6 research outputs found
Risk of Colorectal Cancer and Cancer Related Mortality After Detection of Low-risk or High-risk Adenomas, Compared With No Adenoma, at Index Colonoscopy: A Systematic Review and Meta-analysis
BACKGROUND & AIMS: The risk of metachronous colorectal cancer (CRC) among patients with no adenomas, low-risk adenomas (LRAs), or high-risk adenomas (HRAs), detected at index colonoscopy, is unclear. We performed a systematic review and meta-analysis to compare incidence rates of metachronous CRC and CRC-related mortality after a baseline colonoscopy for each group. METHODS: We searched the PubMed, Embase, Google Scholar, and Cochrane databases for studies that reported the incidence of CRC and adenoma characteristics after colonoscopy. The primary outcome was odds of metachronous CRC and CRC-related mortality per 10,000 person-years of follow-up after baseline colonoscopy for all the groups. RESULTS: Our final analysis included 12 studies with 510,019 patients (mean age, 59.2 ± 2.6 years; 55% male; mean duration of follow up, 8.5 ± 3.3 years). The incidence of CRC per 10,000 person-years was marginally higher for patients with LRAs compared to those with no adenomas (4.5 vs 3.4; odds ratio [OR], 1.26; 95% CI, 1.06-1.51; I(2)=0), but significantly higher for patients with HRAs compared to those with no adenoma ( 13.8 vs 3.4; odds ratio [OR], 2.92; 95% CI, 2.31-3.69; I(2)=0 ) and patients with HRAs compared to LRAs (13.81 vs 4.5; OR, 2.35; 95% CI, 1.72-3.20; I(2)=55%). However, the CRC-related mortality per 10,000 person-years did not differ significantly for patients with LRAs compared to no adenomas (OR, 1.15; 95% CI, 0.76-1.74; I(2)=0) but was significantly higher in persons with HRAs compared with LRAs (OR, 2.48; 95% CI, 1.30-4.75; I(2)=38%) and no adenomas (OR, 2.69; 95% CI, 1.87-3.87; I(2)=0). CONCLUSIONS: The results of this systematic review and meta-analysis demonstrate that the risk of metachronous CRC and mortality is significantly higher for patients with HRAs, but this risk is very low in patients with LRAs, comparable to patients with no adenomas. Follow-up of patients with LRAs detected at index colonoscopy should be the same as for persons with no adenomas
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Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.
PurposeRadiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody.Experimental design[225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity.ResultsBiodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line-derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi.Conclusions[225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen-positive and prostate-specific membrane antigen-deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer