BACKGROUND:

Based on review of patient data in case conferences over time, we hypothesized that clinically relevant data are omitted in routine soft tissue sarcoma staging.

METHODS:

We examined subsets of a prospectively collected single institution soft tissue sarcoma database with respect to criteria of the AJCC versions 6 (2002) and 7 (2010) staging systems and examined their clinical outcomes.

RESULTS:

Relapse-free survival decreases with increasing primary tumor size in four categories, versus two categories used in AJCC 6 and 7 staging. Disease-specific survival decreases over three categories. Conversely, omission of tumor depth as a prognostic factor in version 7 appears supported, since tumor depth is not an independent risk factor for disease-specific survival by multivariate analysis. Patients with nodal disease and no other metastases fare better than patients with other metastases, but have inferior outcomes compared with patients with large high-grade tumors without nodal metastasis. Multivariate analysis identified size, site, grade, age, nodal metastatic disease, and other metastatic disease as independent risk factors for disease-specific survival. Versions 6 and 7 criteria are tacit regarding anatomic site and histology for tumors with identical FNCLCC grade.

CONCLUSIONS:

Improved patient risk assessment may be achieved by staging using a larger number of size categories. Staging system refinements come at the cost of a larger number of staging categories. Histology or site-specific staging systems, nomograms or Bayesian belief networks may provide more accurate means to assess clinical outcomes.

BACKGROUND:

Hepatic pedicle clamping (HPC) has been demonstrated to be effective for short-term outcomes during hepatic resection. However, HPC-induced hepatic ischemia/reperfusion injury can accelerate the outgrowth of hepatic micrometastases in experimental studies. The conclusive evidence regarding effects of HPC on long-term patient outcomes after hepatic resection for colorectal liver metastasis (CRLM) has not been determined.

METHODS:

A comprehensive electronic literature search was performed to identify studies evaluating the oncological effects of HPC after hepatic resection for CRLM. The main outcome measures were intrahepatic recurrence (IHR), disease-free survival (DFS), and overall survival (OS). A meta-analysis was performed using the random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (CI).

RESULTS:

Four studies, with a total of 2,114 patients (73.7 % HPC, 26.3 % non-HPC), matched the inclusion criteria. Meta-analyses revealed that IHR (OR 0.88; 95 % CI 0.69-1.11; P = 0.27), DFS (OR 0.88; 95 % CI 0.70-1.10; P = 0.27) and OS (OR 0.99; 95 % CI 0.79-1.24; P = 0.90) did not differ significantly between the HPC and non-HPC groups.

CONCLUSIONS:

This meta-analysis provides persuasive evidence that HPC during hepatic resection for CRLM has no significant adverse oncological outcomes. HPC should be considered an option during parenchymal liver resection from current available evidence.

BACKGROUND:

We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-).

METHODS:

A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis.

RESULTS:

A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates.

CONCLUSIONS:

Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

BACKGROUND:

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths around the world, and a high recurrence rate after complete resection is an important issue reducing the cure rate and survival of patients with early stage NSCLC. Several pathologic biomarkers are associated with recurrence in early stage lung cancer after complete resection.

METHODS:

We evaluated the expression and prognostic value of the α1 subunit of the nicotinic acetylcholine receptor (CHRNA1) as well as other pathologic features of tumor tissues resected from patients with stage I adenocarcinoma of the lung.

RESULTS:

A high ratio (173/185) of CHRNA1 expression (93.5 %) was found in stage I lung adenocarcinoma. In the multivariate survival analysis, tumor necrosis, angiolymphatic invasion, perineural invasion, and CHRNA1 expression were independent poor prognostic factors for both recurrence-free and overall survival (OS). Patients expressing CHRNA1 had worse median recurrence-free survival (60.6 vs. 77.9 months, P = 0.03) and OS (65.1 vs. 77.9 months, P = 0.04) compared with CHRNA1-negative patients.

CONCLUSIONS:

CHRNA1 expression could be directly tested from the tumor after complete resection. In early stage NSCLC, it could be a useful prognostic factor for recurrence and survival.

BACKGROUND:

AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored.

METHODS:

ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions.

RESULTS:

Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11.

CONCLUSIONS:

We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.

PURPOSE:

The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB).

METHODS:

Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias.

RESULTS:

From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61-0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93-1.18) and NoAdjuvant (index).

CONCLUSIONS:

Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC.

BACKGROUND:

Chronic hepatitis B virus (HBV) infection induces persistent but ineffective immune activation that contributes to necroinflammation, fibrosis, and risk of hepatocellular carcinoma (HCC). This study aims to determine the relationship of intrahepatic total HBV (ih HBV) DNA and covalently closed circular DNA (cccDNA) with necroinflammation and fibrosis, and their impact on prognosis after resection in HBV HCC patients.

METHODS:

Data are from 111 patients treated with primary liver resection for HBV HCC at Mount Sinai, New York (1991-2008). ih HBV DNA and cccDNA were quantitated by real-time PCR. Necroinflammation was graded according to histologic activity index (HAI), and liver fibrosis was staged by the modified Ishak method.

RESULTS:

A total of 106 (95 %) and 89 patients (80 %) had detectable ih HBV DNA and cccDNA, respectively, while 43 % had detectable serum HBV DNA. cccDNA made up a small proportion of ih HBV DNA (median cccDNA/ih HBV DNA ratio = 0.022). Higher levels of ih HBV DNA were associated with higher HAI and serum alanine aminotransferase (ALT), while a lower ratio of cccDNA/ih HBV DNA was associated with higher HAI, ALT, and Ishak fibrosis stage. ih HBV and cccDNA were not associated with survival, but the lowest quintile of cccDNA/ih HBV DNA ratio (<0.0024) was independently associated with poor overall survival.

CONCLUSIONS:

A lower cccDNA/ih HBV DNA ratio was associated with greater necroinflammation and liver fibrosis, and was independently associated with poor overall survival. Thus, intracellular virus loads and relative proportions of virus DNA reflect histologic damage in the liver and influence the clinical outcome of HBV HCC patients.

BACKGROUND:

Racial disparities in colorectal cancer persist. Late stage at presentation and lack of stage-specific treatment may be contributing factors. We sought to evaluate the magnitude of disparity remaining after accounting for gender, stage, and treatment using predicted survival models.

METHODS:

We used institutional tumor registries from a public health system (two hospitals) and a not-for-profit health system (nine hospitals) from 1995 to 2011. Demographics, stage at diagnosis, treatment, and survival were recorded. Hazard ratios (HRs) and predicted HRs were determined by Cox regression and postestimation analyses.

RESULTS:

There were 6,990 patients: 55.7 % white, 23.6 % African American, 15.1 % Hispanic, and 5.6 % Asian/other. Predictors of survival were surgery (HR 0.57, 95 % confidence interval [CI] 0.46-0.70), chemotherapy (HR 0.7, 95 % CI 0.62-0.79), female gender (HR 0.87, 95 % CI 0.83-0.90), age (HR 1.04, 95 % CI 1.03-1.05), and African American race (HR 3.6, 95 % CI 1.5-8.4). Balancing for stage, gender, and treatment reduced the predicted HRs for African Americans by 28 % and Hispanics by 17 %. In this model, African American and Hispanics still had the worst predicted HRs at younger ages, but whites had the worst predicted HR after age 75.

CONCLUSIONS:

Gender, stage, and treatment partially accounted for worsened survival in African Americans and Hispanics at all ages. At younger ages, race-related disparities remained which may reflect tumor biology or other unknown factors. Once gender, stage, and treatment are balanced at older ages, the increased mortality observed in whites may be due to factors such as comorbidities. Further system- and patient-level study is needed to investigate reasons for colorectal cancer survival disparities.

BACKGROUND:

When feasible, surgical treatment of colorectal liver metastases (CRLM) is the treatment of choice. Regional hepatic artery infusional (HAI) chemotherapy effectively treats CRLM. The combination of HAI and systemic chemotherapy may downsize tumors and allow for complete resection and/or ablation (R/A). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on conversion to complete R/A.

METHODS:

All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Survival was compared using a landmark analysis to account for bias.

RESULTS:

A total of 373 patients were included; 93 patients (25 %) subsequently underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16 % during 2000-2003 to 30 % during 2004-2009. Factors associated with conversion on multivariate analysis were more recent treatment (2004-2009), no prior chemotherapy, clinical risk score <3, treatment on clinical protocol, and younger age. Median and predicted 5-year survival from the time of HAI pump placement was 59 months and 47 %, respectively, in the patients who converted to complete R/A, compared with 16 months and 6 %, respectively in those who did not (p < 0.001).

CONCLUSIONS:

Despite extensive disease, 25 % of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Combination HAI and systemic chemotherapy is an effective strategy to convert patients to complete resection with an associated excellent long-term survival.

BACKGROUND:

There is a paucity of evidence regarding incidence and predictors of survival in pancreatic neuroendocrine tumors (PNETs) ≤2 cm in size.

METHODS:

Patients having undergone resection for nonfunctioning PNETs were selected from the SEER database (1988-2009) and an institutional pathology database (1996-2012). PNETs ≤2 cm were compared with PNETs >2 cm. Data were analyzed with χ (2) tests, ANOVA, the Kaplan-Meier method, log rank tests, and Cox proportional hazard, and binary logistic regression.

RESULTS:

The incidence of PNETs ≤2 cm in the United States has increased by 710.4 % over the last 22 years. Rates of extrapancreatic extension, nodal metastasis, and distant metastasis in PNETs ≤2 cm in the SEER database were 17.9, 27.3, and 9.1 %, respectively. The rate of nodal metastasis in our institutional series was 5.7 %. Disease-specific survival at 5, 10, and 15 years for PNETs ≤2 cm was 91.5, 84.0, and 76.8 %. Decreased disease-specific survival was not associated with nodal metastasis, but rather with high grade [moderately differentiated, hazard ratio (HR) 37.2, 95 % confidence interval (CI) 2.7-518.8; poorly differentiated, HR 94.2, 95 % CI 4.9-1,794.4; reference, well differentiated], and minority race (Asian, HR 30.2, 95 % CI 3.1-291.7; Black, HR 60.1, 95 % CI 2.1-1,027.9; reference, White).

CONCLUSIONS:

Pancreatic neuroendocrine tumors ≤2 cm are increasingly common, and the most significant predictors of disease-specific survival are grade and race. The SEER database excludes PNETs considered to be benign, and rates of extrapancreatic extension, nodal metastasis, and distant metastasis are overestimated. Small size, however, does not preclude malignant behavior.