Tumor Irradiation Research Articles

Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5–2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

ESTRO-EANO guideline on target delineation and radiotherapy for IDHmutant WHO CNS grade 2 and 3 diffuse glioma

PurposeThis guideline will discuss radiotherapeutic management of IDH mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation. MethodsThe ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation. A literature search was performed, and available literature was discussed. A modified two-step Delphi process was used with majority voting resulted in a decision or highlighting areas of uncertainty. ResultsKey issues identified and discussed included imaging needed to define target definition, target delineation and the size of margins, and technical aspects of treatment including different planning techniques such as proton therapy. ConclusionsThe GTV should include any residual tumour volume after surgery, as well as the resection cavity. Enhancing lesions on T1 imaging should be included if they are indicative of residual tumour. In grade 2 tumours, T2/FLAIR abnormalities should be included in the GTV. In grade 3 tumours, T2/FLAIR abnormalities should also be included, except areas that are considered to be oedema which should be omitted from the GTV. A GTV to CTV expansion of 10 mm is recommended in grade 2 tumours and 15 mm in grade 3 tumours. A treatment dose of 50.4 Gy in 28 fractions is recommended in grade 2 tumours and 59.4 Gy in 33 fractions in grade 3 tumours. Radiation techniques with IMRT are the preferred approach.

Real-Time Fluorescence Monitoring System for Optimal Light Dosage in Cancer Photoimmunotherapy.

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (-0.05%/s or -0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system.

722: Standard versus highly hypofractionated tumor irradiation in LA-NSCLC with durvalumab consolidation

722: Standard versus highly hypofractionated tumor irradiation in LA-NSCLC with durvalumab consolidation

Phase Ib trial of durvalumab plus tremelimumab in combination with particle therapy in patients with advanced hepatocellular carcinoma with macrovascular invasion: DEPARTURE trial.

34 Background: The HIMALAYA trial established the combination of durvalumab and tremelimumab (STRIDE) as first-line treatment for advanced hepatocellular carcinoma (HCC). Carbon ion radiotherapy (C-ion RT) allows precise tumor targeting while sparing nearby normal tissue. Our strategy used C-ion RT to target a key tumor with macrovascular invasion (MVI) for disease management and potential MVI control, complemented by STRIDE. Recognising that C-ion RT stimulates immune responses, we posited that merging C-ion RT with STRIDE might enhance therapeutic effects. We present updated data of additional follow-up. Methods: This is a Phase Ib, multicenter study evaluating durvalumab with particle beam radiotherapy in HCC patients with MVI (Cohort A) and STRIDE (Cohort B). Both cohorts began with patients resistant to standard treatments. After safety confirmation, the study expanded to include therapy-naïve patients, totaling 15. C-ion RT begins after day 8 of the first cycle, following the initial drug dose. The relative biological effectiveness weighted dose is set at 60 Gy in four fractions over one week, targeting one representative intrahepatic nodule with MVI. The primary endpoint is adverse event rates, including dose limiting toxicity (DLT), with secondary endpoints on progression free survival (PFS) and overall survival (OS) (jRCT2031210046). This analysis of OS was conducted from the additional follow-up data from the primary analysis. Results: From July 2021 to January 2023, 15 advanced HCC patients were enrolled in our study (Cohort A: 3, Cohort B: 12). Four in Cohort B were systemic therapy-naïve. All cases confirmed MVI radiologically; with tumor invasion observed in the main portal vein for 4 patients and in the inferior vena cava for one. DLT evaluations in 3 from each cohort showed no incidents. While Cohort A had no adverse events, 4 patients in Cohort B (26.7%) experienced serious treatment-related adverse events. The median PFS was a significant 4.67 months (95%CI, 1.35–6.64). At the clinical cut-off date of March 31, 2024, 10 OS events were observed. The median OS was 10.4 months (95% CI, 5.6–15.2), and the 6- and 12-month OS rates were 66.7% and 46.7%, respectively. Conclusions: The safety of STRIDE in combination with particle therapy has been confirmed in advanced HCC with MVI. This combination, especially the irradiation of tumors with MVI using C-ion RT, holds promise in managing prognostic determinant tumors and potentially enhancing OS. Clinical trial information: jRCT2031210046 .

A prospective evaluation of succinct prednisone tapering after brain tumor irradiation in dogs.

To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid-associated morbidity and may be unnecessary. Determine whether long-term corticosteroid dependency can be minimized by use of succinct prednisone tapering. Fifty-five pet dogs undergoing brain tumor irradiation. Nineteen dogs were treated using a "rapid-taper" protocol wherein corticosteroid dose reduction began 0 to 20 days after completing RT. Outcomes were compared with a retrospectively studied control group ("slow-taper"; N = 36 dogs) in which corticosteroids were tapered more slowly according to individual clinician recommendations. Patient demographics were similar between groups. Mean time to lowest prednisone dose was 41 days postirradiation in the rapid-taper group and 117 days in the slow-taper group (P = .003). In the rapid-taper group, 15 of 19 dogs (84%) were completely tapered off prednisone, vs 18 of 36 (50%) in the slow-taper group (P = .04). Rates at which corticosteroids had to be reinstituted later were similar for the 2 groups (approximately 1 in 3 dogs). Adverse effect rates were similar for the 2 groups. Although no comparable questionnaire-derived data were available for the "slow-taper" group, overall and neurologic quality of life remained stable after RT in the rapid-taper group. For many dogs, lengthy courses of PO prednisone are avoidable after intracranial RT. Future efforts should aim to identify which dogs benefit most from accelerated prednisone tapering.

The Effects of Gynecological Tumor Irradiation on the Immune System.

Radiobiology has evolved from a mechanistic model based on DNA damage and response factors into a more complex model that includes effects on the immune system and the tumor microenvironment (TME). Irradiation has an immunomodulatory effect that can manifest as increased anti-tumor immunity or immunosuppression. Irradiation promotes an inflammatory microenvironment through the release of pro-inflammatory cytokines and endothelial damage, which recruit immune system cells to the irradiated area. Radiation-induced immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and tumor antigens, triggers an anti-tumor immune response of both innate and adaptive immunity. Anti-tumor immunity can manifest at a distance from the irradiated area, a phenomenon known as the abscopal effect (AE), which involves dendritic cells and CD8+ T cells. Irradiation also produces an immunosuppressive effect mediated by tumor-associated macrophages (TAMs) and regulatory T lymphocytes (Tregs), which counterbalances the immunostimulatory effect. In this work, we review the mechanisms involved in the radiation-induced immune response, which support the combined treatment of RT and immunotherapy, focusing, where possible, on gynecologic cancer.

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

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

Novel time-synchronized immune-guided partial tumor irradiation: Proof of principle trial

Background and purposeRadiotherapy for bulky tumors often results in palliation with suboptimal outcomes. The prognosis is worsened by immunosuppression caused by radio-chemotherapy, negatively impacting on survival. Novel Partial Tumor Irradiation (PTI) was designed to spare the Peritumoral Immune Microenvironment (PIM) and to be delivered synchronously with immune activity peaks, thus enhancing both local and distant tumor control through immunostimulation. Materials and methodsPresent proof-of-principle trial enrolled 26 patients with bulky tumors, comparing outcomes between treatments administered at immune activity peaks versus troughs. The primary endpoint was local-bystander and distal-abscopal response-rate. Secondary endpoints included overall-, progression-free-, cancer-specific survival, neoadjuvant and immunomodulatory potential. ResultsAll measured outcomes were significantly influenced by treatment-timing. The bystander and abscopal response rates were 77% and 41%, respectively. PTI significantly upregulated pro-inflammatory and cell-death-inducing pathways improving the efficacy of radiotherapy by highly complex tumors. ConclusionsThis study highlights the profound impact PTI can have on a highly palliative patient cohort previously deemed beyond therapeutic hope. With 41 % of these patients still alive after a median follow-up of 50 months, PTI offers a potential lifeline for those facing advanced, treatment-resistant cancers. This approach generated also distant immunogenic anti-tumor responses, offering a promising new avenue for the treatment of advanced cancers.

CSF biomarkers of neurotoxicity in childhood cancer survivors after cranial radiotherapy or surgery.

Treatment of pediatric brain tumors is associated with potential long-term cognitive sequelae. Patients treated with craniospinal irradiation for posterior fossa tumors are at high risk. New biomarkers that could help to differentiate treatment effects from other causes of cognitive dysfunction would be valuable in tailoring optimal survivorship care. Biomarkers that reflect biological mechanisms behind treatment-associated cognitive decline would also be important in the evaluation of future treatment regimens for pediatric brain or skull base tumors. In this biomarker-finding study, 10 adult survivors of pediatric medulloblastoma, skull base tumors, and posterior fossa low-grade glioma underwent study specific lumbar puncture at a minimum of 17 years following treatment. We analyzed cerebrospinal fluid biomarkers reflecting neuron and astrocyte integrity, amyloid metabolism, inflammation, extracellular matrix, synaptic integrity, and blood-brain barrier function. The values were compared with biomarker levels in healthy controls of comparable age. Biomarkers reflecting neuronal injury (neurofilament light chain protein), astrocyte injury or activation (glial fibrillary acidic protein) as well as inflammation (YKL-40) were significantly elevated in cancer survivors compared to controls. Biomarkers reflecting amyloid metabolism showed a pattern of decrease in patients treated for medulloblastoma. The results suggest a potential chronic low-grade neurodegeneration and astrocyte activation in patients treated for pediatric brain or skull base tumors. Protein biomarkers of CNS disease could potentially be used to increase our understanding of the contribution from different tumor treatments with regard to long-term symptoms in cancer patients.

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

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

Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

Sinonasal Malignancy Following Cranial Irradiation: A Scoping Review and Case Report of Sinonasal Teratocarcinosarcoma.

Background Radiation therapy is a mainstay of treatment for brain tumors, but delayed complications include secondary malignancy which may occur months to years after treatment completion. Methods We reviewed the medical records of a 41-year-old female treated with 60 Gy of radiation for a recurrent astrocytoma, who 6 years later developed a locally advanced sinonasal teratocarcinosarcoma. We searched MEDLINE, Embase, and Web of Science to conduct a scoping review of biopsy-proven sinonasal malignancy in patients who previously received cranial irradiation for a brain tumor. Results To our knowledge, this is the first report of a patient to present with a sinonasal teratocarcinosarcoma after receiving irradiation for a brain tumor. Our scoping review of 1,907 studies produced 14 similar cases of secondary sinonasal malignancy. Median age of primary cancer diagnosis was 39.5 years old (standard deviation [SD]: 21.9), and median radiation dose was 54 Gy (SD: 20.3). Median latency time between the primary cancer and secondary sinonasal cancer was 9.5 years (SD: 5.8). Olfactory neuroblastoma was the most common sinonasal cancer ( n = 4). Fifty percent of patients died from their sinonasal cancer within 1.5 years. Conclusion Patients who receive radiation exposure to the sinonasal region for treatment of a primary brain tumor, including low doses or scatter radiation, may be at risk of a secondary sinonasal malignancy later in life. Physicians who monitor at-risk patients must be vigilant of symptoms which may suggest sinonasal malignancy, and surveillance should include radiographic review with careful monitoring for a secondary malignancy throughout the entire irradiated field.

Analytical and fine Monte Carlo Kerma coefficients evaluation for a wide range photon energy relevant to some chemotherapy agents

Simultaneously combination of chemotherapy drugs and ionizing radiations has become a common treatment method for advanced cancers. Tumor irradiation in presence of chemotherapy drugs can affect deposited energy within tissue. Hence, to evaluate how chemotherapy drugs affect the absorbed dose within tissues during chemoradiotherapy, Kerma coefficient values for 26 anti-cancer agents were estimated for photon energies ranging from 1 keV to 20 MeV through analytical analysis and Monte Carlo (MC) simulation approaches.Estimation of Kerma coefficients through MC simulation relevant to different chemotherapy drugs was performed with MCNPX V.2.6.0 MC code. Besides, Kerma coefficient values were calculated using the reported mass energy absorption coefficients, as the theoretical method. Significant statistical test was also employed to evaluate the accordance of obtained Kerma coefficients by two considered methods.Simulation results were consistent with evaluated Kerma coefficients by analytical method which minimum and maximum mean relative differences are found for Bevacizumab and Methotrexate, respectively. Furthermore, a significant correlation is found with chemical composition of selected chemotherapy drugs at considered photon energy range. Fluorouracil showed the closest Kerma ratio to unity among the studied anti-cancer drugs. Kerma coefficient ratios for most of selected drugs were close to unity at higher energy regions (100 keV–20 MeV) while greater values were found at lower photon energies (below 100 keV).From the results, presence of these anti-cancer agents can impact Kerma coefficient and subsequently alter the absorbed dose within tissue during the cancer treatment with chemoradiotherapy technique.

KCa channel targeting impairs DNA repair and invasiveness of patient‐derived glioblastoma stem cells in culture and orthotopic mouse xenografts which only in part is predictable by KCa expression levels

AbstractPrognosis of glioblastoma patients is still poor despite multimodal therapy. The highly brain‐infiltrating growth in concert with a pronounced therapy resistance particularly of mesenchymal glioblastoma stem‐like cells (GSCs) has been proposed to contribute to therapy failure. Recently, we have shown that a mesenchymal‐to‐proneural mRNA signature of patient derived GSC‐enriched (pGSC) cultures associates with in vitro radioresistance and gel invasion. Importantly, this pGSC mRNA signature is prognostic for patients' tumor recurrence pattern and overall survival. Two mesenchymal markers of the mRNA signature encode for IKCa and BKCa Ca2+‐activated K+ channels. Therefore, we analyzed here the effect of IKCa‐ and BKCa‐targeting concomitant to (fractionated) irradiation on radioresistance and glioblastoma spreading in pGSC cultures and in pGSC‐derived orthotopic xenograft glioma mouse models. To this end, in vitro gel invasion, clonogenic survival, in vitro and in vivo residual DNA double strand breaks (DSBs), tumor growth, and brain invasion were assessed in the dependence on tumor irradiation and K+ channel targeting. As a result, the IKCa‐ and BKCa‐blocker TRAM‐34 and paxilline, respectively, increased number of residual DSBs and (numerically) decreased clonogenic survival in some but not in all IKCa‐ and BKCa‐expressing pGSC cultures, respectively. In addition, BKCa‐ but not IKCa‐blockade slowed‐down gel invasion in vitro. Moreover, systemic administration of TRAM‐34 or paxilline concomitant to fractionated tumor irradiation increased in the xenograft model(s) residual number of DSBs and attenuated glioblastoma brain invasion and (numerically) tumor growth. We conclude, that KCa‐blockade concomitant to fractionated radiotherapy might be a promising new strategy in glioblastoma therapy.

Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood.

State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. Objective: We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. Methods: the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). Results: In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. Conclusions: The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. clinicaltrials.gov, identifier NCT04431674.

Polymer‐Protected Gold Nanoparticles for Photothermal Treatment of Ehrlich Adenocarcinoma: In Vitro and In Vivo Studies

AbstractPhotothermal therapy (PTT) is recognized as an effective tool for the treatment of cancer and it has attracted considerable attention of scientists. In this work, gold nanospheres (AuNSs) and gold nanorods (AuNRs) stabilized using poly(N‐vinylpyrrolidone) (PVP), pristine gellan gum (PGG), and poly(2‐ethyl‐2‐oxazoline)‐grafted gellan gum (GG‐g‐PEtOx) are synthesized and evaluated as PTT agents in Ehrlich cancer cells. The physicochemical characteristics of these AuNSs and AuNRs, including their surface plasmon resonance absorption spectra, size, zeta potential, and aspect ratio are studied using UV–vis‐spectroscopy, dynamic light scattering, zeta potential, transmission electron microscopy, and optical microscopy techniques. The polymer‐protected AuNSs exhibit light‐to‐heat conversion, raising the temperature from 37 to 43 °C when irradiated using a visible light source. In the case of AuNSs, considerable damage to Ehrlich cancer cells is observed following irradiation and 40 days of examination. However, with regard to AuNSs, the damage to Ehrlich cancer cells is slightly lower than observed in AuNRs. In vivo experiments demonstrate that laser irradiation of tumors in mice after injecting AuNSs leads to a statistically significant decrease in tumor size as compared to those not irradiated and the control samples.

3138: Mediastinal irradiation for thymic epithelial tumors: A deep focus on coronary arteries’ exposure

3138: Mediastinal irradiation for thymic epithelial tumors: A deep focus on coronary arteries’ exposure

Dosimetric Advantage of Combined IMRT for Whole Lung and Abdomen Irradiation for Wilms Tumor

In patients with Wilms tumor with lung metastases, a cardiac-sparing intensity modulated radiation therapy (CS-IMRT) technique is increasingly being adopted for whole lung irradiation. However, the standard technique for flank and whole abdomen radiation remains 2-dimensional anterioposterior (AP), and overlap at the junction between the whole lung CS-IMRT and abdominal AP fields can result in overdose to normal organs. Here, we compared the dosimetry of patients who received whole lung irradiation and flank or abdominal radiation therapy with CS-IMRT with AP abdominal field (IMRT-AP) versus CS-IMRT with IMRT abdominal field (combined IMRT). We retrospectively reviewed the radiation plans of 2 patients with Wilms tumor who received CS-IMRT and flank or whole abdomen irradiation with a combined IMRT approach. Comparison IMRT-AP plans were generated with equivalent target coverage of 95% receiving the prescribed dose. Maximum doses to normal organs were compared at the junctional overlap. Overlap at the junction between CS-IMRT and abdominal fields resulted in a significantly lower dose with combined IMRT plans compared with IMRT-AP plan. Differences in maximum doses (in cGy) to normal organs between combined IMRT versus IMRT-AP plans were most significant in the vertebral body (patient 1 = 1277 vs 2065; patient 2 = 1334 vs 2287), lungs (patient 1 = 1298 vs 2081; patient 2 = 1234 vs 1820), spinal cord (patient 1 = 1235 vs 1975; patient 2 = 1345 vs 2253), stomach (patient 1 = 1264 vs 1977; patient 2 = 1118 vs 2062), and liver (patient 1 = 1297 vs 1889; patient 2 = 1334 vs 2237). The combined IMRT approach for Wilms patients who require whole lung and abdomen irradiation can provide more uniform dose distribution in the junction area and significantly lower doses to normal organs at the junctional overlap.