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1.
Sci Rep ; 14(1): 8250, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589494

RESUMO

Personalized, ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) is designed to administer tumoricidal doses in a pulsed mode with extended intervals, spanning weeks or months. This approach leverages longer intervals to adapt the treatment plan based on tumor changes and enhance immune-modulated effects. In this investigation, we seek to elucidate the potential synergy between combined PULSAR and PD-L1 blockade immunotherapy using experimental data from a Lewis Lung Carcinoma (LLC) syngeneic murine cancer model. Employing a long short-term memory (LSTM) recurrent neural network (RNN) model, we simulated the treatment response by treating irradiation and anti-PD-L1 as external stimuli occurring in a temporal sequence. Our findings demonstrate that: (1) The model can simulate tumor growth by integrating various parameters such as timing and dose, and (2) The model provides mechanistic interpretations of a "causal relationship" in combined treatment, offering a completely novel perspective. The model can be utilized for in-silico modeling, facilitating exploration of innovative treatment combinations to optimize therapeutic outcomes. Advanced modeling techniques, coupled with additional efforts in biomarker identification, may deepen our understanding of the biological mechanisms underlying the combined treatment.


Assuntos
DEAE-Dextrano , Radiocirurgia , Animais , Camundongos , Imunoterapia/métodos , Redes Neurais de Computação , Terapia Combinada , Antígeno B7-H1
2.
BMC Cancer ; 24(1): 431, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589860

RESUMO

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Qualidade de Vida , Estudos Prospectivos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Intervalo Livre de Progressão , Progressão da Doença , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos
3.
Radiología (Madr., Ed. impr.) ; 66(2): 166-180, Mar.- Abr. 2024. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-231516

RESUMO

La resonancia magnética es la piedra angular en la evaluación de las metástasis cerebrales. Los retos clínicos residen en discriminar las metástasis de imitadores como infecciones o tumores primarios y en evaluar la respuesta al tratamiento. Este, en ocasiones, condiciona un crecimiento, que debe encuadrarse como una pseudoprogresión o una radionecrosis, ambos fenómenos inflamatorios atribuibles al mismo, o bien considerarse como una recurrencia. Para responder a estas necesidades, las técnicas de imagen son objeto de constantes investigaciones. No obstante, un crecimiento exponencial tras la radioterapia debe interpretarse con cautela, incluso ante resultados sospechosos de progresión por técnicas avanzadas, ya que puede tratarse de una radionecrosis. El objetivo de este trabajo es familiarizar al lector con los fenómenos inflamatorios de las metástasis cerebrales tratadas con radioterapia y describir dos signos radiológicos relacionados: la «nube inflamatoria» y el «realce en anillo incompleto», con el fin de adoptar un manejo conservador en estos casos.(AU)


MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: «the inflammatory cloud» and «incomplete ring enhancement», in order to adopt a conservative management with close follow-up.(AU)


Assuntos
Humanos , Masculino , Feminino , Neoplasias Encefálicas/diagnóstico por imagem , Recidiva Local de Neoplasia , Radiocirurgia , Anormalidades Induzidas por Radiação , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Encefálicas/radioterapia , Linfócitos do Interstício Tumoral , Espectroscopia de Ressonância Magnética/uso terapêutico
4.
Radiat Oncol ; 19(1): 50, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637844

RESUMO

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Estudos de Coortes , Estudos Retrospectivos , Estadiamento de Neoplasias , Análise de Sobrevida , Carcinoma de Pequenas Células do Pulmão/patologia , Radiocirurgia/métodos , Resultado do Tratamento
5.
Neurosurg Rev ; 47(1): 172, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639882

RESUMO

Stereotactic radiosurgery (SRS) is an option for brain metastases (BM) not eligible for surgical resection, however, predictors of SRS outcomes are poorly known. The aim of this study is to investigate predictors of SRS outcome in patients with BM secondary to non-small cell lung cancer (NSCLC). The secondary objective is to analyze the value of volumetric criteria in identifying BM progression. This retrospective cohort study included patients >18 years of age with a single untreated BM secondary to NSCLC. Demographic, clinical, and radiological data were assessed. The primary outcome was treatment failure, defined as a BM volumetric increase 12 months after SRS. The unidimensional measurement of the BM at follow-up was also assessed. One hundred thirty-five patients were included, with a median BM volume at baseline of 1.1 cm3 (IQR 0.4-2.3). Fifty-two (38.5%) patients had SRS failure at follow-up. Only right BM laterality was associated with SRS failure (p=0.039). Using the volumetric definition of SRS failure, the unidimensional criteria demonstrated a sensibility of 60.78% (46.11%-74.16%), specificity of 89.02% (80.18%-94.86%), positive LR of 5.54 (2.88-10.66) and negative LR of 0.44 (0.31-0.63). SRS demonstrated a 61.5% local control rate 12 months after treatment. Among the potential predictors of treatment outcome analyzed, only the right BM laterality had a significant association with SRS failure. The volumetric criteria were able to identify more subtle signs of BM increase than the unidimensional criteria, which may allow earlier diagnosis of disease progression and use of appropriate therapies.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Estudos de Coortes , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Radiocirurgia/métodos , Resultado do Tratamento , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia
6.
Neurosurg Rev ; 47(1): 171, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639892

RESUMO

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.


Assuntos
Neurilemoma , Radiocirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Neurilemoma/cirurgia , Nervos Cranianos/cirurgia , Procedimentos Neurocirúrgicos/métodos , Radiocirurgia/métodos , Seguimentos
7.
Sci Rep ; 14(1): 9028, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641673

RESUMO

The primary objective of the present study was to identify a subset of radiomic features extracted from primary tumor imaged by computed tomography of early-stage non-small cell lung cancer patients, which remain unaffected by variations in segmentation quality and in computed tomography image acquisition protocol. The robustness of these features to segmentation variations was assessed by analyzing the correlation of feature values extracted from lesion volumes delineated by two annotators. The robustness to variations in acquisition protocol was evaluated by examining the correlation of features extracted from high-dose and low-dose computed tomography scans, both of which were acquired for each patient as part of the stereotactic body radiotherapy planning process. Among 106 radiomic features considered, 21 were identified as robust. An analysis including univariate and multivariate assessments was subsequently conducted to estimate the predictive performance of these robust features on the outcome of early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy. The univariate predictive analysis revealed that robust features demonstrated superior predictive potential compared to non-robust features. The multivariate analysis indicated that linear regression models built with robust features displayed greater generalization capabilities by outperforming other models in predicting the outcomes of an external validation dataset.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , 60570 , Tomografia Computadorizada por Raios X , Radiocirurgia/métodos
8.
Nat Commun ; 15(1): 3260, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627377

RESUMO

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Humanos , Terapia Neoadjuvante , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Radiocirurgia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Adjuvantes Imunológicos
9.
Cancer J ; 30(2): 102-107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527263

RESUMO

ABSTRACT: Development of brain metastasis is one of the most serious complications of advanced melanoma, carrying a significant burden of morbidity and mortality. Although advances in local treatment modalities such as stereotactic radiosurgery and breakthrough systemic therapies including immunotherapy and targeted therapies have improved the outcomes of patients with metastatic melanoma, management of patients with melanoma brain metastases (MBMs) remains challenging. Notably, patients with MBMs have historically been excluded from clinical trials, limiting insights into their specific treatment responses. Encouragingly, a growing body of evidence shows the potential of systemic therapies to yield durable intracranial responses in these patients, highlighting the need for inclusion of patients with MBMs in future clinical trials. This is pivotal for expediting the advancement of novel therapies tailored to this distinct patient population. In this review, we will highlight the evolving landscape of MBM management, focusing on local and systemic treatment strategies.


Assuntos
Neoplasias Encefálicas , Melanoma , Radiocirurgia , Humanos , Melanoma/tratamento farmacológico , Neoplasias Encefálicas/terapia , Terapia Combinada , Imunoterapia
10.
Eur J Cancer ; 201: 113972, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430868

RESUMO

It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof. This work seeks to address these discrepancies, and uses the lessons learned from both positive and negative trials, including the most cutting-edge data available, in order to guide future clinical trial design and clarify the ideal/expected role of combinatorial therapy going forward. Because RT offers two distinct contributions (cytoreductive (local) effects & immune-stimulating (systemic) effects), RT should complement immunotherapy by addressing immunotherapy-resistant clones, and immunotherapy should complement RT by addressing RT-resistant or out-of-field clones. RT is not merely a single "drug", but rather a constellation of diverse "drugs" that can be varied based on dose regimens, previous systemic therapy regimens, number of irradiated sites, treatment intent/location/timing, tumor biology, and individual patient immunological circumstances. These factors are discussed as an important explanation for the discrepancies in results of various randomized trials in heterogeneous populations and clinical settings, and these discrepancies may continue until trials of more uniform circumstances are designed to use particular RT paradigms that meaningfully add value to systemic therapy.


Assuntos
Imunoterapia , Radiocirurgia , Humanos , Terapia Combinada , Imunoterapia/métodos , Radiocirurgia/métodos
11.
J Neurooncol ; 167(2): 275-283, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526757

RESUMO

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fraturas por Compressão , Neoplasias Pulmonares , Radiocirurgia , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Masculino , Feminino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Seguimentos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Receptores ErbB/genética
12.
Support Care Cancer ; 32(4): 230, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488881

RESUMO

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.


Assuntos
Neoplasias Pulmonares , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Pulmão/patologia , Pescoço , Estudos Retrospectivos
13.
J Med Radiat Sci ; 71 Suppl 2: 90-98, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38504608

RESUMO

Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.


Assuntos
Terapia com Prótons , Radiocirurgia , Radioterapia de Intensidade Modulada , Adolescente , Humanos , Criança , Lactente , Adulto Jovem , Adulto , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
14.
BMC Cancer ; 24(1): 332, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475765

RESUMO

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/métodos , Estudos Prospectivos , Resultado do Tratamento , Neoplasias Encefálicas/secundário , Necrose/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
15.
Neuro Oncol ; 26(12 Suppl 2): S56-S65, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437665

RESUMO

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging. In this review article, we explore risk factors associated with the development of radiation necrosis, advanced imaging modalities used to aid in diagnosis, and potential treatment strategies to manage side effects.


Assuntos
Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Humanos , Neoplasias Encefálicas/radioterapia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Radiocirurgia/efeitos adversos , Fatores de Risco , Necrose
16.
Neuro Oncol ; 26(12 Suppl 2): S76-S87, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437670

RESUMO

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.


Assuntos
Radiocirurgia , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/radioterapia , Padrão de Cuidado , Dor
17.
Cancer Control ; 31: 10732748241237331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449377

RESUMO

OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.


Assuntos
Anticorpos Monoclonais Humanizados , Segunda Neoplasia Primária , Radiocirurgia , Sarcoma , Humanos , Inibidores de Checkpoint Imunológico , Projetos Piloto , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia
18.
Otol Neurotol ; 45(4): 430-433, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437820

RESUMO

OBJECTIVE: To describe the experience and results from coordinated and closely scheduled radiosurgery and cochlear implantation (CI) in a vestibular schwannoma (VS) cohort. PATIENTS: Patients with VS who underwent radiosurgery followed by CI on the same or next day. INTERVENTIONS: Interventions included sequential radiosurgery and CI. MAIN OUTCOME MEASURES: Tumor control defined by tumor growth on posttreatment surveillance and audiometric outcomes including consonant-nucleus-consonant words and AzBio sentences in quiet. RESULTS: In total, six patients were identified that met the inclusion criteria, with an age range of 38 to 69 years and tumor sizes ranging from 2.0 to 16.3 mm. All patients successfully underwent radiosurgery and CI on the same or immediately successive day. Postoperatively, all patients obtained open-set speech recognition. Consonant-nucleus-consonant word scores ranged from 40 to 88% correct, and AzBio scores ranged from 44 to 94% correct. During posttreatment magnetic resonance imaging surveillance, which ranged from 12 to 68 months, all tumors were noted to be adequately visualized, and no tumor progression was noted. CONCLUSION: Coordinated radiosurgery and CI can be safely performed in patients with VS on the same or next day, serving to decrease burden on patients and increase access to this vital rehabilitative strategy.


Assuntos
Implante Coclear , Implantes Cocleares , Neuroma Acústico , Radiocirurgia , Percepção da Fala , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Implante Coclear/métodos , Neuroma Acústico/cirurgia , Radiocirurgia/métodos , Estudos Retrospectivos , Audiometria , Resultado do Tratamento
19.
Pathol Oncol Res ; 30: 1611709, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476352

RESUMO

The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Radiocirurgia/métodos , Pulmão/patologia , Fracionamento da Dose de Radiação , Carcinoma de Pequenas Células do Pulmão/patologia , Estadiamento de Neoplasias
20.
J Appl Clin Med Phys ; 25(3): e14181, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470861

RESUMO

PURPOSE: Pencil Beam Scanning (PBS) proton therapy has similar requirements on patient alignment to within 1 mm and 1-degree accuracy as photon radiosurgery. This study describes general workflow, acceptance, and commissioning test procedures and their respective results for an independent robotic arm used for Image Guided Radiotherapy (IGRT) for a Proton Therapy System. METHODS: The system is equipped with kV-imaging techniques capable of orthogonal and Cone-Beam Computed Tomography (CBCT) imaging modalities mounted on an independent robotic arm gantry attached to the ceiling. The imaging system is capable of 360-degree rotation around patients to produce CBCT and kilovoltage orthogonal images. The imaging hardware is controlled by Ehmet Health XIS software, and MIM Software handles the image fusion and registration to an acceptable accuracy of ≤1-mm shifts for patients' alignment. The system was tested according to the requirements outlined in the American Association of Physicists in Medicine (AAPM) Task Group (TG) 142 and TG 179. The system tests included (1) safety, functionality, and connectivity, (2) mechanical testing, (3) image quality, (4) image registration, and (5) imaging dose. Additional tests included imaging gantry isocentricity with a laser tracker and collision-avoiding system checks. RESULTS: The orthogonal and volumetric imaging are comparable in quality to other commercially available On-Board Imagers (OBI) systems. The resulting spatial resolution values were 1.8-, 0.8-, and 0.5-Line Pairs per Millimeter (lp/mm) for orthogonal, full-fan CBCT, and half-fan CBCT, respectively. The image registration is accurate to within 1 mm and 1 degree. The data shows consistent imaging-guided system performance with standard deviations in x, y, and z of 0.7, 0.8, and 0.7 mm, respectively. CONCLUSIONS: The system provides excellent image quality and performance, which can be used for IGRT. The proven accuracy of the x-ray imaging and positioning system at McLaren Proton Therapy Center (MPTC) is 1 mm, making it suitable for proton therapy.


Assuntos
Terapia com Prótons , Radiocirurgia , Radioterapia Guiada por Imagem , Humanos , Terapia com Prótons/métodos , Imagens de Fantasmas , Tomografia Computadorizada de Feixe Cônico/métodos , Tomografia Computadorizada por Raios X
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