Surgical treatment and outcome in patients over 80 years old with intracranial meningioma

Accepted Manuscript Title: Surgical treatment and outcome in patients over 80 years old with intracranial meningioma Authors: Mauro Dobran, Alessandra Marini, Davide Nasi, Valentina Liverotti, Roberta Benigni, Maurizio Iacoangeli, Massimo Scerrati PII: DOI: Reference:

S0303-8467(18)30075-1 https://doi.org/10.1016/j.clineuro.2018.02.024 CLINEU 4935

To appear in:

Clinical Neurology and Neurosurgery

Received date: Revised date: Accepted date:

28-11-2017 19-1-2018 15-2-2018

Please cite this article as: Dobran M, Marini A, Nasi D, Liverotti V, Benigni R, Iacoangeli M, Scerrati M, Surgical treatment and outcome in patients over 80 years old with intracranial meningioma, Clinical Neurology and Neurosurgery (2010), https://doi.org/10.1016/j.clineuro.2018.02.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.

Surgical treatment and outcome in patients over 80 years old with intracranial meningioma.

Mauro Dobran, Alessandra Marini, Davide Nasi, Valentina Liverotti, Roberta Benigni, Maurizio Iacoangeli, Massimo Scerrati.

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Department of Neurosurgery, Umberto I General Hospital, Università Politecnica delle Marche, Ancona, Italy

Corresponding Author:

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Mauro Dobran, M.D.

Department of Neurosurgery, Umberto I General Hospital, Università Politecnica delle Marche, Via Conca 71, Ancona, 60020, Italy Telephone: +39 0715964567

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Mobile: +39 3495721766

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Fax: +39 0715964575

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Email: [email protected]

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HIGHLIGHTS

1) In literature there are few studies about surgical treatment in elderly patients. 2) Surgical indications are controversial in elderly patients 3) Surgical time is significant factor for the outcome of elderly patients.

Abstract Objective: Study of

mortality rate and clinical outcomes in octogenarians patients operated for intracranial

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meningiomas. Patients and Methods: Clinical, radiological and surgical data of 25 elderly patients aging over 80 years old operated

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at our Department from 2013 to 2016 for intracranial meningiomas have been recorded and analyzed. One-month mortality and clinical outcome at six-months after surgery were evaluated. Logistic regression was used for detecting the risk factors influencing mortality and neurological functions.

Results: The median age at diagnosis was 81,85 years (range 80-87). Meningiomas were gross-total removed in 18

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cases out of 25 (72%) and partially resected in 7 (28%).

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One-month post-operative mortality occurred in 2 pts out of 25 (8%). A close correlation was found between operative

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duration over 240 minutes and mortality (p=0,0421). There was a significantly lower mortality in patients with ASA II

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rather than in patients with ASA III (p=0,038).

The median pre-operative KPS value was 74,3 (range 50-90) while at six-month follow-up was 82.

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The surgical time (p=0,0006) and size of the lesion > 4 cm (p=0,02) were a significant prognostic factors for clinical improvement at six-month follow-up.

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Conclusions: The operative time and the ASA score are the most important prognostic factors for the mortality and neurological outcome of elderly patients over 80 years old operated for intracranial meningioma. Even if the number of

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patients is limited, our findings suggest that, after a careful preoperative stratification in elderly patients, it is possible to remove an intracranial meningioma with good results.

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Key Words: meningioma, elderly patients, prognosis, mortality, neurological outcome.

Introduction Meningioma is the most common primary intracranial tumor with incidence ranging from 35% to 40% [2] that is 8.5:100.000 in elderly people and 2,5:100.000 in young people [5, 7]. Still today there is no consensus regarding the surgical management of intracranial meningiomas in elderly patients because of their high mortality and morbidity [6, 16, 23] but, thanks to the evolution of neurosurgical and anesthesiological techniques, nowadays we can perform 2

complex neurosurgical treatments in elderly patients with satisfactory results. The authors analyzed clinical outcomes and mortality rates in a series of operated patients affected by intracranial meningiomas with age over 80 years old.

Material and Methods From January 2013 to January 2016 we operated 82 patients affected by intracranial meningiomas. Twentyfive out of

the cut-off for this study to evaluate outcome in very elderly patients.

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82 are patients over 80 years old; their clinical and radiological data have been analyzed. The age of 80 years old was In all patients surgery was indicated for

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treatment of symptomatic lesions (neurological deficit and/or seizures). The semi-sitting operative position was not used.

Baseline medical data, including patients’ sex and age at admission, lesion size (maximum diameter <4 cm, 4-6 cm or> 6 cm), site (critical if interesting eloquent area or adjacent to large vessels or not-critical area), location (convexity,

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parasagittal/falx, anterior, midlle or posterior skull-base), extent of edema in pre-operative MRI imaging (divided into

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three types: absent, moderate if present with no shift of the median line structures, severe with shift) were collected and

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analyzed. Co-morbidities were evaluated in the pre-operative period according to the American Society of

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Anesthesiologist Score (ASA) and Geriatric Score System (GSS). Neurological and clinical status were evaluated before surgery with the Karnofsky Performance Scale (KPS) and the Barthel Index (BI). The cut-off of the scores were

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based on previous original articles in literature [1, 2, 6, 8, 7, 20, 21, 24, 28]. Grade of resection by means of the Simpson Classification System were evaluated on post-operative MRI. Also operative time was recorded. After surgery,

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meningioma subtype and histopathological grading, according to the WHO criteria, were determined from

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neuropathological reports.

The primary outcomes of this study were one-month’s mortality and functional status at six months. Follow-up was assessed through the KPS score system. Minimum follow-up ranged from 12 months to 4 years. Statistical tests were

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performed using SPSS software (Chicago, Illinois). For univariate analysis chi-square test and logistic regression were used for comparison of non-parametric data. Comparison of quantitative parameters was performed using a t-test.

Results. In this study 8 patients were males and 17 females, with mean age of 81,8 years old (range 80-87 years). Baseline data are summarized in Table 1. In our series of 25 patients, meningiomas tumor resection was gross-total (Simpson Grades

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I and II) in 18 cases out of 25 (72%), and partial (Simpson Grades III and IV) in 7 (28%). There were no cases of decompression (Simpson Grade V). The mean surgical time was 248,5 minutes (range 110-780 minutes). No patients underwent reoperation for hematoma of the surgical site (in all cases preoperative antiplatelet therapy was discontinued three days before surgery) or had epileptic seizures in the immediate post-operative time. Other post-operative complications were cerebral-spinal fluid

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(CSF) leakage in two patients and wound infection in one patient. The mean blood loss was 360 mL.

A statistical close correlation was found between surgical time over 240 minutes and one month post-operative

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mortality (p=0,0421).

One-month post-operative mortality occurred in 2 pts out of 25 (8%) both for cardiovascular failure, and meningioma recurrence occurred in 3 patients after 3 years. ASA score was used to evaluate surgery risk in all patients: 15 pts out of 25 had ASA score II and 10 patients had ASA score III. ASA value showed a close correlation with one month

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postoperatively mortality with statistically significance (p=0,038). There was no significant correlation between age,

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sex, KPS preoperative, BI, GSS, size of tumor and at one month mortality (p>0,005) as reported in Table 2. The

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median pre-operative KPS value was 74,3 (range 50-90) while post-operative at six-month follow-up was 82. The

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functional status at six, see Table 3.

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surgical time (p= 0,0006) and size of the lesion > 4 cm (p=0,02) were the only significant prognostic factors for

Discussion.

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Meningioma is a benign intracranial tumor and surgery is the gold standard for its treatment. Many studies have shown an increased perioperative mortality and morbidity for elderly patients especially those who underwent neurosurgical

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procedures [3, 14, 25, 26]. However the treatment of intracranial meningiomas in elderly patients has become an everyday issue due to prolonged life expectation and the availability of minimally invasive surgical techniques in elderly patients reduce post-operative complications [ 17, 18, 19, 22].

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This study concern 25 patients over 80 years old (mean age 81,85 years, range 80-87 years) operated for intracranial meningiomas. The peculiarity of our work is the advanced age of the patients. To our knowledge, in current literature only three papers included series of patients over 80 years old operated for intracranial meningiomas [4, 9, 23, 30]. Among these, the papers of Konlgund and Sacko, which included 51 and 74 patients respectively, founded that Sex, Karnofsky Performance Scale, American Society of Anesthesiology Class, Location of Tumor, and Peritumoral Edema grading system were correlated with mortality rates at 1 year following primary surgery (15,7% and 9,4% respectively).

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The study of D’Andrea et al. reported that the risk of postoperative mortality was lower in patients with ASA I-II and a KPS score > 70. The strict selection of patients in regard to their advanced age is the reason of the small simple in the present study. In our series the rate of total gross removal was 73,6 %, slightly lower than Shyamal et al. [31] who obtained complete resection in 84% of Simpson Grade I - II meningiomas. This different data may be due to the lower mean age (76 y.o.) of Shymal series and the prevalent location of meningiomas close to eloquent areas in our study (68%).

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In this series the one-month postoperative mortality was 8% (2 patients out of 25) higher than younger patients’one [2, 27]. However, most patients had numerous preoperative comorbidities and the result may be satisfactory in the light of

this series

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their condition. ASA and GSS scores are routinely used to evaluate comorbidities in elderly patients before surgery. In ASA value showed a close correlation with one month postoperatively mortality

with statistically

significance (p=0,038). This data is important for the correct selection of elderly candidates to surgery and this study confirms the accuracy of this grading system. On the contrary, the GSS score associated with 30-day mortality was not

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statistically significant. The GSS value is underestimated probably due to the small size of sample with many sub-

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classification.

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Furthermore, one month mortality is significantly related also to surgical time: when the duration of surgery exceeded

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240 minutes, mortality increased as well and this is statistically significant (p=0,04) . In our study , two patients died for cardiovascular failure; this is due to a frailty of elderly patients so cardiovascular impairment should be carefully

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studied. As widely reported in literature the duration of operative time is independently associated with increased risk of complications as surgical site infections, sepsis, wound dehiscence, pneumonia and deep vein thrombosis [10, 11, 12,

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13, 18, 29]. A long operation could be dangerous in elderly mostly for their low immune-competence and increased vulnerability to stress factors. This data support the choice to operate elderly patients with mininvasive techniques

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reducing operation time, blood loss and wide expositions of cerebral tissue[17, 18, 19]. In this cohort of elderly patients a significant improvement of neurological status was observed six-months after surgery: the mean KPS value improved from 74,3 % to 82 %, which is a very satisfactory data considering the frailty of

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elderly patients.

In our study, only size of the lesion > 4 cm and the surgical time were a significant prognostic factors for clinical improvement (respectively p= 0,0006 and 0,02. Literature reports that, in elderly group, tumor size is significantly larger than in younger people [4]. This may be due to a wrong suspicion of dementia in elderly patients which delays tumor diagnosis.

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Recurrences occurred in 3 patients grade II; in this type of meningiomas we start radiotherapy when recurrence occurs. A recent study showed that, in partial removed meningiomas Grade II, observation alone is not associated with increased tumor risk recurrence or mortality [15, 17]. This study has several limitations; data collection was retrospective so some clinical information were partially missed.

Conclusions. Although the complete tumor resection is the goal standard for intracranial meningiomas, in elderly

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patients the surgical approach must be tailored to every single case considering its comorbidities and preoperative ASA score

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The surgical time seems to be the most important prognostic factor for the outcome of elderly patients. Even if the number of patients is limited, our findings suggest that after a careful preoperative stratification in elderly patients it is possible to remove an intracranial meningioma with satisfactory results.

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Funding No funding was received for this research.

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Compliance with ethical standards

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Conflict of interest The authors have no known conflicts of interest to declare. The manuscript submitted does not

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contain information about medical device(s)/drug(s). All authors contributed to the design of the study. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical

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standards of the institutional committee and with the latest amendment of the Helsinki declaration. Informed consent Informed consent was obtained from all individual participants included in the study.

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Acknowledgements: None

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Characteristics

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Number of patients Age (mean; range) < 85

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> 85

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Sex

Karnofsky Performance Scale (mean;range)

n°

%

25

/

81,5 (80-87) 18

72 %

7

28 %

8

32 %

17

68 %

74,37 (50-90) 21

84 %

< 70

4

16 %

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≧ 70

Barthel index (mean;range)

68,75 (40-90)

Geriatric Score System (mean;range)

17,05 (13-22)

< 15

19

76 %

≧ 15

6

24 %

I

0

0%

II

15

60 %

ASA

9

III

10

40 %

IV

0

0%

< 4 cm

6

24 %

> 4 cm < 6 cm

12

48 %

> 6 cm

7

28 %

Eloquent area

17

68 %

Non eloquent area

8

32 %

Convexity

16

64 %

Parasagittal/Falx

5

Anterior Skull-Base

3

Middle Skull-Base

1

Size

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Location

20 % 12 % 4%

5

Severe

20

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Moderate

A

0

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Edema Absent

Symptom

Seizure

0% 20 % 80 %

21

84 %

4

16 %

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Neurological deficit

360 cc

Post-operative complication Hematoma

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Median blood-loss

0

0%

0

0%

2

8%

1

4%

4

16 %

14

56 %

5

20 %

2

8%

0

0%

I

17

68 %

II

8

32 %

III

0

0%

CSF leakage

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Wound infection

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Seizure

Simpson Grade I II III

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IV V

WHO Grading System

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Site

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Table 1. Baseline characteristics and surgical results of the present series.

OR (95% CI)

Age (< 85 or ≧85)

4,67 (0,22-97,50)

Sex

0,79 (0,06-10,38)

0,87

Geriatric Score System (< 15 or ≧15)

0,25 (0,02-3,34)

0,27

Karnofsky Performance Scale (< 70 or ≧70)

1,63 (0,11-22,98)

0,87

Barthel Index

0,44 (0,03-5,88)

0,53

American Society of Anesthesiologist Scale (ASA)

15 (0,90-251,07)

Edema

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Surgical Time

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Simpson Grade

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0,28

0,038

0,55 (0,03-10,37)

0,59

0,55 (0,03-10,37)

0,59

0,42 (0,02-8,05)

0,55

7,50 (0,32-173,29)

0,042

3,25 (0,16-64,62)

0,42

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P

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Size

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Location (convexity / skull base / parasagittal)

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Variables

Table 2. Results of univariate analysis using a logistic regression model for association between pre and post-operative

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factors and one-months mortality.

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One-month follow-up

Six-month follow-up

OR (95% CI)

P

OR (95% CI)

P

Age (< 85 vs ≧85)

3,75 (0,44-31,62)

0,21

3,75 (0,44-31,62)

0,21

Sex

0,95 (0,14-6,28)

0,95

1,56 (0,12-20,86)

0,73

0,17 (0,01-2,04)

0,13

1,20 (0,15-9,77)

0,86

0,95

1,56 (0,12-20,86)

0,73

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0,95 (0,14-6,28)

0,13

1,20 (0,15-9,77)

0,86

0,07

1,60 (0,83-3,12)

0,07

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0,17 (0,01-2,04)

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Geriatric Score System (< 15 vs ≧15) Karnofsky Performance Scale (< 70 vs ≧70) Barthel Index

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Variables

1,60 (0,83-3,12)

Size

2,33 (1,27-4,27)

0,02

2,33 (1,27-4,27)

0,02

0,22 (0,03-1,75)

0,14

0,22 (0,03-1,75)

0,14

8,10 (1,26-52,00)

0,0006

8,10 (1,26-52,00)

0,0006

0,08

7,20 (0,62-83,35)

0,08

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Edema

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Surgical Time Simpson Grade

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Location (convexity / skull base / parasagittal)

7,20 (0,62-83,35)

Table 3. Results of univariate analysis using a logistic regression model for association between pre and post-operative

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factors and clinical improvement at one-month and six-month follow-up.

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