tbuckley/cabot-search huggingface dataset:
Mobile Health Interventions for Improving Health Outcomes in Youth
Authors: David A. Fedele, Christopher C. Cushing, Alyssa Fritz, Christina M. Amaro, Adrian Ortega
Journal: JAMA Pediatrics (2017)

Mobile health interventions are increasingly popular in pediatrics; however, it is unclear how effective these interventions are in changing health outcomes.To determine the effectiveness of mobile health interventions for improving health outcomes in youth 18 years or younger.Studies published through November 30, 2016, were collected through PubMed, Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, and PsychINFO. Backward and forward literature searches were conducted on articles meeting study inclusion criteria. Search terms included telemedicine, eHealth, mobile health, mHealth, app, and mobile application.Search results were limited to infants, children, adolescents, or young adults when possible. Studies were included if quantitative methods were used to evaluate an application of mobile intervention technology in a primary or secondary capacity to promote or modify health behavior in youth 18 years or younger. Studies were excluded if the article was an unpublished dissertation or thesis, the mean age of participants was older than 18 years, the study did not assess a health behavior and disease outcome, or the article did not include sufficient statistics. Inclusion and exclusion criteria were applied by 2 independent coders with 20% overlap. Of 9773 unique articles, 36 articles (containing 37 unique studies with a total of 29 822 participants) met the inclusion criteria.Of 9773 unique articles, 36 articles (containing 37 unique studies) with a total of 29 822 participants met the inclusion criteria. Effect sizes were calculated from statistical tests that could be converted to standardized mean differences. All aggregate effect sizes and moderator variables were tested using random-effects models.Change in health behavior or disease control.A total of 29 822 participants were included in the studies. In studies that reported sex, the total number of females was 11 226 (53.2%). Of those reporting age, the average was 11.35 years. The random effects aggregate effect size of mobile health interventions was significant (n = 37; Cohen d = 0.22; 95% CI, 0.14-0.29). The random effects model indicated that providing mobile health intervention to a caregiver increased the strength of the intervention effect. Studies that involved caregivers in the intervention produced effect sizes (n = 16; Cohen d = 0.28; 95% CI, 0.18-0.39) larger than those that did not include caregivers (n = 21; Cohen d = 0.13; 95% CI, 0.02-0.25). Other coded variables did not moderate study effect size.Mobile health interventions appear to be a viable health behavior change intervention modality for youth. Given the ubiquity of mobile phones, mobile health interventions offer promise in improving public health.
A phase III randomized trial of niraparib versus physician’s choice in previously treated, HER2-negative, germline-BRCA mutated breast cancer patients: Intergroup study EORTC-1307-BCG and BIG5-13.
Authors: Konstantinos Tryfonidis, Jan Bogaerts, Robert E. Martell, George W. Sledge, Judith Balmaña, M. William Audeh, Angelique Deleersnijder, Felicia Favorito, Shefali Agarwal, Giovanna Rizzetto, Carlo G. M. Messina, Leen Slaets, Theodora Goulioti, Andrew Tutt, David A. Cameron, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2014)

TPS659 Background: Germline mutations of BRCA1/BRCA2 genes are a cause of hereditary breast or ovarian cancer. Cancers arising in women with germline BRCA1/BRCA2 mutations are defective in DNA repair, and BRCA deficient cancer cells are hypersensitive to PARP inhibitors (Bryant et al., 2005;Farmer et al., 2005). Niraparib is a potent,selective inhibitor of PARP-1 and PARP-2 that demonstrated activity in BRCA1 or BRCA2 mutated cancer cell lines. Responses have been reported with Niraparib in women with BRCA1.2 related breast and ovarian cancer. (Michie et al, 2013). Methods: Patients with HER2 negative metastatic breast cancer (306), with centrally confirmed BRCA1 or BRCA2germline mutations, will be randomized 2:1 open-label study, to either niraparib 300mg (3x 100 mg niraparib capsules) administered orally QD continuously or physician's choice of single-agent chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine) administered in 3 weekly cycles. Patients must have received prior therapy that included a taxane and anthracycline and should be pretreated with up to 2 prior cytotoxic regimens for advanced/metastatic disease. Patients with hormone receptor positive disease can be included if they progressed during one prior hormonal therapy. The primary objective is to compare the progression-free survival (PFS) (RECIST v 1.1) on niraparib versus physician's choice, assessed by blinded, central review. The key secondary objective is to compare overall survival between patients in niraparib versus physician's choice. Sample size is based on Overall Survival (OS). The hypothesis of median PFS improvement is 3 versus 6 months for physician's choice and niraparib respectively, with a hazard ratio of 0.5, and power of 99.6% for the primary PFS analysis. Assuming an increase in OS from 9 to 13 months, the study has 80% power at a 1-sided alpha of 0.025. Secondary endpoints are PFS by investigator-based assessment, safety, time to treatment failure, Response Rate, Duration of response, HRQoL. This trial is enrolling patients from European, North American countries and Israel and is sponsored by TESARO. Clinical trial information: NCT01905592.
New graded prognostic index for breast cancer patients (pts) with brain metastases (BCBM).
Authors: Manmeet Singh Ahluwalia, Lingling Du, Vyshak Alva Venur, Lilyana Angelov, Samuel T. Chao, Paul Elson, Alireza Mohammad Mohammadi, David M. Peereboom, G. Thomas Budd, Gene H. Barnett, John H. Suh, Jame Abraham
Journal: Journal of Clinical Oncology (2014)

637 Background: Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) is frequently used for prognosis for BCBM. We evaluated DS-GPA plus other potential prognostic factors for overall survival (OS) in BCBM pts treated at a single tertiary care institution in a contemporary cohort (Preliminary data was presented at ASCO 2013). Methods: With IRB approval, the Cleveland Clinic's database was used to identify BCBM pts treated between 2000 and 2010. OS from the diagnosis of BCBM was the primary end point.Cox proportional hazards models with stepwise variable selection were used for data analysis. Results: 371 female patients were included for this analysis. Karnofsky performance scale (KPS) was 90-100 in 142 patients (42%), 70-80 in 146 (43%) and <70 in 48 (15%) patients. Median OS for the entire group was 11.9 months (95% C.I. 9.8-13.6). Median OS in Luminal B, Her 2, Luminal A and basal groups of pts was 23.3, 13.7, 11.9 and 6.0 months respectively (using Sperduto e.t al. 2012 criteria to define the subgroups). DS-GPA for BCBM is based on KPS, age at diagnosis, and subtype. Overall it was prognostic for OS (p<.0001) however separation between groups was variable. Using DS-GPA as a starting point, the number of extracranial metastases (ECM) present, control of the primary, and leptomeningeal metastases (LEP), were found to be additional independent prognostic factors (Table). Combining these factors a revised DS-GPA with 3 groups was defined: unfavorable (total points <6), intermediate (6-8 points), and favorable (>8 points) with median OS of 4.3, 11.9, and 23.4 months, respectively. Conclusions: A revised DS-GPA for BCBM based on the conventional GPA, and 3 additional factors is proposed. Factor No. of points Hazard ratio1 p No. ECM 0 or 1 3 1.98 (1.49-2.62) <0.0001 >1 0 Primary controlled Yes 2 1.51 (1.13-2.00) 0.005 No 0 LEP No 2 1.54 (1.12-2.11) 0.008 Yes 0 DS-GPA 3.5-4 6 1.55 (1.34-1.78) <0.0001 2.5-3 4 1.5-2 2 0-1 0 Revised GPA No. Points Median OS (mo) N (%) Unfavorable <6 4.3 68 (25%) Intermediate 6-8 11.9 118 (44%) Favorable >8 23.4 85 (31%) 1 First group is the reference.
Patient screening tool as input to the survivorship summary of care plan appointment.
Authors: Patricia A. Robinson, Julia Rachel Trosman, Pam Khosla, Claudia B. Perez, Shakuntala Shrestha, Sofia F. Garcia, Carol A. Rosenberg, Stephanie Boecher, Javier Macias, Rosa Berardi, Frank J. Penedo, Sheetal Mehta Kircher, Megan Slocum, Christine B. Weldon
Journal: Journal of Clinical Oncology (2017)

140 Background: A review of the literature failed to identify a screening tool specific to the unique needs of cancer survivors. The Coleman Supportive Oncology Collaborative (CSOC) developed a tool to evaluate psychosocial, physical and practical concerns, and emotional distress for concurrent use during the cancer survivorship visit. Based on pilot results of the tool, minor modifications were made and tested. Methods: The CSOC (v.3) survivorship tool was used in patients (n = 49) who had completed their adjuvant therapy at one of two safety net hospitals in Chicago, IL. The CSOC v.3 screening tool items (n = 44) include: PHQ4, fear of another cancer or recurrence, financial, social and religious concerns, nutritional concerns, physical concerns, lifestyle risk factors, and treatment/care concerns. Results: The most common patient concerns included: fear of another cancer 53% (26/49), tingling in my hands/feet 53% (26/49), concerns about diet 51% (25/49), pain 51% (25/49), sleep 51% (25/49), dry skin 47% (23/49); endorsement of these concerns were not significantly associated. Of the 44 items, 16 were reported by at least 30% of patients, and 3 items were reported by less than 10% of patients. There was an average of 15 items/concerns noted by patients with a maximum of 27 items and a minimum of 5 items. Clinicians (n = 7) reported the use of the screening tool results aided the survivorship appointment discussion, directing the focus to reported patient’s concerns. Conclusions: Survivors continue to experience multiple concerns and distress, thus they may benefit from a comprehensive tool that is tailored to capture their unique survivorship needs. Administration of the tool at the beginning of the survivorship appointment provided the framework for the patient’s appointment narrative. An additional study is planned to compare use of the tool versus current practice at a large academic center.
Safety and pharmacokinetic (PK) results from phase 1 of an ongoing phase 1-2 study of onapristone (ONA) in patients (pts) with progesterone receptor (PR)-expressing cancers.
Authors: Antoine Italiano, Jacques Bonneterre, Andrea Varga, Keyvan Rezai, Mario Campone, Anne Floquet, Alexandra Leary, Dominique Berton-Rigaud, Marie-Paule Sablin, Anne Lesoin, Francois Marc Lokiec, Catherine Lhommé, Alice Susannah Bexon, Erard M. Gilles, Joseph Bisaha, Alexander Zukiwski, Paul H. Cottu
Journal: Journal of Clinical Oncology (2015)

e16517 Background: ONA is a type I PR antagonist, which prevents PR-induced DNA transcription. ONA anti-cancer activity is documented in multiple pre-clinical models and clinical studies in pts with breast cancer. An extended-release (ER) oral formulation of ONA has been developed to achieve continuous exposure and PR suppression. Methods: This is an ongoing multi-center, open-label, randomized, parallel-group, 2-stage phase 1-2 study (total n~90; NCT02052128) enrolling female pts ≥ 18 years with PRpostumors. The 1º endpoint was determination of the recommended dose (RD) of ER ONA; 2º endpoints included safety and efficacy. In phase 1, pts were randomized to 5 cohorts of ER ONA tablets 10-50 mg BID, or 100 mg immediate release QD until progressive disease (PD) or intolerability. Phase 2 is a Simon 2-stage design in pts with endometrial cancer. PK sampling: D1 H0, 1, 2, 4, 6, 8, 12 and D8, D29 and D57 at H0. Monolix software was used for PK analysis. We focus here on the phase 1 safety and PK results. Results: Phase 1 is complete (n = 52). The RD is 50 mg ER BID. ONA AUC and Cmax were dose-proportional across doses including 100 mg IR, with coefficients of determination (r2) of 0.76 and 0.79, respectively. Steady state was reached at ~200 hours, with T1/2 of 8-12 hrs. There was no evidence of accumulation through day 57. The most frequent related SAEs were grade 3 LFT elevations (n = 4; 8%) at time of liver PD. The most common related AEs were asthenia (21%) and increased AST/ALT (17%). 10 patients (19%) had at least one related ≥ grade 3 AE, the most frequent being increased GGT (10%) and AST/bilirubin (6%), all associated with liver PD. No treatment-related deaths were reported. One pt died of PD within 30 days of last dose. There was no AE/exposure relationship. Conclusions: AUC and Cmax data support use of the ER administration to potentially mitigate LFT elevations. After repeated dosing, the terminal T1/2 differed substantially from single dose administration. There were no G3-4 LFT elevations in the absence of liver metastases, thus caution is only necessary in pts with rapid liver PD. There were no new safety signals. The highest ONA dose level, 50 mg ER BID, is being used in phase 2. Clinical trial information: NCT02052128.
A new technique of reporting prostate biopsy to predict prostatectomy outcome.
Authors: Carl A. Olsson, Paras Hemant Shah, Oksana Yaskiv, Deepak A. Kapoor
Journal: Journal of Clinical Oncology (2017)

e544 Background: Presently, the highest Gleason Grade Group (GGG) is the metric used to gauge the clinical aggressiveness of tumor and dictate treatment. However, the urologist is limited by lack of consideration of the entire biopsy using that single parameter alone. Intuitively we presumed that the biopsy showing multiple cores of cancer would represent more aggressive disease. Herein, we propose the Weighted Gleason Grade Group (WGGG), a novel scoring system that synthesizes histopathologic data and cancer volume into a single numeric value representing the entire biopsy that provides the urologist with the ability to more accurately predict adverse pathologic outcomes of prostatectomy. Methods: We studied 212 men who underwent radical prostatectomy after standard multi-core prostate biopsy. The highest Gleason score of each biopsy was converted to its final GGG. The WGGG was calculated by summing the Gleason score of each positive core and normalized for a 12 core total. Radical prostatectomy pathology was studied to determine adverse pathological outcomes, specifically, extraprostatic extension (EPE), positive surgical margins (PSM), lymphovascular invasion (LVI), seminal vesical invasion (SVI) and pathological upgrading. Logistic regression analysis was used to compare the ability of conventional GGG versus WGGG to predict the risk of these adverse features. Results: The odds ratio (OR) for predicting EPE, SVI and LVI for increasing GGG versus WGGG (in 10-point incremental increases) were 1.16 (95% CI 1.1-1.2, p &lt; 0.001) versus 1.81 (95% CI 1.42-2.32, p &lt; 0.001), versus 2.05 (95% CI 1.45-2.90, p &lt; 0.001) and versus 3.46 (95% CI 1.99-6.04, p &lt; 0.001), respectively. WGGG, but not GGG was significantly associated with PSM 1.07 (95% CI 1.029-1.104, p = 0.004) and pathologic upgrading 1.621 (95% CI 1.461- 1.837, p = 0.002) of the prostatectomy specimen. Conclusions: The WGGG, by providing a measurable value reflecting the entirety of the prostate biopsy, is more informative than conventional single GGG alone in reliably predicting adverse pathologic outcomes on radical prostatectomy specimens.
Myocardial strain for detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: Results from the St. Jude lifetime cohort study.
Authors: Gregory T. Armstrong, Vijaya Joshi, Kirsten K. Ness, Nan Zhang, Deokumar Srivastava, Brian Griffin, Richard Grimm, James Thomas, Dermot Phelan, Patrick Collier, Daniel A. Mulrooney, Kevin R. Krull, Daniel M. Green, Thomas Marwick, Melissa M. Hudson, Leslie L. Robison, Juan Carlos Plana
Journal: Journal of Clinical Oncology (2014)

10081 Background: Ejection fraction (EF) by echocardiography (echo) is the recommended screening modality for treatment-related cardiac dysfunction in survivors of childhood cancer. Because decreased EF occurs late in its natural history more sensitive detection methods are needed. We hypothesized that myocardial strain would improve identification of survivors with reduced exercise capacity. Methods: Analysis included 1,107 >10 yr survivors of childhood cancer (median age 32 yrs, range 18-59; 593 anthracycline-no chest radiation [RT], 206 chest RT-no anthracycline, and 308 anthracycline + chest RT). Echo included systolic (3D EF, abnormal defined as <50%) and diastolic function (grades 1-3 abnormal), and global longitudinal (>-18.9) and circumferential (>-22.1) myocardial strain. Exercise capacity was assessed with a 6-minute walk (<490 meters abnormal). Associations between echo measures and exercise capacity were assessed using logistic regression adjusted for age, weight, height, pulmonary function, muscle strength, diastolic function, hypertension and diabetes to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results: Systolic dysfunction was detected in 5%, diastolic dysfunction in 12%, and abnormal longitudinal and circumferential strain in 47% and 57%. Longitudinal strain was the only echo measure associated with reduced exercise capacity (OR 1.7, CI 1.1-2.6) with no association for 3D EF (OR 0.6, CI 0.2-1.8), diastolic function (OR 1.1, CI 0.6-1.9), or circumferential strain (OR 1.0, CI 0.7-1.6). Abnormal longitudinal strain was associated with older age, male sex and dose of chest RT. Among survivors with normal EF, abnormal longitudinal strain was significantly associated with detection of survivors with reduced exercise capacity (OR 1.7, CI 1.0-2.7). Conclusions: Among adult survivors of childhood cancer, abnormal global longitudinal strain is prevalent, associated with chest-directed RT exposure, and is the only echo measure independently associated with reduced exercise capacity. Longitudinal strain identifies at-risk survivors who should be targeted for potential clinical interventions.
The prognostic role of IDC-P in mCRPC and its predictive value in those treated with docetaxel or abiraterone as first-line therapy.
Authors: Jinge Zhao, Hao Zeng, Pengfei Shen, Guangxi Sun, Jiandong Liu, Xingming Zhang, Zhibin Chen
Journal: Journal of Clinical Oncology (2017)

e603 Background: Intraductal carcinoma of prostate (IDC-P) is recognized as a newly pathological entity in 2016. Its role in metastatic castration-resistant prostate cancer (mCRPC) remains unknown. The aim of this study is to explore the association of IDC-P with clinical outcomes and to further identify its potential predictive role in making first-line treatment decision for mCRPC patients. Methods: We retrospectively analyzed data of 131 men with mCRPC. IDC-P was diagnosed by re-biopsy at the time of mCRPC. After mCRPC, 45 and 41 patients received abiraterone (Abi) or docetaxel (Doc) as first-line therapy, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed. Kaplan-Meier curves, log-rank test, Cox regression models and Harrell’s C-index were conducted to analyze disease progression, treatment efficacy and outcomes. Results: The incidence of IDC-P in mCRPC reached to 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with 20-month decrease of OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in Abi-treated and Doc-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in Abi-treated vs. Doc-treated group (52.4% vs. 21.7%; p = 0.035), also, PSA-PFS and OS were much longer in Abi-treated group (PSA-PFS:13.5 vs.6.0 months, p = 0.012; OS:23.6 vs.14.7 months, p = 0.128). Cox regression indicated that, for IDC-P(+) patients, Abi was associated with prolonged time of PSA-PFS (HR = 0.33, 95%CI: 0.14-0.79, p = 0.013), and could significantly increase the predictive accuracy of standard model, with an obvious increase of the C-index from 0.719 to 0.778 (p = 0.009). Conclusions: The presence of IDC-P in mCRPC from re-biopsy was not only an independent prognosticator for clinical outcomes, but also strongly associated with poor response to Doc-based chemotherapy. We also found that IDC-P status could be considered as a novel predictive marker in helping physicians precluding Doc as first-line therapy in IDC-P(+) patients. Also, these findings require large-scale prospective validation.
Long-term follow-up of the Rotterdam study on prophylactic mastectomy versus surveillance in BRCA1/2 mutation carriers
Authors: J. G. M. Klijn, A. N. Van Geel, H. Meijers-Heijboer, M. Tilanus-Linthorst, C. C. M. Bartels, C. M. G. Crepin, C. Seynaeve, M. B. Menke-Pluymers, C. T. M. Brekelmans
Journal: Journal of Clinical Oncology (2004)

9502 Background: Previously we reported on the efficacy of prophylactic bilateral total mastectomy (PM) in the first prospective study of 139 healthy women with a pathogenic BRCA1 or BRCA2 mutation (Meijers-Heijboer et al, NEJM 345: 159–164, 2001). At 3 years of follow-up PM significantly reduced the incidence of breast cancer (no cases after PM in 76 BRCA1/2 carriers) in comparison with regular surveillance (8 breast cancers in 63 carriers). In the present study, we report our data at 5.2 years of follow-up of the same cohort of 139 women. Methods: We updated the incidence of breast cancer, PM and prophylactic oophorectomy (PO). Regular surveillance for breast cancer consists of clinical breast examination every six months, and yearly mammography (increasingly in combination with MRI). Statistical analysis was performed by Cox proportional-hazards modeling. Results: In the surveillance group (n=63; mean age 39.5 yr) 3 women opted as yet for PM and were censored for the date of PM; the number of breast cancers increased from 8 to 9 cases during longer follow-up. Strikingly in one out of the 76 healthy women (mean age 37.7 yr) with PM, distant metastases were detected 3.5 yrs. after PM, suggesting the presence of an occult breast cancer at the time of PM; in this group no primary breast cancers occurred after PM. The risk reduction for breast cancer by PM was 92 % (p 0.02). This reduction remained significant after adjustment for PO and age (p<0.03). Conclusion: In women with a BRCA1/2 mutation without a history of breast cancer, PM strongly reduced the incidence of breast cancer, also at five years of follow-up. No significant financial relationships to disclose.