The value of metabolic parameters and textural analysis in predicting prognosis in locally advanced cervical cancer treated with chemoradiotherapy.

OBJECTIVE: The aim of the study was to assess the impact of clinical and metabolic parameters derived from 18F-FDG PET/CT (positron emission tomography-computed tomography) in patients with locally advanced cervical cancer (LACC) on prognosis. METHODS: Patients with LACC of stage IB2-IVA treated by primary radiochemotherapy followed by brachytherapy were enrolled in this retrospective study. Indexes derived from standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features of the primary tumor were measured for each patient. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated according to Kaplan-Meier and survival curves were compared using the log-rank test. Uni- and multivariate analyses were performed using the Cox regression model. RESULTS: A total of 116 patients were included. Median follow-up was 58 months (range: 1-129). A total of 36 (31%) patients died. Five-year OS and RFS rates were 69 and 60%, respectively. Univariate analyses indicated that FIGO stage, the presence of hydronephrosis, high CYFRA 21.1 levels, and textural features had a significant impact on OS and RFS. MTV as well as SCC-Ag concentration were also significantly associated with OS. On multivariate analysis, the presence of hydronephrosis, CYFRA 21.1, and sphericity were independent prognostics factors for OS and RFS. Also, SCC-Ag level, MTV, and GLZLM (gray-level zone length matrix) ZLNU (zone length non-uniformity) were significantly associated with OS. CONCLUSION: Classical prognostic factors and tumor heterogeneity on pretreatment PET/CT were significantly associated with prognosis in patients with LACC.

Automatic Skeleton Segmentation in CT Images Based on U-Net.

Bone metastasis, emerging oncological therapies, and osteoporosis represent some of the distinct clinical contexts which can result in morphological alterations in bone structure. The visual assessment of these changes through anatomical images is considered suboptimal, emphasizing the importance of precise skeletal segmentation as a valuable aid for its evaluation. In the present study, a neural network model for automatic skeleton segmentation from bidimensional computerized tomography (CT) slices is proposed. A total of 77 CT images and their semimanual skeleton segmentation from two acquisition protocols (whole-body and femur-to-head) are used to form a training group and a testing group. Preprocessing of the images includes four main steps: stretcher removal, thresholding, image clipping, and normalization (with two different techniques: interpatient and intrapatient). Subsequently, five different sets are created and arranged in a randomized order for the training phase. A neural network model based on U-Net architecture is implemented with different values of the number of channels in each feature map and number of epochs. The model with the best performance obtains a Jaccard index (IoU) of 0.959 and a Dice index of 0.979. The resultant model demonstrates the potential of deep learning applied in medical images and proving its utility in bone segmentation.

Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10-4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10-57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10-89.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials.

Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

Amyloid pet in primary progressive aphasia: case series and systematic review of the literature.

Primary progressive aphasia (PPA) is considered a heterogeneous syndrome, with different clinical subtypes and neuropathological causes. Novel PET biomarkers may help to predict the underlying neuropathology, but many aspects remain unclear. We studied the relationship between amyloid PET and PPA variant in a clinical series of PPA patients. A systematic review of the literature was performed. Patients with PPA were assessed over a 2-year period and classified based on language testing and the International Consensus Criteria as non-fluent/agrammatic (nfvPPA), semantic (svPPA), logopenic variant (lvPPA) or as unclassifiable (ucPPA). All patients underwent a Florbetapir (18-F) PET scan and images were analysed by two nuclear medicine physicians, using a previously validated reading method. Relevant studies published between January 2004 and January 2016 were identified by searching Medline and Web of Science databases. Twenty-four PPA patients were included (13 women, mean age 68.8, SD 8.3 years; range 54-83). Overall, 13/24 were amyloid positive: 0/2 (0%) nfvPPA, 0/4 (0%) svPPA, 10/14 (71.4%) lvPPA and 3/4 (75%) ucPPA (p = 0.028). The systematic review identified seven relevant studies, six including all PPA variants and one only lvPPA. Pooling all studies together, amyloid PET positivity was 122/224 (54.5%) for PPA, 14/52 (26.9%) for nfvPPA, 6/47 (12.8%) for svPPA, 101/119 for lvPPA (84.9%) and 12/22 (54.5%) for ucPPA. Amyloid PET may help to identify the underlying neuropathology in PPA. It could be especially useful in ucPPA, because in these cases it is more difficult to predict pathology. ucPPA is frequently associated with amyloid pathology.