Prospective assessment of stress and health concerns of radiation oncology staff during the COVID-19 pandemic.

Introduction and background: The COVID-19 pandemic has required rapid and repetitive adjustment of radiotherapy practice, hospital-level and department-level organization and hygiene measures. To prospectively monitor and manage stress levels and health concerns, employees of a radiation oncology department were invited to participate in weekly online surveys during the first year of the pandemic. Materials and methods: Starting March 31st, 2020, cross-sectional online surveys were distributed to all employees of the Department of Radiation Oncology, University Hospital Zurich. The survey included questions about the profession, the work setting, the global stress level as well as the health concerns during the past work week. Stress levels and health concerns were assessed on a 10-point scale. SurveyMonkey® was used to conduct the survey. Distribution was performed via email. Participation was anonymous and voluntary. Results: Between March 2020 and February 2021, 50 weekly surveys were distributed to 127 employees on average and resulted in 1,877 individual responses. The average response rate was 30%. The mean global stress level varied significantly by profession, ranging from 2.7 (±2.5) points for administrative staff to 6.9 (±2.3) points for radiation therapy technicians (p < 0.001). The mean global stress level was highest with 4.8 (±2.9) points for in-hospital work with direct patient contact. Health concerns were highest regarding family and friends with 4.0 (±3.1) points on average. Changes of the stress level varied in correlation with infection waves. Conclusion: Weekly online surveys for prospective assessment of stress levels and health concerns were successfully conducted during the first year of the COVID-19 pandemic, indicating their feasibility and value to monitor profession and workplace specific stress patterns and to allowed for tailored interventions. The physical and mental health of frontline healthcare workers in radiation oncology should remain a top priority for departmental leadership beyond the COVID-19 pandemic.

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer.

INTRODUCTION: In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. METHODS: A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. RESULTS: PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. CONCLUSION: PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care.

Impact of image filtering and assessment of volume-confounding effects on CT radiomic features and derived survival models in non-small cell lung cancer.

Background: No evidence supports the choice of specific imaging filtering methodologies in radiomics. As the volume of the primary tumor is a well-recognized prognosticator, our purpose is to assess how filtering may impact the feature/volume dependency in computed tomography (CT) images of non-small cell lung cancer (NSCLC), and if such impact translates into differences in the performance of survival modeling. The role of lesion volume in model performances was also considered and discussed. Methods: Four-hundred seventeen CT images NSCLC patients were retrieved from the NSCLC-Radiomics public repository. Pre-processing and features extraction were implemented using Pyradiomics v3.0.1. Features showing high correlation with volume across original and filtered images were excluded. Cox proportional hazards (PH) with least absolute shrinkage and selection operator (LASSO) regularization and CatBoost models were built with and without volume, and their concordance (C-) indices were compared using Wilcoxon signed-ranked test. The Mann Whitney U test was used to assess model performances after stratification into two groups based on low- and high-volume lesions. Results: Radiomic models significantly outperformed models built on only clinical variables and volume. However, the exclusion/inclusion of volume did not generally alter the performances of radiomic models. Overall, performances were not substantially affected by the choice of either imaging filter (overall C-index 0.539-0.590 for Cox PH and 0.589-0.612 for CatBoost). The separation of patients with high-volume lesions resulted in significantly better performances in 2/10 and 7/10 cases for Cox PH and CatBoost models, respectively. Both low- and high-volume models performed significantly better with the inclusion of radiomic features (P<0.0001), but the improvement was largest in the high-volume group (+10.2% against +8.7% improvement for CatBoost models and +10.0% against +5.4% in Cox PH models). Conclusions: Radiomic features complement well-known prognostic factors such as volume, but their volume-dependency is high and should be managed with vigilance. The informative content of radiomic features may be diminished in small lesion volumes, which could limit the applicability of radiomics in early-stage NSCLC, where tumors tend to be small. Our results also suggest an advantage of CatBoost models over the Cox PH models.

Operating procedures, risk management and challenges during implementation of adaptive and non-adaptive MR-guided radiotherapy: 1-year single-center experience.

BACKGROUND: Main purpose was to describe procedures and identify challenges in the implementation process of adaptive and non-adaptive MR-guided radiotherapy (MRgRT), especially new risks in workflow due to the new technique. We herein report the single center experience for the implementation of (MRgRT) and present an overview on our treatment practice. METHODS: Descriptive statistics were used to summarize clinical and technical characteristics of treatment and patient characteristics including sites treated between April 2019 and end of March 2020 after ethical approval. A risk analysis was performed to identify risks of the online adaptive workflow. RESULTS: A summary of the processes on the MR-Linac including workflows, quality assurance and possible pitfalls is presented. 111 patients with 124 courses were treated during the first year of MR-guided radiotherapy. The most commonly treated site was the abdomen (42% of all treatment courses). 73% of the courses were daily online adapted and a high number of treatment courses (75%) were treated with stereotactic body irradiation. Only 4/382 fractions could not be treated due to a failing online adaptive quality assurance. In the risk analysis for errors, the two risks with the highest risk priority number were both in the contouring category, making it the most critical step in the workflow. CONCLUSION: Although challenging, establishment of MRgRT as a routinely used technique at our department was successful for all sites and daily o-ART was feasible from the first day on. However, ongoing research and reports will have to inform us on the optimal indications for MRgRT because careful patient selection is necessary as it continues to be a time-consuming treatment technique with restricted availability. After risk analysis, the most critical workflow category was the contouring process, which resembles the need of experienced staff and safety check paths.

Assessment of extracranial metastatic disease in patients with brain metastases: How much effort is needed in the context of evolving survival prediction models?

Survival prediction models may serve as decision-support tools for clinicians who have to assign the right treatment to each patient, in a manner whereby harmful over- or undertreatment is avoided as much as possible. Current models differ regarding their components, the overall number of components and the weighting of individual components. Some of the components are easy to assess, such as age or primary tumor type. Others carry the risk of inter-assessor inconsistency and time-dependent variation. The present publication focuses on issues related to assessment of extracranial metastases and potential surrogates, e.g. blood biomarkers. It identifies areas of controversy and provides recommendations for future research projects, which may contribute to prognostic models with improved accuracy.

Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement.

BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.

Accounting for Range Uncertainties in the Optimization of Combined Proton-Photon Treatments Via Stochastic Optimization.

PURPOSE: Proton treatment slots are a limited resource. Combined proton-photon treatments, in which most fractions are delivered with photons and only a few with protons, may represent a practical solution to optimize the allocation of proton resources over the patient population. We demonstrate how a limited number of proton fractions can be optimally used in multimodality treatments and address the issue of the robustness of combined treatments against proton range uncertainties. METHODS AND MATERIALS: Combined proton-photon treatments are planned by simultaneously optimizing intensity modulated radiation therapy and proton therapy plans while accounting for the fractionation effect through the biologically effective dose model. The method was investigated for different tumor sites (a spinal metastasis, a sacral chordoma, and an atypical meningioma) in which organs at risk (OARs) were located within or near the tumor. Stochastic optimization was applied to mitigate range uncertainties. RESULTS: In optimal combinations, proton and photon fractions deliver similar doses to OARs overlaying the target volume to protect these dose-limiting normal tissues through fractionation. Meanwhile, parts of the tumor are hypofractionated with protons. Thus, the total dose delivered with photons is reduced compared with simple combinations in which each modality delivers the prescribed dose per fraction to the target volume. The benefit of optimal combinations persists when range errors are accounted for via stochastic optimization. CONCLUSIONS: Limited proton resources are optimally used in combined treatments if parts of the tumor are hypofractionated with protons and near-uniform fractionation is maintained in serial OARs. Proton range uncertainties can be efficiently accounted for through stochastic optimization and are not an obstacle for clinical application.

Feasibility and Usability Aspects of Continuous Remote Monitoring of Health Status in Palliative Cancer Patients Using Wearables.

BACKGROUND: Mobile health is a promising strategy aiming to anticipate and prevent the deterioration of health status in palliative cancer patients. A prerequisite for successful implementation of this technology into clinical routine is a high level of usability and acceptance of devices. OBJECTIVES: We aimed to evaluate feasibility as well as patients' acceptance of remote monitoring using wearables in palliative cancer patients. METHODS: In this prospective single-center observational feasibility study, 30 cancer patients treated with palliative intent in an inpatient setting with an estimated life expectancy of >8 weeks and <12 months were provided with a smartphone including a pre-installed "Activity Monitoring" app and a sensor-equipped bracelet and monitored over a period of 12 weeks starting at discharge from hospital. We report detailed feasibility and usability aspects and comment on patients' acceptance of the wearables. RESULTS: Between February 2017 and May 2018 a total of 30 patients were included in the study. From these, 25 participants (83%) completed the whole study period. On average, the bracelet was worn on 53% and smartphone used on 85% of the study days. The completion rate of daily digital questionnaires for subjective ratings (pain and distress scale) was 73%, and 28 patients were able to handle the wearables and to operate the app without major problems. Use of the bracelet was low during the night hours, with a wearing time of 1.7% of all night hours (8 p.m. to 8 a.m.). CONCLUSIONS: Remote monitoring of health care status in palliative cancer patients with a limited life expectancy is feasible and patients are able to handle the smartphone and the sensor-equipped bracelet. Feedback towards use of this monitoring system was mostly positive.

Mobile Health Technologies for Continuous Monitoring of Cancer Patients in Palliative Care Aiming to Predict Health Status Deterioration: A Feasibility Study.

Background: Unplanned readmissions or emergency visits (EVs) after discharge from hospital are frequent in patients in palliative care. Strategies to anticipate and prevent rapid deterioration of health are needed. Objective: Assessing feasibility and predictive ability of remote monitoring using wearables. Design: Prospective observational feasibility study in a single center. Setting/Subjects: Thirty cancer patients with an estimated life expectancy of >8 weeks to <12 months, aged >18 years and being discharged from inpatient to outpatient care were included. Measurements: Patients were provided with a smartphone, including the preinstalled "Activity Monitoring" application and a sensor-equipped bracelet. Follow-up was 12 weeks. Both devices recorded several features (e.g., vital signs). Visual analog scale (VAS) for pain and distress was reported once daily and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) once weekly. Statistical methods were applied to explore relationship between sensor data, self-reports, and EVs or readmissions or death. Results: Between February 2017 and May 2018, 30 patients were included. Twenty-five of 30 participants (83%) completed 12 weeks of follow-up. On average, bracelet was worn on 53% and smartphone on 85% of study days. Completion rate of daily digital questionnaires for subjective ratings was 73%. Eight unplanned hospital readmissions occurred. Ratings of pain, distress, and QLQ-C30 scores were not associated with readmission, whereas resting heart rate, resting heart rate variability, as well as speed of steps differed significantly in patients with and without readmission. Conclusions: Monitoring of palliative cancer patients using wearables is feasible. First results indicate that mobile health features might be promising biomarkers to predict unplanned readmissions.

Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report.

Background: Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group. Methods: The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches. Results: Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity. Conclusions: Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).

Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Required target margins for image-guided lung SBRT: Assessment of target position intrafraction and correction residuals.

PURPOSE: With increased use of stereotactic body radiotherapy (SBRT) for early-stage lung cancer, quantification of intrafraction variation (IFV) is required to develop adequate target margins. METHODS AND MATERIALS: A total of 409 patients with 427 tumors underwent 1593 fractions of lung SBRT between 2005 and 2010. Translational target position correction of the mean target position (MTP) was performed via onboard cone-beam computed tomography (CBCT). IFV was measured as the difference in MTP between the post-correction CBCT and the post-treatment CBCT and was calculated on 1337 fractions. RESULTS: Mean IFV-MTP was 0.0 ± 1.7 mm, 0.6 ± 2.2 mm, and -1.0 ± 2.0 mm in the mediolateral (ML), anteroposterior (AP), and craniocaudal (CC) dimensions, and the vector was 3.1 ± 2.0 mm; 67.8% of fractions had an IFV vector greater than 2 mm, and 14.3% greater than 5 mm. Weight, excursion, forced expiratory volume in the first second of expiration, diffusing capacity of the lung for carbon monoxide, and treatment time were found to be significant predictors of IFV-MTP greater than 2 mm and 5 mm. Significant differences in IFV-MTP were seen between immobilization devices with a mean IFV of 2.3 ± 1.4 mm, 2.7 ± 1.6 mm, 3.0 ± 1.7 mm, 3.0 ± 2.5 mm, 3.3 ± 1.7 mm, and 3.3 ± 2.2 mm for the body frame, hybrid device, alpha cradle, body fix, wing board, and no immobilization, respectively (P < .001). Estimated required target margins for the entire cohort were 4.3, 6.1, and 6.0 mm in the ML, AP, and CC dimensions, with differences in margins based on immobilization. CONCLUSIONS: IFV is dependent on several factors: immobilization device, treatment time, pulmonary function, and bodyweight. These factors are responsible for a significant portion of target margins with a mean IFV vector of 3 mm. Target margins of 6 mm or greater are required to encompass IFV in all dimensions when using four-dimensional CT with CBCT without respiratory gating or compression.

Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy.

PURPOSE: To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n=21) or pulmonary metastases (n=54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n=29) or three fractions of 12.5 Gy to 65% (n=40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/ß ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ≥ grade II SWOG were fitted using NTCP models. RESULTS: Eleven patients developed RP grade II. With an average MLD of 10.3±5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5±4.3 Gy and 9.9±5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V(2.5)-V(50)) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses. CONCLUSIONS: The MLD and V(2.5)-V(50) of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.