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d prostate cancer, especially in a setting where matched tumor tissue may be unavailable (ie, active surveillance or treatment monitoring).Simulation studies have shown that novel designs such as the continual reassessment method and the Bayesian optimal interval (BOIN) design outperform the 3 + 3 design by recommending the maximum tolerated dose (MTD) more often, using less patients, and allotting more patients to the MTD. However, it is not clear whether these novel designs would have yielded different results in the context of real-world dose-finding trials. This is a commonly mentioned reason for the continuous use of 3 + 3 designs for oncology trials, with investigators considering simulation studies not sufficiently convincing to warrant the additional design complexity of novel designs.

We randomly sampled 60 published dose-finding trials to obtain 22 that used the 3 + 3 design, identified an MTD, published toxicity data, and had more than two dose levels. We compared the published MTD with the estimated MTD using the continual reassessment method and BOIN using target toxicity rates of 25% and 30% and toxicity data from the trial. Moreover, we compared patient allocation and sample size assuming that these novel designs had been implemented.

Model-based designs chose dose levels higher than the published MTD in about 40% of the trials, with estimated and observed toxicity rates closer to the target toxicity rates of 25% and 30%. They also assigned less patients to suboptimal doses and permitted faster dose escalation.

This study using published dose-finding trials shows that novel designs would recommend different MTDs and confirms the advantages of these designs compared with the 3 + 3 design, which were demonstrated by simulation studies.

This study using published dose-finding trials shows that novel designs would recommend different MTDs and confirms the advantages of these designs compared with the 3 + 3 design, which were demonstrated by simulation studies.Advances in precision oncology, including RAS testing to predict response to epidermal growth factor receptor monoclonal antibodies (EGFR mAbs) in colorectal cancer (CRC), can extend patients' lives. Avacopan ic50 We evaluated uptake and clinical use of KRAS molecular testing, guideline recommended since 2010, in the Veterans Affairs Healthcare System (VA).

We conducted a retrospective cohort study of patients with stage IV CRC diagnosed in the VA 2006-2015. We gathered clinical, demographic, molecular, and treatment data from the VA Corporate Data Warehouse and 29 commercial laboratories. We performed multivariable analyses of associations between patient characteristics,

testing, and EGFR mAb treatment.

Among 5,943 patients diagnosed with stage IV CRC, only 1,053 (17.7%) had

testing. Testing rates increased from 2.3% in 2006 to 28.4% in 2013. In multivariable regression, older patients (odds ratio, 0.17; 95% CI, 0.09 to 0.32 for ≥ age 85

< 45 years) and those treated in the Northeast and South regions were understand barriers to precision oncology are needed to maximize patient benefit.This study examines oncologist-reported reasons for not using multimarker tumor panel testing and the association between these reasons and oncologist-level, facility-level, and patient-mix characteristics.

We used data collected from a nationally representative sample (N = 1,281) of medical oncologists participating in the National Cancer Institute's

.

In addition to

(87%) and

(77%), the most frequently reported reasons for not ordering a multimarker tumor panel test was

(57%) and

(72%). These reasons were more likely to be reported by oncologists practicing in rural clinics and less likely to be reported by oncologists with an academic affiliation or with access to genetic services such as on-site genetic counselors and internal genetic testing policies.

Modifiable, organizational factors were associated with ordering multimarker tumor panels. Receipt of genomics training and organizational policies related to the use of genomics were associated with lower reporting of barriers to ordering multimarker tumor panels, pointing to potential targets for future studies aimed at increasing appropriate multimarker tumor panel testing in cancer treatment management.

Modifiable, organizational factors were associated with ordering multimarker tumor panels. Receipt of genomics training and organizational policies related to the use of genomics were associated with lower reporting of barriers to ordering multimarker tumor panels, pointing to potential targets for future studies aimed at increasing appropriate multimarker tumor panel testing in cancer treatment management.

The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic

mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated.

Data on patients with neuroblastoma harboring

mutations were retrospectively analyzed.

sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot

mutation profiling. The differential impact of

mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all

mutations was compared with wild-type



Of 641 patients with neuroblastoma with

status analyzed on at least one tumor sample, 103 (16%) had tumors harboring

mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, inmutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.The objectives of the study were to characterize the tumor burden dynamics on serial computed tomography scans in patients with advanced non-small-cell lung cancer treated with first-line pembrolizumab and to identify imaging markers for prolonged overall survival (OS).

Eighty-eight patients treated with first-line pembrolizumab monotherapy were evaluated on serial computed tomography scans to characterize their quantitative tumor burden during therapy. Tumor burden dynamics were studied for the association with OS.

The overall response rate was 42% (37/88), with the median tumor burden changes at the best overall response of -18.3% (range, -100.0% to +103.6%). Response rates were higher in men than in women (

= .05) and in patients with higher programmed cell death ligand-1 expression levels (

= .02). Tumor burden stayed below the baseline burden throughout therapy in 55 patients (63%). In an 8-week landmark analysis, patients with tumor burden below the baseline burden during the first 8 weeks of therapy had longer OS compared with patients who had ≥ 0% increase (median OS, 30.