Épidémiologie des lésions métastatiques cérébrales

doi:10.1016/j.canrad.2014.11.001

Cancer/Radiothérapie

Volume 19, Issue 1, February 2015, Pages 3-9

https://doi.org/10.1016/j.canrad.2014.11.001 Get rights and content

Résumé

Les métastases cérébrales représentent la majorité des tumeurs intracrâniennes. Bien que tout cancer soit à même de développer des métastases cérébrales, chez l’adulte, dans deux tiers des cas celles-ci proviennent d’un cancer bronchique, d’un cancer du sein ou d’un mélanome. Pour ces trois cancers primitifs, l’incidence, les facteurs de risque, le délai médian de survenue après le diagnostic, le pronostic et la survie sont documentés pour chaque type histologique, une attention particulière a été donnée aux implications cliniques de ces données. Les différents scores pronostiques sont également discutés, notamment le Diagnostic-Specific Graded Prognostic Assessment (DS-GPA), avec leurs applications possibles ainsi que les enseignements qui en émanent pour la prise en charge des patients atteints de métastases cérébrales, toutes origines histologiques confondues. L’objectif de ces scores est double : favoriser une meilleure stratification dans les essais cliniques incluant des patients atteints de métastases cérébrales, mais également de proposer au clinicien un outil juste et simple d’utilisation qui facilite la prise de décision thérapeutique, au cas par cas, en fonction de la survie attendue de chaque patient. Dans ce cas, il est entendu que le DS-GPA est un outil parmi d’autres éléments à prendre en compte individuellement.

Abstract

The most frequent intracranial brain tumours are brain metastases. All types of cancer can develop brain metastases but two thirds of brain metastases occurring in adult patients are secondary to one of these three cancers: lung cancer, breast cancer and melanoma. In accordance with these data, this review is focusing on the epidemiology of these three types of cancer. We report here the incidence, risk factors, median time of brain metastases occurrence after diagnosis of the primary cancer, prognosis and median survival for these three types of cancer. We also discuss the clinical implications of these data. The second part of this review is focusing on the Graded Prognostic Assessment scores in all types of primary cancer with brain metastases, how they can be applied in clinical research for a better stratification of patients, and to some extent in clinical practice to guide decisions for personalized treatments. These scores provide a better understanding of the different profiles of clinical evolution that can be observed amongst patients suffering from brain metastases according to the type of primary cancer. We highlighted the most remarkable and useful clinical implications of these data.

Introduction

Les métastases cérébrales représentent la majorité des tumeurs intracrâniennes. Bien que tout cancer soit à même de développer des métastases cérébrales, chez l’adulte, dans deux tiers des cas celles-ci proviennent d’un cancer bronchique, d’un cancer du sein ou d’un mélanome. À lui seul, le cancer d’origine bronchique est le plus grand pourvoyeur de métastases cérébrales, à l’origine de 30 % à 50 % des cas [1]. C’est aussi le cancer le plus fréquemment associé à des métastases cérébrales sans autre manifestation métastatique extracérébrale. Le cancer du sein et le mélanome sont chacun à l’origine de 10 à 20 % des cas de métastases cérébrales. De plus en plus fréquemment, on peut observer des métastases cérébrales de cancers du rein, de cancers d’origine digestive ou gynécologique. Malgré les progrès constants de l’imagerie médicale, le cancer primitif ne peut être mis en évidence dans 10 % des cas. La dernière partie de l’article est consacrée aux scores pronostiques et à leur application possible.

Section snippets

Incidence des métastases cérébrales

Une femme sur huit est atteinte d’un cancer du sein au cours de sa vie, 5 à 15 % d’entre sont atteintes de métastases cérébrales [2], [3]. Les données autopsiques objectivent une prévalence nettement plus élevée, autour de 30 %, chez les femmes atteintes d’un cancer métastatique, ce qui laisse supposer une sous-estimation de la fréquence des métastases cérébrales dans les séries publiées [4]. L’incidence des métastases cérébrales varie selon le sous-type moléculaire de cancer du sein [5], [6],

Incidence des métastases cérébrales

Le cancer bronchopulmonaire est la première cause de métastases cérébrales (à l’origine de 40–50 % de toutes les métastases cérébrales) [1]. Une scanographie cérébrale après injection de produit de contraste systématique chez les patients chez qui un cancer bronchopulmonaire vient d’être diagnostiqué retrouve des métastases cérébrales dans 3 à 10 % des cas [19]. La scanographie cérébrale après injection ou l’IRM cérébrale est systématique dans le bilan d’extension initial des cancers

Incidence des métastases cérébrales

L’incidence des métastases cérébrales dans les séries cliniques varie de 15 à 50 % alors qu’elle est estimée à 70 à 90 % dans les séries autopsiques. Le cerveau apparaît comme site métastatique initial dans 15 à 20 % des cas [41], [42], [43].

Facteurs de risque possibles de métastases cérébrales

Les facteurs de risque potentiels sont décrits ci-dessous [41], [42], [43], [44], [45] : une concentration élevée de LDH, un indice de Breslow élevé, la présence de plus de deux sites viscéraux métastatiques, des mutations du gène BRAF, les

Métastases cérébrales secondaires à d’autres cancers primitifs

L’analyse des données épidémiologiques récentes a montré une augmentation de l’incidence de métastases cérébrales secondaires aux cancers rénaux, colorectaux et ovariens [52], [53], [54]. Dans ces trois cas, une amélioration de la durée de survie globale secondaire à l’introduction de traitements plus efficaces, ainsi qu’une meilleure détection diagnostique des métastases cérébrales peuvent expliquer au moins en partie ces observations.

Scores pronostiques

La connaissance des facteurs de risque cliniques et biomoléculaires de survenue de métastases cérébrales a pour objectif d’améliorer la surveillance radioclinique des patients à risque élevé et à terme de développer des interventions préventives ciblant la population adéquate.

Néanmoins, la prise en charge des patients atteints de métastases cérébrales et le choix des modalités thérapeutiques reposent essentiellement sur l’évaluation du pronostic chez chaque patient. Différents scores

Conclusion

Une augmentation de l’incidence des métastases cérébrales est observée en raison de l’allongement de survie secondaire à l’efficacité accrue des traitements disponibles d’une part, ainsi que « l’effet sanctuaire » propre au système nerveux central concernant le passage de certaines drogues et thérapies ciblées d’autre part [7]. La survie après le diagnostic de métastase(s) cérébrale(s) varie selon le sous-type tumoral, le nombre et la localisation des métastases cérébrales et ainsi des

Déclaration d’intérêts

Les auteurs déclarent ne pas avoir de conflits d’intérêts en relation avec cet article.

Remerciements

Les auteurs remercient :

•
le groupe de travail Métastases SNC Anocef (par ordre alphabétique) : Antoine Carpentier (Paris), Frédéric Dhermain (Paris), Émilie Le Rhun (Lille), Emmanuel Mandonnet (Paris), Philippe Métellus (Marseille), Georges Noël (Strasbourg), Nicolas Reyns (Lille), Sophie Taillibert (Paris) ;
•
les relecteurs du référentiel : Thomas Bachelot (Lyon), Fabrice Barlési (Marseille), Chantal Bernard-Marty (Toulouse), Benjamin Besse (Villejuif), Jacques Bonneterre (Lille), Antoine

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Cited by (62)

Stereotactic Radiosurgery (SRS) experience on brain metastases: A 3-year retrospective study at King Abdulaziz University Hospital
2021, Saudi Journal of Biological Sciences
Citation Excerpt :
The incidence of brain metastases can reach more up to 65% in the period of the disease trajectory, considering the type of primary tumor (Lassman and DeAngelis, 2003; Bilger et al., 2017; Tsao et al., 2018). For unselected patients with varying tumor types, such incidence is estimated to fall between 8% and 10% (Taillibert and Le Rhun, 2015; Liu et al., 2019). Alarmingly, the median survival of patients with brain metastases is estimated to only last for 4 months relative to the time they were diagnosed (Fonkem et al., 2012; Tazi et al., 2015).
Stereotactic radiosurgery (SRS), a non-invasive surgical procedure had been utilized for treatment of patients with brain metastases. This study aims to determine the survival, local control of brain metastases and treatment outcome to SRS-treated patients based on radiological imaging.
The MRI scans of SRS-treated patients with brain metastases (n = 24) from the Radiology Department of King Abdulaziz University from January 2016 to September 2019 were examined. The data was analyzed using descriptive statistics and Chi-square test.
Out of 24 patients, most had brain metastases (95.8%, n = 23) with mean interval development (after primary site) of 21.88 ± 25.2 months. Radiological imaging revealed tumor characteristics of smallest (n = 11) and biggest lesions (n = 24) of patients to be 0.98 ± 0.7 and 2.23 ± 0.9, respectively and number of lesion to be 4–5 lesions (n = 3), 3 lesions (n = 6), 2 lesions (n = 4) and 1 lesion (n = 11). After SRS treatment, findings showed 17.6% (n = 3) no recurrence among the patients. Those with recurrences have decrease in lesion enhancement (11.8%, n = 2), decrease in size (29.4%, n = 5) and decrease in both enhancement and size (29.4%). Overall survival obtained was 16.7% (n = 2) at 313.83 ± 376.0 days (n = 23) survival period. Chi-square test showed that radiological findings were significantly associated with tumor recurrence (p = 0.010), having SRS-treated patients with recurrences (n = 12) to experience significant decrease (p = 0.010) in tumor enhancement, size, and both enhancement and size.
A significant decrease in tumor size and enhancement was observed in SRS-treated patients, suggesting SRS treatment to have associated benefit with prolonged survival duration.
HER2 Receptor Conversion Is a strong Survival Predictor in Patients with Breast Cancer Brain Metastases
2021, World Neurosurgery
Citation Excerpt :
Breast cancer (BC) is the most common cancer in women,1,2 and the prognosis of patients with BC is mainly limited owing to the occurrence of distant metastases,3,4 which preferentially occur in the bone, lung, liver, and brain.5
Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs).
Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics.
The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival.
Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.
Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases
2021, Cancer/Radiotherapie
Stereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity.
From 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤ 30 days) were included. The prescribed dose was 20 Gy/1f or 33 Gy/3f at the isocentre and 14 Gy or 23.1 Gy (70%) respectively at the PTV envelope (PTV = GTV + 2 mm). The mean tumour diameter was 14 mm (4–52 mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤ 7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days).
The mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P = 0.86), while the histology was (P < 0.001). The proportion of grade ≥ 3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P = 0.03).
The time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.
La radiothérapie stéréotaxique est le traitement standard des métastases cérébrales des cancers bronchiques non à petites cellules et des mélanomes. Ces patients ont dans une grande majorité reçu en association une immunothérapie. L’objectif était d’évaluer rétrospectivement l’influence du temps écoulé entre l’immunothérapie et la radiothérapie stéréotaxique sur la toxicité.
De 2016 à 2019 ont été inclus 59 patients traités pour 103 métastases cérébrales de cancer bronchique non à petites cellules (60 %) et de mélanome (40 %) par irradiation stéréotaxique avec une immunothérapie concomitante (délai ≤ 30 jours). La dose prescrite était respectivement de 20 Gy en une séance ou 33 Gy trois fractions à l’isocentre et 14 Gy en une séance ou 23,1 Gy en trois fractions en enveloppe (isodose 70 %) dans le volume cible prévisionnel (PTV: GTV [volume tumoral macroscopique] + 2 mm). Le GTV moyen était de 0,9 cc et son grand diamètre de 14 mm (4–52 mm). Les différents types d’immunothérapie étaient le nivolumab (61,2 %), le pembrolizumab (30,1 %), l’atezolizumab (4,9 %) et le durvalumab (3,9 %). Les 103 métastases ont été classées en trois groupes en fonction du temps écoulé entre l’immunothérapie et la radiothérapie stéréotaxique: 7 (7 %) dans le groupe A (temps ≤ 7j), 38 (37 %) dans le groupe B (7j < temps ≤ 14j) et 58 (56 %) dans le groupe C (14j < temps ≤ 30j).
Le suivi moyen était 10,1 mois. La médiane de survie globale des patients était de 11,5 mois pour les cancers bronchiques non à petites cellules et 12,5 mois pour les mélanomes. Le taux de contrôle local à un an était de 65,1 % (93,6 % pour les cancers bronchiques non à petites cellules et 26,5 % pour les mélanomes). Le délai entre immunothérapie et la radiothérapie stéréotaxique n’était pas un facteur prédictif significatif de contrôle local (p = 0,86) contrairement à l’histologie (p < 0,001) et au statut PDL1 (p = 0,008). Le taux de toxicité de grade ≥ 3 était de 5,1 %. Le taux de radionécrose était 9,7 %, 80 % étaient asymptomatiques. Il était respectivement de 0 %, 13,1 % et 8,6 % pour les groupes A, B et C (NS). Le délai entre immunothérapie et radiothérapie stéréotaxique n’était pas un facteur prédictif significatif de toxicité. Seul le volume tumoral l’était (p = 0,03).
Le délai entre immunothérapie et radiothérapie stéréotaxique n’influence pas la toxicité cérébrale. Le volume tumoral reste le principal facteur prédictif de toxicité.
Repeated irradiation of brain metastases under stereotactic conditions: A review of the literature
2021, Cancer/Radiotherapie
La radiothérapie en conditions stéréotaxiques est devenue un standard dans la prise en charge des patients atteints de métastases cérébrales ; son principal intérêt est de différer la radiothérapie de l’encéphale en totalité pourvoyeur de toxicité neurocognitive et d’augmenter le taux de contrôle local. La répétition de sessions de radiothérapie en conditions stéréotaxiques n’est quant à elle pas codifiée, ni sur le nombre de sessions techniquement et cliniquement possible, ni sur le nombre, ni le volume de métastase à traiter. L’objectif de cette revue est d’analyser les données de la littérature concernant les irradiations répétées en conditions stéréotaxiques. La seconde réirradiation en conditions stéréotaxiques montre des résultats satisfaisants en termes de survie globale, de contrôle local et de toxicité. Cependant, nous manquons de données pour les patients recevant plus de deux sessions de radiothérapie en conditions stéréotaxiques, ainsi que pour définir des contraintes de dose aux tissus sains réirradiés. Des essais prospectifs restent nécessaires pour valider la prise en charge des métastases cérébrales après radiothérapie en conditions stéréotaxiques initiale.
Stereotactic radiotherapy has become a standard in the management of patients with brain metastases; its main interest is to differ whole brain radiotherapy, provider of neurocognitive toxicity and to increase the rate of local control. The repetition of radiotherapy sessions under stereotactic conditions is not codified, neither on the number of technically and clinically possible sessions, nor on the maximum total number or volume of metastases to be treated. The purpose of this review is to analyse the data in the literature concerning repeated irradiations under stereotactic conditions. The second reirradiation in stereotactic condition shows satisfactory results in terms of overall survival, local control, and toxicity. However, we lack data for patients receiving more than two sessions of SRS as well as to define dose constraints to reirradiated healthy tissues. Prospective trials are still needed to validate the management of recurrent brain metastases after initial SRS.
Epidemiology of Brain Metastases
2020, Neurosurgery Clinics of North America
Citation Excerpt :
Of those with lung cancer who developed BM, 6.7% had received prophylactic cerebral irradiation. Compared with breast cancer patients with BMs who had an average survival of 8 months, lung cancer patients with BMs had a statistically significantly worse average survival of 6 months.44 Because the incidence of breast cancer is so high, it represents the second leading cause of BMs; 5% of patients with underlying breast malignancy are found to have BM.45
Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases From 1985 to Today
2020, International Journal of Radiation Oncology Biology Physics
Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.
A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively.
Median survival (MS) for cohorts A, B, and C improved over time (from 11, to 14 to 16 months, respectively; P < .01), despite the subtype distribution becoming less favorable. PF significant for survival were tumor subtype, Karnofsky Performance Status, age, number of BCBMs, and extracranial metastases (all P < .01). MS for GPA 0 to 1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 was 6, 13, 24, and 36 months, respectively. Between cohorts B and C, the proportion of human epidermal receptor 2 + subtype decreased from 31% to 18% (P < .01) and MS in this subtype increased from 18 to 25 months (P < .01).
MS has improved modestly but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free online calculator available at brainmetgpa.com). The Breast GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM.

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^☆: Travail soutenu par l’Association des neuro-oncologues d’expression française (Anocef) – groupe métastases SNC. Le référentiel Anocef est disponible sur le site : www.anocef.org.

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Revue généraleÉpidémiologie des lésions métastatiques cérébralesEpidemiology of brain metastases☆

Résumé

Abstract

Introduction

Section snippets

Incidence des métastases cérébrales

Incidence des métastases cérébrales

Incidence des métastases cérébrales

Facteurs de risque possibles de métastases cérébrales

Métastases cérébrales secondaires à d’autres cancers primitifs

Scores pronostiques

Conclusion

Déclaration d’intérêts

Remerciements

Breast

Oncol

J Clin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Lung Cancer

Lung Cancer

Lung Cancer

Lung Cancer

Bull Cancer

Lancet Oncol

Lancet Oncol

Eur J Cancer

Urology

J Urol

J Urol

J Urol

Cancer Radiother

Clin Colorectal Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Brain metastases. Histology, multiplicity, surgery, and survival

Cancer

Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System

J Clin Oncol

Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma

Cancer

Central nervous system metastasis from breast carcinoma. Autopsy study

Cancer

Metastatic behavior of breast cancer subtypes

J Clin Oncol

Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases

Cancer

Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER

Clin Cancer Res

The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma

Cancer

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer

Br J Cancer

Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma

Cancer

Predictors of central nervous system metastasis in patients with metastatic breast cancer: a competing risk analysis of 579 patients treated with epirubicin-based chemotherapy

Breast Cancer Res Treat

The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer

J Neurooncol

Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis

Cancer

Revue générale
Épidémiologie des lésions métastatiques cérébralesEpidemiology of brain metastases☆