Age: 13 y/o Gender: male

This 13 y/o male patient,郭恆均, suffered from progressive proptosis ,OS, for 1 week, and there was no traumatic history related. He went to LMD and was sent to our OPH OPD. PE at our OPD showed left eyeball proptosis with increased IOP,OS. Under the impression of suspected orbital cellulites or orbital tumor ,OS, he was admitted for further management.

MRI of orbits showed a large enhancing soft tissue mass lesion with adjacent bone destruction involving mainly in left ethmoid sinus, left frontal sinus, left nasal cavity and left maxillary sinus with crossing midline to involve right ethmoid sinus, right frontal sinus and right nasal cavity. The study also shows intracranial extension of the aforementioned tumor with cribriform plate destruction to bilateral frontal base regions(mainly on left side) as well as tumor invasion to left side orbital cavity and causing ptosis. Biopsy revealed rhabdomyosarcoma. Under impression of rhabdomyosarcoma leading to left optic nerve compression with progressive eye vision and visual acuity loss, he was referred to our department for CCRT (chemotherapy was given in ward).

2008/12/18--Cytology exam - C.S.F 2008/12/15 bone scan 2008/12/01--CT orbits 2008/12/02—MRI, orbits 2008/12/04—frozen section: Nasal cavity, labelled tumor, frozen section and biopsy --- Compatible with rhabdomyosarcoma 2008/12/18--Cytology exam - C.S.F Negative for malignant cells 2008/12/15 bone scan 2008/12/19 sono, upper abd/ chest CT No evidence of distant metastases

Treatment planning Indication: Rhabdomyosarcoma with left optic nerve compression Technique: 6 MV X-rays IMRT technique Target and dose: CTV1 (tumor at left nasal cavity, orbit , maxillary and frontal sinus): 50.4Gy/28Fx Portal arrangement: P180, RAO 345 IAO 10,Vertex 290, Vertex 260 (table=90°)

Down size of treatment volume on 2008/12/25(6 fx), 2009/01/12(17 fx) R/T started on 2008/12/17 Down size of treatment volume on 2008/12/25(6 fx), 2009/01/12(17 fx) Combine with weekly chemotherapy given in ward Vincristine 1.85mg Cyclophosphamide 2720mg Dactinomycin 1.64mg

2008/12/03 2008/12/16

2008/12/25 2009/01/13

2009/02/02 Radiotherapy was completed on 2009/02/04 with total dose of 50.4Gy/28Fx

rhabdomyosarcoma

Rhabdomyosarcoma is the most common of the childhood soft tissue sarcomas two peak age ages 2 to 6 Adolescence children <1 year and >10 years having inferior survival

in association with several congenital disorders,including congenital pulmonary cysts, Gorlin's basal cell nevus syndrome, and neurofibromatosis Multiple tumors can occur in siblings and relatives of children with rhabdomyosarcoma, Li-Fraumeni syndrome adrenocortical carcinoma, Brain tumors (particularly glioblastoma), lung cancer, breast cancer

Pattern of spread locally invasive tumor often with a pseudocapsule, has the potential for local spread along fascial or muscle planes, lymphatic extension, and hematogenous dissemination regional lymphatic spread-15% Hematogenous metastases-15%

Clinical presentation asymptomatic mass mass effect on associated organs and tissues grow rapidly

Staging systems

Pathologic Classification Embryonal spindle cell subtype Botryoid subtype of embryonal Alveolar “solid” alveolar pattern Pleomorphic Diffuse anaplastic variant

--5 year survival rate: 88-95% --3 year failure-free rate: 83% --3 year failure-free survival rate: 55%

Prognostic Factors and Therapeutic Considerations Orbit favorable prognostic site lymphatic extension/hematogenous metastasis is rare embryonal histology

Treatment: no surgical procedure CCRT: Primary treatment usually consists of vincristine, actinomycin D,and Cytoxan (VAC) chemotherapy with local radiotherapy beginning between the 3rd and 12th week of treatment. Radiation doses of approximately 50 Gy are often used, 45Gy may be sufficient cure rates of >90% tumor plus a margin without necessarily irradiating the entire orbit. minimizing corneal and lacrimal gland dose and for preserving useful vision in the treated eye Photon irradiation with the eyelid open minimizes corneal dose when an anterior field is used and may be associated with improved long-term functional outcome

Chemotherapy without irradiation has resulted in local relapse and inferior event-free survival When radiation therapy alone was used, the entire orbit be included in the treated volume

Head and Neck: Parameningeal Sites Nonorbital rhabdomyosarcomas of the head and neck are grouped into parameningeal sites nasopharynx, nasal cavity, paranasal sinuses, middle ear, pterygopalatine fossa, and infratemporal fossa propensity for invading the base of the skull, creating a potential for cranial nerve palsy and direct extension into the central nervous system A radiation dose of 50.4 Gy in 28 fractions to the primary site is most commonly used and started within 2 weeks of diagnosis

Head and Neck: Non-Parameningeal Sites include the scalp, parotid, oral cavity, larynx, oropharynx, and cheek complete gross surgical excision Approximately 15% of these patients present with regional lymph node metastases Radiotherapeutic management is based on the amount of residual tumor after surgery. Draining regional lymph nodes are not routinely irradiated unless they contain metastatic tumor.

Bladder and Prostate Tumors half of all pelvic rhabdomyosarcomas 75% of patients are age <5 years at presentation male predominance More than 90% of these tumors are of the embryonal histologic subtype, with approximately one-third having a botryoid morphology anterior pelvic exenteration (or partial cystectomy for small tumors arising from the dome of the bladder) combined with chemotherapy and irradiation for microscopic or gross residual disease has been associated with a survival rate of approximately 70%

Paratesticular Tumors represent approximately 7% of all rhabdomyosarcomas and may arise anywhere along the spermatic cord inguinal orchiectomy and no further local therapy is necessary.

Gynecologic Tumors 4% of all rhabdomyosarcomas vagina is the most common site of origin before the age of 3 years botryoid morphology These tumors are often quite sensitive to chemotherapy Radiation therapy usually is reserved for patients with residual disease after resection or as part of a preoperative treatment regimen to help limit the extent of surgery. Intracavitary and interstitial brachytherapy are useful irradiation techniques

Extremity alveolar or undifferentiated subtypes Because radiation therapy and multi-agent chemotherapy have been shown to provide excellent local control, it is advisable to avoid disfiguring and mutilating surgical procedures

Treatment Radiotherapy: As part of a multimodality treatment program, radiation doses of 40 to 41.4 Gy given in 4.5 weeks provide a 90% likelihood of local control of microscopic disease, with 50.4 to 55.8 Gy in 5.5 to 6 weeks recommended for gross residual disease 36 to 41.4 Gy to the operative bed of completely resected patients

The clinical target volume includes the gross tumor volume and any involved regional nodal chain, plus a 1-cm margin The planning target volume adds a patient-specific margin, which is typically about 5 mm Interstitial radiation therapy may play an important role as primary treatment or as a boost

Earlier irradiation, particularly in high-risk patients, may provide better local tumor control and survival dactinomycin and Adriamycin can produce undesirable early and late effects vincristine and cyclophosphamide can often be continued concurrently with the administration of irradiation.

Local control after intensity-modulated radiotherapy for head and-neck rhabdomyosarcoma Int. J. Radiation Oncology Biol. Phys., Vol. 73, No. 1, pp. 173–177, 2009 Methods and Materials: 1998~2005, 19 (male:11, female: 8, median age:6)patients with a diagnosis of head-and-neck RMS received IMRT at The Methodist Hospital. parameningeal in 7, obital in 6, other head-and-neck RMS in 6. Chemotherapy was given to all patients, with vincristine, actinomycin D, and cyclophosphamide Radiotherapy: The median prescribed dose was 5040 cGy. CTV:the gross tumor volume with a 1.5-cm margin. The median duration of follow-up for surviving patients was 56 months. Results: The 4-year overall survival and local control rates were 76% and 92.9%, respectively. Overall survival was 42.9% for parameningeal sites and 100% for other sites (p < 0.01). Late toxicities were seen in 7 patients. Two secondary malignancies occurred in 1 child with embryonal RMS of the face and a p53 mutation. Conclusions: Local control was excellent in patients receiving IMRT for head-and-neck RMS. Patterns of local failure reveal no marginal failures in this group of patients

Intensity-modulated Radiotherapy With Use Of Cone-down boost For Pediatric Head-and-neck Rhabdomyosarcoma Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 3, pp. 884–891, 2008 Methods and Materials: A review of institutional treatment records identified children treated with IMRT for head-and-neck RMS between January 2000~ February 2007. A total of 20 patients. 4 had Group II 15 Group III 1 Group IV disease. parameningeal in 12 nonparameningeal in 6 orbit primary in 2.

Radiotherpay: Patients received a median total dose of 50.4 Gy Of the 20 patients, 14 were treated with a cone-down boost after a median dose of 36 Gy (range, 30–45.6). The initial planning target volume (PTV) covered the prechemotherapy tumor extent with variable margins, generally 1–2 cm. The boost PTV covered the postchemotherapy tumor volume, usually with a margin of 0.5–1 cm. The mean initial PTV was 213.5 cm3, and the mean boost PTV was 76.9 cm3. The median follow-up time was 29 months. All patients had undergone chemotherapy

Results: The 3-year Kaplan-Meier local control rate was 100% (1 patient developed an in-field recurrence 50 months after IMRT). The 3-year event-free survival rate 74%,overall survival rate 76%, and risk of central nervous system failure was7% Conclusions: Our preliminary follow-up of pediatric head-and-neck RMS patients treated with IMRT revealed excellent local control. The initial targeting of the prechemotherapy tumor volume with 1–2-cm margin to 30.6 or 36 Gy followed by a cone-down boost to the postchemotherapy tumor volume with a 0.5–1-cm margin allowed for significant sparing of normal tissues and provided good local control.