Rhabdomyosarcoma

Summarize

1. General

OVERVIEW: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in childhood, accounting for about 6.5% of childhood tumors. The primary site is the head and neck, followed by the trunk, limbs and genitourinary system.

Prevalence: Most common in children and adolescents, especially those under 10 years of age.

Clinical manifestations: rhabdomyosarcoma can occur in all parts of the body, with tumors on the head and neck, genitourinary organs and limbs being the most common. According to the different parts of the body, there will be different symptoms. In the early stage, it is mostly manifested as painless lump found unintentionally, with no local redness, swelling, heat and pain.

Treatment: rhabdomyosarcoma is sensitive to chemotherapy and radiotherapy, but the effect of single treatment is poor, and multidisciplinary combined integrated treatment of medical oncology, surgery and radiotherapy is needed.

Prognosis: The overall five-year survival rate for rhabdomyosarcoma is about 70% in children under 15 years of age.

2. Definition of disease

Rhabdomyosarcoma is a rare malignant tumor and is the most common soft-tissue sarcoma in children, most commonly in children under the age of 10. Rhabdomyosarcoma cells develop from abnormally growing early-stage muscle cells and can occur in all parts of the body, commonly in the head and neck, limbs, and genitourinary organs.

Epidemiological

epidemiological

Rhabdomyosarcoma commonly occurs in children and adolescents, with rare cases occurring in adults, and children under the age of 10 accounting for about 50 percent of all cases. According to the National Cancer Institute (NCI), the incidence of rhabdomyosarcoma in children is 4.5 cases per million.

There are gender and ethnicity differences in the incidence of different pathologic types of rhabdomyosarcoma. For example, embryonal rhabdomyosarcoma is more prevalent in men, while mesenchymal rhabdomyosarcoma is slightly more prevalent in blacks than in other races.

Etiolog & Risk factors

1. General

Rhabdomyosarcoma develops from early muscle cells that have abnormal development, and these abnormalities are usually caused by mutations in genes. A number of specific gene mutations are known to cause rhabdomyosarcoma, but can only explain a very small number of cases. For the majority of cases, no clear cause of the disease has been identified.

2. Underlying causes

Rhabdomyosarcoma originates from rhabdomyoblasts. Rhabdomyoblasts are muscle cells that are early in development. When there is an abnormality in the division and proliferation of rhabdomyoblasts, they may develop into rhabdomyosarcoma.

Currently, certain specific genes or chromosomes are known to be associated with the development of rhabdomyosarcoma. For example, a heterozygous deletion of chromosome 11 is present in some embryonal rhabdomyosarcomas. Chromosomal translocations t(2;13)(q35;q14) or t(1;13)(q36;q14) are present in some follicular rhabdomyosarcomas, forming the corresponding fusion genes PAX3-FKHR and PAX7-FKHR, respectively, with the PAX3- FKHR fusion gene is associated with poor prognosis. However, for most cases of rhabdomyosarcoma, the cause of pathogenesis is not known.

3. Triggers

Some genetic disorders and congenital syndromes are associated with an increased risk of developing rhabdomyosarcoma, including:

● Li-Fraumeni cancer susceptibility syndrome, a genetic disorder in which patients have inherited mutations in the TP53 gene

● DICER1 syndrome (DICER1)

● Neurofibromatosis type 1

● Costello syndrome, a genetic disorder in which patients have an inherited mutation in the HRAS gene

● Beckwith-Wiedemann syndrome (BWS)

● Noonan syndrome.

● Neonatal overweight at birth correlates with increased risk of embryonal rhabdomyosarcoma

It is important to note that these genetic or congenital risks are usually very rare, and having these risk factors does not necessarily mean that you will develop rhabdomyosarcoma. If you do have a particular risk factor, you need to be screened promptly, but there is no need to be overly anxious.

Classification & Stage

Type of disease

(1) Disease typing

The World Health Organization (WHO) classifies rhabdomyosarcoma into the following three subtypes according to histologic type:

● Embryonic type (ERMS)

According to a U.S. database, embryonal rhabdomyosarcoma accounts for 57% of all rhabdomyosarcoma cases and includes both the grape cluster cell type and the spindle cell type. Embryonal rhabdomyosarcoma usually occurs in the head and neck, bladder, vagina, prostate, and testes, and most often occurs in children under the age of 5, but may occur in other age groups as well. The ratio of male to female patients is 3:2. Embryonal rhabdomyosarcoma has one of the best prognoses of all rhabdomyosarcomas.

● Adenoidal (ARMS)

According to a U.S. database, adenoid rhabdomyosarcoma accounts for 23% of all rhabdomyosarcoma cases and occurs most often on the trunk and extremities. The incidence of adenoid rhabdomyosarcoma does not vary by age or gender and can occur in children, adolescents, and young adults. It is also true that adenoid rhabdomyosarcoma is more common than the embryonal type in children over the age of 5 years. Vesicular rhabdomyosarcoma tends to progress more rapidly than the embryonal type and therefore requires more intense treatment.

● pleomorphic or anaplastic RMS

Polymorphic or mesenchymal rhabdomyosarcoma is very rare, occurs most often in adults, and is extremely rare in children. Pleomorphic rhabdomyosarcoma progresses rapidly, has a less favorable prognosis, and requires intense treatment.

(2) Disease Staging

Currently used staging methods for rhabdomyosarcoma combine two staging/grouping systems: the TNM clinical staging system developed by the International Society for Pediatric Oncology Research based on pretreatment imaging, and the American Rhabdomyosarcoma Study Group's (IRS) postoperative-pathologic clinical grouping system.

● Pre-treatment clinical staging system for TNM based on pre-treatment imaging developed by the International Society for Pediatric Oncology Research:

Stage 1: Tumor originates in a location with a good prognosis, including the orbit, head and neck (except for the parietal meningeal region), biliary tract, and genitourinary tract (not kidneys, bladder, or prostate), tumor is confined to the primary anatomical site or the tumor extends beyond the primary anatomical site and invades adjacent organs or tissues, tumor is ≤5 cm or >5 cm in diameter, no or concomitant regional lymph node metastasis or regional lymph node metastasis unknown, and no distant metastasis .

Stage 2: Tumor originates in locations with poor prognosis, including bladder, prostate, limb, meninges, back, retroperitoneum, pelvis, perineum, perianal area, gastrointestinal tract, and liver, tumor is confined to the primary anatomical site or tumor extends beyond the primary anatomical site and invades neighboring organs or tissues, tumor does not exceed 5 cm in diameter, there are no regional lymph node metastases or regional lymph node metastases are unknown, and there are no distant metastases.

Stage 3: Tumor originates in a location with poor prognosis (including bladder, prostate, limb, meninges, back, retroperitoneum, pelvis, perineum, perianal, gastrointestinal tract, liver), tumor is confined to the primary anatomical site or the tumor extends beyond the primary anatomical site and invades neighboring organs or tissues, the tumor is ≤5 cm or >5 cm in diameter, there is no or concomitant regional lymph node metastasis or regional lymph node metastasis is not known, there is no distant metastasis, and does not belong to stage 2.

Stage 4: Tumor originates in a good prognostic site or a poor prognostic location, tumor is confined to the primary anatomical site or the tumor extends beyond the primary anatomical site and invades adjacent organs or tissues, tumor diameter ≤ 5 cm or > 5 cm, without or with regional lymph node metastasis, and the tumor has distant metastasis.

● The American Rhabdomyosarcoma Study Group (IRS) postoperative-pathologic clinical grouping system:

Stage I: limited lesion with complete resection of the tumor and pathologically confirmed complete resection without regional lymph node metastasis (except for head and neck lesions, which require lymph node biopsy or resection to confirm the absence of regional lymph node involvement).

Stage Ia: Tumor is confined to the primary muscle or primary organ.

Stage Ib: Tumor invades into adjacent tissues beyond the primary muscle or organ, such as through the fascial layer.

Stage II: complete resection of the tumor as seen by the naked eye, and the tumor has local infiltration (meaning that the tumor infiltrates or invades the tissues adjacent to the primary site) or regional lymph node metastasis (meaning that the tumor migrates to the lymph nodes in the drainage area of the primary site).

Stage IIa: complete resection of the tumor as seen by the naked eye, but with microscopic residuals and no metastasis in the regional lymph nodes.

Stage IIb: complete resection of the tumor as seen by the naked eye, with no residue microscopically, but with metastasis in the regional lymph nodes.

Stage IIc: complete resection of the tumor as seen by the naked eye, with microscopic residuals and metastases in the regional lymph nodes.

Stage III: Tumor not completely removed or only biopsy sampling with residual tumor in the meatus.

Stage IIIa: biopsy sampling only.

Stage IIIb: The tumor is mostly removed as seen by the naked eye, but there is significant residual tumor in the naked eye.

Stage IV: There are distant metastases (meaning that the tumor has entered the blood circulation and metastasized to other parts of the body), lung, liver, bone, bone marrow, brain, distant muscle or lymph node metastases (positive cytology of cerebrospinal fluid, pleural or abdominal effusion, and presence of tumor in the pleura or peritoneum).

(3) Disease Risk Grouping

According to the pathological subtype, clinical stage before TNM treatment and postoperative pathological stage, rhabdomyosarcoma was divided into low-risk group, intermediate-risk group, high-risk group and central invasion group according to the risk level in order to stratify the treatment. The specific groupings were as follows: low-risk group: embryonal rhabdomyosarcoma with TNM pre-treatment clinical stage 1 and IRS stage I-III, and embryonal rhabdomyosarcoma with TNM pre-treatment clinical stage 2-3 and IRS stage I-II.

Intermediate-risk group: embryonal or pleomorphic rhabdomyosarcoma with clinical stage 2-3 and IRS stage III prior to TNM treatment, and vesicular or pleomorphic rhabdomyosarcoma with TNM stage 1-3 and IRS stage I-III.

High-risk group: rhabdomyosarcoma with clinical stage 4 and IRS stage IV before TNM treatment.

Central invasion group: rhabdomyosarcoma with clinical stage 3-4 and IRS stage III-IV prior to TNM treatment, with any of intracranial diffuse metastasis, cerebrospinal fluid positivity, skull base invasion, or cranial nerve palsy.

Clinical manifestations

1. General

Rhabdomyosarcoma can occur anywhere in the body, most commonly in the head and neck, genitourinary organs, and extremities. It is easier to detect early because the site of development is usually obvious. The most common early symptom is a painless lump that grows over time. However, depending on the site of onset, the specific presenting symptoms may vary.

2. Typical symptoms

Symptoms of rhabdomyosarcoma vary depending on where the tumor is growing.

● Tumors that grow in the nasal passages: may cause nasal congestion, similar to the symptoms of a sinus infection, and may lead to nosebleeds.

● Tumors that grow in the ear: may cause ear pain, bleeding or fluid in the ear canal, and lumps may be found in the ear canal.

● Tumors that grow behind the eye: may cause the eye to swell or protrude, and the child may develop a crossed eye.

● Tumors that grow in the bladder, urethra, vagina, and testicles: may cause difficulty urinating or blood in the urine, vaginal bleeding, and lumps may be found in the vagina and around the testicles.

● Tumors growing in the abdominal or pelvic cavity: may cause abdominal pain, vomiting, and constipation.

● Tumors that grow on the extremities: they usually present as lumps on the extremities and are usually painless.

If the tumor metastasizes, the child may also develop a chronic cough, bone pain, swollen lymph nodes, weakness, and weight loss.

Clinical Department

1. General

Most of the initial symptoms of rhabdomyosarcoma are relatively obvious, and many cases can be diagnosed early if early symptoms are detected and timely medical treatment is provided. The diagnosis of rhabdomyosarcoma is usually made by combining the results of clinical manifestations, imaging examinations, pathological tissue examinations and other aspects.

2. Consultation room

Through the specifics of the hospital's departmental scope of care, you can be seen in oncology, pediatrics, pediatric surgery, orthopedics or bone oncology.

Examination & Diagnosis

1. Relevant examinations

(1) Imaging

Imaging tests can identify the location of the tumor and determine if it has spread. For rhabdomyosarcoma, common imaging tests are:

● Ultrasound (primary tumor site): Because ultrasound is quick, easy to perform, and non-radioactive, it is generally used as one of the first tests for patients with suspected tumors. It is usually used to look for tumors growing in the abdomen.

● CT: CT tests are often used to look for tumors in the abdomen, pelvis and chest and can measure the size of the tumor.

● Magnetic Resonance Imaging (MRI): MRI is better than CT for viewing the brain and spinal cord and other soft tissues without radiation and can also measure the size of tumors.

● Bone scan: allows scanning of bone structures and is used to assist in checking for bone metastases from rhabdomyosarcoma.

● Positron Emission Computed Tomography (PET-CT) Scan: A combination of PET scan and CT. Although PET scans are not as detailed as CT and MRI, they can directly scan the entire body and are often used as an adjunct to CT. For patients with rhabdomyosarcoma, a whole body PET-CT scan may be considered if available.

(2) Pathologic and histologic examination

While imaging can effectively assist in the diagnosis of rhabdomyosarcoma, pathologic tissue examination is the gold standard for confirming the diagnosis of the disease. Pathological tissue examination may be performed by puncture or surgical biopsy of a sample, which is sent to the laboratory for morphology, immunohistochemistry and molecular biology in order to determine the type of tumor and its specific staging.

(3) Blood biochemistry tests

Blood is drawn for electrolytes, liver and kidney function, and lactate dehydrogenase.

(4) Organ function tests

Routine blood, urine, and stool, electrocardiogram, echocardiogram, and hearing test (before application of platinum-based chemotherapy).

(5) Other inspections

Bone marrow cytology routine.

If the tumor is primary or metastatic to the orbit, middle ear, nasal cavity, sinuses, nasopharynx, infratemporal fossa, pterygopalatine, parapharyngeal region, and other paraspinal areas, cerebrospinal fluid should be examined.

2. Differential diagnosis

Embryonal and alveolar rhabdomyosarcomas can be differentiated based on age of onset, location, and molecular biological features. Embryonal rhabdomyosarcomas are most common in children younger than 5 years of age and are found in the head and neck, bladder, vagina, prostate, and testes; whereas, there is no age-specific difference in the incidence of adenomatous rhabdomyosarcomas, so that adenomatous rhabdomyosarcomas predominate in older children and adolescents and are more likely to be found on the trunk and extremities. Also, some embryonal rhabdomyosarcomas have heterozygous deletions on chromosome 11 and have a higher rate of background and single nucleotide mutations than adenoid rhabdomyosarcomas. In contrast, some of the vesicular rhabdomyosarcomas have characteristic chromosomal translocations t(2;13)(q35;q14) or t(1;13)(q36;q14), which form the corresponding fusion genes PAX3-FKHR and PAX7-FKHR, respectively.These molecular biological features can be used as a basis for the development of embryonic-type and vesicular rhabdomyosarcoma differential diagnosis.

Rhabdomyosarcoma of the face needs to be differentiated and diagnosed from hemangioma, a benign tumor that can regress on its own. Hemangiomas have a characteristic growth pattern, usually slowing down after 6 months of age and hardly growing after 1 year of age. Rhabdomyosarcoma, on the other hand, will continue to grow if left untreated.

Clinical Management

1. General

Treatment of rhabdomyosarcoma requires a combination of treatments such as surgery, radiation therapy and chemotherapy. Surgery is usually the preferred option. If the tumor is difficult to remove completely, radiation and chemotherapy can be used to shrink the tumor before surgery. Chemotherapy is required after surgery, and most patients also require radiation therapy.

2. Surgery

Surgery for rhabdomyosarcoma is usually performed with a wide local excision, which will remove the tumor and some of the surrounding tissue (including lymph nodes). Rhabdomyosarcoma should ideally undergo complete tumor resection, or resection with only microscopic residue. However, complete surgical resection is more difficult to achieve in most cases of childhood rhabdomyosarcoma. If complete resection is not possible or if the lesion involves the orbit, vagina, bladder, or biliary tract, chemotherapy or radiation therapy may be used to shrink the tumor before surgery in order to preserve the organs and their function. If the first surgery only partially removes the tumor, it can be operated after 3 to 6 months (4 to 8 courses) of chemotherapy and/or radiotherapy. In order to achieve complete removal of the primary tumor lesion, a second surgery may be performed to remove the original remaining positive margins or the original biopsy-only site.

3. Radiotherapy

Rhabdomyosarcoma embryonal type IRS stage I does not do radiotherapy, while stage II-IV needs radiotherapy. The adenomatous type is prone to local recurrence, so IRS stage I also requires radiotherapy. In terms of risk grouping, patients in the low-risk group with TNM stage 1 or with primary tumors located in the uterus and cervix that have been completely resected and have negative local lymph nodes can be treated without radiotherapy, while the rest of the patients need radiotherapy. Smaller doses of radiotherapy can be administered in fractions and over a longer period of time to minimize early and late radiation damage. The specific radiotherapy doses are as follows:

● Vesicular IRS stage I: 36.0 Gy

● IRS Staging IIa: 36.0 Gy

● IRS staging stages IIb, IIc (stage IIc radiotherapy includes lymph node regions): 41.4 Gy

● IRS stage III, orbital radiotherapy only: 45.0 Gy

● IRS stage III, radiotherapy to sites other than orbits: 50.4 Gy

● Secondary biopsy negative: 36.0 Gy

● Positive secondary biopsy: 41.4 Gy

● Naked eye residue or large mass: 50.4 Gy

Patients in the nonmaxillofacial or craniocerebral region may be treated with radiotherapy within 1 week after surgery if the tumor has been completely removed by surgery. If the patient has skull base invasion with significant compression symptoms and requires urgent radiotherapy, radiotherapy may be given before chemotherapy. In other patients, including those with tumors occurring in the maxillofacial and genitourinary systems, if the tumor is large and inoperable, radiotherapy is recommended for the primary tumor at week 13 of chemotherapy, and for metastatic tumors can be delayed until week 25 of chemotherapy.

If the primary tumor is located in a vital organ that cannot be surgically removed, a trial of built-in particle radiotherapy, in which low-dose radiation pellets are placed into or near the tumor, may be considered, and is usually used for tumors of the genitourinary system and the head and neck.

4. Chemotherapy

All patients with rhabdomyosarcoma in the risk grouping require chemotherapy.

● Chemotherapy regimens used in the low-risk group include the VAC regimen (vincristine + actinomycin D + cyclophosphamide) and the VA regimen (vincristine + actinomycin D).

● Chemotherapy regimens used in the intermediate-risk group include the VAC regimen (vincristine + actinomycin D + cyclophosphamide) and the VI regimen (vincristine + irinotecan).

● Chemotherapy regimens used in the high-risk group include the VAC regimen (vincristine + actinomycin D + cyclophosphamide), the VI regimen (vincristine + irinotecan), the VDC regimen (vincristine + adriamycin + cyclophosphamide) and the IE regimen (cyclophosphamide + etoposide).

● Chemotherapy regimens used in the central invasion group include the VAI regimen (vincristine + actinomycin D + isocyclophosphamide), the VACa regimen (vincristine + actinomycin D + carboplatin), the VDE regimen (vincristine + adriamycin + etoposide) and the VDI regimen (vincristine + adriamycin + isocyclophosphamide).

It should be noted that irinotecan may cause adverse reactions such as severe granulocytopenia and diarrhea, the severity of which is related to the UGT1A1 gene.

The specific chemotherapy regimen for rhabdomyosarcoma may be adjusted depending on the patient's condition and should be followed.

The general rules of chemotherapy for rhabdomyosarcoma are as follows:

(1) Based on imaging and other examinations, it is estimated that the tumor can be basically completely resected by surgery first; those who have difficulty in completely resecting the tumor will be biopsied only, and the diagnosis will be clarified by chemotherapy before surgery. If surgery is chosen, chemotherapy will be started within 7 d after surgery. Pay attention to the results of pathology consultation at the 1st chemotherapy, if it is vesicular type, it is recommended to check the fusion genes PAX3-FKHR and PAX7-FKHR to correct the risk grouping.

(2) Avoid actinomycin D (ACTD) and adriamycin (ADR) during radiotherapy and reduce the chemotherapy dose to half the dose.

(3) Chemotherapy is necessary in all stages. Different intensities of chemotherapy were used according to risk grouping (Table 5, Table 6, Table 7, Table 8). The maximum amount of vincristine was 2.0 mg, and the maximum amount of ACTD was 2.5 mg. Discontinuation of the drug could be considered 4-6 courses after complete remission, and individualized adjustment of the regimen was considered when the total number of courses exceeded 12. Tumor foci were evaluated at 12 weeks of chemotherapy, and the group was discharged if the tumor enlarged or new foci appeared.

(4) Dosage and pre-chemotherapy requirements: age <12 months old, chemotherapy dose was reduced by half or weight ≤12 kg was calculated according to body weight, dose = body surface area dose/30×body weight (kg), each course of treatment was separated by 21 d. Before each course of chemotherapy, neutrophils (ANC) >0.75×109/L and platelets (PLT) >100×109/L were injected, 24-48 hours after the end of chemotherapy, granulocyte stimulating factor (GCSF) or granulocyte stimulating factor (GM-CSF) was injected. ～48 h, granulocyte stimulating factor (G-CSF) or granulocyte stimulating factor (GM-CSF) was started. Those with bone marrow recovery >28 d had a 25% reduction in the next course of treatment.

(5) Determination of toxic and side effects of chemotherapeutic drugs: based on the grading standard of NCI adverse effects (CTCAE version 4.0, 2009). Cardiac, hepatic, renal function and hearing should be tested before and after chemotherapy. Alanine aminotransferase (ALT) should be <2 times the normal value and total bilirubin <1.5 times the normal value. In case of renal insufficiency, the dosage should be reduced in proportion to the decrease in creatinine clearance (Ccr).

(6) Routine oral cotrimoxazole [25 mg/(kg-d), 2 times/d] was administered 3 d weekly from the start of chemotherapy until 3 months after the end of chemotherapy.

5. Cutting-edge treatment

(1) Proton therapy

Proton therapy is a new type of radiotherapy. Compared with conventional radiotherapy, proton therapy is able to deliver radiotherapy to the tumor site more precisely and with less radiation to the surrounding tissues. Rhabdomyosarcoma can be treated with proton therapy, but whether the treatment effect is necessarily better than that of conventional radiotherapy is still controversial and is still under further study.

(2) Immunotherapy

Immunotherapy uses the body's own immune system to kill tumor cells. Several immunotherapies are currently being investigated in the treatment of rhabdomyosarcoma:

● Tumor vaccine: for the treatment of metastatic rhabdomyosarcoma, currently under investigation.

● CTLA-4 inhibitors and PD-1 therapy: These two immunotherapies allow the immune system to better recognize and kill tumor cells, and their use in rhabdomyosarcoma is currently under investigation.

(3) Targeted therapy

Targeted therapies are therapies designed to target specific markers on tumor cells. Two targeted therapies for rhabdomyosarcoma are currently under investigation:

● mTOR inhibitors: This targeted drug inhibits the division and survival of tumor cells. Its use against recurrent rhabdomyosarcoma is currently under investigation.

● Tyrosine kinase inhibitors: This small molecule targeted drug blocks signaling pathways within tumor cells, thereby inhibiting cell division and proliferation. Its use against recurrent rhabdomyosarcoma is currently under investigation.

● Inhibition of angiogenesis-targeted drugs: this type of targeted drugs such as bevacizumab injection, apatinib, pazopanib and anrotinib, etc., have been applied to children's rhabdomyosarcoma in the domestic clinical research, and have a certain degree of efficacy.

Prognosis

1. General

The overall 5-year survival rate for rhabdomyosarcoma is above 70%. The 5-year survival rate varies by risk subgroup: the 5-year survival rate is 70-90% in the low-risk group, 50-70% in the intermediate-risk group, and 20-30% in the high-risk group. Factors affecting prognosis are:

● Age of patient at diagnosis: Pediatric rhabdomyosarcoma patients usually have a better prognosis than adult patients, with 5-year overall survival rates of 61% (children) and 27% (adults), respectively, according to U.S. statistics. Among children, those aged 1-9 years have the best prognosis. According to recent clinical studies conducted by the U.S. Rhabdomyosarcoma Study Group (IRS), the 5-year survival rates for patients under 1 year of age and patients 10 years of age or older were both 76%, and for patients 1-9 years of age, the 5-year survival rate was 87%.

● Location of the primary tumor: according to clinical studies conducted by the U.S. Rhabdomyosarcoma Study Group (IRS) in recent years, the 5-year survival rates for primary rhabdomyosarcomas located in different sites are: orbital tumors 95%, superficial head and neck (except paramedian region) 78%, cranial paramedian region 74%, genitourinary organs (not bladder and prostate) 89%, bladder or prostate 81%, extremities 74%, trunk or abdomen or perineum 67%, biliary tract 78%.

● Tumor size at diagnosis: Children with small tumors (less than 5 cm in diameter) at diagnosis have a relatively good prognosis.

● Whether the tumor is completely removed at the time of surgery: the less tumor remains after surgery, the better the prognosis usually is. In a clinical study by the American Rhabdomyosarcoma Study Group (IRS), the 5-year survival rate of patients who had complete removal of the tumor at the time of surgery was more than 90%; the 5-year survival rate of patients who had complete removal of the tumor seen with the naked eye at the time of surgery but with microscopic residuals was about 80%; and the 5-year survival rate of patients who had residuals of the tumor visible to the naked eye after the surgery, but without metastases, was about 70%.

● Tumor type: In general, embryonal rhabdomyosarcoma has a better prognosis than the follicular type and much better than the pleomorphic type.

● Presence of genetic and chromosomal variants associated with prognosis: In vesicular rhabdomyosarcoma, patients with the PAX3-FKHR fusion gene have a relatively poor prognosis.

● Whether the tumor has metastasized to the lymph nodes at the time of diagnosis: patients with lymph node metastasis at the time of diagnosis usually have a relatively poor prognosis.

● Whether the tumor has developed distant metastasis at the time of diagnosis: Patients with distant metastasis at the time of diagnosis usually have a less favorable prognosis.

2. Complications

Secondary tumors may develop in a small number of patients. Tumors of the genitourinary system and their treatment may affect the function of the relevant organs, such as bladder dysfunction or infertility. In pediatric patients, tumors of other sites and their treatment may also cause developmental problems in the corresponding organs, such as long and short legs. If symptoms of complications are observed, prompt medical attention should be sought.

3. Recurrence

Recurrence of rhabdomyosarcoma usually occurs within 3 years of treatment. In patients with rhabdomyosarcoma who achieve 5-year event-free survival, recurrence is very rare, and the rate of distant recurrence at 10 years is 9%. However, the probability of recurrence is higher if the tumor is growing in a poor prognostic location at the time of the patient's initial diagnosis (including the bladder, prostate, limbs, meninges, back, retroperitoneum, pelvis, perineum, perianal area, gastrointestinal tract, and liver) and complete resection is not possible or if the patient's tumor has already metastasized at the time of the initial diagnosis.

Common sites of recurrence of rhabdomyosarcoma include the primary site of the tumor, lungs, bone, and bone marrow. Recurrence in the breast (female adolescents) and liver has also been reported, but is very rare. Treatment of recurrent rhabdomyosarcoma requires a combination of tools, such as surgery, radiation therapy, and chemotherapy.

Overall, the prognosis for recurrent rhabdomyosarcoma is less favorable. Factors that affect the prognosis include the site of tumor recurrence, the interval between the end of treatment for the primary tumor and recurrence, and whether radiation therapy was done to treat the primary tumor.

Follow-up & Review

1. General

Complete treatment as prescribed and maintain good lifestyle habits. Regular follow-up should be performed after completion of treatment to monitor recurrence and distant adverse effects in general.

2. Review and follow-up

● Physical examination, routine blood tests, blood biochemistry, blood pressure, chest X-rays, and imaging of the primary site of the tumor were performed at 3-month intervals in year 1.

● Physical examination, routine blood tests, blood biochemistry, blood pressure, chest X-rays, and imaging of the primary site of the tumor were performed at intervals of 4 months in the second to third year.

● Physical examination, routine blood tests, blood biochemistry, blood pressure, chest X-rays, and imaging of the primary site of the tumor were performed at 6-month intervals in year 4.

● Physical examination, blood tests, biochemistry and blood pressure were performed annually in the 5th to 10th year.

● After 10 years, annual follow-ups are performed whenever possible, with attention to the child's marriage and childbearing, and the status of the second tumor.

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

It is recommended to provide patients with a nutritious and well-balanced diet, guaranteeing the intake of high-quality proteins (e.g. meat, eggs, milk, poultry, fish and shrimp, soybeans and soybean products, quinoa, etc.), as well as more grains and cereals, vegetables and fruits to ensure the intake of other nutrients. Patients with reduced immunity during treatment should avoid expired, spoiled, unclean and potentially food-safe foods. Specific dietary advice can be obtained from the dietitian at your hospital.

2. Special considerations

Keep a record of all patient visits and treatments to be used as a reference for future reviews and medical appointments.

If a pediatric patient has received radiation therapy to the eyes or mouth at the time of treatment, he or she should visit an eye or dental surgeon for regular checkups after completing treatment.

If a pediatric patient's tumor grows in the limbs, he or she should keep an eye on the development of the limbs after treatment, and seek orthopedic care if developmental problems such as long or short legs appear.

3. Prevention

There is no better way to prevent rhabdomyosarcoma due to the unknown cause of the disease, but regular follow-up and maintenance of good lifestyle habits can help prevent and early detection of recurrence of the disease or the emergence of long-term effects.

Cutting-edge Therapeutic & Clinical Research

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References

1. Pediatric Oncology Specialized Committee of the Chinese Anti-Cancer Association, Hematology Group of the Pediatrics Branch of the Chinese Medical Association, Oncology Group of the Pediatric Surgery Branch of the Chinese Medical Association. Recommendations for the diagnosis and treatment of rhabdomyosarcoma in children and adolescents in China (CCCG-RMS-2016). Chinese Journal of Pediatrics, 2017, 55(10): 724-728.

2. https://www.cancer.gov/types/soft-tissue-sarcoma/hp/rhabdomyosarcoma-treatment-pdq

3. https://www.cancer.gov/types/soft-tissue-sarcoma/patient/rhabdomyosarcoma-treatment-pdq#_1