K.A. Higgins

Paranasal sinus squamous cell carcinoma incidence and survival based on Surveillance, Epidemiology, and End Results data, 1973 to 2009

Paranasal sinus squamous cell carcinomas (PNSSCC) account for 3% of all head and neck malignancies. There has been little information on the trends in incidence and survival, and no randomized trials have been conducted to guide therapy.

Survival After Sublobar Resection versus Lobectomy for Clinical Stage IA Lung Cancer: An Analysis from the National Cancer Data Base

Background: Recent data have suggested possible oncologic equivalence of sublobar resection with lobectomy for early-stage non–small-cell lung cancer (NSCLC). Our aim was to evaluate and compare short-term and long-term survival for these surgical approaches. Methods: This retrospective cohort study utilized the National Cancer Data Base. Patients undergoing lobectomy, segmentectomy, or wedge resection for preoperative clinical T1A N0 NSCLC from 2003 to 2011 were identified. Overall survival (OS) and 30-day mortality were analyzed using multivariable Cox proportional hazards models, logistic regression models, and propensity score matching. Further analysis of survival stratified by tumor size, facility type, number of lymph nodes (LNs) examined, and surgical margins was performed. Results: A total of 13,606 patients were identified. After propensity score matching, 987 patients remained in each group. Both segmentectomy and wedge resection were associated with significantly worse OS when compared with lobectomy (hazard ratio: 1.70 and 1.45, respectively, both p < 0.001), with no difference in 30-day mortality. Median OS for lobectomy, segmentectomy, and wedge resection were 100, 74, and 68 months, respectively (p < 0.001). Finally, sublobar resection was associated with increased likelihood of positive surgical margins, lower likelihood of having more than three LNs examined, and significantly lower rates of nodal upstaging. Conclusion: In this large national-level, clinically diverse sample of clinical T1A NSCLC patients, wedge and segmental resections were shown to have significantly worse OS compared with lobectomy. Further patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Ongoing prospective study taking into account LN upstaging and margin status is still needed.

Lymphovascular Invasion in Non–Small-Cell Lung Cancer: Implications for Staging and Adjuvant Therapy

Background: Lymphovascular space invasion (LVI) is an established negative prognostic factor and an indication for postoperative radiation therapy in many malignancies. The purpose of this study was to evaluate LVI in patients with early-stage non–small-cell lung cancer, undergoing surgical resection. Methods: All patients who underwent initial surgery for pT1-3N0-2 non–small-cell lung cancer at Duke University Medical Center from 1995 to 2008 were identified. A multivariate ordinal regression was used to assess the relationship between LVI and pathologic hilar and/or mediastinal lymph node (LN) involvement. A multivariate Cox regression analysis was used to evaluate the relationship of LVI and other clinical and pathologic factors on local failure (LF), freedom from distant metastasis (FFDM), and overall survival (OS). Kaplan-Meier methods were used to generate estimates of LF, FFDM, and OS in patients with and without LVI. Results: One thousand five hundred and fifty-nine patients were identified. LVI was independently associated with the presence of regional LN involvement (p < 0.001) along with lobar (versus sublobar) resections (p < 0.001), and an open thoracotomy (versus video-assisted thoracoscopic surgery). LVI was not independently associated with LF on multivariate analysis (hazard ratio [HR] = 1.23, p = 0.25), but was associated with a lower FFDM (HR 1.52, p = 0.005) and OS (HR 1.26, p = 0.015). In addition, multivariate analysis showed that LVI was strongly associated with increased risk of developing distant metastases (HR = 1.75, p = 0.006) and death (HR = 1.53, p = 0.003) in adenocarcinomas but not in squamous carcinomas. Conclusions: LVI is associated with an increased risk of harboring regional LN involvement. LVI is also an adverse prognostic factor for the development of distant metastases and long-term survival.

Stereotactic body radiation therapy versus no treatment for early stage non–small cell lung cancer in medically inoperable elderly patients: A National Cancer Data Base analysis

Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non–small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older.

Lymph node ratio influence on risk of head and neck cancer locoregional recurrence after initial surgical resection: Implications for adjuvant therapy

The purpose of this study was to determine if lymph node ratio is associated with locoregional recurrence for patients with oral cavity or laryngeal cancer treated with initial surgical management.

Postoperative Radiotherapy is Associated with Better Survival in Non–Small Cell Lung Cancer with Involved N2 Lymph Nodes: Results of an Analysis of the National Cancer Data Base

Introduction: Use of postoperative radiotherapy (PORT) in non–small-cell lung cancer remains controversial. Limited data indicate that PORT may benefit patients with involved N2 nodes. This study evaluates this hypothesis in a large retrospective cohort treated with chemotherapy and contemporary radiation techniques. Methods: The National Cancer Data Base was queried for patients diagnosed 2004–2006 with resected non–small-cell lung cancer and pathologically involved N2 (pN2) nodes also treated with chemotherapy. Multivariable Cox proportional hazards model was used to assess factors associated with overall survival (OS). Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce selection bias. OS was compared between patients treated with versus without PORT using the adjusted Kaplan–Meier estimator and weighted log-rank test based on IPTW. Results: Two thousand and one hundred and fifteen patients were eligible for analysis. 918 (43.4%) received PORT, 1197 (56.6%) did not. PORT was associated with better OS (median survival time 42 months with PORT versus 38 months without, p = 0.048). This effect was significant in multivariable and IPTW Cox models (hazard ratio: 0.87, 95% confidence interval: 0.78–0.98, p = 0.026, and hazard ratio: 0.89, 95% confidence interval: 0.79–1.00, p = 0.046, respectively). No interaction was seen between the effects of PORT and number of involved lymph nodes (p = 0.615). Conclusions: PORT was associated with better survival for patients with pN2 nodes also treated with chemotherapy. No interaction was seen between benefit of PORT and number of involved nodes. These findings reinforce the benefit of PORT for N2 disease in modern practice using the largest, most recent cohort of chemotherapy-treated pN2 patients to date.

Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck.

Platinum‐based therapy combined with cetuximab is standard first‐line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN.

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

Purpose: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities are the result of a common biological phenotype, such as regulatory pathways. Experimental Design: Lung cancer cell lines with corresponding gene expression data and genes associated with an embryonic stem cell identity were used to develop a signature of embryonic stemness (ES) activity specific to lung adenocarcinoma. Biological characteristics were elucidated as a function of cancer biology/oncogenic pathway dysregulation. The ES signature was applied to three independent early-stage (I-IIIa) lung adenocarcinoma data sets with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin (current standard of care) sensitivity was evaluated. Results: Pathway analysis identified specific regulatory networks [Ras (P = 0.0005), Myc (P = 0.0224), wound healing (P < 0.0001), chromosomal instability (P < 0.0001), and invasiveness (P < 0.0001)] associated with the ES phenotype. The prognostic relevance of the ES signature, as related to patient survival, was characterized in three cohorts [CALGB 9761 (n = 82; P = 0.0001), National Cancer Institute Directors Challenge Consortium (n = 442; P = 0.0002), and Duke (n = 45; P = 0.06)]. The ES signature was not prognostic in prostate, breast, or ovarian adenocarcinomas. Lung tumors (n = 569) and adenocarcinoma cell lines (n = 31) expressing the ES phenotype were more likely to be resistant to cisplatin (P < 0.0001 and P = 0.006, respectively). Conclusions: Lung adenocarcinomas that share a common gene expression pattern with normal human embryonic stem cells were associated with decreased survival, increased biological complexity, and increased likelihood of resistance to cisplatin. This indicates the aggressiveness of these tumors. (Clin Cancer Res 2009;15(24):7553–61)

Racial disparities in squamous cell carcinoma of the oral tongue among women: A SEER data analysis

OBJECTIVES The incidence of oral tongue cancer (OTC) in the US is increasing in women. To understand this phenomenon, we examined factors influencing OTC incidence and survival. MATERIALS AND METHODS We identified women diagnosed with OTC that were reported to the Surveillance, Epidemiology and End Results (SEER) program from 1973 to 2010. Incidence and survival rates were compared across metropolitan, urban and rural residential settings and several other demographic categories by calculating rate ratios (RRs) with the corresponding 95% confidence intervals (CIs). We examined changes in incidence of OTC across racial groups using joinpoint analyses since 1973, and assessed factors associated with survival. Patients diagnosed prior to 1988 were excluded from the survival analysis due to lack of data on treatment. RESULTS OTC incidence in white females demonstrated a significant upward trend with 0.53 annual percentage change (APC) between 1973 and 2010. The change seems to be limited to white women under the age of 50years and appears to have become pronounced in the 1990s. For African Americans (AA) on the other hand, the incidence has decreased. Incidence estimates did not differ in metropolitan, small urban and rural setting. The 1-, 5- and 10-year relative survival estimates were 86%, 63% and 54% for white women, and 76%, 46% and 33% for AA women. On multivariable analyses factors significantly associated with better survival included lower stage, younger age, married status, and receipt of surgical treatment, but not race. CONCLUSION The racial disparity in OTC survival is evident, but may be attributable to the differences in stage at diagnosis as well as access to and receipt of care. As the incidence of OTC is increasing in young white women, identifying the risk factors in this group may lead to a better understanding of OTC causes.

Socioeconomic Risk Factors for Long-Term Mortality after Pulmonary Resection for Lung Cancer: An Analysis of More than 90,000 Patients from the National Cancer Data Base

BACKGROUND Several clinical variables, such as tumor stage and age, are well established factors associated with long-term survival after surgical resection of lung cancer. Our aim was to examine the impact of other clinical and demographic variables, controlling for known predictors of long-term survival, in order to investigate how outcomes varied according to important nonclinical factors. STUDY DESIGN The National Cancer Data Base, jointly supported by the Commission on Cancer of the American College of Surgeons and the American Cancer Society, was used to identify patients undergoing pulmonary resection for lung cancer and perform a retrospective cohort study. The cohort consisted of patients diagnosed with nonsmall cell lung cancer from 2003 to 2006, who underwent resection; overall survival data are available only for patients diagnosed through 2006. A Cox proportional hazards survival model was used to examine factors associated with risk of mortality. RESULTS A total of 92,929 patients were identified as diagnosed during the study period and undergoing surgical resection for lung cancer. On multivariable analysis, several socioeconomic factors such as lack of insurance, lower income, less education, and treatment at community centers vs academic or research programs predicted worse overall survival after controlling for disease characteristics known to be predictors of worse survival, such as tumor stage, histology, age, and extent of resection. CONCLUSIONS Diminished long-term survival after pulmonary resection was associated with a number of socioeconomic factors. To date, this represents the largest database analysis of long-term mortality in patients undergoing surgical resection for lung cancer. The disparities in survival outcomes reported here require further detailed investigation.