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1.
Radiother Oncol ; 163: 221-228, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34506830

RESUMO

OBJECTIVES: Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. MATERIALS AND METHODS: Case records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004-2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. RESULTS: During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1-4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p < 0.001). Positive smoking history, optic nerve involvement, and longer duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences. CONCLUSION: Durable recovery of most cranial neuropathies in advanced T4 NPC was observed in the era of modern IMRT and effective systemic chemotherapy. Both patient and disease factors affected the chance of neurological recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

2.
J Radiat Res ; 62(3): 483-493, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33899102

RESUMO

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.


Assuntos
Hepatopatias/etiologia , Neoplasias Hepáticas/complicações , Modelos Biológicos , Probabilidade , Lesões por Radiação/complicações , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
3.
Breast J ; 26(10): 1946-1952, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648331

RESUMO

To compare patient-rated cosmetic and satisfactory outcomes between conventional fractionation with simultaneously integrated boost (C-SIB) vs hypofractionation with SIB (H-SIB) in early breast cancer. Patients with stage I and II breast cancer who received breast-conserving surgery followed by radiation with SIB to tumor bed and completed questionnaire were included in this study. Radiotherapy was as follows: C-SIB arm = 50 Gy and 65 Gy in 25 fractions and H-SIB arm = 43.2 Gy and 52.8 Gy in 16 fractions to the whole breast and tumor bed, respectively. Single cross-sectional assessment of the breast cosmesis was done by patients and radiation oncologist at a follow-up visit. Breast cosmetic and satisfaction scores were collected using a four-point Harvard/NSABP/RTOG cosmesis criteria scale and a four-point Likert-type scale, respectively. Of a total of 114 patients (C-SIB = 57) and (H-SIB = 57) arms, a median time from radiotherapy completion to questionnaire response was 7.2 years. Patient-rated cosmetic outcome in C-SIB vs H-SIB was "excellent" in 40.3% vs 45.6%, "good" in 33.3% vs 42.1%, "fair" in 21.1% vs 10.5%, and "poor" in 5.3% vs 1.8% (P = .288). Corresponding satisfaction was "very satisfied" in 52.6% vs 57.9%, "satisfied" in 40.4% vs 35.1%, "neutral" in 7.0% vs 5.2%, and "unsatisfied" in 0% vs 1.8% (P = .683). Stage I and older age at radiotherapy were predictors for favorable (good or excellent) cosmesis and satisfaction, respectively. In early-stage breast cancer, H-SIB provided a trend for better cosmesis than C-SIB while maintaining satisfaction. The reduction in treatment duration and cost as well as favorable cosmesis outcomes encourages the use of H-SIB.


Assuntos
Neoplasias da Mama , Hipofracionamento da Dose de Radiação , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos Transversais , Feminino , Humanos , Mastectomia Segmentar , Estadiamento de Neoplasias , Radioterapia Adjuvante , Resultado do Tratamento
4.
Jpn J Clin Oncol ; 49(12): 1100-1113, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31334768

RESUMO

OBJECTIVE: To validate the eighth edition of the AJCC/UICC staging system in nasopharyngeal cancer (NPC) patients who were uniformly treated in a prospective randomized study using intensity-modulated radiation therapy and to investigate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level when incorporated into the TNM staging. METHODS: Between October 2010 and September 2015, non-metastatic NPC patients were treated with concurrent chemoradiation followed by adjuvant chemotherapy. Pretreatment images of 205 patients were reviewed by two radiologists to determine the TNM classification according to the seventh and eighth editions of the AJCC/UICC staging system. Overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated. Harrell's C concordance index (C-index) and Akaike information criterion (AIC) were used to compare the staging models. Recursive partitioning analysis (RPA) was conducted and incorporated with plasma EBV DNA. RESULTS: Overall, the eighth edition showed higher C-indexes and lower AIC values in nodal classification and stage groups, indicating a better discrimination performance and better goodness of fit, but showed similar separation for T classification compared with the seventh edition. The integration of pretreatment EBV values (<2300 vs ≥2300 copies/ml) to the eighth edition AJCC/UICC staging system allowed the classification of patients into three RPA categories and further lowered the AIC value and increased the C-index for OS. CONCLUSION: The eighth edition of the AJCC/UICC staging system had higher prognostic values in terms of OS, PFS and DMFS than the previous edition. An integration of pretreatment plasma EBV DNA into the next AJCC/UICC staging could improve the outcome prediction especially in poor risk groups who might benefit from treatment intensification.


Assuntos
DNA Viral/sangue , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/diagnóstico , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
5.
Radiother Oncol ; 135: 100-106, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015154

RESUMO

PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/ß ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.


Assuntos
Neoplasias Hepáticas/radioterapia , Fígado/efeitos da radiação , Lesões por Radiação/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Incerteza
6.
Radiol Oncol ; 52(2): 195-203, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30018524

RESUMO

Background: Plasma EBV DNA concentrations at the time of diagnosis (pre-EBV) and post treatment (post-EBV) have significant value for predicting the clinical outcome of nasopharyngeal cancer (NPC) patients. However, the prognostic value of the EBV concentration during radiation therapy (mid-EBV) has not been vigorously studied. Patients and methods: This was a post hoc analysis of 105 detectable pre-EBV NPC patients from a phase II/III study comparing sequential (SEQ) versus simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT). Plasma EBV DNA concentrations were measured by PCR before commencement of IMRT, at the 5th week of radiation therapy and 3 months after the completion of IMRT. The objective was to identify the prognostic value of mid-EBV to predict overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Results: A median pre-EBV was 6880 copies/ml. Mid-EBV and post-EBV were detectable in 14.3% and 6.7% of the patients, respectively. The median follow-up time was 45.3 months. The 3-year OS, PFS and DMFS rates were 86.0% vs. 66.7% (p = 0.043), 81.5% vs. 52.5% (p = 0.006), 86.1% vs. 76.6% (p = 0.150), respectively, for those with undetectable mid-EBV vs. persistently detectable mid-EBV. However, in the multivariate analysis, only persistently detectable post-EBV was significantly associated with a worse OS (hazard ratio (HR) = 6.881, 95% confident interval (CI) 1.699-27.867, p = 0.007), PFS (HR = 5.117, 95% CI 1.562-16.768, p = 0.007) and DMFS (HR = 129.071, 95%CI 19.031-875.364, p < 0.001). Conclusions: Detectable post-EBV was the most powerful adverse prognostic factor for OS, PFS and DMFS; however, detectable mid-EBV was associated with worse OS, PFS especially Local-PFS (LPFS) and may facilitate adaptive treatment during the radiation treatment period.

7.
J Radiat Res ; 59(4): 446-455, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29750261

RESUMO

This study aimed to validate previously reported dosimetric parameters, including thyroid volume, mean dose, and percentage thyroid volume, receiving at least 40, 45 and 50 Gy (V40, V45 and V50), absolute thyroid volume spared (VS) from 45, 50 and 60 Gy (VS45, VS50 and VS60), and clinical factors affecting the development of radiation-induced hypothyroidism (RHT). A post hoc analysis was performed in 178 euthyroid nasopharyngeal cancer (NPC) patients from a Phase III study comparing sequential versus simultaneous-integrated boost intensity-modulated radiation therapy. RHT was determined by increased thyroid-stimulating hormone (TSH) with or without reduced free thyroxin, regardless of symptoms. The median follow-up time was 42.5 months. The 1-, 2- and 3-year freedom from RHT rates were 78.4%, 56.4% and 43.4%, respectively. The median latency period was 21 months. The thyroid gland received a median mean dose of 53.5 Gy. Female gender, smaller thyroid volume, higher pretreatment TSH level (≥1.55 µU/ml) and VS60 < 10 cm3 were significantly associated with RHT in univariate analyses. Only pretreatment TSH ≥ 1.55 µU/ml and VS60 < 10 cm3 were significant predictors in multivariate analysis. Our results suggested that patients with pretreatment TSH ≥ 1.55 µU/ml should be cautious about the risk of RHT. The VS60 ≥ 10 cm3 is recommended for treatment planning.


Assuntos
Hipotireoidismo/etiologia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Curva ROC , Dosagem Radioterapêutica
8.
Clin Lung Cancer ; 19(4): 289-293, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29665993

RESUMO

New randomized data from Japan have raised questions regarding the use of prophylactic cranial irradiation for patients with extensive-stage small-cell lung cancer but without detectable brain metastases on magnetic resonance imaging. In the present focused review, we examine the general role of prophylactic cranial irradiation in the management of small-cell lung cancer and present relevant controversies from both sides of the discussion. Future directions for clinical investigation and research are also highlighted. Strategies for neurocognitive protection, including memantine use and hippocampal sparing using modulated radiotherapy techniques, are also presented.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Irradiação Craniana , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/secundário , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Humanos , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia
9.
J Radiat Res ; 59(suppl_1): i72-i76, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29529229

RESUMO

Particle beam therapy (PBT), including proton and carbon ion therapy, is an emerging innovative treatment for cancer patients. Due to the high cost of and limited access to treatment, meticulous selection of patients who would benefit most from PBT, when compared with standard X-ray therapy (XRT), is necessary. Due to the cost and labor involved in randomized controlled trials, the model-based approach (MBA) is used as an alternative means of establishing scientific evidence in medicine, and it can be improved continuously. Good databases and reasonable models are crucial for the reliability of this approach. The tumor control probability and normal tissue complication probability models are good illustrations of the advantages of PBT, but pre-existing NTCP models have been derived from historical patient treatments from the XRT era. This highlights the necessity of prospectively analyzing specific treatment-related toxicities in order to develop PBT-compatible models. An international consensus has been reached at the Global Institution for Collaborative Research and Education (GI-CoRE) joint symposium, concluding that a systematically developed model is required for model accuracy and performance. Six important steps that need to be observed in these considerations include patient selection, treatment planning, beam delivery, dose verification, response assessment, and data analysis. Advanced technologies in radiotherapy and computer science can be integrated to improve the efficacy of a treatment. Model validation and appropriately defined thresholds in a cost-effectiveness centered manner, together with quality assurance in the treatment planning, have to be achieved prior to clinical implementation.


Assuntos
Consenso , Radioterapia com Íons Pesados , Internacionalidade , Modelos Teóricos , Terapia com Prótons , Humanos , Neoplasias/radioterapia , Probabilidade
10.
Jpn J Clin Oncol ; 48(5): 467-475, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522203

RESUMO

Objective: Plasma Epstein-Barr virus (EBV) DNA concentration at the time of diagnosis (pre-EBV) can be used to stratify risk for nasopharyngeal cancer (NPC) patients. However, pre-EBV cut-off values vary among studies. Methods: This was a post hoc analysis of 208 NPC patients from a phase II/III study comparing sequential (SEQ) vs. simultaneous integrated boost (SIB) intensity modulated radiation therapy. The objective was to identify the optimal pre-EBV cut-off value to predict overall survival (OS), progression free survival (PFS) and distant metastatic free survival (DMFS) rates. Results: The pre-EBV and post-treatment EBV DNA (post-EBV) were detectable in 59.1% and 3.8% of the patients, respectively. A new pre-EBV cut-off value of 2300 copies/ml was identified by the receiver operating characteristics analysis. This cut-off value showed 82% sensitivity, 59% specificity and 31.7% positive and 93.5% negative predictive values in predicting OS. The 3-year OS, PFS and DMFS were 95.6 vs. 73.8%, 89.8 vs. 55.3% and 93 vs. 70.1% for pre-EBV < vs. ≥2300 copies/ml, respectively. Older age group (≥45 years), high pre-EBV and detectable post-EBV concentration were independent predictors for OS, PFS and DMFS in a multivariate analysis. When the stage grouping and pre-EBV value were combined, a subgroup of patients with stage II-III and pre-EBV values <2300 copies/ml. had the best survival outcomes, while the worst survival subgroup was the patients with stage III-IVb with pre-EBV values ≥2300 copies/ml. Conclusions: Pre-EBV cut-off of 2300 copies/ml is an optimal value predicting OS, PFS and DMFS.


Assuntos
Infecções por Vírus Epstein-Barr/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Prognóstico , Estudos Prospectivos
11.
J Radiat Res ; 59(suppl_1): i50-i57, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538699

RESUMO

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.


Assuntos
Neoplasias Hepáticas/terapia , Fígado/patologia , Fígado/efeitos da radiação , Probabilidade , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Incerteza , Terapia por Raios X , Algoritmos , Humanos
12.
Strahlenther Onkol ; 194(5): 375-385, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29302704

RESUMO

PURPOSE: This study was performed to compare the acute and late toxicities between sequential (SEQ) and simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT. SEQ-IMRT consisted of two plans: 2 Gy × 25 fractions to low-risk planning target volume (PTV) followed by a sequential boost (2 Gy × 10 fractions) to high-risk PTV, while SIB-IMRT treated low- and high-risk PTVs with doses of 56 and 70 Gy in 33 fractions. Toxicities and survival outcomes were analyzed. RESULTS: Between October 2010 and September 2015, of the 209 patients who completed treatment, 102 in the SEQ and 107 in the SIB arm were analyzed. The majority had undifferentiated squamous cell carcinoma (82%). Mucositis and dysphagia were the most common grade 3-5 acute toxicities. There were no statistically significant differences in the cumulative incidence of grade 3-4 acute toxicities between the two arms (59.8% in SEQ vs. 58.9% in SIB; P = 0.892). Common grade 3-4 late toxicities for SEQ and SIB included hearing loss (2.9 vs. 8.4%), temporal lobe injury (2.9 vs. 0.9%), cranial nerve injury (0 vs. 2.8%), and xerostomia (2 vs. 0.9%). With the median follow-up of 41 months, 3­year progression-free and overall survival rates were 72.7 vs. 73.4% (P = 0.488) and 86.3 vs. 83.6% (P = 0.938), respectively. CONCLUSION: SEQ and SIB provide excellent survival outcomes with few late toxicities. According to our study, SIB with a satisfactory dose-volume constraint to nearby critical organs is the technique of choice for NPC treatment due to its convenience.


Assuntos
Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica
13.
J Radiat Res ; 59(suppl_1): i63-i71, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29309691

RESUMO

This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.


Assuntos
Terapia com Prótons/efeitos adversos , Síncrotrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
14.
J Radiat Res ; 59(suppl_1): i2-i10, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29373709

RESUMO

Physically precise external-beam radiotherapy (EBRT) technologies may not translate to the best outcome in individual patients. On the other hand, clinical considerations alone are often insufficient to guide the selection of a specific EBRT approach in patients. We examine the ways in which to compare different EBRT approaches based on physical, biological and clinical considerations, and how they can be enhanced with the addition of biophysical models and machine-learning strategies. The process of selecting an EBRT modality is expected to improve in tandem with knowledge-based treatment planning.


Assuntos
Neoplasias/radioterapia , Radioterapia , Fenômenos Biofísicos , Humanos , Neoplasias Pulmonares/radioterapia , Aprendizado de Máquina , Modelos Biológicos
15.
Neurooncol Pract ; 5(1): 37-45, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31385968

RESUMO

Background: Stereotactic radiosurgery (SRS) is an established treatment for brain metastases, yet little is known about SRS for neuroendocrine tumors given their unique natural history. Objective: To determine outcomes and toxicity from SRS in patients with brain metastases arising from neuroendocrine tumors. Methods: Thirty-three patients with brain metastases from neuroendocrine tumors who underwent SRS were retrospectively reviewed. Median age was 61 years and median Karnofsky performance status was 80. Primary sites were lung (87.9%), cervix (6.1%), esophagus (3%), and prostate (3%). Ten patients (30.3%) received upfront SRS, 7 of whom had neuroendocrine tumors other than small cell lung carcinoma. Kaplan-Meier survival and Cox regression analyses were performed to determine prognostic factors for survival. Results: With median follow-up after SRS of 5.3 months, local and distant brain recurrence developed in 5 patients (16.7%) and 20 patients (66.7%), respectively. Median overall survival (OS) after SRS was 6.9 months. Patients with progressive disease per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) criteria at 4 to 6 weeks after SRS had shorter median time to developing recurrence at a distant site in the brain and shorter OS than patients without progressive disease: 1.4 months and 3.3 months vs 11.4 months and 12 months, respectively (both P < .001). Toxicity was more likely in lesions of small cell histology than in lesions of other neuroendocrine tumor histology, 15.7% vs 3.3% (P = .021). No cases of grade 3 to 5 necrosis occurred. Conclusions: SRS is an effective treatment option for patients with brain metastases from neuroendocrine tumors with excellent local control despite slightly higher toxicity rates than expected. Progressive disease at 4 to 6 weeks after SRS portends a poor prognosis.

16.
Adv Radiat Oncol ; 2(3): 301-307, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29114596

RESUMO

Purpose: Intensity-modulated proton therapy (IMPT) is an emerging advanced radiation technique. Although dosimetric studies demonstrate the superiority of IMPT for improving target conformity and reducing unnecessary dose to critical normal tissues, clinical experience is limited. We aim to describe our preliminary experience implementing IMPT concurrently with chemotherapy in esophageal carcinoma (EC). Methods and materials: From May 2011 through February 2016, 19 patients with EC (median age, 73 years) were treated with IMPT using 180 to 250 MV protons with a median dose of 50.4 Gy relative biological effectiveness in 28 fractions concurrently with chemotherapy. Beam arrangement was most commonly in the posteroanterior and bilateral posterior oblique beams. The Kaplan-Meier method was used to assess survival outcomes. Treatment-related toxicities were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Results: Single-field and multifield optimization was performed in 13 and 6 patients, respectively. The average gross tumor volume was 69.1 cm3; mean lung and heart dose delivered were 4.94 and 7.86 Gy, respectively; and the maximal spinal cord dose was 32.81 Gy. Clinical complete response was achieved in 84%. Only 4 patients underwent surgery. The most common grade 3 acute toxicities were esophagitis and fatigue (3 patients). Grade 3 esophageal stricture occurred in 1 patient. With a median follow-up time of 17 months, overall survival was 39.2 months, with 1-year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates of 100%, 88.8%, and 72.9%, respectively. Locoregional and distant failures occurred in 3 and 5 patients, respectively. Conclusions: IMPT is an effective treatment for EC, with high tumor response, good local control, and acceptable acute toxicity.

17.
Thorac Cancer ; 8(3): 219-228, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28322515

RESUMO

BACKGROUND: Locoregional failure is a major problem associated with chemoradiation treatment for squamous cell esophageal carcinoma. The aim of this study was to assess the feasibility, efficacy, and toxicity of preoperative radiation (dose > 50 Gy) with platinum-based chemotherapy followed by esophagectomy in locally advanced squamous cell carcinoma. METHODS: Data of patients with cT2-cT4 or node positive squamous cell carcinoma of the esophagus who received trimodality treatment between February 2006 and June 2015 were reviewed. RESULTS: Forty-four patients were treated with intensity-modulated radiation therapy, volumetric-modulated arc therapy or three-dimensional radiation therapy. The median radiation dose was 60 Gy. The average volume of the lungs receiving 10 Gy was 48.1%, 20 Gy was 24.5%, and the average mean lung dose was 14 Gy. After chemoradiation, R0 resection was achieved in 31 patients (71%). Patients who received >60 Gy had a higher pathologic complete remission rate than those in the lower dose group (59.1% vs. 36.4%). R0 resection and radiation dose >60 Gy were associated with better overall survival in Cox proportional hazards regression analysis. The median follow-up duration was 22.4 months and median survival was 25.6 months. Two-year overall, progression-free survival and locoregional control rates were 55.9%, 28.6%, and 56%, respectively. The most common grade 3-4 toxicities were esophagitis (63.6%) and neutropenia (25%). Grade 3-4 postoperative morbidities included surgical wound infection (2.3%), acute renal failure (2.3%), and anastomosis stricture (2.3%). CONCLUSION: Trimodality treatment with a high preoperative radiation dose and chemotherapy yielded a good pathologic complete response rate, and long-term survival with low toxicities.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Terapia Combinada , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Terapia de Salvação
18.
Sci Rep ; 7: 42624, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28211482

RESUMO

The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACT + CCRT and CCRT groups). Survival rates were calculated by Kaplan-Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACT + CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, P = 0.021; 70.3% vs. 54.1%, P < 0.001; 81.9% vs. 67.3%, P < 0.001, respectively). Although the rates of grade 3-4 leucopenia and mucositis were higher in NACT + CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/terapia , Quimiorradioterapia/métodos , Terapia Combinada/métodos , Neoplasias Nasofaríngeas/terapia , Necrose/terapia , Terapia Neoadjuvante/métodos , Adulto , Carcinoma/diagnóstico por imagem , Carcinoma/mortalidade , Carcinoma/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Quimiorradioterapia/efeitos adversos , Feminino , Seguimentos , Humanos , Leucopenia/etiologia , Leucopenia/mortalidade , Leucopenia/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Mucosite/mortalidade , Mucosite/patologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Necrose/diagnóstico por imagem , Necrose/mortalidade , Necrose/patologia , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Cooperação do Paciente , Estudos Retrospectivos , Análise de Sobrevida
19.
J Radiat Res ; 58(4): 509-516, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28204596

RESUMO

Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I-IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P < 0.001). Our study demonstrated the clinical significance of the plasma EBV DNA level at specific time points, as well as of the dynamic changes in the EBV DNA level. Disappearance of plasma EBV DNA after treatment was associated with better survival.


Assuntos
Carcinoma/sangue , DNA Viral/sangue , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/sangue , Adolescente , Adulto , Criança , Demografia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Prognóstico , Resultado do Tratamento , Adulto Jovem
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