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2.
Radiother Oncol ; 148: 140-142, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32361663

RESUMO

Advances in diagnostic imaging create opportunities for improved therapeutic targeting of cancer but conceptual thinking about radiotherapy target volume definition and dose-prescription is not keeping up. In this opinion paper we discuss how modern imaging can contribute to new concepts for radiotherapy dose-prescription and target volume definition illustrated by the example of head and neck cancer. These new insights have the potential to significantly reduce radiation associated toxicity and may have important impact on the combination of radiotherapy with systemic cancer therapies.

3.
Radiother Oncol ; 149: 181-188, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32417345

RESUMO

BACKGROUND: No randomized controlled trials (RCT) have yet identified the optimal palliative radiotherapy scheme in patients with incurable head and neck squamous cell carcinoma (HNSCC). We conducted RCT to compare two radiation schemes in terms of efficacy, toxicity and quality-of-life (QoL). MATERIALS AND METHODS: Patients with locally-advanced HNSCC who were ineligible for radical treatment and those with limited metastatic disease were randomly assigned in 1:1 ratio to arm 1 (36 Gy in 6 fractions, twice a week) or arm 2 (50 Gy in 16 fractions, four times a week). RESULTS: The trial was discontinued early because of slow accrual (34 patients enrolled). Objective response rates were 38.9% and 57.1% for arm 1 and 2 respectively (p = 0.476). The median time to loco-regional progression was not reached. The loco-regional control rates at 1 year was 57.4% and 69.3% in arm 1 and 2 (p = 0.450, HR = 0.56, 95%CI 0.12-2.58). One-year overall survival was 33.3% and 57.1%, with medians of 35.4 and 59.5 weeks, respectively (p = 0.215, HR = 0.55, 95%CI 0.21-1.43). Acute grade ≥3 toxicity was lower in arm 1 (16.7% versus 57.1%, p = 0.027), with the largest difference in grade 3 mucositis (5.6% versus 42.9%, p = 0.027). However, no significant deterioration in any of the patient-reported QoL-scales was found. CONCLUSION: No solid conclusion could be made on this incomplete study which is closed early. Long-course radiotherapy did not show significantly better oncologic outcomes, but was associated with more acute grade 3 mucositis. No meaningful differences in QoL-scores were found. Therefore, the shorter schedule might be carefully advocated. However, this recommendation should be interpreted with great caution because of the inadequate statistical power.

4.
Eur Arch Otorhinolaryngol ; 277(6): 1753-1761, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32100130

RESUMO

PURPOSE: Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral centers, the post-surgical radiation target volume changed from the bilateral neck including the pharyngeal axis to the unilateral neck only, in the course of the last decade. This study aims to investigate the outcome of patients with CUP before and after de-escalation of post-surgical radiotherapy. METHODS: Data of two Dutch tertiary referral centers were merged. Disease-free survival (DFS), overall survival (OS), and regional control rate (RCR) of 80 patients diagnosed with CUP (squamous cell and undifferentiated carcinomas) between 1990 and 2009 were retrospectively analyzed. RESULTS: Thirty patients received bilateral neck and pharyngeal axis radiotherapy and 42 patients ipsilateral radiotherapy only. In another eight patients, the postsurgical radiation target volume was expanded to the contralateral neck or to the pharyngeal axis, due to suspicious lesions on imaging. The 5-year DFS, OS and RCR were 60%, 51.2%, and 80%, respectively, in the total patient population. RCR did not differ in patients treated with ipsilateral as compared to bilateral radiotherapy nor did 5-year OS and DFS. No tumors occurred in the pharyngeal axis. CONCLUSION: In this study, omitting elective treatment of the contralateral neck and pharyngeal axis did not lead to a decrease in locoregional control or survival rates when treating patients with CUP.

5.
Otolaryngol Head Neck Surg ; 162(4): 446-457, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32093572

RESUMO

OBJECTIVE: An increased interval between symptomatic disease and treatment may negatively influence oncologic and/or functional outcomes in head and neck cancer (HNC). This systematic review aims to provide insight into the effects of time to treatment intervals on oncologic and functional outcomes in oral cavity, pharyngeal, and laryngeal cancer. DATA SOURCES: PubMed, EMBASE, and Cochrane library were searched. REVIEW METHODS: All studies on delay or time to diagnosis or treatment in oral, pharyngeal, and laryngeal cancer were included. Quality assessment was performed with an adjusted version of the Newcastle-Ottawa scale. Outcomes of interest were tumor volume, stage, recurrence, survival, patient-reported outcome measures (PROMs), toxicity, and functionality after treatment. RESULTS: A total of 51 studies were included. Current literature on the influence of delay in HNC is inconsistent but indicates higher stage and worse survival with longer delay. The effects on PROMs, toxicity, and functional outcome after treatment have not been investigated. The inconsistencies in outcomes were most likely caused by factors such as heterogeneity in study design, differences in the definitions of delay, bias of results, and incomplete adjustment for confounding factors in the included studies. CONCLUSION: Irrespective of the level of evidence, the unfavorable effects of delay on oncologic, functional, and psychosocial outcomes are undisputed. Timely treatment while maintaining high-quality diagnostic procedures and decision making reflects good clinical practice in our opinion. This review will pose practical and logistic challenges that will have to be overcome.


Assuntos
Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/terapia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapia , Neoplasias Faríngeas/diagnóstico , Neoplasias Faríngeas/terapia , Tempo para o Tratamento , Humanos , Resultado do Tratamento
6.
Radiother Oncol ; 142: 107-114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439447

RESUMO

BACKGROUND AND PURPOSE: Multimodality imaging including 18F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV). MATERIALS AND METHODS: Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed. FDG-PET/CT-based NTV was performed in 46% of the patients. The median follow-up was 31 months. Diagnostic imaging depicting the regional recurrence was co-registered with the initial CT-scan to reconstruct the exact site of the recurrence. Multivariate Cox regression analysis was performed to identify variables associated with radiotherapy outcome. RESULTS: FDG-PET/CT-based NTV improved control of disease in the CTVelective-nodal (HR: 0.33, p = 0.026), overall regional control (HR: 0.62, p = 0.027) and overall survival (HR: 0.71, p = 0.033) compared to CT-based NTV. The risk for recurrence in the CTVelective-nodal was increased in case of synchronous local recurrence of the primary tumor (HR: 12.4, p < 0.001). CONCLUSION: FDG-PET/CT-based NTV significantly improved control of disease in the CTVelective-nodal, overall regional control and overall survival compared to CT-based NTV. A significant proportion of CTVelective-nodal recurrences are potentially new nodal manifestations from a synchronous local recurrent primary tumor. These results support the concept of target volume transformation and give an indication of the potential of FDG-PET to guide gradual radiotherapy dose de-escalation in elective neck treatment in HNSCC.

7.
Radiother Oncol ; 144: 114-120, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31805515

RESUMO

BACKGROUND AND PURPOSE: The role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT. MATERIALS AND METHODS: Data from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis. RESULTS: Of 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45-68.4 Gy) in 1.6-2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors. CONCLUSION: Addition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.

8.
Thorac Cancer ; 10(12): 2289-2299, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31668020

RESUMO

BACKGROUND: Both hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism-related markers were examined in stage I - resectable stage IIIA non-small cell lung cancer (NSCLC). Furthermore, expression of metabolism-related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism. METHODS: Mutation analysis was performed for 97 tumors. Glucose and glutamine metabolism-related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81). RESULTS: Glutamine metabolism-related markers were significantly higher in adeno- than squamous cell NSCLCs. Glucose transporter 1 (GLUT1) protein expression was higher in solid compared to lepidic adenocarcinomas (P < 0.01). In adenocarcinomas, mRNA expression of glutamine transporter SLC1A5 correlated with tumor size (r(p) = 0.41, P = 0.005). Furthermore, SLC1A5 protein expression was significantly higher in adenocarcinomas with worse pTNM stage (r(s) = 0.39, P = 0.009). EGFR-mutated tumors showed lower GLUT1 protein (P = 0.017), higher glutaminase 2 (GLS2) protein (P = 0.025) and higher GLS2 mRNA expression (P = 0.004), compared to EGFR wild-type tumors. GLS mRNA expression was higher in KRAS-mutated tumors (P = 0.019). TP53-mutated tumors showed higher GLUT1 expression (P = 0.009). CONCLUSIONS: NSCLC is a heterogeneous disease, with differences in mutational status and metabolism-related marker expression between adeno- and squamous cell NSCLCs, and also within adenocarcinoma subtypes. GLUT1 and SLC1A5 expression correlate with aggressive tumor behavior in adenocarcinomas but not in squamous cell NSCLCs. Therefore, these markers could steer treatment modification for subgroups of adenocarcinoma patients. TP53, EGFR and KRAS mutations are associated with expression of glucose and glutamine metabolism-related markers in NSCLC.

9.
Cancer Med ; 8(12): 5810-5819, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400079

RESUMO

INTRODUCTION: Routine follow-up after curative treatment of patients with oral squamous cell carcinoma (OSCC) is common practice considering the high risk of second primaries and recurrences (ie second events). Current guidelines advocate a follow-up period of at least 5 years. The recommendations are not evidence-based and benefits are unclear. This is even more so for follow-up after a second event. To facilitate the development of an evidence- and personalized follow-up program for OSCC, we investigated the course of time until the second and subsequent events and studied the risk factors related to these events. MATERIALS AND METHODS: We retrospectively studied 594 OSCC patients treated with curative intent at the Head and Neck Cancer Unit of the Radboud University Medical Centre from 2000 to 2012. Risk of recurrence was calculated addressing death from intercurrent diseases as competing event. RESULTS: The 1-, 5- and 10-year cumulative risks of a second event were 17% (95% CI:14%;20%), 30% (95% CI:26%;33%), and 37% (95% CI:32%;41%). Almost all locoregional recurrences occurred in the first 2 years after treatment. The incidence of second primary tumors was relatively stable over the years. The time pattern of presentation of third events was similar. DISCUSSION: Our findings support a follow-up time of 2 years after curative treatment for OSCC. Based on the risk of recurrence there is no indication for a different follow-up protocol after first and second events. After 2 years, follow-up should be tailored to the individual needs of patients for supportive care, and monitoring of late side-effects of treatment.

10.
Int J Radiat Oncol Biol Phys ; 105(3): 514-524, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306734

RESUMO

PURPOSE: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. METHODS AND MATERIALS: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. RESULTS: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. CONCLUSIONS: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.


Assuntos
Benchmarking/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/normas , Benchmarking/normas , Pesquisas sobre Serviços de Saúde , Humanos , Países Baixos , Tratamentos com Preservação do Órgão/normas , Órgãos em Risco/diagnóstico por imagem , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Músculos Faríngeos/diagnóstico por imagem , Músculos Faríngeos/efeitos da radiação , Melhoria de Qualidade , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Glândula Submandibular/diagnóstico por imagem , Glândula Submandibular/efeitos da radiação , Fatores de Tempo , Língua/diagnóstico por imagem , Língua/efeitos da radiação , Neoplasias Tonsilares/diagnóstico por imagem , Neoplasias Tonsilares/radioterapia
11.
Acta Oncol ; 58(1): 57-65, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30474448

RESUMO

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada
12.
Int J Radiat Oncol Biol Phys ; 103(4): 913-921, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30458233

RESUMO

PURPOSE: To evaluate the efficacy of modern image guided brachytherapy for squamous cell carcinoma of the nasal vestibule, to explore tumor volume as a prognostic factor for local and regional recurrence, and to assess patient satisfaction with nasal function and appearance after treatment. METHODS AND MATERIALS: In a retrospective analysis, we reviewed the medical records of 102 patients with Wang T1-T2 nasal vestibule cancer treated at a single institution with brachytherapy as the sole treatment. Median follow-up time was 42 months (range, 3-210 months). A patient satisfaction study using the validated Nasal Appearance and Function Evaluation Questionnaire was conducted among 42 patients more than 1 year after treatment. A statistically significant cutoff point for tumor volume as a prognostic factor of local control was established using Youden's index method. RESULTS: Seventy-seven of 102 patients were treated with interstitial implants, and 25 patients were treated by an intracavitary mould technique. The 5-year control rates were 95%, 91%, and 83% for local, regional, and locoregional control, respectively. Tumor volume ≥2.3 cm3 resulted in worse 3-year regional control compared to tumor volume <2.3 cm3 (62% vs 96%; P = .01). Ultimate regional control after salvage treatment was 96%, with no significant difference observed between subgroups by tumor volume (92% for ≥2.3 cm3 vs 96% for <2.3 cm3; P = .57). Three patients with regional failure developed distant metastases. Five-year disease-specific survival and overall survival were 94% and 74%, respectively. Patient-assessed cosmetic and functional satisfaction were both rated high (mean 3.7 and 4.0 of 5, respectively). CONCLUSION: We report the largest cohort to date treated with brachytherapy as the sole treatment for nasal vestibule carcinoma. Brachytherapy offers excellent local control for Wang T1-T2 tumors with high patient satisfaction. Tumor volume is an adequate predictive factor for patients at risk of regional recurrence, but ultimate control rates after salvage treatment are high. Therefore, we do not recommend elective treatment of the neck.


Assuntos
Braquiterapia , Cosméticos , Cavidade Nasal/efeitos da radiação , Cirurgia Assistida por Computador , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/patologia , Neoplasias Nasais/radioterapia , Satisfação do Paciente , Prognóstico , Estudos Retrospectivos , Cirurgia Assistida por Computador/efeitos adversos , Inquéritos e Questionários , Análise de Sobrevida , Carga Tumoral/efeitos da radiação
13.
Radiother Oncol ; 130: 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30005954

RESUMO

BACKGROUND: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting. MATERIALS AND METHODS: Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland-Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients. RESULTS: Bland-Altman's analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort. CONCLUSION: The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches.


Assuntos
Medula Cervical/diagnóstico por imagem , Medula Cervical/efeitos da radiação , Fluordesoxiglucose F18/farmacocinética , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Medula Cervical/metabolismo , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Análise de Regressão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carga Tumoral
14.
Head Neck ; 41(2): 488-494, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30536479

RESUMO

BACKGROUND: This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m2 (cis40+ART). METHODS: Sixty-two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment. RESULTS: A complete dataset of audiometric data was available of 12 patients treated with high-dose cisplatin and of 11 patients treated with intermediate-dose cisplatin. Patients in the high-dose group showed significant more hearing loss than in the intermediate group at 4 kHz ([z = 1.98; P = .04] and 8 kHz [z = 2.07; P < .03]). Interindividual variation was high in both groups. CONCLUSION: After induction TPF, more ototoxicity was observed in chemoradiotherapy with cis100+RT than after chemoradiotherapy with cis40+ART.

15.
Clin Otolaryngol ; 43(6): 1566-1572, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30160027

RESUMO

OBJECTIVES: To identify the risks associated with surgery, radiotherapy or a combined treatment approach for Fisch class C and D jugulotympanic paraganglioma, in order to develop an individualised approach for each patient depending on Fisch class, age, mutation presence, tumour size growth rate and presenting symptoms. DESIGN: A retrospective multicenter cohort study with all patient records of patients with a head and neck paraganglioma in the Radboudumc, Nijmegen and the St. Elisabeth Hospital, Tilburg, the Netherlands. MAIN OUTCOME MEASURES: Local control, cranial nerve damage, complications, function recovery. RESULTS: We found highest local control rates after tumour debulking with postoperative radiotherapy in case of residual tumour growth, referred to as the combined treatment group, (100%; n = 19), which was significantly higher than the surgical group (82%; n = 17; P = 0.00), but did not differ from the radiotherapy group (90%; n = 29). There were significantly less complications in the radiotherapy group, when compared to surgery (63 vs 27%; P = 0.002) and the combined group (44 vs 27%; P = 0.016). Furthermore,: using a logistic regression model, we found that pretreatment tumour growth was a negative predictor for post-treatment cranial nerve function recovery (OR = 50.178, P = 0.001), reducing the chance of symptom recovery (67.3% vs 35.7%) post-treatment. CONCLUSIONS: Radiotherapy should be the treatment of choice for the elderly. For younger patients, tumour debulking should be considered, with potential radiotherapy in case of residual tumour growth.


Assuntos
Neoplasias da Orelha/terapia , Tumor do Glomo Jugular/terapia , Neoplasias de Cabeça e Pescoço/terapia , Audição/fisiologia , Procedimentos Cirúrgicos Otológicos/métodos , Paraganglioma/terapia , Adolescente , Adulto , Idoso , Terapia Combinada/métodos , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/epidemiologia , Feminino , Seguimentos , Tumor do Glomo Jugular/diagnóstico , Tumor do Glomo Jugular/epidemiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Paraganglioma/diagnóstico , Paraganglioma/epidemiologia , Radioterapia Adjuvante/métodos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Adulto Jovem
16.
Radiother Oncol ; 128(3): 472-478, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29731161

RESUMO

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Idoso , Feminino , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Dosagem Radioterapêutica , Carga Tumoral
17.
Support Care Cancer ; 26(4): 1233-1242, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29230548

RESUMO

PURPOSE: The CONDOR study showed that docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100 + RT; n = 27)) versus accelerated radiotherapy with cisplatin weekly 40 mg/m2 (cis40 + ART; n = 29) in locally advanced head and neck cancer (LAHNC) patients was not feasible. Here, we report the analysis of health-related quality of life (HRQOL) of the patients entered in this study. METHODS: HRQOL was assessed at baseline, after two TPF, before start of chemoradiotherapy, and 1, 4, 8, 12, and 24 months after completion of chemoradiotherapy using the EORTC-QLQ-C30 and QLQ-H&N35 in 62 patients. RESULTS: Compliance with the QOL questionnaires was 94% (59/62) at baseline and 61% (30/49) at 12 months, respectively. HRQOL decreased after TPF and further decreased during chemoradiohteray in both arms equally. Pain and swallowing dysfunction improved significantly during TPF but deteriorated below baseline levels during chemoradiotherapy, cis40 + ART > cis100 + RT (p < 0.05). HRQOL and symptoms restored to baseline within 12 months in both arms and remained at that level until 24 months. CONCLUSIONS: After TPF, cis40 + ART had a larger negative impact on symptoms than cis100 + RT, probably due to the ART. HRQOL and symptoms restored to baseline levels within 12 months after end of treatment in both arms, which is an important perspective for patients during the phase of most serious acute side effects of treatment. TRIAL REGISTRATION: NCT00774319.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/psicologia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
18.
Int J Radiat Oncol Biol Phys ; 98(3): 555-573, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28581396

RESUMO

Positron emission tomography (PET) is an imaging modality widely applied in oncology for tumor staging, volume delineation in radiation therapy planning, and therapy response assessment. F-18 fluorodeoxyglucose (FDG) PET combined with computed tomography plays a significant role in the management of locally advanced head and neck cancer patients in the pretreatment setting to predict outcome and prognosis and after chemoradiation therapy (CRT) to assess tumor response. This review aims to evaluate the use of FDG PET acquired during CRT, ad interim FDG (FDGint), to identify tumor response at an early stage, modify the treatment plan if necessary, or set up alternative strategies to enhance the therapeutic ratio. Most of the studies confirmed the value of FDGint in predicting the response to CRT, whereas a few highlighted the poor predictive value of FDGint compared with FDG acquired 2 to 4 months after the end of CRT, which was well correlated with local and regional control and survival. Such findings deserve to be further analyzed in more homogeneous series with greater patient numbers according to the tumor site and CRT schedules. The best time to assess tumor response during radiation therapy remains a matter of debate, although 2 weeks seems most favorable, still providing the opportunity to adapt the treatment strategy.


Assuntos
Quimiorradioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Prognóstico , Dosagem Radioterapêutica , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
19.
BMC Cancer ; 17(1): 208, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28327089

RESUMO

BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. METHODS: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). DISCUSSION: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02442375 .


Assuntos
Carcinoma de Células Escamosas/radioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Dosagem Radioterapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Método Simples-Cego
20.
Head Neck ; 39(6): 1122-1130, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28263446

RESUMO

BACKGROUND: The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. METHODS: We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. CONCLUSION: Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Lesões por Radiação/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Reirradiação/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/métodos , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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