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1.
Lancet Oncol ; 21(9): 1173-1187, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32758455

RESUMO

BACKGROUND: Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. METHODS: This double-blind, multicentre, randomised, phase 2 study by the French Head and Neck Radiotherapy Oncology Group (GORTEC) was run at 19 hospitals in France and Switzerland. Eligible patients were aged 18-75 years with locoregionally advanced, squamous cell carcinoma of the head and neck (characterised as non-metastatic, measurable stage III, IVa, or IVb [limited to T ≥2, N0-3, and M0] disease), Eastern Cooperative Oncology Group performance status of 0 or 1, a history of heavy tobacco smoking (>10 pack-years) with no previous or current treatment for invasive head and neck cancer, and no previous treatment with inhibitor of apoptosis protein antagonists. Patients were randomly assigned (1:1) to receive oral Debio 1143 (200 mg per day on days 1-14 of 21-day cycles, for three cycles) or oral placebo (20 mg/mL, administered at the same dosing schedule) using a stochastic minimisation technique according to node involvement and primary tumour site, and HPV-16 status in patients with an oropharyngeal primary tumour site. All patients received standard high-dose cisplatin chemoradiotherapy. The primary endpoint was the proportion of patients with locoregional control 18 months after chemoradiotherapy, analysed in the intention-to-treat population (primary analysis), and repeated in the per-protocol population. Responses were assessed according to Response Evaluation Criteria in Solid Tumors (version 1.1). This trial is registered with ClinicalTrials.gov, NCT02022098, and is still active but not recruiting. FINDINGS: Between Jan 25, 2016, and April 24, 2017, 48 patients were randomly assigned to the Debio 1143 group and 48 to the placebo group (one patient in the placebo group did not receive the study drug and was not included in the safety analysis). Median duration of follow-up was 25·0 months (IQR 19·6-29·4) in the Debio 1143 group and 24·2 months (6·6-26·8) in the placebo group. Locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39-69) of 48 patients in the Debio 1143 group versus 16 (33%; 20-48) of 48 patients in the placebo group (odds ratio 2·69 [95% CI 1·13-6·42], p=0·026). Grade 3 or worse adverse events were reported in 41 (85%) of 48 patients in the Debio 1143 group and in 41 (87%) of 47 patients in the placebo group. The most common grade 3-4 adverse events were dysphagia (in 24 [50%] patients in the Debio 1143 group vs ten [21%] in the placebo group), mucositis (in 15 [31%] vs ten [21%]), and anaemia (in 17 [35%] vs 11 [23%]). Serious treatment-emergent adverse events were recorded in 30 (63%) of 48 patients in the Debio 1143 group and 28 (60%) of 47 in the placebo group. In the placebo group, two (4%) deaths were due to adverse events (one multiple organ failure and one asphyxia; neither was considered to be related to treatment). No deaths due to adverse events occurred in the Debio 1143 group. INTERPRETATION: To our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients. FUNDING: Debiopharm.


Assuntos
Cisplatino/administração & dosagem , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
2.
Cancer Radiother ; 24(6-7): 559-566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32753240

RESUMO

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Algoritmos , Humanos , Metástase Neoplásica/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
Oncology ; 98(11): 763-770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32629446

RESUMO

OBJECTIVES: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. PATIENTS AND METHODS: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. RESULTS: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). CONCLUSION: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.


Assuntos
Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/efeitos adversos , Quimiorradioterapia , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução , Masculino , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
4.
Tumour Biol ; 42(7): 1010428320938494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32628088

RESUMO

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.


Assuntos
Proteína Ligante Fas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Receptor fas/genética , Adulto , Idoso , Álcoois/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Tabaco/efeitos adversos , Proteína Supressora de Tumor p53/genética
5.
J Cancer Res Ther ; 16(3): 530-533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719262

RESUMO

Context: An objective conformal radiotherapy treatment planning criteria that can predict severity of early effects of radiotherapy would be quite useful in reducing the side effects of radiotherapy thereby improving quality of life for head and neck cancer patients. Aim of Study: Retrospective study aimed at correlating the maximum dose in planning target volume (PTV) with early effects of radiation. Materials and Methods: Patients with squamous cell carcinoma of H and N region who received radical radiotherapy and concomitant chemotherapy were retrospectively analyzed for maximum dose in PTV and the requirement of gap during radiotherapy or else hospitalization for supportive care during or up to 1 month after completion of radical radiotherapy. Results: Of a total of 23 patients, 8 patients (34.7%) required a gap of 2-14 days during their treatment. Twelve patients (52.1%) required hospitalization for 1-4 days and 4 patients (17.3%) required hospitalization for supportive care after completion of radiotherapy. The maximum dose in PTV ranged from 105.1% to 132.8% with an average of 112.68%. Subgroup analysis revealed a nonsignificant highest maximum dose of 114.72% in subset of patients requiring gap during radiotherapy (n= 8). Conclusion: It was concluded that maximum dose in PTV is a useful predictor of need for inhospital supportive care.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Determinação de Necessidades de Cuidados de Saúde/estatística & dados numéricos , Cuidados Paliativos/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Segurança do Paciente , Qualidade de Vida , Dosagem Radioterapêutica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento
6.
J Cancer Res Ther ; 16(3): 565-568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719268

RESUMO

Context: Head-and-neck cancer patients undergoing chemoradiation. Aims: The aim of the study was to see if there is any correlation between the planning target volume (PTV) and mucositis. Settings and Design: This was a single-arm prospective study. Subjects and Methods: A total of forty head-and-neck cancer patients undergoing chemoradiation were assessed for mucositis at the 5th week. The grades of mucositis were correlated with PTVs of low risk (54 Gy) and high risk (60-66 Gy). Statistical Analysis Used: The data were analyzed using the statistical software, SPSS Inc. Release 2009, predictive analytics software statistics for windows version 20.0, Chicago. Log transformation was done as the data were skewed. Independent t-test was used to compare between the two grades of toxicity. P <0.01 was considered for statistical significance. Results: The mean PTVlow risk was 522cc (228-771) and PTVhigh risk was 254cc (20-780). Grade II mucositis was seen in 27 (67%) patients and Grade III in 11 (28%) patients. The mean PTVlow risk was higher for patients, who had Grade III compared to Grade II mucositis (571 vs. 517 cc, P = 0.052). Conclusions: The same was seen for PTVhigh risk(367 vs. 222 cc, P = 0.017). PTV is a better predictor of mucositis, and those patients with larger PTV require close monitoring and early intervention of mucositis.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Mucosite/etiologia , Lesões por Radiação/etiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/diagnóstico , Mucosite/patologia , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estomatite/diagnóstico , Estomatite/etiologia , Estomatite/patologia
7.
J Cancer Res Ther ; 16(3): 575-580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719270

RESUMO

Aims: This study aims at assessing the volume changes that occur in the targets (gross tumor volume and planning target volume [PTV]) and the organs at risk in squamous cell carcinoma of the head and neck during radiotherapy and assessing the dose changes that occur as a result of them. Settings and Design: This was a prospective observational study in a tertiary care center after obtaining the appropriate scientific and ethics committee clearance. Subjects and Methods: Forty-five patients diagnosed with squamous cell carcinoma of the head and neck, who were treated with intensity-modulated radiotherapy in the time period from March 2018 to May 2019, were enrolled in the study. A planning computed tomography (CT) scan (CTplan) was done for all patients, followed by scans after 15 fractions (CT15) and after 25 fractions (CT25). The volume changes and the subsequent dose changes were assessed and recorded. Statistical Analysis Used: Data entry was done in MS Excel spreadsheet. The continuous variables were expressed as mean + standard deviation. The comparison of normally distributed continuous variables was done by paired t-test. Data analysis was done by SPSS (Statistical Package for the Social Sciences) version 16.0. P < 0.05 was considered statistically significant. A multivariate linear regression model was constructed to study the correlation between mean dose to the parotid glands and the other variables. All statistical modeling and analysis were done using SAS (Statistical Analysis Software) version 9.4. Results: Of the 45 patients, 25 were male and 20 were female. The majority of the patients had malignancies in the oral cavity (16) and hypopharynx (14). Most of them had Stage III/IV (AJCC v 8) disease (41). There were a 36% decrease in the PTV-high risk (PTV-HR) volume and a 6.05% decrease in the PTV-intermediate risk (PTV-IR) volume CT15. In CT25, the volume decrease in the PTV-HR and the PTV-IR was 47% and 9.06%, respectively. The parotid glands also underwent a reduction in their volume which has been quantified as 21.7% and 20.9% in the ipsilateral and contralateral parotids in CT15 and 36% and 33.6% in CT25, respectively. The D2 (dose received by 2% of the volume) and D98 (dose received by 98% of the volume) of the PTV-IR showed changes of +3.5% and -0.2% in CT15 and + 4.6% and -0.31% in CT25, respectively. The homogeneity index and conformity number of the PTV-IR changes by 0.03 and 0.08 in CT15 and by 0.04 and 0.12 in CT25, respectively. The mean dose to the ipsilateral parotid gland increased by 14% in CT15 and 19% in CT25. The mean dose to the contralateral parotid gland increased by 17% in CT15 and 25% in CT25. Conclusion: The dose to the parotid glands increases as a result of the changes that occur during the course of radiation. The changes are significant after 15 fractions of radiation. A replanning at this juncture might be considered to reduce the dose to the parotid glands.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Glândula Parótida/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Glândula Parótida/patologia , Estudos Prospectivos , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
8.
Rev Assoc Med Bras (1992) ; 66(3): 380-384, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32520162

RESUMO

INTRODUCTION: Radiotherapy (RT) plays an important role in the treatment of patients with head and neck neoplasia, and is frequently used as postoperative adjuvant therapy. This study aimed to review the literature about timing factors that may influence the clinical outcomes of patients with advanced head and neck neoplasia treated with adjuvant RT. RESULTS: Timing factors such as total treatment time, length of adjuvant RT, and the absence of interruptions during RT may influence the clinical outcome of these patients. CONCLUSIONS: In the same way that certain tumor factors can affect the prognosis of patients with squamous cell carcinoma of the head and neck, some therapeutic timing factors are also prognostic factors and therefore, must be carefully orchestrated in order to avoid loss at therapeutic outcomes for these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Terapia Combinada , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Radioterapia Adjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Taxa de Sobrevida , Fatores de Tempo
9.
Cancer ; 126(15): 3426-3437, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478895

RESUMO

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Hipofracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virologia , Pandemias , Infecções por Papillomavirus/complicações , Pneumonia Viral/epidemiologia , Radioterapia de Intensidade Modulada , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do Tratamento
10.
Health Qual Life Outcomes ; 18(1): 195, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571349

RESUMO

BACKGROUND: To compare quality of life of patients treated with cetuximab with or without radiation therapy (±RT) vs. cisplatin±RT for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) in the real-world setting. METHODS: In this retrospective observational study, electronic medical records and Patient Care Monitor (PCM) survey data from the Vector Oncology Data Warehouse were utilized from adult patients in the United States who received initial treatment with cetuximab±RT or cisplatin±RT for locoregionally advanced SCCHN between January 1, 2007 and January 1, 2017. Quality of life was assessed using PCM index scores and individual PCM items. Cetuximab±RT and cisplatin±RT cohorts were balanced using propensity score weighting. Linear mixed models were used to assess the impact of baseline demographic and clinical characteristics on PCM endpoints. RESULTS: Of 531 patients with locoregionally advanced SCCHN, 187 received cetuximab±RT, and 344 received cisplatin±RT. Before propensity score weighting, the cetuximab±RT cohort was older (mean [SD] age of 63.9 [9.6] years vs. 57.4 [8.6] years), and more likely to be white (82.4% vs. 72.4%) compared to the cisplatin±RT cohort. After propensity score weighting, the two cohort subsamples (cetuximab±RT, N = 60; cisplatin±RT, N = 177) with PCM data showed no significant differences in General Physical Symptoms, Treatment Side Effects, Impaired Ambulation, or Impaired Performance index scores. Patients in the cetuximab±RT cohort had higher Acute Distress index (p = 0.023), Despair index (p = 0.011), and rash (p = 0.003) scores but lower numbness/tingling scores (p = 0.022) than patients in the cisplatin±RT cohort. CONCLUSIONS: Significant group differences were observed in this comparative analysis, as the cetuximab±RT cohort had significantly higher Acute Distress index, Despair index, and rash scores compared with the cisplatin±RT cohort but lower numbness/tingling scores. These patterns of symptoms appear consistent with previously reported symptoms associated with the treatment of SCCHN.


Assuntos
Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Qualidade de Vida/psicologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Anticancer Res ; 40(5): 2645-2655, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366409

RESUMO

BACKGROUND/AIM: Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells. MATERIALS AND METHODS: Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system. RESULTS: MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC50 value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G2/M phase, DNA damage and apoptotic cell death. CONCLUSION: MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G2/M cell cycle arrest resulting in DNA damage and apoptosis.


Assuntos
Cisplatino/uso terapêutico , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
12.
Free Radic Res ; 54(4): 254-270, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32462956

RESUMO

Aberrant expression of LINC00520 has been identified in head and neck squamous carcinoma (HNSCC). However, its function in the radiosensitivity of HNSCC remain unclear. Herein, we aimed to define the role LINC00520 in the radiosensitivity of HNSCC and identify the underlying mechanism. Tumour tissues and adjacent normal tissue were collected from HNSCC patients. Differentially expressed genes (DEGs) in HNSCC tumour were obtained from the cancer genome atlas (TCGA) database. Interactions between LINC00520 and miR-195, homeobox A10 (HOXA10) and miR-195 were evaluated by dual-luciferase reporter gene assay, RNA Immunoprecipitation (RIP), and RNA pull-down assay. The effects of LINC00520/miR-195/HOXA10 on radiosensitivity of HNSCC were analysed in the evaluation of radiotherapy outcome. Cell proliferation, invasion, migration, and apoptosis of HNSCC cells were accessed via gain- and loss-of-function approaches. Tumour xenograft in nude mice was conducted in order to confirm the results in vivo. LINC00520 was upregulated while miR-195 was downregulated in HNSCC cells and tissues. Silencing LINC00520 or overexpressing miR-195 promoted radiosensitivity and inhibited cell proliferation, invasion, migration, and apoptosis in HNSCC. Moreover, these in vitro findings were reproduced in vivo in human HNSCC xenograft in nude mice. LINC00520/miR-195/HOXA10 is involved in the radiosensitivity mediation, providing potential therapeutic target for HNSCC treatment.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Tolerância a Radiação
13.
Br J Radiol ; 93(1111): 20190464, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391712

RESUMO

OBJECTIVES: To analyze survival outcomes in patients with oropharygeal cancer treated with primary intensity modulated radiotherapy (IMRT) using decision tree algorithms. METHODS: A total of 273 patients with newly diagnosed oropharyngeal cancer were identified between March 2010 and December 2016. The data set contained nine predictor variables and a dependent variable (overall survival (OS) status). The open-source R software was used. Survival outcomes were estimated by Kaplan-Meier method. Important explanatory variables were selected using the random forest approach. A classification tree that optimally partitioned patients with different OS rates was then built. RESULTS: The 5 year OS for the entire population was 78.1%. The top three important variables identified were HPV status, N stage and early complete response to treatment. Patients were partitioned in five groups on the basis of these explanatory variables. CONCLUSION: The proposed classification tree could help to guide future research in oropharyngeal cancer field. ADVANCES IN KNOWLEDGE: Decision tree method seems to be an appropriate tool to partition oropharyngeal cancer patients.


Assuntos
Neoplasias Orofaríngeas/mortalidade , Radioterapia de Intensidade Modulada/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Árvores de Decisões , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/radioterapia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Resultado do Tratamento
14.
Curr Opin Oncol ; 32(3): 196-202, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32251158

RESUMO

PURPOSE OF REVIEW: The role of the immune system is important in both initiation and development of head and neck cancers. Various immune checkpoints have been discovered that can be exploited by cancer to evade immune mediated destruction. Therefore, immune checkpoint inhibitors have been developed to overcome cancer immune-evasion and are currently in clinical use in head and neck cancers. In addition, the immune system appears to play an important role in the response to radiotherapy. The combination of immunotherapy with radiotherapy may increase the ability to induce immunogenic death by removing the locks blocking the immune system. RECENT FINDINGS: Although the antitumour efficacy of radiotherapy is based primarily on the toxicity of DNA damage, studies have suggested that this efficacy is based not only on this local cytotoxic and antiproliferative effect, but also on the interactions between the tumor and its microenvironment that are altered. Thus, the cytotoxic action of radiotherapy on tumor cells provides T lymphocytes with tumor neoantigens, and releases proinflammatory cytokines that promote the immune response. Cell death inducing this type of immune response is called immunogenic death. Therefore, several phase 3 clinical trials are currently ongoing evaluating the combination of radiotherapy and immune checkpoint inhibitors in head and neck cancers. SUMMARY: Combining immunotherapy and radiotherapy in head and neck cancers is promising. Several phase 3 clinical trials are ongoing that may be practice changing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Imunoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia
15.
Asian Pac J Cancer Prev ; 21(3): 799-807, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212810

RESUMO

PURPOSE: The aim of this prospective randomized study is to compare cisplatin at 2 dose levels given concurrently with intensity modulated radiation therapy (IMRT) in the treatment of locally advanced HNSCC. The main objectives were to evaluate treatment toxicities, loco-regional control, tumor response and patients compliance. METHODS: Patients were randomized into two groups that either received 30 mg/m2 cisplatin weekly (arm A) or 100 mg/m2 once every 3 weeks (arm B). Radiotherapy prescribed dose was 70Gy in 33 fractions. Treatment adverse events were documented. RESULTS: Sixty patients with locally advanced HNSCC were included in this study. Recruitment started at the beginning of July 2016 and ended in July 2019. The Median follow-up was 24 months. Acute non-hematological toxicities of grade 3 or higher during the treatment course were significantly more observed in Arm B patients (76.6%) compared to Arm A patients (56.6%) with a P-value of 0.007. Hematological toxicities in the form of anemia, leucopenia and neutropenia were also significantly higher in Arm B patients with a p-value of 0.435, 0.002 & 0,002, respectively. The median 2 year loco-regional control rate in Arm B was 72.8% versus 57.6% in Arm A with a p-value of 0.015. Complete responses were similar between both groups (77%). Compliance to treatment was better in Arm A with 70% of the patients received at least 6 weekly doses where as 60% of the patients in Arm B completed the three cycles of treatment and 40 % received only 2 cycles. CONCLUSION: Once weekly low dose cisplatin treatment showed lower acute toxicity and a better compliance compared to once every 3 weeks high dose cisplatin treatment at the expense of a lower loco-regional control.


Assuntos
Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Cisplatino/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação
16.
Radiat Oncol ; 15(1): 31, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019576

RESUMO

BACKGROUND: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, and the number of elderly patients diagnosed with HNSCC is increasing. However, as elderly HNSCC patients are underrepresented in clinical trials, current clinical decision making for this cohort largely lacks clinical evidence. METHODS: Elderly patients (≥65 years) with HNSCC undergoing (chemo)radiotherapy from 2010 to 2018 at Freiburg University Medical Center were assessed for patterns of care, locoregional control (LRC), progression-free (PFS) and overall survival (OS) regarding definitive and adjuvant treatments. Acute and late therapy-associated toxicities were quantified according to CTCAE v5.0. RESULTS: Two hundred forty-six patients were included in this analysis, of whom 166 received definitive and 80 adjuvant treatment. Two-year rates for OS, PFS and LRC were 56.9, 44.9 and 75.5%, respectively. Survival differed significantly between age groups with an OS of 40 and 22 months and a PFS of 23 and 12 months for patients aged 65-74 or ≥ 75 years, respectively (p < 0.05). Concomitant chemotherapy resulted in improved OS in patients aged 65-74 years compared to radiotherapy alone (p < 0.05) for definitive treatments, while patients ≥75 years did not benefit (p = 0.904). For adjuvant chemoradiotherapy, a trend towards superior OS rates was observed for patients aged 65-74 years (p = 0.151). Low performance status (HR = 2.584, 95% CI 1.561-4.274; p < 0.001) and smoking (HR = 1.960, 95% CI 1.109-3.464, p < 0.05) were the strongest independent prognostic factor in the multivariate analysis for decreased OS. One hundred thirty-eight patients (56.1%) experienced acute grade 3/4 and 45 patients (19.9%) chronic grade 3 toxicities. CONCLUSION: Radiotherapy is a feasible treatment modality for elderly HNSCC patients. The relatively low OS compared to high LRC may reflect age and comorbidities. Concomitant chemotherapy should be critically discussed in elderly HNSCC patients.


Assuntos
Quimiorradioterapia/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida
17.
Sci Rep ; 10(1): 2716, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066820

RESUMO

A growing proportion of head and neck cancers (HNC) result from HPV infection. Between HNC aetiological groups (HPV positive and HPV negative) clinical evidence demonstrates significantly better treatment response among HPV positive cancers. Cancer stem cells (CSCs) are identified in HNC tumour populations as agents of treatment resistance and a target for tumour control. This study examines dynamic responses in populations of a CSC phenotype in HNC cell lines following X-irradiation at therapeutic levels, and comparing between HPV statuses. Variations in CSC density between HPV groups showed no correlation with better clinical outcomes seen in the HPV positive status. CSC populations in HPV positive cell lines ranged from 1.9 to 4.8%, and 2.6 to 9.9% for HPV negative. Following 4 Gy X- irradiation however, HPV negative cell lines demonstrated more frequent and significantly greater escalation in CSC proportions, being 3-fold that of the HPV positive group at 72 hours post irradiation. CSC proportions of tumour populations are not fixed but subject to change in response to radiation at therapeutic dose levels. These findings imply a potential effect of aetiology on radio-responsiveness in CSCs, illustrating that clonogen treatment response may be more informative of therapy outcomes than inherent population density alone.


Assuntos
Aldeído Desidrogenase/genética , Receptores de Hialuronatos/genética , Células-Tronco Neoplásicas/efeitos da radiação , Papillomaviridae/patogenicidade , Tolerância a Radiação/genética , Idoso , Aldeído Desidrogenase/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Contagem de Células , Linhagem Celular Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Receptores de Hialuronatos/imunologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Papillomaviridae/crescimento & desenvolvimento , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/radioterapia , Tolerância a Radiação/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Raios X
18.
Br J Radiol ; 93(1108): 20190154, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31944856

RESUMO

OBJECTIVE: This work focused on the function role and underlying mechanism of BLACAT1 in regulating the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cells via PSEN1. METHODS: BLACAT1 and PSEN1 expression in HNSCC tissues and cells were measured by qRT-PCR. Kaplan-Meier method and Spearman's correlation analysis determined the prognostic roles and association of BLCAT1 and PSEN1 in HNSCC. The impacts of BLACAT1 and PSEN1, alone and in combination, on radiosensitivity of HNSCC cells were separately assessed through CCK-8, colony formation, flow cytometry, western blot and γH2AX foci staining assays. RESULTS: Our study disclosed that BLACAT1 and PSEN1 were both in association with poor prognosis and radioresistance of HNSCC cells. BLACAT1 knockdown improved the radiosensitivity of HNSCC cells by changing cellular activities containing repressed cell viability, accelerated cell apoptosis, induced cell cycle arrest, and stimulated DNA damage response. Further, we found that PSEN1 was positively correlated with BLACAT1. Rescue assays confirmed that BLACAT1 regulated the radiosensitivity of HNSCC cells by modulating PSEN1. CONCLUSION: We revealed that BLACAT1 knockdown enhanced radioresistance of HNSCC cells via regulating PSEN1, exposing the probable target role of BLACAT1 in HNSCC. ADVANCES IN KNOWLEDGE: This was the first time that the pivotal role of BLACAT1 was investigated in HNSCC, which provided a novel therapeutic direction for HNSCC patients.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Presenilina-1/metabolismo , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Dano ao DNA , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/radioterapia , Masculino , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/radioterapia , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Regulação para Cima
19.
Arq. bras. med. vet. zootec. (Online) ; 72(1): 119-124, Jan.-Feb. 2020. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1088905

RESUMO

This case report describes the outcome of treatment of dogs with advanced (deeply invasive) nasal planum squamous cell carcinomas with palliative or definitive radiation therapy. All dogs were diagnosed with nasal planum squamous cell carcinoma by histopathology, and their owners declined aggressive surgery. Dogs were treated with a cobalt-60 unit, definitive-intent radiation protocol consisting of 15 daily fractions (Monday-Friday) of 2.8 Gy, and palliative radiation protocol consisting of 4 fractions of 8 Gy performed once a week. Three dogs had T3 tumors and three had T4 tumors according to the WHO staging system. Two dogs had tumor complete remission and four had tumor partial remission. Survival time of dogs submitted to radiation therapy was 95-417 days. Radiation acute side effects involved only mild epilation and cutaneous erythema in palliative protocols, and moist desquamation, epilation, mild rhinitis and oral mucositis in definitive-intent RT. Radiation therapy, especially palliative protocols, can be a treatment option for nasal planum squamous cell carcinoma in dogs, when the owner declines aggressive surgery. It may contribute to partial or complete tumor remission and better patient quality of life, even at advanced stages, leading to mild side effects.(AU)


Este relato descreve seis casos de carcinoma de células escamosas de plano nasal canino tratados com radioterapia definitiva ou paliativa. Em todos os casos, o diagnóstico definitivo foi feito mediante biópsia, e os tutores declinaram da cirurgia agressiva. A radioterapia foi realizada utilizando-se um equipamento de cobalto-60, e o protocolo definitivo consistiu de 15 frações de 2,8 Gy, cinco vezes por semana (segunda a sexta), enquanto o protocolo paliativo consistiu de quatro frações de 8 Gy, uma vez por semana. Seis cães foram tratados, entre os quais três tinham tumores em estágio T3 e três em estágio T4, de acordo com a tabela TNM da Organização Mundial da Saúde. Dois animais apresentaram remissão completa do tumor após o tratamento e quatro apresentaram remissão parcial. O tempo de sobrevida variou entre 95-417 dias, sendo que dois animais ainda estão vivos e em observação. Os efeitos colaterais da radioterapia foram apenas epilação e eritema leve, no protocolo paliativo, e epilação, radiodermite úmida, rinite e mucosite oral, no protocolo definitivo. A radioterapia, especialmente no protocolo paliativo, pode ser considerada uma opção de tratamento quando os tutores declinam da cirurgia agressiva. Ela pode contribuir para remissão (parcial ou completa) do tumor e melhor qualidade de vida do paciente, mesmo nos casos avançados, levando a efeitos colaterais mínimos.(AU)


Assuntos
Animais , Cães , Neoplasias Nasais/veterinária , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/veterinária , Cuidados Paliativos
20.
Br J Radiol ; 93(1107): 20190573, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31778315

RESUMO

OBJECTIVE: Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). METHODS: Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. RESULTS: cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2 pp/-0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. CONCLUSION: Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. ADVANCES IN KNOWLEDGE: The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Incerteza , Humanos , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente , Lesões por Radiação/prevenção & controle , Erros de Configuração em Radioterapia , Radioterapia de Intensidade Modulada/normas , Estudos Retrospectivos
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