Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Neoadjuvant treatment may be useful in inoperable pancreatic neuroendocrine neoplasms (pNEN). A 41-year-old man complained for severe gastrointestinal symptoms (severe dysphagia, gastroesophageal reflux, postprandial diarrhoea, and weight loss); abdominal ultrasound showed two liver nodules and computerized tomography (CT) showed multiple liver metastases and a 4 cm highly vasularized pancreatic mass, suspected for NEN (Fig. 1a, b). Chromogranin A (CgA), Neuron Specific Enolase, gastrin, glucose and insulin levels, blood count, and liver, kidney, adrenal, and pituitary function were normal. Calcitonin levels were high (151 pg/ml). Somatostatin receptor (SSTR) scintigraphy (Octreoscan) showed a strong uptake in the pancreatic tumor and liver metastases (Fig. 1c); the patient started medical therapy with a long acting somatostatin analogue (SSA) in keeping with current guidelines [1] and with a strong Octreoscan positivity. Surgical exploration with multiple biopsies showed a locally invasive, well-differentiated G1 (Ki-67 index <2%) NEN with positive immunohistochemistry for calcitonin, CgA and SSTR subtypes 1, 2, 3, and 5 (pNEN cT4NXM1A; Stage IV), according to AJCC TNM classification (8th edition). Surgical management was contraindicated at that time due to portal and splenic vein involvement. A systemic neoadjuvant treatment was needed in order to manage the disease with the perspective of a future surgical treatment to allow tumor removal and prolong survival of this young patient. Everolimus and sunitinib are approved treatments after SSA failure, but were unavailable at that time. Cytotoxic chemotherapy is indicated as first-line therapy in G2 pNEN, which was not our case. Ablative loco-regional therapies could have addressed liver disease, leaving untreated the pancreatic mass [2]. Therefore, we opted for peptide receptor radionuclide therapy (PRRT), despite this approach is not routinely employed in neoadjuvant and adjuvant settings in pNEN, in keeping with the inclusion criteria indicated by the ENETS 2009 Consensus Guidelines [3]. PRRT is recommended in nonfunctional G1–G2 unresectable pNEN after failure of medical therapy and it may improve symptoms and quality of life in patients with functioning pNEN [4]. Our patient underwent five PRRT cycles with 90Yttrium (90Y)-DOTATOC (10.619 MBq cumulative dose in 9 months), without side effects. The patient was treated with Y-DOTATOC because that was the only PRRT treatment available at the time the patient was addressed to this approach.
×
Post PRRT abdominal CT showed a >50% reduction in pancreatic tumor size (maximum diameter from 4 to 1.3 cm) and disappearance of liver metastases (Fig. 1d, e), but persistence of splenic vein occlusion, as confirmed by 68Gallium-DOTANOC PET-CT (Fig. 1f). Calcitonin levels (2.7 pg/ml), blood glucose and insulin levels were normal. The case was discussed in the NEN tumor board and the patient was found eligible for distal pancreatectomy and splenectomy. Histopathology showed a 2 cm well-differentiated NEN with Ki-67 index = 1% (Grade 1) with perineural invasion (pNEN pT1N0M0, Stage I). Post-surgical abdominal CT showed the absence of liver metastases, portal vein invasion and pancreatic recurrence (Fig. 1g, h), as confirmed by 68Gallium-DOTANOC PET-CT (Fig. 1i). Calcitonin levels were undetectable (<1 pg/ml). Long-term yearly follow-up (>9 years) evaluated biochemistry, abdominal CT and 68Gallium-DOTATOC PET-CT and allowed to observe a progression-free survival (PFS) after neoadjuvant PRRT of > 108 months, which is threefold to fourfold longer as compared to previously observed results. PRRT indeed caused a tumor down-staging from Stage IV to Stage I, allowing complete surgical resection. Eight years after PRRT and 7 years after surgery, SSA therapy was stopped. Two years after SSA treatment withdrawal, no biochemical nor morpho-functional evidence of recurrence has been detected and the patient is free of disease 11 years after initial diagnosis (Fig. 1l–n).
Anzeige
Neoadjuvant PRRT has already been reported to reduce NEN bulk in cases that were not eligible for surgery at diagnosis [5‐10] also in pNEN. Recently, PRRT efficacy was demonstrated in pNEN in neoadjuvant settings, showing that patients previously treated with PRRT have a lower incidence of nodal metastases at the time of surgery, reduced intra- and post-surgical complications and longer PFS (52 months) as compared to patients treated only with surgery (37 months) [11]. We found 6 studies describing a total of 21 patients undergoing neoadjuvant PRRT for an unoperable pNEN, who eventually underwent surgery obtaining a complete tumor resection (R0 resection) [5, 12‐16].
Our clinical experience is in line with current literature on pNEN and proves the potential efficacy of neoadjuvant 90Y-PRRT in G1 metastatic pNEN. PRRT, indeed, may improve life expectancy and long-term prognosis after surgery, without major side effects. Current guidelines do not provide specific indication concerning adjuvant SSA therapy duration after PRRT: our case underlines the importance of a multidisciplinary evaluation in order to tailor the treatment according to patient’s characteristics.
Acknowledgements
The Authors would like to thank their Colleagues for their precious support for this manuscript Fabio Pellegrino and Melchiore Giganti, of the Section of Radiology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; Massimo Falconi of the Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Hospital IRCCS, “Vita-Salute” University, Milan, Italy; Mirco Bartolomei of the Nuclear Medicine Department, “S. Anna” Hospital, Ferrara, Italy; Irene Gagliardi of the Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Compliance with ethical standards
Conflict of interest
The author declares no competing interests.
Anzeige
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.
Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.
Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.
Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.
„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.
Update Innere Medizin
Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.