Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the ...temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 95% confidence interval (C.I.): 0.61-0.90, significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.
We performed a meta-analysis of the risk of cutaneous toxicities associated with immune checkpoint inhibitors.
Eligible studies included randomized trials of patients with solid tumors on immune ...checkpoint inhibitors (ipilimumab, nivolumab, tremelimumab, pidlizumab and pembrolizumab); describing events of rash, vitiligo and pruritus.
A total of nine clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade rash, vitiligo and pruritus was 4.06 (95% CI: 3.35-4.91; p < 0.0001), 16.3 (95% CI: 3.21-82.8; p = 0.0008) and 3.4 (95% CI: 2.24-5.16; p < 0.00001), respectively.
Our meta-analysis demonstrates that immune checkpoint inhibitors are associated with an increased risk of all grade skin rash, vitiligo and pruritus. Clinicians should perform regular clinical cutaneous monitoring.
We performed a meta-analysis of the risk of selected gastrointestinal toxicities associated with immune checkpoint inhibitors.
Eligible studies included randomized trials of patients with solid ...tumors on ipilimumab, nivolumab, pembrolizumab, tremelimumab, pidilizumab and atezolizumab, describing events of diarrhea, vomiting or colitis.
After exclusion of ineligible studies, a total of ten clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade diarrhea, vomiting and colitis was 1.64 (95% CI: 1.19-2.26; p = 0.002), 0.72 (95% CI: 0.49-1.07; p = 0.1), 10.35 (95% CI: 5.78-18.53; p < 0.00001), respectively.
Our meta-analysis has demonstrated that immune checkpoint inhibitors are associated with a significantly increased risk of all grade and high-grade colitis.
•GTVs on the 60 kV and 140 kV from DECT, and the T1c and T2 from MRI were compared.•Delineation was the most consistent using T1c (no interobserver difference in DSC).•T1c MRI provided higher ...interobserver agreement for skull base tumors.•60 kV DECT provided higher interobserver agreement for non-skull base tumors.
In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0–0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.
•Head and neck cancers radiotherapy (RT) leads to inevitable injury to parotid glands.•We sought to quantify delta-changes of 18FDG-PET metrics in these parotid glands.•Parotid PET delta-changes and ...clinical variables could predict xerostomia severity.
Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury.
Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3–6 months post-RT (Xero 3–6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0–5 Gy, 5–10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT.
432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3–6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10–50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC = 0.78 (95%CI: 0.66–0.85; p < 0.0001).
We sought to quantify pre- and post-RT 18FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables.
Background: This meta-analysis has been conducted to determine the risk of elevated transaminases associated with immune checkpoint inhibitors use in patients with cancer.
Methods: Studies eligible ...for our analysis included randomized Phase II and III trials of patients with cancer on ipilimumab, nivolumab, pembrolizumab, tremelimumab and pidilizumab, which describe events of elevated transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Results: Initial database search revealed 210 relevant citations. After excluding noneligible studies, 10 trials were considered eligible for the quantitative synthesis. The RR of all-grade elevated ALT and AST was 2.36 (95% CI 1.20-4.66; p = 0.01) and 1.53 (95% CI 0.73-3.22; p = 0.26), respectively, whereas for high-grade elevated ALT and AST, it was 11.27 (95% CI 5.38-23.63; p < 0.0001) and 4.9 (95% CI 2.97-8.09; p < 0.0001), respectively.
Conclusions: Our study has shown that the use of immune checkpoint inhibitors has a causal relationship to an increased risk of high-grade elevated ALT and AST. Clinicians using these agents should be attentive of this risk.
Abstract Background We performed a systematic review and meta-analysis of the risk of cardiovascular adverse events associated with ramucirumab. Patients and methods Eligible studies included ...randomized phase II and III trials of patients with solid tumors on ramucirumab; describing events of hypertension, bleeding, arterial/venous thrombosis and congestive heart failure. Results Our search strategy yielded 160 potentially relevant citations from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The RR of all-grade hypertension, bleeding, ATE, VTE and congestive heart failure were 2.83 (95% CI 2.43–3.29; p < 0.0001), 1.98 (95% CI 1.77–2.21; p < 0.0001); 0.97 (95% CI 0.62–1.52; p = 0.91), 0.83 (95% CI 0.52–1.35; p = 0.46), 1.36 (95% CI 0.77-2.4; p = 0.28), respectively. Conclusions Our meta-analysis has demonstrated that ramucirumab is associated with an increased risk of hypertension and bleeding. Clinicians should be aware of this risk and perform regular clinical monitoring.
•The paper describes the first challenge on head and neck tumor segmentation in PET/CT.•Training (n=201, 4 centers) and test sets (n=53, 1 unseen center) amount to 254 cases.•All ground truth ...segmentations underwent cleaning to ensure quality and homogeneity.•The winning team obtained a DSC of 0.759, showing a larg improvement over the baseline.•Additional post-challenge analyses (e.g. false positives analysis, ranking stability).
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This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge’s task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs.
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•We aimed at quantifying inter-observer Pancoast tumors delineation variability.•Experts’ delineations were used to define ground truth.•Other observers’ delineations were compared ...against ground truth.•High degree of variability was noted for most target volumes except GTV_P.•This unveils potentials for protocol modification for future IMRT studies.
Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee’s multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a “dry run” for trial implementation.
CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).
Six board-certified thoracic radiation oncologists were designated as the ‘Experts’ for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants’ contours were then compared with Experts’ STAPLE contours.
When compared to the Experts’ STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans.
High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.
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