tbuckley/cabot-search huggingface dataset:
Histopathologic correlation of PI-RADS V.2 lesions on 3T multiparametric prostate MRI.
Authors: Aaron Katz, Corinne Liu, Kaitlin E. Kosinski
Journal: Journal of Clinical Oncology (2016)

10 Background: Prostate Imaging Reporting and Data System (PIRADS) Version 2 was recently issued by The American College of Radiology. Each score, from 1 to 5, corresponds to the likelihood of clinically significant cancer. We aim to evaluate the correlation between a higher PIRADS score and the presence of high grade tumor on histopathology. Methods: 300 consecutive 3T Multiparametric Prostate MRI (MP-MRI) were identified from March 26, 2012, to June 29, 2015. We reviewed patient charts and a total of 102 patients underwent either a transrectal ultrasound guided (TRUS) biopsy or a total prostatectomy after the MP-MRI. Thirty-four patients were excluded due to prior radiation or cryoablation to the prostate, leaving 68 treatment-naive patients (44-84 years). MP-MRIs were re-interpreted utilizing the new PIRADS V.2 scoring system and correlated with pathology findings. Statistical comparisons were made using R (v.3.1.2) and Fisher’s exact test. Results: High grade (Gleason 8-10) tumors were found only in MP-MRI with a PIRADS score of 5 and a higher percentage of tumor is found in MP-MRI with PIRADS scores of 4 and 5 (80%) when compared to PIRADS scores of 2 and 3 (32%). Low grade (Gleason 6-7) tumors were also found in both PIRADS 4 and 5 categories. There was a significant relationship between a higher PIRADS score and a finding of cancer on pathology (p = 0.0003, OR=0.118, 95% CI 0.03-0.41). Conclusions: The PIRADS scoring system is a useful tool in suggesting the likelihood of clinically significant cancer, with high grade tumors found only in MP-MRI with a score of PIRADS 5. However, MP-MRI and PIRADS criteria alone are not sufficient for determining clinically significant prostate cancer since both high grade and low grade tumors were found in PIRADS 5 and 4 categories. Correlation with other clinical parameters and biopsy is required for confirmation. A larger scale study would be helpful for further delineation. [Table: see text]
An observational study on the efficacy and safety of zoledronic acid (ZA) in patients with non-small cell lung cancer (NSCLC) patients with bone metastases with high urine n-telopeptide (uNTX) at diagnosis (C-TONG 0801).
Authors: S. Lu, L. Zhang, Y. L. Wu, Y. Zhang, C. Zhou, G. Chen, M. Hou, X. Song, J. Wang
Journal: Journal of Clinical Oncology (2011)

e19541 Background: A retrospective study showed that bone metastatic NSCLC patients with high uNTX levels at diagnosis had a higher skeletal related event (SRE) and an increased death risk than that with lower uNTX levels. However, Patients with normalized uNTX levels after three months ZA treatment associated with lower SRE and better overall survival compared with those patients with continuously elevated uNTX levels. The present study prospectively investigated the relationship between SRE incidence and normalization of uNTX as well as the long-term safety of ZA in Chinese NSCLC patients with bone metastases. Methods: The NSCLC patients with bone metastasis, high uNTX levels (≥50 nmol/mmol) at diagnosis and treated with ZA (4mg, iv drip, every 3-4 weeks) more than 3 months were included to the study. All the patients continuously received ZA treatment and the standard chemotherapy. Urinary NTX was measured at baseline and 3, 6, 9 months. Clinical efficacies were measured with SREs rate at 12 months, annual SRE incidence, time to first SRE and survival. Patients were stratified into continued elevated uNTX levels group (CEG) and normalized uNTX levels group (NG). Results: 158 patients were enrolled. 51 and 99 patients were included into CEG and NG group respectively. uNTX Normalization rate after 3 month ZA treatment was 62.7% (99/158). For the all group, the SRE rate at 12 months is 14.65%, the mean annual SRE incidence was 0.48 events/year and median time to first SRE was 6.03 months. There are no differences between CEG and NG in term of annual SRE incidence (0.51 vs 0.47 events/year, P=0.89), SRE rate at 12 months (15.69% v 14.14%, P=0.80) and time to first SRE (4.61 vs 7.40 months, P=0.72). However, the patients in CEG had significantly poor overall survival than NG patients (16 vs >21 months, P=0.05). ZA was generally well tolerated. Conclusions: This is first prospectively study of the value of normalization uNTX in NSCLC patient with bone metastasis. The results confirmed that continued elevated NTX level during ZA treatment was a poor prognostic fact.
SDF-1 and VEGF-C as potential circulating angiogenic biomarkers for bevacizumab in patients with metastatic colorectal cancer.
Authors: Mitsukuni Suenaga, Satoshi Matsusaka, Eiji Shinozaki, Mariko Ogura, Masato Ozaka, Izuma Nakayama, Takeru Wakatsuki, Keisho Chin, Nobuyuki Mizunuma, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2014)

480 Background: Bevacizumab (BV) plus chemotherapy (chemo) has been shown to improve survival for metastatic colorectal cancer (mCRC). Stromal cell-derived factor-1 (SDF-1) is known as a ligand for CXCR-4. We previously reported that proportion of CXCR4-positive circulating endothelial cells at baseline was correlated with the prognosis of BV plus chemo (Matsusaka, et al. Cancer. 2011). The aim of this study was to investigate changes during treatment in serum candidate cytokines including SDF-1 as potential markers of treatment response to BV. Methods: Patients receiving first-line BV plus chemo with mCRC were enrolled in this prospective study. Serum samples were analyzed before initiation of treatment and during treatment (on days 14 and 56) and at the time of progressive disease. Correlation between tumor response and changes in serum levels of the cytokines (such as VEGF, SDF-1, Ang-1 and -2, etc.) were investigated. Differences in the means of continuous measurements were tested by the Student’s t test. A two-way repeated-measures analysis of variance was used to evaluate differences between sequential continuous variables. Results: 24 were enrolled at the first interim analysis. 14 patients were assessable; some who got conversion surgery or discontinued treatment due to toxicity in early were excluded. Tumor response was achieved in 57% of the patients. SDF-1 levels at baseline (p=0.045) and on days 14 (p=0.049) were significantly lower in tumor responder, while a trend toward higher on days 56 compared to non-responder. The results of a two-way repeated-measures analysis of variance to evaluate differences between sequential continuous variables showed significant differences in VEGF-C (p=0.043) and SDF-1 (p=0.02), influenced by tumor response. Serum levels of SDF-1 trended toward increase on days 14 and decrease on days 56, whilst VEGF-C trended toward decrease on days 14 and 56. Conclusions: Changes Serum levels of SDF-1 and VEGF-C showed correlation with tumor response to BV plus chemo, suggesting that these surrogate markers may represent anti-angiogenic condition for BV treatment. This study is currently ongoing, and further analysis will be performed in more population.
Predictors of long-term survival with metastatic pancreatic cancer (mPC) in the gemcitabine era: The Fox Chase Cancer Center experience.
Authors: Namrata Vijayvergia, Efrat Dotan, Karthik Devarajan, Bianca Lewis, Steven J. Cohen
Journal: Journal of Clinical Oncology (2015)

253 Background: Although median survival (OS) for patients (pts) with mPC was ~6 months (m) in the gem era, a subset of pts lived significantly longer as long term survivors (LTS). We compared the patterns of care and outcomes of pts living &lt; 12 m (Gp 1) and ≥ 12 m (Gp 2) to identify predictors for LTS. Methods: With IRB approval, we retrospectively analyzed medical charts of mPC pts treated at our center between 2000 and 2010. Gp 1 and Gp 2 were compared with respect to pt, tumor and treatment characteristics. Fisher’s exact and Mann-Whitney tests were used, respectively, to compare categorical and continuous variables, and the log-rank test to compare OS. All tests were two-sided and a Type I Error of 5% was used to determine statistical significance. Results: 579 mPC pts (median age 64 y, 56% males) were identified, 476 pts in Gp1 and 103 in Gp 2 (OS 4m vs 18 m, respectively). There was no significant difference in the age, site of pancreatic primary, comorbidities, tobacco use or stage at diagnosis between the two. 341 (72%) pts in Gp1 and 86 (83%) in Gp 2 had an initial PS &lt;2 (p 0.06). Alcohol use was more prevalent in LTS [170 (36%) in Gp1 vs 50 (49%) in Gp2 (OR 1.8, p 0.008)]. 170 (36%) pts in Gp 1 and 55 (52%) in Gp 2 had serum albumin (alb) &gt; 3.5 gm/dl (p&lt; 0.001) and this predicted survival (OS 4m if Alb &lt; 3.5 and 7m if Alb &gt; 3.5, p &lt;0.001). Use of chemotherapy in the metastatic setting (66% in Gp1 vs 93% in Gp 2) and number of agents used also predicted survival with 202 (42%) pts in Gp 1 and 79 (87%) in Gp 2 having received &gt; one agent in the metastatic setting (p &lt; 0.001). Liver metastases were more common as an initial site in Gp1 vs Gp2 [329 (70%) vs 48 (47%) respectively, p &lt; 0.001]. In contrast, lung metastases were more common in Gp 2 [42 (9%) Gp 1 vs 20 (19%) in Gp 2, p&lt; 0.001]. The median survival for pts with liver as initial metastatic site was worse than those with lung metastases (5m vs 7m, p &lt; 0.001). Conclusions: Use of chemotherapy and increasing number of agents are associated with better survival in mPC, in line with the current practice of using combination chemotherapy. The site of initial metastasis and serum albumin also predict for survival. Clinical trial designs should consider the latter as stratification factors.
Incidence and prediction of venous thromboembolism (VTE) in ambulatory patients (pts) with pancreas cancer receiving chemotherapy.
Authors: Ana Belen Ruperez Blanco, Andrés Jesús Muñoz Martin, Pilar Garcia Alfonso, Sonsoles Alvarez Suarez, Mercedes Cavanagh Podesta, Sara Custodio Cabello, Rebeca Mondejar Solís, Daniel Lopez-Trabada Ataz, Montserrat Blanco-Codesido, Miguel Martin
Journal: Journal of Clinical Oncology (2012)

368 Background: VTE is considered a main cause of mortality and morbidity in cancer pts and is commonly underestimated by oncologists. Pancreatic cancer is associated with the highest risk of VTE and the true incidence remains uncertain. Chemotherapy has been identified as an independent risk factor for VTE. The aim of this study is to analyze the incidence of cancer-associated thrombosis in ambulatory pts with pancreatic cancer receiving chemotherapy. Methods: We performed a retrospective review to determine the incidence of VTE in the gastrointestinal cancer unit of our centre. Between 2008 and 2010, 64 consecutives pts were identified and included in the analysis. Pancreatic neuroendocrine tumors were excluded. Results: Clinical characteristics ( table 1). Twenty pts (31.2%) experienced VTE including 7 pulmonary emboli (PE), 8 deep-vein thromboses (DVT) and 8 visceral vein thromboses (VVT). PE:25%. DVT:25%. VVT:35%. PE+DVT:10%. DVT+VVT:5%. Arterial thromboembolism (ATE): 2 pts (3.1%). 56% of the events were diagnosed during the first six months after diagnosis. Khorana’s predictive model for chemotherapy-associated thrombosis (risk category): intermediate risk (IR) 17 pts (27.9%) and high risk (HR) 44 pts (72.1%). VTE in HR and IR category: 14/44 pts (31.8%) and 6/17 pts (35.3%). Conclusions: The high incidence of VTE observed in this study is consistent with prior reports. Primary antithrombotic prophylaxis should be considered in this setting. Specific predictive model for chemotherapy-associated thrombosis in pancreas cancer must be investigated. [Table: see text]
Real-world treatment patterns and outcomes in HER2 positive MBC patients with brain metastasis in the U.S. community oncology setting.
Authors: Debra A. Patt, Eileen Fonseca, Bongin Yoo, Thomas Wilson, Hans-Peter Goertz, Catherine Lai
Journal: Journal of Clinical Oncology (2016)

92 Background: Patients (pts) with HER2 positive (HER2+) metastatic breast cancer (MBC) have different patterns of disease and treatment (tx) from HER2 negative MBC. Brain metastasis (BM) frequently occurs and txs vary. Methods: This retrospective study included adult HER2+ MBC pts from a community oncology network electronic health record (EHR) database and diagnosed between 2009-2011, with follow-up until 11/2014. Pts with other primary tumors were excluded. Two cohorts were defined: pts diagnosed with BM and pts with no evidence of BM (NBM), and were initially matched on age and performance status at MBC diagnosis (dx) and stage. Eligibility and txs were examined in electronic chart review. Overall survival (OS) from MBC dx was estimated using a weighted Kaplan-Meier method. Results: The final sample consisted of 86 BM and 101 NBM pts. All baseline MBC demographics were similar across cohorts. Median age was 54 and 52 years for BM and NBM, respectively. The cohorts (BM:NBM) included 57%:75% Caucasians, 12%:6% Blacks, and 31%:19% other/unknown. There were fewer estrogen receptor positive pts in the BM cohort (58%:74%; p = 0.02). Except for bone (p = 0.01), both cohorts had similar prevalence of metastatic sites: liver 35%:35%; lung 31%:30%; bone 41%:62. Of all the BM pts, 54% had first CNS imaging after symptoms, 37% were first imaged for other known reasons. After BM dx, 20% had surgical resection, 67% whole brain radiation (XRT), 37% stereotactic XRT, and 22% palliative XRT (not mutually exclusive). 25% of pts had both XRT and surgery while 72% had only XRT. Among pts receiving systemic therapy after BM dx, the first regimen contained trastuzumab in 55% of pts and lapatinib in 41% of pts. Among pts changing txs after BM dx, 1/3 switched to a trastuzumab but not lapatinib-based regimen; 1/3 to a lapatinib but not trastuzumab-based regimen; 17% to a lapatinib + trastuzumab-based regimen; and 17% to non-HER2-based therapy. Weighted median OS from MBC dx for BM vs. NBM pts was 30.2 and 46.1 months (p = 0.01). Conclusions: For HER2+ MBC pts, survival was shorter for pts with BM vs. NBM and a high degree of tx variability for BM existed. Understanding how detection and tx impacts outcomes will improve care of BM pts.
Dose-painted intensity-modulated radiation therapy (DP-IMRT) for anal cancer: No differences in treatment toxicity and early outcomes between human immunodeficiency virus (HIV) positive and negative patients.
Authors: Paul B. Romesser, Joseph D. Mancias, Muhammad M. Qureshi, Kevan L. Hartshorn, John D. Willins, Theodore S. Hong, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2012)

565 Background: HIV-infected patients are reported to experience increased treatment toxicity with standard concurrent chemoradiation (CRT) protocols for anal cancer. IMRT is a novel radiation (RT) delivery technique that allows the oncologist to conform or “dose paint (DP)” the RT dose to the tumor while sparing surrounding normal organs. We report our multi-institutional experience with DP-IMRT in regards to acute toxicities and treatment outcomes in HIV positive (HIV+) patients on highly active antiretroviral therapy (HAART). Methods: From August 2005 to December 2010, 63 patients, (10 HIV+), were treated with CRT for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. HIV+ and HIV- patients received a median DP-IMRT dose of 50.4 Gy over 43.5 and 42.0 days, respectively. Acute toxicities were graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Two year actuarial control and survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up was 29.3 and 24.3 months for HIV+ and HIV- patients, respectively. No significant differences were noted in acute grade 3+ toxicity in HIV+ versus HIV- patients: dermatologic 10.0% vs. 13.21%, p=1.0; genitourinary 10.0% vs. 3.77%, p=0.410; gastrointestinal 20.0% vs. 15.09%, p=0.653; and hematologic 80.0% vs. 64.15%, p=0.474. Multivariate analysis confirmed that HIV infection was not predictive of acute grade 3/4 toxicity. No significant differences were noted in 2-year local control (90.0% vs. 95.0%), distant control (90.0% vs. 89.7%), overall survival (90.0% vs. 89.2%), and colostomy-free survival (90.0% vs. 83.7%) rates among HIV+ vs. HIV- patients. Conclusions: HIV+ patients on HAART receiving concurrent chemotherapy with DP-IMRT for anal canal cancer showed similar two-year outcomes and no significant differences in acute toxicity compared to HIV- patients. As such, HIV+ patients with anal cancer should be considered eligible for all national trials in which IMRT is employed.
Drug-Response Signature Predicts Outcome in Adult Acute Myeloid Leukemia and Associates Poor Response with Molecular Characteristics of Hematopoietic Stem Cells.
Authors: Michael Heuser, Luzie U. Wingen, Doris Steinemann, Gunnar Cario, Nils von Neuhoff, Marcel Tauscher, Lars Bullinger, Hartmut Dohner, Brigitte Schlegelberger, Arnold Ganser
Journal: Blood (2004)
Metastasis-associated mutations in clear cell renal cell carcinoma.
Authors: Banumathy Gowrishankar, Manickam Janakiraman, Chung-Han Lee, Venkata Jaganmohan Thodima, Ana M. Molina, Premal H Patel, Theresa Margaret Gold, Robert J. Motzer, Raju S.K. Chaganti, Sitharthan Kamalakaran, Jane Houldsworth
Journal: Journal of Clinical Oncology (2016)

600 Background: Over 30% of patients with clear cell renal cell carcinoma (ccRCC) exhibit metastasis at the time of diagnosis and exhibit poor outcome. About 20-50% of patients with localized disease eventually develop metastasis after nephrectomy. The goal of the current study was to identify target gene mutations associated with ccRCC metastasis. Methods: In this IRB approved study, genomic DNA from 128 ccRCC resected specimens (128 unique patients) were profiled using a custom targeted next-generation sequencing (NGS) panel comprising 70 frequently mutated genes and prognostic SNPs in renal cancer. The specimen cohort consisted of 78 primary (29 stage I-III, 30 stage IV, 19 unknown) and 50 metastatic (10 lung, 9 bone, 25 other sites, 6 unknown) lesions. Following hybrid capture, sequencing was performed (MiSeq, Illumina) and variants identified using CLCbio (Qiagen). Chi-square test was used to test for significance. Results: The median specimen had 4 non-synonymous mutations (123/128 samples had at least one mutation). 66 genes showed a non-synonymous mutation in at least one specimen. There was no significant difference between total mutation count between primary and metastatic specimens (Mann-Whitney test). TSC1 mutation was significantly enriched in metastatic (8/50) compared with primary lesions (3/78). No TSC1 mutation was found in the 29 localized (stage I-III) primary lesions. Interestingly, TSC1 maps to 9q34 and our prior copy number studies indicated that loss of 9q is also enriched in metastatic lesions. Of the 11 specimens bearing TSC1 mutation in this cohort, 5 also had loss of 9q. In 44 specimens with known sites of resection, SETD2 and TSC1 mutations were not found in metastases to the lung but found in 30-40% of lesions at other sites, KDM5C and TSC1 mutations were not found in metastases to the bone while 25-30% of lesions at other sites exhibited these mutations. Due to the limited sample size, significance could not be determined for these associations. Conclusions: Preliminary results of this study implicated TSC1 in the metastasis of ccRCC. Since TSC1 mutation is known to confer sensitivity to mTOR inhibitors, our initial finding of absence of TSC1 mutation in lung and bone sites of metastasis may have therapeutic implications.
Second-line chemotherapy (CTx) outcomes in advanced biliary cancers (ABC): A retrospective multicenter analysis.
Authors: Maeve Aine Lowery, Laura Williams Goff, Emmet Jordan, Rui Wang, Andrea Grace Bocobo, Joanne F. Chou, Eileen Mary O'Reilly, James J. Harding, Nancy E. Kemeny, Marinela Capanu, Ann Griffin, Joseph P. McGuire, Alan P. Venook, Ghassan K. Abou-Alfa, Robin Kate Kelley
Journal: Journal of Clinical Oncology (2016)

437 Background: While gemcitabine in combination with platinum has been well established as first line systemic therapy for ABC, there remains no standard of care regimen in the second line setting. We evaluated current practice and outcomes for second line chemotherapy in patients with ABC across three geographically diverse, large US academic medical centers. Methods: 198 pts who received second line chemotherapy for ABC after 1/1/11 were identified from institutional databases following IRB approval. Records were reviewed for demographic, treatment and response data. Overall survival (OS) was calculated from start of second line chemotherapy and estimated using Kaplan-Meier methods. Results: Median follow up among survivors was 5 months and median OS for all patients from start of second line therapy was 11 months (mo) (95% CI 8.8-13.1): intrahepatic (61.1%): 13.4 mo (95%CI: 10.7-17.8); extrahepatic (14.1%): 6.8 mo (95%CI: 5-11); and gallbladder (24.8%): 9.4 mo (95%CI: 7.2-12.3). Median duration of second line chemotherapy was 2.2 mo (range 0-32.5). 103 pts (52%) received ≥ 3 lines of chemotherapy. Median OS from start of first line of gemcitabine plus cisplatin or oxaliplatin was 22.4 mo (95% CI 17.9 – 25.5). Conclusions: In highly selected pts with ABC treated at academic medical centers, survival following progression on first line chemotherapy was higher than previously reported, and patients received multiple lines of treatment. This multicenter collaboration provides a contemporary benchmark to inform the hypotheses and design of future clinical trials of second line chemotherapy in ABC. [Table: see text]
Quality of life in RCT of pasireotide to reduce pancreatic complications following resection.
Authors: Anne Eaton, Mithat Gonen, Paul Jack Karanicolas, Michael Ian D'Angelica, Ronald P. DeMatteo, T. Peter Kingham, William R. Jarnagin, Peter J. Allen
Journal: Journal of Clinical Oncology (2015)

393 Background: A recent trial demonstrated that prophylactic pasireotide reduces pancreatic complication (PC) rates (primary objective). In this secondary analysis, we describe quality of life (QoL) in this population before and after resection using a standard instrument (the EORTC QLQ-C30) and the EORTC pancreatic cancer module (PAN26), which was recently developed to address the unmet need for QoL assessment in this subpopulation. Also of interest is assessing the association between PC and QoL and testing the hypothesis that pasireotide improves QoL. Methods: We conducted a randomized, double-blind, placebo-controlled trial of preoperative subcutaneous pasireotide in 300 patients undergoing pancreaticoduodenectomy or distal pancreatectomy. Participants completed the C30 and PAN26 preoperatively and on postoperative days 14 and 60. Scores were compared using paired t-tests. Results: All patients completed at least one questionnaire and 87% of patients completed all three. No major differences in QoL were seen between treatment groups so pooled results were reported. A significant worsening of function at 14 days was detected on all PAN26 and C30 function scales except hepatic and emotional functioning (EF), and all C30 symptom scales (all p&lt;.01). These effects lessened by 60 days, but scores remained significantly worse than baseline with the exception of the sexuality, cognitive functioning, nausea and vomiting, insomnia and constipation scales, which returned to near baseline, and EF, which was significantly better than baseline (p=0.03). PC occurred in 45 patients and was associated with worse body image, dyspnea, financial difficulties and physical, role, emotional and social functioning at 14 and 60 days (all p&lt;.05). Conclusions: During the first 14 days following resection, patients can be expected to have a significant decline in QoL. Many symptoms abate by 60 days, and EF improves. Although pasireotide effectively reduced PC, its effect did not appear to translate to improved QoL based on this sample of 300 patients. While PC was associated with worse QoL, most patients in both pasireotide and placebo groups did not experience PC, which may explain why no significant difference in QoL was observed. Clinical trial information: NCT00994110.