tbuckley/cabot-search huggingface dataset:
Significance of stress myocardial perfusion scans in predicting cardiovascular events and mortality in cancer patients
Authors: S. Chandra, A. T. Tong, A. Wei Wei, S. W. Yusuf, S. Javaid, D. Liu, J. Durand, D. J. Lenihan
Journal: Journal of Clinical Oncology (2007)

17009 Background: Cardiac risk assessment in cancer patients has not extensively been studied. We evaluated the role of stress myocardial perfusion scan (SMPS) in predicting cardiovascular outcomes in cancer patients. Methods: A retrospective chart review was performed on 787 patients who had a SMPS from 01/2002 - 03/2003. All patients were followed for at least 1.5 years. Cox proportional hazard model was used to determine the time-to-first event [cardiac death, myocardial infarction (MI) and coronary revascularization]. Cardiac death was defined as documented cardiac death or sudden unexplained death. Results: A total of 501/787 (64%) patients had normal SMPS, whereas 286/787 (36%) had abnormal SMPS. Adenosine [430/787 (55%)] and dobutamine [144/787 (14%)] were used for chemical stress while 213/787 (23%) patients underwent exercise testing. Mean age was 66±11 years and median follow-up duration was 1.8 years. The 3- year event-free survival rate was 0.71 (0.64–0.78) for abnormal SMPS and 0.87 (0.8–0.94) for normal SMPS (p&lt;0.0001). Of all abnormal scans (n=286), 3-year event free-survival rate based on type of vascular defects varied from 0.79(0.67–0.93) for fixed defects, 0.68 (0.58-.08) for reversible defects and 0.63 (0.5–0.8) for co-existent fixed and reversible defects (p&lt;0.0001). Other factors adversely affecting event-free survival were male gender (p=0.025), cardiomyopathy (p=0.001), coronary artery disease (p&lt;0.0001), previous MI (p&lt;0.0001), congestive heart failure (p=0.001) and hypercholesterolemia (p&lt;0.0001). When we analyzed cardiac death as a separate event, SMPS results still made a significant difference with 3-year cardiac-survival rate of 0.79 (0.69–0.91) for abnormal scan group versus 0.88 (0.81–0.95) for normal scan group (p=0.05). Furthermore, the 3-year cardiac-survival rate in patients with both fixed and reversible defects was 0.4 (0.1–1), which was much worse than those with fixed [0.87 (0.76–0.99)] or reversible [0.85 (0.74–0.99)] defects alone (p=0.028). Conclusions: SMPS is a highly useful modality for predicting cardiac events and mortality in cancer patients. The characteristics of the perfusion defect further stratifies the patients at higher risk. No significant financial relationships to disclose.
Phase 2 study of talabostat and cisplatin in stage IV melanoma
Authors: M. J. Uprichard, S. J. O’Day, A. C. Pavlick, D. A. Richards, G. Frenette, J. Stephenson, S. Anthony, P. A. Pacciucci, V. Vrhovac, C. Cunningham
Journal: Journal of Clinical Oncology (2005)

7563 Background: Talabostat (T) is an oral inhibitor of dipeptidyl peptidases including fibroblast activation protein found on the stroma of tumors and in melanomas. T stimulates cytokine and chemokine production resulting in specific T-cell immunity and T-cell-independent activity. T significantly enhances cisplatin (C) activity in mice, and reduced tumor size >60% in melanoma xenografts (A375, A2058) in immunodeficient mice. Therefore, a clinical trial of this combination in patients with metastatic melanoma was warranted. Methods: An open-label, single-arm, Phase 2 study is underway in up to 54 evaluable patients with Stage IV melanoma. Six 3-week cycles of C-100mg/m2 (Day1) and T-300μg administered orally BID on Days 2–15. Dose-escalation of T to 400μg BID is allowed in subsequent cycles depending on tolerability. Single-agent T can then be continued beyond 6 cycles at the discretion of the investigator. Eligible patients have received no more than 1 prior bio- or chemotherapy regimen, have an ECOG PS 0–2 with measureable disease per RECIST, no symptomatic CNS metastases, LDH, ALT, and AST <3X ULN. The primary endpoint is disease response with secondary endpoints including survival, duration of response, time-to-progression, and incidence of clinically-significant events of neutropenia or anemia. Results: 23 patients have been enrolled to date, 15 men and 8 women with a median age of 55 (range 27–78). Sixteen patients had 1 prior treatment and 7 are treatment-naive for Stage IV disease. Thirteen patients are continuing on study with four out to at least 12 weeks of treatment. Three patients have evidence of clinical activity with significant decreases in measureable skin lesions (2 patients) or thoracic adenopathy (1 patient). The most frequently reported adverse events are nausea (56%), fatigue (35%), and vomiting (26%). Edema/peripheral swelling and anxiety are reported in 17%. Grade 3/4 events included nausea/vomiting in 3 patients, pain, dizziness, and pneumonia (in one patient each). Conclusions: The combination of T and C shows activity in metastatic melanoma and can be safely administered. Nausea, fatigue, and vomiting are the most common AEs. Enrollment is continuing and updated study results will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Point Therapeutics Point Therapeutics Point Therapeutics Point Therapeutics
Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb ticilimumab
Authors: A. Ribas, B. Comin-Anduix, V. Bozon, L. H. Camacho, C. A. Bulanhagui, J. Jalil, E. Seja, A. Gualberto, J. S. Economou, J. A. Glaspy, J. Gomez-Navarro
Journal: Journal of Clinical Oncology (2006)

8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical immunologic response to ticilimumab was evidenced by immune-related toxicity (G3 diarrhea in 2 pts, G2 hypophysitis in 1 pt, G3 hepatitis in 2 pts) and by anti-tumor activity: CR in 1 pt (15+ mo), PR in 2 pts (9+, 8 mo), and SD in 3 pts (11, 8+ and 4 mo); the rest had PD at 4 mo or less. A mean of 2 baseline and 7 follow up (range 5–9) time points were tested by tetramer and ELISPOT assays. 4 pts had an increase in MART-1-specific T cells beyond the RCV on 1 or more occasions, but no pt had a consistent pattern of change over time. Indeed, there was no consistent pattern of change in any pt in circulating T cells specific for MART-1, gp100, tyrosinase, EBV, or CMV by tetramer or by ELISPOT assay. One pt had accessible regressing lesions which on biopsy showed heavy infiltration by CD8+/Granzyme B+ CTL and a 10-fold enrichment of gp100-specific T cells compared to his peripheral blood. Conclusion: Ticilimumab administered monthly induces immune-related phenomena and tumor responses in patients with melanoma without a demonstrable expansion of circulating melanoma antigen-specific T cells. Evaluation of melanoma antigen-specific T cells within the tumor may be a better way to study the mechanism of antitumor activity of CTLA4 blocking mAb. [Table: see text]
Phase I study of PM02734: Association of dose-limiting hepatotoxicity with plasma concentrations
Authors: J. Y. Bruce, D. Geary, B. de las Heras, A. Soto, P. Garcia Paramio, A. Yovine, R. L. Schilsky, S. D. Undevia, M. J. Ratain
Journal: Journal of Clinical Oncology (2008)

2513 Background: PM02734 is a chemically synthesized depsipeptide with a broad spectrum of activity against solid tumors in vitro (breast, colon, lung, neuroblastoma, prostate, sarcoma and thyroid) and in vivo (breast, prostate, melanoma); as well as an acceptable non-clinical toxicology profile. Methods: Patients (n=20) with metastatic or advanced solid tumors were enrolled in a phase I, open-label, dose-escalating study to assess safety, tolerability, and pharmacokinetics (PK) of PM02734 infused over 30 min every 21 days (d). The starting dose was 90 mcg/m2. Cohorts of 1–6 patients (pts) were treated at doses of 90, 180, 360, 540, 1,080, 1,620 and 1,350 mcg/m2, and the maximal administered dose was 1,620 mcg/m2. Results: Median age of pts was 66 years (24–83 y), with 16 males and 4 females. The median PS was 1 (range 0–2). The most frequent cancer types were colorectal tumors (n=12). Most patients were heavily pretreated prior to enrollment. Common toxicities grade <2 included pruritus during infusion, nausea/emesis, lymphopenia, thrombocytopenia, and asymptomatic elevated transaminases (TAs). Dose-limiting toxicities (DLT) were grade 3–4 asymptomatic, reversible TA elevations lasting > 7 d at the 2 higher dose levels: 2/2 pts at 1,620 mcg/m2 and 2/4 pts at 1,350 mcg/m2. Premedication with dexamethasone ameliorated the pruritus but did not prevent the hepatotoxicity. Preliminary PK data showed a considerable degree of variability in clearance (10.6±4.6 L/h), half life (162±271 h) and Vss (876±1546 L). At dose levels < 1,080 mcg/m2, plasma PM02734 concentrations were not consistently detectable after 48 hours (h). Clearance was not correlated with dose or body surface area (BSA). At dose levels > 1,080 mcg/m2, grade > 3 TA elevations were correlated with PM02734 concentrations, with the highest correlation at 1 h after the end of the infusion (p=0.016). Conclusions: The DLT of PM02734 in a 30-minute infusion schedule is grade 3–4 asymptomatic and reversible TA elevation, which is associated with early plasma concentrations. Future studies aim to ameliorate the hepatotoxicity using a 3-h infusion schedule (with BSA-independent dosing). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration PharmaMar PharmaMar PharmaMar
Physiological lung growth between infancy and early childhood – Impact of gender, body growth, and tobacco smoke exposure
Authors: Anne Schmidt, Elena Proietti, Oliver Fuchs, Claudia Kuehni, Urs Frey, Philipp Latzin
Journal: European Respiratory Journal (2014)

Background:

Little is known of the natural course of lung growth during early childhood and its influencing factors. We studied the impact of gender, body growth and exposure to tobacco smoke on lung growth in healthy children.

Methods:

We measured Functional Residual Capacity (FRC) in 213 term-born children from a prospective birth cohort (BILD study: Basel & Bern Infant Lung Development). At the age of 5 weeks, FRC was measured using Multiple Breath Washout (MBW, FRCMBW). At the age of 6 years, FRC was measured using both MBW and plethysmography (FRCpleth). Sex-specific z-scores were calculated based on a subgroup of children not exposed to tobacco smoke. We investigated potential influencing variables using regression analysis.

Results:

High quality measurements of n=121 children (50% females) were included in the analysis at mean (SD) group ages of 34 (4.1) days and 6.1 (0.2) years. At neonatal age, mean (SD) FRCMBW was 100 (16) mL. At the age of 6 years, mean (SD) FRCMBW was 662 (155) mL, and FRCpleth was 1096 (209) mL.

Regression analysis showed a higher increase in absolute FRCMBW values in males compared to females (p=0.03). A higher increase in FRCMBW z-score was found in children with increased body growth (p=0.04), and in children where tobacco smoke exposure was stopped (p=0.04).

Analyses based on FRCpleth values showed comparable results.

Discussion:

This is the first study examining lung volume from infancy to early childhood in healthy children in a longitudinal data set. Our observations indicate an impact of intrinsic and extrinsic factors on lung growth.
Adherence to extracolonic cancer screening in Lynch syndrome kindreds
Authors: Z. K. Stadler, R. Stern, V. Devlin, E. Glogowski, N. Kauff, K. Offit, K. Hurley
Journal: Journal of Clinical Oncology (2009)

1513 Introduction: In addition to colorectal cancer (CRC), Lynch syndrome (LS) patients are at increased risk of extracolonic malignancies including endometrial (EC), ovarian (OC), upper gastrointestinal and urothelial tract cancers. Although the efficacy of extracolonic cancer screening in LS has not been clearly demonstrated, multi-organ screening is routinely recommended for LS patients (Lindor et al., JAMA 2006). Anecdotal evidence suggests that adherence to such screening may be inferior to CRC screening. Methods: 35 adults, identified in the context of genetic counseling and testing (GCT) as being from LS kindreds, were given recommendations for multi-organ screening and enrolled on a prospective follow-up study. For participants with relevant organs at risk, these included colonoscopy, urine cytology, transvaginal ultrasound (TVUS), CA-125 level and endometrial sampling all to be performed at least annually. Adherence with screening, perceived risk of cancer subtype and future intentions regarding screening were evaluated at least 12 months after GCT. Results: Median age at time of GCT was 44, 66% were female and 69% were diagnosed with a LS- related cancer prior to GCT (15 CRC; 9 EC). At time of follow-up, 89% of patients without CRC had a colonoscopy within the year. Among women at-risk for OC, 25% had TVUS and 38% had CA-125 level within the year. Among women at risk for EC, 22% had TVUS and 22% had endometrial sampling within the year. Of all participants, 40% had urine cytology within the year. Of participants with relevant organs at-risk, 72%, 33%, 75% and 12% reported their risk of developing CRC, EC, OC, and urothelial tract cancer, respectively, as “moderately”, “very” or “extremely” high. Of patients with previous colonoscopy, 93% had definitive intentions to continue on schedule screening. However, only 68%, 50%, 60% and 50% of patients who underwent previous urine cytology, TVUS, CA-125 or endometrial sampling, respectively, had definitive intentions of continuing on schedule screening. Conclusions: Adherence with extracolonic cancer screening in LS kindreds is poor and patients persistently underestimate their extracolonic risk despite GCT. Possible interventions should be aimed at better educating patients about extracolonic cancer risk and importance of on-going surveillance. No significant financial relationships to disclose.
How should we measure arm exercise capacity in COPD? A systematic review
Authors: Tania Janaudis-Ferreira, Marla K. Beauchamp, Roger S. Goldstein, Dina Brooks
Journal: European Respiratory Journal (2011)

Background:  There are no recommendations on how to measure arm exercise capacity in individuals with chronic obstructive pulmonary disease (COPD). The objectives of this study were to: (i) synthesize the literature on measures of arm exercise capacity in individuals with COPD; (ii) describe the psychometric properties and the target construct of each measure and (iii) make recommendations for clinical practice and research.   Methods:  Studies conducted in COPD that included a measure of arm exercise capacity were identified after searches of 5 electronic databases (MEDLINE, CINAHL, EMBASE, Physiotherapy Evidence Database and Cochrane Library) and reference lists of pertinent articles. One reviewer performed data extraction and two assessed quality of studies that described measurement properties using the Consensus-based standards for the selection of health measurement instrument.   Results:  Of 654 reports, 41 met the study criteria. Five types of arm exercise tests were indentified: arm ergometry, ring shifts, dowel lifts, proprioceptive neuromuscular facilitation, and activities of daily living (ADL) tests. Four studies assessed measurement properties of the Unsupported Upper Limb Exercise test (UULEX), 6-minute Pegboard and Ring test (6PBRT), a test involving weight shifts and the Grocery Shelving Task (GST). Validity studies were of fair to good quality, whereas reliability studies were of poor quality.   Conclusions:  Arm ergometry may be best for measuring peak arm exercise capacity and endurance during supported exercises, while the UULEX, 6PBRT and GST may better reflect ADL and should be the tests of choice to measure peak unsupported arm exercise capacity (UULEX) and arm function (6PBRT and GST).
Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases.
Authors: A. Niwinska, M. Murawska, K. Pogoda
Journal: Journal of Clinical Oncology (2010)

1029 Background: To assess the role of systemic treatment after whole-brain radiotherapy (WBRT) in immunohistochemically defined biological subsets of patients with breast cancer with brain metastases. Methods: The group of 420 consecutive patients with breast cancer with brain metastases treated at the same institution between the years of 2003-2009 was analyzed prospectively. Patients were divided into four immunohistochemically biological subsets, based on the levels of estrogen (ER), progesterone (PgR), and HER2 receptors, and labeled as (1) triple-negative (estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, HER2/neu(HER2-negative), (2) HER2 (HER2-positive, ER-negative, PgR-negative), (3) luminal B (HER2-positive, ER-positive, and/or PgR-positive) and (4) luminal A (ER-positive and/or PgR-positive, HER2-negative). Survival from brain metastases with and without systemic treatment after WBRT was calculated in four subsets. Results: In the entire group, median survival from brain metastases in patients without and with systemic treatment after WBRT was 3 and 10 months, respectively (p<0.0001). In triple-negative subtype, median survival from brain metastases with and without systemic treatment was 4 and 3 months (p=0.16), in luminal A it was – 12 and 3 months (p=0.003), respectively. In luminal B median survival without further treatment, after chemotherapy/hormonal therapy and after chemotherapy/hormonal therapy with targeted therapy was 2, 9, and 15 months, respectively (p=0.000). In HER2 subset it was 4, 6, and 13 months, respectively (p=0.000). Cox multivariate analysis revealed, that good performance status, one brain metastasis, lack or controlled extracranial disease, biological subtype other than triple-negative and systemic treatment after WBRT had beneficial effect on survival after WBRT. Conclusions: Systemic therapy, ordered after WBRT, improves survival in Luminal A, Luminal B, and HER2 subtype, but not in triple-negative subtype. Targeted therapy had additional positive impact on survival. No significant financial relationships to disclose.
Factors associated with appropriate use of radiation therapy after mastectomy in women with Stage I-II breast cancer treated within the National Comprehensive Cancer Network (NCCN)
Authors: R. S. Punglia, M. E. Hughes, S. B. Edge, R. L. Theriault, M. A. Bookman, W. E. Burak, R. Ottesen, J. C. Niland, J. C. Weeks
Journal: Journal of Clinical Oncology (2004)

6032 Background: Since 1996, the NCCN has published breast cancer practice guidelines. We examined rates and determinants of appropriate use of post-mastectomy radiation (RT), as defined by the guidelines, among women with Stage I-II breast cancer. Methods: Using detailed clinical characteristics, 1,620 consecutive patients at eight NCCN institutions who received mastectomy as definitive surgery between July 1997 and June 2002 were classified according to whether they fell onto guidelines that (1) recommended RT, (2) recommended against RT, or (3) made no definitive recommendation. We considered no RT in the first group as underuse, and RT in the third group as overuse. Multivariable logistic regression was applied to each group to investigate the association of clinical and sociodemographic factors with RT. Results: Of the entire cohort, 23.8% of women received RT; 83.6% (199/238), 5.6% (58/1029), and 38.6% (127/329) in the recommend, do not recommend, and consider groups, respectively. On multivariable analysis, the only factor associated with underuse was not receiving chemotherapy (p<0.0001). In addition to tumor characteristics, factors associated with overuse included younger age (p=0.048, <50 versus 50 years or older), NCCN institution (p=0.03), college education (p=0.001), and no immediate reconstruction (p=0.02). RT in the “consider” subgroup was strongly associated with NCCN institution (p<0.0001), mastectomy performed at a non-NCCN institution (p=0.004), younger age (p=0.04), as well as tumor characteristics. Conclusions: Overall, rates of concordance with definitive guidelines were high. The only factor associated with underuse was non-receipt of chemotherapy, suggesting these women may have chosen to forego aggressive treatment. Older age did not predict for underuse, but younger age was a significant predictor of overuse. When current evidence does not support a definitive recommendation for post-mastectomy RT, treatment decisions appear to be influenced by patient age, tumor factors and particularly by institution-specific patterns of care. No significant financial relationships to disclose.
registHER: Patient characteristics, treatment patterns, and preliminary outcomes in patients with HER2-positive (HER2+), hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: D. A. Yardley, P. A. Kaufman, M. Mayer, M. Ulcickas Yood, E. Tan-Chiu, A. M. Brufsky, H. S. Rugo, D. Tripathy, S. Paik, M. G. Brammer
Journal: Journal of Clinical Oncology (2007)

21007 Background: Approximately 50% of HER2+ breast cancers are HR+, however, the interaction between HER2 and HR is not completely understood. Patients with HR+/HER2+ or HR-/HER2+ tumors treated with trastuzumab + chemotherapy (CT) achieve similar clinical benefit. Retrospective analyses suggest that HER2+ tumors are resistant to hormone therapy (HT), particularly anti-estrogens, possibly due to estrogen receptor /HER2 interactions and quantitatively lower HR expression in HER2+/HR+ tumors. Conducting randomized clinical trials in HER2+/HR+ MBC is challenging given the small patient population. Methods: registHER is a prospective observational study of approximately 1000 patients with newly diagnosed (&lt;6 months) HER2+ MBC treated in community or academic settings. Baseline characteristics and treatment patterns in patients with HR+ vs HR-, HER2+ MBC receiving first-line therapy were studied in this analysis. The influence of adjuvant HT on disease-free intervals (DFI) from time of diagnosis and MBC treatment selection in patients with HR+/HER2+ tumors was examined. Results: Of 976 patients with HER2+ MBC and recorded tumor HR status, those with HR+ MBC (54.9%) tended to be white (81.7% vs 77.0%), were more likely to have bone only metastases (18.1% vs 6.4%), less likely to have CNS metastases (2.8% vs 8.2%), and have fewer metastatic sites at diagnosis (49.1% vs 43.2%) than those with HR- MBC. Of patients with HR+ MBC, who were stage I- III at initial diagnosis, 51.3% received adjuvant HT, of which 73.2% received tamoxifen. Median DFI was 48.8 vs 29.4 mo for patients receiving tamoxifen vs an aromatase inhibitor. First-line MBC treatment regimens included: HT only (13.8%); HT + trastuzumab (8.4%); HT + trastuzumab + CT (6.2%); trastuzumab only (6.0%); CT only (11.0%); trastuzumab + CT (53.5%). Analyses of progression-free survival by HR status and first-line treatments (HT only, trastuzumab ± HT or ± CT), are ongoing and will be described. Conclusions: registHER represents the largest dataset of patients with HER2+/HR+ MBC and provides a unique opportunity to characterize treatment patterns, efficacy and safety, and the natural history of this subset of breast cancer patients. [Table: see text]