Interim analysis of patient-reported outcome compliance and dosimetry in a phase 3 randomized clinical trial of oesophagus-sparing spinal radiotherapy.

BACKGROUND: The randomized clinical trial ESO-SPARE investigates if oesophagus-sparing radiotherapy (RT) can reduce dysphagia in patients with metastatic spinal cord compression (MSCC). Patient-reported outcome (PRO) is the only follow-up measure. Due to the fragile patient population, low respondent compliance was anticipated. We performed a planned interim analysis of dosimetry and respondent compliance, to ensure that the protocol requirements were met. METHODS: Patients >18 years referred for cervical/thoracic MSCC radiotherapy in 1-10 fractions were included from two centres. Patients were randomized (1:1) to standard RT or oesophagus-sparing RT, where predefined oesophageal dose constraints were prioritized over target coverage. Patients completed a trial diary with daily reports of dysphagia for 5 weeks (PRO-CTC-AE) and weekly quality of life reports for 9 weeks (QLQ-C30, EQ-5D-5L). According to power calculation, 124 patients are needed for primary endpoint analysis. The sample size was inflated to 200 patients to account for the fragile patient population. The co-primary endpoints, peak patient-reported dysphagia, and preserved ability to walk (EQ-5D-5L), are analysed at 5 and 9 weeks, respectively. The interim analysis was conducted 90 days after the inclusion of patient no 100. Respondent compliance was assessed at 5 and 9 weeks. In all RT plans, oesophagus and target doses were evaluated regarding adherence to protocol constraints. RESULTS: From May 2021 to November 2022, 100 patients were included. Fifty-two were randomized to oesophagus-sparing RT. In 23% of these plans, oesophagus constraints were violated. Overall, the dose to both target and oesophagus was significantly lower in the oesophagus-sparing plans. Only 51% and 41% of the patients were evaluable for co-primary endpoint analysis at five and nine weeks, respectively. Mortality and hospitalization rates were significantly larger in patients who completed <4 days PRO questionnaires. CONCLUSION: Compliance was lower than anticipated and interventions to maintain study power are needed.

Reduction of oesophageal toxicity with VMAT dose-sparing radiotherapy in thoracic metastatic spinal cord compression: A feasibility study.

Background: Palliative radiotherapy for metastatic spinal cord compression (MSCC) is given to halt disease progression and sustain quality of life for patients with advanced cancer. Radiotherapy can however induce toxicity, contradicting treatment intention. Advanced radiotherapy offers possibility of sparing organs at risk (OARs). The purpose of this dosimetric study is to establish the feasibility and potential benefits of dose sparing of the oesophagus. Materials and methods: 30 patients receiving radiotherapy of 30 Gy/10# for MSCC were retrospectively included and the oesophagus delineated. Two new dose plans were created for each patient (eso-crop and PTV-crop) with the intention of optimising the oesophageal dose. In the eso-crop plan maintaining full target volume coverage was prioritised, for the PTV-crop plan oesophageal dose was further reduced through cropping the planning target volume (PTV) overlapping oesophageal/PTV-area. Time added for delineation was measured. Plans were compared using Wilcoxon signed rank test with p < 0.05 considered statistically significant. Bivariate associations between dose metrics and patient characteristics were quantified using linear regression models. Results: Oesophageal delineation took a mean of 8.6 min. There was significant dose reduction for both V7.7 Gy, D2% and mean oesophageal dose, without significant change in CTV coverage. The mean achievable oesophageal dose reduction was 29.1% and 50.4% for the eso-crop and PTV crop plans, respectively. Minor changes in dose distribution to the lungs was observed, with increased mean and V20Gy for the eso-crop plan and decreased V5Gy to the PTV-crop plan. Conclusion: This study demonstrated the possibility of significant dose sparing of the oesophageal dose using single arc VMAT without impacting on CTV coverage.

New Pulmonary Infiltrates Observed on Computed Tomography-Based Image Guidance for Radiotherapy Warrant Diagnostic Workup for Coronavirus Disease 2019.

INTRODUCTION: Screening for coronavirus disease 2019 (COVID-19) exposure, coupled with engaged decision making to prioritize cancer treatment in parallel with reducing risk of exposure and infection, is crucial in the management of COVID-19 during cancer treatment. After two reported case studies of imaging findings during daily computed tomography (CT)-based image-guided radiotherapy (RT) scans, a call for submission of anonymized case reports was published with the objective of rapidly determining if there was a correlation between the onset of new pulmonary infiltrates found during RT and COVID-19. We hereby report the results of the aggregate analysis. METHODS: Data of deidentified case reports for patients who developed biochemically confirmed COVID-19 during RT were submitted through an online portal. Information requested included a patient's sex, age, cancer diagnosis and treatment, and COVID-19 diagnosis and outcome. Coplanar CT-based imaging was requested to reveal the presence or absence of ground-glass opacities or infiltrates. RESULTS: A total of seven reports were submitted from Turkey, Spain, Belgium, Egypt, and the United States. Results and imaging from the patients reported by Suppli et al. and McGinnis et al. were included for a total of nine patients for analysis. All patients were confirmed COVID-19 positive using polymerase chain reaction-based methods or nasopharyngeal swabs. Of the nine patients analyzed, abnormalities consistent with ground-glass opacities or infiltrates were observed in eight patients. CONCLUSIONS: This is the largest case series revealing the potential use of CT-based image guidance during RT as a tool for identifying patients who need further workup for COVID-19. Considerations for reviewing image guidance for new pulmonary infiltrates and immediate COVID-19 testing in patients who develop new infiltrates even without COVID-19 symptoms are strongly encouraged.

Premature Termination of a Randomized Controlled Trial on Image-Guided Stereotactic Body Radiotherapy of Metastatic Spinal Cord Compression.

LESSONS LEARNED: It is possible to plan and treat some patients with stereotactic body radiotherapy (SBRT) in a timely fashion in an acute setting. Advanced and, in some indications, already implemented technologies such as SBRT are difficult to test in a randomized trial. BACKGROUND: Stereotactic body radiotherapy (SBRT) in metastatic spinal cord compression (MSCC) could be an alternative to decompressive surgery followed by fractionated radiotherapy. METHODS: In a randomized, single-institution, noninferiority trial, patients with MSCC were assigned to stereotactic body radiotherapy of 16 Gy in 1 fraction or decompression surgery followed by fractionated radiotherapy of 30 Gy in 10 fractions. Primary endpoint was ability to walk by EQ5D-5L questionnaire. Based on power calculations, 130 patients had to be included to be 89% sure that a 15% difference between the treatment arm and the experimental arm could be detected. RESULTS: Ten patients were accrued in 23 months, with six patients allocated to surgery and four patients to stereotactic body radiotherapy. The trial was closed prematurely because of poor accrual. One patient undergoing surgery and one patient undergoing stereotactic body radiotherapy were unable to walk at 6 weeks. Two patients were not evaluable at 6 weeks. CONCLUSION: A randomized, phase II, clinical trial comparing surgery followed by fractionated radiotherapy or image-guided SBRT of MSCC was initiated. SBRT was shown to be feasible, with three out of four patients retaining walking function. The trial was determined futile as a result of low accrual.

Patient reported upper gastro-intestinal symptoms associated with fractionated image-guided conformal radiotherapy for metastatic spinal cord compression.

BACKGROUND AND PURPOSE: Palliative radiotherapy is given to sustain or improve quality of life for patients with advanced cancer. Radiotherapy may however result in symptomatic side effects, which may affect the patient negatively. This prospective longitudinal study of 30 patients aimed at investigating the incidence and severity of early toxicity, particularly focusing on dysphagia, esophagitis and mucositis, following fractionated radiotherapy for cervical and thoracic metastatic spinal cord compression (MSCC), as well as determining the relationship between esophageal dose and early upper gastro-intestinal symptoms. MATERIALS AND METHODS: Thirty patients receiving radiotherapy of 3Gyx10 for MSCC were included in the study. Patients were assessed for a total of 7 weeks from onset of radiotherapy using the Edmonton Symptom Assessment System (ESAS) questionnaire. Upper gastro-intestinal symptoms and severity were assessed from the tenth and eleventh question section of the ESAS questionnaire of "other problems" and how much this affected them. The relationships between the mean and maximum esophageal doses and incidence of dysphagia, esophagitis or mucositis were estimated and dose response curves determined. RESULTS: Eleven patients reported esophageal symptoms (average duration eleven days, range 1-18 days). Incidence of esophageal toxicity in patients treated at Th8 or above was 79 percent, while no patients treated below Th8 reported any symptoms (p < 0.001). Furthermore, 2 out of 3 patients irradiated at the cervical region reported substantial changes in taste sensation.Risk of symptoms correlated with both mean and maximum esophageal dose and may be a useful tool in planning radiotherapy for MSCC, potentially reducing early upper gastro-intestinal toxicity.

Prognostic implication of gait function following treatment for spinal cord compression in men diagnosed with prostate cancer.

Background: Malignant spinal cord compression (MSCC) is a severe complication of metastatic prostate cancer (PCa) and may compromise neurological functions, including gait function. This study aimed to evaluate the association between survival and gait function prior to, immediately after and 6 weeks following radiotherapy for MSCC in PCa patients.Patient sample: All PCa patients admitted with MSCC at Rigshospitalet, Denmark from January 1, 2010 to December 31, 2011 were included. Patients were followed until death to analyze gait function as a prognostic factor.Methods: Of the 76 included patients, four patients underwent surgical decompression followed by radiotherapy and 72 patients received only radiotherapy. Gait was evaluated prior to radiotherapy, immediately after radiotherapy and at 6 weeks follow-up.Results: Before radiotherapy, 88% had normal gait function and 12% had complete loss of gait function. Corresponding percentages after radiotherapy were 72% and 28%, respectively. Median overall survival following MSCC was 4.9 months (95% CI = 3.6-6.2) with a 3-, 6-, and 12-months survival probability of 64%, 42%, and 21%, respectively. Multivariate analyses demonstrated that patients without gait function after radiotherapy had a 2.6-2.8-fold increased risk of dying compared to men with gait function. Patients with more than two vertebrae involved had a 2.3-3.4-fold increased risk of dying when compared to patients with 1-2 vertebral metastases.Conclusions: PCa patients with MSCC have a poor prognosis. Most likely reflecting differences in tumor burden, preserved gait function following radiotherapy is associated with better prognosis. Further prospective studies are required to confirm this association.

Diabetes increases the risk of serious adverse events after re-irradiation of the spine.

INTRODUCTION: In this study we investigate the risk of radiation-induced serious adverse event of the spine in a large cohort of consecutive retreated patients with palliative radiotherapy (RT) for metastatic cancer in the spine. METHODS AND MATERIALS: From 2010 to 2014, 2387 patients received spinal irradiation with a palliative intent for metastatic spinal cord compression at our institution. The patients were reviewed for prior RT and 220 patients had received re-irradiation of the spine. Clinical and treatment data were obtained from the patients' records and the RT planning system. RESULTS: Patients had metastatic disease from breast, prostate, lung, hematological or other cancers (22.7%, 21.8%, 21.4%, 3.2% and 30.9%, respectively). Median follow-up was 99 days. Median cumulative EQD2 was 57.6 Gy2; range: 20.0-90.0 Gy. Spinal events related to re-irradiation were observed in fourteen patients; six patients were diagnosed with radiation-induced myelopathy (RIM) and nine patients with radiation-induced vertebral fracture (RIF). In a multivariate analysis, diabetes was related to increased risk of toxicity (HR = 7.9; P = 0.003). CONCLUSION: The incidence of RIM and RIF (6 and 9 out of 220 patients, respectively) was low in our cohort of re-irradiated patients. Patients with diabetes had a higher risk of adverse events which should be considered before re-irradiation of the spine.