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1.
Anticancer Res ; 40(4): 2053-2057, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234896

RESUMO

BACKGROUND: The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. PATIENTS AND METHODS: We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. RESULTS: The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. CONCLUSION: SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.


Assuntos
Androgênios/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Neoplasias da Próstata/radioterapia , Radiocirurgia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Fracionamento da Dose de Radiação , Trato Gastrointestinal/patologia , Humanos , Masculino , Terapia Neoadjuvante , Próstata/patologia , Próstata/efeitos da radiação , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Planejamento da Radioterapia Assistida por Computador , Medição de Risco , Resultado do Tratamento
2.
Cancer Radiother ; 24(2): 88-92, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32156457

RESUMO

PURPOSE: The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: All consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. RESULTS: A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54-66) and 48Gy (44.8-56) delivered in 30 (27-35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3-31.3) with a median V40 of 3.3% (0.0-25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9-4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). CONCLUSION: We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Tolerância a Radiação , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Feminino , Fluoruracila/administração & dosagem , Coração/efeitos da radiação , Humanos , Leucovorina/administração & dosagem , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
3.
Cancer Radiother ; 24(2): 99-105, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32201058

RESUMO

PURPOSE: During radiotherapy (RT) for prostate cancer (PCa), interfraction and intrafraction movements can lead to decreased target dose coverage and unnecessary over-exposure of organs at risk. New image-guided RT techniques accuracy allows planning target volume (PTV) margins reduction. We aim to assess the feasibility of a kilovoltage intrafraction monitoring (KIM) to track the prostate during RT. METHODS AND MATERIALS: Between November 2017 and April 2018, 44 consecutive patients with PCa were included in an intrafraction prostate motion study using the Truebeam Auto Beam Hold® tracking system (Varian Medical Systems, United State) triggered by gold fiducials localization on kilovoltage (kV) imaging. A 5-mm PTV was considered. A significant gating event (SGE) was defined as the occurrence of an automatic beam interruption requiring patient repositioning following the detection of one fiducial outside a 5-mm target area around the marker during more than 45seconds. RESULTS: Six patients could not benefit from the KIM because of technical issues (loss of one fiducial marker=1, hip prosthesis=4, morbid obesity causing table movements=1). The mean rate of SGE per patient was 14±19%, and the fraction average delivery time was increased by 146±86seconds. For a plan of 39 fractions of 2Gy, the additional radiation dose increased by 0.13±0.09Gy. The mean rates of SGE were 2% and 18% (P=0.002) in patients with planned fraction<90 and>90seconds respectively, showing that duration of the session strongly interfered with prostate intrafraction movements. No other significant clinical and technical parameter was correlated with the occurrence of SGE. CONCLUSION: Automated intrafraction kV imaging can effectively perform autobeam holds due to intrafraction movement of the prostate in the large majority of patients. The additional radiation dose and delivery time are acceptable. This technique may be a cost-effective alternative to electromagnetic transponder guidance.


Assuntos
Movimentos dos Órgãos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Marcadores Fiduciais , Ouro , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Glândulas Seminais , Fatores de Tempo , Incerteza
4.
Cancer Radiother ; 24(2): 153-158, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32089502

RESUMO

The radiobiological concepts described for conventional doses per fraction (1.8 to 2Gy) seem difficult to translate to high doses per fraction radiobiology. In fact, specific mechanisms are involved during high dose per fraction irradiation, involving vascular microenvironment damage and anti tumor immune response. The "5R's" of "classical" radiobiology (factors influencing the response of healthy or cancer cells to irradiation) seem to play a less important role in case of high doses per fraction. In addition, applicability of the linear quadratic model in this context is debated. It is therefore difficult to obtain reliable equivalent doses, hence the importance of including our patients in clinical trials, especially in case of concomitant systemic treatments. In addition to stereotactic radiotherapy, flash irradiations defined by a dose rate approximately 2000 times faster than "conventional" irradiation can also deliver high doses per fraction, with a much better tolerance for normal tissue without loss of anti tumor efficacy. Finally, availability of robust prospective data is a prerequisite to answer the question of short and long-term risk/benefit ratio of these different irradiation techniques.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias/radioterapia , Radiobiologia , Radiocirurgia , Vasos Sanguíneos/efeitos da radiação , Ciclo Celular/efeitos da radiação , Morte Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Imunidade Celular/efeitos da radiação , Modelos Teóricos , Consumo de Oxigênio , Tolerância a Radiação , Radiobiologia/legislação & jurisprudência , Radioimunoterapia/métodos , Radiocirurgia/legislação & jurisprudência , Medição de Risco
5.
Anticancer Res ; 40(2): 977-981, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014942

RESUMO

BACKGROUND/AIM: The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points). PATIENTS AND METHODS: We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy). RESULTS: All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal. CONCLUSION: In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Irradiação Craniana , Neoplasias Pulmonares/patologia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Irradiação Craniana/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
6.
Br J Radiol ; 93(1107): 20190807, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003574

RESUMO

After years of lethargy, studies on two non-conventional microstructures in time and space of the beams used in radiation therapy are enjoying a huge revival. The first effect called "FLASH" is based on very high dose-rate irradiation (pulse amplitude ≥106 Gy/s), short beam-on times (≤100 ms) and large single doses (≥10 Gy) as experimental parameters established so far to give biological and potential clinical effects. The second effect relies on the use of arrays of minibeams (e.g., 0.5-1 mm, spaced 1-3.5 mm). Both approaches have been shown to protect healthy tissues as an endpoint that must be clearly specified and could be combined with each other (e.g., minibeams under FLASH conditions). FLASH depends on the presence of oxygen and could proceed from the chemistry of peroxyradicals and a reduced incidence on DNA and membrane damage. Minibeams action could be based on abscopal effects, cell signalling and/or migration of cells between "valleys and hills" present in the non-uniform irradiation field as well as faster repair of vascular damage. Both effects are expected to maintain intact the tumour control probability and might even preserve antitumoural immunological reactions. FLASH in vivo experiments involving Zebrafish, mice, pig and cats have been done with electron beams, while minibeams are an intermediate approach between X-GRID and synchrotron X-ray microbeams radiation. Both have an excellent rationale to converge and be applied with proton beams, combining focusing properties and high dose rates in the beam path of pencil beams, and the inherent advantage of a controlled limited range. A first treatment with electron FLASH (cutaneous lymphoma) has recently been achieved, but clinical trials have neither been presented for FLASH with protons, nor under the minibeam conditions. Better understanding of physical, chemical and biological mechanisms of both effects is essential to optimize the technical developments and devise clinical trials.


Assuntos
Tratamentos com Preservação do Órgão/métodos , Terapia com Prótons/métodos , Animais , Gatos , Proliferação de Células , Dano ao DNA , Reparo do DNA , Fracionamento da Dose de Radiação , Linfoma Cutâneo de Células T/radioterapia , Camundongos , Órgãos em Risco/efeitos da radiação , Oxigênio , Consumo de Oxigênio , Lesões por Radiação/prevenção & controle , Tolerância a Radiação , Radiometria/métodos , Neoplasias Cutâneas/radioterapia , Análise Espaço-Temporal , Suínos , Peixe-Zebra
7.
Nat Commun ; 11(1): 573, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996677

RESUMO

Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.


Assuntos
Fracionamento da Dose de Radiação , Processamento de Imagem Assistida por Computador/métodos , Oxigênio/química , Radioterapia/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Engenharia Biomédica/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Xenoenxertos , Humanos , Hipóxia , Metaloporfirinas , Camundongos , Pressão Parcial , Aceleradores de Partículas
8.
Br J Radiol ; 93(1107): 20190845, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31904261

RESUMO

OBJECTIVES: The purpose of this study is to investigate the dosimetric effect and clinical impact of delivering a focal radiotherapy boost dose to multiparametric MRI (mp-MRI)-defined dominant intraprostatic lesions (DILs) in prostate cancer using proton therapy. METHODS: We retrospectively investigated 36 patients with pre-treatment mp-MRI and CT images who were treated using pencil beam scanning (PBS) proton radiation therapy to the whole prostate. DILs were contoured on co-registered mp-MRIs. Simultaneous integrated boost (SIB) plans using intensity-modulated proton therapy (IMPT) were created based on conventional whole-prostate-irradiation for each patient and optimized with additional DIL coverage goals and urethral constraints. DIL dose coverage and organ-at-risk (OAR) sparing were compared between conventional and SIB plans. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were estimated to evaluate the clinical impact of the SIB plans. RESULTS: Optimized SIB plans significantly escalated the dose to DILs while meeting OAR constraints. SIB plans were able to achieve 125, 150 and 175% of prescription dose coverage in 74, 54 and 17% of 36 patients, respectively. This was modeled to result in an increase in DIL TCP by 7.3-13.3% depending on α/ß and DIL risk level. CONCLUSION: The proposed mp-MRI-guided DIL boost using proton radiation therapy is feasible without violating OAR constraints and demonstrates a potential clinical benefit by improving DIL TCP. This retrospective study suggested the use of IMPT-based DIL SIB may represent a strategy to improve tumor control. ADVANCES IN KNOWLEDGE: This study investigated the planning of mp-MRI-guided DIL boost in prostate proton radiation therapy and estimated its clinical impact with respect to TCP and NTCP.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Reirradiação/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Próstata/diagnóstico por imagem , Próstata/efeitos da radiação , Neoplasias da Próstata/patologia , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Uretra/diagnóstico por imagem
9.
Br J Radiol ; 93(1107): 20190584, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977241

RESUMO

OBJECTIVE: We compared the sensitivity of intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) plans to setup uncertainties in locally advanced non-small cell lung cancer (NSCLC) using probabilistic scenarios. METHODS: Minimax robust (MM) and planning target volume (PTV) optimised IMPT and VMAT nominal plans were created with physical dose of 70 Gy in 35 fractions in 10 representative patients. Using population data of setup errors, a fractionated treatment course was simulated, summed (Dsum) and compared to the nominal plan. Three treatment-course simulations were done for each plan. Target robustness criteria were: dose deviation of ≤5% to clinical target volume (CTV) D98% and CTV V95% ≥ 99.9%. Voxelwise simulation repeatability was analysed using Bland-Altman plots. Acceptable limits of agreement were 2% of the prescription dose. RESULTS: All Dsum met target robustness criteria. While fraction VMAT and MM-IMPT doses were excellent, simulated fraction doses in PTV-IMPT were suboptimal. Almost all (>99%) of VMAT and MM-IMPT fraction doses met both target robustness criteria. For PTV-IMPT, only 96.9 and 80.3% of fractions met CTVD98% and V95% criteria respectively. Simulation repeatability was excellent (limits of agreement range: 0.41-1.1 Gy) with strong positive correlations. CONCLUSION: When considering the whole treatment course, setup errors do not influence robustness irrespective of planning techniques used. However, on a fraction level, VMAT and MM-IMPT plans are superior compared to PTV-IMPT plans. ADVANCES IN KNOWLEDGE: Probabilistic analysis provides a fast and practical method for evaluating VMAT and IMPT plan sensitivity against setup uncertainty. VMAT and robust-optimised IMPT plans have comparable sensitivity to setup uncertainties in conventionally fractionated treatment for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Erros de Configuração em Radioterapia , Radioterapia de Intensidade Modulada/métodos , Incerteza , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Br J Radiol ; 93(1108): 20190792, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31939310

RESUMO

OBJECTIVES: To evaluate the feasibility and optimal restricted angle of the complete-directional-complete block (CDCB) technique in helical tomotherapy (HT) by including regional nodal irradiation (RNI) with the internal mammary node (IMN) in left-sided breast cancer. METHODS: Ten left-sided breast cancer patients treated with 50 Gy in 25 fractions were compared with five-field intensity-modulated radiation therapy (5F-IMRT) and six types of HT plans. In the HT plans, complete block (CB), organ-based directional block (OBDB) and CDCB with different restricted angles were used. RESULTS: The conformity index (CI) between the CDCB0,10,15,20 and 5F-IMRT groups was similar. Compared to CB, OBDB and 5F-IMRT, CDCB20 resulted in a decreased ipsilateral mean lung dose. The low-dose region (V5) of the ipsilateral lung in OBDB (84.0%) was the highest among all techniques (p < 0.001). The mean dose of the heart in CB was significantly reduced (by 11.5-22.4%) compared with other techniques. The V30 of the heart in CDCB20 (1.9%) was significantly lower than that of CB, OBDB and 5F-IMRT. Compared to the mean dose of the left anterior descending (LAD) artery of 5F-IMRT (27.0 Gy), CDCB0, CDCB10, CDCB15, CDCB20 and OBDB reduced the mean dose effectively by 31.7%, 38.3%, 39.6%, 42.0 and 56.2%, respectively. Considering the parameters of the organs-at-risk (OARs), CDCB10,15,20 had higher expectative values than the other techniques (p = 0.01). CONCLUSIONS: HT with the CDCB technique is feasible for treating left-sided breast cancer patients. The CDCB10-20 techniques not only achieved similar planning target volume coverage, homogeneity and dose conformity but also allowed better sparing of the heart and bilateral lungs. ADVANCES IN KNOWLEDGE: For left-sided breast cancer patients whose RNI field includes the IMN, heart avoidance is an important issue. The CDCB technique achieved good PTV coverage, homogeneity and dose conformity and allowed better sparing of the mean dose of the lung, the LAD artery, and the heart and reduced the V30 of the heart.


Assuntos
Coração/efeitos da radiação , Pulmão/efeitos da radiação , Irradiação Linfática/métodos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Feminino , Humanos , Órgãos em Risco/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Unilaterais da Mama/diagnóstico por imagem
11.
Br J Radiol ; 93(1108): 20190789, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971829

RESUMO

OBJECTIVE: Prostate stereotactic ablative radiotherapy (SABR) delivers large doses using a fast dose rate. This amplifies the effect geometric uncertainties have on normal tissue dose. The aim of this study was to determine whether the treatment dose-volume histogram (DVH) agrees with the planned dose to organs at risk (OAR). METHODS: 41 low-intermediate risk prostate cancer patients were treated with SABR using a linac based technique. Dose prescribed was 35 Gy in five fractions delivered on alternate days, planned using volumetric modulated arc therapy (VMAT) with 10X flattening filter free (FFF). On treatment, prostate was matched to fiducial markers on cone beam CT (CBCT). OAR were retrospectively delineated on 205 pre-treatment CBCT images. Daily CBCT contours were overlaid on the planning CT for dosimetric analysis. Verification plan used to evaluate the daily DVH for each structure. The daily doses received by OAR were recorded using the D%. RESULTS: The median rectum and bladder volumes at planning were 67.1 cm3 (interquartile range 56.4-78.2) and 164.4 cm3 (interquartile range 120.3-213.4) respectively. There was no statistically significant difference in median rectal volume at each of the five treatment scans compared to the planning scan (p = 0.99). This was also the case for median bladder volume (p = 0.79). The median dose received by rectum and bladder at each fraction was higher than planned, at the majority of dose levels. For rectum the increase ranged from 0.78-1.64Gy and for bladder 0.14-1.07Gy. The percentage of patients failing for rectum D35% < 18 Gy (p = 0.016), D10% < 28 Gy (p = 0.004), D5% < 32 Gy (p = 0.0001), D1% < 35 Gy (p = 0.0001) and bladder D1% < 35 Gy (p = 0.001) at treatment were all statistically significant. CONCLUSION: In this cohort of prostate SABR patients, we estimate the OAR treatment DVH was higher than planned. This was due to rectal and bladder organ variation. ADVANCES IN KNOWLEDGE: OAR variation in prostate SABR using a FFF technique, may cause the treatment DVH to be higher than planned.


Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Idoso , Fracionamento da Dose de Radiação , Humanos , Masculino , Próstata , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Reto/diagnóstico por imagem , Estudos Retrospectivos , Bexiga Urinária/diagnóstico por imagem
12.
Eur J Endocrinol ; 182(3): 275-284, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917680

RESUMO

Background: If biochemical control of acromegaly is not achieved by operation and medication, radiotherapy may be indicated. Objective: To describe fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) regarding excess of IGF-1 and pituitary function. Design and methods: A retrospective analysis of 352 patients (4126 patient-years) from the German Acromegaly Registry was performed. Follow-up was 1.0-45.1 years after radiotherapy. Therapeutic success was defined by low or normal IGF-1 according to center-specific reference ranges without (= remission) or on (= controlled disease) suppressive medication. Results: Time between radiotherapy and last follow-up was 13.0 ± 8.2 years for FRT (n = 233) and 8.9 ± 5.0 years for SRS (n = 119, P < 0.001). Median (IQR) basal growth hormone before radiotherapy was 6.3 (2.9-16.2) ng/mL for FRT and 3.5 (1.8-6.9) ng/mL for SRS (P < 0.001). Mean time in uncontrolled state was 3.0 years after FRT and 2.1 years after SRS (95% CI for the difference is 0.1 to 1.6 years, P = 0.021). The 10-year calculated remission rate was 48% for FRT and 52% for SRS (95% CI for the difference is -18 to 26% age points, P = 0.74) and the respective controlled disease rate was 23 and 26%. The odds ratio for adrenocorticotropic or thyreotropic insufficiency was 0.54 (95% CI: 0.30-1.00, P = 0.049) in SRS compared to FRT patients. Conclusion: Both after FRT and SRS about 75% of patients with acromegaly are in remission or controlled after 10 years. A slightly faster achievement of target values was observed after SRS. The rate of pituitary insufficiency in FRT patients is significantly higher.


Assuntos
Acromegalia/radioterapia , Acromegalia/cirurgia , Adenoma/radioterapia , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/radioterapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Radiocirurgia/métodos , Adulto , Estudos de Coortes , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Alemanha , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Br J Radiol ; 93(1107): 20190332, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944824

RESUMO

Proton minibeam therapy (PMBT) is a form of spatially fractionated radiotherapy wherein broad beam radiation is replaced with segmented minibeams-either parallel, planar minibeam arrays generated by a multislit collimator or scanned pencil beams that converge laterally at depth to create a uniform dose layer at the tumor. By doing so, the spatial pattern of entrance dose is considerably modified while still maintaining tumor dose and efficacy. Recent studies using computational modeling, phantom experiments, in vitro and in vivo preclinical models, and early clinical feasibility assessments suggest that unique physical and biological attributes of PMBT can be exploited for future clinical benefit. We outline some of the guiding principle of PMBT in this concise overview of this emerging area of preclinical and clinical research inquiry.


Assuntos
Criatividade , Neoplasias/radioterapia , Terapia com Prótons/métodos , Absorção de Radiação , Algoritmos , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Humanos , Método de Monte Carlo , Tratamentos com Preservação do Órgão , Órgãos em Risco , Radiobiologia , Radiometria
14.
Int J Radiat Oncol Biol Phys ; 106(3): 525-533, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610249

RESUMO

PURPOSE: Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site. METHODS AND MATERIALS: A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive. RESULTS: Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed. CONCLUSIONS: A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.


Assuntos
Braquiterapia/métodos , Micrometástase de Neoplasia/radioterapia , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Braquiterapia/efeitos adversos , Braquiterapia/estatística & dados numéricos , Estudos de Coortes , Bases de Dados Factuais , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Calicreínas/sangue , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de Progressão , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia Conformacional/estatística & dados numéricos , Radioterapia de Intensidade Modulada/estatística & dados numéricos , Reino Unido
15.
World Neurosurg ; 133: e252-e258, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31505283

RESUMO

BACKGROUND: Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. METHODS: Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. RESULTS: From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P = 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. CONCLUSIONS: FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Carcinoma/cirurgia , Terapia Combinada , Irradiação Craniana , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos
16.
Int J Radiat Oncol Biol Phys ; 106(2): 255-260, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654784

RESUMO

PURPOSE: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. METHODS AND MATERIALS: NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher's exact tests. RESULTS: Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03). CONCLUSIONS: This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.


Assuntos
Neoplasias Encefálicas/radioterapia , Transtornos Cognitivos/prevenção & controle , Irradiação Craniana/normas , Melhoria de Qualidade , Radiocirurgia/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Intervalos de Confiança , Irradiação Craniana/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/normas
17.
Int J Radiat Oncol Biol Phys ; 106(2): 340-348, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655197

RESUMO

PURPOSE: Local persistence and relapse of disease in the gross tumor volume (GTV) account for the majority of treatment failures after standard chemoradiation therapy. The primary objective of this phase 1 trial was to define the maximum tolerated dose (MTD) of a hyperfractionated radiation therapy (HFRT) boost to the GTV with concurrent weekly paclitaxel and carboplatin after standard-dose chemoradiation therapy, using image guided intensity modulated radiation therapy techniques. METHODS AND MATERIALS: Eligible patients were given weekly doses of paclitaxel (45 mg/m2) and carboplatin (area under the curve 1.5) for 5 weeks with concurrent radiation therapy (50 Gy), immediately followed by an HFRT boost to the GTV with the same chemotherapy regimen. The boost doses were escalated in increments of 7.2 Gy delivered in 6 twice-daily fractions of 1.2 Gy using a modified Fibonacci design. Once the MTD was established, additional patients were treated at that dose to determine the safety. RESULTS: Thirty-one patients fulfilled the inclusion criteria. The incidence of dose-limiting toxicity was 0 of 3, 0 of 3, 0 of 3, 1 of 6 (grade 4 esophagitis), 0 of 3, and 2 of 3 (1 case each of grade 5 esophageal fistula and grade 3 pneumotitis) at 7.2, 14.4, 21.6, 28.8, 36, and 43.2 Gy, respectively, indicating an MTD of 36 Gy. Ten patients treated with this MTD showed no dose-limiting toxicities. The most common acute grade 3 or greater toxicities were esophagitis (26%) and neutropenia (19%). Late toxicity of grade 2 esophageal stricture occurred in 4 patients. The overall response rate was 84% (95% confidence interval, 42%-93%) in the entire cohort. The 1-year local control rate was 100% among those receiving a cumulative dose of the MTD or greater. CONCLUSIONS: The MTD of the HFRT boost after standard chemoradiation therapy in the setting of concurrent chemotherapy was 36 Gy, resulting in the cumulative tumor dose of 86 Gy in patients primarily with advanced intrathoracic/cervical esophageal squamous cell carcinomas and not adenocarcinomas of the gastroesophageal junction. A phase 2 study to further evaluate this regimen is underway.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Dose Máxima Tolerável , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Carboplatina/administração & dosagem , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Fístula Esofágica/etiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Paclitaxel/administração & dosagem , Pneumonite por Radiação/etiologia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Carga Tumoral
18.
Br J Radiol ; 93(1107): 20190572, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31651185

RESUMO

OBJECTIVE: Approximately 70 patients with large and bulky tumors refractory to prior treatments were treated with photon spatially fractionated GRID radiation (SFGRT). We identified 10 additional patients who clinically needed GRID but could not be treated with photons due to adjacent critical organs. We developed a proton SFGRT technique, and we report treatment of these 10 patients. METHODS: Subject data were reviewed for clinical results and dosimetric data. 50% of the patients were metastatic at the time of treatment and five had previous photon radiation to the local site but not via GRID. They were treated with 15-20 cobalt Gray equivalent using a single proton GRID field with an average beamlet count of 22.6 (range 7-51). 80% received an average adjuvant radiation dose to the GRID region of 40.8Gy (range 13.7-63.8Gy). Four received subsequent systemic therapy. RESULTS: The median follow-up time was 5.9 months (1.1-18.9). At last follow-up, seven patients were alive and three had died. Two patients who had died from metastatic disease had local shrinkage of tumor. Of those alive, four had complete or partial response, two had partial response but later progressed, and one had no response. For all patients, the tumor regression/local symptom improvement rate was 80%. 50% had acute side-effects of grade1/2 only and all were well-tolerated. CONCLUSION: In circumstances where patients cannot receive photon GRID, proton SFGRT is clinically feasible and effective, with a similar side-effect profile. ADVANCES IN KNOWLEDGE: Proton GRID should be considered as a treatment option earlier in the disease course for patients who cannot be treated by photon GRID.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/métodos , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Seguimentos , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Órgãos em Risco/diagnóstico por imagem , Fótons/uso terapêutico , Resultado do Tratamento
19.
Int J Radiat Oncol Biol Phys ; 106(2): 261-268, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628959

RESUMO

PURPOSE: In patients with spinal instability, cord compression, or neurologic deficits, the standard of care is surgery followed by radiation therapy (RT). Recurrence rates after conventional RT remain high. The purpose of this study is to prospectively examine the efficacy of postoperative stereotactic body RT (SBRT) in patients who have undergone surgical intervention for spine metastases. We hypothesize that postoperative SBRT to the spine would be associated with higher local control than historical rates after conventional RT. METHODS AND MATERIALS: Thirty-five adult patients with a Karnofsky Performance Status score ≥40 and spine metastases from solid tumors with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. Thirty-three patients were treated. Two patients underwent treatment to 2 target volumes for a total of 35 target volumes. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurological examinations and computed tomography and/or magnetic resonance imaging every 3 months. Neurologic function was assessed at the same time points using the American Spinal Injury Association (ASIA) impairment score. Pain was rated according to the 10-point visual analogue scale and MD Anderson Cancer Center brief pain index. Toxicity was recorded according to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4. The primary objective was the rate of radiographic local recurrence at 12 months after completion of SBRT. RESULTS: Patient characteristics were as follows: 34.3% had radioresistant primaries; 71.4% were ASIA E and the remainder ASIA D; and the median baseline Karnofsky Performance Status score was 70 (range, 50-100). Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval, 76%-98%). The median time to recurrence in these 3 patients was 3.5 months (range, 3.4-5.8 months), all had radiosensitive tumors, and all recurrences were epidural. No patients experienced wound dehiscence, hardware failure, or spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range, 0-9.4 months). CONCLUSIONS: This prospective study of postoperative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared with conventional RT; however, a formal comparative study is warranted.


Assuntos
Recidiva Local de Neoplasia , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Adulto , Idoso , Dor do Câncer/diagnóstico , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Exame Neurológico/estatística & dados numéricos , Medição da Dor/métodos , Período Pós-Operatório , Estudos Prospectivos , Tolerância a Radiação , Radiocirurgia/efeitos adversos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Int J Radiat Oncol Biol Phys ; 106(2): 291-299, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629838

RESUMO

PURPOSE: We evaluated the use of high dose-rate-like stereotactic body radiation therapy (SBRT) retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. METHODS AND MATERIALS: From 2009 to 2018, 50 patients with biopsy-proven recurrent prostate cancer >2 years after prior treatment were retreated with a high dose-rate-like dose of 3400 cGy over 5 fractions. Previous radiation therapy dose measured 75.6 Gy (64.8-81.0) and median salvage interval was 8.1 years (32-241 mo.). Eighty-three percent of patients had Gleason score 7 or higher disease at retreatment. Those with preexisting toxicity >grade 1 from their prior course were excluded. The planning target volume was comprised of the clinical target volume (prostate + any contiguous extension only) with no additional expansion. Toxicity assessment used CTCAE v.3.0 criteria. RESULTS: Median follow-up was 44 months (3-110). Median pre-SBRT salvage baseline prostate specific antigen (PSA) of 3.97 ng/mL decreased to 0.6 ng/mL and 0.16 ng/mL at 1 and 5 years in nonrelapsed patients, respectively. Actuarial 5-year biochemical disease-free survival (DFS) measured 60%, with corresponding 5-year actuarial local, distant, and salvage androgen deprivation therapy free rates of 94%, 89%, and 69%, respectively. Actuarial 5-year biochemical DFS measured 78% if PSA at salvage was <6.92 ng/mL versus 12% with ≥6.92 ng/mL (P = .0001). Toxicity was primarily in the GU domain, with an 8% 5-year actuarial rate of grade 3+, 3% when limited to salvage of "conventional external beam only" local relapse. No gastrointestinal (GI) toxicity >grade 1 occurred. Of the 30% sexually potent at the time of salvage, 82% subsequently lost potency. CONCLUSIONS: SBRT salvage of local prostate recurrence in previously irradiated patients appears clinically feasible in this challenging group. It demonstrates favorable PSA and DFS response, typically deferring the need for salvage androgen deprivation therapy or other treatment by over 5 years, with low GU and GI toxicity.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Reirradiação/métodos , Terapia de Salvação/métodos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Biópsia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Ereção Peniana/efeitos da radiação , Próstata , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Radiocirurgia/efeitos adversos , Reirradiação/efeitos adversos , Terapia de Salvação/efeitos adversos , Fatores de Tempo
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