tbuckley/cabot-search huggingface dataset:
Association between musculoskeletal symptoms and serum vitamin D levels in women receiving aromatase inhibitor treatment.
Authors: Alice C. Shapiro, Karen K Swenson, MaryJo Nissen, Susan Adlis, Laura Maybon, Elsie Anderson, Karen E Zwicky
Journal: Journal of Clinical Oncology (2013)

e20560 Background: Up to 40% of women with estrogen positive (ER+) breast cancer treated with aromatase inhibitors (AIs) experience musculoskeletal symptoms (AIMSS) such as bone pain, joint pain, joint stiffness, and muscle weakness that negatively impact functional ability. Previous reports indicate that vitamin D insufficiency is common in this patient population and that D supplementation might attenuate AIMSS by affecting muscle, bone and/or nerve metabolism. To test the association between AIMSS and serum 25(OH)D levels, we analyzed data collected as part of a pilot prospective study assessing instrument effect sizes to measure AIMSS. Methods: Data were analyzed from 58 women, age 61 ± 10 y with a history of ER+ breast cancer stage I-IIIa. AIMSS symptoms were measured at baseline (pre AI) and 6 mo using the Breast Cancer Prevention Trial Musculoskeletal Subscale (BCPT-MS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the Australian-Canadian Hand Osteoarthritis Index (AUSCAN). Serum 25(OH)D was measured by radioimmunoassay (Diasorin liaison, Stillwater, MN). Linear regression analysis was used to determine the association between changes in AIMSS scores (dependent variables) and changes in serum 25(OH)D from baseline to 6 mo, adjusting for age and season. Results: From baseline to 6 mo there were significant increases on all AIMSS measures (BCPT-MS, WOMAC and AUSCAN p&lt;0.02). These increases in AIMSS measures were not associated with the change in serum 25(OH)D from baseline to 6 mo (Δ =11 ng/ml ± 12; p&lt;0.001). Conclusions: Worsening of symptoms during the initial 6 months of AI therapy was not associated with changes in serum 25(OH)D levels. These results suggest that short-term supplementation with 25(OH)D does not attenuate the symptoms of AIMSS in post-menopausal women with ER+ breast cancer during the first 6 mo of AI therapy. However vitamin D insufficiency was uncommon in this study population (mean 25(OH)D at baseline 31 ng/ml ± 10 and 42± 13 ng/ml at 6 mo). Well controlled clinical trials are needed to further our understanding of these relationships. Clinical trial information: NCT01074320.
Does change in health-related quality of life (HRQoL) score predict survival? Analysis of a lung cancer RCT.
Authors: Divine Ewane Ediebah, Corneel Coens, Efstathios Zikos, Chantal Quinten, Jolie Ringash, Carolyn Gotay, Elfriede Greimel, John T Maringwa, Madeleine King, Henning Flechtner, Martin J. B. Taphoorn, Jospeh Schmucker-Von Koch, Joachim Weis, Bryce B. Reeve, Egbert F Smit, Andrew Bottomley
Journal: Journal of Clinical Oncology (2012)

7607 Background: Over 60 cancer clinical trials have shown that baseline health-related quality of life (HRQoL) scores are prognostic for patient survival. Few studies have investigated the added value of change in HRQoL scores. Our aim was to investigate if change in HRQoL scores from baseline over time is also associated with survival. Methods: We analyzed data from an EORTC 3-arm randomized clinical trial (RCT) in advanced non-small-cell lung cancer (NSCLC) patients, comparing gemcitabine+cisplatin, versus paclitaxel+gemcitabine, versus standard arm paclitaxel+cisplatin. HRQoL was measured in 394 patients using the EORTC QLQ-C30 at baseline and after each chemotherapy cycle. The prognostic significance of sex, age and WHO performance status (0-1 vs. 2) and the 15 QLQ-C30 subscales were assessed with Cox proportional hazard models stratified for treatment (level of significance 0.05). Changes in HRQoL scores from baseline to each chemotherapy cycle assessment were categorized as “improved”, “stable” and “worsened” using a threshold of 10 points difference. Due to expected attrition, the analysis was limited to changes from baseline up to cycle 3. Results: There were 248 patients in cycle 1, 212 in cycle 2 and 196 in cycle 3. We performed analyses separately using data at cycle 1, cycle 2, and cycle 3. In all analyses, HRQoL in various subscales and socio-demographic and clinical variables (physical functioning (hazard ratio [HR] 0.91, 95% CI 0.85-0.98; p=0.0103), pain (1.11, 1.05-1.17; p= 0.0004), age (0.98, 0.97-1.00, p=0.0413) and WHO performance status (1.77, 1.09-2.89; p=0.0218) at cycle 1; pain (1.11, 1.03-1.20; p=0.0016), age (0.98, 0.96-1.00; p=0.0217) and sex (0.63, 0.42-0.95; p=0.0081) at cycle 2; and role functioning (0.93, 0.88-1.00; p=0.0128) and age (0.98, 0.96-1.00; p=0.0081) at cycle 3) predicted survival; however, change in HRQoL was only an independent predictor for improvement at cycle 1. Conclusions: Our findings suggest that change from baseline over time in HRQoL, as measured on subscales of the EORTC QLQ-C30, contains added prognostic value for survival independent of baseline HRQoL scores. Further work is needed to assess the robustness and sensitivity of these findings.
Effectiveness and limitations of staging laparoscopy for peritoneal metastases in advanced gastric cancer from the results of JCOG0501: A randomized trial of gastrectomy with or without neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer.
Authors: Shinji Hato, Yoshiaki Iwasaki, Junki Mizusawa, Masanori Terashima, Hitoshi Katai, Takaki Yoshikawa, Seiji Ito, Masahide Kaji, Junya Fujita, Motohiro Hirao, Makoto Yamada, Masakazu Takagi, Hiroshi Katayama, Kenichi Nakamura, Takeshi Sano, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2017)

9 Background: In type 4 or large type 3 gastric cancer diagnosed as not having distant metastasis by imaging modalities, the incidence of peritoneal metastasis that was unexpectedly found during laparotomy was approximately 40%. Staging laparoscopy (SL) is a valuable method used for staging gastric cancer. This study aimed to clarify the effectiveness and limitations of SL for patients (pts) with type 4 or large type 3 gastric cancer. Methods: JCOG0501 is a randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for treating type 4 or large type 3 gastric cancer. Eligibility criteria included histologically proven gastric adenocarcinoma that was clinically type 4 or large type 3 gastric cancer and was diagnosed as R0/1-resectable using SL. Pts who underwent gastrectomy without neoadjuvant chemotherapy were included in this study. Results: In total, 316 pts (158 pts with and without neoadjuvant chemotherapy each) were enrolled between October 2005 and July 2013 from 44 institutions. Of the 158 pts without neoadjuvant therapy, 2 pts did not receive laparotomy. The remaining 156 pts were included in this analysis. Among them, except for 1 patient (P1), none were diagnosed with peritoneal metastases (P0) during SL. Among these 155 pts, 24 (15.5%) were diagnosed with peritoneal metastases at subsequent laparotomies (false-negative). Most of the overlooked peritoneal disseminated nodules were located in the intestinal mesentery (8 pts), transverse mesocolon (5 pts), or omental bursa (3 pts). The total number of peritoneal disseminated nodules at laparotomy was often ≤ 9 (1–3 nodules in 14 pts, 4–9 in 4 pts). Of the 156 included pts, 142 underwent R0/1-resection (91.0%) because some overlooked nodules were curatively resected. Conclusions: SL is a useful diagnostic tool to plan the management of type 4 and large type 3 gastric cancers, although the high false-negative rate cannot be ignored. In SL, detailed exploration of the mesentery, mesocolon, and omental bursa is recommended.
Phase II trial of BNC105P as second-line chemotherapy for advanced malignant pleural mesothelioma (MPM): Australasian Lung Cancer Trials Group and NHMRC Clinical Trials Centre Collaboration.
Authors: Anna K. Nowak, Chris Brown, Michael Millward, Brett Gordon Maxwell Hughes, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin, Paul Mitchell, Nick Pavlakis, Xanthi Coskinas, Lucille T Sebastian, Michelle M Cummins, Michael J. Boyer, Francis Parnis, Tina C. Lavranos, Martin R. Stockler
Journal: Journal of Clinical Oncology (2012)

7079^ Background: BNC105P is a tubulin polymerization inhibitor that acts as a Vascular Disrupting Agent (VDA), has direct cytotoxic effects, and had preclinical and phase I activity in MPM. This aim of this study was to determine activity and safety of BNC105P as second-line therapy after pemetrexed and a platin in MPM. Methods: Eligible patients had progressive MPM, prior pemetrexed and platinum, measurable disease by modified RECIST, ECOG 0-1, and adequate organ and cardiovascular function. Important exclusions included recent thromboembolic, cardiovascular or cerebrovascular disease, or therapeutic anticoagulation. Pts received BNC105P (16 mg/m 2 IV) Day 1 + 8 q21d until progression or toxicity. The primary endpoint was centrally reviewed objective tumour response rate (RR); the Simon 2-stage design assumed a RR of interest of 20% and a RR of no interest of 5%, with α = β = 0.05. Continuation past first stage accrual required &gt;1 objective response in 24 patients. Results: 30 subjects were accrued over 10 months (90% male; median age 65 (range 41-83); 77% ECOG PS 1; histology epithelioid (67%), biphasic (10%), sarcomatoid (7%), other/unspecified (17%)). All pts received at least one dose of study drug; pts received a median of 2 cycles and median dose intensity was 100%. No significant haematologic, biochemical, peripheral neurotoxic or cardiac adverse events (AEs) including hypertension were observed. Grade 3 or 4 AEs occurred in 10 pts (33%). There were 2 deaths on study: 1 due to stroke, the other due to pneumonia and respiratory failure. We observed 1 partial response (3%) and 13 pts with SD as their best response (43%). Median progression free survival was 1.5 mo (95% CI 1.4-2.4); median overall survival was 8.7 mo (95% CI 3.8-NR). Lung function and QOL data was collected. Biomarker analyses correlating to pharmacological changes induced by BNC105P are ongoing and will be presented. Conclusions: BNC105P was safe and tolerable but its single agent response rate failed to meet the pre-specified primary endpoint of interest.
Exercise-induced changes in QT interval are smaller in COPD patients and have no impact on mortality
Authors: Afroditi K. Boutou, Russell Franks, Divya Mohan, Lilian Mantziari, Tom Wong, Nicholas S. Hopkinson, Michael I. Polkey
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) is a systemic disorder with significant pulmonary and extrapulmonary manifestations [1]. The right and left heart and the great vessels may be affected [2]. Specifically, patients with COPD (especially those with hypoxaemia) have functional alterations in cardiac autonomic modulation, manifested by tachycardia at rest, reduced baroreflex sensitivity, reduced heart rate variability and abnormal recovery of heart rate following exercise [3]. COPD patients establish a flat shortening of QT interval during maximum exercise, irrespectively of medication taken <http://ow.ly/XMrb308wUZt>
Treatment response monitoring in chronic phase CML (CP-CML) patients receiving tyrosine kinase inhibitor (TKI) therapy in US Oncology network.
Authors: Kathryn S. Kolibaba, Hsing-wen Chung, Rahul Dhanda, Debra Rembert, Stephanie Lustgarten, Jing L. Marantz, Hui Huang
Journal: Journal of Clinical Oncology (2013)

7065 Background: To identify pts with TKI resistance in a timely manner, the National Comprehensive Cancer Network (NCCN) guidelines recommend monitoring pts at specific time points. We evaluated the relationship between NCCN guidelines and current treatment response monitoring patterns and outcomes of CP-CML pts in community practice. Methods: A retrospective longitudinal cohort study was conducted on newly diagnosed CP-CML pts initiating TKI therapy from Jan 1, 2008 to Dec 31, 2010. Data was extracted from the MSH/USON iKnowMed electronic health record database and chart reviews through Jul 31, 2012. Pts were stratified by presence of any cytogenetic monitoring by 12 mos or any molecular monitoring by 18 mos. Results: Of the 410 pts identified, 91% received imatinib and 9% received dasatinib/nilotinib. Median follow-up was 28 mos. Cytogenetic and molecular monitoring did not occur in 69% and 27% of pts, respectively. BCR-ABL mutation testing occurred in 10% of pts who were monitored for response. Pts ≥65 yrs old (vs &lt;65 yrs, p&lt;0.01), with public insurance (vs private insurance, p&lt;0.001), or with Karnofsky Score ≤80 (vs &gt;80, p&lt;0.05) were less likely to have cytogenetic monitoring. Similar differences for age (p&lt;0.05) and insurance (p&lt;0.001) were seen for molecular monitoring. For pts with available monitoring results, 36% had complete cytogenetic response by 12 mos, and 59% had major molecular response by 18 mos. 4-yr overall survival (OS) rates were higher in pts with cytogenetic (98% vs. 89%, P=0.0003) or molecular (95% vs. 82%, P≤0.0001) monitoring vs. those with no monitoring. Conclusions: In these CP-CML pts, 69% did not receive any cytogenetic monitoring by 12 mos and 27% did not receive any molecular monitoring by 18 mos. Obstacles related to monitoring may include age, payer status, and performance status. Pts that were monitored for cytogenetic and molecular responses had significantly higher OS rates at 4 yrs. Increasing the proportion of pts that are monitored according to NCCN guidelines in the community setting could improve patient outcomes.
EXPERIENCIA SOBRE LA UTILIZACIÓN DE LAS PRÓTESIS METÁLICAS AUTOEXPANDIBLES EN CÁNCER COLORRECTAL (CCR) OBSTRUCTIVO
Authors: E Omonte Guzman, I Pinazo Martinez, L Vázquez Pedreño, M Bocanegra Viniegra, E Morcillo Jimenez, E Tenorio Gonzalez, O Sánchez García, R Manteca González
Journal: Endoscopy (2015)

Las prótesis autoexpandibles metálicas (PAM) han supuesto una alternativa válida en el tratamiento de urgencia de la obstrucción maligna colorrectal. Su empleo permite tanto la posibilidad de una cirugía diferida con menores tasas de morbilidad y mortalidad (prótesis puente) como su colocación definitiva paliativa en los casos no candidatos a cirugía.
Predicting disease progression in men with localized high risk prostate cancer undergoing radical prostatectomy.
Authors: Yaw A. Nyame, Jeffrey J. Tosoian, Ridwan Alam, Lamont Wilkins, Kasra Yousefi, Meera Chappidi, Chandana A. Reddy, Elizabeth B. Humphreys, Debasish Sundi, Brian F. Chapin, Andrew J. Stephenson, Eric A. Klein, Ashley Ross
Journal: Journal of Clinical Oncology (2017)

51 Background: Currently utilized pre-treatment nomograms for prostate cancer were developed and validated using populations primarily composed of men with low and intermediate risk disease. This study aims to construct a nomogram that predicts for biochemical recurrence (BCR) and metastasis (mets) from a contemporary cohort of men with with NCCN high (HR) and very high risk (VHR) prostate cancer. Methods: From 2005 to 2015, 1,241 men with NCCN HR or VHR prostate cancer were identified from two large academic medical centers. The cohort was divided into training (n = 620) and validation (n = 621) cohorts. Primary endpoints were BCR and mets. Cox multivariable regression was performed to model characteristics and outcomes in the training cohort. Model accuracy was assessed using the time-dependent area under the receiver operator characteristic curve (AUC) in the validation cohort. Results: 494 men (245 training and 249 validation) developed BCR, and 123 men (64 training and 59 validation) developed mets, with BCR-free and mets-free probability of 49.0% and 86.5% at 5- years, respectively. Predictive nomograms including age, ethnicity, PSA, Gleason grade, clinical stage, and the number of cores with Gleason 8-10 disease were developed. Models for BCR and mets had AUCs of 0.72 and 0.75. By comparison, the MSKCC preoperative nomogram and CAPRA nomogram provided AUCs of 0.69 and 0.68 for predicting BCR and 0.66 and 0.67 for mets. Conclusions: Individualized risk assessment is imperative for optimal decision making and to design and power clinical trials. The nomograms described here, created from a population exclusively comprised of HR/VHR men, have better discrimination than those previously established on cohorts of primarily low and intermediate risk men, and may represent an ideal way by which oncologic outcomes can be predicted in men with HR or VHR disease.
Low Doses of Eltrombopag Are Safe and Effective in the Prophylaxis of the Chemotherapy-Induced Thrombocytopenia (CIT)
Authors: Francesco Iuliano, Eleonora Iuliano, Alessia Perricelli, Maria Aquila Santoro, Angelo Pomillo, Maria Luci, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Blood (2016)
Phi-53: (NCI#7251): Phase I trial of belinostat (PXD101) in combination with 13-cis-retinoic acid (13c-RA) in advanced solid tumor malignancies—A California Cancer Consortium NCI/CTEP sponsored trial.
Authors: Thehang H. Luu, Paul Henry Frankel, Dean Lim, Mihaela C. Cristea, Jan Hendrik Beumer, Leonard Joseph Appleman, Heinz-Josef Lenz, David R. Gandara, Richard Piekarz, Edward M. Newman
Journal: Journal of Clinical Oncology (2013)

2526 Background: Belinostat has a reported maximum tolerated dose (MTD) of 1,000 mg/m 2 given days 1 to 5 every 21 days as a single agent, although in one study in hepatocellular carcinoma belinostat was given at 1,400 mg/m 2 on the same schedule. Pre-clinical evidence suggests HDAC inhibitors enhance retinoic acid signaling with a synergistic impact in a variety of solid tumors. We conducted a phase I study of belinostat and 13c-RA in advanced solid tumors. Methods: Dose limiting toxicity (DLT) was defined as cycle 1 hematologic toxicity: ≥grade 3 that not resolved to &lt;grade 1 within 1 week or non-hematologic toxicity: ≥grade 3. We sought the MTD of belinostat days 1-5 with 13-cRA days 1-14, every 21 days, in patients (pt) with advanced solid tumors. Eligibility criteria included normal organ function and QT/QTc interval; 4 weeks from previous therapy. Results: 51 pt were treated: median age 61 (range 40-80); 29 men; 57% ECOG 0, 41% ECOG 1, 2% ECOG 2; 13 lung, 11 breast, 8 colorectal, 3 pancreatic. 11 dose levels (DL) were tested starting from belinostat 600 mg/m 2 /day and 13c-RA 50 mg/m 2 /day to belinostat 2000 mg/m 2 /day and 13c-RA 100 mg/m 2 /day. Only two DLTs were observed: a grade 3 hypersensitivity reaction with dizziness and hypoxia at DL 8 (belinostat 1700 mg/m 2 /day, 13c-RA 100 mg/m 2 /day); and a grade 3 allergic reaction in a patient with an ECOG PS 2 at DL 11 (belinostat 2000 mg/m 2 /day, 13c-RA 100 mg/m 2 /day). The MTD was not reached. Pharmacokinetics of belinostat suggests dose proportionality. Median number of cycles: 2 (range 1–56). 10 patients had SD including: 1 neuroendocrine pancreatic stable for 56 cycles; 1 breast pt for 12 cycles; 1 lung pt 8 cycles. 2 pt had PRs: a keratinizing squamous cell carcinoma (tonsil) and a lung cancer pt. Conclusions: Belinostat 2000 mg/m 2 days 1-5and 13-cis-Retinoic acid 100 mg/m 2 days 1-14, every 21 days, was well-tolerated and an MTD was not reached despite doubling the established single agent MTD. Future studies building on this combination to belinostat are warranted. Support: U01CA062505 and P30CA033572 (City of Hope); U01CA099168 and P30CA047904 (University of Pittsburgh).
Correlation Between Treatment Outcomes, Baseline Characteristics and Molecular Responses in the Majic Study Which Compared Ruxolitinib to Best Available Therapy in Essential Thrombocythemia
Authors: Claire N. Harrison, Adam Mead, Sonia Fox, Anesh Panchal, Christina Yap, Aimee E Houlton, Samah Aliman, Joanne C Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Robyn M. Scherber, Holly Geyer, Allison H Scotch, Amylou Constance Dueck, Nicholas CP Cross, Ruben A. Mesa, Mary Frances McMullin
Journal: Blood (2016)
Regulation of trastuzumab resistance in gastric cancer by the PTEN gene, downstream AKT, and bypass IGF-IR signaling pathway.
Authors: Qiang Zuo, Jing Liu, Jingwen Zhang, Mengwan Wu, Wenjun Liao, Min Shi, Wangjun Liao
Journal: Journal of Clinical Oncology (2014)

e22079 Background: Trastuzumab has been successfully employed for the treatment of HER-2-positive breast cancer and gastric cancer, and satisfactory therapeutic results have been achieved. However, there are problems with both primary and secondary resistance to trastuzumab. Most studies about trastuzumab resistance have focused on breast cancer, so there have been few reports on gastric cancer. Methods: In this study, we employed the human gastric carcinoma cell line NCI-N87 with high HER-2 expression to create trastuzumab-resistant NCI-N87/TR cells. Results: Compared with NCI-N87 cells, the expression of P-IGF-1R and P-AKT proteins was significantly increased in NCI-N87/TR cells, while PTEN gene and protein expression showed a significant decrease. In addition, mutations of the PTEN gene were detected at exons 5, 7, and 8. The sensitivity of NCI-N87/TR cells to trastuzumab was increased by transfection with the PTEN gene, or by incubation with a PI3K inhibitor (LY294002) or an IGF-IR inhibitor (AG1024). Conclusions: Taken together, our findings showed that activation of the PI3K-AKT signaling pathway was one of the major mechanisms leading to resistance of NCI-N87/TR gastric cancer cells to trastuzumab, which was associated with PTEN gene down-regulation and mutation, as well as with over-activity of the IGF-1R signaling pathway.
Measuring the impact of extended cancer survival on broader aspects of life and wellbeing: The PROACT Study.
Authors: Valerie M Shilling, Rachel Starkings, Valerie A. Jenkins, Lesley Fallowfield
Journal: Journal of Clinical Oncology (2017)

227 Background: Living with cancer and its treatment affects many aspects of life, impacting roles and responsibilities. Formal assessment of these impacts is not normal practice and there is a need for rigorously developed, well-validated measures for both patients (pts) and informal caregivers (cgs). We present an overview of work (PROACT) detailing the development of such tools. Methods: Stage 1: Two systematic reviews of existing PROs used to measure broad life impact in pts and cgs, mapping individual scale items to conceptual domains to identify what is currently being measured and where gaps exist. Stage 2: Qualitative 1: Thematic analysis of in-depth interviews with pt-cg dyads about the impact of extended cancer survival on broader aspects of life and wellbeing to generate potential items for new measures. Qualitative 2: Cognitive interviews with new pt-cg dyad cohort using "think aloud" and specific probes to refine items for new measures. An advisory panel of 5 people with lived experience of cancer or caregiving worked with us throughout the project. Results: Systematic reviews identified gaps in existing measures around changes in occupational, financial, household and family roles and responsibilities and informed topic guides for Qualitative 1. Interviews with 24 pt-cg dyads generated 20 themes and 33 sub-themes from which 31 pt and 64 cg items were devised. Cognitive interviews with 20 pt-cg dyads in Qualitative 2 refined the measures. The final measures consisted of 29 items for pts (intended to be administered alongside FACT-G/QLQ-C30) and 60 for cgs (stand alone). Items cover family responsibilities, financial well-being, jobs and careers and additional sections on relationships and communication, lifestyle and outlook and health and well-being for cgs. Conclusions: We have developed two scales to measure broad life impacts of cancer for patients and informal caregivers. These are currently being evaluated and validated in Stage 3 of the project. Once validated these scales will be useful tools for clinicians and researchers enabling wide-ranging longer-term evaluation of new treatments in clinical trials and to aid decision-making about treatment options and supportive interventions.