Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Head-to-Head Comparison of the Diagnostic Performance of FDG PET/CT and FDG PET/MR in Patients With Cancer: A Systematic Review and Meta-Analysis.

Background: The available evidence on the use of FDG PET/MRI performed using an integrated system in patients with cancer has grown substantially. Objective: To perform a systematic review and meta-analysis comparing the diagnostic performance of FDG PET/CT and FDG PET/MRI in patients with cancer. Evidence Acquisition: MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews were searched from July 1, 2015 to January 25, 2023 for studies reporting a head-to-head comparison of the diagnostic performance of FDG PET/CT and FDG PET/MRI in patients with cancer. The two modalities' diagnostic performance was summarized, stratified by performance endpoint. For endpoints with sufficient data, meta-analysis was performed using bivariate modeling to produce summary estimates of pooled sensitivity and specificity. For remaining endpoints, reported performance in individual studies was recorded. Evidence Synthesis: The systematic review included 29 studies with a total of 1656 patients. For patient-level detection of regional nodal metastases (5 studies), pooled sensitivity and specificity for PET/MRI were 88% (95% CI, 74-95%) and 92% (95% CI, 71-98%), respectively, and for PET/CT were 86% (95% CI, 70-94%) and 86% (95% CI, 68-95%), respectively. For lesion-level detection of recurrence and/or metastases (5 studies), pooled sensitivity and specificity for PET/MRI were 94% (95% CI, 78-99%) and 83% (95% CI, 76-88%), respectively, and for PET/CT were 91% (95% CI, 77-96%) and 81% (95% CI, 72-88%), respectively. In individual studies not included in meta-analysis, PET/MRI in comparison with PET/CT showed staging accuracy in breast cancer of 98.0% versus 74.5% and in colorectal cancer of 96.2% versus 69.2%, sensitivity for primary tumor detection in cervical cancer of 93.2% versus 66.2%, and sensitivity, specificity, and accuracy for lesion-level liver metastasis detection of 91.1-98.0% versus 42.3-71.1%, 100.0% versus 83.3-98.6%, and 96.5-98.2% versus 44.7-86.7%, respectively. In three studies, management was more commonly impacted by information from PET/MRI (5.2-11.1%) than PET/CT (0.0-2.6%). Conclusions: PET/MRI showed comparable or superior diagnostic performance versus PET/CT across a range of cancers and endpoints. Clinical Impact: The findings help to identify clinical settings where PET/MRI may provide particular clinical benefit for oncologic evaluation.

Current Applications of PET/MR: Part II: Clinical Applications II.

Due to the major improvements in the hardware and image reconstruction algorithms, positron emission tomography/magnetic resonance imaging (PET/MR) is now a reliable state-of-the-art hybrid modality in medical practice. Currently, it can provide a broad range of advantages in preclinical and clinical imaging compared to single-modality imaging. In the second part of this review, we discussed the further clinical applications of PET/MR. In the chest, PET/MR has particular potential in the oncology setting, especially when utilizing ultrashort/zero echo time MR sequences. Furthermore, cardiac PET/MR can provide reliable information in evaluating myocardial inflammation, cardiac amyloidosis, myocardial perfusion, myocardial viability, atherosclerotic plaque, and cardiac masses. In gastrointestinal and hepato-pancreato-biliary malignancies, PET/MR is able to precisely detect metastases to the liver, being superior over the other imaging modalities. In genitourinary and gynaecology applications, PET/MR is a comprehensive diagnostic method, especially in prostate, endometrial, and cervical cancers. Its simultaneous acquisition has been shown to outperform other imaging techniques for the detection of pelvic nodal metastases and is also a reliable modality in radiation planning. Lastly, in haematologic malignancies, PET/MR can significantly enhance lymphoma diagnosis, particularly in detecting extra-nodal involvement. It can also comprehensively assess treatment-induced changes. Furthermore, PET/MR may soon become a routine in multiple myeloma management, being a one-stop shop for evaluating bone, bone marrow, and soft tissues.

Comparison of 68Ga-DOTATATE Positron Emmited Tomography/Computed Tomography and Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases from Well-Differentiated Neuroendocrine Tumors.

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET (p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.

Value of Dynamic Contrast-Enhanced MRI for Grade Group Prediction in Prostate Cancer: A Radiomics Pilot Study.

RATIONALE AND OBJECTIVES: To determine the role of dynamic contrast-enhanced (DCE) MRI-radiomics in predicting the International Society of Urological Pathology Grade Group (ISUP-GG) in therapy-naïve prostate cancer (PCa) patients. MATERIALS AND METHODS: In this ethics review board-approved retrospective study on two prospective clinical trials between 2017 and 2020, 73 men with suspected/confirmed PCa were included. All participants underwent multiparametric MRI. On MRI, dominant lesions (per PI-RADS) were identified. DCE-MRI radiomic features were extracted from the segmented volumes following the image biomarker standardisation initiative (IBSI) guidelines through 14 time points. Histopathology evaluation on the cognitive-fusion targeted biopsies was set as the reference standard. Univariate regression was done to evaluate potential predictors across all calculated features. Random forest imputation was used for multivariate modelling. RESULTS: 73 index lesions were reviewed. Histopathology revealed 28, 16, 13 and 16 lesions with ISUP-GG-Negative/1/2, ISUP-GG-3, ISUP-GG-4 and ISUP-GG-5, respectively. From the extracted features, total lesion enhancement (TLE), minimum enhancement intensity and Grey-Level Run Length Matrix (GLRLM) were the most significantly different parameters among ISUP-GGs (Neg/1/2 vs 3/4 vs 5). 16 features with significant cross-sectional associations with ISUP-GGs entered the multivariate analysis. The final DCE partitioning model used only four features (lesion sphericity, TLE, GLRLM and Grey-Level Zone Length Matrix). For the binarized diagnosis (ISUP-GG≤2 vs ISUP-GG>2), the accuracy reached 81%. CONCLUSION: DCE-MRI radiomics might be used as a non-invasive tool for aiding pathological grade group prediction in therapy-naïve PCa patients, potentially adding complementary information to PI-RADS for supporting tailored diagnostic pathways and treatment planning.

Comparison of Multiparametric MRI and the Combination of PSMA Plus MRI for the Intraprostatic Diagnosis of Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus MRI (PSMA + MRI) for detecting intraprostatic clinically significant prostate cancer (csPCa). PATIENTS AND METHODS: Relevant databases were searched through November 2023. Only studies directly comparing mpMRI and PSMA + MRI (PET/MRI or PET/CT + mpMRI) were included. A meta-analysis with a random-effects model was used to estimate pooled sensitivity, specificity, and area under the curve for each approach. RESULTS: A total of 19 studies were included. On a patient-level analysis, PSMA + MRI had higher sensitivity (9 studies) than mpMRI for csPCa detection (96% [95% confidence interval (CI): 92%, 98%] vs 89% [95% CI: 81%, 94%]; P = 0.04). The patient-level specificity (4 studies) of PSMA + MRI was 55% (95% CI: 31%-76%) compared with 50% (95% CI: 44%-57%) of mpMRI ( P = 0.67). Region-level sensitivity (10 studies) was 85% (95% CI: 74%-92%) for PSMA + MRI and 71% (95% CI: 58%-82%) for mpMRI ( P = 0.09), whereas specificity (4 studies) was 87% (95% CI: 76%-94%) and 90% (95% CI: 82%-95%), respectively ( P = 0.59). Lesion-level sensitivity and specificity were similar between modalities with pooled data from less than 4 studies. CONCLUSIONS: PSMA + MRI had superior pooled sensitivity and similar specificity for the detection of csPCa compared with mpMRI in this meta-analysis of head-to-head studies.

Predictive [18F]-FDG PET/CT-Based Radiogenomics Modelling of Driver Gene Mutations in Non-small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: To investigate whether [18F]-FDG PET/CT-derived radiomics may correlate with driver gene mutations in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this IRB-approved retrospective study, 203 patients with surgically treated NSCLC who underwent subsequent genomic analysis of the primary tumour at our institution between December 2004 and January 2014 were identified. Of those, 128 patients (mean age 62.4 ± 10.8 years; range: 35-84) received preoperative [18F]-FDG PET/CT as part of their initial staging and thus were included in the study. PET and CT image segmentation and feature extraction were performed semi-automatically with an open-source software platform (LIFEx, Version 6.30, lifexsoft.org). Molecular profiles using different next-generation sequencing (NGS) panels were collected from a web-based resource (cBioPortal.ca for Cancer genomics). Two statistical models were then built to evaluate the predictive ability of [18F]-FDG PET/CT-derived radiomics features for driver gene mutations in NSCLC. RESULTS: More than half (68/128, 53%) of all tumour samples harboured three or more gene mutations. Overall, 55% of tumour samples demonstrated a mutation in TP53, 26% of samples had alterations in KRAS and 17% in EGFR. Extensive statistical analysis resulted in moderate to good predictive ability. The highest Youden Index for TP53 was achieved using combined PET/CT features (0.70), for KRAS using PET features only (0.57) and for EGFR using CT features only (0.60). CONCLUSION: Our study demonstrated a moderate to good correlation between radiomics features and driver gene mutations in NSCLC, indicating increased predictive ability of genomic profiles using combined [18F]-FDG PET/CT-derived radiomics features.

The [18F]F-FDG PET/CT Radiomics Classifier of Histologic Subtypes and Anatomical Disease Origins across Various Malignancies: A Proof-of-Principle Study.

We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients' histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT.

Gastro-Esophageal Cancer: Can Radiomic Parameters from Baseline 18F-FDG-PET/CT Predict the Development of Distant Metastatic Disease?

We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline 18F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent 18F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, 18F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck: The Phase 2 FIND Nonrandomized Controlled Trial.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects. Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022. Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0. Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings. Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%). Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results.

BACKGROUND: The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. METHODS: The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. RESULTS: The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSIONS: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.