RESUMO
BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.
Assuntos
Neoplasias Infratentoriais , Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Terapia com Prótons/métodos , Neoplasias Infratentoriais/radioterapia , Europa (Continente) , Criança , Planejamento da Radioterapia Assistida por Computador/métodos , Pré-Escolar , Masculino , Feminino , Órgãos em Risco/efeitos da radiação , Tronco Encefálico/efeitos da radiaçãoRESUMO
BACKGROUND: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. MATERIAL AND METHODS: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. RESULTS: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). CONCLUSION: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
Assuntos
Terapia com Prótons , Neoplasias de Tecidos Moles , Humanos , Criança , Prótons , Dosagem Radioterapêutica , Suécia , Terapia com Prótons/métodosRESUMO
Previous studies on dose-escalated radiotherapy in head and neck cancer have shown mixed results, and it is not established which patients would benefit from dose escalation. Further, while dose escalation does not appear to increase late toxicity, this needs to be confirmed with longer follow-up. In this study, we analysed treatment outcome and toxicity in 215 patients with oropharyngeal cancer treated with dose-escalated radiotherapy (>72 Gy, EQD2, α/ß = 10 Gy, boost by brachytherapy or simultaneous integrated boost) and a matched cohort of 215 patients treated with standard dose external-beam radiotherapy (68 Gy) between 2011 and 2018 at our institution. The 5-year overall survival (OS) was 77.8% (72.4-83.6) and 73.7% (67.8-80.1) in the dose-escalated and standard dose group, respectively (p = 0.24). Median follow-up was 78.1 (49.2-98.4) and 60.2 (38.9-89.4) months in the dose-escalated and standard dose groups, respectively. Grade ≥3 osteoradionecrosis (ORN) and late dysphagia were more common in the dose-escalated group compared to the standard dose group, with 19 (8.8%) vs. 4 (1.9%) patients developing grade ≥3 ORN (p = 0.001), and 39 (18.1%) vs. 21 (9.8%) patients developing grade ≥3 dysphagia (p = 0.01). No predictive factors to help select patients for dose-escalated radiotherapy were found. However, the remarkably good OS in the dose-escalated cohort, despite a predominance of advanced tumour stages, encourages further attempts to identify such factors.
RESUMO
BACKGROUND: Local recurrence is the most common pattern of failure in head and neck cancer. It can therefore be hypothesised that some of these patients would benefit from an intensified local treatment, such as radiation dose escalation of the primary tumour. This study compares treatment and toxicity outcomes from two different boost modalities in oropharyngeal cancer: simultaneous integrated boost (SIB) and brachytherapy boost. METHODS: Two hundred and forty-four consecutive patients treated with > 72 Gy for oropharyngeal squamous cell carcinoma between 2011 and 2018 at our institution were retrospectively analysed. Data on side effects were collected from a local quality registry and supplemented with a review of medical records. Patients receiving a brachytherapy boost first had external beam radiotherapy consisting of 68 Gy in 2 Gy fractions to the gross tumour volume (GTV), and elective radiotherapy to the neck bilaterally. The brachytherapy boost was typically given using pulsed dose rate, 15 fractions and 0.56-0.66 Gy per fraction [total dose in EQD2 = 75.4-76.8 Gy (α/ß = 10)]. The typical dose escalated radiotherapy with external beam radiotherapy only, was delivered using SIB with 74,8 Gy in 2.2 Gy fractions [EQD2 = 76.0 Gy (α/ß = 10)] to the primary tumour, 68 Gy in 2 Gy fractions to GTV + 10 mm margin and elective radiotherapy to the neck bilaterally. RESULTS: Dose escalation by SIB was given to 111 patients and brachytherapy boost to 134 patients. The most common type of cancer was base of tongue (55%), followed by tonsillar cancer (42%). The majority of patients had T3- or T4-tumours and 84% were HPV-positive. The 5-year OS was 72,4% (95% CI 66.9-78.3) and the median follow-up was 6.1 years. Comparing the two different dose escalation modalities we found no significant differences in OS or PFS and these results remained after a propensity-score matched analysis was performed. The analysis of grade ≥ 3 side effects showed no significant differences between the two different dose escalation techniques. CONCLUSIONS: We found no significant differences in survival or grade ≥ 3 side effects comparing simultaneous integrated boost and brachytherapy boost as alternative dose escalation modalities in the treatment of oropharyngeal cancer.
Assuntos
Braquiterapia , Neoplasias Orofaríngeas , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Braquiterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/radioterapia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapiaRESUMO
Re-irradiation in head and neck cancer is challenging, and cumulative dose constraints and dose/volume data are scarce. In this study, we present dose/volume data for patients re-irradiated for head and neck cancer and explore the correlations of cumulative dose to organs at risk and severe side effects. We analyzed 54 patients re-irradiated for head and neck cancer between 2011 and 2017. Organs at risk were delineated and dose/volume data were collected from cumulative treatment plans of all included patients. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. The ROC-curve for a logistic model of carotid blowout vs. maximum doses to the carotid arteries showed AUC = 0.92 (95% CI 0.83 to 1.00) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.89). The near-maximum dose to bones showed an association with the risk of osteoradionecrosis: AUC = 0.74 (95% CI 0.52 to 0.95) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.52). Our analysis showed an association between cumulative dose to organs at risk and the risk of developing osteoradionecrosis and carotid blowout, and our results support the existing dose constraint for the carotid arteries of 120 Gy. The confirmation of these dose-response relationships will contribute to further improvements of re-irradiation strategies.
RESUMO
AIM: Data from a local quality registry are used to model the risk of late xerostomia after radiotherapy for head and neck cancer (HNC), based on dosimetric- and clinical variables. Strengths and weaknesses of using quality registry data are explored. METHODS: HNC patients treated with radiotherapy at the Karolinska University hospital are entered into a quality registry at routine follow up, recording morbidity according to a modified RTOG/LENT-SOMA scale. Other recorded parameters are performance status, age, gender, tumor location, tumor stage, smoking status, chemotherapy and radiotherapy data, including prescribed dose and organ-at-risk (OAR) dose. Most patients are entered at several time points, but at variable times after treatment. Xerostomia was modeled based on follow-up data from January 2014 to October 2018, resulting in 753 patients. Two endpoints were considered: maximum grade ≥2 (XERG≥2) or grade ≥3 (XERG≥3) late xerostomia. Univariate Cox regression was used to select variables for two multivariate models for each endpoint, one based on the mean dose to the total parotid volume (Dtot) and one based on the mean dose to the contralateral parotid (Dcontra). Cox regression allows the estimation of the risk of xerostomia at different time points; models were presented visually as nomograms estimating the risk at 9, 12, and 24 months respectively. RESULTS: The toxicity rates were 366/753 (49%) for XERG≥2 and 40/753 (5.3%) for XERG≥3. The multivariate models included several variables for XERG≥2, and dose, concomitant chemotherapy and age were included for XERG≥3. Induction chemotherapy and an increased number of fractions per week were associated with a lower risk of XERG≥2. However, since the causality of these relationships have limited support from previous studies, alternative models without these variables were also presented. The models based on the mean dose to the total parotid volume and the contralateral parotid alone were very similar. CONCLUSION: Late xerostomia after radiotherapy can be modeled with reasonable predictive power based on registry data; models are presented for different endpoints highly relevant in clinical practice. However, the risk of modeling indirect relationships, given the unavoidably heterogeneous registry data, needs to be carefully considered in the interpretation of the results.
RESUMO
BACKGROUND: There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment. METHODS: Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded. RESULTS: The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC. CONCLUSIONS: Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Doses de Radiação , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Seleção de Pacientes , Intervalo Livre de Progressão , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices. MATERIAL AND METHODS: Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume. RESULTS: A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960â¯cm3 (average 669â¯cm3) and for case 2; 65-126â¯cm3 (average 109â¯cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both "compliant" target volumes as well as outliers which are hidden with just the use of concordance indices. CONCLUSIONS: The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.