Comparison of photon intensity modulated, hybrid and volumetric modulated arc radiation treatment techniques in locally advanced non-small cell lung cancer.

Background and purpose: There is no consensus on the best photon radiation technique for non-small cell lung cancer (NSCLC). This study quantified the differences between commonly used treatment techniques in NSCLC to find the optimal technique. Materials and methods: Treatment plans were retrospectively generated according to clinical guidelines for 26 stage III NSCLC patients using intensity modulated radiation therapy (IMRT), hybrid, and volumetric modulated arc therapy (VMATC, and VMATV5 optimized for lower lung and heart dose). Plans were evaluated for target coverage, organs at risk dose (including heart substructures) and normal tissue complication probabilities (NTCP). Results: The comparison showed significant and largest median differences (>1 Gy or >5%) in favor of IMRT for the mediastinal envelope and heart (maximum dose), in favor of the hybrid technique for the lungs (V5Gy of the total lungs and V5Gy of the contralateral lung) and in favor of VMATC for the heart (Dmean), most of the substructures of the heart, and the spinal cord (maximum dose). The VMATV5 technique had significantly lower heart dose compared to the hybrid technique and significantly lower lung dose compared to the VMATC, combining both advantages in one technique. The mean ΔNTCP did not exceed the 2 percent point (pp) for grade 5 (mortality), and 10 pp for grade ≥2 toxicities (radiation pneumonitis and acute esophageal toxicity), but ΔNTCP was mostly in favor of VMATC/V5 for individual patients. Conclusion: This planning study showed that VMATV5 was preferred as it achieved low lung and heart doses, as well as low NTCPs, simultaneously.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study.

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.

Comparative evaluation of autocontouring in clinical practice: A practical method using the Turing test.

PURPOSE: Automated techniques for estimating the contours of organs and structures in medical images have become more widespread and a variety of measures are available for assessing their quality. Quantitative measures of geometric agreement, for example, overlap with a gold-standard delineation, are popular but may not predict the level of clinical acceptance for the contouring method. Therefore, surrogate measures that relate more directly to the clinical judgment of contours, and to the way they are used in routine workflows, need to be developed. The purpose of this study is to propose a method (inspired by the Turing Test) for providing contour quality measures that directly draw upon practitioners' assessments of manual and automatic contours. This approach assumes that an inability to distinguish automatically produced contours from those of clinical experts would indicate that the contours are of sufficient quality for clinical use. In turn, it is anticipated that such contours would receive less manual editing prior to being accepted for clinical use. In this study, an initial assessment of this approach is performed with radiation oncologists and therapists. METHODS: Eight clinical observers were presented with thoracic organ-at-risk contours through a web interface and were asked to determine if they were automatically generated or manually delineated. The accuracy of the visual determination was assessed, and the proportion of contours for which the source was misclassified recorded. Contours of six different organs in a clinical workflow were for 20 patient cases. The time required to edit autocontours to a clinically acceptable standard was also measured, as a gold standard of clinical utility. Established quantitative measures of autocontouring performance, such as Dice similarity coefficient with respect to the original clinical contour and the misclassification rate accessed with the proposed framework, were evaluated as surrogates of the editing time measured. RESULTS: The misclassification rates for each organ were: esophagus 30.0%, heart 22.9%, left lung 51.2%, right lung 58.5%, mediastinum envelope 43.9%, and spinal cord 46.8%. The time savings resulting from editing the autocontours compared to the standard clinical workflow were 12%, 25%, 43%, 77%, 46%, and 50%, respectively, for these organs. The median Dice similarity coefficients between the clinical contours and the autocontours were 0.46, 0.90, 0.98, 0.98, 0.94, and 0.86, respectively, for these organs. CONCLUSIONS: A better correspondence with time saving was observed for the misclassification rate than the quantitative contour measures explored. From this, we conclude that the inability to accurately judge the source of a contour indicates a reduced need for editing and therefore a greater time saving overall. Hence, task-based assessments of contouring performance may be considered as an additional way of evaluating the clinical utility of autosegmentation methods.

Photons, protons or carbon ions for stage I non-small cell lung cancer - Results of the multicentric ROCOCO in silico study.

PURPOSE: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. METHODS: For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. RESULTS: The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. CONCLUSION: On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient.

Clinical evaluation of atlas and deep learning based automatic contouring for lung cancer.

BACKGROUND AND PURPOSE: Contouring of organs at risk (OARs) is an important but time consuming part of radiotherapy treatment planning. The aim of this study was to investigate whether using institutional created software-generated contouring will save time if used as a starting point for manual OAR contouring for lung cancer patients. MATERIAL AND METHODS: Twenty CT scans of stage I-III NSCLC patients were used to compare user adjusted contours after an atlas-based and deep learning contour, against manual delineation. The lungs, esophagus, spinal cord, heart and mediastinum were contoured for this study. The time to perform the manual tasks was recorded. RESULTS: With a median time of 20 min for manual contouring, the total median time saved was 7.8 min when using atlas-based contouring and 10 min for deep learning contouring. Both atlas based and deep learning adjustment times were significantly lower than manual contouring time for all OARs except for the left lung and esophagus of the atlas based contouring. CONCLUSIONS: User adjustment of software generated contours is a viable strategy to reduce contouring time of OARs for lung radiotherapy while conforming to local clinical standards. In addition, deep learning contouring shows promising results compared to existing solutions.

PET-based dose painting in non-small cell lung cancer: Comparing uniform dose escalation with boosting hypoxic and metabolically active sub-volumes.

BACKGROUND AND PURPOSE: We compared two imaging biomarkers for dose-escalation in patients with advanced non-small cell lung cancer (NSCLC). Treatment plans boosting metabolically active sub-volumes defined by FDG-PET or hypoxic sub-volumes defined by HX4-PET were compared with boosting the entire tumour. MATERIALS AND METHODS: Ten NSCLC patients underwent FDG- and HX4-PET/CT scans prior to radiotherapy. Three isotoxic dose-escalation plans were compared per patient: plan A, boosting the primary tumour (PTVprim); plan B, boosting sub-volume with FDG >50% SUVmax (PTVFDG); plan C, boosting hypoxic volume with HX4 tumour-to-background >1.4 (PTVHX4). RESULTS: Average boost volumes were 507 ± 466 cm(3) for PTVprim, 173 ± 127 cm(3) for PTVFDG and 114 ± 73 cm(3) for PTVHX4. The smaller PTVHX4 overlapped on average 87 ± 16% with PTVFDG. Prescribed dose was escalated to 87 ± 10 Gy for PTVprim, 107 ± 20 Gy for PTVFDG, and 117 ± 15 Gy for PTVHX4, with comparable doses to the relevant organs-at-risk (OAR). Treatment plans are available online (https://www.cancerdata.org/10.1016/j.radonc.2015.07.013). CONCLUSIONS: Dose escalation based on metabolic sub-volumes, hypoxic sub-volumes and the entire tumour is feasible. Highest dose was achieved for hypoxia plans, without increasing dose to OAR. For most patients, boosting the metabolic sub-volume also resulted in boosting the hypoxic volume, although to a lower dose, but not vice versa.

The PET-boost randomised phase II dose-escalation trial in non-small cell lung cancer.

PURPOSE: The local site of relapse in non-small cell lung cancer (NSCLC) is primarily located in the high FDG uptake region of the primary tumour prior to treatment. A phase II PET-boost trial (NCT01024829) randomises patients between dose-escalation of the entire primary tumour (arm A) or to the high FDG uptake region inside the primary tumour (>50% SUV(max)) (arm B), whilst giving 66 Gy in 24 fractions to involved lymph nodes. We analysed the planning results of the first 20 patients for which both arms A and B were planned. METHODS: Boost dose levels were escalated up to predefined normal tissue constraints with an equal mean lung dose in both arms. This also forces an equal mean PTV dose in both arms, hence testing pure dose-redistribution. Actual delivered treatment plans from the ongoing clinical trial were analysed. Patients were randomised between arms A and B if dose-escalation to the primary tumour in arm A of at least 72 Gy in 24 fractions could be safely planned. RESULTS: 15/20 patients could be escalated to at least 72 Gy. Average prescribed fraction dose was 3.27±0.31 Gy [3.01-4.28 Gy] and 3.63±0.54 Gy [3.20-5.40 Gy] for arms A and B, respectively. Average mean total dose inside the PTV of the primary tumour was comparable: 77.3±7.9 Gy vs. 77.5±10.1 Gy. For the boost region dose levels of on average 86.9±14.9 Gy were reached. No significant dose differences between both arms were observed for the organs at risk. Most frequent observed dose-limiting constraints were the mediastinal structures (13/15 and 14/15 for arms A and B, respectively), and the brachial plexus (3/15 for both arms). CONCLUSION: Dose-escalation using an integrated boost could be achieved to the primary tumour or high FDG uptake regions whilst keeping the pre-defined dose constraints.