Building personalized treatment plans for early-stage colorectal cancer patients.

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.

Synchronous and metachronous colorectal cancers: distinct disease entities or different disease courses?

BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Synchronous and Metachronous Colorectal Cancers: Distinct Disease Entities or Different Disease Courses?

BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Microsatellite instability screening should be done for right-sided colon cancer patients less than 60 years of age.

BACKGROUND AND AIMS: Microsatellite analysis is a screening tool used for the identification of Lynch syndrome. We evaluated the occurrence of high-frequency microsatellite instability (MSI-H) in 160 patients with colorectal cancer < or =60 years old to determine if these individuals should be routinely tested for microsatellite instability. MATERIALS AND METHODS: From January 2004 and December 2006, we tested specimens of colorectal cancer from 160 patients under 60 years of age for microsatellite instability. The relationships between clinicopathological parameters and MSI-H status were analyzed. RESULTS: MSI-H occurred in 11.3% (18/160) of the tumors assayed, and colorectal tumors with MSI-H status were located predominantly to the right side (56%, P < 0.001) and had a lower pathological stage (72%, P = 0.011). Of the 18 MSI-H tumors, six displayed characteristic MSI histology. Furthermore, of the 18 MSI-H tumors, instability in BAT-26 was 100%, BAT-25 was 94%, D17S250 was 72%, D2S123 was 68%, and D5S346 was 68%. Of the patients with MSI-H tumors, 55.6% were more than 50 years of age, and about 70% of MSI-H tumors did not display characteristic MSI histology. Importantly, up to 40% of the MSI-H patients in this study would have been overlooked using the revised Bethesda guidelines. The revised Bethesda guidelines, broadened to include patients with right-sided colon cancer, could have identified 94% of the MSI-H tumors in this study. CONCLUSIONS: Colorectal cancers with MSI-H were predominantly located on the right side and had an early pathological stage. The results of this study suggest that microsatellite instability test should be used for all patients under 60 years of age with right-sided colon cancer.