tbuckley/cabot-search huggingface dataset:
Financial distress, communication, and cancer treatment decision making: Does cost matter?
Authors: Yousuf Zafar, Amy Pickar Abernethy, James A Tulsky, Peter A Ubel, Deborah Schrag, Christel Rushing, Fumiko Chino, Jonathan Nicolla, Ivy Altomare, Greg Samsa, Jeffrey M. Peppercorn
Journal: Journal of Clinical Oncology (2013)

6506 Background: Financial distress (FD) increases the burden of living with cancer. Even insured patients may experience considerable FD, but little is known about whether patients want to include cost discussions in treatment decision-making. Methods: This is an ongoing cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about FD (via a validated measure), out-of-pocket (OOP) costs, discussion of costs with their doctor, and decision-making. Medical records were reviewed for disease and treatment data. Logistic regression assessed the relationship between FD and cost communication. Results: 119 participants (85% response) had a median age of 60 years (range 27-86). 54% were men, 29% non-white, and 96% completed high school. 81% had incurable cancer. 58% had private insurance. Median income was $50,000/yr. Median OOP costs were $480/mo. The mean FD score (6.7, SD 2.5) corresponded to moderate FD. 19% reported high/overwhelming FD. Overall, 48% (n=57) expressed any desire to discuss costs with their doctor, but only 21% (n=25) had actually done so. Of the 19% with highest FD, 36% (n=8) had discussed costs with a doctor, and 68% (n=15) expressed any desire to discuss costs. The most common reasons for not discussing costs with doctors were: “no problems with costs” (n=47); “want best care regardless of cost” (n=36); and “doctors shouldn’t have to worry about costs” (n=19). Of those who discussed costs with their doctor, 48% (n=12) felt the discussion helped decrease costs. 54% (n=64) wanted their doctors to account for costs in cancer treatment decision-making; 20% (n=24) always wanted costs considered in decision-making. High FD was the only variable associated with greater willingness to discuss costs (adjusted OR 2.81; 95%CI 1.05-7.50; p=0.04). Conclusions: FD was prevalent among insured cancer patients. A large proportion wanted costs discussed with doctors and included in treatment decision-making. Discussing finances may lower costs, but the discussion rarely occurs. Communication and decision-making present a potential focus for intervening on FD.
Patient identification and eligibility insights in the synchronous metastatic RCC population: An update from the ongoing ADAPT* phase 3 study experience.
Authors: Robert A. Figlin, Christopher G. Wood
Journal: Journal of Clinical Oncology (2015)

TPS4582 Background: AGS-003 is an autologous immunotherapy designed to induce a T-cell response specific to a patient’s tumor antigens. Sunitinib is a TKI and first-line therapy for mRCC that also reverses the immune suppression observed in these patients. In a single arm phase 2 study, AGS-003 plus sunitinib was safe and yielded a median overall survival (OS) of over 30 months in newly diagnosed mRCC patients. Methods: The ADAPT study is a randomized (2:1) international phase 3 study comparing standard targeted therapy plus AGS-003 to standard therapy alone. The primary objective is to compare the median OS between treatment arms. The study is enrolling adults with synchronous, metastatic, clear cell RCC who are good candidates for surgery and standard targeted therapy (initiating with, but not limited to, sunitinib), KPS ≥ 70%, life expectancy of at least 6 months, between 1-4 Heng risk factors, and adequate end organ function. Initial enrollment patterns were investigated in order to gain insight on the features of mRCC patients that are candidates for cytoreductive nephrectomy. More than 130 sites in North America and other select countries have been activated and > 840 patients have been consented and tumor samples collected. Enrollment is expected to conclude in the 1st half of 2015. To date, approximately 50% of patients screened for tumor collection were ineligible to participate in the treatment phase of the ADAPT study after surgery, with about half of these being excluded because of non-clear cell histology. Other major reasons include ineligibility for sunitinib and lack of evaluable metastatic disease after nephrectomy. The DMC last reviewed the trial in December 2014 and suggested that the trial continue as planned. Clinical Trials registry number: NCT 1582672 * ADAPT: An International Phase 3 Randomized Trial of Autologous Dendritic Cell Immunotherapy (AGS 003) Plus Standard Treatment in Advanced Renal Cell Carcinoma (RCC) Clinical trial information: NCT1582672.
Sudden Cardiac Arrest Risk Assessment
Authors: Robert J. Myerburg, Jeffrey J. Goldberger
Journal: JAMA Cardiology (2017)

High-resolution stratification of risk of sudden cardiac arrest (SCA) in individual patients is a tool that is necessary for achieving effective and efficient application of data generated by population-based research. This concept is at the core of initiatives for merging cost effectiveness with maximized clinical efficiency and individual patient treatment.For this review, we analyzed data on sudden cardiac death and SCA available from population studies that included large longitudinal and cross-sectional databases, observational cohort studies, and randomized clinical trials. In the context of population science, we treated clinical trials as small, scientifically rigid population studies that generate outcomes focused on defined segments of the population. Application of probabilistic outcomes from these available sources to individual patients generally and patients at risk for SCA and sudden cardiac death in particular is limited by the diversity of the study population based on inclusion criteria and/or the absence of uniformly large effect sizes. Limited information is available on the requirements for defining small high-risk density subgroups that would lead to identification of individuals at a sufficiently high probability of SCA to have a significant effect on clinical decision making.Synthesis of available population and clinical science data demonstrates the limitations for prediction and prevention of SCA and sudden cardiac death and provides justification for a research mandate for improving risk prediction at the level of individual patients. This leads to suggested approaches to new data generation and required research funding to address this large public health burden.
Triple-negative breast cancer: A population-based description of clinical-pathologic correlates and survival outcomes as a function of age at diagnosis.
Authors: James Charles Roger Michael, Jennifer Payne, Kaitlyn Tsuruda, Mohamed Abdolell, Judy Caines, Sian Iles, Penny Barnes, Geoff Porter, Tallal Younis, Daniel Rayson
Journal: Journal of Clinical Oncology (2014)

e12530 Background: Triple Negative Breast Cancer (TNBC) accounts for approximately 10% of invasive breast malignancies and is characterized by a relative lack of adjuvant systemic therapeutic options. Our aim was to describe a population-based cohort of primary TNBC patients including detection method, breast density at diagnosis, pathologic characteristics, and clinical outcomes, as a function of age at diagnosis. Methods: All cases of primary TNBC in Nova Scotia, Canada were identified through the Information System of the Nova Scotia Breast Cancer Screening Program (NSBSP). The study population included all female patients who underwent an open surgical biopsy following an imaging procedure, between January1 2005-13, and for whom pathological confirmation of TNBC was documented. A descriptive analysis of subjects’ clinical profile was performed, stratified by age group at diagnosis (≤49, 50-59, 60-69, and ≥70). Survival analysis techniques were used to model both disease-free (DFS) and overall survival (OS) as a function of age group, controlling for clinical-pathologic features. Results: A total of 421 cases were identified with a median follow-up time of 3.7 years. For the entire cohort, median tumor size was 2.3cm (range 0.1-14cm), and 175 (41.6%) had lymph node involvement. 348 (82.7%) had grade 3 disease with a significant difference in the distribution of grade across age groups (Chi-squared: p=0.01). Twenty-two (19.8%) cases in the 50-59 age group were interval cancers with a trend to shorter median OS in this age group compared to older cohorts (p= 0.07). There have been 100 deaths thus far with breast cancer specific survival rates remaining to be ascertained. Conclusions: Our observations suggest heterogeneity in a number of clinical-pathologic characteristics and survival outcomes within a large population-based cohort of TNBC.
Quantitative proteomic analysis of TUBB3 to identify gastric cancer patients who may benefit from docetaxel: A reevaluation of the ITACA-S trial.
Authors: Fabiola Cecchi, Daniel V.T. Catenacci, Yuan Tian, Rosalba Miceli, Filippo Pietrantonio, Alessandro Pellegrinelli, Antonia Martinetti, Maria Di Bartolomeo, Todd A. Hembrough
Journal: Journal of Clinical Oncology (2017)

59 Background: Chemotherapy (CTX) becomes targeted therapy when biomarkers can predict a patient’s response. A relationship between resistance to taxanes and overexpression of class III b-tubulin (TUBB3) has been suggested by small clinical studies, but not confirmed in randomized trials. The Intergroup Trial of Adjuvant CTX in Adenocarcinoma of the Stomach (ITACA-S) evaluated the survival advantage of postoperative sequential CTX with FOLFIRI followed by docetaxel plus cisplatin in comparison to monotherapy with 5-FU/LV in patients with radically resected gastric cancer (N = 1106). The results showed no difference in survival between the two CTX arms. In a random subset of patients (N = 247) from the ITACA-S trial, we applied mass spectrometry-based proteomics to assess the role of TUBB3 as a predictive biomarker for response to taxane-containing therapy. Methods: Archived tumor tissues were microdissected and solubilized for proteomic analysis. TUBB3 and 44 other protein biomarkers were quantified using a mass spectrometry-based selected reaction monitoring assay. A predetermined TUBB3 cutoff of 700 amol/µg was based on the assay’s limit of detection. The Mantel-Cox log-rank test was used for survival comparisons. Results: Among patients treated with taxane-containing CTX (n = 125), those with TUBB3 levels below the cutoff had nearly twice the median overall survival (OS) as patients with TUBB3 levels above the cutoff (1566 vs. 801 days, p = 0.0282). TUBB3 levels made no statistical difference in survival among patients who did not receive taxane. Of note, among patients with high TUBB3 levels ( &gt; 700 amol), those treated without taxane-containing CTX survived far longer than patients in the taxane arm (OS = 1991 vs 801 days, p = 0.048). Conclusions: Quantitative proteomic analysis of TUBB3 expression identified a subset of gastric cancer patients who benefitted from the addition of docetaxel to adjuvant CTX. Patients with high TUBB3 expression levels had worse outcomes on a taxane-containing regimen than on CTX without taxane. Personalized CTX based on the TUBB3 biomarker is promising and warrants further validation. Clinical trial information: NCT01989858.
Final overall survival (OS) results of a noncomparative phase II study of bevacizumab (B) plus first-line chemotherapy or second-line erlotinib (E) in nonsquamous NSCLC (ns-NSCLC) patients with asymptomatic untreated brain metastases (BM) (BRAIN).
Authors: Benjamin Besse, Sylvestre Le Moulec, Hélène Senellart, Julien Mazieres, Fabrice Barlesi, Eric Dansin, Gilles Robinet, Maurice Perol, Denis Moro-Sibilot, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

8059 Background: The non-comparative BRAIN study (NCT00800202) is the first trial to evaluate efficacy/acceptable safety of B in pts with ns-NSCLC and untreated BM. We report final efficacy/safety results. Methods: Eligible pts (stage IV ns-NSCLC; PS 0–1; untreated, asymptomatic BM ineligible for surgery/radiosurgery) received until unacceptable toxicity/disease progression: 1st-line B ≤6 cycles (15mg/kg q3w) plus carboplatin (AUC 6 q3w) and paclitaxel (200mg/m 2 q3w; B+CP; n=67); or 2nd-line B plus E (150mg/day; B+E; n=24). Primary endpoint is 6-month progression-free survival (PFS). Six-weekly assessments included mandatory brain MRI. The trial could be halted if there were &gt;3 (B+CP) or &gt;2 (B+E) brain hemorrhages (ICH). Results: Baseline (BL) characteristics are reported. With a median follow-up of 16.3 (B+CP) and 11.8 months (B+E), efficacy data are summarized. Adverse events (AE) were comparable with those in previous trials of B. Only 1 grade ≥3 bleeding AE (grade 3, extracranial site; B+E) and only one ICH event (grade 1, resolved; B+CP) occurred. Most frequent cause for B withdrawal was progression: intracranial only in 20.9% (B+CP) and 16% (B+E); extracranial only in 50.7% (B+CP) and 54.2 % (B+E). Conclusions: The finalBRAIN results demonstrate promising efficacy and acceptable safety of B with 1st-line chemotherapy or 2nd-line E in ns-NSCLC pts with asymptomatic untreated BM. Clinical trial information: NCT00800202. [Table: see text]
Chemotherapy-induced ovarian failure in young breast cancer patients: The role of vascular toxicity.
Authors: Irit Ben-Aharon, Tal Granot, Israel Meizner, Shulamith Rizel, Rinat Yerushalmi, Aaron Sulkes, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2014)

9595 Background: Chemotherapy-related amenorrhea is a frequent side effect observed in young breast cancer patients (pts). We had formerly described a mechanism of ovarian toxicity manifested by decreased ovarian blood flow and diminished post-treatment AMH levels. We report herein the continuous prospective evaluation of ovarian function in this cohort. Methods: Young breast cancer pts (<40 years) undergoing adjuvant/neoadjuvant chemotherapy were evaluated by transvaginal ultrasound prior to initiation of chemotherapy, immediately upon completion of chemotherapy, at 6 and 12 months after cessation of chemotherapy . Doppler-flow velocity indices of the ovarian vasculature and size measurements were visualized. Hormonal profile, AMH and menopausal symptoms were assessed at the same time points. Results: Twenty breast cancer pts were enrolled into the study. Median age was 34+5.24 years. Ovarian blood flow was significantly reduced immediately following chemotherapy (p=0.01) after treatment. These parameters were partially recovered at later points of assessment (6 months and 12 months post treatment); patients <35 years exhibited a significant regaining of ovarian blood flow compared with patients >35 years (p<0.05). AMH dropped dramatically in all patients following treatment (P<0.001), and was recovered in only 6 patients (all <35 years). Hormonal profile shortly after chemotherapy depicted a post-menopausal profile for most patients, accompanied by related symptoms. FSH levels were recovered in 14/20 of the patients, and significantly returned to premenopausal range in patients <35 years (p-0.04). The pattern of vascular impairment (reflected by flow velocity) was lessened in patients treated with a trastuzumab-based protocol, though results did not reached statistical significance (p-0.07). Conclusions: Continuous prospective evaluation of ovarian vasculature and function in a cohort of young patients with breast cancer following chemotherapy indicate that ovarian toxicity may derive from acute vascular insult. Regaining ovarian function may be affected by age, whereas recovery of blood flow and premenopausal FSH levels at later assessment were notable in patients <35 years.
TGF-B1 inhibition with losartan in combination with FOLFIRINOX (F-NOX) in locally advanced pancreatic cancer (LAPC): Preliminary feasibility and R0 resection rates from a prospective phase II study.
Authors: Janet E. Murphy, Jennifer Yon-Li Wo, Cristina Ferrone, Wenqing Jiang, Beow Y. Yeap, Lawrence Scott Blaszkowsky, Eunice Lee Kwak, Jill N. Allen, Jeffrey W. Clark, Jason Edward Faris, Andrew X. Zhu, Lipika Goyal, Harvey J. Mamon, Keith D Lillemoe, David P. Ryan, Thomas F. DeLaney, Carlos Fernandez-del Castillo, Yves Boucher, Theodore S. Hong
Journal: Journal of Clinical Oncology (2017)

386 Background: F-NOX is utilized in LAPC due to improved response over gemcitabine, with theoretical potential for curative resection. However the response rate remains well below 50%. Preclinical data suggest that inhibition of the renin-angiotensin system with losartan reduces the activity of TGF-B1, enhancing intratumoral penetration of chemotherapy by remodeling desmoplastic stroma and improving vascular perfusion. In this study, we evaluate the feasibility of adding losartan to F-NOX in LAPC. Methods: Pts ECOG PS 0-1 with LAPC (NCCN criteria) were enrolled in a single institution, NCI-sponsored phase II study (NCT01821729). Pts received F-NOX/losartan for 8 cycles. If the tumor was radiographically resectable after chemotherapy, pts received short-course chemoradiation (CRT) in 5 fractions (protons 25 GyE, capecitabine 825 mg/m2 bid). If it was still abutting vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. The primary endpoint was proportion of pts remaining progression-free after 8 cycles of F-NOX/losartan. Results: 32 pts were enrolled from 8/2013 to 6/2016. One pt withdrew prior to treatment, 6 pts are still receiving F-NOX/losartan or CRT. 25 were included in this analysis. Median age was 62y (46-75). Median tumor size was 42mm (22-68). Tumor was in the head of the pancreas in 16 (64%) pts. Of evaluable pts, 18 (72%) completed F-NOX/losartan followed by CRT. Reasons for discontinuation included losartan intolerance (3), failure to thrive (2), investigator discretion (1), and progression (1). Grade 3 or greater toxicity occurred in 11 (40%) pts, including diarrhea (4, 16%), thrombocytopenia (3, 12%), nausea (3, 12%), neutropenia (2, 8%), and febrile neutropenia (1, 4%). Two pts (8%) had short course CRT, 16 (64%) had long course CRT. In evaluable pts, 4 remained unresectable while one pt had R1 resection. R0 resection was achieved in 13 (52%). Conclusions: Based on the low discontinuation rate of the F-NOX/losartan combination, it met criteria for feasibility. The high R0 resection rate in the feasibility cohort has prompted expansion as a phase II study with an R0 resection endpoint. Clinical trial information: NCT01821729.
Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth
Authors: Anne M. Neilan, Brad Karalius, Kunjal Patel, Russell B. Van Dyke, Mark J. Abzug, Allison L. Agwu, Paige L. Williams, Murli Purswani, Deborah Kacanek, James M. Oleske, Sandra K. Burchett, Andrew Wiznia, Miriam Chernoff, George R. Seage, Andrea L. Ciaranello
Journal: JAMA Pediatrics (2017)

As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care.To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status.Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and ≥500/μL), and a combined measure of VL and ARV status (VL <400 or ≥400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017.Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories.A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/µL compared with 7- to 12-year-old participants (30% and 44% vs 22% of person-time with a VL≥400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count <200/µL; P < .001 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 cell counts, as expected. The mortality rate among older PHIVY was 6 to 12 times that among the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 cell counts after adjusting for age.Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ARV therapy adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY.
Evaluation of safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer
Authors: X.-T. Zhang, L. Li
Journal: Journal of Clinical Oncology (2004)

7093 Background: The aim of the study was to evaluate the safety and efficiency of ZD1839 for Chinese patients with advanced NSCLC. Methods: From Dec 2002 to Aug 2003, 40 eligible patients with unresectable NSCLC (male 25, female 15, Aged from 28–85yrs, Bronchioloalveolar carcinoma 10, Other Adenocarcinoma 21, Squamous cell carcinoma 7, Unspecified 2)enrolled in the study. ZD1839 was administrated orally at the dose of 250 mg/day at about the same time everyday without interruption unless disease progressed or unacceptable adverse event occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with Chinese version of EORTC QLQ-C30 and QLQ-LC13. Results: Daily oral dose of 250mg of ZD1839 was well tolerated in Chinese patients. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were acne-like rash (62.5%) and diarrhea (30.0%). No patient withdrew from the study due to drug-related adverse event. The objective tumor response rate was 32.5%. Disease control rate was 62.5%. Multivariate analysis showed tumor response was associated with bronchioloalveolar carcinoma. The median progression-free survival (PFS) was 22.5w. At the data cutoff, 26 (65%) patients were still alive with median follow-up period of 30w (range: 2 to 60). The QoL response rates for five functioning scales and global QoL varied from 56% to 88%. Main symptom response rates varied from 44% to 84%. QoL and symptom response were correlated with objective tumor response. Conclusion: Our study showed the safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced NSCLC. Treatment with ZD1839 was associated with remarkable symptom release and improvement of QoL. Further clinical study with ZD1839 can be conducted in Chinese patients with NSCLC. No significant financial relationships to disclose.