SHOULD PATIENT SETUP IN LUNG CANCER BE BASED ON THE PRIMARY TUMOR? AN ANALYSIS OF TUMOR COVERAGE AND NORMAL TISSUE DOSE USING REPEATED POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY IMAGING

PURPOSE: Evaluation of the dose distribution for lung cancer patients using a patient set-up procedure based on the bony anatomy or the primary tumor. METHODS AND MATERIALS: For 39 (non-)small cell lung cancer patients the planning FDG-PET/CT scan was registered to a repeated FDG-PET/CT scan made in the second week of treatment. Two patient set-up methods were analyzed: bony anatomy or primary tumor set-up. The original treatment plan was copied to the repeated scan, and target and normal tissue structures were delineated. Dose distributions were analyzed using dose-volume histograms for the primary tumor, lymph nodes, lungs and spinal cord. RESULTS: One patient showed decreased dose coverage of the primary tumor due to progressive disease and required re-planning to achieve adequate coverage. For the other patients, the minimum dose to the primary tumor did not significantly deviate from the planned dose: −0.2±1.7% (p=0.71) and −0.1±1.7% (p=0.85) for the bony anatomy and primary tumor set-up, respectively. For patients (N=31) with nodal involvement, 10% showed a decrease in minimum dose larger than 5% for the bony-anatomy set-up and 13% for the primary tumor based set-up. Mean lung dose exceeded the maximum allowed 20 Gy in 21% of the patients for the bony-anatomy and in 13% for the primary tumor set-up, whereas for the spinal cord this occurred in 10% and 13% of the patients, respectively. CONCLUSIONS: In 10% and 13% of patients with nodal involvement, set-up based on bony anatomy or primary tumor, respectively, lead to important dose deviations in nodal target volumes. Overdosage of critical structures occurred in 10-20% of the patients. In case of progressive disease, repeated imaging revealed underdosage of the primary tumor. Development of practical ways for set-up procedures based on repeated high-quality imaging of all tumor sites during radiotherapy should therefore be an important research focus

Evaluating Tumor Response of Non-Small Cell Lung Cancer Patients With F-18-Fludeoxyglucose Positron Emission Tomography: Potential for Treatment Individualization

Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive F-18-fludeoxyglucose positron emission tomography (FDG-PET) scans. Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, alpha(eff), was determined at the voxel level. Correlations were sought between the average aeff or the fraction of negative aeff values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs). Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average alpha(eff) of 0.003 Gy(-1) in the primary GTV, with a sensitivity of 75% and a specificity of 100% (

An investigation into the risk of population bias in deep learning autocontouring

Background and Purpose: To date, data used in the development of Deep Learning-based automatic contouring (DLC) algorithms have been largely sourced from single geographic populations. This study aimed to evaluate the risk of population-based bias by determining whether the performance of an autocontouring system is impacted by geographic population.Materials and methods: 80 Head Neck CT deidentified scans were collected from four clinics in Europe (n = 2) and Asia (n = 2). A single observer manually delineated 16 organs-at-risk in each. Subsequently, the data was contoured using a DLC solution, and trained using single institution (European) data. Autocontours were compared to manual delineations using quantitative measures. A Kruskal-Wallis test was used to test for any difference between populations. Clinical acceptability of automatic and manual contours to observers from each participating institution was assessed using a blinded subjective evaluation.Results: Seven organs showed a significant difference in volume between groups. Four organs showed statistical differences in quantitative similarity measures. The qualitative test showed greater variation in acceptance of contouring between observers than between data from different origins, with greater acceptance by the South Korean observers.Conclusion: Much of the statistical difference in quantitative performance could be explained by the difference in organ volume impacting the contour similarity measures and the small sample size. However, the qualitative assessment suggests that observer perception bias has a greater impact on the apparent clinical acceptability than quantitatively observed differences. This investigation of potential geographic bias should extend to more patients, populations, and anatomical regions in the future.</p

Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: A hypothesis generating study

BACKGROUND: Many patients with stage I–III small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FDG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC. METHODS: Fifteen stage I–III SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected. The metabolic volume (MV) was defined both within the primary tumour and in the involved nodal stations using the 40% (MV40) and 50% (MV50) threshold of the maximum SUV. Metabolic and CT response was assessed by the relative change in MV and CT volume, respectively, between both time points. The association between response and overall survival (OS) was analysed by univariate cox regression analysis. The minimum follow-up was 18 months. RESULTS: Reductions in MV40 and MV50 were −36 ± 38% (126.4 to 68.7 cm(3)) and −44 ± 38% (90.2 to 27.8 cm(3)), respectively. The median CT volume reduction was −40 ± 64% (190.6 to 113.8 cm(3)). MV40 and MV50 changes showed a significant association with survival (HR = 1.02, 95% CI: 1.00–1.04 (p = 0.042); HR = 1.02, 95% CI: 1.00–1.04 (p = 0.048), respectively), indicating a 2% increase in survival probability for 1% reduction in metabolic volume. The CT volume change was also significantly correlated with survival (HR = 1.01, 95% CI: 1.00–1.03, p = 0.007). CONCLUSIONS: This hypothesis generating study shows that both the early CT and the MV changes show a significant correlation with survival in SCLC. A prospective study is planned in a larger patient cohort to allow multivariate analysis, with the final aim to select patients early during treatment that could benefit from dose intensification or alternative treatment

Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation

Purpose Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-18-HX4 positron emission tomography (PET) imaging of NSCLC. Methods Positron emission tomography imaging data based on the hypoxia tracer F-18-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO(2)) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy. Results Gross target volumes ranged between 6.2 and 859.6 cm(3), and the hypoxic fraction <10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO(2), HTV doses were calculated as 43.6-48.4 Gy for a three-fraction schedule, 51.7-57.6 Gy for five fractions, and 59.5-66.4 Gy for eight fractions. For patients in whom the HTV pO(2) distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single-fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions. Conclusions The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on F-18-HX4-PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume