A systematic review about the role of preoperative 18F-FDG PET/CT for prognosis and risk stratification in patients with endometrial cancer.

OBJECTIVE: To analyse the available literature on the prognostic value of preoperative 18F-FDG PET/CT metabolic parameters and their usefulness in risk stratification in patients with endometrial cancer (EC). MATERIAL AND METHODS: Pubmed searches used "(endometr* OR uter*) AND (PET OR FDG)" as keywords from January-2000 to June-2020. References in included articles were checked for possible publications not included in the first search. Studies evaluating the prognostic value of preoperative 18F-FDG PET/CT and its role for risk stratification in patients with EC were included. Non-original articles (reviews, editorials, letters, legal cases, interviews, case reports, etc.) were not included. RESULTS: Twenty-six studies (1918 patients) were selected according to the inclusion criteria in this review. Thirteen studies (939 patients) related to the prognostic role of preoperative 18F-FDG PET/CT and 14 studies (1036 patients) related to its role in risk stratification were included. Parameters such as SUVmax, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were analysed. CONCLUSIONS: Preoperative SUVmax is useful for non-invasive diagnosis and for deciding the appropriate therapeutic strategy, as it could be used as an independent prognostic marker for recurrence and survival in EC. In addition, both preoperative VTM and GTL could be independent prognostic factors for predicting recurrence and survival, but there is still insufficient scientific evidence. The usefulness of SUVmax for risk stratification is limited (there is insufficient literature that 18F-FDG PET/CT can replace surgical staging), although VTM and GTL are more accurate and have a valuable role in risk stratification of EC. However, larger multicentre studies with adequate follow-up time are needed to confirm these findings.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

OBJECTIVE: as scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). CONCLUSIONS: most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Evolutionary dynamics at the tumor edge reveal metabolic imaging biomarkers.

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

Low-Dose Radioiodine Ablation in Patients with Low-Risk Differentiated Thyroid Cancer.

AIM: Based on the response criteria of the 2015 American Thyroid Associations guidelines, our objectives were to -determine the response rate when using a low dose of -131-I GBq in patients with low-risk differentiated thyroid cancer (LRDTC) and the influence of clinical and analytical variables on the prediction of complete response. METHODS: We performed a multicentre and longitudinal study, including patients who were operated for LRDTC and who underwent radioiodine remnant ablation with a low-dose of 131-I. All patients were assessed at 6-12 months, and their status was classified as complete (excellent response) or incomplete response (structural incomplete, biochemical incomplete or indeterminate response). Various factors including age, gender, histology, tumour focality and size, stage, time from surgery to treatment, type of thyroid-stimulating hormone (TSH) stimulation, preablation serum thyroglobulin (pTg), antiTg antibodies (pAntiTgAb) and TSH (pTSH) levels were also analysed in order to predict the complete response rate. RESULTS: Of 108 patients, 79.6$ achieved complete response and the remaining showed incomplete response (2.9, 5.5 and 12$ due to biochemical incomplete, structural incomplete and indeterminate response respectively). Six patients received a new dose of 131-I. Tumour size and pAntiTgAb were the only factors related to therapeutic response (p = 0.03 and p < 0.01, respectively). However, pAntiTgAb was the only independent factor related to complete -response. Patients with complete response showed lower pTg than those with incomplete response (5.1 ± 12.9 vs. 11.2 ± 25 ng/mL) although without statistical significance (p = 0.14). There was no significant difference in the response rate depending on the thyrotropin stimulation methods. CONCLUSIONS: A low dose of 131-I was sufficient for reaching a complete response at 6-12 months of follow-up in the majority of patients with LRDTC. Tumour size and pAntiTgAb variables were related to therapeutic response.

Role of 99mTc-HYNIC-Tyr3-octreotide scintigraphy in neuroendocrine tumors based on localization of the primary tumor.

BACKGROUND: The aim of our work was to determine the accuracy of 99mTc-HYNIC Tyr3 octreotide scintigraphy (TcOS) in detecting active disease in neuroendocrine tumors (NETs) based on embryological origin of the primary tumor (foregut, midgut or hindgut). METHODS: We analyzed retrospectively 45 studies (12 staging, 26 suspicion of recurrence, and 7 treatment response) belonging to 33 patients with histological confirmation of NETs. Whole body scan and a SPECT-CT were acquired 4 hours post-injection of 740 MBq of 99mTc-HYNIC Tyr3 octreotide. The studies were divided into 3 groups based on the embryological origin of primary tumor (foregut [group 1], midgut [group 2] and hindgut [group 3]). The accuracy of TcOS in each group was assessed, included chi-square analyses. The final diagnosis was established by histopathology or clinical/radiological follow-up greater than 6 months. RESULTS: The localization of the primary tumor per patient revealed that 58% were from the foregut, 30% from the midgut and 12% from the hindgut. In study-based analysis (45 studies), TcOS showed an overall sensitivity, specificity and accuracy of 95%, 92% and 93% respectively. The accuracy per studies for the groups 1, 2 and 3 were: 100%, 92% and 66% respectively, demonstrating a better detection of active disease in primary tumors from foregut and midgut compared to hindgut (P=0.02). CONCLUSIONS: The accuracy of TcOS in the assessment of NETs seems to be better in tumors with foregut and midgut origin, showing a possible relationship between the embryological origin of NETs and detection of active disease by TcOS.