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1.
J Natl Compr Canc Netw ; 22(8)2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39413826

RESUMEN

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Mesotelioma , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/terapia , Mesotelioma/tratamiento farmacológico , Mesotelioma/terapia , Mesotelioma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
2.
J Natl Compr Canc Netw ; 22(4): 249-274, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38754467

RESUMEN

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Terapia Molecular Dirigida/métodos , Estadificación de Neoplasias
3.
J Natl Compr Canc Netw ; 22(2): 72-81, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38503043

RESUMEN

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.


Asunto(s)
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Pleura , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapia
4.
J Natl Compr Canc Netw ; 21(3): 297-322, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36898367

RESUMEN

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.


Asunto(s)
Neoplasias , Cese del Hábito de Fumar , Productos de Tabaco , Humanos , Fumar , Oncología Médica
5.
J Natl Compr Canc Netw ; 21(4): 340-350, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37015337

RESUMEN

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia Neoadyuvante
6.
J Natl Compr Canc Netw ; 21(9): 961-979, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37673108

RESUMEN

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.


Asunto(s)
Mesotelioma Maligno , Mesotelioma , Humanos , Oncología Médica , Mesotelioma/diagnóstico , Mesotelioma/terapia , Peritoneo
7.
J Natl Compr Canc Netw ; 20(5): 497-530, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35545176

RESUMEN

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Inmunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Oncología Médica , Recurrencia Local de Neoplasia
9.
Br J Cancer ; 120(8): 791-796, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30880334

RESUMEN

BACKGROUND: Bypass activation of Src family kinases can confer resistance to EGFR tyrosine kinase inhibitors (TKIs) based on preclinical models. We prospectively assessed the safety and clinical activity of dasatinib and afatinib in combination for patients with resistant EGFR-mutant lung cancer. METHODS: An open-label, dose-escalation phase 1/2 trial (NCT01999985) with 2-stage expansion was conducted with 25 lung cancer patients. Dose expansion required activating EGFR mutations and progression following prior EGFR TKI. RESULTS: Patients were 72% Caucasian and received median of 2 prior lines of therapy. Maximum-tolerated dose was 30 mg afatinib with 100 mg dasatinib. New or increased pleural effusions were observed in 56% of patients. No radiologic responses were observed, although several EGFR-mutant TKI-resistant patients (26%) had prolonged stable disease over 6 months. The combination reduced the EGFR mutation and T790M variant allele frequency in cell-free DNA (p < .05). Nonetheless, the threshold for futility was met, based on 6-month progression-free survival. For EGFR TKI-resistant patients, median progression-free survival was 3.7 months (95% confidence interval (CI), 2.3-5.0) and overall survival was 14.7 months (95% CI, 8.5-20.9). CONCLUSIONS: The combination had a manageable toxicity profile and in vivo T790M modulation, but no objective clinical responses were observed.


Asunto(s)
Afatinib/administración & dosificación , Dasatinib/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Afatinib/efectos adversos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Nucleicos Libres de Células/efectos de los fármacos , Dasatinib/efectos adversos , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Receptores ErbB/genética , Femenino , Frecuencia de los Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/administración & dosificación , Familia-src Quinasas/antagonistas & inhibidores
10.
Cancer Immunol Immunother ; 68(3): 517-527, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30591959

RESUMEN

Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia/terapia , Carcinoma Pulmonar de Células Pequeñas/terapia , Proteína p53 Supresora de Tumor/genética , Vacunación , Adulto , Anciano , Vacunas contra el Cáncer/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Terapia Recuperativa , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Transfección
11.
Psychooncology ; 28(6): 1234-1242, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30932275

RESUMEN

OBJECTIVE: Loneliness, or the discrepancy between perceived and desired level of social connectedness, is an understudied but important psychosocial factor in cancer patients. The current study investigated the relationship between loneliness, depressive symptoms, quality of life, and social cognitive variables (eg, stigma, social constraint, and cancer-related negative social expectations), and explored loneliness as a mediator of the relationship between social cognitive variables and depressive symptoms and quality of life in lung cancer patients beginning treatment. METHODS: Patients within 3 months of beginning treatment for lung cancer completed measures of loneliness, depressive symptoms, quality of life, and social cognitive variables. Correlational, chi-square, and hierarchical regression analyses evaluated relationships among variables. Bias-corrected bootstrapping methods estimated the indirect effect and 95% confidence interval for mediation models. RESULTS: Participants (n = 105, M = 65.5 years, 55% female) endorsed low to moderate levels of loneliness. Greater loneliness was associated with greater depressive symptoms and worse quality of life (P's < .001), and loneliness explained unique variance in depressive symptoms (F = 10.18, P < .001, ΔR2  = .06, Total R2  = .35) and quality of life (F = 19.55, P < .001, ΔR2  = .05, Total R2  = .52) after controlling for significant covariates. Greater stigma, social constraint, and cancer-related negative social expectations were associated with greater loneliness and depressive symptoms and worse quality of life (P's < .001). Loneliness partially mediated the relationship of social cognitive variables with depressive symptoms and quality of life. CONCLUSIONS: Beyond its direct impact on clinically relevant outcomes, the experience of loneliness may be a mechanism by which social cognitive factors influence depressive symptoms and quality of life in lung cancer patients.


Asunto(s)
Depresión/psicología , Soledad/psicología , Neoplasias Pulmonares/psicología , Calidad de Vida/psicología , Percepción Social , Estigma Social , Anciano , Femenino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad
12.
Cancer Immunol Immunother ; 67(12): 1853-1862, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30209589

RESUMEN

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.


Asunto(s)
Adenocarcinoma/terapia , Ligando de CD40/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimiocina CCL21/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Inmunoterapia , Adenocarcinoma/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
13.
J Natl Compr Canc Netw ; 14(11): 1430-1468, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27799513

RESUMEN

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.


Asunto(s)
Oncología Médica , Cese del Hábito de Fumar , Humanos , Oncología Médica/normas , Cese del Hábito de Fumar/estadística & datos numéricos
14.
Ann Surg Oncol ; 21(5): 1480-6, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24158467

RESUMEN

INTRODUCTION: Cytoreduction with heated intraperitoneal chemotherapy (HIPEC) has demonstrated improved overall survival (OS) in malignant peritoneal mesothelioma (MPM). The role of repeated HIPEC for MPM is less clear. METHODS: An institutional review board-approved database of MPM patients was analyzed for clinical factors and outcomes. RESULTS: From June 2004 to March 2012, 29 patients underwent surgical treatment for mesothelioma. HIPEC was aborted in 3 and completed in 26; 8 underwent additional repeat HIPEC. The majority was male (62 %), median age 66 years. There was no significant difference in surgery duration, blood loss, or hospital-stay-duration between initial and repeat HIPEC. Cisplatin was the chemotherapy used. Complications occurred in 17 (65 %) initial and 6 (50 %) repeat HIPEC, with wound complications being most common. Reoperation was less common (4 % initial and 25 % repeat), and perioperative death was rare (4 % initial, 0 % repeat). Fourteen (54 %) initial and seven (58 %) repeat HIPEC patients received adjuvant chemotherapy. Median time from HIPEC to initiation of chemotherapy was not different between initial and repeat HIPEC (8.8 and 4.6 months, respectively, p = 0.68). Median treatment-free time (time from initial to repeat HIPEC or chemotherapy) also was not different between initial and repeat HIPEC (8.8 and 6.3 months, respectively, p = 0.92). Median OS for the cohort was 41.2 months. Patients who underwent repeat HIPEC had improved median OS (80 months) versus single HIPEC (27.2 months; p = 0.007). A lower peritoneal carcinoma index and complete cytoreduction were associated positively with OS. CONCLUSIONS: Cytoreduction and HIPEC for MPM are associated with longer OS. Patients who are candidates for repeat HIPEC may derive an even greater OS advantage.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida , Neoplasias Pulmonares/mortalidad , Mesotelioma/mortalidad , Neoplasias Peritoneales/mortalidad , Reoperación , Adolescente , Adulto , Anciano , Quimioterapia del Cáncer por Perfusión Regional , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patología , Mesotelioma/terapia , Mesotelioma Maligno , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Tasa de Supervivencia , Adulto Joven
15.
Cancer Control ; 21(1): 32-9, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24357739

RESUMEN

BACKGROUND: Genomic or proteomic profiling of cancer can be broadly defined as a systematic grouping of cancer based on its genetic or protein makeup. In the management of non-small-cell lung cancer (NSCLC), genomic and proteomic profiling applications have become useful in early disease detection, diagnosis, treatment, and prognostication. METHODS: We reviewed the recent literature on the applications of genomic and proteomic profiling in NSCLC. Important applications were summarized into those already adopted as standard care and those still under investigation. RESULTS: For genomic profiling, testing for EGFR mutation and ALK rearrangement has become routine for adenocarcinoma. Multiplex assay and malignancy-risk gene signature are both important applications in development. A test to predict outcome after treatment with an epidermal growth factor rector/tyrosine kinase inhibitor and a screening blood test for lung cancer are being investigated for use in proteomic profiling. CONCLUSIONS: Genomic profiling is routine in patients with NSCLC, and proteomic profiling shows promise. Additional genomic and proteomic profiling applications may also prove to be useful contributions in the care of these patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Genómica/métodos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Proteómica/métodos
16.
J Clin Med ; 13(18)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39337087

RESUMEN

Background: Thymic epithelial tumors (TETs) are uncommon malignancies uniquely associated with autoimmunity and immunodeficiency. Previous studies among patients with primary immunodeficiency diseases have shown that a low calculated globulin (CG) level, obtained by subtracting albumin from total protein level, is associated with infection risk. We investigated this association among patients with TET. Methods: A cross-sectional retrospective study was performed based on electronic medical records of patients with TET treated during 2002-2024 at a tertiary care institution. For each patient, their lowest CG level and the date of occurrence were identified. The incidence of serious infection requiring hospitalization during 6 months before and 6 months after the index date was recorded. Multivariable Poisson regression models were constructed. Results: Among 101 TET patients, 96 patients (95%) had the information available to derive at least one CG level. The median lowest CG level was 2.65 g/dL (range 1.0-4.2). There were 33 serious infection episodes. Pneumonia was the most prevalent type of infection in 52% of episodes. In a multivariable analysis, a CG level below 2.0 was independently associated with the prevalence of infection with a prevalence ratio of 6.18 (95% CI: 3.12-12.23, p < 0.001). Furthermore, thymectomy was significantly associated with infection. Conclusions: Among patients with TET, a low CG level was associated with an increased prevalence of serious infections. Our limited experiences suggest that it is feasible to derive the CG level for most patients during routine clinical care.

17.
Clin Lung Cancer ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38825406

RESUMEN

BACKGROUND: ALK or EGFR inhibitor is an ideal frontline treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring targetable alteration in ALK or EGFR. However, in the real-world setting, frontline treatment may be delayed or not ideal. For such patients, the benefit of initiating ALK or EGFR inhibitor at a later timepoint remains uninvestigated. METHODS: We utilized a nationwide electronic health record-derived, deidentified database collected from diverse oncology practices across the United States to investigate the timeliness of preferred targeted therapy (PTT). Individualized data obtained from patients with stage IV NSCLC at diagnosis treated with PTT from 2018 to 2023 were analyzed. RESULTS: Data from 3250 patients were analyzed: 2640 patients (81%) with EGFR mutation and 610 patients (19%) with ALK rearrangement. The median time to PTT was 7 weeks from diagnosis with 26.4% of patients started PTT within 1 month. Landmark analyses using timepoints ranging from 1 to 12 months after diagnosis showed that at all timepoints, patients who had started on PTT had a significantly better survival than those who had not. In a multivariable analysis, time to PTT ≤ 1 month from diagnosis was an independent predictor of survival: HR 0.74 (95% CI: 0.62-0.89), P = .002. Time to PTT was significantly associated with age, smoking status and genomic class. CONCLUSIONS: In this population-based analysis, an initiation of PTT occurring as late as at least 1 year from diagnosis still resulted in a significant survival benefit, though the magnitude of benefit appeared decreased as time passed.

18.
Clin Lung Cancer ; 25(6): 537-549.e2, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38926078

RESUMEN

OBJECTIVES: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients. MATERIALS AND METHODS: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed. RESULTS: Of 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, P = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, P < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (P = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, P = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%. CONCLUSIONS: Our single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non-small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC.


Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Radiocirugia , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Masculino , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Femenino , Radiocirugia/métodos , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Tasa de Supervivencia , Estudios de Seguimiento , Anciano de 80 o más Años , Neumonectomía
19.
J Clin Oncol ; : JCO2400533, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39378386

RESUMEN

PURPOSE: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS). METHODS: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were EGFR mutation type and the presence of CNS metastasis. RESULTS: At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank P = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B; P = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug. CONCLUSION: Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR-mutant NSCLC. The combination is safe and well tolerated.

20.
Cureus ; 15(1): e34033, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36814728

RESUMEN

Advanced cancers may be accompanied by paraneoplastic disseminated intravascular coagulation (DIC), resulting in thromboembolism or thrombocytopenia. Thrombocytopenia can limit the feasibility of myelosuppressive chemotherapy. Therefore, an alternative treatment option is needed. This report described a patient with metastatic pulmonary adenocarcinoma with EGFR exon 20 insertion and paraneoplastic DIC. Frontline chemotherapy failed to control the disease and worsened thrombocytopenia. However, treatment with amivantamab resulted in a rapid resolution of DIC and produced a partial tumor response. Based on our experience, for patients with EGFR exon 20 insertions with paraneoplastic DIC, amivantamab could be considered a preferred frontline treatment.

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