Promising Candidate Prognostic Biomarkers in [18F]FDG PET Images: Evaluation in Independent Cohorts of Non-Small Cell Lung Cancer Patients.

The normalized distances from the hot spot of radiotracer uptake (SUVmax) to the tumor centroid (NHOC) and to the tumor perimeter (NHOP) have recently been suggested as novel PET features reflecting tumor aggressiveness. These biomarkers characterizing the shift of SUVmax toward the lesion edge during tumor progression have been shown to be prognostic factors in breast and non-small cell lung cancer (NSCLC) patients. We assessed the impact of imaging parameters on NHOC and NHOP, their complementarity to conventional PET features, and their prognostic value for advanced-NSCLC patients. Methods: This retrospective study investigated baseline [18F]FDG PET scans: cohort 1 included 99 NSCLC patients with no treatment-related inclusion criteria (robustness study); cohort 2 included 244 NSCLC patients (survival analysis) treated with targeted therapy (93), immunotherapy (63), or immunochemotherapy (88). Although 98% of patients had metastases, radiomic features including SUVs were extracted from the primary tumor only. NHOCs and NHOPs were computed using 2 approaches: the normalized distance from the localization of SUVmax or SUVpeak to the tumor centroid or perimeter. Bland-Altman analyses were performed to investigate the impact of both spatial resolution (comparing PET images with and without gaussian postfiltering) and image sampling (comparing 2 voxel sizes) on feature values. The correlation of NHOCs and NHOPs with other features was studied using Spearman correlation coefficients (r). The ability of NHOCs and NHOPs to predict overall survival (OS) was estimated using the Kaplan-Meier method. Results: In cohort 1, NHOC and NHOP features were more robust to image filtering and to resampling than were SUVs. The correlations were weak between NHOCs and NHOPs (r ≤ 0.45) and between NHOCs or NHOPs and any other radiomic features (r ≤ 0.60). In cohort 2, the patients with short OS demonstrated higher NHOCs and lower NHOPs than those with long OS. NHOCs significantly distinguished 2 survival profiles in patients treated with immunotherapy (log-rank test, P < 0.01), whereas NHOPs stratified patients regarding OS in the targeted therapy (P = 0.02) and immunotherapy (P < 0.01) subcohorts. Conclusion: Our findings suggest that even in advanced NSCLC patients, NHOC and NHOP features pertaining to the primary tumor have prognostic potential. Moreover, these features appeared to be robust with respect to imaging protocol parameters and complementary to other radiomic features and are now available in LIFEx software to be independently tested by others.

The Image Biomarker Standardization Initiative: Standardized Convolutional Filters for Reproducible Radiomics and Enhanced Clinical Insights.

Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking.

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII.

PURPOSE: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. METHODS: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. RESULT: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. CONCLUSION: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. CRITICAL RELEVANCE STATEMENT: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. KEY POINTS: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score ( https://metricsscore.github.io/metrics/METRICS.html ) and a repository created to collect feedback from the radiomics community ( https://github.com/metricsscore/metrics ).

Curative high-dose reirradiation for patients with recurrent head and neck adenoid cystic carcinomas: outcomes and analysis of patterns of failure.

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.

Tumor Location Relative to the Spleen Is a Prognostic Factor in Lymphoma Patients: A Demonstration from the REMARC Trial.

Baseline [18F]FDG PET/CT radiomic features can improve the survival prediction in patients with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate whether characterizing tumor locations relative to the spleen location in baseline [18F]FDG PET/CT images predicts survival in patients with DLBCL and improves the predictive value of total metabolic tumor volume (TMTV) and age-adjusted international prognostic index (IPI). Methods: This retrospective study included 301 DLBCL patients from the REMARC (NCT01122472) cohort. Physicians delineated the tumor regions, whereas the spleen was automatically segmented using an open-access artificial intelligence algorithm. We systematically measured the distance between the centroid of the spleen and all other lesions, defining the SD of these distances as the lesion spread (SpreadSpleen). We calculated the maximum distance between the spleen and another lesion (Dspleen) for each patient and normalized it with the body surface area, resulting in standardized Dspleen (sDspleen). The predictive value of each PET/CT feature for progression-free survival (PFS) and overall survival (OS) was evaluated through univariate and multivariate time-dependent Cox models and Kaplan-Meier analysis. Results: In total, 282 patients (mean age, 68.33 ± 5.41 y; 164 men) were evaluated. The artificial intelligence algorithm successfully segmented the spleen in 96% of the patients. SpreadSpleen, Dspleen, and sDspleen were correlated neither with TMTV (Pearson ρ < 0.23) nor with IPI (Pearson ρ < 0.15). When median values were used as the cutoff, SpreadSpleen, Dspleen, and sDspleen all significantly classified patients into 2 risk groups for PFS and OS (P < 0.001). They complemented TMTV and IPI to classify the patients into 3 risk groups for PFS and OS (P < 0.001). Integrating SpreadSpleen, Dspleen, or sDspleen into a Cox model on the basis of TMTV, IPI, and TMTV combined with IPI significantly improved the concordance index for PFS and OS (P < 0.05). Conclusion: Baseline PET/CT features that characterize tumor spread and dissemination relative to the spleen strongly predicted survival in patients with DLBCL. Integrating these features with TMTV and IPI further improved survival prediction.

[18F]FDG PET/CT for predicting triple-negative breast cancer outcomes after neoadjuvant chemotherapy with or without pembrolizumab.

PURPOSE: To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. METHODS: In this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR. RESULTS: N = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p < 0.01). In univariable analysis, high Ki67, high tumor SUVmax (> 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification (< T3), BRCA1/2 germline mutation, high tumor SUVmax (> 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds. CONCLUSION: High tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients.

European Association of Nuclear Medicine (EANM) Focus 4 consensus recommendations: molecular imaging and therapy in haematological tumours.

Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.

Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

[18F]-FDG PET and MRI radiomic signatures to predict the risk and the location of tumor recurrence after re-irradiation in head and neck cancer.

PURPOSE: To evaluate whether radiomics from [18F]-FDG PET and/or MRI before re-irradiation (reRT) of recurrent head and neck cancer (HNC) could predict the occurrence and the location "in-field" or "outside" of a second locoregional recurrence (LR). METHODS: Among the 55 patients re-irradiated at curative intend for HNC from 2012 to 2019, 48 had an MRI and/or PET before the start of the reRT. Thirty-nine radiomic features (RF) were extracted from the re-irradiated GTV (rGTV) using LIFEx software. Student t tests and Spearman correlation coefficient were used to select the RF that best separate patients who recurred from those who did not, and "in-field" from "outside" recurrences. Principal component analysis involving these features only was used to create a prediction model. Leave-one-out cross-validation was performed to evaluate the models. RESULTS: After a median follow-up of 17 months, 40/55 patients had developed a second LR, including 18 "in-field" and 22 "outside" recurrences. From pre-reRT MRI, a model based on three RF (GLSZM_SZHGLE, GLSZM_LGLZE, and skewness) predicted whether patients would recur with a balanced accuracy (BA) of 83.5%. Another model from pre-reRT MRI based on three other RF (GLSZM_ LZHGE, NGLDM_Busyness, and GLZLM_SZE) predicted whether patients would recur "in-field" or "outside" with a BA of 78.5%. From pre-reRT PET, a model based on four RF (Kurtosis, SUVbwmin, GLCM_Correlation, and GLCM_Contrast) predicted the LR location with a BA of 84.5%. CONCLUSION: RF characterizing tumor heterogeneity extracted from pre-reRT PET and MRI predicted whether patients would recur, and whether they would recur "in-field" or "outside".

Artificial Intelligence in Nuclear Medicine: Opportunities, Challenges, and Responsibilities Toward a Trustworthy Ecosystem.

Trustworthiness is a core tenet of medicine. The patient-physician relationship is evolving from a dyad to a broader ecosystem of health care. With the emergence of artificial intelligence (AI) in medicine, the elements of trust must be revisited. We envision a road map for the establishment of trustworthy AI ecosystems in nuclear medicine. In this report, AI is contextualized in the history of technologic revolutions. Opportunities for AI applications in nuclear medicine related to diagnosis, therapy, and workflow efficiency, as well as emerging challenges and critical responsibilities, are discussed. Establishing and maintaining leadership in AI require a concerted effort to promote the rational and safe deployment of this innovative technology by engaging patients, nuclear medicine physicians, scientists, technologists, and referring providers, among other stakeholders, while protecting our patients and society. This strategic plan was prepared by the AI task force of the Society of Nuclear Medicine and Molecular Imaging.

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure.

PURPOSE: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. RESULTS: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. CONCLUSION: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.

18F-FDG PET Maximum-Intensity Projections and Artificial Intelligence: A Win-Win Combination to Easily Measure Prognostic Biomarkers in DLBCL Patients.

Total metabolic tumor volume (TMTV) and tumor dissemination (Dmax) calculated from baseline 18F-FDG PET/CT images are prognostic biomarkers in diffuse large B-cell lymphoma (DLBCL) patients. Yet, their automated calculation remains challenging. The purpose of this study was to investigate whether TMTV and Dmax features could be replaced by surrogate features automatically calculated using an artificial intelligence (AI) algorithm from only 2 maximum-intensity projections (MIPs) of the whole-body 18F-FDG PET images. Methods: Two cohorts of DLBCL patients from the REMARC (NCT01122472) and LNH073B (NCT00498043) trials were retrospectively analyzed. Experts delineated lymphoma lesions from the baseline whole-body 18F-FDG PET/CT images, from which TMTV and Dmax were measured. Coronal and sagittal MIP images and associated 2-dimensional reference lesion masks were calculated. An AI algorithm was trained on the REMARC MIP data to segment lymphoma regions. The AI algorithm was then used to estimate surrogate TMTV (sTMTV) and surrogate Dmax (sDmax) on both datasets. The ability of the original and surrogate TMTV and Dmax to stratify patients was compared. Results: Three hundred eighty-two patients (mean age ± SD, 62.1 y ± 13.4 y; 207 men) were evaluated. sTMTV was highly correlated with TMTV for REMARC and LNH073B datasets (Spearman r = 0.878 and 0.752, respectively), and so were sDmax and Dmax (r = 0.709 and 0.714, respectively). The hazard ratios for progression free survival of volume and MIP-based features derived using AI were similar, for example, TMTV: 11.24 (95% CI: 2.10-46.20), sTMTV: 11.81 (95% CI: 3.29-31.77), and Dmax: 9.0 (95% CI: 2.53-23.63), sDmax: 12.49 (95% CI: 3.42-34.50). Conclusion: Surrogate TMTV and Dmax calculated from only 2 PET MIP images are prognostic biomarkers in DLBCL patients and can be automatically estimated using an AI algorithm.

Quantitative assessment of radionuclide production yields in in-beam and offline PET measurements at different proton irradiation facilities.

Objective. Reliable radionuclide production yield data are a prerequisite for positron-emission-tomography (PET) basedin vivoproton treatment verification. In this context, activation data acquired at two different treatment facilities with different imaging systems were analyzed to provide experimentally determined radionuclide yields in thick targets and were compared with each other to investigate the impact of the respective imaging technique.Approach.Homogeneous thick targets (PMMA, gelatine, and graphite) were irradiated with mono-energetic proton pencil-beams at two distinct energies. Material activation was measured (i)in-beamduring and after beam delivery with a double-head prototype PET camera and (ii)offlineshortly after beam delivery with a commercial full-ring PET/CT scanner. Integral as well as depth-resolvedß+-emitter yields were determined for the dominant positron-emitting radionuclides11C,15O,13N and (in-beamonly)10C.In-beamdata were used to investigate the qualitative impact of different monitoring time schemes on activity depth profiles and their quantitative impact on count rates and total activity.Main results.Production yields measured with thein-beamcamera were comparable to or higher compared to respectiveofflineresults. Depth profiles of radionuclide-specific yields obtained from thedouble-headcamera showed qualitative differences to data acquired with thefull-ringcamera with a more convex profile shape. Considerable impact of the imaging timing scheme on the activity profile was observed for gelatine only with a range variation of up to 3.5 mm. Evaluation of the coincidence rate and the total number of observed events in the considered workflows confirmed a strongly decreasing rate in targets with a large oxygen fraction.Significance. The observed quantitative and qualitative differences between the datasets underline the importance of a thorough system commissioning. Due to the lack of reliable cross-section data, in-house phantom measurements are still considered a gold standard for careful characterization of the system response and to ensure a reliable beam range verification.

Nuclear Medicine and Artificial Intelligence: Best Practices for Evaluation (the RELAINCE Guidelines).

An important need exists for strategies to perform rigorous objective clinical-task-based evaluation of artificial intelligence (AI) algorithms for nuclear medicine. To address this need, we propose a 4-class framework to evaluate AI algorithms for promise, technical task-specific efficacy, clinical decision making, and postdeployment efficacy. We provide best practices to evaluate AI algorithms for each of these classes. Each class of evaluation yields a claim that provides a descriptive performance of the AI algorithm. Key best practices are tabulated as the RELAINCE (Recommendations for EvaLuation of AI for NuClear medicinE) guidelines. The report was prepared by the Society of Nuclear Medicine and Molecular Imaging AI Task Force Evaluation team, which consisted of nuclear-medicine physicians, physicists, computational imaging scientists, and representatives from industry and regulatory agencies.

Prognostic value of lesion dissemination in doxorubicin, bleomycin, vinblastine, and dacarbazine-treated, interimPET-negative classical Hodgkin Lymphoma patients: A radio-genomic study.

We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. We included patients diagnosed with cHL from 2007 to 2020, initially treated with ABVD, with available baseline PET for review, and with at least two FDG avid lesions. Patients with available RNA from diagnostic biopsy were eligible for gene expression analysis. Dmax was deduced from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR = 2.70, 95% CI 1.1-6.63, pValue = 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET-). Among patients with iPET-low Dmax was associated with a 4-year PFS of 90% (95% CI 82.0-98.9) significantly better compared to high Dmax (4-year PFS 72.4%, 95% CI 61.9-84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. In conclusion our results support tumor dissemination measured through Dmax as novel prognostic factor for cHL patients treated with ABVD.

Fibroblast heterogeneity in solid tumors: From single cell analysis to whole-body imaging.

Cancer-Associated Fibroblasts (CAFs) represent the most prominent component of the tumor microenvironment (TME). Recent studies demonstrated that CAF are heterogeneous and composed of different subpopulations exerting distinct functions in cancer. CAF populations differentially modulate various aspects of tumor growth, including cancer cell proliferation, extra-cellular matrix remodeling, metastatic dissemination, immunosuppression and resistance to treatment. Among other markers, the Fibroblast Activation Protein (FAP) led to the identification of a specific CAF subpopulation involved in metastatic spread and immunosuppression. Expression of FAP at the surface of CAF is detected in many different cancer types of poor prognosis. Thus, FAP recently appears as an appealing target for therapeutic and molecular imaging applications. In that context, 68Ga-labeled radiopharmaceutical-FAP-inhibitors (FAPI) have been recently developed and validated for quantitatively mapping FAP expression over the whole-body using Positron Emission Tomography (PET/CT). In this review, we describe the main current knowledge on CAF subpopulations and their distinct functions in solid tumors, as well as the promising diagnostic and therapeutic implications of radionuclides targeting FAP.

Improved 3D tumour definition and quantification of uptake in simulated lung tumours using deep learning.

Objective.In clinical positron emission tomography (PET) imaging, quantification of radiotracer uptake in tumours is often performed using semi-quantitative measurements such as the standardised uptake value (SUV). For small objects, the accuracy of SUV estimates is limited by the noise properties of PET images and the partial volume effect. There is need for methods that provide more accurate and reproducible quantification of radiotracer uptake.Approach.In this work, we present a deep learning approach with the aim of improving quantification of lung tumour radiotracer uptake and tumour shape definition. A set of simulated tumours, assigned with 'ground truth' radiotracer distributions, are used to generate realistic PET raw data which are then reconstructed into PET images. In this work, the ground truth images are generated by placing simulated tumours characterised by different sizes and activity distributions in the left lung of an anthropomorphic phantom. These images are then used as input to an analytical simulator to simulate realistic raw PET data. The PET images reconstructed from the simulated raw data and the corresponding ground truth images are used to train a 3D convolutional neural network.Results.When tested on an unseen set of reconstructed PET phantom images, the network yields improved estimates of the corresponding ground truth. The same network is then applied to reconstructed PET data generated with different point spread functions. Overall the network is able to recover better defined tumour shapes and improved estimates of tumour maximum and median activities.Significance.Our results suggest that the proposed approach, trained on data simulated with one scanner geometry, has the potential to restore PET data acquired with different scanners.