Treatment Of Neuroendocrine Tumors Research Articles

PRIMARY NEUROENDOCRINE CARCINOMA OF THE CERVIX: RETROSPECTIVE ANALYSIS

Objective: Neuroendocrine carcinoma of the cervix is a rare variant of cervical carcinoma with a poorer prognosis. There is no standard treatment for this variant of cervical carcinoma. Due to the rarity of this malignancy, the management of NECC is difficult and associated with uncertainty. An interdisciplinary approach is necessary because most studies investigating the treatment of neuroendocrine tumors have been performed in patients with tumors in organs other than the cervix, mostly the lung and pancreas. Methods: A retrospective analysis of 32 patients diagnosed by biopsy with neuroendocrine carcinoma of the cervix was done. This study was carried out at Adyar Cancer Institute Chennai. All stage I patients underwent surgery followed by chemotherapy. All stage II and III patients underwent chemoradiotherapy. All stage IV patients underwent palliative chemotherapy. Disease-free survival and overall survival were seen. Results: Overall, while the mean survival time decreases as the disease progresses from Stage I to Stage IV, the variability (SD) is highest in the early stages (I and II) and relatively lower in the advanced stages (III and IV), though the differences in survival times between the stages were not statistically significant. Conclusion: We found that NECC is a rare form of cervical cancer with a poor prognosis. Due to the small number of cases and the retrospective nature of this analysis, conclusions are limited, but multimodality treatment with radical surgery and adjuvant or neoadjuvant chemotherapy with etoposide and cisplatin is the mainstay of treatment for early-stage disease while combined chemoradiotherapy and chemotherapy are appropriate for women with locally advanced or recurrent NECC.

The novel SSTR3 full agonist ITF2984 shows antitumor properties against pancreatic neuroendocrine tumors (Pan-NETs).

Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide), or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptoms control and antiproliferative effects in subsets of NET patients and this was associated to the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2 and SSTR3 and thus should respond to agonists targeting SSTR3. We evaluated the efficacy of ITF2984, a novel multireceptor agonist with specificity for SSTR3, against Pan-NET cells representative of well differentiated, functioning tumors, and expressing high levels of SSTR3. The effect of ITF2984 on cell proliferation/viability, and on its ability to promote apoptosis and suppress hormone secretion was evaluated in 2D and 3D organotypic culture systems. Pasireotide was tested in parallel for comparative purposes. We found that ITF2984 is as effective as pasireotide at inhibiting both proliferation/viability and hormone secretion, as well as at inducing apoptosis of Pan-NET cells grown as both 2D monolayers and 3D spheroids. High-dose ITF2984 elicits structural alterations in Pan-NET 3D spheroids compatible with cell death more effectively than pasireotide. Altogether, ITF2984 may represent a useful alternative to pasireotide for the medical treatment of Pan-NETs and other tumors with elevated SSTR3 expression.

Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center

BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen (TEMCAP) exhibits a certain level of efficacy in treating advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). However, published data from Peru are limited. We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population. AIM To evaluate overall survival (OS) in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima-Perú. METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN. A total of thirty-eight patients were included in the final analysis: Thirty-five received TEMCAP as a first-line treatment, and three as a second-line treatment. The primary objective was to evaluate OS. The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS The median age of the patients was 52 years (range 24-77 years), and 53.3% were female. The most common symptoms at diagnosis were abdominal pain in 31 patients (81.6%). Primary tumors included 12 in the rectum (31.6%), 11 in the pancreas (28.9%), 3 in the ileum (7.9%), 2 in the mesentery (5.3%), 2 in the small intestine (5.3%), 1 in the appendix (2.6%), 1 in the stomach (2.6%) and 6 cases of liver metastasis of unknown primary (15.8%). Five were neuroendocrine tumors (NET) G1 (13.2%), 33 were NET G2 (86.8%), five had Ki67 < 3% (13.2%), and 33 had Ki67 between 3% and 20% (86.8%). TEMCAP was administered to 35 (92.1%) patients as first-line treatment. OS at 12, 36, and 60 months was estimated in 80%, 66%, and 42%, respectively, with a median OS of 49 months. CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.

Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study

BackgroundPeptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs. Data from 37 patients enrolled in a prospective phase II study (LuMEn) were analysed. Treatment consisted of four cycles of [177Lu]Lu-DOTA-TATE administered 8–12 weeks apart. Three-time-point SPECT/CT imaging was performed after each treatment cycle, and dosimetry of tumours and organs-at-risk (kidneys and red marrow) was conducted following the medical internal radiation dose formalism. Coefficients of variation (CoV) assessed the variability of absorbed doses, activity concentrations on day 1, and effective half-lives. Linear mixed effect models (SAS software) were used to investigate the evolution of the dosimetric parameters over cycles, discerning between different primary NET types and grades of tumours.ResultsThere is an important variability in absorbed doses and activity concentrations among patients, particularly in tumours (CoV: ~50%). Tumour absorbed doses and activity concentrations decreased over treatment cycles in pancreatic NETs, although at a limited rate (~-13%/cycle). An opposite trend was observed for the kidneys ( ~ + 8%/cycle). Effective half-lives remained relatively constant across cycles for both organs-at-risk and tumours. The primary NET type significantly influenced effective half-lives in tumours, shorter in pancreatic NETs than intestinal NETs (77 h vs. 107 h, p < 0.0001). No significant effect of the grade was observed on either of the variables investigated.ConclusionsOur study revealed considerable variations in tumour absorbed doses among patients with NETs treated with a standardized protocol. These findings confirm the need for personalized dosimetry approaches in PRRT, considering patient and tumour characteristics.Trial registrationEudraCT Number: 2012-003666-41. Clinicaltrials.gov identifier: NCT01842165. Registered 25 April 2013, https://clinicaltrials.gov/ct2/show/NCT01842165.

Ectopic adrenocorticotrophic hormone syndrome in a 10-year-old girl with a thymic neuroendocrine tumor: a case report

BackgroundThymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children.Case presentationWe report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection. The patient underwent a diagnostic work-up which indicated the possibility of an ACTH-secreting pituitary neuroendocrine tumor. However, after a transsphenoidal surgery, the diagnosis was not confirmed on histopathological examination. Subsequent bilateral inferior petrosal sinus sampling showed strong indications of the presence of ectopic ACTH syndrome. Detailed rereading of functional imaging studies, including 18F-FDG PET/MRI and 68Ga DOTATOC PET/CT, ultimately identified a small lesion in the thymus. The patient underwent videothoracoscopic thymectomy that confirmed a neuroendocrine tumor with ACTH positivity on histopathological examination.ConclusionThis case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child. We can conclude that ketoconazole treatment was effective in managing hypercortisolemia in our patient. Further, a combination of functional imaging studies can be a useful tool in locating the source of ectopic ACTH secretion. Lastly, in cases of discrepancy in the results of stimulation tests, bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome.

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.

Stratification of risk for lymph node metastasis and long-term oncologic outcomes in patients initially treated by endoscopic resection for rectal neuroendocrine tumors

Background and AimsThe treatment of rectal neuroendocrine tumors (NETs) is determined by the risk of lymph node (LN) metastasis. We aimed to stratify the risk of LN metastasis according to the number of risk factors and evaluate the long-term outcomes of patients initially treated endoscopically for rectal NETs. MethodsWe retrospectively analyzed 441 patients initially treated with endoscopy for rectal NETs; those who had at least one of the risk factors for LN metastasis were defined as high-risk patients. We stratified LN metastasis rates according to the number of risk factors. The 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the high- and low-risk groups. ResultsPathologic size (odds ratio [OR], 1.208; 95% confidence interval [CI], 1.062–1.374; P=0.001), (+) resection margin invasion (OR, 2.897; 95% CI, 1.057–7.936; P=0.039), and angiolymphatic invasion (OR, 22.155; 95% CI, 7.563–64.904; P=0.001) were risk factors for LN metastasis. The rate of LN metastasis increased as the number of risk factors increased (P=0.001). The 5-year RFS rates were 98.7% and 99% in the high- and low-risk groups, with no significant difference (P=0.966). The 5-year OS rates were 100% and 99.5% in the high- and low-risk groups, with no significant difference (P=0.571). ConclusionsThe risk of LN metastasis increased significantly when the number of risk factors increased in patients with rectal NETs. Patients who initially underwent endoscopic resection for rectal NETs showed a favorable long-term oncologic outcome if salvage treatments were performed, depending on the stratification of their risk factors.

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

Time toxicity of lutetium 177 in gastroenteropancreatic neuroendocrine tumours.

We aim to investigate the time toxicity of patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate in a single institution. This is a retrospective cohort study. All patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate at the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution. Our cohort included 21 patients with metastatic disease, female sex 86%, and a median age of 55 (IQR 44-63). The primary tumour site was the small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was two (IQR 2-3). The overall response rate was 19%, and 66.6% had clinical benefit. The median calculated 'time toxicity' was 11 days (IQR 8-18), representing 5.7% of the total treatment duration. The main contributors to time toxicity included infusion days, blood draws, radiological scans, and hospitalisations (median of 4 days for each). Lutetium-177 Dotatate treatment for gastroenteropancreatic neuroendocrine tumours was associated with low time toxicity, excellent tolerability, a good response and prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survival and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.

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

Peptide-guided adaptor-CAR T-Cell therapy for the treatment of SSTR2-expressing neuroendocrine tumors

ABSTRACT Somatostatin receptor type 2 (SSTR2) is one of the five subtypes of somatostatin receptors and is overexpressed on the surface of most gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs), pituitary tumors, paraganglioma, and meningioma, as well as hepatocellular carcinoma and breast cancer. Chimeric antigen receptor (CAR) T-cells are genetically engineered to express an artificial, T-cell activating binder, leading upon ligation to biocidal activity against target-antigen expressing cells. Adaptor-CAR T-cells recognize, via the CAR, a tag on an antigen-binding molecule, building an activating bridge between the CAR and the target cell. We hypothesized that a novel fluorescent-peptide antagonist of SSTR2, called Octo-Fluo, in combination with anti-FITC adaptor CAR (AdFITC(E2)-CAR) T-cells, may function as an on-off tunable activating bridge between the CAR and SSTR2 expressing target cells. In vitro studies confirmed the binding of Octo-Fluo to Bon1-SSTR2 mCherry-Luc cells without evidence of internalization. AdFITC(E2)-CAR T-cells were activated and efficiently induced Bon1-SSTR2 cell death in vitro, in an Octo-Fluo concentration-dependent manner. Similarly, AdFITC(E2)-CAR T-cells in combination with Octo-Fluo efficiently infiltrated the tumor and eliminated Bon1-SSTR2 tumors in immunodeficient mice in therapeutic settings. Both, AdFITC(E2)-CAR T-cell tumor infiltration and biocidal activity were Octo-Fluo concentration-dependent, with high doses of Octo-Fluo, saturating both the CAR and the SSTR2 antigen independently, leading to the loss of tumor infiltration and biocidal activity due to the loss of bridge formation. Our findings demonstrate the potential of using AdFITC(E2)-CAR T-cells with Octo-Fluo as a versatile, on-off tunable bispecific adaptor for targeted CAR T-cell immunotherapy against SSTR2-positive NETs.

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.