Corrigendum to "The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management". [Cancer Treat. Rev. 139 (2025) 102998

Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

ED04.01 Surgery in Bronchopulmonary Typical and Atypical Carcinoids

It's not a mystery, it's in the history: Multidisciplinary management of multiple endocrine neoplasia type 1.

Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome

629 Background: The incidence and prevalence of NETs is increasing and diagnosis and pathologic evaluation of NETs is complex. Given the new advances in local and systemic therapies, multidisciplinary management models have been suggested to assist in treatment decisions. However, scientific data showing definite change in management with multidisciplinary clinic (MDC) review is lacking. We aim to address this need in this study. Methods: 113 GI-NET patients from 2012-18 were reviewed from a dedicated MDC where patients are seen simultaneously by multiple subspecialties, and data on patient characteristics, radiology, tumor pathology and treatment strategies were collected. Change in diagnosis was defined as any change in radiographic or pathologic findings that resulted in a change in the tumor type, grade, site or stage of cancer. Change in management was defined as any recommended change in treatment approach for NETs compared to the prior treatment plan. For patients who did not have a prior treatment plan or were seen directly at MDC, a change of management was considered as yes only if there was a change in diagnosis post MDC. Results: The mean age of patients evaluated was 61, with locally advanced or metastatic disease seen in 81% of patients. Small bowel and pancreatic NETs were the most common primaries (36% each). Significant proportion of NETs were well-differentiated (72%) with < 2 mitosis/10 HPF (47.3%) and Ki-67 of < 3% (36%). Patients were referred to MDC at an average of 2.5 years from diagnosis, with 23% having the MDC as their first visit. 40% had prior resection of primary, 25% were on somatostatin analogues (SSAs) previously and 9% of patients had received prior liver directed therapy (LDT). A significant proportion of patients had change in diagnosis post MDC evaluation: change in site (7%), stage of disease (7%), tumor type (3.5%) and grade (0.1%). A change in management was recommended in 50% of patients, with SSAs recommended in 43.8%, surgery in 25.4% and LDT in 17.5% of the patients. Conclusions: The use of a dedicated MDC to manage NETs had a substantial impact in change in management in a significant percentage of patients evaluated. MDC care for patients diagnosed with NET is recommended for optimal management.

Neuroendocrine neoplasms (NEN) are a rare and heterogeneous group of malignancies with rising incidence, requiring multidisciplinary and personalized management. Sex is emerging as a crucial factor in NEN development and progression. Genetic, epigenetic, and hormonal mechanisms have been proposed as potential contributors influencing treatment response and prognosis, but an in-depth analysis of the role of sex hormones and their receptors in NEN is still lacking. This review aims to analyze the impact of sex hormones and their receptors in sporadic NEN to provide potential therapeutic targets in the context of precision medicine. An overview of current preclinical and clinical evidence focused on different primary NEN, including gastroenteropancreatic, lung, prostate, and medullary thyroid cancers, focusing on estrogen, progesterone, and androgen receptors, has been made to clarify their role in NEN. Variable and conflicting results emerged across different primaries. Progesterone receptors appear to play a pivotal role in pancreatic and lung NEN, while estrogen receptors are more frequently involved in small intestine NEN and medullary thyroid carcinoma, suggesting a possible role in metastatic spread. Further studies are required to increase knowledge of the underlying mechanism of sex differences in NEN to define potential therapeutic targets for personalized care.

An estimated 25% to 30% of all neuroendocrine tumors (NETs) have their origin in the bronchial tree and into the lungs. Although lung NETs account for less than 1% of all pulmonary malignancies, the incidence of these neoplasms has risen precipitously since the mid 1970s. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), high-grade large-cell neuroendocrine carcinoma (LCNEC) and small-cell carcinoma (SCLC). Surgery is the treatment of choice for typical and atypical carcinoid lung NETs with loco-regional disease. At diagnosis up to 64% of patients with atypical carcinoid lung NETs present with lymph node metastases, and 5-year survival ranges from 61% to 88%. In contrast, lymph node metastases are present in fewer than 15% of typical carcinoid lung NETs, and 5-year survival exceeds 90%. To date, there is no recognized standard of treatment for advanced carcinoid lung NETs. In recent years only two trials reported intriguing results regarding lung NETs: a phase 2 retrospective study of dacarbazine derivative temozolomide and the phase 3, RADIANT-2 trial in advanced NETs. Successful management requires a multidisciplinary team management. This review is restricted to typical/atypical NETs.

The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management.

Gastroenteropancreatic neuroendocrine tumors (GEPNET) are rare tumors that may be sporadic or develop as part of multiple endocrine neoplasia type 1 syndrome (MEN1). The aim of the present study was to report the experience of a Brazilian multidisciplinary outpatient neuroendocrine tumor clinic regarding the clinical diagnosis of MEN1 in a cohort of GEPNET patients. Patient data, including clinical characteristics and the lag time from the onset of symptoms to diagnosis of the first tumor, and further lag time until the diagnosis of MEN1, were retrospectively reviewed. Among 44 GEPNET patients, 6 had a clinical diagnosis of MEN1. Primary hyperparathyroidism and GEPNET were present in all patients in the cohort, and pituitary neuroendocrine tumors were present in 33.3%. The median time interval from the onset of initial symptoms to the diagnosis of the first tumor was 42 months (range, 0-204 months). The median time interval between the diagnosis of the first tumor and the diagnosis of MEN1 was 22 months (range, 1-109 months). The prolonged lag time between the onset of initial symptoms and MEN1 diagnosis may result in substantial morbidity and loss of opportune interventions for the patients. Therefore, greater efforts should be made to shorten these times and improve the care of patients with MEN1.

Well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract are rare, slow-growing neoplasms. Clinical outcomes in a group of stage IV, well-differentiated patients with NETs with small bowel primaries undergoing cytoreductive surgery and multidisciplinary management at a single center were evaluated. The charts of 189 consecutive patients who underwent surgical cytoreduction for their small bowel NETs were reviewed. Information on the extent of disease, complications, and Kaplan-Meier survival were collected from the patient records. A total of 189 patients underwent 229 cytoreductive operations. Ten percent of patients required an intraoperative blood transfusion and 3% (6 of 229) had other intraoperative complications. For all 229 procedures performed, mean (± SD) stay in the ICU was 4 ± 3 days and in the hospital was 9 ± 10 days. Before discharge, 51% of patients had no postoperative complications and 39% of patients had only minor complications. In a 30-day follow-up period from discharge, 85% of patients had no additional complications and 13% had only minor complications. The 30-day postoperative death rate was 3% (5 of 189). Mean survival from histologic diagnosis of NET was 236 months. The 5-, 10-, and 20-year Kaplan-Meier survival rates from diagnosis were 87%, 77%, and 41%, respectively. Cytoreductive surgery in patients with well-differentiated midgut NETs has low mortality and complication rates and is associated with prolonged survival. We believe that cytoreductive surgery is a key component in the care of patients with NETs.

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with worldwide increasing incidence, high prevalence and survival. Both the tumor itself and the systemic therapy may have an impact on patients' nutrition. Malnutrition negatively impacts on outcome in NETs patients. Moreover, it has been demonstrated that body mass index was a risk factor for NET development and that metabolic syndrome was associated with worse prognosis in these patients. Of note, food could also interact with the metabolism of oral target therapy and antineoplastic agents used for the treatment of progressive NETs. Therefore, the nutritional assessment, based on body composition, and lifestyle modifications should be an integral component of management of the NET patients. The nutrition care plans are an integral part of the multidisciplinary management team for patients with NETs. Nutritionists with expertise in NETs can provide dietary approaches to improve the quality of life and nutritional status during various therapeutic modalities used in patients with NETs. The aim of this review is to critically discuss the importance of nutrition and body composition in patients with NETs.

Nutrition and metabolism are altered in patients with gastroenteropancreatic neuroendocrine tumors, which is related to excessive production of gastrointestinal hormones, peptides, and amines that can cause maldigestion, diarrhea, steatorrhea, and altered gastrointestinal motility. Patients with carcinoid syndrome are at risk of malnutrition due to tryptophan depletion, reduced intake of food, and loss of appetite because of diarrhea and/or flushing. To date, there is limited information on the nutritional issues faced by patients with neuroendocrine tumors, and on what specific recommendations should be made to patients concerning nutrition at various stages of the disease process. Dietary planning should therefore be an integral part of multidisciplinary management for patients with neuroendocrine tumors. Herein, we review current guidance for nutrition in patients with neuroendocrine tumors, focusing on intake of amines and foods to avoid, as well as concurrent medications. We also propose a new and practical food pyramid based on the principles of Mediterranean diet 4.0 that can be easily adapted according to the unmet needs of patients with neuroendocrine tumors at all stages of disease. The overarching goal of the present review is to create greater awareness of nutritional care and considerations that should be given to patients with neuroendocrine tumors.

Purpose: In patients with a neuroendocrine tumour (NET), the extent of disease strongly influences the outcome and multidisciplinary therapeutic management. Thus, systematic analysis of the diagnostic performance of the existing staging modalities is necessary. The aim of this study was to compare the diagnostic performance of 2 whole-body imaging modalities, [68Ga]DOTATOC positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) in patients with NET with regard to possible impact on treatment decisions. Materials and methods: [68Ga]DOTATOC-PET/CT and whole-body magnetic resonance imaging (wbMRI) were performed on 51 patients (25 females, 26 males, mean age 57 years) with histologically proven NET and suspicion of metastatic spread within a mean interval of 2.4 days (range 0–28 days). PET/CT was performed after intravenous administration of 150 MBq [68Ga]DOTATOC. The CT protocol comprised multiphase contrast-enhanced imaging. The MRI protocol consisted of standard sequences before and after intravenous contrast administration at 1.5 T. Each modality (PET, CT, PET/CT, wbMRI) was evaluated independently by 2 experienced readers. Consensus decision based on correlation of all imaging data, histologic and surgical findings and clinical follow-up was established as the standard of reference. Lesion-based and patient-based analysis was performed. Detection rates and accuracy were compared using the McNemar test. P values <0.05 were considered significant. The impact of whole-body imaging on the treatment decision was evaluated by the interdisciplinary tumour board of our institution. Results: 593 metastatic lesions were detected in 41 of 51 (80%) patients with NET (lung 54, liver 266, bone 131, lymph node 99, other 43). One hundred and twenty PET-negative lesions were detected by CT or MRI. Of all 593 lesions detected, PET identified 381 (64%) true-positive lesions, CT 482 (81%), PET/CT 545 (92%) and wbMRI 540 (91%). Comparison of lesion-based detection rates between PET/CT and wbMRI revealed significantly higher sensitivity of PET/CT for metastatic lymph nodes (100% vs 73%; P < 0.0001) and pulmonary lesions (100% vs 87%; P = 0.0233), whereas wbMRI had significantly higher detection rates for liver (99% vs 92%; P < 0.0001) and bone lesions (96% vs 82%; P < 0.0001). Of all 593 lesions, 22 were found only in PET, 11 only in CT and 47 only in wbMRI. The patient-based overall assessment of the metastatic status of the patient showed comparable sensitivity of PET/CT and MRI with slightly higher accuracy of PET/CT. Patient-based analysis of metastatic organ involvement revealed significantly higher accuracy of PET/CT for bone and lymph node metastases (100% vs 88%; P = 0.0412 and 98% vs 78%; P = 0.0044) and for the overall comparison (99% vs 89%; P < 0.0001). The imaging results influenced the treatment decision in 30 patients (59%) with comparable information from PET/CT and wbMRI in 30 patients, additional relevant information from PET/CT in 16 patients and from wbMRI in 7 patients. Conclusion: PET/CT and wbMRI showed comparable overall lesion-based detection rates for metastatic involvement in NET but significantly differed in organ-based detection rates with superiority of PET/CT for lymph node and pulmonary lesions and of wbMRI for liver and bone metastases. Patient-based analysis revealed superiority of PET/CT for NET staging. Individual treatment strategies benefit from complementary information from PET/CT and MRI.

BackgroundNeuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.Case presentationA 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.Discussion and conclusionsThis case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.

Introduction and importancePheochromocytomas are rare tumors (0.1–2% of incidence), arising from the chromaffin cells in the sympathoadrenal system. Approximately 85% of the times are localized in the adrenal medulla; therefore, could be placed extra adrenal in 15% of the population. 10–30% of the cases could be asymptomatic. Classic symptoms vary from palpitations, tachycardia, hypertension.Case presentationCase report of a 37-year-old female patient presented with diffuse abdominal pain, with any associated symptoms. Contrast computed tomography was performed; a retroperitoneal mass was found, contacting the third portion of the duodenum. Intraoperative hypertensive crisis was documented with the manipulation of the mass. Octreotide infusion was administered with the normalization of the clinical condition. Patients do not present any postoperative morbidity after 90 days. Pathology reports chromaffin cells concluding pheochromocytoma.DiscussionPheochromocytomas are rare tumors with an annual incidence between 3 and 8 cases per million population per year in some series of cases. In general terms prevalence rounds 0.1–0.6% of patients with hypertension. Surgical management is the definitive treatment for pheochromocytoma benign or malign. Morbidity described in literature reaches 40% with 20% of mortality in some series of cases. In our patient we do not present postoperative complications.ConclusionIntraoperative hypertension is a clinical and surgical challenge, not only for the surgeon, also anesthesiology. Pheochromocytoma it's a complex entity and could be silent in until 30% of the cases, should be suspected in all neuroendocrine retroperitoneal tumors. Multidisciplinary approach with anesthesia, endocrinology and surgery department is mandatory to have good postoperative outcomes.