Search Results (249)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article

Ultra-high dose rate radiotherapy known as Flash radiotherapy (FLASH-RT) offers tremendous opportunities to improve the therapeutic ratio of radiotherapy by sparing the normal tissue while maintaining similar tumoricidal efficacy. However, the underlying biophysical basis of the FLASH effect remains under active investigation with several proposed mechanisms involving oxygen depletion, altered free-radical chemistry, and differential biological responses. This article provides an overview of available experimental and computational tools that can be utilized to probe the tumor and normal tissue microenvironment. We analyze in vitro, ex vivo, and in vivo systems used to study FLASH responses. We describe various computational and imaging technologies that can potentially aid in understanding the biophysics of FLASH-RT and lead to safer clinical translational. Full article

Very-high-energy electrons, coupled with ultra-high dose rates, are being explored for their potential use in radiotherapy to treat deep-seated tumours. The dose per pulse needed to achieve ultra-high dose rates far exceeds the limit of current medical linear accelerator capabilities. A high dose per pulse has been observed as the limiting factor for many existing dosimeters, resulting in saturation at doses far below what is required. The MOSkin, an existing clinical quality assurance dosimeter, has previously been demonstrated as dose rate independent but has not been subjected to a high dose per pulse. Within this study, the MOSkins dose-per-pulse response was tested for linearity, with a dose per pulse as high as 23 Gy within 200 ns at the ANSTO Australian Synchrotron’s Pulsed Energetic Electrons for Research facility. While using EBT-XD film as a reference dosimeter, a dose rate dependence of the EBT-XD was discovered. Once confirmed and a correction factor established, EBT-XD was used as an independent reference measurement. This work presents confirmation of the MOSkin suitability for ultra-high dose-rate environments with an electron energy of 100 MeV, and a theoretical discussion of its dose-rate and dose-per-pulse independence; the MOSkin is the only detector suitable for both clinical quality assurance, and ultra-high dose-rate measurements in its standard, unmodified form. Full article

Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida two and para two, was admitted for treatment of pelvic organ prolapse. The patient reported an eight-year history of uterine bulging but had not used a pessary. The gynecological examination revealed a complete manually irreducible utero-vaginal prolapse with an ulcerative lesion on the right posterolateral vaginal wall. The histological examination diagnosed an HPV-independent keratinizing squamous cell carcinoma, grade I. Comprehensive imaging showed no evidence of metastasis. The patient underwent radical hysterectomy, bilateral adnexectomy, complete resection of the vaginal mass, and pelvic lymphadenectomy. The histopathological examination confirmed clear surgical margins. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, the disease was classified as stage I vaginal cancer. Postoperatively, the patient received radiotherapy (45 Gy) and high-dose-rate brachytherapy (14 Gy). Conclusions: The co-occurrence of vaginal cancer and utero-vaginal prolapse is exceedingly rare. Surgical intervention followed by radiotherapy is the most common treatment approach. Given the aggressive nature of the disease, comprehensive follow-up is essential. Further research is needed to determine whether long-term genital prolapse increases the risk of vaginal carcinoma. Full article

Background/Objectives: Intraoperative radiotherapy (IORT) has been used for decades to improve local control in advanced and recurrent head and neck cancers by delivering a concentrated dose of radiation directly to the tumor bed during surgery. Despite its potential advantages, IORT remains controversial due to its high complication rates and logistical complexity. This systematic review aims to assess the current evidence on IORT in head and neck oncology, evaluating its indications, effectiveness, and limitations. Methods: A systematic literature review was conducted in accordance with Cochrane systematic review method and reported following PRISMA guidelines. Databases, including Medline, Embase, Cochrane, and Web of Science, were searched for studies evaluating IORT in head and neck cancer. Outcomes of interest included local control rates, overall survival, complications, and treatment logistics. Data were weighted based on patient numbers, and statistical analyses included weighted means and comparative tests. Results: Included in this review are 47 studies that included 2330 patients. The studies were highly heterogeneous, limiting definitive conclusions. IORT was mainly used in stage III/IV or recurrent tumors, with an average dose of 14.7 Gy (range: 1–40 Gy). The five-year local control was 47% to 82%. Complication rates included wound necrosis (22,3%), fistulas 34 (17.8%), and carotid blow-out (14.5%). Logistical constraints remain a major limitation. Conclusions: The heterogeneous data and logistic challenges of IORT in head and neck oncology have limited its use, and the benefits remain uncertain. Full article

Background: Combining external beam radiotherapy (EBRT) with high-dose-rate (HDR) brachytherapy (BT) enables biologically effective dose escalation in prostate cancer. However, comparative evaluation of such regimens using radiobiological modeling remains limited. Methods: Dose regimens based on clinical practice were analyzed using α/β values of 1.5 and 3 Gy for the prostate. Ten patients with available planning CT, pelvic MRI, and ultrasound-guided BT plans were retrospectively evaluated. Physical and biological dose distributions were recalculated for various EBRT and HDR-BT combinations. Biological effective dose (BED) values were determined for the prostate and organs at risk (OARs: anterior rectal wall, bladder base, urethra). Regimens yielding the highest ΔBED between prostate and OARs were considered most favorable. Results: All regimens met clinical dose constraints. The most favorable ΔBED profiles for bladder and rectum were observed with HDR-BT regimens (2 × 15 Gy) combined with either 23 × 2 Gy or 15 × 2.5 Gy EBRT, independent of the assumed α/β value. EBRT-only regimens achieved superior urethral sparing, while higher HDR doses led to increased urethral exposure. Conclusions: This study underscores the value of radiobiological modeling in differentiating and optimizing prostate cancer radiotherapy strategies. While the trade-offs between dose escalation and OAR sparing are clinically known, our biologically driven analysis provides a more quantitative foundation for selecting and tailoring combined EBRT/HDR-BT regimens in practice. Full article

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

Background: Rural patients, including those with rectal cancer, continue to be underrepresented in research and medically underserved with unique challenges to accessing care. Like the rest of America, rural patients are experiencing rising rates of rectal cancer; however, unlike the rest of the country, they also have rising rectal cancer-related mortality. This study aims to review the literature regarding care for patients with rectal cancer in rural settings, from presentation and diagnosis to treatment algorithms, oncologic outcomes, their unique preferences, and the goals of care. Methods: A literature search was performed on PubMed, on 31 October 2024, using synonyms of “rural” and “rectal cancer” to identify relevant articles. Articles from outside the USA and Canada and those offering only commentary were eliminated during the initial screening/retrieval. A full-text review was performed on the remaining articles; all the studies that did not address the identified primary or secondary outcomes in rural rectal cancer patients were then excluded. All the primary and secondary outcomes are briefly summarized in narrative form, with more detail on the primary outcomes provided in tables. The variability in the key criteria between the studies is also summarized in the tables and appendices provided. Results: Thirty studies were identified that addressed the outcomes of interest in rural rectal cancer patient populations. The total number of participants could not be assessed given the use of overlapping databases. Of the articles, 21 addressed treatment modalities (surgery, chemotherapy, radiation), 13 addressed oncologic outcomes, and a mix of additional studies addressed the diagnostic work up, costs, and patient preferences. The studies addressing treatment demonstrated similar practices in regard to chemotherapy and surgical management, aside from lower rates of minimally invasive surgery, along with decreased neoadjuvant radiotherapy use and increased under-dosing in rural patients. The oncologic outcomes were overall similar to worse for rural patients as compared to urban patients, even for those receiving treatment at high-volume urban centers. Additionally, rural patients have higher healthcare costs for rectal cancer care. Discussion/Conclusions: Rural patients are an at-risk group, with a rising disease burden and worsening rectal cancer outcomes, despite advances in rectal cancer care and improving oncologic outcomes in the general population. Analysis of the situation is complicated due to the underrepresentation of rural patients in research and the lack of uniformity in the definition of “rural”. Moreover, significant gaps in the literature remain, such that the evaluation of guideline-concordant care is incomplete, including an absence of literature about watch-and-wait approaches in rural populations. While regionalization of rectal cancer care has shown promise, the improvements in outcomes may not be commensurate for rural patients. Thus, a specific focus on the impact of this shift for rural patients is necessary to mitigate unintended consequences. 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: To evaluate the long-term oncological outcomes and toxicity profile based on 24 years of follow-up in patients with localized very high-risk prostate cancer (VHR PCa) treated with a combination of high-dose-rate brachytherapy (HDR-BT) and pelvic external beam radiation therapy (EBRT). Methods: A retrospective analysis was conducted on 87 patients with VHR PCa, classified according to National Comprehensive Cancer Network (NCCN) criteria, who received HDR-BT and EBRT. Androgen deprivation therapy (ADT) was administered to 72 patients (82.8%). The primary endpoints were biochemical control and cancer-specific survival (CSS), while the secondary endpoints included local control rates, tumor-free survival (TFS), overall survival (OS), and treatment-related toxicity. Results: The 24-year biochemical control rate was 68% (standard deviation [SD]: ±4%), while CSS and TFS at 24 years were 82% (SD ±4%) and 78% (SD ±4%), respectively. Local control rates remained at 98% at 24 years. Furthermore, the OS rate at 24 years was 30%. Multivariate Cox regression analysis identified the T category in the TNM classification as the only factor significantly associated with biochemical control, with 24-year rates of 69%, 71%, and 50% for patients with T-classifications of ≤T2c, T3a, and T3b-T4, respectively (p = 0.024). Notably, no grade ≥3 late toxicities were observed during the follow-up period. Conclusions: The 24-year outcomes support the viability and therapeutic efficacy of EBRT combined with a conformal HDR-BT boost for patients with VHR PCa. Full article

Background/objectives: Brain cancer remains difficult to treat, with survival statistics stagnant for decades. The resistance of glioblastoma brain tumours can greatly challenge the effectiveness of conventional cancer radiotherapy. However, high dose rate radiotherapy has unique effects that allow for normal tissue sparing whilst maintaining tumour control. The addition of targeted radiosensitisers, such as the chemotherapeutic drug methotrexate (MTX) or the high-Z halogenated pyrimidine drug iododeoxyuridine (IUdR), can improve radiotherapy outcomes. Combining these radiosensitiser agents with ultra-high dose rate (UHDR) synchrotron X-rays can bear synergistic effects to enhance the efficacy of these multi-modal UHDR therapies, providing a means to overcome the radioresistance of brain cancer. Methods: Here, we use controlled in vitro assays following treatment, including a clonogenic assay to determine long-term cell survival and γH2AX immunofluorescent confocal microscopy to quantify double-strand DNA breaks (DSBs). Results: We find significant enhancement for highly synergistic combinations of IUdR+MTX with synchrotron X-rays. Cell survival results demonstrate 5.4 times increased 9L gliosarcoma cell killing when these agents are combined with UHDR synchrotron X-rays compared with conventional X-rays alone at the same 5 Gy dose. The underlying mechanisms are unveiled using γH2AX imaging and reveal significant increases in DSBs and dying cells following exposure to UHDR radiation. Conclusions: Our results demonstrate that highly synergistic combination treatments using UHDR synchrotron radiation can yield significantly improved brain cancer killing compared with conventional radiotherapy. We anticipate that these additive, multi-modal combination therapies will provide options for more targeted and effective use of radiotherapies for the future treatment of brain cancer. Full article

Background/Objectives: High-dose-rate (HDR) interventional radiotherapy (IRT) represents a valuable treatment alternative for basal cell carcinoma (BCC) of the midface, especially in the presence of esthetic or functional issues related to surgery. This retrospective study examines the clinical outcomes of patients who underwent HDR-IRT at our institution. Methods: Patients (pts) with histologically confirmed midface BCC were treated with HDR-IRT using superficial, interstitial, or endocavitary implants depending on tumor characteristics. Fractionation regimens were tailored to tumor location: 45 Gy in 9 fractions twice a day (the cheeks/lips) and 44 Gy in 14 fractions (the nose, with the first and last fractions delivering 4 Gy each, administered once daily, and the remaining 12 fractions delivering 3 Gy each, administered twice daily (BID) with an inter-fraction interval of at least 6 h). Treatment efficacy was assessed based on local control rates, toxicity (CTCAE criteria), and cosmetic outcomes. Results: Eight patients were considered. The most common tumor site was the nose (seven patients, 87.5%), followed by the upper lip. Tumors were either primary (three patients, 37.5%) or residual/recurrent after previous surgery with involved margins (five patients, 62.5%). The median follow-up was 6 months (range: 1–19 months). Clinical local control was achieved in all cases, with persistent alteration at dermoscopy in one patient six months after the completion of treatment. Acute toxicities were minimal, with two patients developing grade 3 skin toxicity, which resolved within 1–3 months with topical management. Cosmetic outcomes were favorable across all patients. Conclusions: HDR-IRT is a well-tolerated, effective, and cosmetically favorable treatment for midface BCC. Our institutional experience supports its use as an alternative to surgery in cosmetically sensitive areas and in selected patients/lesions unfit for surgery. Endocavitary implants appear to be an effective option to cover the full thickness nasal wall without resorting to interstitial implants. Full article

Monte Carlo simulation relies on pseudo-random number generators. In general, the quality of these generators can have a direct impact on simulation results. The GATE toolbox, widely adopted in radiotherapy, offers three generators from which users can choose: Mersenne Twister, Ranlux-64, and James-Random. In this study, we used these generators to simulate the head of a medical linear accelerator for 6 MV photons in order to assess their potential impact on the results obtained in radiotherapy simulation. Simulations were conducted for four different field openings. The simulations included a linac head model and a water phantom, all components of the head of the medical linear accelerator, and a water phantom placed at a distance of 100 cm from the electron source. Statistical analysis based on normal probability and Bland–Altman plots were used to compare dose distributions in the voxelized water phantom obtained by each generator. Experimental data (dose profiles, percentage dose at depth, and other dosimetric parameters) were measured using an appropriate quality assurance protocol for comparison with the different simulations. The evaluation of dosimetric criteria shows significant variations, particularly in the physical penumbra of the dose profile for large fields. The gamma index analysis highlights significant distinctions in generator performance. In all simulations, the average time of the primary particle generation rate, number of tracks, and steps in the simulation of different random number generators showed differences. The Mersenne Twister generator was distinguished by high performance in several aspects, particularly in terms of execution time, primary particle production, track and step production flow rate, and coming closer to the experimental results. Regarding computational time, the simulation using the Mersenne Twister generator was about 18% faster than the one using the James-Random generator and 27% faster than the simulation using the Ranlux-64 generator. This suggests that this generator is the most reliable for accurate and fast modeling of the medical linear accelerator head for 6 MV energy. Full article

Background/Aim: Perineal, pelvic and urogenital reconstruction presents a challenge, not only due to defect size but also due to high morbidity resulting from surgery and post-operative complications. The purpose of this study is to review the surgical approach and evaluate the results regarding pelvic/perineal reconstruction after advanced tumor resection. Patients and Methods: The total number of patients was 34 (11 males, 23 females). The histology varied, including sixteen rectal-anal squamous cell carcinomas, five Buschke-Lowenstein tumors, four vulvar-vaginal carcinomas, four sacral chordomas, two cutaneous squamous cell carcinomas, two soft tissue sarcomas and a case of Paget’s disease. Most patients had previously been treated with colectomies and/or gynecological resections and received a full dose of radiotherapy. Reconstruction was performed with the following flaps: oblique/vertical rectus abdominis myocutaneous flap (ORAM/VRAM), gracilis myocutaneous flap, inferior gluteal artery perforator flap (IGAP), internal pudendal artery perforator flap (IPAP) and lotus petal flaps. Results: Most patients had a relatively uncomplicated post-operative course. Surgical site infection and wound dehiscence occurred more commonly with the thigh flaps rather than the abdominal flaps. However, the aggression and the frequent recurrences of these tumors had as a result, only 15 out of 34 patients achieved a five-year disease-free survival. Conclusions: Pelvic and perineal defects are usually massive and the use of myocutaneous flaps to eliminate the dead space is of paramount importance. Although these are mainly salvage operations with a low survival rate, they promote patients’ quality of life. A frequent challenge is the simultaneous achievement of tumor radical resection and pelvis functionality. Full article