Adrienne Groman

Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis.

BACKGROUND Sarcomatoid lung carcinomas are unusual, and reports from small single institution case series suggest poor survival rates. We sought to study the clinical characteristics of this form of non-small cell lung cancer using the Surveillance Epidemiology, End Results database. METHODS The Surveillance, Epidemiology, and End Results database was queried for respiratory tract malignancies of sarcomatoid histology. The demographic information and oncologic characteristics of this population were examined. A propensity score-matched analysis of patients was performed to test the hypothesis that patients with sarcomatoid cancers undergoing lobectomies perform worse that those with other non-small cell lung cancers. RESULTS Of 878,810 patients with lung cancer, only 3,647 patients had a diagnosis of sarcomatoid cancer (0.4%). For the additional analyses of outcomes, only patients with lifetime incidence of a single cancer, known Surveillance, Epidemiology, and End Results historic stage and inpatient reporting were selected (n = 1,921). Demographics, tumor characteristics, and outcomes of these patients were described. Non-small cell lung cancer cohorts (with and without sarcomatoid cancer propensity-matched on age, gender, race, year of diagnosis, grade, and Surveillance, Epidemiology, and End Results historic stage) that underwent lobectomies or pneumonectomies were selected (n = 758). Univariate (hazard ratio, 1.60; 95% confidence interval, 1.31-1.97) and multivariate analysis (hazard ratio, 1.67; 95% confidence interval, 1.36-2.05) revealed a significantly worse overall survival for patients with sarcomatoid cancer compared to matched nonsarcomatoid lung cancer controls. CONCLUSION Sarcomatoid cancer is a rare form of lung malignancy with outcomes significantly worse than other forms of non-small cell lung cancer. Novel multimodality treatment strategies are necessary to improve outcomes of this disease.

Number of Lymph Nodes and Metastatic Lymph Node Ratio Are Associated With Survival in Lung Cancer

BACKGROUND The non-small cell lung cancer TNM classification system uses only the anatomic extent of lymph node (LN) metastases to define the N category. The number of LNs resected and the ratio of positive LNs to total examined LNs are prognostic in other solid tumors. We used the Surveillance, Epidemiology and End Results database to investigate the effect of these factors on the overall survival of non-small cell lung cancer. METHODS All patients with non-small cell lung cancer in the Surveillance, Epidemiology and End Results database from 1988 through 2007 who had curative resections and had at least one LN examined were included. The prognostic value of age, race, sex, tumor size, histologic grade, number of examined LNs, and ratio of positive LNs to total examined LNs was assessed using a multivariate Cox proportional hazards model for overall survival. The number of LNs examined was categorized into four levels. The percentage of positive LNs was stratified into three levels. RESULTS Among patients with localized disease, fewer LNs examined corresponded with a worse prognosis. Prognosis improved as more LNs were examined. For patients with regional disease, the differences were significant only at the extremes. Older patients, males, and those with higher grade or larger tumors did worse. Patients with low or moderate ratios of positive to total LNs had better prognoses than those with high ratios. CONCLUSIONS More LNs resected and lower ratios of positive LNs to total examined LNs are associated with better patient survival after non-small cell lung cancer resection independent of age, sex, grade, tumor size, and stage of disease.

Impact of Body Mass Index on Clinical Outcomes in Triple-Negative Breast Cancer

Obesity is associated with poorer outcomes in patients with hormone receptor‐positive breast cancers. This association is not well established for women with triple‐negative breast cancers (TNBC). In this study, the prognostic effects of body mass index on clinical outcome were evaluated in patients with TNBC.

Increased Expression Levels of WAVE3 Are Associated with the Progression and Metastasis of Triple Negative Breast Cancer

Background Breast Cancer (BC) is a heterogeneous disease comprised of at least five genetically distinct subtypes, which together form the second leading cause of cancer death in women in the United States. Within BC subtypes, those classified as Triple Negative BCs (TNBCs) exhibit dismal survival rates due to their propensity to develop distant metastases. We have identified the WAVE3 protein, which is a critical regulator of actin cytoskeleton dynamics that are required for the motility and invasion of cancer cells through its activation of the Arp2/3 complex, as a key regulator of the different steps of the invasion-metastasis cascade in BC, especially in the more aggressive TNBCs. Our published studies have also shown that elevated expression levels of WAVE3 in the TNBC cell lines directly contribute to their increased invasion and metastasis potentials both in vitro and in vivo in murine models of BC metastasis. Methodology/Principal Findings Herein, we utilized both immunohistochemistry (IHC) of primary human BC tumors as well as quantitative real-time RT-PCR of WAVE3 in the peripheral blood of BC patients to clearly establish that WAVE3 is a predictive marker of overall BC patients’ survival. High levels of WAVE3 were predictive for reduced distant recurrence-free survival as well as for decreased disease-specific mortality. Our analysis of WAVE3 expression levels in the peripheral blood of BC patients showed that WAVE3 is highly expressed in the blood of patients who developed metastatic breast cancer compared to those who did not. WAVE3 expression was also highly upregulated in the blood of BC patients with the more aggressive TNBC subtype. Conclusions Together, these findings establish WAVE3 as a novel marker for increased risk of breast-cancer-specific mortality and for the metastatic potential of the TNBCs, and also identify WAVE3 as an attractive therapeutic target for the treatment of metastatic BC.

Structuring survivorship care: discipline-specific clinician perspectives.

IntroductionSeveral models for survivorship care are prominent within the cancer literature; however, there is little empirical research that examines what oncology clinicians perceive to be the best approach to caring for cancer survivors, what services survivorship programs should include, and how prepared they feel to care for cancer survivors.MethodsAn IRB approved web-based survey of all clinical staff was conducted at a NCI designated comprehensive cancer center with a 49.8% response rate (N = 377). Data were summarized using frequencies and relative frequencies, and pairwise tests of statistical significance were utilized to evaluate differences between clinician type groups.ResultsOverall, the largest proportion of respondents preferred a disease-specific survivorship model (37.6%). This preference was specifically observed in oncology physicians and nurses. When asked where specific survivorship services should be provided, respondents indicated a preference for services directly related to survivors’ medical treatment (i.e. information about late effects) to be delivered in a disease-specific survivorship clinic, and ancillary services (i.e. nutrition and fertility counseling) to be housed in a centralized comprehensive survivorship clinic. Physicians felt that they have significantly more information, training, and resources to care for cancer survivors than did oncology nurses.Discussion/conclusionThese results indicate that oncology clinicians prefer a combination of survivorship care delivery models where continuing medical needs are met in disease-specific clinics, and comprehensive wellness services are offered in a centralized comprehensive survivorship clinic. Results also suggest that planning for survivorship initiatives should include additional resources, education, and training for clinical staff.Implications for cancer survivorsThese findings underscore the need for a universally accepted definition of cancer survivorship, and support a model for delivering care to cancer survivors that is a blend of the disease-specific and comprehensive survivorship programs.

Temporal trends in outcomes following sublobar and lobar resections for small (≤ 2 cm) non-small cell lung cancers--a Surveillance Epidemiology End Results database analysis.

BACKGROUND Since the randomized, controlled study that favored lobectomy for resection of stage I non-small cell lung cancers (NSCLCs) by the Lung Cancer Study Group, there have been improvements in staging. The liberal use of computed tomography also may have altered the types of early lung cancer diagnosed. Studies published since then have drawn contradictory conclusions on the benefit of lobectomy over sublobar resections for early-stage NSCLC. We examined the Surveillance Epidemiology End Results database to test our hypothesis that the relationship between extent of resection and outcome has changed since the Lung Cancer Study Group study was published. METHODS We examined stage I NSCLCs ≤ 2 cm in size over three periods: 1988-1998 (Early), 1999-2004 (Intermediate), and 2005-2008 (Late). For each period, we assessed overall and disease-specific survivals and their associations with the extents of resection, by univariate and multivariate analyses. Sublobar resections in the Early group could not be categorized into segmentectomies and wedge resections because these were not coded separately. RESULTS The proportion of NSCLCs ≤ 2 cm increased from 0.98% in 1988 to 2.2% in 2008. Multivariate analyses showed that sublobar resection was inferior to lobectomy in the Early period (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.21-1.65). This effect decreased in the Intermediate period, in which segmentectomies but not wedge resections were equivalent to lobectomies (wedge versus lobectomy HR, 1.19; 95% CI, 1.01-1.41; segmentectomy versus lobectomy HR, 1.04; 95% CI, 0.8-1.36). The difference disappeared in the Late period, when both wedge resections and segmentectomies were equivalent to lobectomy (wedge versus lobectomy HR, 1.09; 95% CI, 0.79-1.5; segmentectomy versus lobectomy HR, 0.83; 95% CI, 0.47-1.45). Trends for both overall survival and disease-specific survival were identical. CONCLUSIONS The survival benefit of lobectomy over sublobar resection decreased over the past 2 decades with no discernible difference in the most contemporary cases. These results support reevaluation of lobectomy as the standard of care for small (≤ 2-cm) NSCLCs.

Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer.

The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:–A4, MAGE-A1:–C1 and MAGE-A4:–A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01–2.04, p = 0.044 and OR 1.3, CI 1.03–1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42–0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients.

Gastrointestinal stromal tumors (GISTs) at uncommon locations: a large population based analysis.

Sparse information is available about GISTs in uncommon locations. Our large database analysis aims to determine the characteristics of GISTs in the esophagus, colon and rectum and compare to gastric GISTs.

Hospice Utilization and End-of-Life Care in Metastatic Breast Cancer Patients at a Comprehensive Cancer Center

BACKGROUND Metastatic breast cancer patients have many options for therapy and may be at risk for late or absent hospice referrals, which make meaningful improvements in symptoms and quality of life difficult to achieve. OBJECTIVE We aimed to examine hospice utilization, status of patients on admission, and quality of care of patients treated for metastatic breast cancer from 1999 to 2010 at a National Cancer Institute (NCI)-designated comprehensive cancer center located in Western New York. METHODS We conducted a retrospective database review that identified 182 patients with deaths resulting from breast cancer who were eligible for services through a local not-for-profit hospice. Patients with metastatic breast cancer were matched to the hospice database for information on hospice utilization and quality measures. Date of last chemotherapy, medication use, documentation of advance directive and palliative care discussions, and place of death were collected through chart abstraction. RESULTS One-third (33%) of metastatic breast cancer patients treated at the cancer institute during the study period died without a hospice referral. Only 7% of patients who died without a hospice referral had a documented discussion of palliative care as an option by the oncology team (p < 0.001). Those patients referred to hospice were significantly more likely to have an advance directive and to die at home. Patients with a longer duration of metastatic cancer were at risk for late referral. CONCLUSIONS Efforts to enhance end-of-life (EOL) discussions and earlier referral to palliative care and hospice for patients with metastatic breast cancer are critical to improved patient care.

Prognostic implications of signet ring cell histology in esophageal adenocarcinoma

Signet ring cell esophageal adenocarcinoma histology has been difficult to study in single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was examined to assess the prognostic implications of this esophageal adenocarcinoma subtype.