The Potential Role of PSMA-Targeted PET in Salivary Gland Malignancies: An Updated Systematic Review.

BACKGROUND: Recent studies have suggested using positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals for the detection of salivary gland malignancies (SGM), particularly adenoid-cystic carcinoma (ACC). METHODS: The authors conducted an extensive review of the scientific literature to examine the potential diagnostic role of PET/CT using PSMA-targeting radiopharmaceuticals in salivary gland malignancies (SGMs) and adenoid cystic carcinoma (ACC). This study included newly diagnosed SGM patients and those with disease recurrence in their imaging evaluation. RESULTS: This updated systematic review included a total of six studies that examined the diagnostic performance of PSMA-targeted PET/CT in ACC. The articles provided evidence of a high detection rate of PSMA-targeting PET/CT in ACC across all clinical contexts examined. SGMs other than ACC exhibited poorer diagnostic performance. CONCLUSIONS: PSMA-targeted PET/CT seems promising in detecting ACC lesions; moreover, PSMA appears to be a suitable potential target for radioligand therapy. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting radiopharmaceuticals in ACC, as both diagnostic and theragnostic agents.

Diagnostic yield of FAP-guided positron emission tomography in thyroid cancer: a systematic review.

Background: Several recent studies have proposed the possible application of positron emission tomography/computed tomography (PET/CT) administering radiolabelled fibroblast-activation protein (FAP) inhibitors for various forms of thyroid cancer (TC), including differentiated TC (DTC), and medullary TC (MTC). Methods: The authors conducted an extensive literature search of original studies examining the effectiveness of FAP-guided PET/CT in patients with TC. The papers included were original publications exploring the use of FAP-targeted molecular imaging in restaging metastatic DTC and MTC patients. Results: A total of 6 studies concerning the diagnostic yield of FAP-targeted PET/CT in TC (274 patients, of which 247 DTC and 27 MTC) were included in this systematic review. The included articles reported high values of FAP-targeted PET/CT detection rates in TC, ranging from 81 to 100% in different anatomical sites and overall superior to the comparative imaging method. Conclusion: Although there are promising results, the existing literature on the diagnostic accuracy of FAP-guided PET in this context is still quite limited. To thoroughly evaluate its potential significance in TC patients, it is needed to conduct prospective randomized multicentric trials.

Is PET Radiomics Useful to Predict Pathologic Tumor Response and Prognosis in Locally Advanced Cervical Cancer?

This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopathologic features. Methods: The medical records of all consecutive patients with LACC referred between July 2010 and July 2016 were reviewed. [18F]FDG PET/CT was performed before neoadjuvant chemoradiotherapy. Radiomic features were extracted from the primary tumor volumes delineated semiautomatically on the PET images and reduced by factor analysis. A receiver-operating-characteristic analysis was performed, and conventional and radiomic features were dichotomized with Liu's method according to pathologic response (pR) and cancer-specific death. According to the study protocol, only areas under the curve of more than 0.70 were selected for further analysis, including logistic regression analysis for response prediction and Cox regression analysis for survival prediction. Results: A total of 195 patients fulfilled the inclusion criteria. At pathologic evaluation after surgery, 131 patients (67.2%) had no or microscopic (≤3 mm) residual tumor (pR0 or pR1, respectively); 64 patients (32.8%) had macroscopic residual tumor (>3 mm, pR2). With a median follow-up of 76.0 mo (95% CI, 70.7-78.7 mo), 31.3% of patients had recurrence or progression and 20.0% died of the disease. Among conventional PET parameters, SUVmean significantly differed between pathologic responders and nonresponders. Among radiomic features, 1 shape and 3 textural features significantly differed between pathologic responders and nonresponders. Three radiomic features significantly differed between presence and absence of recurrence or progression and between presence and absence of cancer-specific death. Areas under the curve were less than 0.70 for all parameters; thus, univariate and multivariate regression analyses were not performed. Conclusion: In a large series of patients with LACC treated with neoadjuvant chemoradiotherapy followed by surgery, PET radiomic features could not predict histopathologic tumor response and survival. It is crucial to further explore the biologic mechanism underlying imaging-derived parameters and plan a large, prospective, multicenter study with standardized protocols for all phases of the process of radiomic analysis to validate radiomics before its use in clinical routine.

Diagnostic Accuracy of [68Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis.

Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.

Contrast enhanced CT on PET/CT imaging in clinical routine: an international survey.

Aim: To perform an international survey about PET/CT imaging with contrast enhanced CT (PET/ceCT) in clinical routine worldwide. Methods: A questionnaire of ten questions was prepared for health professionals, addressing the following issues: (1) general demographic, hospital, and department information; (2) use and diffusion of PET/ceCT worldwide; (3) factors influencing the use of PET/ceCT. An invitation to the survey was sent to the corresponding authors of NM scientific articles indexed in SCOPUS in 2022 and dedicated to PET/CT imaging. Data were analysed per individual responder. Results: 191 individual responders worldwide participated in this survey. Most of the responders are using PET/ceCT in their center (74%). Interestingly, the relative use of PET/ceCT over the total PET/CT scans has an anti-Gaussian distribution (<20% ceCT and > 80% ceCT were most represented). Most of responders are using PET/ceCT in oncological settings (62%) and irrespectively from radiopharmaceuticals (62%). In most cases, PET/ceCT scans are reported by NM physicians alone or together by NM physicians and radiologists with an integrated report (31%). Conclusion: PET/ceCT imaging is largely used worldwide. Local factors can affect the choice of PET/ceCT in respect to conventional PET/CT imaging. Further cost-benefit analysis could be useful to consider other possible influencing variables, such as technologies, dosimetry, department organization and economics.

Innovations in imaging modalities: a comparative review of MRI, long-axial field-of-view PET, and full-ring CZT-SPECT in detecting bone metastases.

The accurate diagnosis of bone metastasis, a condition in which cancer cells have spread to the bone, is essential for optimal patient care and outcome. This review provides a detailed overview of the current medical imaging techniques used to detect and diagnose this critical condition focusing on three cardinal imaging modalities: positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Each of these techniques has unique advantages: PET/CT combines functional imaging with anatomical imaging, allowing precise localization of metabolic abnormalities; the SPECT/CT offers a wider range of radiopharmaceuticals for visualizing specific receptors and metabolic pathways; MRI stands out for its unparalleled ability to produce high-resolution images of bone marrow structures. However, as this paper shows, each modality has its own limitations. The comprehensive analysis does not stop at the technical aspects, but ventures into the wider implications of these techniques in a clinical setting. By understanding the synergies and shortcomings of these modalities, healthcare professionals can make diagnostic and therapeutic decisions. Furthermore, at a time when medical technology is evolving at a breakneck pace, this review casts a speculative eye towards future advances in the field of bone metastasis imaging, bridging the current state with future possibilities. Such insights are essential for both clinicians and researchers navigating the complex landscape of bone metastasis diagnosis.

Endoscopic Ultrasound-Guided Fine Needle Biopsy in the Diagnostic Work-Up of Deep-Seated Lymphadenopathies and Spleen Lesions: A Monocentric Experience.

EUS-FNB has been introduced in clinical practice as a less invasive diagnostic approach with respect to surgery. We performed a single-center retrospective study on the diagnostic efficacy of EUS-guided FNB, including 171 patients with lymph nodes, splenic, and extranodal lesions that underwent EUS for FNB at our institution. Excluding 12 patients who did not undergo FNB and 25 patients with a previous diagnosis of a solid tumor, we included 134 patients with clinical/radiological suspect of a lymphoproliferative disease, including 20 patients with a previous history of lymphoma. Out of the 134 biopsies, material of diagnostic quality was obtained in 111 procedures (84.3%). Histological examination of the EUS-FNB samples produced an actionable diagnosis in 100 cases (74.6%). Among the patients without an actionable diagnosis, a second, different diagnostic procedure produced a further eight diagnoses of lymphoma. Therefore, the sensitivity of EUS-FNB for diagnosing lymphomas was calculated to be 86.4% (51/59). Assignment of lymphomas to WHO classification subtypes was possible in 47/51 (92%) of the cases. In conclusion, EUS-FNB is an effective procedure for the histological characterization of lesions that are suspected to be lymphoproliferative disease, allowing for an actionable diagnosis in 75% of cases.

Diagnostic Performance of Positron Emission Tomography with Fibroblast-Activating Protein Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis.

Various papers have introduced the use of positron emission tomography (PET) with [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitor (FAPi) radiopharmaceuticals in different subtypes of gastric cancer (GC). Our aim was to assess the diagnostic performance of this novel molecular imaging technique in GC with a systematic review and meta-analysis. A straightforward literature search of papers concerning the diagnostic performance of FAP-targeted PET imaging was performed. Original articles evaluating this novel molecular imaging examination in both newly diagnosed GC patients and GC patients with disease relapse were included. The systematic review included nine original studies, and eight of them were also eligible for meta-analysis. The quantitative synthesis provided pooled detection rates of 95% and 97% for the assessment of primary tumor and distant metastases, respectively, and a pooled sensitivity and specificity of 74% and 89%, respectively, for regional lymph node metastases. Significant statistical heterogeneity among the included studies was found only in the analysis of the primary tumor detection rate (I2 = 64%). Conclusions: Beyond the limitations of this systematic review and meta-analysis (i.e., all the included studies were conducted in Asia, and using [18F]FDG PET/CT as a comparator of the index test), the quantitative data provided demonstrate the promising diagnostic performance of FAP-targeted PET imaging in GC. Nevertheless, more prospective multicentric studies are needed to confirm the excellent performances of FAP-targeted PET in this cluster of patients.

Lung cancer multi-omics digital human avatars for integrating precision medicine into clinical practice: the LANTERN study.

BACKGROUND: The current management of lung cancer patients has reached a high level of complexity. Indeed, besides the traditional clinical variables (e.g., age, sex, TNM stage), new omics data have recently been introduced in clinical practice, thereby making more complex the decision-making process. With the advent of Artificial intelligence (AI) techniques, various omics datasets may be used to create more accurate predictive models paving the way for a better care in lung cancer patients. METHODS: The LANTERN study is a multi-center observational clinical trial involving a multidisciplinary consortium of five institutions from different European countries. The aim of this trial is to develop accurate several predictive models for lung cancer patients, through the creation of Digital Human Avatars (DHA), defined as digital representations of patients using various omics-based variables and integrating well-established clinical factors with genomic data, quantitative imaging data etc. A total of 600 lung cancer patients will be prospectively enrolled by the recruiting centers and multi-omics data will be collected. Data will then be modelled and parameterized in an experimental context of cutting-edge big data analysis. All data variables will be recorded according to a shared common ontology based on variable-specific domains in order to enhance their direct actionability. An exploratory analysis will then initiate the biomarker identification process. The second phase of the project will focus on creating multiple multivariate models trained though advanced machine learning (ML) and AI techniques for the specific areas of interest. Finally, the developed models will be validated in order to test their robustness, transferability and generalizability, leading to the development of the DHA. All the potential clinical and scientific stakeholders will be involved in the DHA development process. The main goals aim of LANTERN project are: i) To develop predictive models for lung cancer diagnosis and histological characterization; (ii) to set up personalized predictive models for individual-specific treatments; iii) to enable feedback data loops for preventive healthcare strategies and quality of life management. DISCUSSION: The LANTERN project will develop a predictive platform based on integration of multi-omics data. This will enhance the generation of important and valuable information assets, in order to identify new biomarkers that can be used for early detection, improved tumor diagnosis and personalization of treatment protocols. ETHICS COMMITTEE APPROVAL NUMBER: 5420 - 0002485/23 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore Ethics Committee. TRIAL REGISTRATION: clinicaltrial.gov - NCT05802771.

Dose-response Analysis in Hepatic Tumors Treated with 90Y-TARE According to a Personalized Dosimetric Workflow: Preliminary Results.

BACKGROUND: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off. METHODS: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values. RESULTS: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn't show sufficient classification capability for response or survival. CONCUSION: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.

18F-FDG primary tumor uptake to improve N status prediction in cT1 non-metastatic non-small cell lung cancer: development and validation of a positron emission tomography model.

Purpose: Occult lymph node involvement is a major issue in the management of non-small cell lung carcinoma (NSCLC), with an estimated prevalence of approximately 2.9-21.6% in 18F-FDG PET/CT series. The aim of the study is to construct a PET model to improve lymph node assessment. Methods: Patients with a non-metastatic cT1 NSCLC were retrospectively included from two centers, one used to constitute the training set, the other for the validation set. The best multivariate model based on Akaike's information criterion was selected, considering age, sex, visual assessment of lymph node (cN0 status), lymph node SUVmax, primary tumor location, tumor size, and tumoral SUVmax (T_SUVmax). A threshold minimizing false pN0 prediction was chosen. This model was then applied to the validation set. Results: In total, 162 patients were included (training set: 44, validation set: 118). A model combining cN0 status and T_SUVmax was selected (AUC 0.907, specificity at threshold: 88.2%). In the validation cohort, this model resulted in an AUC of 0.832 and a specificity of 92.3% versus 65.4% for visual interpretation alone (p = 0.02). A total of two false N0 predictions were noted (1 pN1 and 1 pN2). Conclusion: Primary tumor SUVmax improves N status prediction and could allow a better selection of patients who are candidates for minimally invasive approaches.

Baseline 18F-FDG PET/CT Radiomics in Classical Hodgkin's Lymphoma: The Predictive Role of the Largest and the Hottest Lesions.

This study investigated the predictive role of baseline 18F-FDG PET/CT (bPET/CT) radiomics from two distinct target lesions in patients with classical Hodgkin's lymphoma (cHL). cHL patients examined with bPET/CT and interim PET/CT between 2010 and 2019 were retrospectively included. Two bPET/CT target lesions were selected for radiomic feature extraction: Lesion_A, with the largest axial diameter, and Lesion_B, with the highest SUVmax. Deauville score at interim PET/CT (DS) and 24-month progression-free-survival (PFS) were recorded. Mann-Whitney test identified the most promising image features (p < 0.05) from both lesions with regards to DS and PFS; all possible radiomic bivariate models were then built through a logistic regression analysis and trained/tested with a cross-fold validation test. The best bivariate models were selected based on their mean area under curve (mAUC). A total of 227 cHL patients were included. The best models for DS prediction had 0.78 ± 0.05 maximum mAUC, with a predominant contribution of Lesion_A features to the combinations. The best models for 24-month PFS prediction reached 0.74 ± 0.12 mAUC and mainly depended on Lesion_B features. bFDG-PET/CT radiomic features from the largest and hottest lesions in patients with cHL may provide relevant information in terms of early response-to-treatment and prognosis, thus representing an earlier and stronger decision-making support for therapeutic strategies. External validations of the proposed model are planned.

18F-FDG PET/CT Maximum Tumor Dissemination (Dmax) in Lymphoma: A New Prognostic Factor?

Recently, several studies introduced the potential prognostic usefulness of maximum tumor dissemination (Dmax) measured by 2-deoxy-2-fluorine-18-fluoro-D-glucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Dmax is a simple three-dimensional feature that represents the maximal distance between the two farthest hypermetabolic PET lesions. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane libraries was conducted, including articles indexed up to 28 February 2023. Ultimately, 19 studies analyzing the value of 18F-FDG PET/CT Dmax in patients with lymphomas were included. Despite their heterogeneity, most studies showed a significant prognostic role of Dmax in predicting progression-free survival (PFS) and overall survival (OS). Some articles showed that the combination of Dmax with other metabolic features, such as MTV and interim PET response, proved to better stratify the risk of relapse or death. However, some methodological open questions need to be clarified before introducing Dmax into clinical practice.

Impact of Cold Somatostatin Analog Administration on Somatostatin Receptor Imaging: A Systematic Review.

PURPOSE: The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET. METHODS: After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus. RESULTS: A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (from 6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive. CONCLUSION: Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings.

The Role of Low-Level Laser Therapy in Bone Healing: Systematic Review.

Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone formation remain largely unknown. Factors such as wavelength, energy density, irradiation and frequency of LLLT can influence the cellular mechanisms. Moreover, the effects of LLLT are different according to cell types treated. This review aims to summarize the current knowledge of the molecular pathways activated by LLLT and its effects on the bone healing process. A better understanding of the cellular mechanisms activated by LLLT can improve its clinical application.

Potential Role of PSMA-Targeted PET in Thyroid Malignant Disease: A Systematic Review.

BACKGROUND: Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in radioiodine-refractory thyroid cancer (TC). METHODS: The authors accomplished a comprehensive literature search of original articles concerning the performance of PSMA-targeted PET/CT in TC patients. Original papers exploring this molecular imaging examination in radioiodine-refractory TC patients undergoing restaging of their disease were included. RESULTS: A total of 6 documents concerning the diagnostic performance of PSMA-targeted PET/CT in TC (49 patients) were included in this systematic review. The included articles reported heterogeneous values of PSMA-targeted PET/CT detection rates in TC, ranging from 25% to 100% and overall inferior to [18F]-fluorodeoxyglucose PET/CT when the two molecular imaging examinations were compared. Two studies reported the administration of [177Lu]PSMA-radioligands with theragnostic purpose in three patients. CONCLUSIONS: The available literature data in this setting are limited and heterogeneous. The employment of PET with PSMA-targeting radiopharmaceuticals in this setting did not affect patient management. Nevertheless, prospective multicentric studies are needed to properly assess its potential role in TC patients.

The Emerging Role of PET/CT with PSMA-Targeting Radiopharmaceuticals in Clear Cell Renal Cancer: An Updated Systematic Review.

BACKGROUND: Recent articles proposed the employment of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in clear cell renal cell carcinoma (ccRCC). METHODS: The authors performed a comprehensive literature search of studies on the performance of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Original articles concerning this imaging examination were included in newly diagnosed ccRCC patients and ccRCC patients with disease recurrence. RESULTS: A total of sixteen papers concerning the diagnostic performance of PSMA-targeted PET/CT in ccRCC (331 patients) were included in this systematic review. The included articles demonstrated an excellent detection rate of PSMA-targeting PET/CT in ccRCC. CONCLUSIONS: PSMA-targeted PET/CT seems promising in detecting ccRCC lesions as well as in discriminating the presence of aggressive phenotypes. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting PET/CT in ccRCC.

Predicting time to treatment in follicular lymphoma on watchful waiting using baseline metabolic tumour burden.

PURPOSE: Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. METHODS: We conducted a retrospective study of 54 patients with FL (grade 1-3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34-85), stage was advanced (III-IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. RESULTS: The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51-88) and 64 for WB-TLG (AUC 0.71; 95% CI 52-89) (p < 0.005). The probability of not having started treatment within 24 months was 87% for TMTV < 14 and 53% for TMTV ≥ 14 (p < 0.005). TMTV was independent of the FLIPI score for TTT prediction. Patients with both FLIPI ≥ 2 and TMTV ≥ 14 had only an 18% probability of not having started treatment at 36 months, while this probability was 75% in patients with TMTV < 14. CONCLUSION: Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies.