RESUMO
Sarcomas are a heterogeneous group of tumors that can occur in a wide array of anatomic sites and age ranges with varying histologies. Proton beam therapy, as compared with advanced x-ray radiation therapy techniques, can substantially lower dose to nontarget tissues. This dosimetric advantage can potentially allow for improvement of the therapeutic ratio in the treatment of many of the sarcomas by either increasing the local control, via increased dose to the target, or by decreasing the normal tissue complications, via lowered dose to the avoidance structures. This article reviews the key dosimetric studies and clinical outcomes published to date documenting the potential role proton beam therapy may play in the treatment of sarcomas.
Assuntos
Terapia com Prótons , Sarcoma/radioterapia , Neoplasias Ósseas/radioterapia , Condrossarcoma/radioterapia , Cordoma/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Neoplasias Induzidas por Radiação/prevenção & controle , Osteossarcoma/radioterapia , Neoplasias da Próstata/radioterapia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/economia , Terapia com Prótons/métodos , Doses de Radiação , Sarcoma de Ewing/radioterapia , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can significantly reduce the risk for developing an in-field second malignancy. The risk depends on treatment planning parameters, i.e. an analysis based on our formalism could be applied within treatment planning programs to guide treatment plans for pediatric patients.
Assuntos
Neoplasias Induzidas por Radiação/etiologia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Pré-Escolar , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Glioma do Nervo Óptico/radioterapia , Planejamento da Radioterapia Assistida por Computador , Medição de Risco , Sarcoma de Ewing/radioterapia , Espalhamento de RadiaçãoAssuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Fusão Oncogênica/efeitos dos fármacos , Proteínas de Fusão Oncogênica/genética , Sarcoma de Ewing/tratamento farmacológico , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias Ósseas/radioterapia , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 22 , Indústria Farmacêutica/tendências , Humanos , Prognóstico , Proteína Proto-Oncogênica c-fli-1 , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/genética , Sarcoma de Ewing/radioterapia , Translocação Genética/efeitos dos fármacosRESUMO
Childhood cancer survivors at highest risk of developing a secondary malignancy are those with hereditary retinoblastoma. The majority of such secondary cancers will be sarcomas, most commonly of bone. One-third of these occur outside a typical radiation field, commonly in an extremity. Bone sarcoma is also the most commonly reported secondary cancer to develop among survivors of Ewing's sarcoma. In this group, radiation doses greater than 60 Gy as well as alkylating agent chemotherapy have been identified as contributors to the increased risk. The prognosis for patients with a secondary sarcoma has been poor, with few cures reported to date. However, an aggressive, combined modality approach, including radical resection, postoperative radiation, and adjuvant chemotherapy, may improve the survival rate.