Anna M. Leung

AJCC Cancer Staging Manual 7th Edition Criteria for Colon Cancer: Do the Complex Modifications Improve Prognostic Assessment?

BACKGROUND The 7th edition of the AJCC Cancer Staging Manual (AJCC-7) includes substantial changes for colon cancer (CC), which are particularly complex in patients with stage II and III disease. We used a national cancer database to determine if these changes improved prediction of survival. STUDY DESIGN The database of the Surveillance, Epidemiology and End Results Program was queried to identify patients with pathologically confirmed stage I to III CC diagnosed between 1988 and 2008. Colon cancer was staged by the 6(th) edition of the AJCC Cancer Staging Manual (AJCC-6) and then restaged by AJCC-7. Five-year disease-specific survival and overall survival were compared. RESULTS After all exclusion criteria were applied, AJCC-6 and AJCC-7 staging was possible in 157,588 patients (68.9%). Bowkers test of symmetry showed that the number of patients per substage was different for AJCC-6 and AJCC-7 (p < 0.001). The Akaike information criteria comparison showed superior fit with the AJCC-7 model (p < 0.001). However, although AJCC-7 staging yielded a progressive decrease in disease-specific survival and overall survival of patients with stage IIA (86.3% and 72.4%, respectively), IIB (79.4% and 63.2%, respectively), and IIC (64.9% and 54.6%, respectively) CC, disease-specific survival and overall survival of patients with stage IIIA disease increased (89% and 79%, respectively). Subset analysis of patients with >12 lymph nodes examined did not affect this observation. CONCLUSIONS The AJCC-7 staging of CC does not address all survival discrepancies, regardless of the number of lymph nodes examined. Consideration of other prognostic factors is critical for decisions about therapy, particularly for patients with stage II CC.

Effects of surgical excision on survival of patients with stage IV breast cancer.

BACKGROUND Non-palliative resection of the primary tumor in stage IV breast cancer is controversial. Our aim was to determine whether surgery improves survival in stage IV patients. METHODS We reviewed records of all stage IV breast cancer patients (1990-2000) at our institution. Data collection included demographics, metastasis sites, treatment, and survival. Survival was compared between metastasis type, hormonal therapy versus no hormonal therapy, chemotherapy versus no chemotherapy, radiation versus no radiation, and surgery versus no surgery. To ascertain local therapy effects while accounting for chemotherapy, we analyzed survival among chemotherapy alone versus chemotherapy with radiation versus chemotherapy with surgery. We also performed multivariate analysis by multiple linear regression. RESULTS Of 157 patients, 58 (37%) had bone-only metastases, 99 (63%) had visceral metastases. Both groups had a 17-mo median survival. Eighty (51%) received hormonal therapy while 77 (49%) did not. Both groups had a 15-mo median survival. Eighty-four (54%) received chemotherapy with a 25-mo median survival versus 8 mo for 73 (46%) not receiving chemotherapy, Wilcoxon (P < 0.0001), and log-rank (P = 0.02). Fifty-eight (37%) received radiation and 99 (63%) did not, with both groups having a 17-mo median survival. Fifty-two (33%) with surgery to the breast primary had a 25-mo median survival, while 105 (67%) without surgery had a 13-mo median survival, Wilcoxon (P = 0.004) and log-rank (P = 0.06). Among patients receiving chemotherapy, 37 with chemotherapy alone had a 21-mo median survival versus 40 mo for the 14 with chemotherapy and radiation and 22 mo for the 33 with chemotherapy and surgery. These differences were not significant by Wilcoxon (P = 0.41) or log-rank (P = 0.36). Multivariate analysis determined chemotherapy as the only factor associated with improved survival (P = 0.02). CONCLUSION Our data, when standardized for chemotherapy, suggests loco-regional therapy does not improve survival.

Surgery for Distant Melanoma Metastasis

Traditionally, distant metastatic melanoma has a poor prognosis owing to lack of efficacious, U.S. Food and Drug Administration-approved systemic therapy and the limited use of surgical resection as a therapeutic option. More recently, new biological therapies such as vemurafenib (Zelboraf) and ipilimumab (Yervoy) have shown strong promise and dramatically improved the landscape of stage IV melanoma therapy. Although there are numerous single-institution studies advocating the role for therapeutic surgical intervention, many remain skeptical of nonpalliative surgery for metastatic melanoma. Surgical resection of advanced melanoma has been proven to be effective as long as all disease is removed (R0). Patient selection is paramount. The combination of newer systemic therapies and surgical resection is currently under investigation. Understanding the tumor biology of melanoma and its mechanism of metastatic spread is essential to developing the most efficacious treatment strategy.

A 21-year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

OBJECTIVES Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival. METHODS The National Cancer Institutes Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Coxs regression analyses. RESULTS Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013). CONCLUSIONS In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.

Staging of Regional Lymph Nodes in Melanoma A Case for Including Nonsentinel Lymph Node Positivity in the American Joint Committee on Cancer Staging System

IMPORTANCE Survival varies widely in patients with stage III melanoma. The existence of clinical significance for positive nonsentinel lymph node (NSLN) status would warrant consideration for incorporation into the American Joint Committee on Cancer staging system and better prediction of survival. OBJECTIVE To evaluate whether disease limited to sentinel lymph nodes (SLNs) represents different clinical significance than disease spread into NSLNs. DESIGN, SETTING, AND PARTICIPANTS The database of the John Wayne Cancer Institute at Saint Johns Health Center, Santa Monica, California, was queried for all patients with SLNs positive for cutaneous melanoma who subsequently underwent completion lymph node dissection. MAIN OUTCOMES AND MEASURES Disease-free survival, melanoma-specific survival (MSS), and overall survival. RESULTS A total of 4223 patients underwent SLN biopsy from 1986 to 2012. Of these patients, 329 had a tumor-positive SLN. Of the 329, 250 patients (76.0%) had no additional positive nodes and 79 (24.0%) had a tumor-positive NSLN. Factors predictive of NSLN positivity included older age (P = .04), greater Breslow thickness (P < .001), and ulceration (P < .02). Median overall survival was 178 months for the SLN-only positive group and 42.2 months for the NSLN positive group (5-year overall survival, 72.3% and 46.4%, respectively). Median MSS was not reached for the SLN-only positive group and was 60 months for the NSLN positive group (5-year MSS, 77.8% and 49.5%, respectively). On multivariate analysis, NSLN positivity had a strong association with recurrence (hazard ratio [HR], 1.75; 95% CI, 1.23-2.50; P = .002), shorter overall survival (HR, 2.24; 95% CI, 1.48-3.40; P < .001), and shorter MSS (HR, 2.23; 95% CI, 1.46-3.07; P < .001). To further control for the effects of total positive lymph nodes, comparison was done for patients with only N2 disease (2-3 total positive lymph nodes); the results of this comparison confirmed the independent effect of NSLN status (MSS; P = .04). CONCLUSIONS AND RELEVANCE Nonsentinel lymph node positivity is one of the most significant prognostic factors in patients with stage III melanoma. Subclassification of melanoma by NSLN tumor status should be considered for the American Joint Committee on Cancer staging system.

Factors Affecting Number of Lymph Nodes Harvested in Colorectal Cancer

BACKGROUND Lymph node involvement is a highly important prognostic factor in colorectal cancer staging. Examination of a minimum of 12 nodes is recommended for accurate staging. The purpose of this study was to identify factors affecting the number of lymph nodes harvested in colorectal cancer specimens. MATERIALS AND METHODS Retrospective review of all patients undergoing colectomy for colorectal cancer at our VA hospital from 2002 to 2007 was done. Statistical analysis was done using univariate as well as multivariate analysis. One hundred eighty-three patients were analyzed. RESULTS Average number of nodes retrieved was 14.9 with 92 (51%) containing fewer than 12 lymph nodes. Median number of nodes was 11. The only two factors found to have an effect on nodes harvested were pathologist P<0.05 and surgeon experience P=0.01. Factors not found to have an impact on number of nodes harvested were age of patient, previous operation, T stage of tumor, type of colectomy, bowel prep, laparoscopic versus open technique, or BMI. Multivariate analysis confirmed pathologist and surgeon experience as independent factors associated with number of nodes retrieved P<0.05. CONCLUSIONS Operating surgeon and examining pathologist were the only factors found to have a significant impact on number of nodes harvested. Meticulous dissection both in and outside of the operating room are indicated.

Clinical Benefit from Ipilimumab Therapy in Melanoma Patients may be Associated with Serum CTLA4 Levels.

Stage IV metastatic melanoma patients historically have a poor prognosis with 5–10% 5-year survival. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA4), is one of the first treatments to provide beneficial durable responses in advanced melanoma. However, less than 25% of those treated benefit, treatment is expensive, and side effects can be fatal. Since soluble (s) CTLA4 may mediate inhibitory effects previously ascribed to the membrane-bound isoform (mCTLA4), we hypothesized patients benefiting from ipilimumab have higher serum levels of sCTLA4. We found that higher sCTLA4 levels correlated both with response and improved survival in patients treated with ipilimumab in a small patient cohort [patients with (n = 9) and without (n = 5) clinical benefit]. sCTLA4 levels were statistically higher in ipilimumab-treated patients with response to ipilimumab. In contrast, sCTLA4 levels did not correlate with survival in patients who did not receive ipilimumab (n = 11). These preliminary observations provide a previously unrecognized link between serum sCTLA4 levels and response to ipilimumab as well as to improved survival in ipilimumab-treated melanoma patients and a potential mechanism by which ipilimumab functions.

Small bowel carcinoid: Location isn’t everything!

AIM To investigate the prognostic significance of the primary site of disease for small bowel carcinoid (SBC) using a population-based analysis. METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, tumor-node-metastasis stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. RESULTS Of the 3763 patients, 51.2% were male with a mean age of 62.13 years. Median follow-up was 50 mo. The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries (P = 0.02 and < 0.0001, respectively). On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (P = 0.752 for OS and P = 0.966 DSS) while age, number of primaries, number of LNs examined, T-stage and M-stage were independent predictors of survival. CONCLUSION This 21-year, population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.

Attributable cost of obesity in breast surgery: a matched cohort analysis

BACKGROUND The purpose of this study was to determine the economic impact of obesity on patients undergoing mastectomy and breast conservation (BC) for breast cancer. METHODS An analysis of female patients greater than or equal to 18 years undergoing mastectomy and BC for breast cancer between 2004 and 2010 using the Nationwide Inpatient Sample was conducted. RESULTS Of 55,903 patients in our study (49,985 mastectomy, 5,918 BC), 3,308 patients (5.92%) were obese. After propensity score matching, the cost for obese patients was higher at

677 A 21-Year Analysis of Lymph Node Trends in Colon Cancer: Do Quality Measures Really Matter?

1,826 (P < .0001) for mastectomy and