Driver mutation characteristics of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced non-small cell lung cancer.

OBJECTIVES: The identification and targeting of actionable genomic alterations (AGA) have revolutionized the treatment of cancer in general and mostly for non-small cell lung cancer (NSCLC). We investigated whether in NSCLC patients PIK3CA mutations are actionable. MATERIALS AND METHODS: Chart review was performed of advanced NSCLC patients. PIK3CA mutated patients were analyzed as two groups: Group A: without any non-PIK3CA established AGA; Group B: with coexisting AGA. Group A was compared to a cohort of non-PIK3CA patients (group C), using t-test and chi-square. To evaluate the impact of PIK3CA mutation on outcome, we compared Group A survival to age/sex/histology matched cohort of non-PIK3CA mutated patients (group D) by Kaplan-Meier method. A patient with a PIK3CA mutation was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib). RESULTS: Of a cohort of 1377 patients, 57 are PIK3CA mutated (4.1%). Group A: n-22, group B: n-35. Group A median age is 76 years, 16 (72.7%) men, 10 (45.5%) squamous, 4 (18.2%) never smokers. Two never-smoker female adenocarcinoma patients had solitary PIK3CA mutation. One of them was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib), with rapid clinical and partial radiological improvement. Group B, compared with Group A, included younger patients (p = 0.030), more females (p = 0.028) and more adenocarcinoma cases (p < 0.001). Compared to group C, group A patients were older (p = 0.030) and had more squamous histology (p = 0.011). CONCLUSION: In a small minority of NSCLC patients with PIK3CA mutation there are no additional AGA. PIK3CA mutations may be actionable in these cases.

Cognitive Retraining and Functional Treatment (CRAFT) for adults with cancer related cognitive impairment: a preliminary efficacy study.

PURPOSE: To examine the preliminary efficacy of Cognitive Retraining and Functional Treatment (CRAFT) combining remote computerized cognitive training (CCT) and occupation-based treatment in adults with cancer-related cognitive impairment (CRCI). METHODS: Three-armed randomized controlled trial including 74 individuals with CRCI, randomized into 12 weeks of either CRAFT, CCT alone, or treatment-as-usual. Assessments evaluating participation in daily life, perceived cognition, cognitive performance, quality-of-life, and treatment satisfaction were administered at baseline, post-intervention, and 3-month follow-up. RESULTS: Significant time × group interactions in favor of the CRAFT and CCT groups were found for participation in daily life (F2,34 = 5.31, p = .01, eta = .238), perceived cognition (F2,34 = 4.897, p = .014, eta = .224), and cognitive performance on speed of processing test (F = 5.678, p = .009, eta = .289). The CRAFT group demonstrated significantly larger clinically meaningful gains on participation in daily life (chi-square = 6.91, p = .032) and significantly higher treatment satisfaction. All treatment gains were maintained at a 3-month follow-up (n = 32). CONCLUSIONS: CCT and CRAFT were found to have a positive impact on participation and cognitive outcomes among individuals with CRCI. The CRAFT showed an additional advantage in improving self-chosen occupation-based goals suggesting that a combination of cognitive training with occupation-based intervention has a positive synergistic effect resulting in "real world" health benefits. IMPLICATIONS FOR CANCER SURVIVORS: A combination of cognitive training with occupation-based intervention has a positive effect resulting in clinically meaningful improvements in participation in daily life, objective cognitive performance, and subjective cognitive impairment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04210778, December 26, 2019, retrospectively registered.

Predictors of quality of life among adults with self-reported cancer related cognitive impairment.

OBJECTIVE: The purpose of the current study was to examine the unique contribution of personal and medical factors, objective and subjective cognition, and self-efficacy to the explained variance of quality of life (QoL) among survivors with self-reported cancer related cognitive impairment (CRCI). METHOD: Seventy-three cancer survivors (non-central nervous system) with CRCI (mean age: 50.85 ± 10.82 years old, mean years post-treatment: 3 ± 2.7) participated in this cross-sectional study. QoL was assessed using the Functional Assessment of Cancer Therapy (FACT)-GP, while the cognitive function was assessed both objectively using tests of attentional control, speed of processing and sustained attention, and subjectively using the FACT-Cognition perceived cognitive impairments (FACTcog-PCI) subscale. Self-efficacy was assessed using the New General Self-Efficacy Scale (NGSE). RESULTS: A hierarchical multiple linear regression analysis revealed that sustained attention, perceived cognitive impairment and self-efficacy, accounted for 54% of the variance of QoL (R2 = 0.543, p < 0.000), each providing a unique contribution to the explained variance (15-20% each) after controlling for age and gender. CONCLUSIONS: Considering that these variables may be amenable to change, this model can serve as a conceptual framework for designing effective cognitive treatment options for CRCI. Clinical Trial Registration: ClinicalTrials.gov NCTImplication for rehabilitationCancer related cognitive impairment is characterized by difficulties in the speed of processing performance, severe perceived cognitive impairments, and relatively low general self-efficacy.Multi-dimensional assessments including subjective and objective cognition as well as self-efficacy should be administered to cancer survivors with cognitive complaints to understand the underlying mechanisms of their QoL.Integrative cognitive rehabilitation interventions that aim to improve QoL among people with cancer-related cognitive impairment should target sustained attention, perceived cognitive impairment, and self-efficacy.