RESUMEN
To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54-60) delivered in 1.8-2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts.
Asunto(s)
Ependimoma/radioterapia , Neoplasias Infratentoriales/radioterapia , Terapia de Protones , Neoplasias Supratentoriales/radioterapia , Adolescente , Quimioterapia Adyuvante , Niño , Preescolar , Relación Dosis-Respuesta en la Radiación , Ependimoma/tratamiento farmacológico , Ependimoma/cirugía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Infratentoriales/tratamiento farmacológico , Neoplasias Infratentoriales/cirugía , Masculino , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Neoplasias Supratentoriales/tratamiento farmacológico , Neoplasias Supratentoriales/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: To examine the metastatic and survival rates, eye retention probability, and the visual outcomes of juvenile patients after proton beam radiotherapy (PBRT) for uveal melanoma (UM). DESIGN: Retrospective case-factor matched control study. PARTICIPANTS AND CONTROLS: Forty-three patients younger than 21 years treated with PBRT for UM were compared with 129 matched adult control patients. METHODS: Information on patient demographics and clinical characteristics were recorded before and after treatment from patients' files. The control group was composed of adult patients (>21 years) matched for tumor size (largest tumor diameter, ±2 mm; height, ±2 mm) and anterior margin location (iris, ciliary body, pre-equatorial or postequatorial choroid). For each juvenile patient, 3 adults were selected. MAIN OUTCOME MEASURES: Comparing outcomes of juvenile and adult patients in terms of metastatic and eye retention rates using the log-rank statistic, relative survival using the Hakulinen method, as well as their visual outcomes. RESULTS: Forty-three juvenile and 129 control cases were reviewed. The metastatic rate at 10 years was significantly lower in juvenile UM patients than in adult controls (11% vs. 34%; P <0.01), with an associated relative survival rate of 93% versus 65% (P = 0.02). Six juvenile patients (14%) demonstrated metastases. One patient underwent enucleation because of a presumed local tumor recurrence and 4 additional patients underwent enucleation because of complications (9.3%). In the adult control group, 27% (n = 35) of matched patients demonstrated metastases, there were 2 cases of local recurrence, and 16% (n = 21) underwent enucleation because of complications. A visual acuity of more than 0.10 was maintained in most cases, without any significant differences before or after treatment observed between both groups. CONCLUSIONS: After PBRT, metastatic and survival rates are significantly better for juvenile than for adult patients with UM. Clinically, juvenile and adult eyes react similarly to PBRT, with patients having a comparable eye retention probability and maintaining a useful level of vision in most cases. This is the largest case-control study of proton therapy in juvenile eyes to date and further validates PBRT as an appropriate conservative treatment for UM in patients younger than 21 years.
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Melanoma/radioterapia , Terapia de Protones , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Supervivencia sin Enfermedad , Enucleación del Ojo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Hepáticas/secundario , Masculino , Melanoma/mortalidad , Melanoma/patología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To describe a remote positioning system for accurate and efficient proton radiotherapy treatments. METHODS AND MATERIALS: To minimize positioning time in the treatment room (and thereby maximize beam utility), we have adopted a method for remote patient positioning, with patients positioned and imaged outside the treatment room. Using a CT scanner, positioning is performed using orthogonal topograms with the measured differences to the reference images being used to define daily corrections to the patient table in the treatment room. Possible patient movements during transport and irradiation were analyzed through periodic acquisition of posttreatment topograms. Systematic and random errors were calculated for this daily positioning protocol and for two off-line protocols. The potential time advantage of remote positioning was assessed by computer simulation. RESULTS: Applying the daily correction protocol, systematic errors calculated over all patients (n = 94) were below 0.6 mm, whereas random errors were below 1.5 mm and 2.5 mm, respectively, for bite-block and for mask immobilization. Differences between pre- and posttreatment images were below 2.8 mm (SD) in abdominal/pelvic region, and below 2.4 mm (SD) in the head. Retrospective data analysis for a subset of patients revealed that off-line protocols would be significantly less accurate. Computer simulations showed that remote positioning can increase patient throughput up to 30%. CONCLUSIONS: The use of a daily imaging and correction protocol based on a "remote" CT could reduce positioning errors to below 2.5 mm and increase beam utility in the treatment room. Patient motion between imaging and treatment were not significant.
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Terapia de Protones , Planificación de la Radioterapia Asistida por Computador/métodos , Errores Diagnósticos , Eficiencia , Arquitectura y Construcción de Instituciones de Salud , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Método de Montecarlo , Movimiento , Radiografía , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/normas , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/radioterapia , Tecnología Radiológica/métodos , Telerradiología/métodos , Factores de TiempoRESUMEN
PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.
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Condrosarcoma/radioterapia , Cordoma/radioterapia , Terapia de Protones , Adolescente , Adulto , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Niño , Condrosarcoma/cirugía , Cordoma/cirugía , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Recurrencia Local de Neoplasia/radioterapia , Periodo Posoperatorio , Traumatismos por Radiación/complicaciones , Radioterapia de Intensidad Modulada , Neoplasias de la Base del Cráneo/radioterapia , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/cirugíaRESUMEN
PURPOSE: A retrospective study to investigate the sensitivity of intensity modulated proton therapy (IMPT) to changes in body weight occurring during the course of radiotherapy for patients treated in the sacral region. MATERIALS AND METHODS: During therapy, important weight gain and loss were observed for two patients treated to para-spinal tumors, which resulted in both patients being re-scanned and re-planned. Both patients were treated as part of their therapy, with a narrow-angle IMPT (NA-IMPT) plan delivering a 'dose hole' around the cauda equina (CE), which was mainly formed through modulation of Bragg peaks in depth. To investigate the impact of these weight changes on the proton range and delivered dose, the nominal fields were re-calculated on the new CT data sets. Results were analyzed by comparing these new plans with those originally delivered and by calculating changes in range and delivered doses in target volumes and normal tissues. RESULTS: Maximum differences in proton range in the CE region of up to +8 mm and -13 mm, respectively, for the patient who gained weight and for the patient who lost weight, increased the maximum dose to the CE by only 2%. This indicates that both IMPT plans were relatively insensitive to substantial range uncertainties. Even greater differences in range (16 mm) in the planning target volume only slightly affected its dose homogeneity (differences in V(90%) of 6% in the worst case). Nevertheless, some large undesired local dose differences were observed. CONCLUSIONS: We demonstrated, that, at least for the two analyzed cases, NA-IMPT plans are less sensitive to weight variations than one may expect. Still, we would advise to calculate new plans in case of substantial change in weight for patients treated in the sacral region, primarily due to the presence of new hot/cold area.
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Peso Corporal , Condroma/radioterapia , Osteosarcoma/radioterapia , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Columna Vertebral/radioterapia , Niño , Relación Dosis-Respuesta en la Radiación , Humanos , Masculino , Persona de Mediana Edad , Protones , Dosificación Radioterapéutica , Estudios Retrospectivos , Sacro , Sensibilidad y EspecificidadRESUMEN
Uveal melanoma metastases occur most commonly in the liver. Given the 50% mortality rate in patients at high risk of developing liver metastases, we tested an adjuvant intra-arterial hepatic (i.a.h.) chemotherapy with fotemustine after proton beam irradiation of the primary tumour. We treated 22 high-risk patients with adjuvant i.a.h. fotemustine. Planned treatment duration was 6 months, starting with four weekly doses of 100 mg/m(2), and after a 5-week rest, repeated every 3 weeks. The survival of this patient group was compared with that of a 3 : 1 matched control group randomly selected from our institutional database. Half of the patients experienced > or =grade 3 hepatotoxicity (one patient developing cholangitis 8 years later). Catheter-related complications occurred in 18%. With a median follow-up of 4.6 years for the fotemustine group and 8.5 years for the control group, median overall survival was 9 years [95% confidence interval (CI) 2.2-12.7] and 7.4 years (95% CI 5.4-12.7; P=0.5), respectively, with 5-year survival rates of 75 and 56%. Treatment with adjuvant i.a.h. fotemustine is feasible. However, toxicities are important. Although our data suggest a survival benefit, it was not statistically significant. Confirming such a benefit would require a large, internationally coordinated, prospective randomized trial.
Asunto(s)
Arteria Hepática , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Melanoma/tratamiento farmacológico , Compuestos de Nitrosourea/administración & dosificación , Compuestos Organofosforados/administración & dosificación , Neoplasias de la Úvea/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Arteria Hepática/efectos de los fármacos , Humanos , Infusiones Intraarteriales , Masculino , Melanoma/mortalidad , Melanoma/patología , Melanoma/radioterapia , Persona de Mediana Edad , Compuestos de Nitrosourea/efectos adversos , Compuestos Organofosforados/efectos adversos , Riesgo , Prevención Secundaria , Análisis de Supervivencia , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/radioterapiaRESUMEN
Historically, retinoblastoma was treated with external beam radiotherapy (EBR) and for many years this was the accepted standard of care. With greater knowledge of radiation-induced morbidity and mortality, the trend over the past decade has shifted towards primary chemotherapy for most globe conservative treatments. Such a radical change in treatment modalities has restrained EBR to second-line and salvage indications with little consensus regarding dose, timing and techniques. New radiotherapy options now allow for more focused radiation to the globe with further sparing of adjacent structures in such a way that their role in the management of retinoblastoma need to be reappraised. In this perspective paper, first the historical techniques of using EBR primarily with linear accelerated photons are reviewed. Then modern approaches are described, such as stereotactic conformal radiotherapy using a micromultileaf collimator, and proton therapy using a fixed horizontal beam and tantalum localization, or a rotating ganthry with spot scanning. For the first time, to the authors' knowledge, the benefits of these new irradiation modalities over conventional EBR are illustrated with six successfully treated pilot cases. Finally, some guidelines are provided regarding indications to modern radiation therapy in patients requiring second-line or salvage treatment for intraocular retinoblastoma, as well as adjuvant therapy for orbital involvement.
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Neoplasias de la Retina/radioterapia , Retinoblastoma/radioterapia , Preescolar , Femenino , Historia del Siglo XX , Humanos , Lactante , Masculino , Aceleradores de Partículas , Fotones/uso terapéutico , Radioterapia/historia , Radioterapia/métodos , Radioterapia/tendencias , Radioterapia Adyuvante , Radioterapia Conformacional , Terapia Recuperativa , Técnicas EstereotáxicasRESUMEN
PURPOSE: To evaluate the use of postoperative proton therapy (PT) in extracranial chordoma. PATIENTS AND METHODS: Twenty-six patients were treated. Gross total resection was achieved in 18 patients. Nine patients had cervical, 2 had thoracic, 8 had lumbar, and 7 had sacro-coccygeal chordomas. Thirteen patients had implants. PT was administered after function-preserving surgery, using a gantry and spot scanning, without or with intensity modulation (IMPT; 6 patients), and/or photon-based radiotherapy (RT, 6 patients). Median total dose was 72 cobalt Gray equivalent (CGE; range, 59.4-74.4), with means of 70.5 and 73.2 CGE for patients with and without implants. Median follow-up time was 35 months (range, 13-73 months). Adverse events were scored using the Common Terminology Criteria for Adverse Events grading system (version 3.0). RESULTS: At 3 years, actuarial overall survival (OS) and progression-free survival (PFS) rates were 84% and 77%, respectively. One patient each died of local failure (LF), distant failure (DF), suicide, and secondary tumor. We observed 5 LFs and 3 DFs; 3-year LF-free and DF-free survival rates were 86%. We observed four radiation-induced late adverse events (Grade 2 sensory neuropathy; Grade 3 subcutaneous necrosis, and osteonecrosis; and Grade 5 secondary cancer). In univariate analysis, implants were associated with LF (p = 0.034). Gross residual tumor above 30 mL was negatively associated with OS (p = 0.013) and PFS (p = 0.025). CONCLUSIONS: Postoperative PT for extracranial chordomas delivered with spot scanning offers high local control rates. Toxicity was acceptable. Implants were significantly associated with LF. Residual tumor above 30 mL impacted negatively on OS and PFS.
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Cordoma/radioterapia , Neoplasias de la Columna Vertebral/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Cordoma/mortalidad , Cordoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Radioterapia/métodos , Dosificación Radioterapéutica , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/cirugía , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. METHODS AND MATERIALS: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). RESULTS: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. CONCLUSIONS: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.
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Terapia de Protones , Sarcoma/radioterapia , Adolescente , Niño , Preescolar , Estudios de Factibilidad , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Lactante , Masculino , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/radioterapia , Calidad de Vida , Traumatismos por Radiación/patología , Rabdomiosarcoma Embrionario/tratamiento farmacológico , Rabdomiosarcoma Embrionario/mortalidad , Rabdomiosarcoma Embrionario/radioterapia , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/radioterapia , SobrevivientesRESUMEN
PURPOSE: To assess the safety and efficacy of spot scanning proton beam therapy (PT) in the curative treatment of soft-tissue sarcoma (STS) in adults patients. PATIENTS AND METHODS: We identified 13 STS patients treated with PT between July 1998 and May 2005 in our institutional database. Tumor histology varied with the most common histologic subtypes including liposarcoma and peripheral nerve sheet tumor. All tumors were located in vicinity of critical structures, such as the spinal cord, optic apparatus, bowel, kidney, or bowel. Of the patients, 6 and 5 patients received PT either as adjuvant therapy for non-R0 resection or for recurrence, respectively. Two patients received radical PT for unresectable disease. The median prescribed dose was 69.4 CGE (CGE = proton Gy x 1.1)-Gy (range, 50.4-76.0) at 1.8 to 2 CGE-Gy (median, 1.9) per fraction. Pre-PT anthracycline-based chemotherapy was delivered to 3 patients only. No patient has been lost to follow-up (median 48.1 months, range, 19.1-100.7 months). RESULTS: Of the 13 patients, all but 2 patients were alive. Local recurrence developed in 3 (23%) patients. The administered dose to these patients was < or =60 Gy-CGE. Distant control was achieved in all but 2 patients (lung metastasis), 1 of whom presented with a concomitant local recurrence. The 4-year local control and metastasis-free survival rates were 74.1% and 84.6%, respectively. Late grade > or =2 toxicity was observed in only 2 patients. CONCLUSIONS: Spot scanning PT is an effective and safe treatment for patient with STS in critical locations. The observed toxicity rate was acceptable.
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Recurrencia Local de Neoplasia/radioterapia , Terapia de Protones , Sarcoma/radioterapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protones/efectos adversos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Adyuvante/efectos adversos , Suiza , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To determine the relative biologic effectiveness (RBE) of the Paul Scherrer Institute (PSI) scanning proton beam in reference conditions and to evaluate the influence of intestine motion on the proton dose homogeneity. METHODS AND MATERIALS: First, RBE was determined for crypt regeneration in mice after irradiation in a single fraction. Irradiation was performed at the middle of a 7-cm spread out Bragg peak (SOBP; reference position), as well as in the proximal part of the plateau and at the distal end of the SOBP. Control gamma-irradiation was randomized with proton irradiation and performed simultaneously. Second, motion of mouse intestine was determined by radiographs after copper wire markers had been placed on the jejunum and intestinal wall. RESULTS: Proton RBE (reference (60)Co gamma) was equal to 1.16 for irradiation at the middle of the SOBP and to 1.11 and 1.21 for irradiation in the initial plateau and end of the SOBP, respectively. The confidence intervals for these RBE values were much larger than those obtained in the other proton beams we have tested so far. They exceeded +/-0.20 (compared with the usual value of +/-0.07), which resulted from the unusually large dispersion of the individual proton data. The instantaneous positions of the mice intestines varied by +/-2 mm in the course of irradiation. CONCLUSION: The results of this study have shown that the RBE of the PSI proton beam is in total accordance with the RBE obtained at the other centers. This experiment has corroborated that proton RBE at the middle of the SOBP is slightly larger than the generic value of 1.10 and that there is a slight tendency for the RBE to increase close to the end of the SOBP. Also, excessive dispersion of individual proton data may be considered to result from intestine motion, taking into account that irradiation at the PSI is delivered dynamically by scanning the target volume with a pencil proton beam ("spot scanning"). Because 2-mm movements resulted in significant variations in local dose depositions, this should be considered for moving targets. Strategies to reduce this effect for the spot scanning technique have been developed at the PSI for radiotherapy of humans.
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Intestinos/efectos de la radiación , Movimiento , Terapia de Protones , Efectividad Biológica Relativa , Animales , Calibración , Intervalos de Confianza , Relación Dosis-Respuesta en la Radiación , Femenino , Rayos gamma/uso terapéutico , Mucosa Intestinal/fisiología , Mucosa Intestinal/efectos de la radiación , Intestinos/diagnóstico por imagen , Intestinos/fisiología , Yeyuno/diagnóstico por imagen , Yeyuno/fisiología , Yeyuno/efectos de la radiación , Ratones , Ratones Endogámicos , Radiografía , RegeneraciónRESUMEN
PURPOSE: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). METHOD AND MATERIALS: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. RESULTS: Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. CONCLUSION: These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.
Asunto(s)
Melanoma/radioterapia , Melanoma/cirugía , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/métodos , Neoplasias de la Úvea/radioterapia , Neoplasias de la Úvea/cirugía , Neoplasias Encefálicas/secundario , Fraccionamiento de la Dosis de Radiación , Humanos , Melanoma/diagnóstico por imagen , Melanoma/secundario , Fotones/uso terapéutico , Terapia de Protones , Tomografía Computarizada por Rayos X , Neoplasias de la Úvea/diagnóstico por imagenRESUMEN
PURPOSE: To assess the clinical results of spot scanning proton beam radiation therapy (PT) in the treatment of skull base chordomas and low-grade chondrosarcomas (CS). METHODS AND MATERIALS: Between October 1998 and October 2003, 29 patients (median age, 39 years) with chordomas (n = 18) and CS (n = 11) were treated at the Paul Scherrer Institut (PSI) with protons using the main 510-MeV cyclotron. Tumor conformal application of proton beams was realized by spot scanning technology. The median chordoma and CS dose was 74 and 68 cobalt Gy equivalent, respectively (cobalt Gy equivalent = proton Gy x 1.1). Median gross tumor volumes (GTV) were 16.4 mL (range, 1.8-48.1 mL) and 15.2 mL (range, 2.3-57.3 mL) for chordoma and CS, respectively. Late toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system. The median follow-up time was 29 months (range, 6-68 months). RESULTS: Actuarial 3-year local control rates were 87.5% and 100% for chordoma and CS, respectively. We observed one surgical pathway and one marginal failure in patients with chordomas. No regional failure or distant metastasis was observed. At 3 years, actuarial PFS and OS for the entire cohort was 90% and 93.8%, respectively. Actuarial 3-year complication-free survival was 82.2%. Radiation-induced pituitary dysfunction was observed in 4 (14%) patients (CTCAE Grade 2). No patient presented with post-PT brainstem or optic pathways necrosis or dysfunction. In univariate analysis, age < or =40 years at the time of PT affected favorably on PFS (p = 0.09). CONCLUSION: Spot-scanning PT offers high tumor control rates of skull base chordoma and CS. These results compare favorably to other combined proton-photon or carbon ion irradiation series. Observed toxicity was acceptable. Younger age (< or =40 years) was a favorable prognostic factor of PFS. These preliminary results are encouraging but should be confirmed during a longer follow-up.
Asunto(s)
Condrosarcoma/radioterapia , Cordoma/radioterapia , Terapia de Protones , Neoplasias de la Base del Cráneo/radioterapia , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
PURPOSE: To analyze the long-term results of eye retention after conservative treatment of uveal melanoma with proton beam radiotherapy, and to analyze the causes leading to enucleation after this conservative treatment approach. MATERIALS AND METHODS: This was a prospective, noncomparative, interventional, consecutive case series. A total of 2645 patients (2648 eyes) with uveal melanoma were treated between 1984 and 1999 with proton beam radiotherapy. Data were analyzed as of February 2001. Patients' age ranged from 9 to 90 years, 1284 were men, and 1361 were women. Largest tumor diameter ranged from 4 to 27.5 mm, and tumor height from 0.9 to 15.6 mm. Median follow-up time was 44 months. RESULTS: The overall eye retention rate at 5, 10, and 15 years after treatment was 88.9%, 86.2%, and 83.7%, respectively. In total, 218 eyes had to be enucleated. Enucleation was related to larger tumor size, mainly tumor height, proximity of posterior tumor margin to optic disc, male gender, high intraocular pressure, and large degree of retinal detachment at treatment time. After optimization of the treatment technique, the eye retention rate at 5 years was increased from 97.1% to 100% for small tumors, from 86.7% to 99.7% for medium, and from 71.1% to 89.5% for large tumors. CONCLUSIONS: The treatment technique as used today results in excellent eye retention rates, even in less favorable cases such as large tumors and tumors located close to the optic disc. The experience and a continuous quality control program allowed us to improve the 5-year eye retention rate for all tumor sizes. These findings demonstrate the positive impact of experience and quality control-based efforts for treatment technique optimization.
Asunto(s)
Enucleación del Ojo/estadística & datos numéricos , Melanoma/radioterapia , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Presión Intraocular , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Disco Óptico/anatomía & histología , Modelos de Riesgos Proporcionales , Terapia de Protones , Desprendimiento de Retina/complicaciones , Factores Sexuales , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Agudeza VisualRESUMEN
BACKGROUND AND PURPOSE: To assess the safety and efficacy of spot scanning proton beam radiation therapy (PRT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: Sixteen patients with intracranial meningioma (histopathologically proven in 13/16 cases) were treated with PRT between July 1997 and July 2002. Eight patients had skull base lesions. Thirteen patients received PRT after surgery either as adjuvant therapy for incomplete resection (eight patients) or for recurrence (five patients). Three patients received radical PRT after presumptive diagnosis based on imaging. The median prescribed dose was 56 CGE (range, 52.2-64, CGE=proton Gy X 1.1) at 1.8-2.0 CGE (median, 2.0) per fraction. Gross tumor volume and planning target volume ranged from 0.8 to 87.6 cc (median, 17.5) and 4.6-208.1 cc (median 107.7), respectively. Late ophthalmologic and non-ophthalmologic toxicity was assessed using the Subjective, Objective, Management and Analytic scale (SOMA) of the Late Effects of Normal Tissue scoring system and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system, respectively. The median follow-up time was 34.1 months (range, 6.5-67.8). RESULTS: Cumulative 3-year local control, progression-free survival and overall survival were 91.7, 91.7 and 92.7%, respectively. No patient died from recurrent meningioma. One patient progressed locally after PRT. Radiographic follow-up (median, 34 months) revealed an objective response in three patients and stable disease in 12 patients. Cumulative 3-year toxicity free survival was 76.2%. One patient presented with radiation induced optic neuropathy (SOMA Grade 3) and retinopathy (SOMA Grade 2) 8.8 and 30.4 months after treatment, respectively. These patients with ophthalmologic toxicity received doses higher than those allowed for the optic/ocular structures. Another patient developed a symptomatic brain necrosis (CTCAE Grade 4) 7.2 months after treatment. No radiation-induced hypothalamic/pituitary dysfunction was observed. CONCLUSIONS: Spot-scanning PRT is an effective treatment for patient with untreated, recurrent or incompletely resected intracranial meningiomas. It offers highly conformal irradiation for complex-shaped intracranial meningiomas, while delivering minimal non-target dose. Observed ophthalmologic toxicity is dose-related.
Asunto(s)
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Terapia de Protones , Radioterapia Conformacional/métodos , Adolescente , Adulto , Niño , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica/normas , Radioterapia Adyuvante , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Since the end of 1996, we have treated more than 160 patients at PSI using spot-scanned protons. The range of indications treated has been quite wide and includes, in the head region, base-of-skull sarcomas, low-grade gliomas, meningiomas, and para-nasal sinus tumors. In addition, we have treated bone sarcomas in the neck and trunk--mainly in the sacral area--as well as prostate cases and some soft tissue sarcomas. PTV volumes for our treated cases are in the range 20-4500 ml, indicating the flexibility of the spot scanning system for treating lesions of all types and sizes. The number of fields per applied plan ranges from between 1 and 4, with a mean of just under 3 beams per plan, and the number of fluence modulated Bragg peaks delivered per field has ranged from 200 to 45 000. With the current delivery rate of roughly 3000 Bragg peaks per minute, this translates into delivery times per field of between a few seconds to 20-25 min. Bragg peak weight analysis of these spots has shown that over all fields, only about 10% of delivered spots have a weight of more than 10% of the maximum in any given field, indicating that there is some scope for optimizing the number of spots delivered per field. Field specific dosimetry shows that these treatments can be delivered accurately and precisely to within +/-1 mm (1 SD) orthogonal to the field direction and to within 1.5 mm in range. With our current delivery system the mean widths of delivered pencil beams at the Bragg peak is about 8 mm (sigma) for all energies, indicating that this is an area where some improvements can be made. In addition, an analysis of the spot weights and energies of individual Bragg peaks shows a relatively broad spread of low and high weighted Bragg peaks over all energy steps, indicating that there is at best only a limited relationship between pencil beam weighting and depth of penetration. This latter observation may have some consequences when considering strategies for fast re-scanning on second generation scanning gantries.
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Neoplasias/radioterapia , Terapia de Protones , Garantía de la Calidad de Atención de Salud/métodos , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Alta Energía/métodos , Medición de Riesgo/métodos , Humanos , Modelos Biológicos , Protección Radiológica/métodos , Dosificación Radioterapéutica , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Intensity Modulated Proton Therapy (IMPT) differs from conventional proton therapy in its ability to deliver depth-shifted, arbitrarily complex proton fluence maps from each incident field direction. As the individual Bragg peaks delivered from any field can be distributed in three-dimensions throughout the target volume, IMPT provides many more degrees of freedom for designing dose distributions than IMRT or conventional proton therapy techniques. So how can the flexibility of IMPT best be exploited? Here we argue that IMPT has two main advantages over photon IMRT and conventional proton therapy: the ability to better 'sculpt' the dose to the target and around neighbouring critical structures, and the ability to find clinically acceptable solutions whilst simultaneously reducing the sensitivity of the treatments to potential delivery errors. The concept of IMPT as a tool for generating 'safer' plans opens an interesting new avenue of research from the point of view of plan optimisation, the potential of which is only just beginning to be explored.
Asunto(s)
Terapia de Protones , Radioterapia/métodos , Humanos , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador , SeguridadRESUMEN
PSI is still the only location in which proton therapy is applied using a dynamic beam scanning technique on a very compact gantry. Recently, this system is also being used for the application of intensity-modulated proton therapy (IMPT). This novel technical development and the success of the proton therapy project altogether have led PSI in Year 2000 to further expand the activities in this field by launching the project PROSCAN. The first step is the installation of a dedicated commercial superconducting cyclotron of a novel type. The second step is the development of a new gantry, Gantry 2. For Gantry 2 we have chosen an iso-centric compact gantry layout. The diameter of the gantry is limited to 7.5 m, less than in other gantry systems (approximately 10-12 m). The space in the treatment room is comfortably large, and the access on a fixed floor is possible any time around the patient table. Through the availability of a faster scanning system, it will be possible to treat the target volume repeatedly in the same session. For this purpose, the dynamic control of the beam intensity at the ion source and the dynamic variation of the beam energy will be used directly for the shaping of the dose.
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Ciclotrones , Neoplasias/radioterapia , Terapia de Protones , Radioterapia de Alta Energía/instrumentación , Radioterapia de Alta Energía/métodos , Diseño de Equipo , HumanosRESUMEN
PURPOSE: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. METHODS AND MATERIALS: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. RESULTS: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. CONCLUSIONS: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.
Asunto(s)
Dentición Permanente , Neoplasias/radioterapia , Órganos en Riesgo/efectos de la radiación , Traumatismos por Radiación/complicaciones , Diente Primario , Diente/efectos de la radiación , Adolescente , Antineoplásicos/efectos adversos , Carcinoma/radioterapia , Niño , Preescolar , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Imagenología Tridimensional/métodos , Lactante , Masculino , Neoplasias/tratamiento farmacológico , Órganos en Riesgo/diagnóstico por imagen , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Dosificación Radioterapéutica , Efectividad Biológica Relativa , Estudios Retrospectivos , Rabdomiosarcoma/radioterapia , Sarcoma/radioterapia , Teratoma/radioterapia , Tomografía Computarizada por Rayos X , Diente/diagnóstico por imagen , Germen Dentario/efectos de la radiaciónRESUMEN
PURPOSE: To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. METHODS AND MATERIALS: Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. RESULTS: Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. CONCLUSIONS: Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.