Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: Secondary analysis of NRG Oncology RTOG 0129 and 0522.

BACKGROUND: No risk-stratification strategies exist for patients with recurrent oropharyngeal cancer (OPC). METHODS: Retrospective analysis using data from prospective NRG Oncology clinical trials RTOG 0129 and 0522. Eligibility criteria included known p16 status and smoking history, and locoregional/distant recurrence. Overall survival (OS) was measured from date of recurrence. Recursive partitioning analysis was performed to produce mutually exclusive risk groups. RESULTS: Hundred and fifty-four patients were included with median follow-up after recurrence of 3.9 years (range 0.04-9.0). The most important factors influencing survival were p16 status and type of recurrence, followed by surgical salvage and smoking history (≤20 vs. >20 pack-years). Three significantly different risk groups were identified. Patients in the low-, intermediate-, and high-risk groups had 2-year OS after recurrence of 81.1% (95%CI 68.5-93.7), 50.2% (95%CI 36.0-64.5), and 20.8% (95%CI 10.5-31.1), respectively. CONCLUSION: Patient and tumor characteristics may be used to stratify patients into risk groups at the time of OPC recurrence.

Improving Medical Students' Understanding of Pediatric Diseases through an Innovative and Tailored Web-based Digital Pathology Program with Philips Pathology Tutor (Formerly PathXL).

BACKGROUND: Online "e-modules" integrated into medical education may enhance traditional learning. Medical students use e-modules during clinical rotations, but these often lack histopathology correlates of diseases and minimal time is devoted to pathology teaching. To address this gap, we created pediatric pathology case-based e-modules to complement the clinical pediatric curriculum and enhance students' understanding of pediatric diseases. METHODS: Philips Tutor is an interactive web-based program in which pediatric pathology e-modules were created with pre-/post-test questions. Each e-module contains a clinical vignette, virtual microscopy, and links to additional resources. Topics were selected based on established learning objectives for pediatric clinical rotations. Pre- and post-tests were administered at the beginning/end of each rotation. Test group had access to the e-modules, but control group did not. Both groups completed the pre/post-tests. Posttest was followed by a feedback survey. RESULTS: Overall, 7% (9/123) in the control group and 8% (13/164) in the test group completed both tests and were included in the analysis. Test group improved their posttest scores by about one point on a 5-point scale (P = 0.01); control group did not (P = 1.00). Students responded that test questions were helpful in assessing their knowledge of pediatric pathology (90%) and experienced relative ease of use with the technology (80%). CONCLUSIONS: Students responded favorably to the new technology, but cited time constraints as a significant barrier to study participation. Access to the e-modules suggested an improved posttest score compared to the control group, but pilot data were limited by the small sample size. Incorporating pediatric case-based e-modules with anatomic and clinical pathology topics into the clinical medical education curriculum may heighten students' understanding of important diseases. Our model may serve as a pilot for other medical education platforms.

EGFR molecular testing in African-American non-small cell lung cancer patients - a review of discrepant data.

Substantial discrepancy in the literature has recently emerged regarding epidermal growth factor receptor (EGFR) mutational frequency in African American (AA) NSCLC. The first wave of tissue profiling studies, including by our group in 2009, consistently observed a significantly lower frequency of EGFR mutation in AA vs. White NSCLC, whereas three recent reports appear to directly contradict these findings. Reasons for this discrepancy are unclear, but one plausible explanation arises from Simpson's paradox, the consequence of aggregating heterogeneous study cohorts (in this case, the proportion of never-smokers in the study cohort). Our review of all prior studies (combined total 386 AA NSCLC cases) underscores the wide variation in the proportion of AA never-smokers among various studies (13-57%), calling inter-study comparisons into question. In parallel, we assessed objective response by RECIST to EGFR targeted therapy for AA NSCLC in the community setting, prior to the advent of routine EGFR testing. We observed a trend toward reduced response for community-based treatment of unselected AA NSCLC (5%; 3/57) as compared to overall response rates of 10% reported by large North American trials of primarily White NSCLC patients, but this was not significant (P=0.223).

Genetic abnormalities of the EGFR pathway in African American Patients with non-small-cell lung cancer.

PURPOSE: Previous studies in non-small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) -targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists. PATIENTS AND METHODS: EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC. RESULTS: African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409). CONCLUSION: African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.