Search Results (83)

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article

Although the dosimetric advantages of rectal spacers in prostate cancer radiotherapy have been demonstrated in selected clinical trials, real-world data from routine clinical practice remain limited—particularly within the Portuguese healthcare system. This study offers a detailed dosimetric comparison of Volumetric Modulated Arc Therapy (VMAT), with and without rectal spacer use, in a real-world patient cohort, aiming to assess the clinical relevance of spacer insertion under standard treatment protocols. A retrospective dosimetric evaluation was performed on 80 prostate cancer patients treated at a radiotherapy centre in southern Portugal. Patients were equally divided into two matched groups (n = 40): one receiving VMAT alone, the other receiving VMAT with hydrogel rectal spacer placement. Dose-volume histograms (DVHs) were analysed for the planning target volume (PTV) and key organs at risk (OARs). Standard dosimetric metrics, such as V50–V75 for the rectum and bladder, V50 for femoral heads, and mean dose for the penile bulb, were assessed. PTV coverage was evaluated using conformity and homogeneity indices. Spacer use significantly decreased rectal dose exposure across all evaluated parameters without compromising PTV coverage or increasing dose to other OARs. These findings support routine rectal spacer applications to enhance treatment safety and patient outcomes. Full article

Background: The geriatric nutritional risk index (GNRI), a composite metric of serum albumin and body weight, has emerged as a prognostic tool in various cancers. However, its relevance in nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT) remains unexplored. The aim of this study was to assess the effect of the GNRI in the prediction of the prognosis of nasopharyngeal carcinoma in the era of VMAT. Methods: This retrospective study analyzed 498 newly diagnosed, non-metastatic NPC patients treated with VMAT between 2010 and 2011. The GNRI was calculated using serum albumin and body weight ratios, with receiver operating characteristic (ROC) curve analysis determining its optimal prognostic cutoff. Patients were stratified into training (70%) and validation (30%) cohorts. Cox regression identified independent prognostic factors, which were integrated into a nomogram predicting 3- and 5-year overall survival (OS). Model performance was assessed via the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: In the study, 348 patients were included in the training cohort and 150 patients were included in the validation cohort according to a ratio of 7:3. The median follow-up was 68 months, with 5-year OS rates of 79.3%. A GNRI > 102 independently predicted improved survival (HR = 0.64; p = 0.044), alongside tumor volume, age, and N-stage. The nomogram demonstrated strong discrimination (C-index: 0.757–0.762 for training; 0.737–0.744 for validation) and calibration, aligning closely with observed survival. DCA confirmed superior clinical utility over default strategies. NPC patients treated with VMAT with a high GNRI, female sex, and a lower N-stage exhibited significantly better OS (p < 0.05). Conclusions: The GNRI is a robust prognostic marker for NPC patients receiving VMAT, reflecting the interplay of nutrition, inflammation, and treatment response. The validated nomogram provides a practical tool for individualized risk stratification, enhancing clinical decision-making in the era of precision radiotherapy. Full article

Introduction: Radiotherapy can impact on patients’ reproductive organs and fertility. This study aims (i) to assess whether the doses to the gonads of 70 patients met the tolerance doses used in radiotherapy planning; (ii) to compare Three-Dimensional Conformal Radiotherapy (3DCRT) with Volumetric Modulated Arc Therapy (VMAT) techniques; and (iii) to verify if ovarian transposition reduces the dose to the ovaries. Methods: A retrospective analysis of 70 patients aged 45 or under who underwent pelvic radiotherapy between 2014 and 2023 in a radiotherapy department was carried out. The dose constraints considered were derived from the Dose-Volume Constraints for Organs at Risk in Radiotherapy project. Results: The average number of children of all the patients in the study was 1.25 and the standard deviation was 1.40. No statistically significant differences were detected regarding the doses to the left and right gonads between 3DCRT and VMAT (p > 0.05). There were statistically significant differences between female patients who underwent ovarian transposition and those who did not undergo ovarian transposition regarding the maximum and medium doses in both right and left ovaries (p < 0.05), with a dose reduction that could reduce doses by an average of up to 39 Gy. Conclusions: In the total sample, 58.6% of patients were treated with VMAT, only 18.6% met the maximum dose limits, and 22.9% met the average dose constraints. Only five women underwent ovarian transposition, which proved effective in meeting dose constraints and significantly reducing the dose to the ovaries. Full article

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients. Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. Dose–volume metrics for key OARs and normal tissue complication probabilities (NTCPs) were compared using paired statistical tests. Robustness evaluations accounted for setup and range uncertainties. Results: Proton plans significantly reduced dose to bone marrow (V10Gy: 58% vs. 86%, p < 0.00001; V20Gy: 47% vs. 58%, p < 0.00001), small bowel (V20Gy: 21% vs. 56%, p < 0.00001), and femoral heads (left femoral head mean: 11Gy vs. 13Gy, p = 0.032; right femoral head mean: 11Gy vs. 13Gy, p = 0.022). NTCP modeling predicted significantly lower rates of bowel urgency (9.4% vs. 3.3%, p < 0.001) and hematologic toxicity (10.2% vs. 4.9%, p < 0.001) with proton therapy. Plans remained robust across uncertainty scenarios. Conclusions: IFSO-based scanning proton therapy provides clinically meaningful sparing of bone marrow and bowel, with the potential to reduce hematologic and gastrointestinal toxicities. These findings support its use in patients receiving adjuvant pelvic radiotherapy, particularly those undergoing extended field treatment or chemotherapy. Full article

This study investigates the generation of synthetic CT (sCT) images from zero echo time (ZTE) MRI to support MR-only radiotherapy, which can reduce image registration errors and lower treatment planning costs. Since MRI lacks the electron density data required for accurate dose calculations, generating reliable sCTs is essential. ZTE MRI, offering high bone contrast, was used with two deep learning models: attention deep residual U-Net (ADR-Unet) and derived conditional generative adversarial network (cGAN). Data from 17 head and neck cancer patients were used to train and evaluate the models. ADR-Unet was enhanced with deep residual blocks and attention mechanisms to improve learning and reconstruction quality. Both models were implemented in-house and compared to standard U-Net and Unet++ architectures using image quality metrics, visual inspection, and dosimetric analysis. Volumetric modulated arc therapy (VMAT) planning was performed on both planning CT and generated sCTs. ADR-Unet achieved a mean absolute error of 55.49 HU and a Dice score of 0.86 for bone structures. All the models demonstrated Gamma pass rates above 99.4% and dose deviations within 2–3%, confirming clinical acceptability. These results highlight ADR-Unet and cGAN as promising solutions for accurate sCT generation, enabling effective MR-only radiotherapy. Full article

Purpose: Image-guided radiotherapy (IGRT) has been widely implemented in the treatment of prostate cancer, offering a number of advantages regarding the precision of dose delivery. This study provides an overview of factors, clinical and physical alike, that increase treatment accuracy in prostate cancer radiotherapy in the context of IGRT. The following aspects are explored based on recent literature: the radiotherapy technique used in conjunction with IGRT, the type and frequency of IGRT, the impact of radiotherapy technique/IGRT on target dosimetry and organs at risk, the influence of IGRT on planning target volume margins, the impact of treatment time on dosimetric outcome and clinical outcomes using IGRT repositioning or an online adaptive plan. Methods: A systematic search of the literature was conducted within Pubmed/Medline databases to find relevant studies. Of the 152 articles fulfilling the initial search criteria, 79 were selected for final analysis. Results: The frequency of image guidance, the treatment regimen and the radiation technique are important factors that contribute to the optimization and personalization of the treatment plan. The daily anatomy and volume of the bladder and rectum can vary considerably, which can significantly impact the dosimetric effects on these organs. When used in conjunction with volumetric modulated arc therapy, IGRT allows for shaping the dose distribution to avoid nearby critical structures such as the bladder and rectum. Conclusions: Precise tumor targeting via IGRT can result in fewer geometric uncertainties, thereby improving treatment outcome both in terms of superior target coverage and sparing organs at risk. Full article

Background: Cervical cancer treatment with advanced radiotherapy techniques benefits from image guidance, particularly when anatomical changes occur during therapy. This case emphasizes the need for adaptive radiotherapy when target volume shifts significantly. Methods: A 70-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) IIIC2 9th edition cervical squamous cell carcinoma presented with a distended uterine cavity due to fluid accumulation. She underwent definitive chemoradiotherapy using Volumetric Modulated Arc Therapy (VMAT) and weekly cisplatin. Results: Daily Cone Beam Computed Tomography (CBCT) imaging revealed progressive uterine shrinkage as intrauterine fluid drained, significantly altering target volume and organ-at-risk (OAR) positioning. These changes necessitated two re-planning CT scans during external beam radiotherapy to maintain accurate dosing and avoid OAR toxicity. The patient completed treatment, including image-guided brachytherapy, without complications. Adaptive planning ensured adequate tumor coverage and minimized normal tissue exposure. Conclusions: This case highlights the critical role of daily CBCT in detecting anatomical changes during radiotherapy. Adaptive re-planning, though rarely required more than once, was essential here to preserve treatment accuracy. CBCT should be considered a standard verification tool in cervical cancer radiotherapy, particularly in cases involving intrauterine fluid. Full article

Currently, advanced RT techniques such as VMAT and HT are being developed to optimize tumor coverage while minimizing radiation exposure to the surrounding organs that are at risk. Despite their growing clinical use, comparative studies evaluating the dosimetric and radiobiological effects of these modalities remain limited. In this study, A549, HeLa, and HepG2 cells were exposed to a single 2 Gy dose, using three RT techniques (3D-CRT, dual arc VMAT, and HT). Treatment plans were generated using a water phantom to ensure consistent target coverage and comparable dosimetric parameters across the techniques. Multiple radiobiological endpoints were assessed to evaluate the cellular responses. Although all three techniques yielded similar dosimetric parameters without statistically significant differences, the biological responses varied among the cell lines. Notably, VMAT and HT demonstrated superior tumor cell suppression compared to 3D-CRT. This was likely due to their enhanced dose conformity and modulation precision, which potentially led to improved tumor cell killing. These findings highlight the importance of integrating radiobiological assessments with physical dose metrics to inform the clinical application of advanced RT technologies. However, this study had several limitations. The use of a single radiation dose limited its clinical relevance, and the immediate post-irradiation assessments may not have captured delayed biological responses. Additionally, the small number of replicates may have reduced the study’s statistical power. Future studies incorporating dose fractionation schemes, time course analyses, and larger sample sizes are warranted to better simulate clinical conditions and further elucidate the radiobiological effects of advanced RT techniques. Full article

Background and Objectives: Brain radionecrosis is an under-recognized but potentially life-altering late complication of radiotherapy in patients with locally advanced nasopharyngeal cancer. Temporal lobe radionecrosis and high-dose exposure to the hippocampus are strongly associated with cognitive decline and radiation-induced dementia, negatively impacting patients’ long-term quality of life (QoL). This study aimed to evaluate and compare radiation dose distributions to critical brain structures across three radiotherapy techniques—3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT)—in order to assess potential neurocognitive risks and support hippocampal-sparing protocols. Materials and Methods: Ten patients previously treated with 3D-CRT were retrospectively replanned using IMRT and VMAT techniques on the Eclipse v13.3 (VARIAN) planning system. Bilateral hippocampi and temporal lobes were delineated as organs at risk (OARs) according to the RTOG atlas, and dosimetric parameters including D_max, D_mean, and D_min were recorded. V7.3 values were evaluated for hippocampal avoidance regions. Results: While IMRT and VMAT provided improved target volume coverage and reduced high-dose exposure to many standard OARs, both techniques were associated with increased D_mean and D_min to the hippocampus and temporal lobes compared to 3D-CRT. The highest D_max values to the temporal lobes were observed in 3D-CRT plans, indicating a potential risk of radionecrosis. VMAT plans showed hippocampal mean doses exceeding 10 Gy in some cases, with V7.3 > 40%, breaching established neurocognitive risk thresholds. Conclusions: These findings support the routine delineation of the hippocampus and temporal lobes as OARs in radiotherapy planning for nasopharyngeal cancer. The implementation of hippocampal-sparing strategies, particularly in IMRT and VMAT, is recommended to reduce the risk of radiation-induced cognitive toxicity and preserve long-term QoL in survivors. Full article

Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous integrated boost (VMAT–SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT–SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU–LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with VMAT–SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT–SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0–2) (p < 0.01), negative N status (p < 0.05), and lower stages (I + II) (p < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT–SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes. Full article

Background/Objectives: During radiotherapy for prostate cancer, the risk of radiation cystitis is increased if the volume of the bladder is small. According to previous studies, it is important that bladder volumes are ≥200 mL. Drinking protocols may be helpful in this context. Adherence to such protocols can be challenging, and may be improved by an app reminding patients before each session of radiotherapy to drink a certain amount of water. Our prospective phase 2 trial (REFILL-PAC-HYPO, NCT06784115) evaluates the impact of a reminder app on bladder filling in prostate cancer patients treated with hypo-fractionated radiotherapy. Methods: Twenty-seven patients need to be recruited for the REFILL-PAC-HYPO trial. Radiotherapy, preferably with volumetric-modulated arc therapy, uses hypo-fractionation with 20 × 3.0 Gy over four weeks. An app reminds patients to drink water (300 mL) 45 min before each session of hypo-fractionated irradiation. On the last day of their treatment, patients are asked about their satisfaction with the app. In the case of a dissatisfaction rate of >20%, the app requires modifications. If this rate is >40%, the app is considered not useful. Additionally, patients are asked about the impact of their participation in the trial and using the app on their general attitude towards health technology. Furthermore, the phase 2 cohort is compared to a historical control group treated with hypo-fractionated radiotherapy during recent years but not supported by an app. The REFILL-PAC-HYPO trial will contribute to identifying the potential value of a reminder app for bladder filling during hypo-fractionated radiotherapy for prostate cancer. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases. Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the CyberKnife (CK) plan for the Accuray CyberKnife, the intensity-modulated proton therapy (IMPT) plan for the Hitachi ProBeat-FR proton therapy machine, and the volumetric-modulated arc therapy (VMAT) plan for the Varian TrueBeam STx. These plans were evaluated and compared using two novel gradient indices in addition to traditional dosimetry metrics for targets and organs at risk (OARs). The steepest border gradient quantified the percent prescription dose fall-off per millimeter at the boundary between the target and adjacent critical structures. This gradient index highlighted the system’s ability to spare nearby critical OARs. The volume gradient assessed the extent of dose spread outside the target toward the patient’s body. Results: All plans achieved comparable target coverage and conformity, while IMPT and VMAT demonstrated significantly better uniformity. The GK plans exhibited the highest border gradient, up to 20.9%/mm, followed by small-spot-size IMPT plans and CK plans. Additionally, IMPT plans showed the benefit of reduced dose spread in low-dose regions and the lowest maximum and mean doses to the brainstem and carotid artery. Conclusions: The advanced external beam radiotherapy modalities evaluated in this study are well-suited for SBRT in skull base reirradiation, which demands precise targeting of tumors with highly conformal doses and steep dose gradients to protect nearby normal structures. Full article

Background: Radiotherapy for thymoma is delivered post-operatively in selected cases. Given the particular location of the thymic bed and the excellent prognosis, late cardiac toxicities may be an issue. The purpose of this retrospective dosimetric study is to investigate whether intensity-modulated proton beam therapy (IMPT) compared to photon therapy could better spare cardiac substructures, given prespecified dose constraints. Methods: We retrospectively selected patients treated with adjuvant radiotherapy for thymoma in our institution. We manually contoured fourteen cardiac substructures (CSs), with the supervision of a team of cardioradiologists. The photon-based plans were re-optimized in adherence to the volumetric modulated arc therapy (VMAT) technique with specific dose constraints for the new contoured structures. The proton-based plans were optimized in adherence to intensity-modulated proton therapy (IMPT) using the beam spot scanning technique. Results: Twenty-nine patients treated with adjuvant radiotherapy with a prescribed dose of 50 Gy in 25 daily fractions for radically resected thymoma were selected. IMPT demonstrated better sparing of most cardiac substructures in terms of Dmax, D_mean and V_5Gy. Finally, IMPT plans more easily achieved the proposed dose constraints. Conclusions: Cardiac substructures can be successfully spared with IMPT. Clinical studies are needed to establish a relationship between dose parameters and the development of cardiac events. Full article

(1) Background: Volumetric modulated arc therapy (VMAT) can deliver more accurate dose distribution and reduce radiotherapy-induced toxicities for postoperative cervical and endometrial cancer. This study aims to retrospectively analyze the relationship between dosimetric parameters of organs at risk (OARs) and acute toxicities and provide suggestions for the dose constraints. (2) Methods: A total of 164 postoperative cervical and endometrial cancer patients were retrospectively analyzed, and the endpoints were grade ≥ 2 acute urinary toxicity (AUT) and acute lower gastrointestinal toxicity (ALGIT). The normal tissue complication probability (NTCP) model was established using the logistic regression model. Restricted cubic spline (RCS) curves were used to explore the association between dosimetric parameters and toxicities. The receiver operating characteristic (ROC) curve, calibration curve, Akaike’s corrected information criterion (AICc), decision curve analysis (DCA), and clinical impact curve (CIC) were analyzed to evaluate the performance of NTCP models. (3) Results: Bladder V_40Gy was identified to develop the NTCP model of AUT, and the mean AUC was 0.69 (CI: 0.58–0.80). Three candidate predictors, namely the small intestine V_30Gy, colon D_45%, and rectum D_55%, were identified to develop the NTCP model of ALGIT, and the mean AUC was 0.71 (CI: 0.61–0.80). Both models were considered to have relatively good discriminative accuracy and could provide a high net benefit in clinical applications. (4) Conclusions: We developed NTCP models to predict the probability for grade ≥ 2 AUT and ALGIT. We recommend that bladder V_40Gy, the small intestine V_30Gy, colon D_45%, and rectum D_55% be controlled below 42%, 20.4%, 16.9 Gy, and 32.0 Gy, respectively. Full article