Medulloblastoma

Summarize

Medulloblastoma (MB) is the most common type of intracranial malignancy in children and occurs in the cerebellum. Most medulloblastomas originate from cerebellar neuronal progenitors, cerebellar granule cell progenitors, or pluripotent progenitors of the nervous system in early embryonic development. The most common symptoms are signs and symptoms of cerebellar dysfunction and increased intracranial pressure.

Epidemiological

incidence of a disease

In the United States, there are approximately 500 new cases of medulloblastoma each year, and it is the most common intracranial malignancy in childhood, accounting for 20% of all primary tumors of the central nervous system in children under 19 years of age.

Medulloblastoma is usually seen in children and adolescents under the age of 16 years, with peak incidence between the ages of 5-9 years, a slight increase in incidence between the ages of 20-24 years, and very rare over the age of 40 years.

Etiolog & Risk factors

risk factor

According to current research, SHH-activated medulloblastomas originate from cerebellar granule neuron precursor cells in the outer granule cell layer or the cochlear nucleus, or from pluripotent progenitor cells in the subventricular zone.Group 3 tumors may also originate from cerebellar granule neuron precursor cells in the outer granule cell layer, or from neural stem cells in the subventricular zone. Scientists believe that these granule cell progenitors progress to medulloblastoma when they are persistently stimulated or fail to exit the cell cycle.

Approximately 5-6% of children with medulloblastoma have germline mutations in specific genes that can lead to the development of medulloblastoma as well as other cancers. Several of these gene mutations result in clinical syndromes that are more associated with the development of medulloblastoma:

Nevoid basal cellcarcinoma syndrome (NBCCS, also known as Gorlin syndrome) is the most common inherited syndrome associated with medulloblastoma. It is commonly caused by germline mutations in the patched-1 (PTCH1) gene on chromosome 9. In rare cases, nevoid basal cell carcinoma syndrome may also be caused by germline mutations in the suppressor of fusion protein (SUFU) gene. Mutations in both genes lead to overactivation of the SHH signaling pathway, causing abnormal cerebellar development. Medulloblastoma occurs in 3-5% of patients with nevoid basal cell carcinoma syndrome, often occurring within 3 years of age.

Familial adenomatous polyposis (FAP) is caused by inactivating mutations in the adenomatous polyposis coli (APC) gene on chromosome 5. The product of the adenomatous polyposis coli gene is a component of the WNT signaling pathway and is important for cell proliferation and differentiation during development. Less than 1% of patients with familial adenomatous polyposis develop medulloblastoma, but the risk of developing the disease varies in different families.

Li-Fraumenisyndrome (LFS) is caused by a germline mutation in the oncogene TP53 on chromosome 17 resulting in a loss of function.Deletion of TP53 may cause osteosarcoma, soft tissue sarcoma, breast cancer, adrenocortical carcinoma, and a variety of brain tumors, including medulloblastoma and other gliomas. In SHH-activated medulloblastoma, approximately 8% of patients have germline mutations in TP53.

Other gene mutations associated with medulloblastoma include:

BRCA2: A mutation in a gene that commonly causes familial breast and ovarian cancer. In a study of over 1,000 people, 1% of medulloblastoma patients had a mutation in BRCA2 at a median age of 5.7 years.

PALB2: Rarer, but found in patients with SHH-activated, Group 3 and Group 4 medulloblastomas.

GPR161 (Gprotein-coupled receptor 161): Germline mutations in GPR161 are found in 5% of SHH-activated infantile patients with a median age of 1.5 years.

Classification & Stage

1. Histological subtypes

In 2007, the World Health Organization (WHO) issued guidelines that classified medulloblastoma into four subtypes based on histologic features:

● Classic: Cells are small, round, dense, and have dark-colored nuclei.

● Desmoplastic/nodular (DN): rounded nodules with interstitial spaces rich in collagen and reticulin, and "pale islands" without reticulin.

● Medulloblastoma with extensive nodularity (MBEN): greater number of nodules.

● Large cell Anaplastic (LCA): Tumor cells with larger nuclei or irregular cell shape.

These medulloblastomas are characterized by the presence of cerebrospinal fluid dissemination and a more aggressive clinical progression.

However, there is no good correspondence between histologic typing and clinical symptoms, therapeutic approaches, and prognosis, so molecular typing is more commonly used in clinical practice today.

2. Molecular subtypes

In 2010, an expert panel organized by the World Health Organization (WHO) first classified medulloblastoma into four molecular subtypes by molecular markers: WNT-activated, SHH-activated, Group 3 and Group 4.
3 and Group 4.

● WNT activated

WNT-activated medulloblastomas have mutations in genes associated with the WNT signaling pathway, a cellular pathway responsible for transmitting molecular signals that play an important role in cell development and proliferation. Approximately 6-8% of patients with WNT-activated tumors have germline mutations in the APC gene, which in turn affect cellular signaling through the WNT pathway. 85-90% of patients with WNT-activated tumors have mutations in the CTNNB1 gene, which do not usually occur in the same patient as mutations in the APC gene.

The WNT-activated type accounts for about 10% of medulloblastomas and is most commonly seen in children and adults (median age 10 years) and very rarely in infants. This subtype rarely metastasizes. Histology is generally classic.

In children, the WNT-activated type has the best prognosis of the four subtypes, with a 5-year survival rate of more than 95%.

● SHH activation type

SHH-activated medulloblastomas have mutations in genes associated with the SHH signaling pathway, and the activity of this signaling pathway is associated with the regulation of cell proliferation. For example, deletion or inactivation of genes such as PTCH1, SUFU, or GPR161 results in over-activation of the SHH signaling pathway, leading to excessive cell proliferation.

SHH-activated type accounts for about 25-30% of medulloblastomas. Histologically the pro-fibroproliferative/nodular type is prevalent.

In 2016, the World Health Organization further classified SHH activation types into TP53 mutant and TP53 wild type:

Patients with the TP53 mutant type carry a mutation in the TP53 gene, which causes over-amplification of the oncogene MYCN through the SHH pathway, resulting in chromosomal instability and the development of tumors. These patients have a poor prognosis, with a 5-year survival rate of about 40%.

TP53 wild-type patients without TP53 mutations have an intermediate prognosis with a 5-year survival rate of about 80%.

● Group 3 type

Group 3 types are predominantly seen in children and include about 25% of sporadic (i.e., no family history) medulloblastomas. One of the more common histologic types is the large cell/mesenchymal type, which is often metastatic at the time of diagnosis.

Genomic rearrangements are found in 1/3 of Group3 patients and result in activation of the growth factor independence 1 (GFI1) gene or the GFI1B proto-oncogene.
independence 1 (GFI1) gene or GFI1B proto-oncogene activation. Alterations in the Notch signaling pathway, transforming growth factor-beta, or KBTBD4 may be found in some patients.

Group 3 type has the worst prognosis of the four subtypes, with a 5-year survival rate of about 50% and a higher likelihood of recurrent metastasis than several other subtypes.

Group 4 type

Approximately 35% of sporadic medulloblastomas fall into this category, with a higher incidence in males than in females (approximately 3:1), peak incidence in adolescence, and metastases seen in 35%-40% of tumors at diagnosis. Histology usually shows a classic pattern.

Amplification of the proto-oncogene MYCN and the cyclin-dependent kinase 6 (CDK6) gene is seen in many Group 4 tumors. Typical cytogenetic abnormalities include isochromosome 17q and a deletion of one copy of the X chromosome in females.

The prognosis of Group 4 medulloblastoma is similar to that of SHH-activated type, with a 5-year survival rate of about 75%.

3. Disease staging

According to Chang's staging system, medulloblastoma is staged according to the extent of tumor invasion:

● Stage M0 (limited stage): tumor only at the primary site, no metastasis.

● Stage M1: positive cerebrospinal fluid tumor cells only.

● Stage M2: Nodular implantation in the subarachnoid space of the cerebellum and/or lateral or third ventricles visible to the naked eye.

● Stage M3: Nodular implants are visible to the naked eye in the subarachnoid space of the spinal cord.

● Stage M4: Metastases outside of the central nervous system; skeletal, pulmonary, and hepatic metastases are common.

Disease risk stratification

1) Hazard stratification based on molecular subtypes

The World Health Organization Expert Panel on Medulloblastoma summarized the clinical evidence and delineated risk tiers based on molecular subtypes, combined with the clinical characteristics of the patient, to guide the treatment of pediatric patients (3-17 years of age). The risk levels are categorized into the following different tiers:

● low risk

Survival was greater than 90% and included the following molecular subtypes:

○ WNT activated

○ Group 4 type without metastasis and with chromosome 11 haploid (complete loss of the entire chromosome 11).

● Medium risk/standard risk

Survival is 75-90% and includes the following molecular subtypes:

○ SHH-activated TP53 wild type with no metastasis and no MYCN gene amplification.

○ Group 3 type without metastasis and without MYCN gene amplification.

○ Group 4 type without metastasis and without loss of chromosome 11.

● high risk

Survival is 50-75% and includes the following molecular subtypes:
○ SHH-activated and Group 4 types that have undergone metastasis
○ SHH-activated type with MYCN gene amplification

● extremely high risk

Survival is less than 50% and includes the following molecular subtypes:

○ Group 3 with metastasis

○ TP53 mutant in SHH-activated phenotype (with or without metastasis)

2) Hazard stratification based on clinical information

Medulloblastoma in children over 3 years of age:

● mark a danger

Complete or near-complete resection of the tumor (no residual or residual lesions ≤ 1.5 cm2) and no spread of metastases (staged M0).

● high risk

Subcomplete resection of the tumor (residual lesion >1.5 cm2).

Presence of metastases, including disseminated lesions visible on imaging, tumor cells in lumbar puncture or ventricular cerebrospinal fluid after 14 days postoperatively, or metastases outside the central nervous system.

The histologic pattern was diffuse interstitial variant.

Medulloblastoma in children 3 years of age and younger:

● mark a danger

The tumor was completely resected or nearly completely resected (no residual or residual lesions ≤ 1.5 cm2), without spreading metastasis (staged as M0), and with a histological pattern of pro-connective tissue hyperplasia/nodularity.

● high risk

All cases are high risk except those that fulfill the labeled risk.

Clinical manifestations

Medulloblastoma is often located in the fourth ventricle and compresses the aqueduct, blocking the circulation of cerebrospinal fluid, which accumulates in the ventricles to form hydrocephalus. The tumor grows rapidly and can exhibit signs and symptoms of both increased intracranial pressure and cerebellar dysfunction over a period of weeks to months.

1. Typical symptoms

● Increased intracranial pressure

May be manifested by: night or morning headaches, dizziness, nausea and/or vomiting, altered mental status, decreased energy, diplopia (especially when gazing outward), and optic papillae edema (which can lead to complete or partial loss of vision)

● cerebellar dysfunction

When the tumor is located in the midline, it can cause trunk or gait ataxia, head shaking, and nystagmus. When the tumor is located in the lateral cerebellar hemisphere, it can cause awkward or uncoordinated limb movements.

● Other symptoms in infants

This includes atypical decreased energy, delayed motor development, delayed physical development, and feeding difficulties.

● Possible symptoms of a tumor spreading to the spinal cord

If the tumor spreads to the spinal cord, it may cause: back pain, difficulty walking, difficulty urinating or defecating.

2. Accompanying symptoms

Medulloblastoma of the posterior cranial fossa may lead to obstructive hydrocephalus (also called non-traffic hydrocephalus). This is due to the gradual growth of a tumor in the posterior cranial fossa that presses on the fourth ventricle in front of it, which may cause a blockage in the normal flow of cerebrospinal fluid, resulting in an excessive buildup of cerebrospinal fluid. Obstructive hydrocephalus is almost always accompanied by increased intracranial pressure and may cause signs such as headaches, behavioral changes, developmental delays, nausea and vomiting, lethargy, and an increase in the infant's head circumference.

Clinical Department

The diagnosis of medulloblastoma is determined by histopathologic examination after surgical removal. Histopathologic examination is the gold standard for the diagnosis of medulloblastoma.

For patients with suspected medulloblastoma on imaging, biopsy is usually not routinely performed, but rather direct surgical resection. This is because maximum safe removal is medulloblastoma and other tumors of the posterior cranial fossa is an essential part of treatment.

Clinical Department

Pediatric neurosurgery, or neurosurgery

Examination & Diagnosis

1. Relevant inspections

1) Neurological examination

A neurological examination can reveal abnormalities of the brain, spinal cord and nerves, and the results depend on the exact location of the tumor in the posterior cranial fossa:

Patients with tumors in the midline usually present with trunk or gait ataxia, which manifests as a wide-based gait or heel-toe walking difficulties. Head bobbing (nodding up and down) and nystagmus are also common.

Patients with lateral cerebellar tumors may present with poor distance discrimination on the finger-nose test, intention tremor, or difficulty with the heel-knee-shin test.

In addition to these signs, patients may also have concurrent cranial nerve abnormalities. For example, increased intracranial pressure can lead to dysfunction of the abducens nerve, resulting in diplopia, especially when looking outward.
Prolonged increased intracranial pressure can lead to optic papillae edema and complete or partial loss of vision.

2) Imaging

● Magnetic resonance imaging (MRI) resolves soft tissues better and is the primary diagnostic imaging tool for neurologic disorders. In patients with medulloblastoma, tumors in the midline or paramedian cerebellum that are significantly enhanced by contrast injection often compress the fourth ventricle. If obstruction occurs at the level of the fourth ventricle, hydrocephalus may develop. The presence of significant nodular enhancement or closer to linear enhancement within the ventricles, on the surface of the brain, or in the spinal canal may suggest molluscum contagiosum dissemination. In cases of spinal cord involvement, linear or nodular enhancement along the surface of the spinal cord cartilage and/or tear-drop metastases within the cauda equina are usually seen on MRI.

● It is important to note that medulloblastoma may be missed on CT alone.

3) Cerebrospinal fluid examination

About 1/3 of medulloblastomas spread throughout the central nervous system via the cerebrospinal fluid. In such cases, cerebrospinal fluid cytopathology may reveal tumor cells. Cerebrospinal fluid testing needs to be performed through a lumbar puncture. Since most patients with medulloblastoma will have increased intracranial pressure and/or obstructive hydrocephalus, lumbar puncture must be delayed until after surgery.

Positive preoperative or postoperative cerebrospinal fluid cytology indicates a higher rate of tumor recurrence and a poorer prognosis. However, negative cerebrospinal fluid cytology does not necessarily mean that the tumor has a good prognosis and may be in a more advanced stage.

4) Histopathological examination

Histopathologic examination is the gold standard for the diagnosis of medulloblastoma.

The tumor is a densely cellular tumor with abundant deeply stained, round or ovoid nuclei and little cytoplasm. The range of histopathologic manifestations can vary from an extensive nodular pattern to large cellular/mesenchymal features.

2. Differential diagnosis

The differential diagnosis of medulloblastoma includes other tumors that favor the cerebellum, most commonly hairy cell-type astrocytomas, ventricular meningiomas, and atypical teratoid/rhabdomyosarcoma (ATRT). Certain imaging features can be helpful in identifying these tumors, and after surgery, histopathology can also differentiate between these tumors.

1) Differential diagnosis with hairy cell type astrocytoma

Hairy cell type astrocytoma is usually a cystic structure with wall nodules or a central necrotic structure with annular thick wall enhancement. Medulloblastomas, even with cystic changes, are usually multiple small cyst-like changes.

2) Differential diagnosis with ventricular meningioma

Ventricular meningiomas are usually associated with the ventricles and may grow to fill the fourth ventricle and extend downward through the exit of the fourth ventricle or outward through the lateral foramen. Extension outward through the foramen is rarely seen with medulloblastomas.

3) Differential diagnosis with atypical teratoid/rhabdomyosarcoma

Atypical teratoid/rhabdoid tumors (AT/RT) are significantly rarer than medulloblastomas, but may appear similar on MRI. Atypical teratoid/rhabdoid tumors are more likely to involve both cerebellar hemispheres or the pontine cerebellar angle with intratumoral hemorrhage than medulloblastomas.

Clinical Management

Most patients with medulloblastoma receive a combination of treatments, including safe removal of the tumor through surgery to the greatest extent possible, a combination of radiation therapy to the tumor site and to the whole brain and spinal cord, and systemic chemotherapy.

1. Surgical treatment

Surgery is the treatment of choice for medulloblastoma with a view to safely removing the tumor to the greatest extent possible. Surgical removal of the tumor establishes the diagnosis, relieves increased intracranial pressure and improves quality of life. Surgery is performed to remove as much of the tumor as possible without causing severe neurological sequelae (e.g., persistent ataxia, cranial nerve damage, etc.). Using modern surgical techniques and image guidance in the operating room, total or near-total resection of the tumor under the naked eye can be achieved in most patients.

2. Radiotherapy and chemotherapy

1) Radiotherapy

Radiation therapy (radiotherapy for short) is an important part of medulloblastoma treatment. Radiotherapy can control residual posterior cranial fossa lesions and also treat lesions that have spread along the cerebrospinal axis.

For intermediate-risk disease, the total radiation dose is 54 Gy, of which the whole brain and spinal cord dose is usually 23.4 Gy and the additional dose to the posterior cranial fossa is 30.6 Gy. For advanced disease, the total radiation dose is 54 Gy, of which the whole brain and spinal cord dose is 36 Gy and the additional dose to the posterior cranial fossa is 18 Gy. The exact duration of treatment will depend on the specific disease and staging, see the section "General Treatment". Please refer to the "General Treatment" section.

However, whole-brain whole-spinal cord radiotherapy should be avoided or delayed in children or infants younger than 3 years of age because of the severe toxicity of radiotherapy to the rapidly developing nervous system.

2) Chemotherapy

Chemotherapy (or chemotherapy for short) is usually given during or after radiation therapy and has an important role in the treatment of medulloblastoma.

In children at standard risk, adjuvant chemotherapy reduces the recurrence rate and minimizes radiation exposure to the whole brain and spinal cord. For infants and children under 3 years of age, postoperative use of chemotherapy can delay or avoid irradiation of the developing brain and spinal cord.
Meanwhile, for high-risk medulloblastomas that cannot be surgically removed, peers will treat them with chemotherapy in combination with radiation therapy. The specific treatment regimen will depend on the disease and stage, as described in the "General Treatment" section.

3) Radiotherapy program

(i) Primary medulloblastoma.

3+ years old:

● mark a danger

Where surgical removal is possible, the tumor should be removed as completely as possible by surgery.

Radiotherapy was started 4-6 weeks after surgery, with 54 Gy of irradiation given in the posterior cranial fossa or localized tumor bed, and 23.4 Gy of irradiation given to the whole brain and whole spinal cord.

Chemotherapy was administered 4 weeks after radiotherapy, and the chemotherapy regimen was CCNU+DDP+VCR regimen (cyclophosphamide+cisplatin+vincristine) repeated every 6 weeks for a total of 8 courses. Or CTX+DDP+VCR regimen (cyclophosphamide+cisplatin+vincristine), repeated every 3 weeks for a total of 8 courses.

Studies have shown that chemotherapy given to children during and after radiotherapy significantly improves survival, while chemotherapy given before radiotherapy may decrease survival. According to the Children's Oncology Group (COG) study of vincristine, cisplatin, and lomustine, or vincristine, cisplatin, and cyclophosphamide (all 8 courses of chemotherapy), there was no significant difference in 10-year survival between the two regimens. Electrolyte disturbances were more common in the lomustine group, and infectious complications were higher in the cyclophosphamide group.

● high risk

Where surgical removal is possible, the tumor should be removed as completely as possible by surgery.

Radiotherapy was started 4 weeks after surgery, with 54 Gy of irradiation given in the posterior cranial fossa or localized tumor bed, and 36 Gy of irradiation given to the whole brain and whole spinal cord.

The chemotherapy drugs used in the high-risk group were the same as those used in the standard-risk group. In a study conducted by the American Children's Oncology Group in 161 high-risk children, whole-brain, whole-spinal radiotherapy was given to the children after surgery, along with carboplatin and vincristine chemotherapy, and six cycles of chemotherapy with cyclophosphamide and vincristine, with or without cisplatin, were given at the end of the radiotherapy. The five-year progression-free and overall survival rates were 59% and 68% in the combined cisplatin group and 71% and 82% in the group without cisplatin, with no significant difference.

3 and under:

Due to the toxicity of radiotherapy to the rapidly developing central nervous system, radiotherapy is delayed or avoided as much as possible in favor of surgery combined with chemotherapy in children 3 years of age and younger.

Whenever possible, the tumor should be removed as completely as possible by surgery. The ease of surgical resection is related to the histologic characteristics of the tumor, with medulloblastomas of the fibroproliferative/nodular and extensively nodular types being easier to remove cleanly than the classic type.

● mark a danger

Surgical resection. Adjuvant chemotherapy was started 2-4 weeks after surgery with a CTX + VCR/HD-MT/CBP + VP16 regimen (cyclophosphamide + vincristine/ methotrexate/carboplatin + etoposide), repeated every 2 weeks for 12 courses.

● high risk

Surgical resection. Adjuvant chemotherapy was started 2-4 weeks after surgery with a CTX + VCR/HD-MT/CBP + VP16 (cyclophosphamide + vincristine/ methotrexate/carboplatin + etoposide) regimen, repeated every 2 weeks for 12 courses.

Localized tumor bed radiotherapy or palliative radiotherapy after radiotherapy or chemotherapy after 3 years of age.

ii) Recurrent medulloblastoma

There is no standard treatment option for relapsed medulloblastoma, which is usually a combination of surgery and radiotherapy. Some studies have shown that the use of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in such cases can prolong disease-free survival for 20-25% of patients.

The additional use of whole-brain whole-spinal cord radiotherapy sometimes prolongs disease-free survival in infant and young child patients whose tumors recur after surgery or after chemotherapy alone.

4) Adverse reactions

Whole brain and spinal cord radiotherapy significantly increases the incidence of neurological complications, including neurocognitive dysfunction. In developing children, it may also lead to delayed bone growth, hypothyroidism, adrenal insufficiency and hypogonadism.

Chemotherapy causes cytotoxicity, and general side effects include: hair loss, mouth ulcers, loss of appetite, nausea and vomiting, diarrhea or constipation, increased chance of infection, easy bruising or bleeding, and fatigue. The severity of the side effects is related to the type of drug, the dose, and the duration of chemotherapy. Both cisplatin chemotherapy regimens and radiation therapy may bring about ototoxicity, which can result in hearing loss.

3. Other treatments

High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation is a therapeutic option in the group of high-risk children with a poorer prognosis.

In a study of high-risk children aged 3 years and older, high-dose chemotherapy followed by bone marrow suppression combined with autologous hematopoietic stem cell transplantation resulted in a five-year progression-free event survival rate of 70% with no treatment-related deaths. In a similar study, but in high-risk children 3 years of age and younger, similar treatment also improved five-year survival.

4. Frontline treatment

As research on medulloblastoma-related molecular pathways and mutated genes continues to progress, the medical community has investigated molecularly targeted therapies related to pathogenesis and prognosis, especially for SHH-activated phenotypes.

● Vismodegib, an inhibitor of the SMO gene in the SHH pathway, has been approved by the FDA for the treatment of progressive basal cell carcinoma. Vismodegib has been shown to be effective in some, but not all, SHH-activated medulloblastomas.

● In a phase II clinical trial by the Pediatric Brain Tumor Consortium, 31 adults and 12 children with recurrent medulloblastoma were given 150-300
mg daily of vimodegib. The non-SHH-activated patients did not respond to vimodegib. 4 of the 12 SHH-activated patients, 3 of whom were pediatrics, demonstrated a response to the drug, with the effect sustained for at least 8 weeks, and in one case for more than 6 months. This drug response appeared to be associated with mutations in the PTCH1 or SMO genes, whereas non-responding SHH-activated patients were more likely to have mutations in the SUFU or GLI2 genes. Patients with mutations in the TP53 gene were also less likely to respond to vimodegib.

Prognosis

1. General

Modern comprehensive treatments allow approximately 75% of children with medulloblastoma to survive into adulthood.

The main factors that affect the prognosis are:

l Age at diagnosis, with younger age being less favorable.

l Whether or not there is dissemination or metastasis at the time of diagnosis

l How much tumor remains after surgery

l Histologic type of tumor

l Risk stratification of tumors (including molecular subtype stratification and clinical stratification)

In children under three years of age, European studies have shown that fibroproliferative/nodular and extensive nodular medulloblastomas generally have a better prognosis, with a five-year event-free survival rate of 90% and an overall survival rate of 100%. The five-year event-free and overall survival rates for children with classic medulloblastoma were in the range of 30% and 68%. In the United States, the five-year event-free and overall survival rates for fibroproliferative/nodular and extensive nodular medulloblastoma are 77% and 85%, compared with 17% and 29% for other types.

2. Sequelae

Whole brain whole spinal cord radiotherapy in developing children can lead to neurocognitive dysfunction, which can have an impact on the child's intellectual development and cognitive function. Some studies have shown that the effects of this neurocognitive dysfunction can be most pronounced if the child's age at diagnosis is under 7 years old.

Also, radiotherapy to the brain may affect the functioning of the endocrine system. At the end of tumor treatment, the child may require endocrine therapy depending on the condition.

In addition, radiotherapy increases the risk of secondary cancers, including distant secondary cancers many years later. In one study, the cumulative 10-year incidence of secondary cancers after initial treatment for medulloblastoma was 4.2%, and nearly half were malignant gliomas of the central nervous system.

3. Rehabilitation

If functional or speech impairment occurs as a result of medulloblastoma treatment, rehabilitation in a rehabilitation unit may be considered. There is no standardized protocol for this type of rehabilitation, and it should be done according to the actual condition as prescribed by the doctor.

4. Complications

1) Hydrocephalus

Due to the gradual growth of the tumor in the posterior cranial fossa and the compression of the fourth ventricle in front of it, the normal flow of cerebrospinal fluid (CSF) may be obstructed or the absorption of CSF may be impeded, resulting in the accumulation of excessive CSF and causing obstructive hydrocephalus (also known as non-traffic hydrocephalus). However, after the tumor is removed and the obstruction is lifted, this type of hydrocephalus can usually resolve on its own. However, some patients may still have or develop hydrocephalus after surgery. The causes of hydrocephalus in this case are more complicated and diverse, including decreased arachnoid resorption ability after postoperative radiotherapy, decreased brain tissue compliance, tumor residuals, tumor recurrence, incomplete release of compression, postoperative intracranial infections, intraoperative/postoperative hemorrhage flowing into the subarachnoid space causing arachnoid adhesion, and so on.

The incidence of postoperative hydrocephalus after tumor surgery is usually hydrocephalus caused by impaired absorption of cerebrospinal fluid, called traffic hydrocephalus. For traffic hydrocephalus, there is a lack of etiologic treatment, which relies on ventriculoperitoneal shunting, in which a catheter is placed to shunt the hydrocephalus into the peritoneal cavity. The feasibility of a triventriculostomy can also be evaluated based on the pathologic type of the tumor, the cause of the hydrocephalus, and the current severity of the hydrocephalus.

2) Posterior Cranial Fossa Syndrome

Surgical removal of tumors in the midline area of the cerebellum can cause posterior cranial fossa syndrome, also known as cerebellar mutism, which can be seen in about one-fourth of patients who have medulloblastoma removed, including:

● Delayed speech production or aphasia

● Ataxia (a motor coordination disorder)

● eye movement disorder

● Decreased muscle tone

l Emotional instability or behavioral disorders

l Inability to move spontaneously (temporary)

l Neurocognitive dysfunction

3) Whole Brain Whole Spinal Cord Radiotherapy Side Effects

Whole brain and spinal cord radiotherapy significantly increases the incidence of neurological complications, including neurocognitive dysfunction. Irradiation of the nervous system may result in neurocognitive dysfunction, affecting attention, memory, and processing ability, among other things, with risk factors including young age, high-risk disease, and radiotherapy dose.

In addition, due to radiation to the thyroid, jaw, pharynx and larynx, this may increase the risk of delayed hypothyroidism or mandibular hypoplasia in developing children. It can also lead to delayed bone growth, adrenal insufficiency and hypogonadism.

These side effects may be minimized by reducing the dose of radiotherapy and/or using new radiotherapy techniques. For example, irradiation of the medial temporal lobe, inner ear, thyroid, lungs, heart, and abdominal organs can be avoided or reduced with proton beams, thus reducing side effects.

4) Hearing loss

Both cisplatin chemotherapy regimens and radiation therapy may be ototoxic and, in excess, may cause irreversible hearing loss.

5. Recurrence

Although the prognosis for children with medulloblastoma has been improving, the recurrence rate after initial treatment is still expected to be 20-30%. Most recurrences in children occur within 3 years of the first diagnosis. In the case of recurrence after initial treatment, the patient's likelihood of long-term survival is greatly reduced.

Follow-up & Review

After the completion of medulloblastoma treatment, you should be careful to conduct timely reviews and follow-ups to monitor the side effects caused by the treatment on the one hand, and keep a close eye on the recurrence of the disease on the other hand.

another visit doctor

Because most relapses occur within 3 years of treatment, most protocols recommend close follow-up during this time, with physical examination and imaging (MRI of the brain and spinal cord) every 3 months for the first 1-2 years. This can be done every 6-12 months thereafter. Neurologic examination every 1-2 years.

For endocrine function abnormalities that may result from treatment, a baseline assessment of endocrine status is recommended within one year of completing treatment, followed by annual screening for hypothyroidism, growth hormone deficiency, and adrenal insufficiency by blood tests.

For radiotherapy and chemotherapy that may cause ototoxicity, children should have a baseline assessment of their hearing, and then hearing loss can be detected in time during treatment. Hearing tests should be performed every 1-2 years after completion of treatment.

Routine

1. Management of daily life

1) Rest and exercise

The patient needs to be guaranteed a sleep schedule. Regular and quality sleep is helpful for recovery and immunity. A suitable sleep environment (usually dimly lit, quiet, and at the right temperature) may be helpful in improving the patient's quality of sleep.

If the patient's physical condition permits, you can encourage and assist the patient to perform some simple activities. Moderate exercise is helpful in preventing muscle atrophy, enhancing physical strength and endurance, and promoting appetite.

2) Diet

Relevant studies have shown that many medulloblastoma patients are malnourished and their weight is lower than normal. Therefore, care should be taken to provide patients with a nutritious and balanced diet, guaranteeing the intake of high-quality proteins (e.g. meat, eggs, milk, poultry, fish and shrimp, soybeans and soybean products, etc.), as well as more grains and cereals, vegetables and fruits, and dairy products and nuts in moderation, in order to ensure the intake of other nutrients. Clinical dietitians in the nutrition department of the hospital can be consulted to provide appropriate nutritional programs for patients. If weight loss is severe, nutritional support through tube feeding or parenteral nutrition may be considered.

3) Living habits

If a child has neutropenia due to treatment, care should be taken to prevent infection. It is important to pay attention to personal and living environment hygiene, do not approach patients with infectious diseases and do not go to crowded places.

If the treatment causes thrombocytopenia, care needs to be taken to avoid bleeding by staying away from sharp, prickly toys and objects, as well as avoiding impact-intensive sports (e.g., bouncing, soccer, basketball, etc.).

2. Special considerations

Patients with medulloblastoma are at risk for long-term side effects and secondary tumors, the onset of which may occur many years after the completion of medulloblastoma treatment, and this risk is related to the regimen and dosage of medulloblastoma treatment. Therefore, it is important to keep a record of all patient visits and treatments for future review and reference.

3. Daily disease monitoring

Post-operative complications, chemotherapy-induced side effects (e.g., hair loss, fatigue, vomiting, etc.), recurrence of tumor metastasis, and growth problems need to be attended to. Consult your doctor when fever, worsening of symptoms, new symptoms, and treatment-induced side effects occur.

4. Prevention

Since the exact cause of medulloblastoma is not known, there is no better way to prevent it. However, regular follow-up and maintenance of good healthy lifestyle habits can help prevent and detect the recurrence of the disease or the emergence of long-term effects as early as possible.

Cutting-edge Therapeutic & Clinical Research

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References

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