Influence of body mass index and periprostatic fat on rectal dosimetry in permanent seed prostate brachytherapy

PURPOSE: We examined the influence of body mass index (BMI) and body fat distribution on rectal dose in patients treated with permanent seed brachytherapy for localized prostate cancer. METHODS AND MATERIALS: We analyzed 213 patients treated with I(125) seed brachytherapy for localized prostate cancer. BMI and rectal dosimetry data for all patients were available. Data on visceral and subcutaneous fat distribution at the level of the iliac crest (n = 140) as well as the distribution of periprostatic and subcutaneous fat at the symphysis pubis level were obtained (n = 117). Fat distribution was manually contoured on CT on day 30 after brachytherapy. The correlation between BMI, fat distribution and rectal dose (R100 (in cc), R150 (cc), D2 (Gy)) was analyzed using the Spearman correlation coefficient. Differences in rectal dose between tertiles of body fat distribution were calculated using nonparametric tests. RESULTS: Periprostatic adipose was only weakly correlated with BMI (r = 0.0.245, p = 0.008) and only weakly correlated with the other fat measurements (r = 0.31-0.37, p < 0.001). On the other hand, BMI was correlated with all other fat measurements (≥0.58, p < 0.001). All the other fat measurements were strongly correlated with each other (r = 0.5-0.87, p < 0.001). Patients with an R100 of >1.3 cc (23% of patients) had less visceral fat (p = 0.004), less subcutaneous fat at the level of the iliac crest (p = 0.046) and a lower BMI (26.8 kg/m(2) vs. 28.5 kg/m(2), p = 0.02) than patients with an R100 of <1.3 cc. Results were very similar when comparing an R100 of >1.0 cc (34% of patients) across the tertiles. None of the tested linear regression models were predictive (max 12%) of dose to the rectum. CONCLUSION: Dose to the rectum is dependent on BMI and body fat distribution. Periprostatic fat does not influence rectal dose. Dose to the rectum remains difficult to predict and depends on many factors, one of which is body fat distribution

A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer