Radiation

Background: Patients with advanced breast cancer (BC) may be treated with stereotactic ablative radiotherapy (SABR) for tumor control. Variable treatment responses are a clinical challenge and there is a need to predict tumor radiosensitivity a priori. There is evidence showing that tumor infiltrating lymphocytes (TILs) are markers for chemotherapy response; however, this association has not yet been validated in breast radiation therapy. This pilot study investigates the computational analysis of TILs to predict SABR response in patients with inoperable BC. Methods: Patients with inoperable breast cancer (n = 22) were included for analysis and classified into partial response (n = 12) and stable disease (n = 10) groups. Pre-treatment tumor biopsies (n = 104) were prepared, digitally imaged, and underwent computational analysis. Whole slide images (WSIs) were pre-processed, and then a pre-trained convolutional neural network model (CNN) was employed to identify the regions of interest. The TILs were annotated, and spatial graph features were extracted. The clinical and spatial features were collected and analyzed using machine learning (ML) classifiers, including K-nearest neighbor (KNN), support vector machines (SVMs), and Gaussian Naïve Bayes (GNB), to predict the SABR response. The models were evaluated using receiver operator characteristics (ROCs) and area under the curve (AUC) analysis. Results: The KNN, SVM, and GNB models were implemented using clinical and graph features. Among the generated prediction models, the graph features showed higher predictive performances compared to the models containing clinical features alone. The highest-performing model, using computationally derived graph features, showed an AUC of 0.92, while the highest clinical model showed an AUC of 0.62 within unseen test sets. Conclusions: Spatial TIL models demonstrate strong potential for predicting SABR response in inoperable breast cancer. TILs indicate a higher independent predictive performance than clinical-level features alone. Full article

Humans are constantly exposed to low doses and low-dose rates of ionizing radiation from both natural and man-made sources. For this reason, there is a growing interest in studies on the biological effects of low-dose radiation. Vibrational spectroscopies, such as Fourier transform infrared and Raman micro-spectroscopies, have been fruitfully employed for studying the effects of high doses of ionizing radiation on biosystems. Aiming at clarifying the potential of the above-mentioned spectroscopic techniques to monitor the changes induced in cells, tissues, and other biological samples by low doses of ionizing radiations, we report a review of the literature in this research field. The analysis of published results suggests that vibrational spectroscopies make a valuable contribution. Additional and more systematic investigations could help to fully exploit the capabilities of these spectroscopic techniques. Full article

Background: Quality assurance (QA) programs are designed to improve the quality and safety of radiation treatments, including patient-specific QA (PSQA). The objective of this study was to investigate the conditions in which pretreatment PSQA is performed, to evaluate the root cause of the implementation of more complex techniques, and to identify areas for potential improvement. Materials/Methods: The Octavius 4D (O4D) system accuracy was evaluated using an O4D homogeneous phantom for different field sizes. Tests of the system response to dose linearity, field sizes, and PDD differences were performed against calculated doses for a 6 MV photon beam. The pretreatment verification of 40 VMAT plans was performed using the PTW VeriSoft software (version 8.0.1) for local and global 3D gamma analysis. The reconstructed 3D dose was compared to the calculated dose using 2%/2 mm and 3%/3 mm, 20% of the low-dose threshold, and 95% of the gamma passing rate (%GP) tolerance level. The sensitivity of the O4D system in detecting VMAT delivery and setup errors has been investigated by measuring the variation in %GP values before and after the simulated errors. Results: The O4D system reported good agreement for linearity, field size, and PDD differences with TPS dose, being within ±2% tolerance. The output factors were consistent between the ionization chamber and the O4D detector down to a 4 × 4 cm² field size with a maximum deviation less than 1%. The introduction of deliberate errors caused a decrease in %GP values. In most scenarios, the %GP value of the simulated errors was detected with 2%/2 mm. Conclusion: The results indicate that the O4D system is sensitive enough to detect delivery and setup errors with the restrictive global criterion of 2%/2 mm for routine pretreatment verification. Full article

Salivary glands are common organs at risk in both head and neck external beam radiotherapy (EBRT) and radiopharmaceutical therapy (RPT), but incidences of xerostomia in RPT are inconsistent with the EBRT Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) limits. In EBRT, salivary glands are usually assumed to be parallel organs, with QUANTEC guidelines based on $D_{mean}$, but this is known to be a gross over-simplification of the full complexity of the underlying functional organization. The goal of this work is to combine machine learning of EBRT dose–outcome data with stylized small-scale RPT dosimetry to discover more reliable normal tissue complication probability (NTCP) models of xerostomia across both modalities. A retrospective cohort of 211 EBRT patients was analyzed using a custom-designed in-house machine learning workflow. From this, a hierarchy of three models of increasing complexity was trained, evaluated for performance and generalization, and coupled with stylized small-scale salivary gland dosimetry to assess the influence of model complexity on the predicted NTCP for plausible patterns of RPT dose nonuniformity. The three models in the hierarchy (A, B, C), in increasing order of complexity, associate xerostomia with the following: the mean dose to the whole contralateral parotid (model A), the mean dose to a ductally localized region (model B) and a serial interaction dose term between two ductal sub-compartments (model C). While the difference between the three models for EBRT p-values and AUCs is rather marginal, for physiologically driven ductal dose distributions in RPT, the predicted reduction in TD50 can be as large as a factor of 10. These results provide hints towards a plausible reconciliation of the observed inconsistency of xerostomia in RPT with EBRT dose limits. Full article

Radiomics and deep learning computer vision algorithms can extract clinically relevant information from medical images, providing valuable insights for accurate diagnosis of cancerous lesions, tumor differentiation and molecular subtyping, prediction of treatment response, and prognostication of long-term outcomes. In head and neck squamous cell carcinoma (HNSCC), growing evidence supports the potential role of radiomics and deep learning models in predicting treatment response, long-term outcomes, and treatment complications following radiation therapy. This is especially important given the pivotal role of radiotherapy in early-stage and locally advanced HNSCC, as well as in post-operative and concomitant chemoradiotherapy. In this article, we summarize recent studies highlighting the role of radiomics in predicting early post-radiotherapy response, locoregional recurrence, survival outcomes, and treatment-related complications. Radiomics-guided tools have the potential to personalize HNSCC radiation treatment by identifying low-risk patients who may benefit from de-intensified therapy and high-risk individuals who require more aggressive treatment strategies. Full article

Effective dose calculation is essential for optimizing Gamma Knife (GK) stereotactic radiosurgery (SRS) treatment plans. Modern GK systems allow independent sector activation, enabling complex dose distributions per shot. This study presents a dose approximation method designed to account for shot flexibility and generate 3D doses external to GammaPlan. A treatment plan was created with the TMR10 calculation for individual sector activations using a Radiosurgery Head Phantom. The resulting dose arrays established a basis set of sector-specific distributions, which were then referenced by shot parameters from the plan, allowing dose accumulation through superposition. This superposition approximation (SA) was compared to the original TMR10 using the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and GK deliverability metrics: coverage, selectivity, and gradient index, across an isodose normalization range from 10% to 90%. In a cohort of 30 patients with 71 targets, strong agreement was observed between TMR10 and SA in the clinically used 50–60% isodose range, with DSC above 85% and HD95 under 2.18 mm. The average differences for the coverage, selectivity, and gradient index were 0.014, 0.008, and 0.118, respectively. This method accurately approximates TMR10 calculations within clinically relevant ranges, offering an external tool to assess 3D dose distributions for GK treatment plans. Full article

The image quality index for whole-body bone scintigraphy has traditionally relied on the total count (Total-C) with a threshold of ≥1.5 million counts (MC). However, Total-C measurements are susceptible to variability owing to urine retention. This study aimed to develop a skeletal count (Skel-C)-based index, focusing exclusively on bone regions, to improve the accuracy of image analysis in bone scintigraphy. To determine the optimal Skel-C-based threshold, Skel-C thresholds were set at 0.9, 1.0, 1.1, and 1.2 MC, and Total-C thresholds were set at 1.75, 2.0, and 2.25 MC. Patients were then categorized based on whether their values were above or below these thresholds. The group including all cases was defined as the Total-C 1.5 high group. Sensitivity and specificity were calculated for each group, and receiver operating characteristic analyses and statistical evaluations were conducted. The specificity of the bone scintigraphy image analysis program in the Skel-C < 0.9 MC group was significantly lower than that in the Skel-C ≥ 0.9 MC and Total-C 1.5 high groups. The decrease in specificity was evident only with Skel-C and was not identified based on Total-C levels. These findings highlight the importance of achieving Skel-C ≥ 0.9 MC and suggest that Total-C alone is insufficient for reliable image assessment. Full article

Background: We aimed to measure the pacemaker- and defibrillator-induced distortion at 0.35T and 3.0T magnetic fields. Methods: The pacemaker/defibrillator was placed at the top center of a water-filled/MagPhan phantom, followed by a T1 scan at 3T and a TrueFISP scan at 0.35T. The extent of distortion (i.e., the distance from the device to the furthest signal loss/void/rings) in the water-filled phantom was measured in MIM. For geometrical distortion (i.e., dislocation of geometrical structures), the spheres in the MagPhan phantom were contoured and their distortion was calculated based on their manufacturing coordinate positions. Results: The maximum extent of distortion caused by the defibrillator was 18.8 cm at 0.35T and 5.8 cm at 3.0T. Similarly, the maximum extent of distortion caused by the pacemaker was 9.28 cm at 0.35T and 2.8 cm at 3.0T. Geometrical distortion measurements using the MagPhan phantom showed that the maximum distortion caused by the defibrillator was 12.8 mm at 0.35T and 13.2 mm at 3.0T. Likewise, the maximum distortion caused by the pacemaker was 8.7 mm at 0.35T and 6.0 mm at 3.0T. Conclusions: Defibrillators cause larger distortions/signal voids than pacemakers, and require careful consideration when performing MRI-based treatment planning. To minimize distortion, sequences with lower sensitivity to magnetic field inhomogeneity should be used. Full article

Spatially fractionated radiation therapy (SFRT) has a long history of treating bulky and hypoxic tumors. Recent evidence suggests that, compared to conventional uniform dose radiation therapy, SFRT may utilize different mechanisms of tumor cell killing, potentially including bystander and immune-activating effects. The abscopal effect in radiation therapy refers to the control or even elimination of distant untreated tumors following the treatment of a primary tumor with radiation, a process believed to be immune-mediated. Such effects have been shown to be enhanced by immunotherapy, particularly immune checkpoint inhibition. In this manuscript, we explore the potential synergy of spatially fractionated radiation therapy, in the form of kV x-ray minibeam, combined with PD-L1 checkpoint inhibition in a murine mammary carcinoma model at conventional dose-rate. We found that minibeam of peak/valley doses of 50 Gy/3.7 Gy performed statistically equivalent but trending better than that of 100 Gy/7.4 Gy in its abscopal effect and so 50 Gy/3.7 Gy was selected for further studies. Our findings indicate that the abscopal effect is significantly greater in the minibeam plus anti-PD-L1 treated animals compared to those receiving uniform dose radiation therapy plus anti-PD-L1 (p = 0.04948). Immune cell profiling in the minibeam plus anti-PD-L1 group compared to uniform dose reveals a consistent trend towards greater immune cell infiltration in the primary tumor, as well as a higher percentage of CD8+ T cells, both systemically and at the abscopal tumor site. Full article

Ion radiotherapy requires accurate relative biological effectiveness (RBE) calculations to account for the markedly different biological effects of ions compared to photons. Microdosimetric RBE models rely on descriptions of the energy deposition at the microscopic scale, either through radial dose distributions (RDDs) or microdosimetric probability density distributions. While RDD approaches focus on the theoretical description of the energy deposition around the ion track, microdosimetric distributions offer the advantage of being experimentally measurable, which is crucial for quality assurance programs. As the results of microdosimetric RBE models depend on whether RDD or microdosimetric distributions are used, the model parameters are not interchangeable between these approaches. This study presents and validates a method to reproduce the published reference biological and clinical dose calculations at NIRS-QST for only carbon ion radiotherapy by using the modified microdosimetric kinetic model (MKM) alongside microdosimetric distributions instead of the reference RDD approach. To achieve this, Monte Carlo simulations were performed to estimate the variation of the radiation quality within and outside the field of pristine and spread-out Bragg peaks. By appropriately optimizing the modified MKM parameters for microdosimetric distributions assessed within water spheres, we successfully reproduced the results of calculations using the reference NIRS-QST RDD, generally within 2%. Full article

The pursuit of exploring the outer space environment for biological research has been a topic of interest for nearly 60 years. The success of the next phase of space exploration depends on the ability to increase crew safety by identifying ways to mitigate these threats. Using a universal scientific citation indexing tool, we extracted data on literature production in terms of the most prolific key terms, authors, countries, institutions, and journals for two distinct topic sets related to space radiation research published from 1 January 1990 to 31 December 2023. The focus of space radiation research in relation to its effects on human health has fluctuated over time, as reflected in the term maps that were generated for each decade. Our bibliometric analysis provides insight into the trends in the top producers in the space radiation research field over the years, as well as into how the focus of such studies has evolved throughout the decades. Full article

The rising incidence of prostate cancer necessitates innovative treatment approaches, particularly as diseases such as the COVID-19 pandemic can disrupt traditional cancer care. This study aims to evaluate the impact of hypofractionated versus conventionally fractionated radiotherapy on prostate cancer cell lines in vitro. Prostate cancer cell lines (PC-3 and DU-145) were exposed to varying doses of radiation alongside non-cancerous BPH-1 cells. We assessed radiation effects on cell proliferation, viability, colony formation, DNA repair, migration, invasion, and cytotoxicity. The results demonstrated that the prostate cell lines exhibited varying responses, with hypofractionation favourably impacting aggressive PC-3 cells while preserving non-cancerous cells. In contrast, conventional fractionation led to increased invasion and cytotoxicity in both prostate cancerous cell lines. These findings advocate for personalised radiation therapy approaches that enhance treatment efficacy by considering the distinct behaviours of differing prostate cancer subtypes. Full article

Background: Vertebral augmentation (VA) procedures are used to treat painful vertebral fractures caused by malignancies, but there are few data on the radiation exposure for patients and proceduralists during these VA procedures. We retrospectively examined the radiation dose exposure during VA procedures and defined the characteristics of patients who underwent such procedures. Methods: We conducted a retrospective observational cohort study including patients with cancer who experienced axial back pain from compression fractures caused by malignancies. Participants were identified using an electronic medical records database and must have had evidence of stable vertebral compression fractures upon imaging and documentation of a clinical evaluation. We collected data on patient demographics, fluoroscopy time (FT) and dose (FD) during the procedure, the volume of polymethylmethacrylate injected, and reported complications. Results: Overall, 140 patients were included. Their median age was 69, and they were mostly men (n = 79). The most common diagnosis was multiple myeloma (41.4%). Most patients had a single-level compression fracture of the thoracolumbar spine. The mean FT was 233.80 s, with higher FTs for patients with an elevated body mass index and patients younger than 60 years. The average FD was 157.98 mGy, with higher FDs for patients with an elevated BMI and for male patients. Pain relief was not associated with FT or FD. Conclusions: Patients with cancer who underwent VA experienced longer FT and higher FD compared to their non-cancer counterparts in the literature. However, we found multiple confounders for this relationship. Full article

The objective of this study was to evaluate the effectiveness of utilizing radiomic features from radiation planning computed tomography (CT) scans in predicting tumor progression among patients with cervical cancers. A retrospective analysis was conducted on individuals who underwent radiotherapy for cervical cancer between 2015 and 2020, utilizing an institutional database. Radiomic features, encompassing first-order statistical, morphological, Gray-Level Co-Occurrence Matrix (GLCM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Dependence Matrix (GLDM) features, were extracted from the primary cervical tumor on the CT scans. The study encompassed 112 CT scans from patients with varying stages of cervical cancer ((FIGO Staging of Cervical Cancer 2018): 24% at stage I, 47% at stage II, 21% at stage III, and 10% at stage IV). Of these, 31% (n = 35/112) exhibited tumor progression. Univariate feature analysis identified three morphological features that displayed statistically significant differences (p < 0.05) between patients with and without progression. Combining these features enabled a classification model to be developed with a mean sensitivity, specificity, accuracy, and AUC of 76.1% (CI 1.5%), 70.4% (CI 4.1%), 73.6% (CI 2.1%), and 0.794 (CI 0.029), respectively, employing nested ten-fold cross-validation. This research highlights the potential of CT radiomic models in predicting post-radiotherapy tumor progression, offering a promising approach for tailoring personalized treatment decisions in cervical cancer. Full article

Background: To evaluate p-Cry in 10 years as a feasible and radical approach in patients with small renal masses (<5 cm), we evaluated technical success, side effects, and survival rates. Materials and Methods: We retrospectively evaluated 421 patients with small renal masses (<5 cm) with a median age of 70 years (47–92 C.I.) between June 2014 and July 2024 at our department. We also evaluated side effects, surgical radicality, and therapeutic outcomes of renal functions. Survivals were also evaluated in terms of disease-free, metastasis-free, and cancer-related survival rates. Results: Median follow-up was 90 months (1–120 months C.I.), and median size of the tumor was 3.85 cm (1–4 C.I.). Two cryoprobes were used in median, and two 10-min freeze–thaw cycles were performed. The technical efficacy rate was 100%, whereas only one of 121 lesions required retreatment. No impact on the renal function was registered after p-Cry. Cancer-free survival and metastases-free survival was reached. Conclusions: Compared to surgery, p-Cry is a feasible treatment option in patients with small renal masses, as it does not affect renal function and gives patients good survival rates. Full article

Although radiation therapy is the leading option for effective cancer treatment, a prevalent side effect associated with it is dermatitis. Despite some available literature on this topic, there remain many gaps that need to be addressed. The goal of this study is to determine the incidence of radiation-induced dermatitis (RID) among children receiving proton and photon therapies; a retrospective chart review, at a single institution, was conducted on oncology patients who underwent proton or photon therapy radiation between 2018 and 2023. Significant differences were found between the Radiation Therapy Oncology Group (RTOG) score and the total radiation dose (p = 0.04). The median total dose of radiation received by those with an RTOG score of l was 5040.0 mGy and increased to 7600 mGy for those with a score of 3. A significant association was found between those who received chemotherapy and dermatitis (p = 0.04). No significance was found between the incidence of dermatitis in photon and proton therapy (p = 1.00). The study showed that multiple factors, including total radiation dose and chemotherapy, can affect RID. These relationships can be used to determine the modality, dose, and additional treatment options best suited to treat cancer patients in the pediatric population. Full article

This study investigated the effect of combining radiation with an angiogenesis inhibitor and vascular disrupting agent on tumor response and systemic toxicity. CDF1 mice with 200 mm³ foot implanted C3H mammary carcinomas were treated with TNP-470 (100 mg/kg every second day for 2 weeks; s.c.) and combretastatin A-4 phosphate (CA4P; 1 × 250 mg/kg, i.p.). Radiation (230-kV X-rays) was locally administered to tumors of restrained non-anesthetized mice. Response was tumor growth delay and change in mouse body weight. Radiation induced changes in serum levels of 10 cytokines up to 72-h after irradiation were measured using a Luminex assay. The results showed that TNP-470 (100 mg/kg × 7) or CA4P (250 mg/kg × 1) significantly (Student’s t-test; p < 0.05) inhibited tumor growth; the greatest effect when these two drugs were combined. TNP-470 and CA4P, alone or together, also significantly enhanced tumor response to radiation. No systemic toxicity occurred with drugs administered alone or in combination, but toxicity was observed when TNP-470 was combined with radiation. Serum cytokine levels only showed a significant transient increase in IL-6 1-h after irradiating. In conclusion, combining different acting vascular targeting agents with radiation increased anti-tumor activity. However, this benefit may sometimes be associated with a radiation-induced inflammatory response increasing systemic toxicity. Full article

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome”, p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of the radiation response in cancer cells and developing more effective therapeutic approaches to cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity. Full article