An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a “no-treat zone”

Background Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). Methods The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/β of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. Results Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2–3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. Conclusions This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

Inoperable Early-Stage Non–Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable, early-stage non–small-cell lung cancer. SABR results in high rates of in-field tumor control, but among larger and more biologically aggressive tumors, regional and distant failures are problematic. Cytotoxic chemotherapy is rarely used in this patient population and the benefit is unclear. Alternative systemic therapy options with a milder side-effect profile are of considerable interest, and several randomized phase III trials are currently testing immune checkpoint inhibitors in this setting. We review the rationale, data, and ongoing studies evaluating systemic therapy in medically inoperable, early-stage non–small-cell lung cancer treated with SABR.

Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.

Evaluation of the impact of teaching on delineation variation during a virtual stereotactic ablative radiotherapy contouring workshop

Introduction: Variation in delineation of target volumes/organs at risk (OARs) is well recognised in radiotherapy and may be reduced by several methods including teaching. We evaluated the impact of teaching on contouring variation for thoracic/pelvic stereotactic ablative radiotherapy (SABR) during a virtual contouring workshop. Materials and methods: Target volume/OAR contours produced by workshop participants for three cases were evaluated against reference contours using DICE similarity coefficient (DSC) and line domain error (LDE) metrics. Pre- and post-workshop DSC results were compared using Wilcoxon signed ranks test to determine the impact of teaching during the workshop. Results: Of 50 workshop participants, paired pre- and post-workshop contours were available for 21 (42%), 20 (40%) and 22 (44%) participants for primary lung cancer, pelvic bone metastasis and pelvic node metastasis cases, respectively. Statistically significant improvements post-workshop in median DSC and LDE results were observed for 6 (50%) and 7 (58%) of 12 structures, respectively, although the magnitude of DSC/LDE improvement was modest in most cases. An increase in median DSC post-workshop ≥0·05 was only observed for GTVbone, IGTVlung and SacralPlex, and reduction in median LDE > 1 mm was only observed for GTVbone, CTVbone and SacralPlex. Post-workshop, median DSC values were >0·7 for 75% of structures. For 92% of the structures, post-workshop contours were considered to be acceptable or within acceptable variation following review by the workshop faculty. Conclusions: This study has demonstrated that virtual SABR contouring training is feasible and was associated with some improvements in contouring variation for multiple target volumes/OARs.