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The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Mastectomía , Escisión del Ganglio Linfático , Biopsia del Ganglio Linfático Centinela , Mastectomía Segmentaria , Axila/patología , Ganglios Linfáticos/patologíaRESUMEN
PURPOSE: Quality assessment of the treatment plans in the Danish Breast Cancer Group (DBCG) HYPO trial was carried out based on prospectively reported dosimetric parameters and evidence-based dose constraints for whole breast radiation therapy were derived. MATERIALS AND METHODS: From 2009 to 2014, 1882 patients (pts) were randomised between 50 Gy/25fractions (fr) versus 40 Gy/15fr. Doses to CTVp_breast (V95%, V107%-V110%, Dmax, and in addition for 40 Gy plans V105%-V107%), ipsilateral lung (V20Gy/V17Gy), heart (V20Gy/V17Gy, V40Gy/V35Gy), and left anterior descending coronary artery (LADCA) (Dmax) and use of respiratory gated technique were prospectively reported to the DBCG database. After end of accrual, these dosimetric parameters from all plans in the trial were compared to the pre-specified treatment constraints. RESULTS: In total, 1854 pts from eight radiation therapy (RT) centres in three countries were treated. No statistically significant differences were found between the results for 40 Gy and 50 Gy plans, except for CTVp_breast hot-spot volume (V107%-V110%). Of the 40 Gy pts, 90% with CTVp_breast > 600 mL and 95% with CTVp_breast ≤ 600 mL had a CTVp_breast hot-spot volume (V105%-V107%) <2%. In 95% of the 50 Gy plans, the CTVp_breast absolute hot-spot volume (V107%-V110%) was <0.5 mL and 1.7 mL for CTVp_breast ≤ 600 mL and > 600 mL, respectively. Compliance was >99% for both heart and lung constraints. Largest deviation from protocol constraints was found for the volume of CTVp_breast covered with 95% of the prescription dose or more (V95%). The CTV dose coverage (V95%) was >94.3% in 95% of the right-sided pts, whereas the figures for 95% of the left-sided pts treated with and without respiratory gating were 93.2% and 88.8%, respectively. CONCLUSION: A high degree of compliance with protocol dose constraints was found for treatment plans in the DBCG HYPO trial. New constraints for dose to organs at risk and high-dose volumes in the breast are suggested for breast-only RT planning.
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AIMS: To evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) delineation recommendations for immediate breast reconstruction (IBR). MATERIALS AND METHODS: Seven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives. RESULTS: In total, 35 treatment plans were collected. Half of the submitted plans, for both the left-sided and the right-sided case, used the field-in-field (FiF) technique (nine for each), a quarter used volumetric arc radiation therapy (VMAT; five for right-sided, four for left-sided) and the remaining quarter was a mix of inverse intensity-modulated radiation therapy (IMRT), helicoidal therapy and hybrid (combined open fields and VMAT) techniques. Mean clinical target volume doses were in the range 99-102% of the prescribed dose. The median FiF mean heart dose (MHD) for right-sided radiation therapy was 1 Gy (range 0.8-3.7) and 5.2 Gy for left-sided radiation therapy (range 2.2-6.5). For right-sided radiation therapy, the median VMAT MHD was 3.42 Gy, for IMRT was 2.3 Gy and for helicoidal therapy was 5.1 Gy. For left-sided radiation therapy, the median VMAT MHD was 6.3 Gy, for IMRT was 7.8 Gy and for helicoidal therapy was 7.3 Gy. CONCLUSIONS: Different radiation therapy techniques could be used to plan radiation therapy in the setting of IBR. FiF provided good coverage with acceptable organ at risk doses. The best dose distribution results as a trade-off between the objectives of target volume coverage and high-dose organ at risk inclusion. The radiation therapy technique affects the interplay between these objectives.
Asunto(s)
Neoplasias de la Mama , Planificación de Atención al Paciente/normas , Traumatismos por Radiación/prevención & control , Oncología por Radiación/normas , Dosificación Radioterapéutica/normas , Planificación de la Radioterapia Asistida por Computador/métodos , Implantación de Mama/métodos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Europa (Continente)/epidemiología , Femenino , Adhesión a Directriz , Humanos , Mastectomía/métodos , Órganos en Riesgo , Planificación de Atención al Paciente/organización & administración , Cuidados Posoperatorios/métodos , Cuidados Posoperatorios/normas , Guías de Práctica Clínica como Asunto , Radioterapia de Intensidad Modulada/métodosRESUMEN
AIMS: Moderately hypofractionated breast irradiation has been evaluated in several prospective studies, resulting in wide acceptance of shorter treatment protocols for postoperative breast irradiation. Reimbursement for radiation therapy varies between private and public systems and between countries, impacting variably financial considerations in the use of hypofractionation. The aim of this study was to evaluate the financial impact of moderately hypofractionated breast irradiation by reimbursement system in different countries. MATERIALS AND METHODS: The study was designed by an international group of radiation oncologists. A web-questionnaire was distributed to representatives from each country. The participants were asked to involve the financial consultant at their institution. RESULTS: Data from 13 countries from all populated continents were collected (Europe: Denmark, France, Italy, the Netherlands, Spain, UK; North America: Canada, USA; South America: Brazil; Africa: South Africa; Oceania: Australia; Asia: Israel, Taiwan). Clinicians and/or departments in most of the countries surveyed (77%) receive remuneration based on the number of fractions delivered to the patient. The financial loss per patient estimated resulting from applying moderately hypofractionated breast irradiation instead of conventional fractionation ranged from 5-10% to 30-40%, depending on the healthcare provider. CONCLUSION: Although a generalised adoption of moderately hypofractionated breast irradiation would allow for a considerable reduction in social and economic burden, the financial loss for the healthcare providers induced by fee-for-service remuneration may be a factor in the slow uptake of these regimens. Therefore, fee-for-service reimbursement may not be preferable for radiation oncology. We propose that an alternative system of remuneration, such as bundled payments based on stage and diagnosis, may provide more value for all stakeholders.
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Neoplasias de la Mama , Hipofraccionamiento de la Dosis de Radiación , Mama , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: There is no consensus regarding the impact of oncoplastic surgery (OPS) on rates of re-excision and conversion to mastectomy following breast-conserving surgery (BCS). Here these two outcomes after BCS and OPS were compared in a nationwide population-based setting. METHODS: In Denmark, all OPS is registered and categorized into volume displacement, volume reduction or volume replacement. Patients who underwent BCS or OPS between 2012 and 2018 were selected from the Danish Breast Cancer Group database. Multivariable analyses were performed to adjust for confounders, and propensity score matching to limit potential confounding by indication bias. RESULTS: A total of 13 185 patients (72·5 per cent) underwent BCS and 5003 (27·5 per cent) OPS. Volume displacement was used in 4171 patients (83·4 per cent), volume reduction in 679 (13·6 per cent) and volume replacement in 153 (3·1 per cent). Re-excision rates were 15·6 and 14·1 per cent after BCS and OPS respectively. After adjusting for confounders, patients were less likely to have a re-excision following OPS than BCS (odds ratio (OR) 0·80, 95 per cent c.i. 0·72 to 0·88), specifically after volume displacement and reduction. The rate of conversion to mastectomy was similar after OPS and BCS (3·2 versus 3·7 per cent; P = 0·105), but with a lower risk in adjusted analysis (OR 0·69, 0·58 to 0·84), specifically after volume displacement and reduction procedures. Findings were similar after propensity score matching. CONCLUSION: A modest decrease in re-excision rate and less frequent conversion to mastectomy were observed after OPS compared with BCS.
ANTECEDENTES: No existe consenso con respecto al impacto de la cirugía oncoplástica (oncoplastic surgery, OPS) en las tasas de re-exéresis y conversión a mastectomía tras la cirugía conservadora de la mama (breast conserving surgery, BCS). En este estudio se compararon los dos resultados después de BCS y OPS en una base de datos poblacional de ámbito nacional. MÉTODOS: En Dinamarca, todas las OPS se registran y clasifican en procedimientos que incluyen 1) desplazamiento (o remodelación) de volumen, 2) reducción de volumen o 3) restitución de volumen. Todas las pacientes sometidas a BCS o OPS entre 2012 y 2018 fueron seleccionadas de la base de datos del Grupo de Cáncer de Mama Danés. Se realizaron análisis multivariables para ajustar por factores de confusión y un emparejamiento por puntaje de propensión para limitar las variables de confusión potenciales por el sesgo en la indicación. RESULTADOS: Un total de 13.185 (72,5%) pacientes fueron sometidos a BCS y 5.003 (27,5%) a OPS. Se utilizó el desplazamiento de volumen en 4.171 (83,4%) pacientes, reducción de volumen en 679 (13,6%) pacientes y restitución de volumen en 153 (3,1%) pacientes. Las tasas de re-exéresis fueron del 15,6% y 14,1% tras BCS y OPS, respectivamente. Tras ajustar por factores de confusión, las pacientes tuvieron menos probabilidad (razón de oportunidades, odds ratio, OR 0,80, i.c. del 95%. 0,72-0,88) de requerir re-exéresis tras OPS, específicamente después de desplazamiento y reducción de volumen, en comparación con BCS. La tasa de conversión a mastectomía fue inferior (3,2% versus 3,7%, P = 0,04) y menos probable (OR 0,71, i.c. del 95% 0,58-0,87) tras OPS, específicamente en el desplazamiento y reducción de volumen, en comparación con BCS. Los resultados fueron similares después del emparejamiento por puntuación de propensión. CONCLUSIÓN: Se observó un descenso modesto en las tasas de re-exéresis y una menor frecuencia de conversiones a mastectomía después de la cirugía oncoplástica cuando se comparó con la cirugía conservadora de la mama.
Asunto(s)
Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/cirugía , Mastectomía/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Bases de Datos Factuales , Dinamarca , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Mastectomía Segmentaria , Persona de Mediana Edad , Análisis Multivariante , Puntaje de Propensión , Resultado del TratamientoRESUMEN
Breast cancer is the leading cause of brain metastases in women. Large randomized clinical trials that have evaluated local therapies in patients with brain metastases include patients with brain metastases from a variety of cancer types. The incidence of brain metastases in the breast cancer population continues to grow, which is, aside from the rising breast cancer incidence, mainly attributable to improvements in systemic therapies leading to more durable control of extracranial metastatic disease and prolonged survival. The management of breast cancer brain metastases remains challenging, even more so with the continued advancement of local and highly effective systemic therapies. For most patients, a metastases-directed initial approach (i.e., radiation, surgery) represents the most appropriate initial therapy. Treatment should be based on multidisciplinary team discussions and a shared decision with the patients taking into account the risks and benefits of each therapeutic modality with the goal of prolonging survival while maintaining quality of life. In this narrative review, a multidisciplinary group of experts will address challenging questions in the context of current scientific literature and propose a therapeutic algorithm for breast cancer patients with brain metastases.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias de la Mama/patología , Algoritmos , Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/terapia , Irradiación Craneana , Femenino , HumanosRESUMEN
BACKGROUND: Risk factors for local recurrence after mastectomy in ductal carcinoma in situ (DCIS) emerged as a grey area during the second "Assisi Think Tank Meeting" (ATTM) on Breast Cancer. AIM: To review practice patterns of post-mastectomy radiation therapy (PMRT) in DCIS, identify risk factors for recurrence and select suitable candidates for PMRT. METHODS: A questionnaire concerning DCIS management, focusing on PMRT, was distributed online via SurveyMonkey. RESULTS: 142 responses were received from 15 countries. The majority worked in academic institutions, had 5-20 years work-experience and irradiated <5 DCIS patients/year. PMRT was more given if: surgical margins <1 mm, high-grade, multicentricity, young age, tumour size >5 cm, skin- or nipple- sparing mastectomy. Moderate hypofractionation was the most common schedule, except after immediate breast reconstruction (57% conventional fractionation). CONCLUSIONS: The present survey highlighted risk factors for PMRT administration, which should be further evaluated.
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Neoplasias de la Mama/radioterapia , Carcinoma Intraductal no Infiltrante/radioterapia , Oncología por Radiación , Radioterapia Adyuvante/métodos , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Factores de Riesgo , Encuestas y CuestionariosAsunto(s)
Neoplasias de la Mama/terapia , Conferencias de Consenso como Asunto , Oncología Médica/normas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja Gruesa , Mama/diagnóstico por imagen , Mama/patología , Mama/cirugía , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Quimioradioterapia Adyuvante/métodos , Quimioradioterapia Adyuvante/normas , Ensayos Clínicos como Asunto , Europa (Continente) , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Femenino , Humanos , Medicina Integrativa/métodos , Medicina Integrativa/normas , Mastectomía/métodos , Mastectomía/normas , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Estadificación de Neoplasias , Sociedades Médicas/normas , Resultado del TratamientoRESUMEN
Preoperative breast radiation therapy (RT) is not a new concept, but older studies failed to change practice. More recently, there has been interest in revisiting preoperative RT using modern techniques. This current perspective discusses the indications, summarises the published literature and then highlights current clinical trials, with particular attention to combining with novel drugs and optimising associated translational research.
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Neoplasias de la Mama/radioterapia , Radioterapia Adyuvante/métodos , Neoplasias de la Mama/cirugía , Femenino , Humanos , Periodo Preoperatorio , Dosificación Radioterapéutica , Investigación Biomédica Traslacional/métodosRESUMEN
Adjuvant radiotherapy is the treatment standard for breast cancer with lymph node metastases after breast-conserving surgery or mastectomy. The inclusion of regional lymph nodes into the treatment volumes has been a question in recent clinical trials. Their impact on treatment standards and open questions is discussed.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Metástasis Linfática , Mastectomía , Radioterapia Adyuvante , Factores de RiesgoRESUMEN
BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.
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Neoplasias de la Mama/terapia , Determinación de Punto Final/normas , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normas , Terminología como Asunto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Consenso , Técnica Delphi , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Determinación de Punto Final/clasificación , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/clasificación , Factores de Tiempo , Insuficiencia del TratamientoAsunto(s)
Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Cuidados Intraoperatorios/métodos , Recurrencia Local de Neoplasia/epidemiología , Braquiterapia/métodos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Medicina Basada en la Evidencia , Femenino , Humanos , Incidencia , Mastectomía/métodos , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Dosificación Radioterapéutica , Radioterapia Adyuvante , Radioterapia de Intensidad Modulada/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
AIMS: Immunohistochemical estimates of cell proliferation evaluated with MIB-1 antibody have been suggested as prognostic indicators in different types of carcinoma. This study investigates whether MIB-1 scores add additional prognostic impact when evaluated together with classical clinicopathological parameters at diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system. RESULTS: The systematic random sampling technique resulted in MIB-1 estimates with very high interobserver and intraobserver reproducibilities (P < 0.0001). Median MIB-1 was 16% (range 0-83%). Patients were stratified by MIB-1 in tertiles, and increasing MIB-1 was significantly associated with poor overall and disease-specific survival in node-positive patients, but not in node-negative patients. High MIB-1 was significantly related to large tumour size, and strongly associated with high grade, high mitotic score, negative oestrogen receptor status and young age. In multivariate analysis, both with and without malignancy grade and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer.
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Neoplasias de la Mama/patología , Antígeno Ki-67/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , División Celular , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Análisis Multivariante , Variaciones Dependientes del Observador , Proyectos Piloto , Pronóstico , Modelos de Riesgos Proporcionales , Distribución Aleatoria , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Chalkley counts have been suggested as the primary method for immunohistochemical evaluation of angiogenesis, however, most studies have used microvessel density (MVD). We present paired Chalkley and MVD estimates in carcinomas of the prostate, breast, bladder and lung. The clinical data has previously been reported. In prostate carcinomas, high MVD indicated poor prognosis, whereas high Chalkley counts in breast carcinoma were associated with a poor prognosis. In bladder carcinoma, high estimates using both methods showed good prognosis and were associated with a high degree of inflammation. Neither of the counts revealed prognostic value in lung carcinomas, where the vascular pattern indicated that this cancer was non-angiogenic. We highlight methodological problems with both counting methods. Since angiogenic processes in lung and bladder cancers may be different from those occuring in prostate cancer, we suggest that future analyses also focus on measuring angiogenic factors to obtain more information on the biology of angiogenesis.
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Neoplasias de la Mama/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Neoplasias Pulmonares/irrigación sanguínea , Neovascularización Patológica/patología , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Microcirculación , Análisis Multivariante , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The aim of this study was to investigate the prognostic influence of microvessel density using the hot spot method in 107 patients diagnosed with transitional cell carcinoma of the bladder. In each case, inflammation was found in the invasive carcinoma, therefore we classified the degree of inflammation as minimal, moderate or intense. Microvessel density was then reevaluated in each tumour in areas corresponding to these three categories. Median microvessel density irrespective of degree of inflammation was 71. Areas of minimal, moderate and intense inflammation were found in 48, 92 and 32 tumours. Microvessel density increased significantly with increasing degree of inflammation. Disease-specific survival was improved if areas of intense inflammation were present in the carcinoma (P=0.004). High microvessel density, irrespective of the degree of inflammation, was associated with a significantly better disease-specific survival (P=0.01). Multivariate analysis using death of disease as endpoint demonstrated an independent prognostic value of N-classification (N0, hazard ratio (HR)=1 vs N1, HR=2.89 (range, 1.52-5.52) vs N2, HR=3.61 (range, 1.84-7.08)), and intense inflammation, HR=0.48 (range, 0.24-0.96). Malignancy grade, T classification and microvessel density were not independent significant markers of poor outcome. In conclusion, inflammation was significantly correlated to microvessel density, and areas of intense inflammation were an independent marker of good prognosis.
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Carcinoma de Células Transicionales/irrigación sanguínea , Cistitis/diagnóstico , Neovascularización Patológica/patología , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Cistitis/metabolismo , Supervivencia sin Enfermedad , Factores de Crecimiento Endotelial/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Linfocinas/metabolismo , Masculino , Microcirculación , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neovascularización Patológica/metabolismo , Pronóstico , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Tumor angiogenesis plays a pivotal role in tumor growth, maintenance, and metastasis. The objective of the current study was to evaluate the prognostic value of estimates of tumor angiogenesis and vascular endothelial growth factor (VEGF) status in 143 primary tumors from patients who underwent radical surgery for nonsmall-cell lung carcinoma (NSCLC). METHODS: Tumor sections were stained by immunohistochemistry for CD34 and VEGF. Angiogenesis was estimated both by a modification of the method described by Weidner and by the use of a 25-point Chalkley eyepiece graticule. VEGF intensity was evaluated semiquantitatively in three groups of patients. The vascular data were correlated with histopathologic tumor type and grade, TNM classification, patient age, and the endpoint (death). RESULTS: The estimates of vascular score did not reveal any prognostic information. In 35 patients (24%), invasive tumor growth was identified with a highly ordered alveolar microvessel pattern. In parallel sections, the intensity of VEGF staining was weak in tumors that exhibited an alveolar microvessel pattern only, and it was more intense in tumors that demonstrated a mixed alveolar and diffuse angiogenic pattern. The 35 patients with alveolar microvessel pattern had a significantly better survival (P = 0.007). In a Cox multivariate analysis, the results demonstrated an independent bad prognostic value of high disease stage (P < 0.0001), adenocarcinoma (P = 0.004), greater age (P = 0.01), and angiogenic microvessel pattern (P = 0.01). CONCLUSIONS: The authors believe that the alveolar vascular pattern represented preexisting alveolar vessels, that is, the alveoli were filled up by tumor cells that exploited the existing highly vascular bed of the lungs. Therefore, this subgroup was characterized by tumor progression without the induction of angiogenesis. The current data do not support a significant prognostic role for tumor angiogenesis in patients who are diagnosed with NSCLC. This may have implications for therapy aimed at inhibiting tumor growth by the inhibition of angiogenesis.