Identification and Characterization of Avoidable Hospital Admissions in Patients With Lung Cancer.

BACKGROUND: More than 50% of patients with lung cancer are admitted to the hospital while receiving treatment, which is a burden to patients and the healthcare system. This study characterizes the risk factors and outcomes of patients with lung cancer who were admitted to the hospital. METHODS: A multidisciplinary oncology care team conducted a retrospective medical record review of patients with lung cancer admitted in 2018. Demographics, disease and admission characteristics, and end-of-life care utilization were recorded. Following a multidisciplinary consensus review process, admissions were determined to be either "avoidable" or "unavoidable." Generalized estimating equation logistic regression models assessed risks and outcomes associated with avoidable admissions. RESULTS: In all, 319 admissions for 188 patients with a median age of 66 years (IQR, 59-74 years) were included. Cancer-related symptoms accounted for 65% of hospitalizations. Common causes of unavoidable hospitalizations were unexpected disease progression causing symptoms, chronic obstructive pulmonary disease exacerbation, and infection. Of the 47 hospitalizations identified as avoidable (15%), the median overall survival was 1.6 months compared with 9.7 months (hazard ratio, 2.07; 95% CI, 1.34-3.19; P<.001) for unavoidable hospitalizations. Significant reasons for avoidable admissions included cancer-related pain (P=.02), hypervolemia (P=.03), patient desire to initiate hospice services (P=.01), and errors in medication reconciliation or distribution (P<.001). Errors in medication management caused 26% of the avoidable hospitalizations. Of admissions in patients receiving immunotherapy (n=102) or targeted therapy (n=44), 9% were due to adverse effects of treatment. Patients receiving immunotherapy and targeted therapy were at similar risk of avoidable hospitalizations compared with patients not receiving treatment (P=.3 and P=.1, respectively). CONCLUSIONS: We found that 15% of hospitalizations among patients with lung cancer were potentially avoidable. Uncontrolled symptoms, delayed implementation of end-of-life care, and errors in medication reconciliation were associated with avoidable inpatient admissions. Symptom management tools, palliative care integration, and medication reconciliations may mitigate hospitalization risk.

Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin.

Penile squamous cell carcinoma is a rare disease with very limited data to guide treatment decisions. In particular, there is minimal evidence for effective therapies in the metastatic setting. Here, we present a case of metastatic penile squamous cell carcinoma with response to the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV). EV was selected due to the evidence of the high expression of Nectin-4 in squamous cell carcinomas, including penile carcinoma. The patient had both radiographic and symptomatic improvement after two cycles of treatment, despite having been treated with multiple prior lines of traditional chemotherapy. This case provides support for the use of antibody-drug conjugates (ADC), including EV, in this disease with few other options in the advanced setting. Further studies examining Nectin-4 and ADCs in penile squamous cell carcinoma should be completed, as high-quality evidence is needed to guide treatment after initial progression for these patients.

Economic Impact of Orthopedic Adult Reconstruction Office Practice: The Implications of Hospital Employment Models on Local Economies.

The purpose of this study was to evaluate the economic attributes of private practice adult reconstruction (AR) offices. 458 AAHKS surgeons responded; 65% were in private practice (fee-for-service, non-salaried, non-employed AR surgeons). 54% had considered hospital employment in the past two years. The average group employs 13.4 orthopedic surgeons (3.4 AR), and 105 other employees. The average total budget is $12.5 million per year with $4 million in salaries, and $238,000 in tax revenue generated. Co-management joint ventures are a better model than hospital employment for aligning AR surgeons and hospitals and realizing the cost effectiveness and quality improvement goals of PPACA and AARA while preserving the economic impact of AR private practice.

Revision total hip and knee arthroplasty implant identification: implications for use of Unique Device Identification 2012 AAHKS member survey results.

FDA's Unique Device Identification (UDI) Rule will mandate manufacturers to assign unique identifiers to their marketed devices. UDI use is expected to improve implant documentation and identification. A 2012 American Association of Hip and Knee Surgeons membership survey explored revision total hip and knee arthroplasty implant identification processes. 87% of surgeons reported regularly using at least 3 methods to identify failed implants pre-operatively. Median surgeon identification time was 20 min; median staff time was 30 min. 10% of implants could not be identified pre-operatively. 2% could not be identified intra-operatively. UDI in TJA registry and UDI in EMR were indicated practices to best support implant identification and save time. FDA's UDI rule sets the foundation for UDI use in patient care settings as standard practice for implant documentation.

Variations in surgeons' recovery expectations for patients undergoing total joint arthroplasty: a survey of the AAHKS membership.

Recovery expectations (RE) after total hip and knee arthroplasty (THA-TKA) influence outcomes. We surveyed AAHKS members to determine variation in surgeon RE. Four vignettes depicting patients with high and low expectations after THA and TKA were distributed with a validated RE survey. Responses were analyzed for clinically significant differences between surgeons and within surgeons. Of 1049 surgeons surveyed, 358 (34%) responded. There was a clinically significant difference in 85% (high-THA), 46% (low-THA), 74% (high-TKA), and 57% (low-TKA) of pairs. Disagreement was significantly greater in high expectation vignettes. Individual surgeons distinguished between high and low expectation patients in 76% (THA) and 72% (TKA) of cases. There was no association between surgeon RE and practice demographics. Wide variations in RE were observed, especially among high expectation patients.

Rural barriers and facilitators of lung cancer screening program implementation in the veterans health administration: a qualitative study.

Introduction: To assess healthcare professionals' perceptions of rural barriers and facilitators of lung cancer screening program implementation in a Veterans Health Administration (VHA) setting through a series of one-on-one interviews with healthcare team members. Methods: Based on measures developed using Reach Effectiveness Adoption Implementation Maintenance (RE-AIM), we conducted a cross-sectional qualitative study consisting of one-on-one semi-structured telephone interviews with VHA healthcare team members at 10 Veterans Affairs medical centers (VAMCs) between December 2020 and September 2021. An iterative inductive and deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual model to depict rural barriers and facilitators of lung cancer screening program implementation. Results: A total of 30 interviews were completed among staff, providers, and lung cancer screening program directors and a conceptual model of rural barriers and facilitators of lung cancer screening program implementation was developed. Major themes were categorized within institutional and patient environments. Within the institutional environment, participants identified systems-level (patient communication, resource availability, workload), provider-level (attitudes and beliefs, knowledge, skills and capabilities), and external (regional and national networks, incentives) barriers to and facilitators of lung cancer screening program implementation. Within the patient environment, participants revealed patient-level (modifiable vulnerabilities) barriers and facilitators as well as ecological modifiers (community) that influence screening behavior. Discussion: Understanding rural barriers to and facilitators of lung cancer screening program implementation as perceived by healthcare team members points to opportunities and approaches for improving lung cancer screening reach, implementation and effectiveness in VHA rural settings.

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors.

Background: Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood. Methods: Patients enrolled in this retrospective cohort study were identified from the Vanderbilt BioVU database and their medical records were reviewed. Patients with advanced thoracic cancer who received FV within 3 months prior to or during their ICI treatment period were enrolled in the FV-positive cohort and those who did not were enrolled in the FV-negative cohort. The primary objective was to detect whether FV is associated with decreased IRAE severity. The secondary objectives were to evaluate whether FV is associated with a decreased risk for grade 3-5 IRAEs and better survival times. Multivariable ordinal logistic regression was used for the primary analysis. Results: A total of 142 and 105 patients were enrolled in the FV-positive and FV-negative cohorts, respectively. There was no statistically significant difference in patient demographics or cumulative incidences of IRAEs between the two cohorts. In the primary analysis, FV was inversely associated with the severity of IRAEs (OR 0.63; p=0.046). In the secondary analysis, FV was associated with a decreased risk for grade 3-5 IRAEs (OR 0.42; p=0.005). Multivariable Cox regression showed that FV was not associated with survival times. Conclusions: Our study showed that FV does not increase toxicity for patients with advanced thoracic cancer on ICIs and is associated with a decreased risk for grade 3-5 IRAEs. No statistically significant survival differences were found between patients with and without FV.

A resident survey study of orthopedic fellowship specialty decision making and views on arthroplasty as a career.

A dramatic shortage of total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgeons has been projected because fewer residents enter arthroplasty fellowships, and the demand for THAs/TKAs is rising. The purposes of this study were to ascertain the future supply of THA/TKA surgeons, to identify the criteria residents use to choose their fellowship specialty, and to assess resident perceptions of an arthroplasty career. Four hundred ninety-eight post-graduate year 3 and above residents completed the online survey. Residents most highly prioritize intellectual factors and role models/mentors in determining their fellowship specialty. In the face of a looming patient access-to-care crisis, the data from this study support a policy of highlighting the intellectual challenges and satisfaction of THA/TKA as a career and encouraging mentorship early in a resident's training.

A translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based fall prevention exercise and education program.

Falls in older adults are the leading cause of injury hospitalizations and fatalities in the United States; primary risk factors are muscle weakness, impaired mobility, and balance deficits. This article describes the 12-month translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based public health, public domain fall prevention exercise and education program. Recruitment reached the target goal by 154%; 331 adults (mean age = 74.6) attended more than one class (mean classes attended = 24.8, SD = 26.6, range = 1-120) at nine community sites in one county in the 12-month period; 173 completed health and demographic forms, 132 completed program surveys, and 91 completed baseline and follow-up physical function tests. Physical function test results showed significant improvements in strength, balance, and mobility in those who were below normal limits at baseline, and in those who attended classes twice a week or more for more than 2 months. Survey results found that 93% of respondents reported improved performance of daily activities; 92% reported improved strength, balance, fitness, or flexibility; and 80% found the SAIL information guide education component helpful.

Circulating Tumor DNA as a Biomarker of Radiographic Tumor Burden in SCLC.

INTRODUCTION: Blood-based next-generation sequencing assays of circulating tumor DNA (ctDNA) have the ability to detect tumor-associated mutations in patients with SCLC. We sought to characterize the relationship between ctDNA mean variant allele frequency (VAF) and radiographic total-body tumor volume (TV) in patients with SCLC. METHODS: We identified matched blood draws and computed tomography (CT) or positron emission tomography (PET) scans within a prospective SCLC blood banking cohort. We sequenced plasma using our previously developed 14-gene SCLC-specific ctDNA assay. Three-dimensional TV was determined from PET and CT scans using MIM software and reviewed by radiation oncologists. Univariate association and multivariate regression analyses were performed to evaluate the association between mean VAF and total-body TV. RESULTS: We analyzed 75 matched blood draws and CT or PET scans from 25 unique patients with SCLC. Univariate analysis revealed a positive association between mean VAF and total-body TV (Spearman's ρ = 0.292, p < 0.01), and when considering only treatment-naive and pretreatment patients (n = 11), there was an increase in the magnitude of association (ρ = 0.618, p = 0.048). The relationship remained significant when adjusting for treatment status and bone metastases (p = 0.046). In the subgroup of patients with TP53 variants, univariate analysis revealed a significant association (ρ = 0.762, p = 0.037) only when considering treatment-naive and pretreatment patients (n = 8). CONCLUSIONS: We observed a positive association between mean VAF and total-body TV in patients with SCLC, suggesting mean VAF may represent a dynamic biomarker of tumor burden that could be followed to monitor disease status.

Impact of the economic downturn on adult reconstruction surgery: a survey of the American Association of Hip and Knee Surgeons.

To evaluate the effects of the economic downturn on adult reconstruction surgery in the United States, a survey of the American Association of Hip and Knee Surgeons (AAHKS) membership was conducted. The survey evaluated surgical and patient volume, practice type, hospital relationship, total joint arthroplasty cost control, employee staffing, potential impact of Medicare reimbursement decreases, attitudes toward health care reform options and retirement planning. A surgical volume decrease was reported by 30.4%. An outpatient visit decrease was reported by 29.3%. A mean loss of 29.9% of retirement savings was reported. The planned retirement age increased to 65.3 years from 64.05 years. If Medicare surgeon reimbursement were to decrease up to 20%, 49% to 57% of AAHKS surgeons would be unable to provide care for Medicare patients, resulting in an unmet need of 92,650 to 160,818 total joint arthroplasty procedures among AAHKS surgeons alone. Decreases in funding for surgeons and inadequate support for subspecialty training will likely impact access and quality for Americans seeking adult reconstruction surgery.

Venous thromboembolism: management by American Association of Hip and Knee Surgeons.

A 2008 survey of American Association of Hip and Knee Surgeons membership explored current venous thromboembolism (VTE) protocols for lower-extremity total joint surgery. Fifty-three percent reported a change in VTE-related practices in the last 5 years. More than 70% reported that their primary hospital now mandates VTE prophylaxis. Although 74% of their primary hospitals recognized the American College of Chest Physicians guidelines, 68% of surgeons felt the American Academy of Orthopaedic Surgeons guidelines were more relevant to their practice. Respondents believe low molecular weight heparin to be the most efficacious but aspirin to be the easiest to use and has the lowest risks of bleeding and wound drainage. Warfarin was the most used in hospital prophylaxis, and 90% of respondents targeted an international normalized ratio of 1.6 to 2.5. Practice patterns continue to evolve, and there remains no consensus on specific treatment protocols or preferences.

Blood-Based Surveillance Monitoring of Circulating Tumor DNA From Patients With SCLC Detects Disease Relapse and Predicts Death in Patients With Limited-Stage Disease.

INTRODUCTION: Most patients (70%) with limited-stage SCLC (LS-SCLC) who are treated with curative-intent therapy suffer disease relapse and cancer-related death. We evaluated circulating tumor DNA (ctDNA) as a predictor of disease relapse and death after definitive therapy in patients with LS-SCLC. METHODS: In our previous work, we developed a plasma-based ctDNA assay to sequence 14 genes (TP53, RB1, BRAF, KIT, NOTCH1-4, PIK3CA, PTEN, FGFR1, MYC, MYCL1, and MYCN) that are frequently mutated in SCLC. In this work, we evaluated 177 plasma samples from 23 patients with LS-SCLC who completed definitive chemoradiation (n = 21) or surgical resection (n = 2) and had an end-of-treatment blood collection (median 4 d, range 0-40 d from treatment completion) plus monthly surveillance blood sampling. Median overall survival (OS) and progression-free survival (PFS) were compared using a Wilcoxon test. RESULTS: The median OS among patients in whom we ever detected ctDNA after definitive treatment (n = 15) was 18.2 months compared with a median OS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (n = 8; p = 0.081). The median PFS among patients in whom we ever detected ctDNA after definitive treatment was 9.1 months compared with a median PFS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (p < 0.001). CONCLUSIONS: Detection of ctDNA in patients with LS-SCLC after curative-intent therapy predicts disease relapse and death. Prospective trials using ctDNA as an integral biomarker for therapeutic selection should be considered in SCLC.

Surgeon demographics and medical malpractice in adult reconstruction.

UNLABELLED: Orthopaedic adult reconstruction subspecialists are sued for alleged medical malpractice at a rate over twice that of the physician population as a whole, and the rate appears disproportionately high in the first decade of practice. The overall risk of a malpractice claim is related to years spent in practice. After 30 years in an adult reconstruction practice, the cumulative rate of being sued at least once is over 90%. Previous investigations suggest factors such as practice setting and size, fellowship training, years in practice, volume, and location of practice correlate with malpractice risk. In contrast, we were unable to identify any relationship between the type, size, or location of practice, fellowship training, or surgery volume and the risk of an adult reconstruction surgeon being named as a defendant in a malpractice suit. LEVEL OF EVIDENCE: Level V, economic and decision analysis. See the Guidelines for Authors for a complete description of levels of evidence.

Differential Interaction of Peripheral Blood Lymphocyte Counts (ALC) With Different in vivo Depletion Strategies in Predicting Outcomes of Allogeneic Transplant: An International 2 Center Experience.

Dosing regimens for antithymocyte globulin (ATG) and anti-CD52 antibody (alemtuzumab) for graft vs. host disease prophylaxis (GVHD) are empiric or weight-based, and do not account for individual patient factors. Recently, it has been shown that recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration interacts with the dose of ATG administered to predict transplantation outcome. Similarly, we wanted to analyze if the recipient ALC interacts with alemtuzumab dosing to predict outcomes. We retrospectively compared 364 patients, 124 patients receiving ATG (anti-thymocyte globulin) for GVHD prophylaxis, and undergoing unrelated first allogeneic transplant for myeloid and lymphoid malignancies (group 1) to 240 patients receiving alemtuzumab (group 2), in similar time period. There was no difference in survival or acute and chronic GVHD between 60 and 100 mg of alemtuzumab dosing. Unlike ATG (where the pre-transplant recipient ALC interacted with ATG dose on day of its administration (day 1) to predict OS and DFS (p = 0.05), within alemtuzumab group, the recipient ALC on second day of alemtuzumab administration (day 2) and its interaction with alemtuzumab dose strongly predicted OS, DFS and relapse (p = 0.05, HR-1.81, 1.1-3.3; p = 0.002, HR-2.41, CI, 1.3-4.2; and p = 0.003, HR-2.78, CI, 1.4-5.2), respectively. ALC (day 2) of 0.08 × 109/lit or higher, had a specificity of 96% in predicting inferior DFS. Like ATG, there is definite but differential interaction between the recipient peripheral blood ALC and alemtuzumab dose to predict OS, DFS, and relapses.

Longitudinal Cell-Free DNA Analysis in Patients with Small Cell Lung Cancer Reveals Dynamic Insights into Treatment Efficacy and Disease Relapse.

INTRODUCTION: Patients with SCLC have a poor prognosis and limited treatment options. Because access to longitudinal tumor samples is very limited in patients with this disease, we chose to focus our studies on the characterization of plasma cell-free DNA (cfDNA) for rapid, noninvasive monitoring of disease burden. METHODS: We developed a liquid biopsy assay that quantifies somatic variants in cfDNA. The assay detects single nucleotide variants, copy number alterations, and insertions or deletions in 14 genes that are frequently mutated in SCLC, including tumor protein p53 gene (TP53), retinoblastoma 1 gene (RB1), BRAF, KIT proto-oncogene receptor tyrosine kinase gene (KIT), notch 1 gene (NOTCH1), notch 2 gene (NOTCH2), notch 3 gene (NOTCH3), notch 4 gene (NOTCH4), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), phosphatase and tensin homolog gene (PTEN), fibroblast growth factor receptor 1 gene (FGFR1), v-myc avian myelocytomatosis viral oncogene homolog gene (MYC), v-myc avian myelocytomatosis viral oncogene lung carcinoma derived homolog gene (MYCL1), and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog gene (MYCN). RESULTS: Over the course of 26 months of peripheral blood collection, we examined 140 plasma samples from 27 patients. We detected disease-associated mutations in 85% of patient samples with mutant allele frequencies ranging from 0.1% to 87%. In our cohort, 59% of the patients had extensive-stage disease, and the most common mutations occurred in TP53 (70%) and RB1 (52%). In addition to mutations in TP53 and RB1, we detected alterations in 10 additional genes in our patient population (PTEN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, MYC, MYCL1, PIK3CA, KIT, and BRAF). The observed allele frequencies and copy number alterations tracked closely with treatment responses. Notably, in several cases analysis of cfDNA provided evidence of disease relapse before conventional imaging. CONCLUSIONS: These results suggest that liquid biopsies are readily applicable in patients with SCLC and can potentially provide improved monitoring of disease burden, depth of response to treatment, and timely warning of disease relapse in patients with this disease.

Effectiveness of a community-based multifactorial intervention on falls and fall risk factors in community-living older adults: a randomized, controlled trial.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a 12-month community-based intervention on falls and risk factors (balance, lower extremity strength, and mobility) in community-living older adults. METHODS: Four hundred fifty-three sedentary adults (65 years old or older) were randomized to either a multifaceted intervention (3 times a week group exercise, 6 hours of fall prevention education, comprehensive falls risk assessment results sent to primary health care provider) or control group (written materials on falls prevention). Primary outcome was fall incidence rates calculated from self-reported falls reported monthly for 12 months. Secondary outcomes were tests of leg strength, balance, and mobility prior to and following the 12-month intervention. RESULTS: Twelve-month follow-up was completed on 95% of participants. Intent-to-treat analysis found that the incidence rate of falls was 25% lower among those in the intervention group compared with control group (1.33 vs 1.77 falls/person-year, rate ratio 0.75, 95% confidence interval [CI], 0.52-1.09). This difference was not statistically significant. The risk ratio for any fall was 0.96 (95% CI, 0.82-1.13). Small but significant improvements were found on the Berg Balance Test (adjusted mean difference +1.5 points, 95% CI, 0.8-2.3), the Chair Stand Test (adjusted mean difference +1.2, 95% 0.6-1.9), and the Timed Up and Go Test (adjusted mean difference -0.7, 95% CI, -1.2 to -0.2). CONCLUSIONS: A community-based multifaceted intervention was effective in improving balance, mobility, and leg strength, all known fall risk factors. Although the incidence of falls was lower, the confidence interval included the possibility of no intervention effect on falls.

Current practices of AAHKS members in the treatment of adult osteonecrosis of the femoral head.

BACKGROUND: There is currently no standardized protocol for evaluating and treating osteonecrosis of the femoral head in adults in the United States. We sought to understand current treatment practices of a group of surgeons who commonly treat this disease to determine if there was agreement on some aspects of care. METHODS: We designed a two-staged mixed-mode (mailed and faxed) sixteen-question self-administered descriptive survey questionnaire to be sent to all 753 active members of the American Association of Hip and Knee Surgeons (AAHKS). The survey design was based on Dillman's survey research methodology, and the questionnaire included hypothetical clinical scenarios based on the Steinberg classification system. The responses elucidated the opinions and treatment preferences of high-volume arthroplasty surgeons who treat adult patients with osteonecrosis of the femoral head. RESULTS: Of the 753 active members of the AAHKS, 403 (54%) responded to the questionnaire. Total hip replacement was reported to be the most frequent intervention for treatment of postcollapse (Steinberg stage-IIIB, IVB, V, and VI) osteonecrosis; core decompression was reported to be the most commonly offered intervention for symptomatic, precollapse (Steinberg stage-IB and IIB) osteonecrosis. Less frequently offered treatments included nonoperative management, osteotomy, vascularized and non-vascularized bone-grafting, hemiarthroplasty, and arthrodesis. CONCLUSIONS: The care of adults with osteonecrosis of the femoral head varies among American orthopaedic surgeons specializing in hip and knee surgery. A consensus may evolve with a continued concerted effort on the part of interested surgeons, but it will require randomized, controlled, prospective studies of treatment of each stage of the disease and collaborative multicenter studies. LEVEL OF EVIDENCE: Therapeutic Level V.

EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib.

UNLABELLED: Oncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions in exon 19 or point mutations in exon 21 (L858R), confer sensitivity to EGFR tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD). Through analysis of a larger cohort of tumor samples, we detected additional cases of EGFR-KDD in lung, brain, and other cancers. In vitro, EGFR-KDD is constitutively active, and computational modeling provides potential mechanistic support for its auto-activation. EGFR-KDD-transformed cells are sensitive to EGFR TKIs and, consistent with these in vitro findings, the index patient had a partial response to the EGFR TKI afatinib. The patient eventually progressed, at which time resequencing revealed an EGFR-dependent mechanism of acquired resistance to afatinib, thereby validating EGFR-KDD as a driver alteration and therapeutic target. SIGNIFICANCE: We identified oncogenic and drug-sensitive EGFR-KDD that is recurrent in lung, brain, and soft-tissue cancers and documented that a patient with metastatic lung adenocarcinoma harboring the EGFR-KDD derived significant antitumor response from treatment with the EGFR inhibitor afatinib. Findings from these studies will be immediately translatable, as there are already several approved EGFR inhibitors in clinical use.