Head and neck sites

Orbit. Rhabdomyosarcomas of the orbit should not undergo exenteration, but biopsy is needed for diagnosis.[68,69] Biopsy is followed by chemotherapy and RT, with orbital exenteration reserved for the small number of patients with locally persistent or recurrent disease.[60,70] RT and chemotherapy are the standard of care, with survival rates exceeding 90% to 95%. When RT is omitted, there is risk of local relapse. For patients with orbital tumors, precaution should be taken to limit the RT dose to the lens, conjunctiva, and cornea. The COG investigators have shown that patients with embryonal rhabdomyosarcoma of the orbit who achieve a complete response to induction chemotherapy have improved local control after radiation therapy of 45 Gy, compared with patients who fail to achieve a complete response.[71][Level of evidence B4] For patients in whom a complete response has not been achieved with induction chemotherapy, 50.4 Gy of RT is recommended by the investigators. The COG studied a lower dose of cyclophosphamide to reduce the risk of infertility. In the COG ARST0331 (NCT00075582) trial, only four cycles of therapy contained cyclophosphamide, for a total cyclophosphamide exposure of 4.8 g/m2. Sixty-two patients with Group III orbital embryonal rhabdomyosarcoma were treated. None of the 15 patients with radiographic complete response (CR) had local recurrences, compared with 6 of the 38 patients who had less than a CR after 12 weeks of vincristine, dactinomycin, and cyclophosphamide (VAC) chemotherapy (P = .11). The authors concluded that for patients with Group III orbital embryonal rhabdomyosarcoma achieving a CR after VAC chemotherapy that includes modest-dose cyclophosphamide, 45 Gy of RT may be sufficient for durable FFS. However, for patients with less than a CR who were treated with the ARST0331 systemic therapy, a radiation dose of 50.4 Gy or a higher dose of cyclophosphamide may be needed to achieve the control rate reported in the IRS-IV trial.[71][Level of evidence B4] Long-term outcomes were evaluated in 218 patients with orbital rhabdomyosarcoma enrolled in COG clinical trials between 1997 and 2013. The 192 patients with low-risk orbital rhabdomyosarcoma (clinical groups I–III with mostly embryonal histology treated on the low-risk D9602 and ARST0331 studies) had 10-year EFS and OS rates of 85.5% (95% CI, 77.0%–94.0%) and 95.6% (95% CI, 90.8%–100.0%), respectively. The 26 patients with non–low-risk orbital rhabdomyosarcoma (mostly tumors with alveolar histology that were treated with more intensive intermediate-risk protocols [D9802, D9803 and ARST0531]), had 5-year EFS and OS rates of 88.5% (95% CI, 75.6%–100.0%) and 95.8% (95% CI, 87.7%–100.0%), respectively. Twenty-eight patients experienced a recurrence, including 25 who were treated in low-risk trials (6 patients did not receive radiation therapy during initial therapy). Twenty-seven recurrences were local. One metastatic recurrence occurred in a patient with Group III, PAX3::FOXO1 fusion–positive alveolar rhabdomyosarcoma. Patients with recurrent orbital rhabdomyosarcoma had a 10-year OS rate of 69.4% (95% CI, 50.0%–88.8%) from time of recurrence, showing that a significant number of patients with recurrent orbital rhabdomyosarcoma may achieve long-term survival.[72]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

In a retrospective trial, starting RT within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure but was of borderline significance.[74]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › In a retrospective trial, starting RT within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure but was of borderline significance.[74]

When no signs of meningeal impingement were present, delay of RT for more than 10 weeks did not impact local failure rates.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

A comparison of local control, FFS, and OS rates showed no statistical difference between early irradiation (day 0) for Group III patients in the IRS-IV study with cranial nerve palsy and/or cranial base erosion versus later initiation of RT (week 12) for Group III patients in the D9803 study who had similar evidence of meningeal involvement. This suggested that early RT for this group of patients is not necessary.[75][Level of evidence B4]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

A retrospective analysis of 47 patients with parameningeal primary sites suggested that the subgroup of adolescent patients with alveolar rhabdomyosarcoma (n = 13) might benefit from the addition of prophylactic irradiation (36 Gy) to bilateral cervical nodes.[76][Level of evidence C2]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

A single-institution retrospective review identified 14 patients with head and neck alveolar rhabdomyosarcoma. All patients were treated with multiagent chemotherapy and RT to the primary site and clinically involved nodes.[77][Level of evidence C2]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A single-institution retrospective review identified 14 patients with head and neck alveolar rhabdomyosarcoma. All patients were treated with multiagent chemotherapy and RT to the primary site and clinically involved nodes.[77][Level of evidence C2]

There were ten relapses in the cohort: seven regional nodal, one combination local and regional nodal, and two leptomeningeal.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A single-institution retrospective review identified 14 patients with head and neck alveolar rhabdomyosarcoma. All patients were treated with multiagent chemotherapy and RT to the primary site and clinically involved nodes.[77][Level of evidence C2]

In six of eight patients (75%) with no nodal disease at diagnosis, isolated regional nodal relapse developed.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A single-institution retrospective review identified 14 patients with head and neck alveolar rhabdomyosarcoma. All patients were treated with multiagent chemotherapy and RT to the primary site and clinically involved nodes.[77][Level of evidence C2]

The authors recommended elective nodal irradiation to treat at-risk draining lymph node stations relative to the primary tumor site for patients who present with head and neck alveolar rhabdomyosarcoma.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

The OS rate at 10 years for the entire cohort was 66%.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

Patients with zero or one adverse factor (age <3 or >10 years at diagnosis, presence of meningeal involvement, tumor diameter >5 cm, unfavorable primary parameningeal site) had a 10-year OS rate of 80.7%.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

Patients with two adverse factors had a 10-year OS rate of 68.4%.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

Patients with three or four adverse factors had a 10-year OS rate of 52.2%.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › An analysis of 1,105 patients with localized parameningeal rhabdomyosarcoma treated from 1984 to 2004 in North America and Europe found that several prognostic factors could be used to define subgroups of patients with significantly different survival rates.[78][Level of evidence C1]

Patients who did not receive RT as a component of their initial therapy had a poor prognosis, and their tumors were not salvaged with introduction of RT after relapse. This finding establishes RT as a necessary component of initial treatment.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

A single-institution prospective registry identified 25 patients with head and neck parameningeal rhabdomyosarcoma who were treated with proton-beam RT.[79]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A single-institution prospective registry identified 25 patients with head and neck parameningeal rhabdomyosarcoma who were treated with proton-beam RT.[79]

Of 25 total patients, 11 had intracranial extension at baseline, 6 of whom experienced a local recurrence.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A single-institution prospective registry identified 25 patients with head and neck parameningeal rhabdomyosarcoma who were treated with proton-beam RT.[79]

This recurrence rate is similar to the rate reported in the IRS-IV and D9803 trials for patients with high-risk parameningeal rhabdomyosarcoma.[75]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83]

A study included 15 children and adolescents with intermediate- and high-risk parameningeal rhabdomyosarcoma who were treated with proton RT during cycle 1 or 2 of chemotherapy.[80]

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A study included 15 children and adolescents with intermediate- and high-risk parameningeal rhabdomyosarcoma who were treated with proton RT during cycle 1 or 2 of chemotherapy.[80]

At 3 weeks from RT simulation, most patients demonstrated a significant reduction in initial tumor volume.

Nonorbital and cranial parameningeal. If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), 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 onto or through the dura.[61,73,74] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, 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 patients with high-risk parameningeal tumors. Because complete removal of these tumors is not feasible, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis. Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension bordering the primary tumor and/or signs of meningeal impingement (i.e., cranial base bone erosion and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[73] Patients should receive RT to the site of primary tumor with a 1.5-cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5-cm margin.[74] Evidence (timing of RT for nonorbital and cranial parameningeal tumors): Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG protocols II though IV, eight patients had tumor cells in the CSF at diagnosis. Three of four patients without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of the four patients who had concomitant metastases elsewhere.[81] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system–directed RT in addition to treatment with chemotherapy and RT for the primary tumor. Craniospinal axis RT may also be indicated.[82,83] › A study included 15 children and adolescents with intermediate- and high-risk parameningeal rhabdomyosarcoma who were treated with proton RT during cycle 1 or 2 of chemotherapy.[80]

This finding suggests that for patients who receive early RT after the initiation of chemotherapy, on-treatment imaging should be performed approximately 4 weeks from the initiation of chemotherapy.

Nonparameningeal, nonorbital head and neck. For nonparameningeal, nonorbital head and neck tumors, wide excision of the primary tumor (when feasible without functional impairment) and ipsilateral neck lymph node sampling of clinically involved nodes may be appropriate but requires postoperative RT if margins or nodes are positive.[84]; [85][Level of evidence C1] Narrow resection margins (<1 mm) are acceptable because of anatomical restrictions. Cosmetic and functional factors should always be considered, but with modern techniques, complete resection in patients with superficial tumors is consistent with good cosmetic and functional results. The EpSSG RMS-2005 (NCT00379457) study prospectively enrolled 165 patients with localized head and neck, nonparameningeal rhabdomyosarcoma. Local therapy included surgery (58%) and/or RT (72%). Chemotherapy was given according to the patient’s risk group. Low-risk patients received vincristine and dactinomycin (VA) therapy. High-risk patients were randomly assigned to receive either neoadjuvant therapy with ifosfamide, vincristine, and dactinomycin (IVA) or IVA and doxorubicin for four courses followed by five courses of IVA. The 5-year EFS rate was 75% (95% CI, 67.3%–81.2%), and the OS rate was 84.9% (95% CI, 77.5%–89.7%). Favorable histology was associated with a better EFS rate (82.3% vs. 64.6%, P = .02), and nodal spread was associated with a worse OS rate (88.6% vs. 76.1%, P = .04). Locoregional relapse/progression was the main tumor failure event (84% of events).[86][Level of evidence B4] Specialized, multidisciplinary surgical teams also 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. However, these procedures should be considered only in children with recurrent locoregional disease or residual disease after chemotherapy and RT.