Review on radiomic analysis in 18F-fluorodeoxyglucose positron emission tomography for prediction of melanoma outcomes.

Over the past decade, several strategies have revolutionized the clinical management of patients with cutaneous melanoma (CM), including immunotherapy and targeted tyrosine kinase inhibitor (TKI)-based therapies. Indeed, immune checkpoint inhibitors (ICIs), alone or in combination, represent the standard of care for patients with advanced disease without an actionable mutation. Notably BRAF combined with MEK inhibitors represent the therapeutic standard for disease disclosing BRAF mutation. At the same time, FDG PET/CT has become part of the routine staging and evaluation of patients with cutaneous melanoma. There is growing interest in using FDG PET/CT measurements to predict response to ICI therapy and/or target therapy. While semiquantitative values such as standardized uptake value (SUV) are limited for predicting outcome, new measures including tumor metabolic volume, total lesion glycolysis and radiomics seem promising as potential imaging biomarkers for nuclear medicine. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on radiomics approaches that could improve outcomes in CM.

Diagnostic Performance of 18F-FDG PET/CT According to Delay After Treatment to Detect Subclinical Recurrence of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) remains a malignancy with high rates of locoregional recurrence and poor prognosis for recurrent cases. Early detection of subclinical lesions is challenging but critical for effective patient management. Imaging surveillance after treatment, particularly 18F-FDG PET/CT, has shown promise in the diagnosis of HNSCC recurrence. The aim was to evaluate the diagnostic performance of 18F-FDG PET/CT according to delay after treatment in detecting subclinical recurrence (SCR) in HNSCC patients. Methods: In this retrospective study, all 18F-FDG PET/CT scans were performed at a single center. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2021, were included. They had a normal clinical examination before each scan. Patients who underwent an intensive follow-up strategy after treatment had 18F-FDG PET/CT with an intravenous contrast agent at 3-6 mo and annually thereafter for 5 y. The primary endpoint was diagnostic performance (positive and negative predictive values, sensitivity, specificity, and accuracy). Results: In total, 2,566 18F-FDG PET/CT scans were performed among 852 patients, with an average of 3 scans per patient. The overall diagnostic performance measures were as follows: positive predictive value (88%), negative predictive value (98%), sensitivity (98%), specificity (89%), and accuracy (93%). There were no significant differences in diagnostic performance over time. The scans detected 126 cases of SCR (14.8%) and 118 cases of metachronous cancer (13.8%). The incidence of SCR decreased over time, with the highest detection rate in the first 2 y after treatment. Positive predictive value improved over time, reaching 90% for the digital Vision 600 system (third period) compared with 76% for the analog Gemini GXLi system (first period, P < 0.001). Multivariate analysis identified advanced stage, high body mass index, and initial PET/CT upstaging as predictive factors for detection of SCR. Conclusion: Our study demonstrates that 18F-FDG PET/CT has high diagnostic performance in detecting SCR during follow-up after treatment of HNSCC, especially in the first 2 y. Advanced tumor stage, initial PET/CT upstaging, and high body mass index were associated with a higher likelihood of SCR detection. The routine use of 18F-FDG PET/CT during follow-up seems justified for patients with HNSCC.

Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

PURPOSE: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [18F]-FET PET/CT. MATERIALS AND METHODS: Thirty prospectively included patients with histologically confirmed HGGs underwent a PET/CT and mpMRI including diffusion-weighted imaging (DWI: b0, b1000, ADC), contrast-enhanced T1-weighted imaging (T1-Gado), T2-weighted fluid-attenuated inversion recovery (T2Flair), and perfusion-weighted imaging with computation of relative cerebral blood volume (rCBV) and K2 maps. Nine radiation oncologists delineated the PET/CT and MRI sequences. Spatial similarity (Dice similarity coefficient: DSC) was calculated between the readers for each sequence. Impact of the DSC on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and the log-rank test. RESULTS: The highest DSC mean values were reached for morphological sequences, ranging from 0.71 +/- 0.18 to 0.84 +/- 0.09 for T2Flair and T1Gado, respectively, while metabolic volumes defined by PET/CT achieved a mean DSC of 0.75 +/- 0.11. rCBV variability (mean DSC0.32 +/- 0.20) significantly impacted PFS (p = 0.02) and OS (p = 0.002). CONCLUSIONS: Our data suggest that the T1-Gado and T2Flair sequences were the most reproducible sequences, followed by PET/CT. Reproducibility for functional sequences was low, but rCBV inter-reader similarity significantly impacted PFS and OS.

The dosimetric parameters impact on local recurrence in stereotactic radiotherapy for brain metastases.

OBJECTIVES: Stereotactic radiotherapy (SRT) for brain metastases (BM) allows very good local control (LC). However, approximately 20%-30% of these lesions will recur. The objective of this retrospective study was to evaluate the impact of dosimetric parameters on LC in cerebral SRT. METHODS: Patients treated with SRT for 1-3 BM between January 2015 and December 2018 were retrospectively included. A total of 349 patients with 538 lesions were included. The median gross tumour volume (GTV) was 2 cm3 (IQR, 0-7). The median biological effective dose with α/ß = 10 (BED10) was 60 Gy (IQR, 32-82). The median prescription isodose was 71% (IQR, 70-80). Correlations with LC were examined using the Cox regression model. RESULTS: The median follow-up period was 55 months (min-max, 7-85). Median overall survival was 17.8 months (IQR, 15.2-21.9). There were 95 recurrences and LC at 1 and 2 years was 87.1% (95% CI, 84-90) and 78.1% (95% CI, 73.9-82.4), respectively. Univariate analysis showed that systemic treatment, dose to 2% and 50% of the planning target volume (PTV), BED10 > 50 Gy, and low PTV and GTV volume were significantly correlated with better LC. In the multivariate analysis, GTV volume, isodose, and BED10 were significantly associated with LC. CONCLUSION: These results show the importance of a BED10 > 50 Gy associated with a prescription isodose <80% to optimize LC during SRT for BM. ADVANCES IN KNOWLEDGE: Isodose, BED, and GTV volume were significantly associated with LC. A low isodose improves LC without increasing the risk of radionecrosis.

Mismatch Between Brain MRIs and 18 F-DOPA PET/CT : Impact on the Management of a Long Survivor With EGFR-Mutated Lung Adenocarcinoma.

ABSTRACT: After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.

Potential synergistic effects of cranial radiotherapy and atezolizumab in non-small cell lung cancer: an analysis of individual patient data from seven prospective trials.

Background: The impact of cranial radiotherapy (RT) on overall survival (OS) of patients with brain metastasis (BM) from non-small cell lung cancer (NSCLC) receiving programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors remains unclear. We aimed to examine the effect of previous cranial RT on the efficacy and neurological toxicity of PD-1/PD-L1 inhibitors in the treatment of patients with NSCLC. Methods: Patient-level data from seven prospective trials involving atezolizumab for the treatment of NSCLC [BIRCH (NCT02031458), FIR (NCT01846416), IMpower130 (NCT02367781), IMpower131 (NCT02367794), IMpower150 (NCT02366143), OAK (NCT02008227), and POPLAR (NCT01903993)] were pooled. Patients with baseline BM were divided into two subgroups based on previous cranial RT before initiation of treatment: patients with previously irradiated BM (iBM) and patients with non-irradiated BMs (niBM). Results: The per-protocol population consisted of 4,714 patients, including 3,176 in the atezolizumab group and 1,538 in the comparator chemotherapy group. In the atezolizumab group, OS was better in patients with BM (n=308) compared to patients without BM (n=2,868) [hazard ratio (HR): 0.83; 95% confidence interval (CI): 0.70-0.98; P=0.028]. Among patients with BM, patients with iBM (n=280) had a numerically longer OS (HR: 0.66; 95% CI: 0.41-1.07; P=0.090) than those with niBM (n=28). Intriguingly, OS was longer in patients with iBM than those without BM before (HR: 0.83; 95% CI: 0.70-0.99; P=0.043) and after (HR: 0.40; 95% CI: 0.32-0.49; P<0.0001) propensity score matching, while OS was similar between patients with niBM and those without BM. The survival advantage of patients with iBM over those without BM was not observed in the chemotherapy group. Atezolizumab-related serious neurological adverse events occurred in 16 (0.6%) patients without BM, none in those with niBM, and 2 (0.7%) patients with iBM. Conclusions: These data suggest potential synergistic effects of cranial RT and anti-PD-(L)1 therapy in NSCLC patients, which warrants further validation.

PET/CT-Based Radiogenomics Supports KEAP1/NFE2L2 Pathway Targeting for Non-Small Cell Lung Cancer Treated with Curative Radiotherapy.

In lung cancer patients, radiotherapy is associated with a increased risk of local relapse (LR) when compared with surgery but with a preferable toxicity profile. The KEAP1/NFE2L2 mutational status (MutKEAP1/NFE2L2) is significantly correlated with LR in patients treated with radiotherapy but is rarely available. Prediction of MutKEAP1/NFE2L2 with noninvasive modalities could help to further personalize each therapeutic strategy. Methods: Based on a public cohort of 770 patients, model RNA (M-RNA) was first developed using continuous gene expression levels to predict MutKEAP1/NFE2L2, resulting in a binary output. The model PET/CT (M-PET/CT) was then built to predict M-RNA binary output using PET/CT-extracted radiomics features. M-PET/CT was validated on an external cohort of 151 patients treated with curative volumetric modulated arc radiotherapy. Each model was built, internally validated, and evaluated on a separate cohort using a multilayer perceptron network approach. Results: The M-RNA resulted in a C statistic of 0.82 in the testing cohort. With a training cohort of 101 patients, the retained M-PET/CT resulted in an area under the curve of 0.90 (P < 0.001). With a probability threshold of 20% applied to the testing cohort, M-PET/CT achieved a C statistic of 0.7. The same radiomics model was validated on the volumetric modulated arc radiotherapy cohort as patients were significantly stratified on the basis of their risk of LR with a hazard ratio of 2.61 (P = 0.02). Conclusion: Our approach enables the prediction of MutKEAP1/NFE2L2 using PET/CT-extracted radiomics features and efficiently classifies patients at risk of LR in an external cohort treated with radiotherapy.

Contrastive image adaptation for acquisition shift reduction in medical imaging.

The domain shift, or acquisition shift in medical imaging, is responsible for potentially harmful differences between development and deployment conditions of medical image analysis techniques. There is a growing need in the community for advanced methods that could mitigate this issue better than conventional approaches. In this paper, we consider configurations in which we can expose a learning-based pixel level adaptor to a large variability of unlabeled images during its training, i.e. sufficient to span the acquisition shift expected during the training or testing of a downstream task model. We leverage the ability of convolutional architectures to efficiently learn domain-agnostic features and train a many-to-one unsupervised mapping between a source collection of heterogeneous images from multiple unknown domains subjected to the acquisition shift and a homogeneous subset of this source set of lower cardinality, potentially constituted of a single image. To this end, we propose a new cycle-free image-to-image architecture based on a combination of three loss functions : a contrastive PatchNCE loss, an adversarial loss and an edge preserving loss allowing for rich domain adaptation to the target image even under strong domain imbalance and low data regimes. Experiments support the interest of the proposed contrastive image adaptation approach for the regularization of downstream deep supervised segmentation and cross-modality synthesis models.

Inter-Rater Variability of Prostate Lesion Segmentation on Multiparametric Prostate MRI.

INTRODUCTION: External radiotherapy is a major treatment for localized prostate cancer (PCa). Dose escalation to the whole prostate gland increases biochemical relapse-free survival but also acute and late toxicities. Dose escalation to the dominant index lesion (DIL) only is of growing interest. It requires a robust delineation of the DIL. In this context, we aimed to evaluate the inter-observer variability of DIL delineation. MATERIAL AND METHODS: Two junior radiologists and a senior radiation oncologist delineated DILs on 64 mpMRIs of patients with histologically confirmed PCa. For each mpMRI and each reader, eight individual DIL segmentations were delineated. These delineations were blindly performed from one another and resulted from the individual analysis of the T2, apparent diffusion coefficient (ADC), b2000, and dynamic contrast enhanced (DCE) sequences, as well as the analysis of combined sequences (T2ADC, T2ADCb2000, T2ADCDCE, and T2ADCb2000DCE). Delineation variability was assessed using the DICE coefficient, Jaccard index, Hausdorff distance measure, and mean distance to agreement. RESULTS: T2, ADC, T2ADC, b2000, T2 + ADC + b2000, T2 + ADC + DCE, and T2 + ADC + b2000 + DCE sequences obtained DICE coefficients of 0.51, 0.50, 0.54, 0.52, 0.54, 0.55, 0.53, respectively, which are significantly higher than the perfusion sequence alone (0.35, p < 0.001). The analysis of other similarity metrics lead to similar results. The tumor volume and PI-RADS classification were positively correlated with the DICE scores. CONCLUSION: Our study showed that the contours of prostatic lesions were more reproducible on certain sequences but confirmed the great variability of prostatic contours with a maximum DICE coefficient calculated at 0.55 (joint analysis of T2, ADC, and perfusion sequences).