Resection of the Primary Tumor Followed by Peptide Receptor Radionuclide Therapy as Upfront Strategy for the Treatment of G1-G2 Pancreatic Neuroendocrine Tumors with Unresectable Liver Metastases.
A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery.



From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS).



Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048.



Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.
Division of Hepatobilio-pancreatic Surgery, European Institute of Oncology, Milan, Italy. emilio.bertani@ieo.it.
Emilio
E
Bertani
GI and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy.
Nicola
N
Fazio
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Davide
D
Radice
Surgical Department, Sacro Cuore Hospital, Negrar, Italy.
Claudio
C
Zardini
Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy.
Chiara
C
Grana
Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy.|Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
Lisa
L
Bodei
Division of Radiology, European Institute of Oncology, Milan, Italy.
Luigi
L
Funicelli
Division of Digestive Surgery, European Institute of Oncology, Milan, Italy.
Carlo
C
Ferrari
GI and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy.
Francesca
F
Spada
Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milan, Italy.
Stefano
S
Partelli
Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milan, Italy.
Massimo
M
Falconi
D000328:Adult; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D018000:Receptors, Peptide / Q000627:therapeutic use; D015996:Survival Rate; D047368:Tumor Burden
D019394:Ki-67 Antigen; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C496730:90Y-octreotide, DOTA-Tyr(3)-; C447941:lutetium Lu 177 dotatate; D015282:Octreotide