Surgical Management Treatment Options
        Head and neck
        Extremity sites
        Truncal sites
        Genitourinary system
        Unusual primary sites
        Metastatic sites
Chemotherapy Treatment Options
         Low-risk patients
        Intermediate-risk patients
        High-risk patients
Radiation Therapy Management Options
        Standard treatment options
        Treatment options under clinical evaluation
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence.)

The basic principle for the initial surgical treatment of children with rhabdomyosarcoma is complete resection of the primary tumor with a surrounding margin of normal tissue and lymph node sampling of the draining nodal basin provided that major functional/cosmetic impairment is not necessary.[1][Level of evidence: 3iii] Important exceptions to the rule of normal margin exist (e.g., tumors of the orbit and of the genitourinary region).[2,3] The principle of wide and complete resection of the primary tumor is less applicable to patients known to have metastatic disease at the initial operation, but is a reasonable concept if easily accomplished. Patients with microscopic residual tumor following their initial excisional procedure appear to have improved prognoses if a second operative procedure consisting of re-excision of the primary tumor bed, prior to initiation of chemotherapy, can achieve complete removal of tumor.[4] There is no evidence that debulking surgery that leaves macroscopic residual tumor improves outcome, compared with biopsy alone.[5][Level of evidence: 2A] Because rhabdomyosarcoma can arise from multiple sites, surgical care must be tailored to the unique aspects of each site. Surgical management of the more common primary sites is given below.

If the tumors are parameningeal (in the nasopharynx/nasal cavity, middle ear/mastoid, paranasal sinus, or parapharyngeal/infratemporal fossa region), a magnetic resonance imaging (MRI) scan with contrast of the primary site and brain should be obtained to check for presence of base-of-skull erosion and possible extension through the dura. If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan of the same regions with contrast is indicated. If there is any suspicion of extension down the spinal cord, an MRI scan with contrast of the entire cord should be obtained. The cerebrospinal fluid (CSF) should be examined for malignant cells in all patients with parameningeal tumors. For head and neck tumors that are superficial and nonorbital, wide excision of the primary tumor (when feasible) and ipsilateral neck lymph node sampling of clinically involved nodes are appropriate. Narrower resection margins (<1 mm) are acceptable because of anatomic restrictions. Cosmetic and functional factors should always be considered, but with modern techniques, complete resection in patients with superficial tumors need not be inconsistent with good cosmetic and functional results. Specialized, multidisciplinary surgical teams have performed resections of anterior skull-based tumors in areas previously considered inaccessible to definitive surgical management, including the nasal areas, paranasal sinuses, and temporal fossa. These procedures should only be considered, however, in children with recurrent locoregional disease or residual disease following chemotherapy and radiation therapy. For patients with head and neck primary tumors that are considered unresectable, chemotherapy and radiation therapy are the mainstay of primary management.[6-10] Rhabdomyosarcomas of the orbit do not require orbital exenteration at diagnosis; only a biopsy is needed to establish diagnosis.[11,12] Biopsy is followed by chemotherapy and radiation therapy, with orbital exenteration reserved for the small number of patients with locally persistent or recurrent disease.[8,13] Despite its parameningeal site, middle ear rhabdomyosarcoma has a favorable prognosis.[9]

The definitive surgical procedure involves wide local excision with en bloc removal of a cuff of normal tissue.[2] Primary re-excision may be appropriate in patients whose initial surgical procedure leaves microscopic residual disease that is resectable by a second procedure.[4] Because of the significant incidence of nodal spread for extremity primary tumors (often without clinical evidence of involvement), and because of the prognostic and therapeutic implications of nodal involvement, extensive pretreatment assessment for regional nodal involvement is warranted.[14-17] The Soft Tissue Sarcoma Committee of the Children’s Oncology Group (STS-COG) recommends systematic aggressive axillary node sampling for patients with upper-extremity primary tumors and clinically and radiographically negative nodes. The STS-COG also recommends inguinal and femoral triangle node sampling for patients with lower-extremity primary tumors. If clinically positive nodes are present, biopsy of more proximal nodes is recommended prior to sampling the involved nodal region. Sentinel lymph node (SLN) mapping is employed at some centers to identify the regional nodes that are the most likely to be involved. The contribution of SLN mapping is not yet clearly defined in pediatric patients.[17-19]

The surgical management of patients with lesions of the chest wall or abdominal wall should follow the same guidelines as those used for lesions of the extremities (i.e., wide local excision and an attempt to achieve negative microscopic margins). These resections may require use of prosthetic materials. Very large truncal masses should be biopsied prior to the administration of chemotherapy and/or radiation and should be followed by delayed primary resection to achieve negative margins and reconstruction. Most patients who present with large tumors in these sites have localized disease that is amenable to complete resection with negative margins after preoperative therapy and is therefore associated with excellent long-term survival.[20-22]

Intrathoracic or intra-abdominal disease may not be resectable because of the massive size of the tumor at the time of the diagnosis and extension into vital organs.[23] In two retrospective studies of children with localized retroperitoneal tumors, the outcome was somewhat better for patients who received debulking surgery initially or after chemotherapy and radiation therapy compared with those whose surgical therapy consisted only of initial biopsy.[23,24] Patients with rhabdomyosarcoma arising from tissues around the perineum or anus usually have advanced disease. These patients have a high likelihood of regional lymph node involvement, and many of the tumors have alveolar histology. The current recommendation is to sample the lymph nodes. When feasible, without unacceptable morbidity, removing all gross tumor prior to beginning chemotherapy improves the likelihood of cure. The overall survival (OS) after aggressive therapy for tumors in this location was 49%.[25] An exception is a rhabdomyosarcoma arising within the biliary tree, but even at that location, total resection is rarely feasible. Outcome is good despite residual disease after surgery. External biliary drains significantly increase the risk of postoperative infectious complications. Thus, external biliary drainage and aggressive resection for biliary tract rhabdomyosarcoma are not warranted.[26] For patients with initially unresectable abdominal disease, complete surgical resection following chemotherapy offers a significant survival advantage (73% vs. 34%–44% without resection).[23]

Primary sites for childhood rhabdomyosarcoma within the genitourinary system include the paratesticular area, bladder, prostate, vagina, uterus, and vulva. Specific considerations for the surgical management of tumors arising at each of these sites are discussed in the paragraphs below.

Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the entire spermatic cord, utilizing an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[27] Resection of hemiscrotal skin is required when there is tumor fixation or invasion, or when a previous transscrotal biopsy has been performed. Paratesticular tumors have been found to have a relatively high incidence of lymphatic spread (26% in Intergroup Rhabdomyosarcoma Study [IRS]-I and IRS-II studies),[14] and all patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with contrast to evaluate nodal involvement. For patients who are younger than 10 years with group I disease, and whose CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary but a repeat CT scan every 3 months is recommended.[28,29] For patients with suggestive or positive CT scans, retroperitoneal lymph node sampling (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[3,30,31] In contrast, a staging ipsilateral retroperitoneal lymph node dissection is currently required for all children older than 10 years with paratesticular rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) and STS-COG studies. Node dissection is not routine in Europe for adolescents with resected paratesticular rhabdomyosarcoma. European investigators tend to rely on radiographic rather than surgical assessment of retroperitoneal lymph node involvement.[27,28] It appears, however, that the ability of the CT scan to predict the presence of lymph node involvement needs further study.[32] For patients with paratesticular tumors, repositioning the contralateral testicle prior to scrotal radiation may preserve hormone productivity.[33][Level of evidence: 3iii]

Bladder salvage is an important goal of therapy for patients with tumors arising in the prostate and bladder. An important review providing information about historical, current, and future treatment approaches for prostate and bladder rhabdomyosarcomas has been published.[34] In rare cases, the tumor is confined to the dome of the bladder and can be completely resected. Otherwise, to preserve a functional bladder in patients with gross residual disease, chemotherapy and radiation therapy have been used to reduce tumor bulk,[35,36] followed, when necessary, by a more limited surgical procedure, such as partial cystectomy.[37] Early experience with this approach was disappointing, with only 20% to 40% of patients with bladder/prostate tumors remaining alive and with functional bladders 3 years following diagnosis (3-year OS was 70% in IRS-II studies);[37,38] the more recent experience from IRS-III and IRS-IV studies, which used more intensive chemotherapy and radiation therapy, showed 55% of patients alive with functional bladders at 3 years from diagnosis, with 3-year OS exceeding 80%.[36,39,40] Thus, this approach to therapy remains generally accepted, with the belief that more effective chemotherapy and radiation therapy will continue to increase the frequency of bladder salvage. The initial surgical procedure in most patients consists of a biopsy, which often can be performed using ultrasound guidance, cystoscopy, or by a direct-vision transanal route. For patients with biopsy-proven, residual malignant tumor following chemotherapy and radiation therapy, appropriate surgical management may include partial cystectomy, prostatectomy, or exenteration (usually approached anteriorly with preservation of the rectum). Very few studies have objective long-term assessments of bladder function, and urodynamic studies are important to obtain accurate evaluation of bladder function.

In patients who have been treated with chemotherapy and radiation therapy for rhabdomyosarcoma arising in the bladder/prostate region, the presence of well-differentiated rhabdomyoblasts in surgical specimens or biopsies obtained after treatment does not appear to be associated with a high risk of recurrence and is not an indication for a surgical procedure such as total cystectomy.[39,41,42] One study suggested that in patients with residual bladder tumors with histologic evidence of maturation, additional courses of chemotherapy should be given prior to considering cystectomy.[39] Surgery should be considered only if malignant tumor cells do not disappear over time following initial chemotherapy and radiation therapy. Because of very limited data, it is unclear whether this situation is analogous for patients with rhabdomyosarcoma arising in other parts of the body.

For patients with genitourinary primary tumors of the vagina/vulva/uterus, the initial surgical procedure is usually a transvaginal biopsy. Initial radical surgery is not indicated in rhabdomyosarcoma of the vagina/vulva/uterus.[3] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and adjunctive radiation when necessary, appears to result in excellent disease-free survival.[43] Because of the smaller number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy or radiation therapy is also effective.[43] Exenteration is usually not required for primary tumors at these sites, but if needed it may be done with rectal preservation in most cases.

Rhabdomyosarcoma occasionally arises in sites other than those mentioned above. An unusual site is the diaphragm. Patients with these tumors often have locally advanced disease that is not grossly resectable initially because of fixation to adjacent vital structures such as the lung, great vessels, pericardium, and/or liver. In that circumstance, chemotherapy should be initiated after diagnostic biopsy, with the intent to try to remove residual tumor at a later date.[44] Patients with laryngeal rhabdomyosarcoma will usually be treated with chemotherapy and radiation therapy after biopsy in an attempt to preserve the larynx.[45]

Primary resection of metastatic disease is rarely indicated.[46] Persistent metastatic disease in the lung following radiation and chemotherapy should be resected when possible to render patients disease free, provided that adequate pulmonary function can be preserved.[46]

All children with rhabdomyosarcoma should receive chemotherapy. The intensity and duration of the chemotherapy are dependent on the risk group assignment.[47]

Standard treatment options

• Low-risk patients have a localized embryonal histology tumor in a favorable site, or a localized embryonal rhabdomyosarcoma in an unfavorable site which has been grossly resected (groups I and II). (See Table 2 in the Staging Information section of this summary.)

Certain subgroups of low-risk patients have achieved high cure rates of approximately 90% using two-drug chemotherapy with vincristine and actinomycin D. See Table 5 below:

Other subgroups of low-risk patients have achieved high cure rates using three-drug chemotherapy with vincristine, actinomycin D, and cyclophosphamide. See Table 6 below:

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ARST0331 : The COG low-risk embryonal rhabdomyosarcoma regimen includes four initial courses of cyclophosphamide, using a historically modest dose of 1.2 g/m²/course, with vincristine, actinomycin-D, and cyclophosphamide administered every 3 weeks followed by radiation therapy at week 13 for patients with microscopic, locoregional, or gross residual tumor. Subsequently, patients receive 4 or 12 further courses of vincristine/dactinomycin depending on the tumor stage and clinical group. The protocol is designed to increase efficacy of treatment while shortening the duration of treatment for a subset of low-risk patients and reducing both acute toxicity (myelosuppression) and long-term toxicity (impaired fertility).

Standard treatment options

• Patients with intermediate prognosis have survival rates ranging from 55% to 70%. This category includes patients with embryonal rhabdomyosarcoma at unfavorable sites who have gross residual disease (i.e., group III), and patients with nonmetastatic alveolar rhabdomyosarcoma at any site. For patients with intermediate prognosis, vincristine, dactinomycin, and cyclophosphamide (VAC) is the standard chemotherapy treatment.[48-50] The IRS-IV randomly assigned patients to receive either standard VAC therapy or one of two other chemotherapy regimens. One regimen combined vincristine and dactinomycin with ifosfamide (VAI),[51] based on the activity of ifosfamide against rhabdomyosarcoma.[52,53] The other regimen combined vincristine with ifosfamide and etoposide (VIE).[54] The combination of ifosfamide and etoposide had previously demonstrated substantial activity against rhabdomyosarcoma in phase II trials.[55] In the IRS-IV study, there was no difference in outcome between these three treatments, confirming that VAC remains the standard chemotherapy combination for children with intermediate-prognosis rhabdomyosarcoma.[31] A comparison of survival for patients with tumors of embryonal histology treated on IRS-IV (received higher doses of cyclophosphamide [or ifosfamide equivalent]) with similar patients treated on IRS-III (received lower doses of cyclophosphamide [or ifosfamide equivalent]) suggests a benefit with the use of higher doses for certain groups of intermediate-risk patients. The benefit may accrue patients with tumors at favorable sites and positive lymph nodes, patients with gross residual disease, or patients with tumors at unfavorable sites who underwent grossly complete resections (but not patients with unresectable embryonal rhabdomyosarcoma at unfavorable sites).[56] For other groups of intermediate-risk patients, an intensification of cyclophosphamide was feasible but did not improve outcome.[57]



• The COG has also evaluated whether the addition of topotecan and cyclophosphamide to standard VAC therapy improves outcome for children with intermediate-risk rhabdomyosarcoma. Topotecan was prioritized for evaluation based on its preclinical activity in rhabdomyosarcoma xenograft models as well as its single agent activity in previously untreated children with rhabdomyosarcoma, particularly those with alveolar rhabdomyosarcoma.[58,59] Furthermore, the combination of cyclophosphamide and topotecan demonstrated substantial activity in both the recurrent disease setting as well as in newly diagnosed patients with metastatic disease.[60,61] The COG clinical trial (COG-D9802) for newly diagnosed patients with intermediate-risk disease randomized patients to receive either VAC therapy or VAC therapy with additional courses of topotecan and cyclophosphamide. Patients randomized to receive topotecan and cyclophosphamide fared no better than those treated with VAC alone.[62]



• In a limited institution pilot study, a combination of vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide (IE) has been used to treat patients with intermediate risk rhabdomyosarcoma. The relative efficacy of this approach versus the standard approach requires further investigation.[63][Level of evidence: 3iiiA]

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ARST0531 : The new COG intermediate-risk rhabdomyosarcoma protocol will compare standard VAC chemotherapy versus VAC alternating with vincristine and irinotecan (VI). Radiation therapy will commence at week 4 in conjunction with VI to determine the potential benefit of early local therapy in this group of patients.

Standard treatment options

• High-risk patients have metastatic disease in one or more sites at diagnosis (stage 4). These patients continue to have a relatively poor prognosis (≤50% 5-year survival rate) with current therapy, and new approaches to treatment are needed to improve survival in this group.[50,64,65] In a pooled analysis of high-risk rhabdomyosarcoma patients treated with multiagent chemotherapy (all chemotherapy regimens used a cyclophosphamide or ifosfamide plus dactinomycin and vincristine-based backbone with variation as to the use of additional chemotherapy agents) followed by local therapy (surgery with or without radiation therapy) within 3 to 5 months of starting chemotherapy, adverse prognostic factors in patients presenting with metastatic disease included: age younger than 1 year or age 10 years or older, unfavorable primary site, bone or bone marrow involvement, and three or more metastatic sites. The event-free survival (EFS) rate at 3 years was 50% for patients without any of these adverse prognostic factors. The EFS rates were 42%, 18%, 12% and 5% for patients with one, two, three, or four adverse prognostic factors, respectively.[66][Level of evidence: 3iiiA]

  The standard systemic therapy for children with metastatic rhabdomyosarcoma is the three-drug combination of VAC. Despite many clinical trials attempting to improve outcome by adding additional agents to standard VAC chemotherapy (or substituting new agents for one or more components of VAC chemotherapy), to date, no chemotherapy regimens have been shown to be more effective than VAC. For example, in the IRS-IV study, three combinations of drug pairs were studied in an up-front window: IE, vincristine/melphalan (VM),[67] and ifosfamide/doxorubicin (ID).[68] These patients received VAC after the up-front window agents were evaluated at weeks 6 and 12. OS for patients treated with IE and ID was comparable (31% and 34%, respectively) and better than those treated with VM (22%).[68] However, results with VAC chemotherapy for stage 4 rhabdomyosarcoma in the North American experience are similar. Results from a phase II window trial of patients with metastatic disease at presentation and treated with topotecan and cyclophosphamide showed activity for this two-drug combination, but survival was not different from previous regimens.[60,61] An up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma gave similar results.[59] Irinotecan and irinotecan with vincristine [69] have also been evaluated as up-front windows by the STS-COG; the response rates were better when irinotecan was administered with vincristine than without it, but again, survival in a preliminary analysis was not improved over prior experience.[69] In a French study, 20 patients with metastatic disease at diagnosis received window therapy with doxorubicin for two courses. Thirteen of 20 patients responded to therapy. Four patients had progressive disease.[70]

• High-dose chemotherapy with stem cell rescue has been evaluated in a limited number of patients with rhabdomyosarcoma,[71-75][Level of evidence: 3iiiA] but has failed to improve the prognosis of patients with poor-risk rhabdomyosarcoma.

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ARST0431 : The COG high-risk trial is currently closed and results are pending. This trial was for all patients with rhabdomyosarcoma and metastatic disease, regardless of age and histology. The trial evaluated an intensified treatment regimen which began with two courses of vincristine and irinotecan in conjunction with radiation therapy. Continuation therapy included cycles of vincristine/doxorubicin/cyclophosphamide and IE using interval dose compression. The regimen also included VAC pulses. The feasibility and toxicity of combining VI with radiation therapy was also evaluated.



• A study from the Cooperative Weichteilsarkomstudie (CWS) group demonstrated that oral maintenance chemotherapy with a trofosfamide-containing regimen might offer clinical benefit in selected patients with metastatic rhabdomyosarcoma,[75][Level of evidence: 3iiiA] and this therapeutic alternative is being investigated prospectively in one of the European Soft Tissue Sarcoma Study Group trials using oral vinorelbine and cyclophosphamide.[76]

Radiation therapy is an effective method for achieving local control of tumor for patients with microscopic or gross residual disease following biopsy, initial surgical resection, or chemotherapy. Patients with completely resected tumors (group I) of embryonal histology do well without radiation therapy,[48,49] but radiation therapy benefits patients with group I tumors with alveolar or undifferentiated histology.[77] A review of European trials conducted by the Cooperative Soft Tissue Sarcoma Study Group between 1981 and 1998 in which radiation therapy was omitted for some group II patients demonstrated a benefit to using radiation therapy as a component of local tumor control for all group II patient subsets (defined by tumor histology, tumor size, and tumor site).[78] Local failure is the predominant type of relapse for patients with group III disease. Patients with tumor-involved regional lymph nodes at diagnosis have a higher risk of local and distant failure compared with patients whose lymph nodes are negative.[79] As with the surgical management of patients with rhabdomyosarcoma, recommendations for radiation therapy are dependent on the site of primary tumor and on the amount of residual disease, if any, following surgical resection. For patients with head and neck rhabdomyosarcoma, two studies reported excellent local control in 28 patients treated with intensity-modulated radiation therapy (IMRT) or fractionated stereotactic radiation therapy and chemotherapy over a 4-year period. Further study is needed, but the use of IMRT and chemotherapy in patients with head and neck rhabdomyosarcoma may result in less severe late effects.[80,81]

For optimal care of pediatric patients undergoing radiation treatments, it is imperative to have a radiation oncologist, radiation technicians, and nurses who are experienced in treating children. An anesthesiologist may be necessary to help sedate and immobilize young patients. The facility should be equipped with a linear accelerator and have the capabilities to administer electron beam therapy. Computerized treatment planning with a three-dimensional planning system should be available. Techniques to deliver radiation specifically to the tumor while sparing normal tissue (e.g., conformal radiation, IMRT, proton-beam therapy, or brachytherapy) should be considered.[82-84]

• The radiation therapy dose depends predominantly on the amount of residual disease, if any, following the primary surgical resection. In general, patients with microscopic residual disease (group II) receive radiation therapy to approximately 41 Gy,[77,85] though doses from 30 Gy to 40 Gy may be adequate in patients receiving effective multiagent chemotherapy.[86] IRS-II patients with gross residual disease (group III) who received 40 Gy to more than 50 Gy had locoregional relapse rates greater than 30%; higher doses of radiation (>60 Gy) have been associated with unacceptable long-term toxic effects.[87,88] Group III patients on the IRS-IV standard treatment arm received 50.4 Gy.[89]



• The treated volume should be determined by the extent of tumor at diagnosis prior to surgical resection and prior to chemotherapy. A margin of 2 cm is generally used, including clinically involved regional lymph nodes.[77] While the volume irradiated may be modified based on guidelines for normal tissue tolerance, gross residual disease at the time of radiation should receive full-dose treatment.



• The timing of radiation therapy generally allows for chemotherapy to be given for 1 to 3 months prior to the initiation of radiation therapy. In current COG protocols, patients with parameningeal disease who have evidence of meningeal extension start radiation therapy at the beginning of treatment.[49,90,91] A prospective trial of 26 patients with group III parameningeal rhabdomyosarcoma achieved good local control and survival with radiation therapy administered at the conventional time.[92] Radiation therapy is usually given for 5 to 6 weeks (e.g., 1.8 Gy per day for 28 treatment days), during which time chemotherapy is usually modified to avoid the radiosensitizing agents dactinomycin and doxorubicin.

The IRSG conducted a randomized study within the IRS-IV protocol and showed that giving radiation therapy twice a day, 6 to 8 hours apart, at 1.1 Gy per dose (hyperfractionated schedule), 5 days per week was feasible but difficult to accomplish in small children who required sedation twice daily. Patients with localized, gross residual tumors were randomly assigned to receive conventional radiation therapy (50.4 Gy vs. 59.4 Gy) given by the twice-daily hyperfractionated schedule. There was no demonstrated advantage in terms of local control.[93] Therefore, conventional radiation therapy remains the standard for treating patients with rhabdomyosarcoma and gross residual disease.[31]

Among the modifications of radiation therapy for specific primary sites recommended for IRS-IV patients are the following:[31,89]

• For patients with orbital tumors, precautions should be taken to limit the dose to the lens, cornea, lacrimal gland, and optic chiasm.



• Patients with bladder/prostate primary tumors who present with a large pelvic mass resulting from a distended bladder caused by outlet obstruction receive treatment to a volume defined by imaging studies following initial chemotherapy.



• Girls with genitourinary primaries should have their ovaries shielded, or possibly moved, when receiving radiation to the lower abdomen and pelvis.



• Patients with parameningeal disease with intracranial extension in contiguity with the primary tumor, and/or cranial base bone erosion, and/or cranial nerve palsy do not require whole-brain irradiation nor intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[90] Patients should receive radiation to the site of primary tumor with a 2-cm margin to include the meninges adjacent to the primary tumor [91] and the region of intracranial extension, if present, again with a 2-cm margin. Patients with intracranial extension should begin receiving radiation therapy within 2 weeks after diagnosis.[91]



• Rarely, children (1) can present with tumor cells in the CSF, (2) may have other evidence of diffuse meningeal disease, and/or (3) may have multiple intraparenchymal brain metastasis from a distant primary tumor. They should be treated with central nervous system-directed irradiation in addition to chemotherapy/radiation therapy for the primary tumor. Spinal irradiation may also be indicated.

Very young children (≤36 months) diagnosed with rhabdomyosarcoma pose a therapeutic challenge because of their increased risk for treatment-related morbidity. Recent experience [94] supports using a somewhat reduced dose of radiation therapy in settings where surgery alone is insufficient to provide a high likelihood of local control. For children with initially unresectable tumors, delayed gross total resection followed by 36 Gy beam radiation therapy provides an excellent likelihood of local control. For infants with unresectable tumors, higher doses of radiation therapy remain appropriate. Radiation techniques are designed to maximize normal tissue sparing, and should include conformal approaches, often with intensity modulated techniques.

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• Brachytherapy, using either intracavitary or interstitial implants, is another method of local control and has been used in select situations for children with rhabdomyosarcoma, especially those with primary tumors at vaginal or vulvar sites.[95-99] In a small single-institution study, this treatment approach was associated with a high survival rate (85%) and with retention of a functional vagina in most patients.[96] Other sites, especially head and neck, have also been treated with brachytherapy.[100] Patients with initial group III disease who later have microscopic residual disease after chemotherapy with or without delayed surgery are likely to achieve local control with radiation at doses of 40 Gy or more.[101]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with previously untreated childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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