Intracranial Metastases from Prostate Carcinoma: Classification, Management, and Prognostication

Journal Pre-proof Intracranial Metastases From Prostate Carcinoma: Classification, Management And Prognostication Mario Ganau, Paolo Gallinaro, Helene Cebula, Antonino Scibilia, Julien Todeschi, Arthur Gubian, Beniamino Nannavecchia, Francesco Signorelli, Raoul Pop, HugoAndres Coca, Francois Proust, Salvatore Chibbaro PII:

S1878-8750(19)32753-6

DOI:

https://doi.org/10.1016/j.wneu.2019.10.125

Reference:

WNEU 13596

To appear in:

World Neurosurgery

Received Date: 16 July 2019 Revised Date:

19 October 2019

Accepted Date: 21 October 2019

Please cite this article as: Ganau M, Gallinaro P, Cebula H, Scibilia A, Todeschi J, Gubian A, Nannavecchia B, Signorelli F, Pop R, Coca H-A, Proust F, Chibbaro S, Intracranial Metastases From Prostate Carcinoma: Classification, Management And Prognostication, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.10.125. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.

INTRACRANIAL

METASTASES

FROM

PROSTATE

CARCINOMA:

CLASSIFICATION, MANAGEMENT AND PROGNOSTICATION.

Mario GANAU1, Paolo GALLINARO1, Helene CEBULA1, Antonino SCIBILIA1, Julien TODESCHI1, Arthur GUBIAN1, Beniamino NANNAVECCHIA1, Francesco SIGNORELLI3, Raoul POP2, Hugo-Andres COCA1, Francois PROUST1, Salvatore CHIBBARO1. 1

Neurosurgery Department, Hautepierre University Hospital, Strasbourg, France

2

Neuroradiology Department, Hautepierre University Hospital, Strasbourg, France 3

Neurosurgery Department, Bari University Hospital, Italy

ABSTRACT Background: Prostate carcinomas very rarely metastasize to the central nervous system but, when they do, dural localizations are as common as and far more aggressive than intraparenchymal ones. Those metastases can be further classified according to their extension towards the subdural or extradural space, and can frequently simulate other pathological conditions, including chronic subdural hematomas, abscess and primary bone tumors. Beside the challenges of the preoperative differential diagnostic and the complexity of surgical planning and operative excision, subdural metastases seem to carry a much poorer prognosis. Methods: A series of consecutive patients admitted during a 12 years period through our oncall pathway for subdural/extradural collections or intraparenchymal lesions found, upon histological analysis, to represent intracranial prostate cancer metastases was retrospectively reviewed. 1

Results: A total of 19 patients were included, only 3 were diagnosed with small cell prostate carcinoma, while the majority had a primary prostate adenocarcinoma. Metastases could be classified as pure subdural space lesions, dural based lesions, extradural/bony lesions and pure intra-parenchymal lesions. All patients with subdural metastases, and 3 out of 5 patients with dural based lesions required an emergency intervention due to rapidly deteriorating neurological status. The mean follow-up in our series was 37 months; only subdural localizations had a remarkably unfavorable outcome. Conclusion: Supported by our experience and the review of the literature, we suggest that a low threshold for contrast-enhanced CT/MRI scans is advisable in case of suspicious subdural collection, even in an emergency-setting, for patient with previous medical history of prostate cancer.

Key words: Chronic Subdural Hematoma; Dura-mater Based Lesion; Meningioma; Metastasis; Prostate Carcinoma; Vault Osteolytic Lesion

INTRODUCTION Although prostate cancer usually metastasizes to the spine and lung,1-3 very rarely it also reaches the central nervous system (CNS); as such, the actual rate of intracranial prostate cancer metastases is estimated to range between 0.6 and 4.4%.4-9 The quite low occurrence of CNS involvement suggests that the brain parenchyma might be somehow resistant to the spreading of prostate carcinoma cells, probably due to the protection created by the blood brain barrier.3 Noteworthy, 2

prostate carcinomas are the most common primary tumors responsible for dural metastases.3 This physiophatology aspect has important implications in term of clinical presentation: in fact, given this tendency to infiltrate the dura mater and extend in the extra or subdural space, on plain CT head scan those lesions might be easily mistaken for subdural hematomas, abscesses or meningiomas.4-7,10 In the present study we describe a series of consecutive patients referred to our Institution during a period of 12 years for neurosurgical management of space occupying lesions diagnosed as intracranial metastases from prostate cancer (with or without a known clinical history of primary prostate tumor) after conclusive histological analysis of surgical specimens. The goal of this article is to describe in details the clinical features, imaging and surgical management of patients admitted through our Emergency Department or our oncall pathway, along with presenting a review of the pertinent literature. This descriptive approach will serve as the basis to provide some correlations between our proposal for a novel classification based on the anatomical localization of prostate metastases, and the related aspects of surgical management and prognostication of these rare but aggressive intracranial lesions.

PATIENTS AND METHODS A series of consecutive patients harboring intracranial prostate cancer metastases was retrospectively reviewed; all patients were prospectively enrolled and surgically managed during a 12 years period (from January 2006 to December 2017). Of note, while the fundamental criteria for inclusion in this study was the histological confirmation of intracranial metastases from prostate cancer, knowledge of primary prostate disease prior to the occurrence of these intracranial lesion/s was fairly rare. Since some of the lesions initially appeared to be unspecific subdural/extradural 3

collections, all patients underwent a CT head scan at time of diagnosis, but only those with intraparenchimal space occupying lesions had a preoperative MRI Head with contrast. A baseline disease staging with PSA dosage and CT Chest-AbdomenPelvis was conducted at time of admission if clinically feasible (patients with previous history of prostate cancer, or those with a suspicion of metastatic disease from an unknown primary tumor), or in the immediate postoperative period for all other patients once the diagnosis was established. All patients underwent postoperative brain MRI scan within 48 hours and continued with clinical and radiological follow up (FU) at 3, 6, 12 months, and afterwards every year where applicable. At each FU, overall clinical conditions were evaluated with the Karnofsky Performance Scale (KPS). Variables investigated as independent predictors of subdural location of prostate cancer metastases were age at diagnosis, histotype of prostate cancer, evidence of primary prostate cancer at time of surgery, pre-existent metastases to other organs, PSA values. To shed light on the natural history of this disease, the above variables were correlated for prognostication purposes to postoperative factors such as: length of disease-free survival and time to death. Statistical analysis included a univariate analysis with the Fisher exact test, as well as a multivariate analysis performed through a multiple logistic regression method. To this extent, variables were converted into binary categories to be analyzed in the logistic regression model. Dichotomic variables included all the independent factors predictors of subdural location except for age at time of diagnosis and baseline PSA values. As such, for non-dichotomic variables cut-off values were selected on the basis of clinical and literature criteria as follows: age (<=55 years and >55 years), baseline PSA values (<=4 ng/dl and >4 ng/dl). Statistical significance was defined as a p value <0.05 and the values of Odds Ratio (OR) for each variable were stated.

4

Univariate analysis was performed by using GraphPad Prism version 6.00 for Windows, GraphPad Software, La Jolla, California, USA, www.graphpad.com. The multivariate analysis was accomplished by using the STATCALC 8.2.2 software, AcaStat, Poinciana, Fl, www.acastat.com.

RESULTS A total of 19 patients fulfilled the inclusion criteria and were considered for this retrospective analysis (see Table 1). According to their anatomical localization these metastases could be classified as follows: pure subdural space lesions (7 patients), dural based lesions with surrounding edema causing mass effect on the adjacent brain parenchyma (5 patients), extradural/bony lesions (2 patients), and pure intraparenchymal lesions (5 patients). All patients with subdural metastases, and 3 out of 5 patients with dural based lesions required an emergency treatment due to rapidly deteriorating neurological status. The 2 patients with extradural/bony involvement presented with extensively invasive, almost hemispheric, lesions; finally, intraparenchymal lesions appeared as isolated or multiple metastases with a predominant involvement of the supratentorial (4 cases) versus the infratentorial space (1 case only). Gross total resection was achieved in all patients and was always followed by adjuvant treatment either in form of whole brain radiation (9 patients) or gamma knife stereotactic radiosurgery (10 patients). Of note, only 3 patients were diagnosed with small cell prostate carcinoma, while the majority of our patients had a primary prostate adenocarcinoma. The mean follow up (FU) in our series was 37 months (range: 6 to 132 months). Unfortunately, 9 patients passed away due to disease progression (three at 6 months, two at 10 months, two at 14 months, one at 19 months and the last one at 22 months postoperatively); all 5

the other 10 patients are still alive in good condition with a mean KPS of 80% (range: 60 to 100%) at time of most recent FU: the median disease free survival for this subgroup of patient is 39 months (SD 44 + 5 months). By analyzing the clinical data pertaining to those 19 cases it was noticed that the mean delay between prostate cancer diagnosis and intracranial metastases was 57 months in the 9 patients known to have a prostate cancer, meaning that the intracranial metastases represented the first evidence of a primary prostatic tumor in the majority of the patients in our series. The staging process, conducted either in the preoperative or early postoperative period, revealed in 11 out 19 patients other extracranial metastatic lesions. The statistical analysis of the 19 patients included in this study showed a significantly different behavior between the 7 patients (37%) harboring a subdural metastasis and the rest of our cohort. Subdural localization – oriented analysis The univariate analysis showed that a subdural localization correlated significantly with specific baseline and postoperative characteristics, namely: age < 55 years (p=0.003), a history of prostate cancer at time of diagnosis (p<0.0007), a multi-organ metastatic disease (p< 0.01), a baseline PSA value higher than 4ng/ml (p< 0.01). Additionally, subdural lesions had a remarkably unfavorable outcome (p< 0.0007): unfortunately, all patients harboring them passed away within few months from the surgical excision, despite adjuvant treatments. The multivariate analysis confirmed that prostate adenocarcinoma (p<0.00000; OR 0,0001), a clinical history of prostate cancer at time of diagnosis (p<0.00000; OR 28662,9), the evidence of extracranial metastases at time of diagnosis (p<0.00000; OR 0,0064), and a PSA value higher than 4ng/ml (p< 0,0014; OR 0,0687), were all

6

independent factors related to the subdural localization of the intracranial metastases. Finally, this type of localization had an OR of 28662,9 for an unfavorable outcome (p<0.00000).

DISCUSSION Although prostate carcinoma is the second most common malignancy in males, metastatic prostate adenocarcinoma to the CNS is a rare occurrence.1-8 In a large review of 16.280 patients with prostate cancer, only 0.63% were found to have brain metastases, nonetheless autopsy studies highlighted that the frequency of cerebral metastasis in patients with prostate cancer can range between 1 and 6%.1 Because of the constant progresses in medical oncology, and in particular the diffusion of hormonal therapies and immunotherapy protocols the prevalence of men with intracranial metastases from prostate cancer is increasing. As such, while CNS metastases from prostate carcinoma have been so far considered as a terminal event, with an estimated median of survival of 3.5 months despite adjuvant radiotherapy,1-3 this assumption may not hold true in the future. Among the intracranial localization of metastatic prostate cancer (Figure 1), the dura mater is usually the most common site, accounting for 67% of intracranial secondarisms.1-9 In 25% of cases the lesion infiltrates the cerebral cortex, whilst involvement of the posterior fossa is even rarer, with the cerebellar hemispheres affected in only 8% of cases.9,11 The present series is in keeping with the data from the literature: 37% of patients harbored a subdural lesion, versus 53.5% with intraparenchymal and 9.5% with extradural/bony localizations, respectively. Prostatic carcinoma usually metastasizes via hematogenous or lymphatic spreading. Three different mechanisms have been proposed for CNS metastases: 1) tumor 7

embolism going through a patent foramen ovale, hence bypassing the lung, 2) cancer cells gaining the lung capillary, passing in left heart and subsequently spreading through arterial blood, 3) secondary spreading from lung metastases.4,9,1222

The low rate of intracranial lesions and their typical localization in the dural layers

or subdural space suggests that such migration results from a compromised bloodbrain barrier or a depressed immune function in the late stages of the disease.9 Interestingly in cases with subdural disease, the dura mater, which should act as a barrier to metastatic penetration, despite infiltrated is usually well preserved.12 Of note, dural localizations of metastases arising from prostate cancer have been duly described in the literature, in most cases mimicking a subdural or epidural hematoma without being associated with intraoperative evidence of a proper fluid collection in the surgical site.10,23-28 Whereas in one report, prostate adenocarcinoma was eventually found to be metastatic to membranes of a true chronic subdural hematoma (CSDH).29 Additionally, it is important to mention that oftentimes the osteoblastic changes induced on the dural layers can mimic meningiomas.30 Regarding the association between CSDH and metastatic localization of prostate cancer the following mechanisms can be considered responsible for their origin: 1) hemorrhagic effusion from dural metastases, 2) hemorrhagic evolution of a dural venous obstruction, and 3) dural angio-desmoplastic reaction to tumoral invasion.31 Whereas many neurosurgical pathologies can present as a surgical emergency understanding the natural history of each disease is pivotal to optimize their management: it should be kept in mind that dural metastases can be indolent for long time and usually present as a late neoplastic manifestation. In the differential diagnosis of subdural collections, without any history of relatively recent head injuries (as in the case of CSDH) or red flags for infections (i.e. immunodeficiency, recent

8

otitis, dental surgery, important and chronic steroid treatments, recent craniotomies, etc), a rigorous clinical and radiological workup is of the utmost importance.32 Therefore, few take home messages can be drawn from this series. Firstly, upon admission to Emergency Department, a thorough recording of the previous medical history is the cornerstone to expedite the early phases of the clinical and radiological management of those challenging cases. Secondly, given the likelihood for acute clinical deterioration and the risk of brain herniation, additional investigations like MRI scans cannot be wisely advocated. This said, a contrast-enhanced CT head scan is always advisable, even in emergency case, for patients with atypical imaging and/or in whom dural metastasis can be suspected.33 Thirdly, a solid infiltrating dural lesion extending into the subdural or extradural space and characterized by homogeneous post-contrast enhancement may in fact raise suspicion since posttraumatic subdural or extradural hematomas, either acute or chronic, very rarely enhance. Also, this would help differentiating other subdural collections like subdural/extradural empyema or granuloma, in which only the surrounding membrane enhances intensely and uniformly.32 Overall, the present series highlights also the importance of considering the broad differential diagnosis of CSDH which includes lymphoma, neuro-sarcoidosis, tuberculosis and secondarisms especially from melanoma, breast and prostate cancers.7,12-14,34,35 Additional neuroradiology or nuclear medicine investigations can be helpful when it comes to fine tuning the treatment depending on the nature of the lesion. Again, it is worth stressing the importance of considering them only in nonurgent cases.15 For instance, MRI scan with multi-planar imaging can be used in elective cases or postoperatively to provide a better resolution than the CT study and to detect smaller brain metastatic lesions not identifiable otherwise; PET scans could

9

be of great help in understanding the nature of dural infiltrating lesions, especially in cases where the primary tumor is not known.15 Finally, it is worth remembering that from a clinical perspective the headache is the most common and unspecific symptom, being variably associated to a decreased level of consciousness due to any pathology triggering a raise in intracranial pressure. Cranial nerve involvement as well as facial sensory disturbances can be clinical features of this disease and they could be the result of skull base invasion.16,17 Furthermore, our series confirms that prostate metastases tend to localize in the supratentorial space, possibly due to the gradient in terms of physiologic vascular supply across the tentorium.24 Following a review of the pertinent literature and considering the results of the present study, we may affirm that surgery play an important role in the management of such patients and it should constitute the treatment of choice for accessible lesions in patients with a good functional status. Our results showed that surgery and radiosurgery are really effective to manage intracranial metastases, with remarkable improvement in the patient's quality of life. Adjuvant oncological treatments are the only ones able to prevent disease progression, and responsible for the increase in disease-free survival reported in more recent publications. In fact, also in our series all deaths in our series occurred as a result of systemic spreading despite complete control of the brain pathology. Our analysis demonstrated that an age < than 55 years, a PSA rate > than 4ng/ml and a subdural localization are unfavorable prognostic factor and highlights the importance of using biomarkers for disease stratification and prognostication in the decision-making process.18 In conclusion, surgery should be advocated when feasible with acceptable risks of morbidity; on the other hand, neurosurgeons should be more cautious in patients harboring deep or critically located lesions, for which radiosurgery could represent a

10

safer and more valuable alternative.19-22,36,37 While our review of the literature does not allow to draw a definitive conclusion on whether patients with intracranial metastases from prostate cancer should be offered whole brain radiotherapy or stereotactic radiosurgery, some randomized controlled trials (i.e. NCT00377156) as well as post-hoc analysis of existing radiation therapy registries (i.e. The RSSearch™ Registry) will hopefully answer this question in due time.38-40 In light of the results described in this article, indicating that the prognosis for isolated intraparenchymal lesions might not be as dismal as previously thought, in our Institution we are currently considering these patients, including the ones electively referred for surgical excision, for a tailored adjuvant radiation therapy and spared them from all the side effects of postoperative whole brain irradiation.

Limitation of this study: This series describes all patients admitted to our Institution via our oncall pathway for intracranial space occupying lesions requiring neurosurgical management and later found to be expression of intracranial spreading of prostate cancer. Despite the inner limitation of a single centre study, including the relatively small size of our cohort, the statistical analysis conducted points out a clear behavior pattern of subdural localizations. Few aspects deserve particular consideration: one pertains to the fact that, being exclusively admitted through our Emergency Department, those patients represent a different population compared to the ones referred through the standard oncology pathway and operated or conservatively treated after discussion in a neurooncology multidisciplinary meeting. Hence patients selection might have introduced a bias that justify a slightly different behavior from that usually described in the literature. The second consideration is that while our findings can be used for 11

generation of future research ideas (i.e. regarding usefulness of our anatomical classification for prognostication purposes, responsiveness of dural lesions to adjuvant treatments, etc) one should be careful in over-investigating every patient with CSDH attending Emergency Department, or blindly making inferences on every patient with prostate cancer presenting with headache.

CONCLUSION Intracranial and especially dural metastases should be suspected in all patients with previous history of malignant tumors known for their tendency to give dural secondarisms (like melanoma, prostate and breast cancers). Given the above, a low threshold for contrast-enhanced CT head scan is advisable, even in an emergencysetting. Management of such pathological entities consist essentially in surgical resection

associated

to

high-dose

corticosteroids

and

whole-brain

radiotherapy/stereotactic radiosurgery in the attempt of improving the overall survival which is unfortunately still of few weeks/months in case of advanced systemic disease.

Declarations of interest: none. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors:

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Tasaki K, Shima T, Matsumura S, et al. [A case of subdural effusion secondary to dural metastasis of prostatic cancer: case report]. No Shinkei Geka. 1990;18(6):539-542. Cheng YK, Wang TC, Yang JT, Lee MH, Su CH. Dural metastasis from prostatic adenocarcinoma mimicking chronic subdural hematoma. J Clin Neurosci. 2009;16(8):10841086. Tomlin JM, Alleyne CH. Transdural metastasis from adenocarcinoma of the prostate mimicking subdural hematoma: case report. Surg Neurol. 2002;58(5):329-331; discussion 331. O'Meara C, Mahasneh T, Wilson P, I'Ons B, Alkhawaja D. Dural prostate metastasis resembling a chronic subdural haematoma. J Surg Case Rep. 2012;2012(5):7. Patil S, Veron A, Hosseini P, et al. Metastatic prostate cancer mimicking chronic subdural hematoma: a case report and review of the literature. J La State Med Soc. 2010;162(4):203205. Dorsi MJ, Zenonos G, Hsu W, Huang J. Dural prostate adenocarcinoma metastasis with subdural hematoma mimicking the appearance of an epidural hematoma. Clin Neurol Neurosurg. 2010;112(6):501-504. Cheng CL, Greenberg J, Hoover LA. Prostatic adenocarcinoma metastatic to chronic subdural hematoma membranes. Case report. J Neurosurg. 1988;68(4):642-644. Kwee IL, Nakada T, St John JN. Triple fossa metastasis of prostate cancer. Neurosurgery. 1983;13(5):584-586. Leech RW, Welch FT, Ojemann GA. Subdural hematoma secondary to metastatic dural carcinomatosis. Case report. J Neurosurg. 1974;41(5):610-613. Ganau M, Nicassio N, Tacconi L. Postoperative aseptic intracranial granuloma: the possible influence of fluid hemostatics. Case Rep Surg. 2012;2012:614321. Ganau L, Prisco L, Ganau M. High altitude induced bilateral non-traumatic subdural hematoma. Aviat Space Environ Med. 2012;83(9):899-901. Sweets T, Bracken RB, Geisler EJ, Warnick R. Intracranial treatment for solitary prostatic adenocarcinoma brain metastasis is curative. Urology. 2009;73(3):681 e687-689. Tagle P, Villanueva P, Torrealba G, Huete I. Intracranial metastasis or meningioma? An uncommon clinical diagnostic dilemma. Surg Neurol. 2002;58(3-4):241-245. Erasmus CE, Verhagen WI, Wauters CA, van Lindert EJ. Brain metastasis from prostate small cell carcinoma: not to be neglected. Can J Neurol Sci. 2002;29(4):375-377. Lynes WL, Bostwick DG, Freiha FS, Stamey TA. Parenchymal brain metastases from adenocarcinoma of prostate. Urology. 1986;28(4):280-287. Churilla TM, Ballman KV, Brown PD, Twohy EL, Jaeckle K, Farace E, Cerhan JH, Anderson SK, Carrero XW, Garces YI, Barker FG 2nd, Deming R, Dixon JG, Burri SH, Chung C, Ménard C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2017;99(5):1173-1178. doi: 10.1016/j.ijrobp.2017.07.045. Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Ménard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016;316(4):401-409. doi: 10.1001/jama.2016.9839. Davis JN, Medbery C 3rd, Sharma S, Danish A, Mahadevan A. The RSSearch™ Registry: patterns of care and outcomes research on patients treated with stereotactic radiosurgery and stereotactic body radiotherapy. Radiat Oncol. 2013;8:275. doi: 10.1186/1748-717X-8275.

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FIGURE 1: Imaging of different types of intracranial metastases of prostatic cancer A. T1 injected MRI of right frontal metastasis with dural attachment B. T1 injected MRI of left pontocerebellar angle metastasis with dural attachment C. Injected head CT scan of a bony and epidural right frontal metastasis D. T1 injected MRI of an intraparenchymal left frontal metastasis E. T1 injected MRI of a purely intraparenchymal parieto-occipital right metastasis F. Non injected CT scan of a purely subdural left frontal metastasis, very similar to isodense chronic subdural hematoma

Table 1: Demographic and clinical data of the 19-patients series

N°

Age

Site

Pathology

Known

Other

Preop

ADC/

prostate

organs

PSA

cancer

involvement

SCC

Y/N

Resection

53

R subdural

ADC

Y

Y

2

63

L subdural

ADC

Y

Y

3

57

R frontal

ADC

N

N

59

R Temporal

chemo

PSA

FU Mth, KI

ng/mL

Y/N

14

24

GTR

WB RTX

GTR

WB RTX

GTR

GK,

dura

4

Postop

therapy

ng/mL

Y/N

1

Radio-

9

14

4

10, PAW

6, PAW

132, KI: 100%

hormonal

ADC

N

N

GTR

dura

GK,

6

78, KI: 90%

hormonal

5

48

R subdural

SCC

Y

Y

6

67

R frontal

ADC

N

N

11

GTR

WB RTX

GTR

GK,

10

2.5

6, PAW

121, KI: 80%

hormonal

7

72

L Subdural

ADC

Y

Y

8

70

L frontal

ADC

N

N

32

GTR

WB RTX

GTR

GK,

15

18

14, PAW

98, KI: 80%

hormonal

9

55

R subdural

ADC

Y

Y

10

54

R subdural

ADC

Y

Y

11

59

R Posterior

ADC

N

Y

7

17

GTR

WB RTX

GTR

WB RTX

GTR

GK,

Petrous dura

12

62

R subdural

6

9

2.9

22, PAW

10, PAW

41, KI: 90%

hormonal

SCC

Y

Y

16

GTR

WB RTX

12

19, PAW

13

74

L Frontal

ADC

N

N

GTR

dura

67

Osteo-dural

ADC

Y

Y

15

78

L Parietal

ADC

N

Y

19

GTR

WB RTX

GTR

GK,

dura

51

Osteo-dural

ADC

Y

Y

17

56

L Temporal,

ADC

N

N

21

GTR

WB RTX

GTR

GK,

L Parietal

L occipital,

66

R occipital, L

21

1.98

6, PAW

29, KI: 70%

19

2.3

14, PAW

49, KI: 100%

hormonal

SCC

N

Y

GTR

GK,

6

18, KI: 80%

hormonal

L cerebellar

19

69, KI: 70%

hormonal

16

68

4.9

hormonal

14

18

GK,

ADC

N

Temporal

N

GTR

GK,

3.5

12, KI: 90%

hormonal

R = right, L = left, ADC = adenocarcinoma, SCC = small cell carcinoma, Y = yes, N = No, GTR = gross total resection, WB RTX = whole brain radiotherapy, GK = Gamma Knife, FU Mth: follow-up month, KI = Karnofsky Index, PAW = passed away

Abbreviations: CNS: Central Nervous System CSDH: Chronic Subdural Hematoma CT: Computed Tomography FU: Follow up KPS: Karnofsky Performance Scale MRI: Magnetic Resonance Imaging OR: Odds Ratio PET: Positron Emission Tomography PSA: Prostate-Specific Antigen