tbuckley/cabot-search huggingface dataset:
Effect of chemotherapy on EGFR mutation status in Chinese non-small cell lung cancer patients.
Authors: J. Wang, H. Bai, J. Zhao, Z. Wang, M. Zhuo, M. Wu, J. Duan, S. Wang
Journal: Journal of Clinical Oncology (2010)

e18031 Background: Somatic mutation in the region of EGFR that encoded the tyrosine kinase domain of the receptor (mainly exon 19 and 21) have been identified in non-small cell lung cancer (NSCLC) and many studies suggest that they can be used to predict responsiveness to EGFR-TKI (gefitinib and erlotinib). EGFR-TKIs are often utilized as second- and third-line therapy for the pts with advanced NSCLC. However, whether first-line chemotherapy would influence the EGFR mutation status has not been addressed. This study investigated the effects of chemotherapy on epidermal growth factor receptor mutation (mEGFR) as well as DNA concentration in Chinese NSCLC patients (pts). Methods: A total of 253 pts, consisting of 203 advanced NSCLC and 50 stage IIIa NSCLC, were included in this study. The plasma samples came from pre-first-line chemotherapy (pre-chemo) and post-two-cycle treatment (post-chemo) were collected. Meanwhile, tissues samples from pre-neoadjuvant and post-neoadjuvant chemo were also gained. EGFR mutation (mEGFR) was detected by denaturing high performance liquid chromatograph (DHPLC).The plasma DNA amount was measured by real-time PCR. Results: Among 203 pts, EGFR mutation was 36.5% (74/203) in the plasma of pre-chemo and 29.6% (60/203) in the plasma of post-chemo. Among them, 117 remained to have the same EGFR status after first-line chemotherapy (include 93 with wild-type and 24 with mutant-type EGFR), 36 switched from negative to positive and 50 had reverse matter after chemotherapy. Similar tendency of mEGFR change was observed after neoadjuvant chemotherapy (44%, 22/50, pre–neoadjuvant chemo vs. 36%, 18/50, post-neoadjuvant chemo). Further analysis for the association of mEGFR change in plasma and chemotherapy response is in the Table. The circulating DNA level altered after first-line treatment but had no correlation with chemotherapy response. Conclusions: The data indicated that chemotherapy may affect EGFR mutation status in advanced lung cancer pts, which will be validate by further study. Response to chemotherapy Item PR SD PD Total Variation of EGFR Wild-wild 19 (30%) 42 (51%) 32 (55%) 93 Wild-mutation 12 (19%) 16 (19%) 8 (14%) 36 Mutation-wild 18 (29%) 17 (21%) 15 (26%) 50 Mutation-mutation 14 (22%) 7 (9%) 3 (5%) 24 63 82 58 203 P value 0.018 No significant financial relationships to disclose.
Edmonton Symptom Assessment Scale (ESAS): Time duration of self-completion versus assisted-completion in palliative care patients—A randomized controlled trial.
Authors: Angelique Wong, Alfredo Rodriguez-Nunez, Supakarn Tayjasanant, Minjeong Park, Diane D Liu, Julio Allo, Susan Frisbee-Hume, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

67 Background: ESAS is a multidimensional assessment tool for self-reporting of symptom intensity. Unfortunately, ESAS is not used often in clinical care due to the perception that it may be time consuming. Our aim was to compare the time duration of self-completion (SC) of ESAS for the first time by patients with advanced cancer vs. assisted-completion (AC) with a health care professional (HCP). Methods: In this randomized controlled trial, patients with advanced cancer who have never completed the ESAS at MD Anderson were allocated (1:1) with a web-based system to either to self-completion of the ESAS form vs assisted completion by the research assistant. Time of completion was measured by the research assistant using a stop watch. Patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) test prior to administration of the ESAS. In the self-completion group, the nurse reviewed the responses to verify that the reported ESAS scores were correct (nurse review). Results: 127 patients were enrolled (69 patients to AC and 58 to SC). The median age was 60 years old, and median REALM score was 65. The median (IQR) time of SC alone was significantly less than AC (1.2 minutes (.7, 1.5) vs 1.82 minutes (1.3, 2.3), p = .000). With nurse review time included, the SC time increased to 1.92 minutes (p (vs. AC) = .28). Lower literacy (REALM) score was significantly associated with increased completion time (p = .007). Other demographical and clinical variables were not significantly associated with completion time. 73/127 (58%) patients reported they did not mind completing the ESAS alone or with the help of the nurse. Conclusions: The ESAS can be completed in less than 2 minutes with or without assistance by a HCP. When nurse review time was included, there was no difference in time of completion as compared to assisted completion. Our results support that regular clinical use of ESAS will have minimal impact on clinical time.
Curative versus palliative therapy for patients with colorectal cancer presenting to the emergency department.
Authors: Andy Stuart Barnett, Yiyi Chen, Zunqiu Chen, Mohamud Daya, Charles R. Thomas, Daniel Herzig
Journal: Journal of Clinical Oncology (2012)

433 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States for men and women combined, and can present emergently with symptoms such as abdominal pain, bleeding, and obstruction. Emergency presentation as the first indication of colorectal cancer is generally thought to be associated with advanced disease and poor outcome. The specific aim of this analysis was to describe characteristics of patients (pts) presenting to the Emergency Department (ED) at their index diagnosis, and to determine whether emergency presentation precludes treatment with curative intent. Methods: We performed an IRB-approved retrospective cohort analysis. We queried the prospectively maintained institutional tumor registry to identify pts diagnosed with CRC from 2008-2010. EMRs were reviewed to identify which pts presented to the ED with acute symptoms of CRC as the initial sign of their illness. The primary outcome variable was treatment plan (curative vs. palliative). Secondary outcome variables included demographics, tumor type and location. Descriptive statistics were conducted for major variables. Χ 2 and Fisher’s exact tests were used to detect the association between categorical variables. Two-sample t-test was used to identify the association between continuous and categorical variables. Results: Between Jan 1 2008 and Dec 31 2010, 376 pts were identified with CRC. 214(57%) were male and 162(43%) were female, with mean age 60.6; SD: 13.3. 33 (8.8%) pts initially presented to the ED, of which 5 (15.5%) received palliation. Of 339 pts who initially presented elsewhere, 69 (20.5%) received palliation. Acute ED presentation with CRC symptoms did not preclude treatment with curative intent (p = 0.47). Pts who presented emergently were more likely to be female (64% vs male 41%; p=0.01), and older (65 vs. 60; p=0.02). There was no statistically significant relationship between age, gender, tumor location or type and treatment approach. Conclusions: Pts with CRC may present to the ED with acute symptoms, which ultimately leads to the diagnosis. Emergent presentation of CRC does not preclude patients from receiving therapy with curative intent.
AMC 070: A phase I/II study of lenalidomide in patients with AIDS-associated Kaposi sarcoma.
Authors: K. A. Shimabukuro, E. G. Reid
Journal: Journal of Clinical Oncology (2011)

TPS246 Background: HIV-infected individuals have a high incidence of Kaposi sarcoma (KS), a virus induced endothelial tumor that arises in skin, mucosa, and viscera. When immunosuppression is reversed with highly active antiretroviral therapy (HAART) KS lesions often stabilize or regress suggesting that CD4 T cells are important in immunosurveillance. However, many patients treated with HAART develop or show persistent KS lesions and treatment with conventional anticancer therapy is not sufficient to eradicate disease. Lenalidomide is an IMiD™ compound with potent anti-angiogenic and immunomodulatory properties. Thalidomide, the parent analogue of lenalidomide, showed modest activity against HIV-associated KS. Lenalidomide has higher tumoricidal and immunomodulatory effects, including stimulation of apotosis and enhanced NK cell cytotoxicity making it a promising candidate for KS therapy. The effect of lenalidomide on AIDS-associated KS has not been studied. Methods: This is a multicenter, Phase I/II open label study. Primary objective in Phase I is to determine the maximum tolerated dose (MTD) of lenalidomide using a standard 3x3 dose escalation at four pre-specified doses (10mg/day, 15mg/day, 20mg/day, and 25mg/day). Primary objective in Phase II is to evaluate the clinical response of KS to lenalidomide. Secondary objectives include evaluating the effects of lenalidomide on HIV viral load and T lymphocyte subsets including natural killer cells, time to response, progression, and next treatment, and the ability of dermal adhesive strip samples to detect KS. Inclusion and exclusion criteria are specified and require HAART therapy and CD4>50. Expected enrollment is 12 to 46 subjects, depending upon toxicities during Phase I. Subjects will receive six 28-day cycles and treatment can be extended for up to six additional cycles if criteria for response are met. Statistical analysis of response rates along with Kaplan-Meier estimates of distribution of time to response, time to relapse, and time to death will be calculated. The Phase I portion is ongoing, with cohorts 1 and 2 completed without DLT. Enrollment into Cohort 3 began in January 2011. Funded through AIDS Malignancy Consortium and NCI, grant U01CA121947.
Should all patients (pts) with advanced biliary cancers receive first-line treatment with cisplatin and gemcitabine (GC)?
Authors: Vanessa Costa Miranda, Luiza Dib-Faria, Maria Ignez Freitas Melro Braghiroli, Jorge Sabbaga, Daniel Fernandes Saragiotto, Gilberto Castro, Paulo M. Hoff, Rachel Riechelmann
Journal: Journal of Clinical Oncology (2013)

244 Background: GC is considered the standard of care for pts with advanced biliary tract cancer (BTC), providing median survival of nearly one year. (Valle J et al. NEJM 2010) Nevertheless, many pts experience poor outcomes, leading to a growing interest to identify pts who might benefit from such treatment. Here we aimed to investigate clinical and laboratory factors associated with poor survival among BTC pts treated with GC. Methods: We retrospectively evaluated all consecutive pts with advanced/metastatic BTC who received first line GC at the Instituto do Cancer do Estado de Sao Paulo, Brazil, in a 2 year-period. Clinical and laboratory variables that could influence pts’ outcomes were gathered from medical charts. Cox regression proportional hazard model was used to investigate the following prognostic factors for death: pre-treatment biliary deobstruction, baseline Ca 19.9, any GC interruptions or dose reductions, baseline ECOG status, Charlson Comorbidity Index (CCI) and age. P values &lt; 0.05 in multivariable analysis were considered significant. Results: From January/2009 to July/2011, 72 pts were identified. The median age was 60 years (range 30-80 years), 45 pts (62.5%) were female and 50 (69.4%) presented baseline ECOG 0-1. The median number of cycles of CG was 4 (range 1-9). Grade 3 /4 neutropenia and thrombocytopenia occurred in 16.6% and 12.5% of pts, respectively. Median survival of the whole cohort was 9.53 months (95% CI: 6.2 - 11.4). Median survival in pts with ECOG 0/1 was 13.5 months (95% CI: 9,5 – NR) and among pts with ECOG 2/3 3,5 months (95% CI: 1-7). In the Cox multivariable model, ECOG 2 /3 versus 0/1 (HR: 8.4, 95% CI: 3.4 to 20.7; p&lt;0.001) and CCI score ≥ 2 (HR: 9.5 95% CI: 1.6 to 55.3; p= 0.012) significantly predicted for poor survival. There was a trend for improved survival among pts who had biliary drainage before starting GC (HR: 2.3 95% CI: 1.0 - 5.3; p= 0.051). Conclusions: In this retrospective cohort of unselected pts with advanced BTC treated with first line GC, poor performance status and multiple comorbid illnesses were associated with dismal prognosis. Treatment with GC should be carefully discussed before being offered to these pts.
Using a statewide collaborative approach to improve primary palliative care performance.
Authors: Katie Abstoss, Tallat Mahmood, Claudia Jane Martin, J. Cameron Muir, Jane Alcyne Severson, Jeffrey B. Smerage, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2013)

53 Background: The Michigan Oncology Quality Consortium (MOQC) is a statewide collaborative of oncology practices. Using the Quality Oncology Practice Initiative (QOPI) measurement tool, MOQC identified a gap in the provision of palliative care. We designed and tested interventions to enhance the capacity and capabilities of the oncologist to deliver primary palliative care earlier in a patient’s course. Methods: MOQC created a process to assist oncology care teams in providing primary palliative care services using the Edmonton Symptom Assessment Scale tool. 11 practices participated in two pilots over 18 months. During and after these pilots, we disseminated tools for improvement, including customized palliative care dashboards, to the entire consortium. Pilot teams also shared their successes, insights, and best practices during semiannual live consortium meetings. Results: Shown are palliative care-focused QOPI results, comparing baseline (Fall 2011, F11) and post project (Spring 2013, S13) for all MOQC practices compared with all participating QOPI practices, using a paired t-test. MOQC sites outperformed the QOPI national average on multiple palliative care measures. Furthermore, the MOQC improvement rate since the project initiation was greater than that of national. Although clinically important, the measures did not reach standard statistical significance. Conclusions: Running successive pilot projects improved primary palliative care performance of the teams involved; additionally, this momentum and gain in knowledge facilitated dissemination of innovation and measurable improvement in all members of a statewide consortium. [Table: see text]
Influence of early-phase clinical trial enrollment on patterns of end-of-life care for children with advanced cancer.
Authors: Prasanna Janaki Ananth, Chalinee Monsereenusorn, Clement Ma, Hasan Al-Sayegh, Joanne Wolfe, Carlos Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2016)

151 Background: Early phase clinical trials are critical to enhancing therapies for children with advanced cancer. However, trial enrollment may intensify end-of-life (EOL) care. We evaluated patterns of EOL care for patients at a large cancer center. Methods: Single-center, retrospective cohort study of pediatric oncology patients, ages 6 months-21 years, who died in 2010-2014. We queried electronic medical records to assess frequencies of medical procedures (e.g. intubations), clinic visits, and hospital admissions in the last 6 months of life. We assessed timing of pediatric palliative care (PPC) consultation, initial advance care planning (ACP) discussion, and entry of do-not-attempt resuscitation (DNAR) orders in the chart, in relation to date of death. Patients enrolled in early phase clinical trials for at least 1 cycle (EP) were compared with those not enrolled (NEP), using Wilcoxon rank sum and Fisher exact tests. Results: For N = 125 patients, median age at death was 11.6 years (IQR 5.8-16.3); 46% were female; 70% were White, non-Hispanic. 26% were trial enrollees. Diagnoses included 42% solid tumors, 41% brain tumors, and 18% hematologic malignancies. Most patients had PPC consultation (83%), ACP discussions (91%), and DNAR orders (86%). EP and NEP cohorts did not significantly differ in baseline demographic or clinical characteristics, frequencies of medical procedures, or hospital admissions. EP patients had a higher median number of clinic visits than NEP patients (18.5 [16.3-27.2] vs. 14.1 [6.5-20.7], p = 0.0003) and received PPC consultation significantly closer to death than NEP patients (median days before death = 58 [16-84] vs. 85 [32-173], p = 0.04). There was no difference between EP and NEP patients in timing of initial ACP discussion or of DNAR order entry. Conclusions: Near the EOL, EP patients had more frequent clinic visits and later PPC consultation, but trial enrollment did not appear to delay ACP discussions or increase hospital resource use. These results suggest that early phase clinical trial enrollment does not substantially alter EOL care patterns for children with advanced cancer.
Once-nightly (QD) dual CYP17-Lyase (L) inhibitor / androgen receptor (AR) antagonist VT-464 in patients with CRPC.
Authors: Neal D. Shore, Luke T. Nordquist, Shilpa Gupta, Mark T. Fleming, William R. Berry, Jingsong Zhang, Michael R Kurman, Joel Robert Eisner, William R. Moore
Journal: Journal of Clinical Oncology (2016)

343 Background: VT-464 is an oral, CYP17-L inhibitor and non-clinically an antagonist of the AR and its variants associated with clinical resistance to enzalutamide (ENZ) and abiraterone (AA). The safety, tolerability and initial PD effects (tumor responses, PSA and testosterone (T)-decreases) of QD VT-464 were evaluated in this Phase (Ph) 1/2 study (INO-VT-464-CL-004; NCT02361086). Methods: Chemotherapy-naïve (n = 20) M0 (n = 1) and M1 (n = 19) patients with CRPC prior to (TN, treatment-naïve; n = 9), or after AA (n = 6),ENZ (n = 3) or both (n = 2) were enrolled in sequential dose-cohorts of 600 mg QD with dose titration (DT; 300 mg QD q2w), and 600 and 750 mg QD without DT in 28-day continuous dosing cycles. All doses except the first were given at night with dinner. Patient results through the 750 mg QD cohort are reported (data cut off 17 Aug 2015). Results: Patients received VT-464 without steroids at 600 mg QD+DT (n = 3), 600 mg QD (n = 8) or 750 mg QD (n = 9). Eight patients are on study in cycles 3-12. Most adverse events (AEs) were Grade (Gr) 1 or 2. Fourteen Gr 3 AEs were reported with 7 considered unrelated and 7 ≥ possibly related; 5 of the latter were in the 600 mg QD+DT cohort (bradycardia, hypotension, syncope, hypertension and hyponatremia) with 2 in non-DT cohorts (hypotension, bilateral lower leg weakness). No AEs ≥ Gr 4 were reported. One DLT occurred in the 600 mg QD+DT cohort (syncope). No mineralocorticoid excess syndrome, ACTH response changes, or increased LFTs were observed. Plasma T was below the LOQ (0.03nM) in 67% of patients, with progesterone and cortisol unchanged. Cmax was similar in all cohorts to 450 mg bid (de Bono et al, GU ASCO 2015) but AUC was decreased. All 4 TN patients had PSA declines at 600 mg QD including one 30% and one 50% response; there was one 50% response in the 600 mg QD+DT cohort. Both TN patients treated at 750 mg QD had &gt; 50% response. Of 8 patients with ≥ 1 soft tissue target lesion and ≥ 1 post-baseline scan, 5 had stable disease and 1 had a partial response at Cycle 5. Conclusions: The VT-464 750 mg QD regimen demonstrated potent and selective CYP17 L inhibition and has been selected for all Ph 2 clinical studies based upon improved tolerability, PK and efficacy compared to bid+DT dosing (de Bono et al, GU ASCO 2015). Clinical trial information: NCT02361086.
Early detection of cardiac dysfunction induced by the mTOR inhibitor temsirolimus.
Authors: R. V. Iaffaioli, C. G. Tocchetti, C. Coppola, G. Ragone, A. Barbieri, D. Rea, G. Palma, M. Gala, A. Luciano, C. Arra, N. Maurea
Journal: Journal of Clinical Oncology (2011)

e13612 Background: The mTOR inhibitor temsirolimus is being evaluated for anticancer efficacy in hundreds of clinical trials and is approved for treatment of advanced renal cell carcinoma. The PI3K/Akt pathway converges on mTOR, which is a central regulator of cell growth, including cardiomyocyte growth. Hence, we assess whether the anticancer mTOR inhibitor temsirolimus affects cardiac function. Methods: In vivo cardiac function was measured with left ventricular (LV) fractional shortening (FS) by M-mode echocardiography in sedated C57BL/6 mice (2-4 mo. old) at day 0, and after 2, 7, 14, 21 days from a single i.p. administration of temsirolimus (0.1μg/g, a dose comparable to the one used to treat cancer in humans) or vehicle. Doxorubicin (Doxo, 2.17 μg/g/day for 7 days) was used as a positive control. With speckle tracking echocardiography (ST) we also evaluated radial myocardial strain (%), a very sensitive parameter which can predict LV dysfunction. Results: After 2 days, there was no change in FS with temsirolimus, but FS was already reduced with Doxo: 52±0.2%, p=.0000001 vs sham (60±0.4%). FS was reduced only after 21 days in the temsirolimus group: 50±3%, p=.009 vs sham. Interestingly, with speckle tracking echocardiography we found that radial strain was already decreased at 7 days: 42±5%, p=.01 vs sham (59±1%). Conclusions: The mTOR inhibitor temsirolimus induces LV dysfunction in mice. Such dysfunction occurs later than the one observed with Doxo, but can be identified with speckle tracking echocardiography (reduction in myocardial strain) before a decrease in FS is observed with conventional echocardiography. The clear mechanisms of temsirolimus cardiotoxicity are to be elucidated in further experimental studies. We also plan to apply speckle tracking echocardiography to clinical studies, in order to evaluate the impact of early identification of temsirolimus cardiotoxicity in the treatment of renal cell carcinoma.
Quality cancer-survivorship care: Receipt of guideline-recommended cardiovascular disease (CVD) preventive care among healthy cancer survivors in the United States.
Authors: Kevin A. Pearlstein, Laura H. Hendrix, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

108 Background: Improving cancer survivorship care is a high priority research area. CVD is a major cause of mortality in cancer survivors. Preventive care reduces CVD mortality and is part of guideline recommended care for all individuals. We examined receipt of CVD preventive measures among healthy cancer survivors compared to the non-cancer population using the National Health Interview Survey (NHIS). Methods: NHIS is a population-based, annual survey designed to provide data representative of the health care received by the U.S. population. For this analysis, 1,860 survivors without CVD risk factors (hypertension, diabetes, or hyperlipidemia) were matched to 7,393 controls without CVD risk factors based on age, race, gender, and survey year. Multivariate logistic regression models examined factors associated with receipt of each preventive measure. Results: Cancer survivors were more likely than controls to visit a general doctor and a specialist during the past year (Table). Further, survivors were more likely to have received CVD preventive care (blood pressure and cholesterol check) and undergone behavior modification (tobacco cessation and exercise). Survivors &gt; 5 years versus &lt; 2 years from diagnosis were no better in CVD preventive measures, except slightly higher rate of exercise (51 vs. 48%, p &lt; 0.001). On multivariate analysis, general doctor visitation was associated with receipt of blood pressure check (OR 7.0), cholesterol check (OR 2.9), smoking cessation attempt (OR 1.4) and exercise (OR 1.3); survivors vs. control were no different in CVD preventive care. Conclusions: Care by a general doctor improves receipt of CVD preventive measures for cancer survivors and non-cancer individuals alike. This study supports the integral involvement of primary care physicians in a “shared care model” for the delivery of quality cancer survivorship care. [Table: see text]