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BACKGROUND:
Neuroendocrine tumor (NET) cell lines frequently express both insulin‐like growth factor (IGF) ligand and the cognate IGF‐1 receptor (IGF‐1R) and, as such, potentially depend on the activation of IGF‐1R and its downstream effectors for growth and survival. Preclinical studies suggest that somatostatin analogs and mammalian target of rapamycin (mTOR) inhibitors exhibit antitumor activity against NETs through inhibition of IGF‐1‐dependent signaling, suggesting that IGF‐1R inhibition may be a promising therapeutic approach to NETs. Therefore, the authors of this report evaluated the safety and efficacy of MK‐0646, a fully human monoclonal antibody (MoAb) that binds to the IGF‐1R, as monotherapy in patients with metastatic, well‐differentiated NETs.METHODS:
A phase 2 study was performed in which patients received intravenous MK‐0646 10 mg/kg once weekly over 1 hour. Archived pretreatment tumor tissue was obtained and genotyped for v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol‐3‐kinase, catalytic, alpha polypeptide (PIK3CA); and v‐raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations, and immunohistochemistry was performed to measure the expression IGF‐1R.RESULTS:
Twenty‐five patients received treatment (40% women; median age, 61 years; age range, 37‐83 years), including 15 patients with carcinoid tumors and 10 patients with pancreatic NETs. No partial or complete responses were observed. The median progression‐free survival was 4.2 months in the pancreatic NET cohort (range, 0.7‐6.7 months) and 2.7 months in the carcinoid cohort (range, 2‐3 months). Serious adverse events that were potentially related to MK‐0646 included grade 3/4 hyperglycemia in 8 of 25 patients (32%), grade 2 hypersensitivity reaction in 1 of 24 patients (4%), and grade 3 lipase elevation in 1 of 25 patients (4%).CONCLUSIONS:
Despite a compelling preclinical rationale, MK‐0646 was inactive as a single agent in well‐differentiated NETs. Further studies of MK‐0646 as a monotherapy in unselected NETs are unwarranted. Cancer 2012. © 2012 American Cancer Society. 相似文献The purpose of our study was to retrospectively evaluate and categorize temporal changes in MRI appearances of the prostate in patients who underwent focal therapy with MRI follow-up.
MethodsThe Institutional Review Board approved this retrospective study and waived the requirement for informed consent. Thirty-seven patients (median age 61; 48–70 years) with low-to-intermediate-risk, clinically organ-confined prostate cancer underwent focal ablation therapy from 2009 to 2014. Two radiologists reviewed post-treatment MRIs (n = 76) and categorized imaging features blinded to the time interval between the focal therapy and the follow-up MRI. Inter-reader agreement was assessed (kappa) and generalized linear regression was used to examine associations between an imaging feature being present/absent and days between ablation and MRI.
ResultsInter-reader agreement on MRI features ranged from fair to substantial. Edema was found present at earlier times after ablation (median 16–25 days compared to MRIs without edema, median 252–514 days), as was rim enhancement of the ablation zone (18–22.5 days vs. 409–593 days), a hypointense rim around the ablation zone on T2-weighted images (53-57.5 days vs. 279–409 days) and the presence of an appreciable ablation cavity (48.5–60 days vs. 613–798 days, all p < 0.05). Enhancement of the ablation zone/scar (553–731 days vs. 61.5–162 days) and the formation of a T2-hypointense scar were found to be present on later MRI scans (514–553 days vs. 29–32 days, one reader).
ConclusionsThe MRI appearance of the prostate after focal ablation changes substantially over time. Identification of temporal patterns in the appearance of imaging features should help reduce image interpretation variability and errors when assessing post-therapeutic scans.
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