Chung Yuan Hu

Neoadjuvant treatment response as an early response indicator for patients with rectal cancer

PURPOSE Neoadjuvant chemoradiotherapy for rectal cancer is associated with improved local control and may result in complete tumor response. Associations between tumor response and disease control following radical resection should be established before tumor response is used to evaluate treatment strategies. The purpose of this study was to assess and compare oncologic outcomes associated with the degree of pathologic response after chemoradiotherapy. PATIENTS AND METHODS All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasonography, computed tomography, or magnetic resonance imaging) rectal carcinoma diagnosed from 1993 to 2008 at our institution and treated with preoperative chemoradiotherapy and radical resection were identified, and their records were retrospectively reviewed. The median radiation dose was 50.4 Gy with concurrent chemotherapy. Recurrence-free survival (RFS), distant metastasis (DM), and local recurrence (LR) rates were compared among patients with complete (ypT0N0), intermediate (ypT1-2N0), or poor (ypT3-4 or N+) response by using Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. RESULTS In all, 725 patients were classified by tumor response: complete (131; 18.1%), intermediate (210; 29.0%), and poor (384; 53.0%). Age, sex, cN stage, and tumor location were not related to tumor response. Tumor response (complete v intermediate v poor) was associated with 5-year RFS (90.5% v 78.7% v 58.5%; P < .001), 5-year DM rates (7.0% v 10.1% v 26.5%; P < .001), and 5-year LR only rates (0% v 1.4% v 4.4%; P = .002). CONCLUSION Treatment response to neoadjuvant chemoradiotherapy among patients with locally advanced rectal cancer undergoing radical resection is an early surrogate marker and correlate to oncologic outcomes. These data provide guidance with response-stratified oncologic benchmarks for comparisons of novel treatment strategies.

Increasing Disparities in the Age-Related Incidences of Colon and Rectal Cancers in the United States, 1975-2010

IMPORTANCE The overall incidence of colorectal cancer (CRC) has been decreasing since 1998 but there has been an apparent increase in the incidence of CRC in young adults. OBJECTIVE To evaluate age-related disparities in secular trends in CRC incidence in the United States. DESIGN, SETTING, AND PATIENTS A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting at the age of 20 years. SEER*Stat was used to obtain the annual cancer incidence rates, annual percentage change, and corresponding P values for the secular trends. Data were obtained from the National Cancer Institutes SEER registry for all patients diagnosed as having colon or rectal cancer from January 1, 1975, through December 31, 2010 (N = 393 241). MAIN OUTCOME AND MEASURE Difference in CRC incidence by age. RESULTS The overall age-adjusted CRC incidence rate decreased by 0.92% (95% CI, -1.14 to -0.70) between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years, the incidence rates of localized, regional, and distant colon and rectal cancers have increased. An increasing incidence rate was also observed for patients with rectal cancer aged 35 to 49 years. Based on current trends, in 2030, the incidence rates for colon and rectal cancers will increase by 90.0% and 124.2%, respectively, for patients 20 to 34 years and by 27.7% and 46.0%, respectively, for patients 35 to 49 years. CONCLUSIONS AND RELEVANCE There has been a significant increase in the incidence of CRC diagnosed in young adults, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies.

Population-Based Study of Contralateral Prophylactic Mastectomy and Survival Outcomes of Breast Cancer Patients

BACKGROUND Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain. METHODS We used the Surveillance, Epidemiology, and End Results database to identify 107 106 women with breast cancer who had undergone mastectomy for treatment between 1998 and 2003 and a subset of 8902 women who also underwent CPM during the same period. Associations between predictor variables and the likelihood of undergoing CPM were evaluated by use of chi(2) analyses. Risk-stratified (estrogen receptor [ER] status, stage, and age) adjusted survival analyses were performed by using Cox regression. Statistical tests were two-sided. RESULTS In a univariate analysis, CPM was associated with improved disease-specific survival (hazard ratio [HR] of death = 0.63, 95% confidence interval [CI] = 0.57 to 0.69; P < .001). Risk-stratified analysis showed that this association was because of a reduction in breast cancer-specific mortality in women aged 18-49 years with stages I-II ER-negative cancer (HR of death = 0.68, 95% CI = 0.53 to 0.88; P = .004). Five year-adjusted breast cancer survival for this group was improved with CPM vs without (88.5% vs 83.7%, difference = 4.8%). Although rates of contralateral breast cancer among young women with stages I-II disease undergoing CPM were independent of ER status, women with ER-positive tumors in the absence of prophylactic mastectomy also had a lower overall risk for contralateral breast cancer than women with ER-negative tumors (0.46% vs 0.90%, difference = 0.44%; P < .001). CONCLUSIONS CPM is associated with a small improvement in 5-year breast cancer-specific survival mainly in young women with early-stage ER-negative breast cancer. This effect is related to a higher baseline risk of contralateral breast cancer.

Association between adherence to National Comprehensive Cancer Network treatment guidelines and improved survival in patients with colon cancer

The objective of the current study was to examine the impact of adherence to guidelines on stage‐specific survival outcomes in patients with stage III and high‐risk stage II colon cancer. The National Comprehensive Cancer Network (NCCN) has established working, expert consensus, and evidence‐based guidelines for organ‐specific cancer care, including care of patients with colon cancer.

Practical application of a calculator for conditional survival in colon cancer

PURPOSE Conditional survival (CS) estimates provide important prognostic information for clinicians and patients who have survived a period after diagnosis. In this study we performed a contemporary evaluation of conditional survival among colon cancer patients and created a browser-based tool for real-time determination of conditional survival expectancies. PATIENTS AND METHODS Patients with colon adenocarcinoma diagnosed between 1988 and 2000 were identified from the Surveillance Epidemiology End Results (SEER) registry. Conditional survival estimates were calculated by using the multiplicative law of probability after adjustment for age; sex; ethnicity; grade; and American Joint Commission on Cancer, sixth edition stage. A browser-based calculator was constructed. RESULTS A total of 83,419 patients were analyzed. As the time alive after initial treatment increased from 0 to 5 years, significant improvements in CS were observed for patients in all stages except stage I, which was associated with good CS even at diagnosis and which reflected the high likelihood of cure. Notably, adjusted 5-year CS rates improved from 42% to 80% for stage IIIC cancers and from 5% to 48% for stage IV cancers during the first 5 years. Differences in cancer-related CS at diagnosis were identified on the basis of age, ethnicity, and grade, but these differences decreased over time. A browser-based CS calculator was implemented by using the multivariate survival model (concordance index, 0.81). CONCLUSION For patients with colon cancer who survive over time, 5-year, cancer-specific CS improved dramatically, and the greatest improvements were among patients with poorer initial prognoses. These prognostic data are critical to inform patients for non-treatment-related life decisions and to inform treating physicians for planning of follow-up and surveillance strategies.

Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma‐specific CS estimates to help clinicians promote more informed patient decision making.

Comparative Analysis of Lymph Node Metastases in Patients With ypt0-2 Rectal Cancers After Neoadjuvant Chemoradiotherapy

BACKGROUND: Neoadjuvant chemoradiotherapy before total mesorectal excision for rectal cancer is associated with improved local tumor control, primary tumor regression, and pathologic downstaging. Therefore, tumor response in the bowel wall has been proposed to be used to identify patients for organ-preserving strategies. OBJECTIVE: The aim of this study was to determine the rate of residual lymph node involvement following neoadjuvant chemoradiotherapy among patients with ypT0-2 residual bowel wall tumor and to comparatively assess their oncologic outcomes following total mesorectal excision. DESIGN: This is a retrospective consecutive cohort study, 1993 to 2008. SETTING AND PATIENTS: Patients with stage cII to III rectal carcinoma treated with preoperative chemoradiotherapy and total mesorectal excision were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the rate of lymph node metastasis by ypT stage, recurrence-free survival, and the frequencies of distant metastasis and local recurrence. RESULTS: Among all 406 ypT0-2 patients, 66 (16.3%) had lymph node metastasis: 20.8% among ypT2, 17.1% among ypT1, and 9.1% among ypT0 patients. Local recurrences (2.0% vs 5.5%; p = 0.038) but not distant metastases (9.3% vs 13.5%; p = 0.38) occurred more frequently in ypN+ than in ypN0 patients. Recurrence-free survival was 85.2% among ypT0-2N0 and 79.6% for ypT0-2N+ patients (p = 0.28). The lack of difference in recurrence-free survival persisted after covariate adjustment (HR, 1.29; 95% CI, 0.77–2.16; p = 0.37). However, among ypT3-4patients, 5-year recurrence-free survival was significantly lower with lymph node metastasis (HR, 1.51; 95% CI, 1.07–2.12; p = 0.019). LIMITATIONS: Low local recurrence event rate limited further comparison by ypT0-2 subgroups. CONCLUSIONS: Residual mesorectal lymph node metastasis risk remains high even with good neoadjuvant chemoradiotherapy response within the bowel wall. Complete removal of the mesorectal burden results in excellent disease control. Given the uniquely good outcomes with standard therapy among patients with ypT0-2 disease, the use of ypT stage to stratify patients for local excision risks undertreatment of an unacceptably high proportion of patients.

Prognostic value of lymph node evaluation in small bowel adenocarcinoma: analysis of the surveillance, epidemiology, and end results database.

The presence of distant metastases and the completeness of resection are important prognostic factors in patients with small bowel adenocarcinoma (SBA); however, the influence of lymph node metastasis on patient outcome has not been well characterized. The objective of the current study was to evaluate the impact of the number of positive and negative lymph nodes on survival after curative resection.

Assessing the Utility of Cancer-Registry-Processed Cause of Death in Calculating Cancer-Specific Survival

Cancer registries use algorithms to process cause of death (COD) data from death certificates, but uncertainties remain regarding the accuracy and utility of those data in calculating cancer‐specific survival (CSS). Because it is impractical to reconfirm the COD through meticulous review of the primary medical records, the observed cancer deaths could be compared with the number of attributed deaths, as estimated by using a relative survival (RS) approach, to determine utility in CSS estimation.

Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival.

IMPORTANCE With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary. OBJECTIVE To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study using data from the National Cancer Institutes Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64,157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection. MAIN OUTCOMES AND MEASURES Difference in primary tumor resection rates over time. RESULTS Of the 64,157 patients with stage IV CRC, 43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P<.001), and a significant annual percentage change occurred between 1998-2001 and 2001-2010 (-0.41% vs -2.39%; P<.001). Factors associated with primary tumor resection were age younger than 50 years, female sex, being married, higher tumor grade, and presence of colon tumors. Median relative survival rate improved from 8.6% in 1988 to 17.8% in 2009 (P<.001); the annual percentage change was 2.18% in 1988-2001 and 5.43% in 1996-2009 (P<.001). CONCLUSIONS AND RELEVANCE The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.