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BACKGROUND: Short-term airway stent placement (stent evaluation) has been employed to evaluate whether patients with excessive central airway collapse (ECAC) will benefit from tracheobronchoplasty. Although retrospective studies have explored the impact of stent placement on ECAC, prospective randomized controlled trials are absent. METHODS: This was a randomized open-label trial comparing patients receiving airway stent placement and standard medical treatment (intervention group) versus standard medical treatment alone (control group) for ECAC. At baseline, patients' respiratory symptoms, self-reported measures, and functional capabilities were assessed. Follow-up evaluations occurred 7 to 14 days postintervention, with an option for the control group to crossover to stent placement. Follow-up evaluations were repeated in the crossover patients. RESULTS: The study enrolled 17 patients in the control group [medical management (MM)] and 14 patients in the intervention group. At follow-up, 15 patients in the MM crossed over to the stent group, resulting in a total of 29 patients in the combined stent group (CSG). Subjectively (shortness of breath and cough), 45% of the CSG exhibited improvement with the intervention compared with just 12% in the MM. The modified St. George Respiratory Questionnaire score in the CSG improved significantly from 61.2 at baseline to 52.5 after stent placement (-8.7, P = 0.04). With intervention, the 6-minute walk test in CSG improved significantly from 364 meters to 398 meters (34 m, P < 0.01). The MM did not show a significant change in the St. George Respiratory Questionnaire score or 6-minute walk test distance. CONCLUSION: Short-term airway stent placement in patients with ECAC significantly improves respiratory symptoms, quality of life, and exercise capacity.
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Stents , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Qualidade de Vida , Obstrução das Vias Respiratórias/terapia , Obstrução das Vias Respiratórias/cirurgia , Estudos Prospectivos , Broncoscopia/métodos , TosseRESUMO
OBJECTIVE: Differential use of communal (kindness, cooperation, morality) and agentic terms (competence, assertiveness, decisiveness) may reveal bias and has been extensively reported in letters of recommendation (LoR) for residency but letter writer factors have not been thoroughly studied. We estimate the association between use of agentic and communal language with letter writer and applicant characteristics. DESIGN: Retrospective review of LoR comparing 2 letters written for the same applicant. Applicant demographics and USMLE scores as well as letter writer demographics and academic/departmental rank were compared. Multilevel regression controlling for clustering of letters within applicant was performed. SETTING: Single academic surgery residency program in a tertiary center. PARTICIPANTS: US medical students applying for categorical surgery residency. RESULTS: Applications of 667 US medical students (age 27.1, interquartile range [IQR] 26.2-28.6; female 340, 51%, white 337, 54.2%) were evaluated. Most commonly, letters writers were males (nâ¯=â¯1031, 77.3%), Full Professors (nâ¯=â¯660, 49.48%) and Department Chairs or Division Chiefs (nâ¯=â¯629, 47.151%). Overall, median bias score was 14.29 (interquartile range -4 to 33.33), indicating predominance of agentic terms. Applicant female gender (coef 3.64, 95% confidence interval [CI] 0.33-6.96) and higher Step 1 USMLE scores (coef 0.12, 95% CI 0.0026-0.24) were associated with increased use of agentic terms. For letter writer characteristics, female (coef -4.23, 95% CI -8.14 to -0.32) and fewer years in practice (coef -0.32, 95% CI -0.48 to -0.16) were independent predictors of increased use of communal traits. CONCLUSIONS: Comparing 2 LoR written for the same applicant, male and more senior surgeons use more agentic language in their LoR as compared to female and younger surgeons. Increased use of communal language is expected as the pool of letter writers is diversified and reflects essential characteristics of contemporary surgeons.
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Internato e Residência , Cirurgiões , Adulto , Feminino , Humanos , Idioma , Masculino , Seleção de Pessoal , RedaçãoRESUMO
OBJECTIVES: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied. MATERIALS AND METHODS: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib. RESULTS: A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively. CONCLUSION: Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Piperidinas , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/uso terapêuticoRESUMO
OBJECTIVE: An excessive amount of nonurgent pages may disrupt patient care, reduce efficiency, and contribute to burnout. We present detailed paging data to analyze frequency, content, and urgency of pages received by surgery residents to provide recommendations to reduce resident distractions and fatigue. DESIGN: Prospective review of pages received by surgery residents over 15 weeks in 2019. Pages were analyzed by content and urgency (routine, important, emergent) by author consensus and compared among day and night shifts, and page senders' profession. SETTING: University tertiary-care hospital PARTICIPANTS: Seventeen junior surgery residents (PGY-1 and PGY-2) RESULTS: Total 1,740 resident-hours yielded 1,871 pages. Residents working day and night shift received a median of 11 (IQR 7-14) and 13 (IQR 6-22) pages, respectively. Pages from nurses were most common for both shifts but constituted a significantly increased proportion at night (71.3% vs 36.7%, p < 0.00005). Most pages during day shift were routine (74.4%) and pertained to plan of care and order request (38.4% and 15.7%, respectively). Emergent and important pages were more common at night (8.9% and 24.7% vs 1.8 and 14.8%, p < 0.00005) which paralleled an increase in pages reporting change in patient condition compared to day shift (19.7 from 6.7%, p < 0.00005). Routine pages pertaining care plan and order requests remained common at night (26.5 and 28%, respectively). CONCLUSIONS: Over half of pages received by residents contain routine communications about care plan and request for non-urgent orders, even during night shift. Resident-nurse collaboration and support from technology services might optimizing communication pathways.
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Esgotamento Profissional , Internato e Residência , Esgotamento Profissional/prevenção & controle , Comunicação , Humanos , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Ultrasound guidance has resulted in a continuous evolution in techniques for pain control for video-assisted thoracoscopic surgery (VATS). The objective of this study was to compare erector spinae plane block with intercostal block as multimodal analgesia to elucidate quality of postoperative pain control and preservation of pulmonary function after VATS. METHODS: A consecutive cohort of patients undergoing elective VATS was enrolled in the study and divided into erector spinae plane block and intercostal block groups. Spirometry and visual analog scale pain score exams were performed to measure forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and forced expiratory flow in intervals of 25% to 75%. Chronic pain was assessed by reviewing surgical follow-up notes. RESULTS: Seventy-eight patients were included. Comparing the erector spinae plane block group with the intercostal block group found significant improvement in visual analog scale pain score (3.2 vs 6.4, P < .001), postanesthesia care unit length of stay (127.3 vs 189.5 minutes, P = .045), preservation in lung volume parameters at 2 hours (FVC: 40.5% vs 51.4%, P < .001; FEV1: 40.9% vs 53.8%, P < .001; and forced expiratory flow in intervals of 25%-75%: 39.7% vs 53.7%, P = .019) and at 24 hours (FVC: 37.8% vs 50.5%, P < .001; FEV1: 34.3% vs 51.9%, P < .001; forced expiratory flow in intervals of 25%-75%: 27.1% vs 56.3%, P < .001), respectively. CONCLUSIONS: Erector spinae plane block improves acute and chronic pain control and preserves lung function. Thus, it has the potential for enhanced recovery from VATS as part of a multimodal analgesia regimen.
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Período de Recuperação da Anestesia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Músculos Paraespinais/inervação , Ultrassonografia/métodos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversosRESUMO
The proliferation of computer-aided design and additive manufacturing enables on-demand fabrication of complex, three-dimensional structures. However, combining the versatility of cell-laden hydrogels within the 3D printing process remains a challenge. Herein, we describe a facile and versatile method that integrates polymer networks (including hydrogels) with 3D-printed mechanical supports to fabricate multicomponent (bio)materials. The approach exploits surface tension to coat fenestrated surfaces with suspended liquid films that can be transformed into solid films. The operating parameters for the process are determined using a physical model, and complex geometric structures are successfully fabricated. We engineer, by tailoring the window geometry, scaffolds with anisotropic mechanical properties that compress longitudinally (~30% strain) without damaging the hydrogel coating. Finally, the process is amenable to high cell density encapsulation and co-culture. Viability (>95%) was maintained 28 days after encapsulation. This general approach can generate biocompatible, macroscale devices with structural integrity and anisotropic mechanical properties.
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Materiais Biocompatíveis/química , Fibroblastos/citologia , Hidrogéis/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Desenho Assistido por Computador , Humanos , Impressão Tridimensional/instrumentação , Tensão Superficial , Engenharia Tecidual/instrumentaçãoRESUMO
INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics. RESULTS: The majority of 1009 NSCLC patients had advanced stages of adenocarcinoma with most tissues obtained from the lung, mediastinal/hilar nodes, or pleura. The majority of testing was performed on cytology or small biopsy specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing at our institution for EGFR, ALK, ROS1 and PD-L1 all occurred within the first year following evidence of clinical activity or regulatory body approval of an associated inhibitor. The overall testing failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene identified (EGFR/ALK/ROS1/BRAF V600E) with an approved oral targeted therapy, with the highest prevalence in those patients with no or light (≤15 pack-years) history of tobacco use. CONCLUSIONS: Tumor biomarker testing using clinical NSCLC specimens in routine oncologic care evolves rapidly following approval of targeted therapies linked to diagnostic assays. Our practice's decade plus experience highlights the rapid evolution of biomarker testing and confirms the therapeutic relevance of such testing in all patients-particularly those patients with light/no history of tobacco use.
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Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Neoplasias Pulmonares/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Genômica/tendências , Humanos , Imuno-Histoquímica/tendências , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A nonintrusive e-mail reminder incorporating teaching tips and manuscripts was developed to supplement resident-as-teacher curricula. METHODS: Ten high-yield manuscripts and 10 teaching tips exemplifying the themes of mentorship or role modeling, teaching methods, adult learning theory, feedback, and the resident role of teaching were distributed to general surgery house staff through a weekly e-mail series. House staff completed surveys before and after the 20-week e-mail series. RESULTS: Thirty (43%) and 28 (40%) respondents completed the pre-e-mail and post-e-mail survey, respectively. Residents found teaching tips to be more helpful than manuscripts. Weekly e-mail reminders were "just right" in frequency according to 74% of respondents. Forty percent of residents felt the weekly e-mails helped them teach more often and 50% of residents changed their teaching style. CONCLUSIONS: Weekly reminders are an easy way to encourage resident teaching without a significant resident time commitment. Residents typically find teaching tips to be more useful than manuscripts.
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Correio Eletrônico , Cirurgia Geral/educação , Internato e Residência , Materiais de Ensino , Ensino/educação , Currículo , Feedback Formativo , HumanosRESUMO
BACKGROUND: Mistreatment has potential downstream effects on students. General surgery rotations tend to have a higher incidence of mistreatment reports. This study was undertaken to identify dominant themes contributing to a negative learning environment. METHODS: A qualitative study was performed using Delphi consensus technique to develop a discussion guide. Four focus groups were performed (n = 30 participants) with medical students, residents, nurses, and attending surgeons. Participants were selected using purposive-stratified criterion-based sampling. RESULTS: Multiple themes emerged: 1) unclear expectations for medical students; 2) passive mistreatment (neglect); 3) failure to integrate students into surgical team; 4) witnessed or experienced active mistreatment, 5) negative attitude of residents towards medical students' lack of knowledge. CONCLUSIONS: Medical student mistreatment persists and is a threat to the learning environment and individual learning process. Passive mistreatment (neglect) represents the most distressing component of mistreatment. These findings suggest a need for education aimed at surgical residents and others in the learning environment.
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Atitude do Pessoal de Saúde , Estágio Clínico , Educação de Graduação em Medicina , Relações Interpessoais , Estudantes de Medicina/psicologia , Técnica Delphi , Docentes de Medicina , Grupos Focais , Cirurgia Geral/educação , Humanos , Internato e Residência , Massachusetts , Cultura Organizacional , Pesquisa Qualitativa , Comportamento Social , EnsinoRESUMO
INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib. One of the common mechanisms of resistance to crizotinib is the acquisition of ALK kinase domain mutations. However, the presence of ALK mutations in crizotinib-naïve tumors has not been widely reported and it is unclear if de novo ALK mutations affect the response to crizotinib. METHODS: We analyzed preclinical models of ALK rearranged lung cancers that were sensitive/resistant to ALK inhibitors, probed our institutional and other lung cancer databases for tumors with ALK kinase domain mutations, and evaluated tumor response to crizotinib. RESULTS: ALK rearranged cell lines with ALK kinase domain mutations were heterogeneously less inhibited by increasing concentrations of crizotinib than cells driven solely by EML4-ALK fusions. Previous ALK rearranged lung cancer cohorts did not report ALK kinase mutations in inhibitor-naïve tumors. We identified one TKI-naïve ALK rearranged tumor with an ALK kinase domain mutation: ALK-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models). The never smoker whose tumor harbored de novo EML4-ALK-E5;A20+ALK-S1206F only achieved a 4-month radiographic response to crizotinib 250mg twice daily. CONCLUSIONS: Combining data from our and prior cohorts, ALK kinase domain mutations were uncommon events (<3% of cases) in ALK inhibitor-naïve ALK rearranged lung adenocarcinomas but their effect on intrinsic resistance to ALK inhibitors should be better evaluated.
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Rearranjo Gênico , Neoplasias Pulmonares/genética , Mutação , Domínios e Motivos de Interação entre Proteínas/genética , Receptores Proteína Tirosina Quinases/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Crizotinibe , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/química , Resultado do TratamentoRESUMO
Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.
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Imunidade Adaptativa , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Animais , Antígeno B7-H1/administração & dosagem , Antígeno B7-H1/imunologia , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Receptores Virais/genética , Receptores Virais/imunologiaRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effects of preemptive ultrasound-guided thoracic paravertebral block versus intercostal block on postoperative respiratory function and pain control in patients undergoing video-assisted thoracoscopic surgery. SUBJECTS: 50 consecutive patients undergoing video-assisted thoracoscopic surgery. METHOD: A prospective cohort of patients who received either ultrasound-guided thoracic paravertebral block immediately before the procedure or intercostal block placed by the surgeon at the end of the procedure were studied. Pulmonary function was assessed before surgery and 4 h postoperatively. Pain was assessed with the visual analog scale at 2 and 4 h after surgery both at rest and on coughing. RESULTS: 30 patients on the paravertebral block group and 20 on the intercostal block group were studied. Forced vital capacity (p < 0.001), forced expiratory volume at 1 s (p < 0.001) and forced expiratory flow 25-75% (p = 0.001) were significantly higher at 4 h with paravertebral block compared to the intercostal block group. The visual analog score for pain was significantly improved with paravertebral block at rest (p < 0.05) and with cough (p = 0.00). Perioperative narcotic use was significantly reduced with paravertebral block in comparison to intercostal block (p = 0.04). CONCLUSIONS: When compared to intercostal blocks, ultrasound-guided thoracic paravertebral block appears to preserve lung function and provide better pain control in the immediate postoperative period after video-assisted thoracoscopic surgery.
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Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Analgésicos/uso terapêutico , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Período Pós-Operatório , Estudos Prospectivos , Ultrassonografia de IntervençãoRESUMO
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are present in 10-20% of all non-small-cell lung cancers and predict for response to EGFR tyrosine kinase inhibitors (TKIs). However, the incidence of these mutations and their ability to predict response to TKIs in high-grade pulmonary neuroendocrine carcinomas [i.e. small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC)] is unknown. METHODS: The presence of EGFR mutations, clinicopathologic and anti-cancer therapy response data were retrospectively compiled and analyzed from a cohort of 608 patients-lung tumors to identify EGFR mutated high-grade pulmonary neuroendocrine carcinomas. We identified 126 EGFR-mutated (21.8% of 578 successful genotyped cases) lung cancers and only 2 (1.6%) were high-grade neuroendocrine carcinomas. RESULTS: Case one was of a 63 year-old white never smoker woman with extensive stage SCLC harboring EGFR-delL747_P753insS but without EGFR protein expression. After progression on carboplatin/etoposide, the patient was treated with erlotinib and developed progressive disease with a survival <3 months from start of erlotinib. Case two was of a 73 year-old Asian 30 pack-year smoker man with metastatic LCNEC harboring EGFR-delL747_P753insQS and also lacking EGFR protein expression. The patient received first line therapy with erlotinib and had progressive disease with a survival of 4 months. CONCLUSIONS: The lack of response to EGFR TKIs in EGFR mutated de novo SCLC and LCNEC reported here may indicate that tumor differentiation affects tumor dependency on EGFR as a driver oncogene.
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Carcinoma Neuroendócrino/diagnóstico por imagem , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Radiografia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genéticaRESUMO
INTRODUCTION: Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making. METHODS: Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs). RESULTS: SGAs identified abnormalities in 34 samples, and all patients with advanced EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS was more commonly requested for EGFR, ALK, and KRAS-negative tumors (p<0.0001). NGS was successful in 24/29 (82.7%) tumors. Of 17 adenocarcinomas (ACs), 11 (7 from patients with ≤15 pack-years of smoking) had abnormalities in a known driver oncogene. This led to a change in decision-making in 8 patients, trial consideration in 6, and off-label TKI use in 2. Of 7 squamous cell (SC) carcinomas, 1 had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). In no cases were clinical decisions altered (p=0.0538 when compared to ACs). CONCLUSIONS: Targeted NGS can identify a significant number of therapeutically-relevant driver events in lung ACs; particularly in never or light smokers. For SC lung cancers, NGS is less likely to alter current practice. Further research into the cost effectiveness and optimal use of NGS and improved provider training in genomic oncology are warranted.
RESUMO
INTRODUCTION: Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. METHODS: Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. RESULTS: From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). CONCLUSIONS: Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Técnicas de Genotipagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Quinase do Linfoma Anaplásico , Biópsia , Receptores ErbB/genética , Feminino , Genótipo , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Receptores Proteína Tirosina Quinases/genética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Adequate tumor acquisition is essential to identify somatic molecular alterations in non-small-cell lung cancer (NSCLC), such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations. The success and failure rates for tumor genotyping of tissue obtained from fine-needle aspirates of nodal tissue using a convex probe endobronchial ultrasound (CP-EBUS) and other diagnostic modalities in routine NSCLC care have not been described. METHODS: Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 207 patient-tumor samples sent for routine tumor genotype in clinical practice, including 42 patient-tumor samples obtained from hilar or mediastinal lymph nodes using CP-EBUS. RESULTS: The median age of the patients was 65 years, 62.3% were women, 77.8% were white, 26.6% were never smokers, 73.9% had advanced NSCLC, and 84.1% had adenocarcinoma histology. Tumor tissue was obtained from CP-EBUS-derived hilar or mediastinal nodes in 42 cases (20.2% of total). In this latter cohort, the overall success rate for EGFR mutation analysis was 95.2%, for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation 90.5%, and for ALK fluorescence in situ hybridization 90.5%. In the complete 207 tumors, the success rate for EGFR was 92.3%, for KRAS 91.8%, and for ALK 89.9%. The failure rates were not significantly different when comparing CP-EBUS-derived nodal tissue versus all other samples or versus surgical biopsies of mediastinal nodes, but were significantly lower than image-guided percutaneous transthoracic core-needle biopsies. CONCLUSIONS: The success rate of multiple tumor genomic analyses techniques for EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples obtained from hilar or mediastinal lymph nodes by means of CP-EBUS exceeds 90%, and this method of tissue acquisition is not inferior to other specimen types. Tumor genotype techniques are feasible in most CP-EBUS-derived samples and therefore further expansion of routine tumor genotype for the care of patients with NSCLC may be possible using targeted sample acquisition through CP-EBUS.
Assuntos
Adenocarcinoma/genética , Brônquios/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Endossonografia , Neoplasias Pulmonares/genética , Linfonodos/diagnóstico por imagem , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Brônquios/metabolismo , Brônquios/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Receptores ErbB/genética , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/diagnóstico , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Proteínas ras/genéticaRESUMO
INTRODUCTION: The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient-tumor sample pairs. METHODS: Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples. RESULTS: Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. CONCLUSIONS: The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Fumar/efeitos adversos , Proteínas ras/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/etiologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Hospitais Universitários , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Oncogenes , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Autorrelato , Estados Unidos , População Branca/genéticaRESUMO
Minimally invasive surgical techniques offer several advantages over traditional open procedures, yet the pathway to minimally invasive proficiency can be difficult to navigate. As a part of an effort of the Joint Council of Thoracic Surgical Education to increase access to this skill set in the general thoracic community, recent graduates of thoracic residencies were surveyed to determine the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy proficiency and the merits of various educational opportunities. The objective of this study was to estimate the comfort level of recent graduates with the minimally invasive approach, as this demographic not only reflects the current status of training, but represents the future of the specialty. Surgeons graduating North American thoracic residencies between 2006 and 2008 identifying themselves as practitioners of general thoracic surgery were surveyed. A total of 271 surgeons completed training between 2006 and 2008 and indicated general thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed). One hundred and forty-six surgeons completed the survey (54%) including 74 of 84 (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform general thoracic procedures consider themselves proficient in VATS lobectomies (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P < 0.0001). Of surgeons considering themselves to be proficient at VATS lobectomies, 66% felt thoracic residency was critical or very important to achieving proficiency. Fellowships after completing board residency, animal labs, and follow-up VATS courses put on by experts were much less consistently beneficial. The vast majority of the 25 dedicated general thoracic surgeons who graduate each year consider themselves proficient in VATS lobectomies, largely due to training in their thoracic residencies. On the other hand, the minority of surgeons performing general thoracic procedures as a part of a mixed practice consider themselves proficient in VATS lobectomies. Further study is warranted to enhance the VATS lobectomy experience of mixed practice surgeons particularly during their thoracic residencies.
Assuntos
Atitude do Pessoal de Saúde , Competência Clínica , Educação de Pós-Graduação em Medicina , Conhecimentos, Atitudes e Prática em Saúde , Internato e Residência , Pneumonectomia/educação , Autoimagem , Cirurgia Torácica Vídeoassistida/educação , Currículo , Humanos , Curva de Aprendizado , América do Norte , Inquéritos e QuestionáriosRESUMO
PURPOSE: Evidence-based treatment guidelines for non-small-cell lung cancer (NSCLC) exist to improve the quality of care for patients with this disease. However, how often evidence-based decisions are used for care of NSCLC is poorly understood. PATIENTS AND METHODS: We examined patterns of care and rate of adherence to evidence-based guidelines for 185 new NSCLC patients seen between 2007 and 2009. Evidence-based care status was determined for 150 patients. RESULTS: Eighty-one percent of the patients were white, the mean age was 66 years, 49% were women, 11% were never smokers, 83% had Eastern Cooperative Oncology Group performance status 0 to 1, 49.7% of tumors were adenocarcinomas, 57.1% of never smokers had tumors genotyped (EGFR, ALK, KRAS), and 13.3% participated in clinical trials. The rate of evidence-based treatment adherence was 94.1% (16 of 17), 100% (21 of 21) and 100% (36 of 36) in patients with stages I, II, and III NSCLC, respectively. Stage IV disease, with adherence of 76.3% (58 of 76), was correlated with a higher rate of nonadherence when compared with stages I-III (odds ratio 16.33; 95% CI, 1.94 to 137.73). In patients with stage IV disease, the rate of evidence-based adherence was 95% (72 of 76) for first-line therapy, 95.2% (40 of 42) for second-line therapy, and only 33.3% (6 of 18) for third-line therapy (P < .001). There was no significant correlation between evidence-based adherence status and the patient's age, sex, performance status, smoking history, ethnicity, or the treating physician. CONCLUSION: These data point toward the need for improved evidence-based use of resources in the third-line setting of stage IV NSCLC.