Low-dose Radiotherapy Research Articles

Comparative effectiveness of kilo- and megavoltage energies in low-dose radiotherapy for painful degenerative musculoskeletal diseases: asystematic review and meta-analysis.

This study aimed to assess the impact of different energy levels on the effectiveness of low-dose radiotherapy (LDRT) for treating painful degenerative musculoskeletal diseases, as comparative efficacy data are currently lacking. Asystematic review was conducted in PubMed, Embase, and the Cochrane Library databases to identify studies with response information on the energy used (kilovoltage [kV] vs. megavoltage [MV]). The primary endpoint was the overall response rate (ORR), and the secondary endpoint was the complete response rate (CRR). Exploratory subgroup analyses included treatment site, study period, study design, country, and dose per fraction. Atotal of 33studies involving 12,143patients were analyzed. Short-term follow-up (up to 6months) showed apooled ORR of 64% (95% CI 46-78%) for kV and of 62% (95% CI 54-70%) for MV. Long-term follow-up (at least 12months) revealed apooled ORR of 85% (95% CI 65-95%) for kV and of 69% (95% CI 62-75%) for MV. Subgroup analysis indicated no significant differences in ORR for energy level stratified by treatment site and other factors. Regarding dose per fraction (0.5 Gy vs.1.0 Gy), comparable ORRs were demonstrated between the two energies. No clinical side effects were noted. This meta-analysis suggests that the known effectiveness of LDRT in painful degenerative musculoskeletal disease may not depend on the energy used. Additional studies using standardized evaluation methods are warranted to establish consistency and enhance the comprehensiveness of research. Further research is also needed to explore treatment modality selection considering disease-specific biology.

Identification of a Suitable Subgroup for Radiation Dose Escalation in Definitive Concurrent Chemoradiation Therapy for Nonmetastatic Esophageal Squamous Cell Carcinoma.

Dose escalation may only be suitable for some patients with esophageal cancer (EC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to identify specific subgroups of patients for whom dose escalation was most beneficial. Between January 2008 and December 2022, 187 patients with EC underwent CCRT; 94 patients received high-dose (HD) radiotherapy (RT; >64.8 Gy), and 93 patients received low-dose (LD) RT. We developed a model on the basis of clinical and radiomic features to compare the predicted survival probabilities of patients with EC receiving HD- and LD-RT. Patients suitable for HD-RT could be identified. We validated our findings of a suitable HD subgroup by evaluating the actual overall survival (OS) across different subgroups in the testing set. Our model comprised HD and LD submodels, each predicting patient survival under their respective RT doses. The HD and LD submodels achieved concordance indexes of 0.78 and 0.75 in their respective testing sets. The average areas under the receiver operating characteristic curve over years 1-3 were 0.890 and 0.807 in the HD and LD testing sets, respectively. By comparing patients' predicted survival under HD- and LD-RT in the model, we classified the patients in the testing set into the HD-suitable (HDS) subgroup and the HD-unsuitable subgroup. In the subgroup analysis, HD-RT led to a better OS benefit for the identified HDS subgroup compared with LD-RT (P = .014). Among the HD-treated patients, the HDS subgroup showed better OS than did patients identified as unsuitable (P < .001). We identified a suitable subgroup of patients with EC who might benefit from HD-RT. This model could aid clinicians in prescribing RT doses.

Small dose-big effect? The use of low-dose radiation therapy (LDRT) in Alzheimer's disease (AD)

Small dose-big effect? The use of low-dose radiation therapy (LDRT) in Alzheimer's disease (AD)

Dual-doped metalloporphyrin MOFs-based nanoagent increases low-dose radiotherapy efficacy by apoptosis-ferroptosis for hepatocellular carcinoma

Radiotherapy (RT) represents a cornerstone therapeutic approach in clinical practice for locally control of hepatocellular carcinoma (HCC). However, its efficacy in treating liver cancer is significantly hampered by radiation resistance, which attributed to the insufficient reactive oxygen species (ROS) generation within the tumor microenvironment (TME). To augment RT efficacy, we have developed a novel radiosensitizer termed PTFM. The compound has the features of meso-tetra (4-carboxyphenyl) porphine (TCPP) porphyrin metal–organic frameworks (MOF, PCN-224(Fe)) co-doped with high-atomic element Ta. Under X-ray excitation, the porous PTFM acts as a proficient radio-sensitization, absorbs X-ray energy to promote hydroxyl radicals generation for RT, thereby disrupting the redox balance and intensifying the cytotoxic effect on tumor cells. The incorporation of Fe3+ into the macrocycle of TCPP within the MOFs shell, facilitates the reactions with GSH and H2O2 in the TME, leads to ROS production that promotes ferroptosis and apoptosis, while also releases O2 to alleviate tumor hypoxia. Furthermore, PTFM with thermo-metal serves as a dual-mode MR/CT imaging contrast agent, enabling precise RT monitoring and imaging guidance. In conclusion, the radiosensitizer we developed integrates dual-mode imaging capabilities and enhances RT sensitization for HCC through ROS-induced cell apoptosis and ferroptosis, thereby ameliorating tumor hypoxia.

A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT. Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30Gy in 2-5 fractions. Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed. This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.

DNAR-03. ONCOMAGNETIC TREATMENT KILLS GLIOMA CELLS BY INHIBITING MITOCHONDRIAL ELECTRON TRANSPORT AND BY INDUCING OXIDATIVE STRESS AND DNA DAMAGE

Abstract A new noninvasive cancer therapeutic device developed in our laboratory called the Oncomagnetic device involves repeated stimulation with oscillating magnetic fields (sOMF) produced by spinning permanent magnets. It is technologically and mechanistically distinct from the Optune® device approved by the FDA and provides a novel approach for CNS tumor treatment. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors causing &amp;gt;30% reduction in their contrast-enhanced volumes within 4 – 8 weeks of treatment. Immune-competent mice with implanted mouse glioma cells in their brains also showed marked reduction in tumor size, increased survival (p&amp;lt; 0.05, n = 9) and greater DNA damage (γ-H2AX foci) in implanted tumor after sOMF treatment. Normal mice exposed to sOMF for 4 months had no adverse effects on the brain and other organs. In-vitro, sOMF inhibited mitochondrial ETC complex-I and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of γ-H2AX and 53BP1 foci showed that sOMF caused significant DNA damage in GBM cells and diffuse intrinsic pontine glioma (DIPG) cells but not in normal astroglial SVGp12 cells. GBM cells exposed to sOMF for 4 h caused cell cycle arrest in the G1 phase and 30% - 40% loss of surviving colonies detected by clonogenic cell survival assay, while normal SVGp12 cells were not affected. This loss of survival in GBM cells was rescued by the antioxidant Trolox. These results indicate that sOMF stimulation has high anticancer potency comparable to low dose radiation therapy at the cellular level with an underlying mechanism of action that is substantially different from that proposed for Optune® TTF.

Enhancing low-dose radiotherapy efficacy with PARP inhibitors via FBL-mediated oxidative stress response in colorectal cancer.

The effectiveness of radiotherapy in colorectal cancer (CRC) relies on its ability to induce cell death via the generation of reactive oxygen species (ROS). However, genes responsible for mitigating oxidative stress can impede radiotherapy's efficacy. In this study, we elucidate a significant association between the nucleolar protein Fibrillarin (FBL) and the oxidative stress response in CRC tumors. Our findings reveal elevated expression of FBL in colorectal cancer, which positively correlates with oxidative stress levels. Mechanistically, FBL demonstrates direct accumulation at DNA damage sites under the regulation of PARP1. Specifically, the N-terminal GAR domain of FBL is susceptible to PARylation by PARP1, enabling FBL to recognize PARylated proteins. The accumulation of damaged FBL plays a pivotal role in facilitating short-patched base excision repair by recruiting Ligase III and disassociating PCNA and FEN1. Moreover, tumors with heightened FBL expression exhibit reduced DNA damage levels but increased sensitivity to combined low-dose radiotherapy and olaparib treatment. This underscores the potential of leveraging PARP inhibitors to augment radiotherapy sensitivity in CRC cases characterized by elevated FBL expression, offering a promising therapeutic avenue.

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.

Enhanced tumor control and survival in preclinical models with adoptive cell therapy preceded by low-dose radiotherapy.

Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone. We investigated this hypothesis using two NSG mouse models bearing GSU or CAPAN-2 solid tumors. The mice were treated with engineered CAR-T cells targeting guanyl cyclase-C (GCC) or mesothelin as monotherapy or in combination with LDRT. Additionally, we extended this approach to a C57BL/6 mouse model implanted with MC38-gp100+ cells, followed by adoptive transfer of pmel+ T cells before and after LDRT. Tumor growth and survival outcomes were monitored in all models. Furthermore, we employed atomic force microscopy (AFM) in a small cohort to assess the effects of radiotherapy on tumor stiffness and plasticity, exploring the role of tumor nanomechanics as a potential biomarker for treatment efficacy. Our results demonstrated enhanced tumor control and prolonged survival in mice treated with LDRT followed by T-cell therapy across all models. The combination of LDRT with CAR-T or pmel+ T-cell therapy led to superior tumor suppression and survival compared to monotherapy, highlighting the synergistic impact of the combined approach. Additionally, AFM analysis revealed significant changes in tumor stiffness and plasticity in response to LDRT, suggesting that the nanomechanical properties of the tumor may be predictive of therapeutic response. The findings of this study highlight the transformative potential of incorporating LDRT as a precursor to adoptive T-cell therapy in solid tumors. By promoting CAR-T and pmel+ T-cell infiltration into the tumor microenvironment, LDRT enhanced tumor control and improved survival outcomes, offering a promising strategy to overcome the challenges associated with CAR-T therapy in solid tumors. Additionally, the changes in tumor nanomechanics observed through AFM suggest that tumor stiffness and plasticity could be biomarkers for predicting treatment outcomes. These results support further investigation into the clinical application of this combined approach to improve the efficacy of cell-based therapies in patients with solid tumors.

A Comparative Analysis of Postoperative Single Fraction of 9.5 Gy Versus 10 Gy for Ear Keloids.

The optimal radiotherapy doses for postoperative treatment of ear keloids are currently a topic of debate. The authors compared the efficacy of 9.5-Gy and 10-Gy single-fraction electron beam radiation therapy after surgical excision and evaluated the impact of radiation timing on outcomes. This study was conducted on patients with ear keloid who underwent surgical excision and postoperative electron beam radiotherapy between May 2021 and June 2024. Patients were divided into groups based on radiation dose (9.5 vs 10) and timing (within 8 hours vs 24 hours postoperatively). Recurrence rates and complications were also compared. The study included 182 patients (21 men and 161 women). The overall recurrence rate was 3.3% (6/182). The 10-Gy group had a significantly lower recurrence rate than the 9.5-Gy group (0.81% vs 8.47%; p = .014). Radiation timing did not significantly influence recurrence rates (2.59% vs 3.80%, p = 1). Complications were not significantly different. A postoperative single dose of 10 Gy is the most effective low-dose single fractional electron beam radiotherapy for preventing ear keloid recurrence. Once administered within 24 hours after surgery, the timing of radiotherapy has no significant impact on treatment outcomes.

Mitigating Oxidative Stress and Lung Fibrosis with Low Dose Radiation Therapy in Paraquat Poisoning: A Case Series

Paraquat poisoning, a frequent cause of fatalities in India, has become a significant public health issue, particularly among farmers. This herbicide, known for its high toxicity, results in severe pulmonary damage, with no specific antidote available. Ingestion of even small amounts of paraquat can lead to rapid multiorgan failure and death, largely due to its accumulation in the lungs, triggering oxidative stress and alveolar fibrosis. The toxicological mechanism involves the generation of free radicals that damage cellular membranes, eventually causing extensive lung fibrosis and alveolitis. Mortality rates remain high, with no definitive treatment. Recent advancements in low-dose radiotherapy (LDRT) have shown promise in treating lung injury caused by paraquat. LDRT’s anti-inflammatory properties have been previously explored in non-cancerous conditions like musculoskeletal disorders. Its ability to modulate inflammatory responses in lung tissue suggests potential benefits in mitigating paraquat-induced lung fibrosis. While preliminary evidence from small-scale studies has shown some improvement in patients treated with LDRT, the efficacy remains uncertain. At our center, we have treated five patients using LDRT, with mixed outcomes. Some patients showed improvement, while others succumbed to early pulmonary fibrosis. Further research is needed to establish the role of LDRT in managing paraquat poisoning. Larger studies are required to assess its ability to prevent lung fibrosis and improve long-term survival in patients with severe poisoning.

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue (BALT) Lymphomas than in Non-Cancerous Lung Tissues.

It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation NGS method. DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Ultra–Low-Dose Radiation for Extranodal Marginal Zone Lymphoma of the Lung

PurposeDefinitive intent radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma typically includes a dose of 24 to 30 Gy. While modest, these doses may have associated toxicity. For patients with indolent B-cell lymphoma, there is increasing support for the use of ultra–low-dose RT (ULDRT) using 4 Gy in 2 fractions as part of a response-adapted approach, as high rates of complete response have been documented. This paradigm has been prospectively evaluated in the management of orbital and gastric indolent B-cell lymphomas; however, there is limited data guiding the use of ULDRT for lung MALT. MethodsWe conducted a retrospective review of 20 patients at our institution with lung MALT treated with ULDRT as part of a response-adapted approach. Clinical variables including prior systemic therapy and symptoms were abstracted from the electronic health record. Responses were assessed using the revised Lugano criteria. ResultsAt a median follow up of 17 months following 4 Gy (IQR, 8-37 months), we observed 100% local control. Nineteen patients (95%) experienced a complete response. No patients with stage IE disease at RT (17/20; 85%) experienced distant progression. Nine patients (45%) were symptomatic prior to RT, with improvement or resolution of symptoms in 7 (7/9; 78%). One patient developed grade 2 pleuritic pain following RT, which resolved with a brief course of steroids. No other toxicities were noted. ConclusionsULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT.

Radiotherapy for painful shoulder syndrome: aretrospective evaluation.

We evaluated the efficacy of low-dose radiotherapy for painful shoulder syndrome from an orthopedic perspective. Patients with painful shoulder syndrome were recruited for this retrospective clinical quality assessment from January 2011 to December 2017. Patients were treated with alinear accelerator or an orthovoltage device at individual doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy. To assess response, we used the von Pannewitz score with five levels: "worsened," "unaffected," "improved," "significantly improved," and "symptom free." "Good treatment success" was defined as "significantly improved" and "symptom free." Within-group and between-group differences were statistically evaluated. Of 236 recruited patients (150 women, 86men; mean age66.3 [range 31-96] years), 180 patients underwent radiotherapy with alinear accelerator and 56with an orthovoltage device. Fractionation was 12 × 0.5 Gy in 120 patients, 6 × 0.5 Gy in 74, and 6 × 1 Gy in 42patients. Treatments were completed in one series for 223 and in two series at least 6weeks apart for 13patients. Of the 236 patients, 163 patients (69.1%) agreed to be re-interviewed at amedian of 10.5 (range 4-60) months after radiotherapy completion. Directly after radiotherapy, 30.9% (73patients) had "good treatment success," which had increased to 55.2% (90patients) at follow-up. Protracted pain improvement with low-dose radiotherapy is possible in painful shoulder syndrome. Patients with refractory pain because of subacromial syndrome or shoulder osteoarthritis should also be evaluated for radiotherapy.

Biomimetic Nanosensitizer Potentiates Efficient Glioblastoma Gene-Radiotherapy through Synergistic Hypoxia Mitigation and PLK1 Silencing.

Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593-5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.

Local radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration

AbstractChimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas. However, a significant portion of patients either relapse or fail to respond. Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy. We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects on tumor growth in irradiated masses. Notably, a significant additional increase in antitumor effect was observed in nonirradiated tumors. Mechanistically, our results validate activation of the cyclic guanosine adenosine synthetase/stimulator of interferon genes pathway, tumor-associated antigen crosspriming, and elicitation of epitope spreading. Collectively, our findings suggest that RT may serve as an optimal priming and bridging modality for CAR T-cell therapy, overcoming treatment resistance and improving clinical outcomes in patients with CD19+ hematologic malignancies.

812MO Initial results of the multicenter phase II trial of a novel hypofractionated low-dose radiotherapy for indolent non-Hodgkin lymphoma

812MO Initial results of the multicenter phase II trial of a novel hypofractionated low-dose radiotherapy for indolent non-Hodgkin lymphoma

129 Low-Dose Radiotherapy for Heel Spurs: A 20-Year Safety and Efficacy Study

129 Low-Dose Radiotherapy for Heel Spurs: A 20-Year Safety and Efficacy Study

Imaging-Guided Metabolic Radiosensitization of Pediatric Rhabdoid Tumors.

Tumor hypoxia leads to increased resistance to radiation therapy (RT), resulting in markedly worse clinical outcomes in the treatment and management of pediatric malignant rhabdoid tumors (MRT). To alleviate hypoxia in MRT, we repurposed an FDA approved, mitochondrial oxidative phosphorylation (OXPHOS) inhibitor, Atovaquone (AVO), to inhibit oxygen consumption and thereby enhance the sensitivity of tumor cells to low dose RT in MRT by hypoxia alleviation. Additionally, to better understand the tumor response induced by AVO and optimize the combination with RT, we employed an emerging, noninvasive imaging modality, known as multispectral optoacoustic tomography (MSOT), to monitor and evaluate real-time dynamic changes in tumor hypoxia and vascular perfusion. Oxygen-Enhanced (OE)-MSOT could measure the change of tumor oxygenation in the MRT xenograft models after AVO and RT treatments, indicating its potential as a response biomarker. OE-MSOT showed that treating MRT mouse models with AVO resulted in a transient increase in oxygen saturation (ΔsO 2 ) in tumors when the mice were subjected to oxygen challenge, while RT or saline treated groups produced no change. In AVO+RT combination groups, the tumors showed an increase in ΔsO 2 after AVO administration followed by a significant decrease after RT, that correlated with a strong anti-tumor response, demarcated by complete regression of tumors, with no relapse on long-term monitoring. These observations were histologically validated. In MRT models of acquired AVO resistance, combination therapy failed to alleviate tumoral hypoxia and elicit any therapeutic benefit. Together, our data highlights the utility of repurposing anti-malarial AVO as an anticancer adjuvant for enabling low dose RT for pediatric patients.

Experiences with Volumetric Modulated Arc Therapy (VMAT) for treating symptomatic peripheral joint osteoarthritis (OA) with Low Dose Radiotherapy (LDRT) – a case series

Introduction: Peripheral joint osteoarthritis (OA) in Australia is the third leading cause of life-years lost. Implant surgery is a great help, but patients who are waiting or are inoperable suffer. Low Dose Radiotherapy (LDRT) is well established in some countries. Three-dimensional conformal radiotherapy (3DCRT) is recommended. However, some departments may only have Volumetric Modulated Arc Therapy (VMAT). We present our experiences treating ten volumes of symptomatic OA treated with VMAT in nine consecutive patients to two months post-LDRT. Methods: The hypothesis was that LDRT using VMAT was feasible and effective at two months. Patient response data was collected prospectively. The Visual Analog Scale Pain (VASP) for pain was used. A Visual Analog Scale Mobility (VASM) was created for mobility. Bones within radiation oncologists (RO) skin marks around the joint were auto-contoured for clinical target volume (CTV) with 2 mm expansion to planning target volume (PTV). Treatment was titrated to clinical response. Phase 1 was 3 Gray (Gy) in 6 fractions at 2-3 fractions per week. There was RO review at 2 months post-phase 1 for consideration of phase 2. If no response, then phase 2 was 6 Gy in 6 fractions, if a partial response (PR), then a repeat of phase 1. A third phase similar to phase 2 was possible. RO follow-up was done 2 months after the last phase. Results: Nine consecutive patients, eight males and one female, average age of 69 years (60-84), with ten volumes of symptomatic OA were treated. Joints were three single knees, two cases of both knees, three cases of both hands, one hip and one carpometacarpal joint. They had suffered from OA for an average of eight years (1-20). All were on at least one systemic therapy. All were using some sort of local therapy or device. Eight had a PR to phase 1 and proceeded to phase 2. Two had an equivocal response. No patient had a third phase. Average VASP pain scores fell from baseline of 7.4 to 3.6 after phase 1, and to 2.3 after phase 2. Average VASM immobility scores fell from baseline of 6.9 to 4.4 after phase 1 and to 3.3 after phase 2. Conclusion: In this small Australian cohort LDRT using VMAT is feasible and clinically effective when measured at 2 months. More study is needed.