European Journal of Nuclear Medicine and Molecular Imaging

Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery

Abstract Purpose The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. Methods The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. Results The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. Conclusion We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. Trial registration HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995

Homodimeric peptide radiotracer [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 imaging of cervical cancer patients

Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors. Homodimeric peptides have better targeting ability than monomeric peptides, and it is worth exploring whether homodimers of TMVP1 ((TMVP1) In this study, we developed a TMVP1 homodimer that was conjugated with 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) via tetraethyleneglycol (PEG Both molecular docking and cellular experiments showed that homodimeric TMVP1 had a higher affinity for VEGFR-3 than monomeric TMVP1. [ The favorable characterizations of [ ChiCTR-DOD-17012458. Registered August 23, 2017 (retrospectively registered).

Imaging CAR-NK cells targeted to HER2 ovarian cancer with human sodium-iodide symporter-based positron emission tomography

AbstractChimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.

CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology

Abstract Background C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings. Methods A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients’ tumor tissue and investigated possible correlations with SUVmax (by providing Spearman’s rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10). Results One hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05–24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort. Conclusions In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.

Predicting aggressive disease and poor outcome in endometrial cancer using preoperative [18F]FDG PET primary tumor radiomics

Abstract Purpose To develop a [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography (PET) primary tumor radiomic model for predicting disease-specific survival (DSS), and compare it with conventional PET markers in a large endometrial cancer cohort. Methods Radiomic features were extracted from preoperative [ 18 F]FDG PET scans of 489 endometrial cancer patients using a standardized uptake value (SUV) threshold > 2.5 to define primary metabolic tumor volumes (MTVs). A second reader extracted features in 154/489 patients, in which intraclass correlation coefficients (ICCs) were calculated. Radiomic features with ICCs > 0.75 were retained and ComBat harmonization was applied to reduce scanner/protocol effects on the extracted features. Patients were divided into training ( n  = 343) and test ( n  = 146) sets. A radiomic DSS score (R dss ) was developed in the training set using least absolute shrinkage and selection operator (LASSO) Cox regression. A combined model (C dss ), incorporating R dss , PET positive lymph nodes (LN PET ) and preoperative histology risk was constructed using multivariable Cox hazard analyses. Prediction performances were assessed by comparing areas under time-dependent receiver operating characteristic curves (tdROCs AUCs) for R dss , C dss , and conventional PET markers: SUV max , SUV mean , MTV, tumor lesion glycolysis (TLG) and LN PET . Results In the test set, AUCs for 2- and 5-year DSS were higher for R dss (0.855, 0.720) compared to SUV max (0.548, 0.572) and SUV mean (0.549, 0.554) ( p  ≤ 0.04 for all), while similar to MTV (0.863, 0.696), TLG (0.814, 0.672) and LN PET (0.802, 0.626) ( p  ≥ 0.12 for all). C dss predicted 2-year DSS with AUC of 0.909 in the test set, outperforming all conventional imaging markers ( p  ≤ 0.04 for all) except MTV ( p  = 0.29). For 5-year DSS, C dss (AUC: 0.817) outperformed all conventional imaging markers, including MTV (AUC ≤ 0.696, p  ≤ 0.05, for all). Conclusion R dss predicts short-term survival with high accuracy, outperforming tumor SUV max/mean , but not MTV, TLG and LN PET . The combined C dss model yields high accuracy for predicting both short- and long-term survival, outperforming all conventional PET imaging markers.

Lymphoscintigraphy and sentinel lymph node biopsy in vulvar carcinoma: update from a European expert panel

This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-

68Ga-FAPi-46 diffuse bilateral breast uptake in a patient with cervical cancer after hormonal stimulation

Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer

The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62-0.87), 0.59 (0.44-0.76), 0.75 (0.60-0.90), and 0.71 (0.56-0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37-0.78), 0.82 (0.68-0.95), 0.77 (0.61-0.94), 0.85 (0.72-0.98), 0.69 (0.51-0.87), and 0.74 (0.57-0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection.

Value of integrated PET-IVIM MRI in predicting lymphovascular space invasion in cervical cancer without lymphatic metastasis

To evaluate the contributory value of positron emission tomography (PET)-intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the prediction of lymphovascular space invasion (LVSI) in patients with cervical cancer without lymphatic metastasis. A total of 90 patients with cervical cancer without signs of lymph node metastasis on PET/MRI were enrolled in this study. The tumours were classified into LVSI-positive (n = 25) and LVSI-negative (n = 65) groups according to postoperative pathology. The PET-derived parameters (SUV PET-derived parameters (SUV The combination of TLG and D

Tumor lesion detection in patients with cervical cancer by indocyanine green near-infrared imaging

To investigate the feasibility and accuracy of near-infrared fluorescence (NIRF) imaging for detecting the extent of tumor invasion in cervical cancer using indocyanine green (ICG). We enrolled 51 patients who were diagnosed with cervical cancer with FIGO stage IB1-IIA2 disease. Patients were administered indocyanine green (ICG) at a dose of 5 mg/kg 24 h prior to surgery. A customized near-infrared fluorescence (NIRF) imaging system was used to identify the extent of tumor invasion when radical hysterectomy specimens were harvested. The relationship between tumor fluorescence intensity and clinicopathological characteristics was analyzed. Of the 51 enrolled patients, 3 patients did not have residual tumors after cervical conization, and tumor lesions were identified by NIRF imaging in all the remaining 48 patients. The results of NIRF imaging were in agreement with the postoperative pathological findings in 95.8% of the patients with stromal invasion, 100% of those with surgical margin invasion, 100% of those with parametrial tumor involvement, and 100% of patients with uterine corpus invasion. The mean signal-to-background ratio (SBR) of the cervical tumors was 2.91 ± 1.64, and the SBR was independent of clinicopathological characteristics. Fluorescence microscopy confirmed that ICG fluorescence was present in the tumor nests. NIRF imaging enables objective, accurate, and safe identification of tumor invasion during cervical cancer surgery. ClinicalTrials.gov NCT04224467.

Sentinel node detection and imaging concordance in Early-Stage ovarian cancer: A MELISA trial analysis of tracer, timing, and intraoperative gamma camera

To evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [ This was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [ Among 63 patients, sentinel lymph nodes (SLNs) were detected in 79.4% using [ SLN mapping in ovarian cancer using a dual tracer approach is feasible and yields a higher detection rate than single tracers. The gamma camera identified SLN localization mainly in aortic regions. This combination may improve nodal staging in early ovarian cancer and reduce the need for systematic lymphadenectomy. Post-adnexectomy injection is a practical alternative to injection before adnexectomy for immediate surgeries, although caution is needed due to potential variations in lymphatic drainage.

Predicting the early response to neoadjuvant chemotherapy in high-grade serous ovarian cancer by intratumoral habitat heterogeneity based on 18F-FDG PET/CT

To explore the predictive value of intratumoral habitat heterogeneity for the early therapeutic response to neoadjuvant chemotherapy (NACT) in patients with high-grade serous ovarian cancer (HGSOC). A total of 258 patients with HGSOC receiving [ The automatic segmentation model had a Dice coefficient of 0.82 and showed excellent performance in the validation cohort. The predictive efficacy of the subregion model in the test dataset was significantly better than that of the traditional model [Area Under the Curve (AUC): 0.83 vs. 0.71, P = 0.007. There was no statistically significant difference between the union model and the subregion model (AUC: 0.89 vs. 0.83, P = 0.077). Radiomics features involved in the modeling were significantly correlated with Ki67 before NACT (pre-Ki67) and the change value of Ki67 before NACT-after IDS(ΔKi67) respectively (P < 0.05). The PET/CT radiomics model based on habitat analysis can effectively predict the early response to NACT in patients with HGSOC, which can be explained by the tumor proliferative activity and provide reliable imaging biomarkers for individualized treatment decisions.

Surface-engineered erythrocyte membrane-camouflage fluorescent bioprobe for precision ovarian cancer surgery

Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P). AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance. We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.

[68Ga]Ga-FAPI-04 PET/MR imaging strategy in management of Krukenberg tumors (KTs) from gastric signet-ring-cell carcinoma: to overcome limitation of [68Ga]Ga-FAPI-04 PET imaging in KTs

A rare case of intravenous leiomyomatosis extending along the right ovarian vein, right internal iliac, and inferior vena cava to the right atrium observed by [18F]F-FAPI PET/CT

Surgical evidence-based comparison of [68Ga]Ga-FAPI-04 PET and MRI-DWI for assisting debulking surgery in ovarian cancer patients

Imaging assessment of abdominopelvic tumor burden is crucial for debulking surgery decision in ovarian cancer patients. This study aims to compare the efficiency of [ Thirty-six patients with suspected/confirmed ovarian cancer were enrolled and underwent integrated [ [ [

[68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT

To compare the efficacy of [ Forty-nine patients (median age, 57 years; IQR, 51-66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [ Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [ [ NCT05034146. Registered February 23, 2021.

Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer

Abstract Background This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery. Materials and methods Central review was performed by two readers blinded to the received treatment and to the patients’ outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG). Results Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease &lt; 0.25 cm/0.25–2.5 cm/&gt; 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle. Conclusion 18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival. Trial registration NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012

Diagnostic performance of quantitative measures from [18F]FDG PET/CT, [18F]FEC PET/CT, and DW-MRI in the detection of lymph node metastases in endometrial and cervical cancer: data from the MAPPING study

Abstract Purpose To evaluate the diagnostic performance of quantitative measures derived from [ 18 F]FDG PET/CT, [ 18 F]FEC PET/CT, and DW-MRI in the detection of lymph node metastases in endometrial and cervical cancer with comparison to standard visual PET analysis with histology as the reference standard. Methods Subanalysis of quantitative data from the prospective multicentre MAPPING study. Nodal and tumour SUV max from [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT and ADC mean from DW-MRI were documented. Nodal-to-tumour ratios (NTR) and SUV max -to-ADC mean ratio (STAR) were calculated. Optimal cut-offs of quantitative measures were compared to visual assessment on a regional basis using histopathology as the reference standard. Results Scans from 112 patients (36 cervical and 76 endometrial cancers; 340 nodal regions) were eligible for quantitative image analysis. Lower ADC mean on DW-MRI was observed in metastatic nodes for cervical cancer but not for endometrial cancer. Quantitative measures were significantly higher in malignant than benign nodal regions on [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT in endometrial cancer. SUV max cut-offs showed similar performance to visual assessment in the diagnosis of metastatic lymph nodes in endometrial cancer whilst ADC mean cut-offs showed significantly lower specificity than visual assessment. Interobserver agreement was excellent for SUV max measurements on both [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT, but poor for ADC mean on DW-MRI. Conclusion Quantitative measures from [ 18 F]FDG PET/CT, [ 18 F]FEC PET/CT, or DW-MRI did not outperform visual assessment in the detection of nodal metastases in endometrial cancer. Therefore, the implementation of these quantitative measures as standalone diagnostic tools in routine clinical practice is not recommended.

[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer

Abstract Background Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. Patients and methods We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m2). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [18F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. Results Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki following pazopanib indicating reduced radioligand delivery and retention. Conclusions Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.

[18F]FDG PET radiomics to predict disease-free survival in cervical cancer: a multi-scanner/center study with external validation

Abstract Purpose To test the performances of native and tumour to liver ratio (TLR) radiomic features extracted from pre-treatment 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT and combined with machine learning (ML) for predicting cancer recurrence in patients with locally advanced cervical cancer (LACC). Methods One hundred fifty-eight patients with LACC from multiple centers were retrospectively included in the study. Tumours were segmented using the Fuzzy Local Adaptive Bayesian (FLAB) algorithm. Radiomic features were extracted from the tumours and from regions drawn over the normal liver. Cox proportional hazard model was used to test statistical significance of clinical and radiomic features. Fivefold cross validation was used to tune the number of features. Seven different feature selection methods and four classifiers were tested. The models with the selected features were trained using bootstrapping and tested in data from each scanner independently. Reproducibility of radiomics features, clinical data added value and effect of ComBat-based harmonisation were evaluated across scanners. Results After a median follow-up of 23 months, 29% of the patients recurred. No individual radiomic or clinical features were significantly associated with cancer recurrence. The best model was obtained using 10 TLR features combined with clinical information. The area under the curve (AUC), F1-score, precision and recall were respectively 0.78 (0.67–0.88), 0.49 (0.25–0.67), 0.42 (0.25–0.60) and 0.63 (0.20–0.80). ComBat did not improve the predictive performance of the best models. Both the TLR and the native models performance varied across scanners used in the test set. Conclusion [18F]FDG PET radiomic features combined with ML add relevant information to the standard clinical parameters in terms of LACC patient’s outcome but remain subject to variability across PET/CT devices.

A comparative study of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in the diagnostic accuracy and resectability prediction of ovarian cancer

To provide a theory for guiding clinical treatment by comparing the clinical application value of [ Thirty patients with high clinical suspicion of ovarian malignancies were enrolled from July 2021 to October 2022 and underwent [ There was no significant difference between PET/MR and PET/CT in SUVs [

Comparison of the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study

To compare the diagnostic value of [ Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [ Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [ [

A common [18F]-FDG PET radiomic signature to predict survival in patients with HPV-induced cancers

Locally advanced cervical cancer (LACC) and anal and oropharyngeal squamous cell carcinoma (ASCC and OPSCC) are mostly caused by oncogenic human papillomaviruses (HPV). In this paper, we developed machine learning (ML) models based on clinical, biological, and radiomic features extracted from pre-treatment fluorine-18-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET) images to predict the survival of patients with HPV-induced cancers. For this purpose, cohorts from five institutions were used: two cohorts of patients treated for LACC including 104 patients from Gustave Roussy Campus Cancer (Center 1) and 90 patients from Leeds Teaching Hospitals NHS Trust (Center 2), two datasets of patients treated for ASCC composed of 66 patients from Institut du Cancer de Montpellier (Center 3) and 67 patients from Oslo University Hospital (Center 4), and one dataset of 45 OPSCC patients from the University Hospital of Zurich (Center 5). Radiomic features were extracted from baseline [18F]-FDG PET images. The ComBat technique was applied to mitigate intra-scanner variability. A modified consensus nested cross-validation for feature selection and hyperparameter tuning was applied on four ML models to predict progression-free survival (PFS) and overall survival (OS) using harmonized imaging features and/or clinical and biological variables as inputs. Each model was trained and optimized on Center 1 and Center 3 cohorts and tested on Center 2, Center 4, and Center 5 cohorts. The radiomic-based CoxNet model achieved C-index values of 0.75 and 0.78 for PFS and 0.76, 0.74, and 0.75 for OS on the test sets. Radiomic feature-based models had superior performance compared to the bioclinical ones, and combining radiomic and bioclinical variables did not improve the performances. Metabolic tumor volume (MTV)-based models obtained lower C-index values for a majority of the tested configurations but quite equivalent performance in terms of time-dependent AUCs (td-AUC). The results demonstrate the possibility of identifying common PET-based image signatures for predicting the response of patients with induced HPV pathology, validated on multi-center multiconstructor data.

Head-to-head comparison of [18F]-FDG and [68 Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer

Precise radiological evaluation is pivotal for the management of platinum-sensitive recurrent ovarian cancer. We aimed to compare the value of [ Twenty-nine suspected platinum-sensitive recurrent ovarian cancers were enrolled from January 2022 to July 2022. [ Up to 22 (75.86%) patients displayed inconsistency between two scans. Among them, 4 patients with negative [ [

The role of 18F-FDG-PET/CT in predicting the histopathological response in locally advanced cervical carcinoma treated by chemo-radiotherapy followed by radical surgery: a prospective study

This prospective study aimed to evaluate whether Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUV In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of

Is it time to include [18F]FDG-PET/CT in the diagnostic work-up for lymph node staging in cN0 vulvar cancer patients?

Diagnostic performance of preoperative [18F]FDG-PET/CT for lymph node staging in vulvar cancer: a large single-centre study

Abstract Purpose This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.

Intraoperative near-infrared fluorescence imaging can identify pelvic nerves in patients with cervical cancer in real time during radical hysterectomy

Abstract Purpose Radical hysterectomy combined with pelvic lymphadenectomy is the standard treatment for early-stage cervical cancer, but unrecognized pelvic nerves are vulnerable to irreversible damage during surgery. This early clinical trial investigated the feasibility and safety of intraoperative near-infrared (NIR) fluorescence imaging (NIR-FI) with indocyanine green (ICG) for identifying pelvic nerves during radical hysterectomy for cervical cancer. Methods Sixty-six adults with cervical cancer were enrolled in this prospective, open-label, single-arm, single-center clinical trial. NIR-FI was performed in vivo to identify genitofemoral (GN), obturator (ON), and hypogastric (HN) nerves intraoperatively. The primary endpoint was the presence of fluorescence in pelvic nerves. Secondary endpoints were the ICG distribution in a nerve specimen and potential underlying causes of fluorescence emission in pelvic nerves. Results In total, 63 patients were analyzed. The ON was visualized bilaterally in 100% (63/63) of patients, with a mean fluorescence signal-to-background ratio (SBR) of 5.3±2.1. The GN was identified bilaterally in 93.7% (59/63) of patients and unilaterally in the remaining 4 patients, with a mean SBR of 4.1±1.9. The HN was identified bilaterally in 81.0% (51/63) of patients and unilaterally in 7.9% (5/63) of patients, with a mean SBR of 3.5±1.3. ICG fluorescence was detected in frozen sections of a nerve specimen, and was mainly distributed in axons. No ICG-related complications were observed. Conclusion This early clinical trial demonstrated the feasibility and safety of NIR-FI to visualize pelvic nerves intraoperatively. Thus, NIR-FI may help surgeons adjust surgical decision-making, avoid nerve damage, and improve surgical outcomes. Trial registration ClinicalTrials.gov NCT04224467