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1.
Cell ; 138(1): 51-62, 2009 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-19576624

RESUMO

Metastasis from lung adenocarcinoma can occur swiftly to multiple organs within months of diagnosis. The mechanisms that confer this rapid metastatic capacity to lung tumors are unknown. Activation of the canonical WNT/TCF pathway is identified here as a determinant of metastasis to brain and bone during lung adenocarcinoma progression. Gene expression signatures denoting WNT/TCF activation are associated with relapse to multiple organs in primary lung adenocarcinoma. Metastatic subpopulations isolated from independent lymph node-derived lung adenocarcinoma cell lines harbor a hyperactive WNT/TCF pathway. Reduction of TCF activity in these cells attenuates their ability to form brain and bone metastases in mice, independently of effects on tumor growth in the lungs. The WNT/TCF target genes HOXB9 and LEF1 are identified as mediators of chemotactic invasion and colony outgrowth. Thus, a distinct WNT/TCF signaling program through LEF1 and HOXB9 enhances the competence of lung adenocarcinoma cells to colonize the bones and the brain. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Metástase Neoplásica , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Transplante de Neoplasias , Fatores de Transcrição TCF/metabolismo , Transplante Heterólogo , Proteínas Wnt/metabolismo
2.
J Natl Compr Canc Netw ; 20(13)2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991065

RESUMO

The NCCN Best Practices Committee, which is composed of senior physician, nursing, and administrative leaders from NCCN Member Institutions, evaluated the status of cancer center operations after 1 year of operating during the COVID-19 pandemic. Two major initiatives stood out: the increase in the utilization of network sites, and the gains made in telemedicine operations and reimbursement. Experts from NCCN Member Institutions participated in a webinar series in June 2021 to share their experiences, knowledge, and thoughts on these topics and discuss the impact on the future of cancer care.


Assuntos
COVID-19 , Neoplasias , Médicos , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Neoplasias/epidemiologia , Neoplasias/terapia
3.
J Natl Compr Canc Netw ; 20(10): 1099-1106.e2, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36240846

RESUMO

BACKGROUND: Oral chemotherapy performance measures were first introduced into ASCO's Quality Oncology Practice Initiative (QOPI) in 2013. This study examined performance on these measures among QOPI-participating practices and evaluated whether it differed among practices based on meeting QOPI Certification Program standards. METHODS: A total of 192 QOPI-participating practices (certified, n=50 [26%]; not certified, n=142 [74%]) reported performance on oral chemotherapy measures in 2017 and 2018. Inclusion was limited to practices reporting on ≥3 charts for ≥1 oral chemotherapy measure. Performance was defined as the percentage of charts examined that adhered to the measure. Descriptive analyses were used to characterize performance within and across practices, and mixed-effects logistic regression models were conducted to compare performance based on certification status. RESULTS: Median performance across practices for the 9 oral chemotherapy measures examined ranged from 44% (education before the start of treatment addressing missed doses, toxicities, and clinical contact instructions [composite measure]) to 100% (documented dose, documented plan, and education about toxicities). Certified practices were more likely to provide education about clinic contact instructions than noncertified practices (odds ratio, 4.87; 95% CI, 1.00-24.0). Performance on all other measures was not significantly associated with certification status. CONCLUSIONS: There is wide variability in quality related to performance on oral chemotherapy measures across all QOPI-participating practices, and several areas were identified in which administration of oral chemotherapy could be improved. Our findings highlight the need for the development and implementation of appropriate standards that apply to oral chemotherapy and address the complexities that set it apart from parenteral treatment.


Assuntos
Certificação , Oncologia , Administração Oral , Humanos
4.
J Natl Compr Canc Netw ; 19(12): 1441-1464, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34902832

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The "Summary of the Guidelines Updates" section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Oncologia , Recidiva Local de Neoplasia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia
5.
Lancet Oncol ; 21(5): 655-663, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32251621

RESUMO

BACKGROUND: We did a phase 2 trial of pembrolizumab in patients with non-small-cell lung cancer (NSCLC) or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort. METHODS: This was an open-label, phase 2 study of patients from the Yale Cancer Center (CT, USA). Eligible patients were at least 18 years of age with stage IV NSCLC with at least one brain metastasis 5-20 mm in size, not previously treated or progressing after previous radiotherapy, no neurological symptoms or corticosteroid requirement, and Eastern Cooperative Oncology Group performance status less than two. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was used to evaluate CNS disease; systemic disease was not required for participation. Patients were treated with pembrolizumab 10 mg/kg intravenously every 2 weeks. Patients were in two cohorts: cohort 1 was for those with PD-L1 expression of at least 1% and cohort 2 was patients with PD-L1 less than 1% or unevaluable. The primary endpoint was the proportion of patients achieving a brain metastasis response (partial response or complete response, according to mRECIST). All treated patients were analysed for response and safety endpoints. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT02085070. FINDINGS: Between March 31, 2014, and May 21, 2018, 42 patients were treated. Median follow-up was 8·3 months (IQR 4·5-26·2). 11 (29·7% [95% CI 15·9-47·0]) of 37 patients in cohort 1 had a brain metastasis response. There were no responses in cohort 2. Grade 3-4 adverse events related to treatment included two patients with pneumonitis, and one each with constitutional symptoms, colitis, adrenal insufficiency, hyperglycaemia, and hypokalaemia. Treatment-related serious adverse events occurred in six (14%) of 42 patients and were pneumonitis (n=2), acute kidney injury, colitis, hypokalaemia, and adrenal insufficiency (n=1 each). There were no treatment-related deaths. INTERPRETATION: Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression at least 1% and is safe in selected patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted. FUNDING: Merck and the Yale Cancer Center.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno B7-H1/genética , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
6.
BMC Cancer ; 20(1): 356, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345265

RESUMO

BACKGROUND: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first-/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. METHODS: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first-/second-generation EGFR-TKI were described. RESULTS: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. CONCLUSIONS: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Tomada de Decisões , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Radiology ; 289(3): 862-870, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30226453

RESUMO

Purpose To compare survival rates of thermal ablation and stereotactic radiation therapy (SRT) for stage 1 non-small cell lung cancer (NSCLC). Materials and Methods In this retrospective study, patients with stage 1 NSCLC treated by thermal ablation (TA) or SRT were identified in the 2004-2013 National Cancer Database. Patients who underwent TA and SRT were one-to-one propensity matched to undergo thermal ablation. Outcomes were overall survival and unplanned hospital readmission within 30 days after treatment. Results This study included 28 834 patients (TA, 1102 patients; SRT, 27 732 patients). Patients treated with TA had more comorbidities (Charlson comorbidity index of 1 vs ≥2, 32.8% [362 of 1102] vs 19.7% [217 of 1102], respectively) compared with SRT (Charlson comorbidity index of 1 vs ≥2, 26.9% [7448 of 27 732] vs 15.3% [4251 of 27 732], respectively; P , .001) and smaller tumor size (mean tumor size, TA vs SRT: 19 mm vs 22 mm, respectively; P , .001). In the propensity score-matched cohort with balanced distribution of potential confounders, there was no significant difference in overall survival between TA and SRT at a mean follow-up of 52.4 months (survival difference, P = .69). Overall survival rates were comparable between TA and SRT (1 year, 85.4% vs 86.3%, respectively, P = .76; 2 years, 65.2% vs 64.5%, respectively, P = .43; 3 years, 47.8% vs 45.9%, respectively, P = .32; 5 years, 24.6% vs 26.1%, respectively, P = .81). Unplanned hospital readmission rates were higher for patients who underwent TA versus those who underwent SRT (3.7% [40 of 1070] vs 0.2% [two of 1070], respectively; P , .001). Conclusion Regarding overall survival, thermal ablation was noninferior to stereotactic radiation therapy for primary treatment of stage 1 non-small cell lung cancer. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Shyn in this issue.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Ablação por Cateter/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Pulmão/efeitos da radiação , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
8.
JAMA ; 320(5): 469-477, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30088010

RESUMO

Importance: Broad-based genomic sequencing is being used more frequently for patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the association between broad-based genomic sequencing and treatment selection or survival among patients with advanced NSCLC in a community oncology setting. Objective: To compare clinical outcomes between patients with advanced NSCLC who received broad-based genomic sequencing vs a control group of patients who received routine testing for EGFR mutations and/or ALK rearrangements alone. Design, Setting, and Participants: Retrospective cohort study of patients with chart-confirmed advanced NSCLC between January 1, 2011, and July 31, 2016, and who received care at 1 of 191 oncology practices across the United States using the Flatiron Health Database. Patients were diagnosed with stage IIIB/IV or unresectable nonsquamous NSCLC who received at least 1 line of antineoplastic treatment. Exposures: Receipt of either broad-based genomic sequencing or routine testing (EGFR and/or ALK only). Broad-based genomic sequencing included any multigene panel sequencing assay examining more than 30 genes prior to third-line treatment. Main Outcomes and Measures: Primary outcomes were 12-month mortality and overall survival from the start of first-line treatment. Secondary outcomes included frequency of genetic alterations and treatments received. Results: Among 5688 individuals with advanced NSCLC (median age, 67 years [interquartile range, 41-85], 63.6% white, 80% with a history of smoking); 875 (15.4%) received broad-based genomic sequencing and 4813 (84.6%) received routine testing. Among patients who received broad-based genomic sequencing, 4.5% received targeted treatment based on testing results, 9.8% received routine EGFR/ALK targeted treatment, and 85.1% received no targeted treatment. Unadjusted mortality rates at 12 months were 49.2% for patients undergoing broad-based genomic sequencing and 35.9% for patients undergoing routine testing. Using an instrumental variable analysis, there was no significant association between broad-based genomic sequencing and 12-month mortality (predicted probability of death at 12 months, 41.1% for broad-based genomic sequencing vs 44.4% for routine testing; difference -3.6% [95% CI, -18.4% to 11.1%]; P = .63). The results were consistent in the propensity score-matched survival analysis (42.0% vs 45.1%; hazard ratio, 0.92 [95% CI, 0.73 to 1.11]; P = .40) vs unmatched cohort (hazard ratio, 0.69 [95% CI, 0.62 to 0.77]; log-rank P < .001). Conclusions and Relevance: Among patients with advanced non-small cell lung cancer receiving care in the community oncology setting, broad-based genomic sequencing directly informed treatment in a minority of patients and was not independently associated with better survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , DNA de Neoplasias/análise , Feminino , Genes erbB-1 , Genômica , Genótipo , Humanos , Imunoterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Receptores Proteína Tirosina Quinases/genética , Estudos Retrospectivos , Análise de Sequência de DNA , Análise de Sobrevida
9.
Lancet Oncol ; 17(7): 976-983, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27267608

RESUMO

BACKGROUND: Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC). METHODS: In this non-randomised, open-label, phase 2 trial, we enrolled patients aged 18 years or older with melanoma or NSCLC with untreated brain metastases from the Yale Cancer Center. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in diameter without associated neurological symptoms or the need for corticosteroids. Patients with NSCLC had tumour tissue positive for PD-L1 expression; this was not required for patients with melanoma. Patients were given 10 mg/kg pembrolizumab every 2 weeks until progression. The primary endpoint was brain metastasis response assessed in all treated patients. The trial is ongoing and here we present an early analysis. The study is registered with ClinicalTrials.gov, number NCT02085070. FINDINGS: Between March 31, 2014, and May 31, 2015, we screened 52 patients with untreated or progressive brain metastases (18 with melanoma, 34 with NSCLC), and enrolled 36 (18 with melanoma, 18 with NSCLC). A brain metastasis response was achieved in four (22%; 95% CI 7-48) of 18 patients with melanoma and six (33%; 14-59) of 18 patients with NSCLC. Responses were durable, with all but one patient with NSCLC who responded showing an ongoing response at the time of data analysis on June 30, 2015. Treatment-related serious and grade 3-4 adverse events were grade 3 elevated aminotransferases (n=1 [6%]) in the melanoma cohort, and grade 3 colitis (n=1 [6%]), grade 3 pneumonitis (n=1 [6%]), grade 3 fatigue (n=1 [6%]), grade 4 hyperkalemia (n=1 [6%]), and grade 2 acute kidney injury (n=1 [6%]) in the NSCLC cohort. Clinically significant neurological adverse events included transient grade 3 cognitive dysfunction and grade 1-2 seizures (n=3 [17%]) in the melanoma cohort. INTERPRETATION: Pembrolizumab shows activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, which suggests that there might be a role for systemic immunotherapy in patients with untreated or progressive brain metastases. FUNDING: Merck and the Yale Cancer Center.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Neoplasias Encefálicas/secundário , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
10.
Prev Chronic Dis ; 12: E197, 2015 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-26564013

RESUMO

INTRODUCTION: Finding ways to provide better and less expensive health care for people with multiple chronic conditions or disability is a pressing concern. The purpose of this systematic review was to evaluate different approaches for caring for this high-need and high-cost population. METHODS: We searched Medline for articles published from May 31, 2008, through June 10, 2014, for relevant studies. Articles were considered eligible for this review if they met the following criteria: included people with multiple chronic conditions (behavioral or mental health) or disabilities (2 or more); addressed 1 or more of clinical outcomes, health care use and spending, or patient satisfaction; and compared results from an intervention group with a comparison group or baseline measurements. We extracted information on program characteristics, participant characteristics, and significant (positive and negative) clinical findings, patient satisfaction, and health care use outcomes. For each outcome, the number of significant and positive results was tabulated. RESULTS: Twenty-seven studies were included across 5 models of care. Of the 3 studies reporting patient satisfaction outcomes, 2 reported significant improvements; both were randomized controlled trials (RCTs). Of the 14 studies reporting clinical outcomes, 12 reported improvements (8 were RCTs). Of the 13 studies reporting health care use and spending outcomes, 12 reported significant improvements (2 were RCTs). Two models of care - care and case management and disease management - reported improvements in all 3 outcomes. For care and case management models, most improvements were related to health care use. For the disease management models, most improvements were related to clinical outcomes. CONCLUSIONS: Care and case management as well as disease management may be promising models of care for people with multiple chronic conditions or disabilities. More research and consistent methods are needed to understand the most appropriate care for these high-need and high-cost patients.


Assuntos
Doença Crônica/economia , Pessoas com Deficiência , Custos de Cuidados de Saúde/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde , Administração de Caso , Gerenciamento Clínico , Humanos , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Autocuidado , Estados Unidos
11.
Am Soc Clin Oncol Educ Book ; 44(3): e432520, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830134

RESUMO

Small cell lung cancer (SCLC) is an uncommon, aggressive high-grade neuroendocrine carcinoma, associated with tobacco use. It is a highly chemosensitive disease that initially responds quickly to systemic therapy, although patients with SCLC tend to develop relapse. Although the landscape of SCLC treatment has remained stagnant for many decades, the field has seen notable advances in the past few years, including the use of immunotherapy, the development of further lines of systemic therapy, the refinement of thoracic and intracranial radiotherapy, and-most recently-the promise of more targeted therapies. Patients with SCLC also must face unique psychosocial burdens in their experience with their cancer, distinct from patients with other lung cancer. In this article, we review the latest literature and future directions in the management and investigation of SCLC, as well as the critical decisions that providers and patients must navigate in the current landscape. We also present the perspectives of several patients with SCLC in conjunction with this summary, to spotlight their individual journeys in the context of this challenging disease.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Gerenciamento Clínico , Terapia Combinada , Tomada de Decisão Clínica
12.
Adv Radiat Oncol ; 9(4): 101413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38778819

RESUMO

Purpose: The landmark randomized trial on chest irradiation in extensive disease small cell lung cancer (CREST) demonstrated that consolidative thoracic radiation therapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer, with potentially increased benefit in women compared with men. It is unknown whether similar findings would apply after chemoimmunotherapy became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. Methods and Materials: We included patients from de-identified electronic health record-derived database diagnosed with stage IV small cell lung cancer (2014-2021) who completed 4 to 6 cycles of first-line systemic therapy (platinum-doublet chemotherapy or chemoimmunotherapy). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. Results: A total of 1227 patients were included (850 chemotherapy, 377 chemoimmunotherapy). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio [HR], 0.67; 95% CI, 0.52-0.87) and PFS (HR, 0.63; 95% CI, 0.49-0.82) compared with those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men (OS HR, 1.03; 95% CI, 0.80-1.31; PFS HR, 1.12; 95% CI, 0.85-1.47). Findings were similar in weighted analyses. Conclusions: The survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. Although the underpinnings of this association need to be elucidated, stratification by sex should be considered for randomized-controlled trials studying cTRT in extensive-stage small cell lung cancer.

13.
Nature ; 446(7137): 765-70, 2007 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-17429393

RESUMO

Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/secundário , Neovascularização Patológica , Animais , Neoplasias da Mama/irrigação sanguínea , Capilares/crescimento & desenvolvimento , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Epirregulina , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Camundongos
14.
Hematol Oncol Clin North Am ; 37(3): 595-607, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024387

RESUMO

Small cell lung cancer (SCLC) is a rare yet aggressive lung cancer subtype with an extremely poor prognosis of around 1 year. SCLC accounts for 15% of all newly diagnosed lung cancers and is characterized by rapid growth with high potential for metastatic spread and treatment resistance. In the article the authors review some of the most notable efforts to improve outcomes, including trials of novel immunotherapy agents, novel disease targets, and multiple drug combinations.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Imunoterapia , Neoplasias Pulmonares/terapia , Fatores Imunológicos/uso terapêutico , Prognóstico
15.
JCO Oncol Pract ; 19(4): e520-e526, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36669136

RESUMO

PURPOSE: Despite the growing calls for early and ubiquitous completion of advance directives (ADs), studies exploring links between AD completion and their impact on outcomes of patients with cancer have mixed conclusions. We used the ASCO Quality Oncology Practice Initiative (QOPI) registry to compare end-of-life (EOL) quality measures and the effect of QOPI certification among patients with and without early AD completion, defined as completion within the first three oncology visits after cancer diagnosis. METHODS: Deidentified patient-level data were analyzed from the QOPI database from 2015 through 2017. Associations were assessed using Chi-square tests between early AD completion and patient enrollment in hospice < 7 days before death, chemotherapy receipt in the last 14 days of life, or with emergency room visits or intensive care unit admissions in the last 30 days of life. RESULTS: Data from 31,558 patients eligible for the AD question were analyzed. Patients treated at QOPI-certified practices had higher rates of early AD completion than patients at non-certified practices. Early AD completion was not associated with differences in hospice enrollment for < 7 days before death, chemotherapy receipt in the last 14 days of life, or emergency room visits or intensive care unit encounters in the last 30 days of life. CONCLUSION: The study found that QOPI certification is associated with higher rates of early AD completion. However, early AD completion was not associated with recognized EOL quality measures. Future research should focus on the timing, frequency, and content of AD conversations to demonstrate the impact on care at the EOL.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Humanos , Oncologia , Diretivas Antecipadas , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Qualidade de Vida
16.
JCO Oncol Pract ; 18(8): e1367-e1373, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35353546

RESUMO

PURPOSE: For patients with nonmetastatic rectal cancer, the National Comprehensive Cancer Network guidelines recommend initial staging using pelvic magnetic resonance imaging or endorectal ultrasound to determine the stage of the disease before initial therapy or surgery. This imaging workup helps determine the T and N staging, which is essential to determine optimal treatment for a patient. The current study examined practice concordance with this guideline using a quality measure in ASCO's Quality Oncology Practice Initiative (QOPI) that specifically addressed staging workup for patients with rectal cancer. METHODS: From Fall 2016 through Fall 2019, 103 QOPI-participating practices reported performance on QOPI measure Colorectal 78, which addresses staging workup for patients with rectal cancer. The percentage and 95% CI of patients who received guideline-concordant imaging were calculated for each of the seven assessment time points. Difference of concordance rates between subsequent time points and the initial time point was assessed using logistic regression with random-effects models. In addition, 69 practices that submitted data in 2016 and 2017 were surveyed to gain insight on potential reasons for nonconcordance and the results were described. RESULTS: At each time point, a total of 20-33 practices reported data across 1,158 unique patients. Adherence appeared to increase over time, with 38% of patients receiving guideline-recommended staging in Fall 2016, to 56% in Fall 2019. The practice survey revealed that nonconcordance was mostly because of lack of care coordination between oncology and surgery disciplines (n = 16 practices of 28, 57.1%) and a lack of awareness of appropriate staging scans (n = 8 practices, 28.6%). CONCLUSION: As one half to one third of patients still do not receive appropriate imaging, our findings highlight the need for concerted quality improvement efforts that involve the multidisciplinary team to close this gap.


Assuntos
Oncologia , Neoplasias Retais , Humanos , Melhoria de Qualidade , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia
17.
JCO Oncol Pract ; 18(7): e1209-e1218, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35467961

RESUMO

PURPOSE: In the first decade of this millennium, ASCO pioneered a quality measurement tool, the Quality Oncology Practice Initiative (QOPI). Despite an Accreditation Council for Graduate Medical Education (ACGME) requirement since 2012 for oncology fellows to participate in quality improvement (QI) projects, the uptake of QOPI remains modest. METHODS: This study examined reasons for low QOPI participation by surveying participating and nonparticipating HemOnc Fellowship Programs. The survey elicited views toward QI and QOPI as well as ideas about making the program more helpful. RESULTS: Among 69 fellowship programs, only 39% (n = 27) participated in QOPI. Other findings were that (1) the majority of programs considered their fellows' QI projects beneficial but were not fulfilling the ACGME standard for all fellows' QI participation; (2) nonparticipating programs were unfamiliar with but interested in QOPI; (3) participating programs tended to view QI as easier to conduct and more beneficial than nonparticipating programs; and (4) programs that withdrew from QOPI and participating programs alike were dissatisfied with the educational benefit and data abstraction burden for fellows. CONCLUSION: Academic oncology programs generally valued QI but many have not fully engaged in it. Fellows in programs participating in QOPI may have had less difficulty conducting QI and their projects may have been more beneficial than that of nonparticipating programs. However, perceived lack of educational benefits for fellows and the burden of manual data abstraction from the electronic medical record are impediments to satisfaction with the program. Higher faculty involvement and longitudinal reports for each fellow may significantly increase participation.


Assuntos
Bolsas de Estudo , Hematologia , Acreditação , Educação de Pós-Graduação em Medicina , Hematologia/educação , Humanos , Oncologia
18.
JCO Oncol Pract ; 18(8): e1350-e1356, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35363501

RESUMO

PURPOSE: Medical oncologists have a variety of options for demonstrating proficiency in providing high-quality patient care. Perhaps, the best-known opportunity for demonstrating individual expertise and lifelong learning is the American Board of Internal Medicine (ABIM) maintenance of certification (MOC) program. At the practice level, ASCO has offered the Quality Oncology Practice Initiative (QOPI) as a means of optimizing cancer care delivery. In this study, we assess the association between active involvement in MOC on an individual basis and whether that individual's practice is involved with the QOPI program. METHODS: We evaluated 13,600 US medical oncologists initially certified by the ABIM and divided them into those initially certified before 1990 (the year in which ABIM started to require periodic recertification), those from 1990 to 2007, and those from 2008 to 2016. It was then determined which of these had let their certificates expire by 2020. These data were then compared with practices that participated in QOPI from 2017 to 2019, resulting in the matching of 97% of physicians. RESULTS: Of individuals initially certified before 1990 (and technically with lifelong certification), 22% were in QOPI practices. Among those who did not have lifelong certification, there was an association between QOPI participation and maintenance of ABIM certification. For those initially certified between 1990 and 2007, 35% of oncologists with up-to-date ABIM certification were in QOPI practices, whereas only 11% with expired ABIM certification were QOPI participants (P < .0001). For those in the 2008-2016 category, the numbers were 36% v 16%, respectively (P < .0001). CONCLUSION: Our analysis identifies a relationship between participation in these ABIM and ASCO proficiency programs. The reasons for this are likely complex and based on a variety of institutional, professional, monetary, and personal factors.


Assuntos
Certificação , Médicos , Humanos , Oncologia , Qualidade da Assistência à Saúde , Estados Unidos
19.
Cancer J ; 26(6): 502-506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33298721

RESUMO

Immunotherapy has improved first-line therapy for small cell lung cancer and has activity in the relapsed setting as well. The immunobiology of small cell lung cancer poses challenges for immunotherapy, and efforts are underway to unlock to the potential of immunotherapy through the identification of meaningful disease subsets and the development of novel combination therapies.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Terapia Combinada , Humanos , Sistema Imunitário , Imunoterapia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia
20.
JCO Oncol Pract ; 16(2_suppl): 4s-9s, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32045539

RESUMO

Immunotherapy with programmed cell death-1 (PD-1) receptor and programmed death ligand 1 (PD-L1) inhibitors has improved outcomes for certain patients with advanced lung cancer. As use of these therapies has expanded in first-line settings, in patients with different histologies, and in combinations with chemotherapeutic and targeted agents, more patients with lung cancer may benefit from these therapies. However, with expanded use comes greater potential exposure to the immune-related adverse events (irAEs) associated with these immune checkpoint inhibitors (ICIs). This article uses two case examples to illustrate the presentation, evaluation, and management of pulmonary and neurologic symptoms in two patients receiving PD-1-based therapy for non-small-cell lung cancer. These cases illustrate the challenges associated with recognizing pneumonitis and neuropathy in patients receiving ICIs for lung cancer. Although pneumonitis and neuropathy are relatively rare irAEs, they can have devastating or even fatal outcomes if not promptly recognized and managed appropriately. Specific use of guideline-based, multidisciplinary management is emphasized, as illustrated in the Immuno-Oncology Essentials Care Step Pathways.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/induzido quimicamente , Receptor de Morte Celular Programada 1
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