Influences of breath sample re-use on the accuracy of lung cancer detection dogs.

Evaluations of dogs as lung cancer detectors using breath samples have produced a variety of results, some quite promising. Breath samples are typically collected onto a substrate and stored in a sealed container when not in use, but volatile compounds dissipate when the substrate is exposed during training and evaluation sessions. Collection of appropriate samples for training and testing dogs requires significant resources and strict control of recruitment and sample collection processes. Therefore, some researchers re-use samples while training dogs. No systematic evaluation of the effect of sample re-use on dogs' training performance has been conducted, so the influence of this potentially important training factor is not known. We trained seven dogs to indicate the presence of lung cancer positive breath samples using an automated apparatus. The samples were stored at -60 °C or -80 °C. Samples from 460 individuals who were classified as positive or negative for lung cancer were used for training samples. Individual samples were presented to dogs up to four times over a period of 2 years. As sample re-use increased, sensitivity declined (-6.65,p= < .001, 95% CI [-10.56, -2.76]), specificity increased (2.87,p= .036, 95% CI [.19, 5.55]), and the dogs' bias shifted in the direction of a negative indication bias (-.094,p= < .001, 95% CI [-.149, -.39]). However, there were no significant changes in the measure associated with the detectability of the target (-0.30,p= .285, 95% CI [-.087, .26]). All observed changes in performance across sample re-use were small. Therefore, these findings suggest that sample re-use may be appropriate for training, but additional research is required to determine which factors underly changes in performance as breath samples are re-used.

Overexpression of TP53 protein is associated with the lack of adjuvant chemotherapy benefit in patients with stage III colorectal cancer.

TP53 mutations drive colorectal cancer development, with missense mutations frequently leading to accumulation of abnormal TP53 protein. TP53 alterations have been associated with poor prognosis and chemotherapy resistance, but data remain controversial. Here, we examined the predictive utility of TP53 overexpression in the context of current adjuvant treatment practice for patients with stage III colorectal cancer. A prospective cohort of 264 stage III patients was tested for association of TP53 expression with 5-year disease-free survival, grouped by adjuvant treatment. Findings were validated in an independent retrospective cohort of 274 stage III patients. Overexpression of TP53 protein (TP53+) was found in 53% and 52% of cases from the prospective and retrospective cohorts, respectively. Among patients receiving adjuvant chemotherapy, TP53+ status was associated with shorter disease-free survival (p ≤ 0.026 for both cohorts), while no difference in outcomes between TP53+ and TP53- cases was observed for patients treated with surgery alone. Considering patients with TP53- tumors, those receiving adjuvant treatment had better outcomes compared with those treated with surgery alone (p ≤ 0.018 for both cohorts), while no treatment benefit was apparent for patients with TP53+ tumors. Combined cohort-stratified analysis adjusted for clinicopathological variables and DNA mismatch repair status confirmed a significant interaction between TP53 expression and adjuvant treatment for disease-free survival (pinteraction = 0.030). For the combined cohort, the multivariate hazard ratio for TP53 overexpression among patients receiving adjuvant chemotherapy was 2.03 (95% confidence interval 1.41-2.95, p < 0.001), while the hazard ratio for adjuvant treatment among patients with TP53- tumors was 0.42 (95% confidence interval 0.24-0.71, p = 0.001). Findings were maintained irrespective of tumor location or when restricted to mismatch repair-proficient tumors. Our data suggest that adjuvant chemotherapy benefit in stage III colorectal cancer is restricted to cases with low-level TP53 protein expression. Identifying TP53+ tumors could highlight patients that may benefit from more aggressive treatment or follow-up.