Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2020; 26(13): 1513-1524
Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1513
Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors
Estephany Abou Jokh Casas, Virginia Pubul Núñez, Urbano Anido-Herranz, María del Carmen Mallón Araujo, Maria del Carmen Pombo Pasín, Miguel Garrido Pumar, José Manuel Cabezas Agrícola, José Manuel Cameselle-Teijeiro, Ashraf Hilal, Álvaro Ruibal Morell
Estephany Abou Jokh Casas, Virginia Pubul Núñez, María del Carmen Mallón Araujo, Maria del Carmen Pombo Pasín, Miguel Garrido Pumar, Álvaro Ruibal Morell, Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
Urbano Anido-Herranz, Department of Oncology, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
José Manuel Cabezas Agrícola, Department of Endocrinology, Santiago de Compostela´s University Hospital, Santiago de Compostela, 15706, A Coruña, Spain
José Manuel Cameselle-Teijeiro, Department of Pathology, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
Ashraf Hilal, Department of Statistics, University of Santiago de Compostela, Santiago de Compostela 15706, A Coruña, Spain
Author contributions: Abou Jokh Casas E, Pubul Núñez V, del Carmen Mallón Araujo M and del Carmen Pombo Pasín M designed the research and wrote the paper; Anido-Herranz U, Hilal A and Garrido Pumar M contributed new reagents/analytic tools; Cabezas Agrícola JM, Cameselle-Teijeiro JM and Ruibal Morell Á analyzed the data.
Institutional review board statement: The study was reviewed and approved by the ethics committee.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Estephany Abou Jokh Casas, MD, Occupational Physician, Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Avenida Choupana, Santiago de Compostela 15706, A Coruña, Spain. estephanyaboujokh@gmail.com
Received: December 8, 2019
Peer-review started: December 8, 2019
First decision: January 9, 2020
Revised: March 6, 2020
Accepted: March 19, 2020
Article in press: March 19, 2020
Published online: April 7, 2020
Abstract
BACKGROUND

177Lu peptide receptor radionuclide therapy (PRRT) is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors.

AIM

To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity.

METHODS

Thirty-six patients treated with 177Lu-PRRT from 2016 to 2019 were included. The most frequent location of the primary tumor was the gastrointestinal tract (52.8%), pancreas (27.8%), and nongastropancreatic neuroendocrine tumor (11.1%). The liver was the most common site of metastasis (91.7%), followed by distant nodes (50.0%), bone (27.8%), peritoneum (25.0%) and lung (11.1%). Toxicity was evaluated after the administration of each dose. Treatment efficacy was evaluated by two parameters: stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested.

RESULTS

From 36 patients, 55.6% were men, with a median age of 61.1 ± 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8–15.2), being inversely proportional to toxicity in previous treatments (P < 0.02), tumor grade (P < 0.01) and the presence of bone lesions (P = 0.009) and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01), , primary tumor surgery (P = 0.03) and metastasis surgery (P = 0.045). In a multivariate Cox regression analysis, a high Ki67 index (P = 0.003), a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01) and a preceding toxicity in previous treatments (P < 0.05) were risk factors to overall survival.

CONCLUSION

Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.

Keywords: Peptide receptor radionuclide therapy, Gastropancreatic neuroendocrine tumors, Radiological response, Metabolic response

Core tip: Peptide receptor radionuclide therapy has been used successfully in patients diagnosed with metastatic gastroenteropancreatic somatostatin receptor positive tumors when cytoreductive options are limited. In this study we found that overall survival was inversely proportional to toxicity to previous treatments, tumor grade, bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-peptide receptor radionuclide therapy and primary tumor and metastasis surgery. Also, pseudo-progression in the middle of the treatment was a common finding that should be taken into consideration by clinicians in daily practice.