Publications by authors named "Jared Foster"

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

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Background: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.

Methods: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS.

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Article Synopsis
  • The STEEP 2.0 criteria, updated in 2021, established standardized definitions for adjuvant breast cancer end points and emphasized the importance of defining neoadjuvant clinical trial end points separately.
  • A specialized working group, NeoSTEEP, focused on neoadjuvant systemic therapy end points, considering various factors like cancer subtypes, imaging, and FDA regulations.
  • The group recommended defining pathologic complete response (pCR) as no residual invasive cancer present and suggested additional methodologies for evaluating treatment efficacy, including unique end points for hormone receptor-positive cases.
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We consider the design of phase II trials evaluating combinations of experimental therapies. In the modern era, many immunotherapy and targeted therapy regimens are being developed as combination regimens, including combinations consisting only of experimental agents. In some clinical or drug development scenarios, it may be difficult to isolate the effect of the individual agents composing a combination of this type, which makes the evaluation of the combination challenging.

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Article Synopsis
  • Many cancer patients are older adults (65+), but they are often not well-represented in clinical trials, leading to a lack of relevant data for treating this group.
  • Recommendations from a working group suggest designing trials specifically for older adults or including them in existing trials through various cohort methods to improve participation.
  • Key considerations for these trials include taking into account the varied fitness levels of older adults and incorporating geriatric assessments to ensure appropriate patient selection and trial integrity.
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Purpose: Soft-tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated vascular endothelial growth factor (VEGF) levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population.

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Purpose: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.

Methods: We conducted systematic searches of ClinicalTrials.

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Unlabelled: This trial assessed the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient's aberrant pathway (experimental arm) or not matched to that pathway (control arm).

Materials And Methods: Adult patients with an actionable mutation of interest were randomly assigned 2:1 to receive either (1) a study regimen identified to target the aberrant pathway found in their tumor (veliparib with temozolomide or adavosertib with carboplatin [DNA repair pathway], everolimus [PI3K pathway], or trametinib [RAS/RAF/MEK pathway]), or (2) one of the same four regimens, but chosen from among those not targeting that pathway.

Results: Among 49 patients treated in the experimental arm, the objective response rate was 2% (95% CI, 0% to 10.

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Importance: Anti-programmed death 1 and anti-programmed death ligand 1 (anti-PD1/PDL1) immune checkpoint blockade (ICB) constitutes the therapeutic backbone for multiple malignant neoplasms. People living with HIV (PLWH) have routinely been excluded from ICB clinical trials, thus inhibiting broad implementation of ICB to PLWH with cancer.

Objective: To evaluate trends in the inclusion of PLWH in ICB cancer clinical trials that have occurred in association with ongoing efforts by the Cancer Therapy Evaluation Program (CTEP), National Cancer Institute, to promote inclusion of PLWH.

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Background: With the development of targeted agents, the approach to combination cancer therapy has evolved to focus on identifying ways in which pathway inhibition by one agent may enhance the activity of other agents. In theory, this implies that under this new paradigm, agents are no longer required to show single-agent activity, as the pathway inhibited by the targeted agent may only have a therapeutic effect when given with other agents. This raises the question of the extent to which anticancer agents without single-agent activity can contribute to effective combination regimens.

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Designing and interpreting single-arm phase II trials of combinations of agents is challenging because it can be difficult, based on historical data, to identify levels of activity for which the combination would be worth pursuing. We identified Cancer Therapy Evaluation Program single-arm combination trials that were activated in 2008-2017 and tabulated their design characteristics and results. Positive trials were evaluated as to whether they provided credible evidence that the combination was better than its constituents.

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Objective: Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown.

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This exploratory longitudinal study examined behavioral outcomes and parenting stress among families with children adopted from foster care, taking into account environmental and biological risk factors. Child internalizing and externalizing problems and parenting stress were assessed in 82 adopted children and their families at 2 months post-placement, 12 months post-placement, and then yearly until 5 years post-placement. A history of abuse/neglect predicted significantly higher externalizing and internalizing problems at a borderline level of statistical significance.

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Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases.

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Background: A nocebo is an inert substance associated with adverse events. Although previous studies have examined the positive (placebo) effects of such inert substances, few have examined negative (nocebo) adverse event profiles, particularly in older patients who have higher morbidity and can experience frequent and severe adverse events from cancer therapy.

Methods: This study focused on placebo/nocebo-exposed patients who participated in 2 double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Therapy Group trial NCCTG 97-24-51 and American College of Surgeons Oncology Group trial Z9001, with the goal of reporting the comparative, age-based adverse event rates, as reported during the conduct of these trials.

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Longitudinal monitoring of biomarkers is often helpful for predicting disease or a poor clinical outcome. In this paper, We consider the prediction of both large and small-for-gestational-age births using longitudinal ultrasound measurements, and attempt to identify subgroups of women for whom prediction is more (or less) accurate, should they exist. We propose a tree-based approach to identifying such subgroups, and a pruning algorithm which explicitly incorporates a desired type-I error rate, allowing us to control the risk of false discovery of subgroups.

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Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.

Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.

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Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression.

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We consider the problem of using permutation-based methods to test for treatment-covariate interactions from randomized clinical trial data. Testing for interactions is common in the field of personalized medicine, as subgroups with enhanced treatment effects arise when treatment-by-covariate interactions exist. Asymptotic tests can often be performed for simple models, but in many cases, more complex methods are used to identify subgroups, and non-standard test statistics proposed, and asymptotic results may be difficult to obtain.

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We consider the use of randomized clinical trial (RCT) data to identify simple treatment regimes based on some subset of the covariate space, A. The optimal subset, A, is selected by maximizing the expected outcome under a treat-if-in-A regime, and is restricted to be a simple, as it is desirable that treatment decisions be made with only a limited amount of patient information required. We consider a two-stage procedure.

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A recent article (Zhang et al., 2012, Biometrics 168, 1010-1018) compares regression based and inverse probability based methods of estimating an optimal treatment regime and shows for a small number of covariates that inverse probability weighted methods are more robust to model misspecification than regression methods. We demonstrate that using models that fit the data better reduces the concern about non-robustness for the regression methods.

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Purpose/objectives: To determine whether improved monitoring through close follow-up with a nurse practitioner (NP) could enhance treatment compliance and decrease frequency of hospitalizations.

Design: Retrospective chart review.

Setting: An academic National Cancer Institute-designated comprehensive cancer center.

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