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Introduction: While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aimed to assess the impact of the Geriatric-8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients. Methods: Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45–66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients. Results: In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months, respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p = 0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6–48.4) and 19 months (95% CI, 0–39.4), respectively (p = 0.832). The median overall survival (OS) was 38 months (95% CI, 23.8–52.2) in geriatric patients, while it was not reached in younger patients (p = 0.745). There was no significant difference between the two groups. The pretreatment and post-treatment G8 values of the geriatric patients were 9.25 (6–13.5) and 9.5 (6–14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 months vs. 11 months, p = 0.001) and OS (median 85 months vs. 14 months, p = 0.001) compared to those with unchanged or decreased G8 scores. Conclusion: Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value. [ABSTRACT FROM AUTHOR]

We report a case of a 79-year-old male patient with a history of radical prostatectomy for prostate cancer. The patient presented with biochemical reoccurrence; however, previous conventional PSMA PET/CT using [18F]PSMA-1007 showed two indetermined findings with low uptake in the right iliac lymph nodes. Further MRI evaluation provided no additional information. A recently introduced PSMA tracer, [89Zr]Zr-PSMA-617 (half-life: 3.3 days), was administered in an attempt to confirm the diagnosis and aid in potential radiation planning. [89Zr]Zr-PSMA-617 PET/CT clearly revealed the previously indetermined right iliac lymph nodes as definitely metastatic and also identified additional lymph node metastases that were undetected in prior scans. This case highlights the potential superior sensitivity of [89Zr]Zr-PSMA-617 PET/CT in detecting recurrent disease, especially in unclear settings of [18F]PSMA-1007 PET/CT and demonstrates its potential for guiding targeted radiation therapy with curative intent. [ABSTRACT FROM AUTHOR]

Simple Summary: Our research addresses the challenges in informed consent in postoperative radiotherapy for breast cancer. Traditional consent processes often rely on verbal explanations of sometimes complicated treatment options, which can overwhelm patients and lead to misunderstandings. To improve this fundamental process, we developed an educational video using a modified Delphi method, incorporating input from experts and former patients to ensure comprehensive and patient-friendly content. With our study, we demonstrated that this video, if viewed by breast cancer patients prior to their subsequent verbal consultation, can significantly improve patients' understanding and speed up the informed consent process without compromising patients' satisfaction. To conclude, this innovation supports a more comprehensive and efficient informed consent process, which is in line with evolving healthcare practices that prioritise patient engagement and education. Background/Objectives: Informed consent is crucial in medical practice, especially for complex treatments such as postoperative radiotherapy for patients with breast cancer. Conventional consent procedures are often based on verbal declarations with a highly condensed but nevertheless large amount of information, which can exceed the recording capacity of patients and lead to misunderstandings. The aim of this study was to develop and test an educational video on breast cancer patients to enhance the informed consent process by improving patients' understanding and reducing the duration of the subsequent consultation. Methods: The educational video was created after the underlying content was determined by a modified Delphi method in which a panellist of radiation oncologists, nurses, radiation therapists, and former patients participated in successive rounds of topic scoring. After achieving content consent, the video included 19 items to cover key aspects of postoperative radiotherapy in a patient-friendly manner. Fifty breast cancer patients scheduled for postoperative radiotherapy were randomised to watch the video prior to their verbal consultation (n = 25) or to the control group participating in the traditional informed consent process only (n = 25). The duration of the informed consent processes in both arms was recorded. To assess the educational effect of the video, a multiple-choice test was created. In addition, patients' satisfaction was recorded using a separate questionnaire. Both questionnaires were completed by the patients one to two hours after signing the consent form. Results: The patients in the video group evidenced significantly higher knowledge scores than those who received standard verbal explanations (median number of correct answers 9 vs. 8 out of 10, p = 0.0039). The whole informed consent process was also completed faster in the video group (mean duration 34.7 vs. 46.2 min, p < 0.001). Median satisfaction scores were high in both groups (34 vs. 33 out of 35 points), with no significant differences observed (p > 0.05). Conclusion: The educational video effectively improved patient understanding and streamlined the informed consent process without compromising patients' satisfaction. This approach also helps to standardise the delivery of complex medical information, and it can also be adapted to improve the informed consent process for other cancer treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancers (HNCs) represent 4–5% of all malignancies globally. Salivary metabolites, as metabolic intermediates and signalling molecules, are gaining attention as diagnostic biomarkers for several diseases, including HNC; however, the metabolites' role in cancer treatment outcomes and oral side effects remains underexplored. Current studies focus on the oral microbiome's significance in promoting a pro-inflammatory environment that facilitates tumour development and invasion. Specific microorganisms and their metabolites influence chemotherapy efficacy through several mechanisms. Radiotherapy (RT), a standard HNC treatment, can modify the oral microbiota and salivary metabolite profiles, leading to a wide range of side effects. To reduce oral complications, intensity-modulated radiotherapy (IMRT) was developed; however, cancer survivors often experience a reduced quality of life. This review highlights the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors' quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: We discuss the role of risk-stratification and personalized treatment for various pediatric cancer patients, with the goal being to improve tumor control and decrease late effects of radiation in long-term survivors. We discuss settings in which radiation can be safely omitted or de-escalated, such as Hodgkin lymphoma, Wilms tumor with lung metastases and WNT pathway Medulloblastoma, and settings that warrant treatment escalation such as larger tumors with rhabdomyosarcoma or Ewing sarcoma, poor responders to chemotherapy and oligometastatic disease settings. We also summarize currently enrolling COG and other cooperative group trials. While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible for late toxicity. In the past decade, radiotherapy has been omitted in patients achieving excellent response to chemotherapy, such as in Hodgkin lymphoma and some Wilms tumors with lung metastases. Likewise, response to chemotherapy has been used to determine whether lower doses of radiation can be delivered in intracranial germinoma and pediatric nasopharyngeal carcinoma. Molecular subtyping in medulloblastoma is currently being employed, and in WNT-pathway M0 tumors, the reduction in radiotherapy dose to the craniospinal axis and tumor bed is currently being investigated. Finally, dose escalation was recently evaluated in patients with rhabdomyosarcoma > 5 cm who do not achieve a complete response to initial 9 weeks of chemotherapy as well as for unresectable Ewing sarcoma patients to improve local control. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the current practices in the real world for grade 2 glioma, an uncommon primary brain cancer. Leveraging the prospective BRAIN registry, this study demonstrates that whilst sequential radiotherapy and chemotherapy improve progression-free survival in high-risk grade 2 glioma, the majority of patients are observed following surgery. In high-risk patients who are observed, 61% remain progression-free at 12 months, with 10% being progression-free at 5 years. This clinically meaningful progression-free survival suggests that validated biomarkers beyond the usual definition of high-risk are required to better inform patient management. Factors contributing to decision-making are underway. Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016–December 2019 (TP1) and January 2020–December 2022 (TP2), were defined. Survival was estimated using the Kaplan–Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusion: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultra-high dose rate radiotherapy with particle beams such as proton and carbon is a major technical challenge. Fast beam delivery and the concentration of the Bragg peak to the tumor must be achieved in the order of milliseconds and can therefore only be realized with 3D range-modulators (3D RM). This work analyzed the robustness of the dose distribution, resulting from a 3D RM for a cube target volume. Firstly, a high-precision dose measurement was performed, and a very good agreement was found between the measured and Monte Carlo simulated dose distribution. Further simulations were conducted to determine how sensitively the resulting dose distribution responds to misalignments of the 3D RM. The results show that the 3D RM must be aligned with accuracy less than 1° to preserve the planned desired dose distribution. As the research and pre-clinical adoption of 3D RMs in particle therapy has become more widespread recently, these results are of high general utility. A 3D range-modulator (RM), optimized for a single energy and a specific target shape, is a promising and viable solution for the ultra-fast dose delivery in particle therapy. The aim of this work was to investigate the impact of potential beam and modulator misalignments on the dose distribution. Moreover, the FLUKA Monte Carlo model, capable of simulating 3D RMs, was adjusted and validated for the 250 MeV single-energy proton irradiation from a Varian ProBeam system. A 3D RM was designed for a cube target shape rotated 45° around two axes using a Varian-internal research version of the Eclipse treatment planning software, and the resulting dose distribution was simulated in a water phantom. Deviations from the ideal alignment were introduced, and the dose distributions from the modified simulations were compared to the original unmodified one. Finally, the FLUKA model and the workflow were validated with base-line data measurements and dose measurements of the manufactured modulator prototype at the HollandPTC facility in Delft. The adjusted FLUKA model, optimized particularly in the scope of a single-energy FLASH irradiation with a PMMA pre-absorber, demonstrated very good agreement with the measured dose distribution resulting from the 3D RM. Dose deviations resulting from modulator-beam axis misalignments depend on the specific 3D RM and its shape, pin aspect ratio, rotation angle, rotation point, etc. A minor modulator shift was found to be more relevant for the distal dose distribution than for the spread-out Bragg Peak (SOBP) homogeneity. On the other hand, a modulator tilt (rotation away from the beam axis) substantially affected not only the depth dose profile, transforming a flat SOBP into a broad, Gaussian-like distribution with increasing rotation angle, but also shifted the lateral dose distribution considerably. This work strives to increase awareness and highlight potential pitfalls as the 3D RM method progresses from a purely research concept to pre-clinical studies and human trials. Ensuring that gantry rotation and the combined weight of RM, PMMA, and aperture do not introduce alignment issues is critical. Given all the other range and positioning uncertainties, etc., not related to the modulator, the RM must be aligned with an accuracy below 1° in order to preserve a clinically acceptable total uncertainty budget. Careful consideration of critical parameters like the pin aspect ratio and possibly a novel robust modulator geometry optimization are potential additional strategies to mitigate the impact of positioning on the resulting dose. Finally, even the rotated cube 3D modulator with high aspect ratio pin structures (~80 mm height to 3 mm pin base width) was found to be relatively robust against a slight misalignment of 0.5° rotation or a 1.5 mm shift in one dimension perpendicular to the beam axis. Given a reliable positioning and QA concept, the additional uncertainties introduced by the 3D RM can be successfully managed adopting the concept into the clinical routine. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a common eye malignancy and is managed by surgery, brachytherapy or external beam radiation for early-stage disease. Proton therapy is a newer form of radiation therapy and is especially suited to treat large uveal melanoma because of its unique physical characteristics. This review describes the physics, radiobiology, treatment techniques, and clinical outcomes when using proton therapy to treat uveal melanoma, with a focus on choosing between brachytherapy and proton therapy. Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles. [ABSTRACT FROM AUTHOR]

Simple Summary: Pericardial disease is a common and severe complication in patients with cancer, often presenting as acute pericarditis, pericardial effusion, or constrictive pericarditis. Causes include direct tumor invasion, metastasis, and cancer treatments like chemotherapy and radiotherapy. Lung cancer is the most frequent etiology, followed by breast cancer and lymphomas. Early detection and multidisciplinary management are crucial. Acute pericarditis requires careful diagnosis and treatment with NSAIDs and colchicine. Pericardial effusion is commonly incidental but can lead to cardiac tamponade, necessitating pericardiocentesis or a pericardial window. Immunotherapy-related effusions typically respond to treatment cessation and steroids. Constrictive pericarditis, although rare, requires prompt diagnosis and may necessitate surgical intervention. Multidisciplinary care and early intervention are vital for improving patient outcomes and quality of life. Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient's clinical status, thereby improving the quality of life and prognosis. [ABSTRACT FROM AUTHOR]

Background: To date, in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) has preceded adjuvant radiotherapy (A-RT). In the last twenty years, the adjuvant treatment of BC has quickly evolved due to better knowledge of its molecular biology, genetic profile, and α/β ratio of 3/4 Gy for tumor and normal tissue radiosensitivity. Thus, new schedules with hypofractionated radiotherapy have been tested, and a third generation of A-CT has been introduced, raising the question of whether it is time to rethink the sequencing between these two approaches. Methods: In the last 20 years, many attempts have been made worldwide to optimize the best sequencing strategy between these two approaches in terms of sequential CT-RT and RT-CT and concomitant and sandwich modalities using drugs and schedules. This paper presents a comprehensive review of the state of the art, analyzing all the available studies to assess the sequencing between A-CT and A-RT with different generations of chemotherapy schedules. Results: More than 8000 patients from 30 studies treated with adjuvant chemotherapy and whole breast radiotherapy who were enrolled in randomized, retrospective, and prospective studies were analyzed. Sequential, concomitant, and sandwich modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies were included. The most used sequence was adjuvant chemotherapy followed by conventional or hypofractionated radiotherapy. In the concomitant approach, i.v. CMF has been the most important adopted schedule, while the concomitant use of anthracyclines and taxanes with conventional or hypofractionated radiotherapy has been found to be more toxic. One study analyzed the benefit in terms of reducing adjuvant treatment time with upfront hypofractionated radiotherapy and third-generation chemotherapy. Conclusions: At present, the best sequencing strategy has not yet been defined. This comprehensive review is a journey among the most important randomized, retrospective, and prospective studies that highlights the past, current, and novel time sequencing proposals between A-CT and A-RT to assess the state of the art and provide useful information for future adjuvant approaches in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Myeloid sarcoma (MS), an extramedullary form of acute myeloid leukemia (AML) is a rare tumor mass of myeloid blasts. It can disseminate to any one or multiple anatomical sites, with (synchronous MS) or without (isolated MS) bone marrow (BM) involvement. The aim of this review is to describe the most recent advances in MS regarding diagnosis, molecular background, various clinical manifestations from several organs, and treatment approaches. Due to the lack of prospective, randomized clinical trials, therapeutic decisions are a challenge for the clinician. In the era of novel targeted AML treatments, a critical analysis of how to decide the best option for individual patients, also covering the possible central nervous system (CNS) prophylaxis is provided. For the majority of the patients, AML induction chemotherapy, followed by hematopoietic stem cell transplantation (HSCT) is generally recommended. This paper discusses the role of radiotherapy, the treatment of refractory and relapsed disease, along with the therapeutic approach of difficult-to-treat patients, due to specific problems related to different anatomical sites of MS. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle's biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered. [ABSTRACT FROM AUTHOR]

Objective To observe the radiotherapy sensitivity of esophageal carcinoma cells with down-regulated expression of hypoxia-inducible factor-1α (HIF-1α) and to explore its mechanism. Methods Human esophageal cancer cell lines EC9706, TE-2, TE-7 and TE-8 were cultured and were given 2, 4 and 6 Gy X-ray radiotherapy, respectively. The cell proliferation inhibition rate was observed by CCK-8 method, and the cell line with the lowest cell proliferation inhibition rate was selected as the cell line with the best radiotherapy tolerance for follow-up study, and the radiotherapy dose with inhibition rate of cell proliferation less than 50% at 72 h after X-ray irradiation was selected as the radiotherapy dose for follow-up study. The selected cell lines were further divided into the control group, radiotherapy group, HIF-1α down-expression group, and radiotherapy +HIF-1α down-expression group, respectively; siRNA-HIF-1α was transfected into the HIF-1α down-expression group and radiotherapy +HIF-1α down-expression group by the liposome transfection. According to the selected radiotherapy dose, the cells in the radiotherapy group and the radiotherapy +HIF-1α down-expression group were treated with single radiotherapy, while cells in the control group and HIF-1α down-expression group were cultured without radiotherapy. The cell radiotherapy sensitivity of each group was observed by CCK-8 method, and vascular endothelial growth factor (VEGF), E-cadherin, and Vimentin were detected by Western blotting. Results The proliferation inhibition rate of EC9706 cells was the lowest at 2, 4 and 6 Gy radiotherapy dose, and the proliferation inhibition rate of EC9706 cells was less than 50% at 2 Gy radiotherapy dose. Therefore, 2 Gy was selected as the follow-up radiation dose. Cell proliferation inhibition rate was as follows: control group < radiotherapy group < HIF-1α down-expression group < radiotherapy+HIF-1α down-expression group, VEGF protein expression was as follows: control group > radiotherapy group, HIF-1α down-expression group > radiotherapy + HIF-1α down-expression group, Vimentin protein expression was in the following order: control group > radiotherapy group > HIF-1α down-expression group > radiotherapy+HIF-1α down-expression group, and the E-cadherin protein expression was as follows: control group < radiotherapy group, HIF-1α down-expressionn group < radiotherapy+HIF-1α down-expression group (all P<0. 05) . Conclusion Esophageal cancer cells with down-regulated HIF-1α expression are more sensitive to radiotherapy, and the mechanism may be related to the inhibition of tumor angiogenesis and epithelial-mesenchymal transformation. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO3−x is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO3−x nanoreactors exhibit strong absorption of X‐ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme‐mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst‐like activity and are sensitive to H2O2 in the tumor microenvironment (TME) under near infrared‐II (NIR‐II) light stimulation. They efficiently catalyze the conversion of H2O2 to O2, thereby ameliorating hypoxia, inhibiting the expression of HIF‐1α, and enhancing RT‐induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high H2O2 levels in TME, the Ir@WO3−x nanoreactor also exerts peroxidase‐like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS‐dependent death signaling. Furthermore, Ir@WO3−x can serve as a high‐quality computed tomography contrast agent due to its high X‐ray attenuation coefficient and generation of pronounced tumor‐tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer management in patients with pacemakers presents unique challenges. This report examines the utilization of stereotactic body radiation therapy (SBRT) in such a patient population. Case Presentation: A 75-year-old former smoker with a dual-chamber pacemaker presented with inoperable lung adenocarcinoma. SBRT (48 Gy in 4 fractions) was chosen following multidisciplinary consultation and thorough pretreatment evaluation by a rhythmologist to assess pacemaker integrity. Continuous cardiac monitoring during SBRT detected no arrhythmias. Adjuvant therapy consisted of radiotherapy alone due to the patient’s health status and limited evidence supporting chemotherapy in this context. At the 18-month follow-up, no cancer recurrence was observed, and regular device checks confirmed pacemaker integrity. Conclusion: This case demonstrates the successful management of inoperable lung adenocarcinoma with SBRT in a patient with a pacemaker. It underscores the significance of interdisciplinary cooperation and careful patient assessment to optimize treatment outcomes in this challenging clinical scenario. [ABSTRACT FROM AUTHOR]

Background: Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren's syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow–derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow–derived MSCs. Methods: This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren's syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow–derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow–derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study. Discussion: Both adipose-derived and bone marrow–derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow–derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial. Systematic review registration: PROSPERO ID CRD42024527183. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact that adjuvant therapies like radiotherapy, chemotherapy, and immunotherapy have on osteobiologic properties and bony regeneration in patients with metastatic spine disease (MSD) undergoing spinal fusion surgery. Methods: PubMed and ClinicalTrials.gov searches were performed. MSD patients undergoing fusion surgery with an osteobiologic and radiotherapy, chemotherapy and/or immunotherapy were included. Demographics, primary tumor, surgery, adjuvant treatments, osteobiologic type, fusion rates with scoring criteria, hardware failure, reoperation rates, follow-up, and survival were extracted. 1487 studies were screened, 20 included. Results: 585 patients (464 with MSD) had fusion rates ranging from 17.9 to 100%. In the setting of radiotherapy, fusion rates of 10 studies using autologous bone graft (autograft), 5 studies using allogenic bone graft (allograft), 5 studies using combination autograft/allograft, 4 studies using biomaterial scaffolds (BMS), 3 studies using demineralized bone matrices (DBM), and 1 study using growth factors (GF), were 50–100%, 17.9–100%, 57.8–100%, 52.9–100%, 20–100%, and 100%, respectively. A higher incidence of fusion in patients with autograft or allograft receiving stereotactic body radiotherapy (SBRT) at lower biologically effective doses (BED) and at least 1-month postoperatively was noted. Chemotherapy had no impact on fusion. No studies evaluated the impact of immunotherapy on fusion. Conclusions: SBRT at lower doses given greater than 1-month postoperatively may enhance bony fusion in patients receiving autograft, allograft, or autograft/allograft. Chemotherapy may delay bony fusion without affecting overall fusion rates. Preclinical studies suggest immunotherapy may prevent osteolysis and promote osteogenesis, but no studies have yet evaluated the clinical impact of these findings on spinal fusion. Further research is needed on osteobiologics in bony regeneration in the MSD population. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Cone beam computed tomography (CBCT) can be used to evaluate the inter‐fraction anatomical changes during the entire course for image‐guided radiotherapy (IGRT). However, CBCT artifacts from various sources restrict the full application of CBCT‐guided adaptive radiation therapy (ART).Inter‐fraction anatomical changes during ART, including variations in tumor size and normal tissue anatomy, can affect radiation therapy (RT) efficacy. Acquiring high‐quality CBCT images that accurately capture patient‐ and fraction‐specific (PFS) anatomical changes is crucial for successful IGRT.To enhance CBCT image quality, we proposed PFS lung diffusion models (PFS‐LDMs). The proposed PFS models use a pre‐trained general lung diffusion model (GLDM) as a baseline, which is trained on historical deformed CBCT (dCBCT)‐planning CT (pCT) paired data. For a given patient, a new PFS model is fine‐tuned on a CBCT‐deformed pCT (dpCT) pair after each fraction to learn the PFS knowledge for generating personalized synthetic CT (sCT) with quality comparable to pCT or dpCT. The learned PFS knowledge is the specific mapping relationships, including personal inter‐fraction anatomical changes between personalized CBCT‐dpCT pairs. The PFS‐LDMs were evaluated on an institutional lung cancer dataset, quantified by mean absolute error (MAE), peak signal‐to‐noise ratio (PSNR), normalized cross‐correlation (NCC), and structural similarity index measure (SSIM) metrics. We also compared our PFS‐LDMs with a mainstream GAN‐based model, demonstrating that our PFS fine‐tuning strategy could be applied to existing generative models.Our models showed remarkable improvements across all four evaluation metrics. The proposed PFS‐LDMs outperformed the GLDM, demonstrating the effectiveness of our proposed fine‐tuning strategy. The PFS model fine‐tuned with CBCT images from four prior fractions, reduced the MAE from 103.95 to 15.96 Hounsfield units (HU), and increased the mean PSNR, NCC, and SSIM from 25.36 dB to 33.57 dB, 0.77 to 0.98, and 0.75 to 0.97, respectively. Applying our PFS fine‐tuning strategy to a Cycle GAN model also showed improvements, with all four fine‐tuned PFS Cycle GAN (PFS‐CG) models outperforming the general Cycle GAN model. Overall, our proposed PFS fine‐tuning strategy improved CBCT image quality compared to both the pre‐correction and non‐fine‐tuned general models, with our proposed PFS‐LDMs yielding better performance than the GAN‐based model across all metrics.Our proposed PFS‐LDMs significantly improve CBCT image quality with increased HU accuracy and fewer artifacts, thus better capturing inter‐fraction anatomical changes. This lays the groundwork for enabling CBCT‐based ART, which could enhance clinical efficiency and achieve personalized high‐precision treatment by accounting for inter‐fraction anatomical changes. [ABSTRACT FROM AUTHOR]

Radiotherapy, a traditional cancer treatment, not only controls local tumor growth but also potentially induces immunogenic cell death, initiating systemic immune responses. However, radiotherapy resistance and immunosuppressive tumor microenvironments often limit the potency of radiation‐induced anti‐tumor immune responses, rendering them insufficient for clinical applications. Consequently, trimetallic nanoparticles are constructed with dual enzymatic activity, AuBiCu‐distearoyl phosphoethanolamine‐PEG nanoparticles (AuBiCu‐PEG NPs), to synergistically improve radiotherapy resistance through X‐ray deposition, hypoxia alleviation, and ferroptosis and cuproptosis induction. This approach promotes radiotherapy‐induced immunogenic cell death and boosts anti‐tumor immune responses. Furthermore, AuBiCu‐PEG NPs effectively reversed radiation‐induced upregulation of programmed cell death 1 ligand 1 (PD‐L1), inhibit tumor immune evasion, and reshaped the immune microenvironment. Non‐invasive and real‐time longitudinal monitoring of nanoparticle accumulation in tumors can be achieved using spectral computed tomography (CT) and photoacoustic (PA) imaging. In summary, the designed AuBiCu‐PEG NPs serve as promising nanoplatforms for immune microenvironment remodeling and can be used in multimodal molecular imaging‐guided ferroptosis‐cuproptosis‐enhanced radiotherapy. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethods and materialsResultsConclusionsBoron Neutron Capture Therapy (BNCT) is an innovative radiation therapy with significant potential in cancer treatment. This systematic review aimed to comprehensively evaluate the efficacy, safety, and applicability of BNCT across various cancer types.Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic search in PubMed, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and ICTRP from inception until May 27, 2023. Eligible studies were selected based on predefined criteria, and statistical analyses were performed using IBM SPSS (Statistical Package for the Social Sciences) to assess correlations between histological factors, treatment outcomes, and adverse effects.The initial search identified 925 studies (498 from Scopus, 333 from PubMed, 16 from ClinicalTrials.gov, 41 from ICTRP, and 30 from Cochrane CENTRAL). After removing duplicates and applying selection criteria, 121 full-text articles were assessed, with 39 studies meeting the inclusion criteria. An additional study published in 2024 was included during the peer review process, bringing the total to 40 studies. The analysis revealed that BNCT demonstrates promising efficacy across various cancers, with a manageable safety profile. However, outcome variability and adverse effects were noted among the studies.BNCT shows substantial promise as a treatment modality for multiple cancer types, offering potential benefits with acceptable safety profiles. Nonetheless, further research is essential to refine its clinical application and ensure consistent safety and efficacy. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is a pillar of cancer therapy used by more than half of all cancer patients. Clinically, RT is mostly delivered as external beam radiation therapy (EBRT). However, the scope of EBRT is limited in the metastatic setting, where all sites of disease need to be irradiated. Such a limitation is attributed to radiation-induced toxicities, for example on bone marrow and hematologic toxicities, resulting from a large EBRT field. Radiopharmaceutical therapy (RPT) has emerged as an alternative to EBRT for the irradiation of all sites of metastatic disease. While RPT can reduce tumor burden, it can also impact the immune system and anti-tumor immunity. Understanding these effects is crucial for predicting and managing treatment-related hematological toxicities and optimizing their integration with other therapeutic modalities, such as immunotherapies. Here, we review the immunomodulatory effects of α- and β-particle emitter-based RPT on various immune cell lines, such as CD8+and CD4+ T cells, natural killer (NK) cells, and regulatory T (Treg) cells. We briefly discuss Auger electron-emitter (AEE)-based RPT, and finally, we highlight the combination of RPT with immune checkpoint inhibitors, which may offer potential therapeutic synergies for patients with metastatic cancers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the impact of oral nutritional supplements (ONS) on nutritional intake, body weight, and body composition in head and neck cancer (HNC) patients undergoing chemoradiotherapy. The study evaluated whether ONS could prevent treatment-related nutritional deterioration. Methods: This prospective observational pilot study included 30 HNC patients randomized into two groups: ONS (n = 15) and No ONS (n = 15). All participants underwent chemoradiotherapy, with the ONS group receiving 200 mL of a high-calorie, high-protein supplement twice daily. Nutritional status, including body weight, BMI, fat mass, fat-free mass, and bone mass, was assessed at three time points: baseline, mid-treatment, and end of treatment. Data were analyzed using the Mann–Whitney U test, with a p-value of ≤0.05 considered statistically significant. Results: At baseline, there were no significant differences between the two groups in body weight, BMI, or body composition. By the end of radiotherapy, the No ONS group showed significant reductions in body weight (p < 0.001), BMI (p < 0.001), fat mass (p < 0.001), and fat-free mass (p < 0.001), while the ONS group maintained more stable nutritional parameters. Acute radiotherapy toxicities, including nausea, dysphagia, and oral mucositis, were not significantly different between the two groups. Conclusion: ONS effectively mitigates weight loss and preserves body composition in HNC patients undergoing chemoradiotherapy. While no significant reduction in radiation-induced toxicities was observed, the nutritional benefits of ONS support its use in preventing malnutrition in this patient population. Larger studies are needed to further validate these findings. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes. Materials/ Methods: We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy. Metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were extracted from F18-fluorodeoxyglucose positron emission tomography (PET) scans acquired prior to bRT and between completion of bRT and CAR Tcell infusion. Delta radiomics based on changes of these values were then calculated. The association between delta radiomics and oncologic outcomes [progression-free survival (PFS), freedom from distant progression (FFDP), and local control (LC)] were then examined. Results: Thirty-three sites across 23 patients with LBCL were irradiated. All metabolically active disease was treated in 10 patients. Following bRT, median overall decreases (including unirradiated sites) in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. Median follow-up was 15.2 months. A decrease in SUVmax of at least 54% was associated with improved PFS (24-month PFS: 83.3% vs. 28.1%; p = 0.037) and FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). A decrease in MTV of at least 90% was associated with improved FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). LC was improved in sites with decreases in SUVmax of at least 71% (24-month LC: 100% vs. 72.7%; p < 0.001). Decreases of MTV by at least 90% (100% vs. 53.3%; p = 0.038) and TLG by at least 95% (100% vs. 56.3%; p = 0.067) were associated with an improved complete response rate. Conclusion: bRT led to substantial reductions in MTV, SUVmax, SUVmean, and TLG. The relative extent of these decreases correlated with improved outcomes after CAR T-cell infusion. Prospective cohorts should validate the value of interim PET following bRT for quantifying changes in disease burden and associated prognosis. [ABSTRACT FROM AUTHOR]

Gut microbiota substantially impacts pathogenic and normal immune responses and is associated with common chronic diseases. Moreover, it has a considerable effect on the efficacy of cancer therapy. Variant gut microbiota is linked with immune checkpoint inhibitors, chemo drugs, and radiotherapy resistance. Therefore, a comprehensive interpretation of the interactions between microbiota and cancer therapies is required to encourage researchers to develop new cancer prevention strategies and weaken the consequences of the different cancer therapies. This review discusses the modulating role of gut microbiota that impacts the efficacy of cancer therapies and focuses on its influence on each treatment method, in addition to delivering an overview of the gut microbiota's role and forming relationships between bacteria, inflammation, and cancer therapies. Highlighting the mechanism of action of probiotics, antibiotics, fecal microbiota transplantation, and prebiotics promotes cancer therapies' efficacy. Consequently, this makes the gut microbiota essential as a new adjunct augmenting the cancer therapeutic response. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution. Materials/Methods: The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk. Results: A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups. Conclusion: Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy. [ABSTRACT FROM AUTHOR]

Thoracic bulky esophageal cancer shrinks during radiotherapy, changing the location and shape of the surrounding heart and lungs. The current study aimed to explore how replanning by volumetric-modulated arc radiotherapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) influences the target coverage and dose to organs at risk in locally advanced unresectable middle to lower thoracic esophageal cancer. We retrospectively collected CT simulation images of initial and boost radiotherapy plans for locally advanced unresectable thoracic esophageal cancer in 17 consecutive patients. First, we created boost plans of 20 Gy using 3DCRT and VMAT on the initially acquired CT images. Second, we replicated the process on CT images acquired after 20–40 Gy of radiotherapy. We then compared non-replanned boost radiotherapy plans with replanned boost plans. Replanned radiotherapy delivered more conformal doses to the target and reduced heart and lung doses. VMAT reduced more irradiated mean doses to the heart than 3DCRT in the case of replanning (1.7 and 1.1 Gy, p < 0.001). Replanning to accommodate tumor shrinkage during radiotherapy effectively lowers the irradiated doses to the heart and lungs in patients with locally advanced unresectable middle to lower thoracic esophageal cancer, especially those treated with VMAT. [ABSTRACT FROM AUTHOR]

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty.We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information.The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6–67.2) years and a median (IQR) age at transplantation of 58.6 (52.7–65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate‐specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5–10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow‐up of 5.8 (2.5–10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow‐up of 5.3 (1–8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer.A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Monte Carlo (MC) modeling of MR‐guided radiotherapy (MRgRT) treatment machines enables the characterization of photon/electron interactions in the presence of a magnetic field. The EGSnrc MC code system is a well‐established system for radiation dose calculations. The multi‐leaf collimator (MLC) component modules presently available within the EGSnrc MC code system do not include a model of the double‐focused MLC available on a low‐field (0.35T) MRI linear accelerator (MR linac).Here we developed and validated a new component module (CM) for the low‐field MRgRT MLC using the EGSnrc/BEAMnrc/DOSXYZnrc code system. We performed detailed modeling of the treatment head and validated the model using measurements and calculations from the vendor‐specific treatment planning system (TPS).The detailed geometry of the low‐field MR linac MLC and other treatment head structures were modeled using BEAMnrc. Comparisons of DOSXYZnrc simulated dose against measurements and the low‐field MR linac TPS for a variety of AAPM TG‐53 task group report suggested square and shaped fields, as well as a step‐and‐shoot intensity‐modulated radiotherapy (IMRT) plan, are presented.Our model agrees with both measured and TPS calculated data on average within 2%/2 mm (dose/DTA) criterion for square field profiles. Output factors agreed within 1% for field sizes down to 2.49 × 2.49 cm2 and within 2% of TPS data for the smallest field size of 0.83 × 0.83 cm2. Shaped field and IMRT MC calculations agreed with measured and TPS data such that the gamma pass rates (3%/2 mm) were 99.5% and (3%/3 mm) 96.2%, respectively.We developed and validated an MLC CM (SYNCVRMLC) for the low‐field MR linac using the EGSnrc MC code systems. This new CM will facilitate MC computation of fluence and dose distributions using BEAMnrc/DOSXYZnrc for patients treated on the low‐field MR linac. [ABSTRACT FROM AUTHOR]

Introduction: This report presents a case of an exceptionally delayed distant recurrence of a choroidal melanoma, occurring 4 decades after the enucleation of the affected eye. Case Presentation: In 1977, a 29-year-old man underwent enucleation for a choroidal melanoma. At the age of 68 years, he was diagnosed with advanced prostate cancer. Although the metastatic prostate cancer responded to treatment, a persistent lung lesion warranted further examination. A lung biopsy, somewhat surprisingly, confirmed the presence of melanoma metastasis, 4 decades after the enucleation. The cells were positive for Melan-A, while no BRAF mutation was identified. Two years later, new lesions appeared in the liver, and CT showed progression with multiple new sites. A liver biopsy revealed again melanoma recurrence, and its choroidal origin was verified by the presence of a GNA11 mutation. The patient underwent radiation therapy for the lung and liver lesions, followed by immunotherapy. However, the patient died 11 months after the recurrence in the liver. In this case report, the micrometastatic melanoma cells appear to have remained dormant for an extended period, before the patient’s treatment in 1977, but the reason for the late reactivation from the dormant state remains unclear. Conclusion: The recurrence of a choroidal melanoma is substantiated by the histopathological and molecular analyses, including the finding of a GNA11 mutation. This case exemplifies a remarkably delayed distant recurrence of a choroidal melanoma, which manifested clinically 40 years following enucleation. [ABSTRACT FROM AUTHOR]

Isolated ocular relapses of leukemia are rare and typically present as infiltrative lesions of the optic nerve. This report presents a case of an isolated ocular relapse of leukemia in a female patient, characterized by occult infiltrative optic neuropathy. Despite the absence of leukemic cell infiltration on MRI, a 33-year-old female patient presented with optic neuritis, which resolved after intrathecal administration of chemotherapeutic agents. However, due to her non-compliance with the treatment regimen, leukemia progressed to infiltrative optic neuropathy. She refused radiation therapy, and while intrathecal injections provided temporary stabilization, they were insufficient for sustained disease control. This case uniquely documents the extended progression of an isolated ocular relapse of leukemia, evolving from an occult infiltrative lesion initially presenting as optic neuritis to a more pronounced infiltrative lesion. It suggests that leukemic optic nerve infiltration can occur in patients with leukemia even in the absence of MRI-detectable abnormalities. Radiation therapy emerges as a critical modality in the management of infiltrative lesions of the optic nerve. [ABSTRACT FROM AUTHOR]

The activation of the stimulator of interferon genes (STING) protein by cyclic dinucleotide metabolites plays a critical role in antitumor immunity. However, synthetic STING agonists like 4‐(5,6‐dimethoxybenzo[b]thiophen‐2‐yl)‐4‐oxobutanoic acid (MSA‐2) exhibit suboptimal pharmacokinetics and fail to sustain STING activation in tumors for effective antitumor responses. Here, we report the design of MOF/MSA‐2, a bifunctional MSA‐2 conjugated nanoscale metal–organic framework (MOF) based on Hf6 secondary building units (SBUs) and hexakis(4′‐carboxy[1,1′‐biphenyl]‐4‐yl)benzene bridging ligands, for potent cancer radio‐immunotherapy. By leveraging the high‐Z properties of the Hf6 SBUs, the MOF enhances the therapeutic effect of X‐ray radiation and elicits potent immune stimulation in the tumor microenvironment. MOF/MSA‐2 further enhances radiotherapeutic effects of X‐rays by enabling sustained STING activation and promoting the infiltration and activation of immune cells in the tumors. MOF/MSA‐2 plus low‐dose X‐ray irradiation elicits strong STING activation and potent tumor regression, and when combined with an immune checkpoint inhibitor, effectively suppresses both primary and distant tumors through systemic immune activation. [ABSTRACT FROM AUTHOR]

Background: This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. Methods: This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. Discussion: Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. Trial registration: Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity. Methods: A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis. Results: The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05). Conclusion: This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow. Methods: Seventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTVelective) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTVboost). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (Dclin) and automatic contours (Dauto). Results: The bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTVboost these differences were larger, namely 0.71, 7 mm and 78%. For the CTVboost the median target coverage was 0.42% lower for Dauto compared to Dclin. For CTVelective this difference was 0.03%. The target coverage of Dauto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTVboost and 95% of the sessions for the CTVelective. Conclusions: While an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target. [ABSTRACT FROM AUTHOR]

Background: Meningiomas are common central nervous system tumors, predominantly intracranial, they rarely develop extracranially. Moreover, benign meningiomas seldom metastasize. Case presentation: This article presents a case report of a 55-year-old Chinese male patient with a primary World Health Organization grade 1 meningioma originating from the petrous apex of the temporal bone, accompanied by pulmonary metastasis. Following two incomplete resections of the primary tumor, the patient underwent radiotherapy and has since maintained a stable condition. Conclusion: The case report highlights the rare occurrence of pulmonary metastasis in a benign World Health Organization grade 1 meningioma originating from an extracranial site. It also illustrates the important role of radiotherapy in treating patients with meningioma. Additionally, a review of related literature is provided to gain insights for the diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy. [ABSTRACT FROM AUTHOR]

Brain tumor volumes as assessed by magnetic resonance imaging (MRI) do not always spatially overlap with biological tumor volumes (BTV) measured by [18F]Fluoroethyltyrosine positron emission tomography ([18F]FET PET). We prospectively investigated volumetric patterns based on the extent of tumor volume overlap between the two modalities. Eighty-six patients with newly diagnosed glioma who had undergone MRI and [18F]FET PET between 2007 and 2009 were included in this prospective study and (re-)classified according to CNS WHO 2021 (Classification of Tumors of the Central Nervous System by the World Health Organization). Four different patterns of volume overlap were defined mathematically according to the extent of overlap between MRI-based T2 tumor volume (non-enhancing tumor volume, nCEV) and BTVs. Progression-free (PFS) and overall survival (OS) were determined. Seventy patients were diagnosed with isocitrate dehydrogenase wildtype (IDHwt) glioblastoma and 16 with IDH-mutant glioma, respectively. The most common pattern was characterized by a larger non-contrast-enhancing tumor volume (nCEV) that enclosed all or most of the BTV and was observed in 46 patients (54%) (pattern 1). This pattern was more frequent in IDH-mutant gliomas than in IDH-wildtype glioblastoma (81% versus 47%, p = 0.02). In multivariate analyses, pattern 1 was associated with prolonged PFS (HR 0.59; 95 CI 0.34-1.0; p = 0.05), but not OS (HR 0.66; 95 CI 0.4–1.08; p = 0.1). For OS, presence of an IDH mutation (p = 0.05) and lower age (p = 0.03) were associated with prolonged OS. The spatial relation between nCEV and BTV varies within and between glioma entities. Most frequently, a larger nCEV encases the BTV. Some patients show spatially dissociated nCEVs and BTVs. Not accounting for this phenomenon in surgery or radiotherapy planning might lead to undertreatment. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer. Methods: CYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes. Discussion: Previous research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes. Protocol version: Version 2.1 dated from January 18, 2023. Trial registration: The CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961. [ABSTRACT FROM AUTHOR]

The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy. Radiation therapy (RT) can induce immunogenic cell death and elicit anti-tumor immune responses. Here the authors report the design and characterization of a risedronate-manganese-based nanosystem for in situ vaccination, amplifying RT-mediated anti-tumor immunity in preclinical models. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). Material and methods: Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan–Meier method and long-rank test. Results: 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3–4) in patients with innate resistance vs 14 months (range 7–36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7–72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. Conclusion: Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. Methods: In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. Results: The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76 cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. Conclusion: Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors. [ABSTRACT FROM AUTHOR]

Background: In this retrospective study, we aimed to identify key risk factors and establish an interpretable model for HCC with a diameter = 5 cm using Lasso regression for effective risk stratification and clinical decision-making. Methods: In this study, 843 patients with advanced hepatocellular carcinoma (HCC) and tumor diameter = 5 cm were included. Using Lasso regression to screen multiple characteristic variables, cox proportional hazard regression and random survival forest models (RSF) were established. By comparing the area under the curve (AUC), the optimal model was selected. The model was visualized, and the order of interpretable importance was determined. Finally, risk stratification was established to identify patients at high risk. Result: Lasso regression identified 8 factors as characteristic risk factors. Subsequent analysis revealed that the lasso-cox model had AUC values of 0.773, 0.758, and 0.799, while the lasso-RSF model had AUC values of 0.734, 0.695, and 0.741, respectively. Based on these results, the lasso-cox model was chosen as the superior model. Interpretability assessments using SHAP values indicated that the most significant characteristic risk factors, in descending order of importance, were tumor number, BCLC stage, alkaline phosphatase (ALP), ascites, albumin (ALB), and aspartate aminotransferase (AST). Additionally, through risk score stratification and subgroup analysis, it was observed that the median OS of the low-risk group was significantly better than that of the middle- and high-risk groups. Conclusion: We have developed an interpretable predictive model for middle and late HCC with tumor diameter = 5 cm using lasso-cox regression analysis. This model demonstrates excellent prediction performance and can be utilized for risk stratification. [ABSTRACT FROM AUTHOR]

Background: Bone metastases are common in patients with progressive cancer and often present in long bones, leading to adverse events such as pathologic fractures. In the acute care setting, physical therapists (PTs) may be the initial providers who identify symptoms associated with fracture risk and communicate concerns to help prevent such adverse events. Case description: A 39-year-old female patient with metastatic breast cancer was admitted to the hospital due to uncontrolled pain. She had a history of bone metastases to the left femur; however, no restrictions or precautions were noted during the initial PT examination. During this initial PT examination, she reported worsening hip pain with weight-bearing activities. Outcomes: With the PT's recognition of red flag symptoms, an MRI was completed, which revealed extensive metastatic disease in her left femur with concern for an imminent fracture; as a result, prophylactic fixation was performed. Her functional abilities improved after surgery and consistent therapeutic intervention, allowing her to achieve a level of independence sufficient to return home safely. Discussion and conclusion: This case demonstrates the successful identification of imminent fracture risk by a PT in a patient with metastatic breast cancer, as well as the therapeutic management that accompanied this process in the acute care setting. [ABSTRACT FROM AUTHOR]

FLASH radiotherapy (FLASH-RT) is a new modality of radiotherapy that delivers doses with ultra-high dose rates. The FLASH effect was defined as the ability of FLASH-RT to suppress tumor growth while sparing normal tissues. Although the FLASH effect has been proven to be valid in various models by different modalities of irradiation and clinical trials of FLASH-RT have achieved promising initial success, the exact underlying mechanism is still unclear. This article summarizes mainstream hypotheses of the FLASH effect at physicochemical and biological levels, including oxygen depletion and free radical reactions, nuclear and mitochondria damage, as well as immune response. These hypotheses contribute reasonable explanations to the FLASH effect and are interconnected according to the chronological order of the organism's response to ionizing radiation. By collating the existing consensus, evidence and hypotheses, this article provides a comprehensive overview of potential mechanisms of the FLASH effect and practical guidance for future investigation in the field of FLASH-RT. [ABSTRACT FROM AUTHOR]

Introduction: Evaluation of Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma This study investigated the effectiveness of adding neoadjuvant chemotherapy, a course of drugs given before radiotherapy, to standard chemoradiation treatment for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) in a rural medical college in India. The researchers enrolled 252 patients with LAHNSCC who had not spread to other parts of the body. Half of the patients received neoadjuvant chemotherapy with paclitaxel and carboplatin followed by concurrent chemoradiation with cisplatin and radiation therapy. The other half received only concurrent chemoradiation. The analysis showed that a slightly higher percentage of patients achieved a complete response with neoadjuvant chemotherapy followed by chemoradiation compared to those who received only chemoradiation. However, the difference was not statistically significant, meaning it may have occurred by chance. Additionally, no significant difference was observed in terms of side effects between the two groups. In conclusion, the study did not find strong evidence that neoadjuvant chemotherapy improves response rates in patients with LAHNSCC when compared to standard chemoradiation treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy is an effective treatment method for cervical cancer and is typically administered as external beam radiotherapy followed by intracavitary brachytherapy. In Japan, center shielding is used in external beam radiotherapy to shorten treatment time and reduce the doses delivered to the rectum or bladder. However, it has several challenges, such as uncertainties in calculating the cumulative dose. Recently, external beam radiotherapy has been increasingly performed with intensity‐modulated radiotherapy, which reduces doses to the rectum or bladder without center shielding. In highly conformal radiotherapy, uncertainties in treatment delivery, such as inter‐fractional anatomical structure movements, affect treatment outcomes; therefore, image‐guided radiotherapy is essential for appropriate and safe performance. Regarding intracavitary brachytherapy, the use of magnetic resonance imaging‐based image‐guided adaptive brachytherapy is becoming increasingly widespread because it allows dose escalation to the tumor and accurately evaluates the dose delivered to the surrounding normal organs. According to current evidence, a minimal dose of D90% of the high‐risk clinical target volume is significantly relevant to local control. Further improvements in target coverage have been achieved with combined interstitial and intracavity brachytherapy for massive tumors with extensive parametrical involvement. Introducing artificial intelligence will enable faster and more accurate generation of brachytherapy plans. Charged‐particle therapies have biological and dosimetric advantages, and current evidence has proven their effectiveness and safety in cervical cancer treatment. Recently, radiotherapy‐related technologies have advanced dramatically. This review provides an overview of technological innovations and future perspectives in radiotherapy for cervical cancer. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the predictive ability of radiation‐induced cataract between maximum point dose of the lens (Lens Dmax) ≥7 Gy, mean lens dose (Lens Dmean) ≥7 Gy, Lens Dmax ≥10 Gy, and Lens Dmean ≥10 Gy. Methods: Patients aged 3–18 years received cranial irradiation or radiation therapy at head and neck area between January 2010 and December 2019 at our institute were included. Patients without baseline and/or follow‐up eye examination were excluded. Receiver operating characteristic (ROC) curves identified potential predictors and Cox regression analysed correlations between potential factors and cataract occurrence. Results: Sixty‐three patients (122 eyes) were analysed. Cataracts were detected in 14 eyes (11.5%). Median follow‐up time was 4 years (range 0.5–10 years), with cataract developing in a median of 2.5 years (range 0.3–7 years). Three patients (21.4%) developed grade ≥3 cataract. Lens Dmean ≥10 Gy was associated with cataract formation. Conclusion: Lens Dmean ≥10 Gy showed the highest ability for predicting radiation‐induced cataract in paediatric patients. Net reclassification improvement (NRI) suggested that changing lens dose constraint from Dmax <7 Gy to Dmean <10 Gy would miss 7% of cataract cases but avoid 28% of unnecessary restrictions. Adopting a mean lens dose <10 Gy was suggested as a constraint for lens dose. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy improves local control and overall survival of breast cancer but the dose to normal tissues may lead to cardiotoxic effect. Deep inspiration breath-hold (DIBH) technique is widely implemented to reduce the dose to heart in left breast radiotherapy. This manuscript aimed to describe the implementation of voluntary-DIBH radiotherapy (vDIBH-RT) in left breast cancer patients without surface-guided imaging system. Materials and methods: A workflow of vDIBH-RT technique was developed and implemented at the Advanced Medical and Dental Institute (AMDI) by monitoring the breath-hold skin marks and laser light congruence observed on zoomed CCTV images during each delivery. The initial setup was verified using cone beam computed tomography (CBCT) during breath-hold. This CBCT imaging took only 20 seconds to tolerate patient ability to breath-hold. Planning target volume (PTV) margin was computed based on van Herk's margin recipe. Results: The vDIBH technique was successfully implemented on 13 left breast cancer patients in this study cohort. The calculated PTV margin required for vDIBH-RT using CCTV/Laser monitoring technique is 7.77 mm, 10.85 mm, and 10.93 mm in the x, y, and z axes, respectively, which is smaller than the recommended margin for breast cancer. Conclusion: It is feasible to implement vDIBH-RT among left breast cancer patients without special equipment. The breath-hold monitoring technique is radiation-free, easy to implement, cost-effective and suitable for implementation in Low- and Middle-income Countries (LMIC) that has limited access to DIBH assisting devices. To address this gap, a study to identify current DIBH practice in Malaysia radiotherapy centres will be performed. In addition, a retrospective study on the dosimetric accuracy of the dose delivered to the plan will be done to optimise DIBH patient selection and protocol. [ABSTRACT FROM AUTHOR]