Outcome analysis in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with Lu-177-DOTATATE.

Background: Patients with neuroendocrine tumors (NET) of the gastroenteropancreatic tract (GEP-NET) were effectively treated with peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE in the NETTER-1 trial. The aim of this study was to assess the outcome of metastatic GEP-NET patients within a European Neuroendocrine Tumor Society (ENETS) certified center of excellence after this treatment. Methods: A total of 41 GEP-NET patients who received PRRT with Lu-177-DOTATATE between 2012 and 2017 at a single center were included in this analysis. Data on pre- and post-PRRT treatments [selective internal radiation therapy (SIRT), somatostatin analogue therapy (SSA), blood parameters, patient symptomatic burden and overall survival] was extracted from patient records. Results: Overall, PRRT was well tolerated and did not increase patient symptomatic burden. Blood parameters were not significantly affected by PRRT (means before and after therapy: hemoglobin: 125.4 vs. 122.3 mg/L, P=0.201; creatinine: 73.8 vs. 77.7 µmol/L, P=0.146), while leukocytes (6.6 vs. 5.6 G/L, P<0.01) and platelets (269.9 vs. 216.7 G/L, P<0.001) were significantly decreased yet without clinical significance in our study. Seven of 9 patients with SIRT treatment prior to PRRT were deceased (mortality odds ratio =4.083). The mortality odds ratio of patients with a pancreatic tumor and SIRT was 1.33 compared to patients with a different tumor origin. 6 of 15 patients (40%) with post-PRRT SSA were deceased (mortality odds ratio =0.429 without SSA after PRRT). Conclusions: Patients with advanced GEP-NET might benefit from PRRT with Lu-177-DOTATATE as it can provide a valuable treatment modality in advanced disease stages. Safety profiles of PRRT were manageable without increasing the symptomatic burden. SIRT before PRRT or lack of SSA after PRRT seem to impair the response and reduce survival.

A descriptive analysis of the characteristics, treatment response and prognosis of hepatic dominant solid tumors undergoing selective internal radiation therapy (SIRT).

Background: Selective internal radiotherapy is widely used for liver dominant diseases of solid tumors. However, data about sequential treatment and prognostic factors are lacking. Methods: We consecutively included all 209 patients who received a selective internal radiotherapy intervention between January 2015 and May 2019. A retrospective analysis of their electronic patient records was performed regarding diagnosis of cancer, previous therapies and applied radioactive activity. A multicenter follow-up at least 6 weeks after intervention to assess radiological response and irregular subsequent follow-ups to asses disease progression were conducted. In addition, subgroup analyses were carried out. Results: The most frequently treated indications were hepatocellular carcinoma (37%), colorectal cancers (14%), neuroendocrine tumors (9%), and breast cancer (8%). In hepatocellular carcinoma, selective internal radiotherapy was most performed without prior systemic therapy (40%), and for the remaining indications, most often after surgery with systemic therapy in sequence. Local radiological response, defined as either regression or stable disease, was assessed at least 6 weeks after intervention and showed 52% across all indications. Hepatocellular carcinoma (59%) and breast cancer (67%) showed an excellent, colorectal cancers (29%) a particularly poor response rate. Neuroendocrine tumors showed the third longest median post-selective internal radiation therapy (SIRT) survival with 12.4 months and the second longest median progression-free time with 5.2 months. Hepatocellular carcinoma showed even better results with a post-SIRT survival of 15.7 months and a median progression-free time of 5.3 months. Pancreatic neuroendocrine tumors showed significantly worse outcomes than other neuroendocrine tumors, regarding median post-SIRT survival and median progression-free time. No relevant SIRT related differences among sexes were detected. Conclusions: Patients with neuroendocrine tumors, breast cancer in late therapy lines and early-stage hepatocellular carcinoma seem to show better responses to SIRT than other entities. Colorectal cancers were mainly treated with SIRT in a second or third therapy line but with considerably weaker results than other entities.

Impact of PET data driven respiratory motion correction and BSREM reconstruction of 68Ga-DOTATATE PET/CT for differentiating neuroendocrine tumors (NET) and intrapancreatic accessory spleens (IPAS).

To evaluate whether quantitative PET parameters of motion-corrected 68Ga-DOTATATE PET/CT can differentiate between intrapancreatic accessory spleens (IPAS) and pancreatic neuroendocrine tumor (pNET). A total of 498 consecutive patients with neuroendocrine tumors (NET) who underwent 68Ga-DOTATATE PET/CT between March 2017 and July 2019 were retrospectively analyzed. Subjects with accessory spleens (n = 43, thereof 7 IPAS) and pNET (n = 9) were included, resulting in a total of 45 scans. PET images were reconstructed using ordered-subsets expectation maximization (OSEM) and a fully convergent iterative image reconstruction algorithm with ß-values of 1000 (BSREM1000). A data-driven gating (DDG) technique (MOTIONFREE, GE Healthcare) was applied to extract respiratory triggers and use them for PET motion correction within both reconstructions. PET parameters among different samples were compared using non-parametric tests. Receiver operating characteristics (ROC) analyzed the ability of PET parameters to differentiate IPAS and pNETs. SUVmax was able to distinguish pNET from accessory spleens and IPAs in BSREM1000 reconstructions (p < 0.05). This result was more reliable using DDG-based motion correction (p < 0.003) and was achieved in both OSEM and BSREM1000 reconstructions. For differentiating accessory spleens and pNETs with specificity 100%, the ROC analysis yielded an AUC of 0.742 (sensitivity 56%)/0.765 (sensitivity 56%)/0.846 (sensitivity 62%)/0.840 (sensitivity 63%) for SUVmax 36.7/41.9/36.9/41.7 in OSEM/BSREM1000/OSEM + DDG/BSREM1000 + DDG, respectively. BSREM1000 + DDG can accurately differentiate pNET from accessory spleen. Both BSREM1000 and DDG lead to a significant SUV increase compared to OSEM and non-motion-corrected data.

Fat-pad impingement after total knee arthroplasty with the LCS A/P-Glide system.

Early follow-up (15.8 months;1-48) of 230 knee replacements with an LCS A/P Glide component indicated an increased occurrence of anterior knee pain due to a fat-pad impingement, necessitating early revision surgery. Unsatisfactory results were observed in 28 knees (12.2%). Thirteen knees (5.7%) were revised on finding the fat-pad impingement, and four knees (1.7%) were scheduled for later revision surgery; the remaining 11 subjects (4.8%) had revision surgery for a different reason. Twenty-six subjects (11.3%) complained about milder but typical symptoms of a fat-pad impingement, and 22 subjects (9.6%) had unspecific mild symptoms. 151 knees (65.7%) were free of pain and demonstrated an excellent result. The total revision rate of 10.4% (24 knees) is higher than described for other implant systems. However, the revision needed to treat the fat-pad impingement (5.7%) consisted of minor surgery only, such as exchange of the mobile bearing or reduction of the fat pad by arthroscopy. The femoral and tibial components were able to be left untouched. Resection of the Hoffa's fat pad is recommended when such an implant system is used, and possible impingement should be investigated intraoperatively before closure.