tbuckley/cabot-search huggingface dataset:
Agent orange as a risk factor for high-grade prostate cancer detected on initial prostate biopsy.
Authors: N. J. Ansbaugh, J. Shannon, M. Mori, P. E. Farris, L. Collins, M. Garzotto
Journal: Journal of Clinical Oncology (2011)

4667 Background: Exposure to Agent Orange (AO), a defoliate used during the Vietnam War, is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether individuals exposed to AO are at risk of a more aggressive phenotype of PCa than individuals not exposed to AO. The goal of this study was to determine the association between AO exposure and risk of high-grade PCa in a cohort of veterans referred for an initial prostate biopsy. Methods: Risk factors were identified using historical clinical data from individuals referred to the Portland VA Hospital for a prostate biopsy between 1993 and 2010. Covariates evaluated include AO exposure, prostate-specific antigen density (PSAD), digital rectal exam (DRE), age, family history, body mass index (BMI), race, and service history. Outcomes of the biopsies were defined as high-grade PCa (HGPCa, Gleason ≥ 7) vs. other [low-grade PCa (LGPCa, Gleason ≤ 6) or no PCa]. Multivariate logistic regression was used to estimate the risk of HGPCA in those with AO exposure. To determine whether AO exposure increased the risk of both HGPCa and LGPCa, separate multivariate models compared the odds of AO exposure in individuals with HGPCa or LGPCa vs. no PCa. Results: Of the 2720 veterans who underwent prostate biopsy, 896 (32.9%) were found to have PCa and 459 (16.9%) were found to have HGPCa. After adjustment for significant confounders including PSAD, DRE, and age, HGPCa cases were more likely to have been exposed to AO as compared to those with LGPCa or no PCa (aOR = 1.73, 95% CI: 1.14 to 2.62). In an analysis of HGPCa vs. no PCa, AO was strongly associated with HGPCa (aOR = 1.74, 95% CI: 1.12 to 2.73). In contrast, in an analysis of LGPCa vs. no cancer, AO exposure was not associated with the detection of LGPCa (aOR = 1.21, 95% CI: 0.80 to 1.85). Thus, AO exposure appeared to uniquely increase the risk of HGPCa in men presenting for an initial prostate biopsy. Conclusions: Agent Orange exposure was associated with a significant increase in the risk of HGPCa in men referred for an initial prostate biopsy. If validated, these findings could aid in the development of effective PCa screening strategies for Vietnam-era veterans.
Kaiser Permanente Georgia: Colon cancer care through the science of performance improvement.
Authors: Carlee Terrell
Journal: Journal of Clinical Oncology (2016)

250 Background: While our patients reported high satisfaction with the care they received, Kaiser Permanente Georgia’s baseline assessment found variation in the way our colon cancer patients were diagnosed and received care. This variation also effects the cycle time from diagnosis to initiation of treatment (surgery or first infusion). Methods: Using Kaiser Permanente’s Performance Improvement methodology and interdisciplinary cooperation, this project launched in January of 2014. A multidisciplinary team representing the GI, Surgery, Oncology, Nursing, Radiology, Palliative Care and Patient Safety departments, was formed and facilitated by a PI specialist to examine the different workflows. The team performed an in-depth baseline analysis of the current state, including patient interviews and surveys. At the completion of the baseline analysis all clinical departments came to an agreement for future state process design. In addition to developing workflows, an order bundle was developed to bridge the gap between the baseline and future states. The improvements were tested and both qualitative and quantitative feedback was collected on effectiveness of the changes. Results: This project resulted in an agreed upon standardized nursing and provider workflow and identified a diagnostic bundle to be carried out on the day of colonoscopy for treating suspected CRC patients. These improvements resulted in a reduction to the average time from diagnosis to treatment for Colorectal Cancer patients by 40.3%. The variation in time from diagnosis to treatment was reduced by 60.5%. Conclusions: We are pleased these positive results improve on the cancer care we provide to our patients. Multidisciplinary communications and agreements were key to the success of this project. Our next steps involve migrating the CRC diagnostic bundle into KPs EMR, developing a reliable surveillance follow-up method, and further reducing the time to treatment by focusing on the surgical pathway.
Brief Chemoimmunotherapy Rituximab (R)-FND ± R Maintenance as First Line Treatment in Elderly Patients with Advanced Follicular Lymphoma (FL): Preliminary Analysis of a Prospective Randomized IIL Trial
Authors: Umberto Vitolo, Marco Ladetto, Carola Boccomini, Enrica Gamba, Isabel Alvarez, Luca Baldini, Annalisa Chiappella, Paolo Corradini, Amalia De Renzo, Francesco Di Raimondo, Andrea Evangelista, Andrea Gallamini, Attilio Guarini, Giuseppe Leone, Anna Marina Liberati, Barbara Mantoan, Maurizio Martelli, Lorella Orsucci, Guido Parvis, Mario Petrini, Antonello Pinto, Enrico Pogliani, Samantha Pozzi, Alessandro Pulsoni, Luigi Rigacci, Corrado Tarella, Alessandra Tucci, Francesco Zaja, Eugenio Gallo
Journal: Blood (2008)
Association of tissue factor pathway inhibitor gene polymorphism -33T→C with disease-free survival in colorectal cancer.
Authors: Amy K Bazzarelli, Adena S Scheer, Lee-Hwa Tai, Rashmi Seth, Christiano Tanese de Souza, Derek J. Jonker, Jean Alfred Maroun, Marc Carrier, Rebecca Ann C Auer
Journal: Journal of Clinical Oncology (2013)

395 Background: Tissue Factor Pathway Inhibitor (TFPI) is an anticoagulant protein exhibiting antimetastatic properties in preclinical models. The homozygous CC polymorphism on intron 7 of TFPI (-33T--&gt;C) is associated with higher TFPI protein levels and a lower risk of venous thromboembolism (VTE). The present study is the first to evaluate the impact of the inherited TFPI polymorphism on disease-free survival (DFS) in cancer patients following curative resection. Methods: A prospectively maintained colorectal tumour bank with associated clinical data was used to identify patients who underwent curative surgery for colorectal cancer between 1994 and 2006. Germline DNA was extracted from formalin fixed, paraffin embedded normal colonic mucosa. Single nucleotide polymorphisms (SNPs) for Tissue Factor Pathway Inhibitor (TFPI, -33T--&gt;C), Factor V Leiden (FVL, G1691A), and Prothrombin (PT, G20210A) were determined by polymerase chain reaction. DFS was described using the Kaplan-Meier method. Multivariable regression analysis, with known prognostic factors, was performed using the Cox Proportional Hazard model. Results: Of the 139 patients identified, the prevalence of the wildtype (TT) TFPI genotype was found in 57.3% of samples, the heterozygous genotype (TC) in 29.4%, and the homozygous genotype (CC) in 10.5%. The incidence of VTE was 21.6% in the TT/TC genotypes and 6.7% in the CC genotype (p=0.4). The CC genotype was associated with superior DFS (HR 0.38, [95%CI 0.17-0.88]; p=.02) with 5 year DFS 56.3% vs. 24.6% for CC vs. TT/TC respectively. In multivariate analysis female sex (HR=0.61, p=.02), chemotherapy (HR=0.66, p=.05), node negative (HR=0.47, p=.005) and TFPI CC polymorphism (HR=0.35, p=.01) were independently associated with improved DFS. The prevalence of FVL (0.7%) and PT (2.2%) polymorphisms was too low to detect any interaction with TFPI polymorphism and DFS. Conclusions: These findings indicate that the inherited anticoagulant homozygous -33T--&gt;C TFPI polymorphism may protect against colon cancer recurrence, and suggest a causal role for the coagulation system in cancer outcomes.
Circulating endothelial cells (CECs) in metastatic colorectal cancer (mCRC) patients (pts) treated with bevacizumab (BEV) and sorafenib.
Authors: J. M. Lafky, B. M. Bot, B. W. Morlan, S. K. Anderson, T. K. Kimlinger, T. M. Halling, S. Kumar, J. T. Reynolds, P. J. Stella, S. R. Dakhil, W. S. Loui, S. R. Alberts, A. Grothey
Journal: Journal of Clinical Oncology (2011)

e14063 Background: Surrogate biomarkers are lacking for predicting or monitoring anti-angiogenesis therapies. We investigated if CECs were correlated to treatment efficacy in mCRC pts treated with BEV and sorafenib. Methods: Peripheral blood samples were obtained for CEC analysis from mCRC pts enrolled in the NCCTG phase II study N054C [Grothey, ASCO 2010]. Blood collection time points were: baseline (BL), cycle 1 day 3, prior to treatment cycles 2, 3, 5, 7, 9, 11, 13, and after the pt went off study. CECs, defined as CD146(+), CD3(-), and CD31(+), were enumerated by flow cytometry. Unequal variance two-sample and paired t-tests were performed to compare values between pt outcome groups and serial measurements within a pt, respectively. Results: 78/79 eligible N054C pts went off study and had their CECs analyzed. 76 pts had BL blood evaluable for CEC analysis. Median BL CECs were 80.0 (mean: 177.5; range: 1.02-1718) cells/mL. We found no correlation between BL CECs and 3 month progression-free survival for mCRC pts treated with BEV/sorafenib (p=0.56). The absolute change and log2-fold change (FC) from BL CECs were decreasing at all time points, with the exception of cycle 1 day 3. The percent change in CEC from BL was significantly decreased in cycles 2, 3, 5, and 7 (p-values: 0.01, 0.008, 0.04, and 0.018, respectively). This remained consistent when examining the CEC log2-FC at cycles 3, 5, and 7 (p = 0.008, 0.014, and 0.0004, resp.). The CEC log2-FC was significantly decreased from BL to end of treatment draws (≤14 days) for pts off study for progression (p=0.0007), but not for pts off study for other reasons (p=0.96). Conclusions: Baseline CECs do not appear to be prognostic in mCRC pts treated with a salvage protocol of BEV/sorafenib. CECs, however, decrease on this anti-angiogenic therapy. The significance of decreasing CECs is unclear and further evaluation of serial CECs to determine their predictive value is warranted.
A phase I study of chemoradiation with weekly panitumumab following neoadjuvant chemotherapy and pelvic lymph node dissection as an organ preserving treatment of invasive bladder cancer.
Authors: Elisabeth E. Fransen van de Putte, Floris J. Pos, Barry Doodeman, Bas W.G. van Rhijn, Elsbeth van der Laan, Michiel Simon Van Der Heijden, Jan M. Kerst, Simon Horenblas, Andre M. Bergman
Journal: Journal of Clinical Oncology (2016)

392 Background: Radical Cystectomy (RC) is the standard treatment of Invasive Bladder Cancer (IBC). Although organ sparing, external beam Radiation Treatment (RT) alone is considered inferior to RC. Since the Epidermal Growth Factor receptor (EGFr) is frequently overexpressed in IBC, combined EGFr inhibition by Panitumumab (P) and RT might improve treatment outcome. In this study, the safety and efficacy of concurrent RT and P (RT/P) following Neoadjuvant Chemotherapy (NAC) and Pelvic Lymph Node Dissection (PLND) was evaluated. Methods: cT2-4N0-2M0 or cT1N1-2M0 bladder cancer patients were enrolled in the study. NAC consisted of a maximum of 4 cycles platinum-based chemotherapy. cN0 patients received NAC after PLND, while cN+ patients (confirmed by fine needle aspiration) received NAC prior to PLND. RT/P consisted of concurrent P (7 weekly doses of 2.5 mg/kg) and bladder RT (66Gy in 33 fractions). Primary end-points were treatment-related toxicity and complete clinical response (CR) assessed by Computed Tomography and cystoscopy 3 months after therapy completion. Partial response (PR) was defined as cT &lt; 2N0. Results: A total of 31 patients were included (mean age: 60±10 years), 3/31 patients were cN1-2. Three patients discontinued NAC after 3 cycles due to toxicity. After NAC (24 cisplatin-based and 7 gemcitabine/carboplatin) 13 (41.9%) patients had remaining visible disease. All patients completed RT, while 4/31 patients terminated P prematurely (2-6 doses) due to toxicity. Preliminary response results after RT/P were available for 29/31 patients. Twenty-six/29 (89.7%) patients had a CR, 3 patients PR (10.3%) of which 2 were treated with transurethral resection and intravesical treatment (TaG1-2) and 1 patient underwent immediate cystectomy after histologic confirmation of T1G3. Conclusions: These preliminary results suggest that concurrent P and RT following NAC and PLND is an organ-preserving option for IBC. Toxicity, EGFr expression, mutational status and long-term oncologic outcomes have to be awaited. Clinical trial information: NL31148.031.10.
Radiographic pattern of progression of recurrent GBM treated with bevacizumab with or without irinotecan.
Authors: P. Dory-Lautrec, E. Tabouret, M. Barrie, C. Boucard, M. Matta, D. Autran, N. Girard, O. L. Chinot
Journal: Journal of Clinical Oncology (2011)

2091 Background: Bevacizumab (BEV) with or without irinotecan (IRI) have demonstrated activity in patients with recurrent GBM. However, conflicting results raise the implication of BEV in facilitating infiltrative progression associated with a shorter survival. While Pope et al. (Neuro-Oncol, 2009) proposed 4 pattern of disease progression, it appear that these pattern definition may not fully identify the “gliomatosis phenotype progression”. We tested a more extensive anatomical analysis as previously described in gliomatosis cerebri (Peretti, J Neuro-Oncol, 2002) Methods: Consecutive MRI performed every 2 months from 25 patients with recurrent GBM treated with BEV+IRI were retrospectively analysed. Status (Local, multifocal, diffuse), number of lobes involved, and tumor infiltration of corpus callosum (CC), basal ganglia or thalamus (BG) and brainstem (BS) were analysed at the time of BEV-+IRI initiation up to progression. Results: At the time of BEV+IRI initiation, 9 (36%), 11 (44%), and 5 (20%) pts presented a local (L1), multifocal (M1), and diffuse (D1) phenotype respectively. According to RANO criterias, 7/25 (28%) pts presented an objective response. At the time of progression, among 9 pts with (L1) presentation, 2 progressed as diffuse (DP), 2 as multifocal (MP) and 5 maintained their local pattern (LP). Of the 11 patients with M1 presentation, 3 progressed as diffuse, and 8 maintained their multifocal phenotype. All pts with D1 status maintained their diffuse phenotype. As a whole, 10/25 pts progressed with a diffuse phenotype, that involved 4 to 6 lobes and, in 8/10 cases, basal ganglia or thalamus and brainstem or corpus callosum. Survival at the time of progression under BEV was <3 mo in 6/10 pts, while survival of M1 or L1 was < 3 mo in 4/15 pts. Conclusions: Recurrent GBM frequently present a diffuse or multifocal presentation while the change of pattern from local to diffuse phenotype associated to BEV trt is uncommun. When observed, diffuse phenotype with extended lobes and midleline involvement, may be associated to a shorter survival. Extended anatomical infiltration analysis prior to BEV administration and at the time of progression should be considered in ongoing and future trials.
Identifying barriers to oncologist referral to palliative care: A dual approach.
Authors: Kyle Whelan
Journal: Journal of Clinical Oncology (2016)

121 Background: Longitudinal palliative care has demonstrated benefits for cancer patients, and the American Society for Clinical Oncology recommends that palliative care be used along with standard anti-cancer therapy at the diagnosis of serious disease. However, studies have shown that oncologists still often refer to palliative care within days of the end of life, or not at all. This indicates that oncologists face barriers, systems-based or self-imposed, to palliative care referral. This study aims to identify specific barriers that prevent oncologists from referring cancer patients to palliative care services. Methods: Barriers to referral were identified via a dual approach. A literature review was performed using a PubMed search of articles published since 2012, when the ASCO provisional opinion was issued. This was narrowed down to 27 articles that meaningfully commented on barriers that oncologists face in referring to palliative care. Additionally, a qualitative analysis of semi-structured interviews of five practicing oncologists was performed. Oncologists interviewed for the study practice in a cancer center affiliated with an academic tertiary hospital. Results: 20 distinct barriers to referral, both systems-based and at the individual provider level, were enumerated from the literature review and interview analysis. Conclusions: Oncologists face a wide range of specific barriers that prevent appropriate referral to palliative care, related both to the logistics of the healthcare system and to providers’ preconceptions about palliative care. A significant barrier at the oncologist level is a tendency to associate palliative care exclusively with the end of life, despite demonstrated benefits earlier in the course of disease.
The prognostic factors in cervical carcinoma treated by radical hysterectomy combined with pelvic radiotherapy.
Authors: Q. Fan, J. Fu, Y. Zhu, W. Mao, P. Zhao, Y. Tian
Journal: Journal of Clinical Oncology (2011)

e15584 Background: Local regional lymp node is the main recurrence site in cervical carcinoma after radical hysterectomy. A retrospective analysis is used to evaluate the efficacy of pelvic radiotherapy and prognostic factors for stage IB-IIB (FIGO Stage) cervical carcinoma initially treated by surgery. Methods: From May 1998 to Dec 2006, a total of 77 patients of cervical carcinoma staged IB-IIB patients were eligible for this retrospective analysis. The diseases were staged IB in 20, IIA in 27 and IIB in 30 patients. All of them received external beam irradiation with 6MV X-ray 50Gy/25 fractions to pelvic field after radical hysterectomy. Overall survival rate was estimated by using Kaplan-Meier method. The prognostic factors were analyzed using univariate (Log rank) and multivariate Cox model. Results: The follow-up time was 5-152 months (median 33 months). The overall 5-year survival rate of stage IB, IIA and IIB were 79.4%, 69.8% and 51.9%, respectively. On univariate analysis, variables significantly associated with positive included age≤35 years (χ2=4.569, P=0.033), anaemia (χ2=4.806, P=0.028), stage≥IIB (χ2=6.120, P=0.013), tumor diameter ≥ 4cm (χ2=8.238, P=0.004)and pelvic lymph node metastasis (χ2=5.582, P=0.018). However in the multivariate analysis, only age ≤ 35 years (χ2=5.637, P=0.018), tumor diameter ≥ 4 cm (χ2=4.377, P=0.036) and pelvic lymph node metastasis (χ2=7.814, P=0.005) were significant factors associated with poorer prognosis. Conclusions: Postoperative adjuvant pelvic radiotherapy can improve the efficacy of patients for stage IB-IIB cervical carcinoma. Age ≤ 35 years, tumor diameter ≥ 4 cm and pelvic lymph node metastasis were confirmed as the independent prognostic factors.
JASPAC 06: Observational study of FOLFIRINOX therapy for unresectable and recurrent pancreatic cancer—Preliminary report on serious adverse events.
Authors: Masato Ozaka, Akiko Todaka, Keita Mori, Narikazu Boku, Nobumasa Mizuno, Hideki Ueno, Satoshi Kobayashi, Kazuhiro Uesugi, Noritoshi Kobayashi, Hideyuki Hayashi, Kentaro Sudo, Naohiro Okano, Yosuke Horita, Keiko Kamei, Seigo Yukisawa, Shoji Nakamori, Yutaka Yachi, Toshiyuki Henmi, Marina Kobayashi, Akira Fukutomi
Journal: Journal of Clinical Oncology (2016)

407 Background: In Japan, indication of FOLFIRINOX for unresectable and recurrent pancreatic cancer was approved in 2013. Because clinical data of FOLFIRINOX in Japanese patients based on only one exploratory trial is limited, this observational study was conducted to survey practical use of FOLFIRINOX and to evaluate incidences of adverse events in Japanese patients. Methods: The subjects were patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX therapy during one year from Dec. 20, 2013 (approval date of this study). All the subjects were registered and their clinical data were sent to the data center. In this preliminary report, we analyzed patients’ characteristics related to serious adverse event (SAE). This study was approved by the IRB in each institution. Results: Four hundred patients (pts) were registered from 27 institutions in Japan. Median age was 63 years (range 27-80). Sixty-four percent (n = 254) had no prior treatment and 254 pts (60%) had distant metastatic lesions. The UGT1A1 genotype was wild-type in 56.8% of the subjects, heterozygous (*1/*6, *1/*28) in 39.3%, and homozygous (*6/*6, *6/*28, *28/*28) in 3.9%. One hundred forty-one SAEs in 115 pts (28.8％) were reported until Aug. 10, 2015. Most common SAEs were febrile neutropenia (n = 26), neutrophil count decreased (n = 26), anorexia (n = 21) and biliary tract infection (n = 18). Of these 141 events, five events were results in death. The proportion of patients who met the inclusion criteria (as follows: ECOG PS of 0 or 1; age 20-75 years; adequate hematological, liver and renal functions) used in the phase II trial of FOLFIRINOX for Japanese patients was significantly lower in the subjects with SAEs than those without SAE (60.5% vs. 72.4%, p = 0.023). Four of the 5 pts who resulted in death did not fulfill the inclusion criteria; C-reactive protein in 4, platelet count in 1 and hemoglobin in 1. Conclusions: This is a first report to evaluate the safety profile of FOLFIRINOX in Japanese pancreatic cancer patients. These data highlight the importance of patient selection for FOLFIRINOX. The final safety and efficacy results of this study will be reported at the coming meeting. Clinical trial information: UMIN000014658.
Unit redesign to improve safety, quality, and patient and nurse satisfaction.
Authors: Theresa Woodrum, Missy Kneifl, Christina Aning
Journal: Journal of Clinical Oncology (2013)

179 Background: Increased emphases have been placed on hospital safety, and patient and nurse satisfaction in the competitive cancer care arena. The current climate demands critical attention to stakeholder input in cancer care delivery. Methods: Stakeholder (patients, families, nurses, physicians, and other members of the multidisciplinary care team) input directed efforts in an adult/pediatric oncology/hematology unit renovation. A true focus on stakeholder involvement was evident by uniting the patient advisory council from the cancer care service line, multidisciplinary staff, and unit-based shared governance structures to form the design team. Uniting multiple perspectives and eliciting design team ideas and recommendations ensured renovation plans remained focused on improved care delivery and processes. The design team discussed all aspects of renovation, including work flow, equipment/technology needs, safety and security, and family/child friendly spaces. A key feature of the renovation was the universal room concept, which meant that rooms needed to be adaptable to a cancer patient’s changing needs: from standard care to critical care. Stakeholder input was sought on as all aspects progressed as final decisions were made on aesthetics, family-focused amenities, work flow structures such as location of equipment and supplies, and patient safety features (especially in bathroom spaces). Results: Total falls decreased from 6.17 to 3.1 per 1,000/pt days and falls with injury decreased from 2.9 to 1.8 per 1,000/pt days. Improvements in patient satisfaction scores were seen in “overall room” scores increasing from 79.9 to 90.5 and “visitor /family” satisfaction increased from 87.9 to 92.1. Overall nursing satisfaction improved from 56.68 to 64.58 and job plans to remain on unit rose from 63-89. Conclusions: Avoiding a top-down, hierarchical decision-making process from conceptualization to realization resulted in measurable changes in patient safety and patient and staff satisfaction from pre- to post-renovation. This process can utilized to address the changing needs in cancer care.