Management Of Well-Differentiated Neuroendocrine Tumors Research Articles

Impact of FDG PET/CT Scan in Changing Management of Well-Differentiated Neuroendocrine Tumors With Ki67 Index Less Than or Equal to 5.

This study aimed to see the impact of FDG PET/CT with somatostatin receptor PET (SSTR PET) in directing the treatment plan in lower-grade well-differentiated neuroendocrine tumors (NETs) with Ki67 index ≤5%. Sixty-three NET cases with Ki67 index ≤5% with both FDG PET and SSTR PET ( 68 Ga-DOTANOC PET) were included for this retrospective observational study. FDG PET findings were classified into positive, weakly positive, and negative based on a visual scale. Clinical factors considered while referring for FDG PET scan were audited from electronic medical records. The addition of chemotherapy was considered as FDG-directed change in treatment. Sixty patients showed intense SSTR expression in the primary and metastatic sites (if present). Three patients showed no evidence of SSTR expression, in whom the scans were done after resection of the primary tumor. The FDG PET was positive in 25 (39.6%), weakly positive in 11 (17.4%), and negative in 27 (42.8%). Specific clinical reason for doing FDG PET was found in 34 patients, and in the remaining 29, there was no justification or specific indication for doing the FDG study; 73.5% of patients from the former group was either FDG positive or weakly positive, and 26.5% were negative; in the other group, 62.1% were FDG-negative, and 37.9% were positive ( P = 0.004). Treatment-naive patients with symptom duration of ≤5 months were associated with more FDG positivity than patients with >5 months' symptom duration ( P = 0.006). FDG PET/CT led to change in management in 17.4% of all the patients, 9.6% of grade 1, and 25% of grade 2 patients. In lower-grade NET, FDG positivity was seen in a sizable number of the cases, and this led to change in management in 17.4% of the cases. Specific clinical features could be utilized to successfully discriminate between FDG-avid and non-FDG-avid disease in lower-grade NETs, and this had impact in management change as well.

Pharmacotherapeutic Management of Well-Differentiated Neuroendocrine Tumors in Older Patients: Current Status and Potential Therapies.

Neuroendocrine tumors are a rare and heterogenous group of neoplasms that arise from hormone-producing cells throughout the body, with the greatest increase in incidence occurring among older adults aged ≥65 years. Despite this, there is currently a lack of data regarding the safety and efficacy of systemic treatment for older adults with neuroendocrine tumors. In this review, we provide a synopsis of the current standard-of-care pharmacotherapeutic treatments for neuroendocrine tumors, with an emphasis on available data in older adults. The benefits of various systemic options such as somatostatin analogs, tryptophan hydroxylase inhibition, moleculartargeted agents, peptide receptor radionuclide therapy, and chemotherapy were similar between older adults compared to younger patients. However, real-worlddata regarding tolerance in the older adult populationwith neuroendocrine tumors are needed. Future development of novel systemic therapies in the neuroendocrine tumor treatment landscape and their inclusion ofand potential impact on older adults living with neuroendocrine tumors is warranted.

Immunotherapy in Neuroendocrine Neoplasms: Where Are We Now?

Immune checkpoint inhibitors (ICIs) represent a breakthrough in the management of many hard-to-treat cancers over the past decade with demonstrable improvement in survival outcomes. We reviewed the state of the art of ICIs in neuroendocrine neoplasms (NENs). While ICIs have become part of the standard of care for the management of small cell lung cancer (SCLC), their role is still unclear in the management of extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) as well as in the management of well-differentiated neuroendocrine tumors (NETs). Conflicting results derived from the various studies in NETs and EP NECs therefore for specific settings, such as the lung NETs, or therapeutic regimen, e.g., combo vs single agent, for ICIs benefit. Therefore, at the moment, no ICIs approach is justified for NETs and EP NECs in clinical practice. Future investigations should be designed with the aim to overcome the several limitations of the current trials, e.g., lacking of a central pathology review or heterogeneity of the cohorts, in order to reduce the risk of biases. Future trials combining ICIs with other biological agents are welcome. This review aims to provide a comprehensive overview of the biological rationale and evolving clinical applications of the use of ICIs in the management of NENs (both well-differentiated and poorly differentiated groups).

Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors.

Challenges in the Diagnosis and Management of Well-Differentiated Neuroendocrine Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future Considerations.

Neuroendocrine tumors (NET) of the lung represent approximately 25% of all primary lung tumors and can be classified as low grade (typical carcinoids), intermediate grade (atypical carcinoids), or high grade (large cell neuroendocrine carcinoma or small cell lung carcinoma). Low- and intermediate-grade lung NET are increasingly recognized as biologically distinct from high-grade lung NET based on clinical behavior and underlying molecular abnormalities. This review summarizes current knowledge and challenges in the diagnosis and management of low- and intermediate-grade lung NET. Accurate histopathologic classification of lung NET is critical to determining appropriate treatment options but can be challenging even for experts. For low- and intermediate-grade lung NET, surgery remains the mainstay of treatment for localized disease. Although no standard systemic therapy has been established for the treatment of advanced, unresectable disease, a number of promising treatment options are emerging, including somatostatin analogs, temozolomide-based chemotherapy, targeted therapy with mammalian target of rapamycin or vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. Given the difficulty in accurately diagnosing these tumors, and the paucity of data supporting establishment of standard systemic therapy options, management of patients within the setting of a multidisciplinary team, including specialists with expertise in NET, is recommended. Ongoing and future clinical trials hopefully will provide stronger evidence to support treatment recommendations for low- and intermediate-grade lung NET.

Management of Well-Differentiated Gastrointestinal Neuroendocrine Tumors Metastatic to the Liver

Neuroendocrine tumors (NETs) can have indolent clinical courses and patients with metastatic disease may live many years after the initial diagnosis. Recent studies have suggested that aggressive treatments may extend survival. In this review, we assess the recent literature regarding management of well-differentiated NETs from the gastrointestinal (GI) tract metastatic to the liver. We focus on studies regarding surgical resection, embolization, or ablation of hepatic lesions. We also present a management algorithm for patients who present with metastatic lesions but the primary lesion cannot be located. Since NETs are rare, all of the available evidence is based on retrospective studies that have limited sample size. As a result, recommendations are offered with caution.