PurposeTo determine the value of 68Ga-DOTA-TOC and 18F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT).MethodsWe evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined 68Ga-DOTA-TOC and 18F-FDG PET/CT studies. 68Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 – 9 months. 18F-FDG PET/CT was done within 2 months of 68Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months).ResultsAll patients were 68Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 18F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were 18F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were 18F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were 18F-FDG-negative initially but 18F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were 18F-FDG-positive initially but 18F-FDG-negative during follow-up (group 4).18F-FDG PET showed more and/or larger metastases than 68Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 – 82 % from the first to the last follow-up investigation.ConclusionIn NET patients, the presence of 18F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with 18F-FDG-negative NET may show 18F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have 18F-FDG-positive tumours. Therefore, 18F-FDG PET/CT is a complementary tool to 68Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation.
PurposeHealth-related quality of life (HRQOL) in differentiated thyroid cancer (DTC) research has so far received little attention and available results are conflicting. We studied the HRQOL of radioiodine-naive DTC patients in comparison with the general population (GP), investigated the course of HRQOL up to 30 months after radioiodine remnant ablation (RAA) and sought to identify patient characteristics associated with HRQOL.MethodsWe analysed data from routine HRQOL monitoring at a nuclear medicine department. Between 2005 and 2013, a total of 439 thyroid cancer patients (all histologies) completed the EORTC Quality of Life Questionnaire Core-30 (QLQ-C30) at least once during their treatment at the department. We compared patients’ baseline HRQOL scores before RAA with scores from age-matched and sex-matched controls from the Austrian GP. We then determined the course of HRQOL over the 30 months after RAA and assessed the impact of the following clinical variables on HRQOL: method of thyroid-stimulating hormone (TSH) stimulation, histology (papillary vs. follicular) and disease stage.ResultsA total of 284 patients (mean age 48.3 years, SD 15.0 years; 71.6 % women; 80.7 % papillary type) with a baseline HRQOL assessment before RAA were available. We found clinically meaningful differences in the detriment in patients on almost all domains. These were largest for fatigue (23 points) and role functioning (25 points). Data from 241 patients (mean age 48.6 years, SD 15.9 years; 68.9 % women; 76.3 % papillary type) were included in the longitudinal analysis. Investigating the course of HRQOL, a significant improvement over time was found for role and emotional functioning, fatigue, pain, and dyspnoea. A range of HRQOL scores were improved in patients with exogenous TSH stimulation, but some scores both in patients with exogenous TSH stimulation and in those followed for 30 months, especially fatigue and role functioning, did not reach levels in the GP sample.ConclusionOur results show that the favourable prognosis of DTC does not directly translate into good HRQOL in these patients. Persistent restrictions in regaining their normal daily life in terms of work and leisure highlight the importance of more detailed investigation of DTC patients’ wellbeing, support needs, and disease experience.
The short chain fatty acid (SCFA) buyrate is a product of colonic fermentation of dietary fibers. It is the main source of energy for normal colonocytes, but cannot be metabolized by most tumor cells. Butyrate also functions as a histone deacetylase (HDAC) inhibitor to control cell proliferation and apoptosis. In consequence, butyrate and its derived drugs are used in cancer therapy. Here we show that aggressive tumor cells that retain the capacity of metabolizing butyrate are positively selected in their microenvironment. In the mouse xenograft model, butyrate-preselected human colon cancer cells gave rise to subcutaneous tumors that grew faster and were more angiogenic than those derived from untreated cells. Similarly, butyrate-preselected cells demonstrated a significant increase in rates of homing to the lung after intravenous injection. Our data showed that butyrate regulates the expression of VEGF and its receptor KDR at the transcriptional level potentially through FoxM1, resulting in the generation of a functional VEGF:KDR autocrine growth loop. Cells selected by chronic exposure to butyrate express higher levels of MMP2, MMP9, ␣2 and ␣3 integrins, and lower levels of E-cadherin, a marker for epithelial to mesenchymal transition. The orthotopic model of colon cancer showed that cells preselected by butyrate are able to colonize the animals locally and at distant organs, whereas control cells can only generate a local tumor in the cecum. Together our data shows that a butyrate-rich microenvironment may select for tumor cells that are able to metabolize butyrate, which are also phenotypically more aggressive.Short chain fatty acids are the final product of bacterial fermentation of dietary fibers (1). Butyrate, a 4-carbon fatty acid, is the main energy source for normal colonocytes (2, 3), which are found in high concentrations in the colonic lumen. It is also thought to be responsible for colorectal cancer prevention, as butyrate can also function as a histone deacetylase (HDAC) 4 inhibitor to inhibit cell proliferation and induce apoptosis of cancer cells (4 -6); probably because of this, cancer cells are normally unable to metabolize butyrate.The anti-tumor effects of butyrate were described in studies using colorectal cancer cell lines, in which butyrate inhibits growth, and induces differentiation and apoptosis (7). In other studies butyrate was able to inhibit tumor growth in vivo in murine models (8, 9). Despite these findings, there is an unresolved paradox concerning the putative protective role of butyrate in colon cancer, colorectal cancers still develop and grow despite the high concentrations of butyrate in the colon. Furthermore, several studies have now shown that butyrate-resistant cells may be selected and give rise to more aggressive cancers (8,10,11). The mechanisms by which cancer cells develop resistance to butyrate and progress remain unknown.Here, we demonstrate that chronic exposure of colon cancer cells to butyrate may result in the selection of more aggressive clones. Our data ...
Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three 68Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these 68Ga-sstr-binding peptides in the imaging setting. On 68Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with 68Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.
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