tbuckley/cabot-search huggingface dataset:
Positive margin length and Gleason grade of tumor focus at the margin predict for biochemical failure after radical prostatectomy in patients with pT2 prostate cancer.
Authors: Jenny N. Nguyen, Brian Francis Chapin, Ina N. Prokhorova, Xuemei Wang, John W. Davis, Patricia Troncoso
Journal: Journal of Clinical Oncology (2014)

103 Background: While three prospective trials have demonstrated benefit from adjuvant radiation (XRT) after radical prostatectomy (RP) in patients with positive surgical margins (PSM), its use varies amongst physicians. Many rely on clinical acumen to determine the optimal strategy for application of XRT post RP. We aim to determine if the length of PSM and highest Gleason grade (GG) of tumor at the PSM (hGGPSM) can be used to identify patients at greatest risk of biochemical failure (BCF) post RP. Methods: A retrospective review of all RP patients at The University of Texas MD Anderson Cancer Center from 2002 to 2010 was performed. After a single pathologist review, patients with organ confined disease (pT2), pathologic N0/Nx and a PSM were included. BCF was defined as 2 sequential PSA values of ≥0.2 or any detectable PSA prompting XRT. Patients receiving adjuvant XRT or with &lt;12 months follow-up were excluded. Results: 205 patients met the inclusion criteria. Median PSA was 5.3 ng/mL (0.5-33) and median follow-up was 64 months (13-130). The majority were low clinical stage (cT1c: 65%), low (11%)/intermediate (82%) grade and had a single site of a PSM (90%). BCF occurred in 47 patients for a 5 yr BCF free survival (BCFFS) of 69%. PSM length was significantly associated with BCFFS (≤1mm vs &gt;1, p=0.02). When accounting for hGGPSM, Gl 3 tumors were less likely to experience BF (5 yr BCFFS-96%) regardless of PSM length, while BCFFS for Gl &gt;3 tumors were significantly lower dependent upon length of PSM ( ≤1mm vs &gt;1mm, p=0.03). On multivariable analysis length of PSM (p=0.05) and hGGPSM (p=0.007) remained independent predictors of BCF (Table). Conclusions: Length of PSM and hGGPSM are independent predictors of BCF. These should be considered when evaluating patients for adjuvant XRT and in risk stratifying patients in prospective clinical trials. [Table: see text]
Salvage chemotherapy with rituximab, oxaliplatin, cytosine arabinoside, and dexamethasone (ROAD) in patients with relapsed CD20+ aggressive B-cell lymphoma
Authors: P. B. Johnston, B. LaPlant, P. Kurtin, T. Habermann, D. Moore, N. Nabbout, D. Nikcevich, K. Rowland, T. Witzig
Journal: Journal of Clinical Oncology (2009)

8556 Background: In the original PARMA trial it was demonstrated that salvage chemotherapy with DHAP followed by autologous bone marrow transplant resulted in increased overall survival over salvage chemotherapy with DHAP alone in patients with aggressive lymphomas. The current study was designed to assess safety and feasibility of ROAD as a salvage chemotherapy regimen which could be administered as an inpatient or outpatient. Methods: Patients received immunochemotherapy on the following schedule: rituximab 375 mg/m2 weekly × 4, oxaliplatin 130 mg/m2 on day 2, Ara C 2000mg/m2 x 2 doses on day 2 and dexamethasone 40 mg on days 2–5, with OAD repeated at 3 week intervals (up to 6 cycles). Patients were considered for autologous stem cell transplantation after 2 cycles if eligible. Eligible histologies included diffuse large B cell lymphoma, mantle cell lymphoma and transformed lymphoma in first relapse. Results: 50 patients were accrued from Aug 2006 through Jul 2008: 5 patients were deemed ineligible after central pathology review. Baseline characteristics of eligible patients included median age 69 (range 23 - 77), 53% were male, 53% had advanced stage at relapse, LDH was elevated in 58% and all patients had an ECOG PS of 2 or less. Patients received a median of 2 cycles of therapy (range 1–6) with 39/45 receiving treatment in cycle 2, with 12 patients continuing beyond 2 cycles. 31 patients experienced grade III/IV hematologic toxicity and 22 patients had grade III/IV non-hematologic toxicity, primarily febrile neutropenia. One patient developed grade III nephrotoxicity due to disease progression. Twenty patients received their treatments exclusively as outpatients. 26 responses were seen in the 45 eligible patients (58%, 95% CI: 44–74%), with 20 responding patients proceeding to autologous SCT. Conclusions: ROAD is a safe and effective salvage chemotherapy regimen for relapsed aggressive lymphoma, including as a preparatory regimen prior to stem cell transplant. It appears to have similar response rates to R-DHAP in a similar patient population, but without the potential nephrotoxicity (data from prior published study from NCCTG). ROAD can be safely administered as an inpatient or outpatient. No significant financial relationships to disclose.
Tumor necrosis as prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer.
Authors: Ji Han Jung, Hyung Jin Kim, Ho Jung An, Sung Whan Kim, Hyun Min Cho, Byoungyong Shim
Journal: Journal of Clinical Oncology (2015)

722 Background: Association between treatment response on the basis of pathologic stage evaluated after radical tumor resection and patient prognosis was well established. The object of this study is that tumor necrosis factor after CRT is also important as treatment response. Methods: A total of 243 patients with locally advanced rectal cancer that underwent neoadjuvant CRT was included. Three treatment response groups were classified by their pathologic stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified by tissue pathologic results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). Results: Overall survival (OS) and recurrence free survival (RFS) rate at 3 years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR were 83.7%, 75.9%, and 69.7%, respectively (p&lt;0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p&lt;0.001). The 3-year OS rates of the CNR, INR, and PNR were 83.7%, 80.6%, and 61.8%, respectively (p&lt;0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p&lt;0.001). When compared to CTR / CNR, PTR / PNR was strongly related to an increased risk of recurrence (hazard ratio, 5.53; 95% CI, 2.01 to 15.23 / 6.37; 95% CI, 2.29 to 17.74) respectively in the univariate Cox regression. Therefore in the two models using multivariate Cox regression, both PTR and PNR were strongly associated to RFS and OS compared with CTR and CNR. Conclusions: The tissue response factor to neoadjuvant CRT is one surrogate marker for recurrence and oncologic outcomes and almost as important as the treatment response factor in rectal cancer patients treated with neo-adjuvant CRT.
Clinical profile and outcome of patients with cervical cancer submitted to hemodialysis at the Brazilian National Cancer Institute (INCA).
Authors: D. G. Candido Reis, C. C. Carmo, L. M. Soares, P. C. Val, C. G. Duque, D. Herchenhorn
Journal: Journal of Clinical Oncology (2010)

e16502 Background: Cervical Cancer (CC) is a public health problem in Brazil. Yearly almost 650 CC patients (pts) are admitted at our center for treatment. Locally advanced disease represents 67.5% of all cases. Acute renal failure is a frequent consequence of local dissemination as well as treatment toxicity in these pts, leading to the necessity of hemodialysis (HD). Available data on the clinical spectrum and outcome of these hemodialysis-treated patients are inconclusive. Methods: This is a retrospective observational study. All cervical cancer diagnosed pts submitted to HD during the year of 2008 at INCA were included irrespective of age, stage or treatment modality. Primary end point was to describe the clinical profile and survival of patients submitted to HD. Clinical features, treatment and outcome were analyzed. Results: Data were available from 40 consecutive patients, 45% of them had PS Performance 0-I. Median age at diagnosis was 50y (33-83), 60% was white; squamous cell cancer represented 95% of cases; most patients were stage IIIB (65%) and IV (20%); only 20% of pts had chronic renal failure (nondialytic); the most common indication for hemodialysis was postrenal failure due to local progression and hydronephrosis (70%) and septic shock (15%); 25% received no treatment, 40% received only radiotherapy/brachytherapy during and after HD, and 35% received combined chemo/radiotherapy before/during HD; with 17 months (14- 24) of follow up, only 2 pts were alive, the median overall survival from the beginning of HD was 18 days (1-210). Conclusions: In this study, HD in pts with CC was associated with locally advanced tumors, and a poor overall survival. Further studies are necessary to better evaluate the real effects of this procedure in these pts in order to better define treatment selection. No significant financial relationships to disclose.
Previous enzalutamide therapy and response to subsequent taxane therapy in metastatic castration-resistant prostate cancer.
Authors: Marco Gizzi, Giulia Baciarello, Aude Flechon, Philippe Beuzeboc, Antoine Angelergues, Guilhem Roubaud, Emmanuelle Bompas, Sylvestre Le Moulec, Igor Latorzeff, Remy Delva, Eric Voog, Frank Priou, Brigitte Duclos, Brigitte Laguerre, Cecile Vassal, Marine Gross Goupil, Anna Patrikidou, Karim Fizazi, Yohann Loriot
Journal: Journal of Clinical Oncology (2015)

227 Background: Cross-resistance between taxanes and androgen receptor axis targeted agents is a matter of debate in metastatic castration-resistant prostate cancer (mCRPC). Preclinical data about response to taxanes after prior enzalutamide suggest some level of cross-resistance (van Soest et al, Eur J Cancer 2013) though this was not confirmed in other models (Al Nakouzi N, Eur Urol 2014). The first objective of this study was to assess the impact of previous enzalutamide therapy on the efficacy of subsequent taxane-based chemotherapy. The second objective was to investigate the prognosis of patients when chemotherapy was initiated in enzalutamide-pretreated patients. Methods: Data from 96 enzalutamide- and placebo-treated patients enrolled in the Prevail phase III trial were retrospectively collected from 14 centers in France. Changes in prostate specific antigen (PSA) levels, progression free survival (PFS) and RECIST criteria v 1.1 were used to determine the activity of docetaxel (n=89) or cabazitaxel (n=7) treatment. The Halabi model was used to predict survival probabilities for the enzalutamide- or placebo-pretreated patients when chemotherapy was initiated (Halabi et al, J Clin Oncol 2014). Results: Overall, 96 patients were included in this analysis (58 in the placebo arm vs. 38 in enzalutamide arm). PSA response to taxanes (defined as a decline of ≥50% from baseline) was marginally lower in enzalutamide-vs. placebo-pretreated patients (34% vs. 53%, p=0.10). PSA response in enzalutamide-pretreated patients was not different from that observed with docetaxel given every 3 weeks in TAX 327 trial (Tannock et al, NEJM 2004) (45%, p=0.20, binomial test). Median PFS and objective response rates were similar between the two groups (4.8m vs 6.7 m;p=0.14 and 45% vs 43%;p=0.83 respectively). Halabi score was well-balanced between the two groups (p=0.30). Conclusions: Taxanes retain efficacy in enzalutamide-pretreated mCRPC. At the time of first-line taxane-based chemotherapy initiation, the prognosis of enzalutamide-treated patients according to the Halabi score was not different from that of enzalutamide-naïve patients.
Mono/Oligoclonal T and NK Cells Are Common in Philadelphia Chromosome Positive (Ph+) Leukemia Patients at Diagnosis and Expand During Successful Tyrosine Kinase Inhibitor Therapy.
Authors: Anna Kreutzman, Vesa Juvonen, Veli Kairisto, Marja Ekblom, Leif Stenke, Ruth Seggewiss, Kimmo Porkka, Satu Mustjoki
Journal: Blood (2009)
Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis.
Authors: E Ingulli, A Singh, N Baqi, H Ahmad, S Moazami, A Tejani
Journal: Journal of the American Society of Nephrology (1995)

Short-term cyclosporine (CsA) has been shown to reduce the proteinuria in refractory nephrotic syndrome, but the effect on disease progression has not been evaluated. This study was undertaken to evaluate whether maintenance CsA therapy in steroid-resistant focal segmental glomerulosclerosis (FSGS) will prevent progression to ESRD. Twenty-one black and Hispanic children (mean age, 8.4 +/- 4.5 yr) with biopsy-proven, steroid/cyclophosphamide-resistant FSGS were treated with CsA (initiated at 6 mg/kg per day and titrated to the serum cholesterol level to achieve a response). The mean CsA dose was 7 (4 to 20) mg/kg per day, the duration of CsA therapy was 27.5 (3 to 97) months, and the duration of follow-up was 8.5 +/- 4.7 yr. At the end of CsA therapy, the mean (+/- SE) proteinuria fell from 6.2 +/- 0.2 to 2.0 +/- 0.1 g/24 h (P < 0.001), the mean albumin rose from 1.95 +/- 0.04 to 3.41 +/- 0.04 g/dL (P < 0.001), the mean cholesterol decreased from 472 +/- 12.7 to 257 +/- 5.3 mg/dL (P < 0.005), and the mean creatinine rose from 0.79 +/- 0.02 to 1.16 +/- 0.03 mg/dL (P < 0.005). Seven children continue to receive maintenance CsA therapy, and 14 patients have had CsA stopped: 6 for an increase in serum creatinine and/or continued proteinuria, 5 for sustained remission, 2 for noncompliance, and 1 for pregnancy. Five (24%) of the 21 patients progressed to ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)
Azacitidine As Post-Remission Therapy in Elderly Patients with Acute Myeloid Leukemia Significantly Prolongs Disease-Free Survival: Interim Results from a Prospective, Randomized, Open-Label, Phase III Multicenter Trial
Authors: Esther Natalie Oliva, Caterina Alati, Prassede Salutari, Alessandra Freyrie, Anna Candoni, Erica Simeone, Giovanna Ventura, Agostino Cortelezzi, Debora Capelli, Pietro Leoni, Paolo Di Bartolomeo, Antonio Giovanni Marino, Patrizia Cufari, Francesco Di Raimondo, Elisa Mauro, Antonio Volpe, Nicola Cascavilla, Pellegrino Musto, Fortunato Morabito, Pasquale Niscola, Giorgina Specchia, Francesca Ronco
Journal: Blood (2014)
Imaging kinase target inhibition with SU11248 by FDG-PET in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (I-R GIST)
Authors: A. van den Abbeele, Y. Melenevsky, D. de Vries, J. Manola, P. Dileo, R. Tetrault, C. Baum, R. Badawi, G. Demetri
Journal: Journal of Clinical Oncology (2005)

9006 Background: SU11248 is an oral multitargeted tyrosine kinase inhibitor, with antiangiogenic and direct anti-tumor activity resulting from signal blockade of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), KIT, and FLT3 receptors. Objective responses to SU11248 were reported in phase 1/2 studies of I-R GIST pts (Demetri et al. Proc ASCO 2004; abstr 3001) and visualized very early using FDG-PET imaging, a reliable and sensitive measure of metabolic activity in GIST. Methods: Pts with I-R or -intolerant GIST received 1 of 3 schedules of SU11248 administered daily: 25–75mg/m2 2wks on/2wks off; 50mg/m2 4wks on/2wks off; and 50mg/m2 2wks on/1wk off. FDG-PET was performed at baseline (scan 0, n=75), after the first 7 days on therapy (scan 1, n=64), after the first period off therapy (scan 2, n=54), and after 4 subsequent cycles (scan 3, n=28). Maximum standardized uptake values (SUV max) were measured for 28 pts who had imaging at all 4 time points (n=74 lesions, 1–3 lesions/pt). SUV distributions are approximately Gaussian after a logarithmic transformation, so mean log SUV max was calculated at each time point. To test the significance of differences in means over time, we used mixed models assuming correlation within pts among lesions and over time. Linear contrasts were examined for pair-wise comparisons. Results: Mean SUV max (±SE, n=74) for the 4 time points were: 9.7 (± 0.6), 5.6 (±0.6), 8.0 (±0.6), and 5.1 (±0.5). Comparisons of mean log SUV max are shown in the table. Conclusion: FDG-PET revealed a significant response to SU11248 in I-R GIST pts as early as 7 days after initiation of therapy. Target inhibition was confirmed by rebound of FDG uptake after a break in SU11248 therapy, followed by a second response with subsequent SU11248 treatment cycles. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Microscopic tumor burden in sentinel lymph nodes (SLNs) best predicts nonsentinel lymph node (NSLN) involvement in patients with melanoma
Authors: R. H. Andtbacka, J. E. Gershenwald, V. G. Prieto, M. Johnson, H. Diwan, J. E. Lee, P. F. Mansfield, C. W. Schacherer, M. I. Ross
Journal: Journal of Clinical Oncology (2006)

8004 Background: Therapeutic lymph node dissection (TLND) has long been the standard of care for melanoma metastatic to the regional LNs and is commonly used for patients (pts) with microscopic disease identified by SLN biopsy. We and others have demonstrated that additional histologically positive (pos) nodes are identified in 8%-33% of completion LN dissection (CLND) specimens. The purpose of this study was to determine predictors of additional LN involvement in pts. with pos SLNs. Methods: Pts with clinically node-negative melanoma who underwent SLN biopsy at our institution between 1991 and 2003 and had pos SLNs were identified. Patient and primary tumor factors, number of pos SLNs, and extent of microscopic disease within the SLN were evaluated as potential predictors of pos NSLNs. Results: Overall, 359 (16%) of 2,203 pts had a pos SLN. Pos NSLNs were identified in 48 (14%) of the 343 pts with pos SLNs who underwent CLND. On univariate analysis, several markers of SLN microscopic tumor burden, tumor thickness &gt;2mm, age &gt;50 years, and Clark level &gt;III were predictive of additional pos nodes in the TLND specimen. Primary tumor ulceration was not predictive. On multivariable logistic regression analysis, markers of microscopic tumor burden (large SLN met focus, large SLN tumor square area, presence of SLN extracapsular extension, and synchronous subcapsular and intramedullary SLN deposits) were the most powerful independent predictors of pos NSLNs; tumor thickness &gt;2mm also predicted additional disease. A model was established using tumor thickness and SLN tumor burden to identify pts with low, intermediate, or high risk for NSLN involvement (Table). Conclusions: In melanoma pts with ≥1 pos SLN, SLN tumor burden and primary tumor thickness may be useful in identifying a group at low risk for pos NSLNs. This information is valuable in designing clinical trials in which pts may be randomly assigned to TLND versus observation alone after removal of a pos SLN. [Table: see text] No significant financial relationships to disclose.
Abstract 14042: FoxO1 Ablation Rescues Metabolic Stress-induced Cardiac Remodeling
Authors: Pavan K Battiprolu, Cyndi R Morales, Lauren Baker, Zully Pedrozo, Dan L Li, Annie Nguyen, Nan Jiang, John M Shelton, Thomas G Gillette, Sergio Lavandero, Joseph A Hill
Journal: Circulation (2013)

Introduction: Diabetic cardiomyopathy is typified by alterations in cardiac metabolism, morphology, and function independent of hypertension and coronary artery disease. We have shown previously th...
Barriers to screening mammogram in southeastern Kentucky.
Authors: Raymond Elsoueidi, Eyob Adane, Elie Maroun Richa
Journal: Journal of Clinical Oncology (2014)

6 Background: Breast cancer is the most common cancer in females. Screening mammogram has been linked to reduced breast cancer mortality through early detection and effective treatment following diagnosis. Despite the dramatic improvement in the use of screening mammogram nationwide, disparities still exist. Southeastern Kentucky has multiple barriers to healthcare access with screening mammogram rates of around 63% compared to 80% in urban areas. We performed this observational study to identify the barriers to screening mammogram in southeastern Kentucky. Methods: Questionnaires were distributed to women age 40 and older at local churches and hospitals in 10 counties of southeastern Kentucky. Questions included age, healthcare coverage, having a primary care physician, having a mammogram within the past 2 years, and reasons for not having a mammogram. Results: Among the 328 females that participated in the survey, 36.3% did not have a mammogram. The median age (interquartile range) was 57 (50 to 63) and there were no difference between respondents with a mammogram and those without. Among the 119 females without a mammogram, the most common reasons for not having a mammogram were as follows: no interest in having a mammogram (33%), not being referred by their primary physician (24%), lack of time (12%), and lack of insurance (11%). Other responses included old age (5%), fear of pain of the procedure (3%), lack of knowledge/information (3%), and lack of transportation (2%). Seven percent did not provide reasons. Conclusions: Based on this survey, the most common barrier to obtaining a screening mammogram is patient perception, as evidenced by lack of interest, time, and knowledge/information, followed by failure of referral by physicians. Interventions that target these barriers will likely improve adherence to screening mammogram.
Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer
Authors: Andrea Sartore-Bianchi, Elena Ardini, Roberta Bosotti, Alessio Amatu, Emanuele Valtorta, Alessio Somaschini, Laura Raddrizzani, Laura Palmeri, Patrizia Banfi, Erica Bonazzina, Sandra Misale, Giovanna Marrapese, Antonella Leone, Rachele Alzani, David Luo, Zachary Hornby, Jonathan Lim, Silvio Veronese, Angelo Vanzulli, Alberto Bardelli, Marcella Martignoni, Cristina Davite, Arturo Galvani, Antonella Isacchi, Salvatore Siena
Journal: JNCI Journal of the National Cancer Institute (2015)

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib.