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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine
Last Updated: 04/25/2012

SCIENTIFIC ADVANCES

Results of Selected ACRIN Clinical Trials

See http://www.acrin.org/RESEARCHERS/PUBLICATIONS.aspx for additional ACRIN abstracts and posters, invited presentations, editorials, and published manuscripts.

  • National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011:365;395-409. Epub 2011 Jun 29
    http://www.ncbi.nlm.nih.gov/pubmed/21714641

    See also: http://www.cancer.gov/newscenter/pressreleases/2011/NLSTprimaryNEJM

    This study found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray.

  • Hara AK, Kuo MD, Blevins M, Chen MH, Yee J, Dachman A, Menias CO, Siewert B, Cheema JI, Obregon RG, Fidler JL, Zimmerman P, Horton KM, Coakley K, Iyer RB, Halvorsen RA Jr, Casola G, Johnson CD. National CT Colonography Trial (ACRIN 6664): Comparison of three full-laxative bowel preparations in more than 2500 average-risk patients. AJR Am J Roentgenol 2011:196;1076-82.
    http://www.ncbi.nlm.nih.gov/pubmed/21512073

    This study compared the effect of three different full-laxative bowel preparations on patient compliance, residual stool and fluid, reader confidence, and polyp detection at CT colonography (CTC) and found that polyp detection was comparable for all three preparations.

  • Weinstein SP, Hanna LG, Gatsonis C, Schnall MD, Rosen MA, Lehman CD. Frequency of malignancy seen in probably benign lesions at contrast-enhanced breast MR imaging: Findings from ACRIN 6667. Radiology 2010:255;731-7.
    http://www.ncbi.nlm.nih.gov/pubmed/20501712

    This study determined the frequency of malignancy in probably benign lesions seen at MR screening of the contralateral breast in patients with known breast cancer. The frequency of malignancy in MR-detected BI-RADS category 3 lesions was 0.9% (95% confidence interval: 0.02%, 5.14%).

  • Hendrick RE, Pisano ED, Averbukh A, Moran C, Berns EA, Yaffe MJ, Herman B, Acharyya S, Gatsonis C. Comparison of acquisition parameters and breast dose in digital mammography and screen-film mammography in the American College of Radiology Imaging Network digital mammographic imaging screening trial. Am J Roentgenol 2010:194;362-9.
    http://www.ncbi.nlm.nih.gov/pubmed/20093597

    This study compared the technical performance of full-field digital mammography (FFDM) and screen-film mammography. The results show that differences between screen-film mammography and FFDM in compression force and indicated compressed breast thickness were small. On average, FFDM had 22% lower mean glandular dose than screen-film mammography per acquired view, with sizeable variations in average FFDM doses by manufacturer.

Scientific Advances from CIP Grantees

  • Morse DL, Balagurunathan Y, Hostetter G, Trissal M, Tafreshi NK, Burke N, Lloyd M, Enkemann S, Coppola D, Hruby VJ, Gillies RJ, Han H. Identification of novel pancreatic adenocarcinoma cell-surface targets by gene expression profiling and tissue microarray. Biochem Pharmacol 2010:80;748-54.
    http://www.ncbi.nlm.nih.gov/pubmed/20510208

    Pancreatic cancer has a high mortality rate, which is generally related to the initial diagnosis coming at late stage disease combined with a lack of effective treatment options. Using complementary assays of mRNA expression profiling to determine elevated expression in pancreatic cancer tissues relative to normal pancreas tissues, and validation of protein expression by immunohistochemistry on tissue microarray (TMA), the scientists have identified cell-surface targets with potential for imaging and therapeutic agent development. These validated targets have potential for the development of diagnostic imaging and therapeutic agents for pancreatic cancer.

  • Qiao Y, Huang X, Nimmagadda S, Bai R, Staedtke V, Foss CA, Cheong I, Holdhoff M, Kato Y, Pomper MG, Riggins GJ, Kinzler KW, Diaz LA Jr, Vogelstein B, Zhou S. A robust approach to enhance tumor-selective accumulation of nanoparticles. Oncotarget 2011:2;59-68.
    http://www.ncbi.nlm.nih.gov/pubmed/21378416

    While nanoparticles have shown great promise as drug carriers in cancer therapy, their effectiveness is critically dependent on the structural characteristics of the tumor vasculature. In this study it is demonstrated that several agents capable of inducing vascular responses akin to those observed in inflammatory processes enhance the accumulation of nanoparticles in tumors. The vascular-active agents tested in this study included a bacterium, a pro-inflammatory cytokine, and microtubule-destabilizing drugs. Using radiolabeled nanoparticles, the grantees show that such agents can increase the tumor-to-blood ratio of radioactivity by more than 20-fold compared to nanoparticles alone. Moreover, vascular-active agents dramatically improved the therapeutic effect of nanoparticles containing radioactive isotopes or chemotherapeutic agents. This resulted in cures of animals with subcutaneous tumors and significantly prolonged the survival of animals with orthotopic brain tumors.

  • Liu K, Lepin EJ, Wang MW, Guo F, Lin WY, Chen YC, Sirk SJ, Olma S, Phelps ME, Zhao XZ, Tseng HR, Michael van Dam R, Wu AM, Shen CK. Microfluidic-Based 18F-labeling of biomolecules for immuno-positron emission tomography. Mol Imaging 2011:10;168-76.
    http://www.ncbi.nlm.nih.gov/pubmed/21496447

    Methods for tagging biomolecules with fluorine-18 as immuno-positron emission tomography (immunoPET) tracers require tedious optimization of radiolabeling conditions and can consume large amounts of scarce biomolecules. This study describes an improved method using a digital microfluidic droplet generation (DMDG) chip, which provides computer-controlled metering and mixing of fluorine-18 tag, biomolecule, and buffer in defined ratios, allowing rapid scouting of reaction conditions in nanoliter volumes. The identified optimized conditions were then translated to bench-scale, fluorine-18 labeling of a cancer-specific engineered antibody fragments, enabling microPET imaging of tumors in xenografted mice at 0.5 to 4 hours post injection.