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Journal of Neuroimaging : Official... Mar 2023Postradiation treatment necrosis is one of the most serious late sequelae and appears within 6 months. The magnetic resonance spectroscopy imaging (MRSI) has been used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Postradiation treatment necrosis is one of the most serious late sequelae and appears within 6 months. The magnetic resonance spectroscopy imaging (MRSI) has been used for the detection of brain tumors. The study aimed to determine the radiological accuracy and efficacy in distinguishing recurrent brain tumor from radiation-induced necrosis by identifying pseudoprogression.
METHODS
The research was performed in accordance with the preferred reporting items for systematic review and meta-analysis guidelines. International electronic databases including 15 English sources were investigated. A total of 4281 papers with 2159 citations from 15 databases from 2011 to 2021 met the search strategies of magnetic resonance (MR) spectroscopy in recurrent brain tumors and postradiation necrosis.
RESULTS
Nine studies were enrolled in the meta-analysis with a total of 354 patients (203 male and 151 female) whose average age ranged from 4 to 74 years. Anbarloui et al., Elias et al., Nemattalla et al., Smith et al., Zeng et al., and Weybright et al. showed strong evidence of heterogeneity regarding choline/N-acetylaspartate (Cho/NAA) ratio in the evaluation of the nine studies. Elias et al., Nemattalla et al., Bobek-Billewicz et al., and Smith et al. showed a high heterogeneity in Cho/creatine (Cr) ratio. Elias et al., Nemattalla et al., Smith et al., and Weybright et al. revealed high heterogeneity in NAA/Cr ratio estimates.
CONCLUSION
MR spectroscopy is effective in distinguishing recurrent brain tumors from necrosis. Our meta-analysis revealed that Cho/NAA, Cho/Cr, and NAA/Cr ratios were significantly better predictor of detected recurrent tumor. Therefore, the MRSI is an informative tool in the distinction of tumor recurrence versus necrosis.
Topics: Humans; Male; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Neoplasm Recurrence, Local; Diagnosis, Differential; Aspartic Acid; Brain Neoplasms; Magnetic Resonance Spectroscopy; Creatine; Radiation Injuries; Choline; Necrosis; Brain
PubMed: 36631883
DOI: 10.1111/jon.13080 -
The Science of the Total Environment Nov 2023Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary...
Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.
Topics: Mice; Animals; Cadmium; Glutamine; Gastrointestinal Microbiome; Ki-67 Antigen; Mammary Neoplasms, Experimental; Cell Transformation, Neoplastic; Mice, Transgenic; Carcinogenesis; Necrosis
PubMed: 37429473
DOI: 10.1016/j.scitotenv.2023.165348 -
Neuro-oncology Sep 2019Cancer therapy-induced adverse effects on the brain are a major challenge in neuro-oncology. Brain tissue necrosis (treatment necrosis [TN]) as a consequence of brain... (Review)
Review
Cancer therapy-induced adverse effects on the brain are a major challenge in neuro-oncology. Brain tissue necrosis (treatment necrosis [TN]) as a consequence of brain directed cancer therapy remains an insufficiently characterized condition with diagnostic and therapeutic difficulties and is frequently associated with significant patient morbidity. A better understanding of the underlying mechanisms, improvement of diagnostic tools, development of preventive strategies, and implementation of evidence-based therapeutic practices are pivotal to improve patient management. In this comprehensive review, we address existing challenges associated with current TN-related clinical and research practices and highlight unanswered questions and areas in need of further research with the ultimate goal to improve management of patients affected by this important neuro-oncological condition.
Topics: Antineoplastic Agents, Alkylating; Brain; Brain Neoplasms; Chemoradiotherapy; Diagnosis, Differential; Disease Progression; Glioblastoma; Humans; Necrosis; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Protein Kinase Inhibitors; Radiation Injuries; Radiotherapy; Temozolomide
PubMed: 30828724
DOI: 10.1093/neuonc/noz048 -
The Laryngoscope Jun 2022To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.
OBJECTIVES/HYPOTHESIS
To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.
STUDY DESIGN
Randomized, prospective study using an in vivo rat model.
METHODS
Experimental animal study utilizing Sprague-Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA-408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points.
RESULTS
The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16-45) in the radiation control group, 3% (95% CI 0-11) in the nonirradiated control, and 3% (95% CI 0.2-10) in the radiation group treated with RTA-408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis.
CONCLUSIONS
Administration of RTA-408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery.
LEVEL OF EVIDENCE
Foundational Evidence, Animal Research Laryngoscope, 132:1196-1204, 2022.
Topics: Animals; Dimethyl Sulfoxide; Humans; Necrosis; Prospective Studies; Rats; Rats, Sprague-Dawley; Triterpenes
PubMed: 34709651
DOI: 10.1002/lary.29930 -
World Neurosurgery Nov 2023Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have...
OBJECTIVE
Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of RN in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required.
METHODS
The iatrogenic RN model included 50 Sprague-Dawley rats of both sexes. There were 7 treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30 mg/kg/day in a single dose) and pentoxifylline (50 mg/kg/day in 2 doses). Control magnetic resonance scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations.
RESULTS
The intensity of hypoxia - inducible factor 1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of vascular endothelial growth factor immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups. When compared with other groups, the therapeutic pentoxifylline group had significantly fewer vascular endothelial growth factor-immunoreactive cells in the perinecrotic area, with an accompanying decreased contrast enhancement pattern.
CONCLUSIONS
Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of RN, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.
Topics: Humans; Rats; Male; Female; Animals; Vitamin E; Pentoxifylline; Vascular Endothelial Growth Factor A; Rats, Sprague-Dawley; Radiation Injuries; Models, Animal; Necrosis
PubMed: 37689362
DOI: 10.1016/j.wneu.2023.08.135 -
International Journal of Radiation... Feb 2023
Topics: Humans; Brain Neoplasms; Brain; Necrosis; Radiosurgery; Retrospective Studies
PubMed: 36400622
DOI: 10.1016/j.ijrobp.2022.07.036 -
International Journal of Radiation... Jun 2024A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for... (Review)
Review
PURPOSE
A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities.
METHODS AND MATERIALS
A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models.
RESULTS
The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 59.8 Gy or 63.6 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively.
CONCLUSIONS
This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.
Topics: Humans; Necrosis; Child; Cancer Survivors; Methotrexate; Intelligence; Brain; Radiation Injuries; Brain Neoplasms; Cranial Irradiation; Intelligence Tests; Child, Preschool; Adolescent; Radiotherapy Dosage; Organs at Risk; Cognition; Antimetabolites, Antineoplastic
PubMed: 33810950
DOI: 10.1016/j.ijrobp.2020.11.073 -
Journal of Stomatology, Oral and... Dec 2023Few articles discuss the management of a free fibula flap (FFF) necrosis in maxillofacial reconstruction. (Review)
Review
INTRODUCTION
Few articles discuss the management of a free fibula flap (FFF) necrosis in maxillofacial reconstruction.
MATERIAL & METHODS
Between 2005 and 2020, 170 FFF were used for maxillofacial reconstruction at the University Hospital of Caen, among which 16 cases suffered total necrosis and flap removal. The authors categorized these 16 cases into three groups based on the proposed salvage treatment and analyzed the post-operative follow-up, including complications, length of hospital stay and delay in radiotherapy.
RESULTS
In Group A, two patients underwent immediate reconstruction with a new free flap. There were no postoperative complications, and the average hospitalization duration after removal of the first flap was 10 days. In Group B, eleven patients underwent reconstruction with a pedicled musculocutaneous pectoralis major flap. These patients experienced numerous complications, with 73% of them requiring at least one additional surgery, and all of them had an indication for later FFF reconstruction. The average hospitalization duration in this group was 37 days. In Group C, three patients underwent conservative management with debridement and mucosal closure. Two of them experienced complications, and all of them underwent later FFF reconstruction. The average hospitalization duration in this group was 15 days.
DISCUSSION
Based on our experience and the literature review, the use of an immediate new free flap appears to be the best approach after the removal of a FFF. This generates shorter healing times and shorter hospitalization stays, and this allows better results in terms of function and aesthetics. At least, this is the approach that causes the least delay for radiation therapy if indicated. The other approaches should only be proposed in case of patient's poor general condition or in case of refuse of the patient.
Topics: Humans; Fibula; Free Tissue Flaps; Necrosis; Plastic Surgery Procedures; Postoperative Complications; Wound Healing
PubMed: 37562713
DOI: 10.1016/j.jormas.2023.101586 -
Journal of Neuro-oncology Jan 2023Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis... (Review)
Review
PURPOSE
Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis. The purpose of this article is to review the imaging modalities used in differentiating radiation necrosis from tumor progression following radiation therapy for brain metastases.
METHODS
We performed a review of the literature addressing the radiographic modalities used in the diagnosis of radiation necrosis.
RESULTS
Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis.
CONCLUSION
Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed.
Topics: Humans; Radiosurgery; Brain Neoplasms; Magnetic Resonance Imaging; Positron-Emission Tomography; Radiation Injuries; Neoplasm Recurrence, Local; Diagnosis, Differential; Necrosis
PubMed: 36633800
DOI: 10.1007/s11060-022-04225-y -
Cancer Letters Oct 2020Stereotactic Radiosurgery has become the main treatment for patients with limited number of brain metastases (BM). Recently, with the increasing use of this modality,... (Review)
Review
Stereotactic Radiosurgery has become the main treatment for patients with limited number of brain metastases (BM). Recently, with the increasing use of this modality, there is a growth in recurrence cases. Recurrence after radiation therapy can be divided in changes favoring either tumor recurrence or radiation necrosis (RN). Laser Interstitial Thermal Therapy (LITT) is minimally invasive treatment modality that has been used to treat primary and metastatic brain tumors. When associated with real-time thermometry using Magnetic Resonance Imaging, the extent of ablation can be controlled to provide maximum coverage and avoid eloquent areas. The objective of this study was to investigate the use of LITT in the treatment of BM. An extensive review of the relevant literature was conducted and the outcome results are discussed. There is an emphasis on safety and local control rate of patients treated with this modality. The findings of our study suggest that LITT is a viable safe technique to treat recurrent BM, especially in patients with deep-seated lesions where surgical resection is not an option.
Topics: Brain Neoplasms; Humans; Laser Therapy; Necrosis; Radiation Injuries; Radiosurgery
PubMed: 32504657
DOI: 10.1016/j.canlet.2020.05.014