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1.
Front Immunol ; 15: 1373497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720889

RESUMO

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.


Assuntos
Neoplasias da Mama , Imunomodulação , Cuidados Intraoperatórios , Mastectomia Segmentar , Microambiente Tumoral , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos da radiação , Imunomodulação/efeitos da radiação , Idoso , Adulto , Terapia Combinada
2.
Lasers Med Sci ; 39(1): 127, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722392

RESUMO

Orofacial pain can significantly affect physical, psychological, and overall quality of life. This study aimed to compare the effectiveness of combining photobiomodulation (PBM) with orofacial myofunctional therapy (OMT) in managing orofacial pain disorders. An electronic search of randomized controlled trials in electronic databases was performed until March 2024. Randomized controlled trials (RCTs) focusing on PBM and OMT for the management of orofacial pain were included. Risk of bias across individual studies was performed using the Cochrane risk of bias tool for interventions. A total of 10 RCTs were included, out of which 7 RCTs revealed that the combined approach of PBM and OMT had a more pronounced impact on diminishing pain and enhancing functional activity in patients with orofacial disorders. One study reported significant increases in pressure pain threshold for TMJ, masseter, and anterior temporalis muscles at both sides in the post-treatment compared with the pre-treatment in both groups. The risk of bias was low in 7, moderate in 2, and high in 1 study. The efficacy of a combined modality treatment of PBM with OMT for orofacial pain disorder shows promising results. However, further randomized controlled trials with extended follow-up periods standardized PBM and OMT parameters are warranted to obtain firm conclusions.


Assuntos
Dor Facial , Terapia com Luz de Baixa Intensidade , Terapia Miofuncional , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Terapia Miofuncional/métodos , Dor Facial/radioterapia , Dor Facial/terapia , Terapia com Luz de Baixa Intensidade/métodos , Resultado do Tratamento , Terapia Combinada , Qualidade de Vida
3.
JCO Glob Oncol ; 10: e2300462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38723217

RESUMO

PURPOSE: Radiation oncology in the Philippines, a large lower- and middle-income country in Southeast Asia, is facing a critical shortage in manpower, with only 113 radiation oncologists (ROs) over 55 radiotherapy (RT) centers serving 100 million population. Paramount to workforce expansion is ensuring that training programs can produce adequately trained specialists. In this study, we describe the current state of radiation oncology training programs in the Philippines. METHODS: This is a cross-sectional observational analysis of the nine radiation oncology residency training programs in the Philippines. Data were collected from a survey of the program directors, the Philippine Radiation Oncology Society database, and a PubMed literature search. RESULTS: Eight of the nine programs are in the National Capital Region. Since program standardization in 2005, there have been 82 four-year residency graduates, with up to 18 new graduates annually. Faculty-to-trainee ratio ranges from 0.5 to 2.67. In terms of technology, all programs have intensity-modulated RT and high-dose-rate brachytherapy, but only six are equipped with computed tomography-based image guidance and stereotactic capabilities. Clinical education schemes vary per institution regarding curriculum implementation, resident activities, and methods of evaluation. Required resident case logs are not met for lung, GI, genitourinary, bone and soft tissue, and hematologic malignancies. In total, there are only 22 resident-led publications from 10 unique individuals in two training programs. CONCLUSION: Program expansions are warranted to meet the projected demand for ROs in the Philippines, but training programs must first improve key aspects of staffing, technology, clinical education, and research. Addressing training challenges related to resource limitations necessitates local and international collaborations with higher-capacity centers to bridge gaps for continued quality improvement with the aim of ultimately delivering better overall cancer care.


Assuntos
Países em Desenvolvimento , Radioterapia (Especialidade) , Filipinas , Humanos , Radioterapia (Especialidade)/educação , Estudos Transversais , Neoplasias/radioterapia , Internato e Residência/estatística & dados numéricos
4.
Lasers Med Sci ; 39(1): 128, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724798

RESUMO

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.


Assuntos
Alopecia , Lasers de Estado Sólido , Humanos , Alopecia/terapia , Alopecia/radioterapia , Lasers de Estado Sólido/uso terapêutico , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Finasterida/administração & dosagem , Finasterida/uso terapêutico , Minoxidil/administração & dosagem , Terapia Combinada , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/instrumentação
5.
Mol Biol Rep ; 51(1): 633, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724835

RESUMO

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.


Assuntos
Docetaxel , Nanopartículas Metálicas , Neoplasias da Próstata , Radiossensibilizantes , Prata , Humanos , Docetaxel/farmacologia , Masculino , Prata/farmacologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Linhagem Celular Tumoral , Radiossensibilizantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Peróxido de Hidrogênio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Caspase 3/metabolismo , Caspase 3/genética , Antineoplásicos/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caderinas/metabolismo , Caderinas/genética
7.
Sci Rep ; 14(1): 10787, 2024 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734765

RESUMO

Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.


Assuntos
alfa-Globulinas , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Lutécio , Animais , alfa-Globulinas/metabolismo , Camundongos , Masculino , Humanos , Dipeptídeos/farmacologia , Rim/patologia , Rim/efeitos da radiação , Rim/efeitos dos fármacos , Rim/metabolismo , Compostos Radiofarmacêuticos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/patologia , Nitrogênio da Ureia Sanguínea , Antígeno Prostático Específico
8.
Sci Rep ; 14(1): 10546, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719979

RESUMO

Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.


Assuntos
Radioisótopos do Iodo , Metabolômica , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Feminino , Masculino , Pessoa de Meia-Idade , Metabolômica/métodos , Adulto , Iodo/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Idoso , Metaboloma
9.
World J Surg Oncol ; 22(1): 125, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720338

RESUMO

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Invasividade Neoplásica , Carga Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Hepatectomia/métodos , Idoso , Seguimentos , Estudos Retrospectivos , Adulto , Planejamento da Radioterapia Assistida por Computador/métodos , Cirrose Hepática/patologia
10.
Photodermatol Photoimmunol Photomed ; 40(3): e12974, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728444

RESUMO

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.


Assuntos
Terapia Ultravioleta , Vitiligo , Humanos , Vitiligo/terapia , Vitiligo/radioterapia , Feminino , Masculino , Adulto , Terapia Ultravioleta/métodos , Pigmentação da Pele , Pessoa de Meia-Idade , Adolescente , Tacrolimo/uso terapêutico , Tacrolimo/administração & dosagem
11.
Medicine (Baltimore) ; 103(19): e37956, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728510

RESUMO

This study, based on a population, explored the prognostic value of postoperative radiotherapy (PORT) for Masaoka-Koga IIB stage thymomas. Patients diagnosed with thymoma from 2004 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the retrospective study. Through propensity score matching, the baseline characteristics of the patients were successfully matched to mitigate the selection bias of PORT. Survival rates and survival curves were compared between the PORT and non-PORT groups, with potential confounding factors addressed using a multivariate Cox regression model. In this study, 785 cases of IIB stage thymoma were included from the SEER database, and 303 patients were successfully matched between PORT and non-PORT groups through propensity score matching, with no significant differences in baseline characteristics. In the PORT and non-PORT groups, 10-year overall survival rates were 65.2% versus 59.6%, and cancer-specific survival rates were 87.0% vs. 84.4%, PORT did not yield statistically significant improvements in overall survival (P = .275) or cancer-specific survival (P = .336) for stage IIB thymomas. Based on the SEER database, the results of our study indicated that PORT does not confer a significant survival benefit for IIB stage thymomas.


Assuntos
Estadiamento de Neoplasias , Pontuação de Propensão , Programa de SEER , Timoma , Neoplasias do Timo , Humanos , Timoma/radioterapia , Timoma/mortalidade , Timoma/cirurgia , Timoma/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Timo/radioterapia , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Idoso , Adulto , Radioterapia Adjuvante , Taxa de Sobrevida , Prognóstico
12.
Otol Neurotol ; 45(5): 587-593, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38728563

RESUMO

OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN: Multi-institutional historical cohort study. SETTING: Five tertiary care referral centers. PATIENTS: Adults ≥18 years old with sporadic VS. INTERVENTION: Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS. RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.


Assuntos
Neuroma Acústico , Radiocirurgia , Reoperação , Falha de Tratamento , Humanos , Neuroma Acústico/cirurgia , Neuroma Acústico/radioterapia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Reoperação/estatística & dados numéricos , Estudos de Coortes , Resultado do Tratamento , Microcirurgia/métodos
13.
Biomed Phys Eng Express ; 10(4)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697028

RESUMO

Background and purpose. To investigate models developed using radiomic and dosiomic (multi-omics) features from planning and treatment imaging for late patient-reported dysphagia in head and neck radiotherapy.Materials and methods. Training (n = 64) and testing (n = 23) cohorts of head and neck cancer patients treated with curative intent chemo-radiotherapy with a follow-up time greater than 12 months were retrospectively examined. Patients completed the MD Anderson Dysphagia Inventory and a composite score ≤60 was interpreted as patient-reported dysphagia. A chart review collected baseline dysphagia and clinical factors. Multi-omic features were extracted from planning and last synthetic CT images using the pharyngeal constrictor muscle contours as a region of interest. Late patient-reported dysphagia models were developed using a random forest backbone, with feature selection and up-sampling methods to account for the imbalanced data. Models were developed and validated for multi-omic feature combinations for both timepoints.Results. A clinical and radiomic feature model developed using the planning CT achieved good performance (validation: sensitivity = 80 ± 27% / balanced accuracy = 71 ± 23%, testing: sensitivity = 80 ± 10% / balanced accuracy = 73 ± 11%). The synthetic CT models did not show improvement over the plan CT multi-omics models, with poor reliability of the radiomic features on these images. Dosiomic features extracted from the synthetic CT showed promise in predicting late patient-reported dysphagia.Conclusion. Multi-omics models can predict late patient-reported dysphagia in head and neck radiotherapy patients. Synthetic CT dosiomic features show promise in developing successful models to account for changes in delivered dose distribution. Multi-center or prospective studies are required prior to clinical implementation of these models.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Humanos , Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Reprodutibilidade dos Testes , Dosagem Radioterapêutica , Medidas de Resultados Relatados pelo Paciente , Multiômica
15.
Nano Lett ; 24(19): 5894-5903, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709593

RESUMO

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.


Assuntos
Quimiocina CCL21 , Células Dendríticas , Hidrogéis , Animais , Hidrogéis/química , Camundongos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Linhagem Celular Tumoral , Humanos , Alginatos/química , Neoplasias/radioterapia , Neoplasias/patologia , Neoplasias/imunologia , Colágeno/química , Imunoterapia/métodos
16.
Radiat Environ Biophys ; 63(2): 297-306, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722389

RESUMO

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.


Assuntos
Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Feminino , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radiometria , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Metástase Linfática/radioterapia
17.
Eur J Med Res ; 29(1): 282, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735974

RESUMO

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.


Assuntos
Neoplasias da Mama , Aprendizado de Máquina , Humanos , Feminino , Neoplasias da Mama/radioterapia , Pessoa de Meia-Idade , Adulto , Idoso , Pele/efeitos da radiação , Pele/patologia , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Dosagem Radioterapêutica
18.
Front Immunol ; 15: 1355130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742103

RESUMO

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/terapia , Terapia Neoadjuvante/métodos , Camundongos , Humanos , Receptor ErbB-2/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Modelos Animais de Doenças , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias da Mama/imunologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/terapia
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