tbuckley/cabot-search huggingface dataset:
Safety for trifluridine/tipiracil (TAS-102) with bevacizumab combination in patients with refractory metastatic colorectal cancer in real-world clinical practice: The single-institutional experience.
Authors: Kayo Yasuda, Daisuke Kotani, Yasutoshi Kuboki, Shota Fukuoka, Hideaki Bando, Akihito Kawazoe, Yoshiaki Nakamura, Kohei Shitara, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2018)

865 Background: Trifluridine/tipiracil (TAS-102) is an oral combination therapy approved for the treatment of patients with metastatic colorectal cancer (mCRC). Phase 1/2 C-TASK FORCE study of TAS-102 plus bevacizumab for patients with refractory mCRC demonstrated a promising efficacy results with mild toxicity profile (Kuboki Y, et al. Lancet Oncology, 2017). The retrospective single-institutional study is aiming to investigate safety of TAS-102 plus bevacizumab for patients with refractory mCRC in real-world clinical practice. Methods: M CRC patients who were refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (if wild-type RAS) and consecutively received TAS-102 plus bevacizumab between January 2016 and June 2017, were analyzed. Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results: A total of 33 patients were identified for safety analysis. Patient characteristics were as follows; male/female, 19/14; median age, 59.0 (range 38-81); ECOG Performance Status of 0/1, 21/12; and All wild/ RAS mutant/ BRAF mutant/ unknown, 16/15/1/1. Six patients had received prior regorafenib. The relative dose intensities of TAS-102 and bevacizumab were 87% and 79%, respectively. Grade 3 or higher hematological and non-hematological AEs were follows; leucopenia, 33%; neutropenia, 42%; anemia, 9%; and proteinuria, 12%. There were no febrile neutropenia or treatment-related death. G-CSF was given in 8 patients (24%), while intravenous antibiotics was in one patient. There were four patients with emergency admission, and out of these, the two patients had intestinal perforation, and perianal abscess, which were regarded as treatment-associated; ultimately these AEs were fully recovered. Conclusions: Our findings suggested safety for TAS-102 plus bevacizumab combination in real-world clinical practice is consistent with those in clinical trial setting.
Abstract 17862: Dynamic Augmentation of the Left Ventricular Ejection Using Implantable Soft Robotic Device
Authors: Mossab Y Saeed, David Van Story, Christopher J Payne, Isaac Wamala, Borami Shin, Daniel Bautista-Salinas, Thomas Thalhofer, Pedro J del Nido, Conor J Walsh, Nikolay V Vasilyev
Journal: Circulation (2017)

Introduction: Despite recent technological advances, use of current mechanical circulatory support (MCS) devices often results in thromboembolic complications. Other approaches for therapy of end-s...
Mediation of MiR-30e* suppressing Bmi1 expression by tumor-associated macrophage in gastrointestinal cancer.
Authors: Hidetaka Sugihara, Takatsugu Ishimoto, Daisuke Izumi, Hiroshi Sawayama, Yu Imamura, Satoshi Ida, Shiro Iwagami, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Journal of Clinical Oncology (2014)

e15020 Background: Bmi1 is a member of the polycomb-repressive complex 1 with an essential role in maintaining chromatin silencing. The expression of Bmi1 is associated with poor prognosis of gastrointestinal cancer patients. On the other hand, tumor-associated macrophages (TAMs) contribute to tumor progression by producing various mediators. This study was performed to identify the TAMs-mediated regulation of Bmi1 expression in gastrointestinal cancers. Methods: The relationship between the expression of Bmi1 and TAMs was assessed by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and 3D sphere culture. miRNAs microarray in gastric cancer cell co-cultured with macrophages was conducted, and Bmi1 expression and miR-30e* expression were analyzed by qRT-PCR and luciferase assay. Results: We revealed the positive relationship between with tumor-infiltrating macrophages and Bmi1 expression in cancer cells. We showed co-culture with TAMs triggered Bmi1 expression in cancer cell lines and enhanced sphere formation ability. Based on microRNA screening analysis and in silico microRNA search, we focused on miR-30e* that could regulate Bmi1 expression. Western blot analysis revealed significantly reduced Bmi1 protein levels in high Bmi1 expressing cancer cell lines transfected with miR-30e* mimics compared with controls, and increased levels in low Bmi1 expressing cancer cell lines cells transfected with miR-30e* inhibitors compared with controls. And Bmi1 was a direct target for miR-30e* by interactions with the putative miR-30e* binding sites. MiR-30e* expression was down-regulated in tumor region compared with in non-tumor one. Furthermore Bmi1 expression was inverse correlation with miR-30e* expression. Conclusions: TAMs may cause increased Bmi1 expression through miR-30e* suppression, leading to tumor progression.
Utilization of triage phone encounters and after hours appointments in the COME HOME program.
Authors: Jennifer Webster, Laura Stevens, Teresa Waters, Barbara L. McAneny
Journal: Journal of Clinical Oncology (2014)

e17673 Background: Health care costs are an increasing burden for payers, providers and for patients. There is growing evidence that patient centered medical homes (PCMH) can be successful in achieving the Triple Aim of improved quality, lower cost, and higher patient satisfaction in primary care settings. We have developed a related Oncology Medical Home (OMH) model that provides patients with enhanced access by extending practice hours into the evenings and weekends, active disease management via symptom specific triage pathways and evidence-based clinical pathways. We have implemented this model at seven independent community oncology practices in six states. Methods: Implementation was rolling, with the first practice going live September 14, 2012, an additional three practices launching January 1, 2013 and the remaining three practices on April 1, 2013. The initial roll out included triage pathways for symptom management and a gradual roll out of extended hours services in the evenings and weekends. By October 6, 2013, all seven practices were offering at least two hours of extended service on weeknights and at least four hours on the weekends. Results: From the beginning of the grant, through the end of 2013, there were 22,650 calls to the triage lines at the COME HOME practices, resulting in 6,360 triage nursing phone encounters and 1,836 face to face encounters. System utilization varied from 1.1 calls/month/1,000 active patients to 7.6 calls/month/1,000 active patients. Maximum triage nurse capacity seems to be four calls per day, per nurse, with a median phone encounter length of 45 minutes. Conclusions: Patients who utilized COME HOME services tended to be younger (64.2 vs 68.9 years of age, p=0.013), were more likely female (68.1% of COME HOME patients are female vs. 58.9% of the non-COME HOME patients, p<0.001) and had been diagnosed more recently (79.9% of COME HOME patients had been diagnosed within the preceding 6 months vs. 53.1% of the non-COME HOME patients, p<0.001). There was not a significant difference in race or ethnicity. The final outcomes analysis will include ED visit rate, inpatient hospitalization rate, all-cause mortality and total episodic cost of care.
Social determinants and disparities in quality radiation therapy in early-stage breast cancer.
Authors: Alliric Isaac Willis, Adam Davey
Journal: Journal of Clinical Oncology (2014)

e17562 Background: Radiation therapy receipt and quality duration (QRTD, # days RT start to end) after breast conserving surgery (BCS) are associated with optimal outcomes in early-stage breast cancer (ESBC). Our aim was to identify social determinants and disparities in RT receipt and duration among women with ESBC. Methods: The National Cancer Database was queried for women <70 years, stage I or II BC, with BCS in years 2004-2009. Outcomes were QRTD (28-49 days), prolonged RTD (PRTD ≥50 days) or no RT given (NORT). Multinomial logistic regression was performed for predictors: ethnicity, age years, insurance, zip code-based median income and education [% adults in zip who are high school grads (HG)]. Relative risk ratios (RRR) use QRTD as base outcome and referents: White, age 60-69, private insurance, >$46,000 ($46K), ≤71% HG. Results: 27,390 patients analyzed. Demographics: White 79.1%, Black 12.0%, Hispanic 4.6%, Asian/Pacific Islander (API) 4.4%. Age: <50, 27.8%; 50-59, 35.5%; 60-69, 36.7%. Income: <$30K, 10.2%; $30K-<35K, 15.2%; $35K-<46K, 26.2%; ≥$46K, 48.4%. Education: ≤71% HG, 14.8%; 71.1-80% HG, 19.7%; 80.1-86% HG, 22.4%; >86% HG, 43.1%. Insurance: Private 18.9%, managed care 56.8%, Medicaid 6.2%, Medicare 5.8%, Medicare w/ supplement 12.3%. Outcomes: QRTD 51.7%, PRTD 31.0%, NORT 17.3%. Predictors of increased RRR for PRTD: Black [RRR 1.163 (CI 1.035-1.307), P=.011], ages <50 [1.243 (1.146-1.348), P<.001] and 50-59 [1.116 (1.033-1.206), P=.006], <$30K [1.351 (1.125-1.623), P=.001], Medicaid [1.304 (1.115-1.526), P=.001], Medicare [1.235 (1.061-1.437), P=.006]. API had decreased RRR for PRTD [.819 (.676-.991), P=.040]. Increased RRR for NORT: Black [1.363 (1.162-1.598), P<.001], Hispanic [1.619 (1.231-2.130), P=.001], API [1.352 (1.079-1.696), P=.009], and Medicare [1.385 (1.137-1.688), P=.001]. Decreased RRR for NORT: HG 80.1-86% [.729 (.575-.925), P=.009], and HG >86% [.677 (.533-.857), P=.001], income $35-<46K [.802 (.676-.953), P=.012]. Conclusions: This national study elucidates the prevalence of NORT, the substantial prevalence of PRTD, and the impact of ethnicity, age, and social status. Future research on PRTD may identify associations with persistent disparities in outcomes.
Chemoradiation with or without nimotuzumab in locally advanced esophageal cancer (LAEC): A randomized phase II study (NICE trial).
Authors: Gilberto Castro, Nils G Skare, Carlos J C Andrade, J.G.M. Segalla, Sergio Jobim De Azevedo, Ismael D C G Silva, Fauze Maluf Filho, Lucienne Pereira Del Grossi Neusquen, Cassiano Ricardo de Oliveira Berto
Journal: Journal of Clinical Oncology (2014)

4078 Background: Chemoradiation is the standard therapy for patients (pts) with inoperable LAEC. We sought to assess the safety and activity of chemoradiation combined with nimotuzumab, a humanized antibody against the epidermal growth factor receptor, in LAEC. Methods: We randomized pts with inoperable LAEC, previously untreated, and with no distant metastases 1:1 to chemoradiation (cisplatin 75 mg/m2 D1, and 5-FU 1 g/m2/d CI D1-4, both for four 28-day cycles, combined with external-beam radiation 50.4 Gy) or the same chemoradiation plus nimotuzumab 200 mg IV, once weekly for 26 wks. The primary endpoint was endoscopic complete response (eCR, defined as absence of elevated, vegetative or exophytic lesions), whereas combined eCR/pathologic CR (pCR), overall survival (OS), quality of life and safety were secondary endpoints. Results: We enrolled 107 pts, 82% male, mean age 59 y. 100 pts (93%) had squamous cell carcinoma (SCC); performance status (ECOG-PS) was 0/1 in 34%/60% of cases. The relative dose intensity of chemotherapy and radiotherapy was nearly identical in both arms, and the median number of nimotuzumab doses was 24. We performed post-treatment endoscopy in 67 pts, in 60 of whom with biopsy. In the ITT population, eCR rates with vs. without nimotuzumab were 47.2% vs. 33.3% (p=0.17), whereas combined eCR/pCR rates were 62.3% vs. 37.0% (p=0.02). In a median follow-up of 14.7 mo., the hazard ratio (HR) for OS was 0.68 (95%CI 0.44-1.07; p=0.09), with a median OS of 15.9 vs. 11.5 months, respectively. In an unplanned subgroup analyses, the HR for OS in pts with ECOG-PS 0 was 0.32 (95%CI 0.12-0.85; p=0.02). We found no significant differences in quality of life between arms. Toxicity was manageable in both arms, with no significant differences in adverse events or serious adverse events. Conclusions: Combined chemoradiation and nimotuzumab is safe in pts with LAEC, and appears to increase the combined eCR/pCR rate and to impact favorably on OS. This is a promising regimen in pts with locally advanced esophageal SCC, and a phase III trial is under consideration. Clinical trial information: NCT01249352.
Longitudinal diffusion MRI in PCNSL treated with methotrexate, rituximab, and temozolomide (MRT).
Authors: Vyshak Chandra, Yangming Ou, Jayashree Kalpathy-Cramer, John Evans, Sara Sprinkhuizen, Tracy Batchelor, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2014)

8579 Background: High-dose methotrexate (HD-MTX) is the backbone of therapy for PCNSL but induction chemotherapy can also include temozolomide and rituximab (MRT). We evaluated baseline tumor ADC values and change in ADC values as markers of response. Methods: After receiving IRB consent, we retrospectively evaluated PCNSL patients treated at our hospital with MRT. Patients were treated in 28-day induction cycles: HD-MTX (8g/m2- dose adjusted based on creatinine clearance) on days 1 and 15; rituximab (375 mg/m2) weekly for 6 doses; and temozolomide (150-200 mg/m2) on days 7-11 of each cycle for a goal of 12 cycles. HD-MTX was continued every 2 weeks until complete response (CR). Brain MRI was done after every other MTX treatment to assess response. Volume of contrast enhancing tumor and median tumor ADC values at baseline, 1 month, and 2 months after treatment began was measured. Results: From August 2003 to September 2013, 42 patients received MRT as first-line therapy at the time of initial diagnosis and 10 received MRT as salvage therapy at first or second recurrence. The median age of all patients was 63 (range 49-84). With first-line MRT therapy, there were 34 CRs (median cycles to CR = 4), 5 PRs, 2 PD’s, and 1 nonevaluable for response. With salvage MRT therapy, there were 6 CRs (median cycles to CR = 4), and 4 PR’s. After a median follow-up of 23.5 months in the first-line group and 51.6 months in the relapse group, 14 patients have progressed and 6 died (1 from an unrelated heart attack). After analysis of 22 imaging datasets, 18/22 patients saw a reduction of >70% in enhancing volume from baseline to month 2 of treatment. Shorter time to CR was associated with lower baseline median tumor ADC (p=0.035). There was no statistically significant association in baseline or change in ADC and PFS or OS. Conclusions: MRT resulted in a promising early response rate. Lower baseline tumor ADC was associated with shorter time to CR so may be a helpful biomarker. Lower ADC may reflect hypercellular, rapidly proliferating tumor that is more sensitive to chemotherapy. The lack of association with tumor ADC and survival was likely because of the few progression/death events in our dataset and longer term follow-up is needed with more imaging time points.
Tumor microenvironment-dependent heterogeneity and cytogenetic abnormality of tumor endothelial cells in human colorectal carcinoma.
Authors: Elisabeth Naschberger, Vera S. Schellerer, Ute Schaal, Sandra Grenz, Andrea Liebl, Maximilian Jenzer, Nathalie Britzen-Laurent, Arif B. Ekici, Ludger Klein-Hitpass, Bastian Keck, Sven Wach, Tilman T. Rau, Susanne Merkel, Roland S. Croner, Werner Hohenberger, Michael Stürzl
Journal: Journal of Clinical Oncology (2014)

e22012 Background: Tumor endothelial cells (TECs) were considered to be genetically stable and despite being different from normal endothelial cells (NECs) to exhibit a relatively homogeneous phenotype within a distinct tumor. It is not known whether TECs from human solid tumors exhibit the same genotype as NECs and whether phenotypic heterogeneity may be induced in TECs by intratumoral variations of the microenvironment. Methods: TECs and corresponding NECs were isolated from untreated CRC tumors. Cell purity was confirmed by analysis of CD31/vWF expression (>99%). Transcriptomes of TECs were evaluated by GeneChip arrays and GSEA/SAM analysis. Quality controls included senescence and microvessel density measurements. Copy number variations (CNVs) in TECs were analyzed by CGH analysis (n=1) and SNP arrays (n=6) in comparison to NECs (CGH n=1, SNP n=6) and PBMCs (SNP n=2) of the same donors. Results: We have shown that a Th1-like tumor micromilieu is associated with reduced angiogenic activity of the tumor and a significantly increased survival of the patients in CRC (Naschberger, Int J Cancer 2008). Significantly different transcriptomes (205 up-, 97 downregulated genes, FDR<20%, fc ≥2-fold) were detected between TECs from tumors with (n=8) and without (n=8) a Th1-like angiostatic microenvironment. The target genes were preferentially regulated by soluble factors associated with the specific tumor microenvironments and were not identified due to differential cell age or microvessel density between the two groups. Functional classification of the target genes revealed accordance with the tumor microenvironment they were isolated from. Moreover, TECs showed tumor-specific CNVs as compared to corresponding NECs and PBMCs. Conclusions: These results show for the first time that TECs isolated from a human solid tumor exhibit tumor-specific genetic aberrations and microenvironment dependent transcriptome changes stably maintained in culture. TECs may respond differentially to anti-angiogenic treatment according to the microenvironment induced alterations. Therefore, these findings will be of relevance for the optimization of anti-angiogenic treatment in CRC.
Disparities among older women with de novo stage IV breast cancer treated with trastuzumab from 1999 to 2009.
Authors: Ines Maria Vaz Duarte Luis, Nancy Lynn Keating, Nancy U. Lin, Joyce Lii, Eric P. Winer, Rachel A. Freedman
Journal: Journal of Clinical Oncology (2014)

646 Background: To characterize trastuzumab utilization and survival by race/ethnicity in older women with de novo stage IV breast cancer who were treated with trastuzumab. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients (pts) ≥66 years with de novo stage IV BC diagnosed between 1999-2009 who received trastuzumab. We examined treatment patterns, including time to trastuzumab initiation. We then examined survival time by race/ethnicity using Kaplan-Meier methods and Cox proportional hazards models, adjusting for clinical, sociodemographic, and treatment characteristics. Results: Among 579 pts, 452 (78.1%) were non-Hispanic white and 76 (13.1%) were non-Hispanic black. Overall, death was recorded among 418 women (72.2%); the median survival time was 2.4 years (95% CI: 2.1-2.7) and there was a 22% survival rate at 5 years. Compared with white women, black women had a significantly increased adjusted hazard of death (hazard ratio=1.4, 95% CI: 1.04-2.0). Survival for all pts improved over time (Table 1). Overall the odds of early (within 6 months from diagnosis) vs. later (after 6 months) trastuzumab initiation did not differ by race/ethnicity (OR=1.0, 95% CI: 0.5-1.7), but when stratified by hormone receptor (HR) receptor status, white (vblack) pts with HR negative disease were more likely to have initiated trastuzumab within 6 months (OR: 2.8, 95% CI: 1.4-5.6). Conclusions: Although survival times among pts receiving trastuzumab for de novo metastatic disease improved over time, we identified racial/ethnic disparities in survival and differences in patterns of care. Additional analyses will include examination of trastuzumab duration and associations with survival. Characteristic Hazard of death (95%CI) Race Non-Hispanic White 1.0 Non-Hispanic Black 1.4 ( 1.04- 2.0) Hispanic-Other/Unknown 1.0 (0.7-1.6) Year of diagnosis 1999-2001 1.0 2002-2005 0.7 (0.5-0.9) 2006-2009 0.6 (0.4-0.8) HR Positive 1.0 Negative 1.3 (1.03-1.6) Initiation of trastuzumab Within 6 months 1.0 After 6 months 1.6 (1.2-2.0) * Adjusting for all variables in Table and age, race, SEER region, location of residence, socioeconomic status, marital status, comorbidity score, grade.
Association of angiosarcoma/lymphangiosarcoma with rosacea.
Authors: Frank E. Johnson, Stephen P Olsen, Scott Fosko, Eric Armbrecht, M Yadira Hurley, Nathalie Zeitouni
Journal: Journal of Clinical Oncology (2014)

e21511 Background: Case reports have suggested that rosacea (and particularly rhinophyma, a consequence of rosacea), might cause angiosarcoma (AS) or lymphangiosarcoma (LAS) in rosacea-affected sites. As in Stewart-Treves syndrome, AS/LAS in rosacea-affected sites features lymphatic obstruction, edema, prominent varicose veins, and other features of chronic inflammation. No reports aiming to quantitatively establish a causal relationship have been published, to our knowledge. Recent evidence points to an aberrant innate immune response, mediated by altered endogenous polypeptides known as cathelicidins, as a primary pathogenic event in rosacea. Cathelicidins are proinflammatory and vasoactive agents that cause the prominent inflammation in rosacea. It is thus plausible that rosacea is an authentic risk factor for AS and LAS. We sought to carry out a population-based analysis to confirm or refute an association between rosacea and sarcoma. Methods: IRB approval was obtained. We abstracted pertinent data from the records of patients with head and neck sarcomas of all subtypes. We requested and received data from Roswell Park Cancer Institute and calculated the crude odds ratio for this classic case-control study. Results: We received record abstractions from 228 patients spanning years 1969-2012. We excluded the 30 cases of Kaposi’s sarcoma, Ewing’s sarcoma, sarcomas not in the head and neck region, and carcinomas. We included 198 soft tissue and skeletal cases with head and neck sarcomas of all subtypes. The calculated odds ratio was 11.9 (95% confidence interval 1.05, 136.0). Thus, the odds of having a history of rosacea were 11.9 times greater than for subjects with AS or LAS than for all other soft tissue or skeletal sarcomas. Conclusions: Ours is the first analysis designed to detect an association between rosacea and head and neck angiosarcoma and lymphangiosarcoma, as far as we know. An association was demonstrated, but the confidence interval is wide. We seek access to additional large data sets suitable for analysis. Rosacea No rosacea Total Angiosarcoma or lymphangiosarcoma cases 2 28 30 All other soft tissue or skeletal sarcoma cases 1 167 168 Total 3* 195 198 * All three were in sites where rosacea commonly occurs.