Dosimetric Impact of Inter-Fraction Variability in the Treatment of Breast Cancer: Towards New Criteria to Evaluate the Appropriateness of Online Adaptive Radiotherapy.

Purpose: As a discipline in its infancy, online adaptive RT (ART) needs new ontologies and ad hoc criteria to evaluate the appropriateness of its use in clinical practice. In this experience, we propose a predictive model able to quantify the dosimetric impact due to daily inter-fraction variability in a standard RT breast treatment, to identify in advance the treatment fractions where patients might benefit from an online ART approach. Methods: The study was focused on right breast cancer patients treated using standard adjuvant RT on an artificial intelligence (AI)-based linear accelerator. Patients were treated with daily CBCT images and without online adaptation, prescribing 40.05 Gy in 15 fractions, with four IMRT tangential beams. ESTRO guidelines were followed for the delineation on planning CT (pCT) of organs at risk and targets. For each patient, all the CBCT images were rigidly aligned to pCT: CTV and PTV were manually re-contoured and the original treatment plan was recalculated. Various radiological parameters were measured on CBCT images, to quantify inter-fraction variability present in each RT fraction after the couch shifts compensation. The variation of these parameters was correlated with the variation of V95% of PTV (ΔV95%) using the Wilcoxon Mann-Whitney test. Fractions where ΔV95% > 2% were considered as adverse events. A logistic regression model was calculated considering the most significant parameter, and its performance was quantified with a receiver operating characteristic (ROC) curve. Results: A total of 75 fractions on 5 patients were analyzed. The body variation between daily CBCT and pCT along the beam axis with the highest MU was identified as the best predictor (p = 0.002). The predictive model showed an area under ROC curve of 0.86 (95% CI, 0.82-0.99) with a sensitivity of 85.7% and a specificity of 83.8% at the best threshold, which was equal to 3 mm. Conclusion: A novel strategy to identify treatment fractions that may benefit online ART was proposed. After image alignment, the measure of body difference between daily CBCT and pCT can be considered as an indirect estimator of V95% PTV variation: a difference larger than 3 mm will result in a V95% decrease larger than 2%. A larger number of observations is needed to confirm the results of this hypothesis-generating study.

Clinical Validation of a Deep-Learning Segmentation Software in Head and Neck: An Early Analysis in a Developing Radiation Oncology Center.

BACKGROUND: Organs at risk (OARs) delineation is a crucial step of radiotherapy (RT) treatment planning workflow. Time-consuming and inter-observer variability are main issues in manual OAR delineation, mainly in the head and neck (H & N) district. Deep-learning based auto-segmentation is a promising strategy to improve OARs contouring in radiotherapy departments. A comparison of deep-learning-generated auto-contours (AC) with manual contours (MC) was performed by three expert radiation oncologists from a single center. METHODS: Planning computed tomography (CT) scans of patients undergoing RT treatments for H&N cancers were considered. CT scans were processed by Limbus Contour auto-segmentation software, a commercial deep-learning auto-segmentation based software to generate AC. H&N protocol was used to perform AC, with the structure set consisting of bilateral brachial plexus, brain, brainstem, bilateral cochlea, pharyngeal constrictors, eye globes, bilateral lens, mandible, optic chiasm, bilateral optic nerves, oral cavity, bilateral parotids, spinal cord, bilateral submandibular glands, lips and thyroid. Manual revision of OARs was performed according to international consensus guidelines. The AC and MC were compared using the Dice similarity coefficient (DSC) and 95% Hausdorff distance transform (DT). RESULTS: A total of 274 contours obtained by processing CT scans were included in the analysis. The highest values of DSC were obtained for the brain (DSC 1.00), left and right eye globes and the mandible (DSC 0.98). The structures with greater MC editing were optic chiasm, optic nerves and cochleae. CONCLUSIONS: In this preliminary analysis, deep-learning auto-segmentation seems to provide acceptable H&N OAR delineations. For less accurate organs, AC could be considered a starting point for review and manual adjustment. Our results suggest that AC could become a useful time-saving tool to optimize workload and resources in RT departments.

Shoulder girdle impairment in breast cancer survivors: the role of range of motion as predictive factor for dose distribution and clinical outcome.

BACKGROUND: Pain and functional impairment of the ipsilateral shoulder girdle in patients who underwent surgery and radiotherapy for breast cancer (BC) is a late complication reported in the literature. We analyze a correlation with dosimetric parameters and propose an algorithm for sparing strategies. METHODS: A total of 111 patients treated for BC were included in this observational analysis during follow-up protocol visits. Exclusion criteria were the presence of moderate or severe arthrosis history and/or rheumatologic diseases. All the patients had complete physical and multidimensional examinations during joint (physiatrist and radiotherapy oncology) follow-up visits. A scapula-humeral articulation (SHA) standardized contouring was performed retrospectively on Eclipse® treatment plans. A possible correlation between patients' characteristics, radiotherapy, and dosimetry analysis and functional impairment was investigated at statistical analysis. Results of analysis were summarized into a proposal of algorithm for sparing SHA. RESULTS: A total of 111 patients were selected during follow-up visits. Mean age of patients was 60 years (range 41-85 years). A total of 103 patients (93%) underwent conservative surgery, with 110 patients (99%) undergoing axilla surgery as well. Fifty-two patients (46.8%) presented a reduction of range of motion (ROM) abduction on the treated side at the observational analysis. Mean ROM abduction reduction was 13°06' (range 0°-100°). Disability of the Arm, Shoulder and Hand questionnaire (DASH) score results were excellent in 79 patients (71.2%), discrete in 15 patients (13.5%), good in 15 patients (13.5%), and sufficient in 2 patients (1.8%). Median EQD2 Dmax at SHA was 18 Gy (range 0.22-51.9 Gy) and median EQD2 mean dose at SHA was 2 Gy (range 0.04-24.32 Gy). Univariate analysis showed a linear correlation between DASH score and ROM of abduction of treated side (ρ=-0.7), ROM of abduction and ROM of flexion in ipsilateral arm (ρ=0.8), or ROM of abduction and ROM of flexion in contralateral arm (ρ=0.8). A statistically significant difference in ROM abduction between the 2 arms was found at χ2 test (P<0.05 at χ2 confidence interval = 95%). Cox linear regression analysis showed ROM abduction on treated arm as a predictive factor of DASH score (P<0.0001). Age (P<0.05), DASH score (P=0.006), and ROM abduction on treated arm (P=0.005) were found as independent predictive factors of mean dose at multivariate analysis. A mean dose higher than 7 Gy and ROM abduction reduction more than 30° were related to DASH score level reduction. CONCLUSIONS: This hypothesis-generating study introduces an algorithm to be validated for management of sparing SHA and improving quality of survivorship. ROM evaluation after surgery, early physiotherapy, standard contouring, and planning adaptation represent possible indications to preserve shoulder impairment. Further prospective studies are needed to discriminate impairment of surgery and radiotherapy in order to personalized therapeutic plan programs.

Hybrid Tri-Co-60 MRI radiotherapy for locally advanced rectal cancer: An in silico evaluation.

INTRODUCTION: Aim of this paper is to investigate the plan quality of a tri-Co-60 MRI-Hybrid system for intensity-modulated radiation therapy (IMRT) in patients affected by locally advanced rectal cancer (LARC) undergoing neo-adjuvant radiotherapy. MATERIALS AND METHODS: Ten consecutive LARC patients were selected. Tri-Co-60 step and shoot IMRT plans were generated simulating the presence of the magnetic field (Bon) or not (Boff) with the dedicated treatment planning system (TPS).The total planned dose was 45 Gy in 25 fractions to the mesorectum and the pelvic nodes (planning target volume 2, PTV2) and 55 Gy to the tumor and correspondent mesorectum (PTV1) through simultaneous integrated boost (SIB). Tri-Co-60 IMRT plans were compared with Volumetric Modulated Arc Therapy (VMAT) and IMRT plans for Linear Accelerator (Linac). RESULTS: Bon and Boff tri-Co-60 IMRT plans showed no relevant differences. Mean values of PTV1 and PTV2 receiving at least 95% of the Dp (V95%) were higher than 95% in all treatment plans. All plans met the V105% constraint for the PTV1. Mean values of V105% for the PTV2 were 14.8, 5.0, and 7.3% respectively for tri-Co-60, VMAT and IMRT. Mean Wu's HI values were similar in all plans (7.4-7.8%). All plans met the V45Gy constraint for small bowel, but mean V45Gy value was higher with tri-Co-60.Bladder irradiation was comparable and always lower than the chosen D max 65 Gy constraint.Mean values of V5Gy and V20Gy to the body and median skin doses were higher with tri-Co-60 plans. DISCUSSION: Treatment plans with Tri-Co-60 step and shoot IMRT met the dose-volume objectives in patients with LARC. Nevertheless, a larger volume of normal tissue received low-moderate doses when compared with Linac based VMAT and IMRT.

Beyond geometrical overlap: a Dosimetrical Evaluation of automated volumes Adaptation (DEA) in head and neck replanning.

INTRODUCTION: Automated target volumes adaptation could be useful in H&N replanning, but its dosimetric impact has not been analyzed.Primary aim of this investigation is dose coverage assessment in fully automated and edited PTV adaptation settings, compared to manual benchmark. MATERIALS AND METHODS: Ten IMRT patients were selected and replanning CTs were acquired.A deformable registration with PTV adaptation was performed defining PTVA.PTV B was obtained through manual editing and a benchmark PTV C was manually segmented by a delineation team.The Dice Similarity Index (DSI) and the mean Hausdorff Distance (mHD) were calculated between PTV A and PTV C, and between PTV B and PTV C.One IMRT plan was realized for each PTV: the plans optimized on PTV A and PTV B were proposed on PTV C to evaluate their dosimetric reliability compared to the benchmark plan in terms of PTV V95% dose coverage. RESULTS: The comparisons between PTV A with PTV C and PTV B with PTV C showed that the better DSI (high) and mHD values (low) are, the smaller difference when compared to PTV C V95% is described.Evaluating plan A and B, PTV C V95% reduced by 6.1 ± 3.0% and by 4.1 ± 2.3% respectively when compared to plan C PTV C V95%.PTV B reaches acceptable dose coverage values (PTV V95% >95%) when DSI is >0.91 and a mHD < 0.17 mm and it has better results when compared to PTV A in 70%. DISCUSSION: The results show a correlation between the DSI-mHD and the PTV V95% variation, in the comparisons PTV A and PTV B vs PTV C.Furthermore, we observed that PTV V95% coverage is higher in PTV B than in PTV A: the use of automated propagation may not be definitive and requires manual correction.