Conventional Radiotherapy Research Articles

Berberine and berberine nanoformulations in cancer therapy: Focusing on lung cancer.

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.

Sustainable Green Synthesis and Molecular Docking Study of a Bis-Fused System Incorporating Pyrido[2,3-d]pyrimidine using Nanocatalyst under Microwave Condition

Aims: This study aimed to employ sustainable green methods in the synthesis of bisfused cycles incorporating pyrido[2,3-d]pyrimidine moiety using a green catalyst nano ZnO catalyst by one-pot, multicomponent reaction among 2,2'-(propane-1,3-diylbis(sulfanediyl)) bis(6-aminopyrimidin-4(3H)-one) 3, 1H-indene-1,3(2H)-dione 4, and aromatic aldehydes 5. Method: The reactions proceeded with both conventional and microwave (MW) irradiation methods. Result:: The microwave-assisted method carried out the reaction in 10 min and had high yields (89-95%). Conclusion: A molecular docking simulation study was conducted using human serum albumin (PDB: ID (2XVQ)). The study revealed that compounds strongly fit into the active sites of the target protein.

Radiation Exposure During Invasive Cardiovascular Procedures: Portable Shielding System Versus Standard Lead Aprons.

Introduction Significant progress in the field of interventional cardiology has led to a rise in percutaneous procedures and an increase in the risk of radiation exposure at the workplace. Staff health has been put at risk due to the limitations of conventional radiation protective techniques. Innovative methods, such as RAMPART, have promising prospects for enhancing radiation safety. The purpose of this study was to evaluate RAMPART's effectiveness and practicality in comparison to conventional protective techniques with a lead apron and shield (LAS) during cardiac interventional procedures. Method One hundred elective cardiac procedures were enrolled in this prospective single-center research study. Two groups were formed from the participants: standard protection (group A) and RAMPAT system (group B). Real-time dosimeters were used to track the radiation dosage, dosage reduction factor, dosage reduction percentage, and likelihood of exceeding the limit, which were included in the data. Proceduralists were urged to use different strategies to reduce exposure. The study was approved by an ethical committee and ran from June 2023 to August 2023. Results When comparing the RAMPART group to the conventional protection group, neck-level radiation exposure was considerably lower for all workers. There were no notable variations in the exposure of the waist. The RAMPART group was shown to be superior in minimizing radiation exposure, as evidenced by dose reduction metrics. The groups had comparable procedural characteristics. Conclusion Compared to conventional LAS, the RAMPART system dramatically reduces radiation exposure to the entire body.

Feasibility of Flash Radiation Therapy Using X-ray Sources Based on Simulation Method

Background: The main challenge in radiation therapy (RT) has been the destruction of tumor or cancerous tissue while causing the least damage to healthy and normal tissues around the tumor. This is despite the fact that the maximum tolerated dose for normal tissue is limited, and this factor limits tumor destruction with radiation, thus lowering the efficiency of RT. The flash effect was initially proposed as a solution for the movement of the organ under treatment, such as the lung, demonstrating that tissue displacement occurs with breathing. Methods: In this study, the feasibility of achieving the flash effect, in the direction of the beam and perpendicular to the direction of the radiation beam was investigated using X-rays with energies in keV. Results: The results of this study, which is the only examination of the effect of distance on radiation, revealed that the amount of energy received in the target increased with the shortening of the distance, and on the other hand, in the direction perpendicular to the radiation, the extent and dispersion of the beam were reduced with the shortening of the distance between the source and the surface of the phantom. Conclusion: This issue can justify in flash effect, the beam will be more concentrated and theside tissues will be less affected by the radiation compared to conventional radiation therapy

Carbon - 12C ion radiation-induced cell death and molecular mechanisms in malignant cells: Evidence from in vivo and in vitro

Conventional radiotherapy has been revolutionized for several decades. Recently, the delivery of high linear energy transfer (LET) radiation such as heavy carbon ion therapy has gained more attention. Among all low-energy therapies such as photon, X-ray, and gamma radiation therapy, 12C heavy carbon ion therapy is the best therapy for cancer treatment due to its high relative biological effectiveness (RBE). It has been studied that many tumors show resistance to chemotherapy and low energy transfer radiation. The unique nature of high LET shows unique Bragg peaks where very little radiation are applied on the tumor cells and better results can be achieved. It effectively kills the tumor cells without affecting the normal cells. There are some limitations to conventional radiotherapy. Radiotherapy with the low LET group may not work properly. Carbon ion radiation (CIR) induces malignant cell death in different modes, such as apoptosis, senescence, autophagy, immunogenic cell death and necrosis. Heavy carbon ion therapy enhances cell death by altering different molecular signalling pathways such as p53, AKT, MEK, caspase and STAT–3. Investigation of the major molecular cell death by carbon ion irradiation is very essential to understand the modalities of heavy carbon ion induced cell death. In this context, the investigation of different signaling cascades may open new horizons in cancer treatment. The therapeutic efficacy and application of heavy carbon ion beams along with some molecular inhibitors, radio sensitizers, and gene therapy would be helpful for future cancer treatment. Therefore, a more thorough investigation in this field is needed. The current review article highlights the recent advances in cancer therapy research based on Carbon 12C Ion radiation-induced cell death.

Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.

Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors.

The Landscape of Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Cancer (RCC).

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

Failure analysis of a separator under various thermal loading: A numerical study

In the present study, Computational Fluid Dynamics (CFD) simulations were carried out on a separator subjected to three different fire scenarios: pool fire, jet fire and fireballs. The empirical models applicable to such plants are not developed and conventional radiation models leads to an overestimation of the heat flux and safety distances. Therefore an alternative tool like CFD along with empirical models is used to model the potential scenarios mentioned above in a model oil and gas separator plant. The developed model were validated by comparing literature data on the flame length, maximum flame temperature and its location above pan surface in case of pool fire and comparing them with literature data. It is found that in case of flame length the deviation from literature data was about 10% and less than 5% for the maximum flame temperature. For jet fire the average surface temperature was 561 K while this value is 423 K in case of pool fire and 317 K for fireballs. When it comes to the radiative flux, an average value of 29 kW/m2 is found for jet fires while this value was only 14 kW/m2 for pool fire and 23 kW/m2 for fireballs. The thermal loads on the separator vessel due to above fire scenarios were also calculated. The obtained value of thermal stresses were around 285 MPa and 600 MPa for pool and jet fires respectively. Thus it can be concluded that from safety point of view jet fires are the most critical one. The results obtained form simulations were also compared with that of data from empirical models.

Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.

Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) protects against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity of granule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. To explore the sensitivity of different neuronal populations to cranial irradiation and dose-rate modulation, hippocampal CA1 and medial prefrontal cortex (PFC) pyramidal neurons were analyzed by electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in PFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3×10Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are more radioresistant irrespective of radiation dose-rate.

Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up.

Higher risk of secondary brain tumor, carotid stenosis and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion and stroke after SRS. In this multicentric retrospective study, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. There were 9,840.1 patient-years at risk for the SRS and 5,266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95%CI:0.5%, 4.1%) for SRS and 3.7% (95%CI:0%, 8.7%) for the control group (p=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95%CI: 0.2, 1.6) in the SRS and 2% (95%CI: 0, 4.4) in the control group (p=0.8). The 15-year probability of stroke was 2.6% (95%CI: 0.6%, 4.6%) in the SRS and 11.1% (95%CI: 6%, 15.9%) in the control group (p<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.

Upconverting Ultra-Thin Bi2O2CO3 Nanosheets for Synergistic Photodynamic Therapy and Radiotherapy.

Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.

Validation of Acuros for total body irradiation at extended distance.

Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30cm from the surface of the phantoms as per our clinical set up. The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500cm.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization

Objective. This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART). Approach. The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection. Main results. Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose, V 20, and V 5 were significantly reduced by 1.13 Gy (p < .001), 2.01% (p < .001), and 6.66% (p < .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p < .01), fV 20 by 0.90% (p = 0.099), and fV 5 by 5.07% (p < .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection. Significance. AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Technologies for retrospective radiation dosimetry.

Radiation dosimetry is an important task for assessing the biological damages created in human being due to ionising radiation exposure. Ionising radiation being invisible and beyond the perception of human natural sensors, the dosimetry equipments/systems are the utmost requirement for its measurement. Retrospective measurement of radiation doses is a challenging task as conventional radiation dosemeters are not available at the exposure site. The material/s in close proximity of exposed individual or individuals' biological samples may be used as retrospective radiation sensor for dosimetry purpose. Environment materials such as sand, bricks, ceramics, sand stones, quartz, feldspar, glasses and electronic chips have been utilised using TL (Thermoluminescence) techniques for retrospective gamma dose (min 10cGy) measurement. Electron Spin Resonance techniques have been employed to human biological samples such as tooth enamel, bones, nails, hair, etc. and reported for dosimetry for ~20cGymin dose measurement. Some commercial glasses have been found sensitive enough to measure the minimum gamma doses of the order of 100cGy using TL techniques. For internal retrospective dosimetry, the radioactivity contamination assessment in food items, water, other edible product and ambient air are the prerequisites. The radioactivity concentration vis-à-vis their consumption rate may help in controlling the internal contamination and estimation of dose absorption in human body. Defence Laboratory, Jodhpur has been working extensively on the dosimetry techniques for external dose measurement using environmental material and developed portable contamination monitoring systems for food and water radioactivity measurement in the range of 50Bq kg-1 to 1000kBq kg-1 in 60s measurement time. The recent research and development in the methodologies, equipments and systems undertaken towards capacity building and self-reliance in retrospective radiation dosimetry is reported in this paper.

Time to first remission and survival in patients with acromegaly: Evidence from the UK Acromegaly Register Study (UKAR).

This study aimed to understand the effect of time to remission of acromegaly on survival in people living with acromegaly. This cross-sectional study used data from the UK Acromegaly Register. We considered remission of acromegaly growth hormone controlled at ≤2 μg/L following the diagnosis of acromegaly. We used the accelerated failure time model to assess the effect of time to remission on survival in acromegaly. The study population comprises 3569 individuals with acromegaly, with a median age of diagnosis of 47.3 (36.5-57.8) years, 48% females and a majority white population (61%). The number of individuals with the first remission of acromegaly was 2472, and the median time to first remission was 1.92 (0.70-6.58) years. In this study, time to first remission in acromegaly was found to have a significant effect on survival (p < .001); for every 1-year increase in time to first remission, there was a median 1% reduction in survival in acromegaly. In an analysis adjusted for covariates, the survival rate was 52% higher (p < .001) in those who underwent surgery as compared to those who did not have surgery, 18% higher (p = .01) in those who received treatment with somatostatin analogues (SMA) as compared to those with dopamine agonists and 21% lower (p < .001) in those who received conventional radiotherapy as compared to those who did not receive radiotherapy. In conclusion, this population-based study conducted in patients with acromegaly revealed that faster remission time, surgical intervention and treatment with SMA are linked to improved survival outcomes.

A novel treatment planning method via scissor beams for uniform-target-dose proton GRID with peak-valley-dose-ratio optimization.

Proton spatially fractionated RT (SFRT) can potentially synergize the unique advantages of using proton Bragg peak and SFRT peak-valley dose ratio (PVDR) to reduce the radiation-induced damage for normal tissues. Uniform-target-dose (UTD) proton GRID is a proton SFRT modality that can be clinically desirable and conveniently adopted since its UTD resembles target dose distribution in conventional proton RT (CONV). However, UTD proton GRID is not used clinically, which is likely due to the lack of an effective treatment planning method. This work will develop a novel treatment planning method using scissor beams (SB) for UTD proton GRID, with the joint optimization of PVDR and dose objectives. The SB method for spatial dose modulation in normal tissues with UTD has two steps: (1) a primary beam (PB) is halved with interleaved beamlets, to generate spatial dose modulation in normal tissues; (2) a complementary beam (CB) is added to fill in previously valley-dose positions in the target to generate UTD, while the CB is angled slightly from the PB, to maintain spatial dose modulation in normal tissues. A treatment planning method with PVDR optimization via the joint total variation and L1 (TVL1) regularization is developed to jointly optimize PVDR and dose objectives. The plan optimization solution is obtained using an iterative convex relaxation algorithm. The new methods SB and SB-TVL1 were validated in comparison with CONV. Compared to CONV of relatively homogeneous dose distribution, SB had modulated spatial dose pattern in normal tissues with UTD and comparable plan quality. Compared to SB, SB-TVL1 further maximized PVDR, with comparable dose-volume parameters. A novel SB method is proposed that can generate modulated spatial dose pattern in normal tissues to achieve UTD proton GRID. A treatment planning method with PVDR optimization capability via TVL1 regularization is developed that can jointly optimize PVDR and dose objectives for proton GRID.

Treatment Strategies for Locoregional Recurrence in Esophageal Squamous-Cell Carcinoma: An Updated Review.

Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant metastasis after curative treatment. For cases of locoregional recurrence in the cervical lymph nodes alone, salvage surgery with lymph node dissection generally provides a good prognosis. However, if recurrence occurs in multiple regions, the oncological efficacy of surgery may be limited. Radiotherapy/chemoradiotherapy can be employed for unresectable or recurrent cases, as well as for selected cases in neo- or adjuvant settings. Dose escalation and toxicity are potential issues with conventional three-dimensional conformal radiotherapy; however, more precise therapeutic efficacy can be obtained using technical modifications with improved targeting and conformality, or with the use of proton beam therapy. The introduction of immune checkpoint inhibitors, including pembrolizumab or nivolumab, in addition to chemotherapy, has been shown to improve the overall survival in unresectable, advanced/recurrent cases. For patients with lymph node recurrence in multiple regions, chemotherapy (5-fluorouracil [5-FU] plus cisplatin) and combination therapy with nivolumab and ipilimumab have shown comparable oncological efficacy. Further prospective studies are needed to improve the treatment outcomes in patients with esophageal cancer with locoregional recurrence.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 3. Genitourinary and gynecological cancers.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

Preclinical photon minibeam radiotherapy using a custom collimator: Dosimetry characterization and preliminary in-vivo results on a glioma model

PurposeThe purpose of this study is to investigate the dosimetric characteristics of a collimator for minibeam radiotherapy (MBRT) with film dosimetry and Monte Carlo (MC) simulations. The outcome of MBRT with respect to conventional RT using a glioma preclinical model was also evaluated. MethodsA multi-slit collimator was designed to be used with commercial small animal irradiator. The collimator was built by aligning 0.6 mm wide and 5 mm thick parallel lead leaves at 0.4 mm intervals. Dosimetry characteristics were evaluated by Gafchromic (CG) films and TOPAS Monte Carlo (MC) code.An in vivo experiment was performed using a glioma preclinical model by injecting two million GL261cells subcutaneously and treating with 25 Gy, single fraction, with MBRT and conventional RT. Survival curves and acute radiation damage were measured to compare both treatments. ResultsA satisfactory agreement between experimental results and MC simulations were obtained, the measured FWHM and distance between the peaks were respectively 0.431 and 1.098 mm.In vivo results show that MBRT can provide local tumor control for three weeks after RT treatment and a similar survival fraction of open beam radiotherapy. No severe acute effects were seen for the MBRT group. ConclusionsWe developed a minibeam collimator and presented its dosimetric features. Satisfactory agreement between MC and GC films was found with differences consistent with uncertainties due to fabrication and set-up errors. The survival curves of MBRT and open field RT are similar while atoxicity is dramatically lower with MBRT, preliminarily confirming the expected effect.

Targeted delivery of CEBPA-saRNA for the treatment of pancreatic ductal adenocarcinoma by transferrin receptor aptamer decorated tetrahedral framework nucleic acid

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.