tbuckley/cabot-search huggingface dataset:
The effects of very low doses of chemotherapeutic drugs on endothelial cells.
Authors: Fatma Gizem Sonugur, Muge Ocal, Cansu Babahan, Samira Abdi Abgarmi, Fikri Icli, Hakan Akbulut
Journal: Journal of Clinical Oncology (2017)

e23014 Background: Angiogenesis is one of the key processes leading tumor progression and metastasis. Conventional chemotherapeutic drugs are usually cytotoxic to tumor cells at the therapeutic doses. The lowered doses of those drugs have been shown to induce apoptosis in endothelial cells and implemented as metronomic schedule in the clinic. We aimed to study the effects of very low doses of chemotherapeutic drugs on endothelial cell functions and gene and protein expression of pro-and anti-angiogenic factors. Methods: We first determined the IC50 doses of 5-fluorouracil, irinotecan, and oxaliplatin in a human umbilical endothelial cell line (HUVEC). Then we’ve tested the effects of the IC50, -1log, -2log and -3log of IC50 doses on endothelial cell migration and tube formation. We’ve also studied the effects of the assigned doses on expression levels of the genes VEGF-A, VEGFR2, PDGF-B, angiopoietin-2 (Ang-2), endothelin-1 (End-1), thrombospondin-1 (Tbs-1), iNOS, eNOS by real-time PCR, protein secretion levels of VEGF-A, PDGF-BB, Ang-2, End-1 and Tbs-1 by ELISA and nitrate/nitrite production by a colorimetric assay. Results: The IC50 dose levels of 5-FU, irinotecan, and oxaliplatin were 9,2 μM, 9,8 μM and 11,8 μM, respectively. We found that all the -1log, -2log and -3log of IC50 doses of the drugs tested in the study significantly decreased the migration capacity of the HUVEC cells. However, no significant changes were observed in tube formation of endothelial cells. Likewise, the expression levels of pro-angiogenic genes including Ang-2, iNOS, eNOS, PDGF-B and VEGF-A were significantly decreased at the same doses of the drugs. Accordingly, the levels of Tbs-1 were significantly increased at all 3 dose levels of the drugs. The most efficacious doses of the drugs to decrease NO levels in HUVEC cells were -1logIC50 for 5-FU, -2logIC50 for irinotecan and -3logIC50 for oxaliplatin. Conclusions: In conclusion, our results suggest that 5-FU, irinotecan, and oxaliplatin could decrease the pro-angiogenic and increase anti-angiogenic factor production in endothelial cells at the doses much lower than the usual metronomic schedules and warrant further research in animal models and clinical trials as an anti-angiogenic treatment modality.
Patient experiences with low-dose CT lung cancer screening in an integrated healthcare system.
Authors: Joshua A. Roth, Susan Brandzel, Karen Wernli
Journal: Journal of Clinical Oncology (2016)

e18042 Background: Low-dose CT (LDCT) lung cancer screening of heavy smokers ( ≥ 30 pack-year history, age 55-80) gained widespread insurance coverage in the U.S. in 2015. The objective of this study was to use qualitative inquiry to understand patient experiences with the early use of LDCT lung cancer screening in a major healthcare system. Methods: We conducted a semi-structured telephone-based qualitative evaluation of patient experiences with LDCT screening at Group Health, an integrated healthcare system in Washington State. Participants met U.S. Preventive Services Task Force screening criteria and had Lung-RADS negative results. Trained survey staff contacted a total of 25 randomly selected eligible participants and completed 20 interviews (80% response rate) in fall of 2015. The 30-minute interviews were recorded, transcribed, and independently evaluated by three study investigators using Glaserian methods to identify major themes. Results: Among the 20 participants, mean age was 68 years, 40% were male, 90% were Caucasian, 35% were current smokers, and mean time from screening to interview was 55 days. The majority of participants (80%) were unaware of lung cancer screening before it was offered by their physician. Most participants (75%) were able to name a screening benefit (‘early detection’ was most common). A minority (45%) were able to name a screening harm (radiation exposure was most common).Nearly all (95%) described the experience of the screening scan as “easy”, “quick”, and/or “painless”. Few participants (45%) reported receiving a detailed explanation to supplement telephone/online results. 80% stated intention to be screened again next year. Conclusions: Among participants who recently received LDCT screening in an integrated healthcare system, screening was frequently introduced by physicians, screening benefits were considered more often than harms, the screening exam was often described as easy, and most intended to remain adherent to screening guidelines. The issue of false-positives was rarely raised. Our findings provide insights to help stakeholders to understand patient perspectives on LDCT screening, and can be used to inform efforts to improve lung cancer screening processes.
Histological features and survival in NSCLC patients treated with surgery with curative intention.
Authors: Nuria Cárdenas Quesada, Ana Laura Ortega Granados, Bélgica Márquez Lobo, María Carmen Vivo Molina, Carmen Rosa Garrido, Inmaculada Piedra Fernández, Sebastián Sevilla López, Antonio Bravo Cerro, Celia Lacárcel Bautista, Gerardo Pérez Chica, José Nieto Serrano, Francisco José García Verdejo, Natalia Luque Caro, David Fernández Garay, Miguel Angel Moreno Jimenez, Yessica Plata Fernández, María Isabel Núñez Torres, Pedro Sánchez Rovira
Journal: Journal of Clinical Oncology (2017)

e20080 Background: New classification of adenocarcinomas and better typing of histological characteristics of lung tumors leads us to wonder if these histological data could have a prognostic repercussion in the NSCLC who were into curative intent surgery Methods: We followed 95 patients with stage I-III NSCLC underwent surgery in a 4 year period (2010-2013), until August 2016. Most patients were male (82%), smokers (90%, 44% exsmokers and 56% active , median age at diagnosis was 64 years, 47% had a previous COPD, and 52% were diagnosed of NSCLC without any symptom of lung cancer. 79% patients had lobectomy or sleeve resection, and 21% pneumonectomy. 47% patients had adjuvant chemotherapy (CT) Results: We found no significant differences in age of diagnosis between men (64.95 y) and women (58.65 y) (p = 0.066) nor in survival time. Median disease-free survival (DFS) is 15 months and overall survival (OS) is 49 months. If we analyze DFS from surgery to the first relapse, most happen at first 2 years (80%). By stage, OS at 5 years is 73% in stage IA, 58% stage IB, 46% stage IIA, 36% stage IIB, 24% for stage IIIA and 9% in IIIB. We had 49% adenocarcinomas (most frequent, 53%, acinar subtype), and 51% squamous, and we found no significant difference between histologies, nor between subtypes. But there was a significant difference between DFS, favorable for mild lymphoid response (20 months) with respect to moderate or intense response (11 months) Conclusions: We found that we are underusing adjuvant CT. In our group there is no difference in survival for tumor size, linfovascular invasion, histological grade or histology, but we found a better DFS for mild lymphoid response vs moderate-intense pattern. This finding may be related to the antitumor activity of the immune system, and we want to validate it prospectively, and its relationship with subsequent immune therapy response.
Treating recurrent tuboovarian carcinoma with multiple lines of bevacizumab-based therapy: Feasibility and effectiveness in the clinical routine.
Authors: Christian M. Kurbacher, Valérie Kallage, A. Tabea Kurbacher, Susanne Herz, Alexander Schott, Gabriele Kolberg, Claudia Schweitzer, Jutta A. Kurbacher
Journal: Journal of Clinical Oncology (2018)

e17541 Background: Retreatment with bevacizumab (Bev) in tuboovarian carcinoma (TOC) has not been intensively investigated so far. This retrospective study sought to yield more concise data on both feasibility and effectiveness of multiple lines of Bev-based systemic treatment (Tx) in patients (pts) with recurrent TOC. Methods: A total of 90 pts with recurrent TOC who did not qualify for recruitment into a controlled trial receiving at least one line of Bev-based therapy were included. 37 (41.1%) pts had one, 20 (22.2%) had two, 13 (14.4%) had three and 20 had (22.2%) 4-9 lines of Bev. A total of 225 courses of Bev-based treatment were administered: 58 (25.8%) as monotherapy (Bev), 63 (28.0%) in combination with conventional Ctx (Bev+cCtx), and 104 (46.2%) in combination with metronomic Ctx (Bev+mCtx). Time to progression (TTP) was calculated from the start of each Bev-based Tx until progression, overall survival (OS) was calculated from the start of the first Bev-based Tx until death from any reason or loss to follow-up. Adverse effects in regard to Bev Tx were scored according to CTCAE vs 4.02. Results: Toxicities G3-4 were rare and generally manageable with hypertension in 2.2%, bowel obstruction in 0.9%, small bowel perforation in 0.9%, nephrotic syndrome in 0.4% and infection seen in 1.3% of treatments. Both TTP and OS did not differ between different types of Tx. TTP: Bev, 5.4 months (ms); Bv+cCtx, 6.1 ms; Bev+mCtx, 6.3 ms. OS: Bev, 28.6 ms, Bev+cCtx, 31 ms; B+mCtx, 21.4 ms. TTP was comparable between one and multiple lines of Bev: one line, 6.6 ms; two lines, 6.3 ms, three lines 5.9 ms, and ≥4 lines 3.7 ms (p = 0.130). However, OS increased significantly with the number of Bev-based lines of Tx: one line, 8.8 ms; two lines, 16.8 ms; three lines 25.4 ms; ≥4 lines, 36.6 ms (p = 0.0001). Conclusions: Our results demonstrate that retreatment with Bev is safe and effective in a real-world population of pts with recurrent TOC. The incidence of severe side effects was low and did not increase by the line of Bev-based Tx. However, the number of Bev-based lines had a significant impact on overall survival. Thus, rechallenge with Bev may be a valuable option in the treatment of recurrent TOC.
The MetAction project: Biomarker-directed molecularly matched therapy for end-stage cancer implemented in clinical practice.
Authors: Anne Hansen Ree, Kjersti Flatmark, Vigdis Nygaard, Daniel Heinrich, Kjetil Boye, Svein Dueland, Vegard Nygaard, Eivind Hovig, Klaus Beiske, Marius Lund-Iversen, Vivi A Flørenes, Christin Johansen, Inger Riise Bergheim, Menaka Sathermugathevan, Sigve Nakken, Gry A Geitvik, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Hege G Russnes, Gunhild M Mælandsmo
Journal: Journal of Clinical Oncology (2017)

e14033 Background: The MetAction project consists of two clinical trial phases. The completed first phase established the required diagnostic infrastructure, implemented security-approved systems for handling of sensitive information, educated the entire project staff within the context of tumor boards, and estimated costs of the initiative within public health services. The endeavor enabled expedite and safe mutation profiling of metastatic tumors in order to offer biomarker-based treatment with molecularly matched medication to patients with end-stage cancer, as reported in Ree et al., ESMO Open 2017. The ongoing second trial phase investigates the feasibility of the established MetAction pipeline in clinical practice. Methods: An eligible patient has end-stage metastatic disease from a solid cancer. Metastatic tissue is analyzed by DNA sequencing (Ion Oncomine™ Comprehensive Panel), where called variants are filtered prior to assessment and prioritization, supplemented with fluorescence in situ hybridization to cover relevant biomarkers. The Molecular Tumor Board interprets the findings within the likelihood of signaling pathway activity, and the sequential Clinical Tumor Board (CTB) may conclude on treatment with any systemic tumor-directed medication. Results: At the time of writing, 19 patients enrolled onto the second trial phase have accomplished the diagnostic procedures from sampling of metastatic tissue to CTB conclusion. Biopsy procedures were undertaken at lung or pleural sites (five cases), liver or superficial or deep peritoneal sites (13 cases), and an inguinal lymph node (one case) and did not cause adverse events. Histologic entities were 12 adenocarcinomas and one case each of squamous cell and undifferentiated carcinoma, cholangiocarcinoma, and four different sarcoma entities. Twelve patients have been found eligible for off-label use of molecularly matched therapy (inhibitor of ALK-, BRAF-, EGFR-, FGFR-, mTOR-, PARP-, or PD-1-mediated signaling). Conclusions: We will report on patient outcome (progression-free survival, overall response rate, and tolerance) to this biomarker-directed treatment in end-stage cancer. Clinical trial information: NCT02142036.
Efficacy of clofarabine and low-dose cytarabine combination for genetically high-risk acute myeloid leukemia prior to allogeneic stem cell transplantation.
Authors: Carlos Enrique Vigil, Nusrat Jahan, Oana Valeria Paun, Jennifer Weis, Kevin Heckman, Margarida De Magalhaes-Silverman, Thomas H. Carter
Journal: Journal of Clinical Oncology (2017)

e18515 Background: The outcome of genetically high risk acute myeloid leukemia (AML) patients (pts) remains poor, with a median overall survival (OS) of a few months after the failure of regimens. Long-term survival requires complete remission followed by allogeneic stem cell transplantation (ASCT).Clofarabine, a deoxyadenosine analog, at 20mg/m2 days 1-5, in combination with low-dose cytarabine (LDAC) has reported efficacy and tolerability in older newly diagnosed AML pts (Cancer 2015;121:2375). We have therefore prioritized this combination for relapsed/refractory(R/R) pts. Aims:Determine the efficacy of Clofarabine and low dose cytarabine in R/R AML pts who are eligible for ASCT. Methods: Using Holden Comprehensive Cancer Center database, we performed a retrospective chart review on 16 pts of R/R AML who were treated with Clofarabine and LDAC between January 2014 and Dec 2016. Each patient received Clofarabine 20mg/m 2 on days 1-5 IV and LDAC on days 1-10 subcutaneous. The primary endpoint was complete remission (CR) or complete remission with incomplete marrow recovery (CRi). Secondary endpoint was median OS. Results: Sixteen pts were analyzed. The median age was 58 years (range 27-78). Nine pts (56%) had AML with high risk characteristics (complex karyotype and/or presence of FLT3-ITD). Nine pts achieved either a CR or CRi. Responses were observed in 7of 9 pts with genetically high-risk features. 2 pts had mutated TP53, and both of them achieved CR. The median OS time was 13.25 months (range 3.6-19.2 months). 4 pts received ASCT after treatment combination. Conclusions: These results suggest that Clofarabine is well-tolerated and effective in the treatment of R/R AML pts, especially those with high-risk genetics. Clofarabine and LDAC could be used as a bridging therapy prior to ASCT for high-risk R/R AML pts. Future clinical trials are warranted to explore additional modifications to this combination in order to optimize therapy for this group of high-risk and heavily treated R/R AML pts.
Utility of PETCT over conventional imaging in ovarian cancer.
Authors: Sarah Cook, Don Wilson, Maral Pourghiasian, Anna Tinker
Journal: Journal of Clinical Oncology (2018)

e17522 Background: Evidence supports PETCT in nodal assessment of epithelial ovarian cancer (EOC) during staging; and investigation of recurrence, where its sensitivity and specificity is superior over conventional imaging (CI). Limited data suggests PETCT impacts EOC management in 34% to 57% of cases, including when CI has recently been performed. This study evaluated whether PETCT provides additional information over CI in EOC and if results change management. Methods: All EOC patients who underwent publicly funded PETCT at BC Cancer Agency AND recent ( < 6 weeks) CI were eligible. Medical charts were retrospectively reviewed with descriptive analysis performed. Results: Of 270 PETCT scans performed between January 2007 and September 2017, 106 had recent CI, thus were eligible. Most common PETCT indications were: 1) investigating first recurrence (30.2%), 2) assessment for secondary debulking (21.7%) and 3) investigating progression in documented relapse (19.8%). PETCT identified greater disease burden than CI in 39.6%, typically greater nodal involvement. PETCT identified lower disease burden than CI in 14.2%. However, in 77.4% of all cases, PETCT and CI had the same clinical implications. In 33.0%, management changed following PETCT from; no treatment to treatment (17.9%), adoption of a different treatment (10.4%) and from treatment to no treatment (4.7%). In the 22.6 % of cases where PETCT and CI drew different clinical implications, management changed in 41.7%. Conclusions: Overall, PETCT was relatively rarely used to investigate EOC. Although PETCT provided greater detail regarding disease burden which may be important in select cases, we found PETCT and CI often drew the same clinical implications. Thus, for the majority CI was sufficient. While treatment changes following PETCT were frequently seen, impact on true clinical outcomes is unknown. PETCT in EOC should remain individualised.
Impact of palliative care (PC) on aggressive end-of-life (EOL) care indicators among advanced cancer patients (ACPs).
Authors: Carlos Eduardo Paiva, Talita Caroline de Oliveira Valentino, Bianca Sakamoto Ribeiro Paiva
Journal: Journal of Clinical Oncology (2016)

e21505 Background: Among other aims, PC is intended to improve EOL quality of care. Our aim was to evaluate the impact of PC on aggressive EOL quality of care indicators among ACPs. Methods: In this retrospective study, a randomly selected sample of ACPs who died between 2011 and 2013 and with clinical follow-up in the last three months of life in a tertiary Brazilian Cancer Hospital was reviewed. Data were retrieved on PC referral and quality of EOL care indicators, including emergency room visits, hospitalization, intensive care unit admissions, and systemic anticancer therapy use within the last 30 days of life. A modified composite score for aggressiveness of care (mCSAC) was used (range: 0-5; the higher the score, the more aggressive the care). Early PC was defined a priori as ≥ 90 days from first PC consultation until death. We determined the association between PC evaluation and aggressiveness of care using chi-square and Kruskal-Wallis tests. Results: The median age was 62.4 yrs, the most common cancer types were gastrointestinal (30.2%), breast (12.8%) and lung (12.8%). From 563 decedents, 359 (63.8%) were referred to PC. Median time from PC consultation to death was 78 days. In the last 30 days of life, ACPs not referred to PC were more likely to receive aggressive care compared with patients consulted by PC (mCSAC = 0: 13.2% vs. 45.9%, p < 0.001). mCSAC were not different between early and late PC. However, patients later referred to PC were more likely to have ≥ 2 emergency room visits (12.5% vs. 6.5%, p = 0.055), ≥ 2 hospitalizations (17.2% vs 10.1%; P = 0.051), systemic anticancer use (14.6% vs. 7.1%, p = 0.024), and less likely to die at home (3.1% vs 11.3%; P = 0.002) compared with early PC. Median times from the last anticancer treatment until death were 41.5, 54.5, and 108 days for 'no PC', 'late PC' and 'early PC', respectively (p < 0.001). Conclusions: ACPs consulted by the PC team receive less aggressive care at the EOL compared with patients never consulted. Early PC referral seems to add further benefits.
Relationship between symptom burden and hospital length of stay (LOS) in patients with incurable cancer.
Authors: Ryan David Nipp, Areej El-Jawahri, Samantha M.C. Moran, Sara D'Arpino, Connor Johnson, Daniel Lage, Risa Wong, Yian Xiao, Harry VanDusen, William F. Pirl, Lara Traeger, Pallavi Kumar, Inga Tolin Lennes, Barbara J. Cashavelly, Holly S Martinson, Vicki A. Jackson, Joseph A. Greer, David P. Ryan, Ephraim P. Hochberg, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2016)

10123 Background: Patients with incurable cancer often require hospitalizations for symptom management, but the relationship between patients’ symptom burden and their hospital LOS is unknown. We sought to investigate symptoms as predictors of hospital LOS in patients with incurable cancer. Methods: We prospectively enrolled incurable cancer patients with unplanned hospital admissions from 9/1/2014-11/1/2015. Within the first week of admissions, we assessed symptoms using the Edmonton Symptom Assessment System (ESAS), with moderate/severe symptoms defined as scores ≥ 4 on a 0-10 scale. On 11/15/2014, we began using the Patient Health Questionnaire 4 (PHQ-4), scored categorically, to assess depression and anxiety. To identify predictors of LOS, we used linear regression, adjusting for age, gender, marital status, comorbidity, education, cancer type and time since incurable diagnosis. Results: We enrolled 751 of 913 (82%) eligible patients (mean age = 63.3 years; 378 (50%) female) who provided data for 1,088 admissions (mean LOS = 6.3 days). Depression and anxiety were reported in over one-fourth of admissions. Patients reported moderate/severe fatigue, drowsiness, poor appetite and pain in most admissions. In unadjusted analyses, depression, anxiety, pain, drowsiness, nausea, poor appetite, dyspnea and constipation predicted longer LOS. In multivariable analysis, depression and pain remained significant predictors of longer LOS, adding approximately one day to mean LOS. Conclusions: Hospitalized patients with incurable cancer experience substantial symptom burden, which correlates with their LOS. Both depression and pain predict for longer admissions. These findings will inform interventions targeting patients’ symptoms, particularly depression and pain, earlier during hospital admissions in an effort to improve care delivery and decrease LOS. Symptoms Symptom Prevalence Multivariable Model Predicting LOS N % Beta P PHQ-4 (N = 859) Depression 262 31 1.07 < 0.01 Anxiety 220 26 0.12 0.78 Moderate/Severe ESAS Symptoms (N = 1,088) Fatigue 952 88 -0.40 0.51 Drowsy 804 74 0.53 0.23 Appetite 741 68 0.06 0.88 Pain 730 67 0.97 0.01 Nausea 428 40 0.12 0.74 Dyspnea 422 39 0.31 0.39 Constipation 408 38 0.44 0.21