tbuckley/cabot-search huggingface dataset:
Enrollment of high-risk patients with diffuse large B-cell lymphoma in clinical trials.
Authors: Kah Poh Loh, Andrea Baran, John Hu, Carla Casulo, Paul M. Barr, Jonathan W. Friedberg, Patrick Michael Reagan
Journal: Journal of Clinical Oncology (2017)

6536 Background: Contemporary precision medicine trials in DLBCL often require real-time central pathology review for enrollment. Central review may lead to treatment delays and prevent high risk patients (pts) with aggressive presentations from enrolling onto clinical trials. We explored reasons pts with DLBCL were not enrolled on trials and the implication of non-enrollment on trial design and interpretation. Methods: We retrospectively analyzed all pts with histologic diagnosis of DLBCL or HGBL from 4/14 to 6/16 at the University of Rochester. Therapeutic trials open during this time included 3 sponsored and 2 NCTN studies. The Kaplan-Meier method was used to estimate the distribution of progression-free survival (PFS; time from start of treatment until progression/death or until the last date the patient was known to be progression free) and overall survival (OS). Results: 140 pts were identified; 22% enrolled on a trial. Reasons for non-enrollment included: 1) Protocol ineligibility (n=58); (2) Physician choice (n=24) and; 3) Patient choice (n=20). Reasons were unclear in 8 pts. Of the 24 pts who were not enrolled due to physician choice, 21 required urgent treatment secondary to symptoms or rapid progression. Compared to pts treated on trial, pts with rapid progression had higher risk clinical features (table). There was a trend towards a lower 1-year PFS rate in pts who required urgent treatment compared to those on trial (72.1% vs. 56.1%; p=0.08). There was no statistical difference in OS. Conclusions: At our institution, for patients with DLBCL meeting trial eligibility criteria, 42% required urgent chemotherapy and failed to enroll. Exclusion of these high risk patients in precision medicine trials has important implications in the interpretation and generalizability of clinical trials in DLBCL. In this curable malignancy, excluding high risk patients from trials limits the event rate, and associated power to demonstrate impact of novel therapies. [Table: see text]
Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: Results of a decision analysis.
Authors: Jin Choi, Ryan David Nipp, Angela Tramontano, Ayman Ali, Tiannan Zhan, Chung Yin Kong, Pari Pandharipande, Emily Dowling, Cristina Ferrone, Theodore S. Hong, Deborah Schrag, Carlos Fernandez-del Castillo, David P. Ryan, Chin Hur
Journal: Journal of Clinical Oncology (2017)

4117 Background: With the advent of more effective therapies for metastatic pancreatic ductal adenocarcinoma (PDAC), efforts to incorporate these agents, such as FOLFIRINOX, into the neoadjuvant setting are increasing. However, the efficacy and cost-effectiveness of using neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced PDAC are unknown. We performed a decision analysis to assess the value of neoadjuvant FOLFIRINOX versus upfront surgery and adjuvant therapy. Methods: We developed a mathematical simulation model to evaluate the efficacy and cost-effectiveness of neoadjuvant FOLFIRINOX compared to upfront surgery and adjuvant therapy. We used published and institutional data as inputs to inform model development. Model outcomes included overall and disease-free survival, net benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. We used deterministic and probabilistic sensitivity analyses to explore the uncertainty of model assumptions. Results: Model estimated median overall survival (29 vs 23 months) and disease-free survival (14 vs 13 months) were better for neoadjuvant strategy compared with upfront surgery. Neoadjuvant strategy resulted in an additional 0.68 life-years gained, or 0.57 QALYs, at a cost of $59,000/QALY gained. Sensitivity analysis found that cancer recurrence rates affected model results the most. Our findings were otherwise robust with respect to changes in other model parameters, including chemotherapy toxicity, surgical complications and cancer mortality. Probabilistic sensitivity analyses showed that neoadjuvant strategy was cost-effective 80% of the time with a willingness-to-pay threshold of $100,000/QALY. Conclusions: Our model results demonstrate that neoadjuvant strategy is preferable to upfront surgery for patients with borderline resectable or locally advanced PDAC from both an efficacy and cost-effectiveness standpoint. Additional clinical data are needed to further define the long-term effectiveness of neoadjuvant FOLFIRINOX to confirm our results.
Phase II trial of AZD1775 in combination with carboplatin and paclitaxel in stage IV squamous cell lung cancer (sqNSCLC): Preliminary results.
Authors: Jhanelle Elaine Gray, Tawee Tanvetyanon, Ben C. Creelan, Scott Joseph Antonia, Eric B. Haura, Charles C. Williams, Raheel Yaseen, Michael J. Schell, Robert Godin, Uwe Rix, Alvaro Monteiro
Journal: Journal of Clinical Oncology (2017)

e20672 Background: WEE1, a dual serine/threonine and tyrosine kinase involved in regulation of the G2/M cell cycle checkpoint, is an essential component for proper DNA damage response. In combination with platinum agents, the inhibition of WEE1 is expected to lead to unstable DNA replication structures, inability to repair DNA damage, loss of G2/M arrest and ultimately mitotic catastrophe. In NSCLC cell lines, we previously demonstrated that cisplatin exhibited enhanced effects in combination with AZD1775 (a WEE1 inhibitor). This trial tests AZD1775 combined with a platinum doublet in patients with sqNSCLC. Methods: In this single-arm phase II trial, patients with stage IV sqNSCLC receive intravenous (IV) carboplatin AUC 5, IV paclitaxel 175 mg/m 2 , and oral AZD1775 225 mg twice/day for 2.5 days every 21 days for 4-6 cycles followed by maintenance AZD1775 at the same doses. Antiemetics prior to each dose of AZD1775 are mandatory. The primary endpoint is response rate per RECIST v1.1, with overall and progression-free survival as secondary endpoints. Archival tissue specimens are collected for correlative analyses of p53, PAXIP1, and WEE1. Results: Interim analysis of the 15 patients [3/15 (20%) female] enrolled through 11/2016 show 14/15 (93%) were ECOG 1, and 1/9/5 (7%/60%/33%) were never/former/current smokers. The most frequent adverse events of any grade were diarrhea (53%), nausea (40%), and vomiting (33%). The 2 most common grade 3-4 adverse events were neutropenia (13%) and fatigue (20%). No patients required treatment discontinuation due to toxicity. Of the 10 patients evaluable for response, 3 (30%) had confirmed partial responses (PR), 1 (10%) had unconfirmed PR, 5 (50%) had stable disease (SD), and 1 (10%) had progressive disease for a disease control rate of 90%. In those with SD, tumors regressed by -15%, -22%, -23%, -26% and -28% at first scan. Conclusions: AZD1775 combined with carboplatin and paclitaxel is tolerable and demonstrates promising activity in advanced sqNSCLC patients. Nausea and vomiting are manageable with antiemetics. The study continues to enroll. Correlative biomarker analyses of the tissue are planned. More mature data will be presented. Clinical trial information: NCT02513563.
TCT-106 Are Outcomes Following CABG for Left Main Disease Improving Over the Last Decade? A Propensity-Matched Analysis From the EXCEL and SYNTAX Randomized Trials
Authors: Patrick Serruys, Rodrigo Modolo, Taku Asano, Ply Chichareon, Ovidiu Dressler, Aaron Crowley, Ori Ben-Yehuda, John Puskas, David Taggart, A. Pieter Kappetein, Joseph Sabik, Yoshinobu Onuma, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Validation of a financial toxicity (FT) grading system.
Authors: Jonas A. De Souza, Kristen Wroblewski, Ellie Proussaloglou, Laura Nicholson, Andrew Hantel, Yichen Wang
Journal: Journal of Clinical Oncology (2017)

6615 Background: FT is an important adverse event (AE) that should be objectively measured in clinical practice. We previously developed an evidence-based FT grading system based on differences in HRQoL, analogous to the NCI-Common Terminology Criteria for Adverse Events (grade 1, mild AE; grade 2, moderate AE; grade 3, severe AE ,de Souza et al - ASCO 2015). We aimed to validate this grading system using a new sample of cancer patients (pts) and report its association with bankruptcy. Methods: FT was assessed by the COST (COmprehensive Score for financial Toxicity) in 2 sets of cancer pts. In the previously reported Development Set (DS), gradations of FT were determined by ROC analyses based on conventions for clinically meaningful small (0.2), medium (0.5) and large (0.8) effect sizes (e.s.) for independent FACT-G differences attributable to FT in pts with Stage IV cancers on chemotherapy. In the Validation Set (VS), differences in HRQoL and the odds ratio for a pt to have declared bankruptcy after the cancer diagnosis were assessed in a larger cohort of cancer pts on chemotherapy. Results: The grading system was developed in 888 cancer pts with cancer (233 pts in the DS and 655 in the VS). In the DS, ROC analyses produced 4 FT grades (G): G0, no FT, COST ≥26 (99 pts, 42%); G1, mild FT: ≥ 14-26 (71 pts, 31%); G2, moderate FT: &gt; 0-14 (58 pts, 25%); and G3, severe FT: COST = 0 (5 pts, 2%). Applying the FT grading to the 655 pts in VS, we had: G0, 146 pts (22%); G1, 281 (43%); G2, 215 (33%); and G3, 13 (2%). The decreases in FACT-G HRQoL measured in e.s. per FT grading in comparison with G0 were small for G1: -0.4 (95%CI: -0.6 – -0.25); large for G2: -0.9 (95%CI: -1.1 – -0.7); and even larger for G3: -1.5 (95%CI: -2.0 – -0.9), all with p &lt; 0.001. In the VS, 23 pts (4%) had declared bankruptcy after their cancer diagnosis. Compared to FT G0, the odds of having declared bankruptcy were 8.6 (95%CI: 1.1 – 67, p = 0.04) times higher for pts with FT G2, and 29 times higher (95% CI: 2.4 – 355, p = 0.008) for those with G3 FT. Conclusions: We developed a FT grading system anchored on independent differences in HRQoL. We applied the system in a different set of cancer pts and it retained its validity. We also found an larger incidence of bankruptcy after the cancer diagnosis in higher grades of FT, adding to the grading’s meaningful use.
Delivery of meaningful cancer care: Evaluating benefit and cost of cancer therapies using ASCO and ESMO frameworks.
Authors: Joseph Del Paggio, Richard Sullivan, Deborah Schrag, Wilma M Hopman, Biju Azariah, C S. Pramesh, Ian Tannock, Christopher M. Booth
Journal: Journal of Clinical Oncology (2017)

6609 Background: ASCO and ESMO have developed frameworks to evaluate the benefit of cancer therapies. Here, we apply the frameworks to a cohort of contemporary randomized controlled trials (RCTs) to explore agreement and to evaluate the relationship between treatment benefit and cost. Methods: Characteristic and outcome data from RCTs evaluating systemic therapies in non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer (CRC), and pancreatic cancer published and cited in PubMed between 2011-2015 were abstracted. Trial endpoints were evaluated using ASCO and ESMO frameworks. Cohen’s kappa statistic was calculated to determine agreement between the two frameworks, using the median ASCO score as a benefit threshold. Differences in monthly drug cost between RCT experimental and control arms were derived from 2016 average wholesale prices. Analyses included Pearson chi-square tests, Fisher’s Exact tests, independent samples t-tests, and Pearson correlation to assess the association between continuous variables. Results: Fifty percent (136/271) of published RCTs favoured the experimental arm; scoring rubrics were applicable to 109 RCTs (39% NSCLC, 33% breast, 23% CRC, 5% pancreas). ASCO scores ranged from 2 to 72; median score was 25. Thirty seven percent (40/109) of RCTs met benefit thresholds using the ESMO framework. Agreement between frameworks was fair at best (κ = 0.28, p = 0.002). When stratified by treatment intent (19 curative, 90 palliative RCTs), agreement remained poor (κ = 0.23, p = 0.115; κ = 0.34, p &lt; 0.001). Major differences leading to limited agreement includes the relative weights each framework places on HR, endpoints, and toxicity/QOL analysis. Smaller RCT sample size was the only trial characteristic associated with higher ASCO scores (p = 0.015). Among the 100 RCTs for whom drug costing data were available, there was no association between ASCO benefit score and monthly drug costs (r = -0.12, p = 0.22); those meeting ESMO thresholds had a lower mean drug cost than those who did not (p = 0.046). Conclusions: There is only fair correlation between ASCO and ESMO clinical benefit frameworks. Drug costs are not associated with ESMO/ASCO measures of magnitude of clinical benefit.
Comparative assessment of hypofractionated radiation therapy and standard treatment in patients with prostate cancer.
Authors: Mieszko Bialas, Violetta Pankowska, Joanna Bondos, Krzysztof Roszkowski
Journal: Journal of Clinical Oncology (2016)

e16616 Background: A comparative analysis of treatment efficacy was conducted in a group of 774 patients diagnosed with prostate cancer (cT1b-T3b, N0, M0, PSA ≤ 40), divided into six sub-groups, depending on the treatment method, between 2007 and 2010. Methods: All the patients were treated with radiotherapy (EBRT) with 15-MeV photons, 24-hour interval between 2 irradiation exposures, 5 days per week. All the patients received neoadjuvant, concurrent, and adjuvant TAD. Group I: 45 patients, total dose 60 Gy /3.0 Gy/ 20 fr. Group II: 161 patients, total dose 65 Gy /2.6 Gy/ 25 fr. Group III: 49 patients, total dose 67.6 Gy /2.6 Gy/ 26 fr. Group IV: 92 patients, total dose 70.2 Gy /2.6 Gy/ 27 fr. Group V: 385 patients, total dose 74 Gy / 2.0 Gy/ 37 fr. Group VI: 42 patients, total dose 76 Gy / 2.0 gy/ 38 fr. Results: Within 5 years, the Prostate Cancer Specific Overall Survival for each group was: 97.6%, 89.3%, 93.5%, 96.7%, 90.2% and 95.4%, respectively; the Biochemical Disease Free Survival 82.4%, 68.2%, 73.8%, 81.2%, 68.8% and 79.3%, respectively; Distant metastases occurred in 4 patients (8.9%); 11 (6.8%); 4 (8.2%); 7 (7.6%); 16 (4.2%) and 1 (2.9%), respectively. Treatment toxicity was slightly higher in a group of patients treated with higher fractionated doses, yet acceptable for both the patient and the physician. Conclusions: Hypofractionated radiation therapy (60 Gy /3.0 Gy/ 20 fr.) is an effective and safe method of irradiation of locally advanced prostate cancer. The short duration of treatment (4 weeks) can allow a safe application of dose radiation with no significant increase in severe toxicity.
Is Time From Last Hospitalization for Heart Failure to Placement of a Primary Prevention Implantable Cardioverter-Defibrillator Associated With Patient Outcomes?
Authors: Andrew P. Ambrosy, Craig S. Parzynski, Daniel J. Friedman, Marat Fudim, Adrian F. Hernandez, Gregg C. Fonarow, Frederick A. Masoudi, Sana M. Al-Khatib
Journal: Circulation (2018)

Landmark studies have demonstrated the safety and efficacy of implantable cardioverter-defibrillators (ICDs) in selected stable ambulatory patients with heart failure (HF) with a reduced ejection fraction receiving optimal medical therapy. It is not known whether a recent hospitalization for HF before ICD placement is associated with subsequent outcomes.
Erythropoietin and hepatocellular carcinoma: What is patients survival outcome?
Authors: Reham Abdel-Wahab, Manal Hassan, Sahin Lacin, Ahmed S Shalaby, Vahid Afshar-Kharghan, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2017)

e15660 Background: Erythropoietin (Epo) is a glycoprotein that stimulates cell proliferation and angiogenesis. Both, hypoxia and anemia are triggering factors that induce Epo overproduction. Although, previous studies reported that Epo induces angiogenesis in hepatocellular cancer (HCC), the relationship between Epo and HCC remains unclear .Our study aims to assess Epo level in HCC patients and evaluate its prognostic roles. Methods: We enrolled 766 HCC patients from MD Anderson Cancer Center Between 2001 and 2014. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. Based on the plasma level of Epo, we classified our patients into two groups: group 1 (N = 407) had normal serum level ( &lt; 20mIU/ml) and group 2 (N = 359) had higher level (≥20mIU/ml). Median overall survival (OS) was estimated by kaplan meier curve and log rank test. We used multivariate hazard ratio (HR) and 95% Confidence interval (CI) to determine the independent effect of Epo on the prognosis of HCC patients. Results: Univariate analysis showed that higher level of Epo had a statistically significant association to a higher Child Pugh Score (CTP), and an advanced stage in Barcelona clinic liver cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Median OS and 95%CI was 16.1 months (12.7 – 19.4) in group 1 compared to 11.4 months (8.6 – 14.3) in group 2 ( P&lt; .0001). The same significant difference was achieved among HCC patients with cirrhosis ( P = .005) and without cirrhosis ( P= .002). The estimated multivariate HR and 95%CI for elevated Epo level was 1.4 (1.04 – 1.9) (P = .03) in the absence of cirrhosis, while it was 0.97 (0.79 – 1.2) (P = .8) in the presence of cirrhosis after adjustment for several confounding factors. Conclusions: Abnormal Epo level in the plasma is significantly associated with a worse clinico-pathological characteristics and a shorter OS. Previous studies showed that HCC stimulates erythrocytosis and increases Epo production. Although, our study concluded that Epo is an independent prognostic factor among non-cirrhotic HCC patients only. Future studies are warranted to understand the mechanistic pathways of Epo effect in HCC patients and its variation in the presence and absence of cirrhosis.
Survival of patients with advanced solid tumors who receive treatment in community based oncology group practices is comparable to randomized controlled trials (RCT).
Authors: Rudolf Weide, Geothy Chakupurakal, Stefan Feiten, Vera Friesenhahn, Kristina Kleboth, Hubert Koeppler, Julia Lutschkin, Jörg Thomalla, Christoph van Roye, Oswald Burkhard, Marcel Reiser, Peter Ehscheidt, Jochen Heymanns
Journal: Journal of Clinical Oncology (2018)

e18770 Background: RCT are not transferable to routine care due to necessary inclusion and exclusion criteria. Thus data are needed that reflect treatment reality in routine care to decide whether results and treatment recommendations from RCT can be transferred into routine care. Treatment outcome (overall survival) should be compared between RCT and
Abstract 15009: Assessment of Myocardial Adaptation by Speckle Tracking Echocardiography and Clinical Outcome After Isolated Mitral Surgery in Patients With Chronic Mitral Regurgitation
Authors: Zisis Dimitriadis, Thomas Pühler, Olaf Oldenburg, Hazem Omran, Lisa K Wolf, Lech Paluszkiewicz, Kavous Hakim-Meibodi, Cornelia Piper, Dieter Horstkotte, Jan Gummert, Lothar Faber
Journal: Circulation (2016)

Introduction: The risk of left ventricular (LV) functional maladaptation after surgery for isolated MR is poorly defined. We aimed to evaluate LV contractile function using two-dimensional global s...
MCL-1 expression of non-small cell lung cancer as a prognostic factor and MCL-1 as a promising target for gene therapy.
Authors: Takayuki Nakano, Dage Liu, Nariyasu Nakashima, Hiroyasu Yokomise, Kazuhito Nii, Tetsuhiko Go, Shintaro Tarumi, Natsumi Matsuura, Sung soo Chang, Atsushi Fujiwara, Yoshiyuki Kakehi
Journal: Journal of Clinical Oncology (2018)

e24236 Background: MCL-1 is an important member in the pro-survival Bcl-2 family, plays a critical role in multidrug resistance. We investigated the significance for MCL-1 expression of non- small cell lung cancer (NSCLC) and the effect of inhibition of MCL-1 gene with siRNA (si-MCL-1) in NSCLC cells. Methods: Tumor tissues from 80 patients underwent R0 resection with NSCLC without any neoadjuvant therapy were analyzed. The intratumoral expressions of MCL-1 and Ki-67 were evaluated with immunohistochemistry in the tumor nucleus. Apoptotic index (AI) was defined as number of apoptotic cells, detected by TUNEL. Subsequently, we tested two MCL-1 overexpressing lung cancer cells, adenocarcinoma cell H358 and squamous carcinoma cell RERF, were used. Real-time RT-PCR was performed to evaluate gene expressions. The siRNA targeting MCL-1 (si-MCL-1) was transfected into cells. MTT assay was used to evaluate the cell viability and IC50. Results: The percentage of MCL-1 positive tumor nucleus varied greatly (median = 25.0%; mean±SD = 26.8±20.9%). A sample was classified as MCL-1 high tumor if > 25% of the nucleus in the tumor exhibited positive stainings. Among 80 patients with NSCLCs, 36(45.0%) were MCL-1 high status. The 5-year survival rate for patients with MCL-1 high tumors was significantly worse than that for patients with MCL-1 low tumors (68.3% vs. 93.1%, p = 0.0057). Regarding to the tumor proliferation, the Ki-67 index was significantly higher in the MCL-1 high tumor than that in MCL-1 low tumor (19.7±16.3% vs. 8.4±11.1%, p = 0.005). There was no significant relation between the AI and MCL-1 status. Si-MCL-1 effectively downregulated the MCL-1 expression (up to 80% at day 3) and significantly reduced the percentage of viable cells in these two cell lines as detected by MTT assay (p < 0.001, respectively). Multivariate analysis demonstrated MCl-1 expression to be a significant prognostic factor (hazard ratio, 4.069; p = 0.0405) Conclusions: MCL-1 expression is prognostic factor in NSCLC. The si-MCL-1 has an anti-proliferation effect against MCL-1-overexpressing NSCLC cells. MCL-1 appear to be a promising target for gene therapy.