tbuckley/cabot-search huggingface dataset:
A phase 1 trial and pharmacokinetic study of RRx-001, a novel ROS-mediated pan-epigenetic agent.
Authors: Tony R. Reid, Bryan Oronsky, Jeffrey R. Infante, Howard A. Burris, Curtis Scribner, Susan Jane Knox, Janet L. Stephens, Gary Fanger, Jan Scicinski
Journal: Journal of Clinical Oncology (2014)

2578 Background: RRx-001 the first of a new class of pan-epigenetic anticancer agents, binds hemoglobin and drives RBC-mediated redox reactions under hypoxia. RRx-001 inhibits HDACs and Dnmt1 and 3a expression, affecting multiple aspects of cancer cell-cycle regulation and survival, including caspase activation, cyclin-dependent kinase activities, and p53 gene expression. The objectives of this dose-escalation trial were to investigate safety, DLTs, and PK of RRx-001. Methods: Eligible patients had advanced solid tumors; ECOG PS 0-2; adequate bone marrow function. In a 3+3 escalation design, RRx-001 was administered IV for up to 6h weekly for 8 weeks to patients in successive dose-escalating cohorts. Tumor response (CT, PET-CT, biopsy) was determined every 4 or 8 weeks. Subjects were evaluable if they had a baseline CT scan and at least one follow up scan after at least one dose of RRx-001. Results: 25 pts were dosed over 6 cohorts (10, 16.7, 24.6, 33, 55, 83 mg/m2). Tumor types were pancreas (3), CRC (11), head and neck (4), melanoma (1), cholangiocarcinoma (1), ovarian (1), lung (2) and HCC (1) and oligodendroglioma (1). RRx-001 was well tolerated with no DLTs and no formal MTD was established. No RRx-001-induced systemic toxicities were observed. The only drug-related AE across all cohorts was acute and transient injection-site pain and vasodilation, moderate in severity and generally managed by lengthening infusion time, using peripheral venous access and corticosteroids. 20 pts were evaluable for response per protocol criteria, 1 with partial response (parotid adenoid cystic carcinoma), durable for one year. 9 pts (45%) had stable disease of ≥ 4 months. OS for all pts was 16.8 months. PK analysis of the GSH adduct was not representative of exposure to RRx-001. Two pts became responsive to previously failed FOLFIRI post RRx-001, as shown by changes in CEA and by imaging. As responses were seen in all cohorts, 33 mg/m2 was selected as the Phase 2 dose. Conclusions: RRx-001 was well tolerated with infusion-site pain as the only observed AE to date. Toxicities normally associated with anticancer agents were absent. Single agent activity and a renewed response to previously failed chemotherapy was observed. Clinical trial information: NCT01359982.
Impact of access to NCI/NCCN-designated cancer centers (CC) on overall survival (OS) in multiple myeloma (MM) patients (pts).
Authors: Pooja Prem Advani, Dongyun Yang, Radhika Ghosh, Abhisek Swaika, Deepansh Gupta, James M. Foran, Gerardo Colon-Otero, Vivek Roy, Asher Alban Akmal Chanan-Khan, Sikander Ailawadhi
Journal: Journal of Clinical Oncology (2015)

e17570 Background: NCI/NCCN designated CC offer cancer pts state-of-the-art treatment, access to expertise and clinical trials. Their impact on pt outcomes has not been systematically evaluated, especially for racial minorities where disparities in healthcare access and outcomes are known to exist. We undertook such an analysis for MM pts. Methods: Adult pts with MM diagnosed 1973-2011 were identified from Surveillance Epidemiology and End Results (SEER) registry and stratified by county of residence at time of MM diagnosis (Dx) and year (yr) of CC designation (those after 2011 were excluded). Pts and NCI/NCCN CC in counties not contributing to SEER registry were excluded from analysis. Influence of NCI/NCCN CC access (noted as 0, 1 or ≥2 per county), race and yr of Dx on OS was evaluated by Cox regression model. Results: Counties with 0, 1 or >2 NCI CC (4, 13 and 2, respectively) and with 0 or 1 NCCN CC (9 and 5, respectively) were identified with total of 71,364 pts (male: 38,361; female: 33,003). Pts by yr of Dx: 15,031 (21%) before 1992, 5,622 (8%) 1992-1995, 16,182 (23%) 1996-2002; 34,529 (48%) 2003-2011 and race: 49,241 (69%) White; 12,836 (18%) African American (AA); 3,403 (4.8%) Asian; 5,569 (7.8%) Hispanic; 315 (0.4%) Native American (NA). For NCI access, OS improvement was seen after 1996, in >2 CC access areas, pts overall and by race for Whites only (Table). For NCCN access, improvement was seen in 1996-2002 (p=0.003), 2003-2011 (p<0.001), and by race in Whites (HR 0.917, 95% CI 0.88-0.95) and non-Whites (0.94, 95% CI 0.89-0.99), but within that only in AA (HR 0.88, 95% CI 0.81-0.97), not in Asians, Hispanics or NA. Conclusions: Overall, OS improvement was seen in MM pts diagnosed in or after 1996, with 1 NCCN or > 2 NCI CC access. NCI (> 2) access has benefitted Whites only while NCCN access has benefitted Whites and AA pts only among non-Whites. Efforts to eliminate racial disparities in access and healthcare utilization are needed to improve outcomes in these pts. Groups OS Improvement HR (95% CI) >2 NCI CC access Overall 1996-2002 0.90 (0.85-0.95) 2003-2011 0.88 ( 0.84-0.93) Whites 1996-2002 0.85 (0.78-0.91) 2003-2011 0.85 (0.79-0.91) non-Whites 1996-2002 0.96 (0.88-1.05) 2003-2011 0.94 (0.87-1.02)
Patient characteristics associated with dose-limiting sunitinib adverse events
Authors: B. Atkinson, J. Hart, E. Lin, N. Tannir, E. Jonasch
Journal: Journal of Clinical Oncology (2009)

e16110 Background: Sunitinib, an inhibitor of multiple tyrosine kinases, is FDA approved for metastatic renal cell cancer (mRCC). Though better tolerated than historical therapies, sunitinib is associated with adverse events (AEs) that may require dose modifications (DM). We sought to identify 1) baseline patient (pt) characteristics that predispose for DM, 2) the most common AEs requiring DM in a non-protocol setting, and 3) the impact of dose limiting AEs on treatment continuation. Methods: Single-center, retrospective chart review. Pts ≥ 18 years of age with mRCC of clear-cell histology on sunitinib therapy with active follow-up at MDACC were eligible. Univariate and multivariate logistic regression analysis of 66 pt variables (demographics, laboratory analysis, past medical and treatment history, etc) and dose-limiting AEs was completed, with a 6 month endpoint of sunitinib continuation, alternative therapy, or death. Results: From January 1, 2006 through September 30, 2007, 146 pts were identified meeting eligibility criteria. By univariate analysis, increased age (p=0.04; OR 1.04, 1.002–1.081 CI) and elevated BUN (p=0.03; OR 1.06, 1.006 –1.108 CI) were directly associated with increased incidence of dose-limiting AEs. ECOG PS of 2 (p=0.04; OR 0.3, 0.114–0.951 CI) was associated with a decreased incidence of dose limiting AEs. In a multivariate analysis, only BUN remained significant. 57% of patients (n= 83) had dose-limiting AEs. DM were often attributed to multiple AEs (55%), with fatigue, mucositis, hand-foot syndrome and nausea being the most common. At 6 months follow-up, 63% of pts with dose-limiting AEs remained on sunitinib vs. 37% (p=0.18). There was no difference in death rate at 6 months between the two groups. Conclusions: Elevated baseline BUN is associated with an increased rate of DM in patients with RCC receiving sunitinib. Despite the high-incidence of AEs, pts can be maintained on sunitinib with DM and without an adverse impact on outcome. Whether specific AEs are biologic indicators of activity should be evaluated in a larger clinical trial. [Table: see text]
TCR-Alpha/Beta and CD19 Depleted Haploidentical Stem Cell Transplantation Following Reduced Intensity Conditioning in Children: First Results of a Prospective Multicenter Phase I/II Clinical Trial
Authors: Peter J. Lang, Paul G. Schlegel, Roland Meisel, Ansgar S. Schulz, Johann Greil, Peter Bader, Sandra Karitzky, Silke Holtkamp, Christiane Siewert, Michael Schumm, Matthias K. Eyrich, Markus Wiesneth, Halvard Bönig, Rupert Handgretinger
Journal: Blood (2016)
Prostate weight as an independent predictor for both extracapsular extension and positive surgical margins during robotic- assisted laparoscopic radical prostatectomy
Authors: L. Msezane, K. C. Zorn, O. N. Gofrit, G. D. Steinberg, G. P. Zagaja, S. Lin, A. L. Shalhav
Journal: Journal of Clinical Oncology (2007)

15608 Background: Pre-operative prediction of pathological stage represents the cornerstone of prostate cancer management. Patient counseling is routinely based on pre-operative PSA, Gleason score and clinical stage. In this study, we evaluated whether prostate weight (PW) is an independent predictor of extracapsular extension (ECE) and positive surgical margin (PSM). Methods: Between February 2003 and November 2006, 709 men underwent robotic-assisted laparoscopic radical prostatectomy (RLRP). Pre-operative parameters (patient age, pre-operative PSA, biopsy Gleason score, clinical stage) as well as pathological data (prostate weight, pathological stage) were prospectively gathered after IRB approval. Evaluation of the influence of these variables on ECE and PSM outcomes were assessed using both univariate and multivariate logistic regression analysis. Results: Mean overall patient age, pre-operative PSA and PW were 59.6 years, 6.5ng/ml and 52.9g (range 5.5–198.7g), respectively. Of the 393, 209 and 107 men with PW &lt;50g, 50-&lt;70g and &gt;70g, ECE was observed in 20.1%, 15.3% and 9.3%, respectively (p=0.015). In the same patient cohorts, PSM was observed in 25.4%, 14.4% and 7.5%, respectively (p&lt;0.001). In a multivariate logistic regression analysis, PW, in addition to pre-operative PSA, biopsy Gleason score and clinical stage, was an independent risk factor for ECE (p&lt;0.001). Similarly, in multi-variate analysis, PW was observed to be a risk factor for PSM (p&lt;0.001). Conclusions: PW is an independent predictor of both ECE and PSM, with an inverse relationship having been demonstrated between both variables. PW should be considered when counseling patients with prostate cancer treatment. No significant financial relationships to disclose.
Incidence of periprostatic white adipose tissue inflammation in men with prostate cancer.
Authors: Ayca Gucalp, Neil M. Iyengar, Xi K. Zhou, Dilip D. Giri, Domenick J. Falcone, Hanhan Wang, Samantha Williams, Margaret D. Krasne, Ibrahim Yaghnam, Brian Kunzel, Patrick G. Morris, Lee Jones, Michael N. Pollak, Vincent Paul Laudone, Howard I. Scher, Clifford A. Hudis, Peter T. Scardino, James Andrew Eastham, Andrew J. Dannenberg
Journal: Journal of Clinical Oncology (2017)

63 Background: Obesity, a common cause of chronic inflammation, is associated with an increased risk of high grade, lethal prostate cancer (PC) and poor outcomes. The existence or clinical importance of periprostatic white adipose tissue inflammation (WATi) in patients (pts) with PC has not been previously described. We examined the relationships among periprostatic WATi and 1) tumor clinicopathologic features, and 2) host factors including age, body mass index (BMI), and circulating metabolic factors. Methods: Periprostatic WAT was collected prospectively from men with PC undergoing radical prostatectomy. WATi was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS). Tumor characteristics and host factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests were used to examine the relationship between WATi and tumor and host characteristics. Results: From 11/2011-8/2015, periprostatic WAT was obtained from 169 pts (median age 62 years, range: 39 -77). Fasting blood samples were collected from 154 pts. CLS were present in 84 (49.7%) of pts. Presence of CLS was associated with higher median BMI (P = 0.02); 40/65 (61.5%) obese pts, 36/83 (43.4 %) overweight pts, and 8/21 (38.1 %) normal weight pts had CLS. Pts with CLS were more likely to have high grade prostate cancer (Gleason grade group IV/V, P = 0.02), larger adipocytes (P = 0.004), and positive surgical margins at the time of surgery (P = 0.04). WATi correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to pts without WATi (P’s &lt; 0.05). Conclusions: Periprostatic WATi is common in men with PC. It is associated with high grade PC and alterations in systemic factors that contribute to PC development and progression. Periprostatic WATi may represent a therapeutic target for improving PC risk and outcomes.
<sup>18</sup>F-FDG-PET/CT imaging to assess response to treatment with cabozantinib at 4 weeks versus 8 weeks of therapy in patients (pts) with metastatic urothelial carcinoma (mUC).
Authors: Nicole N. Davarpanah, Liza Lindenberg, Dereck W Paul, Seth M. Steinberg, Deneise C Francis, Marilise Anne Berniger, Juanita Weaver, Yolanda McKinney, Howard L. Parnes, Peter L. Choyke, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2017)

317 Background: This study investigates whether changes in 18 F-FDG-PET/CT correlate with response to cabozantinib at an early time point (4 wks) versus the conventional time point of restaging (8 wks) in pts with mUC, using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Methods: 68 pts with mUC in a single arm phase II clinical trial of cabozantinib underwent FDG-PET/CT scans at baseline, 4 and 8 wks. Up to 5 lesions with the highest Standard Uptake Value (SUV) were designated as target lesions. Response was determined using 2 versions of PERCIST (1 lesion vs top 5 lesions with highest FDG uptake) for FDG-PET/CT at 4 and 8 wks. PERCIST response classifications were compared to RECIST v1.1 at 8 wks. Results: 54 pts had evaluable disease. The single lesion 4 wk response by PERCIST showed 40% partial metabolic response (PMR), 33% stable metabolic disease (SMD), and 27% progressive metabolic disease (PMD). The single lesion 8 wk response by PERCIST showed 31% PMR, 31% SMD, and 38% PMD. The single lesion analysis coincided with multiple lesion PERCIST analysis in 86% of pts at 4 wks and 89% at 8 wks. The 4 wk PET/CT was predictive of the 8 wk PET/CT in 75% of single lesion and 76% of multiple lesion analyses. In lesion-based analysis, the 4 wk PET/CT was predictive of the 8 wk PET/CT in 74% of bone, 89% of lung, 77% of lymph node, 74% of soft tissue, and 58% of liver lesions. Only 42% of the 8 wk PERCIST and RECIST classifications coincided. At 8 wks, 40% showed response in FDG PET-CT restaging vs 7% complete/partial response by RECIST. Conclusions: The 4 wk PET/CT scan predicts the therapy response at the 8 wk PET/CT scan however the 4 wk scan overestimates the 8 wk response. The single lesion analysis by PERCIST correlates with the multiple lesion analysis and may have more clinical utility. In the lesion-based analysis, the 4 wk PET/CT scan is predictive of the 8 wk PET/CT for bone, lung, lymph node and soft tissue but not for liver lesions. Response classifications by PERCIST are not in agreement with response classifications by RECIST. Although the methods may be complementary, they are not interchangeable. Further studies are required to validate these findings. Clinical trial information: NCT01688999.
Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities
Authors: T. M. Mayer, W. K. Kelly, J. Concato, H. Chao
Journal: Journal of Clinical Oncology (2009)

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.
Outcomes after proton radiotherapy for localized childhood ependymoma (EP).
Authors: Christine E. Hill-Kayser, Iris Paltin, Robert A. Lustig, Michael J. Fisher, Stefan Both, Jean Bello Belasco, Kristina Ann Cole, Angela J Waanders, Peter Phillips, Jane E. Minturn
Journal: Journal of Clinical Oncology (2014)

10077 Background: Radiotherapy (RT) results in excellent local control and outcomes for resected EP. Proton RT may reduce acute and late RT-related toxicity by reduced exposure of normal brain and other organs at risk (OAR). Methods: From 2010-13, 23 subjects with newly diagnosed EP were enrolled on a prospective registry. All subjects underwent maximal safe resection; none had dissemination. Focal RT was planned after CT simulation and fusion of pre and post-operative MRI scans. The tumor bed, clinical target volume (1 cm expansion), and OAR were contoured using Eclipse treatment planning software. Doses are reported in radiobiologic-equivalent-weighted absorbed dose (cGyRBE). Brainstem planning constraints included maximum dose 6,000 and 95% less than 5,400. Neurocognitive (NC) testing was planned for all subjects prior to start of RT. Results: The median age at start of RT was 4yr (range 1-15) and 70% were male. Disease characteristics included infratentorial in 18, (78%), supratentorial in 5 (22%) [occipital (2), parietal (2), frontal (1)], and anaplastic histology in 11. Baseline NC testing was performed in 13 subjects, with overall pre-RT NC abilities ranging from low average to superior (median IQ=105, range 88-127). In subjects with non-anaplastic histology, average RT dose was 5,565 (range 5,400-5,940). For anaplastic disease, average dose was 5,900 (range 5,580-5,940). Median duration of RT was 44 days (range 37-50). RT was delivered using passive scattered proton beams for 20 subjects, and pencil beam scanning for 3. Toxicities during treatment (CTAEv4) included fatigue (G1, n = 3) headache (G1, n = 3), dermatitis (G1, n = 12; G2, n = 2), nausea (G1, n = 5), vomiting (G1, n = 2), anorexia (G1, n = 2), dysphagia (G1, n = 1). Post-RT chemotherapy was given to 2 subjects. With a maximum follow-up of 43 months (range 1-43, mean 17), 18 subjects are alive without disease, 2-dead of disease, 3-AWD. None have experienced grade 3 or 4 late RT-related toxicity. At 1 yr post-RT, overall IQ was 96-118 (n=5); at 2 years, 99-121 (n = 3). Conclusions: With over 3 years of follow-up, proton RT for pediatric EP appears well-tolerated, resulting in minimal acute toxicity and no serious late toxicity, with excellent disease control.
Treatment patterns of gastrointestinal neuroendocrine tumors (NET).
Authors: Michael S. Broder, Eunice Chang, Beilei Cai, Maureen Neary, Elya Papoyan, Al Bowen Benson
Journal: Journal of Clinical Oncology (2017)

387 Background: NET comprise a broad set of rare tumors. Almost 2/3 arise in the gastrointestinal (GI) tract. NCCN guidelines for unresectable GI NET recommend somatostatin analogues (SSA) first, however, guidelines do not recommend a particular sequence for remaining therapies. Our objective is to describe real world treatment patterns of GI NET. Methods: This retrospective study combined 2 claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included SSA, cytotoxic chemotherapy (CC), targeted therapy (TT), interferon (IF) and combinations. Patients ≥ 18 years, with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who received pharmacologic treatment from 7/1/09-6/30/14 were identified. A 6 month clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment. Results: We identified 2,258 newly treated GI NET patients. 59.6% started first line therapy with SSA monotherapy, 33.3% CC, 3.6% TT, and 0.5% IF. The remainder received combination therapies. Mean follow up was 576 days. Mean duration of first line therapy was 361 days for all newly treated patients (449 SSA, 215 CC, 267 TT). 58.9% of patients had no subsequent pharmarcological treatment after discontinuation of first line therapy.The most common second line was combination therapy with SSA (i.e., CC or TT added). In patients who did not begin with SSA, most received SSA as second line. In graphical pattern analysis, there was no clear pattern visible after first line therapy. Conclusions: More than 1/2 of pharmacologically treated patients began treatment with SSA and 1/3 with CC, with duration of use &gt; 1 year and just over 6 months, respectively. We found treatment patterns after first line were unclear, and more than 1/2 of patients had no subsequent pharmacological treatments after discontinuing first line therapy. It is unclear whether there is underutilization of the pharmacological therapy or this is due to stable disease status after alternative non-pharmacological treatment. Future studies directed at understanding treatment patterns using patient medical records are warranted. As new treatments emerge, reassessment of treatment patterns may be needed.
Screening for depression in adults: U.S. Preventive Services Task Force recommendation statement
Authors: Ned Calonge, Diana B. Petitti, Thomas G. DeWitt, Allen J. Dietrich, Leon Gordis, Kimberly D. Gregory, Russell Harris, George Isham, Michael L. LeFevre, Rosanne M. Leipzig, Carol Loveland-Cherry, Lucy Marion, Virginia Moyer, Judith Ockene, George Sawaya, Barbara Yawn
Journal: Annals of Internal Medicine (2009)