North American Neuroendocrine Tumor Society Research Articles

Surgical Treatment Options for Rectal Carcinoid Cancer: LocalversusLow Radical Excision

R ECTAL CARCINOIDS ARE rare and their biologic behavior and optimal surgical treatment remain poorly defined. Classically, primary tumors less than 2 cm were assumed to be indolent and were treated by transanal excision. We hypothesized that rectal carcinoids are more malignant than previously described and tumors less that 2 cm may warrant more aggressive surgery. The charts of 62 consecutive patients with rectal carcinoids seen at our institution between October 2006 and August 2011 were reviewed. The primary tumor size, extent of disease, and survival data were analyzed. The primary tumor size and the incidence of lymph node metastases were available for 60 of 62 patients and was: less than 1 cm: two of 26 (8%); 1.1 to 2 cm: nine of 13 (69%); 2.1 to 3 cm: four of five (80%), greater than 3 cm: seven of 12 (58%); and multiple primaries: two of four (50%). Small (less than 2 cm) rectal carcinoids have a higher incidence of nodal positivity than previously described. Based on our survival data, we believe that tumors larger than 1 cm should be considered for a low anterior resection with total mesorectal excision as their initial definitive treatment. For tumors less than 1 cm, treatment should be individualized. RECTAL CARCINOIDS ARE relatively rare, with a reported incidence of one in every 100,000 people.1 However, recent reports have indicated that this incidence is on the rise.2 The 5-year survival rate for all rectal carcinoid tumors has been reported to be as high as 88 per cent, and these high survival rates were attributed to the fact that most rectal carcinoids are small and present with localized disease.3, 4 The incidence of lymph node metastasis for rectal primaries less than 1 cm has been reported to be less than 3 per cent. For primaries between 1 and 2 cm, nodal positivity has generally been reported between 10 and 15 per cent,4–9 but has recently been reported as high as 31 per cent.10 In contrast, the nodal positivity rate for tumors greater than 2 cm is classically reported as 80 per cent.3, 4, 6–9 Based on this, the treatment guidelines for rectal carcinoids universally agree that tumors greater than 2 cm demand a formal oncological operation such as a low anterior resection (LAR) with total mesorectal excision (TME) or abdominal–perineal resection (APR) with TME. For local rectal carcinoids, less than 1 cm in size, without evidence of lymphatic involvement on endoscopic ultrasound, a transanal surgical or endoscopic excision has been embraced as the standard in the literature and by the major organizational guidelines: European Neuroendocrine Tumor Society, North American Neuroendocrine Tumor Society, National Cancer Institute, and National Comprehensive Cancer Network.4, 6–9 In contrast, the treatment for rectal carcinoids from 1 to 2 cm is a matter of intense debate. Some authors believe that these intermediate-sized lesions will behave in an indolent manner. These authors recommend a conservative, nonaggressive approach to their resection.4–10 However, we have observed relatively poor clinical outcomes in this intermediate rectal carcinoid population. Based on our clinical experiences in a large tertiary referral center for neuroendocrine tumors (NETs), we conducted a formal review to better define the clinical impact that tumor size has on nodal positivity and the overall survival rate for this rare malignancy. We hypothesized that the malignancy potential of rectal carcinoids has been underestimated and that smalland intermediate-sized rectal carcinoids may warrant more aggressive surgery than what has been traditionally recommended.

Laparoscopic resection of gastrointestinal neuroendocrine tumors with special contribution of radionuclide imaging.

The surgical treatment of neuroendocrine tumors (NETs) draws on experience and guidelines more than on prospective randomized trials. The incidence of NET is increasing in all parts of the gastrointestinal tract. A variety of classifications introduced over the last decade may have led to difficulties in judging clinical relevance and determining the right surgical strategy. The North American Neuroendocrine Tumor Society and the European Neuroendocrine Tumor Society have developed usable guidelines from the available literature. For more than 20 years laparoscopy has developed as the gold standard for various surgical indications. Nevertheless, few trials have compared open and laparoscopic surgery with regard to NET. This review summarizes the recent literature on surgery for NET and incorporates the evidence on laparoscopy for cancer which might be also applied for NET.

Clinical and Prognostic Features of Rectal Neuroendocrine Tumors

Background: Rectal neuroendocrine tumors (NETs) are among the most common NETs. The aim was to validate European Neuroendocrine Tumor Society (ENETS)/North American Neuroendocrine Tumor Society (NANETS) staging and grading systems with regard to clinical outcomes. Methods: A comprehensive database was constructed from existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation. Analysis was performed on 141 patients identified with rectal NETs seen at Mount Sinai Hospital between 1972 and 2011. Results: The median age was 52.7 years; 43% were males. Average tumor size was 0.88 cm. NETs <1 cm accounted for 75.6% of the tumors. Stage I, II, III and IV accounted for 79.4, 2.8, 5.0 and 12.8% of the tumors, respectively. G1 tumors accounted for 88.1%, G2 8.3% and G3 3.6%. Of G1 tumors, 94.6% were stage I and 5.4% were stage IV. The median survival time for all 141 patients was 6.8 years (range, 0.8-34.7 years). The overall 5-year survival rate was 84.4%. The 5-year survival rates for patients in stages I-IV were 92.7, 75.0, 42.9 and 33.2%, respectively. The 5-year survival rates for patients with G1-G3 tumors were 87.7, 47.6 and 33.3%, respectively. Univariate analysis of increased survival showed significance for lower stage, lower grade, smaller size, absence of symptoms and endoscopically treated tumors. Multivariate analysis showed that stage alone was statistically significant as the strongest predictor of survival. Conclusion: The results of our study validated ENETS/NANETS guidelines for staging and grading of rectal NETs in the US setting of a tertiary referral center. Staging according to ENETS/NANETS guidelines should be used in the treatment algorithm rather than size alone.

Consensus Guidelines for the Management and Treatment of Neuroendocrine Tumors

Neuroendocrine tumors are a heterogeneous group of tumors originating in various anatomic locations. The management of this disease poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The recent completion of several phase 3 trials, including those evaluating octreotide, sunitinib, and everolimus, demonstrate that rigorous evaluation of novel agents in this disease is possible and can lead to practice-changing outcomes. Nevertheless, there are many aspects to the treatment of neuroendocrine tumors that remain unclear and controversial. The North American Neuroendocrine Tumor Society published a set of consensus guidelines in 2010, which provided an overview for the treatment of patients with these malignancies. Here, we present a set of consensus tables intended to complement these guidelines and serve as a quick, accessible reference for the practicing physician.

Abstracts Presented at the 5th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 11–13, 2012, San Diego, California

Abstracts Presented at the 5th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 11–13, 2012, San Diego, California

Hereditary Medullary Thyroid Cancer: Age-Appropriate Thyroidectomy Improves Disease-Free Survival

Twenty-five percent of medullary thyroid cancer (MTC) cases are hereditary. The ideal age for prophylactic thyroidectomy is based on the specific RET mutation involved. The purpose of this study was to determine whether such age-appropriate prophylactic thyroidectomy results in improved disease-free survival. Twenty-eight patients underwent thyroidectomy for hereditary MTC at our institution. Age-appropriate thyroidectomy was defined according to the North American Neuroendocrine Tumor Society (NANETS) guidelines. Patients who had age-appropriate surgery (group 1, n = 9) were compared to those who had thyroidectomy past the recommended age (group 2, n = 19). The mean age was 13 ± 2 years, and 61 % were female. Patients in group 1 were younger than in group 2 (4 ± 1 vs. 17 ± 2 years, p < 0.01). There were no significant differences in gender or RET mutation types between these two groups. Group 1 patients were cured with no disease recurrence compared with group 2 patients who had a 42 % recurrence rate (p = 0.05). Subanalysis of group 2 identified that patients who underwent surgery without evidence of disease did so at a shorter period following the guidelines compared with those who underwent therapeutic surgery (2 ± 2 vs. 16 ± 2 years, p = 0.01) and had longer disease-free survival (100 vs. 27 %, p = 0.005). Patients with hereditary MTC should undergo age-appropriate thyroidectomy based on RET mutational status to avoid recurrence. Patients who are past the recommended age should have surgery as early as possible to improve disease-free survival.

Tu1153 Clinical and Prognostic Features of Rectal Neuroendocrine Tumors

Background: Rectal neuroendocrine tumors (NETs) are among the most common NETs. The aim was to validate European Neuroendocrine Tumor Society (ENETS)/North American Neuroendocrine Tumor Society (NANETS) staging and grading systems with regard to clinical outcomes. Methods: A comprehensive database was constructed from existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation. Analysis was performed on 141 patients identified with rectal NETs seen at Mount Sinai Hospital between 1972 and 2011. Results: The median age was 52.7 years; 43% were males. Average tumor size was 0.88 cm. NETs <1 cm accounted for 75.6% of the tumors. Stage I, II, III and IV accounted for 79.4, 2.8, 5.0 and 12.8% of the tumors, respectively. G1 tumors accounted for 88.1%, G2 8.3% and G3 3.6%. Of G1 tumors, 94.6% were stage I and 5.4% were stage IV. The median survival time for all 141 patients was 6.8 years (range, 0.8–34.7 years). The overall 5-year survival rate was 84.4%. The 5-year survival rates for patients in stages I–IV were 92.7, 75.0, 42.9 and 33.2%, respectively. The 5-year survival rates for patients with G1–G3 tumors were 87.7, 47.6 and 33.3%, respectively.

Abstracts Presented at the 4th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 21, 2011, Minneapolis, Minnesota

Abstracts Presented at the 4th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 21, 2011, Minneapolis, Minnesota

Hereditary Medullary Thyroid Cancer: Age-Appropriate Thyroidectomy Improves Disease-Free Survival

Twenty-five percent of medullary thyroid cancer (MTC) cases are hereditary. The ideal age for prophylactic thyroidectomy is based on the specific RET mutation involved. The purpose of this study was to determine whether such age-appropriate prophylactic thyroidectomy results in improved disease-free survival. Twenty-eight patients underwent thyroidectomy for hereditary MTC at our institution. Age-appropriate thyroidectomy was defined according to the North American Neuroendocrine Tumor Society (NANETS) guidelines. Patients who had age-appropriate surgery (group 1, n = 9) were compared to those who had thyroidectomy past the recommended age (group 2, n = 19). The mean age was 13 ± 2 years, and 61 % were female. Patients in group 1 were younger than in group 2 (4 ± 1 vs. 17 ± 2 years, p < 0.01). There were no significant differences in gender or RET mutation types between these two groups. Group 1 patients were cured with no disease recurrence compared with group 2 patients who had a 42 % recurrence rate (p = 0.05). Subanalysis of group 2 identified that patients who underwent surgery without evidence of disease did so at a shorter period following the guidelines compared with those who underwent therapeutic surgery (2 ± 2 vs. 16 ± 2 years, p = 0.01) and had longer disease-free survival (100 vs. 27 %, p = 0.005). Patients with hereditary MTC should undergo age-appropriate thyroidectomy based on RET mutational status to avoid recurrence. Patients who are past the recommended age should have surgery as early as possible to improve disease-free survival.

Abstracts Presented at the 3rd Annual Meeting of the North American NeuroEndocrine Tumor Society, October 29-30, 2010, Santa Fe, New Mexico

Abstracts Presented at the 3rd Annual Meeting of the North American NeuroEndocrine Tumor Society, October 29-30, 2010, Santa Fe, New Mexico

The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors

Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and parasympathetic paragangliomas are neuroendocrine tumors derived from adrenal chromaffin cells or similar cells in extra-adrenal sympathetic and parasympathetic paraganglia, respectively. Serious morbidity and mortality rates associated with these tumors are related to the potent effects of catecholamines on various organs, especially those of the cardiovascular system. Before any surgical procedure is done, preoperative blockade is necessary to protect the patient against significant release of catecholamines due to anesthesia and surgical manipulation of the tumor. Treatment options vary with the extent of the disease, with laparoscopic surgery being the preferred treatment for removal of primary tumors. Medullary thyroid cancer (MTC) is a malignancy of the thyroid C cells or parafollicular cells. Thyroid C cells elaborate a number of peptides and hormones, such as calcitonin, carcinoembryonic antigen, and chromogranin A. Some or all of these markers are elevated in patients with MTC and can be used to confirm the diagnosis as well as to follow patients longitudinally for recurrence. Medullary thyroid cancer consists of a spectrum of diseases that ranges from extremely indolent tumors that are stable for many years to aggressive types associated with a high mortality rate. Genetic testing for RET mutations has allowed identification of familial cases and prophylactic thyroidectomy for cure. The only curative treatment is complete surgical resection.

The North American Neuroendocrine Tumor Society (NANETS) Guidelines

The North American Neuroendocrine Tumor Society (NANETS) had its initial organizational meeting in Portland, Oregon on September 28, 2006 to establish a professional society with the primary purpose to improve neuroendocrine tumor disease management through increased research and educational opportu