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Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure refractory to medical therapy. However, the incidence of ventricular arrhythmias (VAs) is high in this population, both in the acute and delayed phases after implantation. About one-third of patients implanted with an LVAD will experience sustained VAs, predisposing these patients to worse outcomes and complicating patient management. The combination of pre-existing myocardial substrate and complex electrical remodeling after LVAD implantation account for the high incidence of VAs observed in this population. LVAD patients presenting VAs refractory to antiarrhythmic therapy and catheter ablation procedures are not rare. In such patients, treatment options are extremely limited. Stereotactic body radiation therapy (SBRT) is a technique that delivers precise and high doses of radiation to highly defined targets, reducing exposure to adjacent normal tissue. Cardiac SBRT has recently emerged as a promising alternative with a growing number of case series reporting the effectiveness of the technique in reducing the VA burden in patients with arrhythmias refractory to conventional therapies. The safety profile of cardiac SBRT also appears favorable, even though the current clinical experience remains limited. The use of cardiac SBRT for the treatment of refractory VAs in patients implanted with an LVAD are even more scarce. This review summarizes the clinical experience of cardiac SBRT in LVAD patients and describes technical considerations related to the implementation of the SBRT procedure in the presence of an LVAD.
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Insuficiência Cardíaca , Coração Auxiliar , Radiocirurgia , Taquicardia Ventricular , Humanos , Radiocirurgia/efeitos adversos , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Arritmias Cardíacas/cirurgia , Insuficiência Cardíaca/terapia , Resultado do Tratamento , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/radioterapia , Taquicardia Ventricular/cirurgiaRESUMO
PURPOSE: Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity. METHOD: A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose). RESULTS: By limiting the urethra Dmax to 90GyEQD2 (α/ß = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years. CONCLUSION: US-SBRT techniques limiting maximum doses to urethra below a 90GyEQD2 (α/ß = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.
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Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Uretra , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Recidiva Local de Neoplasia/etiologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/etiologia , Sistema UrogenitalRESUMO
PURPOSE: Around 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy (RP). The aim of this review is to describe both toxicity and oncological outcomes following stereotactic body radiation therapy (SBRT) delivered to the prostate bed (PB). METHOD: In april 2023, we performed a systematic review of studies published in MEDLINE or ClinicalTrials.gov according to Preferred Reporting Items for Systematic Reviews, using the keywords "stereotactic radiotherapy" AND "postoperative" AND "prostate cancer". RESULTS: A total of 14 studies assessing either adjuvant or salvage SBRT to the whole PB or macroscopic local recurrence (MLR) within the PB, and SBRT on radiorecurrent MLR within the PB were included. Doses delivered to either whole PB or MLR between 30 to 40 Gy are associated with a low rate of late grade ≥ 2 genitourinary (GU) toxicity, ranging from 2.2 to 15.1%. Doses above 40 Gy are associated with increased rate of late GU toxicity, raising up to 38%. Oncological outcomes should be interpreted with caution, due to both short follow-up, heterogeneous populations and androgen deprivation therapy (ADT) use. CONCLUSION: PB or MLR SBRT delivered at doses up to 40 Gy appears safe with relatively low late severe GU toxicity rates. Caution is needed with dose-escalated RT schedules above 40 Gy. Further prospective trials are eagerly awaited in this disease setting.
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Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/tratamento farmacológico , Próstata , Radiocirurgia/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Prostatectomia , Terapia de SalvaçãoRESUMO
PURPOSE: To evaluate deep learning (DL)-based deformable image registration (DIR) for dose accumulation during radiotherapy of prostate cancer patients. METHODS AND MATERIALS: Data including 341 CBCTs (209 daily, 132 weekly) and 23 planning CTs from 23 patients was retrospectively analyzed. Anatomical deformation during treatment was estimated using free-form deformation (FFD) method from Elastix and DL-based VoxelMorph approaches. The VoxelMorph method was investigated using anatomical scans (VMorph_Sc) or label images (VMorph_Msk), or the combination of both (VMorph_Sc_Msk). Accumulated doses were compared with the planning dose. RESULTS: The DSC ranges, averaged for prostate, rectum and bladder, were 0.60-0.71, 0.67-0.79, 0.93-0.98, and 0.89-0.96 for the FFD, VMorph_Sc, VMorph_Msk, and VMorph_Sc_Msk methods, respectively. When including both anatomical and label images, VoxelMorph estimated more complex deformations resulting in heterogeneous determinant of Jacobian and higher percentage of deformation vector field (DVF) folding (up to a mean value of 1.90% in the prostate). Large differences were observed between DL-based methods regarding estimation of the accumulated dose, showing systematic overdosage and underdosage of the bladder and rectum, respectively. The difference between planned mean dose and accumulated mean dose with VMorph_Sc_Msk reached a median value of +6.3 Gy for the bladder and -5.1 Gy for the rectum. CONCLUSION: The estimation of the deformations using DL-based approach is feasible for male pelvic anatomy but requires the inclusion of anatomical contours to improve organ correspondence. High variability in the estimation of the accumulated dose depending on the deformable strategy suggests further investigation of DL-based techniques before clinical deployment.
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Aprendizado Profundo , Neoplasias da Próstata , Planejamento da Radioterapia Assistida por Computador , Humanos , Masculino , Tomografia Computadorizada de Feixe Cônico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Dosagem RadioterapêuticaRESUMO
Radiotherapy is one of the main treatments for localized head and neck (HN) cancer. To design a personalized treatment with reduced radio-induced toxicity, accurate delineation of organs at risk (OAR) is a crucial step. Manual delineation is time- and labor-consuming, as well as observer-dependent. Deep learning (DL) based segmentation has proven to overcome some of these limitations, but requires large databases of homogeneously contoured image sets for robust training. However, these are not easily obtained from the standard clinical protocols as the OARs delineated may vary depending on the patient's tumor site and specific treatment plan. This results in incomplete or partially labeled data. This paper presents a solution to train a robust DL-based automated segmentation tool exploiting a clinical partially labeled dataset. We propose a two-step workflow for OAR segmentation: first, we developed longitudinal OAR-specific 3D segmentation models for pseudo-contour generation, completing the missing contours for some patients; with all OAR available, we trained a multi-class 3D convolutional neural network (nnU-Net) for final OAR segmentation. Results obtained in 44 independent datasets showed superior performance of the proposed methodology for the segmentation of fifteen OARs, with an average Dice score coefficient and surface Dice similarity coefficient of 80.59% and 88.74%. We demonstrated that the model can be straightforwardly integrated into the clinical workflow for standard and adaptive radiotherapy.
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INTRODUCTION: To evaluate the value of image-based texture analysis for predicting progression-free survival (PFS) and overall survival (OS) in patients with metastatic clear cell renal carcinoma (cCCR) treated with nivolumab. METHODS: This retrospective study included 48 patients with metastatic cCCR treated with nivolumab. Nivolumab was used as a second- or third-line monotherapy. Texture analysis of metastatic lesions was performed on CT scanners obtained within 1 month before treatment. Texture features related to the gray-level histogram, gray-level co-occurrence, run-length matrix features, autoregressive model features, and Haar wavelet feature were extracted. Lasso penalized Cox regression analyses were performed to identify independent predictors of PFS and OS. RESULTS: Median PFS and OS were 5.7 and 13.8 months. 39 patients experienced progression and 27 died. The Lasso penalized Cox regression analysis identified three texture parameters as potential predictors of PFS: skewness, S.2.2. Correlat and S.1.1. SumVarnc. Multivariate Cox regression analysis confirmed skewness (HR (95% CI) 1.49 [1.21-1.85], p < 0.001) as an independent predictor of PFS. Regarding OS, the Lasso penalized Cox regression analysis identified three texture parameters as potential predictors of OS: S20SumVarnc, S22Contrast and S22Entropy. Multivariate Cox regression analysis confirmed S22Entropy (HR (95% CI) 1.68 (1.31-2.14), p < 0.001) as an independent predictor of OS. CONCLUSIONS: Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool that predicts oncological outcomes after starting nivolumab treatment.
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Carcinoma de Células Renais , Nivolumabe , Biomarcadores , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Background: Deformable image registration (DIR) is increasingly used in the field of radiation therapy (RT) to account for anatomical deformations. The aims of this paper are to describe the main applications of DIR in RT and discuss current DIR evaluation methods. Methods: Articles on DIR published from January 2000 to October 2018 were extracted from PubMed and Science Direct. Our search was restricted to articles that report data obtained from humans, were written in English, and address DIR methods for RT. A total of 207 articles were selected from among 2506 identified in the search process. Results: At planning, DIR is used for organ delineation using atlas-based segmentation, deformation-based planning target volume definition, functional planning and magnetic resonance imaging-based dose calculation. In image-guided RT, DIR is used for contour propagation and dose calculation on per-treatment imaging. DIR is also used to determine the accumulated dose from fraction to fraction in external beam RT and brachytherapy, both for dose reporting and adaptive RT. In the case of re-irradiation, DIR can be used to estimate the cumulated dose of the two irradiations. Finally, DIR can be used to predict toxicity in voxel-wise population analysis. However, the evaluation of DIR remains an open issue, especially when dealing with complex cases such as the disappearance of matter. To quantify DIR uncertainties, most evaluation methods are limited to geometry-based metrics. Software companies have now integrated DIR tools into treatment planning systems for clinical use, such as contour propagation and fraction dose accumulation. Conclusions: DIR is increasingly important in RT applications, from planning to toxicity prediction. DIR is routinely used to reduce the workload of contour propagation. However, its use for complex dosimetric applications must be carefully evaluated by combining quantitative and qualitative analyses.
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Neoplasias/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Braquiterapia , Humanos , Imageamento por Ressonância Magnética , Ilustração Médica , Imagem Multimodal/métodos , Neoplasias/radioterapia , Dosagem Radioterapêutica , Reirradiação , IncertezaRESUMO
PURPOSE: To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. MATERIALS AND METHODS: In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T2 -weighted sequences (T2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. RESULTS: Three T2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T2 -w contrast, T2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. CONCLUSION: T2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:103-117.
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Interpretação de Imagem Assistida por Computador/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Seguimentos , Humanos , Aumento da Imagem/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/prevenção & controle , Variações Dependentes do Observador , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.
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Nomogramas , Neoplasias da Próstata/radioterapia , Lesões por Radiação/diagnóstico , Sistema Urinário/efeitos da radiação , Micção , Doenças Urológicas/etiologia , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Próstata/urina , Lesões por Radiação/fisiopatologia , Urinálise , Doenças Urológicas/fisiopatologiaRESUMO
OBJECTIVES: Stereotactic radiotherapy (SRT) for brain metastases (BM) allows very good local control (LC). However, approximately 20%-30% of these lesions will recur. The objective of this retrospective study was to evaluate the impact of dosimetric parameters on LC in cerebral SRT. METHODS: Patients treated with SRT for 1-3 BM between January 2015 and December 2018 were retrospectively included. A total of 349 patients with 538 lesions were included. The median gross tumour volume (GTV) was 2 cm3 (IQR, 0-7). The median biological effective dose with α/ß = 10 (BED10) was 60 Gy (IQR, 32-82). The median prescription isodose was 71% (IQR, 70-80). Correlations with LC were examined using the Cox regression model. RESULTS: The median follow-up period was 55 months (min-max, 7-85). Median overall survival was 17.8 months (IQR, 15.2-21.9). There were 95 recurrences and LC at 1 and 2 years was 87.1% (95% CI, 84-90) and 78.1% (95% CI, 73.9-82.4), respectively. Univariate analysis showed that systemic treatment, dose to 2% and 50% of the planning target volume (PTV), BED10 > 50 Gy, and low PTV and GTV volume were significantly correlated with better LC. In the multivariate analysis, GTV volume, isodose, and BED10 were significantly associated with LC. CONCLUSION: These results show the importance of a BED10 > 50 Gy associated with a prescription isodose <80% to optimize LC during SRT for BM. ADVANCES IN KNOWLEDGE: Isodose, BED, and GTV volume were significantly associated with LC. A low isodose improves LC without increasing the risk of radionecrosis.
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Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Lesões por Radiação/etiologiaRESUMO
Patients treated with cardiac stereotactic body radiation therapy (radioablation) for refractory ventricular arrhythmias are patients with advanced structural heart disease and significant comorbidities. However, data regarding 1-year mortality after the procedure are scarce. This systematic review and pooled analysis aimed at determining 1-year mortality after cardiac radioablation for refractory ventricular arrhythmias and investigating leading causes of death in this population. MEDLINE/EMBASE databases were searched up to January 2023 for studies including patients undergoing cardiac radioablation for the treatment of refractory ventricular arrhythmias. Quality of included trials was assessed using the NIH Tool for Case Series Studies (PROSPERO CRD42022379713). A total of 1,151 references were retrieved and evaluated for relevance. Data were extracted from 16 studies, with a total of 157 patients undergoing cardiac radioablation for refractory ventricular arrhythmias. Pooled 1-year mortality was 32 % (95 %CI: 23-41), with almost half of the deaths occurring within three months after treatment. Among the 157 patients, 46 died within the year following cardiac radioablation. Worsening heart failure appeared to be the leading cause of death (52 %), although non-cardiac mortality remained substantial (41 %) in this population. Age≥70yo was associated with a significantly higher 12-month all-cause mortality (p<0.022). Neither target volume size nor radiotherapy device appeared to be associated with 1-year mortality (p = 0.465 and p = 0.199, respectively). About one-third of patients undergoing cardiac stereotactic body radiation therapy for refractory ventricular arrhythmias die within the first year after the procedure. Worsening heart failure appears to be the leading cause of death in this population.
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BACKGROUND: The onset of castration-resistance is associated with dismal outcomes in patients with prostate cancer (PCa). Metastasis directed therapy has been investigated in multiple disease settings and may improve outcomes in selected patients. Our systematic review aims to summarize evidence with stereotactic body radiotherapy (SBRT) in castration-resistant prostate cancer (CRPC). METHODS: The literature search was performed on March 2024, on Pubmed, using the keywords "SBRT" AND "CRPC", and "stereotactic ablative radiotherapy (SABR)" AND "CRPC". This search retrieved a total of 108 articles, 19 were included. RESULTS: The literature is largely dominated by retrospective series. In men with metachronous oligoprogression, SBRT with androgen receptor pathway inhibitor significantly increased progression-free survival (PFS) including biochemical progression-free survival in a randomized phase II trial (hazard ratio of 0.35, p < 0.001). In patients continuing ADT, the bPFS ranged between 9.5 months to 17.9 months, and next systemic treatment-free survival (NEST-FS) reached up to 2 years. In men with induced oligoprogression, SBRT enabled NEST-FS up to 3 years. SBRT was well tolerated, with less than 5% grade 3 toxicity reported across studies. CONCLUSION: In the population of patients with oligometastatic CRPC, SBRT enables long-term biochemical response and PFS. In the oligoprogressive setting, SBRT could be integrated to prolong the duration and efficacy of systemic therapies. Nevertheless, the level of evidence remains very low and inclusion within prospective trials remain the preferred option for this population of patients.
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Background and purpose: Magnetic resonance imaging (MRI)-to-computed tomography (CT) synthesis is essential in MRI-only radiotherapy workflows, particularly through deep learning techniques known for their accuracy. However, current supervised methods are limited to specific center's learnings and depend on registration precision. The aim of this study was to evaluate the accuracy of unsupervised and supervised approaches in the context of prostate MRI-to-CT generation for radiotherapy dose calculation. Methods: CT/MRI image pairs from 99 prostate cancer patients across three different centers were used. A comparison between supervised and unsupervised conditional Generative Adversarial Networks (cGAN) was conducted. Unsupervised training incorporates a style transfer method with. Content and Style Representation for Enhanced Perceptual synthesis (CREPs) loss. For dose evaluation, the photon prescription dose was 60 Gy delivered in volumetric modulated arc therapy (VMAT). Imaging endpoint for sCT evaluation was Mean Absolute Error (MAE). Dosimetric endpoints included absolute dose differences and gamma analysis between CT and sCT dose calculations. Results: The unsupervised paired network exhibited the highest accuracy for the body with a MAE at 33.6 HU, the highest MAE was 45.5 HU obtained with unsupervised unpaired learning. All architectures provided clinically acceptable results for dose calculation with gamma pass rates above 94 % (1 % 1 mm 10 %). Conclusions: This study shows that multicenter data can produce accurate sCTs via unsupervised learning, eliminating CT-MRI registration. The sCTs not only matched HU values but also enabled precise dose calculations, suggesting their potential for wider use in MRI-only radiotherapy workflows.
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PURPOSE: The occurrence of genitourinary (GU) toxicity is a common adverse event observed after external beam radiation therapy (EBRT) for prostate cancer (PCa). Recent findings suggest that the dose delivered to specific urinary organs at risk (OARs) such as the ureters, bladder trigone, and urethra is involved in the development of GU toxicity. METHODS AND MATERIALS: A multidisciplinary task force including 3 radiation oncologists, a uroradiologist, and a urologist was created in 2022. First, OARs potentially involved in GU toxicity were identified and discussed. A literature review was performed, addressing several questions relative to urinary OARs: anatomic and radiological definition, radiation-induced injury, and dose-volume parameters. Second, results were presented and discussed with a panel of radiation oncologists and members of the "Francophone Group of Urological Radiation Therapy." Thereafter, the "Francophone Group of Urological Radiation Therapy" experts were asked to answer a dedicated questionnaire, including 35 questions on the controversial issues related to the delineation of urinary OARs. RESULTS: The following structures were identified as critical for PCa EBRT: ureters, bladder, bladder neck, bladder trigone, urethra (intraprostatic, membranous, and spongious), striated sphincter, and postenucleation or posttransurethral resection of the prostate cavity. A consensus was obtained for 32 out of 35 items. CONCLUSIONS: This consensus highlights contemporary urinary structures in both the upper and lower urinary tract to be considered for EBRT treatment planning of PCa. The current recommendations also propose a standardized definition of urinary OARs for both daily practice and future clinical trials.
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BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were 41,564 (SD 23,624) and 33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was 162,444 per xerostomia avoided. At 24 months, ICER was 194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.
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Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Análise de Custo-Efetividade , Radioterapia de Intensidade Modulada/efeitos adversos , Análise Custo-Benefício , Neoplasias de Cabeça e Pescoço/radioterapia , Xerostomia/etiologia , Xerostomia/prevenção & controle , Xerostomia/epidemiologia , Glândula Parótida , Dosagem RadioterapêuticaRESUMO
UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is little known about optical spectroscopy techniques ability to evaluate renal tumours. This study shows for the first time the ability of Raman and optical reflectance spectroscopy to distinguish benign and malignant renal tumours in an ex vivo environment. We plan to develop this optical assistance in the operating room in the near future. OBJECTIVE: To evaluate the ability of Raman spectroscopy (RS) and optical reflectance spectroscopy (ORS) to distinguish benign and malignant renal tumours at surgery. MATERIALS AND METHODS: Between March and October 2011, RS and ORS spectra were prospectively acquired on surgical renal specimens removed for suspicion of renal cell carcinoma (RCC). Optical measurements were done immediately after surgery. Optical signals were normalised to ensure comparison between spectra. Initial and final portions of each spectrum were removed to avoid artefacts. A support vector machine (SVM) was built and tested using a leave-one-out cross-validation. Classification scores, including accuracy, sensitivity and specificity were calculated on the entire population and in patients with tumours of <4 cm. RESULTS: In all, 60 nephrectomies were performed for 53 malignant tumours (41 clear-cell, eight papillary and four chromophobe carcinomas) and seven benign tumours (four oncocytomas, two angiomyolipomas and a haemorrhagic cyst). In all, >700 optical spectra were obtained and submitted to SVM classification. The SVM could recognise benign and malignant renal tumours with an accuracy of 96% (RS) and 88% (ORS) in the whole population and with an accuracy of 93% (RS) and 95% (ORS) in the present subset of small renal tumours (<4 cm). Histological subtype could be determined in 80% and 88% of the cases with RS and ORS, respectively. The SVM was able to differentiate chromophobe carcinomas and benign lesions with an accuracy of 96% in RS and 98% in ORS. CONCLUSION: Benign and malignant renal tumours can be accurately discriminated by a combination of RS and ORS. In vivo experiments are needed to further assess the value of optical spectroscopy techniques.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Nefrectomia/métodos , Análise Espectral Raman , Carcinoma de Células Renais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
This dosimetric study investigated the impact of multileaf collimators (MLC) leaf width in volumetric-modulated arc therapy (VMAT) for head and neck cancers (HNC), either with a "standard" simultaneously integrated boost technique (S-SIB) or with a "dose painting" SIB technique (DP-SIB). HNC patients were planned either with an S-SIB comprising three dose levels, from 56 to 70 Gy (16 patients), or with a DP-SIB comprising five dose levels, from 56 to 84 Gy (8 patients), in 35 fractions. Two VMAT plans were calculated for each SIB technique using two Elekta MLCs: MLCi2 with 10 mm leaf width and Beam Modulator (BM) with 4 mm leaf width. Dose distributions were evaluated by comparing doses on PTVs, main OARs, and healthy tissue, and by comparing conformation indexes. Treatment efficiencies were evaluated by comparing the number of monitor units and the number of needed arcs. Comparisons of the two MLCs depending on the two SIB techniques showed: i) Regarding PTVs: Dmean and D2% on lower doses PTV decreased respectively by 0.5 Gy (p = 0.01) and 0.9 Gy (p = 0.01) with BM than with MLCi2 for S-SIB; no significant difference was found for DP-SIB;ii) Regarding OARs: for spinal cord and brainstem, D2% decreased respectively by 1.2 Gy (p = 0.03) and 4.2 Gy (p = 0.04) with BM than with MLCi2 for S-SIB; for controlateral parotid, D50% decreased by 1.5 Gy (p = 0.01) with BM than with MLCi2 for S-SIB; iii) Regarding treatment efficiency: the number of monitor units was 44% (p = 0.00) and 51% (p = 0.01) higher with BM for S-SIB and DP-SIB, respectively. Two arcs were more frequently needed with BM to reach an acceptable dose distribution. This study demonstrated that Beam Modulator (4 mm leaf width) and MLCi2 (10 mm leaf width) MLCs from Elekta provided satisfactory dose distributions for treatment delivery with VMAT technique for complex HNC cases with standard and dose painting prescriptions. OAR sparing was better with BM, mainly for brainstem and spinal cord. However, delivery efficiency of VMAT plans was better with MLCi2.
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Neoplasias de Cabeça e Pescoço/radioterapia , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios XRESUMO
Purpose: Immune system modulation, with the use of immune checkpoint inhibitors, has drastically changed the field of oncology. Strong preclinical data indicate that radiation therapy (RT) may enhance the response rate to such drugs via in situ vaccination, although these data do not consider immune radiotoxicity. This meta-analysis investigates whether radio-induced lymphopenia (RIL) is associated with overall survival (OS). Methods and Materials: A systematic literature search and quantitative analysis were planned, conducted, and reported per the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Quality of Reporting of Meta-analyses checklists. The literature from January 1990 to March 2021 was searched to identify clinical studies with OS data in patients treated with RT and presenting with lymphopenia. A random-effect model was employed for the meta-analysis. Heterogeneity was assessed using the I2 statistic. Publication bias was estimated using a P-curve analysis. Results: A total of 56 studies with 13 223 patients and 11 types of cancers were selected. The mean follow-up time was 35.9 months. Over a third of patients had RIL (37.25%). After removing outlying studies (n = 14), the between-study heterogeneity variance was estimated at t2 = 0.018 (P = .01) with an I2 value of 36.0% (95% confidence interval, 6%-56%). The results showed that RIL was significantly associated with worse OS (hazard ratio: 1.70; 95% confidence interval, 1.55-1.86; P < .01; 95% prediction interval, 1.27-2.26). A subgroup analysis was performed based on the type of primary tumor, and a difference between the subgroups was found (P < .01). Based on the P-curve analysis, a significant evidential value was found, and no significant publication bias was identified among the studies. Conclusions: RIL is a significant prognostic factor for mortality in virtually all solid cancers. Pooled-effect estimates indicate a significantly reduced risk of death in patients without RIL. Tailoring RT regimens to spare the immune system and updating dosimetric constraints for new organs at risk, such as major blood vessels, organs with rich blood supplies, bones, and all lymph node areas, may improve prognoses.
RESUMO
PURPOSE: Stereotactic body radiation therapy has been proposed as a salvage treatment for recurrent prostate cancer after irradiation. One crucial issue is choosing appropriate dose-volume constraints (DVCs) during planning. The objectives of this study were to (1) quantify the proportion of patients respecting the DVCs according to the Urogenital Tumor Study Group GETUG-31 trial, testing 36 Gy in six fractions, (2) explain geometrically why the DVCs could not be respected, and (3) propose the most suitable DVCs. METHODS AND MATERIALS: This retrospective dosimetric analysis included 141 patients treated for recurrent prostate cancer with Cyberknife (Accuray), according to GETUG-31 DVCs: V95% ≥ 95% for the planning target volume (PTV), V12Gy < 20% and V27Gy < 2 cc for the rectum, and V12Gy < 15% and V27Gy < 5 cc for the bladder. The percentage of patients not respecting the DVCs was quantified. Correlations between the DVCs and anatomic structures were examined. New DVCs were proposed. RESULTS: Only 19% of patients respected all DVCs, with a mean PTV of 18.5 cc (range, 3-48 cc), although the mean PTV was 40.5 cc (range, 3-174 cc) in the whole series. A total of 98% of the patients with a clinical target volume (CTV)/prostate ratio >0.5 could not respect the DVCs in the organs at risk. The target coverage and organ-at-risk sparing decreased significantly with increase in the values of PTV, CTV, CTV/prostate ratio, the overlapping volume between the PTV and bladder wall and between the PTV and rectal wall. Threshold values of PTV, >20 cc and 40 cc, allowed for the PTV and bladder DVCs, respectively. To improve DVC respect in case of large target volume, we proposed the following new DVCs: V12Gy < 25% and 25% and V27Gy < 2 cc and 5 cc for the rectum and bladder, respectively. CONCLUSIONS: GETUG-31 DVCs are achievable only for small target volumes (CTV more than half of the prostate). For a larger target volume, new DVCs have been proposed.
Assuntos
Neoplasias da Próstata , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Reirradiação , Masculino , Humanos , Radioterapia Conformacional/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Reto/efeitos da radiação , Radioterapia de Intensidade Modulada/métodosRESUMO
Radiation therapy is moving from CT based to MRI guided planning, particularly for soft tissue anatomy. An important requirement of this new workflow is the generation of synthetic-CT (sCT) from MRI to enable treatment dose calculations. Automatic methods to determine the acceptable range of CT Hounsfield Unit (HU) uncertainties to avoid dose distribution errors is thus a key step toward safe MRI-only radiotherapy. This work has analysed the effects of controlled errors introduced in CT scans on the delivered radiation dose for prostate cancer patients. Spearman correlation coefficient has been computed, and a global sensitivity analysis performed following the Morris screening method. This allows the classification of different error factors according to their impact on the dose at the isocentre. sCT HU estimation errors in the bladder appeared to be the least influential factor, and sCT quality assessment should not only focus on organs surrounding the radiation target, as errors in other soft tissue may significantly impact the dose in the target volume. This methodology links dose and intensity-based metrics, and is the first step to define a threshold of acceptability of HU uncertainties for accurate dose planning.