This work surveys current interventions to mitigate burnout and organizes them into a scaffold that can be used by residency programs interested in a complete framework to supporting wellness.

Introduction Genomic aberrations involving ALK, ROS1 and MET can be driver oncogenes in lung adenocarcinomas. Identification of tyrosine kinase inhibitors (TKIs) with activity against these tumors and of preclinical systems to model response are warranted. Methods We analyzed cases with lung adenocarcinomas for representative genomic aberrations, evaluated the response to the multitargeted MET/ALK/ROS1 crizotinib TKI in cases with MET aberrations and profiled lung cancer cell lines with the aforementioned genomic changes. Results Lung cancer cell lines with ALK rearrangement, ROS1 rearrangement or MET amplification had expected in vitro responses to crizotinib and the ALK/ROS1 TKI ceritinib. However, a commercially-available cell line with MET exon 14 skipping mutation and co-occurring PIK3CA-p.Glu545Lys mutation did not respond to crizotinib; suggesting the latter abrogated response. 10% of MET exon 14 skipping mutation co-occurred with PIK3CA mutation in the TCGA cohort. Putative crizotinib-responsive somatic mutations (ALK rearrangements, ROS1 rearrangements, high level MET amplification or MET exon 14 skipping mutations) were present in 10% of lung adenocarcinomas analyzed at our service and in 9.5% of the TCGA lung adenocarcinoma database. One patient each whose advanced tumors harbored high level MET amplification with wild-type PIK3CA or MET exon 14 skipping mutation with PIK3CA-p. Glu542Lys had significant responses to crizotinib; suggesting that PIK3CA co-mutation did not affect clinical response. Conclusions Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to MET TKIs in human lung adenocarcinomas but co-occurrence of PIK3CA mutation needs to be better evaluated as a modifier of response to TKI therapy. MET TKIs should not be omitted from MET exon 14 skipping mutated tumors until further preclinical and clinical data can confirm or refute mechanisms of primary or acquired resistance to crizotinib and other MET TKIs in these recalcitrant cancers.

Introduction Genomic aberrations involving erb-b2 receptor tyrosine kinase 2 (ERBB2) are driver oncogenes in ∼2% of lung adenocarcinomas. However, the use of daily dosing of ERBB2 tyrosine kinase inhibitors (TKIs) - including afatinib - has been fraught by plasma concentrations that barely achieve preclinical model inhibition, significant patient-reported toxicities and limited clinical activity. We hypothesized that alternative dosing strategies could improve tolerability and efficacy. Methods We profiled lung cancer cell lines against TKIs and retrospectively evaluated the toxicity/response to pulse afatinib (280mg once weekly) in lung cancers with ERBB2 mutations. Results An ERBB2 exon 20 insertion mutated lung cancer cell line had 50% inhibitory concentration to afatinib higher than the reported plasma concentration of afatinib 40mg daily. Three patients with advanced ERBB2 mutated lung adenocarcinomas were treated with off-label pulse afatinib. The 280mg weekly dose was well tolerated with no reported rash and minimal diarrhea. One TKI-naïve patient achieved a partial response for 5 months and another stable disease for 11 months. Conclusions Pulse afatinib at a weekly dosing scheme induced anti-tumor activity in ERBB2 exon 20 insertion mutated lung adenocarcinomas. Future clinical trials of alternative dosing schemes of ERBB TKIs as monotherapy or in combination with other therapies are warranted for ERBB2 mutated tumors.

Medical educators seeking to maximize their effectiveness would benefit from an understanding of how body language affects a learning environment and how body language techniques can be used to engage audiences, maintain attention, control challenging learners, and convey passion for a topic. Understanding and using body language effectively is an important instructional skill.

Rasburicase-induced methemoglobinemia is a known adverse effect of patients administered rasburicase for tumor lysis syndrome who have concomitant glucose-6-phosphate dehydrogenase deficiency. This phenomenon has been described in multiple case reports but has been limited to male patients. We present the first case series illustrating this adverse effect in two female patients where morbidity and mortality associated with rasburicase-induced methemoglobinemia were evident. Screening protocols at the reporting institutions were lacking. The prevalence of G6PD may be underestimated based on the epidemiology of sample subjects in previous studies of rasburicase. We argue that both male and female patients should be suspected of G6PD in this setting; however, more data on prevalence and cost-effectiveness are needed on screening protocols for G6PD.

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Consultation amongst providers is a foundation of modern health care and one of the most frequent means of interdisciplinary communication. Accordingly, clear and efficient communication between providers and across medical specialties during consultation is essential to patient care and a collegial work environment. Traditionally, consultation requests are felt to require a clear question that falls within the purview of the consultant’s expertise. However, this narrow constraint is often lacking in the real-world clinical environment and may in fact be detrimental to physician communication and patient care. In this Perspective, the authors propose an organizing framework of seven specific consultation types, which apply broadly across disciplines: ideal, obligatory, procedural, S.O.S., confirmatory, inappropriate, and curbside. The authors describe what factors define each type and the benefits and pitfalls of each. The proposed framework may help providers have more productive, efficient, and collegial conversations about patient care, which may facilitate improved work satisfaction and an enhanced learning environment.

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