Real-World Analysis of Post-Progression Treatment Patterns and Outcomes for EGFR Mutation-Positive Patients Treated with First-Line Osimertinib.

Introduction: The use of osimertinib in the first-line (1L) setting is an effective treatment option for sensitizing EGFR-mutations (EGFRm+) and has significantly altered the standard of care practice for EGFRm+ disease in Canada. Unfortunately, acquired resistance to osimertinib is almost universal, and outcomes are disparate. Post-progression treatment patterns and the outcome of real-world Canadian EGFRm+ patients receiving 1L osimertinib were the focus of this retrospective review. Methods: The Glans-Look Lung Cancer Research database was used to identify and collect demographic, clinical, treatment, and outcome data on EGFRm+ patients who received 1L osimertinib in the Canadian province of Alberta between 2018 and 2022. Results: A total of 150 patients receiving 1L osimertinib were identified. In total, 86 developed progressive disease, with 56 (65%) continuing systemic therapy, 73% continuing osimertinib, and 27% switching to second-line (2L) systemic therapy. Patients were similar both in clinical characteristics at 1L osimertinib initiation and patterns of treatment failure at progression; those continuing 1L osimertinib post-progression had a longer time to progression (13.5 vs. 8.8 months, p = 0.05) and subsequent post-osimertinib initiation survival (34.7 vs. 22.8 months, p = 0.11). Conclusions: The continuation of osimertinib post-progression is an effective disease management strategy for select real-world EGFRm+ patients, providing continued clinical benefit, potentially due to different underlying disease pathogenesis.

Immune-Related Adverse Events and Survival Among Patients With Metastatic NSCLC Treated With Immune Checkpoint Inhibitors.

Importance: Immune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy reportedly improve overall survival (OS) in patients with non-small cell lung cancer (NSCLC). However, studies have been small and the association between irAE severity and OS remains poorly defined. Objective: To examine the association between irAEs and their severity with OS in patients with locally advanced or metastatic NSCLC receiving ICIs. Design, Setting, and Participants: This retrospective observational cohort study included patients with NSCLC receiving ICIs between March 1, 2014, and November 30, 2021, with follow-up until March 31, 2023. Data analysis was completed April 26, 2023. The Alberta Immunotherapy Database, a provincial, multicenter cohort, was used to capture data from patients receiving ICIs in Alberta, Canada. Participants included 803 patients 18 years or older who received at least 1 cycle of ICI (alone or with chemotherapy), agnostic to treatment line. Exposure: Developing an irAE mandating delay or discontinuation of ICI therapy and/or systematic corticosteroids for management of toxic effects (hereinafter referred to as clinically meaningful irAEs). Main Outcomes and Measures: The primary outcome was association between irAEs and OS according to Kaplan-Meier analysis. Clinically meaningful irAEs were identified. Patients with poor prognosis (survival <3 months) who may have died prior to irAE development were excluded from OS analysis, mitigating immortal time bias. Adjusted Cox proportional hazards regression analyses ascertained variables associated with OS. Results: Among the 803 patients included in the analysis, the median age of patients with irAEs was 69.7 (IQR, 63.1-75.2) years and the median age of those without irAEs was 67.5 (IQR, 60.4-73.3) years, with comparable sex distribution (139 of 295 men [47.1%] and 156 of 295 women [52.9%] with irAEs vs 254 of 505 men [50.3%] and 251 of 505 women [49.7%] without irAEs). Mitigating immortal time bias (n = 611), irAEs were associated with OS (median OS with irAEs, 23.7 [95% CI, 19.3-29.1] months; median OS without irAEs, 9.8 [95% CI, 8.7-11.4] months; P < .001). No OS difference was associated with treatment in hospital vs as outpatients for an irAE (median OS, 20.8 [95% CI, 11.7-30.6] vs 25.6 [95% CI, 20.1-29.8] months; P = .33). Developing irAEs remained associated with OS in the total cohort after Cox proportional hazards regression with known prognostic characteristics (hazard ratio, 0.53 [95% CI, 0.40-0.70]; P < .001). Conclusions and Relevance: In this cohort study of 803 patients with locally advanced or metastatic NSCLC receiving ICIs, developing a clinically meaningful irAE was associated with improved OS. This association was not compromised by hospitalization for severe toxic effects. Whether and how ICI therapy resumption after an irAE is associated with OS warrants further study.

Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P =0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P =0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival ( P =0.103) or progression-free survival ( P =0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P =0.025)] but not overall survival ( P =0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

Genome-wide Detection of Chimeric Transcripts in Early-stage Non-small Cell Lung Cancer.

BACKGROUND/AIM: Lung cancer remains the main culprit in cancer-related mortality worldwide. Transcript fusions play a critical role in the initiation and progression of multiple cancers. Treatment approaches based on specific targeting of discovered driver events, such as mutations in EGFR, and fusions in NTRK, ROS1, and ALK genes led to profound improvements in clinical outcomes. The formation of chimeric proteins due to genomic rearrangements or at the post-transcriptional level is widespread and plays a critical role in tumor initiation and progression. Yet, the fusion landscape of lung cancer remains underexplored. MATERIALS AND METHODS: We used the JAFFA pipeline to discover transcript fusions in early-stage non-small cell lung cancer (NSCLC). The set of detected fusions was further analyzed to identify recurrent events, genes with multiple partners and fusions with high predicted oncogenic potential. Finally, we used a generalized linear model (GLM) to establish statistical associations between fusion occurrences and clinicopathological variables. RNA sequencing was used to discover and characterize transcript fusions in 270 NSCLC samples selected from the Glans-Look specimen repository. The samples were obtained during the early stages of disease prior to the initiation of chemo- or radiotherapy. RESULTS: We identified a set of 792 fusions where 751 were novel, and 33 were recurrent. Four of the 33 recurrent fusions were significantly associated with clinicopathological variables. Several of the fusion partners were represented by well-established oncogenes ERBB4, BRAF, FGFR2, and MET. CONCLUSION: The data presented in this study allow researchers to identify, select, and validate promising candidates for targeted clinical interventions.

Social engagement and loneliness in school-age autistic girls and boys.

OBJECTIVES: This study examines the relationship between social engagement and loneliness in female and male autistic children and adolescents in school-based social settings. Secondary aims sought to explore the emergence of loneliness across different age groups and differences in social engagement and loneliness between genders. METHODS: This study conducted an analysis of previously collected data from two multi-site randomized control trials. This study included 58 autistic students (29 females, 29 males) between the ages 6 through 18 years. Female and male participants were matched on age and intelligence quotient. Concurrent mixed methods were used to examine participants' social engagement and loneliness. RESULTS: Findings revealed a significant relationship between joint engagement and loneliness, such that autistic students reported more loneliness when they were mutually engaged with social groups than when they were isolated or alone. Positive correlations between joint engage and loneliness were identified in elementary-age girls and secondary-age boys, suggesting that being mutually engaged with peers leads to increased loneliness. Negative correlations between parallel and loneliness identified in secondary-age boys suggested that boys in close proximity to peers felt less lonely than boys who were mutually engaged with peers. Qualitative analysis of social behaviors indicated that elementary girls and secondary boys were more likely to be mutually engaged or in close proximity to activities, but they had difficulty sustaining this engagement throughout the entire social period. Secondary girls and elementary boys, on the other hand, were more likely to be solitary and less likely to engage with peer groups. CONCLUSION: Study findings highlight the relationship between social engagement and loneliness in school-based autistic populations, and that more engagement itself can lead to more loneliness for younger girls and older boys. The influence of age and gender on engagement and loneliness highlights a need to tailor social interventions to leverage existing social strengths.

Short report: Autistic adults' recommendations on how to improve autistic portrayals in TV-series and movies.

BACKGROUND: TV-series and movies are important sources of knowledge about autism for the general public. AIMS: This study's purpose was to elicit autistic adults' opinions on portrayals of autistic characters in film and television productions and how this can be improved. METHODS AND PROCEDURE: In this study, we examined the recommendations of autistic adults (n = 798, Mage = 30.3, 48% female) and non-autistic adults (n = 1463, Mage = 35.0, 62% female) from 90 countries on how film and television productions can improve autistic portrayals. OUTCOMES AND RESULTS: Autistic adults rated three improvement factors as most important: (1) Appointing autistic writers, (2) Having an autistic consultant, and (3) Representing greater diversity in autistic characters. Compared to the non-autistic groups, autistic adults rated "Appointing autistic writers" as more important. Autistic participants also endorsed "Having an autism-expert consultant" and "Making the character display all relevant diagnostic criteria" significantly less than non-autistic groups. CONCLUSIONS AND IMPLICATIONS: Participants strongly endorsed that autistic adults should to a much larger extent be included as writers, consultants and actors to enhance the making of autistic characters in film and TV.

Real-World Treatment Patterns and Effectiveness of Targeted and Immune Checkpoint Inhibitor-Based Systemic Therapy in BRAF Mutation-Positive NSCLC.

Introduction: BRAF mutations (present in 2%-3% of NSCLC) are a known oncogenic driver and emerging therapeutic target. There is a scarcity of real-world data describing the clinical characteristics, treatment patterns, and effectiveness of targeted BRAF-inhibiting and immune checkpoint inhibitor (ICI)-based systemic therapies, yet this is required for appropriate treatment decisions that optimize patient outcome. Methods: Demographic, clinical, treatment, and outcome data of patients with BRAF mutation-positive NSCLC diagnosed between 2018 and 2022 were identified from the Glans-Look Lung Cancer Research database and included in this analysis. Results: A total of 53 BRAF mutation-positive patients were identified (V600E, n = 35; non-V600E, n = 18). Furthermore, 46 patients (87%) were diagnosed with metastatic disease, of whom 61% were treated with systemic anticancer therapy, which significantly improved overall survival (34.1 versus 2.2 mo, p = 0.01). ICI-based regimens were found to have effectiveness in the first-line setting for both V600E and non-V600E cohorts (objective response rate: 38%-43%; real-world calculations of median progression-free survival: 10.5-10.8 mo, respectively). Dual-targeted BRAF/MEK inhibition was also found to have effectiveness in the first-line setting for V600E patients (objective response rate: 33%, real-world calculations of median progression-free survival: 15.2 mo). Conclusions: This study of real-world patients with BRAF mutations confirms the importance of effective systemic therapies. Both dual-targeted BRAF/MEK inhibition and ICI-based regimens have evidence of benefit in this population revealing that real-world populations can experience similar clinical response and outcome to clinical trial cohorts on these treatment regimens. Future studies to clarify the role of co-mutations on response to both dual-targeted BRAF/MEK inhibition and ICI-based regimens may be important to treatment selection and optimization of patient outcome.

Expected Cost Savings From Low-Dose Computed Tomography Scan Screening for Lung Cancer in Alberta, Canada.

Introduction: The expensive modern therapeutic regimens for advanced lung cancer (LC) stages have been recently approved. We evaluated whether low-dose computed tomography (LDCT) LC screening of high-risk Albertans is cost saving. Methods: We used a decision analytical modeling technique with a health system perspective and a time horizon of 3 years to compare benefits associated with reduced health service utilization (HSU) from earlier diagnosis to the costs of screening. Using patient-level data, HSU costs by stage of disease were estimated for patients with LC, including inpatient, outpatient, and physician services, and costs for prescription drugs and cancer treatments. Results: Of 101,000 people aged 55 to 74 years eligible for screening, an estimated 88,476 scans would be performed in Alberta in 3 years. Given LDCT sensitivity and specificity of 90.5% and 93.1%, respectively, we estimated that a stage shift toward earlier diagnosis would be expected whereby 43% more patients would be identified at stage 1 or 2 as compared with without screening. The estimated cost of screening is $35.6 million (M), whereas the stage shift associated with screening would avoid $42M in HSU costs. The net cost avoidance associated with screening is therefore $6.65M. The probability for the screening to be cost saving is estimated at 72%. Conclusions: This study has revealed that LDCT LC screening is likely to be cost saving in Alberta. Adoption of this program into the provincial health care system is worth considering provided constraints in the system related to surgical capacity and CT wait times could be addressed.

Real-World Management and Outcomes of Crizotinib-Treated ROS1-Rearranged NSCLC: A Retrospective Canadian Cohort.

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.

A Real-World Evaluation of Atezolizumab Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC in Canada.

INTRODUCTION: The real-world data evaluating treatment outcomes of atezolizumab plus carboplatin-etoposide chemotherapy (atezolizumab) for extensive-stage SCLC (ESCLC) are lacking. Our objective was to evaluate real-world outcomes of ESCLC treated with atezolizumab. METHODS: A retrospective analysis of provincial patients with ESCLC who started first-line (1L) systemic treatment was conducted. We primarily evaluated the progression-free survival (PFS) and overall survival (OS) outcomes in association with atezolizumab compared with platinum-etoposide chemotherapy (chemotherapy) while adjusting for relevant demographic and clinical factors. Adverse events (AEs) during 1L were evaluated. RESULTS: A total of 67 patients were identified. Of the 34 patients who received atezolizumab, 24% had Eastern Cooperative Oncology Group performance status greater than or equal to 2, approximately 50% were more than or equal to 65 years, 21% received cisplatin-etoposide chemotherapy before atezolizumab, and 12% had thoracic radiation (tRT).Within the atezolizumab versus chemotherapy group, the median PFS equals to 6.0 versus 4.3 months (p = 0.03) whereas OS = 12.8 versus 7.1 months (p = 0.01). Relative to chemotherapy, the hazard ratio (95% confidence interval) for PFS was 0.53 (0.28-1.02) and OS was 0.42 (0.20-0.88) with atezolizumab. tRT compared with no tRT receipt correlated with reduced death risk (hazard ratio [95% confidence interval] = 0.33 [0.13-0.88]).AE-related treatment withdrawal with atezolizumab was 32% and 15% with chemotherapy (p = 0.02). Within the tRT subgroup, 25% versus 20% in atezolizumab versus chemotherapy group, respectively, discontinued 1L owing to AE. CONCLUSIONS: This is the first real-world study revealing comparable survival with that in the IMpower133 trial. Treatment discontinuation from AEs was higher with atezolizumab among Canadian patients with ESCLC. Our data suggest safe use of tRT and chemoimmunotherapy, but its efficacy for ESCLC warrants further study.

Retrospective Real-World Outcomes for Patients With ALK-Rearranged Lung Cancer Receiving ALK Receptor Tyrosine Kinase Inhibitors.

INTRODUCTION: This study explored the use, safety, and efficacy of initial use of an ALK-inhibiting targeted therapy (ALK tyrosine kinase inhibitor [TKI]) in patients with ALK-rearranged NSCLC in a population-based, real-world clinical population within the province of Alberta, Canada. METHODS: Demographic, clinical, treatment, and outcome data of the patients with advanced or metastatic ALK-rearranged NSCLC receiving their first ALK TKI between 2014 and 2019 were included in the analysis. RESULTS: A total of 92 patients with ALK-rearranged NSCLC treated with ALK TKI (78% crizotinib, 22% alectinib) were identified. In the ALK-rearranged cohort, 1-year survival rate was 73% and median overall survival (OS) and progression-free survival (PFS) were 48.5 months and 17.0 months, respectively. An objective response rate of 49% was observed, and adverse events were reported in 70% of the patients, primarily of low grade (84%). Case-matched comparison to patients with ALK-wildtype disease treated with cytotoxic chemotherapy revealed the benefit of ALK TKI in the context of an ALK rearrangement (ALK-rearranged versus ALK-wildtype) (median post-treatment initiation OS: 46.8 versus 14.2 mo, p < 0.001). Outcomes, measured from the time of ALK TKI initiation, differed by Eastern Cooperative Oncology Group (ECOG) (ECOG < 2 versus ECOG ≥ 2) (median OS: not reached versus 6.8 mo, p < 0.001; median PFS 17.6 versus 7.4 mo, p = 0.02), disease presentation (relapsed versus de novo) (median PFS: 30.8 versus 15.0 mo, p = 0.04), and brain metastasis onset (brain metastases development during ALK TKI versus baseline brain metastases) (not reached versus 12.8 mo, p = 0.04). CONCLUSIONS: Clinical trials have firmly established that ALK TKIs are safe, well tolerated, and effective; these findings reveal that their impact in a real-world setting is just as profound. The availability and use of ALK TKI therapies contribute to the impressive gains in survival experienced by contemporary patients with ALK-rearranged disease, rendering patients with this oncodriven form of NSCLC among the longest surviving patients with lung cancer.

A systematic review of school-based social skills interventions and observed social outcomes for students with autism spectrum disorder in inclusive settings.

LAY ABSTRACT: Most social skills interventions for students with autism spectrum disorder have been conducted in clinic-based settings. While students with autism spectrum disorder are able to acquire new skills, the generalization of these skills to authentic social environments, like school, is more difficult. To address this issue, there is an increase in research examining the implementation of social skills interventions for students with autism spectrum disorder who are educated in inclusive school settings. This review included 18 research studies that focused on school-based social interventions for students with autism spectrum disorder who were educated in inclusive school settings. Typically developing peers also participated in the interventions to varying degrees. Secondary aims explored naturalistic observation instruments and subsequent social outcomes used to record the social behaviors of students with autism spectrum disorder at school. Social intervention components varied across studies, but all studies reported improvement in the targeted social behaviors of students with autism spectrum disorder. There were many similarities in the ways in which researchers measured and defined social outcomes. Observation protocols were able to measure change in the social behaviors of students with autism spectrum disorder across a wide age range. The recognition of evidence-based practices used in school-based social skills interventions, as well as the identification of observation protocols and salient social outcomes, provides a starting point for school practitioners to consider as they move to implement social skills interventions for students with autism spectrum disorder into inclusive school settings.

CXCR4 expression in lung carcinogenesis: Evaluating gender-specific differences in survival outcomes based on CXCR4 expression in early stage non-small cell lung cancer patients.

INTRODUCTION: Evidence suggests that the expression of certain cytokine receptors increases with lung cancer evolution. Overexpression of the cytokine receptor CXCR4 is associated with poor outcomes in stage IV non-small cell lung cancer (NSCLC), with shorter survival in females with high CXCR4 expression. This study quantifies CXCR4 expression in early stage disease and evaluates its association with gender-specific recurrence-free (RFS) and overall survival (OS) in resected stage I-III NSCLC patients. METHODS: Patient characteristics and clinical outcomes were obtained from the Glans-Look Lung Cancer (G-LLC) database for early stage NSCLC patients diagnosed between 2003-2006 at the Tom Baker Cancer Centre (TBCC). CXCR4 expression was quantified on tissue microarrays (TMA). Median RFS and OS were evaluated by gender using Kaplan-Meier analyses. CXCR4 expression and outcome data were analyzed using Cox proportional hazards (PH) and multi-state models (MSM). RESULTS: 176 stage I-III NSCLC patients were identified. CXCR4 expression was lower in early stage NSCLC patients, with a mean CXCR4 expression of 1729 (SD 1083) compared to 2640 (SD 1541) in stage IV patients. On Kaplan-Meier, median RFS by gender was similar (male 52.8 months vs. female 54.5 months) as was median OS (male 80.9 months vs. female 89.0 months), and there was no significant difference in RFS (p = 0.60) or OS (p = 0.30) by gender and CXCR4 groups over follow-up. By multivariable analysis, CXCR4 expression was not prognostic for RFS (Hazard Ratio (HR) = 1.00, p = 0.73) or OS (HR = 1.00, p = 0.44), and no gender difference was observed. CONCLUSIONS: CXCR4 expression increases with stage progression in NSCLC but is not prognostic in early stage NSCLC patients of either gender. Mechanisms by which CXCR4 expression increases during lung carcinogenesis warrant further exploration and testing in clinical trials.

Adolescents with autism spectrum disorder and social skills groups at school: A randomized trial comparing intervention environment and peer composition.

This study used a randomized controlled trial to compare two distinct models of group social skills interventions with adolescents with autism spectrum disorder (ASD). Participants had a confirmed diagnosis of ASD, an IQ greater than or equal to 70, and were educated in the general education setting. Data from 62 adolescent participants who were randomized to one of two treatment conditions (SKILLS vs. ENGAGE) were analyzed. SKILLS participants had a diagnosis of ASD, or social difficulties. ENGAGE groups included adolescents with ASD and typically developing (TD) peer mentors. SKILLS and ENGAGE participants both improved joint engagement and reduced solitary engagement, however, SKILLS participants reported higher social stress and lower quality interpersonal relationships at exit, and increased emotional symptoms and problem behaviors at follow-up compared to the ENGAGE group. The findings suggest that within inclusive secondary school settings, it may be beneficial to include TD peers in social intervention groups.

Disordered Eating Attitudes and Behaviors in Maltreated Children and Adolescents Receiving Forensic Assessment in a Child Advocacy Center.

Previous studies have indicated that childhood sexual abuse (CSA) and other forms of child maltreatment (CM), as well as their subsequent posttraumatic symptoms, are significant risk factors for the development of disordered eating behaviors and attitudes and eating disorders (EDs). However, there are no known reports of CM based on forensic interview and assessment that have been linked to disordered eating behaviors and attitudes, or eating disorders (EDs), especially in children and adolescents. We, therefore, examined the hypothesis that ED-related symptoms would be significantly associated with trauma-related symptoms in children with reported maltreatment. Girls (n = 179, 11.9 ± 2.4 years) and boys (n = 99, 11.7 ± 2.8 years) referred for forensic assessment of alleged maltreatment completed the Kids' Eating Disorders Survey, the Eating Disorders Inventory for Children (EDI-C), the Trauma Symptom Checklist for Children, and the Adolescent Dissociative Experiences Scale, among others. Significant positive correlations between most EDI-C subscale scores and most TSC-C subscale scores (PTSD, dissociation, anxiety, depression, sexual concerns) were found (p ≤.001) in the total sample and girls alone. Participants with credible, substantiated disclosures had significantly higher scores on several ED-related measures than those with non-credible, non-substantiated disclosures. Linear regression analysis indicated that PTSD and dissociative symptoms were significant predictors of EDI-C scores in those with substantiated disclosures (p ≤.001). Findings support the hypothesis that ED-related symptoms are significantly linked to authenticated CM.

PIK3CA mutation and CNV status and post-chemoradiotherapy survival in patients with cervical cancer.

PURPOSE: This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer. EXPERIMENTAL DESIGN: Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR. RESULTS: 190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03-2.92; p = .037) but not PFS (HR 1.38; 0.84-2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01-2.81; p = .046) but not PFS (HR 1.50; 0.93-2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18-5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90-3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA. CONCLUSIONS: PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.

The prevalence and prognostic significance of estrogen receptor beta expression in non-small cell lung cancer.

BACKGROUND: Estrogen receptor beta (ERß) is the predominant estrogen receptor (ER) expressed in non-small cell lung cancer (NSCLC); however, due to methodological disparities among prior studies, the prognostic value of ERß expression in NSCLC remains unclear. Our objective was to apply improved detection and analysis techniques to assess the prognostic value of ERß expression in NSCLC. METHODS: A tissue microarray (TMA) was used which contained resected and biopsy specimens from 299 patients diagnosed at a single center with stages I-IV NSCLC. Sections of this array were stained using high-sensitivity fluorescence immunohistochemistry, with the well-validated PPG5/10 monoclonal antibody. Digital images of the stained array slides were analyzed using software-based image analysis, which reported ERß expression as a continuous variable in different subcellular domains. RESULTS: There were no differences in ERß expression between male and female patients. High expression of ERß was not a prognostic factor, but was significantly associated with stage IV disease in both tumor and stroma (P<0.001). In multivariable analysis, a high nuclear/cytoplasmic (N/C) ratio of ERß expression was significantly associated with shorter overall survival, based on expression in the tumor [hazard ratio (HR): 1.65; 95% confidence interval (CI): 1.25-2.19; P<0.001] and in the stroma (HR: 1.57; 95% CI: 1.16-2.12; P=0.003). CONCLUSIONS: These results suggest that subcellular localization of ERß, but not absolute expression, is a prognostic factor in NSCLC.

Statewide Interagency Collaboration to Support Evidence-based Practice Scale Up: The California Autism Professional Training and Information Network (CAPTAIN).

The California Autism Professional Training and Information Network (CAPTAIN) is a statewide interagency collaboration with the goal of scaling up use of evidence-based practices (EBPs) for individuals with autism spectrum disorder (ASD). CAPTAIN began as a clinical initiative then further developed under the influence of implementation science methodology. The Exploration, Preparation, Implementation and Sustainment framework (EPIS) has impacted targeted strategy use for this statewide scale up of EBPs by informing the development of key partnerships, implementation goals, and collaborative processes within CAPTAIN. Currently, CAPTAIN has over 407 members representing 140 school and community agencies who provide training and coaching in EBP and meet regularly with regional teams. Outcome data indicate 51.9% of members provide training and coaching to more than three direct service providers/programs per year. Primary barriers to implementation of EBP were time for training (25.6%), lack of substitute teachers (16.5%), and staff lacking foundational skills (11.5%). Facilitators of implementation and sustainment of the CAPTAIN model include active participation in effective dissemination practices, creative funding and leveraging of local resources, development of the regional collaboratives with active membership, member commitment to EBP for ASD, and use of implementation science to identify and overcome barriers. The purpose of this paper is to highlight CAPTAIN as a model for statewide scale up of EBP in schools as well as other community agencies. Although these efforts have focused on EBP for ASD, the concepts, partnerships and procedures will likely be transferable to other focal issues and may be generalized across service sectors.

Real-World Adherence to Guideline-Recommended Treatment for Small Cell Lung Cancer.

OBJECTIVES: The authors sought to quantify the treatment patterns and outcomes for limited-stage (LS) and extensive-stage (ES) small cell lung cancer (SCLC) in a real-world setting. METHODS: A review was conducted using the Glans-Look Research Database of patients with SCLC managed at a tertiary cancer center in Canada from 2010 to 2016. Adherence was defined as the commencement of planned SCLC treatment. Rate of compliance with the Alberta Health Services, American Society of Clinical Oncology, and National Comprehensive Cancer Network SCLC treatment guidelines was evaluated. Outcomes were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of 404 patients met our inclusion criteria, 31% were LS. The median age at first treatment receipt was 67 years. LS treatment consisted mostly of chemoradiation (62%). Chemoradiation and surgery±adjuvant predicted better survival (median, 32 and 40 mo, respectively) compared with no treatment. ES treatment consisted mostly of chemotherapy (90%). Chemotherapy and thoracic radiotherapy correlated with longer overall survival (13 vs. 9 mo, respectively) compared with chemotherapy alone. Prophylactic cranial irradiation receipt in LS (50%) and ES (20%) predicted favorable survivals than none (LS: hazard ratio, 0.48; 95% CI, 0.29-0.79; ES: hazard ratio, 0.48; 95% CI, 0.33-0.70). Approximately a quarter of relapsed LS and ES had second-line chemotherapy; improved survival with second line was observed only in ES (P<0.01). CONCLUSIONS: This study highlights high rates of guideline-recommended first treatment among the real-world LS and ES patients but it also revealed important outcome differences in relapsed LS and ES patients treated with second-line chemotherapy.