Brain metastases

Brain metastases

Despite the frequency of brain metastases, prospective trials in this patient population are limited, and the criteria used to assess response and progression in the CNS are heterogeneous 1).

This heterogeneity largely stems from the recognition that existing criteria sets, such as RECIST 2) 3).

Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.

Brastianos et al. detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases 4).










CDH2, KIFC1, and FALZ3




There is a lack of prospective randomized studies. Based on retrospective case series, international guidelines recommend the harvesting (if required, stereotactically guided) of tissue for histological and molecular diagnosis in cases of unknown or possibly competing for underlying systemic malignant diseases, in cases of suspected tumor recurrence, and with regard to the evaluation of targeted therapies taking into account molecular heterogeneity of primary and secondary tumors. Surgical resection is particularly valuable for the treatment of up to three space-occupying cerebral metastases, especially to achieve clinical stabilization to allow further non-surgical treatment For cystic metastasis, a combination of stereotactic puncture and radiotherapy may be useful. Meningeal carcinomatosis can be treated with intrathecal medication via an intraventricular catheter system. Ventriculoperitoneal shunts represent an effective treatment option for patients with tumor-associated hydrocephalus.

Neurosurgical procedures are of central importance in the multimodal treatment of cerebral metastases. The indications for neurosurgical interventions will be refined in the light of more effective radiation techniques and systemic treatments with new targeted therapeutic approaches and immunotherapies on the horizon 5).

Zhu et al. reported a medium-throughput drug screening platform (METPlatform) based on organotypic cultures that allow evaluating inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastases, they identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastases, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. The work validates METPlatform as a potent resource for metastases research integrating drug screening and unbiased omics approaches that are compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere 6).


NU Lin, EQ Lee, H Aoyama, et al. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group Lancet Oncol, 14 (2013), pp. e396–e406

EA Eisenhauer, P Therasse, J Bogaerts, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer, 45 (2009), pp. 228–247

P Therasse, SG Arbuck, EA Eisenhauer, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst, 92 (2000), pp. 205–216

Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG 2nd, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015 Sep 26. [Epub ahead of print] PubMed PMID: 26410082.

Thon N, Karschnia P, Baumgarten LV, Niyazi M, Steinbach JP, Tonn JC. Neurosurgical Interventions for Cerebral Metastases of Solid Tumors. Dtsch Arztebl Int. 2023 Mar 10;(Forthcoming):arztebl.m2022.0410. doi: 10.3238/arztebl.m2022.0410. Epub ahead of print. PMID: 36650742.

Zhu L, Retana D, García-Gómez P, Álvaro-Espinosa L, Priego N, Masmudi-Martín M, Yebra N, Miarka L, Hernández-Encinas E, Blanco-Aparicio C, Martínez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodríguez-Perales S; RENACER, Soffietti R, Bertero L, Cassoni P, Weiss T, Muñoz J, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez Á, Hernández-Laín A, Toldos O, Ruano Y, Alcázar L, Blasco G, Fernández-Alén J, Caleiras E, Lafarga M, Megías D, Graña-Castro O, Nör C, Taylor MD, Young LS, Varešlija D, Cosgrove N, Couch FJ, Cussó L, Desco M, Mouron S, Quintela-Fandino M, Weller M, Pastor J, Valiente M. A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med. 2022 Feb 17:e14552. doi: 10.15252/emmm.202114552. Epub ahead of print. PMID: 35174975.

Brain metastases treatment guidelines

Brain metastases treatment guidelines

Please see the full-text version of this guideline for the target population of each recommendation listed below.

SURGERY FOR METASTATIC BRAIN TUMORS AT NEW DIAGNOSIS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo Brain metastases surgeryStereotactic radiosurgery for brain metastases (SRS), or whole brain radiotherapy (WBRT)?


Level of Evidence 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survivalmedian survival, and local control.

Level of Evidence 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors

Level of Evidence 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits.

SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities?


Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases.

Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival.

Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT.

SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection?


Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS.   SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence?


Level 3: En bloc resection of the tumor, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases.


Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence?


Level 3: Gross total resection is recommended over subtotal resection in Recursive partitioning analysis class 1 class I patients to improve overall survival and prolong time to recurrence1)


Nahed BV, Alvarez-Breckenridge C, Brastianos PK, Shih H, Sloan A, Ammirati M, Kuo JS, Ryken TC, Kalkanis SN, Olson JJ. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors. Neurosurgery. 2019 Mar 1;84(3):E152-E155. doi: 10.1093/neuros/nyy542. PubMed PMID: 30629227.

Cystic brain metastases treatment

Cystic brain metastases treatment

When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decrease the chance of radiation-induced necrosis and provide symptomatic relief from the mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications for improving patient outcomes 1).

Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure 2).

Flickinger 3) reported that tumors with a cystic component greater than 10 mL did not appear to be effectively controlled by radiosurgery alone. Therefore, it is essential to decrease the volume of the cystic components before treating them with radiosurgery. The combination of cyst aspiration and radiosurgery is one possible method 4) 5) 6) 7) that may be more effective and safer than radiosurgery alone.

Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with aspiration, the target lesion tends to exceed the dimensions of an ideal target for stereotactic radiosurgery. In this case, the local tumor control rate and the risk of complication might be a critical challenge.

A study aimed to investigate whether fractionated GKRS (f-GKRS) could solve these problems. Between May 2018 and April 2021, eight consecutive patients with nine lesions were treated with f-GKRS in five or ten sessions after cyst aspiration. The aspiration was repeated as needed throughout the treatment course to maintain the cyst size and shape. The patient characteristics, radiologic tumor response, and clinical course were reviewed using medical records. The mean follow-up duration was 10.2 (2-28) months. The mean pre-GKRS volume and maximum diameter were 16.7 (5-55.8) mL and 39.0 (31-79) mm, respectively. The mean tumor volume reduction achieved by aspiration was 55.4%. The tumor volume decreased for all lesions, and symptoms were alleviated in all patients. The median overall survival was 10.0 months, and the estimated 1-year survival rate was 41.7% (95% CI: 10.9-70.8%). The local tumor control rate was 100%. No irradiation-related adverse events were observed. f-GKRS for aspirated cystic brain metastasis is a safe, effective, and less invasive management option for large cystic brain metastases 8).


Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. PMID: 25977901; PMCID: PMC4426272.

Lv J, Wu Z, Wang K, Wang Y, Yang S, Han W. Case Report: Clinical and Procedural Implications of Ommaya Reservoir Implantation in Cystic Brain Metastases Followed by Radiosurgery Treatment. Front Surg. 2022 May 16;9:901674. doi: 10.3389/fsurg.2022.901674. PMID: 35651693; PMCID: PMC9149303.

Flickinger JC. Radiotherapy and radiosurgical management of brain metastases. Curr Oncol Rep. 2001 Nov;3(6):484-9. doi: 10.1007/s11912-001-0069-5. PMID: 11595116.

Loeffler JS, Barker FG, Chapman PH. Role of radiosurgery in the management of central nervous system metastases. Cancer Chemother Pharmacol. 1999;43 Suppl:S11-4. doi: 10.1007/s002800051092. PMID: 10357553.

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated. Stereotact Funct Neurosurg. 1999;72(Suppl 1):38–44.

Niranjan A, Witham T, Kondziolka D, Lunsford LD. The role of stereotactic cyst aspiration for glial and metastatic brain tumors. Can J Neurol Sci. 2000;27:229–235.

Uchino M, Nagao T, Seiki Y, Shibata I, Terao H, Kaneko I. [Radiosurgery for cystic metastatic brain tumor] No Shinkei Geka. 2000;28:417–421.

Noda R, Akabane A, Kawashima M, Oshima A, Tsunoda S, Segawa M, Inoue T. Fractionated Gamma Knife radiosurgery after cyst aspiration for large cystic brain metastases: case series and literature review. Neurosurg Rev. 2022 Jul 14. doi: 10.1007/s10143-022-01835-y. Epub ahead of print. PMID: 35834076.

Meningioma metastases

Meningioma metastases

Although meningiomas are usually benign, malignant meningiomas with distant metastases occur infrequently. There is little precise information in the literature regarding the frequency of metastases in meningiomas; their incidence has been vaguely reported to be less than 1 per 1,000. Furthermore, most of the previous studies have also included haemangiopericytomas which most recent authorities do not consider meningiomas.

Enam et al. published the management of 396 meningiomas over the past 18 years, 7 meningiomas were classified as malignant by defined histological criteria. After initially presenting as solitary intracranial neoplasms, three of the malignant meningiomas metastasized to extracranial tissues. Collectively, the metastases involved the vertebral bodies, liver, pelvis, long bones, and the spinal cord. This confers an incidence of metastasis of 0.76% when considering all the meningiomas, and an incidence of approximately 43% when considering only malignant meningioma; both percentages are significantly higher than reported previously. This high incidence of metastasis in the malignant meningioma indicates a worse prognosis than formerly assessed and also characterized the malignant meningioma as a primary central nervous system neoplasm with one of the highest rates of metastasis. In addition, when malignant meningioma is classified by following strict criteria, the risk of metastasis in the ensuing clinical course can be predicted with a higher reliability 1).

Systemic imaging of patients with multiply recurrent meningioma or symptoms concerning metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision-making for additional treatments 2).

Primary intracranial meningioma is typically reported as having low FDG uptake, because glucose metabolism in meningioma is similar to that of surrounding tissue 3).

There have been a few isolated reports describing the imaging features of metastatic meningioma on FDG-PET imaging. Ghodsian et al., described a moderately hypermetabolic sacral metastatic mass by FDG-PET/CT. This was a Grade III malignant meningioma on histology 4).

Meirelles et al., described a pulmonary meningioma that manifested as a solitary pulmonary nodule and had very high metabolic activity on PET scan. The current case also showed avid uptake of FDG; the SUV was >7 in each pulmonary lesion. The uptake was more avid in the periphery and slightly less in the centre of both lesions, corresponding to the central areas of low density on CT. It was useful to note that there were no other foci of abnormal FDG uptake elsewhere to suggest other metastases. It is reassuring to note that 10 months after the PET/CT with clinical follow-up, the patient remains asymptomatic with no evidence of local or distant spread. The diagnosis of pulmonary metastatic meningioma was confirmed histologically by CT-guided percutaneous biopsy, which has been previously reported 5).

A patient with multiply recurrent orbital meningioma with metastasis to the neck was found incidentally during neck exploration for composite resection and free tissue reconstruction.

Nguyen et al. performed a systematic review for all records pertaining to metastatic meningiomas to the cervical regions.

They found 9 previous reports of cervical metastatic meningiomas. Almost all cases underwent extensive local resection. There was no evidence of an association between the histological grade of the tumor and the risk of metastasis to the neck. Cervical lymph node dissemination is more common in patients presenting after previous primary tumor resection.

In the context of a neck mass, the findings suggest that metastatic meningioma should be included in the differential diagnosis, especially in patients with previous resections 6).

a 78-year-old man with a history of recurrent World Health Organization grade I meningioma managed who presented for evaluation of weakness and urinary retention. A computed tomography scan obtained in the emergency department revealed multiple scattered low-density liver lesions. Subsequent magnetic resonance imaging showed a 5.5-centimeter heterogeneous enhancing mass with 2 smaller enhancing lesions suspicious for a primary or secondary malignant neoplasm. Microscopic examination of a tissue sample obtained via liver biopsy demonstrated a metastatic spindle cell neoplasm with histologic features compatible with a diagnosis of World Health Organization grade I transitional meningioma. The patient was referred to hematology/oncology for systemic therapy 7).

A 54-year-old female who presented with an incidental liver mass by ultrasound. Her clinical history and physical examination were unremarkable. A partial hepatectomy revealed a meningioma on histology. Further investigation by imaging studies showed a frontal parasagittal dural mass which was confirmed to be a World Health Organization (WHO) grade 1 meningioma. To our knowledge, this is the first report of a clinically silent metastatic meningioma to the liver without either a concurrent or a previous history of meningioma. Precise diagnosis of this challenging case requires high clinical suspicion, histopathology, and immunohistochemistry 8).

A case of a 58 year old man who presented with a mobile mass within the left trapezius muscle. The patient had previously undergone surgery for a right frontal lobe high grade anaplastic meningioma. Histology of the soft tissue lesion showed metastatic anaplastic meningioma with clumps of pleomorphic tumour cells which expressed epithelial membrane antigen, cytokeratin and P63 but were negative for other epithelial and mesenchymal markers. A PET-CT scan revealed additional metastatic lesions in the left pleura, liver and iliac bone.

Conclusions: Metastatic malignant meningioma can very rarely present as a high grade pleomorphic malignant soft tissue tumour and needs to be distinguished from soft tissue sarcomas and metastatic carcinomas that express epithelial antigens 9).

Mutnuru PC, Ahmed SF, Uppin SG, Lachi PK. Pulmonary metastases from intracranial meningioma. Lung India. 2015 Nov-Dec;32(6):661-3. doi: 10.4103/0970-2113.168120. PMID: 26664187; PMCID: PMC4663884.

a patient who was treated for an atypical brain meningioma with multiple surgeries and multiple sessions of stereotactic radiosurgery with good control of his brain disease. Thirteen years after diagnosis, he developed bilateral large sacroiliac and abdominal metastases 10).

a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He was reoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorsolumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwent T11 total en bloc spondylectomy (Tomita’s procedure), fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I).

Discussion: Distant metastases from intracranial meningiomas are rare entities, arising from benign lesions in, at least, 60% of cases. Enam et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40% in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson’s perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease 11).


Enam SA, Abdulrauf S, Mehta B, Malik GM, Mahmood A. Metastasis in meningioma. Acta Neurochir (Wien). 1996;138(10):1172-7; discussion 1177-8. doi: 10.1007/BF01809747. PMID: 8955436.

Dalle Ore CL, Magill ST, Yen AJ, Shahin MN, Lee DS, Lucas CG, Chen WC, Viner JA, Aghi MK, Theodosopoulos PV, Raleigh DR, Villanueva-Meyer JE, McDermott MW. Meningioma metastases: incidence and proposed screening paradigm. J Neurosurg. 2019 Apr 5;132(5):1447-1455. doi: 10.3171/2019.1.JNS181771. PMID: 30952122.

Kaminski JM, Movsas B, King E, Yang C, Kronz JD, Alli PM, et al. Metastatic meningioma to the lung with multiple pleural metastases. Am J Clin Oncol 2001;24:579–82

Ghodsian M, Obrzut SL, Hyde CC, Watts WJ, Schiepers C. Evaluation of metastatic meningioma with 2-deoxy-2-[18F] fluoro-d-glucose PET/CT. Clin Nucl Med 2005;30:717–20

Brennan C, O’Connor OJ, O’Regan KN, Keohane C, Dineen J, Hinchion J, Sweeney B, Maher MM. Metastatic meningioma: positron emission tomography CT imaging findings. Br J Radiol. 2010 Dec;83(996):e259-62. doi: 10.1259/bjr/11276652. PubMed PMID: 21088084; PubMed Central PMCID: PMC3473618.

Nguyen HCB, Mady LJ, Panara K, Andrianus S, Cooper K, Chen IH, Chalian AA, Brody RM. Metastatic Meningioma of the Neck: A Case Report and Systematic Review. ORL J Otorhinolaryngol Relat Spec. 2022 Feb 3:1-9. doi: 10.1159/000521076. Epub ahead of print. PMID: 35114675.

Beutler BD, Nguyen ET, Parker RA, Tran C, Acharya J, Torres FA, Gullapalli N. Metastatic meningioma: Case report of a WHO grade I meningioma with liver metastases and review of the literature. Radiol Case Rep. 2019 Nov 15;15(2):110-116. doi: 10.1016/j.radcr.2019.10.027. PMID: 31762868; PMCID: PMC6864214.

Obiorah IE, Ozdemirli M. Incidental Metastatic Meningioma Presenting as a Large Liver Mass. Case Reports Hepatol. 2018 May 7;2018:1089394. doi: 10.1155/2018/1089394. PMID: 29854500; PMCID: PMC5964563.

McCarthy C, Hofer M, Vlychou M, Khundkar R, Critchley P, Cudlip S, Ansorge O, Athanasou NA. Metastatic meningioma presenting as a malignant soft tissue tumour. Clin Sarcoma Res. 2016 Dec 30;6:23. doi: 10.1186/s13569-016-0063-1. PMID: 28042470; PMCID: PMC5200959.

Abboud M, Haddad G, Kattar M, Aburiziq I, Geara FB. Extraneural metastases from cranial meningioma: a case report. Radiat Oncol. 2009 Jul 6;4:20. doi: 10.1186/1748-717X-4-20. PMID: 19580667; PMCID: PMC2717105.

Delgado-López PD, Martín-Velasco V, Castilla-Díez JM, Fernández-Arconada O, Corrales-García EM, Galacho-Harnero A, Rodríguez-Salazar A, Pérez-Mies B. Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature. Neurocirugia (Astur). 2006 Jun;17(3):240-9. doi: 10.1016/s1130-1473(06)70346-3. PMID: 16855782.

Intracranial metastases surgery

Intracranial metastases surgery

see Intracranial metastases surgery indications.

Intracranial Metastases Surgical Technique.

Automated classification of brain metastases and healthy brain tissue is feasible using optical coherence tomography imaging, extracted texture features, and machine learning with principal component analysis (PCA) and support-vector machines (SVM). The established approach can prospectively provide the surgeon with additional information about the tissue, thus optimizing the extent of tumor resection and minimizing the risk of local recurrences 1).

Wolpert et al. defined risk profiles for the development of BM-related epilepsy and derived a score which might help to estimate the risk of post-operative seizures and identify individuals at risk who might benefit from primary prophylactic antiepileptic drug therapy 2).


Möller J, Bartsch A, Lenz M, Tischoff I, Krug R, Welp H, Hofmann MR, Schmieder K, Miller D. Applying machine learning to optical coherence tomography images for automated tissue classification in brain metastases. Int J Comput Assist Radiol Surg. 2021 May 30. doi: 10.1007/s11548-021-02412-2. Epub ahead of print. PMID: 34053010.

Wolpert F, Lareida A, Terziev R, Grossenbacher B, Neidert MC, Roth P, Poryazova R, Imbach L, Le Rhun E, Weller M. Risk factors for the development of epilepsy in patients with brain metastasis. Neuro Oncol. 2019 Sep 10. pii: noz172. doi: 10.1093/neuonc/noz172. [Epub ahead of print] PubMed PMID: 31498867.

Bone metastases

Bone metastases

The most frequent site of bone metastases are vertebral metastases, likely related to the high hematopoietic activity and vascularization of the spine 1).

The spine is the commonest site for bone metastases, and the incidence of spinal metastases is increasing 2).

Approximately two-thirds of cancer patients will develop bone metastases and it is estimated that over 10% of patients with cancer will develop symptomatic spinal metastases.

More than 50% of patients with spinal metastases have multiple levels involved.

see Skull metastases

see Spinal metastases

Cancer cells that break off from a primary tumor and enter the bloodstream or lymph vessels can reach nearly all tissues of the body. Bones are a common place for these cancer cells to settle and start growing. Tumors that result from these cells entering the bones are called bone metastases.

Presence of bone metastases at baseline was associated with a worse prognosis for patients with Non-Small Cell Lung Cancer treated with Immune Checkpoint Inhibitor after controlling for multiple clinical characteristics. Use of bone-modifying agents (BMAs) was not associated with reduced skeletal-related events (SREs) or a difference in survival 3).

see 18F positron emission tomography for bone metastases.

For pain Steroids, aspirin, or NSAIDs are especially helpful, probably by reducing prostaglandin mediated sensitization of A-delta and C fibers, and therefore may be preferred to acetaminophen.


Husband DJ. Malignant spinal cord compression: Prospective study of delays in referral and treatment. BMJ 1998; 317:18-21.

Hatrick NC, Lucas JD, Timothy AR, Smith MA. The surgical treatment of metastatic disease of the spine. Radiother Oncol. 2000 Sep;56(3):335-9. PubMed PMID: 10974383.

Qin A, Zhao S, Miah A, Wei L, Patel S, Johns A, Grogan M, Bertino EM, He K, Shields PG, Kalemkerian GP, Gadgeel SM, Ramnath N, Schneider BJ, Hassan KA, Szerlip N, Chopra Z, Journey S, Waninger J, Spakowicz D, Carbone DP, Presley CJ, Otterson GA, Green MD, Owen DH. Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors. J Natl Compr Canc Netw. 2021 Apr 20:1-7. doi: 10.6004/jnccn.2020.7668. Epub ahead of print. PMID: 33878726.

Pituitary metastases

Pituitary metastases

Although rare, metastatic involvement of the pituitary gland has been reported with increasing frequency during the last decades. Pituitary metastasis can be the initial presentation of an otherwise unknown malignancy and should be considered in the differential diagnosis of pituitary lesions, irrespective of a history of malignancy. The sudden onset and rapid progression of visual or endocrine dysfunction from a pituitary lesion should strongly raise the suspicion of metastatic disease. MRI features of pituitary metastasis can overlap with those of other pituitary lesions, including hypophysitis; however, rapid pituitary growth is highly suggestive of metastatic disease. Survival after pituitary metastasis detection has improved over time, encouraging individualized interventions directed to metastasis to improve quality of life and increase survival 1).

Pituitary metastases (PM) is a rare complication of advanced malignancy, first reported by L. Benjamin in 1857 as a case of melanoma spread to the pituitary identified in an autopsy 2) and later in 1913Cushing 3) reported this unique phenomenon as the cause of diabetes insipidus.

Pituitary metastases epidemiology.

see Breast cancer pituitary metastases.

see Lung cancer pituitary metastases.

The most common primary malignancies to be found in the pituitary are breast cancer in women and lung cancer in men, presumably merely due to a large number of cerebral metastases from these two cancers . Many other primary tumours have also been described.

It is interesting to note that the posterior lobe and the infundibulum of the pituitary gland are more frequently involved than the anterior lobe (although this may not be the case in breast cancer). Presumably due to the fact that the anterior pituitary receives its blood via the portal circulation rather than directly from the hypophyseal arteries.

Pituitary metastases clinical features.

Pituitary metastases diagnosis.

Pituitary metastases differential diagnosis.

Pituitary metastases treatment.

Pituitary metastases outcome.

A systematic review was performed according to PRISMA recommendations. All cases of MP were included, excepted primary pituitary neoplasms and autopsy reports. Descriptive and survival analyses were then conducted.

The search identified 2143 records, of which 157 were included. A total of 657 cases of MP were reported, including 334 females (50.8%). The mean ± standard deviation age was 59.1 ± 11.9 years. Lung cancer was the most frequent primary site (31.0%), followed by breast (26.2%) and kidney cancers (8.1%). Median survival from MP diagnosis was 14 months. Overall survival was significantly different between lung, breast and kidney cancers (P < .0001). Survival was impacted by radiotherapy (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.35-0.67; P < .0001) and chemotherapy (HR 0.58; 95% CI 0.36-0.92; P = .013) but not by surgery. Stereotactic radiotherapy tended to improve survival over conventional radiotherapy (HR 0.66; 95% CI 0.39-1.12; P = .065). Patients from recent studies (≥ 2010) had longer survival than others (HR 1.36; 95% CI 1.05-1.76; P = .0019).

This systematic review based on 657 cases helped to better identify clinical features, oncological characteristics, and the effect of current therapies in patients with MP. Survival patterns were conditioned upon primary cancer histologies, the use of local radiotherapy and systemic chemotherapy, but not by surgery 4)

Pituitary metastases case series.

Pituitary metastases case reports.


Lopes AM, Pereira J, Ribeiro I, Martins da Silva A, Queiroga H, Amaral C. Pituitary metastasis unveiling a lung adenocarcinoma. Endocrinol Diabetes Metab Case Rep. 2021 Feb 26;2021:EDM200211. doi: 10.1530/EDM-20-0211. Epub ahead of print. PMID: 33865234.

Chiang MF, Brock M, Patt S. Pituitary metastases. Neurochirurgia (Stuttg). 1990 Jul;33(4):127-31. doi: 10.1055/s-2008-1053571. PMID: 2203980.

Cushing H. Concerning diabetes insipidus and the polyuria of the hypophysial origin. Boston Med Surg J. 1913;168(25):901–10.

Ng S, Fomekong F, Delabar V, Jacquesson T, Enachescu C, Raverot G, Manet R, Jouanneau E. Current status and treatment modalities in metastases to the pituitary: a systematic review. J Neurooncol. 2020 Jan;146(2):219-227. doi: 10.1007/s11060-020-03396-w. Epub 2020 Jan 13. PMID: 31933258.

Non-small cell lung cancer intracranial metastases treatment

Non-small cell lung cancer intracranial metastases treatment

Brain metastases are common in patients with non-small cell lung cancer (NSCLC). Because of associated poor prognosis and limited specific treatment options, there is a real need for the development of medical therapies and strategies for affected patients 1).

EGFR and ALK tyrosine kinase inhibitors (TKIs) provide significantly superior systemic response rates and progression free survival compared to standard chemotherapy in the molecularly defined Non-small cell lung cancer (NSCLC) subpopulations. An apparent intracranial activity of new generation TKIs triggered the discussion on their role in brain metastases in lieu of local therapies 2).

The discovery of Epidermal Growth Factor Receptor (EGFR)-activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPKAKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, cancer progresses. These activating gene mutations for the EGFR are present in 10-20% of lung adenocarcinomas. Approximately 3-7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway stimulates the proliferation of tumor cells and inhibits apoptosis. A new group of drugs-small-molecule tyrosine kinase inhibitors-has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases 3).

KPS score ≥ 70, RPA class I/II, and postoperative chemotherapy could benefit post-metastasectomy patients with brain metastases (BM) from Non-small cell lung cancer (NSCLC). Conversely, the initial onset of intracranial lesions is an unfavorable factor that increases the risk of death. These findings support the use of personalized therapy for patients with BM from NSCLC 4).

A article of Preusser et al., is the result of a round table discussion held at the European Lung Cancer Conference (ELCC) in Geneva in May 2017. Its purpose was to explore and discuss the advances in the knowledge about the biology and treatment of brain metastases originating from non-small cell lung cancer. The authors propose a series of recommendations for research and treatment within the discussed context 5).

PUBMEDEMBASE, the Cochrane LibraryWeb of Knowledge, Current Controlled Trials, Clinical Trials, and 2 conference websites were searched to select NSCLC patients with only single brain metastasis (SBM) who received brain surgery or SRS. SPSS 18.0 software was used to analyze the mean median survival time (MST) and Stata 11.0 software was used to calculate the overall survival (OS).

A total of 18 trials including 713 patients were systematically reviewed. The MST of the patients was 12.7 months in surgery group and 14.85 months in SRS group, respectively. The 1, 2, and 5 years OS of the patients were 59%, 33%, and 19% in surgery group, and 62%, 33%, and 14% in SRS group, respectively. Furthermore, in the surgery group, the 1 and 3 years OS were 68% and 15% in patients with controlled primary tumors, and 50% and 13% in the other patients with uncontrolled primary tumors, respectively. Interestingly, the 5-year OS was up to 21% in patients with controlled primary tumors.

There was no significant difference in MST or OS between patients treated with neurosurgery and SRS. Patients with resectable lung tumors and SBM may benefit from the resection of both primary lesions and metastasis 6).

Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms 7).

Response rates after platinum based antineoplastics, range from 23% to 45%. Development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): gefitinib or erlotinib, was an improvement in treatment of advanced NSCLC patients. EGFR mutations are present in 10-25% of NSCLC (mostly adenocarcinoma), and up to 55% in never-smoking women of East Asian descent. In the non-selected group of patients with BMF-NSCLC, the overall response rates after gefitinib or erlotinib treatment range from 10% to 38%, and the duration of response ranges from 9 to 13.5 months. In the case of present activating EGFR mutation, the response rate after EGRF-TKIs is greater than 50%, and in selected groups (adenocarcinoma, patients of Asian descent, never-smokers, asymptomatic BMF-NSCLC) even 70%. Gefitinib or erlotinib treatment improves survival of BMF-NSCLC patients with EGFR mutation in comparison to cases without the presence of this mutation. There is no data on the activity of the anti-EML4-ALK agent crizotinib. Bevacizumab, recombinant humanised monoclonal antibody anti-VEGF, in the treatment of advanced non-squamous NSCLC patients is a subject of intense research. Data from a clinical trial enrolling patients with pretreated or occult BMF-NSCLC proved that the addition of bevacizumab to various chemotherapy agents or erlotinib is a safe and efficient treatment, associated with a low incidence of CSN haemorrhages. However, the efficacy and safety of bevacizumab used for therapeutic intent, regarding active brain metastases is unknown 8).

see Non small cell lung cancer intracranial metastases whole brain radiotherapy

see Non small cell lung cancer intracranial metastases radiosurgery

see Non small cell lung cancer intracranial metastases surgery.


Bulbul A, Forde PM, Murtuza A, Woodward B, Yang H, Bastian I, Ferguson PK, Lopez-Diaz F, Ettinger DS, Husain H. Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer. Oncology (Williston Park). 2018 Apr 15;32(4):156-63. Review. PubMed PMID: 29684234.

Wrona A, Dziadziuszko R, Jassem J. Management of brain metastases in non-small cell lung cancer in the era of tyrosine kinase inhibitors. Cancer Treat Rev. 2018 Dec;71:59-67. doi: 10.1016/j.ctrv.2018.10.011. Epub 2018 Oct 21. Review. PubMed PMID: 30366200.

Rybarczyk-Kasiuchnicz A, Ramlau R, Stencel K. Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma. Int J Mol Sci. 2021 Jan 8;22(2):593. doi: 10.3390/ijms22020593. PMID: 33435596; PMCID: PMC7826874.

She C, Wang R, Lu C, Sun Z, Li P, Yin Q, Liu Q, Wang P, Li W. Prognostic factors and outcome of surgically treated patients with brain metastases of non-small cell lung cancer. Thorac Cancer. 2018 Nov 28. doi: 10.1111/1759-7714.12913. [Epub ahead of print] PubMed PMID: 30485664.

Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C. Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO Open. 2018 Jan 26;3(1):e000262. doi: 10.1136/esmoopen-2017-000262. eCollection 2018. Review. PubMed PMID: 29387475; PubMed Central PMCID: PMC5786916.

Qin H, Wang C, Jiang Y, Zhang X, Zhang Y, Ruan Z. Patients with single brain metastasis from non-small cell lung cancer equally benefit from stereotactic radiosurgery and surgery: a systematic review. Med Sci Monit. 2015 Jan 12;21:144-52. doi: 10.12659/MSM.892405. PubMed PMID: 25579245.

Kim SY, Hong CK, Kim TH, Hong JB, Park CH, Chang YS, Kim HJ, Ahn CM, Byun MK. Efficacy of surgical treatment for brain metastasis in patients with non-small cell lung cancer. Yonsei Med J. 2015 Jan 1;56(1):103-11. doi: 10.3349/ymj.2015.56.1.103. PubMed PMID: 25510753; PubMed Central PMCID: PMC4276743.

Cedrych I, Kruczała MA, Walasek T, Jakubowicz J, Blecharz P, Reinfuss M. Systemic treatment of non-small cell lung cancer brain metastases. Contemp Oncol (Pozn). 2016;20(5):352-357. doi: 10.5114/wo.2016.64593. Epub 2016 Dec 20. Review. PubMed PMID: 28373815; PubMed Central PMCID: PMC5371701.

Brain metastases from Head and Neck Cancer

Brain metastases from Head and Neck Cancer

Limited data is available on head and neck cancer (HNC) patients presenting with brain metastases (BM) at initial diagnosis.

Survival was significantly influenced by Eastern Cooperative Oncology Group (ECOG) performance score, number of cerebral lesions and extracranial metastatic disease. These characteristics were included in a score.

Scoring was based on 6-month survival data: ECOG 0-1=1 point, ECOG 2-3=0 points, 1-3 cerebral lesions=1 point, ≥4 cerebral lesions=0 points, lack of extracranial metastases=1 point, and presence of extracranial metastases=0 points. Addition of these points for each patient resulted in 0-3 points. Three groups were built comprising 0-1, 2 and 3 points. Six-month survival rates for these groups were 0%, 50% and 100%, respectively.

This instrument guides physicians in choosing optimal irradiation programs for patients with cerebral metastases from head-and-neck cancer 1),

Messing et al. sought to evaluate the incidencemanagement, and treatment outcomes of these patients using the National Cancer Database (NCDB).

They identified 465,925 patients diagnosed with HNC between 2010 and 2015 in the NCDB. 14,583 of these patients presented with metastatic disease to any site. 440 of these patients had BM at the time of initial diagnosis. Overall survival was compared using the Kaplan-Meier estimatorCox Proportional hazards modelpropensity score matching, and subgroup analyses were performed.

The median age overall was 62.0 years. Nasopharynx NOS (13.2%) and Parotid Gland (10.9%) were the most common anatomical sites with the highest frequency of BM. The overall median survival time was 7.1 months. Predictors for the presence of BM included distant metastasis to the bone, liver, or lung on univariate analysis, and bone or lung on multivariate analysis. High-risk Human Papilloma Virus status was associated with a lower chance of BM. No pattern was determined when comparing lymph node level involvement and BM. The median survival for patients receiving radiation therapy and multi-agent chemotherapy was 8.4 and 11.7 months, respectively. Immunotherapy administered as first course therapy did not influence median survival. Most patients received radiation (62.7%) therapy and chemotherapy (50.2%).

The data extracted and analyzed from the NCDB should work to aid in the surveillance and management of BM in patients with HNC 2).

Out of 9432 HNC patients, 88 patients developed BM (0.9%, median follow-up 3.4 years). On average, the BM were diagnosed 18.5 months after the primary diagnosis and tended to arise after distant metastases to extracranial sites (85%) such as the lungs (78%). At BM presentation, 84% were symptomatic and two thirds had a poor performance status (ECOG ≥ 2, 68%). The median post-BM survival was 2.5 months (95% CI 2.1-3.3 months). On multivariable analysis, management of BM with radiotherapy (RT) alone (3.3 months, 95% CI 2.3-4.6, p = 0.005) and RT with surgery (4.4 months, 95% CI 2.8-6.9, p < 0.001) was associated with longer survival compared to best supportive care alone (1.4 months, 95% CI 1.0-2.0 months). Age, sex, performance status, sub-localization of the primary HNC, presence of extracranial metastases, and number of intracranial metastases were not associated with post-BM survival (all p ≥ 0.05).

BM occur late in the course of HNC and carry a poor prognosis. Treatment with intracranial radiotherapy both with and without surgery was associated with improved survival 3).

see Brain metastases from Head and Neck squamous cell carcinoma.


Rades D, Dziggel L, Hakim SG, Rudat V, Janssen S, Trang NT, Khoa MT, Bartscht T. Predicting Survival After Irradiation for Brain Metastases from Head and Neck Cancer. In Vivo. 2015 Sep-Oct;29(5):525-8. PMID: 26359409.

Messing I, Goyal S, Sherman JH, Thakkar P, Siegel R, Joshi A, Goodman J, Ojong-Ntui M, Rao YJ. Incidence and Prognosis of Brain Metastases in Head and Neck Cancer Patients at Diagnosis. Laryngoscope. 2021 Feb 18. doi: 10.1002/lary.29448. Epub ahead of print. PMID: 33599979.

Liu AK, Wu J, Berthelet E, Lalani N, Chau N, Tran E, Hamilton SN. Clinical features of head and neck cancer patients with brain metastases: A retrospective study of 88 cases. Oral Oncol. 2021 Jan;112:105086. doi: 10.1016/j.oraloncology.2020.105086. Epub 2020 Nov 10. PMID: 33186892.

Brain metastases recurrence diagnosis

Brain metastases recurrence diagnosis

It is difficult to differentiate local brain metastases recurrence from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and Amino Acid Positron Emission tomography allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method.

Whereas positron emission tomography (PET) with the widely used 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) has low diagnostic accuracy after SRS, the use of radiolabelled amino acids or amino acid analogues such as L-methyl-11C-methionine (11C-MET) and O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) reaches sensitivity and specificity values in the range of 78 and 100 % rendering especially 18F-FET a highly reliable tracer in glioma imaging.

In patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, 18F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions 1).

Tran et al. performed a feasibility study to prospectively evaluate 11C methionine positron emission tomography and11C PBR28 positron emission tomography in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate tumor regrowth (TR) from radiation necrosis (RN).

Sequential imaging with dual tracers was well-tolerated. [11C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [11C]PBR28 was only accurate in 3/7 lesions. Tumor PBRTSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [11C]PBR28-PET.

Sequential use of PET tracers is safe and effective. [11C]Methionine was a reliable TR marker, but [11C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging 2).

The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains 3).

An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases. 4).


Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn JC, Nachbichler SB, Muacevic A, Bartenstein P, Kreth FW, Albert NL. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties? Radiat Oncol. 2016 Oct 21;11(1):139. doi: 10.1186/s13014-016-0713-8. PMID: 27769279; PMCID: PMC5073742.

Tran TT, Gallezot JD, Jilaveanu LB, Zito C, Turcu G, Lim K, Nabulsi N, Huang H, Huttner A, Kluger HM, Chiang VL, Carson R. [11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis. Mol Imaging. 2020 Jan-Dec;19:1536012120968669. doi: 10.1177/1536012120968669. PMID: 33147119.

Patsouris A, Augereau P, Tanguy JY, Morel O, Menei P, Rousseau A, Paumier A. [Differentiation from local tumour recurrence and radionecrosis after stereotactic radiosurgery for treatment of brain metastasis.]. Cancer Radiother. 2014 Jan 13. pii: S1278-3218(13)00444-7. doi: 10.1016/j.canrad.2013.10.013. [Epub ahead of print] French. PubMed PMID: 24433952.

Bette S, Gempt J, Wiestler B, Huber T, Specht H, Meyer B, Zimmer C, Kirschke JS, Boeckh-Behrens T. Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases? Rofo. 2017 Jan;189(1):63-70. doi: 10.1055/s-0042-119686. PubMed PMID: 28002859.