Therapeutic Doses Of Radiation Research Articles

Targeting Oxidative Stress: The Potential of Vitamin C in Protecting against Liver Damage after Electron Beam Therapy.

Background: Radiation-induced liver disease (RILD) is a severe complication arising from radiotherapy, particularly when treating abdominal malignancies such as hepatocellular carcinoma. The liver's critical role in systemic metabolism and its proximity to other abdominal organs make it highly susceptible to radiation-induced damage. This vulnerability significantly limits the maximum safe therapeutic dose of radiation, thereby constraining the overall efficacy of radiotherapy. Among the various modalities, electron beam therapy has gained attention due to its ability to precisely target tumors while minimizing exposure to surrounding healthy tissues. However, despite its advantages, the long-term impacts of electron beam exposure on liver tissue remain inadequately understood, particularly concerning chronic injury and fibrosis driven by sustained oxidative stress. Objectives: to investigate the molecular and cellular mechanisms underlying the radioprotective effects of vitamin C in a model of radiation-induced liver disease. Methods: Male Wistar rats (n = 120) were randomly assigned to four groups: control, fractionated local electron irradiation (30 Gy), pre-treatment with vitamin C before irradiation, and vitamin C alone. The study evaluated the effects of electron beam radiation and vitamin C on liver tissue through a comprehensive approach, including biochemical analysis of serum enzymes (ALT, AST, ALP, and bilirubin), cytokine levels (IL-1β, IL-6, IL-10, and TNF-α), and oxidative stress markers (MDA and SOD). Histological and morphometric analyses were conducted on liver tissue samples collected at 7, 30, 60, and 90 days, which involved standard staining techniques and advanced imaging, including light and electron microscopy. Gene expression of Bax, Bcl-2, and caspase-3 was analyzed using real-time PCR. Results: The present study demonstrated that fractional local electron irradiation led to significant reductions in body weight and liver mass, as well as marked increases in biochemical markers of liver damage (ALT, AST, ALP, and bilirubin), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and oxidative stress markers (MDA) in the irradiated group. These changes were accompanied by substantial histopathological alterations, including hepatocyte degeneration, fibrosis, and disrupted microvascular circulation. Pre-treatment with vitamin C partially mitigated these effects, reducing the severity of the liver damage, oxidative stress, and inflammation, and preserving a more favorable balance between hepatocyte proliferation and apoptosis. Overall, the results highlight the potential protective role of vitamin C in reducing radiation-induced liver injury, although the long-term benefits require further investigation. Conclusions: The present study highlights vitamin C's potential as a radioprotective agent against electron beam-induced liver damage. It effectively reduced oxidative stress, apoptosis, and inflammation, particularly in preventing the progression of radiation-induced liver fibrosis. These findings suggest that vitamin C could enhance radiotherapy outcomes by minimizing liver damage, warranting further exploration into its broader clinical applications.

The influence of different radiotherapy doses on the mechanical properties and microstructure of the enamel and dentin of human premolar teeth.

Radiation therapy is applied in the treatment of head and neck cancer patients. However, oral-health-related side effects like hyposalivation and ahigher prevalence of caries have been shown. This study aims to assess the influence of different radiotherapy doses on the mechanical properties, roughness, superficial microstructure, and crystallinity of the enamel and dentin of human premolar teeth. Specimens (n = 25) were categorized into five groups based on the radiation dose received (0, 10, 30, 50, and 70 Gy). The enamel and dentin of these specimens were subjected to amicrohardness tester, profilometer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and X‑ray diffraction (XRD) before and after different irradiation doses and compared to hydroxylapatite in each group. The data were analyzed using repeated-measures analysis of variance (ANOVA). Therapeutic radiation doses of 30, 50, and 70 Gy led to adecrease in the microhardness and an increase in the average roughness of the enamel, and rougher surfaces were observed in the mixed three-dimensional images. Moreover, in the dentin, asimilar outcome could be observed for more than 10 Gy. The main crystalline phase structure remained hydroxylapatite, but the crystallinity decreased and the crystalline size increased above 10 Gy. The superficial micromorphology revealed granulation, fissures, and cracks in adose-dependent manner. Radiation below 70 Gy had little effect on the hydroxylapatite concentration during the whole experiment. Above aradiation dose of 30 Gy, the micromorphology of the tooth enamel changed. This occurred for dentin above 10 Gy, which indicates that dentin is more sensitive to radiotherapy than enamel. The radiation dose had an effect on the micromorphology of the hard tissues of the teeth. These results illustrate the possible mechanism of radiation-related caries and have guiding significance for clinical radiotherapy.

Exploring predictive molecules of acute adverse events in response to volumetric‑modulated arc therapy for prostate cancer using urinary metabolites.

Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.

The effect of therapeutic dose of gamma radiation on fracture resistance of endodontically treated tooth obturated using different types of sealers (An in-vitro study)

The effect of therapeutic dose of gamma radiation on fracture resistance of endodontically treated tooth obturated using different types of sealers (An in-vitro study)

Targeted Alpha Therapy for Glioblastoma: Review on In Vitro, In Vivo and Clinical Trials.

Glioblastoma (GB), a prevalent and highly malignant primary brain tumour with a very high mortality rate due to its resistance to conventional therapies and invasive nature, resulting in 5-year survival rates of only 4-17%. Despite recent advancements in cancer management, the survival rates for GB patients have not significantly improved over the last 10-20 years. Consequently, there exists a critical unmet need for innovative therapies. One promising approach for GB is Targeted Alpha Therapy (TAT), which aims to selectively deliver potentially therapeutic radiation doses to malignant cells and the tumour microenvironment while minimising radiation exposure to surrounding normal tissue with or without conventional external beam radiation. This approach has shown promise in both pre-clinical and clinical settings. A review was conducted following PRISMA 2020 guidelines across Medline, SCOPUS, and Embase, identifying 34 relevant studies out of 526 initially found. In pre-clinical studies, TAT demonstrated high binding specificity to targeted GB cells, with affinity rates between 60.0% and 84.2%, and minimal binding to non-targeted cells (4.0-5.6%). This specificity significantly enhanced cytotoxic effects and improved biodistribution when delivered intratumorally. Mice treated with TAT showed markedly higher median survival rates compared to control groups. In clinical trials, TAT applied to recurrent GB (rGB) displayed varying success rates in extending overall survival (OS) and progression-free survival. Particularly effective when integrated into treatment regimens for both newly diagnosed and recurrent cases, TAT increased the median OS by 16.1% in newly diagnosed GB and by 36.4% in rGB, compared to current standard therapies. Furthermore, it was generally well tolerated with minimal adverse effects. These findings underscore the potential of TAT as a viable therapeutic option in the management of GB.

Methods of intrinsic and probe fluorescence in assessment of the effect of therapeutic radiation doses &lt;i&gt;in vitro&lt;/i&gt; on the albumin molecule

Objective. To study in vitro the effect of therapeutic doses of radiation on the albumin molecule using intrinsic and probe fluorescence methods. Materials and methods. In order to study radiation-induced changes in serum albumin during in vitro irradiation with therapeutic doses (2 Gy, 40 Gy and 70 Gy), the study was conducted in 2 directions: therapeutic doses of ionizing radiation irradiated a buffer, which was then used to prepare an albumin solution (pre-irradiation of the buffer); therapeutic doses of ionizing radiation irradiated an albumin buffer solution. The presence of structural and functional (conformational) changes in the albumin molecule was judged by changes in the values of intrinsic (λexc=280 nm) and probe (λexc=280nm, λexc=320 nm) fluorescence. Statistical processing of the obtained data was carried out using the program GraphPad Prism 6.0. Results. Irradiation with therapeutic doses of 2 Gy, 40 Gy and 70 Gy causes conformational changes (a statistically significant decrease in fluorescence intensity) in the albumin molecule, both during preliminary irradiation of the buffer solution used later for the preparation of albumin, and during irradiation of the buffer solution of albumin. Conclusions. Quantitative changes in the fluorescence intensity, both intrinsic and probe, differ under different modes of albumin irradiation.

Functional information guided adaptive radiation therapy.

Functional informaton is introduced as the mechanism to adapt cancer therapies uniquely to individual patients based on changes defined by qualified tumor biomarkers. To demonstrate the methodology, a tumor volume biomarker model, characterized by a tumor volume reduction rate coefficient, is used to adapt a tumor cell survival bioresponse radiotherapy model in terms of therapeutic radiation dose. Tumor volume, acquired from imaging data, serves as a surrogate measurement for tumor cell death, but the biomarker model derived from this data cannot be used to calculate the radiation dose absorbed by the target tumor. However, functional information does provide a mathematical connection between the tumor volume biomarker model and the tumor cell survival bioresponse model by quantifying both data sets in the units of information, thus creating an analytic conduit from bioresponse to biomarker. The information guided process for individualized dose adaptations using information values acquired from the tumor cell survival bioresponse model and the tumor volume biomarker model are presented in detailed form by flowchart and tabular data. Clinical data are used to generate a presentation that assists investigator application of the information guided methodology to adaptive cancer therapy research. Information guided adaptation of bioresponse using surrogate data is extensible across multiple research fields because functional information mathematically connects disparate bioresponse and biomarker data sets. Thus, functional information offers adaptive cancer therapy by mathematically connecting immunotherapy, chemotherapy, and radiotherapy cancer treatment processes to implement individualized treatment plans.

Delivery of High-Intensity Proton Beam for the Study of Flash-Effect in Radiotherapy

Flash-therapy is a rapidly developing field of radiology that has the potential to revolutionize future cancer treatment techniques. The method involves delivery the therapeutic radiation dose to the tumor volume at an ultra-high dose rate in the beam, several orders of magnitude higher than that usually used in conventional radiotherapy. In this mode of irradiation, the degree of damage to normal tissues surrounding the tumor and falling under the influence of radiation decreases, at the same time, the effect on cancer cells remains at the same level, which preserves the prospect of local control of the tumor with a lower frequency of side effects.&#x0D; The paper presents the results on the delivery of a high-intensity proton beam with an energy of 660 MeV from the Phasotron of the Joint Institute for Nuclear Research, Dubna, designed for radiobiological studies under flash therapy irradiation of cell cultures and small laboratory animals (mice, rats). In addition, the main design features and parameters of the created detectors for measuring the characteristics of this beam are presented.

Architecture, flexibility and performance of a special electron linac dedicated to Flash radiotherapy research: electronFlash with a triode gun of the centro pisano flash radiotherapy (CPFR)

The FLASH effect is a radiobiological phenomenon that has garnered considerable interest in the clinical field. Pre-clinical experimental studies have highlighted its potential to reduce side effects on healthy tissues while maintaining isoeffectiveness on tumor tissues, thus widening the therapeutic window and enhancing the effectiveness of radiotherapy. The FLASH effect is achieved through the administration of the complete therapeutic radiation dose within a brief time frame, shorter than 200 milliseconds, and, therefore, utilizing remarkably high average dose rates above at least 40 Gy/s. Despite its potential in radiotherapy, the radiobiological mechanisms governing this effect and its quantitative relationship with temporal parameters of the radiation beam, such as dose-rate, dose-per-pulse, and average dose-rate within the pulse, remain inadequately elucidated. A more profound comprehension of these underlying mechanisms is imperative to optimize the clinical application and translation of the FLASH effect into routine practice. Due to the aforementioned factors, the undertaking of quantitative radiobiological investigations becomes imperative, necessitating the utilization of sophisticated and adaptable apparatus capable of generating radiation beams with exceedingly high dose-rates and dose-per-pulse characteristics. This study presents a comprehensive account of the design and operational capabilities of a Linear Accelerator (LINAC) explicitly tailored for FLASH radiotherapy research purposes. Termed the “ElectronFlash” (EF) LINAC, this specialized system employs a low-energy configuration (7 and 9 MeV) and incorporates a triode gun. The EF LINAC is currently operational at the Centro Pisano FLASH Radiotherapy (CPFR) facility located in Pisa, Italy. Lastly, this study presents specific instances exemplifying the LINAC’s adaptability, enabling the execution of hitherto unprecedented experiments. By enabling independent variations of the temporal parameters of the radiation beam implicated in the FLASH effect, these experiments facilitate the acquisition of quantitative data concerning the effect’s dependence on these specific parameters. This novel approach hopefully contributes to a more comprehensive understanding of the FLASH effect, shedding light on its intricate radiobiological behavior and offering valuable insights for optimizing its clinical implementation.

Efficacy of different remineralizing agents on primary teeth exposed to therapeutic gamma radiation: An in vitro randomized control study

BackgroundTherapeutic radiation-induced caries is a major side effect. Dental and oral heath are adversely affected by the direct effects of radiotherapy. Preventive procedures are preferred to reinforce dental tissue resistance against radiation damage. ObjectiveResearch aim is to test the impact of different remineralizing protocols on the mineral content of deciduous enamel exposed to a therapeutic dose of gamma radiation. MethodsThirty deciduous enamel specimens were divided randomly into three experimental categories based on the type of remineralizing agent used. Group I (gamma irradiated teeth, then painted with fluoride varnish), Group II (gamma irradiated teeth, then treated with bioactive glass) and Group III (gamma irradiated teeth, and then treated with a diode laser 980 nm). Prepared specimens were assessed for mineral content by environmental Energy Dispersive X-ray Analysis. SEM photomicrographs were performed simultaneously. Results were investigated concerning pre- and post-irradiation values difference. The paired-samples t-test was performed to compare the atomic and weight percentages of the selected elements obtained from the samples in the control groups before and after therapeutic radiation. One-way analysis of variance and post hoc Tukey tests were used to compare between the categories regarding weight and atomic percentages. ResultsCalcium/Phosphorus (Ca/P) ratio and Fluoride content decreased significantly after radiotherapy. Fluoride content significantly increased after remineralizing agents' application with the greatest increase in Bioactive glass group followed by fluoride varnish (F.varnish) group and the least increase was in diode laser group. Significant increase in Ca/P ratio in bioactive glass group followed by insignificant increase in F.varnish group (I) with the least increase noticed in the Diode laser group. ConclusionTherapeutic radiation caused marked decrease in enamel mineral content. However, the reminralizing agents applied have an improving effect on the caused damage.

Heavy Ion Radiation Directly Induced the Shift of Oral Microbiota and Increased the Cariogenicity of Streptococcus mutans.

Radiation caries is one of the most common complications of head and neck radiotherapy. A shift in the oral microbiota is the main factor of radiation caries. A new form of biosafe radiation, heavy ion radiation, is increasingly being applied in clinical treatment due to its superior depth-dose distribution and biological effects. However, how heavy ion radiation directly impacts the oral microbiota and the progress of radiation caries are unknown. Here, unstimulated saliva samples from both healthy and caries volunteers and caries-related bacteria were directly exposed to therapeutic doses of heavy ion radiation to determine the effects of radiation on oral microbiota composition and bacterial cariogenicity. Heavy ion radiation significantly decreased the richness and diversity of oral microbiota from both healthy and caries volunteers, and a higher percentage of Streptococcus was detected in radiation groups. In addition, heavy ion radiation significantly enhanced the cariogenicity of saliva-derived biofilms, including the ratios of the genus Streptococcus and biofilm formation. In the Streptococcus mutans-Streptococcus sanguinis dual-species biofilms, heavy ion radiation increased the ratio of S. mutans. Next, S. mutans was directly exposed to heavy ions, and the radiation significantly upregulated the gtfC and gtfD cariogenic virulence genes to enhance the biofilm formation and exopolysaccharides synthesis of S. mutans. Our study demonstrated, for the first time, that direct exposure to heavy ion radiation can disrupt the oral microbial diversity and balance of dual-species biofilms by increasing the virulence of S. mutans, increasing its cariogenicity, indicating a potential correlation between heavy ions and radiation caries. IMPORTANCE The oral microbiome is crucial to understanding the pathogenesis of radiation caries. Although heavy ion radiation has been used to treat head and neck cancers in some proton therapy centers, its correlation with dental caries, especially its direct effects on the oral microbiome and cariogenic pathogens, has not been reported previously. Here, we showed that the heavy ion radiation directly shifted the oral microbiota from a balanced state to a caries-associated state by increasing the cariogenic virulence of S. mutans. Our study highlighted the direct effect of heavy ion radiation on oral microbiota and the cariogenicity of oral microbes for the first time.

Transformative Technology for FLASH Radiation Therapy.

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams.

Radiation-induced inferior brachial plexopathy after stereotactic body radiotherapy: Pooled analyses of risks

IntroductionRadiation-induced brachial plexopathy (RIBP), resulting in symptomatic motor or sensory deficits of the upper extremity, is a risk after exposure of the brachial plexus to therapeutic doses of radiation. We sought to model dosimetric factors associated with risks of RIBP after stereotactic body radiotherapy (SBRT). MethodsFrom a prior systematic review, 4 studies were identified that included individual patient data amenable to normal tissue complication probability (NTCP) modelling after SBRT for apical lung tumors. Two probit NTCP models were derived: one from 4 studies (including 221 patients with 229 targets and 18 events); and another from 3 studies (including 185 patients with 192 targets and 11 events) that similarly contoured the brachial plexus. ResultsNTCP models suggest ≈10% risks associated with brachial plexus maximum dose (Dmax) of ∼32–34 Gy in 3 fractions and ∼40–43 Gy in 5 fractions. RIBP risks increase with increasing brachial plexus Dmax. Compared to previously published data from conventionally-fractionated or moderately-hypofractionated radiotherapy for breast, lung and head and neck cancers (which tend to utilize radiation fields that circumferentially irradiate the brachial plexus), SBRT (characterized by steep dose gradients outside of the target volume) exhibits a much less steep dose–response with brachial plexus Dmax > 90–100 Gy in 2-Gy equivalents. ConclusionsA dose–response for risk of RIBP after SBRT is observed relative to brachial plexus Dmax. Comparisons to data from less conformal radiotherapy suggests potential dose-volume dependences of RIBP risks, though published data were not amenable to NTCP modelling of dose-volume measures associated with RIBP after SBRT.

Optimal timing of a γH2AX analysis to predict cellular lethal damage in cultured tumor cell lines after exposure to diagnostic and therapeutic radiation doses.

Phosphorylated H2AX (γH2AX) is a sensitive biomarker of DNA double-strand breaks (DSBs). To assess the adverse effects of low-dose radiation (<50mGy), γH2AX levels have typically been measured in human lymphocytes within 30min of computed tomography (CT) examinations. However, in the presence of DSB repair, it remains unclear whether γH2AX levels within 30min of irradiation completely reflect biological effects. Therefore, we investigated the optimal timing of a γH2AX analysis to predict the cell-surviving fraction (SF). Three tumor cell lines were irradiated at different X-ray doses (10-4000mGy), and the relationships between SF and relative γH2AX levels were investigated 15min and 2, 6, 12 and 24h after irradiation. Data were analyzed for high-dose (0-4000mGy) and low-dose (0-500mGy) ranges. Correlations were observed between SF and the relative number of γH2AX foci/nucleus at 12h only (R2 = 0.68, P = 0.001 after high doses; R2 = 0.37, P = 0.016 after low doses). The relative intensity of γH2AX correlated with SF 15min to 12h after high doses and 2 to 12h after low doses, with the maximum R2 values being observed 2h after high doses (R2 = 0.89, P < 0.001) and 12h after low doses (R2 = 0.65, P < 0.001). Collectively, cellular lethal damage in tumor cells was more accurately estimated with residual DSBs 12h after low-dose (10-500mGy) irradiation. These results may contribute to determination of the optimal timing of biodosimetric analyses using γH2AX in future studies.

Paper based radiochromic film for the detection and measurement of therapeutic radiation doses in radiotherapy: A preliminary study

Radiotherapy is an effective and complex treatment modality for the ablation of malignant tumors. Despite several technological advances, precise determination of the radiation dose delivered to the tumor and its neighbouring healthy tissues remains a challenge. This work focuses on the synthesis and characterisation of a symmetrically substituted diacetylene which is coated on a paper to function as a radiochromic film. The paper-based film exhibits distinct color change from white to varying shades of blue from the 0.5–20 Gy dose range administered in radiotherapy. The difference in the color intensity of the radiochromic film is used as a quantitative indicator of the radiation dose delivered. A comprehensive evaluation of general optical characteristics, dosimetric properties and stability of the dose response is performed. The prepared film is tissue-equivalent with weak dependence on dosimetric parameters like energy, dose rate and dose accumulation. It can be stored under normal room conditions as the influence of variation in temperature, light intensity and post irradiation time was found to be <2%. The uncertainty in the dose response based on the calibration curve was found to be 2.74%. The therapeutic range of radiation dose detection, facile fabrication and implementation of this radiochromic film can be potentially translated into different radiotherapy clinical applications.

Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma.

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques. Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes.

Combining Targeted Radionuclide Therapy and Immune Checkpoint Inhibition for Cancer Treatment.

The development of immunotherapy, in particular immune checkpoint inhibitors (ICI), has revolutionized cancer treatment in the past decades. However, its efficacy is still limited to subgroups of patients with cancer. Therefore, effective treatment combination strategies are needed. Here, radiotherapy is highly promising, as it can induce immunogenic cell death, triggering the release of pro-inflammatory cytokines, thereby creating an immunogenic phenotype and sensitizing tumors to ICI. Recently, targeted radionuclide therapy (TRT) has attained significant interest for cancer treatment. In this approach, a tumor-targeting radiopharmaceutical is used to specifically deliver a therapeutic radiation dose to all tumor cells, including distant metastatic lesions, while limiting radiation exposure to healthy tissue. However, fundamental differences between TRT and conventional radiotherapy make it impossible to directly extrapolate the biological effects from conventional radiotherapy to TRT. In this review, we present a comprehensive overview of studies investigating the immunomodulatory effects of TRT and the efficacy of combined TRT-ICI treatment. Preclinical studies have evaluated a variety of murine cancer models in which α- or β-emitting radionuclides were directed to a diverse set of targets. In addition, clinical trials are ongoing to assess safety and efficacy of combined TRT-ICI in patients with cancer. Taken together, research indicates that combining TRT and ICI might improve therapeutic response in patients with cancer. Future research has to disclose what the optimal conditions are in terms of dose and treatment schedule to maximize the efficacy of this combined approach.

Ectopic Recurrence of Skull Base Chordoma after Proton Therapy.

Simple SummaryChordoma are very rare tumors of the spine and skull base. Due to close proximity of crucial organs, like the brain stem, complete removal can often not be achieved, and tumor tissue, either macroscopic or microscopic, remains in situ. Local recurrence up to 88% occurs in 10 years. Ectopic recurrence as an early sign of treatment failure is considered rare. We retrospectively reviewed five patients with ectopic recurrence as a first sign of treatment failure after treatment with surgery and proton therapy, and studied the applied treatment strategies and imaging follow-up. We found 18 ectopic recurrences in these five patients, of which 17 (94%) could be related to prior surgical tracts. Our theory is that these relapses occur due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival.Background: Chordoma are rare tumors of the axial skeleton. The treatment gold standard is surgery, followed by particle radiotherapy. Total resection is usually not achievable in skull base chordoma (SBC) and high recurrence rates are reported. Ectopic recurrence as a first sign of treatment failure is considered rare. Favorable sites of these ectopic recurrences remain unknown. Methods: Five out of 16 SBC patients treated with proton therapy and surgical resection developed ectopic recurrence as a first sign of treatment failure were critically analyzed regarding prior surgery, radiotherapy, and recurrences at follow-up imaging. Results: Eighteen recurrences were defined in five patients. A total of 31 surgeries were performed for primary tumors and recurrences. Seventeen out of eighteen (94%) ectopic recurrences could be related to prior surgical tracts, outside the therapeutic radiation dose. Follow-up imaging showed that tumor recurrence was difficult to distinguish from radiation necrosis and anatomical changes due to surgery. Conclusions: In our cohort, we found uncommon ectopic recurrences in the surgical tract. Our theory is that these recurrences are due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival.

Monte Carlo Code Calculation for the Characterization of 10nm Nano-Layers Coated 50nm 90Y Radionuclide Nanospheres Radiation in the Liver Radionuclide Therapy

Purpose: Cancer radionuclide therapy is an effective, beneficial, and crucial method of cancer treatment that uses unsealed radioactivated radionuclides sources that are attached to a targeting vector to deliver therapeutic radiation doses from the ionizing radiation source to specific disease sites either for curative intent or for disease control and palliation for the patient pain decreasing. For this aim, Monte Carlo N–Particle 5 (MCNP5) MC computational code was employed for simulations and calculations as well as radiation transport. Materials and Methods: 50nm 90Y radionuclide nanosphere was modelled coated by a 10nm coating layer with some non-toxic high and low Z materials. Physical interactions, such as β-ray and the simulated coating materials were studied and radiological parameters were scored by the used MC code. Attenuation of β-ray, and production of the bremsstrahlung X-ray photons and other phenomena were simulated by the code and analyzed. MC code estimated the effect of the simulated coating materials, such as Gold, Platinum, Gaddolonium, Silver, and Epoxy-Resin on the radiation characteristics around the modelled nano-radionuclide per 2nm from the radiation source surface to 1µm distance. Produced bremsstrahlung X-ray by the source coating material and tissue atoms, emitted β-particle number, flux over the surfaces (per 2nm), radiation fluence of photon and β- ray, deposited energy per gr of the cell medium, and average dose to the cells around the 500nm and 1µm distance from the radionuclide source surface also was derived. Results: Our results showed that coating the radionuclide with the materials especially high Z (Gold and Platinum) materials may produce a dual emitter radiation source, X-ray photon and β- ray and is capable of killing the cancer cells more than the source with not-coated source. Conclusion: Our conclusion was that coating the β- ray emitter radionuclides, especially high-energy β- ray, enhances its therapeutical capability with X-ray and β- ray emission. The studied coated sources in our study were performed as a dual radiation source; produced X-ray and β-ray, which increases the therapeutic efficiency of the source.

Development of spreadsheet for rapid assessment of therapeutic radiation dose delivery with electron and photon beams at various energies

Development of spreadsheet for rapid assessment of therapeutic radiation dose delivery with electron and photon beams at various energies