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PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Feminino , Idoso , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Fragilidade , Idoso de 80 Anos ou maisRESUMO
The Veterans Health Administration (VHA) has pioneered teleoncology to address access challenges faced by Veterans requiring cancer care. This ASCO Educational Book highlights the development of teleoncology programs within the VHA: the local VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Center, the National TeleOncology Program (NTO), and the regional Clinical Resource Hub (CRH) Oncology Program. These initiatives provide oncology care using a hub-and-spoke model, which centralizes expertise at hub sites and reaches Veterans at distant spoke sites through synchronous and asynchronous care. The deployment of these teleoncology programs has resulted in significant benefits, such as decreased travel for Veterans, high levels of patient satisfaction, and improved access to specialized treatments. Despite these advancements, disparities in teleoncology utilization and access to clinical trials persist. This educational manuscript highlights the successes and challenges of tele-oncology within the VHA, underscoring the critical role of telehealth in overcoming access barriers.
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Oncologia , Telemedicina , United States Department of Veterans Affairs , Veteranos , Humanos , Estados Unidos , Oncologia/métodos , Saúde dos Veteranos , Neoplasias/terapia , Acessibilidade aos Serviços de SaúdeRESUMO
PURPOSE: Identification and documentation of Veterans' symptoms are crucial for optimal lung cancer care delivery. The objective of this study was to determine whether a volunteer-led proactive telephone symptom assessment intervention could improve comprehensive symptom documentation. METHODS: Veterans with lung cancer were randomly assigned to usual care (control group) or usual care with proactive symptom assessment in which a peer volunteer made weekly phone calls to assess patient symptoms under nurse practitioner supervision. The primary outcome was oncologist documentation of symptoms in the electronic health record at all clinical visits within 6 months after enrollment. Secondary outcomes included patient satisfaction with decision, patient activation, health-related quality of life (HRQOL), and symptom burden, measured at baseline, and 3, 6, and 9 months after enrollment, and acute care use within 9 months after enrollment. RESULTS: Among 60 Veterans randomly assigned, median (range) age was 70.2 (50-86) years; 57 (95.0%) were male. More intervention participants had oncologist documentation of symptoms than control group participants (24 [77.4%] v seven [24.1%], respectively; odds ratio, 16.46 [95% CI, 4.58 to 59.16]). Intervention group participants had greater improvements over time in HRQOL (expected mean difference, 25.3 [95% CI, 15.00 to 35.70]) and patient activation (expected mean difference, 13.6 [95% CI, 3.79 to 23.39]), lower symptom burden (expected mean difference, -6.39 [95% CI, -15.21 to -2.46]), lower rates of emergency room visits (incidence rate ratio, 0.48 [95% CI, 0.30 to 0.75]), and hospitalizations (incidence rate ratio, 0.47 [95% CI, 0.28 to 0.77]) than control group participants. CONCLUSION: This symptom assessment intervention is an effective strategy for Veterans with lung cancer.
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Neoplasias Pulmonares , Veteranos , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Qualidade de Vida , Avaliação de Sintomas , Medidas de Resultados Relatados pelo Paciente , Documentação , Participação do PacienteRESUMO
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of UCHL1 inhibitors with cisplatin, the standard of care used for neuroendocrine carcinomas, significantly delays tumor growth in pre-clinical settings. Our study reveals mechanisms of UCHL1 function in regulating the progression of neuroendocrine carcinomas and identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosing and monitoring treatment responses in these malignancies.
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Carcinoma Neuroendócrino , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Glicoproteínas de MembranaRESUMO
INTRODUCTION: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). METHODS: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint. CONCLUSION: PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Adolescente , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Teorema de Bayes , Quimiorradioterapia/métodos , Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase I como AssuntoRESUMO
PURPOSE/OBJECTIVES: Adoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection. MATERIALS/METHODS: We evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.2 Gy per fraction) or standard fractionated radiation therapy (SFRT; 2-2.2 Gy fractions). Dosimetric parameters to key organs at risk were compared, and toxicity, patterns of recurrence and survival were calculated for the cohorts. RESULTS: Fifty-three patients treated with HART were compared with 100 patients treated with SFRT. Median dose per fraction for the HART cohort was 2.75 Gy (range 2.4-3 Gy). HART patients had significantly lower doses to the lung, heart, and esophagus due to patient selection. The HART group and had rates of grade 2+ pneumonitis (9.4 vs. 19%, P = .16) and grade 2+ esophagitis (20.8 vs. 45%, P < .01) that compared favorably to SFRT. Cumulative incidence of in-field recurrence trended lower in the HART cohort (7.6% vs. 23.1%, P = .058). Among the HART group, 88.7% (47/53) met the newly proposed lung constraints based on the degree of hypofractionation CONCLUSION: In select patients with favorable dosimetry to organs at risk, definitive HART with concurrent chemotherapy achieved excellent local control with low toxicity. These results are being used to inform a prospective study on the safety and efficacy of HART with concurrent chemotherapy for select NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Estudos Prospectivos , Seleção de PacientesRESUMO
Brain metastases represent an important clinical problem for patients with small-cell lung cancer (SCLC). However, the mechanisms underlying SCLC growth in the brain remain poorly understood. Here, using intracranial injections in mice and assembloids between SCLC aggregates and human cortical organoids in culture, we found that SCLC cells recruit reactive astrocytes to the tumour microenvironment. This crosstalk between SCLC cells and astrocytes drives the induction of gene expression programmes that are similar to those found during early brain development in neurons and astrocytes. Mechanistically, the brain development factor Reelin, secreted by SCLC cells, recruits astrocytes to brain metastases. These astrocytes in turn promote SCLC growth by secreting neuronal pro-survival factors such as SERPINE1. Thus, SCLC brain metastases grow by co-opting mechanisms involved in reciprocal neuron-astrocyte interactions during brain development. Targeting such developmental programmes activated in this cancer ecosystem may help prevent and treat brain metastases.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Astrócitos/patologia , Neoplasias Pulmonares/metabolismo , Ecossistema , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Microambiente TumoralRESUMO
PURPOSE: To provide evidence-based recommendations to practicing clinicians on the management of patients with small-cell lung cancer. METHODS: An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2022. Outcomes of interest included response rates, overall survival, disease-free survival or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 95 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations were developed to address systemic therapy options, timing of therapy, treatment in patients who are older or with poor performance status, role of biomarkers, and use of myeloid-supporting agents in patients with small-cell lung cancer.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Oncologia/métodos , Ontário , Qualidade de Vida , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
Importance: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. Objective: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. Design, Setting, and Participants: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Intervention: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Main outcome: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. Results: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT01463423.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Masculino , Idoso , Feminino , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Radiocirurgia/efeitos adversos , Radiocirurgia/métodosRESUMO
PURPOSE: Veteran populations have higher lung cancer incidence and worse overall survival compared with non-Veteran populations. Although recent clinical advancements have reduced lung cancer death rates, these advances are not routinely received among Veteran populations because of multilevel factors, including Veterans' complex comorbidities, limited health literacy, and other economic and social disadvantages. This study aimed to assess Veterans' perspectives regarding their lung cancer care with a specific focus on identifying modifiable barriers to evidence-based care delivery. METHODS: We conducted 1:1 semistructured interviews with 24 Veterans diagnosed with lung cancer at the Veterans Affairs Palo Alto Health Care System. All interviews were recorded, transcribed, and analyzed using the constant comparative method of qualitative analysis. RESULTS: Four themes emerged. These included (1) social and economic disadvantages can prevent routine delivery of evidence-based cancer care; (2) fragmented care contributes to worsening patient mental and emotional well-being; (3) lack of health system interventions to address limited health literacy inhibits patient engagement in shared decision making regarding diagnosis, genomic and molecular testing, targeted and other treatments, and end-of-life care; and (4) deep appreciation for care and VA trustworthiness facilitates adherence to cancer care recommendations. CONCLUSION: This study revealed critical gaps in lung cancer care delivery and the role of institution-engendered trust in overcoming barriers in the VA system. Targeted solutions should address the identified barriers to routine, evidence-based lung cancer care delivery among Veterans.
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Neoplasias Pulmonares , Veteranos , Estados Unidos/epidemiologia , Humanos , Veteranos/psicologia , Acessibilidade aos Serviços de Saúde , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , United States Department of Veterans Affairs , Pesquisa QualitativaRESUMO
Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.
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Are we getting closer to the promise of cure? New Progress and Future Directions in the Treatment of Early Stage Non-Small Cell Lung Cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
INTRODUCTION: Severe pulmonary hemorrhage can occur in patients treated with thoracic stereotactic ablative radiotherapy (SABR) and vascular endothelial growth factor inhibitors (VEGFis). There is limited understanding of which patients are at risk for toxicity with the combination of thoracic SABR and VEGFis or how the risk differs over either therapy alone. METHODS: We evaluated a prospectively maintained cohort of 690 patients with 818 pulmonary tumors treated with highly conformal SABR. Rates of any-grade and grade 3 plus (G3+) pulmonary hemorrhage were compared between patients treated with or without VEGFi therapy across tumor locations. Outcomes were compared between patients treated with SABR plus VEGFi and a propensity-matched cohort of those treated with VEGFi therapy alone. RESULTS: Treatment with VEGFi plus SABR was associated with higher rates of G3+ pulmonary hemorrhage compared with those treated with SABR alone for the overall cohort (3-y incidence: 7.9% versus 0.6%, p < 0.01) and those with central tumors (19.1% versus 3.3%, p = 0.04). When further subdivided, there were significantly higher toxicity rates with VEGFi for the ultracentral (9.0% versus 45.0%, p = 0.044), but not central nonabutting tumors (0.0% versus 1.3%, p = 0.69). There was an increased incidence of G3+ hemorrhage in patients treated with VEGFi plus SABR compared with VEGFi alone (9.6% versus 1.3%, p = 0.04). CONCLUSIONS: The combination of VEGFi and SABR was associated with an increased risk of high-grade pulmonary hemorrhage over either therapy alone. Low rates of toxicity were observed when excluding patients with SABR to ultracentral tumors and applying highly conformal SABR techniques.
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Neoplasias Pulmonares , Radiocirurgia , Humanos , Neoplasias Pulmonares/patologia , Inibidores da Angiogênese/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Hemorragia/epidemiologia , Hemorragia/etiologiaRESUMO
Aim: Atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) as adjuvant treatment following resection and platinum-based chemotherapy for stage II-IIIA PD-L1+ NSCLC in IMpower010. Materials & methods: This cost-effectiveness study evaluated atezolizumab versus BSC (US commercial payer perspective) using a Markov model with DFS, locoregional recurrence, first- and second-line metastatic recurrence and death health states, and a lifetime time horizon with 3% annual discounting. Results: Atezolizumab provided 1.045 additional quality-adjusted life-years (QALY) at an incremental cost of $48,956, yielding an incremental cost-effectiveness ratio of $46,859/QALY. Scenario analysis showed similar findings in a Medicare population ($48,512/QALY). Conclusion: At a willingness-to-pay threshold of $150,000/QALY and an incremental cost-effectiveness ratio of $46,859/QALY, atezolizumab is cost-effective versus BSC for adjuvant NSCLC treatment.
Atezolizumab treatment is 'cost-effective' for people in the USA with stage IIIIIA PD-L1+ non-small-cell lung cancer after surgery and chemotherapy. Until recently, people whose doctors told them they have stage IIIIIA non-small-cell lung cancer with PD-L1 expression on ≥1% of tumor cells (known as 'PD-L1+') did not have many treatment options beyond chemotherapy after surgery. Their cancer often returns even after chemotherapy. One treatment called atezolizumab showed good survival results in clinical trials and is approved in the USA for treatment after the lung tumor has been removed in surgery. Understanding how better survival and quality of life is related to the costs of treatment (known as 'costeffectiveness') is important. For example, insurance companies in the USA may use this information to decide what cancer drugs are preferred for insurance coverage. This study found that atezolizumab treatment was 'cost-effective' for people in the USA with stage IIIIIA PD-L1+ non-small-cell lung cancer when it was given after surgery and chemotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/tratamento farmacológico , Análise Custo-Benefício , Antígeno B7-H1 , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures. METHODS: In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis. RESULTS: In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures (P = .04). CONCLUSION: Combining a computer prognosis model with care coaches increased ACP documentation.
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Planejamento Antecipado de Cuidados , Neoplasias , Assistência Terminal , Humanos , Neoplasias/terapia , Comunicação , Aprendizado de MáquinaAssuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologiaRESUMO
PURPOSE: Stereotactic ablative radiation therapy (SABR) results in high rates of primary tumor control for early-stage non-small cell lung cancer (NSCLC). For patients with isolated hilar or mediastinal nodal recurrence (INR) after SABR, the optimal salvage treatment strategy is unclear. The purpose of this study was to determine the rate of INR after SABR for early-stage NSCLC and to describe patterns of care and treatment outcomes after salvage therapy. METHODS AND MATERIALS: This retrospective cohort study included 342 patients with stage T1-3N0M0 NSCLC treated with definitive SABR from 2003 to 2018. We evaluated the incidence of INR and baseline factors between patients who did and did not experience INR. Among patients who experienced INR, we described treatment patterns and outcomes including overall survival (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method. RESULTS: With a median follow-up of 3.3 years, the 3-year INR rate was 10.6% (95% CI, 6.6%-13.4%). Among the 34 patients experiencing INR, the 3-year rates of OS and PFS were 39.3% (24.4%-63.3%) and 26.7% (14.1%-0.3%), respectively. The 34 patients with INR were treated with radiation therapy alone (26.7%), concurrent chemoradiation therapy (43.3%), chemotherapy alone (13.3%), or observation (16.7%). Patients treated with concurrent chemoradiation therapy had the best survival outcomes, with a 3-year OS and PFS of 81.5% (61.1%-100.0%) and 63.9% (40.7%-100.0%), respectively. Of the patients treated with salvage radiation therapy or concurrent chemoradiation therapy, 14.3% experienced grade 3 toxic effects, and no patients had grade ≥4 toxic effects. CONCLUSIONS: In this study, INR occurred in approximately 10% of patients treated with SABR for early-stage NSCLC. The highest rates of OS and PFS among patients with INR were observed in those treated with salvage chemoradiation therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estadiamento de NeoplasiasRESUMO
PURPOSE: Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone. METHODS: We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB. RESULTS: We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB. CONCLUSIONS: Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.
Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Compostos de Anilina/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
PURPOSE: Because of the limitations of current staging systems and evolving definitions, there are limited data on oligometastatic non-small cell lung cancer (NSCLC) epidemiology. The purpose of this study was to evaluate metastatic disease burden and the incidence of oligometastatic disease using recent clinical trial eligibility criteria. METHODS AND MATERIALS: A cohort of patients with metastatic NSCLC, diagnosed from 2016 to 2019, were randomly sampled from a curated tumor registry. Definitions for oligometastatic disease were obtained from relevant clinical trials. The Stanford Cancer Institute Research Database was used to identify baseline patient factors, systemic and local therapy, extent and location of metastatic lesions, and survival outcomes. RESULTS: Among 120 patients presenting with metastatic NSCLC, the majority had de novo metastatic disease (75%) with a median of 4 metastatic lesions involving 3 organ systems. Of these, 37.5% would have been eligible for at least 1 oligometastatic trial, with 28.3% meeting criteria for the MD Anderson Cancer Center trial, 20.0% for NRG-LU002, 6.7% for SINDAS, and 16.7% for SABR-COMET. By adding malignant pleural effusions and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs 42.4 months; P < .001), whereas presence of malignant pleural effusions was not. Of those tumors identified as oligometastatic, 44.4% received local therapy and 28.9% underwent ablative therapy to all sites. There was a trend toward greater overall survival (44.4 vs 24.9 months; P = .055) and progression-free survival (8.0 vs 5.4 months; P = .06) in patients meeting eligibility for at least 1 oligometastatic trial. CONCLUSIONS: Around 48% of patients with metastatic NSCLC had ≤3 metastases at presentation and 28% met clinical trial criteria for oligometastatic disease. Future research is needed to better define the oligometastatic state and identify patients most likely to benefit from local therapy.