Treatment Of Neuroendocrine Tumors Research Articles

Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide

BackgroundKi67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem).MethodRetrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence.ResultsIn control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001).ConclusionGrade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

Chinese multidisciplinary expert consensus on the rational use of surufatinib in clinical practice（2024 edition）

Neuroendocrine neoplasms are a group of heterogeneous tumors originating from the neuroendocrine system, which can occur in any part of the body. Pulmonary and gastroenteropancreatic neuroendocrine tumors are the most common. In recent years, the global incidence of neuroendocrine tumors has increased more significantly than other types of tumors, especially in the past 40 years. The drug treatment of neuroendocrine tumors includes somatostatin analogues, anti-angiogenesis targeting drugs, nuclide therapy and chemotherapy. Surufatinib is an oral tyrosine kinase receptor inhibitors that targets for vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor 1 (FGFR1), and colony-stimulating factor-1 receptor (CSF-1R), has received approval in 2020 and 2021 for the treatment of locally advanced or metastatic, progressive nonfunctional, well-differentiated (G1, G2) neuroendocrine tumors (NETs) of both pancreatic and extrapancreatic origin that are unresectable. Ongoing exploratory studies are investigating its potential application in other tumor types. Common adverse reactions observed during surufatinib treatment include hypertension, proteinuria, bleeding events, and hepatic lab test abnormal and diarrhea. Chinese multidisciplinary expert consensus on the rational use of surufatinib in clinical practice (2024 edition) aims to provide standardized guidance for its rational use and enhance patient compliance to maximize therapeutic benefits.

Treatment sequencing in gastroenteropancreatic neuroendocrine tumors

SummaryThe oncological treatment of neuroendocrine tumors (NET) has improved significantly in the last few years. Several informative clinical studies on NET have been conducted recently and updated NET guidelines have been published by the European Neuroendocrine Tumor Society (ENETS) in 2023 and 2024. With the growing number of positive phase III trials in NET, the main difficulty today is selecting the most appropriate treatment for a patient at the right time. The purpose of this short review is to delineate the main concepts and important changes in the therapy sequences for gastroenteropancreatic NET (gepNET) outlined in current European guidelines. In clinical practice, more individualized treatment decisions are often required that go beyond these general recommendations.

The current status of somatostatin analogs in the treatment of neuroendocrine tumors and future perspectives.

Somatostatin analogs (SSAs) were developed as antisecretory agents to palliate hormonal symptoms in patients with functioning neuroendocrine tumors (NETs). Their antiproliferative activity has been established in the phase 3 PROMID and CLARINET trials. SSAs currently represent the standard first-line therapy for the majority of well-differentiated G1/G2 gastroenteropancreatic NETs as well as for pulmonary NETs. An update on the clinical applications of established SSAs for the treatment of NETs is provided. Perspectives on emerging nonpeptide SSAs such as paltusotine and innovative formulations of octreotide (CAM2029) are included. SSAs represent the cornerstone of treatment for both functioning and nonfunctioning NETs. While standard-dose SSAs have a defined place in the therapeutic algorithm of well-differentiated NETs, uncertainties remain on how to best integrate above-label doses of SSAs in the treatment sequence, particularly when tumor control is the goal. Octreotide and lanreotide appear to be clinically interchangeable, and no signs of superiority of one agent over the other has been observed so far. Whether SSAs may be exploited in the maintenance setting following more aggressive treatments, whether continuing SSAs beyond-progression after first-line therapy could be an effective treatment strategy, and whether new-generation SSAs such as pasireotide could overcome resistance to established SSAs are key areas of investigation.

P3.13C.09 First-Line Treatments for Advanced Pure Large Cell Neuroendocrine Tumors (LCNEC):Insights from a Global Clinico-Genomic Study

P3.13C.09 First-Line Treatments for Advanced Pure Large Cell Neuroendocrine Tumors (LCNEC):Insights from a Global Clinico-Genomic Study

6743 Decline in IGF-1 after surgery of the nonfunctioning pituitary neuroendocrine tumor

Abstract Disclosure: J. Sugata: None. S. Fujio: None. R. Makino: None. T. Hanada: None. R. Hanaya: None. Background: Patients undergoing surgical treatment for nonfunctioning pituitary neuroendocrine tumors (PitNET) may experience impaired secretion of growth hormone (GH). The optimal timing for assessing GH secretory function postoperatively remains unclear. In our department, we typically conduct hormone-loading tests three months after surgery. However, even in some cases without a diagnosis of growth hormone deficiency (GHD) at that point, there might be a gradual decline in Insulin-like growth factor-1 (IGF-1). Methods: We studied patients who exhibited peak GH levels &amp;gt; 1.8ng/ml in an insulin tolerance test (ITT) three months after undergoing surgery for nonfunctioning PitNET. We evaluated the levels of IGF-1 during the last observation, excluding cases where reoperation or radiosurgery was performed. Results: We identified 67 cases (29 males, 38 females) meeting the study criteria, with a median age of 54 years. The median follow-up time spanned 6 years (range 1-13 years). The median standard deviation (SD) scores of IGF-1 three months after surgery were -0.96, with 14 cases (21%) below -2.0 SD. At the end of the follow-up period, the median SD scores of IGF-1 were -1.31. This was significantly lower than the three-month time point (p&amp;lt;0.01), and 21 cases (31%) recorded were below -2.0 SD. In 6 cases suspected of severe GHD due to subjective symptoms or decreased IGF-1, ITT, or GH-releasing peptide-2 were retested. Among these, 2 cases were diagnosed with severe GHD, while the remaining demonstrated normal secretion of GH despite the low concentration of IGF-1. The IGF-1 SD scores at the end of follow-up and the three-month time-point exhibited a significant correlation (R2=0.74, p&amp;lt;0.01). However, no correlation was found between IGF-1 scores and peak GH concentration, age, tumor size, pituitary apoplexy, or preoperative IGF-1 SD scores. Conclusions: IGF-1 exhibited a progressive decrease in the majority of cases without severe GHD, with some cases showing reductions greater than -2.0 SD. Our findings emphasize the importance of cases with long-term clinical follow-up low IGF-1 after PitNET surgery, even when GH secretion appears normal. Presentation: 6/1/2024

7559 TRIM21 Regulates Activation of ERK1/2 to Promote Growth and Drug Resistance in Pituitary Neuroendocrine Tumors

Abstract Disclosure: Y. Liu: None. F. Liu: None. C. Li: None. T. Zhang: None. L. Xue: None. Z. Wu: None. Objective: To investigate the role of the TRIM family genes in pituitary neuroendocrine tumors (PitNETs) and provide new targets and strategies for the clinical treatment of these tumors. Methods: A CRISPR screening system targeting the TRIM family was constructed and validated using next-generation sequencing. Stable cell lines overexpressing or knocking out TRIM21 were generated, and functional validation was performed using assays such as CCK-8, colony formation, and xenograft tumor growth in nude mice. RNA-seq, mass spectrometry, immunohistochemistry, and immunoblotting were employed to explore the signaling pathways and mechanisms underlying TRIM21's actions. Immunoprecipitation, immunofluorescence, GST-pulldown, NanoBiT assays, and ubiquitination experiments were conducted to investigate the effects of TRIM21 on ERK1/2. Immunohistochemistry and immunoblotting were used to explore the role of TRIM21 in drug- resistant prolactinomas and the correlation between TRIM21 and p-ERK. Results: Through screening the proliferative and drug-resistant effects of the TRIM family in MMQ and GH3 cells, we found that knocking out TRIM21 may inhibit cell growth and enhance drug sensitivity. Subsequently, stable cell lines overexpressing or knocking out TRIM21 were generated in MMQ and GH3 cells, revealing that TRIM21 overexpression promotes pituitary tumor cell growth and resistance to drug treatment, while TRIM21 knockout inhibits cell growth and enhances drug sensitivity. Cell-derived xenograft models showed that TRIM21 overexpression promoted growth of GH3 cells in vivo and resistance to cabergoline (CAB), while TRIM21 knockout suppressed growth of MMQ cells in vivo. Further exploration of the signaling pathways influenced by TRIM21 revealed that TRIM21 knockout downregulates the MAPK signaling pathway, while TRIM21 overexpression upregulates it. TRIM21 overexpression upregulates p-ERK1/2 in the MAPK pathway, while TRIM21 knockout decreases p-ERK. However, there is no significant influence on ERK1/2, JNK, p-JNK, p38, or p-p38. Mechanically, TRIM21 interacted with ERK1/2, enhancing the K27-linked ubiquitination of ERK1/2 and promoting their interaction with MEK1/2. In addition, the TRIM21 with D-docking mutant or ERK1/2 with CD-domain mutant resulted in the loss of their interaction. Furthermore, TRIM21 and p-ERK levels were significantly elevated in drug-resistant prolactinomas and immunohistochemical semi-quantitative analysis demonstrated a positive correlation between TRIM21 and p-ERK. Conclusion: The ubiquitin ligase TRIM21 catalyzes K27-linked ubiquitination of ERK1/2, enhancing its interaction with MEK1/2 and activation, thereby promoting growth and drug resistance in pituitary neuroendocrine tumors. TRIM21 may serve as a potential target for the treatment of pituitary neuroendocrine tumors. Presentation: 6/3/2024

Surgery enhances the effectiveness of peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumors

BackgroundWith the advent of peptide receptor radionuclide therapy, the timing and sequence of surgery in the treatment of metastatic gastroenteropancreatic neuroendocrine tumors merits further study. We hypothesized that surgery before peptide receptor radionuclide therapy might enhance its effectiveness in patients with metastatic gastroenteropancreatic neuroendocrine tumors. MethodsEighty-nine patients with metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors treated with 177Lutetium-dotatate peptide receptor radionuclide therapy between 2018 and 2023 were included. Fifty-six patients underwent surgery (primary tumor resection and/or liver debulking) before peptide receptor radionuclide therapy and 33 patients did not. Primary outcome was progression-free survival according to Response Evaluation Criteria in Solid Tumors. Pretreatment dotatate positron emission tomography/computed tomography was used to calculate tumor volumes. ResultsThe surgery and no-surgery groups were well-matched. Median progression-free survival after peptide receptor radionuclide therapy was 15.6 months (interquartile range, 9.1–22.7 months) in the no-surgery group compared with 26.1 months (interquartile range, 12.7–38.1 months) in the surgery group (P = .04). On subgroup analysis, median progression-free survival was 18.1 months (interquartile range, 11.9–38.4 months) in patients who underwent primary tumor resection only compared with 26.2 months (interquartile range, 14.0–38.1 months) in patients who underwent liver debulking (P = .04). Tumor volume was lowest in patients who underwent liver debulking (median 146.07 mL3) compared with no surgery (median 626.42 mL3) (P = .001). On univariable analysis, a tumor volume <138.8 mL3 was associated with longer progression-free survival (hazard ratio, 2.03; 95% confidence interval, 0.95–4.34, P = .05), with a median progression-free survival of 38.1 months (interquartile range, 16.9–41.3 months) compared with 17.8 months (interquartile range, 10.8–28.7 months). ConclusionSurgery may enhance the effectiveness of 177Lutetium-dotatate in the treatment of metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors. This positive effect may be the result of a lower tumor volume in patients after surgery. Our findings fortify the concept of using surgical debulking to improve systemic therapies such as peptide receptor radionuclide therapy.

Long-term experience with octreotide and lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors.

The somatostatin analogs (SSA) octreotide and lanreotide are a mainstay in the treatment of neuroendocrine tumors (NET). The two pivotal trials differed considerably in terms of patient characteristics and are not directly comparable. Further comparative data are lacking. This retrospective chart review study included patients with gastroenteropancreatic NET grade 1 or 2 who were treated with octreotide LAR or lanreotide autogel. The main aim was to compare the two SSA based on progression-free survival (PFS) and overall survival (OS) from treatment start. In total, 129 patients were analyzed, 60% (n = 77) had a small intestinal NET and 31% (n = 40) a pancreatic NET. Histologically, 34% (n = 44) had NET G1, 55% (n = 71) a NET G2, and 11% (n = 14) a NET G1/G2 unclassified. Lanreotide was used in 90 patients (70%) and octreotide in 39 patients (30%). Overall, the median PFS was 32.2months (95%CI 23.0-42.9months). No PFS difference (p = 0.8) was observed between lanreotide (29.8months, 95%CI 18.7-48.5months) and octreotide (36.0months, 95%CI 23.2-68.2months). Median OS from treatment start was calculated at 93.5months (95%CI 71.1-132.9months). Again, the median OS following lanreotide (113.4months, 95%CI 62.3-NA months) or after octreotide (90.3months, 95%CI 71.1-NA months) did not differ significantly (p > 0.9). Our long-term experience with octreotide and lanreotide in NET did not reveal differences in antitumor effectiveness. This is consistent with previous reports and might suggest that both SSA can be used interchangeably if needed.

Less frequent radiological exams to avoid futile response assessments from 177-LuDOTATE therapy for patients with advanced neuroendocrine tumors.

177-LuDOTATE is an effective but expensive treatment for neuroendocrine tumors (NETs). Reducing treatment-related costs, such as the number of images, could improve access to 177-LuDOTATE. We evaluated early radiological tumor progression and prognostic factors in patients with NETs treated with 177-LuDOTATE. We retrospectively included all patients with NETs who received at least one cycle of 177-LuDOTATE. The primary endpoint was the rate of early radiological progression between cycles 2 and 3 (in 10-16 weeks). Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to prognostic factors (tumor grade, primary site, functioning syndrome, 177-LuDOTATE treatment line) in Cox proportional hazards models. The median number of 177-LuDOTATE cycles was 3 (range 1-6) among 59 patients included. Ten (17%) patients had early progression. Among 14 patients who received ≤2 cycles of 177-LuDOTATE, ten (72%) stopped treatment due to disease progression, with five patients having a G2 (ki67: 5-25%) and 4, a G3 (ki67: 25-90%) NET. In the Cox multivariable analysis, higher grade (G2 or G3 vs G1) were significantly associated with inferior PFS and OS. The median PFS of G1, G2 and G3 NET patients were: 34.1, 11.7 and 6.1 months (P = 0.015), respectively. It is feasible to perform imaging tests after 177-LuDOTATE completion for patients with indolent NETs with the intent to avoid futile assessments. For patients with more aggressive diseases, such as G3 NETs and G2 tumors with high tumor burden, we advise to perform more frequent images during 177-LuDOTATE therapy.

Experiences and Fundamental Care Needs in Patients With Small Intestinal Neuroendocrine Tumours-An Interview Study in a Surgical Context.

The study aimed to describe patients' fundamental care needs and their experiences of nursing care, throughout surgical treatment of small intestinal neuroendocrine tumours. A qualitative descriptive study was performed. Patients' interviews (n = 19) were conducted in Sweden from May 2021 to January 2022 and analysed using directed qualitative content analysis guided by the Fundamentals of Care framework. The results are presented in three descriptive categories chronologically throughout the care chain. In the preoperative phase of care, the category was 'Feeling safe but lonely and frightened, and struggling with existential thoughts'; experiences in the postoperative phase of care resulted in the category 'Feeling cared for but suffering from physical symptoms and feelings of loneliness'; and the category in the discharge phase was 'Lacking self-care information and feeling worried about the future'. There were deficiencies in the delivery of fundamental care for patients with a rare tumour diagnosis throughout surgical treatment. Nursing care is mostly task focused and fragmented, and there is a lack of psychosocial and relational care across the care chain. Registered nurses and nursing managers need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs. The Fundamentals of Care framework could be used for work improvements to include all aspects of nursing care. High-quality nursing care is needed throughout the care chain, including self-care after discharge, for patients with this rare tumour diagnosis. A higher awareness of patients' experiences and the importance of psychosocial support is warranted. Registered nurses and nursing managers must revise and improve routines to support patients' psychosocial needs. Registered nurses need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs. What problem did the study address? This study highlights patients' fundamental care needs and experiences of nursing care throughout surgical treatment of small intestinal neuroendocrine tumours. What were the main findings? There are deficiencies in fulfilling patients' fundamental care needs across the care chain and in all dimensions of the Fundamental of Care framework throughout surgical treatment of small intestinal neuroendocrine tumours. Patients struggled with loneliness and existential thoughts, as well as worries about the future. Patients experienced a lack of information about plans for the day, self-care, and follow-ups. Where and on whom will the research have an impact? For clinicians to develop an understanding of, and improve, fundamental care needs for patients with small intestinal neuroendocrine tumours in a surgical context. For registered nurses to understand the importance of their leadership and nursing responsibility to fulfil fundamental care needs. The consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. The patients shared their experiences during the interviews, which has contributed to a deeper knowledge and understanding of the phenomena under study.

Effective utilization of polypectomy in endoscopic salvage treatment of rectal neuroendocrine tumors: a retrospective cohort study.

Current guidelines recommend endoscopic resection for rectal neuroendocrine tumors (RNETs) under 10 mm. Incomplete resections necessitate salvage procedures, highlighting the need for complete R0 resection. This study evaluates the efficacy and safety of wide hot snare polypectomy (WHSP) compared to endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the salvage treatment of small RNETs. This retrospective study was conducted at Korea University Guro Hospital from January 2018 to December 2022. It compared the outcomes of salvage resections for RNETs ≤10 mm using 2 approaches: ESD and EMR vs. WHSP. Demographics, tumor characteristics, and clinical outcomes were compared. Efficacy was evaluated by the histological complete resection rate and procedure time, while safety was assessed by the incidence of complications. Out of 135 patients undergoing salvage resection for RNET, 14 who underwent transanal excision were excluded. Of the remaining 121, 99 underwent EMR or ESD, and 22 underwent WHSP. Baseline characteristics were similar between the 2 groups. The WHSP group demonstrated a significantly higher R0 resection rate (72.7% vs. 49.5%, P = 0.010) and a shorter median procedure time (3.5 minutes vs. 8.3 minutes). No complications were reported in the WHSP group. WHSP is a rapid, straightforward, safe, and effective approach for the salvage treatment of RNETs less than 10 mm in diameter, particularly in patients without additional risk factors.

177Lu-labeled somatostatin receptor targeted radionuclide therapy dosimetry in meningioma: a systematic review.

Few therapeutic options are currently available for refractory meningiomas. Encouraging results have been reported for 177Lu-labeled somatostatin receptor-targeted radiopeptide therapy (SSTR-RT). The current therapeutic scheme is based on the fixed doses that are recommended for neuroendocrine tumor treatment. However, in personalized medicine, tumor dosimetry can be determined from repeat 177Lu scintigraphy. The aim of this review was to report on the methods used for calculating the tumor absorbed dose (AD) in meningioma patients treated with 177Lu-SSTR-RT and their values. The search was performed in Medline, Embase and the Cochrane Library until March 1st, 2024 to retrieve papers related to the topic. The following terms were used for searching: (meningioma) AND ((sstr) OR (receptors somatostatin) OR (somatostatin) OR (octreotide)) AND ((PRRT) OR (radionuclide therapy) OR (dotatate) OR (dotatoc) OR (177Lu-DOTATOC) OR (177Lu-DOTATATE) OR (radiopeptide)). Seven articles (including 46 patients and 108 cycles of treatment) reporting on tumor AD during 177Lu-SSTR-RT were included in the analysis. The methods of acquisition, reconstruction parameters and postimage processing to determine tumor AD were very heterogeneous among the studies. The meningioma AD associated with the agonist 177Lu-SSTR-RT reported in the majority of studies ranged from 0.1-1.5 Gy/GBq, which was lower than that reported for neuroendocrine tumors (1.3-22.9 Gy/GBq). The tumor AD that was reported during treatment with 177Lu-SSTR-RT in refractory meningioma patients is generally low. Harmonization of the methodology for dosimetry calculations is needed to compare the different reported values and optimize treatment at the individual level.

Endoscopic therapy versus surgical resection for elderly patients with colorectal neuroendocrine tumors

BackgroundEndoscopic therapy (ET) and surgical resection (SR) are common surgical methods for the treatment of colorectal neuroendocrine tumors (CRNETs). However, for elderly patients, it remains unclear which surgical method yields better long-term outcomes.MethodsElderly patients ≥ 65 years with CRNETs diagnosed from 2000 to 2020 were identified from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan–Meier method and Cox proportional hazards models were utilized to evaluate the effects of diverse demographic and clinical factors on overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 2214 patients were included in the study, with 1417 patients in the ET group and 797 patients in the SR group. After PSM, the ET group outperformed the SR group in terms of OS (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.44–0.70) and CSS (HR 0.21, 95% CI 0.11–0.40). Similarly, the ET group maintained its advantage in mean 1-, 3-, and 5-year OS and CSS rates compared to the SR group (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, marital status, and treatment modality as independent risk factors affecting OS, while age, sex, marital status, and treatment modality were identified as independent risk factors affecting CSS.ConclusionsET offered superior long-term outcomes for elderly patients ≥ 65 years with CRNETs.

Surgical treatment of neuroendocrine tumors

Surgical treatment of neuroendocrine tumors

Clinical feasibility of duodenum-preserving pancreatic head resection for neuroendocrine tumors of the pancreatic head as an intermediate procedure between enucleation and pancreaticoduodenectomy.

This study was performed to demonstrate the clinical application of duodenum-preserving pancreatic head resection (DPPHR) as a surgical treatment for pancreatic neuroendocrine tumors (PNETs) in terms of both curability and maintenance of postoperative quality of life. Seven patients diagnosed with PNETs underwent DPPHR from January 2011 to December 2021 at our institution. We investigated the clinical relevance of DPPHR based on the patients' clinicopathological findings. The median operative time was 492min, and the median blood loss was 302g. Postoperative complications were evaluated according to the Clavien-Dindo classification, and postoperative intra-abdominal bleeding was observed in one patient. Pathological examination revealed a World Health Organization classification of G1 in six patients and G2 in one patient. Microvascular invasion was observed in two patients (29%); however, no patients developed lymph node metastasis or recurrence during the follow-up period. A daughter lesion was observed near the primary tumor in one patient. All patients achieved curative resection, and no tumor specimens showed positive margins. DPPHR facilitates anatomical resection of the pancreatic head in patients with PNETs as well as detailed pathological evaluation of the resected specimen. Therefore, this surgical procedure is an acceptable alternative to pancreaticoduodenectomy or enucleation for patients with PNETs.

Spleen Volume Reduction Is a Reliable and Independent Biomarker for Long-Term Risk of Leukopenia Development in Peptide Receptor Radionuclide Therapy.

177Lu-DOTATATE therapy is an effective treatment for advanced neuroendocrine tumors, despite its dose-limiting hematotoxicity. Herein, the significance of off-target splenic irradiation is unknown. Our study aims to identify predictive markers of peptide receptor radionuclide therapy-induced leukopenia. Methods: We retrospectively analyzed blood counts and imaging data of 88 patients with histologically confirmed, unresectable metastatic neuroendocrine tumors who received 177Lu-DOTATATE treatment at our institution from February 2009 to July 2021. Inclusion criterium was a tumor uptake equivalent to or greater than that in the liver on baseline receptor imaging. We excluded patients with less than 24 mo of follow-up and those patients who received fewer than 4 treatment cycles, additional therapies, or blood transfusions during follow-up. Results: Our study revealed absolute and relative white blood cell counts and relative spleen volume reduction as independent predictors of radiation-induced leukopenia at 24 mo. However, a 30% decline in spleen volume 12 mo after treatment most accurately predicted patients proceeding to leukopenia at 24 mo (receiver operating characteristic area under the curve of 0.91, sensitivity of 0.93, and specificity of 0.90), outperforming all other parameters by far. Conclusion: Automated splenic volume assessments demonstrated superior predictive capabilities for the development of leukopenia in patients undergoing 177Lu-DOTATATE treatment compared with conventional laboratory parameters. The reduction in spleen size proves to be a valuable, routinely available, and quantitative imaging-based biomarker for predicting radiation-induced leukopenia. This suggests potential clinical applications for risk assessment and management.

Spect/Ct with a New Radiopharmaceutical “99mtc, Octreotide” in Diagnosis and Evaluation of the Effectiveness of Treatment of Neuroendocrine Tumor of the Lung (Clinical Case)

Spect/Ct with a New Radiopharmaceutical “99mtc, Octreotide” in Diagnosis and Evaluation of the Effectiveness of Treatment of Neuroendocrine Tumor of the Lung (Clinical Case)

Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

Key updates and interpretation of the ninth version of AJCC staging system for neuroendocrine tumors of the stomach

The cancer staging system of the American Joint Committee on Cancer (AJCC) is the most widely used clinical basis for tumor staging. In October 2023, AJCC released the staging system (ninth version) for the neuroendocrine tumors of stomach (NET), which has been implemented in January 2024. The ninth version of NET staging system mainly updated the histopathologic classification, diagnosis and staging methods, clinical and pathological staging, prognosis grade, tumor and non-tumor prognostic features. The update and implementation of the staging system provide a more detailed reference for the accurate diagnosis, staging and precise treatment of gastric neuroendocrine tumors. Moreover, it is convenient for clinicians to carry out clinical practice. The purpose of our article is to provide a high-level overview of the major changes in AJCC staging system (version 9) for gastric NET based on the latest evidence-based medical research.