In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 377-377
Abstract:
377 Background: Assignment of patients (pts) with UICC-stage II colorectal cancer (CRC) to adjuvant therapy remains controversial. The clinical utility of histo-pathological parameters (pT 4 , L+, V+) as well as tumor RNA expression signatures like Oncotype Dx Colon Cancer Assay, ColoPrint, or Predictor C is low given their positive predictive value (PPV) of 0.13, 0.22, 0.19, and 0.33, respectively, when adjusted to an incidence of 10% for occurrence of metastatic disease (mets) within 3 years after diagnosis. Methods: We applied deep amplicon sequencing of 48 well-known cancer genes to DNA samples of primary tumors from 173 pts with UICC-stage II CRC using the Illumina MiSeq technology. Patients were selected from a prospective, multicenter clinical diagnostic study named MSKK. More than 6,500 patients with CRC have been recruited into this study conducted by 39 hospitals in Germany. 79 of the 173 pts had progression of disease events within 3 years after R0 resection including 40 pts with mets, 12 pts with local recurrences, and 27 pts with secondary malignancies. 94 pts remained progression-free. Results: Deep sequencing revealed a total of 2,221 sequence variations (SV) including missense, stop, InDel, noncoding, nonsense SV. 401 SV were in COSMIC, 750 SV in normal tissue. The remaining 1471 SV served as basis for development of SV-signatures (SVS) for prediction of progression events in a classical double-nested bootstrap approach in order to generate second order unbiased estimates of performance of SVS, namely sensitivity(S + ), specificity (S - ), PPV, and negative predictive value (NPV). The best SVS for prediction of metastases contained SV in less than 15 genes and has a S + of 0.41, S - of 0.93, PPV of 0.40, and NPV of 0.93 (incidence of metastasis: 10%). The best SVS for prediction any progression event has a S + of 0.33, S - of 0.93, PPV of 0.54, and NPV of 0.84 (incidence for any progression = 20.5%). Conclusions: This deep sequencing based prognostic tissue test with a PPV of 40% and a NPV of 93% represents a milestone over prognostic tests based on RNA expression. The increased PPV leads to more patients being treated correctly with adjuvant therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.4_suppl.377
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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