Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 471
Filtrar
1.
Br J Radiol ; 93(1107): 20190582, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31778317

RESUMO

Range uncertainty is a much discussed topic in proton therapy. Although a very real aspect of proton therapy, its magnitude and consequences are sometimes misunderstood or overestimated. In this article, the sources and consequences of range uncertainty are reviewed, a number of myths associated with the effect discussed with the aim of putting range uncertainty into clinical context and attempting to de-bunk some of the more exaggerated claims made as to its consequences.


Assuntos
Terapia com Prótons/métodos , Incerteza , Absorção de Radiação , Humanos , Neoplasias Induzidas por Radiação , Posicionamento do Paciente , Fótons/uso terapêutico , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Resultado do Tratamento , Água
2.
Int J Radiat Oncol Biol Phys ; 106(3): 621-629, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759074

RESUMO

PURPOSE: Preclinical research into ultrahigh dose rate (eg, ≥40 Gy/s) "FLASH"-radiation therapy suggests a decrease in side effects compared with conventional irradiation while maintaining tumor control. When FLASH is delivered using a scanning proton beam, tissue becomes subject to a spatially dependent range of dose rates. This study systematically investigates dose rate distributions and delivery times for proton FLASH plans using stereotactic lung irradiation as the paradigm. METHODS AND MATERIALS: Stereotactic lung radiation therapy FLASH-plans, using 244 MeV scanning proton transmission beams, with the Bragg peak behind the body, were made for 7 patients. Evaluated parameters were dose rate distribution within a beam, overall irradiation time, number of times tissue is irradiated, and quality of the FLASH-plans compared with the clinical volumetric-modulated arc therapy (VMAT) plans. RESULTS: Sparing of lungs, thoracic wall, and heart in the FLASH-plans was equal to or better than that in the VMAT-plans. For a spot peak dose rate (SPDR, the dose rate in the middle of the spot) of 100 Gy/s, ∼40% of dose is delivered at FLASH dose rates, and for SPDR = 360 Gy/s this increased to ∼75%. One-hundred percent FLASH dose rate cannot be achieved owing to small contributions from distant spots with lower dose rates. The total irradiation time varied between 300 to 730 ms, and around 85% of the dose-receiving body volume was irradiated by either 1 or 2 beams. CONCLUSIONS: Clinical implementation of FLASH using scanning proton beams requires multiple treatment planning considerations: dosimetric, temporal, and spatial parameters all seem important. The FLASH efficiency of a scanning proton beam increases with SPDR. The methodology proposed in this proof-of-principle study provides a framework for evaluating the FLASH characteristics of scanning proton beam plans and can be adapted as FLASH parameters are better defined. It currently seems logical to optimize plans for the shortest delivery time, maximum amount of high dose rate coverage, and maximum amount of single beam and continuous irradiation.


Assuntos
Neoplasias Pulmonares/radioterapia , Terapia com Prótons/métodos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Coração , Humanos , Pulmão , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco , Estudo de Prova de Conceito , Terapia com Prótons/efeitos adversos , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Medula Espinal , Parede Torácica , Fatores de Tempo
3.
Br J Radiol ; 93(1107): 20190028, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31322969

RESUMO

OBJECTIVE: To assess the radiation-induced optic neuropathy (RION) prevalence, following high dose pencil beam scanning proton therapy (PBSPT) to skull base and head and neck (H&N) tumours. METHODS: Between 1999 and 2014, 216 adult patients, median age 47 years (range, 18-77), were treated with PBS PT for skull base or H&N malignancies, delivering ≥45 GyRBE to the optic nerve(s) (ON) and/or optic chiasma (OC). The median administered dose to the planning target volume was 74.0 GyRBE (range, 54.0-77.4). The median follow-up was 5.3 years (range, 0.8-15.9). RESULTS: RION was observed in 14 (6.5%) patients at a median time of 13.2 months (range, 4.8-42.6) following PBSPT. Most (92.9%) of RION were symptomatic. Most affected patients (11/14; 79%) developed unilateral toxicity. Grade 4, 3, 2 and 1 toxicity was observed in 10, 2, 1 and 1 patients, respectively. On univariate analyses, age (<70 vs ≥70 years; p < 0.0001), hypertension (p = 0.0007) and tumour abutting the optic apparatus (p = 0.012) were associated with RION. OC's V60 GyRBE was of border line significance (p = 0.06). None of the other evaluated OC-ON dose/volume metrics (Dmax, Dmean, V40-60) were significantly associated with this complication. CONCLUSION: These data suggest that high-dose PBS PT for skull base and H&N tumours is associated with a low prevalence of RION. Caution should be however exercised when treating elderly/hypertensive patients with tumours abutting the optic apparatus. ADVANCES IN KNOWLEDGE: This is the first study reporting the risk of developing RION following proton therapy with PBS technique, demonstrating the safety of this treatment.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Doenças do Nervo Óptico/etiologia , Nervo Óptico/efeitos da radiação , Terapia com Prótons/efeitos adversos , Lesões por Radiação/complicações , Neoplasias da Base do Crânio/radioterapia , Adolescente , Adulto , Fatores Etários , Idoso , Análise de Variância , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Hipertensão/complicações , Pessoa de Meia-Idade , Quiasma Óptico/efeitos da radiação , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/patologia , Prevalência , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Radioterapia Adjuvante , Fatores de Risco , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/cirurgia , Adulto Jovem
4.
Br J Radiol ; 93(1107): 20190873, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31860337

RESUMO

The UK has an important role in the evaluation of proton beam therapy (PBT) and takes its place on the world stage with the opening of the first National Health Service (NHS) PBT centre in Manchester in 2018, and the second in London coming in 2020. Systematic evaluation of the role of PBT is a key objective. By September 2019, 108 patients had started treatment, 60 paediatric, 19 teenagers and young adults and 29 adults. Obtaining robust outcome data is vital, if we are to understand the strengths and weaknesses of current treatment approaches. This is important in demonstrating when PBT will provide an advantage and when it will not, and in quantifying the magnitude of benefit.The UK also has an important part to play in translational PBT research, and building a research capability has always been the vision. We are perfectly placed to perform translational pre-clinical biological and physical experiments in the dedicated research room in Manchester. The nature of DNA damage from proton irradiation is considerably different from X-rays and this needs to be more fully explored. A better understanding is needed of the relative biological effectiveness (RBE) of protons, especially at the end of the Bragg peak, and of the effects on tumour and normal tissue of PBT combined with conventional chemotherapy, targeted drugs and immunomodulatory agents. These experiments can be enhanced by deterministic mathematical models of the molecular and cellular processes of DNA damage response. The fashion of ultra-high dose rate FLASH irradiation also needs to be explored.


Assuntos
Institutos de Câncer/estatística & dados numéricos , Terapia com Prótons/estatística & dados numéricos , Medicina Estatal/estatística & dados numéricos , Adolescente , Adulto , Institutos de Câncer/provisão & distribução , Fortalecimento Institucional , Criança , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Dano ao DNA , Inglaterra , Humanos , Modelos Teóricos , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Avaliação de Programas e Projetos de Saúde , Terapia com Prótons/efeitos adversos , Radioterapia (Especialidade)/educação , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Pesquisa , Pesquisa Médica Translacional , Resultado do Tratamento , Incerteza , Adulto Jovem
5.
Br J Radiol ; 93(1107): 20190412, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31868525

RESUMO

Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is low, concerns were raised about late effects like secondary cancer caused by dose depositions far away from the treated area. This is especially true for neutrons and therefore the stray dose contribution from neutrons in proton therapy is still being investigated. The higher biological effectiveness of neutrons compared to photons is the main cause of these concerns. The gold-standard in neutron dosimetry is measurements, but performing neutron measurements is challenging. Different approaches have been taken to overcome these difficulties, for instance with newly developed neutron detectors. Monte Carlo simulations is another common technique to assess the dose from secondary neutrons. Measurements and simulations are used to develop analytical models for fast neutron dose estimations. This article tries to summarize the developments in the different aspects of neutron dose in proton therapy since 2017. In general, low neutron doses have been reported, especially in active proton therapy. Although the published biological effectiveness of neutrons relative to photons regarding cancer induction is higher, it is unlikely that the neutron dose has a large impact on the second cancer risk of proton therapy patients.


Assuntos
Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Nêutrons/efeitos adversos , Terapia com Prótons/métodos , Humanos , Método de Monte Carlo , Fótons/uso terapêutico , Terapia com Prótons/efeitos adversos , Radiometria/instrumentação , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa
6.
Int J Radiat Oncol Biol Phys ; 106(1): 82-89, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580927

RESUMO

PURPOSE: To investigate the efficacy and safety of proton beam therapy (PBT) for the treatment of stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Six hundred sixty-nine patients with 682 tumors histologically or clinically diagnosed stage I NSCLC according to the seventh edition of Union for International Cancer Control who received passive-scattering PBT from April 2004 and December 2013 in Japan were retrospectively reviewed to analyze survival, local control, and toxicities. RESULTS: Of 669 patients, 486 (72.6%) were men, with a median age of 76 years (range, 42-94 years). NSCLC was histologically confirmed in 440 patients (65.7%). Clinical T stages included T1a (n = 265; 38.9%), T1b (n = 216; 31.7%), and T2a (n = 201; 29.4%). The total irradiation doses of PBT ranged from 74.4 to 131.3 biological effective dose GyE (median, 109.6 biological effective dose GyE). The median follow-up period was 38.2 months (range, 0.6-154.5 months) for all patients. The 3-year overall survival and progression-free survival rates for all patients were 79.5% and 64.1%, respectively. For patients with stage IA tumors, the 3-year overall survival and progression-free survival rates were 82.8% and 70.6%, respectively, and the corresponding rates for patients with stage IB tumors were 70.8% and 47.3%, respectively. The 3-year local progression-free rates for all, stage IA, and stage IB patients were 89.8%, 93.5%, and 79.4%, respectively. The incidence of grade 2, 3, 4, and 5 pneumonitis was 9.8%, 1.0%, 0%, and 0.7%, respectively. The incidence of grade ≥3 dermatitis was 0.4%. No grade 4 or severe adverse events, other than pneumonitis, were observed. CONCLUSIONS: PBT appears to yield acceptable survival rates, with a low rate of toxicities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Terapia com Prótons/efeitos adversos , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/patologia , Radiodermatite/epidemiologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Taxa de Sobrevida
7.
Bull Cancer ; 106(12): 1160-1176, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31757405

RESUMO

Radiation induced optic neuropathy (RION) is a rare but disastrous complication of radiation therapy in treatment of periorbital tumors. The objective of this study is to investigate the incidence of RION in series of patients treated from peri orbital tumors by recent photon and proton irradiation modalities. We searched the Pub Med database for studies in periorbital tumors including base of skull, sinonasal, pituitary, nasopharyngeal tumors and craniopharyngioma treated with Intensity modulated radiotherapy (IMRT) and with proton beam therapy (PBT) between 1992 and 2017 excluding metastatic tumors, lymphomas, pediatric series, those treated mainly with chemotherapy, target therapy and those written in languages other than English and French. The result retrieved 421 articles that were revised by the panel. Fourteen articles with IMRT and 27 with PBT reported usable data for the review from which 31studies that had pointed to the doses to the optic nerve (ON) and/or optic chiasm (OC) and incidence of RION have been analyzed. We have found that the incidence of RION had been reported fairly in both modalities and many other factors related to the patient, tumor, and irradiation process interplay in its development. We have concluded that proper treatment planning, good selection of treatment modality, adherence to dose constraints applied to critical structures all along with regular oncological and ophthalmological follow up, control of co-morbidities and early intervention, could help reducing its magnitude.


Assuntos
Terapia com Prótons/efeitos adversos , Lesões por Radiação/complicações , Radioterapia de Intensidade Modulada/efeitos adversos , /etiologia , Adenoma/radioterapia , Craniofaringioma/radioterapia , Humanos , Incidência , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasais/radioterapia , Neoplasias dos Seios Paranasais/radioterapia , Neoplasias Hipofisárias/radioterapia , Neoplasias da Base do Crânio/radioterapia , /epidemiologia
8.
Phys Med ; 65: 219-226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31525620

RESUMO

PURPOSE: Under geometrical uncertainties, different plan evaluation methods have been suggested but the dose distribution at a specified confidence level being highly desirable is lacking. In this work, we used the DVPH (Dose Volume Population Histogram) tool to evaluate the dose distribution of CTVs and OARs (Organs at Risk) and validate the PTV concept at a certain confidence level. METHODS: The plans were evaluated using PTV DVH and the DVPH approach. The DVPH approach is based on statistical analyzing of multiple CTV DVHs under geometrical errors with corresponding occurring probabilities. The random and systematic geometrical errors, assumed to follow a Gaussian distribution, are simulated by shifting the CT images. RESULTS: For target doses, the results showed that the minimum dose to PTV does not represent the minimum dose to the CTV. For two prostate cases, the minimum doses reduced from 98% and 95% of prescribed dose from PTV DVH to 89% and 92% of prescribed dose from CTV 90% CL-DVPH (90% Confidence Level-DVPH). This reduction was also seen in head and neck cases, from 95% to 68% and 74% of prescribed dose. For OAR doses, OAR DVHs underestimated the OAR dose receiving. CONCLUSIONS: With the DVPH tool, the results showed that the minimum dose to the PTV is not a representative of the minimum dose to the CTV in IMPT at the 90% confidence level. The OAR DVH does not match any OAR CL-DVPHs.


Assuntos
Terapia com Prótons , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Humanos , Masculino , Neoplasias/radioterapia , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança
9.
Pediatr Blood Cancer ; 66(11): e27952, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397065

RESUMO

PURPOSE/OBJECTIVE(S): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. MATERIALS/METHODS: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. RESULTS: The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). CONCLUSIONS: PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons , Rabdomiossarcoma Embrionário/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Cistectomia , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Proctite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Lesões por Radiação/etiologia , Sistema de Registros , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Alveolar/radioterapia , Rabdomiossarcoma Alveolar/cirurgia , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/cirurgia , Risco , Carga Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia
10.
Int J Radiat Oncol Biol Phys ; 105(5): 1043-1054, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419513

RESUMO

PURPOSE: The standard of care of childhood parameningeal rhabdomyosarcoma (pRMS) is chemotherapy and local radiation therapy. Protons are increasingly being used to decrease late effects. The aim of the present study is to analyze the pattern of relapse and the correlation with dosimetric factors in pRMS treated with proton therapy. METHODS AND MATERIALS: This retrospective evaluation includes children treated in our institution for pRMS. Information on demographics, treatment, tumor characteristics, and toxicities and outcome was prospectively collected within the in-house registry. For patients presenting with local relapse, a fusion of the dosimetry with magnetic resonance imaging displaying site and geometry of recurrence was performed. RESULTS: Median follow-up time was 2.9 years (0.5-4.7). Forty-six patients were identified in our institution between July 2013 and November 2017. Main characteristics of patients were as follows: 56.5% male, median age 5.1 years (1.3-17.5), 39.1% alveolar histology, 26.1%, 52.2%, 8.7%, and 13% patients with subgroup risk classification D, E/F/G, H, or metastatic, respectively, median total prescribed dose 55.8 Gy (50.4-56.4). Estimated 2-year local control, metastasis-free survival, event-free survival, and overall survival were 83.8%, 87.8%, 76.9%, and 88.9%, respectively. No acute or late local toxicity exceeding grade 3 was observed. Risk-group was identified as prognostic factor for metastasis-free survival in univariate analysis but not in multivariate analysis (trend: P = .09). In this cohort, dosimetric factors did not correlate with outcome. Isolated local failure happened in 5 of the 11 relapses. Local relapses were matched with dosimetry for 6 patients: 4 of them occurred in the high dose volume and 2 in the intermediate or low dose volume. CONCLUSIONS: Proton therapy was effective and well feasible even in a critical cohort. Still, local relapse within the target volume of the radiation therapy remains an important issue in pRMS and new treatment strategies are needed.


Assuntos
Neoplasias Meníngeas/radioterapia , Recidiva Local de Neoplasia , Terapia com Prótons , Rabdomiossarcoma/radioterapia , Adolescente , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Terapia com Prótons/efeitos adversos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/cirurgia , Rabdomiossarcoma Alveolar/diagnóstico por imagem , Rabdomiossarcoma Alveolar/mortalidade , Rabdomiossarcoma Alveolar/radioterapia , Rabdomiossarcoma Alveolar/cirurgia , Fatores de Tempo , Resultado do Tratamento
11.
Cancer Sci ; 110(9): 2867-2874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237050

RESUMO

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re-plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high-risk clinical target volume (CTV), and 36 Gy in 18 parts to low-risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re-plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity-score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow-up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Recidiva Local de Neoplasia/epidemiologia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/epidemiologia , Mucosite/etiologia , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Resultado do Tratamento , Adulto Jovem
12.
Int J Radiat Oncol Biol Phys ; 105(4): 713-722, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31199994

RESUMO

PURPOSE: Moderately hypofractionated radiation therapy represents an effective treatment for localized prostate cancer (PC). Although large randomized trials have reported the efficacy of photon-based hypofractionated therapy, hypofractionated proton therapy (HFPT) has not been extensively studied. This study was performed to determine the clinical and patient-reported outcomes for patients with PC treated with HFPT. METHODS AND MATERIALS: Between 2010 and 2017, 184 men were enrolled on a trial of 70 Gy in 28 fractions of HFPT for low- to intermediate-risk PC. Acute and late toxicity was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Patient-reported outcomes were measured by International Prostate Symptom Score, International Index of Erectile Function Questionnaire, and Expanded Prostate Cancer Index Composite scores. RESULTS: Median follow-up was 49.2 months. Enrolled patients had low-risk (n = 18), favorable intermediate-risk (n = 78), and unfavorable intermediate-risk (n = 88) PC. Four-year rates of biochemical-clinical failure-free survival were 93.5% (95% confidence interval, 89%-98%), 94.4% (89%-100%), 92.5% (86%-100%), and 93.8% (88%-100%) in the overall group and the low-risk, favorable intermediate-risk, and unfavorable intermediate-risk cohorts, respectively (log-rank P > .4). The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic toxicities were 3.8% and 12.5%, respectively. The 4-year incidence of late grade 2 or higher urologic and GI toxicity was 7.6% (4%-13%) and 13.6% (9%-20%), respectively. One late grade 3 GI toxicity was reported. All late toxicities were transient. Patient-reported International Prostate Symptom, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite scores had no significant long-term changes after completion of HFPT (Supplementary Table 1, available at https://doi.org/10.1016/j.ijrobp.2019.05.069). CONCLUSIONS: HFPT is associated with low rates of toxicity and does not appear to negatively affect 4-year patient reported urinary and bowel health. Further comparative analyses are warranted to better understand differences between proton and photon HFRT.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Disfunção Erétil/etiologia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Terapia com Prótons/efeitos adversos , Hipofracionamento da Dose de Radiação , Lesões por Radiação/complicações , Planejamento da Radioterapia Assistida por Computador/métodos , Doenças Retais/etiologia , Fatores de Tempo , Resultado do Tratamento , Transtornos Urinários/etiologia
13.
Acta Oncol ; 58(9): 1238-1245, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31155998

RESUMO

Background and purpose: Recurrent nasopharyngeal carcinoma (NPC) has limited curative treatment options. Reirradiation is the only potential definitive treatment in advanced stages at a cost of substantial severe and often life-threatening toxicity. Proton therapy (PT) reduces irradiated volume compared with X-ray radiotherapy and could be advantageous in terms of safety and efficacy in a population of heavily pretreated patients. We report the retrospective results of PT reirradiation in recurrent NPC patients treated at our Institution Methods: All recurrent NPC patients treated since the beginning of clinical activity entered the present analysis. Clinical target volume consisted of Gross Tumor volume plus a patient-specific margin depending on disease behavior, tumor location, proximity of organs at risk, previous radiation dose. No elective nodal irradiation was performed. Active scanning technique with the use of Single Field Optimization (SFO) or Multifield Optimization (MFO) was adopted. Cumulative X-ray -PT doses were calculated for all patients using a dose accumulation tool since 2016. Treatment toxicity was retrospectively collected. Results: Between February 2015, and October 2018, 17 recurrent NPC patients were treated. Median follow-up (FUP) was 10 months (range 2-41). Median PT reirradiation dose was 60 Gy RBE (range 30.6-66). The majority of patients (53%) underwent concomitant chemotherapy. Acute toxicity was low with no ≥ G3 adverse events. Late events ≥ G3 occurred in 23.5% of patients. Most frequent late toxicity was hearing impairment (17,6%). G2 soft tissue necrosis occurred in two patients. Fatal bleeding of uncertain cause (either tumor recurrence or G5 carotid blowout) occurred in one patient. Kaplan-Meier 18 months Overall Survival (OS) and Local control (LC) rates were 54.4% and 66.6%, respectively. Conclusions: Our initial results with the use of modern PT for reirradiation of recurrent NPC patients are encouraging. Favorable LC and OS rates were obtained at the cost of acceptable severe late toxicity.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Terapia com Prótons/métodos , Reirradiação/métodos , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Audição/efeitos da radiação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Órgãos em Risco , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Reirradiação/efeitos adversos , Estudos Retrospectivos , Carga Tumoral
14.
Int J Radiat Oncol Biol Phys ; 105(1): 90-95, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128146

RESUMO

PURPOSE: Definitive chemoradiation with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) is an effective treatment for localized anal cancer, but it is associated with significant acute long-term treatment-related toxicity. Pencil beam scanning proton beam (PBS-PT) radiation therapy may potentially reduce this toxicity. This is a multi-institutional pilot study evaluating the feasibility of definitive concurrent chemoradiation with PBS-PT in combination with 5-FU and MMC for carcinoma of the anal canal. METHODS AND MATERIALS: Patients were enrolled on a National Cancer Institute-sponsored, prospective, multi-institutional, single-arm pilot study (NCT01858025). Key eligibility criteria included Eastern Cooperative Oncology Group 0 to 2, age ≥18 years, histologically confirmed invasive squamous cell carcinoma of the anal canal, and clinically staged T1-4, N0-3 disease. Patients were treated with PBS-PT per Radiation Therapy Oncology Group 0529 dose schema and concurrent 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with concurrent 5-FU/MMC, defined as grade 3+ dermatologic toxicity less than 48% (reported grade 3+ dermatologic toxicity from Radiation Therapy Oncology Group 98-11). Secondary objectives were to determine the rates of overall grade 3+ toxicities, clinical complete response rate, and disease outcomes. RESULTS: Between February 2014 and April 2017, we enrolled 25 patients into our study, all of whom were analyzed. Twenty-three patients (92%) completed treatment per protocol, and 2 patients died on treatment. Median time to completion of treatment was 42 days (range, 38-49). The grade 3+ radiation dermatitis rate was 24%. Median follow-up is 27 months (range, 21-50) among the 21 patients still alive. The overall rate of clinical complete response was 88%. The 2-year local failure, colostomy-free survival, progression-free survival, and overall survival are 12%, 72%, 80%, and 84%, respectively. CONCLUSIONS: In our prospective, multi-institutional pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. A phase 2 study of proton beam radiation therapy is currently underway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Terapia com Prótons/métodos , Radiodermatite/patologia , Idoso , Canal Anal , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Colostomia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Projetos Piloto , Intervalo Livre de Progressão , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica
15.
Med Phys ; 46(8): e678-e705, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125441

RESUMO

PURPOSE:  Task Group (TG) 224 was established by the American Association of Physicists in Medicine's Science Council under the Radiation Therapy Committee and Work Group on Particle Beams. The group was charged with developing comprehensive quality assurance (QA) guidelines and recommendations for the three commonly employed proton therapy techniques for beam delivery: scattering, uniform scanning, and pencil beam scanning. This report supplements established QA guidelines for therapy machine performance for other widely used modalities, such as photons and electrons (TG 142, TG 40, TG 24, TG 22, TG 179, and Medical Physics Practice Guideline 2a) and shares their aims of ensuring the safe, accurate, and consistent delivery of radiation therapy dose distributions to patients. METHODS:  To provide a basis from which machine-specific QA procedures can be developed, the report first describes the different delivery techniques and highlights the salient components of the related machine hardware. Depending on the particular machine hardware, certain procedures may be more or less important, and each institution should investigate its own situation. RESULTS:  In lieu of such investigations, this report identifies common beam parameters that are typically checked, along with the typical frequencies of those checks (daily, weekly, monthly, or annually). The rationale for choosing these checks and their frequencies is briefly described. Short descriptions of suggested tools and procedures for completing some of the periodic QA checks are also presented. CONCLUSION:  Recommended tolerance limits for each of the recommended QA checks are tabulated, and are based on the literature and on consensus data from the clinical proton experience of the task group members. We hope that this and other reports will serve as a reference for clinical physicists wishing either to establish a proton therapy QA program or to evaluate an existing one.


Assuntos
Terapia com Prótons/instrumentação , Garantia da Qualidade dos Cuidados de Saúde , Humanos , Terapia com Prótons/efeitos adversos , Terapia com Prótons/normas , Radiometria , Cintilografia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Segurança
16.
Nucl Med Commun ; 40(6): 618-625, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31095527

RESUMO

INTRODUCTION: Radiation pneumonitis is a major dose-limiting complication in thoracic radiation therapy (RT) and presents clinically in the first few months after RT. We evaluated the feasibility of quantifying pulmonary parenchymal glycolysis (PG) as a surrogate of global lung inflammation and radiation-induced pulmonary toxicity using a novel semiautomatic lung segmentation technique in non-small-cell lung cancer (NSCLC) patients and compared PG in patients treated with photon or proton RT. PATIENTS AND METHODS: We evaluated 18 consecutive locally advanced NSCLC patients who underwent pretreatment and post-treatment F-FDG PET/CT treated with definitive (median: 66.6 Gy; 1.8 Gy fractions) photon or proton RT between 2010 and 2014. Lung volume segmentation was conducted using 3D Slicer by performing simple thresholding. Pulmonary PG was calculated by summing F-FDG uptake in the whole lung. RESULTS: In nine patients treated with photon RT, significant increases in PG in both ipsilateral (mean difference: 1400±510; P=0.02) and contralateral (mean difference: 1200±450; P=0.03) lungs were noted. In nine patients treated with proton therapy, no increase in pulmonary PG was observed in either the ipsilateral (P=0.30) or contralateral lung (P=0.98). CONCLUSION: We observed a significant increase in global lung inflammation bilaterally as measured by quantification of PG. However, no significant change in global lung inflammation was noted after proton therapy. Future larger studies are needed to determine whether this difference correlates with lower risks of radiation pneumonitis in NSCLC patients treated with proton therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/terapia , Fótons/efeitos adversos , Pneumonia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Terapia com Prótons/efeitos adversos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fótons/uso terapêutico , Pneumonia/etiologia , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Estudos Retrospectivos
17.
J Pediatr Hematol Oncol ; 41(4): e247-e253, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31026252

RESUMO

BACKGROUND: Radiotherapy for pediatric head and neck tumors often results in mucositis and pain, limiting oral intake and compromising patients' nutrition. There are little pediatric data available regarding enteral tube use and risk factors. Our objective was to estimate nutrition needs, identify risk factors contributing to nutritional decline and explore quality of life measures regarding enteral nutrition during proton radiotherapy. PROCEDURE: Nutritional metrics and status were collected throughout radiation treatment for 32 patients. We surveyed patients/caregivers about their perceptions of enteral nutrition. Risk factors for progression to non-oral nutrition or >5% weight loss were evaluated using univariate analysis. RESULTS: Patients who received any esophageal radiation or >30 Gy mean dose to the pharyngeal constrictors were more likely to experience >5% weight loss. These patients, as well as those who received a mean dose >30 Gy to the oropharynx or concurrent chemotherapy, were also more likely to require non-oral supplementation. Patients expressed the importance of maximizing nutrition and feared pain associated with a tube placement. CONCLUSIONS: Pediatric patients with head and neck cancer can be risk-stratified based on clinical and dosimetric factors. This data, combined with parent and patient perceptions, is key to the development of rational guidelines.


Assuntos
Nutrição Enteral/psicologia , Neoplasias de Cabeça e Pescoço/radioterapia , Conhecimentos, Atitudes e Prática em Saúde , Terapia com Prótons/efeitos adversos , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Percepção , Terapia com Prótons/psicologia , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
18.
Int J Radiat Oncol Biol Phys ; 104(5): 1084-1090, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31028831

RESUMO

PURPOSE: Acute skin toxicity in the form of radiation dermatitis (RD) or skin hyperpigmentation (SH) is a common problem experienced by patients undergoing breast irradiation. Proton radiation has been thought to deliver higher doses to skin compared with photon radiation because of differences in the physical properties between photons and protons; however, limited literature exists directly comparing toxicity outcomes. METHODS AND MATERIALS: The highest recorded grades of acute RD and SH were analyzed in 86 patients undergoing adjuvant radiation therapy to the breast with or without regional lymph nodes after lumpectomy (breast-conserving surgery) or mastectomy with either proton pencil-beam scanning (n = 39) or photon (n = 47) radiation therapy within a single institution to analyze differences in severity of acute skin reactions. For 34 of 47 photon and 33 of 39 proton patients, a "skin" contour was retroactively created in our treatment planning systems, and multiple dosimetric parameters were calculated to quantify objective radiation doses received by skin. RESULTS: On χ2 analysis, the highest reported grade of RD was significantly higher in women undergoing proton radiation compared with photon radiation; grade ≥2 RD was present in 69.2% versus 29.8% of patients receiving proton and photon therapy, respectively (P = .002). Rates of grade 3 RD were 5.1% versus 4.3% for proton versus photon radiation, respectively (P = .848). Overall, there were no significant differences in rates of SH between modalities. There were no grade 4 to 5 toxicities in either cohort. CONCLUSIONS: In a comparison with patients receiving photon radiation, a significantly higher rate of grade ≥2 RD was observed in patients undergoing proton radiation, with very low rates of grade 3 toxicity in both groups. Rates of SH did not differ significantly between modalities. Women should be counseled regarding the possibility of increased grade 2 toxicities, although this might present a dosimetric advantage for physicians when treating patients in the postmastectomy setting or when skin was involved on presentation.


Assuntos
Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Fótons/efeitos adversos , Terapia com Prótons/efeitos adversos , Radiodermatite/diagnóstico , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/radioterapia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Mastectomia Segmentar , Pessoa de Meia-Idade , Fótons/uso terapêutico , Doses de Radiação , Radiodermatite/patologia , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante/efeitos adversos , Adulto Jovem
19.
Acta Oncol ; 58(6): 934-942, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30938217

RESUMO

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.


Assuntos
Neoplasias da Mama/radioterapia , Linfonodos/efeitos da radiação , Terapia com Prótons/efeitos adversos , Lesões por Radiação/mortalidade , Radioterapia de Intensidade Modulada/efeitos adversos , Comportamento de Redução do Risco , Dermatopatias/prevenção & controle , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Órgãos em Risco/efeitos da radiação , Prognóstico , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Dermatopatias/induzido quimicamente , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos
20.
Phys Med ; 64: 304-310, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30992172

RESUMO

Re-treatment, using megavoltage photon radiotherapy, can benefit carefully selected patients with new or recurrent tumours. Such re-treatments may involve the further exposure of tissues such as the brain or spinal cord. A time-dependent model has been developed, which incorporates data from all published radiobiological experiments concerned with the in vivo re-irradiation of the spinal cord using photons. It allows an estimation of the increasing recovery in tissue tolerance with elapsed time after the initial treatment course. In accordance with the experimental evidence, the recovery rate depends on the biological effective dose (BED) of the initial treatment. Various degrees of conservatism have been introduced in the model to allow for potential changes in CNS tissue tolerance due to patient age, chemotherapy, surgery etc. An estimation of the re-treatment dose-fractionation schedule is made easier by the use of a downloadable Graphical User Interface (GUI). Worked examples of its use are given forconventional photon (X-ray) based treatments, and also for protons, where relative biological effectiveness (RBE) considerations must be respected within the BED estimates. The model provides boundary conditions for clinical practice. The responsible clinician can choose to usemore 'forgiving' BED values and from this to calculate the re-irradiation dose-fractionation schedule. For protons, greater care is required sincethe inter-relationship between linear energy transfer (LET) and RBE can lead to significant over-dosage relative to accepted CNS tolerance doses, especially with the use of scanned proton beams. LET and RBE factors are important in order to deliver safe and effective re-treatment doses.


Assuntos
Fótons/efeitos adversos , Fótons/uso terapêutico , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Doses de Radiação , Medula Espinal/efeitos da radiação , Humanos , Dosagem Radioterapêutica , Retratamento/efeitos adversos , Segurança
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA