tbuckley/cabot-search huggingface dataset:
Three years of reimbursement decisions regarding novel oncology drugs in Israel: A retrospective evaluation of correspondence with the ESMO Magnitude of Clinical Benefit Scale.
Authors: Ariel Hammerman, Sari Greenberg-Dotan, Ilan Feldhamer, Yair Birnbaum, Nathan Cherny
Journal: Journal of Clinical Oncology (2016)

e18258 Background: The Israeli Health Insurance Law stipulates a National List of Health Services (NLHS) which all residents are entitled to. Every year, the government allocates an additional budget for funding new health technologies. The decision which technologies to reimburse is taken by a public national advisory committee (PNAC). The PNAC takes into account mainly the efficacy demonstrated in the clinical trials, but also economic, social and ethical aspects of the novel technology. Yet, until now, The PNAC did not utilize any standard tool for grading the extent of benefit of new therapies. The European Society for Medical Oncology published recently its Magnitude of Clinical Benefit Scale (ESMO MCBS) for cancer medicines. The scale is graded 5, 4, 3, 2, 1, 0 for treatments of advanced/metastatic cancers (the 'palliative setting'), where grades 5 and 4 represent the highest level of proven clinical benefit. Our objective was to evaluate the association between Israel's reimbursement decisions in the years 2013-2015 (before ESMO MCBS was available), and the later published ESMO MCBS scores. Methods: ESMO MCBS scores were obtained retrospectively for the cancer drugs that were candidates for reimbursement in 2013-2015 NLHS updates. The drugs were categorized to 'high benefit' (ESMO MCBS 3-5) and 'low benefit' (ESMO MCBS 0-2). The PNAC's decisions for all candidate drugs were accessed and compared with the categorized ESMO scores. Results: 38 cancer drugs were candidates for the 2013-2015 NLHS update deliberations. An ESMO-MCBS score was available for 19/22 approved drugs and 15/16 non-approved drugs. Median ESMO MCBS score for approved drugs was 4 and 1 for non-approved drugs. 89% of the approved drugs gained a 'high benefit' score and 87% of the non-approved drugs gained a 'low benefit' score (p < 0.001). Conclusions: The Israeli PNAC's past decisions regarding reimbursement of novel cancer drugs, demonstrated concordance with the ESMO MCBS scores. Incorporation of ESMO MCBS data in future reimbursement deliberations may assist in framing the appropriate use of limited public resources, to deliver effective and affordable cancer care.
A novel prognostic prediction model for recurrence in patients with stage II colon cancer after curative resection.
Authors: Kazuhiro Saso, Norikatsu Miyoshi, Shiki Fujino, Yusuke Takahashi, Junichi Nishimura, Masayoshi Yasui, Masayuki Ohue, Yoshihito Ide, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
Journal: Journal of Clinical Oncology (2018)

e15615 Background: There is a subset of patients with stage II colon cancer who have a high likelihood of recurrence and have attained a clinically significant benefit from chemotherapy. However, few studies have examined to define the subset of patients with stage II colon cancer who are at high risk of recurrence. This study aimed to clarify the risk factors for recurrence of stage II colon cancer in patients and to determine possible treatment options for postoperative adjuvant chemotherapy. We developed a prediction model for recurrence in patients with stage II colon cancer after curative surgical resection. Methods: This study retrospectively investigated 436 patients who underwent curative resection for stage II colorectal cancer at Osaka International Cancer Institute and Yao Municipal Hospital from 2004 to 2012. Several clinicopathological factors were examined, and the Cox regression model was used to develop a prediction model for recurrence. The prediction model was validated in an independent group of 212 patients who underwent surgery at Osaka University Hospital from 2001 to 2012. Results: Univariate analysis revealed that preoperative serum carcinoembryonic antigen (CEA) level, (P = 0.038), pre-obstruction (P = 0.005), tumor invasion (P = 0.034), lymphatic invasion (P = 0.029), and venous invasion (P = 0.011) were significantly correlated with the disease-free survival (DFS). A classification and regression tree (CART) was structured as a prediction model for DFS by variables, with the limit to enter a variable in the analysis set at P < 0.05. The prediction models were validated by external datasets in an independent patient group. The concordance indices for DFS after current surgical resection were 0.675 in the learning set and 0.552 in the validation set. Conclusions: We developed a new prediction model that indicates the risk of recurrence and prognosis in patients with stage II colon cancer, which will facilitate the appropriate introduction of adjuvant chemotherapy in high-risk stage II patients.
TCT-497 Predictors of Post-Dilatation after Self-Expanding Transcatheter Aortic Valve Replacement: Large Single Center Experience
Authors: Run Du, Hasan Jilaihawi, Cezar Staniloae, Eleonora Vapheas, Zhen-Gang Zhao, Moyang Wang, Muhamed Saric, Peter Neuburger, Michael Querijero, Alan Vainrib, Kazuhiro Hisamoto, Nicholas Amoroso, Tara Collins, Emily Clark, Illya Pushkar, Tonya Robin, Danielle Sin, Binita Shah, Zachary Taylor, Hanah Lee, Daniel Bamira, Samantha Vidal, Ricardo Benenstein, Mathew Williams
Journal: Journal of the American College of Cardiology (2018)
TCT-116 Spot Stenting Versus Full Coverage Stenting After Endovascular Therapy for Femoro-popliteal Artery Lesions
Authors: Yusuke Tomoi, Yoshimitsu Soga, Mitsuyoshi Takahara, Osamu Iida, Masahiko Fujihara, Daizo Kawasaki, Kenji Ando
Journal: Journal of the American College of Cardiology (2018)
Population-based analysis of hospital readmissions within 1 year of esophagectomy.
Authors: Biniam Kidane, Binu Jose Jacob, John Peel, Refik Saskin, Rinku Sutradhar, Thomas K. Waddell, Gail Elizabeth Darling
Journal: Journal of Clinical Oncology (2016)

e15580 Background: Hospital readmission after esophagectomy is a useful metric for measuring resource utilization. Our objective was to evaluate readmission rates within 1 year of discharge home after esophagectomy. Methods: We conducted a population-based retrospective cohort study using linked health administrative data on all patients who had an esophagectomy for cancer between 2000 and 2012 in Ontario, Canada. Ontario utlizes a single-payer healthcare system with a population of 13.8 million people. Univariable and multivariable analyses were used to identify factors associated with readmission within 1 year of discharge. Results: We identified 3344 patients who had an esophagectomy. In-hospital mortality was 5.8% (n = 193). Readmission within 1 year occurred in 1651 patients ( 49.4%) and 803 patients (24%) died within 1 year following esophagectomy. On multivariable analysis, higher comorbidity status (adjusted odds ratio [aOR] = 1.04, 95%CI 1.01-1.06), use of chemotherapy (aOR = 1.46, 95%CI 1.22-1.75) or radiation therapy (aOR = 1.63, 95%CI 1.33-2.01) were significantly associated with higher rates of readmission. Age, sex, income and rural status were not significantly associated with higher rates of readmission (p > 0.20).There were significantly lower rates of readmission over the 2000-2012 study period (aOR = 0.95, 95%CI 0.93-0.97). There was a consistent annual reduction in readmission rates with 52.8% readmission in 2000 versus 43.8% in 2012 (p < 0.0001). The point at which readmission rates went below 50% occurred between 2006 & 2008. Conclusions: Readmission after surgery is a potential quality indicator but may also be related to underlying disease, in this case cancer of the esophagus or gastroesophageal junction. We found a high (49.4%) rate of hospital readmission within 1 year of discharge following esophagectomy. Higher comorbidity status & use of chemo/radiation therapy were independently associated with higher rates of readmission whereas age or socioeconomic or rural status were not. There was a consistent & significant trend of reduced readmission rates over the study period. Regionalization of esophagectomy occurred over this time period and may have contributed to this trend.
Influence of age on outcomes in pancreas adenocarcinoma (PAC): A single institution experience.
Authors: Gabriel Tinoco, Sofia Palacio, Ana Sandoval-Leon, Deukwoo Kwon, Terri Pollack, Ikechukwu Immanuel Akunyili, Caio Max S. Rocha Lima, Lorraine Portelance
Journal: Journal of Clinical Oncology (2016)

e15744 Background: The mean age at diagnosis of PAC is 71. However, many apply age rather than performance status and organ function to decide therapy. Additionally, the elderly are underrepresented in clinical trials. We hypothesize that poorer outcomes are independent of age. Herein we report our institution experience Methods: We conducted an IRB approved retrospective case-control study of PAC patients stratified by age < and > 75, Group A and B respectively diagnosed at our institution between Jan 2007 and Jan 2014. The Charlson comorbidity index (CCI) was recorded. Progression-free survival (PFS) and overall survival (OS) were calculated. Kaplan-Meier method and Cox proportional hazards model were used for statistical analysis. Results: 604 patients were recorded: Group A (252) and Group B (352). The median age was 54 in Group A and 77 in Group B (p = 0.0001). The stages at diagnosis were not different between the two groups.The median CCI was 3 in Group A vs 4 in Group B (p = 0.06). Surgical resection with curative intent was done in 36% in Group A compared to 31% in Group B (p = 0.2). Group A was more likely to receive adjuvant therapy 11.16% vs 7.94% (p = 0.0217). 7.45% were lost to follow up. Elderly patients had worse survival compared to their younger counterparts; stage I/II OS 14.4 vs 65 months (p < 0.001) and stage III/IV OS 6 vs 10.3 months (p = < 0.0035). Elderly Hispanic patients were found to have better outcomes compared with non-Hispanics, OS 13 vs 7 months (p 0.0009). The CCI was an independent poor prognostic factor in both Univariate and Multivariate analysis, HR 1.34; 95% CI 1.24-1.44 (p = 0.0001), which remained significant after adjusting for age, ethnicity and stage. No difference between albumin at diagnostic or number of transfusions among the groups. (p = 0.2). Conclusions: In this study elderly patients had worse OS despite similar stage at diagnosis. Most baseline characteristics were well balanced. However, elderly patients received less adjuvant therapy. A trend towards worse CCI was observed in elderly, but was non-significant. This analysis suggests that PAC patients should be treated according to their physiologic condition rather than age since the only independent predictor of poor prognosis was the CCI.
Chronic hepatitis C as an adverse prognostic factor in myelodysplastic syndromes.
Authors: Santiago Thibaud, Justin D. Kaner, Aditi Shastri, Anjali Budhathoki, Ashwin Sridharan, Swati Goel, Ioannis Mantzaris, Murali Janakiram, Noah Saul Kornblum, Ira Braunschweig, Amit Verma
Journal: Journal of Clinical Oncology (2017)

e18557 Background: Chronic hepatitis C virus (HCV) infection has been associated with hematologic malignancies such as B-cell non-Hodgkin lymphoma. In contrast, there is very little known about the relationship between HCV and myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). To determine the effect of HCV on MDS/AML clinical outcomes we conducted a retrospective analysis in a large inner city cohort of patients (pts) Methods: 478 pts with MDS and MDS-transformed AML were identified between 1997 and 2016; 13 pts were HCV-positive (HCV+/MDS) and 465 were HCV-negative (HCV-/MDS). Demographics, hematologic parameters, cytogenetics, IPSS-R scores and molecular profiles were compared for both groups (grp). Survival (surv) analysis was done using the Kaplan-Meier method Results: HCV+/MDS had significantly worse surv than HCV-/MDS pts on univariate analysis (UA) (median surv 16 vs 52 months, HR 2.8, 95% CI 1.4-5.5, p &lt; 0.01). Difference remained strongly significant after exclusion of HIV-coinfected pts (HR 2.7, p = 0.02) and pts w/ AML on presentation (HR 3.1, p &lt; 0.01). Cytopenias were worse in HCV+/MDS (mean Hgb level 8.2 vs 9.4 g/dl, p = 0.04; mean plt count 64 vs 139 10 3 /µL, p = 0.03). Average IPSS-R score was higher in HCV+/MDS pts (5.5 vs 3.8, p = 0.02). IDH1 mutation was more prevalent in HCV+/MDS (25% vs 2%, p &lt; 0.01). Differences in age between HCV+/MDS and HCV-/MDS were non-significant (mean 64 vs 69 respectively, p = 0.2). Male-to-female ratio was higher in HCV+/MDS but difference was non-significant (2.3 vs 0.9, p = 0.2). Interestingly, high HCV viral load and cirrhosis did not correlate with poor surv in the HCV+/MDS grp, suggesting deleterious effect occurs even in early stages of HCV infection. Conclusions: Our analysis suggests that chronic HCV infection strongly correlates with worse surv in UA and is associated with lower blood counts and higher IPSS-R scores at the time of diagnosis of MDS. We observed a high rate of MDS refractory to standard therapies and speculate that HCV may affect biology of the disease. Larger studies are warranted to determine the effect of HCV on surv in this population and to provide a rationale for trials of anti-HCV drugs concomitantly with MDS Tx.
TCT-52 Intravascular Imaging-guided Urgent Percutaneous Coronary Intervention for Acute Myocardial Infarction and Long-term (3 years) Prognosis: A Land Mark Analysis of J-MINUET
Authors: Hiroyuki Okura, Yoshihiko Saito, Tsunenari Soeda, Koichi Nakao, Yukio Ozaki, Kazuo Kimura, Junya Ako, Teruo Noguchi, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Takashi Morita, Wataru Shimizu, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Masaaki Uematsu, None Kazuhito Hirata, Kengo Tanabe, Yoshisato Shibata, Mafumi Owa, Kenichi Tsujita, Kunihiro Nishimura, Yoshihiro Miyamoto, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)
Safety and tolerability of FOLFIRABRAX [5-Fluourouracil (5-FU), irinotecan (IRI), and nab-paclitaxel (NP)] with genotype-guided dosing of IRI in previously untreated advanced gastrointestinal (GI) cancer patients (pts): A multicenter trial of the University of Chicago Personalized Cancer Care Consortium.
Authors: Smita Suhas Joshi, Theodore Karrison, Daniel V.T. Catenacci, Jaclyn D Peterson, Mark Zalupski, Brooke Elizabeth Phillips, Ahad Ali Sadiq, Amikar Sehdev, James Lloyd Wade, Vincent J. Picozzi, Andrea Louise Amico, Robert de Wilton Marsh, Mark Kozloff, Blase N. Polite, Hedy L. Kindler, Manish Sharma
Journal: Journal of Clinical Oncology (2018)

e16241 Background: 5-FU, IRI, and NP are active in GI cancers; the combination, FOLFIRABRAX, has not been evaluated. UGT1A1 clears SN-38, the active metabolite of IRI. UGT1A1*28 polymorphism reduces enzymatic activity and predisposes to severe IRI toxicity. Dose adjustment in pts with this allele may be warranted. Primary endpoint: dose-limiting toxicity (DLT) rate of FOLFIRABRAX with genotype-guided dosing of IRI. Secondary endpoints include objective response rates (RR) in select GI cancers. Methods: Pts with previously untreated GI cancers and ECOG performance status 0/1 received FOLFIRABRAX with prophylactic pegfilgrastim Q14 days. CT scans were obtained Q8 weeks. UGT1A1 *1/*1, *1/*28, and *28/*28 pts received initial IRI doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2400 mg/m2 over 46 hours (no bolus), leucovorin 400 mg/m2, and NP 125 mg/m2 were given IV Q14 days. DLT during cycle 1 was defined as Grade (Gr) 3/4 febrile neutropenia (FN), Gr 4 neutropenia ≥ 5 days, Gr 3/4 non-hematologic toxicity despite medical management, or treatment delay > 14 days due to toxicity. Doses were tolerable if DLT rate during cycle 1 was ≤ 35%. Enrollment of 17 pts per genotype allowed for an alpha level of 0.05 with 80% power under a sequential toxicity monitoring procedure, with 6 or fewer DLTs deemed tolerable. Results: 50 pts are evaluable for toxicity: 30 pancreatic cancer (PC), 9 biliary tract cancer (BTC), 6 gastroesophageal adenocarcinoma (GEA), 4 unknown GI primary, and 1 neuroendocrine. DLTs were observed in 5/23 (21.7%) *1/*1 pts, 1/20 (5%) *1/*28 pts, and 0/7 *28/*28 pts. DLTs were Gr 3 diarrhea (3 pts), Gr 3 nausea (2 pts), and Gr 3 FN (1 pt). RR is 12/39 (30.7%), with responses in PC (9/25 evaluable pts, 36%), GEA (3/6 pts, 50%), but not in BTC (0/8 pts). Ten pts continued therapy beyond 24 weeks. Conclusions: FOLFIRABRAX with genotype-guided dosing of IRI is tolerable in pts with advanced GI cancers and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Responses were observed in PC and GEA but not in BTC. Clinical trial information: NCT02333188.
A quantitative systems pharmacology (QSP) model to assess the action of blinatumomab in NHL patients (pts).
Authors: Theresa Yuraszeck, Derek Bartlett, Indrajeet Singh, Mike Reed, Sharan Pagano, Min Zhu
Journal: Journal of Clinical Oncology (2016)

e14511 Background: Blinatumomab is a bispecific T cell engager (BiTE) antibody construct with dual specificity for CD3+ T cells and CD19+ B cells. We developed a QSP model to explore the blinatumomab target dose and factors influencing response in pts with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods: The QSP model (PhysioPD) integrates blinatumomab pharmacokinetics and mechanism of action (MOA) with NHL pathophysiology, including dynamics of T and B cells in circulation, lymph node and bone marrow. Virtual DLBCL and FL pts, sensitive or resistant to blinatumomab treatment, were constructed using data from clinical study MT103-104 (ClinicalTrials.gov NCT00274742). Parametric sensitivity analysis was performed; target treatment dose was explored through simulation. Results: The model well described the observed clinical data and identified key drivers of response to blinatumomab: tumor doubling time, effector-to-target ratio, blinatumomab density on target B cells, drug partitioning between plasma and lymph node, and efficiency of redirected T cell lysis. It showed that ~2% of bound surface CD19 is needed to achieve a CD19-bound blinatumomab density of ~1/µm2 and to initiate T cell activation; redirected T cell lysis can occur at drug concentrations ≥ 20 pM at effective sites. In silico simulations predicted that shorter infusion durations and lower doses may be effective in sensitive pts, whereas continuous IV (cIV) infusion at either 60 µg/m2/day for ≥ 5 wks or > 70 µg/m2/day for 4 wks could be target treatments in resistant pts. Similar efficacy was predicted for daily IV bolus of 75 µg/m2/day for 3 wks if the regimen can be tolerated. The model suggested that T cell infiltration of the tumor, tumor growth rate, and the “fitness” of tumor-infiltrating lymphocytes could be biomarkers for predicting response. Conclusions: The QSP model provided novel insights into the MOA of blinatumomab and drug regimen optimization in NHL pts. It showed that antitumor efficacy was a result of the interplay among blinatumomab and its surface presentation, rate of redirected T cell lysis, malignant cell growth rate and effector-to-target cell ratio. This provided direction for enhancing efficacy.
Sonic hedgehog inhibitors: Potential targeted therapy for squamous cell carcinoma of the vulva.
Authors: Jason Yap, Raji Ganesan, Richard Fox, Christopher Dawson, Sean Kehoe
Journal: Journal of Clinical Oncology (2017)

e17035 Background: Vulval squamous cell carcinoma (VSCC) is predominantly a disease of the elderly; with three-quarters of cases occurring in those aged over 60 years. Currently, chemotherapy is only used as an adjunct to surgery in advanced disease or for palliation. Unfortunately, the treatment response of VSCC to chemotherapies is variable, and toxicity remains a major problem, rendering it unsuitable for most patients. Dysregulation of the Hedgehog (HH) pathway has been described in many cancers, and HH inhibitors are being employed for the treatment of many cancers displaying aberrant pathway activation. To this end, we set out to evaluate 1) whether the HH pathway is dysregulated in VSCC and 2) the therapeutic utility of using HH inhibitors in the treatment of VSCC. Methods: Immunohistochemical staining of HH pathway components was performed on formalin-fixed paraffin-embedded sections of a well-characterized cohort of 201 patients with primary VSCC. Expression of HH pathway proteins was then correlated with clinico-pathological data, disease recurrence and survival. A panel of VSCC-derived cell lines was examined for HH pathway activity using an HH-GLI luciferase reporter assay. The effects of HH inhibitors on the growth and viability of VSCC cell lines, alone and in combination with cisplatin, was examined by BrdU label incorporation and XTT viability assays. Results: The HH signaling pathway was found to be over-expressed in approximately 80% of VSCC cases. Moreover, patients whose tumours displayed Sonic HH (SHH) ligand overexpression were more likely to develop a local recurrence within 3 years. Two HH inhibitors, Itraconazole and LDE225, not only inhibited the growth of VSCC cell lines in a dose-dependent manner, but also sensitized cells to the genotoxic affects of Cisplatin. Conclusions: We have shown for the first time that HH pathway is overexpressed in VSCC and that SHH overexpression may serve as a useful biomarker to predict local disease recurrence. In addition, results from our laboratory studies have shown that HH inhibitors may be used as a neo-adjuvant therapy to augment the actions of chemotherapeutic agents in this disease.
The impact of age on complications, survival, and cause of death following colon cancer surgery.
Authors: Christopher Thomas Aquina, Supriya Gupta Mohile, Mohamedtaki Abdulaziz Tejani, Adan Becerra, Bradley J Hensley, Zhaomin Xu, Reza Arsalanizadeh, Francis P. Boscoe, Maria J. Schymura, Katia Noyes, John R. Monson, Fergal J Fleming
Journal: Journal of Clinical Oncology (2016)

10012 Background: Little is known regarding age-related differences in the rate and cause of death for patients beyond the 30-day postoperative period. This study analyzed the impact of age on complications, 1-year survival, and cause of death following colon cancer surgery. Methods: Patients with stage I-III colon adenocarcinoma who underwent colectomy from 2004-2011 were extracted from the New York State Cancer Registry and Statewide Planning and Research Cooperative System (SPARCS). Patients were characterized into age groups of < 65, 65-74, and ≥ 75 years old and by occurrence of a major complication. The age groups were then compared with causes of death at 1 year following surgery. Results: Of the 26,420 patients, 3.3% died within 30 days and 11.6% died within 1 year of surgery. Older age was associated with higher rates of a major complication ( < 65 = 23.3%, 65-74 = 29.9%, ≥ 75 = 38.2%). Postoperative complications significantly increased the risk of death at 1 year for all age groups ( < 65: 6.4% vs. 1.9%, p < 0.0001; 65-74: 12.8% vs. 3.8%, p < 0.0001; ≥ 75: 22.4% vs. 9.2%, p < 0.0001). Increasing age was associated with a decrease in the proportion of deaths from colon cancer with a concomitant increase in the proportion of deaths from cardiovascular disease (table). Conclusions: Perioperative complications have an impact well beyond the 30-day period and are associated with a higher risk of 1-year mortality for patients of all age groups. Nearly a quarter of all deaths in patients > 65 years old are attributed to cardiovascular disease, emphasizing the importance of cardiovascular optimization in older patients. Cause of Death Age < 65 (N = 311) (3.8%) Age 65-74 (N = 528) (8.3%) Age ≥ 75 (N = 2,215) (18.8%) Colon Cancer 131 (58.0%) 181 (45.1%) 678 (43.9%) Cardiovascular 21 (9.3%) 83 (20.7%) 429 (27.8%) Respiratory 10 (4.4%) 22 (5.5%) 106 (6.9%) Other Primary Cancer 22 (9.7%) 40 (10.0%) 111 (7.2%) Infection 6 (2.6%) 18 (4.5%) 39 (2.5%) Gastrointestinal 8 (3.5%) 13 (3.2%) 27 (1.7%) Neuropsychiatric 1 (0.4%) 5 (1.2%) 23 (1.5%) Trauma 5 (2.2%) 5 (1.2%) 18 (1.2%) Renal 2 (0.9%) 2 (0.5%) 13 (0.8%) Diabetes Mellitus 5 (2.2%) 8 (2.0%) 16 (1.0%) Other 5 (2.2%) 7 (1.8%) 16 (1.0%)