2013)

e19125 Background: EGFR-mutated advanced NSCLC pts treated with EGFR TKI typically progress after an initial tumor response. Most pts continue TKI beyond RECIST progression, and an objective guide for treatment decisions is needed. We analyzed the volumetric tumor growth in these pts as an initial step to develop criteria for slow progression to aid therapeutic decision making. Methods: The study population included 58 advanced NSCLC pts with sensitizing EGFR mutations, treated with first-line single-agent gefitinib or erlotinib between 2002-2011, who had baseline CT showing measurable lung lesion and at least two follow-up CTs while on TKI and experienced volumetric tumor growth. Tumor volume (mm 3 ) of the dominant lung lesion was measured on baseline and all follow-up chest CT scans during therapy, using volume analysis software [Nishino et al. Acad Radiol. 2011]. A total of 405 volume measurements from nadir to the end of TKI therapy or last follow-up, with data closure on 6/1/12, were analyzed in a linear mixed effects model, fitting time as a random effect [Laird and Ware, Biometrics, 1982]. Results: Among 58 pts, 46 (79%) were female, median age was 62 (range: 35-84), 29 (50%) were never-smokers, 53 (91%) were stage IV at diagnosis, and 53 (91%) received erlotinib. The median time on TKI was 15.8 months. The median time to tumor nadir was 6.3 months. A linear mixed effects model was fitted to predict growth of the logarithm of tumor volume (log e V), adjusting for time in months from baseline. The growth rate of log e V, obtained as the regression coefficient for time, was 0.12/month (SE: 0.015; p&lt;0.001; log e V=0.12*months+7.68). The model provided a reference value for the volumetric tumor growth rate in EGFR-mutant NSCLC pts after they have achieved their nadir. Conclusions: Tumor volume analysis defined volumetric tumor growth after the nadir in EGFR-mutant advanced NSCLC pts receiving TKI. This provides a reference value for the tumor growth rate in pts progressing after the nadir on TKI. Based on these data which can be studied in additional cohorts, we are currently developing practical radiographic criteria to help define patients as slow progressors who can safely remain on EGFR TKIs.
Placental growth factor and the angiogenic environment based on analysis of baseline plasma biomarkers from the VELOUR trial.
Authors: Josep Tabernero, Caroline Paccard, Marielle Chiron, Emmanuelle Dochy, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2017)

592 Background: A number of available agents (e.g., bevacizumab [bev], ziv-aflibercept, ramucirumab, regorafenib) for metastatic colorectal cancer (mCRC) target the VEGF pathway; biomarkers for anti-VEGF response are thus valuable. The Ph III VELOUR study (NCT00561470) demonstrated that addition of aflibercept to FOLFIRI improved survival and response rates in mCRC patients (pts) who had failed oxaliplatin-based therapy, including pts treated with prior bev. We report the correlation between biomarkers and bev pre-treatment in baseline plasma samples from VELOUR pts. Methods: 98 biomarkers were examined in baseline plasma samples from pts enrolled in VELOUR. Biomarker concentration was determined using multiplex assays or ELISA. Results: Plasma samples were available for 553 pts (placebo n = 265; aflibercept n = 288), of whom 169 had received prior bev. Nine biomarkers implicated in angiogenesis or bev resistance correlated with prior bev therapy (Table), including VEGF-A (~5-fold higher concentration) and PlGF (~2-fold higher concentration). Conclusions: These data indicate that prior bev therapy is likely to modulate expression of biomarkers associated with acquired resistance to anti-VEGF treatment (e.g., VEGF-A &amp; PlGF). However, the improvement in clinical outcomes with aflibercept + FOLFIRI (vs placebo + FOLFIRI) in bev pretreated pts in VELOUR suggests that aflibercept remains active despite the development of bev-induced angiogenic resistance. Clinical trial information: NCT00561470. [Table: see text]
A phase II study of galunisertib monotherapy or galunisertib plus lomustine compared to lomustine monotherapy in recurrent glioblastoma.
Authors: Alba Ariela Brandes, Antoine F Carpentier, Santosh Kesari, Juan Sepulveda, Helen Wheeler, Olivier L. Chinot, Lawrence Cher, Joachim Peter Steinbach, Pol Specenier, Ann Cleverly, Claire Smith, Ivelina Gueorguieva, Susan C. Guba, Durisala Desaiah, Michael M. F. Lahn, Wolfgang Wick
Journal: Journal of Clinical Oncology (2015)

2014 Background: Based on preclinical data suggesting an additive antitumor effect of galunisertib (G), a TGF-β RI kinase inhibitor, and lomustine (L), this study evaluated the activity of G+L in patients (pts) with recurrent glioblastoma (GB). We report safety, population pharmacokinetics (PK), and efficacy final results. Methods: G (300 mg/day) was given as intermittent dosing (each cycle = 14 days on/14 days off). L was given on day 7 of cycle 1 every 6 weeks as approved. Pts received L with either G or placebo (P) thereby blinding for G; pts who received G alone were unblinded (randomization 2:1:1). Primary objective was overall survival (OS) assessed by Bayesian analysis incorporating prior clinical data for L. Secondary objectives were safety, progression-free survival (PFS), tumor response assessed by Response Assessment in Neurooncology (RANO) criteria, and population PK analysis. Results: 158 pts were randomized to treatment: G+L (N = 79), G alone (N = 39), P+L (N = 40). Study included, male (64.6%), Caucasian (75.3%); mean age 57 years, 63% had ECOG PS 1, 93.7% had primary GB. The median number of cycles for G was 2 in all 3 arms. G PK was not altered by co-administration with L. G was rapidly absorbed and had median half-life of ~8h with moderate between-patient variability on exposure (CV 41%). The median OS (95% CI) for G+L was 6.7 months (5.3-8.5), [HR (G+L):(L+P) 1.13 (0.8-1.7)], 8.0 months (5.7-11.7) for G alone, [HR (G):(L+P) 0.93 (0.6-1.5)], 7.5 months (5.6-10.3) for L+P control arm. Success criteria for superiority of G+L to L+P was not met [P (HR < 1) < 85%]. The median PFS in months (95% CI) were 1.8 (1.7-1.8) for G+L, 1.8 (1.6-3.0) for G, and 1.9 (1.7-1.9) for P+L. Best overall response according to RANO included 1 CR in G+L and 2 PR in G. 34 pts had Grade 3/4 adverse events (AEs) related to study drug, 24% G+L, 13% G, 26% L+P. The most common drug-related Grade 3/4 AEs (G+L, G, L+P) were: thrombocytopenia (8%, 0%, 13%); lymphopenia (9%, 3%, 0%); neutropenia (8%, 0%, 5%). Conclusions: The observed efficacy outcomes including OS and PFS were similar in all 3 treatment arms suggesting no efficacy improvement when adding G to L. The treatment was safe and well tolerated in all arms. Clinical trial information: NCT01582269.
Prognostic value of lemur tyrosine kinase-3 (LMTK3) polymorphism in Japanese (J) patients (PTS) with localized gastric adenocarcinoma (GAC).
Authors: Afsaneh Barzi, Takeru Wakatsuki, Wu Zhang, Dongyun Yang, Fotios Loupakis, Yan Ning, Rita El-Khoueiry, Melissa Janae Labonte, Mizutomo Azuma, Pierre Oliver Bohanes, Leonor Benhaim, Armin Gerger, Wasaburo Koizumi, Masahiko Watanabe, Justin Stebbing, Georgios Giamas, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

4088 Background: LMTK3 is an estrogen receptor α (ERα) regulator. Recent studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression are prognostic in breast and colon cancers. Our group demonstrated that r9AA is associated with shorter time to recurrence in Caucasian(C) and Hispanic(H) females(F) with GAC. We investigated the significance of LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples of 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT) were analyzed. Genomic DNA was extracted using the QIAmp kit; all samples were analyzed using PCR-based direct DNA-sequencing. The endpoints of the study were disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were used for univariate analysis. Multivariate analysis was performed to test the interaction between polymorphism and gender adjusting for other variables. Results: 60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II, 36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% of PTS received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with AA vs 99% (95% CI 91-99%) of AG/GG were alive (p= 0.039). Median survival was not reached in the AG/GG group; in the AA group median DFS and OS was 1yr (p= 0.03) and 2ys (p= 0.039) respectively. In the multivariate analysis adjusting for s, age, and ACT, males carrying AA had increased risk of disease recurrence (HR 3.84 95%CI 1.86-7.92, p&lt; 0.001) and dying (HR 3.47 95%CI 1.58-7.62 p=0.002) compared to those with AG/GG (HR=1, reference). Conclusions: r9 AA was associated with significantly worse DFS and OS in J male with GAC. These results confirm our previous findings that LMTK3 is an independent prognostic factor for localized GAC; interestingly the relationship between gender and prognostic significance is the opposite in J vs. C/H. The gender disparity can be due to the differences in the etiology (histological subtypes), management strategies, allele frequency, and degree of estrogen exposure in the two populations. Additional studies are warranted to identify the underlying biological mechanism.
Utilization of palliative chemotherapy for advanced bladder cancer: Patterns of care in routine clinical practice.
Authors: Andrew George Robinson, Xuejiao Wei, William J. Mackillop, Christopher M. Booth
Journal: Journal of Clinical Oncology (2015)

6525 Background: Although palliative chemotherapy for advanced bladder cancer is recommended in clinical practice guidelines, patterns of care in routine care is not described. Here we describe utilization rates of chemotherapy and referral rates to medical oncology in the last year of life among patients who die of bladder cancer. Methods: A population based cohort of bladder cancer patients was identified from the Ontario Cancer Registry; the study population included those patients who died of bladder cancer 1995-2009. Electronic records of treatment and physician billing records were used to identify treatment patterns and referral to medical oncology (MO). Log-binomial and poisson regression were used to examine factors associated with chemotherapy utilization and MO consultation. Results: 8005 patients died of bladder cancer; 25% (1964/8005) of whom received chemotherapy in the last year of life. Use of chemotherapy was independently associated with patient age (Relative risk (RR) 0.49 70-79 vs < 50 years, p < 0.001), comorbidity (RR 0.61 moderate comorbidity vs none, p < 0.001), socioeconomic status (RR 0.84 lowest quintile vs highest, p = 0.01) and gender (RR 0.91 females vs males, p = 0.012). Utilization increased over time (from 22% to 26%, p < 0.001) and varied across geographic regions (range 18-30%, p < 0.001); these findings persisted on adjusted analyses. 68% (5426/8005) of patients were seen by MO in the last year of life. Factors independently associated referral rates to MO include age (RR 0.82 70-79 vs < 50 years, p < 0.001), comorbidity (RR 0.90 moderate comorbidity vs none, p < 0.001), socioeconomic status (RR 0.90 lowest quintile vs highest, p < 0.001), and gender (RR 0.96 females vs males, p = 0.023). Referral rates modestly increased over time (66% to 69%, p = 0.006) and varied widely across geographic regions (range (57% to 79%, p < 0.001); these findings persisted on adjusted analyses. Conclusions: Despite clinical practice guideline recommendations, utilization of palliative chemotherapy for bladder cancer in routine practice remains low. Treatment patterns and referral rates to MO vary substantially across geographic regions.
Prognostic Impact of the MRD Status After Induction Treatment with Rituximab Plus Fludarabine, Cyclophosphamide and Mitoxantrone (R-FCM) in Patients with Chronic Lymphocytic Leukemia Receiving Rituximab Maintenance Therapy
Authors: Pau Abrisqueta, Neus Villamor, María José Terol, Eva González-Barca, Marcos González, Christelle Ferrà, Eugenia Abella, Julio Delgado, Jose Antonio García-Marco, Yolanda González, Felix Carbonell, Secundino Ferrer, Encarna Monzo, Isidro Jarque, Ana Muntanola, Mireia Constants, Lourdes Escoda, Emili Montserrat, Francesc Bosch
Journal: Blood (2012)