A Dosimetric Comparison of Intensity-Modulated Proton Therapy, Volumetric-Modulated Arc Therapy, and 4π Non-Coplanar Intensity-Modulated Radiation Therapy for a Patient with Parameningeal Rhabdomyosarcoma (original) (raw)
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Proton Radiotherapy for Parameningeal Rhabdomyosarcoma: Clinical Outcomes and Late Effects
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts. Ó 2012 Elsevier Inc.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014
Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects. Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans. Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for H&N (p<0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p<0.01), and 3.5 times higher for orbit (p<0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for or...
International Journal of Radiation Oncology*Biology*Physics, 2009
Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with at least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.
Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS). Fifty-seven patients with localized RMS (age 21 years or younger) or metastatic embryonal RMS (age 2 to 10 years) were enrolled between February 2005 and August 2012. All patients were treated with chemotherapy based on either vincristine, actinomycin, and cyclophosphamide or vincristine, actinomycin, and ifosfamide-based chemotherapy and proton radiation. Surgical resection was based on tumor site and accessibility. Common Terminology Criteria for Adverse Events, Version 3.0, was used to assess and grade adverse effects of treatment. Concurrent enrollment onto Children's Oncology Group or European Pediatric Sarcoma Study Group protocols was allowed. All pathology and imaging were reviewed at the treating institution. Median follow-up was 47 months (range, 14 to 102 months) for survivo...
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: To report our initial experience using intensity-modulated radiotherapy (IMRT) with a cone-down boost for pediatric head-and-neck rhabdomyosarcoma (RMS). Methods and Materials: A review of institutional treatment records identified children treated with IMRT for head-and-neck RMS between January 2000 and February 2007. All patients had undergone chemotherapy according to cooperative group RMS protocols. 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. Results: A total of 20 patients were treated with IMRT for head-and-neck RMS. Of these 20 patients, 4 had Group II, 15 Group III, and 1 Group IV disease. The site was parameningeal in 12, nonparameningeal in 6, and orbit primary in 2. Of the 20 patients, 14 were treated with a cone-down boost after a median dose of 36 Gy (range, 30-45.6). The mean initial PTV was 213.5 cm 3 , and the mean boost PTV was 76.9 cm 3 . Patients received a median total dose of 50.4 Gy. The median follow-up time was 29 months. The 3-year Kaplan-Meier local control rate was 100%, although 1 patient developed an in-field recurrence 50 months after IMRT. The 3-year event-free survival rate, overall survival rate, and risk of central nervous system failure was 74%, 76%, and 7%, respectively. 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. Ó
Journal of Radiation Oncology, 2012
Objective The impact of radiation therapy (RT) timing and use of intensity-modulated radiation therapy (IMRT) in nonhead and neck pediatric rhabdomyosarcoma (RMS) is underreported. Methods Children with non-head and neck RMS treated definitively with chemotherapy and RT from December 2000 through May 2010 at our institution were identified for analysis. Kaplan-Meier estimates of time to local progression-free survival (PFS), disease-free survival, and overall survival were performed, and Cox proportional hazard model examined the relationship between local control and RT timing and the use of IMRT.
European Journal of Cancer, 2007
To evaluate the local control rates and survival rates of patients with Group III parameningeal rhabdomyosarcoma (PM-RMS) treated with a dose intensive chemotherapy regimen followed by irradiation. Materials and methods: Twenty-six patients with group III, PM-RMS were enrolled in a prospective pilot trial at the Mayo Clinic, Rochester, MN and Children's Hospital and Regional Medical Center Seattle, WA. The median age at diagnosis was 8.5 years (range 1.5-19 years). The male to female patient ratio was 1.6:1. Twenty-three patients had embryonal histology with the remaining three alveolar. Risk factors indicating high risk disease included intracranial extension (10 patients), base of skull erosion (12 patients), and cranial nerve palsy (10 patients). The median follow-up period for all patients was 82 months (range 17-148 months). Patients were treated with an intensified chemotherapy regimen followed by definitive local irradiation at week 12 following further chemotherapy. The median time from initiation of chemotherapy to irradiation was 16 weeks (range 6-23). The median dose delivered was 50.4 Gy (50.4-66.6 Gy). Results: Response was assessed after the fourth course of chemotherapy. Three patients exhibited a complete response, 22 a partial response, and 1 patient had no response after two cycles of chemotherapy and proceeded to irradiation at week 6. The 5-year estimated event free survival was 81% (±15%, 95% CI). Two patients died from progressive metastatic disease; 1 patient died from secondary malignancy; and 2 patients died from locally progressive disease. The 5-year local control rate was 92% (±10.6%, 95% CI). Conclusions: Treatment of group III PM-RMS patients with neo-adjuvant, intensive chemotherapy with a delay in irradiation resulted in excellent local-regional control rates and survival rates and may allow for a response-based radiotherapy approach.
International Journal of Radiation Oncology*Biology*Physics, 2000
To evaluate the outcome and toxicity of hyperfractionated radiotherapy (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group III rhabdomyosarcoma (RMS). Five hundred fifty-nine children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group III RMS. Sixty-nine were ineligible for the analysis because of incorrect group or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4 Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy daily fractions). The age range was <1-21 years. All patients received chemotherapy. RT began at Week 9 after induction chemotherapy for all but those with high-risk parameningeal tumors who received RT during induction chemotherapy. The patient groups were equally balanced. The median follow-up was 3.9 years. Analysis by randomized treatment assignment (intent to treat) revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall survival (OS) of 75%. In the univariate analysis, the factors associated with the best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5 cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or head and neck; and embryonal histologic features (p = 0.001 for all factors). No differences in the FFS or OS between the two RT treatment methods and no differences in the FFS or OS between HFRT and CFRT were found when analyzed by age, gender, tumor size, tumor invasiveness, nodal status, histologic features, stage, or primary site. Treatment compliance differed by age. Of the children <5 years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT. Of the children >or=5 years, 88% assigned to both HFRT and CFRT received their assigned treatment. The reasons for not receiving the appropriate randomized treatment were progressive disease, early death, parent or physician refusal, young age, or surgery. The toxicity assessment revealed more mucositis with HFRT (66%) than with CFRT (46%) (p = 0.03) for the parameningeal patients, and more skin reactions (16%) and nausea/vomiting (13%) with HFRT than with CFRT (7% and 5%, respectively) for patients with nonparameningeal primary tumors (p = 0.03 and p = 0.02, respectively). The analysis by treatment actually received revealed a 5-year FFS rate of 73% and OS rate of 77%, with no difference between CFRT and HFRT. As well, there was no difference in FFS or OS between CFRT and HFRT when analyzed by age, gender, tumor size, tumor invasiveness, modal status, histology, stage or site of primary. The 5-year estimated cumulative incidence of failure for the irradiated patients was local, 13%; regional, 3%; and distant, 13%; with no differences between HFRT and CFRT. The 5-year local failure rate by site was orbit, 5%; head and neck, 12%; parameningeal, 16%; bladder/prostate, 19%; extremity, 7%; and all others, 14%. The 5-year regional failure rate was parameningeal,1%; extremity, 20%; and all others, 5%. The 5-year distant failure rate was orbit, 2%; head and neck, 6%; parameningeal, 11%; bladder/prostate, 15%; extremity, 28%; and all others, 17%. HFRT, as given in this study, did not improve local/regional control, FFS, or OS compared with CFRT. The risk of local/regional failure was comparable to that of distant failure in children with Group III RMS. The standard of care for Group III RMS continues to be CFRT with chemotherapy.