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Asian Pacific Journal of Cancer... May 2024The current research compared radiobiological and dosimetric results for simultaneous integrated boost (SIB) plans employing RapidArc and IMRT planning procedures in...
Assessment of the Dosimetric Index from IMRT and Rapid arc Plan for Oropharyngeal Cancer with Simultaneous Integrated Boost (SIB) Technique in Combination with EUD-based NTCP and TCP Radiobiological Models.
PURPOSE
The current research compared radiobiological and dosimetric results for simultaneous integrated boost (SIB) plans employing RapidArc and IMRT planning procedures in oropharyngeal cancer from head-and-neck cancer (HNC) patients.
MATERIALS AND METHODS
The indigenously developed Python-based software was used in this study for generation and analysis. Twelve patients with forty-eight total plans with SIB were planned using Rapid arc (2 and 3 arcs) and IMRT (7 and 9 fields) and compared with radiobiological models Lyman, Kutcher, Burman (LKB) and EUD (Equivalent Uniform Dose) along with physical index such as homogeneity index(HI), conformity index(CI) of target volumes.
RESULTS
These models' inputs are the dose-volume histograms (DVHs) calculated by the treatment planning system (TPS). The values obtained vary from one model to the other for the same technique and patient. The maximum dose to the brainstem and spinal cord and the mean dose to the parotids were analysed both dosimetrically and radiobiologically, such as the LKB model effective volume, equivalent uniform dose, EUD-based normal tissue complication probability, and normal tissue integral dose. The mean and max dose to target volume with conformity, homogeneity index, tumor control probability compared with treatment times, and monitor units.
CONCLUSION
Rapid arc (3 arcs) resulted in significantly better OAR sparing, dose homogeneity, and conformity. The findings indicate that the rapid arc plan has improved dose distribution in the target volume compared with IMRT, but the tumor control probability obtained for the two planning methods, Rapid arc (3 arcs) and IMRT (7 fields), are similar. The treatment time and monitor units for the Rapid arc (3 arcs) were superior to other planning methods and considered to be standard in head & neck radiotherapy.
Topics: Humans; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Oropharyngeal Neoplasms; Radiotherapy Dosage; Organs at Risk; Prognosis; Radiometry; Radiobiology
PubMed: 38809623
DOI: 10.31557/APJCP.2024.25.5.1515 -
Frontiers in Public Health 2024Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on...
INTRODUCTION
Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy Co gamma-radiation in mice.
METHODS
The gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation.
RESULTS
No significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in , , and . Ciprofloxacin generally led to lower Shannon diversity and prevalence with increases in and compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in and compared to Neulasta alone.
DISCUSSION
This study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.
Topics: Animals; Ciprofloxacin; Gastrointestinal Microbiome; Mice; Anti-Bacterial Agents; Acute Radiation Syndrome; Gamma Rays; Male; Female
PubMed: 38807988
DOI: 10.3389/fpubh.2024.1365161 -
NPJ Systems Biology and Applications May 2024Mass spectrometry imaging (MSI) allows to study cancer's intratumoral heterogeneity through spatially-resolved peptides, metabolites and lipids. Yet, in biomedical...
Mass spectrometry imaging (MSI) allows to study cancer's intratumoral heterogeneity through spatially-resolved peptides, metabolites and lipids. Yet, in biomedical research MSI is rarely used for biomarker discovery. Besides its high dimensionality and multicollinearity, mass spectrometry (MS) technologies typically output mass-to-charge ratio values but not the biochemical compounds of interest. Our framework makes particularly low-abundant signals in MSI more accessible. We utilized convolutional autoencoders to aggregate features associated with tumor hypoxia, a parameter with significant spatial heterogeneity, in cancer xenograft models. We highlight that MSI captures these low-abundant signals and that autoencoders can preserve them in their latent space. The relevance of individual hyperparameters is demonstrated through ablation experiments, and the contribution from original features to latent features is unraveled. Complementing MSI with tandem MS from the same tumor model, multiple hypoxia-associated peptide candidates were derived. Compared to random forests alone, our autoencoder approach yielded more biologically relevant insights for biomarker discovery.
Topics: Humans; Peptides; Animals; Neoplasms; Mice; Mass Spectrometry; Tumor Hypoxia; Biomarkers, Tumor; Cell Line, Tumor; Hypoxia
PubMed: 38802379
DOI: 10.1038/s41540-024-00385-x -
F1000Research 2023Preclinical models of radiotherapy (RT) response are vital for the continued success and evolution of RT in the treatment of cancer. The irradiation of tissues in mouse...
BACKGROUND
Preclinical models of radiotherapy (RT) response are vital for the continued success and evolution of RT in the treatment of cancer. The irradiation of tissues in mouse models necessitates high levels of precision and accuracy to recapitulate clinical exposures and limit adverse effects on animal welfare. This requirement has been met by technological advances in preclinical RT platforms established over the past decade. Small animal RT systems use onboard computed tomography (CT) imaging to delineate target volumes and have significantly refined radiobiology experiments with major 3Rs impacts. However, the CT imaging is limited by the differential attenuation of tissues resulting in poor contrast in soft tissues. Clinically, radio-opaque fiducial markers (FMs) are used to establish anatomical reference points during treatment planning to ensure accuracy beam targeting, this approach is yet to translate back preclinical models.
METHODS
We report on the use of a novel liquid FM BioXmark developed by Nanovi A/S (Kongens Lyngby, Denmark) that can be used to improve the visualisation of soft tissue targets during beam targeting and minimise dose to surrounding organs at risk. We present descriptive protocols and methods for the use of BioXmark in experimental male and female C57BL/6J mouse models.
RESULTS
These guidelines outline the optimum needle size for uptake (18-gauge) and injection (25- or 26-gauge) of BioXmark for use in mouse models along with recommended injection volumes (10-20 µl) for visualisation on preclinical cone beam CT (CBCT) scans. Injection techniques include subcutaneous, intraperitoneal, intra-tumoral and prostate injections.
CONCLUSIONS
The use of BioXmark can help to standardise targeting methods, improve alignment in preclinical image-guided RT and significantly improve the welfare of experimental animals with the reduction of normal tissue exposure to RT.
Topics: Animals; Mice; Fiducial Markers; Male; Feasibility Studies; Tomography, X-Ray Computed; Disease Models, Animal; Injections; Radiotherapy, Image-Guided; Female; Radiotherapy Planning, Computer-Assisted
PubMed: 38799243
DOI: 10.12688/f1000research.130883.1 -
Cancers May 2024Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on... (Review)
Review
Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response.
PubMed: 38792019
DOI: 10.3390/cancers16101942 -
Cancers May 2024The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and...
INTRODUCTION
The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies.
METHODS
We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications.
RESULTS
A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21-94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2-3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy (range 45.0-109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy ( = 0.015). Deep tumors were associated with worse OS ( < 0.05), and grade 2-3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS ( < 0.05). IMRT was associated with longer LC than 3DRT ( = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS ( < 0.05) and that patients with distant relapse had shorter OS ( < 0.0001).
CONCLUSION
RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS.
PubMed: 38791868
DOI: 10.3390/cancers16101789 -
International Journal of Molecular... May 2024This work reports on a model that describes patient-specific absorbed dose-dependent DNA damage response in peripheral blood mononuclear cells of thyroid cancer patients...
This work reports on a model that describes patient-specific absorbed dose-dependent DNA damage response in peripheral blood mononuclear cells of thyroid cancer patients during radioiodine therapy and compares the results with the ex vivo DNA damage response in these patients. Blood samples of 18 patients (nine time points up to 168 h post-administration) were analyzed for radiation-induced γ-H2AX + 53BP1 DNA double-strand break foci (RIF). A linear one-compartment model described the absorbed dose-dependent time course of RIF (Parameters: characterizes DSB damage induction; and are rate constants describing fast and slow repair). The rate constants were compared to ex vivo repair rates. A total of 14 patient datasets could be analyzed; ranged from 0.012 to 0.109 mGy, from 0 to 0.04 h. On average, 96% of the damage is repaired quickly with (range: 0.19-3.03 h). Two patient subgroups were distinguished by -values ( = 6, > 1.1 h; = 8, < 0.6 h). A weak correlation with patient age was observed. While induction of RIF was similar among ex vivo and in vivo, the respective repair rates failed to correlate. The lack of correlation between in vivo and ex vivo repair rates and the applicability of the model to other therapies will be addressed in further studies.
Topics: Humans; Thyroid Neoplasms; Middle Aged; Male; Female; DNA Repair; DNA Breaks, Double-Stranded; Adult; Aged; DNA Damage; Iodine Radioisotopes; Tumor Suppressor p53-Binding Protein 1; Histones; Leukocytes, Mononuclear; Models, Biological
PubMed: 38791531
DOI: 10.3390/ijms25105493 -
Insects May 2024In this study, oxidative stress and lipid peroxidation in honey bee larvae, pupae and the midguts of adult bees were investigated during a one-year exposure to...
In this study, oxidative stress and lipid peroxidation in honey bee larvae, pupae and the midguts of adult bees were investigated during a one-year exposure to radiofrequency electromagnetic fields (RF-EMFs) at a frequency of 900 MHz under field conditions. The experiment was carried out on honey bee colonies at three locations with electric field levels of 30 mV m, 70 mV m and 1000 mV m. Antioxidant enzymes, glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation were measured spectrophotometrically. The GST activity within the same developmental stage showed no significant differences regardless of electric field level or sampling time. The highest GST activity was found in the pupae, followed by activity in the larvae and midguts. Both CAT activity and TBARS concentration were the highest in the midguts, regardless of field level and sampling time. The larvae showed a significantly higher TBARS concentration at the location with an electric field level of 1000 mV m compared to the locations with lower levels. Our results show that RF-EMFs at a frequency of 900 MHz can cause oxidative stress in honey bees, with the larval stage being more sensitive than the pupal stage, but there was no linear relationship between electric field level and effect in any of the developmental stages.
PubMed: 38786928
DOI: 10.3390/insects15050372 -
Life Science Alliance Aug 2024Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE)...
Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the classification accuracy in two FFPE-RNA datasets with matched fresh-frozen (FF) RNA data, and an FF-derived RNA set. An FFPE-RNA application cohort of metastatic CRC patients was established, partly treated with anti-EGFR therapy. Key characteristics per CMS were assessed. Cross-referenced with matched benchmark FF CMS calls, the CMSFFPE classifier strongly improved classification accuracy in two FFPE datasets compared with the original CMSClassifier (63.6% versus 40.9% and 83.3% versus 66.7%, respectively). We recovered CMS-specific recurrence-free survival patterns (CMS4 versus CMS2: hazard ratio 1.75, 95% CI 1.24-2.46). Key molecular and clinical associations of the CMSs were confirmed. In particular, we demonstrated the predictive value of CMS2 and CMS3 for anti-EGFR therapy response (CMS2&3: odds ratio 5.48, 95% CI 1.10-27.27). The CMSFFPE classifier is an optimized FFPE-curated research tool for CMS classification of clinical CRC samples.
Topics: Humans; Colorectal Neoplasms; Paraffin Embedding; Biomarkers, Tumor; ErbB Receptors; Female; Consensus; Tissue Fixation; Male; Gene Expression Profiling; Aged; Middle Aged; Prognosis; Gene Expression Regulation, Neoplastic; Formaldehyde
PubMed: 38782602
DOI: 10.26508/lsa.202402730 -
Heliyon May 2024It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in...
OBJECTIVE
It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in large-scale nuclear accidents.
METHODS
C57BL/6J mice were subjected to whole-body and partial-body γ irradiation, as well as whole-body X-ray irradiation to explore the response of serum sSelectin-L to radiation injury. Then, it was compared with its response to lipopolysaccharide-induced acute infection and doxorubicin-induced DNA damage to study the specificity of sSelectin-L response to radiation. Furthermore, it was further evaluated in serum samples from nasopharyngeal carcinoma patients before and after radiotherapy. Simulated rescue experiments using Amifostine or bone marrow transplantation were conducted in mice with acute radiation syndrome to determine the potential for establishing sSelectin-L as a prognostic marker. The levels of sSelectin-L were dynamically measured using the ELISA method.
RESULTS
Selectin-L is mainly expressed in hematopoietic tissues and lymphatic tissues. Mouse sSelectin-L showed a dose-dependent decrease from 1 day after irradiation and exhibited a positive correlation with lymphocyte counts. Furthermore, the level of sSelectin-L reflected the degree of radiation injury in partial-body irradiation mice and in nasopharyngeal carcinoma patients. sSelectin-L was closely related to the total dose of γ or X ray. There was no significant change in the sSelectin-L levels in mice intraperitoneal injected with lipopolysaccharide or doxorubicin. The sSelectin-L was decreased slower and recovered faster than lymphocyte count in acute radiation syndrome mice treated with Amifostine or bone marrow transplantation.
CONCLUSIONS
Our study shows that sSelectin-L has the potential to be an early biomarker to classify injured individuals after radiation accidents, and to be a prognostic indicator of successful rescue of radiation victims.
PubMed: 38778981
DOI: 10.1016/j.heliyon.2024.e30527