Individualized Prediction of Colon Cancer Recurrence Using a Nomogram

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2008; 26(3):380-5. DOI: 10.1200/JCO.2007.14.1291
Source: PubMed

ABSTRACT Estimates of recurrence after curative colon cancer surgery are integral to patient care, forming the basis of cancer staging and treatment planning. The categoric staging system of the American Joint Committee on Cancer (AJCC) is commonly used to convey risk by grouping patients based on anatomic elements. Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence.
An institutional database of 1,320 patients with nonmetastatic colon cancer was used to develop a nomogram to estimate recurrence after curative surgery. Prognostic factors were assessed with multivariable analysis using Cox regression, whereas nonlinear continuous variables were modeled with cubic splines. The model was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve.
The colon cancer recurrence nomogram predicted relapse with a concordance index of 0.77, improving on the stratification provided by either the AJCC fifth or sixth staging scheme. Factors in the model included patient age, tumor location, preoperative carcinoembryonic antigen, T stage, numbers of positive and negative lymph nodes, lymphovascular invasion, perineural invasion, and use of postoperative chemotherapy.
Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.

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    • "Nodal invasion is a critical step for defining colon cancer patients prognosis and therapy. However, 25% of lymph node-negative patients experience recurrence and not all patients with positive lymph nodes have a poor prognosis [30]–[32]. "
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    ABSTRACT: MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor.
    PLoS ONE 06/2014; 9(6):e96670. DOI:10.1371/journal.pone.0096670 · 3.23 Impact Factor
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    • "As expected, adjuvant chemotherapy for the stage III patients improved five-year disease-free survival rates, a finding consistent with those from the randomized clinical trials [2]. In a prognostic nomogram of all stages of colon cancer [13], adjuvant chemotherapy negated the negative prognostic factors of advanced T and N stage, and the c-index was 0.77 in predicting relapse for all stages of colon cancer. Although their reported c-index is promising, the model is driven by a larger proportion of stage I and IIA patients in the cohort and not by the stage III patients. "
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    ABSTRACT: Background The aim of this study was to evaluate clinico-pathologic specific predictors of recurrence for stage II/III disease. Improving recurrence prediction for resected stage II/III colon cancer patients could alter surveillance strategies, providing opportunities for more informed use of chemotherapy for high risk individuals. Methods 871 stage II and 265 stage III patients with colon cancers were included. Features studied included surgery date, age, gender, chemotherapy, tumor location, number of positive lymph nodes, tumor differentiation, and lymphovascular and perineural invasion. Time to recurrence was evaluated, using Cox’s proportional hazards models. The predictive ability of the multivariable models was evaluated using the concordance (c) index. Results For stage II cancer patients, estimated recurrence-free survival rates at one, three, five, and seven years following surgery were 98%, 92%, 90%, and 89%. Only T stage was significantly associated with recurrence. Estimated recurrence-free survival rates for stage III patients at one, three, five, and seven years following surgery were 94%, 78%, 70%, and 66%. Higher recurrence rates were seen in patients who didn’t receive chemotherapy (p = 0.023), with a higher number of positive nodes (p < 0.001). The c-index for the stage II model was 0.55 and 0.68 for stage III. Conclusions Current clinic-pathologic information is inadequate for prediction of colon cancer recurrence after resection for stage II and IIII patients. Identification and clinical use of molecular markers to identify the earlier stage II and III colon cancer patients at elevated risk of recurrence are needed to improve prognostication of early stage colon cancers.
    BMC Cancer 05/2014; 14(1):336. DOI:10.1186/1471-2407-14-336 · 3.36 Impact Factor
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    • "The model is based on an institutional database of 1,320 patients, of whom 243 had developed disease recurrence at last follow-up. The nomogram was developed, validated, and compared with the American Joint Committee on Cancer fifth and sixth editions with a concordance rate of 0.77, with regards to identifying those most at risk for recurrence at 10 years.12 This decision aid takes into account site of disease, preoperative carcinoembryonic antigen, lymphovascular invasion, and perineural invasion (,13 "
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    ABSTRACT: Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence.
    Journal of Cancer 03/2014; 5(4):272-280. DOI:10.7150/jca.8871 · 3.27 Impact Factor
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