Return to work, activities of daily living and sports after spinal ependymoma resection: a monocenter experience with long-term follow-up


 Introduction: Adult spinal ependymoma presents a rare benign tumor entity. Due to its incidence peak in the fourth decade of life, it mostly affects patients during a professionally and physically active time of life.Methods: We performed a retrospective monocentric study, including all patients operated upon for spinal ependymoma between January 2009 and September 2020. We prospectively collected data on professional reintegration, physical activities and quality-of-life parameters using EQ-5D and SF-36. Issues encountered in returning to work and physical activities were assessed using existing spinal-cord-specific questionnaires and free-text questions.Results: In total, 65 of 114 patients operated on for spinal ependymomas agreed to participate. Most patients suffered from only mild pre- and postoperative impairment on the modified McCormick scale, but 67% confirmed difficulties performing physical activities in which they previously engaged due to pain, coordination problems and fear of injuries. We observed a shift from full- to part-time employment and patients unable to work, independently from tumor dignity and neurological function.Conclusion: Despite its benign nature and formal only mild neurological deficits occurring in patients suffering from spinal ependymoma, the studied population described severe difficulties returning to their preoperative physical activity and profession. Clinical scores such as the McCormick grade and muscle strength may not reflect the entire self-perceived impairment appropriately.


Introduction
Spinal cord ependymoma presents the most common spinal intradural neoplasm in adults and most often affects male patients in their forties [1][2][3]. Ependymomas usually show a benign growth pattern with a favorable outcome and are classi ed as WHO Grade 1 (myxopapillary, extramedullary) or 2 (mostly intramedullary) tumors [4] while anaplastic ependymoma presents the least common subgroup of all ependymomas (WHO Grade 3 tumors) [5,6]. Due to their mostly benign nature, gross total resection whilst preserving healthy surrounding tissue represents the rst-line therapy, with promising 10-year, progression-free survival rates of 80-90% [7][8][9].
Compared to other benign neoplasms, the incidence of ependymomas peaks in the fourth to fth decade of life, i.e., during a rather active and social life period. At this stage of life, even slight professional, or physical handicaps, such as reduced ability to work and participate in sport activities, may signi cantly impair quality of life in otherwise healthy adult patients [10][11][12]. As most published studies on spinal ependymoma focus on surgical technique, progression-free survival and quanti able neurological signs, the real burden of disease may be underestimated regarding impairment in performance of daily life activities, such as sports and recreation, due to subclinical de cits. Our aim was to investigate the actual impairment in patients who underwent spinal ependymoma resection, focusing on di culties encountered in daily living activities and reintegration into work.

Patient cohort
We performed a retrospective assessment of all patients operated on for spinal ependymomas between January 2009 and September 2020 in our neurosurgical department in a tertiary care hospital. Patients' medical records were retrospectively reviewed, and each patient was contacted individually by mail or telephone. Patient consent was required, and when obtained, a speci c questionnaire was sent via mail with a stamped return envelope.

Questionnaire
The questionnaire used in our study included an assessment of quality-of-life items using the European Quality of Life 5 Dimensions (EQ-5D) and the Short Form Health (SF-36).
We created a list of questions addressing education, occupational reintegration, and sport activities (with questions focusing on the pre-and postoperative situation, the frequency and the type of sports performed). The questionnaires were validated for patients suffering from spinal cord injuries and modi ed according to previously conducted research [13]. At the end of the questionnaire, patients were able to answer free-text questions and add comments on di culties encountered during their postoperative recovery.

Health utility
We assessed patients' health utility corresponding to a quanti ed number describing their health state or outcomes ranging between 0 (worst state imaginable) and 1 (perfect health) using the EQ-5D questionnaire. Health states were correlated with potential risk factors and neurological outcomes after surgery.

Statistics
Statistical analyses were performed using SPSS Statistics 26 (IBM, Chicago, IL). Categorical data were compared using the chisquare test or Fisher's exact test as appropriate. Mean values were compared using the independent samples t test.
The association between potential factors and reduced quality of life or sport activities was analyzed using an ANOVA. We assumed the following factors to be potentially predictive: presence of neurological de cits, perioperative complications, modi ed McCormick grade and age. To assess the correlation, we used Kendall's tau correlation coe cient. All tests were twosided; a p-value <0.05 was considered signi cant.

Ethical considerations
We executed the presented study in accordance with the ethical standards outlined in the Declaration of Helsinki. We also obtained a positive vote by a local ethics committee beforehand (number 570/20 S). Prospective patient written consent was obtained prior to data collection.

Cohort population
Overall, 114 consecutive patients were operated for spinal ependymomas between January 2009 and June 2020 in our department. We excluded 21 foreign patients living abroad due to missing follow-up reports. Thirteen patients declined participation (reasons included the personal aspect of the questions or non-willingness to participate in clinical trials), and 13 patients did not respond to our contact attempt. Two patients were deceased, leaving 65 patients included in the study assessment. Complete data and answered questionnaires were available for all patients ( owchart, Figure 1).  Figure 2).

Quality of life
The analyzed questionnaires included the EQ-5D assessment and SF-36 patient-reported survey. The assessment was performed after a median interval of 5.4 years after surgery (IQ range 3-8.5 years).
The mean utility (u) evaluated by the EQ-5D questionnaire was 0.676 (range 0-1), indicating a high burden of disease and selfperceived disability. Most patients were restrained in the pain category, demonstrating the lowest scores in this part of the questionnaire. Utility differed signi cantly between patients concerning di culties returning to physical activities (u: 0.58 vs. 0.81, p = 0.03). We also found a strong dependence on sex: female patients demonstrated signi cantly lower levels of overall quality of life, with a mean u of 0.573 vs. 0.788 in male patients (p = 0.006, correlation coe cient 0.287). Health utilities were signi cantly lower in patients suffering from intramedullary ependymoma (u = 0.50) compared to patients operated on for extramedullary tumors (u = 0.80, p = 0.000). Furthermore, a correlation was found between the overall quality of life and the modi ed McCormick grade at follow-up (I: 0.828, II: 0.627, III: 0.432, p = 0.001, correlation coe cient -0.447) as well as the presence of postoperative neurological de cits at follow-up (u: 0.554 vs. 0.809, p = 0.001, correlation coe cient -0.417). Age did not affect health-related quality of life (p = 0.364).
Assessing the SF-36 general health questionnaires, the lowest scores were observed for vitality (mean 49.8%, range 10-95%) and role limitations due to physical constraints (mean 51.4%, range 0-100%). The highest scores were reported in the categories of social functioning (mean 72.9%, range 12.5-100%) and emotional role limitation (mean 67.7%, range 0-100%). Patients suffering from di culties returning to sport activities after surgery had signi cantly lower scores in all categories on the SF-36 survey compared to patients denying any problems in returning to daily living (Table 1). Patients with intramedullary ependymoma scored signi cantly lower compared to patients with extramedullary ependymoma (p = 0.001 to 0.005 in all subgroups).

Reintegration into professional employment
Assessing the pre-and postoperative occupations of our patients, we found a shift of full-time to part-time employment and patients who retired/were unable to work. Table 2 describes the ndings focusing on pre-and postoperative education as well as pre-and postoperative occupation. Before surgery, the majority of patients were full-time employees (34/65, 52.3%). After surgery, the amount of full-time employment diminished to 21/65 (32.5%), and the number of patients who retired early increased from 16.9% to 29.2%. Reasons for failure or di culties encountered during reintegration were persistent pain (13/65, 20%), physical stress (11/65, 16.9%), impaired accessibility of work (1/65, 1.5%) and motor de cits in two cases (3.1%). Age, WHO grade, and sex did not signi cantly in uence the ability to return to work (age p = 0.240, WHO grade p = 0.595 and sex p = 0.621).

Sports and daily living activities
Before surgery, 66% of the patients performed individual sports and 15% trained and participated in team sports. After surgery, 63% continued to perform individual sports, but only 6% continued in team sports (Figure 2). Assessing the frequency of sport activities, most patients attended sport activities 2 to 4 times/week before surgery, whil 24.6% trained 5 to 7 times/week. After surgery, the amount of intensive training (5-7 times/week) diminished to 16.9% (11/65), while other patients remained active 2-4 times/week (47.7%, 31/65) (Figure 3).

Prognostic factors
With regards to di culties returning or performing sports related to medical issues, we found a signi cant association between occurrence of di culties and preoperative as well as postoperative McCormick grades (p = 0.012 and p = 0.002, respectively), chosen approach (unilateral approach 56.2% vs. laminectomy 100% and laminoplasty 85%, p = 0.023) and number of operated segments (monosegmental approach 52% vs. 5 or more segments 100%, p = 0.022).
Tumor dignity, sex and age did not affect participation in sport activities after surgery (p = 0.92, p = 0.994 and p = 0.510, respectively).
With regards to di culties with professional reintegration, we found no signi cant association between early retirement or inability to work and tumor WHO grade, number of segments or sex (p = 0.595, p = 0.244 and p = 0.571, respectively). Patients reporting constraints returning to work tended to be younger (median age 42 years vs. 50 years, p = 0.056), but this nding was only suggestive signi cance.

Discussion
In our cohort, most patients experienced signi cant impairment in their daily living and changes in type and frequency of their sport activities after ependymoma resection, despite the benign nature of their tumor and overall mild formal neurological de cits. Even in cases with intact neurological function, patients reported a reduced health-related quality of life compared to the preoperative state.
The overall disease burden seems to be underestimated when only objecti able clinical neurological status is included in the assessment of functional impairment. Disabilities in daily living activities are frequently encountered in cancer patients and widely described in the literature stating half of affected adults require assistance to perform activities of daily living [15]. Up until now, studies focus on malignant tumors and there has been no related data or evidence in benign spinal cord tumor patients. To our knowledge, we provide the rst cohort population describing di culties encountered in sports, recreation and employment after surgery, as well as the rst study assessing health utilities in this disease.
Over 67% of patients encountered di culties when returning to sport activities due to pain, coordination problems, accessibility constraints and fatigue symptoms. While assessing encountered problems, we also evaluated positive reasons to return to sport activities. Patients described improved stability, social interaction, and improvement of pain symptoms with physical exercise. The potential rehabilitative effects of sport have been described in brain cancer patients and neuro-oncology in general [16,17]. Our study shows signi cant issues in accessing and performing sports in a population with benign tumors. These issues should be addressed and discussed with patients at follow-up appointments to improve accessibility of physical activity.
In our study, we assessed critical domains of daily quality of life in patients suffering from spinal ependymoma and evaluated speci c utility scores. While most patients remained functionally independent according to the McCormick grading system, symptoms such as fatigue and depression were not re ected appropriately in our medical follow-up records and were only detected by speci cally addressing issues encountered in daily living activities using our questionnaires. Fatigue has been described as occurring frequently in spinal ependymoma patients, affecting up to 52% [18]. The assessed utility score using the EQ-5D questionnaire was 0.676 in our cohort, which is somewhat lower than previously reported values of patients suffering from intracranial malignant gliomas (0.70-0.80 [19]) [20]. Interestingly, we found a signi cant difference in health-related quality of life between female and male patients, congruent with results presented in studies on quality of life in glioma patients, probably related to the greater dysfunction experienced by women at the same level of pain [21][22][23]. The high disease burden in spinal ependymoma patients may be explained by a disproportionately high impact of subclinical physical disability in an otherwise healthy young patient, who normally do not require adjuvant or disease-related in-hospital or outpatient therapy or medication, as well as by persistent pain symptoms as described by our patients.
We did not compare our patient cohort to other tumor or spinal-trauma entities, as we only included patients undergoing spinal ependymoma surgery. While occupational reintegration data has been described for intracranial glioma patients [24,25] and a small group of spinal ependymoma patients [11], there is no evidence on sport activities and recreation in primary spinal cord tumor patients. The only comparable available studies included patients suffering from spinal cord injuries, with considerably worse neurological and clinical function and more possibilities for systematic reintegration and support programs [13,26]. While the bene ts of physical activity in patients with spinal cord injuries have been extensively discussed and published [27], we did not nd any relevant literature addressing physical activity in spinal intradural tumor patients. Patient in our cohort described impairment of coordination, sensation, fatigue and fear of injuries and accessibility problems, similar to patients suffering from spinal cord injuries, even when described as functionally independent. We therefore hypothesize that physical activity has a potential bene cial effect of in the neuro-oncological context of ependymoma patients. To date, screening programs are nonexistent, but explicit evaluation of daily life di culties should be included during follow-up appointments to nd room for improvement in a patient's quality of life.
Regarding the ability to return to work, most patients were able to return to their profession. Similar results were observed among patients suffering from cerebral gliomas [28]. In contrast to glioma studies, age did not signi cantly affect our patients' abilities to resume their working lives, maybe due to their more homogeneous age group [29].

Limitations
We obtained data from patients in follow-up after surgery, without available preoperative scores. Our cohort might be subject to recall bias due to the time passed between our assessment and initial tumor resection. Also, memories about the preoperative state may have been subjectively disrupted. A prospective study can certainly reduce the occurrence of bias; however, data collection would take an inappropriately long time due to the low incidence of spinal ependymoma, making this option questionable. Our results may contain additional selection bias, since only 65 of 115 patients were included in the analysis. We did not investigate possible solutions to improve participation in sports or help patients in their professional and occupational reintegration. Although we identi ed factors predicting impeded return to physical and leisure activities, we cannot offer modalities to improve reintegration based on our current results. Finally, could not assess the socioeconomic burden of disease, as the time span of patients' returning to their occupations was not investigated.

Declarations
Con ict of Interest All authors report no con ict of interest concerning the materials or methods used in this study or the ndings speci ed in this publication.

Statement of Ethics and consent to participate
The presented study meets the ethical standards outlined in the Declaration of Helsinki, ethics approval was obtained by the local ethics committee (Prof. Dr. Georg Schmidt, Technical University Munich) and the positive vote was registered under the number 570/20 S.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.   Figure 1 Flowchart describing the inclusion process of all patients assessed prospectively Changes of sport frequency and sport participation in team sports before and after surgery