tbuckley/cabot-search huggingface dataset:
Clinician perspectives on electronic health records, communication, and patient safety across diverse medical oncology practices.
Authors: Minal R Patel, Christopher Ryan Friese, Kari Mendelsohn-Victor, Alex J Fauer, Bidisha Ghosh, Arthi Ramakrishnan, Louise Bedard, Jennifer J. Griggs, Milisa Manojlovich
Journal: Journal of Clinical Oncology (2018)

6549 Background: We know little about clinicians’ documentation and communication challenges and how these might affect the safety of ambulatory oncology care. The present study investigated variation in electronic health record (EHR) capability and satisfaction, clinician communication, and clinicians’ actions that enable a safety culture. Methods: We distributed paper questionnaires to nurses and prescribers (physicians, nurse practitioners, and physician assistants) in 28 practices that participate in a statewide quality improvement collaborative. Previously-validated measures included the Safety Organizing Scale (SOS) that reflects actions consistent with a safety culture, satisfaction with clinic technology, and satisfaction with communication with other clinicians. We constructed an index to reflect EHR capability (1 = all paper to 5 = all electronic). Linear regression models (with robust standard errors to account for clustering) were used to examine the relationship between covariates of interest and the SOS, adjusting for practice size and ownership. Results: The survey response rate was 68%. The mean (SD) of the SOS was 5.3(1.1), with a practice-level range of 4.9-5.4 (based on 7-point scale where higher scores reflect increased safety actions). Higher satisfaction with technology and clinician communication was significantly associated with increased SOS scores, while increased EHR capability was associated with lower SOS scores. Prescribers reported lower SOS scores than nurses (see table). Conclusions: Practices vary in their performance of patient safety actions. Supporting clinicians to integrate increased technology is a promising target for interventions. The inverse relationship between EHR capability and safety suggests that technology distracts clinicians from attending to patient safety. Improvement strategies may benefit from tailoring by clinician type to account for observed differences. Variable β(SE) 95% CI Technology satisfaction 0.67(0.1)*** 0.5,0.8 Clinician communication satisfaction 0.29(0.1)*** 0.1,0.4 EHR capability index -0.14(0.03)*** -0.2,-0.1 Prescriber (vs. nurse) -0.38 (0.1)*** -0.7,-0.1 *** p < .001
How to manage ctDNA monitoring with EGFR inhibitors?
Authors: Jerome Solassol, Fanny Leenhardt, Julie Vendrell, Xavier Quantin
Journal: Journal of Clinical Oncology (2018)

e21202 Background: Plasma cell-free DNA (cfDNA) may be a useful tool in order to monitor tumor response and relapse in EGFR mutated patients who are under TKI treatments. Controlling plasma circulating tumor DNA (ctDNA) may help us to adequately tailor the treatments and predict response to the treatment. Our study was conducted to assess the usefulness of this strategy for patients treated initially by TKI (tyrosin kinase inhibitor) of first or second generation, and subsequently by Osimertinib. Methods: cfDNA and CTscan were performed on all patients along the treatment course by TKI therapy (erlotinib, afatinib, osimertinib) and was assessed at each cycle of treatment. Twelve patients had a record comprising enough data (ctDNA) to study the complementary role of liquid biopsy. EGFR mutation detecting is investigated by droplet digital PCR (ddPCR. In this study, we focused on exon 19 deletion, T790M and L858R. Results: All patients had a first or second line of targeted therapy EGFR until the detection of T790m by ctDNA led to a change of treatment for osimertinib. Biological progression with T790m ctDNA quantification was revealed after 10 months of treatment which correlates a radiologic progression one month later, at the 11th month. During the osimertinib treatment, partial response is associated with a decrease of the ctDNA (T790M and exon 19 or L858R) detection in plasma for 100% of the cases. Disease progression has been viewed on imagery at 8.4 month compared to biological monitoring (11.5 month for T790m and 8.3 month for other EGFR mutation). Conclusions: Clinical progression is closely related with T790M detection in patients treated with first or second generation TKI in this selected population. However, monitoring the level of only T790M cannot predict progression in patients under Osimertinib. The lack of usefulness of ctDNA T790M to predict treatment failure may reflect the fact that the mechanisms of tumour escape are not related to T790M. ctDNA monitoring may help to evaluate therapeutic response under target therapy TKI and detect prematurely tumor progression under first and second line therapy erlotinib or afatinib. We need to know if modifying the TKI early could enhance the prognosis.
Hydrolytic activity in tissues of tumors of the upper jaw.
Authors: Marina Engibaryan, Oleg Ivanovich Kit, Elena M. Frantsiyants, Yulia V. Ulianova, Viktoriya L. Volkova, Irina V. Aedinova, Natalia A. Chertova, Mamuka V. Bauzhadze
Journal: Journal of Clinical Oncology (2018)

e18096 Background: Indices of the protease activity are used as markers of invasion and metastatic potential of the tumor, and determination of the activity of acid and alkaline phosphatases is used in clinical practice as diagnostic tests. The total activity of proteolytic enzymes and their inhibitors was determined in tumor tissue to predict the growth tumors and assess their malignancy. Methods: We determined antitrypsic activity (ATA) and the activity of cathepsin D, acid-stable inhibitors (ASI) and alkaline and acidic phosphatases in 20 samples of intact tissues of the upper jaw and tissues of squamous cell carcinoma of the upper jaw. Results: The cathepsin D activity in tumor tissues was 1.6 times higher than in intact tissues. The activity of ASI and ATA in tumors before treatment was similar to the levels in intact tissues. Ratios of cathepsin D/ATA and cathepsin D/ASI exceeded the values in intact tissues on average by 1.6 times indicating disorders in the processes of limited proteolysis. The acidic phosphatase activity was 28.1% higher, and that of alkaline phosphatase – 42.9% lower, compared to intact tissues. The acidic phosphatase/alkaline phosphatase ratio in tumors was 2.2 times higher than in intact tissues. Conclusions: The results demonstrated the tumor cell overexpression and secretion of proteases involved in the degradation of the matrix and histohematic barriers and invasion of tumor cells. The activity of proteases can be considered as a diagnostic/prognostic criterion in assessing the degree of tumor malignancy, and excessive phosphorylation in tumor cells provided an increase in the invasive potential of tumor cells. Thus, parameters of activity of the hydrolytic system in tissues of the tumors of the upper jaw indicated a high degree of tumor malignancy and its significant invasive potential.
Indentification of a CTC-based gene expression signature predicting resistance to abiraterone and enzalutamide in mCRPC.
Authors: Todd Matthew Morgan, Jae-Seung Chung, Yugang Wang, James Henderson, Udit Singhal, Yuanyuan Qiao, Alexander Zaslavsky, Daniel H Hovelson, Ajjai Shivaram Alva, Felix Yi-Chung Feng, Ganesh S. Palapattu, Russell S. Taichman, Arul M. Chinnaiyan, Scott A. Tomlins
Journal: Journal of Clinical Oncology (2017)

5072 Background: Circulating tumor cell (CTC)-based detection of AR-V7 has been shown to be one potential marker for predicting response to 2nd generation androgen receptor (AR) therapies. However, the apparent rarity of AR-V7 positivity is indicative of the importance of other drivers of resistance in this setting. We sought to utilize a multiplex gene expression platform for assessing CTCs in order to determine other predictive biomarkers of response. Methods: Whole blood (~5mL) was obtained from 37 patients with mCRPC starting enzalutamide (n=16) or abiraterone (n=21). CTCs were isolated using anti-EpCAM-conjugated magnetic beads. Following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 92 prostate cancer-related genes. Samples were considered CTC-positive based on a previously established set of epithelial markers. We identified genes associated with PSA and radioclinical progression free survival (PFS) using Cox regression analysis. Muli-gene models were tested using ROC analysis. Results: We identified 20 patients (54%) with detectable CTCs, and patients were followed for a median of 10 months (IQR 3.9-19.4 months). Seven genes were associated with both PSA PFS and radioclinical PFS in the Cox analyses (Table). Combing the 7 genes into a single model gave AUC values of 0.88 for PSA PFS and 0.89 for radioclinical PFS. In comparison, the AR-V7-only model resulted in AUC values of 0.65 and 0.66. Conclusions: We identified seven prostate cancer-related genes that can be determined from CTCs and appear to predict short time to progression in men with mCRPC being treated with 2nd generation hormonal therapies. While this is a small cohort and prospective validation is needed, these findings highlight the potential role for this approach in helping guide therapy choice. Gene PSA PFS Radioclinical PFS HR 95% CI p Value HR 95% CI p Value AR 3.61 1.06-12.29 0.040 4.91 1.38-17.48 0.014 AR-V7 4.35 1.27-14.91 0.019 5.43 1.52-19.35 0.009 ANXA2 3.53 1.06-11.70 0.039 7.90 1.83-34.05 0.006 SOX2 3.70 1.11-12.25 0.032 4.81 1.35-17.05 0.015 PSCA 4.35 1.27-14.91 0.019 5.43 1.52-19.36 0.009 PSA 7.12 1.63-31.03 0.009 6.37 1.75-23.07 0.005 WNT5B 5.40 1.54-18.95 0.008 4.78 1.40-16.25 0.012
The comparison of <sup>18</sup>F-alfatide PET/CT and <sup>18</sup>F-FDG PET/CT in predicting chemoradiotherapy sensitivity in patients with advanced non-small cell lung cancer.
Authors: Xiaohui Luan, Yong Huang, Ning Liu, Song Gao, Jinsong Zheng, Qingxi Yu, Shuqiang Zhao, Chen Hu, Jinming Yu, Shuanghu Yuan
Journal: Journal of Clinical Oncology (2017)

e20558 Background: Both 18 F-alfatide positron emission tomography/computed tomography(PET/CT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT were potential in predicting thearapy sensitivity, in this study,we recruited patients with advanced NSCLC to detect and compare the potential predictive vaue of them on the CRT sensitivity of patients with advanced non-small cell lung cancer (NSCLC). Methods: According to the design of Natural Science Foundation ofChina (NSFC) 81372413, twenty-four patients with advanced NSCLC accepted 18 F-alfatide PET/CT before radiotherapy (T1), another thirty-nine patients underwent 18 F-FDG PET/CT at both T1 and during CRT (40Gy of radiotherapy, T2). Logistic regression analyse was used to evaluate the correlations between PET parameters and CRT sensitivity providing an odds ratio (OR), 95% confidence interval (CI) and p value. Propensity score matching (PSM) approach was used to control confounding. Results: Logistic regression analyse showed that Karnofsky Performance Status (KPS) score was correlative with CRT sensitivity. After PSM, controlling KPS scores, twenty-four pairs of patients were matched. The results showed that SUV max obtained from baseline 18 F-alfatide PET/CT was associated with CRT sensitivity in both univariate and multivariable logistic regression analysis (OR: 0.532, 95% CI: 0.305–0.927, p = 0.026; OR:0.376, 95% CI: 0.165-0.860, p = 0.021), but the baseline 18 F-FDG PET/CT was not. Univariate analyses showed that the percent change in MTV of 18 F-FDG PET/CT between T1 and T2 was correlative with CRTsensitivity (OR: 1.039, 95% CI: 1.003-1.077, p = 0.036). When patients’ KPS score was considered simultaneously, it was still related to CRT sensitivity (OR:1.038, 95% CI: 1.001-1.077, p = 0.045). Conclusions: 18 F-alfatidePET/CT may be better than 18 F-FDG PET/CT in predicting CRT sensitivity, and 18 F-FDG PET/CT is potential in monitoring the tumor response to CRT in patients with advanced NSCLC.
Localized orbital adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation and rituximab: a single institute experience.
Authors: Maria Chaudhry, Allan Louie Cruz, Vera Malkovska
Journal: Journal of Clinical Oncology (2016)

e19034 Background: Standard treatment for patients with orbital mucosa-associated lymphoid tissue (MALT) lymphoma is not established due to paucity of prospective trials, small numbers of patients in published studies, heterogeneity of treatment and short follow up. Local radiation therapy provides excellent disease control but delayed relapses are common. At our institute, we aimed to further decrease the risk of delayed relapse by combining rituximab with radiation. Rituximab is active in marginal zone lymphoma and it may sensitize lymphoma cells to radiation and treat occult systemic disease. Methods: We retrospectively reviewed records of 10 consecutive evaluable patients treated between 1997 and 2015. All had biopsy-proven MALT lymphoma. Median age was 64 years (range 37-92 years). Seven were female and 3 were male. Median duration of symptoms before diagnosis was 6.0 months (range 2 - 24 months). Patients underwent staging including full body PET with diagnostic CT scan and MRI of the orbits. Nine had stage 1E disease and one had stage IIE disease. All patients received radiation, median dose is 36.00 Gy (range 30.60-39.60 Gy). Six received rituximab 375 mg/m2 weekly for 4 doses starting at least one week before radiation. Results: Median follow up duration was 5.8 years (range 0.2-8.0 years). Only one of 10 patients died (from transformation to aggressive large cell lymphoma). Nine patients had complete remission and one had partial remission. One of 6 patients treated with rituximab and radiation and 3 of 4 treated with radiation alone relapsed. Median time to relapse was 4.8 years (range 3.2-11.0 years). All relapsing patients received second line treatment. One patient developed cataract needing surgery and another developed retinopathy requiring steroid injections. Conclusions: In this series of primary orbital MALT lymphoma, radiation combined with rituximab was well tolerated and associated with long-term disease-free survival as compared to radiation alone. This combination therapy should be evaluated in prospective studies with more than 5 year follow up to capture late relapse.
Efficacy and tolerability of first-line abiraterone + prednisone (ABI) versus enzalutamide (ENZ) for metastatic castration-resistant prostate cancer (mCRPC) in men ≥ 80 years: A retrospective cohort study.
Authors: Daniel Khalaf, Kevin Zou, Werner J. Struss, Bernhard J. Eigl, Christian K. Kollmannsberger, Daygen L. Finch, Krista Noonan, Joanna Vergidis, Muhammad Zulfiqar, Kim N. Chi
Journal: Journal of Clinical Oncology (2018)

5051 Background: ABI and ENZ are first-line treatment options for mCRPC with comparable efficacy. In men ≥ 75 years, ABI and ENZ are associated with higher rates of adverse events. For very elderly patients (pts), the efficacy and tolerability of ABI and ENZ have not been directly compared. Methods: Retrospective analysis in pts ≥ 80 years of age who received ABI or ENZ for first-line treatment of mCRPC between July 2009 and September 2016 at the BC Cancer Agency. Medical records were reviewed for clinical characteristics and outcomes including PSA response rate (PSA50) (decrease of ≥50% from baseline), time to first progression (TTP) (PSA, radiographic or clinical progression) and overall survival (OS). Results: There were 106 pts in the ABI cohort and 104 in the ENZ cohort. Baseline characteristics were well balanced including median age 85 years (IQR 83-88); median Charlson Comorbidity Index (CCI) 7 (IQR 7-8); hemoglobin (HB) < 130 in 75%; ECOG PS 0-1 in 60%; serum alkaline phosphatase (ALP)/LDH > upper limit of normal (ULN) in 32%/35% and bone/lung/liver metastasis in 86%/10%/6%. Time from start of androgen deprivation therapy to castration-resistance (TTCR) was < 12 months (m) in 16% vs 29% for ABI vs ENZ (p = 0.031). PSA50 was 43.4 % for ABI vs 77.9 % for ENZ (p < 0.001, Χ2) and median TTP was 4.7 m vs 8.0 m (HR 1.52, 95% CI 1.12-2.08). On multivariable analysis, factors associated with TTP were: treatment arm ABI vs ENZ (HR 1.76, 95% CI 1.27-2.45), ALP > ULN (HR 1.89, 95% CI 1.34-2.68), HB < 130 (HR 1.61, 95% CI 1.13-2.30), CCI > 7 (HR 1.57, 95% CI 1.13-2.19) and TTCR > 12 months (HR 1.73, 95% CI 1.18-2.55). At least one dose reduction due to toxicity was required for 7.5% of pts for ABI vs 29.8% for ENZ (P˂0.001, Χ2). For pts in the ENZ cohort who had a dose reduction, the median TTP was 11.8 m vs 6.2 m for those without (HR 0.65, 95% CI 0.40-1.08). Median OS was 13.2 m for ABI vs 18.7 m for ENZ (HR 1.20, 95% CI 0.89-1.63). Conclusions: In this very elderly cohort, the PSA50 and TTP were superior for the ENZ cohort compared to the ABI cohort despite more dose reductions in the ENZ cohort. The retrospective nature of the analysis is a limitation of this study.
High cost-related medication non-adherence among diabetic cancer patients.
Authors: James Zhang, Jonas A. De Souza, David Meltzer
Journal: Journal of Clinical Oncology (2016)

e18022 Background: Diabetes mellitus (DM) has been reported to be associated with an increased risk of cancer. DM cancer patients are particularly susceptible to cost-related medication non-adherence (CRN) because of multiple morbidities and concurrent treatments. We aimed to assess the prevalence and risk factors for CRN among DM cancer patients using a nationally representative sample. Methods: We used 2010 data from the Health and Retirement Study. We extracted patients with previously diagnosed cancer, excluding minor skin cancer, with or without diabetes. A multivariate logistic regression analysis was performed to assess the relationship between CRN and age, type of insurance, the number of hospitalizations and functional limitations including Activities of Daily Living (ADLs). Results: Among 2,953 cancer patients, 789 (26.7%) had DM. Within this group, 101 (12.8%) reported CRN, compared to 192 (8.9%) among cancer patients without DM (p < 0.01). Those younger than 65 years old with DM and cancer were 2.25 times (p < 0.01) more likely to report CRN than older patients. Compared to those with Medicare-only insurance coverage, those with no health insurance and those with Medicare-Medicaid dual eligibility were 2.08 times (p = 0.02) and 3.23 times (p = 0.06) more likely to report CRN, respectively. Those with Medicaid only or private insurance were 0.79 (p = 0.04) and 0.43 times (p = 0.04) less likely to report CRN. After controlling for insurance type and socio-demographic factors, our multivariate logistic regression analysis found that respondents with 1, 2, and 3 or more ADL limitations were 1.31 times (p < 0.01), 1.25 times (p = 0.08), and 2.27 times (p < 0.01) more likely to report CRN than those without any ADL limitations. Respondents with 2 hospitalizations were 1.05 times (p = 0.03) more likely to report CRN than those without any hospitalizations. Conclusions: DM cancer patients had high CRN and sicker DM patients were even more likely to report CRN. Dual-eligible patients and patients without health insurance were at very high risk of CRN. These results suggest an opportunity to decrease CRN and improve outcomes by expanding insurance coverage and improving insurance benefit design for cancer patients.
Chronic myeloid leukemia among veterans from 2006-2015: Trends in utilization of tyrosine kinase inhibitors.
Authors: Catherine Chanfreau, Kristine E. Lynch, Jiwon Chang, Daniel Jacob Becker, Daphne Ruth Friedman, Donna Rivera, Scott DuVall, Julie Ann Lynch
Journal: Journal of Clinical Oncology (2018)

e18832 Background: Oral tyrosine kinase inhibitors (TKIs) have substantially improved treatment and outcomes of chronic myeloid leukemia (CML) since Imatinib approval in 2001. Treatment options for newly diagnosed adult patients expanded with the addition of newer-generation TKIs (NGTKIs), Dasatinib and Nilotinib, as first-line therapies. We examined CML treatment with the three TKIs across the Department of Veterans Affairs (VA) in the period 2006-2015. Methods: We identified Veterans newly diagnosed with CML in 2006-2015 using national data from the VA cancer registry and Corporate Data Warehouse. We collected patient characteristics at diagnosis, including age, race, rural/urban residence, clinical comorbidities, and TKI prescriptions through December 2015. We examined patient characteristics associated with treatments using logistic regression, and overall survival using a Cox proportional hazards model. Results: Among 468 patients diagnosed with CML, 436 (93%) initiated TKI treatment with a median time of 21 days from diagnosis (interquartile range, 8 to 89 days). Patients not treated with TKI were significantly older than those treated (mean age, 74years (SD 10) versus 64 (SD 14), P < 0.001). In 2010-2015 Imatinib remained the common first-line TKI (average % of first TKI prescriptions per year: 79%, [95%CI, 75%-83%]; versus Dasatinib, 13% [9%-16%], and Nilotinib, 8% [6%-12%]). Controlling for diagnosis year, the use of NGTKIs versus Imatinib was less likely with older age (OR 0.97 [95%CI, 0.95-0.99]), higher comorbidity (OR 0.47 [95%CI, 0.26-0.88] and among patients in rural areas (OR 0.38 [95%CI, 0.17-0.83]; we observed no difference by patient race. Adjusting for age, race and comorbidities, overall survival at three years with use of any TKI was 91%, with no differences by treatment with Imatinib versus NGTKIs. Conclusions: Most Veterans diagnosed with CML in 2009-2015 received treatment with TKIs, and Imatinib remained the predominant TKI used at VA for CML. Lower use of Dasatinib and Nilotinib among older patients and those with more comorbidities warrant further study, as evidence is growing that they present the same safety profile than Imatinib but may lead to faster and deeper response.
Cost-effectiveness of new therapies in first-line treatment of advanced melanoma for BRAF mutant patients from a Brazilian private payer perspective.
Authors: Joao PsDN Lima, Christina Matteucci, Graziela Bernardino, Ana Paula Oliveira, Daniela Galdeano Maia
Journal: Journal of Clinical Oncology (2018)

e21556 Background: The objective of this study was to assess the cost-effectiveness of current first-line therapies (nivolumab, ipilimumab+nivolumab, dabrafenib+trametinib, vemurafenib+cobimetinib) for BRAF mutant advanced melanoma patients from a Brazilian private payer perspective. All therapies are approved by the Brazilian Health authority. Methods: A CEA using a 3-state partitioned survival structure was developed to estimate accrued life years, total drug acquisition, follow-up and toxicity costs over a lifetime horizon (30 years). The model utilized the intent-to-treat 24-month PFS and OS data from reported 36-month follow-up from CM067 trial and a network meta-analysis, which considers time-varying hazard ratios. The model takes the perspective of a Brazilian private payer, hence no indirect costs are taken into account. Drug acquisition, administration, follow-up and adverse event costs were estimated using a micro-costing approach and prices were obtained from official Brazilian price lists–CMED, Simpro, Planserv2008 and CBHPM2015. EAs frequencies were derived from the CM067 trial and published literature. Results: All selected interventions were compared to verumabenib monotherapy and the resultant Incremental cost-effectiveness ratios were R$80,645 for nivo+ipi, R$70,463 for nivo monotherapy, R$360,909 for dabrafenib+trametinib, R$255,068 for vemurafenib+cobimetinib. In this study, the combination of nivo+ipi resulted in the greatest accrued survival with 6.111 LY over the 30-year time horizon. Furthermore, nivo+ipi, nivo monotherapy constitute cost-effective interventions when a 3-times GDP per capita threshold is considered. Conclusions: Considering a 3-times GDP per capita threshold, the survival gains brought by nivo+ipi and nivo monotherapy can be considered cost-effective options for BRAF-mutant advanced melanoma patients.