tbuckley/cabot-search huggingface dataset:
Relationship of initial quality-of-life deficit and survival in esophageal cancer (EC): The Mayo Clinic Romero Registry experience.
Authors: Bradley W. Anderson, Terence Tai Weng Sio, Heshan Liu, Brenda F. Ginos, Yvonne Romero, Aminah Jatoi, Claude Deschamps, Jeff A. Sloan, Robert Clell Miller
Journal: Journal of Clinical Oncology (2014)

97 Background: A diagnosis of EC significantly impairs patient (pt)’s survival and quality of life (QoL). We explored the relationship between pt-assessed QoL and survival. Methods: The Mayo Clinic Romero (formerly Esophageal Adenocarcinoma-Barrett's Esophagus) Registry prospectively collects clinical data during a pt's treatment course. QoL is recorded at enrollment (baseline) and annually using a validated 12-item Linear Analog Self-Assessment (LASA). A 10-pt scale is applied; ≤5 was termed clinically deficient QoL. Initial TNM staging, clinical (age, sex, prior chemotherapy, and esophagectomy), and socioeconomic variables (marital/employment status) were analyzed using Cox proportional hazards regression models. Results: 836 pts were analyzed. Median age was 64 years. 166, 506 and 164 pts had early, locally advanced, and metastatic EC, with 5-year survival rates of 75.1%, 33.6%, and 8.1%, respectively (P≤.0001). Poorer survival rates were seen in clinically QoL deficient pts in the following categories: Overall QoL (Hazard Ratio [H.R.] 0.66; 95% C.I., 0.54-0.80; P≤.0001) and LASA subsets for physical (H.R. 0.68; 95% C.I., 0.57-0.82; P≤.0001), emotional well-being (H.R. 0.69; C.I., 0.57-0.84; P=.0003), and social activity (H.R. 0.76; C.I., 0.63-0.91; P=.0028). No difference in survival was observed for marital or employment status, familial support, and financial/legal concerns. Pts with esophagectomy prior to LASA evaluation had improved survival (H.R. 0.68; 95% C.I., 0.55-0.85; P=.0005). No survival difference was observed whether pts received chemotherapy, before or after their baseline LASA evaluation. Conclusions: A strong association exists between pt’s overall survival and better overall QOL, physical, emotional well-being, and social activities. Using LASA to clinically monitor QoL at specified intervals may afford providers the opportunity to intervene when patients begin to experience QoL decline. The determinants of clinically deficit QoL and its impact on survival warrant further translational and prospective research.
PAM50 breast cancer intrinsic classifier: Clinical validation of a multianalyte laboratory developed test.
Authors: M. T. W. Ebbert, R. R. L. Bastien, L. R. Rowe, P. A. Miller, D. Anderson, K. M. Boucher, L. M. Pappas, C. Fauron, B. W. Lyons, T. Dowell, D. E. Wall, L. Barley, P. S. Bernard
Journal: Journal of Clinical Oncology (2011)

10597 Background: Invasive breast cancers can be classified by gene expression profiling into 4 major biologic subtypes referred to as Luminal A, Luminal B, HER2-enriched, and Basal-like. Subtypes have been identified using several technologies including microarray, immunohistochemistry, and RT-qPCR. In 2009, a 50-gene signature (PAM50) was proposed to standardize breast cancer subtyping. We present the clinical validation of this signature by RT-qPCR. Methods: RNA was extracted from 171 breast samples (155 invasive cancers and 16 "normal" breast tissues) procured in formalin-fixed paraffin-embedded tissue blocks. The RNA was reverse transcribed and cDNA was amplified by PCR using the LC480 instrument (Roche®). A statistical analysis (SigClust) was applied to hierarchical clustering of RT-qPCR data to identify prototypes for each subtype. Robustness of the PAM50 subtype assignment was assessed using a 10-fold cross validation. Subtype centroids were used to develop a single-sample subtype predictor by Spearman rank correlation. There was additional evaluation of PCR efficiency, limits of detection, limits of quantification, reproducibility, and interference. Accuracy was assessed by comparing the PAM50 clinical subtype predictions to those previously published from microarray data. Results: Within platform cross validation of the clinical subtype predictor showed 91.6% concordance. There was 100% reproducibility in subtype predictions across 46 runs testing different subtypes. Subtype predictions across platforms showed 88.1% concordance. Dilution experiments, introducing "normal" breast tissue RNA into breast cancer RNA, showed a systematic switch towards the "normal" signature with Luminal A and Luminal B being most susceptible. Conclusions: The PAM50 Breast Cancer Intrinsic Classifier is highly reproducible within and across platforms. The clinical test has utility in the management of ER+ and ER- invasive breast cancers of all stages. It provides a necessary tool for identifying differences in tumor biology that are important for guiding patient care.
Patient barriers to participation in clinical trials in a community cancer center.
Authors: Praveen Ramakrishnan Geethakumari, Joann R. Ackler, Mahasweta Gooptu, Leonard E Braitman, William J. Tester
Journal: Journal of Clinical Oncology (2013)

e17578 Background: Clinical trials are fundamental to research and innovative oncology treatment. Participation rates in trials have declined nationally to &lt; 5%. Barriers to participation exist at patient, physician and protocol levels. Methods: We conducted a descriptive cross-sectional study in a community cancer center serving a diverse patient population. A total of 160 eligible patients offered enrollment in various clinical trials from July 2010-December 2012 were included. A standardized questionnaire was delivered by mail or in person. Electronic medical records and patient charts were used for disease specific data. Acceptors and decliners were compared using Fisher’s exact test for nominal variables and t test for normally distributed continuous variables. Results: Forty-nine patients (males: 9, females: 40) returned the questionnaire. Twenty-eight had accepted and 21 declined trial participation. Mean age of acceptors was 56.2 ± 2.2 compared to 63.96 ± 1.6 for decliners (p=0.007). Acceptance was highest for stage IV disease (85.71%) [p=0.077]. Of foreign-born patients, 71.4% patients were decliners [p=0.122]. Of those “comfortable with randomization,” 85.2% were acceptors compared to 22.7% who were not [p&lt;0.001]. Of respondents encouraged by knowing that they could leave the study at any time and receive standard treatment, 79.4% were acceptors [p&lt;0.001]. Of patients who valued trust in their doctor, 85.7% accepted compared to 19.05% who did not [p&lt;0.001]. Among most important reasons for their decision, acceptors valued altruism, contribution to research, trust in doctor and hope for cure while decliners mentioned uncertainty in research, drug side effects, depression and need for family support. Conclusions: Results confirm barriers among diverse patients treated in a community cancer center and suggest the type of patient likely to participate in clinical trials. Study limitations include small sample size and majority of female respondents. Key factors included age, patient’s insight into the conduct of randomized trials, perceived drug side effects and the doctor-patient bond. Success lies in bridging knowledge and communication gaps, careful protocol design, and establishing trusting relationships.
Does metformin use influence outcome in diabetic women with invasive breast cancer?
Authors: B. Oppong, S. Oskar, M. Stempel, A. Eaton, S. Patil, T. A. King
Journal: Journal of Clinical Oncology (2011)

600 Background: Preclinical and clinical data suggest complex associations between diabetes mellitus (DM) and breast cancer (BC). Emerging evidence suggests that use of the hyperglycemic agent, metformin, may have a beneficial impact on tumor characteristics and outcome in diabetic women with BC. Methods: Retrospective review of institutional databases from 1998-2005 identified 313 diabetic patients who received systemic treatment for invasive BC. Male patients, those with type I DM, gestational or steroid-induced diabetes were excluded. We also excluded those diagnosed with DM >6 months after BC diagnosis. The 164 remaining women with type II DM formed our study cohort. Kaplan-Meier methods were used for comparisons between patients taking metformin and those using other DM management agents. Results: Of 164 women receiving systemic therapy for invasive BC, 76 (46%) were using metformin at cancer diagnosis. Patients using metformin had a longer history of DM, median 5 vs. 3 years (p=0.025), and were more likely to use >1 agent for DM 45% vs. 30% (p=0.002). There was no difference in clinical presentation (palpable mass vs. mammography), mean tumor size, histology, grade, lymphovascular invasion, nodal status, hormone receptor or Her2 status between the two groups. There was also no difference in receipt of neo-adjuvant or adjuvant chemotherapy, hormone therapy or trastuzumab. At a median follow-up of 72.4 months, there was no difference in the rate of local, regional, or distant recurrence, contralateral BC or overall survival. Conclusions: In this sample of patients with Type II DM receiving systemic therapy for primary invasive BC, there was no difference in primary tumor features or short term BC outcomes between those using metformin and those using other DM agents. These data do not support a beneficial effect of metformin on BC outcome. A prospective study with longer follow-up is needed to further clarify this relationship. Metformin (N=76) No metformin (N=88) P value (log-rank test) Median follow-up (mos) 70.1 74.9 5-year event rate Overall survival 92.7% 91.3% 0.80 Recurrences Local 1.3 3.8 0.24 Regional 1.3 2.6 0.84 Distant 8.6 9.8 0.63 Contralateral breast cancer 4.7 9.1 0.23
Preliminary activity of veliparib (V) in <i>BRCA2</i>-mutated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Shalu Pahuja, Leonard Joseph Appleman, Chandra Prakash Belani, Alice Chen, Edward Chu, Jan Hendrik Beumer, Shannon Puhalla
Journal: Journal of Clinical Oncology (2015)

170 Background: Male BRCA mutation carriers have a 2-8-fold increased risk of prostate cancer when compared to the general population, and up to 3% of patients (pts) with prostate cancer carry an inherited mutation in BRCA1 or 2. The therapeutic implications of germline BRCA mutations in prostate cancer are largely unknown. BRCA mutation enhances sensitivity to inhibition of the PARP1 and PARP2 enzymes, due to a synthetic lethal effect on DNA repair. We therefore conducted a phase 1 study of the PARP 1, 2 inhibitor, veliparib (V), in 2 cohorts of pts- BRCA germline mutated (BRCA+) and BRCA-wild type (BRCA-wt; consisting of serous ovarian cancer and triple-negative breast cancer). Methods: A 3+3 dose escalation phase I trial was performed to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). V was administered orally continuously on a 28-day cycle. Results: A total of98 (70 BRCA+ and 28 BRCA-wt) pts were enrolled. The maximum administered dose (MAD) was 500 mg BID and the MTD/RP2D was 400 mg BID. In BRCA+ cohort at doses ≥ 400 mg BID, overall response rate (ORR) defined as complete response (CR)+ partial response (PR) was 37%, and clinical benefit rate (CBR) defined as CR+PR+stable disease (SD) &gt; 6 cycles was 40%. Three pts with BRCA2+ metastatic castration-resistant prostate cancer (mCRPC) were enrolled on the RP2D and were evaluable for response. In these pts, the ORR was 2/3 (66%) and CBR 3/3 (100%) (summarized in table). One pt with rapidly progressive mCRPC involving liver and bone achieved PR and undetectable serum PSA, and remains on therapy at 19+ cycles. The most common adverse effects in these pts were grade 1/2 nausea/vomiting, fatigue, and leukopenia consistent with the overall study population. Conclusions: Single-agent V demonstrates evidence of activity in BRCA2+ mCRPC. These data support the role of genotype-directed therapy in prostate cancer. Clinical trial information: NCT00892736. [Table: see text]
The role of obesity in the incidence of lymphatic spread, disease-free, and overall survival: Data from the ARISER clinical trial.
Authors: Karim Chamie, Pia Kloepfer, Barbara Fall, Jonathan W. Said, Stephan Störkel, Paul Bevan, Arie S. Belldegrun, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2014)

435 Background: The role of obesity and the incidence of high-risk clear cell renal cell carcinoma (ccRCC) are poorly understood. We examined the association of obesity with lymphatic spread and survival using data from an international Phase III clinical trial testing the efficacy of adjuvant treatment with cG250 antibody in subjects with non-metastatic (ccRCC) at high risk for recurrence. Methods: We reviewed the clinical and pathologic records of 864 patients across three continents and 14 countries that were enrolled in a prospective, double blind, placebo controlled study of adjuvant cG250 Ab treatment for high-risk ccRCC. Clinical features analyzed included age, gender, race, body mass index (BMI), and performance status. A single pathologist centrally reviewed the specimens for TNM stage and nuclear grade. BMI was stratified into normal (&lt;25 kg/m 2 ), overweight (25.0–29.9 kg/m 2 ), obese (30.0–34.9 kg/m 2 ), and morbidly obese (≥35 kg/m 2 ). We examined the association between BMI, disease severity, and survival using logistic and Cox regression analyses, respectively. Results: Mean BMI was 28.2 kg/m 2 . The vast majority of our cohort was overweight (43%) and an additional 29% were obese (or morbidly obese). The incidence of lymphatic spread decreased with rising BMI: normal was 11%; overweight was 8%; obese was 5%; and morbidly obese was 2%. Obesity was associated with improved disease-free and overall survival, log rank=0.01 and &lt;0.01, respectively. When compared with those who were normal in weight, subjects who were obese (HR 0.50, p&lt;0.01) and morbidly obese (HR 0.22, p&lt;0.01) had significantly improved overall survival. A trend towards improved disease-free survival was found among subjects who were obese (HR 0.77, p=0.10) and morbidly obese (HR 0.69, p=0.09). Conclusions: While we cannot speak to the association between obesity and ccRCC, our study demonstrates that in a cohort of nephrectomized patients with high-risk disease, obesity is associated with a lower risk of lymphatic spread and improved overall survival.
A phase I, open-label study of the safety and pharmacokinetics (PK) of pazopanib (P) and lapatinib (L) administered concurrently
Authors: M. Dejonge, S. Savage, J. Verweij, T. S. Collins, F. Eskens, B. Whitehead, A. B. Suttle, L. B. Pandite, P. T. Ho, H. Hurwitz
Journal: Journal of Clinical Oncology (2006)

3088 Background: P is a potent tyrosine kinase inhibitor of VEGF-R1, -R2, and R3, PDGF-α/β, and c-Kit. L is a potent inhibitor of ErbB1 and ErbB2 tyrosine kinases. Several lines of evidence support combined inhibition of VEGFR and Erb in the treatment of malignancies. Methods: Patients (pts) with solid tumors received P and L daily. Safety, limited PK, biomarkers, and clinical activity were evaluated. Dose escalation occurred in cohorts of 3–6 pts based on DLT. Results: Thirty-three pts received L/P doses of 750/250 (n=4), 750/500 (n=6), 1000/250 (n=3), 1000/400 (n=2), 1000/500 (n=4), 1250/250 (n=6), 1250/400 (n=5) and 1500/200 (n=3) mg once daily (qd). Preliminary mean plasma P concentrations 24 h after administration (C24) on Day 22 were ∼19 μg/mL and 23 μg/mL after administration of 250 mg and 500 mg, respectively. These values are similar to mean C24 values observed after administration of 800 mg P alone (23.1 μg/mL). Plasma L concentrations at 750 - 1500 mg qd were similar to those observed after monotherapy. The most frequent AE’s were diarrhea (Grade (G)1 n=10, G2 n=2, G3 n=3), fatigue (G1: n=7, G2 n=5, G4 n=1), nausea (G1 n=9, G2 n=2), anorexia (G1 n=8, G2 n=3), vomiting (G1 n=9), hair depigmentation (n=7), rash (G1 n=6, G2 n=1) and abdominal cramps (G1 n=3, G2 n=2, G3 n=1). Prolonged disease stabilization of &gt; 16 wks (median 21.5 wks) occurred in 10 pts (RCC n=3, CRC n=3, GIST n=1, mesothelioma n=1, adenocarcinoma GE junction n=1, aggressive fibromatosis n=1). 3 pts (renal cancer n=2, and giant cell tumor of the bone n=1) demonstrated tumor shrinkage of &lt; 30% (i.e. SD by RECIST). Conclusions: Concurrent administration of pazopanib and lapatinib was generally well tolerated. Coadministration of lapatinib may alter the PK of pazopanib. [Table: see text]
Treatment patterns and outcomes in metastatic colorectal cancer (mCRC).
Authors: Thomas H. Cartwright, Lonnie Kent Wen, Robyn K. Harrell, Patricia S. Fox, Janet L. Espirito, Ed Wang
Journal: Journal of Clinical Oncology (2016)

699 Background: Treatment (tx) selection for mCRC is multifactorial and affected by patient (pt) and disease factors, comorbidities, and previous tx. Few agents existed for therapy after second progression (i.e. third line (3L) at the time of this study. We aimed to capture mCRC tx patterns up to 3L and associated clinical and economic outcomes. Methods: A retrospective observational study of mCRC pts initiating 1L tx from 1/1/07 to 6/30/11 and 3L tx before 6/30/12. Data was extracted from The US Oncology Network (USON)/McKesson Specialty Health EHR and claims database. Pts on clinical trial or with another cancer diagnosis were excluded. Tx was organized into tx backbone categories and lines of therapy (LOTs), and adherence to NCCN guidelines and USON pathways assessed. The Kaplan-Meier method was used to estimate overall survival (OS). A multivariable generalized linear regression model was used to evaluate total costs during 3L tx as a function of 3L covariates by Medicare allowable. Clinical outcomes in 3L have been previously reported. Additional information on cost and other utilization is provided. Results: Of756 eligible 1L pts, 577 pts received 3L tx. At 1L, median age was 61 yrs (range 26-90+), male (55%), normal BMI (43%), ECOG performance status (PS) of 1 (65%), and Medicare (39%) insurance. The most utilized txs in 1L, 2L, and 3L were oxaliplatin-based (FOLFOX + bevacizumab, 46%), irinotecan-based (FOLFIRI + bevacizumab, 23%), and irinotecan + anti-EGFR (irinotecan + cetuximab, 24%) respectively. Adherence to NCCN and USON recommendations for 1L, 2L, and 3L was 88%/75%/55% and 84%/62%/38% respectively. OS in 3L was influenced by PS, BMI, and KRAS (p &lt; 0.05), but was not different by tx backbone (p = 0.47). In the multivariable model of total cost per pt in 3L, there were no significant predictors. Conclusions: Knowledge of tx sequencing aids in understanding selection choices and outcomes in pts who are candidates for later lines of therapy of mCRC. High utilization of targeted therapies was observed in each line. Adherence to guidelines decreased with increasing lines of therapy. Utilization and costs by tx backbone in the 3L during this time frame varied. 3L OS did not differ according to tx backbone.
Nutritional status and outcomes of older versus younger patients (pts) with metastatic pancreatic cancer (mPC).
Authors: Namrata Vijayvergia, Jenny Y Seo, Karthik Devarajan, Crystal Shereen Denlinger, Steven J. Cohen, Efrat Dotan
Journal: Journal of Clinical Oncology (2016)

386 Background: Older mPC pts are less likely to receive chemotherapy (Ctx) and receive fewer agents compared to younger pts, yet have similar overall survival (OS). Both obesity and malnutrition are linked with poorer outcomes in pancreatic cancer. We evaluated the effect of body mass index (BMI) and nutritional state on survival in &lt; 65 y (GpA) and &gt; 65 y (GpB) mPC pts. Methods: With IRB approval, we retrospectively analyzed charts of 579 mPC pts treated between 2000 and 2010. GpA and GpB were compared based on BMI alone (&lt;19, 20-25 and &gt;25) and also their nutritional status (poor: albumin &lt;3 or weight loss&gt;15% during disease course with any BMI; good: Alb&gt;3.5 + Wt loss&lt;15% + BMI &gt;20; intermediate: all others). Log-rank tests and Cox proportional hazards models were used to analyze OS and Fisher’s exact test to compare categorical variables. Results: There were 299 pts in GpA (median age 57yr) and 280 pts in GpB (median age 73 yr). Information on BMI/albumin was missing for 126 pts; total study population was 454 (GpA 238, GpB 216).Groups were well balanced for gender (majority male), PS (majority ≤1), initial stage (majority IV), and primary site (majority head). There was no significant difference in Ctx and number of agents used between the 3 subgroups across GpA and GpB. BMI alone did not affect survival in both groups. Nutritional status was significantly associated with survival when evaluating the whole population and GpA, but not GpB (Table). Good nutrition GpA pts had a lower relative risk of death versus pts in intermediate and poor nutrition groups (RR 0.83, CI 0.71-0.96, p=0.02). Good nutritional status was associated with better survival in GpA on multivariate analysis (RR=0.81, CI 0.69-0.95; p=0.008,), but not in GpB. Conclusions: Nutritional status (defined by BMI, albumin and weight loss) was associated with survival in younger mPC pts but not in older pts. Greater attention to nutrition and cancer cachexia with possible interventions throughout treatment may improve survival in mPC pts undergoing chemotherapy, especially those &lt; 65 yrs. Table [Table: see text]
High-Sensitivity Troponin Assay Improves the Detection of Cardiac Involvement in AL Amyloidosis and Is the Most Powerful Prognostic Determinant.
Authors: Giovanni Palladini, Alessandra Barassi, Gabriele Sarais, Ruggero Capra, Andrea Foli, Paola Russo, Riccardo Albertini, Letizia Zenone Bragotti, Laura Obici, Stefano Perlini, Remigio Moratti, Gian Vico Melzi D'Eril, Giampaolo Merlini
Journal: Blood (2009)
Paclitaxel poliglumex (PPX)/carboplatin vs paclitaxel/carboplatin for the treatment of PS2 patients with chemotherapy-naïve advanced non-small cell lung cancer (NSCLC): A phase III study
Authors: C. J. Langer, M. A. Socinski, K. J. O’Byrne
Journal: Journal of Clinical Oncology (2005)

LBA7011 Background: The prognosis for patients with advanced NSCLC is strongly impacted by performance status (PS). Although the assumption that PS2 patients cannot tolerate and benefit from platinum-based combination therapy has been challenged, a preferred regimen for this pt population has not yet been established. PPX (XYOTAX) is a macromolecular drug conjugate linking paclitaxel to a biodegradable polymer, poly-L-glutamic acid. Preclinical and clinical findings show that more than 95% of circulating paclitaxel is present as the inactive conjugate, thereby reducing systemic exposure to high concentrations of free paclitaxel. As a single agent, PPX resulted in a median survival > 5 months in PS2 pts with NSCLC, and its feasibility in combination with carboplatin has been demonstrated. This study compares PPX/carboplatin vs paclitaxel/carboplatin in chemotherapy-naïve PS2 patients with NSCLC. Methods: Randomized, open-label, multinational, phase III study. Eligibility included locally advanced NSCLC or recurrent disease previously treated with radiation and/or surgery, no prior NSCLC chemotherapy, and ECOG PS2. Patients were randomized equally to either: A) PPX 210 mg/m2 in combination with carboplatin (AUC 6) Q3W; or B) paclitaxel 225 mg/m2 in combination with carboplatin (AUC 6) Q3W. Stratifications were based on gender, geographic location, disease stage, and history of brain metastases. Treatment continued until completion of 6 cycles, disease progression or intolerable toxicity. The primary endpoint was overall survival (OS). The study was powered at 80% with < 5% type 1 error to detect a hazard ratio of 1.375 in OS (Arm B to Arm A). Sponsor is blinded to treatment group until final analysis (to be conducted when 311 deaths have occurred). Results: 400 pts were randomized between Nov, 2002 and Dec, 2003. Patients were 35–89 years (median 62), 77% were male, 73% had Stage IV disease. Data for the primary endpoint (OS) and key secondary endpoints (time to progression, disease control, response rate, FACT-LCS, and toxicity) will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics Cell Therapeutics