An Update on the Management of Mixed Neuroendocrine-Non-neuroendocrine Neoplasms (MiNEN)

Jacob, Aasems; Raj, Rishi; Allison, Derek B.; Soares, Heloisa P.; Chauhan, Aman

doi:10.1007/s11864-022-00968-y

Cited by 13 publications

(18 citation statements)

References 55 publications

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“…This cancer type can be separated into well-differentiated NET and poorly differentiated NEC, as well as MiNEN. 20 , 28 Mostly developing in the gastrointestinal tract and pancreas, NENs are graded using Ki-67, 20 with G2 NEN having a proliferation index of 3% to 20% (G3, >20%). To date, the number of NEN patients that underwent FAPI-directed PET is rather limited.…”

Section: Discussionmentioning

confidence: 99%

Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors

et al. 2022

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We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)-directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI). Patients and Methods: Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68 Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68 Ga-FAPI-04 PET/CT. Results: Compared with GCI, 68 Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%). Conclusions: In patients affected with digestive system tumors, 68 Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.

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Section: Discussionmentioning

confidence: 99%

Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors

et al. 2022

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“…The mixed neuroendocrine and non-neuroendocrine components make the biological behaviors of MiNENs more complicated. Genetics analysis have shown that this two components share the same clonal origin ( 5 , 30 , 31 ). However, adjuvant treatments for these two components are largely different ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases

et al. 2023

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BackgroundMixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is an extremely rare entity, consisting of neuroendocrine and non-neuroendocrine components. It can occur in various organs throughout the body, with a rising incidence. Its clinical management is a rapidly growing field of interest; however, large-scale patient cohorts are still missing to guide clinical practice.Patients and methodsThe demographic, clinicopathological, and survival information of all patients diagnosed with MiNEN in the national Surveillance, Epidemiology, and End Results (SEER) program database (2000–2017) were extracted and further analyzed. The information of the patients before and after 2010 was compared to understand the epidemiological changes of MiNEN. The characteristics of MiNEN originating in different organs were compared. The clinical significance of surgical resection for metastatic MiNENs was also analyzed.ResultsA total of 1081 patients were screened, and after applying the exclusion criteria, 767 patients were finally analyzed. There was no obvious sex preference (49.2% vs 50.8%, p>0.05) and the majority of the patients were Caucasians (n=627, 81.7%). A total of 88.3% of the patients were older than 50 years old, and the median age was 60 years. 79.3% of the tumors are located in the distal digestive tract, and 67.7% were grade 3/4. Distant metastasis was presented in 33.9% of the patients at diagnosis. A total of 88% of the patients underwent surgical treatments. The number of patients increased 10-fold between 2000 and 2017. There was no significant difference in sex, race, stage, or surgical treatments among the patients diagnosed before and after 2010. More patients older than 60 years were diagnosed after 2010 (p=0.009). The median survival was 61.0 ± 9.8 months for the whole cohort. After multivariate analysis, older age (>60 years, p<0.01), more advanced stage (p<0.01), grade 3/4 (p<0.01), and non-surgical treatment (p<0.01) were independent risk factors for poorer survival. The appendiceal MiNENs showed the best prognosis. A total of 260 metastatic MiNENs were further analyzed. Only patients with metastatic MiNENs originating from the appendix had a potential benefit from surgical resection, compared to other sites (p=0.05).ConclusionThis study provides the epidemiological, clinicopathological, and survival information of the largest number of MiNEN patients. Although MiNEN is an extremely rare malignant neoplasm, its incidence increases rapidly. The majority of the patients suffered from advanced-stage disease, which highlights the need for improvement of early detection in the future. The appendix is the most common primary site of MiNEN, and surgical resection for selected metastatic MiNEN originating in the appendix has favorable survival outcomes.

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“…In our study, the initial liver biopsy revealed GEP-NEC concurrent with adenocarcinoma as NEC with NNE. Although the NNE adenocarcinoma component could be diagnosed from the initial biopsy, the primary tumor site could only be identified using surgically-resected samples, which increases the difficulty in identifying an appropriate treatment strategy ( 7 ). Hence, there remains a dilemma around whether therapy should be selected to target NEC or NNE.…”

Section: Discussionmentioning

confidence: 99%

“…All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and F adenocarcinoma component could be diagnosed from the initial biopsy, the primary tumor site could only be identified using surgically-resected samples, which increases the difficulty in identifying an appropriate treatment strategy (7). Hence, there remains a dilemma around whether therapy should be selected to target NEC or NNE.…”

Section: Case Presentationmentioning

confidence: 99%

“…Thus, apart from the SCNEC and LCNEC, the World Health Organization (WHO) has added another subtype of GEP-NEC known as mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) ( 6 ). It was decided that both NE and NNE components should constitute at least 30% each of the total tumor mass for a GEP-NEC to be classified as MiNEN, assuming that the tumor prognosis is affected by a minor NE component (<30%) in an NNE malignancy ( 5 , 7 ). However, recent studies have shown that the presence of more than 10% of a NE component may also be clinically relevant to the prognosis of such tumors ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

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The efficacy of oxaliplatin, surufatinib, and camrelizumab on neuroendocrine carcinoma: a case report and literature review

Wang¹,

Hu²,

Su³

et al. 2022

Ann Transl Med

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Background: Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are rare, accounting for ~1/100,000 of NECs, aggressive neoplasms and poor prognosis. Sometimes, a non-neuroendocrine component is also accompanying these EP-NECs. Curative surgery is suggested for early stage patients while system chemotherapy and locoregional radiotherapy are considered for advanced inoperable disease.Nonetheless, there was lack of standard second-line treatment strategy. Herein, we report a case of NEC involving a large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma of the gallbladder treated with a surufatinib-containing regimen in the second-line treatment setting and establish the efficacy of this regimen in the treatment of EP-NECs.Case Description: A 58-year-old male presented with symptoms such as distension in the upper right abdomen and a palpable mass. The abdominal magnetic resonance imaging (MRI) scan showed a giant soft tissue mass in the left lobe of the liver, and liver biopsy suggested LCNEC with a non-neuroendocrine (NNE) component. Based on the available literature, a first-line therapy of oxaliplatin + gemcitabine + camrelizumab + apatinib was started initially; however, there was rapid tumor progression. Thus, a second line of treatment was started, where apatinib was replaced with surufatinib, which was given along with oxaliplatin and camrelizumab and continued for seven complete cycles. The patient was re-examined with MRI, which showed a significant decrease in tumor size. And a partial response was achieved. Main adverse events included hand and foot numbness, hypertension, proteinuria, hematuria, and hyperthyroidism.The patient underwent surgery after the second line of treatment and the post-operative pathology report revealed the presence of LCNEC and adenocarcinoma of the gallbladder. Two months later, re-examination result showed no tumor recurrence.Conclusions: As yet, the criteria strategy for unresectable EP-NECs to improve survival outcomes is scarce. EP-NECs are badly in need of effective second-line therapy to carry out survival benefits after resistance to first-line regimen. The case report demonstrated that a surufatinib-containing regimen including oxaliplatin and camrelizumab could be an effective treatment strategy for the second-line treatment of EP-NECs. Furthermore, this strategy is well tolerated and treatment-related toxicity are manageable.More clinical trials are warranted to further confirm the efficacy.

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An Update on the Management of Mixed Neuroendocrine-Non-neuroendocrine Neoplasms (MiNEN)

Cited by 13 publications

References 55 publications

Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors

Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors

Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases

The efficacy of oxaliplatin, surufatinib, and camrelizumab on neuroendocrine carcinoma: a case report and literature review

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