Purpose: KRAS mutations are predictive of nonresponse to anti-EGFR therapies in metastatic colorectal cancer (mCRC). However, only 50% of nonmutated patients benefit from them. KRAS-mutated subclonal populations nondetectable by conventional methods have been suggested as the cause of early progression. Molecular analysis technology with high sensitivity and precision is required to test this hypothesis.Experimental Design: From two cohorts of patients with mCRC, 136 KRAS, NRAS, and BRAF wild-type tumors with sufficient tumor material to perform highly sensitive picodroplet digital PCR (dPCR) and 41 KRAS-mutated tumors were selected. All these patients were treated by anti-EGFR therapy. dPCR was used for KRAS or BRAF mutation screening and compared with qPCR. Progression-free survival (PFS) and overall survival (OS) were analyzed according to the KRASmutated allele fraction.Results: In addition to the confirmation of the 41 patients with KRAS-mutated tumors, dPCR also identified KRAS mutations in 22 samples considered as KRAS wild-type by qPCR. The fraction of KRAS-mutated allele quantified by dPCR was inversely correlated with anti-EGFR therapy response rate (P < 0.001). In a Cox model, the fraction of KRAS-mutated allele was associated with worse PFS and OS. Patients with less than 1% of mutant KRAS allele have similar PFS and OS than those with wild-type KRAS tumors.Conclusions: This study suggests that patients with mCRC with KRAS-mutated subclones (at least those with a KRAS-mutated subclones fraction lower or equal to 1%) had a benefit from anti-EGFR therapies.

No abstract

This study examined the relationship among three constructs that frequently form the basis for parent consultation in early intervention, parenting stress, family coping, and developmental/educational status. Parents (N = 116) of kindergarten children completed the Parenting Stress Index (PSI) and the Family Crisis Oriented Personal Evaluation Scales (F-COPES), while their children were administered the Early Screening Profiles (ESP). Pearson correlations among the PSI, F-COPES, and the ESP revealed low positive to moderately negative correlations; most of the correlations were negative. These negative correlations were expected because coping and developmental/educational attainment may be related inversely to parenting stress. A stepwise multiple regression analysis revealed that the ESP Total Score and two coping strategies, Passive Appraisal and Reframing, accounted for 27.1%o of the variance on the PSI Total Scores. Implications for parent consultation are discussed.

No abstract

This is the largest retrospective series evaluating PET treatment failure. Clear predictors of failure have been identified, which can be used to facilitate treatment decision making. These results support previous analyses, further validating our results.