Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb 21;8(8):13805-13817.
doi: 10.18632/oncotarget.14638.

Building personalized treatment plans for early-stage colorectal cancer patients

Hung-Hsin Lin  1   2 , Nien-Chih Wei  3 , Teh-Ying Chou  4   5 , Chun-Chi Lin  1   2 , Yuan-Tsu Lan  1   2 , Shin-Ching Chang  1   2 , Huann-Sheng Wang  1   2 , Shung-Haur Yang  1   2 , Wei-Shone Chen  1   2 , Tzu-Chen Lin  1   2 , Jen-Kou Lin  1   2 , Jeng-Kai Jiang  1   2
Affiliations

Building personalized treatment plans for early-stage colorectal cancer patients

Hung-Hsin Lin et al. Oncotarget. .

Abstract

We developed a series of models to predict the likelihood of recurrence and the response to chemotherapy for the personalized treatment of stage I and II colorectal cancer patients. A recurrence prediction model was developed from 235 stage I/II patients. The model successfully distinguished between high-risk and low-risk groups, with a hazard ratio of recurrence of 4.66 (p < 0.0001). More importantly, the model was accurate for both stage I (hazard ratio = 5.87, p = 0.0006) and stage II (hazard ratio = 4.30, p < 0.0001) disease. This model performed much better than the Oncotype and ColoPrint commercial services in identifying patients at high risk for stage II recurrence. And unlike the commercial services, the robust model included recurrence prediction for stage I patients. As stage I/II CRC patients usually do not receive chemotherapy, we generated chemotherapy efficacy prediction models with data from 358 stage III patients. The predictions were highly accurate: the hazard ratio of recurrence for responders vs. non-responders was 4.13 for those treated with FOLFOX (p < 0.0001), and 3.16 (p = 0.0012) for those treated with fluorouracil. We have thus created a prognostic model that accurately identifies patients at high risk for recurrence, and the first accurate chemotherapy efficacy prediction model for individual patients. In the future, complete personalized treatment plans for stage I/II patients may be developed if the drug prediction models generated from stage III patients are verified to be effective for stage I and II patients in prospective studies.

Keywords: colorectal cancer; drug efficacy; microarray; personalized treatment; recurrence.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

N Wei owns company stocks. No potential conflicts of interest were disclosed by the other authors.

Figures

Figure 1
Figure 1. Recurrence prediction separates patient into high-risk and low-risk groups
Disease-free (A) and overall survival (B) of the training samples. Disease-free (C) and overall survival (D) of the test samples. The training (A and B) and blind testing (C and D) performed similarly.
Figure 2
Figure 2
The final performance of the recurrence prediction model including all stage I and II samples is shown in (A) and (B). The performances with separated stage I and II samples are shown in (C) and (D). Patients in stages I and II had similar long-term DFS rates.
Figure 3
Figure 3
Drug efficacy prediction results for 5FU (A) and FOLFOX (B).
See this image and copyright information in PMC

References

    1. Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-Term Survival Results of Surgery Alone Versus Surgery Plus 5-Fluorouracil and Leucovorin for Stage II and Stage III Colon Cancer: Pooled Analysis of NSABP C-01 Through C-05. A Baseline from Which to Compare Modern Adjuvant Trials. Ann Surg Oncol. 2010;17:959–66. - PMC - PubMed
    1. Sargent DJ, Patiyil S, Yothers G, Haller DG, Gray R, Benedetti J, Buyse M, Labianca R, Seitz JF, O'Callaghan CJ, Francini G, Grothey A, O'Connell M, et al. End points for colon cancer adjuvant trials: Observations and recommendations based on individual patient data from 20,898 patients enrolled onto 18 randomized trials from the ACCENT group. J Clin Oncol. 2007;25:4569–74. - PubMed
    1. Manfredi S, Bouvier AM, Lepage C, Hatem C, Dancourt V, Faivre J. Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population. Br J Surg. 2006;93:1115–22. - PubMed
    1. Weiss JM, Schumacher J, Allen GO, Neuman H, Lange EO, Loconte NK, Greenberg CC, Smith MA. Adjuvant chemotherapy for stage II right-sided and left-sided colon cancer: analysis of SEER-medicare data. Ann Surg Oncol. 2014;21:1781–91. - PMC - PubMed
    1. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, Kosary C, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis D, Chen H, et al. SEER Cancer Statistics Review, 1975–2012, National Cancer Institute. Bethesda, MD.: 2015.