RESUMO
INTRODUCTION: Treatment planning using a five-millimetre geometrical margin from GTV to high-dose CTV (CTV1) has been used in DAHANCA treatment centres since 2013. We aimed to evaluate changes in CTV1 volumes, local control (LC), and recurrence pattern after the implementation of five-millimetre geometrical margins nationally. MATERIALS AND METHODS: 1,948 patients with pharyngeal, and laryngeal squamous cell carcinomas completed definitive IMRT-based treatment in 2010-2012 and 2013-2015 in three centres. The patient-specific margin was calculated as median surface distance from primary tumour GTV (GTV-T) to CTV1. Radiologically verified local recurrences were analysed using a centre of mass (COM) of the delineated recurrence volume, measuring the shortest distance between COM to GTV-T and CTV1 boundaries. RESULTS: Median GTV-CTV1 was 0.9 (0.0-0.97) and 0.47 cm (0.4-0.5) for 2010-2012 and 2013-2015, respectively. Median CTV1 changed in three centres from 76, 28, 42 cm3 to 61, 53, 62 cm3 for 2010-2012 and 2013-2015, respectively. Local failures occurred at 247 patients during first three years after radiotherapy. The 3-year LC rate for 2010-2012 and 2013-2015 was 0.84 and 0.87 (p = 0.06). Out of 146 radiology-verified analysable local recurrences, 102 (69.9%) were inside the CTV1. In 74.6% and 91% of cases, the LRs were covered by 95% isodose in 2010-2012 and 2013-2015, respectively. CONCLUSION: DAHANCA radiotherapy guidelines based on a geometrically generated isotropic CTV1 margin led to less variation in treatment volumes and between centres than previous guidelines. The transition towards consensus GTV-CTV1 margins did not influence local tumour control. The majority of local recurrences were inside CTV1 and covered by the prescription dose.
Assuntos
Neoplasias Laríngeas , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Masculino , Feminino , Recidiva Local de Neoplasia/radioterapia , Pessoa de Meia-Idade , Idoso , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Guias de Prática Clínica como Assunto , Neoplasias Faríngeas/radioterapia , Neoplasias Faríngeas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Idoso de 80 Anos ou mais , AdultoAssuntos
Carcinoma de Células Escamosas , Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias Faríngeas , Radioterapia (Especialidade) , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Transtornos de Deglutição/etiologia , Neoplasias Faríngeas/radioterapia , Carcinoma de Células Escamosas/etiologia , Dosagem RadioterapêuticaAssuntos
Carcinoma de Células Escamosas , Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias Faríngeas , Radioterapia (Especialidade) , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Transtornos de Deglutição/etiologia , Neoplasias Faríngeas/radioterapia , Carcinoma de Células Escamosas/etiologia , Dosagem RadioterapêuticaAssuntos
Carcinoma de Células Escamosas , Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias Faríngeas , Radioterapia (Especialidade) , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Transtornos de Deglutição/etiologia , Neoplasias Faríngeas/radioterapia , Carcinoma de Células Escamosas/radioterapia , Dosagem RadioterapêuticaRESUMO
BACKGROUND: The relative biological effectiveness (RBE) of proton is considered to be dependent on biological parameters and fractional dose. While hyperfractionated photon therapy was effective in the treatment of patients with head and neck cancers, its effect in intensity-modulated proton therapy (IMPT) under the variable RBE has not been investigated in detail. PURPOSE: To study the effect of variable RBE on hyperfractionated IMPT for the treatment of pharyngeal cancer. We investigated the biologically effective dose (BED) to determine the theoretical effective hyperfractionated schedule. METHODS: The treatment plans of three pharyngeal cancer patients were used to define the ΔBED for the clinical target volume (CTV) and soft tissue (acute and late reaction) as the difference between the BED for the altered schedule with variable RBE and conventional schedule with constant RBE. The ΔBED with several combinations of parameters (treatment days, number of fractions, and prescribed dose) was comprehensively calculated. Of the candidate schedules, the one that commonly gave a higher ΔBED for CTV was selected as the resultant schedule. The BED volume histogram was used to compare the influence of variable RBE and fractionation. RESULTS: In the conventional schedule, compared with the constant RBE, the variable RBE resulted in a mean 2.6 and 2.7 Gy reduction of BEDmean for the CTV and soft tissue (acute reaction) of the three plans, respectively. Moreover, the BEDmean for soft tissue (late reaction) increased by 7.4 Gy, indicating a potential risk of increased RBE. Comprehensive calculation of the ΔBED resulted in the hyperfractionated schedule of 80.52 Gy (RBE = 1.1)/66 fractions in 6.5 weeks. When variable RBE was used, compared with the conventional schedule, the hyperfractionated schedule increased the BEDmean for CTV by 7.6 Gy; however, this was associated with a 7.8 Gy increase for soft tissue (acute reaction). The BEDmean for soft tissue (late reaction) decreased by 2.4 Gy. CONCLUSION: The results indicated a potential effect of the variable RBE on IMPT for pharyngeal cancer but with the possibility that hyperfractionation could outweigh this effect. Although biological uncertainties require conservative use of the resultant schedule, hyperfractionation is expected to be an effective strategy in IMPT for pharyngeal cancer.
Assuntos
Neoplasias Faríngeas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Terapia com Prótons/métodos , Órgãos em Risco , Fracionamento da Dose de Radiação , Prótons , Neoplasias Faríngeas/radioterapia , Neoplasias Faríngeas/etiologia , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Eficiência Biológica Relativa , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is an ideal treatment for advanced head and neck squamous cell carcinoma (HNSCC). The performance of CCRT induces severe toxicities in HNSCC patients and decreases the quality of life (QOL). Maitake D-Fraction is proteoglycan which has anti-tumor function associated with its immunomodulatory capacity. The polysaccharides of Maitake also have anti-radiation effect in radiation therapy during cancer treatment. This research aimed to illustrate Maitake D-Fraction effects on CCRT-associated adverse events and QOL. METHODS: During CCRT, Maitake capsules were taken orally 3 times a day, each time 4 capsules, one hour before meals. QOL were analyzed by EORTC QLQ-C30-Chinese version and EORTC QLQ-HandN-35-Chinese version. 141 patients were recruited and divided into an intervention group and a placebo group. RESULTS: Frequencies of severe CCRT-associated adverse events in intervention group were less than in placebo group. Global QOL score in intervention group was higher than in placebo group 5 weeks post treatment. The proportion of patients returning to baseline global QOL score at 6-month was increased by Maitake D-Fraction administration. CONCLUSION: In conclusion, this randomized clinical trial demonstrated that in advanced laryngeal and pharyngeal cancer patients, the oral administration of Maitake D-Fraction alleviated CCRT-related adverse events and deterioration in QOL.
Assuntos
Quimiorradioterapia , Grifola , Neoplasias de Cabeça e Pescoço , Neoplasias Faríngeas , Proteoglicanas , Quimiorradioterapia/efeitos adversos , Grifola/química , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Polissacarídeos , Proteoglicanas/uso terapêutico , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapiaRESUMO
The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5-117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.
Assuntos
Neoplasias Faríngeas/radioterapia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/mortalidade , Neoplasias Faríngeas/psicologia , Prognóstico , Estudos Retrospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Adulto JovemRESUMO
RATIONALE: Synovial sarcoma is a rare malignant tumor that typically originates from the soft tissue of the extremities. The occurrence of primary pharyngeal synovial sarcoma is even rarer, and few studies have reported its radiological features. Here, we report a case of pediatric primary pharyngeal synovial sarcoma and describe the conventional and advanced magnetic resonance imaging (MRI) findings with pathologic correlation. PATIENT CONCERNS: An 11-year-old girl presented to the otolaryngologic clinic with dysphagia. DIAGNOSIS: Laryngoscopy revealed a large mass in the oropharynx. MRI revealed a well-defined soft tissue mass with a maximal diameter of approximately 5âcm originating from the submucosal space of the oropharynx. The mass was primarily solid and showed homogeneous contrast-enhancement. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass showed a homogeneously low apparent diffusion coefficient value on diffusion-weighted imaging, which indicated high tumor cellularity. Dynamic contrast-enhanced MRI revealed a hypovascular tumor with low values of the volume transfer constant between the extracellular extravascular space and blood plasma and blood plasma volume per unit tissue volume. Amide proton transfer-weighted MRI revealed a relatively high amide proton transfer signal in the tumor, indicating a high protein/peptide component. The patient underwent partial surgical resection of the tumor, and the diagnosis of biphasic synovial sarcoma was confirmed on postoperative pathological examination. INTERVENTION: The patient was started on chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide. OUTCOMES: The tumor did not respond to the 3 cycles of the chemotherapy. Thus, the patient underwent second surgery and subsequent radiation therapy. The patient is now under ifosfamide/carboplatin/etoposide chemotherapy. LESSON: Synovial sarcoma should be considered in the differential diagnosis of pediatric oropharyngeal submucosal tumors. Multimodal MRI may aid diagnosis, although the final diagnosis should be based on the postoperative pathological examination findings.
Assuntos
Neoplasias Faríngeas , Sarcoma Sinovial , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Transtornos de Deglutição/etiologia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Neoplasias Faríngeas/diagnóstico por imagem , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Neoplasias Faríngeas/cirurgia , Reoperação , Sarcoma Sinovial/diagnóstico por imagem , Sarcoma Sinovial/tratamento farmacológico , Sarcoma Sinovial/radioterapia , Sarcoma Sinovial/cirurgia , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND: Hypothyroidism is a common adverse event after radiotherapy for head and neck tumors and the incidence need to be re-evaluated because of using intensity-modulated radiotherapy (IMRT). AIMS/OBJECTIVES: Confirm the dose-volume effect of IMRT for pharyngeal cancer on hypothyroidism. MATERIALS AND METHODS: This was a retrospective analysis of patients underwent IMRT for pharyngeal cancer from June 2011 to May 2018. Patients were classified into group A (thyroid stimulating hormone (TSH) <5µU/ml), group B (5< =TSH < 10), and group C (10< =TSH) based on TSH over 36 months post-radiation. Radiation dose, thyroid volume, and the proportion of the thyroid that received X Gy or greater (Vx) were measured. RESULTS: Fifty-two patients were included in this work. Hypothyroidism developed in 33/52 (63%) patients, 13 in group B and 20 in group C. The mean radiation dose to the thyroid was 49.4 Gy and the median time until hypothyroidism was 39 months after irradiation. Hypothyroidism was significantly related to neck dissection (ND) and radiation dose to the thyroid. Patients whose thyroid received 45 Gy or more (V45) >67% had a significantly higher incidence of hypothyroidism. CONCLUSIONS AND SIGNIFICANCE: Patients with pharyngeal cancer who had ND and V45 to the thyroid >67% are at risk of hypothyroidism.
Assuntos
Hipotireoidismo/etiologia , Neoplasias Faríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Glândula Tireoide/efeitos da radiação , Idoso , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Neoplasias Faríngeas/cirurgia , Lesões por Radiação , Dosagem Radioterapêutica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
PURPOSE: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. MATERIAL AND METHODS: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. RESULTS: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. CONCLUSION: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.
Assuntos
Benchmarking , Neoplasias de Cabeça e Pescoço/radioterapia , Radiocirurgia/normas , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , França , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica/radioterapia , Órgãos em Risco , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/radioterapia , Garantia da Qualidade dos Cuidados de Saúde , Radiometria , Radiocirurgia/instrumentação , Radiocirurgia/métodos , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundárioRESUMO
Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.
Assuntos
Neoplasias Faríngeas/radioterapia , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Faríngeas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Raios X , Adulto JovemRESUMO
PURPOSE: To externally validate the previously published pre-treatment prediction models for lymph nodes failure after definitive radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: This external validation cohort consisted of 143 node positive HNSCC patients treated between July 2007 and June 2016 by curative radiotherapy with or without either cisplatin or cetuximab. Imaging and pathology reports during follow-up were analyzed to indicate persisting or recurring nodes. The previously established clinical, radiomic and combined models were validated on this cohort by assessing the concordance index (c-index) and model calibration. RESULTS: Overall 113 patients with 374 pLNs were suitable for final analysis. There were 20 (5.3%) nodal failures from 15 patients after a median follow-up of 36.1 months. Baseline characteristics and radiomic features were comparable to the training cohort. Both the radiomic model (Least-axis-length of lymph node (LALLN) and correlation of gray level co-occurrence matrix (Corre-GLCM)) and the combined model (T stage, gender, WHO performance score, LALLN and Corre-GLCM) showed good agreement between predicted and observed nodal control probabilities. The radiomic (c-index: 0.71; 95% confidence interval (CI): 0.59-0.84) and combined (c-index: 0.71; 95% CI: 0.59-0.82) models performed better than the clinical model (c-index: 0.57; 95% CI: 0.47-0.68) on this cohort, with a significant difference between the combined and clinical models (z-score test: p = 0.005). CONCLUSION: The combined model including clinical and radiomic features was externally validated and proved useful to predict nodal failures and could be helpful to guide treatment choices before and after curative radiation treatment for node positive HNSCC patients.
Assuntos
Linfonodos/patologia , Linfonodos/efeitos da radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Faríngeas/diagnóstico por imagem , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/radioterapia , Radiossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Falha de TratamentoRESUMO
OBJECTIVE: To explore the relationships between swallowing functional outcomes and nutritional status in patients with head and neck cancer undergoing radiotherapy (RT). METHODS: This longitudinal study included 122 patients. Data were collected at three time points: baseline (T1), the third week of RT (T2) and the completion of RT (T3). The Common Terminology Criteria for Adverse Events was used to assess the symptom of dysphagia and other toxicities; the MD Anderson Dysphagia Inventory (MDADI) was used to assess the patient-perceived swallowing functional outcomes; the nutritional status was evaluated by the weight ratio and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalised estimating equation (GEE) was used to measure the correlation of MDADI with the weight ratio or PG-SGA and also to analyse the influential factors of swallowing functional outcomes. RESULTS: The participants' acute dysphagia rates were 5.7% at T1, 69.7% at T2 and 77.9% at T3. The swallowing functional outcomes worsen over RT (p<0.001) and were associated with weight ratio (ß=0.032, p=0.008) and PG-SGA (ß=-0.115, p<0.001). GEE models showed that patients with cancer of the pharynx region, advanced stage, chemoradiotherapy and high RT dose perceived worse swallowing functional outcomes. Oral mucositis, pharynx mucositis and salivary gland inflammation were positively correlated with swallowing functional outcomes, and the pharynx mucositis presented the highest absolute value of ß. CONCLUSION: The swallowing functional outcomes were negatively correlated with nutritional status. Healthcare professionals should identify early on the population at higher risk and focus on multiple toxicities, especially the management of pharynx mucositis, to improve nutritional status.
Assuntos
Deglutição , Neoplasias de Cabeça e Pescoço/radioterapia , Estado Nutricional , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Transtornos de Deglutição/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Mucosite/fisiopatologia , Neoplasias Faríngeas/complicações , Neoplasias Faríngeas/fisiopatologia , Neoplasias Faríngeas/radioterapia , Estudos Prospectivos , Doses de Radiação , Resultado do Tratamento , Adulto JovemRESUMO
The present study aimed to evaluate whether knowledge-based plans (KBP) from a single optimization could be used clinically, and to compare dose-volume histogram (DVH) parameters and plan quality between KBP with (KBPCONST) and without (KBPORIG) manual objective constraints and clinical manual optimized (CMO) plans for pharyngeal cancer. KBPs were produced from a system trained on clinical plans from 55 patients with pharyngeal cancer who had undergone intensity-modulated radiation therapy or volumetric-modulated arc therapy (VMAT). For another 15 patients, DVH parameters of KBPCONST and KBPORIG from a single optimization were compared with CMO plans with respect to the planning target volume (D98%, D50%, D2%), brainstem maximum dose (Dmax), spinal cord Dmax, parotid gland median and mean dose (Dmed and Dmean), monitor units and modulation complexity score for VMAT. The Dmax of spinal cord and brainstem and the Dmed and Dmean of ipsilateral parotid glands were unacceptably high for KBPORIG, although the KBPCONST DVH parameters met our goal for most patients. KBPCONST and CMO plans produced comparable DVH parameters. The monitor units of KBPCONST were significantly lower than those of the CMO plans (P < 0.001). Dose distribution of the KBPCONST was better than or comparable to that of the CMO plans for 13 (87%) of the 15 patients. In conclusion, KBPORIG was found to be clinically unacceptable, while KBPCONST from a single optimization was comparable or superior to CMO plans for most patients with head and neck cancer.
Assuntos
Neoplasias Faríngeas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Órgãos em Risco , Glândula Parótida/efeitos da radiação , FótonsAssuntos
Veias Braquiocefálicas/diagnóstico por imagem , Hemorragia/etiologia , Toracentese/efeitos adversos , Parede Torácica/irrigação sanguínea , Idoso de 80 Anos ou mais , Constrição Patológica , Humanos , Masculino , Neoplasias Faríngeas/radioterapia , Radioterapia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients' compliance with the CCRT course. METHODS: In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m2 cisplatin every 2 weeks with daily tegafur-uracil (300 mg/m2) and leucovorin (60 mg/day). RESULTS: The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups. CONCLUSION: This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2's application in clinical settings.
Assuntos
Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Polissacarídeos/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astrágalo , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
BACKGROUND: Treatment options for recurrent head and neck tumours in the previously irradiated area are limited, including re-irradiation due to radioresistance of the recurrent tumour and previous dose received by surrounding normal tissues. As an in vitro model to study radioresistance mechanisms, isogenic cells with different radiosensitivity can be used. However, they are not readily available. Therefore, our objective was to establish and characterize radioresistant isogenic human pharyngeal squamous carcinoma cells and to evaluate early radiation response in isogenic parental, radioresistant and radiosensitive cells. METHODS: Radioresistant cells were derived from parental FaDu cells by repeated exposure to ionizing radiation. Radiosensitivity of the established isogenic radioresistant FaDu-RR cells was evaluated by clonogenic assay and compared to isogenic parental FaDu and radiosensitive 2A3 cells. Additional phenotypic characterization of these isogenic cells with different radiosensitivity included evaluation of chemosensitivity, cell proliferation, cell cycle, radiation-induced apoptosis, resolution of DNA double-strand breaks, and DNA damage and repair signalling gene expression before and after irradiation. RESULTS: In the newly established radioresistant cells in response to 5 Gy irradiation, we observed no alteration in cell cycle regulation, but delayed induction and enhanced resolution of DNA double-strand breaks, lower induction of apoptosis, and pronounced over-expression of DNA damage signalling genes in comparison to parental cells. On the other hand, radiosensitive 2A3 cells were arrested in G2/M-phase in response to 5 Gy irradiation, had a prominent accumulation of and slower resolution of DNA double-strand breaks, and no change in DNA damage signalling genes expression. CONCLUSIONS: We concluded that the emergence of the radioresistance in the established radioresistant isogenic cells can be at least partially attributed to the enhanced DNA double-strand break repair, altered expression of DNA damage signalling and repair genes. On the other hand, in radiosensitive isogenic cells the reduced ability to repair a high number of induced DNA double-strand breaks and no transcriptional response in DNA damage signalling genes indicate on a lack of adaptive response to irradiation. Altogether, our results confirmed that these isogenic cells with different radiosensitivity are an appropriate model to study the mechanisms of radioresistance.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Faríngeas/radioterapia , Tolerância a Radiação , Radiação Ionizante , Apoptose , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Histonas/metabolismo , Humanos , Concentração Inibidora 50 , Recidiva Local de Neoplasia , Neoplasias Faríngeas/metabolismo , FenótipoRESUMO
The selection of target volumes for head and neck cancer radiation therapy, particularly prophylactic volumes that reflect infra-clinic spreads, is a complex process. It is based on the knowledge of the natural history of these tumors and must take into consideration the special challenges due to the diversity and complexity of head and neck anatomy. The dosimetric and ballistic precision provided by modern radiation techniques has required strong strategic deliberation to ensure the relevance and reproducibility of target volumes. Specifically, regarding cervical lymph node volumes, two issues emerged. What lymph node area to select depending on the location and the staging of the primary tumor? How to convey that choice in the process of treatment planning and delivery? This debate has been progressively enriched over time resulting in the publication of several international guidelines to standardize the terminology of head and neck lymph node areas and to lay solid science-based foundations to drive practices. This abundance of information makes these guidelines complex, but their accurate understanding is required for adequate usage. We provide an overview of the main published recommendations for the selection of lymph node target volumes when treating oral cavity and pharyngo-laryngeal squamous cell carcinoma with radiation therapy.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Linfonodos/efeitos da radiação , Irradiação Linfática/métodos , Neoplasias Bucais/radioterapia , Neoplasias Faríngeas/radioterapia , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Laríngeas/patologia , Linfonodos/patologia , Neoplasias Bucais/patologia , Pescoço , Neoplasias Faríngeas/patologia , Dosagem RadioterapêuticaRESUMO
PURPOSE: Xerostomia commonly occurs in patients who undergo head and neck radiation therapy and can seriously affect patients' quality of life. In this study, we developed a xerostomia prediction model with radiation treatment data using a 3-dimensional (3D) residual convolutional neural network (rCNN). The model can be used to guide radiation therapy to reduce toxicity. METHODS AND MATERIALS: A total of 784 patients with head and neck squamous cell carcinoma enrolled in the Radiation Therapy Oncology Group 0522 clinical trial were included in this study. Late xerostomia is defined as xerostomia of grade ≥2 occurring in the 12th month of radiation therapy. The computed tomography (CT) planning images, 3D dose distributions, and contours of the parotid and submandibular glands were included as 3D rCNN inputs. Comparative experiments were performed for the 3D rCNN model without 1 of the 3 inputs and for the logistic regression model. Accuracy, sensitivity, specificity, F-score, and area under the receiver operator characteristic curve were evaluated. RESULTS: The proposed model achieved promising prediction results. The performance metrics for 3D rCNN model with contour, CT images, and radiation therapy dose; 3D rCNN without contour; 3D rCNN without CT images; 3D rCNN without the dose; logistic regression with the dose and clinical parameters; and logistic regression without clinical parameters were as follows: accuracy: 0.76, 0.74, 0.73, 0.65, 0.64, and 0.56; sensitivity: 0.76, 0.72, 0.77, 0.59, 0.72, and 0.75; specificity: 0.76, 0.76, 0.71, 0.69, 0.59, and 0.43; F-score: 0.70, 0.68, 0.69, 0.56, 0.60, and 0.57; and area under the receiver operator characteristic curve: 0.84, 0.82, 0.78, 0.70, 0.74, and 0.68, respectively. CONCLUSIONS: The proposed model uses 3D rCNN filters to extract low- and high-level spatial features and to achieve promising performance. This is a potentially effective model for predicting objective toxicity for supporting clinical decision making.
Assuntos
Aprendizado Profundo , Neoplasias Laríngeas/radioterapia , Neoplasias Faríngeas/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Xerostomia/etiologia , Área Sob a Curva , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagem , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/diagnóstico por imagem , Modelos Logísticos , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/radioterapia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Neoplasias Faríngeas/diagnóstico por imagem , Curva ROC , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional , Radioterapia Guiada por Imagem , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Glândula Submandibular/diagnóstico por imagem , Glândula Submandibular/efeitos da radiação , Tomografia Computadorizada por Raios X , Xerostomia/prevenção & controleRESUMO
RATIONALE: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that causes venous infarction and intracerebral hemorrhage (ICH) with occlusion of cerebral veins, and its incidence is estimated to be 5 per 1 million people per year, accounting for 0.5% to 1.0% of all strokes. Despite advances in the recognition of CVT, the diagnosis and treatment may be difficult because of the diversity of underlying risk factors. A rare case of ICH due to CVT during surgery is described. PATIENT CONCERNS: A 69-year-old-man presented to our department with a history of paralyzed extremities after a backward fall and head trauma. The patient had a history of pharyngeal cancer treated with neck dissection and radiotherapy. Computed tomography (CT) images showed continuous ossification of the posterior longitudinal ligament (OPLL) at C2-5 levels and a fracture line at the caudal end plate of the C5 body. The diagnosis was traumatic cervical cord injury, so that posterior cervical decompression and fusion was performed. Immediately after surgery, the patient developed an epileptic seizure and the disturbance of consciousness persisted. MR venography and contrast CT images showed absence of flow from the superior sagittal sinus to the transverse sinus. DIAGNOSES: The diagnosis in this case was ICH due to CVT. INTERVENTIONS: The patient was treated with anticoagulation using unfractionated heparin. OUTCOMES: The patient ultimately made a complete recovery from CVT. LESSONS: Although risk factors for CVT are diverse, head and neck injury, patient's position during surgery, and postoperative radical neck dissection for pharyngeal cancer might have been the factors in this case. While the measures to prevent this disease are uncertain, early diagnosis and treatment are needed to avoid serious complications.