Colleen Leary

One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.

PURPOSE Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). CONCLUSION We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.

Population-based study of islet cell carcinoma

BackgroundWe examine the epidemiology, natural history, and prognostic factors that affect the duration of survival for islet cell carcinoma by using population-based registries.MethodsThe Surveillance, Epidemiology, and End Results (SEER) Program database (1973–2003 release, April 2006) was used to identify cases of islet cell carcinoma by histology codes and tumor site.ResultsA total of 1310 (619 women and 691 men) cases with a median age of 59 years were identified. The annual age-adjusted incidence in the periods covered by SEER 9 (1973–1991), SEER 13 (1992–1999), and SEER 17 (2000–2003) were .16, .14, and .12 per 100,000, respectively. The estimated 28-year limited duration prevalence on January 1, 2003, in the United States was 2705 cases. Classified by SEER stage, localized, regional, and distant stages corresponded to 14%, 23%, and 54% of cases. The median survival was 38 months. By stage, median survival for patients with localized, regional, and distant disease were 124 (95% CI, 80–168) months, 70 (95% CI, 54–86) months, and 23 (95% CI, 20–26) months, respectively. By multivariate Cox proportional modeling, stage (P < .001), primary tumor location (P = .04), and age at diagnosis (P < .001) were found to be significant predictors of survival.ConclusionsIslet cell carcinomas account for approximately 1.3% of cancers arising in the pancreas. Most patients have advanced disease at the time of diagnosis. Despite the disease’s reputation of being indolent, survival of patients with advanced disease remains only 2 years. Development of novel therapeutic approaches is needed.

Risk factors associated with neuroendocrine tumors: A U.S.-based case–control study

Carcinoids are rare neuroendocrine tumors (NETs); however, their incidence has significantly increased in the United States over the past 30 years. Little is known about the epidemiology of these cancers and their associated risk factors. We evaluated the independent effects of multiple risk factors associated with NETs arising at 5 disease sites (small intestine, stomach, lung, pancreas and rectum). We conducted a retrospective, hospital‐based, case–control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on different risk factors was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AORs) and 95% confidence interval (CI) by the maximum‐likelihood method. Smoking and alcohol consumption were not associated with NETs development in either men or women. However, a family history of cancer was a significant risk factor for all NETs. A long‐term history of diabetes mellitus was a significant risk factor for gastric NETs (AOR = 5.6; 95% CI, 2.1–14.5), particularly in women (AOR = 8.4; 95% CI, 1.9–38.1). Diabetes modified the risk among women with a positive family history of cancer for the development of gastric NETs (AOR = 52.2; 95% CI, 5.5–491.5). Our results suggest that the risk of NETs may mostly explained by genetic factors. The increased risk of gastric NETs in women with both diabetes and a positive family history of cancer suggest that women may have a greater genetic susceptibility to NETs than men.

Risk factors associated with neuroendocrine tumors

Carcinoids are rare neuroendocrine tumors (NETs); however, their incidence has significantly increased in the United States over the past 30 years. Little is known about the epidemiology of these cancers and their associated risk factors. We evaluated the independent effects of multiple risk factors associated with NETs arising at 5 disease sites (small intestine, stomach, lung, pancreas and rectum). We conducted a retrospective, hospital‐based, case–control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on different risk factors was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AORs) and 95% confidence interval (CI) by the maximum‐likelihood method. Smoking and alcohol consumption were not associated with NETs development in either men or women. However, a family history of cancer was a significant risk factor for all NETs. A long‐term history of diabetes mellitus was a significant risk factor for gastric NETs (AOR = 5.6; 95% CI, 2.1–14.5), particularly in women (AOR = 8.4; 95% CI, 1.9–38.1). Diabetes modified the risk among women with a positive family history of cancer for the development of gastric NETs (AOR = 52.2; 95% CI, 5.5–491.5). Our results suggest that the risk of NETs may mostly explained by genetic factors. The increased risk of gastric NETs in women with both diabetes and a positive family history of cancer suggest that women may have a greater genetic susceptibility to NETs than men.

Thymic neuroendocrine tumors: A SEER database analysis of 160 patients

Introduction:Thymic neuroendocrine tumors (NETs) are uncommon but malignant tumors of the thymus gland that are usually associated with systemic symptoms due to hypersecretion of biogenic amines from metastatic lesions. Due to the limited number of studies in the literature, very little is known about progress or trends made in the treatment and survival of patients with thymic NET. Methods:We reviewed 160 patients diagnosed with thymic NET in the SEER database to evaluate patient demographics and their clinical course. Specifically, we evaluated the role of surgery and adjuvant radiation in the SEER cohort. We also performed univariable and multivariate Cox proportional hazard modeling of standard prognostic factors. Results:According to our results, thymic NETs afflict males and whites primarily. As expected, advanced stage correlates with poorer long-term survival (P = 0.009) and those patients who undergo surgery do better than their counterpart (P = 0.005). We did not observe any survival benefit for radiation delivered as a part of primary therapy. Univariable and multivariate analyses demonstrated that tumor stage (P = 0.009), grade (P = 0.002), surgical resection (P = 0.005), and tumor size (P = 0.02) correlated with overall survival. Conclusions:Our study demonstrates that surgery continues to be the mainstay of treatment, and that there is a need to define a staging system for thymic NETs that can perhaps allow clinicians to formulate better therapeutic strategies for such patients.

Family history of cancer and associated risk of developing neuroendocrine tumors: A case-control study

Background: Carcinoids are rare neuroendocrine tumors (NET). Familial clusterings of NETs are rarely reported, except for a small proportion associated with multiple endocrine neoplasia syndrome type 1. We evaluated the effect of positive family history of NET as well as other cancers on the development of NETs arising at five different locations. Methods: We conducted a retrospective, hospital-based, case-control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on family history of cancer was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results: The authors observed a significant relationship between first-degree relatives with cancers and the development of NETs arising at the small intestine, stomach, lung, and pancreas; AORs (95% CI) were 1.6 (1.1-2.4), 2.5 (1.1-6.3), 2.6 (1.5-4.5), and 1.8 (1.1-3.1), respectively. A first-degree family history of esophageal cancer was significantly associated with pancreatic NETs; AOR, 5.6 (95% CI, 1.1-29.6). There was a 70% and 130% increased risk of developing small intestinal NETs among subjects with family histories of colorectal cancer and prostate cancer, respectively. Moreover, individuals with a family history of lung cancer had a 2-fold increase in risk of developing pulmonary NETs. Conclusions: Having a first-degree relative with any cancer in general, and NET in particular, was a risk factor for NETs. The elevated risk of developing NETs extended to individuals with a family history of other cancers (not NETs) among first-degree relatives. These results suggested that risk of NETs may be partially explained by genetic factors. (Cancer Epidemiol Biomarkers Prev 2008;17(4):959–65)

Perfusion computed tomography as functional biomarker in randomized run-in study of bevacizumab and everolimus in well-differentiated neuroendocrine tumors

Objectives This study aimed to assess the antitumor activity of everolimus and bevacizumab among patients with advanced neuroendocrine tumors and to assess perfusion computed tomography (CT) as a potential functional biomarker. Methods Patients with low- to intermediate-grade neuroendocrine tumors received one 3-week cycle of 15 mg/kg of bevacizumab on day 1 or 10 mg of everolimus daily. Subsequent cycles consisted of the combination of both drugs. Perfusion CTs were performed at baseline and at the end of cycles 1 and 3. Results Therapy decreased blood flow (BF) proportional to baseline measurements. Bevacizumab was associated with a 44% decrease in BF (P < 0.0001). After the addition of everolimus, a further 29% decrease (P = 0.02) in BF was observed. Everolimus alone was associated with 13% increase in mean transit time (P = 0.02). Clinical activity was demonstrated, with a confirmed response rate of 21% and a median progression-free survival of 14.6 (95% confidence interval, 13.0–16.1) months. Pretreatment tumor permeability surface (P = 0.009), posttreatment mean transit time (P = 0.003), percent reduction in BF (P = 0.03), and percent reduction in blood volume (P = 0.002) were associated with best percent reduction in tumor diameters. Conclusions Bevacizumab and everolimus demonstrated antitumor activity. Perfusion CT is a promising tool for the development of antiangiogenic strategies and for the selection of patients who are likely to benefit from therapy.

Improving the success rate of gluteal intramuscular injections

Objectives This study aimed to improve the success rate of gluteal intramuscular (IM) injection. Methods The outcomes of 328 intended gluteal IM injections in 115 patients receiving depot octreotide were evaluated using computed tomography performed in routine clinical practice. Patient-, nursing-, and technique-dependent factors were correlated with successful delivery of medication. Techniques associated with successful injection were taught to center nurses. Results At baseline, 52% of injections were successfully delivered (66% men, 36% women; P = 0.001). Factors associated with successful delivery included nurses’ frequency of injections (P = 0.008), landmarks use to select injection site (P < 0.001), quick needle insertion (P < 0.001), and use of nonsyringe hand to compress injection site (P < 0.001). Patient-related factors included male sex (P < 0.001), lower body mass index (P < 0.001), and lower skin-to-muscle depth at injection site (P < 0.001). Techniques associated with successful injections were then taught to center nurses. After instruction, the success rate increased from 52% to 75% (P = 0.001). Importantly, improvements were observed in both men (66%–75%; P = 0.43) and women (38%–75%; P < 0.001). Successful injection was associated with better control of flushing among those with carcinoid syndrome (P = 0.005). Conclusions Intended gluteal IM injections often are given into the subcutaneous space. Education in techniques associated with successful injections improves IM delivery rates.