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BACKGROUND: Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases. OBJECTIVES: This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD). METHODS: Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively. RESULTS: Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status. CONCLUSION: Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease.
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Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/secundário , Carcinoma de Célula de Merkel/terapia , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Metástase Linfática , Metástase Neoplásica , Neoplasias Hepáticas/secundário , Estadiamento de NeoplasiasRESUMO
PURPOSE: The purpose of this study is to determine the public's perception of the scope of practice for oculofacial plastic and reconstructive surgeons (OFPRS). METHODS: A 49-question survey was distributed by Qualtricsâ to a panel similar to the US demographic composition. Responses collected underwent bivariate statistical analysis. RESULT: A total of 530 responses were obtained, with most respondents being white, female, over the age of 35, from the Midwest, and with at least a college education or above. Most respondents did not think ophthalmologists or optometrists were surgeons, and only 158 people (29.8%) knew the primary specialty of OFPRS was ophthalmology. Board certification was preferred by 98.87% of respondents, and 95.28% preferred ASOPRS-trained OFPRS. CONCLUSIONS: Our study highlights the gap in knowledge about OFPRS as a field, the qualifications and training required, and the scope of practice. Notably, even for OFPRS-specific procedures, PRS remained the leading subspecialist chosen for interventions such as orbital decompression (58.5% vs. 71.5%), orbital reconstruction (57.9% vs. 74.2%), enucleation/evisceration (48.1% vs. 53.4%), optic nerve-related surgery (39.8% vs. 43.4%), orbital cancer resection (42.8% vs. 46.8%), and tear duct surgery (41.9% vs. 52.5%). Additionally, most respondents did not feel that facial fillers, laser skin resurfacing, eyelid cancer removal, or cataract surgery were within the OFPRS scope of practice.
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Carcinoma de Células Escamosas , DNA Tumoral Circulante , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , DNA Tumoral Circulante/genética , Biomarcadores TumoraisAssuntos
Carcinoma de Célula de Merkel , Linfoma de Célula do Manto , Neoplasias Cutâneas , Humanos , Adulto , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/patologia , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Linfonodos/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Pele/patologiaRESUMO
Background: This study aims to evaluate the treatment and follow-up of bacteriuria in the emergency department (ED). Objective: The primary objective was to determine the frequency of patients discharged from the ED with antibiotics for symptomatic and asymptomatic bacteriuria, and the secondary objectives were to determine the frequency of patients receiving postdischarge antibiotic interventions and antibiotic-related adverse drug reactions (ADRs). Methods: This retrospective study evaluated patients with ED urine cultures sent between October 1, 2015, and November 24, 2015. Patients with indwelling catheters, concurrent antibiotics, and admission for inpatient care were excluded. T tests and contingency tables were applied in SAS; P < .05 was considered significant. Results: Of 429 unique patients with urine cultures drawn in the ED, 13.1% (n = 56) received treatment for a bacteriuria. The majority of patients discharged from the ED with antibiotics had urinary tract infection (UTI) symptoms documented in the medical record (76.8%; n = 43). Of those patients who required postdischarge interventions, 4 out of 13 had appropriate antibiotic adjustments based on culture and sensitivity results at follow-up. In a subset of patients with inappropriately ordered urine cultures (no UTI symptoms documented or antibiotic prescribed), a higher percentage of patients had normal urinalyses (UA) compared to abnormal UAs (83.3% vs 10.4%, P = .0008). No significant ADRs were identified. Conclusions: The majority of patients treated for bacteriuria in the ED had documented symptoms consistent with UTIs and appropriate empiric antibiotics. However, incorporating antimicrobial stewardship activities in the ED targeting unnecessary urine cultures and assuring postdischarge follow-up if treatment modification is needed based on culture results can improve antibiotic prescribing.
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Understanding tumor-host immune interactions and the mechanisms of lung cancer response to immunotherapy is crucial. Current preclinical models used to study this often fall short of capturing the complexities of human lung cancer and lead to inconclusive results. To bridge the gap, we introduce two new murine monoclonal lung cancer cell lines for use in immunocompetent orthotopic models. We demonstrate how our cell lines exhibit immunohistochemical protein expression (TTF-1, NapA, PD-L1) and common driver mutations (KRAS, p53, and p110α) seen in human lung adenocarcinoma patients, and how our orthotopic models respond to combination immunotherapy in vivo in a way that closely mirrors current clinical outcomes. These new lung adenocarcinoma cell lines provide an invaluable, clinically relevant platform for investigating the intricate dynamics between tumor and the immune system, and thus potentially contributes to a deeper understanding of immunotherapeutic approaches to lung cancer treatment.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Animais , Imunoterapia/métodos , Humanos , Linhagem Celular Tumoral , Camundongos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Modelos Animais de Doenças , FemininoRESUMO
Importance: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. Objective: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. Design, Setting, and Participants: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). Exposures: Cemiplimab or pembrolizumab. Main Outcomes and Measures: Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. Results: This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). Conclusions and Relevance: The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas , Terapia Neoadjuvante , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Idoso , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/mortalidade , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodosRESUMO
Background: [11C]-Methionine positron emission tomography (PET; [11C]-MET-PET) is principally used for the evaluation of brain tumors in adults. Although amino acid PET tracers are more commonly used in the evaluation of pediatric brain tumors, data on [11C]-MET-PET imaging of pediatric low-grade gliomas (pLGG) is scarce. This study aimed to investigate the roles of [11C]-MET-PET in the evaluation of pLGGs. Methods: Eighteen patients with newly diagnosed pLGG and 26 previously treated pLGG patients underwent [11C]-MET-PET met the inclusion and exclusion criteria. Tumor-to-brain uptake ratio (TBR) and metabolic tumor volumes were assessed for diagnostic performances (newly diagnosed, 15; previously treated 26), change with therapy (newly diagnosed, 9; previously treated 7), and variability among different histology (nâ =â 12) and molecular markers (nâ =â 7) of pLGGs. Results: The sensitivity of [11C]-MET-PET for diagnosing pLGG, newly diagnosed, and previously treated combined was 93% for both TBRmax and TBRpeak, 76% for TBRmean, and 95% for qualitative evaluation. TBRmax showed a statistically significant reduction after treatment, while other PET parameters showed a tendency to decrease. Median TBRmax, TBRpeak, and TBRmean values were slightly higher in the BRAFV600E mutated tumors compared to the BRAF fused tumors. Median TBRmax, and TBRpeak in diffuse astrocytomas were higher compared to pilocytic astrocytomas, but median TBRmean, was slightly higher in pilocytic astrocytomas. However, formal statistical analysis was not done due to the small sample size. Conclusions: Our study shows that [11C]-MET-PET reliably characterizes new and previously treated pLGGs. Our study also shows that quantitative parameters tend to decrease with treatment, and differences may exist between various pLGG types.
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PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.
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While normal, controlled wound-healing results in scars that are nearly imperceptible, hypertrophic scars (HTS) and keloids are the result of an abnormal wound-healing process that can leave unsightly, difficult-to-treat lesions. While such scars are classically associated with surgical incisions, they may also result from burns or accidental trauma to the skin. Several different measures can be taken to prevent the formation of scars or treat those that have already formed. Prevention focuses on reducing inflammation during the wound-healing process, and minimizing tension in the lesion when appropriate. Treatments range from non-invasive modalities such as pressure therapy, topicals, and symptom management, to invasive methods such as injections, lasers, and even surgery. While some treatments, such as corticosteroid injections, have been used in the treatment of HTS and keloids for decades, other newer therapies have only been described in case reports or are still in early phases of clinical trials. Because optimal scar management will not be the same for every patient, further investigation of newer agents and methods is warranted and may benefit a great number of patients. This paper will review the evidence-based management of scars, including current widely used treatment options and promising newly emerging therapies.
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Cicatriz Hipertrófica , Dermatologia , Queloide , Humanos , Queloide/patologia , Cicatriz Hipertrófica/patologia , Pele/patologia , CicatrizaçãoRESUMO
Mohs micrographic surgery (MMS) may be an effective treatment modality for oral cavity cancers (OCC) due to possibility of more effective visualization of tumor margins and greater preservation of benign tissue. The objective of this study is to review the existing literature on the use of MMS for the treatment of OCC and categorize its uses and limitations. A systematic review was performed in accordance with Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines. PubMed, Scopus, and Google Scholar from inception of databases to January 20, 2023 identified all published studies on the use of MMS for OCC. Nine studies met inclusion criteria. Seventy-seven patients were treated with MMS for OCC, 74 of which (96%) were treated for squamous cell carcinoma (SCC). The tongue was the most common site (n = 57). Six out of seven studies showed no recurrence of disease during the follow-up periods, which ranged from 8 to 42 months, and one study reported significantly lower loco-regional recurrence over a 2-years follow-up period (10.5% vs 25.7%). Mohs technique did not cause a statistically significant increase in operating time. Applicability of MMS is limited by operator comfort with surgical technique and pathological interpretation of specimens in the oral cavity. The main limitation was that various studies did not report specific patient characteristics. In conclusion, MMS may be an effective treatment for OCC, especially for squamous cell carcinomas, and tumors involving the tongue.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Cirurgia de Mohs , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Revisões Sistemáticas como AssuntoRESUMO
Atrophic acne scars are the most common type of acne scars and are classified into three main types: icepick, boxcar, and rolling scars. Various procedures and techniques for atrophic acne scarring are discussed in detail, with stronger evidence-based support for lasers (non-fractional, fractional, ablative, and non-ablative), platelet-rich plasma as adjunctive treatment, chemical peels (glycolic acid, trichloroacetic acid, and Jessner's solution), dermal fillers such as hyaluronic acid, and microneedling, and lesser quality evidence for microdermabrasion, subcision, and lipoaspirate grafting. Further research is needed to optimize treatment protocols, assess the efficacy of monotherapies, and establish standardized guidelines for clinicians. This paper will provide a comprehensive review of the evidence-based management of atrophic acne scars, including currently commonly utilized therapies as well as more innovative treatment options.
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Acne Vulgar , Abrasão Química , Dermatologia , Humanos , Cicatriz/etiologia , Cicatriz/terapia , Cicatriz/patologia , Acne Vulgar/complicações , Acne Vulgar/terapia , Abrasão Química/métodos , Terapia Combinada , Atrofia/terapia , Resultado do TratamentoRESUMO
Hidradenitis suppurativa (HS), is a chronic inflammatory skin disorder that confers a substantial financial burden to patients. The aim of the current study was to assess the patient-reported financial impact of HS. Patients presenting to a wound center between 2010 and 2021 were retrospectively reviewed. Demographics, comorbidities, and disease characteristics were collected. The financial impact of HS was assessed via the Comprehensive Score for Financial Toxicity - Functional Assessment of Chronic Illness Therapy (COST-FACIT) version 2 and investigator-generated surveys. Of 199 patients contacted, 27.1% (n = 54) completed the survey. The majority were women (77.8%, n = 42) and had private health insurance (n = 30; 55.6%). Most patients (66.7%, n = 36) had Hurley stage III disease. Mean follow-up was 2.3 + 2.8 years. The overall COST score was 19.7 + 12.4, indicating grade 1 financial toxicity (FT). Grade 0 FT was reported in 31.5% (n = 17) of patients, grade 1 in 37.0% (n = 20), grade 2 in 27.8% (n = 15), and grade 3 in 3.7% (n = 2). The mean self-reported 12-month out-of-pocket cost and credit scores were $2250 + 3269.24 and 674.6 + 95.3, respectively. Patients with private insurance had lower FT compared with Medicaid and Medicare (p = 0.003). Higher out-of-pocket costs were positively correlated with FT (p = 0.042), while higher credit scores were negatively correlated (p = 0.003). Patients with HS lesions in three or more anatomic regions reported the highest FT (p = 0.031). HS is a debilitating skin disorder that affects the livelihood of patients in a multifaceted manner. These patient-reported outcomes highlight the impact that HS has on an individual's financial security, calling for further attention to this vulnerable population.
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Hidradenite Supurativa , Humanos , Masculino , Feminino , Idoso , Estados Unidos , Hidradenite Supurativa/terapia , Hidradenite Supurativa/epidemiologia , Estudos Retrospectivos , Estresse Financeiro , Medicare , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production. METHODS: Co-culture, syngeneic, and humanize mice models were utilized. C57BL/6 mice were inoculated with either Lewis lung carcinoma mouse cells (LLC) or their platinum-resistant counterpart (LLC-CR) cells. Humanized mice were inoculated with either A (human CS cells) or ALC (human CR cells). Mice were treated with either IDO1 inhibitor or TDO2 (tryptophan 2,3-dioxygenase-2) inhibitor at 200 mg/kg P.O. once a day for 15 days; or with a new-in-class, IDO1/TDO2 dual inhibitor AT-0174 at 170 mg/kg P.O. once a day for 15 days with and without anti-PD1 antibody (10 mg/kg, every 3 days). Immune profiles and KYN and tryptophan (TRP) production were evaluated. RESULTS: CR tumors exhibited a more highly immunosuppressive environment that debilitated robust anti-tumor immune responses. IDO1-mediated KYN production from CR cells suppressed NKG2D on immune effector natural killer (NK) and CD8+ T cells and enhanced immunosuppressive populations of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Importantly, while selective IDO1 inhibition attenuated CR tumor growth, it concomitantly upregulated the TDO2 enzyme. To overcome the compensatory induction of TDO2 activity, we employed the IDO1/TDO2 dual inhibitor, AT-0174. Dual inhibition of IDO1/TDO2 in CR mice suppressed tumor growth to a greater degree than IDO1 inhibition alone. Significant enhancement in NKG2D frequency on NK and CD8+ T cells and a reduction in Tregs and MDSCs were observed following AT-1074 treatment. PD-L1 (programmed death-ligand-1) expression was increased in CR cells; therefore, we assessed dual inhibition + PD1 (programmed cell death protein-1) blocking and report profound anti-tumor growth and improved immunity in CR tumors which in turn extended overall survival in mice. CONCLUSION: Our study reports the presence of platinum-resistant lung tumors that utilize both IDO1/TDO2 enzymes for survival, and to escape immune surveillance as a consequence of KYN metabolites. We also report early in vivo data in support of the potential therapeutic efficacy of the dual IDO1/TDO2 inhibitor AT-0174 as a part of immuno-therapeutic treatment that disrupts tumor metabolism and enhances anti-tumor immunity.
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Invariant NKT (iNKT) cells are a small subset of thymus-generated T cells that produce cytokines to control both innate and adaptive immunity. Because of their very low frequency in the thymus, in-depth characterization of iNKT cells can be facilitated by their enrichment from total thymocytes. Magnetic-activated cell sorting (MACS) of glycolipid antigen-loaded CD1d-tetramer-binding cells is a commonly used method to enrich iNKT cells. Surprisingly, we found that this procedure also dramatically altered the subset composition of enriched iNKT cells. As such, NKT2 lineage cells that express large amounts of the transcription factor promyelocytic leukemia zinc finger were markedly over-represented, while NKT1 lineage cells expressing the transcription factor T-bet were significantly reduced. To overcome this limitation, here, we tested magnetic-activated depletion of CD24+ immature thymocytes as an alternative method to enrich iNKT cells. We found that the overall recovery in iNKT cell numbers did not differ between these 2 methods. However, enrichment by CD24+ cell depletion preserved the subset composition of iNKT cells in the thymus, and thus permitted accurate and reproducible analysis of thymic iNKT cells in further detail.
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BACKGROUND: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. METHODS: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40-41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. RESULTS: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. CONCLUSIONS: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors.