tbuckley/cabot-search huggingface dataset:
Activity of aflibercept (Afli) in combination with FOLFIRI (F) for patients with metastatic colorectal cancer (mCRC) in a real-life setting in Spain: Final results of the retrospective study Named Patient Program.
Authors: Javier Sastre, Jaime Feliu, Purificación Martinez, Cristina Buges, Jose Carlos Mendez, Julia Alcaide, Teresa Garcia, Manuel Valladares, David Marrupe, Ignacio Delgado, Mercedes Salgado Fernandez, Jose Ignacio Martin Valades, Asuncion Juarez, Jose Miguel Martin Martinez, Ana Lopez, Guillermo Alfonso Quintero Aldana, Olga Donnay, Ruth Vera, Nieves del Pozo, Isabela Diaz De Corcuera Frutos
Journal: Journal of Clinical Oncology (2016)

689 Background: InVELOUR trial the addition of aflibercept to FOLFIRI regimen, demonstrated a statistically significant overall survival improvement in mCRC patients (pts) who progressed on or after a prior oxaliplatin based regimen with or without biologic agents. Our goal is to assess in the real-life setting the activity and safety profile of Afli+F in mCRC. Methods: Retrospective data collection (baseline characteristics, progression free survival [PFS], objective response rate [ORR], salvage surgeries, and safety profile) of pts who received Afli+F as a 2nd line treatment on a compassionate use program in Spain. GERCOR prognostic model has been applied to evaluate PFS. These are the final results of the analysis (Cut-off date June 2015). Results: The retrospective study population comprised 71 pts (34 hospitals); 60.6% men and 39.4% women, median age 64 years (19.7% &gt; 70) and 98.6% had ECOG scores = 0-1. 63.4% (n = 45) had ≥ 2 metastatic sites (liver [81.7%], lung [38.0%]) and 67.7% (46/68) patients were K-RAS mutated. 60.6% (n = 43) had received prior bevacizumab (BVZ) treatment, 16.9% (n = 12) had received prior cetuximab and 5.6% (n = 4) panitumumab. Patients received a median of 6 cycles (range: 1-30) of Afli+F. Median PFS with Afli+F was 5.3 months (CI 95%: 3.7-8.6); which was not significantly modified by the presence of K-RAS mutation (HR: 1.1663; 95%CI: 0.6676-2.0373; p = 0.5867), by prior BVZ treatment (HR: 1.2424; 95%CI: 0.7238-2.1327; p = 0.4283) or by anti-EGFRs treatment (HR: 0.5681; 95%CI: 0.3117-1.0356; p = 0.0604). ORR was 19.7% (CI 95%: 11.2-30.9) and 8.5% (n = 6) of salvage surgeries. The most frequent adverse events grade ≥ 3 related with treatment were asthenia (n = 8), neutropenia (n = 7) and diarrhea (n = 6). The characteristic anti-angiogenic events were hypertension (n = 8), proteinuria (n = 1), vascular events (n = 1), and one intestinal perforation resulting in death. GERCOR prognostic model: Median PFS = 8.30 months [1.28-18.71] low risk, 5.29 [4.08-9.93] intermediate risk and 2.56 [1.94-4.57] high risk. Conclusions: In spite of the differences in sample size, in the real-life setting, Afli+F achieve a PFS comparable to VELOUR, regardless of K-RAS status or prior BVZ and anti-EGFR’s treatment, with an appropriate safety profile. Funding: Sanofi.
Efficacy and safety of zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (Alliance).
Authors: Matthew Raymond Smith, Susan Halabi, Charles J. Ryan, Walter Michael Stadler, Arif Hussain, Nicholas J. Vogelzang, Ralph J. Hauke, Ben L. Sanford, Eric Jay Small
Journal: Journal of Clinical Oncology (2013)

27 Background: Zoledronic acid (ZA) decreases risk of skeletal-related events (SREs) in men with castration-resistant prostate cancer (CRPC) and bone metastases. This phase III study evaluated efficacy and safety of earlier treatment with ZA in men with castration-sensitive metastatic prostate cancer. Methods: CALGB 90202 was a randomized, double-blinded, placebo-controlled phase III trial in men with castration-sensitive prostate cancer and bone metastases who had initiated androgen deprivation therapy within six months of study entry. Subjects were randomized 1:1 in blinded manner to receive ZA (4 mg intravenously every 4 weeks) or placebo (P). After progression to CRPC, all patients crossed over to open-label ZA. The primary endpoint was time to first SRE. Target sample size was 680. Time to SRE was defined as interval between date of randomization and date of first SRE (radiation to bone, or clinical fracture, or surgery to bone, or death due to prostate cancer). With 470 SRE events, the log-rank test has 88% power to detect a 23% decrease in hazard rate of SRE event assuming a one-sided type I error rate of 0.05. The study was discontinued prematurely after the corporate supporter withdrew study drug supply. Primary analysis was based on the stratified log-rank statistic adjusting on the stratification factors following observation of 284 SREs (60% of total events). Results: Between June 2004 and April 2012, 645 patients were randomly assigned to ZA or P. Median time to first SRE was 32.5 months in the ZA group and 29.8 months in the P group (hazard ratio (HR) 0.96 [0.76-1.22]; stratified log-rank P=0.74). A total of 271 deaths were observed; median follow-up time for surviving patients was 24.4 months (20.6, 28.3). Overall survival was similar between groups (HR= 0.89 [0.70-1.14]; stratified P=0.34). Rates of grade 3 or higher adverse events were similar between groups (15% vs. 12% in ZA and P). Conclusions: In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs or death. Early termination limited statistical power of the study. Clinical trial information: NCT00079001.
Association of ARV7 expression with molecular and clinical characteristics in prostate cancer.
Authors: Himanshu Joshi, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2016)

109 Background: Prostate cancer (PC) is the most common cancer in men over the age of 60 and the second leading cause of cancer mortality in the United States. Clinicopathological parameters such as Gleason score, tumor volume, surgical margins, prostate-specific antigen (PSA), Ki-67 index and clinical stage are used as prognostic markers for clinical outcomes. Identification of novel molecular markers could improve our understanding of the clinical behavior of this disease. Androgen receptor isoforms, in particular variant 7 (ARV7 or AR3) have been recently studied for elucidating their potential role in PC progression, associated with epithelial-mesenchymal transition (EMT), disease aggressiveness, increased proliferation and therapeutic resistance. Our study is analyzing the association of ARV7 mRNA expression to clinical characteristics and is analyzing the genomic data to identify differentially altered genes by ARV expression status, summarized as a potential functional network. Methods: We obtained the TCGA public dataset of prostate adenocarcinoma tumors (N=499) that included the clinical data, gene and isoform expression and mutation data. Cases were categorized into ARV7 over-expressing (ARV+) and normal or low expression (ARV –/N) by using a cut-off of upper 25th percentile of the background genomic expression. Analysis was performed in R and Perl by using custom-made scripts. Differentially altered genes and pathways were identified and were summarized as potential functional networks. Results: We categorized 30 out of the 499 tumors as ARV+. ARV7 over-expression was found to be significantly associated with older age at diagnosis (&gt;70), advanced clinical stage, nodal involvement, high Gleason score and a poor therapeutic response. We also observed a trend towards shorter disease-free survival among ARV+ tumors. In addition, ARV+ tumors showed significantly higher number of mutations in 20 key regulatory pathways including Jak-STAT signaling, homologous recombination, ErbB and Wnt signaling pathways. Conclusions: ARV7 overexpression is associated with genomic alterations in key regulatory pathways and poorer clinical outcome in PC patients.
A phase I trial of the combination of the antiangiogenic agent sunitinib and radiation therapy for patients with primary and metastatic central nervous system malignancies
Authors: E. J. Wuthrick, W. J. Curran, M. Werner-Wasik, A. Lin, R. A. Axelrod, A. Pereira-Rico, H. Murphy, M. Machtay, A. P. Dicker
Journal: Journal of Clinical Oncology (2008)

2053 Background: Preclinical studies suggest that combining angiogenic blockade with radiation therapy may enhance the therapeutic ratio of radiation via targeting vasculature and tumor cells. Sunitinib is an oral agent that has inhibitory activity against multiple receptor tyrosine kinases (VEGFR1, VEGFR2, VEGFR3, PDGFRα, and PDGFRβ) producing an antiproliferative and antiangiogenic effect. This open-label, phase I clinical trial evaluated the safety and toxicity profile of sunitinib combined with radiation therapy. Methods: Eligible patients had histologically documented malignant solid tumor, required a minimum two week course of radiotherapy to the brain, had WHO performance status of 0–2, and a life expectancy of >3 months. Previous treatment was allowed, however concurrent chemotherapy was not. During radiation therapy sunitinib was administered 37.5 mg daily, including weekends, for the duration of radiotherapy treatment. The primary endpoint was acute toxicity documented according to the Common Toxicity Criteria version 3. Results: A total of 23 patients were enrolled. Twelve patients had primary brain tumors including 8 with recurrent high-grade glioma and 11 patients had brain metastasis. Twenty patients have completed treatment. Total radiation therapy doses delivered ranged from 14–60 Gy and fraction size ranged from 1.8–3.5 Gy. Common acute toxicities included hematologic, nausea, hyperglycemia, hypocalcemia, and diarrhea. Fourteen (61%) patients were limited to grade 1 or 2 toxicities. Twelve grade 3 toxicities occurred in 9 (39%) patients including hematologic, fatigue, and DVT. No grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events (pulmonary embolism and status epilepticus) occurred both of which were attributed to disease progression. Median follow-up was 3.5 months. At this time, 15 patients were evaluable for response. Nine patients (60%) had stable disease and 6 (40%) patients had progressive disease. Conclusions: Sunitinib at a 37.5 mg dose concurrent with radiation therapy to the central nervous system yields acceptable toxicities and adverse events. The results justify future evaluation in a phase II trial. No significant financial relationships to disclose.
Utility of blood oxygen level dependent magnetic resonance imaging in the evaluation of tissue oxygenation patterns of prostate cancer.
Authors: Bishoy A. Gayed, Rami Hallac, Ramy F. Youssef, Franto Francis, Qing Yuan, Robert Sims, Yao Ding, Claus G Roehrborn, Ralph Mason, Ganesh Raj
Journal: Journal of Clinical Oncology (2013)

198 Background: Tumor hypoxia is associated with worse pathologic features and oncological outcomes. Blood Oxygen Level Dependent (BOLD) MRI evaluates changes in endogenous contrast generated by paramagnetic deoxy-hemoglobin to non-invasively evaluate tissue oxygenation. Prior attempts using carbogen-based (95%O 2 + 5%CO 2 ) imaging were limited by patient tolerance. We present the first-in-man evaluation of a novel oxygen breathing challenge technique to monitor tissue oxygenation with BOLD MRI in patients with prostate cancer. Methods: Following IRB approval, 10 patients with clinically localized prostate cancer scheduled for radical prostatectomy underwent preoperative imaging with a 3-Tesla MRI scanner. Images were acquired using a 6-element SENSE body transmit coil and endorectal receive coil. T 2 * signal intensity is dependent on the concentration of deoxy-hemoglobin. Signal intensity measurements were obtained at different time points. Shorter T 2 * times imply the presence of hypoxia. Dynamic T 2 * maps were acquired while subjects breathed air for 2 mins followed by oxygen (15 l/min). Results: 10 patients (median age: 59 years (range 48-73), median PSA 6.9 ng/ml (range 2.5-25), with prostate cancer (Gleason sum 6- 7, 8-9 in 7 and 3 patients respectively) underwent BOLD MRI within 3 weeks of definitive management with a robotic assisted laparoscopic prostatectomy. All patients tolerated BOLD MRI with oxygen challenge without difficulty. Evaluation of BOLD MRI revealed wide variation in T 2 * values within the prostates from a median of 14.7 ± .71 ms to 44.5 ± 3.3ms. Surrounding muscle T 2 * values were similar for all patients, indicating that heterogeneous values were specific to each patient’s prostate. Shorter T 2 * values were seen in Gleason 6-7 than Gleason 8- 9 cancers, indicating more hypoxic areas in these tumors. HIF-1α staining was strongly positive in all tumors. Conclusions: BOLD MRI with oxygen challenge is well tolerated in patients and is a feasible noninvasive technique to study tissue oxygenation in tumors. Differential oxygenation patterns of prostates appear to correlate with pathological features. Further testing is needed to validate these findings.
Circulating biomarkers and outcomes in a single-arm phase II trial of first-line sunitinib alternating with everolimus for advanced renal cell carcinoma (aRCC): EVERSUN ANZUP trial 0901.
Authors: Sonia Yip, Nick Pavlakis, Rozelle Harvie, Andrew Martin, Lidija Jovanovic, Amanda Hudson, Jennifer F. Thompson, Colleen Nelson, Anne Long, Christopher Steer, Michelle L. Harrison, George Kannourakis, David Goldstein, Ganessan Kichenadasse, Raymond M. Lowenthal, Martin R. Stockler, Ian D. Davis
Journal: Journal of Clinical Oncology (2014)

428 Background: We sought biomarkers at baseline associated with clinically important outcomes in this trial of alternating sunitinib and everolimus. Methods: Baseline blood was tested for circulating tumor cells (CTCs) using CellSearch CTC system (Veridex). Baseline serum was tested for protein biomarkers: bFGF, CAIX; e-selectin; HIF1; IL8; NGAL; PDGF; PLGF; vCAM; VEGF-A, C and D; VEGFR1-3; by multiplex immunoassays (Bio-Plex system BioRad) or ELISA (R&amp;D Systems DuoSets). Biomarker levels were dichotomised according to median or limit of detectability. Outcomes were progression free, overall survival (PFS, OS), objective tumour response (OTR) and toxicity (cycle 1 grade 3-5 AEs). Regression models were used for hazard ratios (HR), odds ratios (OR), p-values (p) in univariable analysis, adjusted for established prognostic factors in multivariable analysis. Results: Patient (n=55) characteristics were mean age 61 yrs: male 71%; MSKCC good risk 16%, intermediate risk 84%. There were 47 progression events and 30 deaths after a median follow-up of 20 mos. CTCs were detected in 5/31 (16%). Univariable analysis showed associations between OTR and low levels of bFGF (6 v 0, p 0.009); shorter OS and high levels of both NGAL (HR 2.5, p 0.02) and IL8 (HR 2.3, p 0.04); toxicity with detectable levels of CAIX (OR 4.7, p 0.03); none was associated with PFS. Adjusting for MSKCC prognostic score, age, gender and presence of liver or bone metastases: shorter PFS was associated with high bFGF (HR 2.0, p 0.03), low vCAM1 (HR 0.50, p 0.04), undetectable HIF1 (HR 0.33, p 0.01), shorter OS was associated with high NGAL (HR 2.5, p 0.03) and undetectable HIF1 (HR 0.35, p 0.04). Toxicity was associated with detectable CAIX (OR 5.8, p 0.04). None were statistically significant after adjusting for multi-comparisons. Conclusions: This exploratory study did not find strong statistical evidence for the prognostic value of these circulating baseline biomarkers. Prognostic value of changes from baseline during therapy remains an important area of study. EVERSUN is an ANZUP Cancer Trials Group Ltd trial coordinated by NHMRC Clinical Trials Centre (ACTRN12609000643279).
Diabetes mellitus and survival after a diagnosis of breast cancer: A meta-analysis
Authors: K. S. Peairs, B. B. Barone, C. F. Snyder, H. Yeh, K. B. Stein, R. L. Derr, F. L. Brancati, A. C. Wolff
Journal: Journal of Clinical Oncology (2008)

6560 Background: Small studies suggest a possible negative effect of pre-existing diabetes mellitus on survival (all cause and breast cancer-specific) in patients diagnosed with breast cancer. Methods: We searched the EMBASE and MEDLINE databases from inception to August 2007 using search terms related to diabetes mellitus, cancer, and prognosis, survival or mortality. Paired reviewers independently reviewed articles, extracted data, and assessed quality. Potential sources of heterogeneity between studies were assessed using Q statistics. Publication bias was evaluated using both the Begg's funnel plot and the Egger plot. The pooled hazard ratio (HR) was calculated using the variance-weighted method for a fixed-effects model (Q=2.195 on 3 df, p=0.533). Results: Out of 6,943 titles identified, 213 articles were reviewed and 91 cancer articles met inclusion/exclusion criteria for abstraction. Five of the abstracted articles described outcomes in patients with breast cancer and diabetes mellitus. The effect of diabetes on all-cause mortality was described in four of five studies (total n = 13,019). All four studies adjusted for at least some potentially confounding variables like age, stage, other comorbidities, and systemic therapy. The pooled estimate revealed that, compared to their non-diabetic counterparts, women with breast cancer and diabetes were 61% more likely to die during follow-up (HR=1.61; 95% CI, 1.46-1.79). A few studies suggested that diabetic patients were more likely to have a higher stage at diagnosis and less likely to receive locoregional and systemic therapy after controlling for age/stage. There was no significant publication bias, and quality of the studies was moderate-to-high. Conclusions: Breast cancer patients with diabetes mellitus have a greater risk of death. Studies are needed to explore pathophysiologic interactions and whether improvements in diabetes care can reduce mortality in breast cancer patients. No significant financial relationships to disclose.
Clinical trials of WT1 peptide vaccine to gynecologic malignancies that are resistant to conventional therapies.
Authors: T. Miyatake, T. Enomoto, Y. Oka, S. Nishida, A. Tsuboi, T. Shirakata, S. Morita, J. Sakamoto, H. Sugiyama, T. Kimura
Journal: Journal of Clinical Oncology (2010)

5081 Background: Wilms' tumor gene WT1, which has an oncogenic function, is expressed in various kinds of hematological malignancies and solid cancers. The WT1 protein is highly immunogenic and is considered to be a promising target of cancer treatment. On the clinical trials of WT1 peptide vaccine, the decrease of leukemic cells, shrinkage of solid tumor and long-term dormancy of malignancies are reported. We intend to report the clinical trials of WT1 peptide vaccine to gynecologic malignancies which are resistant to conventional therapies. Methods: Twenty one cases of gynecologic malignancy (12 cases of ovarian cancer, 4 of cervical cancer, 1 of endometrial cancer and 4 cases of other malignant tumor), which are resistant to first-/second-line therapy, were included to the trial. After obtainment of informed consent, modified WT1235 type peptide is injected intracutaneously to the HLA-A*2402- positive patients, whose tumor tissues expressed WT1 protein. The injection was repeated weekly to total of 12 times. Immune response to WT1 peptide was monitored with delayed type hypersensitivity (DTH). Side effect due tothe injection was also monitored. The antitumor effect was assessed based on Response Evaluation Criteria in Solid Tumors (RECIST). If any clinical effect is observed, the injection of the vaccine was continued biweekly. Results: In 15 (71%) of 21 patients, the 12 times of injection are completed. In remaining 6 cases, injection had been stopped due to worsening of performance status. Only 1 patient showed grade 3 vesicle at the injection site, however, no patient was cancelled the injection due to severe side effect. The SD status in RECIST criteria is observed in 5 (24%) patients and the injection is continued for these 5 patients, with the maximum of 29 times. Patients who is positive to DTH reaction during therapy, showed significantly longer overall survival than patients who are negative to DTH through the treatment. Conclusions: It was considered that the induction of WT1-specific immunological responses contributed to the occurrence of clinical responses. Some patients reached long-term dormancy of the tumor. We recognized the WT1 peptide vaccine is a new strategy for gynecologic malignancies. No significant financial relationships to disclose.
Financial and work related impact of cancer in young adult (YA) survivors.
Authors: Kevin Scott Baker, Kelly Ambrose, Sarah R. Arvey, Jacqueline N. Casillas, Patricia A. Ganz, Linda A. Jacobs, Mary S. McCabe, Linda Overholser, Ann H. Partridge, Emily Jo Rajotte, Betsy C Risendal, Donald Rosenstein, Karen Syrjala
Journal: Journal of Clinical Oncology (2016)

15 Background: YA survivors face challenges unique from those of survivors of childhood cancer or of older adults. The potential impact of cancer or its treatment upon employment and finances for YA survivors is unknown. Methods: Eligibility included diagnosis of malignancy between ages 18-39, 1-5 years from diagnosis and &gt; 1 year from therapy completion. Participants (see Table) were randomly selected from tumor registries of 7 academic institutions; 875 (41% of attempted contacts) enrolled and completed online patient reported outcomes survey related to the effects of cancer/treatment on employment, finances, and cancer-related distress. Results: Overall 84% were employed sometime between cancer diagnosis and study enrollment. Of those, 76% took paid time off (40% &lt; 2 mo, 29% 2-5 mo, 31% &gt; 6 mo). Unpaid time off was required by 39% (37% &lt; 2 mo, 25% 2-5 mo, 38% &gt; 6 mo). Other impairments included inability to carry out physical (59%) or mental (55%) tasks required for their job, being less productive (67%), and not pursuing an advancement/promotion (21%). Financial impacts were substantial: 61% worried about medical bills, 31% went into debt related to their cancer/treatment. Of those incurring debt, most (53%) reported this amount to be &lt; $10,000, 29% $10,000-$24,999, and 18% &gt; $25,000; 13 (4.8%) filed for bankruptcy. Chi squares comparing those receiving extensive treatment vs. surgery only indicated greater likelihood of financial debt (10.6, P=.001) and residual distress (13.9, P &lt; .001) if treated with more than surgery. Conclusions: Most YA survivors experience a significant negative impact on employment and finances related to their cancer and treatment, which occurs at a critical time in their careers and at a life phase inherently more financially unstable. Longitudinal follow-up is required to better quantify the long-term burden on work and finances from cancer diagnosed in young adulthood. [Table: see text]