tbuckley/cabot-search huggingface dataset:
Chronic medical conditions, health status, and health care practices at 25 years in 5-year survivors of Wilms tumor: A report from the Childhood Cancer Survivor Study.
Authors: A. M. Termuhlen, J. M. Tersak, Y. Yasui, Q. Liu, M. Stovall, M. Deutsch, C. A. Sklar, K. C. Oeffinger, L. L. Robison, D. M. Green
Journal: Journal of Clinical Oncology (2010)

9514 Background: High proportions of children with Wilms Tumor (WT), cured by surgery, chemotherapy, ± irradiation (RT), risk late effects of therapy. Methods: Self-reported chronic medical conditions (CMCs), health status, and health care practices were analyzed in this retrospective cohort including 1,256 5-yr survivors of WT diagnosed 1970-1986 and a sibling comparison group (n=4023). The risk of specific CMCs was analyzed by treatment. Results: The cumulative incidence at 25 yrs of any CMC was 51% and severe/disabling CMC was 11%. Compared to the siblings, WT survivors were twice as likely to report a CMC (hazard ratio [HR]2.0, 95% confidence interval (CI), 1.8-2.4) and almost five- times more likely to have a severe/disabling CMC (HR4.7, 95%CI, 3.6-6.1). The HR of specific CMCs were: congestive heart failure (CHF) 23.6 (95% CI, 10.8- 51.5), renal failure 50.7 (95% CI, 14.5-177.4), and hypertension (HTN) 8.2 (95% CI, 6.4-10.5). RT to the heart increased the likelihood of reporting CHF without doxorubicin (HR6.6, 95% CI, 1.6-28.3), with ≤ 250 mg/m2 (HR13.0, 95% CI, 1.9-89.7), and with > 250 mg/m2 (HR18.3, 95% CI, 3.8-88.2). Doxorubicin without RT did not increase the likelihood of CHF. RT to the contralateral kidney did not increase the likelihood of reporting renal failure or HTN. The prevalence ratio (PR) of adverse health status was significantly different from the sibling group for general overall health (PR 1.7, p=0.001), functional impairment (PR 3.3, p<0.001) and activity limitations (PR 1.9, p<0.001), but not for mental health status (PR 1.2, p=0.09). WT survivors and the siblings showed no differences in self or professional screening for cancer. WT survivors <30 yrs old reported more general medical exams (PR 1.1, p<0.001). Female WT survivors <30 yrs were more likely to report having had a mammogram (PR 1.6, p=0.008). Of female WT survivors who received chest RT, only 13% <30 yrs and 57% ≥30 yrs reported having had a mammogram. Conclusions: Survivors of WT have an excess risk of chronic medical conditions and adverse health status. The health care practices of WT survivors were similar to their siblings, providing opportunity for intervention. No significant financial relationships to disclose.
Curative treatments and survival benefit in elderly patients with hepatocellular carcinoma: A SEER population-based analysis.
Authors: Oxana V. Makarova-Rusher, Susanna Varkey Ulahannan, Austin G. Duffy, Tim F. Greten, Sean Altekruse
Journal: Journal of Clinical Oncology (2015)

355 Background: Transplant, resection, and ablation are potentially curative treatments for hepatocellular carcinoma (HCC) with limited outcome data in young-old (65-74) and older (≥75) patients. Methods: We evaluated curative treatment and relative survival (RS) outcomes in patients with HCC in 3 age groups (&lt;65 years, 65-74 years, and ≥75 years). Patients with HCC diagnostic codes (histology 8,170-8,175, morphology C22) were identified in the SEER 18 database from 2000 to 2011. Treatments included curative (transplant, resection, radiofrequency ablation (RFA), and other ablations) and palliative therapies. Primary outcome was 5 year RS. Statistical analysis was performed using Kaplan-Meier and Chi-Square tests. Results: We identified 29,654 cases. The mean age was 62 years with almost 40% of HCC cases in patients over 65 years old. Potentially curable, localized stage rates were similar in all age groups, 46%, 48% and 46%, respectively. As a result of less resection and rare transplant use, fewer cases underwent curative treatments in the group 75 years and older in comparison to all other age groups (15% vs. 27%, p = 0.001). Five-year RS in all 3 age groups (&lt;65 years, 65-74 years, and ≥75 years) was better after resection relative to RFA (47% vs. 35% p&lt;0.0001, 44% vs. 37%, p=0.0093, and 43% vs. 28% p=0.0002). The highest survival was seen after liver transplant. Interestingly, among transplanted patients with HCC, 13% were 65-75 years old. Five-year RS was similar in transplanted patients 65-75 vs. those under 65 (76% vs 74% p=0.65). Conclusions: The use of curative treatments for HCC significantly decreases with age, yet there are clear survival benefits in elderly patients receiving such. Even when considering transplant, the data shows that outcome is as good in elderly patients as in younger patients. The benefit of hepatic resection appears to be superior compared to RFA in all age groups, in our analysis. [Table: see text]
Phase I dose-escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), in patients with advanced solid tumors.
Authors: T. Evans, C. R. Lindsay, E. Chan, B. Tait, S. A. Michael, S. Day, A. W. Stephens, A. Franke, S. Poondru, I. Puzanov
Journal: Journal of Clinical Oncology (2010)

2531 Background: OSI-906 is a potent inhibitor of IGF-1R and IR tyrosine kinase activity. Increased IGF-1R activity is observed in human malignancies and implicated in resistance to chemotherapy. Methods: Patients with advanced cancer received escalating doses of OSI-906. Study objectives included determination of MTD and evaluation of safety, pharmacokinetics (PK), pharmacodynamics (PD), and tumor response. Results: 57 pts have been treated (37M/20F, median age 59 yrs) at 10–450 mg QD and at 20–200 mg BID. Median number of weeks on trial was 6 (range 0–44). Six DLTs were observed: 2 DLTs at 450 mg QD (grade 3 hyperglycemia and inability to complete treatment period 1), 1 DLT at 400 mg QD (grade 3 elevated QTc), 2 DLTs at 200 mg BID (grade 3 hyperglycemia and grade 4 elevated ALT/AST), and 1 DLT at 150 mg BID (grade 3 elevated AST). Hyperglycemia (6/54 pts) related to OSI-906 was grade 1–2 (4 pts) and grade 3 (2 pts). Other related adverse events were grade 1–2: nausea (20%), vomiting (20%), lethargy (19%), and fatigue (15%). Preliminary PK analysis indicates the exposure of OSI-906 was dose proportional. The median of both Tmax and t3/4 was 2–4 hours. Steady-state plasma concentrations were achieved by day 8 after BID dosing. Stable disease > 12 weeks was seen in 18/43 pts (range 12–44 weeks), including 1 pt each with thymic cancer (27w), adrenocortical carcinoma (28w), colorectal cancer (34w), and melanoma (44w+). PD effects on the GH-IGF1 and IGF- 1R/IR axes were observed and correlated with plasma OSI-906 concentrations. Conclusions: MTD has been reached for the two dosing schedules: 400 mg QD and 150 mg BID. OSI 906 is well tolerated with linear PK characteristics and no unexpected toxicities. Steady-state plasma concentrations above 1 μ M (predicted efficacious concentration) were reached at doses ≥ 75 mg BID. PD data indicate sufficient exposure can be achieved in some patients for target modulation. Preliminary antitumor activity has been observed. Separate expansion cohorts in colorectal cancer (biomarker focus) and non-insulin-dependent diabetes mellitus will be enrolled at the recommended phase II dose of 150 mg BID. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI OSI
Quantitating the impact of satisfaction drivers on the chemotherapy patient experience: Employing MaxDiff survey analytics to identify key organizational strengths and potential enhancement opportunities.
Authors: David Michael Waterhouse, Patrick J. Ward, Karyn M. Dyehouse, Robert Miller, Richard Schiano
Journal: Journal of Clinical Oncology (2014)

108 Background: Patient satisfaction surveys using Likert-style rating scales are subject to response, level, and dispersion bias. "MaxDiff" or "worst-best" scaling allows opportunity to determine and quantify the relative importance of satisfaction drivers. The focus of this conjoint survey was to assess satisfaction with factors related to the chemotherapy experience, while simultaneously defining the relative importance of these satisfaction drivers. Methods: Sequential chemotherapy pts at four independent office sites were offered an "in chair" electronic tablet survey. The 38 question survey instrument was adapted from the Community Oncology Alliance Oncology Medical Home (COA OMH) patient satisfaction survey. Sample size was calculated to allow maximum sensitivity for analysis of questions/attributes at a 90% confidence level. MaxDiff scaling (Sawtooth Software) was analyzed using hierarchal Bayes estimation. Comparisons were made between male/female pts, age, length of time as OHC pt, and office site; statistical significance was determined by the Mann-Whiney test. Results: In total, 297 pts of 320 pts (92.8%) responded; mean patient age was 61.7 yrs, 197 female/100male. MD and staff wait times, professional skills, concern and communication abilities weighed heavily in driving high satisfaction; whereas scheduling, availability of clinical trials, facilities, account, and pharmacy services had low influence. Wait times (higher importance/lower satisfaction) offered the highest enhancement opportunity for process improvement. Both genders had similar priorities for factors driving chemotherapy satisfaction. Wait time, staff and facility satisfaction differed slightly by office. No significant age or time differences were identified. Conclusions: The addition of MaxDiff scaling to conventional patient satisfaction surveys is novel, feasible and acceptable in the community oncology office setting, and can yield relevant, interpretable data. Results of this survey are currently being used to inform ongoing OHC process and quality improvement initiatives.
Prognostic value of serum androgens, by ultrasensitive assay, in metastatic castration-resistant prostate cancer (mCRPC): Phase III trial data.
Authors: Charles J. Ryan, Arturo Molina, Jinhui Li, Thian San Kheoh, Eric Jay Small, Christopher M. Haqq, Russell P Grant, Johann Sebastian De Bono, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

22 Background: Serum testosterone (T) and precursors, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A4), may be prognostic of overall survival (OS) by identifying patients (pts) with varying dependency on androgen. To test this hypothesis, we investigated the relationship between the distribution of serum androgen concentrations measured by ultrasensitive mass spectrometric assays with OS, in pts with mCRPC treated in COU-AA-301, a randomized phase III study of abiraterone acetate (AA)(1000mg) plus prednisone (P) vs P. Methods: Pts were stratified by ECOG PS (0-1 vs 2), pain (present vs absent), prior chemotherapy regimens (1 vs 2), and type of progression (PSA only vs radiographic). Eligibility required baseline T ≤50 ng/dL. In a post hoc exploratory analysis, the effect of baseline serum androgen levels (T, DHEAS, A4) on OS (95% CI, months), stratified by quartiles of each androgen was determined. T, DHEAS, and A4 serum levels were measured using novel liquid-liquid extraction 1D or 2D-LC/tandem mass spectrometry ((LC)-LC-MS/MS) assays. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed. Results: Baseline T levels were available from 97% of pts (93% with baseline T ≤15 ng/dL). Median OS increased in a step-wise fashion per T quartile, regardless of treatment (p&lt;0.0001) (Table). Similar results were observed for DHEAS and A4. A positive association was observed in the multivariate analysis adjusted for treatment, other androgens, and lab parameters (LDH, HGB, ALKP, PSA; all p&lt;0.0001). In AA and P-treated pts, respectively, the hazard ratio for OS (95% CI) comparing pts with baseline T above and below baseline median was 0.64 (0.53-0.77; p&lt;0.0001) and 0.51 (0.39-0.67; p=0.0004). Conclusions: Baseline serum androgen concentrations as measured by an ultrasensitive mass spectrometric assay may be prognostic of OS in mCRPC pts and bear consideration as a stratification variable in phase III studies. Clinical trial information: NCT00638690. [Table: see text]
A phase II, multicenter, randomized, double-blind, placebo-controlled, ascending, multidose, U.S. study of oral LX1606 (aka LX1032) in patients with refractory symptomatic carcinoid syndrome.
Authors: M. Kulke, T. M. O'Dorisio, A. T. Phan, R. M. Langdon, B. J. Marek, N. Iklaque, E. K. Bergsland, J. Freiman, K. Frazier, J. Jackson, B. Zambrowicz
Journal: Journal of Clinical Oncology (2011)

TPS168 Background: Carcinoid tumors are associated with serotonin (5-HT) secretion. High levels of serotonin are thought to contribute to the flushing, diarrhea, and abdominal discomfort observed in patients with carcinoid syndrome (CS). LX1606 (aka LX1032), an oral peripheral tryptophan hydroxylase (TPH) inhibitor that blocks serotonin synthesis, offers a potential novel therapeutic approach to CS. LX1606 has been granted “Fast Track” designation by the FDA. Methods: This study is evaluating the safety, tolerability, and preliminary efficacy of LX1606 in patients with CS. Endpoints include: reduction in daily bowel movements (BM), cutaneous flushing episodes, abdominal discomfort, and use of rescue short-acting octreotide or other rescue medication. Pharmacokinetics and pharmacodynamics (including whole blood 5-HT and urinary 5-HIAA) will also be assessed. Treatment: Patients with octreotide-refractory CS will be sequentially assigned to receive 4-weeks of LX1606 or placebo, in a 3:1 ratio. Oral LX1606 or placebo are administered 3 times daily; dose cohorts are 150 mg, 250 mg, 350 mg, 500 mg. All patients will continue stable-dose octreotide LAR for the duration of the study. After completing the 4-week blinded portion of the study, patients may receive open-label drug at their previously assigned dose level for 32 additional weeks. After completion of the dose escalation phase, 8 additional patients will receive treatment at the identified optimal dose level. Key eligibility: Patients with octreotide-refractory carcinoid syndrome, (defined as >4 BM/day).Current enrollment: 16 patients have been treated in the dose escalation phase. LX1606 500 mg TID has been identified as the optimal dose. As of 2/2011, enrollment is ongoing in the expansion phase. ClinicalTrials.gov registry: NCT00853047.
Multicenter sequential phase II study of flavopiridol plus oxaliplatin (Alvocidib) with or without 5-FU and leucovorin (LV) for patients (pts) with refractory germ cell tumors (GCT) including late relapse (LR).
Authors: Darren Richard Feldman, Walter Michael Stadler, Leonard Joseph Appleman, David I. Quinn, Brian Addis Costello, Gary K. Schwartz, Victor E. Reuter, Kaitlyn Woo, Sujata Patil, Anne Fusco, Sloane C. Smith, Jeremie Carlson, George J. Bosl, Robert John Motzer
Journal: Journal of Clinical Oncology (2014)

364 Background: Flavopiridol + FOLFOX showed activity in refractory GCT pts in a phase I trial (Rathkopf, Clin Cancer Res, 2009). This phase II study assessed the efficacy of this regimen in refractory GCT and the necessity of including 5-FU/LV. Methods: Previously treated pts with progressive GCT were eligible if they had received or were not candidates for high-dose chemotherapy (HDCT). Pts on Arm A received flavopiridol 70mg/m 2 plus oxaliplatin 85mg/m 2 . Arm B (flavopiridol + FOLFOX) tested identical doses of flavopiridol and oxaliplatin plus 5-FU (400mg/m 2 bolus, then 1800mg/m 2 over 48 hours) and LV 400mg/m 2 . Treatment was every 2 weeks in 6-week cycles. The primary endpoint was response rate (RR) by RECIST. An identical Simon 2-stage design was used for each arm to differentiate between a RR ≥40% vs. ≤20%, with arm B opening only if arm A was ineffective. With ≥3 responses among the first 12 pts, another 13 pts would be enrolled with responses in ≥8/25 pts needed to show efficacy. Tumor biopsies pre-, during, and post-treatment were assessed by IHC for p53, p21, and cleaved caspase-3. Results: Of 36 pts (7 arm A, 29 arm B), 33 had nonseminoma. Primary site was testis in 27 and mediastinum in 7; 22 pts had received prior HDCT and 13 had LR (&gt;2 years), including 2 on arm A and 11 on arm B. Arm A closed early after 0/7 pts responded (2 SD). Of 25 evaluable pts on arm B, 6 achieved a PR, 9 had SD, and 10 had PD. Notably, 5/10 evaluable LR pts on Arm B had a PR, including 1 pathologic CR, 1 PR-negative markers who received radiation (RT) to a residual bone metastasis, and 1 PR-positive markers who received RT to a residual nodal mass. These 3 pts remain disease-free ≥19 months (m) post-chemotherapy and ≥17m post-RT or surgery. Median PFS and OS were 2.3m and 7.3m for all pts and 3.2m and 11.2m for arm B pts. There was 1 treatment-related death due to sepsis. Conclusions: Although neither arm met the prespecified endpoint, flavopiridol plus FOLFOX (arm B) was particularly active in LR pts, with a 50% overall RR, including several durable responses. Further study of FOLFOX with or without flavopiridol is warranted in LR pts. Correlative data will be presented. Clinical trial information: NCT00957905.
Within-day test–retest reliability of the 6-min walk test in patients with pulmonary fibrosis
Authors: Ada E.M. Bloem, Marcel Veltkamp, Jan W.H. Custers, Hanneke M. Dolk, Jan C. Grutters, Martijn A. Spruit
Journal: European Respiratory Journal (2017)

Interstitial lung diseases (ILDs) are a group of more than 150 different disorders characterized by inflammation of the lung parenchyma, or interstitium, often followed by the occurrence of pulmonary fibrosis. Patients with pulmonary fibrosis complain about exertional dyspnoea, exercise intolerance and reduced quality of life [1]. Poor exercise tolerance and oxygen desaturation during exercise are associated with poor survival [2]. Therefore, measuring exercise capacity in patients with pulmonary fibrosis is an important element of clinical management. The 6-min walk test (6MWT) is one of the most widely used clinical tests of functional exercise capacity in people with pulmonary fibrosis [3, 4]. One 6-min walk test may not be enough to obtain the best 6-min walk distance in patients with pulmonary fibrosis <http://ow.ly/cVfK3082RIL>
Transplanted Human Aldehyde Dehydrogenase Expressing Stem Cells Circulate and Engraft Nonhematopoietic Tissues.
Authors: David A. Hess, Louisa Wirthlin, Timothy C. Craft, Phillip E. Herrbrich, Marie Roberts, Michael H. Creer, Mark S. Sands, Jan A. Nolta
Journal: Blood (2005)
Expression of ErbB2 and ErbB3 in resected non-small cell lung cancer (NSCLC) patients (pts).
Authors: E. Felip, M. Salcedo, N. Murtra-Garrell, A. Navarro, C. Teixido, J. Hernandez-Losa, S. Cedres, P. Martinez, E. Lopez, M. A. Montero, V. Freixinos, G. Argiles, I. Nuñez, V. Peg, E. Pallisa, M. Canela, J. Tabernero, S. Ramon y Cajal, N. Tallada
Journal: Journal of Clinical Oncology (2011)

7037 Background: EGFR deregulation has been extensively studied in NSCLC, but less is known about the expression and role of other ErbB receptors. The aim of this study is to determine ErbB2 and ErbB3 expression in NSCLC. Methods: Tumor samples from 126 NSCLC pts who underwent complete resection in our institution from October 2007 to September 2010 were analyzed. Tissue microarrays were used to study ErbB2 and ErbB3 expression by immunohistochemistry; expression was graded by two independent observers and tumors with a 2+/3+ score were classified as “high expression”. ErbB2 by FISH was analyzed in pts with high ErbB2 expression. EGFR-mutation (mut) status was determined in selected pts. Results: Pts characteristics: median age 67 yrs, 81% male, 6% never smokers, 40% adenocarcinoma (ADC)/ 39% squamous-cell (SCC)/ 21% others, p-stage 33% I/28% II/30% III/9% IV. High ErbB2 expression was found in 5 (4%) pts: all 5 male, 1 never smoker, 3 ADC/2 SCC. None of these pts was ErbB2 FISH+. High ErbB3 membranous and cytoplasmic expression was found in 27% and 21% of samples, respectively, with 10% of samples having high expression at both sites. No correlation was found between ErbB3 expression and age and p-stage. High ErbB3 expression was more frequent in females than in males (membranous 46% vs 22% p= .038; cytoplasmic 33% vs 18% p= .099, respectively), in ADC than in the other histologies (membranous 36% vs 21% p= .07; cytoplasmic 32% vs 13% p =.014, respectively). Five of 23 pts had EGFR-mut (2 del exon 19, 3 L858R exon 21): all 5 female with ADC, 4 never smokers. No EGFR-mut pt had concomitant high ErbB2. Four EGFR-mut pts had high cytoplasmic ErbB3 expression (80%), 3 (60%) had membranous expression. Preliminary results (median follow-up, 17 months) showed no association between ErbB3 expression and disease-free or overall survival, although longer follow-up is needed. Conclusions: High ErbB2 expression is infrequent in NSCLC. ErbB3 can be highly expressed in NSCLC and seems more frequent in females, ADC and EGFR-mut tumors. ErbB3 warrants further study in NSCLC to clarify its role and its potential use as therapeutic target.
Monitoring response to imatinib by quantitative real-time polymerase chain reaction (RQ-PCR) in chronic phase, chronic myeloid leukemia patients in complete cytogenetic remission
Authors: C. Pavlovsky, I. Giere, V. Lombardi, P. Negri, B. Moiraghi, J. Garcia, M. A. Pavlovsky, F. Garcia Reinoso, S. Pavlovsky
Journal: Journal of Clinical Oncology (2008)

18013 Background: Chronic myeloid leukemia (CML) landscape has radically changed since treatment with imatinib. As the majority of CML patients (pts) treated with imatinib achieve a complete cytogenetic remission (CCyR), molecular studies that measure the level of bcr/abl transcripts to determine minimal residual disease are mandatory. The degree of reduction of total leukemia cell mass by imatinib as measured by RQ-PCR correlates with progression-free survival. Methods: We monitored bcr-abl transcript levels by RQ-PCR in 169 CML pts in chronic phase (CP) that achieved CCyR with a median follow up of 15 months (range 6–26). Median age was 51 (range 18–82), 83 pts (49%) were newly diagnosed and 86 (51%) had been previously treated with interferon-alfa; 54% had low sokal score, 29% intermediate and 17% were high risk. At baseline, pts were evaluated by FISH and RQ-PCR, transcript quantification by RQ-PCR was measured every 6 months from baseline at 6, 12 and 18 months. Results: At present 78 pts completed 4 evaluations at month 0, 6, 12 and 18. Mayor molecular response (MaMR: > 3 log red in bcr-abl transcript levels) was obtained in 62% at month 18 compared to 45% obtained at study initiation. Minor (Mi)MR at month 18 was of 38% vs 50% at initial evaluation. The pts could be divided into three groups according to molecular responses: 1- in 34 pts transcript levels continued to decline during the observation period, 2- in 38 pts transcript level reached a plateau and 3- in 6 pts transcript levels increased. From pts who obtained MiMR at baseline, 54% showed decrease in transcript levels obtaining MaMR in 44% of pts. Nine pts changed treatment to a second line tyrosine kinase inhibitor, causes were: lost CCyR: 3, lost hematologic response: 1, molecular relapse: 4 and intolerance to treatment: 1. Conclusion: The pattern of residual disease after achieving CCyR on imatinib is variable: some patients show progressive reduction of transcript levels, others reach a plateau showing stable transcript levels and other show rising levels of bcr-abl defining a group of patients were therapeutic decisions are mandatory. No significant financial relationships to disclose.