tbuckley/cabot-search huggingface dataset:
Effect on clinical trial participation by integration of a clinical pathway program into an electronic health record (EHR).
Authors: Corey J. Shamah, Thomas James Saphner
Journal: Journal of Clinical Oncology (2016)

167 Background: Patient enrollment to clinical trials is lower than desired. Even large organizations with extensive research support services have many barriers to recruitment and poor rates of enrollment. Barriers to clinical trial participation can be physician related, system related, or patient related. Physician related issues are the largest barrier to patient accrual. Physicians are often not aware that a trial may be available for a patient. While all initial patients are manually screened in our system, screening for subsequent lines of therapy are not. Provider awareness and appropriate patient identification are areas of potential improvement in a large, multisite, hospital affiliated, community oncology setting. Methods: Our oncology group recently implemented Via Oncology (Via), an EHR-integrated clinical pathway decision support tool. Information about the patient, their disease, and goals of care generate a recommended treatment algorithm. The pathways are expected to speed the integration of new treatments into practice and improve accrual to clinical trials. Use of Via is required for all new therapy changes. Within the decision algorithm, an appropriate available clinical trial is suggested as the first option when available. Clinical trial enrollment statistics are being tracked to determine if this method of potential patient identification results in increased enrollments. Results: After 11 months of Via implementation and 103,515 visits, the visit capture rate was 82.7% suggesting that providers adapted to the pathways quickly. With 3,844 decisions made, 83.9% of all treatment decisions were on pathway. Clinical trial enrollment was 122 patients in the 459 days prior to Via implementation, and 102 patients in the 271 days afterwards. This increase in accrual rate was significant (p = 0.00174.) Conclusions: Early results suggest that Via implementation has resulted in a significant increase in clinical trial accrual. The system will eventually be able to track how often a trial is offered and how often it is accepted. We are hopeful that with complete visit capture of all patients, there will be continued improvement in our rate of clinical trial enrollment.
The angiogenesis-related polymorphisms' role in breast cancer
Authors: G. J. Lourenço, P. M. Silva, C. Cardoso-Filho, A. A. Schenka, A. F. Sagarra, M. S. Gurgel, C. S. Lima
Journal: Journal of Clinical Oncology (2008)

22027 Background: The VEGF C936T and G634C polymorphisms seem to affect the expression of the coded VEGF, involved in stimulation of angiogenesis, in sporadic breast cancer (SBC). The COL18A1 D104N polymorphism apparently affects the function of the coded endostatin (ES), an angiogenesis inhibitor, in SBC. Moreover, the polymorphic GSTM1 gene of the glutathione S- tranferase system seems to stimulate the angiogenesis by facilitating the hypoxia-inducible factor activity. Considering that it is not well established whether VEGF C936T and G634C, COL18A1 D104N, GSTM1 and GSTT1 polymorphisms alter the risk, the VEGF and ES protein levels and intratumoral microvessel density (IMVD) in SBC, these were the aims of this study. Methods: DNA from 207 SBC patients and 207 age, gender and race-matched controls was analyzed using the PCR-RFLP or multiplex-PCR. ELISA for VEGF and ES was performed in serum samples of patients and controls. The IMVD of paraffin-embedded fragments of breast tumors was determined by immunohistochemistry. Results: Similar frequencies of VEGF C936T, GSTM1 and GSTT1 genotypes were seen in patients and controls. Individuals with these distinct genotypes were under SBC similar risks. In contrast, the VEGF 634CC (15.7% versus 8.7%, P= 0.03) and COL18A1 104NN (2.4% versus 0.0%, P= 0.02) genotypes frequencies were significantly higher in patients than in controls. Carriers of the VEGF 634CC genotype and the COL18A1 104NN genotype were under a 1.9-fold increased SBC risk (95% CI: 1.1–3.6) and an infinite increased SBC risk, respectively. Similar VEGF and ES values were seen in patients and controls with the distinct VEGF and COL18A1 genotypes. No difference in IMVD of patients with the distinct VEGF genotypes was found in study. However, the IMVD of patients with the COL18A1 104DD genotype was higher than that the IMVD found in patients with the COL18A1 104NN genotype (19.0 versus 28.7; P= 0.02). Conclusions: These results suggest that the inherited VEGF 634GG and COL18A1 104NN genotypes alter the risk for SBC. Moreover, the COL18A1 104NN genotype is associated to a high angiogenic phenotype in disease. Financial support: FAPESP and CNPq. No significant financial relationships to disclose.
An analysis of ERCC1, hENT1, RRM1, and RRM2 expression in resected pancreas adenocarcinoma: Implications for adjuvant treatment.
Authors: Sarah B. Fisher, Sameer H. Patel, Pelin Bagci, David A. Kooby, Bassel F. El-Rayes, Charles A. Staley, Volkan Adsay, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2012)

206 Background: Tumor overexpression of excision repair cross complementing gene 1 (ERCC1) was recently shown to be associated with decreased survival in patients with pancreas adenocarcinoma (PAC). Ribonucleotide reductase 1 and 2 (RRM) and human equilibrative nucleotide transporter 1 (hENT1) are integral to DNA synthesis and cellular transport and are implicated as poor prognostic factors in other malignancies. Their role in PAC is not well defined. Methods: A prospective database (n=220) was used to randomly select 95 pts who underwent pancreaticoduodenectomy for PAC between 1/00-10/08. IHC analysis was performed on tumor samples for RRM1 and 2, hENT1, and ERCC1. Main outcomes were recurrence-free (RFS) and overall survival (OS). Results: Median age was 63 yrs; median FU, RFS, and OS was 49, 10.6 and 15.5 mo. Median tumor size was 3cm, 26% had a positive margin, 34% were poorly differentiated, 61% had positive lymph nodes (LN), 88% had perineural invasion (PNI), and 45% had lymphovascular invasion (LVI). High expression of RRM1, RRM2, hENT1, and ERCC1 was present in 40%, 17%, 85%, and 16% of patients, respectively. High RRM2 was associated with reduced RFS (6.9 vs 16.0 mo; p&lt;0.0001) and decreased OS (9.1 vs 18.4 mo; p&lt;0.0001). High ERCC1 was associated with reduced RFS (6.1 vs 15 mo; p=0.04) and decreased OS (8.9 vs 18.1 mo; p=0.03). RRM1 and hENT1 were not associated with survival. After accounting for known adverse factors, high RRM2 and ERCC1 persisted as negative prognostic factors for RFS and OS (Table). A subset analysis of those who received adjuvant therapy (n=74) revealed the same negative effect of high RRM2 and ERCC1 on RFS and OS. Conclusions: High RRM2 and ERCC1 tumor expression are associated with reduced RFS and OS after resection of pancreas cancer. These biomarkers may help personalize adjuvant therapy. [Table: see text]
Risk of second primary malignancy in U.S. men diagnosed with prostate cancer from 1992 to 2007.
Authors: E. Davis, C. A. Salinas, L. A. Okoth, K. A. Cooney
Journal: Journal of Clinical Oncology (2011)

4543 Background: The survival of men diagnosed with prostate cancer (PCa) has increased substantially over time, with 5- and 10-year relative survival at 100% and 99.7%, respectively. PSA screening has also led to earlier detection of disease at younger ages. This increased longevity leaves patients at future risk of second cancers. Methods: Surveillance, Epidemiology and End Results Program (SEER13) data were used to estimate the risk of second primary malignancies in a population-based cohort of 407,781 men diagnosed with PCa. SEER*Stat software was used to calculate standardized incidence ratios (SIR) for men who survived ≥ 2 months after PCa diagnosis. Results: Risk of second cancers among PCa survivors differed significantly from that observed in the U.S. general population (Table). Results also differed by race with White patients having significantly reduced risk of liver, lung and bronchus, oral cavity and pharynx, stomach, esophagus, leukemia, pancreas, and colon malignancies and significantly increased risk of melanoma, bladder, kidney, thyroid cancer, and non-Hodgkin lymphoma. Black patients shared significantly lower lung and bronchus cancer risk, but had significantly increased risk of kidney, small intestine, brain, bladder, colon and hematologic malignancies including myeloma and leukemia. Men aged 20-54 years at PCa diagnosis were at notably increased risk of subsequent breast cancer (SIR=2.79, 95% CI 1.34, 5.13) especially compared to those >55 years. Results did not differ by year of PCa diagnosis (1992-1999 vs. 2000-2007). Conclusions: Cancers that occur together may suggest novel strategies for identifying genetic and environmental risk factors for prostate cancer. These results also highlight important risks that exist for the growing population of prostate cancer survivors. Site of second primary tumor SIR 95% CI All solid tumors 0.61 (0.60, 0.61) Liver 0.66 (0.60, 0.72) Lung and bronchus 0.83 (0.81, 0.85) Oral cavity and pharynx 0.84 (0.78, 0.89) Esophagus 0.85 (0.79, 0.92) Stomach 0.90 (0.85, 0.96) Non-Hodgkin lymphoma 1.06 (1.02, 1.11) Melanoma of the skin 1.15 (1.10, 1.20) Urinary bladder 1.12 (1.09, 1.15) Kidney 1.21 (1.16,1.27) Thyroid 1.21 (1.07, 1.37) Small intestine 1.22 (1.07, 1.38)
Isolated Extramedullary Relapses after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukaemia: Single-Center Experience with 220 Patients.
Authors: Dariusz Kata, Jerzy Holowiecki, Jerzy Wojnar, Malgorzata Krawczyk-Kulis, Beata Stella-Holowiecka, Slawomira Krzemien, Maria Sadus-Wojciechowska, Grzegorz Helbig
Journal: Blood (2005)
Variation in gross tumor volume delineation using CT, MRI, and FDG-PET in planning radiotherapy of anal cancer.
Authors: Eva Serup-Hansen, Helle Westergren Hendel, Helle Hjorth Johannesen, Wiviann Ottosson, Christian Hollensen, Gitte Fredberg Persson, Poul F. Geertsen, Hanne Havsteen
Journal: Journal of Clinical Oncology (2012)

652 Background: Radiotherapy (RT) outcome depends on accurate delineation of gross tumor volume (GTV) regarding tumor size and position. CT and MRI are standard image modalities as they provide the necessary structural information. Positron emission tomography with flourodeoxyglucose (FDG-PET) visualizes glucose metabolism in active tumor tissue. The main objective was to explore the intra-observer and inter-modality variation of the GTV delineated on CT, MRI and PET images. Methods: Between November 2006 and July 2009, 22 patients with biopsy-proven anal carcinoma stage T1-T4/N0-3/M0-1 scheduled for curative RT were included in the study. All patients underwent FDG-PET/contrast enhanced CT and MRI. The delineations of GTV were done twice for each imaging modality with a minimum of 3 months in between. Delineations on the CT and MRI were done by routine methods. For the PET part three different cut-off values were used: SUV 2.5, 40% and 50% of maximum SUV. Non-overlap was calculated by subtracting the intersection from the union of two sets both regarding intra-observer variation and inter-modality variation. The GTV were compared for size, intra-observer variation and non-overlap using Wilcoxon rank sum test, where p &lt; 0.05 was considered significant. Results: Volume size: the median GTV-CT was 25.6 cm 3 which was significantly larger compared to GTV-MRI (7.2 cm 3 ) and the GTV from the different PET cut offs (6.2 cm 3 , 10.6 cm 3 and 7.0 cm 3 ). Intra-observer variation: the median GTV delineated on CT, MRI and PET did not vary significant between delineation number 1 and 2. Non-overlap: the non-overlapping regions in GTV between delineation 1 and 2 using CT and MRI (20.5% and 22.5%) were significantly different from the PET cut offs (5.5% , 6.4% and 5.8%). Conclusions: Delineation of anal tumors is difficult; CT gives rise to the largest GTV with considerable intra-observer variation. MRI has the same degree of inaccuracy, but smaller GTV. PET-GTVs are the smallest with significant smaller intra-observer uncertainty.
Impact of prior platinum on patients receiving salvage systemic therapy for advanced urothelial carcinoma (UC).
Authors: Guru Sonpavde, Gregory Russell Pond, Giuseppe di Lorenzo, Carlo Buonerba, Antonio Rozzi, Gaetano Lanzetta, Andrea Necchi, Patrizia Giannatempo, Daniele Raggi, Kazumasa Matsumoto, Toni K. Choueiri, Stephanie A. Mullane, Guenter Niegisch, Peter Albers, Jae-Lyun Lee, Hiroshi Kitamura, Haruki Kume, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

386 Background: Trials of salvage therapy for advanced UC have required prior platinum-based therapy. This practice requires scrutiny since non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients (pts). We examined the impact of prior exposure to first-line platinum vs. non-platinum based chemotherapy on overall survival (OS) with salvage systemic chemotherapy. Methods: Data of pts receiving salvage systemic chemotherapy were collected retrospectively or from trials. Data on prior first-line platinum exposure were required in addition to the known prognostic factors: treatment free interval, hemoglobin, performance status, albumin and liver metastasis status. Cox proportional hazards regression was used to evaluate their association with OS after accounting for salvage therapy with single agent chemotherapy or combination chemotherapy. Results: Data was obtained from 455 pts exposed to prior platinum and 37 pts not exposed to prior platinum. In the group exposed to prior platinum, salvage therapy consisted of a single agent taxane (n = 184) and taxane containing combination chemotherapy (n = 271). In the group not exposed to prior platinum, salvage therapy consisted of single agent taxane or vinflunine (n = 20), single agent 5-fluorouracil (n = 1), taxane containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2) and cisplatin-based combinations (n = 2). The median OS for the prior platinum group was 7.8 (95% CI: 7.0, 8.1) months (mo), and for the prior non-platinum group was 9.0 (6.0, 11.0) mo (p = 0.50). In a multivariable analysis including major prognostic factors and after controlling for single agent or combination salvage chemotherapy, prior platinum vs. no prior platinum exposure conferred no independent impact on OS (HR 1.10 [0.75, 1.64], p = 0.62). Conclusions: Prior platinum vs. non-platinum based chemotherapy did not confer a prognostic impact on OS after accounting for major prognostic factors in pts receiving salvage systemic chemotherapy for advanced UC. Lack of exposure to prior platinum should not disqualify pts from inclusion in trials of salvage therapy after accounting for the 5 known prognostic factors.
Utilization of intensive care resources due to better communication of end-of-life issues.
Authors: Allen Ray Sing Chen, Joyce M. Kane, Barbara Kasecamp, Candace Cottrell, Colleen C. Apostol, Lynn Billing, Donald C. List, Richard J. Jones, John H. Fetting
Journal: Journal of Clinical Oncology (2012)

1 Background: Advanced life support resources are required for optimal care of patients undergoing curative therapy, but their use in patients with terminal disease does not improve patient outcomes. In 2007, our cancer center established the Duffey Pain and Palliative Care team, and one important goal was to help our physicians improve at discussing end-of-life issues with patients. We hypothesized that if this effort was effective, it would result in less utilization of intensive care unit (ICU) management among patients who die in the center. Methods: All inpatient deaths were systematically tabulated and code status displayed at the multidisciplinary Morbidity and Mortality review twice per quarter, beginning in July 2006. Utilization of ICU care, defined as ventilator or dialysis support, was identified from billing data and confirmed by chart review. Survival to discharge among patients who received ICU care was monitored as a component of our patient safety dashboard. Results: From 2008 through 2011, 525 oncology patients died while hospitalized in the cancer center. During this period, among patients who died, there was a gradual increase in no-code status, election of comfort care, or withdrawal of ICU support, from 81% to 95% (OR 1.14 per quarter, p&lt;0.0001). Although the proportion of patients who received any ICU care during their terminal hospitalization did not change, the duration of such care decreased: the proportion with mechanical ventilation for over 14 days decreased from 10% to 5% (OR 0.93 per quarter, p&lt;0.05). There was no decrease in the survival-to-discharge of patients who received ICU care. Conclusions: A multidisciplinary team approach to improve discussion of end-of-life issues, combined with regular feedback to cancer center staff regarding code status at death, resulted in significant changes in patient and family decisions about management at the end of life over a four-year interval. These changes have reduced utilization of ICU care during terminal hospitalizations with no reduction in the survival-to-discharge of all patients who receive ICU care. We propose appropriate establishment of code status and survival-to-discharge of ICU patients as measures of quality oncology care.
The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFR) polymorphisms in the prediction of clinical outcome for advanced hepatocellular carcinoma receiving sorafenib.
Authors: Luca Faloppi, Mario Scartozzi, Samulele De Minicis, Gianluca Svegliati Baroni, Maristella Bianconi, Riccardo Giampieri, Elena Maccaroni, Alessandro Bittoni, Michela Del Prete, Alessandra Mandolesi, Cristian Loretelli, Laura Belvederesi, Simona Biagetti, Italo Bearzi, Antonio Benedetti, Stefano Cascinu
Journal: Journal of Clinical Oncology (2012)

e14561 Background: Hepatocellular carcinoma (HCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic stronghold is a TKIs directed against the VEGF family (sorafenib). Polymorphisms of VEGF and its receptor genes are involved in regulating angiogenesis and lymphangiogenesis and thus in growth tumor control. The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. Methods: 38 histologic samples (biopsies and surgical specimens) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients time to progression (TTP) and overall survival (OS) were analysed. Results: VEGF-AI rs25648 C&gt;T polymorphism was statistically significant in OS (15.0 months for C vs 9.4 months for T; p=0.025). VEGF-AII rs10434 G&gt;A was statistically significant for TTP (4.1 months for G vs 1.2 months for A; p=0.0076) and OS (14.2 months for G vs 1.7 for A; p&lt;0.0001). VEGF-CII rs7664413 C&gt;T was significant in TTP (13.4 months for C vs 2.0 for T; p=0.0125) and OS (14.7 months for C vs 5.6 for T; p=0.0007). VEGR2-I rs1870377 A&gt;T was significant in TTP (19.9 months for A vs 3.0 for T; p=0.0271) and OS (29.6 months for A vs 11.9 for T; p=0.0096). Conclusions: In our analysis patients with G polymorphism at rs10434, C polymorphism at rs7664413 and A polymorphism at rs1870377 seem to have a better response (PFS and OS) during treatment with sorafenib. Patients with C polymorphism of rs25648 seem to have an advantage only for OS. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. VEGF-C is a ligand of VEGR2 and seems to have a closely relationship with lymphangiogenesis.
Time to next line therapy after initiation of sipuleucel-T in metastatic castration-resistant prostate cancer patients.
Authors: Dai Luu, Leanne Goldstein, Przemyslaw Twardowski
Journal: Journal of Clinical Oncology (2016)

341 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for patients with symptomatic or minimally asymptomatic metastatic castration-resistant prostate cancer based on prolongation of overall survival. We sought to retrospectively analyze the type and time to next-line therapy after the initiation of Sipuleucel-T (Sip-T) in the era of multiple new other therapeutic compounds that became available since approval of Sip-T to better understand the context of utilization of this immunotherapy in the current era. Methods: We performed a retrospective analysis of 53 patients with metastatic prostate cancer (PC) who have been treated with Sip-T at The City of Hope Medical Center between September 2010 and April 2013 and subsequently received another therapy. Variables included age at Sip-T treatment, Karnofsky Performance Score (KPS), Gleason score at diagnosis, extent of metastatic disease (limited or extensive), and white blood cell (WBC) count pre and post (Sip-T). PSA was measured at six time points (3 pre and 3 post Sip-T) and these were analyzed using a mixed linear regression model. A Cox Proportional Hazard model was used to examine predictors of time in days to next therapy as a function of the above variables including mixed model slopes of PSA. Results: Kaplan – Meier estimated median time to next treatment among the 53 patients was 122 days (95% CI, 86-177 days) and was significantly predicted by slope of PSA from the mixed model (HR = 25.883, p &lt; .0001), WBC post therapy (HR = 1.352, p = 0.0017), and age at Sip-T (HR = 1.044 p = 0.0492). KPS, Gleason score, pre Sip-T WBC, and the extent of metastatic disease were not predictive. Most patients had abiraterone acetate for next treatment (n = 32, 58.2%). Other treatments included docetaxel (n = 5, 9.1%), orteronel with prednisone or prednisone alone (n = 12, 21.8%), and others (n = 6, 10.9%). Conclusions: In our experience median time to subsequent therapies was shorter than reported in pivotal Phase III study. Shorter time to post-Sip-T therapy was associated with older age, higher levels of WBC post-Sip-T therapy and more rapid rate of increase in the PSA level.