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BACKGROUND: Electromagnetic Tracking (EMT) technology has been integrated in a prototype high-dose-rate brachytherapy (HDR-BT) afterloading device. Its potential for dwell position (DP) monitoring has earlier been demonstrated in prostate phantoms. However, its performance for prostate BT in the clinical setting remains to be assessed. AIM: Assess the reliability and value of EMT measurements in transrectal ultrasound-based (TRUS-based) and computed tomography-based (CT-based) prostate HDR-BT. METHODS: EMT measurements were conducted on 20 patients undergoing dual-fraction prostate HDR-BT monotherapy. In each treatment fraction an individual TRUS-based or CT-based treatment plan was generated. The measurements were compared to DPs of manually reconstructed needles in those TRUS-based or CT-based treatment plans. An internal reference sensor was also placed in one needle to assess internal movement levels and its potential for movement correction. RESULTS: For TRUS-based treatments, median Euclidean distances (ED) of 1.00â¯mm were observed between EMT measurements and manual DP determination. Reference sensor movement was minimal at a median of 0.18â¯mm. For DPs measured in the CT-room and treatment room, median EDs of 1.60â¯mm and 2.24â¯mm compared to CT-based DP determination respectively were observed, indicating the system's ability to detect changes in implant geometry over time and after patient repositioning. Median reference sensor movement of 0.97â¯mm was observed. Implementing reference sensor-based movement correction led to a significant but small decrease in ED for CT-based treatments. CONCLUSION: EMT is suitable for TRUS-based prostate HDR-BT quality assurance and error detection. While EMT can identify changes in implant geometry in CT-based prostate HDR-BT treatments, it showed lower accuracy in this setting.
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In high-dose-rate brachytherapy (HDR-BT) for prostate cancer treatment, interstitial hyperthermia (IHT) is applied to sensitize the tumor to the radiation (RT) dose, aiming at a more efficient treatment. Simultaneous application of HDR-BT and IHT is anticipated to provide maximum radiosensitization of the tumor. With this rationale, the ThermoBrachyTherapy applicators have been designed and developed, enabling simultaneous irradiation and heating. In this research, we present a method to optimize the three-dimensional temperature distribution for simultaneous HDR-BT and IHT based on the resulting equivalent physical dose (EQDphys) of the combined treatment. First, the temperature resulting from each electrode is precomputed. Then, for a given set of electrode settings and a precomputed radiation dose, the EQDphys is calculated based on the temperature-dependent linear-quadratic model. Finally, the optimum set of electrode settings is found through an optimization algorithm. The method is applied on implant geometries and anatomical data of 10 previously irradiated patients, using reported thermoradiobiological parameters and physical doses. We found that an equal equivalent dose coverage of the target can be achieved with a physical RT dose reduction of 20% together with a significantly lower EQDphys to the organs at risk (p-value < 0.001), even in the least favorable scenarios. As a result, simultaneous ThermoBrachyTherapy could lead to a relevant therapeutic benefit for patients with prostate cancer.
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A review of studies on seminal vesicle motion was performed to improve the understanding of these treatment uncertainties. This will aid planning target volume margin reduction, which is necessary for hypofractionation of high-risk prostate cancer. Embase, Medline, Web of science Core collection, Cochrane CENTRAL register of trials and Google scholar were searched for publications including 3D information on seminal vesicle motion. In total 646 publications were found of which 22 publications were eligible for inclusion. The mean, systematic and random error of inter- and intra-fraction translations are reported, as well as rotations. The translations of the seminal vesicles is smallest in the left-right direction, whereas the rotation was largest around this axis. Although rectal and bladder filling status were the main cause for seminal vesicle motion, no apparent effect on magnitude of motion was seen when different bladder and rectal preparation protocols were used. Inter- and intra-fraction motion of the seminal vesicles is significant. In the studies, systematic and random errors range between 1-7 mm and 1-5 mm respectively, and are largely uncorrelated to prostate motion. The maximum correlation between seminal vesicle and prostate motion was reported with an R2 of 0.7, while 3 other studies report lower and/or non-significant correlations. Five studies report a planning target volume margin of approximately 8 mm. This margin is in line with the results of four relevant dosimetric studies. Mitigating the inter- and intra-fraction motion of the seminal vesicles, including prostate tracking, has the potential to reduce planning target volume margins.
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Neoplasias da Próstata , Glândulas Seminais , Humanos , Masculino , Movimento (Física) , Próstata , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios XRESUMO
The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) can improve clinical outcomes since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied as it is regarded as difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from >12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a >99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning.
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Braquiterapia , Hipertermia Induzida , Braquiterapia/métodos , Simulação por Computador , Fenômenos Eletromagnéticos , Hipertermia Induzida/métodos , Dosagem RadioterapêuticaRESUMO
OBJECTIVE: In High Dose Rate Brachytherapy for prostate cancer there is a need for a new way of increasing cancer cell kill in combination with a stable dose to the organs at risk. In this study, we propose a novel ThermoBrachy applicator that offers the unique ability to apply interstitial hyperthermia while simultaneously serving as an afterloading catheter for high dose rate brachytherapy for prostate cancer. This approach achieves a higher thermal enhancement ratio than in sequential application of radiation and hyperthermia and has the potential to decrease the overall treatment time. METHODS: The new applicator uses the principle of capacitively coupled electrodes. We performed a proof of concept experiment to demostrate the feasibility of the proposed applicator. Moreover, we used electromagnetic and thermal simulations to evaluate the power needs and temperature homogeneity in different tissues. Furthermore we investigated whether dynamic phase and amplitude adaptation can be used to improve longitudinal temperature control. RESULTS: Simulations demonstrate that the electrodes achieve good temperature homogeneity in a homogenous phantom when following current applicator spacing guidelines. Furthermore, we demonstrate that by dynamic phase and amplitude adaptation provides a great advancement for further adaptability of the heating pattern. CONCLUSIONS: This newly designed ThermoBrachy applicator has the potential to revise the interest in interstitial thermobrachytherapy, since the simultaneous application of radiation and hyperthermia enables maximum thermal enhancement and at maximum efficiency for patient and organization.
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Braquiterapia , Hipertermia Induzida , Neoplasias da Próstata , Humanos , Masculino , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , TemperaturaRESUMO
BACKGROUND AND PURPOSE: To investigate the accuracy of dwell position detection with a combined electromagnetic tracking (EMT) brachytherapy (BT) system for treatment verification, by quantifying positional errors due to EM field interference in typical pelvic BT clinical settings. MATERIALS AND METHODS: Dedicated prostate and cervix BT phantoms were imaged with CT. For the cervix phantom, the Utrecht applicator + interstitial catheters were used. The implants were reconstructed and treatment plans were created with 270/65 dwell positions for the prostate/cervix phantom. Next, EMT experiments were performed in clinical BT settings using a prototype of a combined EMT/BT system. We quantified positional errors due to EM field interference from surrounding equipment by comparing planned and EMT-measured dwell positions. The mean residual error between planned and EMT-measured dwell positions was calculated in the prostate interstitial catheters and in the whole cervix implant including the applicator. For the cervix phantom, the analysis was repeated for only the interstitial catheters. RESULTS: Mean residual errors of less than 0.5/0.4 mm in the prostate/cervix catheters were found. For the whole cervix implant including the applicator, large deviations up to 2.4 mm were found. Compared to the interference free set-up, the CT and patient bed environments showed larger residual errors in the interstitial catheters, but residual errors remained <1 mm in all cases. CONCLUSION: Dwell position detection with the combined system in interstitial catheters is sufficiently accurate to perform EMT-based treatment verification. The effect of EM interference from the surrounding equipment was limited.
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Braquiterapia , Catéteres , Fenômenos Eletromagnéticos , Feminino , Humanos , Masculino , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: The aim of this study was to clinically validate a multivariable normal tissue complication probability (NTCP) model for grade 2-4 swallowing dysfunction at 6months after radiotherapy or chemoradiation (SWALM6) in head and neck cancer patients treated with swallowing sparing intensity modulated radiotherapy (SW-IMRT) and to test if SW-IMRT resulted in a reduction of the prevalence of SWALM6. MATERIALS AND METHODS: The primary endpoint was SWALM6. For all 186 patients, a standard IMRT (parotid sparing) and a SW-IMRT plan (additional constraints for swallowing organs at risk) was created. The difference in NTCP for SWALM6 (ΔNTCPSWALM6=NTCPstandard-NTCPSW-IMRT) was calculated. Patients were treated with SW-IMRT. The external validation of the NTCP model was analyzed by comparing performance measures. RESULTS: The mean ΔNTCPSWALM6 was 4.9% (range 0.01-17.3%), with a significant lower mean predicted NTCPSW-IMRT of 22.6% (95% CI 20.2-24.9%), compared to NTCPstandard of 27.5% (95% CI 24.9-29.9%) (p<0.001). There was a perfect correspondence of NTCPSW-IMRT with the observed prevalence of SWALM6 (22.6%). The overall model performance, discrimination and 'goodness of fit' were good. CONCLUSION: We externally validated the multivariable NTCP model for SWALM6 in SW-IMRT treated patients, showing reduced swallowing dysfunction by reducing the dose parameters included in this NTCP model.
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Transtornos de Deglutição/prevenção & controle , Deglutição/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adolescente , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Probabilidade , Estudos Prospectivos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Adulto JovemRESUMO
OBJECTIVES: To identify patterns of long-term, radiation-induced swallowing dysfunction after definitive radiotherapy with or without chemotherapy (RT or CHRT) and to determine which factors may explain these patterns over time. MATERIAL AND METHODS: The study population consisted of 238 consecutive head and neck cancer patients treated with RT or CHRT. The primary endpoint was ⩾grade 2 swallowing dysfunction at 6, 12, 18 and 24months after treatment. Cluster analysis was used to identify different patterns over time. The differences between the mean dose to the swallowing organs at risk for each pattern were determined by using dose maps. RESULTS: The cluster analysis revealed five patterns of swallowing dysfunction: low persistent, intermediate persistent, severe persistent, transient and progressive. Patients with high dose to the upper pharyngeal, laryngeal and lower pharyngeal region had the highest risk of severe persistent swallowing dysfunction. Transient problems mainly occurred after high dose to the laryngeal and lower pharyngeal regions, combined with moderate dose to the upper pharyngeal region. The progressive pattern was mainly seen after moderate dose to the upper pharyngeal region. CONCLUSIONS: Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes.
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Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/terapia , Lesões por Radiação/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Progressão da Doença , Feminino , Humanos , Laringe/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Faringe/efeitos da radiação , Estudos Prospectivos , Radioterapia/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Curative radiotherapy/chemo-radiotherapy for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence 6 months (TUBEM6) after definitive radiotherapy, radiotherapy plus cetuximab or concurrent chemoradiation based on pre-treatment and treatment characteristics. MATERIALS AND METHODS: The study included 355 patients with HNC. TUBEM6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBEM6 as the endpoint. RESULTS: The prevalence of TUBEM6 was 10.7%. The multivariable model with the best performance consisted of the variables: advanced T-stage, moderate to severe weight loss at baseline, accelerated radiotherapy, chemoradiation, radiotherapy plus cetuximab, the mean dose to the superior and inferior pharyngeal constrictor muscle, to the contralateral parotid gland and to the cricopharyngeal muscle. CONCLUSIONS: We developed a multivariable NTCP model for TUBEM6 to identify patients at risk for tube feeding dependence. The dosimetric variables can be used to optimize radiotherapy treatment planning aiming at prevention of tube feeding dependence and to estimate the benefit of new radiation technologies.
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Quimiorradioterapia/efeitos adversos , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/terapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Cetuximab , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Métodos Epidemiológicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Tratamentos com Preservação do Órgão/métodos , Radiometria , Radioterapia de Intensidade Modulada/métodos , Adulto JovemRESUMO
BACKGROUND: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients. PATIENTS AND METHODS: Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (nâ=â427). The model was then validated in a test cohort (nâ=â183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months). RESULTS: Most important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001). CONCLUSION: We established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6.
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Quimiorradioterapia/efeitos adversos , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/terapia , Modelos Estatísticos , Adolescente , Adulto , Idoso , Estudos de Coortes , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Recently, the Quantitative Analysis of Normal Tissue Effect in the Clinic (QUANTEC) Group defined dose-volume constraints for the parotid glands to avoid severe xerostomia. The aim of this study was to determine if application of these QUANTEC criteria also protected against moderate-to-severe patient-rated xerostomia. MATERIAL AND METHODS: The study population consisted of 307 head and neck cancer patients treated with primary (chemo)radiotherapy, either with 3D-CRT (56%) or with IMRT (44%). All patients participated in a standard follow-up program in which radiation-induced toxicity and quality of life were prospectively assessed. Patients who met the QUANTEC criteria were classified as low risk and otherwise as high risk. RESULTS: In total, 41% of the patients (treated with 3D-CRT and IMRT) were classified as low risk patients. In the group treated with 3D-CRT and IMRT, it was possible to meet the QUANTEC criteria in 47% and 32% of the patients, respectively. Sparing the parotid glands with IMRT was considerably more difficult in patients with lymph node metastases and in patients with nasopharyngeal and oropharyngeal tumours. Low risk patients reported significantly less moderate-to-severe xerostomia than high risk patients. However, the predicted risk of elderly patients and patients with pre-existing minor patient-rated xerostomia at baseline was > 20%, even when the QUANTEC criteria were met. CONCLUSIONS: Significantly lower rates of radiation-induced patient-rated xerostomia were found among low risk patients treated according to the QUANTEC criteria, but these criteria do not completely protect against xerostomia. Particularly in elderly patients and patients already suffering from minor xerostomia at baseline, the QUANTEC criteria do not sufficiently protect against persistent, moderate-to-severe patient-rated xerostomia.
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Neoplasias de Cabeça e Pescoço/radioterapia , Glândula Parótida/efeitos da radiação , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Xerostomia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Xerostomia/prevenção & controleRESUMO
PURPOSE: To report on the potential benefits of swallowing-sparing intensity-modulated radiation therapy (SW-IMRT) in the first 100 SW-IMRT treated patients, as well as on the factors that influence the potential benefit of SW-IMRT relative to standard parotid sparing (ST)-IMRT. MATERIAL AND METHODS: One hundred consecutive head and neck cancer patients, scheduled for primary radiotherapy, were included in this prospective cohort study. For each patient, ST-IMRT and SW-IMRT treatment plans were created. All patients were eventually treated with SW-IMRT. Objectives for SW-IMRT were identical to those with ST-IMRT, with additional objectives to spare the swallowing organs at risk (SWOARs). After 20 patients, interim results were evaluated by a multidisciplinary committee. RESULTS: The mean gain of SW-IMRT relative to ST-IMRT in the first 20 patients was less than expected based on our previous planning comparative study. A critical review of all plans revealed that the results with SW-IMRT could be improved by: (1) gaining experience and attempting to reduce SWOAR dose as much as possible; (2) accepting a moderate shift of dose to unspecified tissues; (3) maximizing SWOAR sparing while keeping PTV coverage exactly according to protocol. In the additional 80 patients, the mean dose to the various SWOARs was further reduced significantly compared to ST-IMRT. Dose reductions with SW-IMRT were largest for patients who received neck irradiation, had a tumour located in the larynx, oropharynx, nasopharynx or oral cavity, and had <75% overlap between SWOARs and PTVs. The mean absolute reduction in predicted physician-rated RTOG grade 2-4 swallowing dysfunction for patients numbered 21-100 was 6.1%, ranging from 0.0% to 17.2%. CONCLUSIONS: The benefit of SW-IMRT depends significantly on neck radiotherapy, tumour site and the amount of overlap between SWOARs and PTVs. Optimal clinical introduction requires a detailed evaluation and comparison between the standard (ST-IMRT) and new technique (SW-IMRT) in order to fully exploit the potential benefits.
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Deglutição/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Glândula Parótida/efeitos da radiação , Estudos Prospectivos , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. MATERIAL AND METHODS: Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. RESULTS: All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2-4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5-11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7-21.7%) with 7B-SW-IMPT. CONCLUSION: SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons.
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Carcinoma/radioterapia , Transtornos de Deglutição/prevenção & controle , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Carcinoma/epidemiologia , Carcinoma/patologia , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Relação Dose-Resposta à Radiação , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Carga Tumoral , Adulto JovemRESUMO
PURPOSE: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. METHODS AND MATERIALS: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. RESULTS: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85. CONCLUSIONS: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.
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Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Hipotireoidismo/etiologia , Modelos Estatísticos , Glândula Tireoide/efeitos da radiação , Adolescente , Adulto , Idoso , Análise de Variância , Área Sob a Curva , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tamanho do Órgão , Órgãos em Risco/anatomia & histologia , Órgãos em Risco/efeitos da radiação , Estudos Prospectivos , Doses de Radiação , Glândula Tireoide/anatomia & histologia , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Adulto JovemRESUMO
PURPOSE: The purpose of this multicentre prospective study was to develop multivariable logistic regression models to make valid predictions about the risk of moderate-to-severe patient-rated xerostomia (XER(M6)) and sticky saliva 6 months (STIC(M6)) after primary treatment with intensity modulated radiotherapy (IMRT) with or without chemotherapy for head and neck cancer (HNC). METHODS AND MATERIALS: The study population was composed of 178 consecutive HNC patients treated with IMRT. All patients were included in a standard follow up programme in which acute and late side effects and quality of life were prospectively assessed, prior to, during and after treatment. The primary endpoints were XER(M6) and STIC(M6) as assessed by the EORTC QLQ-H&N35 after completing IMRT. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate-to-severe xerostomia or sticky saliva, respectively, at baseline were excluded. The optimal number of variables for a multivariate logistic regression model was determined using a bootstrapping method. RESULTS: Eventually, 51.6% of the cases suffered from XER(M6). The multivariate analysis showed that the mean contralateral parotid gland dose and baseline xerostomia (none vs. a bit) were the most important predictors for XER(M6). For the multivariate NTCP model, the area under the receiver operating curve (AUC) was 0.68 (95% CI 0.60-0.76) and the discrimination slope was 0.10, respectively. Calibration was good with a calibration slope of 1.0. At 6 months after IMRT, 35.6% of the cases reported STIC(M6). The mean contralateral submandibular gland dose, the mean sublingual dose and the mean dose to the minor salivary glands located in the soft palate were most predictive for STIC(M6). For this model, the AUC was 0.70 (95% CI 0.61-0.78) and the discrimination slope was 0.12. Calibration was good with a calibration slope of 1.0. CONCLUSIONS: The multivariable NTCP models presented in this paper can be used to predict patient-rated xerostomia and sticky saliva. The dose volume parameters included in the models can be used to further optimise IMRT treatment.
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Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Saliva , Xerostomia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Probabilidade , Estudos Prospectivos , Radiometria , Glândulas Salivares/efeitos da radiaçãoRESUMO
PURPOSE: The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). METHODS AND MATERIALS: The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6 months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6 months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. RESULTS: The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. CONCLUSIONS: Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Modelos Biológicos , Radioterapia Conformacional/efeitos adversos , Saliva , Xerostomia/etiologia , Idoso , Feminino , Humanos , Masculino , Probabilidade , Estudos Prospectivos , Radiometria , Análise de RegressãoRESUMO
BACKGROUND AND PURPOSE: The purpose of this large multicentre prospective cohort study was to identify which dose volume histogram parameters and pre-treatment factors are most important to predict physician-rated and patient-rated radiation-induced swallowing dysfunction (RISD) in order to develop predictive models for RISD after curative (chemo) radiotherapy ((CH) RT). MATERIAL AND METHODS: The study population consisted of 354 consecutive head and neck cancer patients treated with (CH) RT. The primary endpoint was grade 2 or more swallowing dysfunction according to the RTOG/EORTC late radiation morbidity scoring criteria at 6 months after (CH) RT. The secondary endpoints were patient-rated swallowing complaints as assessed with the EORTC QLQ-H&N35 questionnaire. To select the most predictive variables a multivariate logistic regression analysis with bootstrapping was used. RESULTS: At 6 months after (CH) RT the bootstrapping procedure revealed that a model based on the mean dose to the superior pharyngeal constrictor muscle (PCM) and mean dose to the supraglottic larynx was most predictive. For the secondary endpoints different predictive models were found: for problems with swallowing liquids the most predictive factors were the mean dose to the supraglottic larynx and radiation technique (3D-CRT versus IMRT). For problems with swallowing soft food the mean dose to the middle PCM, age (18-65 versus >65 years), tumour site (naso/oropharynx versus other sites) and radiation technique (3D-CRT versus IMRT) were the most predictive factors. For problems with swallowing solid food the most predictive factors were the mean dose to the superior PCM, the mean dose to the supraglottic larynx and age (18-65 versus >65 years). And for choking when swallowing the V60 of the oesophageal inlet muscle and the mean dose to the supraglottic larynx were the most predictive factors. CONCLUSIONS: Physician-rated and patient-rated RISD in head and neck cancer patients treated with (CH) RT cannot be predicted with univariate relationships between the dose distribution in a single organ at risk and an endpoint. Separate predictive models are needed for different endpoints and factors other than dose volume histogram parameters are important as well.
Assuntos
Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Previsões , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Laringe/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Músculos Faríngeos/efeitos da radiação , Estudos Prospectivos , Dosagem Radioterapêutica , Análise de RegressãoRESUMO
PURPOSE: The purpose of this study was to investigate the ability of predictive models for patient-rated xerostomia (XER(6M)) and sticky saliva (STIC(6M)) at 6 months after completion of primary (chemo)radiation developed in head and neck cancer patients treated with 3D-conformal radiotherapy (3D-CRT) to predict outcome in patients treated with intensity modulated radiotherapy (IMRT). METHODS AND MATERIALS: Recently, we published the results of a prospective study on predictive models for patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with 3D-CRT (3D-CRT based NTCP models). The 3D-CRT based model for XER(6M) consisted of three factors, including the mean parotid dose, age, and baseline xerostomia (none versus a bit). The 3D-CRT based model for STIC(6M) consisted of the mean submandibular dose, age, the mean sublingual dose, and baseline sticky saliva (none versus a bit). In the current study, a population consisting of 162 patients treated with IMRT was used to test the external validity of these 3D-CRT based models. External validity was described by the explained variation (R(2) Nagelkerke) and the Brier score. The discriminative abilities of the models were calculated using the area under the receiver operating curve (AUC) and calibration (i.e. the agreement between predicted and observed outcome) was assessed with the Hosmer-Lemeshow "goodness-of-fit" test. RESULTS: Overall model performance of the 3D-CRT based predictive models for XER(6M) and STIC(6M) was significantly worse in terms of the Brier score and R(2) Nagelkerke among patients treated with IMRT. Moreover the AUC for both 3D-CRT based models in the IMRT treated patients were markedly lower. The Hosmer-Lemeshow test showed a significant disagreement for both models between predicted risk and observed outcome. CONCLUSION: 3D-CRT based models for patient-rated xerostomia and sticky saliva among head and neck cancer patients treated with primary radiotherapy or chemoradiation turned out to be less valid for patients treated with IMRT. The main message from these findings is that models developed in a population treated with a specific technique cannot be generalised and extrapolated to a population treated with another technique without external validation.
Assuntos
Radioterapia de Intensidade Modulada/efeitos adversos , Saliva , Xerostomia/etiologia , Idoso , Feminino , Previsões , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imageamento Tridimensional , Masculino , Modelos Teóricos , Estudos ProspectivosRESUMO
PURPOSE: To apply recently developed predictive models for swallowing dysfunction to compare the predicted probabilities of swallowing dysfunction for standard intensity modulated radiotherapy (ST-IMRT) and swallowing sparing IMRT (SW-IMRT). MATERIALS AND METHODS: Thirty head and neck cancer patients who previously underwent radiotherapy for the bilateral neck were selected for this study. For each patient, ST-IMRT and SW-IMRT simultaneous integrated boost treatment plans were created. ST-IMRT treatment plan optimisation aimed at obtaining adequate target volume coverage and sparing of the parotid and submandibular glands as much as possible. Objectives for SW-IMRT were similar, with additional objectives to spare the organs at risk related to swallowing dysfunction (SWOARs). Dose-volume data with ST-IMRT and SW-IMRT and normal tissue complication probabilities for physician-rated and patient-rated swallowing dysfunction were calculated with recently developed predictive models. RESULTS: All plans had adequate target volume coverage and dose to critical organs was within accepted limits. Sparing of parotid glands was similar for ST-IMRT and SW-IMRT. With SW-IMRT, the mean dose to the various SWOARs was reduced. Absolute dose values and dose reductions with SW-IMRT differed per patient and per SWOAR and depended on N stage and tumour location. The mean reduction in predicted physician-rated Radiation Therapy Oncology Group (RTOG) grade 2-4 swallowing dysfunction was 9% (range, 3-20%). Mean reductions of the probability of patient-rated moderate to severe complaints with regard to the swallowing of solid food, soft food, liquid food and choking when swallowing were 8%, 2%, 1% and 1%, respectively. CONCLUSIONS: New predictive models for swallowing dysfunction were applied to show potential reductions in physician and patient-rated swallowing dysfunction with IMRT that was specifically optimised to spare SWOARs.
Assuntos
Transtornos de Deglutição/prevenção & controle , Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem RadioterapêuticaRESUMO
BACKGROUND AND PURPOSE: Radiotherapy, alone or combined with chemotherapy, is a treatment modality used frequently in head and neck cancer. In order to report, compare and interpret the sequelae of radiation treatment adequately, it is important to delineate organs at risk (OARs) according to well-defined and uniform guidelines. The aim of this paper was to present our institutional Computed Tomography (CT)-based delineation guidelines for organs in the head and neck at risk for radiation-induced swallowing dysfunction (SWOARs). MATERIAL AND METHODS: After analyses of the human anatomy of the head and neck area and literature review, CT-based guidelines for delineation of the most relevant SWOARs were described by a panel of experts. RESULTS AND CONCLUSIONS: This paper described institutional guidelines for the delineation of potential SWOARs, accompanied by CT-based illustrations presenting examples of the delineated structures and their corresponding anatomic borders. This paper is essential to ensure adequate interpretation of future reports on the relationship between dose distribution in these SWOARs and different aspects of post-treatment swallowing dysfunction.