Management of tracheobronchial amyloidosis: a review of the literature.

Introduction: Tracheobronchial amyloidosis is a rare idiopathic disorder characterised by extracellular deposition of misfolded protein fibrils in the tracheobronchial tree. It presents with nonspecific symptoms. Deciding on the best treatment approach can be challenging due to the lack of a treatment guideline. We undertook a review to assess the therapeutic options for tracheobronchial amyloidosis and to highlight gaps within the existing evidence. Methods: We performed a literature search from 1 January 1990 until 1 March 2022 to identify relevant literature regarding patient characteristics, symptoms, management and prognosis for patients with tracheobronchial amyloidosis. Results: 77 studies consisting of 300 patients were included. We found a great heterogeneity in the management of tracheobronchial amyloidosis patients. Although a fifth of the reported patients were managed with a wait-and-see approach, many different treatments were used as a single intervention, or multiple treatments were combined. An interesting finding is the slightly higher percentage of patients with Sjögren syndrome (n=5, 1.7%) and tracheobronchial amyloidosis compared to the normal population (0.5-1.0%). Conclusions: There is a great heterogeneity in the management of tracheobronchial amyloidosis patients. The treatment is still based on expert opinion due to the lack of a treatment guideline. Various treatment approaches include a wait-and-see approach, external beam radiotherapy, therapeutic bronchoscopy, immunosuppressive treatment and surgery.

Accuracy of deformable image registration-based intra-fraction motion management in Magnetic Resonance-guided radiotherapy.

Background and Purpose: Intra-fraction motion management is key in Stereotactic Ablative Radiotherapy (SABR) gated delivery. This study assessed the accuracy of automatic tumor segmentation in the delivery of MR-guided radiotherapy (MRgRT) by comparing it to manual delineations performed by experienced observers. Materials and Methods: Twenty patients previously treated with MR-guided SABR for thoracic and abdominal tumors were included. Five observers with at least two years of experience in MRgRT manually delineated the gross tumor volume (GTV) for 20 patients on 240 frames of a cine MRI on a sagittal plane. Deformable Image Registration (DIR) based GTV contours were propagated using four different algorithms from a reference frame to subsequent frames.Geometrical analysis based on the Dice Similarity Coefficient (DSC), centroid distance and Hausdorff Distance (HDD) were performed to assess the inter-observer variability and the accuracy of automatic segmentation. A Confidence Value (CV) metric for the reliability of the tumor auto-contouring was also calculated. Results: Inter-observer delineation variability resulted in mean DSC of 0.89, HDD of 5.8 mm and centroid distance of 1.7 mm. Tumor auto-contouring by the four DIR algorithms resulted in an excellent agreement with the manual delineations by the experienced observers. Mean DSC for each algorithm across all patients was greater than 0.90, whereas the HDD and centroid distances were below 4.0 mm and 1.5 mm, respectively. The CV showed a strong correlation with the DSC. Conclusions: DIR-based auto-contouring in MRgRT exhibited a high level of agreement with the manual contouring performed by experts, allowing accurate gated delivery.

Impact of daily plan adaptation on organ-at-risk normal tissue complication probability for adrenal lesions undergoing stereotactic ablative radiation therapy.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework. METHODS: Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression. RESULTS: Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7-15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2-13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3-20.4%], p < 0.001) than right-sided lesions (2.1% [-1.6-5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings. CONCLUSION: NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP.

Role of Daily Plan Adaptation in MR-Guided Stereotactic Ablative Radiation Therapy for Adrenal Metastases.

PURPOSE: To study interfractional organ changes during magnetic resonance (MR)-guided stereotactic ablative radiation therapy for adrenal metastases and to evaluate the dosimetric advantages of online plan adaptation. METHODS AND MATERIALS: Seventeen patients underwent a total of 84 fractions of video-assisted, respiration-gated, MR-guided adaptive radiation therapy to deliver either 50 Gy (5 fractions), 60 Gy (8 fractions), or 24 Gy (3 fractions). An MR scan was repeated before each fraction, followed by rigid coregistration to the gross tumor volume (GTV) on the pretreatment MR scan. Contour deformation, planning target volume (PTV) (GTV + 3 mm) expansion, and online plan reoptimization were then performed. Reoptimized plans were compared with baseline treatment plans recalculated on the anatomy-of-the-day ("predicted plans"). Interfractional changes in organs at risk (OARs) were quantified according to OAR volume changes within a 3 cm distance from the PTV surface, center of mass displacements, and the Dice similarity coefficient. Plan quality evaluation was based on target coverage (GTV and PTV) and high dose sparing of all OARs (V36Gy, V33Gy, and V25Gy). RESULTS: Substantial center of mass displacements were observed for stomach, bowel, and duodenum, 17, 27 and 36 mm, respectively. Maximum volume changes for the stomach, bowel, and duodenum within 3 cm of PTV were 23.8, 20.5, and 20.9 cm3, respectively. Dice similarity coefficient values for OARs ranged from 0.0 to 0.9 for all fractions. Baseline plans recalculated on anatomy-of-the-day revealed underdosage of target volumes and variable OAR sparing, leading to a failure to meet institutional constraints in a third of fractions. Online reoptimization improved target coverage in 63% of fractions and reduced the number of fractions not meeting the V95% objective for GTV and PTV. Reoptimized plans exhibited significantly better sparing of OARs. CONCLUSIONS: Significant interfractional changes in OAR positions were observed despite breath-hold stereotactic ablative radiation therapy delivery under MR-guidance. Online reoptimization of treatment plans led to significant improvements in target coverage and OAR sparing.

Molecular screening of oral precancer.

OBJECTIVES: Early detection and treatment of high risk premalignant mucosal changes of the oral cavity, will expectedly improve survival and reduce treatment-related morbidity. Aims of this study were to evaluate a non-invasive screening approach and to assess the value of molecular markers to identify patients at risk for oral cancer. MATERIALS AND METHODS: Exfoliated cells and biopsies were obtained from oral leukoplakia lesions of 43 patients, of whom six developed oral cancer. All samples were investigated for loss of heterozygosity (LOH) at chromosomes 3p, 9p, 11q and 17p using microsatellite markers. On the biopsy specimen additional immunohistochemical staining for p53, TP53 mutation analysis and histopathological grading were performed. RESULTS: The analytical sensitivity of the non-invasive assay using exfoliated cells to detect genetic changes present in the lesions was 45% (9 of 20), the specificity was 100% (19 of 19), and the positive predictive value was also 100% (9 of 9). LOH was present in 20 of 39 (51%) of the biopsies with uniformly LOH at 9p. Mutated TP53 and LOH at 9p in the biopsy, as single markers and in combination, were significant risk factors for malignant progression of leukoplakia to oral cancer (Kaplan-Meier analysis, p<0.05). CONCLUSION: A non-invasive genetic screening approach using LOH in exfoliated cells has limited value for monitoring patients with leukoplakia. However, LOH at 9p, but also mutated TP53 in biopsies of oral leukoplakia have a significant association with malignant transformation and are promising candidate biomarkers to predict the risk for malignant progression.