Individualized prediction of colon cancer recurrence using a nomogram
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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ABSTRACT: The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin (FL). Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting. We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival. A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent). Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer.New England Journal of Medicine 07/2004; 350(23):2343-51. DOI:10.1056/NEJMoa032709 · 54.42 Impact Factor
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ABSTRACT: To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice. An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003. A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology. Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.Journal of Clinical Oncology 09/2004; 22(16):3408-19. DOI:10.1200/JCO.2004.05.063 · 17.88 Impact Factor
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ABSTRACT: The prediction of patient prognosis has always been essential to the practice of medicine. By the early 20th century, Halsted (1) and others believed that solid tumors spread contiguously over time through a series of stages, from the primary tumor site, through the lymphatics, to distant organs, with each stage con- ferring an increasingly poor prognosis. A corollary of this view, supported by later research, was that, at diagnosis (clinical tumor-node-metastasis (TNM) stage) or after surgery (patho- logic TNM stage), tumor size or location (T), regional lymph node involvement (N), and distant metastases (M) were indices of disease spread and could be used to predict patient outcome. In 1953, the French surgeon Pierre Denoix proposed to the Union Internationale Centre le Cancer that these three factors be standardized and integrated into a prognostic system that could be used, with some accommodation for anatomic site, across all solid tumors (2). His proposal for a common language of solid tumor prognosis was adopted as the TNM staging system, which is currently used throughout the world. The TNM system has undergone six revisions and, in the United States, these changes have been guided by the American Joint Committee on Cancer (AJCC), which was established in 1959 and which has published N1, M0} patients. What O'Connell et al. found was that IIb patients had a worse prognosis than IIIa patients. This finding violates the rules of the stage model upon which the TNM system is based. The use of the colon cancer staging in the sixth edition may result in uncertain clinical trials and potentially incorrect patient therapy. Therefore, until the advent of the seventh edition, clinicians and researchers should not use the sixth edition's colon cancer staging; rather, they should rely on the fifth edition, and the AJCC should insert an erratum into the sixth edition. Why did this problem arise? The TNM staging system is based on a temporal model. It assumes the contiguous spread of disease over time (temporal determinism), and it measures time. If a bin with a better prognosis is placed below a bin with a worse prognosis, the result will be the observed crossover in prognosis. How might this temporal error occur? The TNM staging system does not provide information regarding the nat- ural history of the cancer. Rather, it has, since its inception, been a surgical system. The ordering of the patients assumes that all the patients will undergo surgery and no other therapy. The ordering does not take into account which patients received chemotherapy. If one places, in a separate bin, T4 colon cancer (stage IIb), and if there were an effective adjuvant therapy for lymph node-positive (stage IIIa) colon cancer, then the worse survival of the stage IIb and the improved survival of the stage IIIa patients could result in the observed survival crossover. The future utility of the TNM staging system depends on its ability to deal with the increase in population screening for cancer, the discovery of new therapies, and the use of the new molecular (genomic and proteomic) biomarkers. First, the pre- dictive accuracy of the TNM system depends on patients pre- senting across the entire temporal range of the disease. Because the system depends on the temporal progression of tumors for its predictive accuracy, anything that reduces the temporal dimen- sion reduces its accuracy. The early detection of disease because of screening results in a shift in populating the stages to earlier disease so that the majority of patients are in stage I or at most stages I and II. This stage compression reduces the accuracy of the TNM staging system. Adding to the stage compression problem are the trends of very small surgical specimens and to neoadjuvant therapy. Both these changes in the clinical approach to disease further reduceCancerSpectrum Knowledge Environment 11/2004; 96(19):1408-9. DOI:10.1093/jnci/djh293 · 14.07 Impact Factor