{"product_id":"new-italian-guidelines-for-managing-advanced-gep-nens-a-patient-rsquo-s-guide-to-the-2024-recommendations","title":"New Italian Guidelines for Managing Advanced GEP-NENs: A Patient\u0026rsquo;s Guide to the 2024 Recommendations","description":"\u003cp\u003eItalian medical organizations have released updated 2024 clinical practice guidelines for managing advanced non-functioning gastroenteropancreatic neuroendocrine tumors (GEP-NENs), a rare and complex group of digestive system cancers. Using a rigorous standardized method called GRADE, a multidisciplinary panel of experts developed recommendations on 15 key clinical questions, ranging from which imaging tests to use to which treatments work best for different tumor types. The guidelines strongly support somatostatin analogs as first-line therapy for slow-growing tumors, recommend PET-CT scans over older imaging techniques, and endorse peptide receptor radionuclide therapy for progressive disease. The cornerstone message: patients with GEP-NENs should be managed by experienced, multidisciplinary teams.\u003c\/p\u003e\n\n\u003ch1\u003eNew Italian Guidelines for Managing Advanced GEP-NENs: A Patient’s Guide to the 2024 Recommendations\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eWhat Are GEP-NENs?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#why\"\u003eWhy These Guidelines Matter\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Guidelines Were Developed\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#grade\"\u003eThe GRADE Approach: How Evidence Was Evaluated\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Recommendations: The 15 Clinical Questions\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#imaging\"\u003eImaging and Diagnosis (Questions 1, 2, and 12)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#surgery-adjuvant\"\u003eTreatment After Surgery (Question 3)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#first-line\"\u003eFirst-Line Treatment for Advanced Tumors (Question 4)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#prrt\"\u003ePRRT for Progressive Disease (Question 5)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#chemotherapy-nec\"\u003eChemotherapy for Poorly Differentiated Tumors (Questions 6–8)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#chemotherapy-net\"\u003eChemotherapy for Pancreatic NETs (Question 9)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#surgical-locoregional\"\u003eSurgery and Locoregional Treatments (Questions 10, 11, and 13)\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eClinical Implications: What This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Guidelines\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003ePatients with GEP-NENs should be managed by experienced, multidisciplinary teams.\u003c\/li\u003e\n\u003cli\u003e[68Ga]Ga-DOTA-peptides PET-CT is strongly recommended over Octreoscan for staging GEP-NETs.\u003c\/li\u003e\n\u003cli\u003eSSA is strongly recommended as first-line therapy for advanced slow-growing, SSTR-2-positive GEP-NETs.\u003c\/li\u003e\n\u003cli\u003ePRRT with lutetium-177 oxodotreotide is strongly recommended for patients whose disease progresses on SSA.\u003c\/li\u003e\n\u003cli\u003eChemotherapy for GEP-NEC typically uses platinum-based regimens; temozolomide-based options are considered for select Ki-67 ranges and pancreatic NETs.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eWhat Are GEP-NENs?\u003c\/h2\u003e\n\n\u003cp\u003eNeuroendocrine neoplasms (NENs) are a broad family of rare tumors that arise from neuroendocrine cells — specialized cells that behave partly like nerve cells and partly like hormone-producing endocrine cells. These tumors are marked by significant biological and clinical diversity.\u003c\/p\u003e\n\n\u003cp\u003eSome NENs grow very slowly and behave in an indolent, low-grade manner, while others are high-grade and carry a poor prognosis. The behavior of the tumor is closely tied to how differentiated (how similar to normal cells) it appears under a microscope:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eWell-differentiated tumors\u003c\/strong\u003e (neuroendocrine tumors, or NETs) tend to grow slowly and are generally less aggressive.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePoorly differentiated neoplasms\u003c\/strong\u003e (neuroendocrine carcinomas, or NECs) grow quickly and are much more aggressive.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eNENs can arise anywhere in the body, but they most frequently originate in the gastroenteropancreatic (GEP) tract — the stomach, intestines, and pancreas — and in the thorax (chest area). Because these cells can produce and secrete peptides and biogenic amines (chemical messengers), NENs are broadly divided into two categories:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e“Functioning” tumors\u003c\/strong\u003e, which release hormones that cause distinct clinical syndromes (such as excessive insulin or serotonin production).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e“Non-functioning” tumors\u003c\/strong\u003e, which do not cause such syndromes. \u003cstrong\u003eNon-functioning tumors represent the most prevalent subgroup\u003c\/strong\u003e and are the focus of this guideline.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp class=\"medium-paragraph\"\u003eAlthough historically considered rare, the incidence of NENs has greatly increased over recent decades. This trend is due, at least in part, to improved disease awareness, wider use of large-scale screening programs, and advances in diagnostic tools. Interestingly, because of their often indolent nature, NENs are actually \u003cstrong\u003emore prevalent than gastric and pancreatic adenocarcinomas combined\u003c\/strong\u003e, making them a greater public health concern than previously recognized.\u003c\/p\u003e\n\n\u003ch2 id=\"why\"\u003eWhy These Guidelines Matter\u003c\/h2\u003e\n\n\u003cp\u003eIn recent years, major advances have been made in understanding NEN epidemiology, classification, biology, diagnostics, and treatment. The therapeutic arsenal for advanced disease has expanded significantly — and with it, the complexity of choosing the right treatment.\u003c\/p\u003e\n\n\u003cp\u003eTreatment selection must take into account many factors, including:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eExtent of the disease\u003c\/li\u003e\n  \u003cli\u003eGrowth rate (how quickly the tumor is progressing)\u003c\/li\u003e\n  \u003cli\u003ePrimary site (where the tumor started)\u003c\/li\u003e\n  \u003cli\u003eHistological grade (how abnormal the cells look)\u003c\/li\u003e\n  \u003cli\u003eFunctional status (whether the tumor secretes hormones)\u003c\/li\u003e\n  \u003cli\u003ePatient characteristics and overall health\u003c\/li\u003e\n  \u003cli\u003eTreatment availability\u003c\/li\u003e\n  \u003cli\u003ePotential side effects and safety profile of each therapy\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eGiven this complexity, the guideline authors emphasize that managing GEP-NENs \u003cstrong\u003erequires a coordinated multidisciplinary approach by experienced teams\u003c\/strong\u003e. No single specialist can navigate this landscape alone; oncologists, surgeons, pathologists, radiologists, nuclear medicine physicians, endocrinologists, and others must work together.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Guidelines Were Developed\u003c\/h2\u003e\n\n\u003cp\u003eThe Italian Association of Medical Oncology (AIOM), in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET) and several other Italian scientific societies, has produced evidence-based clinical practice guidelines for GEP-NENs since 2013. This 2024 version represents the latest update. Here is how the panel went about its work:\u003c\/p\u003e\n\n\u003ch3\u003eThe Working Group\u003c\/h3\u003e\n\u003cp\u003eThe NEN Guidelines Working Group was selected by an AIOM representative (appointed as Guideline Coordinator) together with the Chairs of the other collaborating scientific societies, many of whom are also affiliated with ITANET. Multidisciplinarity was a core criterion. The team included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eOncologists\u003c\/li\u003e\n  \u003cli\u003eGastroenterologists\u003c\/li\u003e\n  \u003cli\u003ePathologists\u003c\/li\u003e\n  \u003cli\u003eRadiologists\u003c\/li\u003e\n  \u003cli\u003eRadiotherapists\u003c\/li\u003e\n  \u003cli\u003eSurgeons\u003c\/li\u003e\n  \u003cli\u003eEndocrinologists\u003c\/li\u003e\n  \u003cli\u003eNuclear medicine physicians\u003c\/li\u003e\n  \u003cli\u003eMethodologists (experts in research methodology)\u003c\/li\u003e\n  \u003cli\u003e\u003cstrong\u003ePatients affected by cancer\u003c\/strong\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBefore final publication on the AIOM website (www.aiom.it) and approval by the Italian National Health Institute (ISS), the guideline was reviewed by external reviewers from major Italian scientific societies, including the Italian Society of Gastroenterology and Endoscopy, the Italian Society of Radiotherapy and Clinical Oncology, the Italian Society of Nuclear Medicine, the Italian Society of Endocrinology, the Italian Society of Oncological Surgery, the Italian Society of Medical Radiology and Interventional Radiology, the Italian Society of Dermatology and Venereology, the Italian Society of Pathology, and the Italian Society for the Study of the Pancreas. The guideline is also published on the ITANET website (www.ita-net.org).\u003c\/p\u003e\n\n\u003ch3\u003eDeveloping Clinical Questions\u003c\/h3\u003e\n\u003cp\u003eThe panel used the PICO framework (Population, Intervention, Comparison, Outcomes) to structure clinical questions. Working group members selected, prioritized, and voted on these questions based on clinical needs, then ranked them by relative importance. Outcomes were identified as either \u003cstrong\u003e“critical”\u003c\/strong\u003e or \u003cstrong\u003e“important”\u003c\/strong\u003e based on priority.\u003c\/p\u003e\n\n\u003cp\u003eIn total, the main NEN guideline includes \u003cstrong\u003e56 clinical questions\u003c\/strong\u003e. For this publication, the authors selected \u003cstrong\u003e15 of those 56 questions\u003c\/strong\u003e, all focused on the management of non-functioning advanced GEP-NENs.\u003c\/p\u003e\n\n\u003ch3\u003eSearching the Evidence\u003c\/h3\u003e\n\u003cp\u003eFor each question, a systematic literature search was conducted in three major medical databases — \u003cstrong\u003ePubMed, Embase, and the Cochrane Library\u003c\/strong\u003e — without language or date restrictions. Key articles were cross-referenced to ensure all relevant literature was identified. The full search strategy and PRISMA flowcharts (diagrams showing how studies were screened and selected) for each question are available in the supplementary material of the original article.\u003c\/p\u003e\n\n\u003cp\u003eThe search process prioritized systematic reviews and randomized controlled trials (RCTs), which provide the strongest evidence. When these were not available, non-randomized studies were considered. Narrative reviews and case reports were excluded.\u003c\/p\u003e\n\n\u003ch2 id=\"grade\"\u003eThe GRADE Approach: How Evidence Was Evaluated\u003c\/h2\u003e\n\n\u003cp\u003eThe guidelines used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach to assess the certainty of evidence. GRADE evaluation examines \u003cstrong\u003efive main domains\u003c\/strong\u003e:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStudy limitations\u003c\/strong\u003e — flaws in study design or conduct\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eImprecision\u003c\/strong\u003e — wide confidence intervals or small sample sizes\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eIndirectness\u003c\/strong\u003e — evidence that doesn’t directly address the question\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eInconsistency\u003c\/strong\u003e — conflicting results across studies\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePublication bias\u003c\/strong\u003e — studies with negative results not being published\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eBased on study design, the certainty level starts at a pre-specified level (high for randomized controlled trials). If limitations are found in one or more of the five domains, the certainty can be downgraded. The final judgment is expressed as one of four levels:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHigh\u003c\/strong\u003e — High confidence that the estimated effect is similar to the true effect.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModerate\u003c\/strong\u003e — Moderate confidence, but with limited possibility that the effect is substantially different.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLow\u003c\/strong\u003e — Limited probability that the estimated effect matches the true effect, with high possibility it could be substantially different.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eVery low\u003c\/strong\u003e — Very limited probability that the estimate matches the true effect, with very high possibility of substantial difference.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eHow Recommendations Were Made\u003c\/h3\u003e\n\u003cp\u003eFor benefit\/harm balance, panel members voted on one of four options: in favor of the comparison, probably in favor of the comparison, probably in favor of the intervention, or in favor of the intervention. They also voted on the \u003cstrong\u003estrength of the recommendation\u003c\/strong\u003e, choosing among:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eStrong in favor\u003c\/li\u003e\n  \u003cli\u003eConditional in favor\u003c\/li\u003e\n  \u003cli\u003eConditional against\u003c\/li\u003e\n  \u003cli\u003eStrong against the intervention\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAccording to the GRADE approach, a recommendation is adopted when it receives a \u003cstrong\u003esimple majority\u003c\/strong\u003e — defined as 50% plus one of all eligible voting panel members (those with no conflicts of interest).\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Recommendations: The 15 Clinical Questions\u003c\/h2\u003e\n\n\u003cp\u003eThe table below summarizes all 15 clinical questions addressed in this guideline article, along with the strength of each recommendation and the overall certainty of the supporting evidence.\u003c\/p\u003e\n\n\u003ctable border=\"1\" cellpadding=\"6\" cellspacing=\"0\" style=\"border-collapse:collapse; width:100%;\"\u003e\n  \u003ctr style=\"background-color:#f0f0f0;\"\u003e\n    \u003cth\u003eQuestion Topic\u003c\/th\u003e\n    \u003cth\u003eRecommendation\u003c\/th\u003e\n    \u003cth\u003eStrength\u003c\/th\u003e\n    \u003cth\u003eCertainty of Evidence\u003c\/th\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e1. Staging imaging: PET-CT vs. Octreoscan\u003c\/td\u003e\n    \u003ctd\u003e[68Ga]Ga-DOTA-peptides PET-CT should be the primary staging option compared with [111In]In-pentetreotide scintigraphy (Octreoscan).\u003c\/td\u003e\n    \u003ctd\u003eStrong in favor\u003c\/td\u003e\n    \u003ctd\u003eModerate\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e2. Dual PET-CT for G2-G3 tumors\u003c\/td\u003e\n    \u003ctd\u003eDual [68Ga]Ga-DOTA-peptides PET-CT and [18F]F-FDG-PET-CT could be considered in selected patients with G2-G3 tumors.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eLow\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e3. Adjuvant SSA after radical surgery\u003c\/td\u003e\n    \u003ctd\u003eAdjuvant treatment with somatostatin analogs (SSA) should NOT be recommended after radical surgery of the primary tumor.\u003c\/td\u003e\n    \u003ctd\u003eConditional against\u003c\/td\u003e\n    \u003ctd\u003eExpert opinion\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e4. SSA vs. no therapy for advanced non-functioning NET\u003c\/td\u003e\n    \u003ctd\u003eIn patients with advanced, non-functioning, not rapidly progressive, low Ki-67, SSTR-2-positive GEP-NET, SSA should be the primary option compared with follow-up without any therapy.\u003c\/td\u003e\n    \u003ctd\u003eStrong in favor\u003c\/td\u003e\n    \u003ctd\u003eModerate\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e5. PRRT after progression on SSA\u003c\/td\u003e\n    \u003ctd\u003eIn patients progressive on SSA, [177Lu]Lu-oxodotreotide (PRRT) should be recommended.\u003c\/td\u003e\n    \u003ctd\u003eStrong in favor\u003c\/td\u003e\n    \u003ctd\u003eLow\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e6. First-line chemotherapy for GEP-NEC\u003c\/td\u003e\n    \u003ctd\u003eCisplatin or carboplatin + etoposide should be proposed as first-line systemic chemotherapy for advanced GEP-NEC.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eVery low\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e7. Temozolomide for Ki-67 20–55% GEP-NEC\u003c\/td\u003e\n    \u003ctd\u003eTemozolomide-based chemotherapy could be preferred to cisplatin\/carboplatin + etoposide as first-line treatment when Ki-67 is \u0026gt;20% and \u0026lt;55%.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eVery low\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e8. Second-line chemotherapy for GEP-NEC\u003c\/td\u003e\n    \u003ctd\u003eAfter progression on first-line cisplatin\/carboplatin + etoposide, second-line treatment with temozolomide, irinotecan, oxaliplatin, or fluoropyrimidine could be preferred to best supportive care alone.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eVery low\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e9. Chemotherapy for progressive G1-G2 pancreatic NET\u003c\/td\u003e\n    \u003ctd\u003eTemozolomide-based chemotherapy could be preferred to other chemotherapies (e.g., oxaliplatin or irinotecan).\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eVery low\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e10. Surgery for borderline resectable disease with liver metastases\u003c\/td\u003e\n    \u003ctd\u003eIn borderline resectable primary tumors with liver metastases where \u0026gt;90% of liver disease is expected to be resected, a surgical approach could be preferred to a non-surgical approach.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eVery low\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e11. Vascular interventional locoregional treatments\u003c\/td\u003e\n    \u003ctd\u003eVascular interventional locoregional treatments could be preferred to other therapies.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eLow\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e12. MRI with biliary excretion for liver metastases\u003c\/td\u003e\n    \u003ctd\u003eAbdominal MRI with biliary excretion could be preferred to standard MRI or CT scan with contrast for patients with liver metastases.\u003c\/td\u003e\n    \u003ctd\u003eConditional in favor\u003c\/td\u003e\n    \u003ctd\u003eLow\u003c\/td\u003e\n  \u003c\/tr\u003e\n  \u003ctr\u003e\n    \u003ctd\u003e13. Liver transplantation\u003c\/td\u003e\n    \u003ctd\u003eThe guideline addressed liver transplantation in patients with GEP-NETs with concomitant liver metastases; the full recommendation text was not available in the published excerpt.\u003c\/td\u003e\n    \u003ctd\u003eNot specified in excerpt\u003c\/td\u003e\n    \u003ctd\u003eNot specified in excerpt\u003c\/td\u003e\n  \u003c\/tr\u003e\n\u003c\/table\u003e\n\n\u003ch2 id=\"imaging\"\u003eImaging and Diagnosis (Questions 1, 2, and 12)\u003c\/h2\u003e\n\n\u003ch3\u003eQuestion 1: Which imaging test is best for staging?\u003c\/h3\u003e\n\u003cp\u003eFor staging GEP-NETs, the panel recommends that \u003cstrong\u003e[68Ga]Ga-DOTA-peptides PET-CT should be considered the primary imaging option\u003c\/strong\u003e, rather than the older [111In]In-pentetreotide scintigraphy (commonly known as Octreoscan). This recommendation was rated \u003cstrong\u003estrong in favor\u003c\/strong\u003e with \u003cstrong\u003emoderate certainty\u003c\/strong\u003e of evidence.\u003c\/p\u003e\n\n\u003cp\u003eWhat does this mean for patients? PET-CT using gallium-68-labeled DOTA-peptides is a modern, more sensitive imaging technique that can detect smaller or more numerous tumor deposits than the traditional Octreoscan. It provides better information for staging and treatment planning.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 2: Should patients with intermediate or high-grade tumors receive two PET scans?\u003c\/h3\u003e\n\u003cp\u003eFor patients with G2-G3 GEP-NETs, the panel considered whether performing both a [68Ga]Ga-DOTA-peptides PET-CT and an [18F]F-FDG-PET-CT provides added value compared with the DOTA-peptide PET-CT alone. The recommendation was \u003cstrong\u003econditional in favor\u003c\/strong\u003e with \u003cstrong\u003elow certainty\u003c\/strong\u003e: dual PET-CT \u003cem\u003ecould\u003c\/em\u003e be taken into account in selected cases.\u003c\/p\u003e\n\n\u003cp\u003eThe FDG-PET scan measures glucose metabolism and can identify more aggressive areas within a tumor. This approach helps doctors understand the tumor’s biological behavior more completely, but it is not necessary for every patient.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 12: What is the best way to image liver metastases?\u003c\/h3\u003e\n\u003cp\u003eIn patients with GEP-NETs and liver metastases, the panel suggests that \u003cstrong\u003eabdominal MRI with biliary excretion\u003c\/strong\u003e could be preferred over standard MRI or CT scan with contrast. This was rated \u003cstrong\u003econditional in favor\u003c\/strong\u003e with \u003cstrong\u003elow certainty\u003c\/strong\u003e. The biliary-excretion contrast agent may provide better detection and characterization of liver lesions, which is crucial for surgical planning.\u003c\/p\u003e\n\n\u003ch2 id=\"surgery-adjuvant\"\u003eTreatment After Surgery (Question 3)\u003c\/h2\u003e\n\n\u003cp\u003eAfter a patient with a non-functioning GEP-NET has undergone radical (complete) surgery to remove the primary tumor, should they receive adjuvant treatment with somatostatin analogs (SSA)?\u003c\/p\u003e\n\n\u003cp\u003eThe panel’s answer is \u003cstrong\u003eno\u003c\/strong\u003e: adjuvant SSA should \u003cstrong\u003enot\u003c\/strong\u003e be recommended. This recommendation was rated \u003cstrong\u003econditional against\u003c\/strong\u003e and was based on \u003cstrong\u003eexpert opinion\u003c\/strong\u003e, meaning there was insufficient high-quality evidence to support routine use of SSA after surgery. Patients who have had complete resection should instead be followed with regular monitoring. This avoids unnecessary treatment and potential side effects when there is no evidence of remaining disease.\u003c\/p\u003e\n\n\u003ch2 id=\"first-line\"\u003eFirst-Line Treatment for Advanced Tumors (Question 4)\u003c\/h2\u003e\n\n\u003cp\u003eFor patients with \u003cstrong\u003enon-functioning, advanced (locally advanced not resectable or metastatic) GEP-NET\u003c\/strong\u003e that is \u003cstrong\u003enot rapidly progressive\u003c\/strong\u003e, has a \u003cstrong\u003elow Ki-67\u003c\/strong\u003e (a marker of cell proliferation; lower means slower-growing), and is \u003cstrong\u003eSSTR-2-positive\u003c\/strong\u003e (meaning the tumor cells have receptors that somatostatin analogs can bind to), the panel made a \u003cstrong\u003estrong recommendation in favor\u003c\/strong\u003e of using \u003cstrong\u003esomatostatin analogs (SSA) as the primary option\u003c\/strong\u003e instead of follow-up without any therapy. The certainty of evidence was \u003cstrong\u003emoderate\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003eIn plain terms: if your tumor is slow-growing and has the right receptor profile, starting SSA treatment (rather than waiting and watching) is strongly supported by the evidence. SSAs help control tumor growth and can keep the disease stable for long periods.\u003c\/p\u003e\n\n\u003ch2 id=\"prrt\"\u003ePRRT for Progressive Disease (Question 5)\u003c\/h2\u003e\n\n\u003cp\u003eWhen a patient with advanced, SSTR-2-positive GEP-NET has \u003cstrong\u003eprogressed despite SSA treatment\u003c\/strong\u003e, what is the next step?\u003c\/p\u003e\n\n\u003cp\u003eThe panel issued a \u003cstrong\u003estrong recommendation in favor\u003c\/strong\u003e of \u003cstrong\u003e[177Lu]Lu-oxodotreotide\u003c\/strong\u003e — a form of peptide receptor radionuclide therapy (PRRT). The certainty of evidence was \u003cstrong\u003elow\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003ePRRT works by attaching a radioactive isotope (lutetium-177) to a peptide that binds to somatostatin receptors on tumor cells, delivering targeted radiation directly to the cancer. This recommendation means that for patients whose disease is progressing on SSA, PRRT is a preferred subsequent treatment option.\u003c\/p\u003e\n\n\u003ch2 id=\"chemotherapy-nec\"\u003eChemotherapy for Poorly Differentiated Tumors (Questions 6–8)\u003c\/h2\u003e\n\n\u003cp\u003eNeuroendocrine carcinomas (NECs) are the poorly differentiated, aggressive form of GEP-NENs. They grow quickly and require chemotherapy. The guideline addresses three chemotherapy scenarios for these patients.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 6: First-line chemotherapy for GEP-NEC\u003c\/h3\u003e\n\u003cp\u003eThe panel recommends that \u003cstrong\u003ecisplatin or carboplatin combined with etoposide\u003c\/strong\u003e should be proposed as first-line systemic chemotherapy for patients with advanced GEP-NEC. This was rated \u003cstrong\u003econditional in favor\u003c\/strong\u003e, with \u003cstrong\u003every low certainty\u003c\/strong\u003e of evidence. This platinum-based doublet has long been the standard of care for these aggressive tumors, though the evidence base is limited.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 7: A temozolomide-based alternative for certain Ki-67 ranges\u003c\/h3\u003e\n\u003cp\u003eFor patients with GEP-NEC and a \u003cstrong\u003eKi-67 between 20% and 55%\u003c\/strong\u003e (a somewhat intermediate range, though still classified as NEC), the panel suggested that \u003cstrong\u003etemozolomide-based chemotherapy could be preferred\u003c\/strong\u003e to cisplatin\/carboplatin + etoposide as first-line treatment. This was rated \u003cstrong\u003econditional in favor\u003c\/strong\u003e with \u003cstrong\u003every low certainty\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003eTemozolomide is an oral chemotherapy drug that is generally easier to tolerate than platinum-based regimens. For certain patients whose tumors fall in this Ki-67 window, it may offer a reasonable alternative with less toxicity — though the evidence supporting this choice remains weak.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 8: Second-line treatment after progression\u003c\/h3\u003e\n\u003cp\u003eFor patients with advanced GEP-NEC who progress after first-line treatment with cisplatin\/carboplatin + etoposide, the panel considered whether second-line treatment with \u003cstrong\u003etemozolomide, irinotecan, oxaliplatin, or fluoropyrimidine\u003c\/strong\u003e should be preferred over best supportive care alone. The recommendation was \u003cstrong\u003econditional in favor\u003c\/strong\u003e, with \u003cstrong\u003every low certainty\u003c\/strong\u003e of evidence.\u003c\/p\u003e\n\n\u003cp\u003eThis means that although the evidence is weak, offering one of these chemotherapy options to patients who have progressed on first-line treatment is considered reasonable, rather than switching exclusively to comfort-focused care.\u003c\/p\u003e\n\n\u003ch2 id=\"chemotherapy-net\"\u003eChemotherapy for Pancreatic NETs (Question 9)\u003c\/h2\u003e\n\n\u003cp\u003eFor patients with \u003cstrong\u003eadvanced, progressive G1-G2 pancreatic neuroendocrine tumors (Pan-NETs)\u003c\/strong\u003e, the panel considered whether temozolomide-based chemotherapy should be preferred over other chemotherapy options such as oxaliplatin or irinotecan.\u003c\/p\u003e\n\n\u003cp\u003eThe recommendation was \u003cstrong\u003econditional in favor\u003c\/strong\u003e of \u003cstrong\u003etemozolomide-based chemotherapy\u003c\/strong\u003e, with \u003cstrong\u003every low certainty\u003c\/strong\u003e of evidence. This suggests that temozolomide may be a good choice for treating progressive pancreatic NETs, but the evidence is not robust enough to make a stronger statement. The choice between chemotherapy agents should be individualized based on the patient’s specific situation.\u003c\/p\u003e\n\n\u003ch2 id=\"surgical-locoregional\"\u003eSurgery and Locoregional Treatments (Questions 10, 11, and 13)\u003c\/h2\u003e\n\n\u003ch3\u003eQuestion 10: Surgery for borderline resectable primary tumors with liver metastases\u003c\/h3\u003e\n\u003cp\u003eIn patients with non-functioning GEP-NEN whose primary tumor is \u003cstrong\u003eborderline resectable\u003c\/strong\u003e and who have \u003cstrong\u003econcomitant liver metastases where more than 90% of the liver disease is expected to be resected\u003c\/strong\u003e, the panel suggested that \u003cstrong\u003ea surgical approach could be preferred\u003c\/strong\u003e over a non-surgical approach. This was rated \u003cstrong\u003econditional in favor\u003c\/strong\u003e with \u003cstrong\u003every low certainty\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003eThis is a highly selected group of patients. The key condition — that more than 90% of liver disease can be removed — means surgery is only considered when the metastatic burden in the liver is largely removable. Patients who meet this criterion may benefit from aggressive surgical management.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 11: Vascular interventional locoregional treatments\u003c\/h3\u003e\n\u003cp\u003eFor patients with non-functioning GEP-NEN, the panel considered whether \u003cstrong\u003evascular interventional locoregional treatments\u003c\/strong\u003e (such as hepatic arterial embolization or chemoembolization, which cut off or deliver treatment directly to the blood supply of liver tumors) should be preferred over other therapies. The recommendation was \u003cstrong\u003econditional in favor\u003c\/strong\u003e with \u003cstrong\u003elow certainty\u003c\/strong\u003e of evidence.\u003c\/p\u003e\n\n\u003cp\u003eThese treatments are typically used for patients with liver-dominant disease who are not candidates for surgery. The panel’s conditional endorsement reflects that these approaches can be useful, but patient selection is important.\u003c\/p\u003e\n\n\u003ch3\u003eQuestion 13: Liver transplantation\u003c\/h3\u003e\n\u003cp\u003eThe guideline also addressed whether liver transplantation should be considered in patients with GEP-NETs with concomitant liver metastases. The full text of this recommendation was not available in the published article excerpt, but its inclusion in the guideline reflects the ongoing interest in transplantation as a potential option for carefully selected patients with liver-only or liver-dominant metastatic disease.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eClinical Implications: What This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThese guidelines provide a clear roadmap for doctors treating patients with advanced non-functioning GEP-NENs. Several messages stand out:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModern imaging matters.\u003c\/strong\u003e Ga-68 DOTA-peptide PET-CT is now the preferred staging tool over Octreoscan. In selected intermediate\/high-grade cases, adding FDG-PET provides valuable information about tumor aggressiveness.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDon’t overtreat after complete surgery.\u003c\/strong\u003e Adjuvant SSA after radical resection is not recommended. Monitoring is the standard approach.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStart SSA early in advanced slow-growing NETs.\u003c\/strong\u003e Rather than watchful waiting, strong evidence supports initiating SSA in patients with advanced, non-functioning, SSTR-2-positive, low Ki-67 tumors.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePRRT is a key second-line option.\u003c\/strong\u003e For patients who progress on SSA, lutetium-177 oxodotreotide (PRRT) is strongly recommended.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eChemotherapy choices depend on tumor type and Ki-67.\u003c\/strong\u003e Platinum-based regimens remain the backbone for NECs, but temozolomide-based approaches may be appropriate for certain Ki-67 ranges and for pancreatic NETs.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSurgery and liver-directed therapies have a role.\u003c\/strong\u003e In highly selected patients (e.g., \u0026gt;90% of liver disease resectable), surgery can be preferred. Liver-directed interventional treatments are also reasonable options.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003ePerhaps the most important takeaway: \u003cstrong\u003eGEP-NENs are complex, and treatment must be individualized.\u003c\/strong\u003e No single recommendation fits every patient. The panel emphasizes that multidisciplinary management by experienced teams remains essential to achieve the best outcomes.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Guidelines\u003c\/h2\u003e\n\n\u003cp\u003eIt is important for patients to understand that this guideline — like all medical guidelines — has limitations:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLow certainty of evidence for many recommendations.\u003c\/strong\u003e Of the 15 recommendations, only two (Questions 1 and 4) were supported by moderate certainty evidence. Six recommendations were based on \u003cstrong\u003every low certainty\u003c\/strong\u003e, meaning the true effect could be substantially different from what the evidence suggests.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOne recommendation relied on expert opinion.\u003c\/strong\u003e The recommendation against adjuvant SSA (Question 3) was not based on direct clinical trial evidence but on expert consensus.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRare disease challenges.\u003c\/strong\u003e Because GEP-NENs are uncommon, conducting large, high-quality randomized controlled trials is difficult. Many treatment decisions are supported by smaller, non-randomized studies.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOnly 15 of 56 questions were presented.\u003c\/strong\u003e This publication focuses on non-functioning advanced GEP-NENs; other aspects of NEN management are covered in the full guideline.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRapidly evolving field.\u003c\/strong\u003e New treatments and data are continually emerging. Recommendations may change as new evidence becomes available.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eContext-specific recommendations.\u003c\/strong\u003e These guidelines were developed for the Italian healthcare context, though they draw on international evidence. Availability of specific treatments may vary by country.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations for Patients\u003c\/h2\u003e\n\n\u003cp\u003eIf you or a loved one has been diagnosed with a GEP-NEN, here are several practical points based on these guidelines:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSeek a specialized, multidisciplinary center.\u003c\/strong\u003e The guidelines strongly recommend that GEP-NEN patients be treated by experienced teams. Look for centers with dedicated neuroendocrine tumor programs (often designated as ENETS Centers of Excellence).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about modern imaging.\u003c\/strong\u003e If staging is being done, ask whether [68Ga]Ga-DOTA-peptides PET-CT is available. It is now the preferred imaging tool over Octreoscan for staging.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss Ki-67 and SSTR status.\u003c\/strong\u003e These biomarkers guide treatment selection. Know your tumor’s Ki-67 index (proliferation rate) and somatostatin receptor status, as they directly influence whether SSA, PRRT, or chemotherapy is recommended.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnderstand the rationale for SSA therapy.\u003c\/strong\u003e If your tumor is slow-growing and SSTR-positive, SSA is the first-line standard. It can stabilize disease for extended periods with relatively mild side effects.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eIf you progress on SSA, ask about PRRT.\u003c\/strong\u003e Lutetium-177 oxodotreotide is strongly recommended for patients who progress on SSA. It delivers targeted radiation to tumor cells and can be highly effective.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDon’t expect chemotherapy if you have a low-grade NET.\u003c\/strong\u003e Chemotherapy is mainly reserved for poorly differentiated NECs or for progressive pancreatic NETs where other options have been exhausted. Temozolomide-based regimens are emerging as preferred options in select situations.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSurgical evaluation is important.\u003c\/strong\u003e Even with metastatic disease, surgery may be an option if a high percentage of liver disease can be removed. Always have your case reviewed by a surgical team experienced in NENs.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eParticipate in shared decision-making.\u003c\/strong\u003e Several recommendations in this guideline are “conditional,” meaning the right choice depends on individual circumstances. Discuss the benefits, risks, and uncertainties of each option with your care team.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eRemember that guidelines are not rigid rules — they are tools to support decision-making. Your doctors will adapt these recommendations to your specific situation, preferences, and overall health.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is the difference between well-differentiated and poorly differentiated GEP-NENs?\u003c\/h3\u003e\n\u003cp\u003eWell-differentiated tumors, called neuroendocrine tumors or NETs, tend to grow slowly and are generally less aggressive. Poorly differentiated neoplasms, called neuroendocrine carcinomas or NECs, grow quickly and are much more aggressive. This difference is based on how similar the cells look to normal cells under a microscope.\u003c\/p\u003e\n\u003ch3\u003eWhat imaging test is now preferred for staging GEP-NETs?\u003c\/h3\u003e\n\u003cp\u003eThe guidelines strongly recommend using a [68Ga]Ga-DOTA-peptides PET-CT scan instead of the older Octreoscan for staging. This modern PET-CT is more sensitive and can detect smaller or more numerous tumor deposits, providing better information for staging and treatment planning. The recommendation is based on moderate certainty evidence.\u003c\/p\u003e\n\u003ch3\u003eShould I receive somatostatin analog therapy after complete surgery?\u003c\/h3\u003e\n\u003cp\u003eNo. The panel recommends against adjuvant somatostatin analog (SSA) treatment after radical surgery for non-functioning GEP-NET. This recommendation is based on expert opinion because there is insufficient high-quality evidence to support routine use. After complete resection, regular monitoring is the standard approach.\u003c\/p\u003e\n\u003ch3\u003eWhat is the first-line treatment for advanced slow-growing non-functioning GEP-NET?\u003c\/h3\u003e\n\u003cp\u003eFor patients with advanced, non-functioning, not rapidly progressive, low Ki-67, SSTR-2-positive GEP-NET, the panel strongly recommends starting somatostatin analogs (SSA) as the primary option rather than follow-up without therapy. This is supported by moderate certainty evidence. SSAs help control tumor growth and can keep the disease stable.\u003c\/p\u003e\n\u003ch3\u003eWhat treatment is recommended if my tumor progresses on SSA?\u003c\/h3\u003e\n\u003cp\u003eIf your advanced SSTR-2-positive GEP-NET progresses despite SSA treatment, the guidelines strongly recommend peptide receptor radionuclide therapy (PRRT) with lutetium-177 oxodotreotide. PRRT delivers targeted radiation directly to tumor cells. The recommendation is strong in favor, though the certainty of evidence is low.\u003c\/p\u003e\n\u003ch3\u003eIs chemotherapy used for low-grade NETs?\u003c\/h3\u003e\n\u003cp\u003eChemotherapy is mainly reserved for poorly differentiated NECs or for progressive pancreatic NETs where other options have been exhausted. For GEP-NEC, first-line chemotherapy is cisplatin or carboplatin plus etoposide. Temozolomide-based regimens may be preferred for certain Ki-67 ranges and for pancreatic NETs, but evidence is weak.\u003c\/p\u003e\n\u003ch3\u003eWhen can surgery be considered for metastatic GEP-NEN?\u003c\/h3\u003e\n\u003cp\u003eSurgery could be preferred in patients with a borderline resectable primary tumor and liver metastases when more than 90% of liver disease is expected to be resected. The recommendation is conditional and based on very low certainty evidence. It applies only to this highly selected group, and multidisciplinary review is essential.\u003c\/p\u003e\n\u003ch3\u003eCan a second opinion change the treatment plan for advanced GEP-NEN?\u003c\/h3\u003e\n\u003cp\u003eFor advanced GEP-NEN, many guideline recommendations are conditional rather than strong, and most are based on low or very low certainty evidence. This means the right choice depends on individual tumor grade, Ki-67 index, somatostatin receptor status, extent of disease, and patient health. Different experienced specialists may reasonably weigh the benefits and risks differently, especially for choices like surgery, liver-directed therapies, or temozolomide-based chemotherapy. A second opinion can help confirm that your treatment plan reflects the latest evidence and your specific situation. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal Article Title:\u003c\/strong\u003e Clinical practice guidelines for the management of non-functioning advanced GEP-NENs: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology (AIOM) in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET).\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eLicense:\u003c\/strong\u003e CC BY-NC-ND (open access)\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Spada F, Gelsomino F, Rinzivillo M, Cinquini M, Fittipaldo VA, Tralongo A, Moschetti I, Albertelli M, Ambrosini V, Amoroso V, Antonuzzo L, Badalamenti G, Bajetta E, Baldari S, Barberis M, Berruti A, Bertani E, Bonomo G, Bodei L, Buzzoni R, Brizzi MP, Campana D, Capurso G, Casadei R, Castellano M, Cingarlini S, Cives M, Colao AM, Coppa J, Cremonini N, Davì MV, De Angelis CG, de Braud F, De Robertis R, Faggiano A, Falconi M, Fassan M, Ferolla P, Ferone D, Filice A, Fiore F, Funicelli L, Granata V, Giuffrida D, Grana CM, Grimaldi F, Ibrahim T, La Salvia A, Laghi A, Luppi G, Maccauro M, Marconcini R, Massironi S, Mazzaferro V, Merola E, Milione M, Modica R, Ortolani S, Papotti MG, Partelli S, Pelosi G, Pusceddu S, Ramundo V, Ravizza D, Razzore P, Reimondo G, Ricci C, Rindi G, Rizzo FM, Rossi RE, Tafuto S, Tiberio GAM, Versari A, Vigorito R, Zatelli MC, Di Maio M, Perrone F, Cinieri S, Panzuto F, Fazio N.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCorresponding Authors:\u003c\/strong\u003e Dr. Nicola Fazio (European Institute of Oncology, IEO, IRCCS, Milan, Italy; nicola.fazio@ieo.it) and Dr. Francesco Panzuto (Sant’Andrea University Hospital, Sapienza University of Rome, Rome, Italy; francesco.panzuto@uniroma1.it)\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e ESMO Open, Volume 10, Issue 11, 2025\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e https:\/\/doi.org\/10.1016\/j.esmoop.2025.105878\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublisher:\u003c\/strong\u003e Published by Elsevier Ltd on behalf of European Society for Medical Oncology. Open access article under the CC BY-NC-ND license.\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eNote: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not replace professional medical advice. Always consult your healthcare team about your specific condition and treatment options.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47471121825948,"sku":null,"price":0.0,"currency_code":"KRW","in_stock":true}],"url":"https:\/\/diagnosticdetectives.kr\/products\/new-italian-guidelines-for-managing-advanced-gep-nens-a-patient-rsquo-s-guide-to-the-2024-recommendations","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}