tbuckley/cabot-search huggingface dataset:
Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.
Authors: Fernando Arias, Clara Eito, Antonio Viudez, Gemma Asin, Berta Ibañez, Irene Hernandez, Koldo Cambra, Marta Errasti, Marta Barrado, Maider Campo, Ignacio Visus, Elena Mata, Miguel Ciga
Journal: Journal of Clinical Oncology (2016)

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our study. Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group without adjuvant OXA was 6.0 (1.0-11.25), being for group that received adjuvant OXA of 5.0 (1.0-10.0). Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC, due to its absent of deleterious influence over the sphincter anal function. Because of the retrospective nature of our study, prospective studies should be warranted in similar scenarios. This study has been supported by a grant of “Mutua Madrileña Fundation.”
Utilization of breast preservation treatments in Hispanic patients with breast cancer: An analysis from the National Cancer Data Base (NCDB) from 2000 to 2011.
Authors: Alvaro Martinez, Elisabeth E. Arrojo, Frank A. Vicini
Journal: Journal of Clinical Oncology (2014)

76 Background: In contrast to mastectomy, radiotherapy (RT) treatments for breast cancer (BC) patients, allows for the benefits of breast preservation therapy and brachytherapy (BT) is a very convenient and short course of RT. BT use in BC has increased since FDA approval in 2002, however, has it been used evenly among races? Methods: Trends of treatment were analyzed for BC patients stages Tis to IV using the NCDB and 2.015.671 cases were found. Specific analysis of treatment differences between Black, White and Hispanic races, and the use of BT was performed. Results: The use of surgery as the only treatment in BC patients has decreased in stages 0 to IV (-7%, -11%, -8%, -6% and -6%; p&lt;0.0001), while the use of RT has increased in stages 0 to III (+5%, +1%, +3%, +8%; p&lt;0.0001). The use of chemotherapy has also increased in stages 0, I, III, IV (+3%, +4%, +7%, +5%; p&lt;0.0001), while decreased in stage II (-3%; p&lt;0.0001). Hispanic patients, received less RT in stages I to III (-4.11%, -5.46%, -4.84%; p&lt;0.05), while White’s in stage I and III (58.11%, 65.98%), and Black’s in stage II (52.19%) received more RT (p&lt;0.05). In addition, Hispanic’s received significantly more mastectomy in stages I, II and IV. BT as a type of RT was used mainly in stages 0 to II. In stages III and IV its use was &lt;0.13%. 50.836 patients stage 0-II received BT. In this group of patients, BT increased from 0.35% in 2000 to 9,76% in 2008 (p&lt;0,0001), and from then, decreased to 8.28% in 2011 (p&lt;0.0001). There are also significant differences between races. In White’s BT increased 11.33% in 2008 which is 1.46 more times than in Black’s and 1.79 more than Hispanic, and then decreased to 9.52% in 2011 which is 1.61 more than in Black’s, and 1.64 more than Hispanic’s. Conclusions: The use of breast preservation RT has increased significantly in stages 0 to III from year 2000 to 2011. BT use increased until year 2008, when it begun to decrease until year 2009, stabilizing in 2010 and 2011 at around 8%. There are significant differences between races in the use of RT in general, and BT in particular, being Hispanic’s the ones which significantly received less breast preservation RT treatment. This finding raises important questions.
The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-cre PTEN knockout mice.
Authors: Naokazu Ibuki, Kiyoshi Takahara, Mazyar Gaffari, Howard Tearle, Christopher J. Ong, Michael N. Pollak, Martin E. Gleave, MIchael E. Cox
Journal: Journal of Clinical Oncology (2012)

66 Background: Signaling through GH/IGF-I axis has been linked to PCa risk. The GH/IGF-I axis is an important regulator of growth, survival, and metastatic potential in a variety of malignancies and is strongly implicated in PCa etiology. A range of therapeutic approaches including reducing ligand availability by GH antagonist, IGF-I antibodies, and recombinant IGFBPs, reducing IGF-1R expression by antisense and RNA interference, or inhibiting of IGF-1R signaling by IGF-1R antibodies and small molecule tyrosine kinase inhibitors are under investigation in PCa. Methods: To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) using serum from lit/lit or lit/+ mice was examined. Results: No obvious differences in prostatic dysplasia were observed in lit/lit mice at 15 and 20 weeks of age when compared to lit/+ littermates measured as normalized prostatic wet weight or for expression of the murine prostatic differentiation markers, probasin and PSP94. However the rate of decreased expression of E-cadherin and increased expression of N-cadherin was slightly delayed in PTEN-/- prostates from lit/lit mice as compare to lit/+ mice. In vitro, growth of MPPK cells was decreased when cultured in serum from lit/lit mice as compared with serum from lit/+ mice. Suppressed growth of MPPK cells in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased steady-state activation of AKT without affecting ERK1/2 activation. Conclusions: Our data suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that such factors may affect the progression of dysplasic phenotype.
Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing
Authors: Jenny M. Despotovic, Linda M. Polfus, Jonathan M. Flanagan, Carolyn M. Bennett, Michele P Lambert, Cindy Neunert, Manjusha Kumar, Robert J. Klaassen, Courtney Thornburg, Michael Jeng, Michael Recht, Susan E. Kirk, Alexis A. Thompson, Diane J. Nugent, Ellis J. Neufeld, James B. Bussel, Eric Boerwinkle, Rachael F. Grace
Journal: Blood (2015)
Prognostic factors for achieving resection following neoadjuvant radiation therapy for borderline resectable pancreatic adenocarcinoma.
Authors: Avani Satish Dholakia, Amy Hacker-Prietz, Aaron Tyler Wild, Siva P. Raman, Laura D. Wood, Daniel A. Laheru, Lei Zheng, Ana De Jesus-Acosta, Dung Thi Le, Zeshaan Rasheed, Susannah G. Ellsworth, Rachit Kumar, Katherine Y. Fan, Timothy M. Pawlik, Martin Makary, Ralph H. Hruban, John L. Cameron, Elliott K. Fishman, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2013)

285 Background: Margin-negative (R0) surgical resection is the only potentially curative therapy for pancreatic cancer. For patients deemed borderline resectable (BL), neoadjuvant chemoradiotherapy (NCRT) increases the likelihood of subsequent R0 resection and improves overall survival. Prognostic factors for achieving resection following NCRT have yet to be clearly identified. Methods: 50 consecutive patients diagnosed with BL pancreatic cancer by a multidisciplinary tumor board from 2008-12 were retrospectively identified. Pre- and post-NCRT CT scans and surgical specimens were centrally reviewed by a blinded radiologist and pathologist, respectively. Results: 29 patients underwent resection following NCRT, while 21 remained unresectable. Between the two groups, age, gender, mean RT dose, and proportion of pancreatic head tumors were not significantly different. Lack of the following factors was favorably associated with resection: SMV/PV encasement (p=0.01), SMA involvement (p=0.02), ascites (p=0.01), and questionable/overt metastases (p=0.01). Notably, celiac artery involvement/encasement, common hepatic artery encasement, and percentage change in tumor volume were not significant predictors of resectability (all p&gt;0.05). Additionally, tumor volume and degree of individual vessel involvement did not significantly change from scans before and after NCRT (all p&gt;0.05). Median OS was 22.9 vs.13.0 months in resected and unresected patients, respectively (p&lt;0.001). Of resected patients, 93% had negative margins, 28% had positive nodes, 27% demonstrated &lt;10% viable tumor, and 12% had pathologic complete response at surgery. Conclusions: Certain radiographic features appear more strongly associated with resectability after NCRT than others. Despite the fact that tumor-vessel interactions do not change significantly due to NCRT, subsequent R0 resection rates are high, nodal involvement is low, nearly 1/3 of patients have minimal residual tumor, and outcomes are improved. Further studies are needed to elucidate novel biomarkers or functional imaging predictors for successful resection following neoadjuvant therapy.
Safety and immunogenicity of heat-treated zoster vaccine (ZV<sub>HT</sub>) in adults with solid tumor malignancy (STM).
Authors: K. M. Mullane, M. R. Mullane, B. M. Y. Wong, Y. Zhao, T. Sterling, S. Manoff, P. W. Annunziato
Journal: Journal of Clinical Oncology (2011)

2551 Background: Herpes zoster incidence is higher in patients undergoing chemotherapy for solid tumor malignancy [STM] (12-15 cases/1000 person-years) than the general population (~3-5 cases/1000 person-years). A heat-treated zoster vaccine [ZVHT] was assessed in adults with STM. Methods: Randomized, double-blind, placebo-controlled, multicenter Phase I study of 4 doses of ZVHT or placebo [Pbo] (~30 days apart) in adults ≥18 years with STM. Of 79 subjects enrolled, 59 received ZVHT and 20 Pbo. All vaccinated patients evaluated for adverse events [AEs] through day 28 postdose 4. Blood collected at baseline & ~28 days after each dose to measure (1) VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay [gpELISA], and (2) varicella zoster virus [VZV] T-cell responses by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay. Primary hypothesis: 4 doses of ZVHT would elicit a statistically significant VZV-specific immune response (lower bound 90% CI on geometric mean fold rise [GMFR] >1.0) in adults with STM. Results: Injection-site AEs occurred in 36.8% of ZVHT group and 5.3% of Pbo group. No reported vaccine-related serious AEs. One AE resulting in death was reported in the ZVHT group (acute respiratory failure, 31 days postdose 1); deemed not vaccine-related by investigator. One ZVHT recipient discontinued due to a vaccine-related AE (injection site erythema, 1 day postdose 3). No ZVHT recipient had a rash that was PCR positive for the vaccine strain of VZV. At baseline in the ZVHT group, VZV-specific gpELISA geometric mean titer (GMT) was 235 (90% CI: 163, 338) and the IFN-γ ELISPOT geometric mean count (GMC) was 24 (90% CI: 16, 37). Both measures increased Postdose 4: gpELISA GMT was 452 (90% CI: 342, 597); IFN-γ ELISPOT GMC was 89 (90% CI: 57, 138). The primary hypothesis was met, as Postdose 4 immune responses in the ZVHT group were significantly higher than baseline for both gpELISA (GMFR=2.4 [90% CI: 1.8, 3.0], p<0.0001) and IFN-γ ELISPOT (GMFR=3.0 [90% CI: 2.0, 4.6], p<0.0001). Conclusions: In the STM population, ZVHT had an acceptable safety profile and elicited statistically significant VZV-specific antibody and functional T-cell responses at 28 days Postdose 4.
Early detection of tumor recurrence in patients with asymptomatic breast cancer with tumor marker kinetics and whole body imaging.
Authors: D. Di Gioia, G. Schmidt, A. Baur-Melnyk, D. Nagel, V. Heinemann, P. Stieber
Journal: Journal of Clinical Oncology (2011)

e11113 Background: To evaluate the diagnostic potential of tumor marker monitoring combined with whole-body MRI (WB-MRI) for the early detection of asymptomatic tumor recurrence in breast cancer patients (pts). This analysis was performed as part of a large follow-up study evaluating 813 pts with a median follow-up of 63 months. Methods: After curative surgery, breast cancer pts underwent regular tumor marker monitoring for CEA (Abbott, AxSYM), CA 15-3 and CA-125 (Roche, Elecsys) at 6-week intervals. A reproducible previously defined increase (CEA 100%, CA 15-3 75%, CA 125 150%) of single or combined markers was considered as a strong indicator of recurrent disease. In the period from 2007 to 2010 diagnostic evaluation followed by WB-MRI (Avanto, Siemens Healthcare, Erlangen). FDG-PET-CT was performed for verification. Follow-up investigations by MRI or CT scan after individualized therapy was performed within 3 to 6 months. Presence and distribution of tumor recurrence, disease free interval (DFS), progression free survival (PFS) and overall survival (OS) were assessed. Results: 39 pts showed the predefined reproducible increase of one or several tumor markers based upon the individual baseline values. Tumor recurrence was detected by imaging in 74% (29/39) of pts. Twenty-four pts had recurrent metastatic breast cancer after a median DFS of 63 months (range, 3.8 to 136 months). Of these pts, 38% (9/24) showed limited metastatic disease defined as less than 5 malignant lesions confined to a single organ. Distribution of organ metastases was 54% to the bone, 33% liver, 33% lung and 38% to other sites. In 13% of pts secondary malignancies were found: 2 pts with a carcinoma of the ovaries and uterus (CA-125), 1 pt with a carcinoma of the parotid gland (CEA), 1 pt with non-small cell lung cancer (CEA) and 1 pt with gastric cancer (CEA and CA 15-3). The median PFS and OS have not been reached so far. Conclusions: Monitoring of tumor marker kinetics combined with whole body imaging is effective for the early detection of tumor recurrence in clinically asymptomatic breast cancer pts. The defined increase of CEA and/or CA 15-3/CA-125 is highly specific for recurrence in breast cancer pts.
Improving prophylactic growth factor (pGCSF) use in non-small cell lung cancer (NSCLC) patients (pts) receiving chemotherapy (CT) at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Lindsey Martin Goodman, Machelle Moeller, Carole Kathleen Dalby, Amy E. Guthrie, Marc A. Earl, Nathan A. Pennell, Marc A. Shapiro, Vamsidhar Velcheti, Patrick C. Ma, James Stevenson
Journal: Journal of Clinical Oncology (2014)

83 Background: Per guidelines (ASCO, NCCN, EORTC), pGCSF is not recommended for pts receiving CT regimens with low risk (&lt; 10%) for febrile neutropenia (FN). Inappropriate use of pGCSF increases pt morbidity and healthcare costs. In the current healthcare environment, it is critical to maximize value via alignment with accepted care standards and elimination of unnecessary costs. Methods: A multidisciplinary team was created to perform a quality improvement (QI) project under ASCO’s Quality Training Program. We reviewed all NSCLC pts at TCI who initiated a new CT regimen from April to November 2013. First-cycle pGCSF use was identified and deemed appropriate if prescribed for CT associated with high risk of FN (&gt;20%) or intermediate risk (10-20%) if other risk factors for FN were present (age, gender, performance status, renal/hepatic function, prior treatment with radiation or CT, and pre-existing neutropenia, wounds, or infection). Use with low-risk CT was recorded as inappropriate. Results: 179 NSCLC pts received a new CT regimen during the specified time period. 22/90 pts (24%) treated with low-risk CT received pGCSF. Each pt received an average of 3 doses with 69 total doses administered. In all other instances pGCSF was prescribed in accordance with guidelines. Using QI strategies, we identified and implemented three PDSA cycles: education of NSCLC providers, development of TCI Consensus Guidelines for the use of pGCSF in NSCLC, and removal of standing pGCSF orders from low-risk CT regimens in the EMR. Cost analysis shows the potential to save 1.6 million dollars in charges over 1 year when pGCSF is not administered to NSCLC pts receiving low risk CT. Conclusions: pGCSF was excessively prescribed for NSCLC pts at a tertiary care academic medical center. Factors contributing to inappropriate pGCSF use included providers’ lack of familiarity with guidelines and the risk of FN for CT regimens as well as EMR CT templates with standing pGCSF. Appropriate pGCSF administration leads to significant cost savings without adverse impact on pt outcomes. Re-measurement is in progress and will be presented at the time of the meeting.
Poor prognostic indicators for patients treated with radiosurgery for brain metastases.
Authors: Michael A Garcia, Wendy Anderson, Shannon E. Fogh, Jean L. Nakamura, Philip Theodosopoulos, Michael McDermott, Patricia Penny Sneed, Steve E. Braunstein
Journal: Journal of Clinical Oncology (2016)

32 Background: Radiosurgery (SRS) is a standard palliative treatment for patients with limited number of brain metastases. Growing evidence supports the use of SRS for more extensive disease. As SRS is increasingly used in advanced cancer, we sought to identify predictors of survival after SRS to help better inform patients about prognosis. Methods: We reviewed patients treated with SRS for brain metastases at the University of California, San Francisco (UCSF) from Jan 2010-Dec 2013. Before SRS, all patients were screened for appropriateness of SRS at a multidisciplinary conference. Post-SRS overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank tests. Frequencies of death within 30 days of SRS were compared by chi-squared tests. Results: Demographic and imaging data was available for 326 SRS patients. At SRS consult, 90% patients were Karnofsky Performance Status (KPS) ≥ 70. Median number of brain metastases at consult was 2 (range 1-37). Median follow up was 13 months. Median OS after SRS was 11 months. Median OS was shorter for patients with KPS &lt; 70 (4 months) compared to those with KPS ≥ 70 (12 months) (p &lt; 0.001). Overall, frequency of death within 30 days of SRS was 5.4%. Within 30 days of SRS, 13% of patients with KPS &lt; 70 died compared to 3.8% with KPS ≥ 70 (p = 0.03). Death within 30 days of SRS was more common among patients with uncontrolled (10%) versus controlled primary tumors (3%) (p = 0.02). Both uncontrolled primary tumor and KPS &lt; 70% were associated with death within 30 days of SRS on multivariate analysis (p = 0.02 and p = 0.03, respectively). Patients with both KPS &lt; 70 and uncontrolled primary tumors had frequency of death within 30 days of 29%. Factors not associated with death within 30 days were age, extracranial metastatic disease burden, histology, number of brain metastases, prior whole brain radiotherapy, SRS, or neurosurgery. Conclusions: Death within 30 days of SRS within the UCSF cohort is uncommon, likely due to multidisciplinary screening for patients expected to live long enough to benefit from SRS. Most patients who die within 30 days of SRS have both KPS &lt; 70 and uncontrolled primary tumors. The potential for poor prognosis should be discussed with these patients during shared-decision making.
Serum angiopoietin-like protein 2 as a novel biomarker of diagnosis and prognosis in gastric cancer.
Authors: Yuji Toiyama, Yasuhiro Inoue, Takahito Kitajima, Tadanobu Shimura, Hiroki Imaoka, Satoru Kondo, Shozo Ide, Masato Okigami, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Koji Tanaka, Yasuhiko Mohri, Masato Kusunoki
Journal: Journal of Clinical Oncology (2014)

9 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and is known to act as a causative mediator of chronic inflammation and inflammatory carcinogenesis. Recently, we demonstrated that ANGPTL2 overexpresses in gastric cancer (GC) compared to normal gastric mucosa and high ANGPTL2 is associated with poor prognosis. Therefore, if tumor-derived ANGPTL2 over-secretes systemically, focusing ANGPTL2 in blood is logical to evaluate its ability as a biomarker. Accordingly, we quantified serum ANGPTL2 level and assessed its clinical significance in GC patients. Methods: We screened serum ANGPTL2 levels from 32 GC and 24 normal controls (NC) by ELISA (cohort 1). Next, we validated 194 serum samples from GC and 48 NC (cohort 2). Finally, we examined ANGPL2 expression in matched GC tissues of cohort 2 (n=194) by immunohistochemistry (IHC). The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: In cohort 1,serum ANGPTL2 levels in GC were significantly higher than that in NC (p&lt;0.05). Serum ANGPTL2 differentiated GC from NC with high accuracy (AUC=0.814). Analysis of cohort 2 also indicated that serum ANGPTL2 levels in GC were significantly higher compared to NC (p&lt;0.0001), and increased according to UICC stage progression. In addition, serum ANGPTL2 had a promising AUC (0.831) with high sensitivity (73.0%) and specificity(82.2%) to distinguish GC from NC. High serum ANGPTL2 was significantly associated with lymphatic invasion (p=0.03), vessel invasion (p=0.02), distant metastases (p=0.0002), early recurrence (p=0.004) and poor survival (p=0.01), consequently emerged as an independent predicting recurrence marker (HR=5.06, p=0.0004) and prognostic marker (HR=3.6, p=0.01) in GC. Of interest, ANGPTL2 levels in serum from GC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 at the invasive margin of matched GC tissues (r= 0.16, p=0.02). Conclusions: Serum ANGPTL2 levels, which might be secreted from primary or metastatic site into blood stream, have extremely strong potential as a novel biomarker for diagnosis, predicting recurrence and poor prognosis in GC patients.