tbuckley/cabot-search huggingface dataset:
The fraction of circulating endothelial progenitor cells (EPCs)is inversely correlated with the median oxygen tension in the tumor tissue of patients with cervical cancer
Authors: M. Raida, T. Weiss, C. Leo, D. Lenz, A. Tarnok, D. Niederwieser, M. Hockel
Journal: Journal of Clinical Oncology (2005)

9572 Background: Tumor expansion is characterized by an inability of the local vasculature to supply enough oxygen to the extensively proliferating tumor cells. Evidence is growing that hypoxia has a profound impact on malignant progression and on responsiveness to therapy. Hypoxia leads to adaptive responses that will help the cells survive including an induction of vasculogenesis initiated by circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs). The aim of the present study was to correlate the number of EPCs and/or CECs with the oxygenation status of locally advanced cervical carcinoma. Methods: Blood concentrations of EPCs were analysed by FACS with antibodies for the hematopoietic stem cell (HSC) marker CD34 and the endothelial marker vascular endothelial growth factor receptor 2 (VEGFR2, KDR). CECs were detected by double staining of DiLDL-uptake and lectin binding with laser scanning cytometry (LSC). A study population of 10 patients with cervical cancer was compared with 10 healthy volunteers. Oxygen tension in the tumor tissue of the patients with cervical cancer was assessed polarographically with the computerized Eppendorf histography system. Within the tumor tissue pO2 measurements were taken in each electrode track starting at a tissue depth of 5 mm. Results: Analysis of the CEC numbers neither revealed any difference between patients and controls nor did it show a correlation to the intratumoral oxygen tension. However, cervical cancer patients had a significantly higher fraction of EPCs related to total number of HSCs (1.09% versus 0.53%). This fraction was significantly inversely correlated to intratumoral oxygen tension (r=-0.76, p=0.011). Conclusions: Our study shows for the first time a significant inverse correlation between the fraction of EPCs and the median oxygen tension in cancer tissue. The fraction of EPCs might therefore be a useful marker in the prediction of the responsiveness to radiotherapy or other antitumoral strategies that rely on a certain tissue oxygenation. No significant financial relationships to disclose.
Impact of accurate staging with <sup>18</sup>F-FDG-PET and brain MRI on clinical benefit of prophylactic cranial irradiation (PCI) in patients with limited stage (LS) small cell lung cancer (SCLC).
Authors: Mihong Choi, Young Joo Lee, Sung Ho Moon, Ji-Youn Han, Heung Tae Kim, Jin Soo Lee
Journal: Journal of Clinical Oncology (2015)

7579 Background: The latest randomized study using brain MRI as initial brain assessment has suggested PCI had a negative survival effect in extensive stage SCLC (Abstr 7503, ASCO, 2014), which is contrary to the results of earlier studies that had not necessarily included brain MRI and PET as initial evaluation. Furthermore, as the survival of LS-SCLC pts improves, there has been a great need to critically address the benefit-risk issue of PCI (Lee J et al, J Clin Oncol, 2006). Thus, we sought to evaluate the effect of initial brain MRI and PET evaluation on the clinical outcome and benefit of PCI in LS-SCLC pts. Methods: We retrospectively collected data from 264 pts with histologically-proven LS-SCLC who had complete or partial response after concurrent chemoradiotherapy including platinum-based regimen from April 2001 to April 2013 at National Cancer Center Hospital (Goyang, Korea). Among them, 130 pts who had both brain MRI and whole body 18F-FDG-PET as initial staging work-up are included in this analysis. Results: In the 130 pts, the 5-year cumulative brain metastasis (BM) rate was 39.6% and the 5-year overall survival rate was 53.2%. Among them, 46 received PCI (25 or 30Gy in total) and 84 did not. There was no difference in clinical characteristics such as age (60 v 63 years; p = 0.140) and TNM stage (I-II/IIIA/IIIB) (22/28/45% v 24/43/33%; p = 0.147). Between the two groups (PCI vs No PCI), there was no significant difference in the 5-year cumulative BM rate (36.7 vs 41.8%, p = 0.231) and the 5-year overall survival rate (56.9 vs 51.5%, p = 0.985). Subgroup analysis showed PCI tended to decrease the 5-year cumulative BM rate in patients with stage I-IIIA SCLC (n = 79) (29.5 vs 41.7%, p = 0.104) but not in patients with stage IIIB SCLC (n = 51) (46.5 vs 41.3%, p = 0.876). Conclusions: LS-SCLC pts accurately staged with brain MRI and PET exhibited excellent overall survival with the 5-year survival rates after achieving objective response after CCRT, exceeding 50% regardless of PCI. Considering the risk of neurotoxicity, the role of PCI should be more critically readdressed in this group of LS-SCLC pts with greater potential for long-term survival and even cure.
HER2 gene amplification is a marker for global genomic instability
Authors: R. E. Ellsworth, D. L. Ellsworth, B. Deyarmin, L. R. Hoffman, J. A. Hooke, C. D. Shriver
Journal: Journal of Clinical Oncology (2005)

9571 Background: Genomic alterations of the proto-oncogene c-erbB-2 (HER2/neu) are associated with poor prognosis in patients with breast cancer. While HER2 status has predictive value for the efficacy of different therapies, its long-term prognostic relevance remains controversial. Because some patients with HER-2 gene amplification do not exhibit corresponding over-expression of the HER-2 protein, it is unclear how genomic alterations predict clinical response. To assess the implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER-2 status in patients with invasive breast cancer. Methods: DNA was extracted after laser microdissection from 75 paraffin-embedded invasive breast tumor specimens, 24% of which had HER-2 amplification determined by the PathVysion FISH assay. Referent DNA was extracted from blood, disease-free skin, or negative lymph node samples. Allelic imbalance (AI) was assessed using a panel of microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer. The threshold normalized peak height ratio to detect AI was set at 0.35 and t-tests were used to investigate relationships between genomic instability and HER-2 status. Results: Overall levels of AI did not differ significantly in patients stratified by stage, lymph node, or menopausal/hormonal status. The frequency of AI was significantly higher (P<0.001) however, in patients with HER-2 amplification (39%) compared to those without (21%). When individual chromosomal regions were examined, samples with HER-2 amplification showed significantly higher levels of AI (P<0.0001at chromosome 17q12 (which is located <5 Mb centromeric to the HER-2 locus and includes BRCA1), as well as chromosomes 17p13.1 and 22q12.3 (P<0.05). Conclusions: HER-2 gene amplification may serve as a marker of global genomic instability. Concurrent genetic alterations in other regions of the genome may contribute to poor prognosis and influence associations between HER-2 status and outcomes of adjuvant chemotherapy and Herceptin treatment. The addition of molecular profiling for AI may thus enhance treatment decisions for individuals with HER-2 amplified breast cancer. No significant financial relationships to disclose.
Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?
Authors: Claire Dewas-Vautravers, Philippe Maingon, Cecile Dalban, Aurelie Petitfils, Karine Peignaux-Casasnovas, Gilles Truc, Etienne Martin, Cedric Khoury, Sylvain Dewas, Gilles Crehange
Journal: Journal of Clinical Oncology (2013)

584 Background: Chemoradiation is the standard treatment for anal cancer. The purpose of this study was to compare outcomes and toxicities in patients treated with either intensity-modulated radiation therapy (IMRT) or 3D conformal radiotherapy (3D-CRT). Methods: Between 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Thirty-nine patients (76.5%) had concomitant chemotherapy: capecitabine alone (1), MMC combined with 5FU or capecitabine (36), MMC and CDDP (4). Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6]. Results: Median duration of the treatment was 56 days [22-103] (59 versus 47 days with 3D-CRT and IMRT respectively, p= 0.0007). A gap was planned in 29 patients (57%), 23 with 3D-CRT and 6 with IMRT (p&lt; 0.0001). Treatment was stopped for toxicity in 9 patients (17.6%), 4 with 3D-CRT and 5 with IMRT (p= 0.48). There was no difference between the two groups for response to treatment (p= 0.46). Two-year overall survival (OS), locoregional relapse-free survival (LRS) and colostomy-free survival (CFS) rates were 88.5%, 63% and 60.3%, respectively for the IMRT group and 81%, 76.5% and 81.1% for the 3D-CRT group (all NS). Ten patients (37%) in 3D-CRT and 11 patients (45.8%) in IMRT (p= 0.524) had grade 3 (G3) acute toxicity. No grade 4 (G4) toxicity occurred. Conclusions: Our study suggests that further investigations concerning the use of IMRT to treat cancer of the anus are warranted. IMRT makes it possible to reduce treatment time, notably by abandoning the gap, but with no impact on the prognosis. Nonetheless, a longer follow-up is essential to determine whether or not IMRT has an impact on late toxicity, local control and survival compared with conventional 3D-CRT.
Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection
Authors: Javier Crespo, Jose Luis Calleja, Inmaculada Fernández, Begoña Sacristan, Belén Ruiz-Antorán, Javier Ampuero, Marta Hernández-Conde, Javier García-Samaniego, Francisco Gea, Maria Buti, Joaquin Cabezas, Sabela Lens, Rosa Maria Morillas, Jose Ramon Salcines, Juan Manuel Pascasio, Juan Turnes, Federico Sáez-Royuela, Juan Arenas, Diego Rincón, Martin Prieto, Francisco Jorquera, Juan Jose Sanchez Ruano, Carmen A. Navascués, Esther Molina, Adolfo Gallego Moya, José Maria Moreno-Planas, Silvia Montoliu, Miguel Angel Serra, Raul Andrade, Conrado Fernandez, Miguel Fernández Bermejo, Miguel Angel Simon, Lucia Bonet, Juan de la Vega, Moises Diago, José Ramón Fernández, Gloria Sanchez Antolin
Journal: Clinical Gastroenterology and Hepatology (2017)
Central nervous system venous thrombosis in cancer: Frequency and clinical characteristics in a prospective observational study of 339 patients.
Authors: V. Ortega, L. Gaba, C. Font, O. Reig, I. Victoria, L. Visa, E. Pineda, L. Oleaga, P. Gascon
Journal: Journal of Clinical Oncology (2011)

e19597 Background: The aim of the present study was to analyze the epidemiology and clinical characteristics of cancer patients with central nervous system venous thrombosis (CNSVT), an uncommon manifestation of the hypercoagulable state in cancer patients. Methods: From May 2006 to April 2009 a prospective observational study including consecutive cancer patients with newly-diagnosed venous thrombosis was performed in our Medical Oncology Department. Results: In 3 out of 339 patients (1%) the venous thrombosis event presented with CNSVT. There were 2 women and 1 man with a median age of 59 years (range 54 to 63 years). Two patients were actively receiving platin-based chemotherapy schemes at the time of the thrombotic event (1 in the adjuvant setting for colon cancer and 1 while receiving palliative chemotherapy for metastatic lung cancer). The other one was receiving 5FU in the adjuvant setting for cholangiocarcinoma). The clinical CNSVT presentation consisted of sudden headache and seizures. CT scan was performed in the Emergency room to rule out brain metastasis. In two patients (66%) evidence for cerebral sinus thrombosis was diagnosed and in one case the thrombus extended to the internal jugular vein without carrying any venous catheter. In the remaining patient the CT scan was assessed as normal at first evaluation and the CNSVT diagnosis required a reassessment of the initial CT scan by an experienced neuroradiologist and further study by cerebral MRI. All patients were safely anticoagulated with low molecular weight heparin with a favourable outcome of the acute thrombotic event. Conclusions: CNSVT must be taken into account in the differential diagnosis of acute neurological symptoms in cancer patients.
Ten-year expericence of percutaneous radiofrequency ablation for hepatocelluar carcinoma.
Authors: S. Shiina, R. Tateishi, T. Goto, Y. Kondo, E. Goto, R. Masuzaki, H. Nakagawa, F. Kanai, H. Yoshida, K. Koike
Journal: Journal of Clinical Oncology (2010)

4055 Background: Ten years have passed since radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) was introduced at the authors’ institution. The aim of this study was to elucidate long-term efficacy of RFA in a large series from a single center. Methods: We enrolled all patients with HCC who underwent RFA at the authors’ hospital between 1999 and 2008. The primary endpoint was overall survival. Secondary endpoint was time to recurrence and safety. We assessed overall survival in patients who underwent RFA as initial treatment (n = 1,030), time to recurrence in patients who showed complete response (n = 999), and safety in all admissions for RFA (n = 4,638). Kaplan Meier method was utilized to estimate cumulative survival and recurrence. Cox regression was applied to determine independent factors for survival. Results: Mean age at initial treatment was 68.2 ± 8.4 years with 665 males and 365 females. Mean size of maximal tumor and number of nodules were 2.5 ± 1.1 cm and 1.8 ± 1.2, respectively. HCV- and HBV-related patients were 786 (76%) and 126 (12%), respectively. Hepatic reserve was 73% in Child-Pugh A, 26% in B and 1% in C. The cumulative survival rate at 3, 5, 7 and 10 years was 82%, 62%, 47%, and 30%, respectively. The cumulative recurrence rate at 1, 3, 5 and 7 years was 22%, 61%, 86%, and 86%, respectively. The cumulative local progression rate at 1, 3, 5 and 7 years was 2.1%, 3.8%, 3.8% and 3.8%, respectively. Major complication was observed in 129 cases out of 4638 treatments (2.8%) including neoplastic seeding in 49, hepatic abscess in 14, hemoperitoneum in 12, hepatic infarction in 10, intestinal perforation and penetration in 8, and hemothorax in 6. Multivariate Cox regression revealed that age, Child-Pugh score, maximal tumor size, number of tumor nodules, and tumor marker values (DCP and AFP-L3) were independent risk factors for overall survival. The cumulative survival rate at 3, 5, 7 and 10 years in patients with 3 cm or smaller tumor, 3 or fewer nodules and Child-Pugh A hepatic reserve (n = 525) was 86%, 68%, 59%, and 41%, respectively. Conclusions: RFA was potentially curative, minimally invasive, and easily re-performed for recurrence. Long-term efficacy of RFA was confirmed in a large series. No significant financial relationships to disclose.
Diagnostic Evaluation of t[4;14] in Multiple Myeloma.
Authors: Keith Stewart, Suzanne Trudel, Hong Chang, Kenneth C. Anderson, Paul Richardson, Melissa Alsina, Donna E. Reece, Philip Greipp, Steven Young, Alicia Sable-Hunt, ZhiHua Li, Jonathon Keats, Scott Van Wier, Gregory Ahmann, Tammy Price-Troska, Kathy Giusti, Rafael Fonseca
Journal: Blood (2006)
Enabling quality data reporting: National implementation of standardization pathology reporting.
Authors: Avril Kwiatkowski
Journal: Journal of Clinical Oncology (2014)

122 Background: The Canadian Partnership Against Cancer (the Partnership) launched its Electronic Synoptic Pathology Reporting Initiative (ESPRI) to advance the implementation and promote the wide adoption of standardized synoptic pathology reporting tools in Canada. This presentation will highlight strategies to ensure successful implementation of this program across the Canadian health system as well as lessons learned. Methods: Upon consultation with clinical and system leaders, clear and measureable program targets (such as 90% completeness rates against mandatory elements of the College of American Pathology cancer protocols and disease-specific clinical indicators) were agreed upon. Thorough provincial planning to understand the variances across provincial current states, establish strategies and solidify plans was supported by the Partnership; followed by implementation of those plans. Key approaches to enable adoption and implementation include coordination of Pathologist and Vendor-led education sessions, establishment of clinical expert panels and assignment of Canadian representatives to the College of American Pathologists’ (CAP) Cancer Protocol Review Panels. The Partnership continues to collaborate with national/international standards organizations such as NAACCR, CAP, and Canada Health Infoway to support standards maintenance. Results: As a result of ESPRI, approximately 80% of Canadian pathologists will be reporting synoptically by 2017, across 7 of 10 provinces. It is expected that this will reflect approximately 25,000 reports per year for the five cancer types of focus (breast, colorectal, lung, prostate and endometrial) from about 950 pathologists. The Partnership, with CAP-ACP, has partnered with pathology communities from the US, UK, and Australasia to form the International Collaboration on Cancer Reporting (ICCR) to collaborate on internationally-harmonized core datasets for cancer pathology. Conclusions: Adoption of structured pathology reporting in Canada will enable better patient care, improve data quality, create efficiencies and enable interoperability. Through adoption and implementation efforts, this will impact patient care.
Effect of inpatient radiation delivery on length of stay and health care costs.
Authors: Sofya Pintova, Randall F. Holcombe, Seth Blacksburg, Philip Adam Friedlander
Journal: Journal of Clinical Oncology (2014)

225 Background: Healthcare costs continue to rise. Identifying areas for healthcare utilization savings may be useful in reducing costs. The goal of this pilot study was to identify oncologic patients who remained in the hospital to receive radiotherapy treatment with the purpose of measuring length of stay (LOS) and charges associated with delivering inpatient radiation. Methods: Between July 1, 2013 and July 31, 2013 patients receiving inpatient radiation were identified. Actual LOS and end of acuity LOS were determined from the chart review. Expected LOS was calculated using the UHC database. Charges associated with actual LOS, end of acuity LOS and expected LOS were then reported. Comparisons of the actual and expected LOS were made between the radiation and non-radiation cohorts. Results: Seven patients were identified as remaining in the hospital to receive radiation treatment. There were 50 solid oncology patients admitted during July 2013 that did not receive radiation therapy. The seven patient cohort accounted in total for 281 days of hospitalization, with an average of 40.1 (+/-43.3) days per patient. The end of acuity LOS averaged 25.6 (+/-42.8) days per patient. The mean LOS attributed to radiation alone was 10.7 days. In contrast, the actual LOS for the 50 patients admitted to the solid tumor oncology service without radiation treatment, was 6.7 +/-4.9 days. The patients receiving radiation had a statistically significant longer actual LOS 40.1 vs 6.7 days (p&lt;0.0001). The expected LOS for patients who received radiation was on average 7.7 days versus 5.2 days in the cohort that did not receive radiation, (p=0.0098). In the radiation cohort, the charges associated with the actual LOS per patient, end of acuity LOS per patient and expected LOS per patient were respectively $48,724, $34,089 and $10,028. The charges attributed to radiation alone amounted to $12,514 per patient. Conclusions: Delivery of radiation therapy during inpatient hospitalization extends LOS and contributes to higher healthcare costs. Methods to address this issue may result in cost savings.
Impact of STAT4 expression on cellular immunity and prognosis in hepatocellular carcinoma.
Authors: Toshiaki Yoshimoto, Daichi Ishikawa, Masato Yoshikawa, Hiroki Teraoku, Shinichiro Yamada, Yu Saito, Shuichi Iwahashi, Yusuke Arakawa, Tetsuya Ikemoto, Satoru Imura, Yuji Morine, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2015)

307 Background: Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of IL-12, leading to the production of IFN-γ and cytotoxicity. However, the significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains unknown. Herein, we investigated the association of STAT4 expression with cellular immunity and clinicopathological factors in HCC. Methods: A total of 66 HCC patients who underwent hepatic resection were enrolled. RT-PCR was performed to determine STAT4 mRNA and IFN gamma mRNA expression. Immunohistochemistry was performed to examine CD8+ T cells. Results: STAT4 was differentially expressed in tumor and non-tumor tissues (p &lt; 0.01), and positively correlated with IFN gamma and CD8+ T-cell infiltration (p &lt; 0.01). Significant correlations were observed between STAT4 expression and tumor TNM stage, hepatic venous invasion, tumor size, and tumor differentiation. Patients with high STAT4 expression had significantly better disease-free survival (p &lt; 0.01). In addition, low STAT4 expression (p &lt; 0.03) were independent risk factors for tumor recurrence. Conclusions: Down-regulation of STAT4 in HCC indicated aggressive tumor behavior and predicted worse clinical outcome. STAT4 might be a useful biomarker to identify patients with high risk of tumor recurrence after hepatic resection.