Indirect Evidence of Increased Cerebral Plasticity of Musicians with Malignant Cerebral Tumors; Longer Overall Survival Status according to Nonmusicians

Background There are some reported musicians with cerebral tumors, but no comparative study of the survival status of musician and nonmusician patients with malignant cerebral tumors was made. This subject was investigated. Material and methods Musician people list with cerebral tumors was searched from the English Wikipedia Their survival status, ages, and gender were statistically compared with 30 nonmusician patients with cerebral malign tumors. Results 66 (Group 1 or Musician Group; MG) musicians with malignant tumors list were found from Wikipedia. Survival times of only 47 musicians could be reached from Wikipedia. The mean Survival of this group is 20.06 months, however, it was 13.10 months non-musician group, and the difference of survival was statistically signicant (p < 0.05), however, ages and gender were not. There is an interaction between music and brain anatomic structures. Our study showed that the survival status of musicians and non-musician with malign cerebral tumors is not the same. This result may be dependent on the altered musician's brain or neuronal plasticity, and the response of the musician's brain's to malign tumor. More studies are needed.


Introduction
Currently, there have been major changes in medical science [1], and important progress in surgical techniques and medical devices have been also been observed [2]. In this era, neuro-oncology is a rapidly developing eld by investigating the understanding of the basic mechanisms of carcinogenesis. but brain tumors still affect many people worldwide every year with poor outcomes. Malign cerebral tumors also affect musicians at some time during their lives [3]. Recently, Gasenzer et al suggested that musical training may lead to changes in some anatomic structures of the brain [4], so musical training might have some effect on the survival times of these patients with cerebral lesions. Rapid advances in neurosurgical knowledge and technology are putting increased pressure on neuroscientist [5], and bring some question(s) about neuroplasticity, musician's brain. The musician's brain with high plastic potential may have a different reorganization with malign cerebral tumors. Musical training in humans leads to enhanced executive functions. Recovery of the injured brain by malign tumors of musicians is an ideal opportunity to investigate. Human cancers have the potential to affect the nervous system in different ways, but the brain has plasticity might have a role in this interaction. We hypothesized that the plasticity of the brain may lead to different survival times for musician and non-musician people. The goal of this article is to focus on the possible existence of differences between musicians and nonmusician patients after affected by the malign cerebral tumor. Knowledge of the survival of the patient with cerebral tumors is an important issue. There is no study investigating this subject.

Material And Procedures
The study protocol was approved by the local ethics committee. Patient consent was not required because of the retrospective nature of the study. The musicians with malign brain tumors from the English Wikipedia. (https://en.wikipedia.org/wiki/List_of_people_with_brain_tumors) were searched, then the patients were divided into two groups. The rst group consisted of musician patients with malign cerebral tumors. The second group was non-musician people with malign cerebral tumors who were operated on in the XXXXXX University Hospital between January 2015-February 2019. Patients with biopsy only were excluded. The age, gender, survival status of both groups were compared.
Statistical analysis: SPSS (20.0) was used. The null hypothesis the median of a distribution of age, gender, and survival times is equal. Mann-Whitney U test was used.
Results 66 (Group 1 or Musician Group; MG) musicians with malignant tumors list were found from Wikipedia, but survival times of only 47 musicians were reached from Wikipedia. The mean survival of this group is 20.06 months; however, it was 13.10 months non-musician group ( Table 1). The difference was statistically signi cant. In subgroup assessment, survival times were 20,84 months for pop-rock musicians, and 19,9259, months for classical music performers. (Table 2). Ages distributions of the patient were given in Table 3 Mean age was 56,58 years in the musician group (Group 1),56,56 in the nonmusician group (Group 2) which was not statistically signi cant between groups. There was male dominance in both groups, 50 cases of group 1 (75,75%), 17 patients of group 2: %56,66 were male, however, the gender of musicians and nonmusicians group was not statistically signi cant (Table 3).

Discussion
Summary of the results Investigating the differences in survival times of musician and non-musician patients with a malign cerebral tumor is a central aspect of this present study. In this paper, musician's brains affected by malignant brain tumors were investigated by looking at the survival times of a total of n=47 such patients reported in the literature, and concluded that "there is an interaction between music and brain anatomic structures." Different survival times for musician and non-musician patients are the key result of the present study. The difference was statistically signi cant (p<0.05) (table 1).

Survival status:
Glioblastoma multiforme is the most frequent and most malignant primary brain tumor in adults[6], [7].
It confers a poor prognosis[8] despite good surgical resection and medical therapy. Its median survival is 14 months. Therapeutic resistance and tumor recurrence after surgical removal may be a cause of the poor prognosis. Recent studies herald important advances in our understanding and management of malignant cerebral tumors, but understanding mechanisms of progression and recurrence of these tumors are still not su cient. Different survival statuses in this study between musician and nonmusician groups in an important nding. The mean survival of this group is 20.06 months; however, it was 13.10 months non-musician group (table 2). A multidisciplinary therapy approach including surgery, radiotherapy, chemotherapy was performed in this patient group. The exact diagnosis of the nonmusician malign tumor group (Group 2) was GBM. Age and gender were not different between the musician and non-musician groups (table 3). However, the survival status of musicians is better than this non-musician-group. The difference in survival was statistically signi cant between musicians and nonmusician (p<0.05).

Neuroplasticity of the Musician's Brain
Music is one of the unique abilities of the human brain. Music therapy may be used with positive results [4]. The novel coronavirus disease 2019 (COVID-19) is a global pandemic with international concern [9]. Music may reduce anxiety and stress in this pandemic. Great skills are required for playing a musical instrument. To examine the outcomes of a study, it is necessary to have testable hypotheses [10].
Outcomes are then expressed about the implied goals [10]. Long musical training of musicians may affect the neuronal functions and organization of the brain and some functional and structural changes may occur. Musicians, because of the different anatomic structures of their brains are an excellent model to investigate [11]. Currently, MRI can demonstrate some different cerebral structural changes of musicians. There is good interaction between music and neuroscience [3]. Several factors such as the neural development genes of humans and their regulators might play critical roles in the pathogenesis and treatment of malignant cerebral tumors, which is likely different in the studied groups of this study. The brain with GBM may exert complex changes, and this study indicates that there are differences in the survival status of musicians and nonmusicians with malignant cerebral tumors depending on music education-related potential changes.
The plasticity of the brain with malign tumors In the medical literature, the consequences of craniotomies, neurosurgical interventions musicians' activities have been published [12], [13], [14], [15], [16]. [17], [18]. Our clinical practice is being guided by scienti c principles [19], [20]. After the damage to the brain by a tumoral lesion, a functional reshaping with clinical recovery shows the plastic potential of the brain. The functional outcome means the alterations in how the patient functions or feels after cerebral tumor surgery. The functional outcome cannot be the same in musician and nonmusician patients with cerebral tumors. Early music learning and active music-making can help a damaged brain to recover. In this study, longer survival times of the musician's group may be related to the plasticity of the musician's brain. Because of the greater brain plasticity of musicians, the recovery of musicians with cerebral tumors can be different from the recovery of non-musician. The mirror neuron system is a brain network implicated in the understanding of action and imitation [21]. This system may activate in some situations such as playing a musical instrument, maybe different in musician people than non-musician and affect the outcome of patients with malign cerebral tumors. This subject should be investigated.

The effect of Neuroplasticity
Neuroplasticity means a remodeling of the brain, and it is underestimated in neurosurgical practice. It is increasingly acknowledged that the brain is highly plastic [22]. The brain has a capacity for reorganizing itself [23]. The picture shows a reorganization of the brain after musical training (see gure). The conventional approach in our clinical practice is to determine the response of the cerebral tumor to surgical and nonsurgical management, but brain plasticity itself may have a role in the response of the patients. Musical training may affect the plastic potential of the brain. Some differences in anatomic structures between musicians´ and non-musicians' brains have been reported [24]. Musical training leads to a good functional network of regions both in the left and in the right cerebral hemisphere [25]. Studying and performing music leads to some changes in the brain. An increased grey matter volume of the musician has been reported [26]. In musician's brains, the planum temporale of the left and the right side is larger than in nonmusicians [27], [28]. Thicker corpus callosum has been reported in musicians who begin their training at an early age [27], [29]. Our study shows that there is a possibility that musicians have the potential of unique brain structure and brain plasticity according to non-musicians. The gure shows the reorganization of the brain after musical training. We are the rst time reporting the evidence of prolonged overall survival of musicians. If indeed one is the rst to report something and that something is of value [30].

Limitations
As authors, we made a comparison between musicians and non-musicians. As we mentioned above, the difference in survivals could have been the intellectual capacity of the patients, but we aware that it is not clear at which rate there is/or not a difference between research groups (historical cohort vs. operated patients by the authors). There are some limitations to this study. Firstly, we could only investigate the musician, which appeared on the Wikipedia list. Because of the nature of the retrospective investigation of the study, some important clinical, histological facts and molecular parameters like methylation could not be investigated. Molecular biological factors may be important in the survival of patients with malignant cerebral tumors. Treatment of brain tumors depends on many factors such as the type and stage of the tumor, and the patient's age, and another co-morbid disease of the patients. Surgical resection plays a central role in the management of gliomas [31]. The extent of tumor resection and the tumor grade is an important factor for the survival duration of patients with malignant brain tumors [31], [6]. We don't know the resection rate of the tumors of musicians. Over the last decades, the outcomes of malignant cerebral tumors have improved as a result of numerous innovations in imaging technology, such as CT, MRI [32], functional MRI, SPECT, PET. However, the mean survival of nonmusician patients with cerebral tumors (13.10 months) was shorter than musician patients (20.06 months) ( Table 1). In this study, 66 musicians with malignant tumors list could be found from Wikipedia, but survival times of only 47 musicians were reached from Wikipedia. Many of them underwent possibly chemotherapy and radiotherapy after surgery. Some of these musicians suffered malignant cerebral tumors. The quality and outcomes of musicians live as well as their musical activities after surgery have been published [12], [13], [15], [14][16], [17], [18], [33], [34], but it was not possible to nd MRI nding of musicians with brain lesions from Wikipedia. This point is one of the major disadvantages of the study. The lack of the histologic type of tumor and the clinical and neuro-pathological data in the musician's group may be caused by unconvincing conclusions. Missing key clinical data of the musician group include histology of the tumor, treatment modalities, extent of surgical resection, RT/ Chemo/location of the tumor, adjuvant treatment, etc. Therefore, it can be said that the comparison is not equitable. We think that our results should be validated in more studies, and this study will lead to more studies in this subject. We know that the calculation of sample size is one of the important components of the design of a study [35]. If a researcher selects fewer cases, it may lead to missing any signi cant difference even if it exists in the population [36]. A small sample size may not generalize the ndings. We know that the sample size is important in a medical study. Equal sample sizes can give a greater power to detect differences [37]. Another limitation is the heterogeneities of malignant cerebral tumors. These tumors are characterized by several heterogeneities. We are aware that histology of the tumor, treatment modalities used in both groups, the extent of surgical resection, radio and chemotherapy of patients, location of the tumor, and adjuvant treatment are important factors in patients with malignant cerebral tumors.

Conclusion
In this study, we observed that the survival times of musicians and non-musician with malign cerebral tumors are different. CNS diseases have some features that are distinct from other diseases [38]. The result of this study may be dependent on the altered musician's brain or neuronal plasticity, and the response of the musician's brain's to malign tumors. We think that the nding of the present study shows indirect evidence of increased cerebral plasticity of musicians with malignant cerebral tumors because the musicians have had longer overall survival status than nonmusicians patients. This nding likely occurred by musical training, in this regard, this study will lead to a high neuro-scienti c interest in this subject. This study indicates that there can be some positive effects of music-making and music perception in musicians with brain tumors. There can be a high bene t of musical training of musicians for the recovering brain. Our results need further investigations, carried out with more appropriate methods. The impact of this study will further increase the understanding of the pathophysiology of malignant cerebral tumors and will lead to neurosurgeons pay more attention to the cerebral plastic potential of musicians. More studies are required on this subject.

Declarations
Con ict of Interest: None Compliance with ethical standards: This study procedure was approved by the Ethics Committee of the xxxxxxx.
Funding-No funding was received for this research.
Data availability statement; The data that support the ndings of this study are available from the corresponding author, upon reasonable request.