Tumor SUVmax Research Articles

18F-FDG PET/CT features of Meigs syndrome induced by ovarian sex cord stromal tumors: a retrospective clinical study

The objective of this study was retrospectively to analyze the clinical characteristics and 18F-FDG PET/CT findings in Meigs syndrome (MS) patients. A total of 21 patients with MS induced by ovarian stromal tumors and 69 patients with pseudo-MS caused by ovarian cancer (OC-PMS) were subjected to evaluation using 18F-FDG PET/CT. Visual and semi-quantitative methods were employed to analyze the PET/CT findings. Visual analysis included recording whether the density of the primary tumor was uniform, whether there were cystic changes and calcifications, and the location of serous fluid accumulation. Semi-quantitative analysis involved the measurement of the tumor size, SUVmax, and SUVmean. No significant difference was observed in the size and density of primary tumors between the MS group and the OC-PMS group. However, the SUVmax and SUVmean of tumors in the MS group were found to be significantly lower than those in the OC-PMS group. The amount of serous cavity effusion caused by ovarian sex cord stromal tumors was found to be unrelated to the size of the tumor, SUVmax, and SUVmean but was positively correlated with the level of Ca125. MS patients have both benign ovarian tumors and ascites and/or pleural effusion, which may be accompanied by elevated Ca125 levels. This should be considered as one of the differential diagnoses for ovarian cancer. Understanding the PET/CT features of MS can facilitate the attainment of an accurate diagnosis before surgery.

Comparison between 18F-FDG PET/CT and diffusion-weighted imaging in detection of invasive ductal breast carcinoma.

Breast carcinoma is the most common type of cancer in females. This study aims to compare fluorine-18-fluorodeoxyglucose (18F-FDG) uptake pattern and apparent diffusion coefficient (ADC) value for the detection of the primary tumour and axillary metastases of invasive ductal breast carcinoma. This study included 40 breast carcinoma lesions taken from 39 patients. After staging by positron emission tomography-computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (MRI), breast surgery with axillary lymph node dissection or sentinel lymph node biopsy was performed. Primary lesion detection rate for PET/CT and diffusion-weighted MRI was high with 39 of 40 lesions (97.5%). The sensitivity and specificity for the detection of metastatic lymph nodes in axilla were 40.9%, 88.9%, with 18F-FDG PET/CT scans and 40.9%, 83.3%, for dw-MRI, respectively. No significant correlation was detected between ADC and SUVmax or SUVmax ratios. Estrogen receptor (p=0.007) and progesterone receptor (p=0.036) positive patients had lower ADC values. Tumour SUVmax was lower in T1 than T2 tumour size (p=0.027) and progesterone receptor-positive patients (p=0.029). Tumour/background SUVmax was lower in progesterone receptor-positive patients (p=0.004). Tumour/liver SUVmax was higher in grade III patients (p=0.035) and progesterone receptor negative status (p=0.043). This study confirmed the high detection rate of breast carcinoma in both modalities. They have same sensitivity for the detection of axillary lymph node metastases, whereas the PET/CT scan had higher specificity. Furthermore, ADC, SUVmax and SUVmax ratios showed some statistical significance among the patient groups according to different pathological parameters.

Long-term assessment of clinical parameters and positron emission tomography parameters in predicting recurrence in uterine cervical cancer patients receiving definitive chemoradiotherapy.

The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy. The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS. With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis. We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max .

Early response monitoring during [177Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study

PurposeTo assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy.MethodsSingle-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021–01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan–Meier methodology (log-rank test).ResultsBetween 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4–26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09–0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07–0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16–0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01–0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02–0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively).ConclusionSix weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.

Low Tmtv Influences Response and Outcomes in R/R DLBCL 3L+ Patients Treated with CAR-T Cells : First Results of FDG-PET/CT Analysis in the French Descar-T Registry

Context : DESCAR-T is a French national registry designed by LYSA/LYSARC including real-life patients receiving commercial CAR T-cells for hematologic malignancies. We initiated a project to conduct a centralized review of Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) performed before CAR T-cells infusion, and during follow-up, to evaluate the impact of several metabolic imaging parameters at baseline and response assessment. Materials and methods : Patients with relapsed/refractory (R/R) DLBCL who initiated at least a third line of therapy (3L+) from the DESCAR-T registry and treated with commercial anti-CD19 CAR T-cells, with at least one central reviewed PET before CAR T-cell infusion (PRE-CAR T), at one month (M1) or three months (M3) after infusion, were included. For each visit, Total Metabolic Tumor Volume (TMTV) and SUVmax of the tumor were measured. Deauville score (DS) and response according to 2014 Lugano classification were registered on follow-up FDG-PET/CT. TMTV optimal cut-off for survival prediction (PFS and OS) was determined using X-tile analysis and association of DS with prognosis was studied. Progression-free survival (PFS) was defined as the time between CAR T-cell infusion and progression during follow-up. Overall survival (OS) was defined as the time between CAR T-cell treatment and death during follow-up. Results : Our analysis included FDG-PET/CT data from 212 R/R DLBCL patients (59 treated with tisagenlecleucel and 153 with axicabtagene ciloleucel). Median follow-up was 24.1 months and overall response rate was 47.1% with 112 patients presenting progression or relapse. On PRECAR-T FDG-PET/CT, the median SUVmax was 16.1 (25th-75th percentiles, 8.55-25.30) and median TMTV was 43.91 cm3 (25th-75th percentiles, 12.79-140.43 cm3). Tumor burden significantly affected survival using a TMTV optimal cut-off of 30 cm3. It was associated with a shorter PFS in patients with PRECAR-T TMTV ≥30 cm3 compared with &amp;lt;30 cm3 (median of 3 vs 22.2 months; p=0.0001; respectively) and a shorter OS (median of 9.4 vs 32 months ; p=0.0001; respectively). Regarding metabolic response at M1, reported in 192 patients, DS 1-3 (n=120; 62.5%) was significantly associated with better PFS and OS than DS4-5 (n=72; 37.5%) (for PFS: median of 1.3 vs 21.8 months ; p&amp;lt;0.0001; for OS: median of 4.5 vs 30.6 months; p&amp;lt;0.0001). Of note, considering only DS5 (n=46; 24%) as unequivocally insufficient response onM1 evaluation, identified patients with the poorest outcomes (for PFS: median of 0 month vs 21.2 months ; p&amp;lt;0.0001; for OS: median of 4.5 months vs 31.1 months; p&amp;lt;0.0001). Conclusion : Low PRECAR-T TMTV influences response and retains its predictive and prognostic value in R/R DLBCL patients treated with anti-CD19 CAR T-cells. Moreover, metabolic response assessed with DS is significantly associated with patients' outcome.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation

PurposeDisease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20–40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression. Materials/MethodsPublished CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122). Features were associated with progression-free survival (PFS) using bootstrapped Cox regression (Bonferroni-corrected univariate predictor: p ≤ 0.002) and only non-strongly correlated predictors were retained (|Rs|<0.70) in forward-stepwise multivariate analysis. ResultsTumor diameter and SUVmax were the two most frequently reported features associated with progression/survival (in 6/20 and 10/20 identified studies). These two features and 12 of the 15 additional features (CT: 6; PET: 6) were candidate PFS predictors. A re-fitted model including diameter and SUVmax presented with the best performance (c-index: 0.78; log-rank p-value < 0.0001). A model built with the two best additional features (CTspiculation1 and SUVentropy) had a c-index of 0.75 (log-rank p-value < 0.0001). ConclusionsA re-fitted pre-treatment model using the two most frequently published features – tumor diameter and SUVmax – successfully stratified early-stage NSCLC patients by PFS after receiving SBRT.

Prognostic Value of Serum Neutrophil to Lymphocyte Ratio and SUVmax in Stage I and II Colon Cancer.

This study aimed to evaluate the correlation between maximal standardized uptake value (SUVmax) of primary colon cancer and serum neutrophil-to-lymphocyte ratio (NLR), and to assess the prognostic value of SUVmax and serum NLR in stage I and II colon cancer patients. In this retrospective study a total of 128 patients with pathologically confirmed stage I and II colon cancer diagnosed between January 2014 and December 2017 were included. All patients underwent F-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and differential white blood cell (WBC) counts before surgery. The correlations between SUVmax and NLR were assessed. The prognostic value of SUVmax and NLR for predicting recurrence-free survival (RFS) was investigated. The mean NLR was 2.2 ± 1.2, and the mean SUVmax of primary tumor was 15.2 ± 7.9. There was significant correlation between NLR and SUVmax (rho=0.2, p=0.02). Mean follow-up period was 59.8 ± 19.2 months and 12 patients experienced a recurrence. In univariable analysis, NLR (p=0.0084, HR=5.0223, 95% CI=1.5117-16.6853), C-reactive protein (CRP) (p=0.021, HR=4.1115, 95% CI=1.2380-13.6551), carbohydrate antigen 19-9 (CA19-9) (p=0.0134, HR=4.2683, 95% CI=1.3519-13.4766), and Kirsten ras sarcoma viral oncogene (KRAS) mutation (p=0.0338, HR=3.4703, 95% CI=1.0998-10.9499) were significant prognostic factors for the recurrence. In multivariable analysis, NLR (p=0.0256, HR=4.1155, 95% CI=1.1887-14.2490) and CA19-9 (p=0.0257, HR=4.139, 95% CI=1.1880-14.4200) were independent prognostic factors for the recurrence. Significant correlation was observed between SUVmax of primary colon cancer and serum NLR. Furthermore, in the multivariable analysis conducted on early colon cancer cases, NLR and CA19-9 were found to be independently associated with RFS. This suggested that NLR could be used as a supplementary tool for identifying patients at high risk of recurrence in early colon cancer. However, SUVmax was not associated with prognosis, suggesting that it cannot be used for predicting prognosis in early colon cancer.

The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma

BackgroundOwing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment.ResultsThe established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05).ConclusionsThe proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.

Quantitative and clinical implications of the EARL2 versus EARL1 [18F]FDG PET-CT performance standards in head and neck squamous cell carcinoma

BackgroundThe EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment.MethodsForty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale.ResultsThere was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients.ConclusionsUsing the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.

Simultaneous 18F-FDG PET/MRI Radiomics and Machine Learning Analysis of the Primary Breast Tumor for the Preoperative Prediction of Axillary Lymph Node Status in Breast Cancer.

In this prospective study, 117 female patients (mean age = 53 years) with 127 histologically proven breast cancer lesions (lymph node (LN) positive = 85, LN negative = 42) underwent simultaneous 18F-FDG PET/MRI of the breast. Quantitative parameters were calculated from dynamic contrast-enhanced (DCE) imaging (tumor Mean Transit Time, Volume Distribution, Plasma Flow), diffusion-weighted imaging (DWI) (tumor ADCmean), and PET (tumor SUVmax, mean and minimum, SUVmean of ipsilateral breast parenchyma). Manual whole-lesion segmentation was also performed on DCE, T2-weighted, DWI, and PET images, and radiomic features were extracted. The dataset was divided into a training (70%) and a test set (30%). Multi-step feature selection was performed, and a support vector machine classifier was trained and tested for predicting axillary LN status. 13 radiomic features from DCE, DWI, T2-weighted, and PET images were selected for model building. The classifier obtained an accuracy of 79.8 (AUC = 0.798) in the training set and 78.6% (AUC = 0.839), with sensitivity and specificity of 67.9% and 100%, respectively, in the test set. A machine learning-based radiomics model comprising 18F-FDG PET/MRI radiomic features extracted from the primary breast cancer lesions allows high accuracy in non-invasive identification of axillary LN metastasis.

18F]NaF PET/CT imaging of response to single fraction SABR to bone metastases from breast cancer.

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level.

Effects of somatostatin analogs on uptake of radiolabeled somatostatin analogs on imaging: a systematic review and meta-analysis.

The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients. The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 vs. 7.62±2.12, P=0.001) and spleen (25.74±7.14 vs. 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique. Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.

Machine Learning Based Prediction of Distant Metastasis in Rectal Cancer Patients with Complete Response following Neoadjuvant Chemoradiotherapy

Distant metastasis (DM) is the leading cause of disease recurrence in rectal cancer patients with clinical or pathological complete response (CR) following neoadjuvant chemoradiotherapy (nCRT). Identifying these patients may help to tailor the treatment approach. The aim of this study was to predict the rectal cancer patients with high risk of DM following CR with nCRT, using machine learning (ML), based on patient, disease and treatment related clinical factors. Data of the rectal cancer patients treated with nCRT at three academic centers between 2010-2022 were collected. Patients with secondary malignancies were excluded. 157 patients with CR were included in the analysis. Median age was 63 (31-85). Female/male ratio was 59/98. Tumor location was proximal-, mid- and distal-rectum in 9, 65 and 83 patients, respectively. cT stage was T2, T3 and T4 in 14, 120 and 23 patients, respectively. 122 patients had cN (+). Median tumor and regional lymph nodes doses were 50.4 (45-56) Gy and 45 (45-50.4) Gy, respectively, in 25-28 fractions, concurrently with capecitabine. 63 patients had clinical CR and were followed up without surgery, and 94 had pathological CR. Median RT-surgery interval was 11 (3.4-59) weeks. 41 patients were managed with total neoadjuvant treatment and 52 received adjuvant systemic treatment. Median follow up time was 37 (3-143) months. DM was detected in 18 patients at median 14 (2-87) months and local tumor recurrence/progression was seen in 9. A ML model was used to predict DM based on patient, disease and treatment related 37 clinical factors. Statistical analysis was conducted using Python (v.3.7). P<0.05 was accepted as statistically significant. Multiple Linear Regression was used to analyze the relationship between DM and independent continuous variables. Chi-square test was used to analyze the difference between the observed frequency distribution of a categorical variable and the expected frequency distribution. Confusion matrix algorithm was used to evaluate the performance of the model. Logistic regression algorithm (LRA) was selected as the best performing algorithm for the ML model that used 37 variables from 157 patients. The model was trained using 75% of the data and the remaining 25% was used for testing. CEA, ratio of post- to pre-RT tumor SUVmax, tumor dose, RT-surgery interval, pre-RT weight loss, smoking history, cN status, and gender were significant parameters to predict DM, based on the LRA of the ML model. Accuracy score of the model was 92% and AUC of the ROC was 74%. Precision (positive predictive value) and recall (sensitivity) of the model were 67% and 50%, respectively. Machine learning has a high rate of correctly classifying patients and good performance in predicting those with DM. Further studies with larger patient numbers are needed.

Validation of the ΔSUVmax for Interim PET Interpretation in Diffuse Large B-Cell Lymphoma on the Basis of the GAINED Clinical Trial.

The GAINED phase 3 trial (ClinicalTrials.gov identifier: NCT01659099) evaluated a PET-driven consolidative strategy in patients with diffuse large B-cell lymphoma. In this post hoc analysis, we aimed to compare the prognostic value of the per-protocol PET interpretation criteria (Menton 2011 consensus) with the change in the SUVmax (ΔSUVmax) alone. Methods: Real-time central review of 18F-FDG PET/CT was performed in 581 patients after 2 cycles (PET2) and 4 cycles (PET4) of immunochemotherapy using the Menton 2011 criteria, combining the ΔSUVmax (cutoffs of 66% and 70% at PET2 and PET4, respectively) and the Deauville scale. In "special cases," when the baseline SUVmax was less than 10.0 or the interim residual tumor SUVmax was greater than 5.0, the Menton 2011 experts' consensus agreed that the ΔSUVmax may not be reliable and that the Deauville score is preferable. Prognostic values of Menton 2011 and ΔSUVmax were evaluated by Kaplan-Meier analyses in terms of progression-free survival (PFS). Results: Seventeen percent of patients at PET2 (100/581) and 8% at PET4 (49/581) had PET-negative results by ΔSUVmax but were considered to have PET-positive results according to Menton 2011 with residual SUVmax of greater than 5.0. For the population with PET2-positive results, 2-y PFS was 70% (range, 58%-80%) with ΔSUVmax alone, whereas the outcome tended to be better for those who were considered to have PET-positive results by Menton 2011, 81% (range, 72%-87%). Conversely, all 10 patients with baseline SUVmax of less than 10.0 had PET2-positive results by ΔSUVmax but were considered to have PET2-negative results by Menton 2011. These patients had the same 2-y PFS as patients with PET2-negative/PET4-negative results, indicating that the ΔSUVmax yielded false-positive results in this situation. Conclusion: We recommend the use of the ΔSUVmax alone rather than the Menton 2011 criteria for assessing the interim metabolic response in patients with diffuse large B-cell lymphoma, except when the baseline SUVmax is less than 10.0.

Baseline [18F]FDG PET features are associated with survival and toxicity in patients treated with CAR T cells for large B cell lymphoma.

Chimeric antigen receptor (CAR) T cells have established themselves as an effective treatment for refractory or relapsed large B cell lymphoma (LBCL). Recently, the sDmax, which corresponds to the distance separating the two farthest lesions standardized by the patient's body surface area, has appeared as a prognostic factor in LBCL. This study aimed to identify [18F]FDG-PET biomarkers associated with prognosis and predictive of adverse events in patients treated with CAR T cells. Patients were retrospectively included from two different university hospitals. They were being treated with CAR T cells for LBCL and underwent [18F]FDG-PET just before CAR T cell infusion. Lesions were segmented semi-automatically with a threshold of 41% of the maximal uptake. In addition to clinico-biological features, sDmax, total metabolic tumor volume (TMTV), SUVmax, and uptake intensity of healthy lymphoid organs and liver were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The occurrence of adverse events, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), was reported. Fifty-six patients were included. The median follow-up was 9.7 months. Multivariate analysis showed that TMTV (cut-off of 36 mL) was an independent prognostic factor for PFS (p < 0.001) and that sDmax (cut-off of 0.15 m-1) was an independent prognostic factor for OS (p = 0.008). Concerning the occurrence of adverse events, a C-reactive protein level > 35 mg/L (p = 0.006) and a liver SUVmean > 2.5 (p = 0.027) before CAR T cells were associated with grade 2 to 4 CRS and a spleen SUVmean > 1.9 with grade 2 to 4 ICANS. TMTV and sDmax had independent prognostic values, respectively, on PFS and OS. Regarding adverse events, the mean liver and spleen uptakes were associated with the occurrence of grade 2 to 4 CRS and ICANS, respectively. Integrating these biomarkers into the clinical workflow could be useful for early adaptation of patients management.

Potential of preoperative fluorodeoxyglucose-positron emission tomography/computed tomography to diagnose contralateral lymph node metastases in patients with oral cancer.

To establish a decision tree using preoperative PET/computed tomography (CT) parameters for detecting contralateral lymph node metastasis (CLNM) in oral cancer patients. In total, 140 patients with a confirmed histopathological diagnosis of oral carcinoma showed fluorodeoxyglucose accumulation of contralateral lymph nodes in PET images. Of 260 lymph nodes, eight were metastatic. We compared metastatic and non-metastatic nodes using Fisher-Freeman-Halton exact and Fisher's exact and Mann-Whitney U tests. The diagnostic performance was analyzed using receiver operating characteristic curves. We established a decision tree using exhaustive chi-squared automatic interaction detection algorithm. Five PET/CT parameters were significantly different between metastatic and non-metastatic nodes: the longest ( P = 0.015) and shortest ( P = 0.023) diameter, and the maximum standardized uptake values (SUVmax) of the contralateral node ( P = 0.030), primary tumor ( P < 0.001), and ipsilateral node ( P < 0.001). The area under the curves of SUVmax of the primary tumor (0.887), ipsilateral node (0.886), and longest diameter (0.752) were the largest and these three parameters were used as predictive criteria in the decision tree. The accuracy of the decision tree was 97.7% with 100% sensitivity and 97.6% specificity. Preoperative PET/CT imaging with a decision tree has the potential to diagnose CLNM in patients with oral cancer.

PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study.

Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n = 7), 200 MBq of [18F]DCFpyl (n = 3), or 200 MBq of [18F]PSMA-1007 (n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n = 40), determined using immunohistochemistry (n = 35) or RNA sequencing (n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUVmax, 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUVmax of tumor by SUVmax of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between invivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood-brain barrier to tracer retention, should still be investigated.

Clinical Utility of Pre-Therapeutic [18F]FDG PET/CT Imaging for Predicting Outcomes in Breast Cancer.

[18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p < 0.01), HER2+ and TNBC subtypes (p < 0.01), high Ki67 (p < 0.01), and low TMTV (p < 0.01). A high TMTV value (>9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3-4.2, p < 0.01). After a median follow-up of 4.5 years, 65 patients experienced recurrence and 39 patients died. High TMTV (>13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9-8.4, p < 0.01). High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients.

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

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. 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. 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. 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.

Radioguided surgery with β decay: A feasibility study in cervical cancer

PurposeRadioguided surgery (RGS) is a technique that helps the surgeon to achieve a tumour resection as complete as possible, by means of the intraoperative detection of particles emitted by a radiotracer that bounds to tumoural cells. This study aimed to investigate the applicability of β-RGS for tumour resection and margin assessment in cervical cancer patients preoperatively injected with [18F]FDG, by means of Monte Carlo simulations. MethodsPatients were retrospectively included if they had a recurrent or persistent cervical cancer, underwent preoperative PET/CT to exclude distant metastases and received radical surgery. All PET/CT images were analysed extracting tumour SUVmax, background SUVmean and tumour-to-non-tumour ratio. These values were used to obtain the expected count rate in a realistic surgical scenario by means of a Monte Carlo simulation of the β probe, assuming the injection of 2 MBq/kg of [18F]FDG 60 min before surgery. ResultsThirty-eight patients were included. A measuring time of ∼2–3 s is expected to be sufficient for discriminating the tumour from background in a given lesion, being this the time the probe has to be over the sample in order to be able to discriminate tumour from healthy tissue with a sensitivity of ∼99% and a specificity of at least 95%. ConclusionThis study presents the first step towards a possible application of our β-RGS technique in cervical cancer. Results suggest that this approach to β-RGS could help surgeons distinguish tumour margins from surrounding healthy tissue, even in a setting of high radiotracer background activity.