tbuckley/cabot-search huggingface dataset:
A strategic roadmap for oncology electronic medical records (EMRs) in Ontario’s complex multiregional health care system.
Authors: Vishal Kukreti, Tim Yardley, Yaron Derman, Margaret Kennedy, Rummy Dhoot, Saul Melamed, John Gilks
Journal: Journal of Clinical Oncology (2014)

159 Background: Ontario’s cancer system comprises 14 regions; from large and sparsely populated to dense urban areas. Each region, and the hospitals within it, is responsible for its own IT solutions to support oncology. In 2011 Oncology EMRs in 4 regions were funded as there are no oncology specific Health Information Systems (HIS). Cancer Care Ontario (CCO) also obtained funding to develop standards, and a roadmap for their use, from eHealth Ontario. Methods: Early work focused on establishing standards based on the integrated patient cancer journey. Work-streams included functional standards, an interoperability framework for CCO tools and provincial assets and information standards to be supported through EMRs. These were evaluated through internal and external review and validation processes. The strategic IT roadmap was developed via interviews with leaders in the clinical, management and IT domains to obtain input on how the standards might be used and what role CCO should play. Results of the consultations were consolidated into key themes and validated through a facilitated workshop with an expert panel. Results: Standards can be incorporated into EMRs in a consistent way by basing the design around the patient journey and by working with the point of care tools that clinicians need to support accurate, timely and relevant data at each stage of the patient journey. This approach is location and vendor neutral. Focusing on the data needed at point of care provides insight into reporting needs and how data can be exchanged between systems; directly, via a provincial repository or via CCO provided tools. CCO’s role should be to provide support to the regions through standards and advocacy with stakeholders rather than development of tools. Conclusions: Oncology has unique IT needs that may not be fully incorporated in hospital wide IT strategic plans or decisions. The standards and roadmap provide a basis for oncology programs to ensure that IT decisions meet their needs. The role of CCO should evolve toward strategic counsel and advocacy rather than provision of IT tools.
Urachal versus nonurachal adenocarcinomas of the bladder: A population-based report.
Authors: Maxine Sun, Guillermo de Velasco, Christian P Meyer, Joaquim Bellmunt, Paul L. Nguyen, Quoc-Dien Trinh, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

450 Background: Previous studies are inconclusive on whether urachal vs. non-urachal adenocarcinomas of the urinary bladder have different prognoses. Our objective was to assess survival differences between urachal vs. non-urachal adenocarcinomas in light of evolving treatment strategies over the past years. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with a diagnosis of adenocarcinoma of the urinary bladder between years 1988 and 2012. The variable of interest was urachal vs. non-urachal adenocarcinomas. Kaplan-Meier curves and log-rank tests were performed to assess the univariable effect of urachal vs. non-urachal adenocarcinomas on survival. Multivariable Cox regression analyses were performed for prediction of cancer-specific mortality (CSM) and overall mortality. Sub-analyses comprised of competing-risks regression models. Results: Overall, 2345 (89%) and 301 (11%) non-urachal and urachal adenocarcinoma patients were identified, respectively. The 5-year CSM-free survival rates for urachal vs. non-urachal adenocarcinomas were 63% vs. 50% (P&lt; 0.001). For the same groups, the 5-year overall survival rates were 50% vs. 32%, respectively (P&lt; 0.001). In multivariable Cox regression analyses, no difference was recorded between urachal vs. non-urachal adenocarcinomas for CSM (hazard ratio [HR]: 0.86, P= 0.2) or any mortality (HR: 0.84, P= 0.07). Important prognosticators of CSM and survival were surgery, lymph node dissection, disease stage and grade. Conclusions: No survival difference was recorded in the current study between urachal vs. non-urachal adenocarcinoma of the bladder. However, surgery and lymph node dissection constitute important factors for both tumor types.
Physician practices in the treatment of brain metastases.
Authors: M. S. Kress, A. L. Potosky, S. B. Makgoeng, N. Ramakrishna
Journal: Journal of Clinical Oncology (2011)

e16506 Background: Despite the many cancer patients with brain metastases, there is limited data to guide treatment. The historic standard of whole brain radiation therapy (WBRT) can have significant morbidity. Alternatives, such as stereotactic radiosurgery (SRS), may have less morbidity and increased local control. The objective of this study was to assess physician practices for treating patients with brain metastases in various clinical conditions. Methods: We surveyed 4357 physician members of ASTRO, 262 of whom completed the survey. We assessed their treatment choices for hypothetical patients with brain metastases: WBRT with SRS, SRS alone, surgery with WBRT, or WBRT alone. The reference scenario was a 55 year-old patient with non-small cell lung cancer, inactive extracranial disease, Karnofsky Performance Status (KPS) 80, and an asymptomatic, small brain lesion. We held constant the number of metastases at 1, 3 and 8 while obtaining treatment choices for subsequent scenarios by varying histology, extracranial disease status, KPS, neurologic deficit, age and lesion size. Results: For the reference scenario, 46% of respondents chose surgery with WBRT, 24% WBRT with SRS and 27% SRS alone. For patients with more lesions, physicians chose WBRT alone more often (3 lesions: 20%; 8: 90%); for those with 3 lesions physicians often chose an approach including SRS (SRS alone 23%; SRS with WBRT 55%). More physicians chose WBRT alone for a patient with active extracranial disease (51%) or KPS 50 (51%). For an 80 year-old patient, respondents chose SRS alone more often for 1 lesion (37%), but WBRT alone more often for 3 or 8 lesions (50%, 90%). Multivariate modeling detailed the characteristics’ impact on the odds of selecting each of the 4 treatments. Conclusions: The treatment of patients with brain metastases is heterogeneous. Number of lesions was an important factor, with increased use of WBRT for increasing number of lesions. However, many physicians still chose SRS as part of their approach for patients with multiple lesions. Factors that could increase the morbidity of WBRT, such as age or KPS, correspond with an increase in its utilization. Additional research is needed to determine causes of heterogeneity in practice and to provide evidence to guide decision-making.
Pretreatment PET and post-treatment pathologic nodal status as a predictor for distant metastasis in locally advanced head and neck squamous cell carcinoma treated with definitive concurrent chemoradiotherapy.
Authors: K. Hu, W. F. Mourad, M. Perksy, M. Urken, A. Jacobson, B. Culliney, T. Tran, S. P. Schantz, P. Costantino, L. B. Harrison
Journal: Journal of Clinical Oncology (2011)

5541 Background: Advances in concurrent chemoradiation (CCRT) and neck dissection (ND) have yielded excellent LR control in node+ve head and neck squamous cell cancer (SCC). Distance metastasis (DM) is a major pattern of failure and obstacle to cure. High metabolic tumor volumes derived from pre-treatment PET and persistent pathologic neck disease after CCRT have been associated with worse outcomes. Methods: From 1/99-12/08, 106 pts with node+ve SCC were treated with CCRT using platinum based chemotherapy. Tumor sites consisted of: oropharynx (87), larynx (11), unknown primary (4), hypopharynx (2) and oral cavity (2). 117 planned ND were performed 6-8 weeks after CCRT. Median age: 56. Males: 70% N1 (6) 6%, N2a (6) 6%, N2b (46) 45%, N2c (39) 38%, and N3 (20) 20%. 46 pts (45%) underwent pretreatment PET and the metabolic nodal volume (MNV) was calculated by the product of the mean standard uptake value and the nodal volume. Results: Residual nodal disease (pN+) was found in 29% of ND; N1-2a 17%, N2b 28%, N2c 31% and N3 45%. At a median followup of 35 months (3-128 ms), the main pattern of failure in pN+ compared to pN- was DM (3yr: 33% vs 12%, p=0.01, respectively). 3yr LR failure was also increased in pN+ vs pN- (18% vs 3%-, p=0.07, respectively). The 3yr incidence of DM according to N-stage was as follows: N1-2a:0, N2b12%, N2c 28%, N3, 35%. Patients with high volume ipsilateral neck disease had a higher incidence of DM if pN+ vs pN- as follows: N2b: (3yr DM 32% vs 4%, p=0.02) and N3 (60% vs 14%, p=0.07), respectively. For the subgroup of 46 pts staged with PET/CT, the median value for MNV was 71. Pts with high MNV values (>71) were at lower risk for having pN+ [17% (4/24) vs. 43% (10/23), p=0.045] but higher risk for DM (2yr: 32% vs 15%, p=0.09) compared to those with low MNV values (<71). In pts with high MNV, the 3yr DM was higher in pLN+ vs pLN- (67% vs 25%, p=0.05, respectively) as it was in low MNV pts (3yr DM 30% vs 0%, p=0.12). Conclusions: Pathologic residual nodal disease after definitive CCRT and high pretreatment MNV predicts a greater risk for DM. N2b-3 pts with high MNV and pN+ after CCRT+ND warrant consideration for additional adjuvant therapy.
Safety and feasibility of enhanced recovery after surgery in the patients underwent pancreaticoduodenectomy for hepatobiliary and pancreatic malignancy.
Authors: Keisuke Kazama, Toru Aoyama, Masaaki Murakawa, Koichiro Yamaoku, Yosuke Atsumi, Amane Kanazawa, Akio Higuchi, Manabu Shiozawa, Norio Yukawa, Takashi Oshima, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
Journal: Journal of Clinical Oncology (2016)

338 Background: Pancreaticoduodenectomy (PD) remains the mainstay of surgical treatment for hepatobiliary and pancreatic malignancy and offers the only chance of long term survival. However, the morbidity and mortality after PD has been reported to be high. Therefore, it is important to determine the most appropriate perioperative care. This study assessed whether enhanced recovery after surgery (ERAS) program is safe and feasible in patients who underwent pancreaticoduodenectomy Methods: The subjects were patients who underwent consecutive PD between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization and 30-day readmission rate. Key ERAS program targets were: nasogastric tube (NGT) removal [postoperative day (POD) 1]; resumption of oral fluids (POD 2); urinary catheter removal (POD 3); tolerating diet (POD 5); drain removal (POD 7). Results: A total of 109 patients were studied. The overall incidence of morbidity was 51.4%, the incidence of mortality was 1.8%, and the incidence of readmission was 1.8%. The median postoperative hospital stay was 23 days. The proportions of patients achieving key targets were: 93.6% for NGT removal; 94.5% for resumption of oral fluids; 31.2% for urinary catheter removal; 79.8% for tolerating diet; 80.7% for meeting mobility targets, and 37.6% for drain removal. Conclusions: ERAS program is safe and feasible in patients who undergo PD. However, achieving compliance on some targets, especially the removal of catcher and drain, were more challenging.
Adherence to hereditary non-polyposis colorectal cancer (HNPCC) screening guidelines
Authors: J. Hansen, T. Garcia-Collins, E. Glogowski, S. Jhanwar, J. Guillem, K. Offit, K. Hurley
Journal: Journal of Clinical Oncology (2008)

22127 Background: HNPCC increases lifetime risk of a constellation of cancers including colorectal (CRC; 80%), endometrial (EC; 43–60%), ovarian (OC; 10–12%) and ureter (5%). Despite provision of screening guidelines during genetic counseling, little is known about adherence to such recommendations. We report preliminary follow-up data on levels and patterns of adherence and intention to commit to multi- organ screening in HNPCC pts. Methods: 25 pts undergoing genetic counseling/testing completed yearly follow-up questionnaires in this ongoing prospective study to assess screening adherence and intentions. 12 pts (75% female, 25% male) were identified as cases with molecularly confirmed HNPCC and/or Amsterdam I/II criteria (Age X=53). 2/3 of pts were affected (33% CRC; 44% EC and/or OC; 25% other non-HNPCC). At baseline, all CRC cases had partial colectomy and 5 females had total abdominal hysterectomy/bilateral salpingo- oophorectomy (TAH/BSO). 4 females had gynecologic (GYN) tissue at risk. Key screening recommendations included annual colonoscopies, TAH/BSO or GYN screening (annual endometrial biopsies, bi-annual transvaginal ultrasounds/CA-125), and annual urine cytology. Results: 25%were overdue for annual colonoscopy. Only 1 female had an endometrial biopsy within the last year; 75% did not adhere to bi-annual OC screening. 58% were overdue for annual urine cytology. Only 25% pts were adherent across all risk recommendations. Patient intention for future screening was as follows: 75% pts were adherent and planned to maintain CRC screening, and 25% were non-adherent and planned to adhere. 75% females planned to return in 6 months for GYN screening, while 1 non-adherent pt did not plan to adhere. 42% were adherent to urine cytology and planned to continue screening while 1 adherent and 1 non-adherent pt did not plan to adhere. Conclusions: MostHNPCC patients were partially adherent to intensive multi-organ screening; however, both adherent and non-adherent pts indicated their intent to initiate or resume screening. Future research will focus on assessing predictors of adherence, as well as identifying strategies to promote adherence, particularly for evidence-based tests such as colonoscopy. No significant financial relationships to disclose.
Efficacy and safety of perioperative chemotherapy with 5FU-cisplatine-cetuximab in gastric and gastroesophageal junction adenocarcinomas (GGOJA): A single-arm multicenter phase II trial (FFCD 0901).
Authors: Christophe Mariette, Guillaume Piessen, Carole Monterymard, Denis Pezet, Aurelie Ferru, Mathieu Baconnier, Xavier Adhoute, David Tavan, Olivier Bouche
Journal: Journal of Clinical Oncology (2015)

154 Background: Whilst perioperative chemotherapy (CT) combined with radical surgery offers a survival benefit over surgery alone in GGOJA, 3-year survival still needs to be improved. The purpose of this phase II study was to evaluate the efficacy and safety of the perioperative use of cetuximab combined with 5-fluorouracil and cisplatin in operable GGOJA. Methods: Untreated operable patients with a WHO Performance Status (PS) ≤ 2 and age ≤ 75 years, with localised GGOJA received 6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT planned for 6-8 weeks after surgery. The primary objective was a combined evaluation of tumoral response, assessed by centrally reviewed computed tomography, and major toxicities leading to neoadjuvant CT being discontinued. Sample size (63 patients) was calculated using Bryant and Day design (α=5%, Power=80%), expecting a rate of objective response of 45% and a percentage of patients without major toxicities of 90%. Results: 65 patients were enrolled from 2011 to 2013 with a median age of 60.5 years. 83.1% were men, 98.5% had a WHO PS&lt;2, 30.8% had a gastric and 69.2% a junctional tumour, 28.5% had a stage II and 71.4% of patients a stage III tumour. With regard to the primary endpoint, 64 patients were evaluated, 29.7% (n=19) had an objective morphological tumour response and 95.3% (n=61) did not stop treatment prematurely due to major toxicity. 58 patients (89.2%) completed neoadjuvant CT as planned. The median duration of CT was 2.3 months and grade 3-4-5 toxicities were observed in 61.5% of patients. 60 patients (92.3%) underwent surgical resection with 24 significant complications (41.7%) and 2 postoperative deaths (3.4%). On histological analysis, 40 patients (71.4%) were non responders. Conclusions: Adding cetuximab to the neoadjuvant chemotherapy regimen in operable GGOJA is safe but does not show enough efficacy in the present study to meet the primary endpoint. Clinical trial information: NCT01360086.
Prospective comparison of recurrence score, uPA/PAI-1, central grade and molecular classification in early breast cancer: Interim results from the WSG-Plan B trial.
Authors: T. Degenhardt, O. Gluz, H. H. Kreipe, R. E. Kates, C. Liedtke, S. Shak, M. R. Clemens, D. Augustin, U. Nitz, N. Harbeck
Journal: Journal of Clinical Oncology (2011)

10594 Background: Both the recurrence score (RS) multi-gene assay and invasion factors uPA/PAI-1 are included in guidelines (ASCO, AGO) for decision support regarding adjuvant chemotherapy in early breast cancer (BC). Here we present the first preplanned WSG-Plan B trial correlation analysis of RS, uPA/PAI-1, and molecular subtypes by protein expression. Methods: Plan B trial (n=2,448) is evaluating anthracycline-free adjuvant chemotherapy (6x TC) vs. 4xEC-4xDOC in HER2-negative BC. RS is used as selection criterion for chemotherapy or hormonal therapy alone; uPA/PAI-1 (by ELISA) is obtained as an optional risk factor. Central and Ki-67-modified grade and luminal B subtype (by 13.25% or 20% KI-67 cut-offs) evaluation are performed by the independent trial pathologist. Results: From April 2009 to February 2011, 2380 patients have been recruited and 1806 randomized to the study. In 1106 pts, both RS and central grade, in 592, both Ki-67 and RS, and in 201 uPA/PAI-1 and RS were available. When considered as continuous variables, RS was weakly positively correlated (Spearman’s coefficient rs) with PAI-1 (rs=0.21, p=0.003), Ki-67 (rs=0.336, p<0.001), and central grade (rs=0.498, p<0.001). When considered as risk categories, there was only a weak concordance between RS and uPA/PAI-1, using either standard RS (18; 30) or PlanB cut-offs (low risk <11 RS), with 67% of patients having high uPA/PAI-1 within the low/intermediate-RS subgroups. 29-33% of G3 tumors are allocated to the RS low-risk group. While RS high-risk was predictive of high risk by uPA/PAI-1, grade and luminal B subtype, the converse was not true; clinically relevant proportions (between 33-66%) of patients identified by uPA/PAI-1 and Ki-67 as being at high risk have low/intermediate RS. Conclusions: For the first time, risk groups according to RS, Ki-67 and uPA/PAI-1 have been prospectively compared. These preliminary data show that the high RS group seems predictive of high uPA/PAI-1, aggressive central grade and luminal B subtype, but the converse is not true; these markers do not predict the RS. Further evaluation within the Plan B trial will clarify the clinical significance of these findings.
A complex role of insulin-like growth factor binding proteins (IGFBPs) in melanoma
Authors: J. Z. Yu, P. Christos, F. Darvishian, H. Yee, M. T. Buckley, L. F. Liebes, A. C. Pavlick, D. Polsky, P. Brooks, I. Osman
Journal: Journal of Clinical Oncology (2008)

9064 Background: Preclinical data suggest that IGFBP4 inhibits melanoma (MM) angiogenesis and tumor growth, while IGFBP3 exhibits both growth-stimulatory and inhibitory activities in different solid tumors. Given the active development of anti-IGF targeted therapy, currently in Phase I and II clinical trials, we aimed to better define a subset of MM patients (pts) who may benefit from anti-IGF targeted therapy by examining both IGFBP4 and IGFBP3 expression in MM tissues and shedding in sera. Methods: 132 MM pts [72 primary (Pri), 60 metastatic (Met)] were prospectively enrolled in the NYU Interdisciplinary Melanoma Cooperative Group (64 Male, 68 Female; median age 56). We used immunohistochemistry to assess tumor IGFBP4 and IGFBP3 protein expression (R&D Systems), and ELISA assays (DSL, Inc.) for sera concentration of IGFBP4 and IGFBP3. Wilcoxon rank-sum tests and Spearman-rank correlation coefficients were used where appropriate. We examined the correlation between IGFBPs, recurrence, and overall survival (OS). Results: IGFBP4 tumor expression was significantly greater in Pri vs. Met pts (median=70% vs. median=10%, respectively, p=0.01). While median IGFBP3 tumor expression was 90% in Met pts vs. 80% in Pri pts, the difference was statistically significant (p=0.039). No significant difference in median IGFBP4 sera concentration was observed between Pri and Met pts (37.2 ng/ml vs. 41.2 ng/ml, respectively, p=0.26). A trend for greater IGFBP3 sera concentration was observed in Met versus Pri pts (median=4.9 mg/ml vs. median=3.4 mg/ml, respectively, p=0.09). The correlation coefficient between IGFBP4 and IGFBP3 tumor expression was 0.29 in Pri pts (p=0.03) and 0.29 in Met pts (p=0.10). There were no associations between IGFBP4 or IGFBP3 and recurrence in Pri pts [median follow up (FU)=30.6m], or with OS in Met pts (median FU=21.8m). Conclusions: Our clinical data suggest complex regulation of IGFBPs in MM and support the interplay of IGFBP3 and IGFBP4 in MM progression. Data also suggest that the tissue expression of both IGFBP3 and IGFBP4 may be more clinically relevant than their sera shedding. Data do not support a prognostic role of measuring IGFBP4 and IGFBP3 in MM pts. No significant financial relationships to disclose.
Use of selective inhibition of nuclear export (SINE) using a CRM1/XPO1 antagonist to overcome resistance to CPT-11 in colon cancer in preclinical models.
Authors: Hye Won Chung, Roberto A. Salas Fragomeni, Sharon Shacham, Michael Kauffman, James C. Cusack
Journal: Journal of Clinical Oncology (2013)

396 Background: Overcoming the resistance of topoisomerase I (TOP1) inhibitors has great clinical potential for treatment of advanced colon cancer. Previously, we showed a kind of novel CRM1-dependent SINEs leads to increase the anti-cancer effects of topoisomerase-1 (topo-1) inhibitor, CPT-11 (SN38), in colon cancer in vitro. However, its underlying mechanisms have not been fully understood. Here, we showed CRM1-dependent SINEs induced the sequestration of TOP1 into nucleus as well as other tumor suppressors or growth regulatory proteins. Methods: The synergism of KPT-251, a novel CRM1-dependent SINE, with SN38 were evaluated using Chou-Talalay method in both CPT-11/SN38-sensitive (SW480) and CPT-11/SN38-resistant colon cancers cells (WiDr) in vitro and animal experiments bearing CPT-sensitive and CPT-resistant cells in vivo. The expression change of TOP1, p-FOXO3a, p27, p53, p21, and IkBa in nucleus were evaluated by western blot. Nuclear trafficking of TOP1 was confirmed by immunofluorescence microscopy and measuring nuclear TOP1 catalytic activity. Increased apoptosis through TOP1 nuclear sequestration were evaluated by comet assay. Results: We found the dramatic synergism of KPT-251 with CPT-11 in both CPT-11/SN38-sensitive and CPT-11/SN38-resistant colon cancers cells in vitro and in vivo. We also found TOP1 was sequestrated into nucleus by KPT-251 through CRM1 inhibition, and this induced overcoming the resistance of CPT-11 in colon cancers, which were demonstrated by western blot, immunofluorescence microscopy, TOP1 catalytic activity, and comet assays. Conclusions: Our results suggest blocking TOP1 nuclear export by a novel CRM1-dependent SINE sensitizes colon cancer to TOP1 inhibitors. Our study supports the development of a novel treatment strategy to overcome the resistance of CPT-11 and other TOP1 inhibitors in colon and potentially other cancers.