Y. Nancy You

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.

MR Imaging for Preoperative Evaluation of Primary Rectal Cancer: Practical Considerations

High-resolution magnetic resonance (MR) imaging plays a pivotal role in the pretreatment assessment of primary rectal cancer. The success of this technique depends on obtaining good-quality high-resolution T2-weighted images of the primary tumor; the mesorectal fascia, peritoneal reflection, and other pelvic viscera; and superior rectal and pelvic sidewall lymph nodes. Although orthogonal axial high-resolution T2-weighted MR images are the cornerstone for the staging of primary rectal cancer, high-resolution sagittal and coronal images provide additional value, particularly in tumors that arise in a redundant tortuous rectum. Coronal high-resolution T2-weighted MR images also improve the assessment of nodal morphology, particularly for superior rectal and pelvic sidewall nodes, and of the relationship between advanced-stage tumors and adjacent pelvic structures. Rectal gel should be used in MR imaging examinations conducted for the staging of polypoid tumors, previously treated lesions, and small rectal tumors. However, it should not be used in examinations performed to stage large or low rectal tumors. Diffusion-weighted imaging is useful for identifying nodes and, occasionally, the primary tumor when the tumor is difficult to visualize with other sequences. Three-dimensional T2-weighted imaging provides multiplanar capability with a superior signal-to-noise ratio compared with two-dimensional T2-weighted imaging.

Adherence to Stage-Specific Treatment Guidelines for Patients With Colon Cancer

PURPOSE Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. We sought to determine rates of and factors associated with adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for colon cancer. PATIENTS AND METHODS Patients within the National Cancer Data Base treated for colon adenocarcinoma (2003 to 2007) were identified. Adherence to stage-specific NCCN guidelines was determined based on disease stage. Hierarchical regression analyses were performed to identify factors predictive of adherence, overtreatment, and undertreatment. RESULTS A total of 173,243 patients were included in the final cohort, 123,953 (71%) of whom were treated according to NCCN guidelines. Patients with stage I disease were more likely to receive guideline-based treatment (96%) than patients with stage II (low risk, 66%; high risk, 36%), III (71%), or IV (73%) disease (P < .001). Adherence to consensus-based guidelines increased over time. Factors associated with adherence across all stages included age, Charlson-Deyo comorbidity index score, later year of diagnosis, and insurance status. Among patients with high-risk stage II or stage III disease, older patients with pre-existing comorbidities and patients with lower socioeconomic status were less likely to be offered adjuvant chemotherapy. Among patients with stage I and II disease, young, healthy patients were more likely to be recommended chemotherapy, in discordance with NCCN guidelines. CONCLUSION Significant variation exists in the treatment of colon cancer, particularly in treatment of high-risk stage II and stage III disease. The impact of nonadherence to guidelines on patient outcomes needs to be further elucidated.

Young-Onset Colorectal Cancer: Is It Time to Pay Attention?

cian note entry; provide alternatives, such as dictation, document scanning, and/or scribes forEMRnotecapture;make the EMR inbox smarter about when, and how, to present messages to PCPs; and train clinic support personnel to manage the same proportion of inbox messages they handled with paper systems and to think whether a message is important or just noise before pushing the soconvenient “Forward-to-PCP” button. If changes are not made to reduce or eliminate these time penalties on PCPs, there will be no PCPs left to penalize.

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.

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.

High prevalence of hereditary cancer syndromes in adolescents and young adults with colorectal cancer

PURPOSE Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. PATIENTS AND METHODS We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. RESULTS Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. CONCLUSION We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.

Association Between Travel Distance and Metastatic Disease at Diagnosis Among Patients With Colon Cancer

PURPOSE Health care access and advanced cancer stage are associated with oncologic outcomes for numerous common cancers. However, the impact of patient travel distance to health care on stage at diagnosis has not been well characterized. METHODS This study used a historical cohort of patients with colon cancer in the National Cancer Data Base from 2003 through 2010. The primary outcome, stage at diagnosis, was evaluated using hierarchical regression modeling. A secondary outcome was time to receipt of initial therapy that was evaluated using Cox shared frailty modeling. RESULTS Among 296,474 patients with colon cancer (mean age, 68 ± 13.6 years; 47.6% male; 78.5% white), 3.9% traveled ≥ 50 miles to the diagnosing facility. Fewer black patients, patients with higher income, and patients with lower education traveled longer distances (trend test P < .001 for all). Patients traveling ≥ 50 miles were more likely to present with metastatic disease compared with those traveling less than 12.5 miles (odds ratio [OR], 1.18; 95% CI, 1.12 to 1.24) or 12.5 to 49.9 miles (OR, 1.18; 95% CI, 1.12 to 1.24). In sensitivity analyses, the association was robust to alternate methods of modeling travel distance (quintile stratification or continuous). Travel distance ≥ 50 miles was also associated with a higher likelihood of earlier initiation of therapy compared with travel distance of less than 12.5 miles (hazard ratio [HR], 1.10; 95% CI, 1.08 to 1.13) or 12.5 to 49.9 miles (HR, 1.11; 95% CI, 1.08 to 1.13). CONCLUSION Advanced colon cancer stage at diagnosis is associated with patient travel distance to health care, which may be a barrier to early cancer screening. Health care reform efforts designed to address only insurance coverage may not mitigate disparities based on difficulties accessing cancer care.

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.