Single-fraction Radiotherapy Research Articles

Radiolytic Escherichia coli Nissle: A Novel Radiosensitizer Delivery Platform Using a Live Bacterial Therapeutic

<h3>Purpose/Objective(s)</h3> There is a critical need to develop novel radiosensitizing strategies targeting the tumor microenvironment (TME). <i>Escherichia coli Nissle</i> (EcN) is a facultative anaerobic bacterium amenable to modification for recombinant protein synthesis. Preclinically, it grows within the hypoxic TME after intratumoral injection. It has been used orally and intratumorally in clinical trials. We have engineered a novel EcN strain, Radiolytic EcN (RLE), which releases therapeutic payloads within the TME following radiation (RT) induced lysis. <h3>Materials/Methods</h3> RLE includes the RT-inducible promoter gene, RecA coupled to a lytic gene obtained from bacteriophages. A second RecA (LexA) promoter with an ablated LexA repressor site enables constitutive expression of encoded therapeutic payloads. Activation of the recA promoter by RT drives the expression of the lytic gene leading to bacterial lysis and release of payload. A luciferase reporter was incorporated for bioluminescence imaging. Based on previous RT synergy, a PD-L1 inhibitor nanobody was used as payload for proof-of-concept in vitro and in vivo studies. All RT experiments were performed with an Xstrahl animal irradiator. <h3>Results</h3> Following construct design, RLE and non-radiolytic EcN were treated in vitro using 0.5, 2, 4, 8, and 25 Gy single fraction RT. Significant cell lysis for RLE was observed in all groups exposed to RT without a dose response. No lysis was observed in the unirradiated RLE group or non-radiolytic EcN group after RT. MC38/C57BL6 subcutaneous tumor models were developed for in vivo testing of lysis. RLE was delivered intratumorally (1 × 10⁷ CFU) and intramuscularly in the flank followed by 4 Gy RT. Following RT, a significant reduction in bioluminescence was observed in the irradiated group compared to untreated controls confirming in vivo lysis. In fractionated experiments using 4 Gy x 2 over 3 days, bioluminescence revealed RLE lysis following RT with repopulation between fractions and return to baseline at day 5. Increased bioluminescence without lysis was observed in untreated RLE and non-radiolytic EcN+ RT over 5 days. Western blot of supernatant and cell fractions in RLE and non-radiolytic EcN clones producing PD-L1 demonstrate selective release of PD-L1 after RT in RLE. Efficacy was examined in flank MC38/C57BL6 models for RLE producing PD-L1+RT and 6 controls (RLE-PD-L1-no RT, EcN-PD-L1+RT, EcN-PD-L1 no RT, RLE+RT, RT alone, untreated). Among all groups, RLE-PD-L1 with RT showed a >2-fold increase in median survival (∼30 days) compared to the control groups with a median survival of 11-18 days. <h3>Conclusion</h3> RLE is a novel platform for delivery of radiosensitizing and immune modulating payloads within the TME. Preclinical data demonstrates in vitro/vivo RT induced payload release, preliminary efficacy, and repopulation between fractions allowing for metronomic payload delivery. Future work will examine combinations of immune modulating payloads and sensitizers with toxicity prohibitive for systemic use.

Radiation-induced electrophysiological remodelling in neonatal rat ventricular cardiomyocytes

Abstract Background Ventricular tachycardia (VT) carries a relatively high risk of recurrence and significantly impacts patients' quality of life, despite state of the art treatment including antiarrhythmic drug therapy and catheter ablation. Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment option for refractory VT. A marked reduction in VT episodes is observed within days of treating high-risk patients with a single fraction SBRT. The cellular mechanisms underlying the clinically demonstrated antiarrhythmic effect are still poorly understood. Radiation-induced fibrosis is observed several months after irradiation, suggesting other mechanisms that explain the immediate benefit of radiotherapy on the VT substrate. Purpose We hypothesized that early antiarrhythmic effects of single-fraction radiation are produced by direct molecular and functional electrophysiological changes, independent of fibrosis. Our aim was to investigate the effects of 20 Gy ionizing photon radiation on the electrophysiology of ventricular neonatal rat cardiomyocytes at time periods from 24 hours to 96 hours after irradiation. Methods Ventricular neonatal rat cardiomyocytes were isolated, cultivated for 24 to 96 hours and then exposed to photon beam with a single dose of 20 Gy. Expression changes of ion channels, calcium handling proteins and structural proteins affecting cellular electrophysiology were assessed via RT-qPCR and Western blotting. Beat frequency was evaluated by video analysis and action potentials (APD) were recorded using the whole-cell voltage clamp technique in current-clamp mode. Intracellular calcium transients in Fura-2 AM loaded cardiomyocytes were recorded with an IonOptix recording system. Results Irradiation lead to significant changes in the mRNA and protein level of ion channels, with most distinct changes being observed 96h after radiation. Increased mRNA and protein expression of (Cav1.2) and of the potassium channels Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1) and Kcnj2 (Kir2.1) was observed. Additionally, Connexin 43 (Cx43) was upregulated. Irradiated cardiomyocytes showed a significant increase in beat rate over time. APD was significantly shortened, with a significantly increased upstroke velocity. Regarding calcium handling, significant upregulations of Ryr2 (RYR2) and Slc8a1 (NCX) transcript and protein level was detected. Additionally, calcium handling properties were altered. Conclusion Our results suggest that acute irradiation effects are associated with electrophysiological remodelling in cardiomyocytes. Changes of cellular ion channel expression and calcium homeostasis lead to normalization and shortening of heart-failure associated APD prolongation. These results reveal new insights into acute antiarrhythmic effects on cardiomyocytes after SBRT-therapy. Funding Acknowledgement Type of funding sources: None.

Palliative radiation therapy pathway for patients on hospice in a statewide quality improvement collaborative.

201 Background: Patients on hospice receive care directed at alleviating symptoms with the goal of reducing burdensome and unnecessary healthcare. Single-fraction radiation therapy is an effective palliative treatment for cancer‐related bleeding. Hospice physicians and radiation oncologists are driven by the same goals of relieving symptoms and decreasing the burden of treatment. In general, hospices are not able to support the costs of providing palliative radiation in eligible patients. The inability to receive radiation therapy may pose a barrier to hospice enrollment. Methods: The Michigan Oncology Quality Consortium (MOQC), a collaborative of nearly 90% of oncologists in Michigan, partnered with radiation oncologists, hospice directors, and patients and caregivers to create a pathway for the referral and treatment of patients with cancer-related bleeding. Through regular meetings, the collaboration created a pathway for patients on hospice or eligible for hospice who were candidates for palliative radiation therapy for bleeding. In patients with cancer-related bleeding, the hospice clinician collaborates with a participating radiation oncologist to confirm eligibility. This decreases the hospice costs of treatment, increases access to palliative radiation, and alleviates the financial and emotional burdens on the patient and family. Results: In Michigan radiation oncology practices and hospices with statewide representation approved the pathway. Radiation oncologists in 19 practices across the state agreed to high value radiation treatment (focused level 3 consultation, complex isodose planning, single fraction treatment). Eligible patients may be seen via virtual consultation and then treated within 1 to 2 days with a single fraction of 8 Gy. A second fraction can be given in patients who continue to have bleeding. MOQC established direct connection to members of the collaborative whose contact information is available on MOQC website. In addition to this treatment pathway, the previously adopted palliative radiation pathway for oncology patients with bone metastases may be found on MOQC website. Conclusions: The radiation therapy pathway for patients with bleeding ensures a unified approach to providing a patient-focused care in patients with limited life expectancy. Challenges to the implementation of the pathway include dissemination of the document across over 100 Michigan hospices and the upfront effort required to screen patients.[Table: see text]

Palliative radiotherapy of bone metastases in octogenarians: How do the oldest olds respond? Results from a tertiary cancer center with 288 treated patients

BackgroundAccompanied by the demographic change, the number of octogenarian cancer patients with bone metastases will increase in the future. Palliative radiotherapy constitutes an effective analgesic treatment; however, as pain perception and bone metabolism change with increasing age, the analgesic efficacy of radiotherapy may be altered in elderly patients. We therefore investigated the treatment outcomes of palliative radiotherapy for bone metastases in octogenarians.MethodsPatients between 80 and 89 years undergoing radiotherapy for bone metastases between 2009 and 2019 at a tertiary cancer center were analyzed for patterns-of-care, pain response and overall survival (OS). Logistic regression analyses were carried out to examine parameters associated with pain response, and Cox analyses were conducted to reveal prognostic parameters for OS.ResultsA total of 288 patients with 516 irradiated lesions were included in the analysis. The majority (n = 249, 86%) completed all courses of radiotherapy. Radiotherapy led to pain reduction in 176 patients (61%) at the end of treatment. Complete pain relief at the first follow-up was achieved in 84 patients (29%). Bisphosphonate administration was significantly associated with higher rates of pain response at the first follow-up (p < 0.05). Median OS amounted to 9 months, and 1-year, 2-year and 3-year OS were 43%, 28% and 17%. In the multivariate analysis, ECOG (p < 0.001), Mizumoto score (p < 0.01) and Spinal Instability Neoplastic Score (SINS) (p < 0.001) were independent prognosticators for OS.ConclusionPalliative radiotherapy for bone metastases constitutes a feasible and effective analgesic treatment in octogenarian patients. ECOG, Mizumoto score and SINS are prognosic variables for survival and may aid treatment decisions regarding radiotherapy fractionation in this patient group. Single-fraction radiotherapy with 8 Gy should be applied for patients with uncomplicated bone metastases and poor prognosis. Prospective trials focusing on quality of life of these very old cancer patients with bone metastases are warranted to reveal the optimal radiotherapeutic management for this vulnerable population.

Shingles After a Single Fraction of Radiation for Ewing Sarcoma

Shingles After a Single Fraction of Radiation for Ewing Sarcoma

Single fraction image guided radiation therapy for management of bone metastases during the COVID-19 pandemic

Aim: Radiation therapy (RT) plays a major role in management of bone metastases, however, various dose-fractionation schemes are utilized taking into account patient, tumor, and treatment characteristics. The aim of this study was to assess Image Guided Single Fraction Radiation Therapy (IG-SFRT) for management of painful bone metastases during the COVID-19 pandemic.&#x0D; Material and Method: Patients receiving IG-SFRT for painful bone metastases were assessed for age, gender, primary cancer diagnosis, location of metastases, performance status, analgesic intake, pain relief, and overall treatment efficacy in this study.&#x0D; Results: Out of the total 65 patients treated with IG-SFRT during the course of COVID-19 pandemic at our department, 54 patients were evaluable for overall treatment efficacy analysis. Based on the international consensus on palliative RT endpoints, rates of complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) were 16.67%, 59.26%, 9.26%, 14.81%, respectively corresponding to an overall response rate of 75.93%. IG-SFRT was well tolerated by all patients without toxicity.&#x0D; Conclusion: For patients with bone metastases, pain palliation is a critical aspect of management. In view of the high rate of overall treatment efficacy achieved with IG-SFRT in our study, we suggest routine utilization of this image guided radiotherapeutic approach for management of painful bone metastases which additionally allows for minimization of treatment visits thereby improving patient and treatment facility convenience under the special circumstances of the recent COVID-19 pandemic.

Do Sustainable Palliative Single Fraction Radiotherapy Practices Proliferate or Perish 2 Years after a Knowledge Translation Campaign?

In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation (KT) campaign to improve the utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12–24 months removed from the KT campaign in a Provincial Cancer Program. This study identified patients receiving palliative radiotherapy for bone metastases in Manitoba in the 2018 calendar year using the provincial radiotherapy database. The proportion of patients treated with SFRT in 2018 was compared to 2017. Logistic regression analyses identified risk factors associated with MFRT receipt. In 2018, 1008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT. Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed, suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. Verification of the study’s findings in larger cohorts would be beneficial. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.

Merkel polyoma virus specific T-cell receptor transgenic T-cell therapy in PD-1 inhibitor refractory Merkel cell carcinoma.

9549 Background: Merkel cell carcinoma is an aggressive neuroendocrine tumor of skin origin with most cases caused by the Merkel polyoma virus (MCPyV). While many patients benefit from PD-1/PD-L1 axis blockade, most patients do not respond or develop resistance. We sought to ask whether adoptive transfer of autologous T cells transduced with MCPyV specific T cells could lead to clinical responses in PD-1 inhibitor refractory patients. Methods: Five MCPyV positive, HLA-A02 patients with PD-1 inhibitor refractory metastatic Merkel cell carcinoma were treated with adoptive transfer of CD62L+ CD8+ and CD4+ autologous T cells transduced with a T cell receptor (TCR) targeting an HLA-A0201 restricted MCPyV epitope. Two different strategies were used to facilitate T cell expansion: In 3 patients, single fraction radiation was administered to a subset of lesions prior to T cell transfer. In 2 patients, lymphodepleting chemotherapy with cyclophosphamide and fludarabine was administered prior to T cell transfer. Anti PD-1/PD-L1 therapy was given 14 days after T cell infusion. Transgenic T cells were visualized in tumor biopsies by multiplex immunohistochemistry. Results: 5 patients were treated, with 4 patients receiving 100 million tetramer positive CD8+ T cells and one patient receiving 500 million cells. 3 patients received second infusions with between 300 million and 900 million tetramer positive cells. No dose limiting toxicities or cytokine release syndrome were observed. T cell persistence was lower in the 2 patients treated with lymphodepleting chemotherapy relative to the 3 patients treated with single fraction radiation. Transgenic T cells persisted at tumor sites greater than 1 month following transfer. 4 patients experienced progressive disease, and a single patient had a mixed response and greater than 1 year disease free interval following local therapy of an isolated site of progression. The responding patient was the only patient with class I MHC staining on tumor cells prior to treatment, and the site of local progression in that patient showed the presence of TCR transgenic T cells but loss of class I MHC expression. Conclusions: MCPyV specific transgenic T cells are safe, traffic to tumor sites, and can result in a clinical response, but their clinical activity may be limited by down-regulation of class I MHC expression on tumors. A future trial will address strategies to increase class I MHC expression on Merkel tumors. Clinical trial information: NCT03747484.

Palliative radiation for bone metastases from hepatocellular carcinoma: practice patterns and the amount of remaining life spent receiving treatment.

Palliative radiation therapy (RT) for bone metastases (BMs) is a common practice. Wide variation exists in clinically used dose schema despite numerous studies demonstrating palliative equipoise between single and multifraction courses. We hypothesize that fraction scheme for palliating BMs for hepatocellular carcinoma (HCC) significantly affects how patients spend their remaining time. Patients with osseous HCC metastases who received RT were identified from the National Cancer Database [2004-2013]. The percentage of remaining life spent receiving radiation therapy (PRLSRT) and the number of incomplete RT courses were calculated. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate trends and predictors. A total of 1,331 patients met the inclusion criteria. Median overall survival (OS) was 3.3 months. Just 49 (3.7%) of patients received single fraction RT and 34% received >10 fractions. The mean and median PRLSRT were as follows: 1 fraction (8.9% and 3.0%), 2-5 fractions (32.9% and 24.3%), 6-10 fractions (27.2% and 15.9%), and >10 fractions (24.1% and 14.4%). Of the patients with PRLSRT >50%, 99.6% received multifraction RT. The proportion of incomplete RT courses increased as fraction size decreased from 17.6% with 4 Gy to 34% with 2 Gy. Single fraction palliative RT is vastly underutilized despite no additional palliative benefit with multifraction RT. PRLSRT significantly increased with multifraction RT. In the palliative treatment of painful BMs from HCC, single fraction treatment reduces time spent receiving radiation treatments and maximizes the number of patients who complete the prescribed treatment.

A Review of Boron Neutron Capture Therapy: Its History and Current Challenges.

Mechanism of ActionExternal beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles.HistoryBNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use.Current Limitations and ProspectsRecently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.

Exploring the utilization of single fraction radiation therapy for bone metastases at a community cancer centre

Bone represents the third most common site of metastatic spread [1] with potential severe effects including pain, fractures, immobility and decrease in quality of life [2]. Many patients suffering from symptomatic bone metastases experience relief from palliative external beam radiation therapy (pRT). Traditionally, pRT can consist of multi-fractionated radiation therapy (MFRT) schedules (such as 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions) or single fraction radiation therapy (SFRT) (such as 8 Gy in 1 fraction) [2]. More recently, high-dose stereotactic techniques have also been investigated [3,4].

Prospective Evaluation of Prostate and Organs at Risk Segmentation Software for MRI-based Prostate Radiation Therapy.

The segmentation of the prostate and surrounding organs at risk (OARs) is a necessary workflow step for performing dose-volume histogram analyses of prostate radiation therapy procedures. Low-dose-rate prostate brachytherapy (LDRPBT) is a curative prostate radiation therapy treatment that delivers a single fraction of radiation over a period of days. Prior studies have demonstrated the feasibility of fully convolutional networks to segment the prostate and surrounding OARs for LDRPBT dose-volume histogram analyses. However, performance evaluations have been limited to measures of global similarity between algorithm predictions and a reference. To date, the clinical use of automatic segmentation algorithms for LDRPBT has not been evaluated, to the authors' knowledge. The purpose of this work was to assess the performance of fully convolutional networks for prostate and OAR delineation on a prospectively identified cohort of patients who underwent LDRPBT by using clinically relevant metrics. Thirty patients underwent LDRPBT and were imaged with fully balanced steady-state free precession MRI after implantation. Custom automatic segmentation software was used to segment the prostate and four OARs. Dose-volume histogram analyses were performed by using both the original automatically generated contours and the physician-refined contours. Dosimetry parameters of the prostate, external urinary sphincter, and rectum were compared without and with the physician refinements. This study observed that physician refinements to the automatic contours did not significantly affect dosimetry parameters. Keywords: MRI, Neural Networks, Radiation Therapy, Radiation Therapy/Oncology, Genital/Reproductive, Prostate, Segmentation, Dosimetry Supplemental material is available for this article. © RSNA, 2022.

Dual Use of the METSSS Model Predicting Survival After Palliative Radiotherapy: An Exploratory Analysis.

Introduction: The recently published METSSS model, which was developed for prediction of survival after palliative radiotherapy, includes age, sex, cancer type, localization of distant metastases, Charlson-Deyo comorbidity score and radiotherapy site. Its ability to predict other relevant endpoints has not been studied yet. Therefore, this exploratory study analyzed the endpoints “unplanned termination of radiotherapy” and “treatment in the last 30 days of life” in the METSSS-defined risk groups (low/medium/high).Methods: The risk group was assigned in the METSSS online calculator for our patient cohort with non-hematological malignancies treated between 2009 and 2014 during the first course of treatment (resembling details of the original METSSS study). All patients were treated with classical palliative dose/fractionation regimes such as five fractions of 4 Gy, 10 fractions of 3 Gy or 13 fractions of 3 Gy. No stereotactic high-dose radiation was utilized. Given that single-fraction radiotherapy cannot be discontinued, patients treated with 8 Gy x1 for uncomplicated painful bone metastases were excluded. Both completed and discontinued multi-fraction radiotherapy courses (at least two fractions intended) were included.Results: The study included 290 patients, 19 of whom failed to complete their prescribed course of palliative radiotherapy (7%). Thirty-nine (13%) were irradiated in the last 30 days of life. Only one patient was classified as low-risk according to the METSSS model (medium: 15, high: 274). Only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was significantly associated with incomplete treatment. All 16 patients with low/medium METSSS risk scores completed their prescribed course of radiotherapy, compared to the 93% completion rate in the high-risk group, p=0.41. With regard to treatment in the last 30 days of life, ECOG PS, metastases to brain, liver and lung, and the number of prescribed fractions were statistically significant. One patient with a low/medium METSSS risk score was treated in the last 30 days of life (6%), compared to 14% in the high-risk group, p=0.49.Conclusion: Unexpected imbalances in the METSSS risk group size resulted in lower statistical power than anticipated. Patients with low/medium METSSS risk scores performed numerically better. However, other predictive factors, especially ECOG PS, which is not part of the METSSS model, maybe more relevant. Further efforts towards the application of the model beyond its original objective cannot be recommended.

Needle track seeding in colorectal carcinoma after local ablation by high-dose-rate brachytherapy: a retrospective study of 1,107 catheter placements

PurposeImage-guided brachytherapy with a single-fraction irradiation (high-dose-rate brachytherapy – HDR-BT) is a promising local ablation technique for unresectable liver metastases. The occurrence of needle track seeding after biopsy and microwave ablation (MWA) has been documented primarily in hepatocellular carcinoma (HCC). Comprehensive data on colorectal metastases and treatment with HDR-BT is missing. The aim of this study was to investigate the incidence of extra- and intra-hepatic track seeding after HDR-BT in patients with colorectal metastases of the liver, and the identification of possible risk factors.Material and methodsPatients with at least one treatment of HDR-BT were included. Two readers identified possible track seeding after at least 3 months of follow-up. For verification, we used image fusion of CT/MRI images from 3D irradiation plan and follow-up. Intra- and extra-hepatic seeding were included. As possible risk factors, demographics, tumor grading, and aspects of catheter placement were identified, and generalized linear mixed model for evaluation was applied.ResultsOn total, 138 patients were included in the study (85 males). We treated 472 liver lesions with 1,107 catheter placements. Sixteen needle track lesions were identified with a catheter-based risk of 1.5% and patient-based risk of 10.9% during a median follow-up of 543 days. Extra-hepatic track seeding (patient-based risk of 1.4%) was found in two patients only. Possible risk factors were tumor grading (p = 0.01) and using MRI-guidance (p = 0.02). There was also a correlation with a high number of interventions per patient (p = 0.009) and number of treated lesions (p = 0.04).ConclusionsBrachytherapy for treatment of colorectal metastases is associated with a similar risk for extra-hepatic track seeding compared to radio-frequency ablation (RFA). Intra-hepatic seeding, which has not been studied extensively before, occurs more often with seeding frequency comparable to biopsy of colorectal metastases. Possible risk factors could be tumor grading and using MRI-guidance.

Radiation exposure to the kidney with interstitial iridium-192 high-dose-rate brachytherapy: Extent and rare morphologic changes of radiation nephropathy.

We sought to investigate functional parameters and morphologic changes of the renal parenchyma after treatment with image-guided brachytherapy using single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) of primary kidney lesions, and primary and secondary lesions of the liver, lymph node, and adrenal gland close to renal structures. Patients ineligible for surgery were included. We prospectively investigated renal function loss within one year via renal scintigraphy and laboratory parameters (KDOQI stage). Radiation exposure to the kidney was measured by volume receiving 5 Gy (V5). We observed morphologic changes on CT or MRI, with follow-up every three months. In total, 35 patients were included (21 males, 14 females). Eight patients were treated for extra-renal malignancies. The mean V5 of the ipsilateral kidney was 70.0 ±42.4 ml equaling to 44.9% parenchymal volume. After renal treatment, V5 renal volume was 77.8 ±42.2 ml (48.7%) compared with 44.0 ±33.0 ml (32.0%) after extra-renal treatment. No significant reduction in KDOQI stage after 12 months of follow-up were found. Three patients developed morphologic changes in the renal parenchyma, with only one showing a decrease in renal function after 12 months. CT-guided HDR-BT is a viable treatment modality for local ablative treatment of renal and adjacent masses, with no significant reduction of the KDOQI stage as a predictor for complications of chronic kidney disease. However, larger cohorts need to be analyzed to identify vulnerable patients, as in rare cases, plain dosimetry seems insufficient to predict renal function loss after HDR-BT.

An Evaluation of Pain Response Between Single Fraction Radiotherapy Versus 10 Fractions RT in Metastatic Vertebral Bone Disease: A Quasi Experimental Study

The prognosis of bone metastasis is poor, with median survival measured in months, not years. Treatment remains an important issue to alleviate the complications and sufferings of the patients. This study was aimed to evaluate the pain response between single versus multiple fraction radiotherapy in metastatic vertebral bone disease. In this prospective quasi experimental study, the sample consisted of 60 patients of Oncology Dept., KYAMCH. Purposive sampling method was used. The respondents were divided into 2 arms, Arm A consisted of 30 patients, receiving 800 cGy single fraction RT, and Arm B consisted 30 patients who received 3000 cGy multiple fractions RT. The data were collected using a semi-structured questionnaire, which was constructed in line with the reviewed literature along with RECIST (Response Evaluation in Solid Tumor) criteria, VAS (Visual Analogue Scale) after 4 weeks of RT completion and Radiation Therapy Oncology Group (RTOG) criteria. Mean age of Arm A was 43.73 years, and Arm B was 46.8 years. Lung cancer was the leading cancer in both arms, 43.3% and 36.6% respectively. Adenocarcinoma was the commonest histopathological type of cancer found in both arms, 39.9% and 36.6% respectively. To determine associations, Chi-Square tests were done. For Arm A, 66.6% initially presented with severe pain, 23.31% with moderate and 10% with mild pain. In arm B 59.94%, 33.3% and 6.66% patients presented with severe, moderate and mild pain respectively. One month after completion of RT, pain significantly reduced in patients of both arms with a p value of < .001. No significant difference was observed between 8 Gy in single fraction versus 30 Gy in 10 fractions radiotherapy in the management of secondary bone tumour. It was found, both the radiation fractionation schedule for the management of secondary bone tumour are equally effective. More patients can be provided with the desired treatment with shorter period of time. It will certainly ease the economic burden on the patients as well as on the country.

Evaluation of the palliative radiotherapy pathway in a single institute: Can an MR Linac improve efficiency?

BackgroundPalliative radiotherapy (RT) is effectively used to relieve cancer related symptoms. The demand for these services is increasing worldwide. Rapid response clinics have been developed as a means to streamline the palliative RT radiotherapy process and increase efficiency and improve patient experiences. Key components to successful rapid response palliative RT are access to care, streamlined services and innovation. To successfully implement a rapid response RT programme, it is essential to identify gaps between currently provided care and ideal or enhanced care. The aims of this work are to audit the current palliative RT workflow at our institution both prior to and during the coronavirus pandemic. This work reports the impact of covid-19 on rate of palliative RT referrals and proposes a radiographer led, MR guided rapid response workflow to reduce wait times MethodsA retrospective audit of palliative radiotherapy booking forms was completed over a two yearperiod (2019-2020) to assess the current pathway both prior to and during the covid-19 pandemic. This audit identified patients who had received urgent/emergency spinal RT in the specified timeframe. Further data on these patients was collected using departmental oncology information systems to form a detailed analysis of the pathway and wait times. Data was recorded and analysed using Microsoft Excel. ResultsA total of 813 patients met the inclusion criteria for this audit. Data was reported for 2019 and 2020 separately to determine any significant impact caused by the covid-19 pandemic. In 2020 there was an 11.5% increase in referrals for palliative radiotherapy with an equal portion (81%) of total referrals in each year being for single fractions. Timelines from referral to treatment delivery were reported, with those patients receiving same day single fraction RT palliative radiotherapy undergoing further analysis to determine the amount of time spent in the department. Mean wait time for these patients was 5 hours and 20 minutes in 2019 but increased by 20.9% in 2020. ConclusionsThe increasing demand for palliative RT due to rising global cancer rates and extended life expectancy due to advanced systemic treatments may lead to increased wait times. An increase in both referrals and mean wait time was seen during the covid-19 pandemic. Improving efficiency and access to care is essential for this population. The MR Linac could play a role in streamlining palliative RT workflows due to its ability to employ a scan, plan and treat model in a single session. This work forms preliminary support for the development of a trial one stop palliative program on the MR Linac.

What Did the Pandemic Teach Us About Palliative Radiation in Head and Neck Cancer?

Objective: To assess the feasibility and efficacy of palliative radiotherapy dose regimens for patients with locally advanced head and neck cancer. Methods: Fifty patients of previously untreated, inoperable, stage IVA and IVB squamous cell carcinoma of the head and neck, deemed unfit for radical treatment, were included in the study from May 2020 to June 2020. Two palliative radiotherapy regimens were used. First was a single fraction radiation with 8 Gy for patients with limited life expectancy and poor performance status, which was repeated after 4 weeks in case of good symptom relief. The second regimen was used for patients with good performance status and consisted of fractionated radiation with 30 Gy in 10 fractions over 2 weeks, which was followed by supplementary radiation with 25 Gy in 10 fractions over 2 weeks in patients with good symptomatic response at 2 weeks. Symptoms were assessed at baseline and at the end of 4 weeks after treatment completion using the numerical rating score. Patients were followed up for a median of 4.5 months and assessed for symptom control and overall survival. Results: Forty-eight patients completed treatment and were included for analysis. Of the 24 patients who received single fraction radiation, 13 (54.2%) were given the second dose. Improvement in pain and dysphagia were reported in 57.9% and 60% patients, respectively. A total of 55.5% noted decrease in size of the neck node. Twenty-four patients received fractionated radiation and 15 (62.5%) were given the second course after 2 weeks. Relief in pain and dysphagia was reported in 68.2% and 63.6% patients, respectively. There were no grade 3/4 toxicities. Symptom control lasted for at least 3 months in 30% of the patients who received single fraction radiation and 54.2% of the patients who received fractionated radiation. The estimated 6-month overall survival of the entire cohort was 51.4%. Conclusion: Judicious use of palliative radiation in advanced incurable head and neck cancers provides effective and durable symptom relief and should be used after careful consideration of patient prognosis, logistics of treatment, and goals of care.

High-Dose Rate Interstitial Spine Brachytherapy Using an Intraoperative Mobile Computed Tomography-Guided Surgical Navigation System.

Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative. To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation). Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment. Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n=3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment. HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease.

Single Fraction Radiotherapy as Postoperative Treatment (SF-PORT) for Resected, Stage I/II Merkel Cell Carcinoma

In the absence of randomized prospective data, the role of postoperative radiotherapy (PORT) for localized Merkel cell carcinoma (MCC) is controversial with varying practice patterns. Although a majority of patients with resected stage I/II MCC without adverse features may be cured with surgery alone, those with adverse features including head and neck (HN) primary tumors have local recurrence rates of 20% or more without PORT (Takagishi et al. Adv Radiat Oncol, 2016). Extrapolating from our experience demonstrating high rates of local control with single fraction radiotherapy (SFRT) for metastatic MCC (Iyer et al. Cancer Med, 2015), we hypothesized that SFRT (8 Gy) may be effective as PORT to optimize local control for stage I/II MCC with adverse risk features (e.g., HN disease, immunosuppression, recurrent disease, non-oncologic resection, lymphovascular space invasion (LVSI)), especially in patients for whom a conventional RT course may not be feasible.A single-institution, retrospective review of patients with clinical or pathological stage I/II MCC receiving SFRT (8 Gy) as postoperative treatment (SF-PORT) was completed from a prospectively-enrolled database.Thirty patients (median age 78 years) were identified who received SFRT after wide local excision (n = 24; 80%), Mohs surgery (n = 1; 3%), shave or excisional biopsy only (n = 5; 17%) of the primary. Patients had pathological stage I (n = 15; 50%), clinical stage I (n = 10: 33%), pathological stage II (n = 3; 10%) or clinical stage II (n = 2; 7%) disease. All patients received SF-PORT (8 Gy) at a median of 43 days (range: 14-203) following resection or biopsy. Five patients (4 with HN disease) received SFRT to draining lymph nodes. The majority of patients had HN tumors (77%), LVSI was present in 23%,17% were immunosuppressed and 7% had locally recurrent disease (n = 2). At median follow-up of 11.3 months (range: 3-45.7), no local or in-field recurrences were observed. No local or distant recurrences, MCC specific deaths, or RT related toxicities grade > 1 (CTCAE v5.0) were observed. There were two out-of-field regional nodal recurrences in HN patients who did not receive elective nodal RT.Our early experience demonstrates a high rate of in-field local control in patients with stage I/II MCC with adverse features managed with SF-PORT. This approach warrants further study.