Subscribe to RSS

DOI: 10.1055/s-0042-1755412
Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE in Advanced Neuroendocrine Tumors (NETs) in a Limited-Resource Environment
Abstract
Background This study was conducted to evaluate the clinical efficacy and safety of peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA0-Tyr3-octreotate (DOTATATE) in patients with neuroendocrine tumors (NETs).
Methods Sixteen patients with pathologically verified NETs including eight females and eight males were enrolled in this study. Before PRRT, the patients underwent 68Ga-DOTATATE positron emission tomography/computed tomography or 99mTc-octreotide scintigraphy for evaluation of somatostatin receptor expression. Response to treatment was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). In addition, for evaluation of toxicity, monthly blood analysis was performed including hematology, renal function (creatinine) test, and liver function test. The Eastern Cooperative Oncology Group (ECOG) status performance was applied to estimate the patients' general condition in a scale of 0 (fully active) to 5 (dead). In addition, overall survival (OS) was calculated as the time interval from the start of PRRT to death from any reason.
Results Sixteen patients including eight females and eight males with a median age of 60.5 years (range: 24–74) were enrolled in this study. The patients underwent PRRT with a median cycle of 3.5 (range: 1–7) and a median dose of 20.35 (range: 7.4–49.95 GBq). At the end of data collection, PR, CR, SD, and PD were seen in 11, 2, 1, and 2 patients according to the RECIST, respectively. Three patients expired during or after the PRRT period. The median ECOG and Karnofsky Performance Scale was 1.5 and 75 before PRRT, which improved significantly to 1 and 80 after PRRT, respectively (p < 0.05). According to the Kaplan–Meier test, the median OS was 23 months (95% confidence interval: 7.90–38.09). According to the National Cancer Institute's Common Terminology Criteria for Adverse Events, three patients showed grade I and three patients showed grade II leucopenia. Furthermore, three and seven patients had grade II and grade I anemia, respectively.
Conclusion Since PRRT using 177Lu-DOTATATE has a favorable response rate and few adverse effects and improves the quality of life in NETs, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.
#
Keywords
neuroendocrine tumors (NETs) - peptide receptor radionuclide therapy (PRRT) - 177Lu-DOTATATE - 68Ga-DOTATATE PET-CT - 99mTc-octreotide scintigraphyIntroduction
Neuroendocrine tumors (NETs) are defined as neoplastic lesions originating from neuroendocrine cells. According to the data from the National Cancer Institute, there has been an increase in the incidence of NETs (0.3 per 100,000), which is contributed to advanced professional diagnostic tools.[1]
Several treatment methods are available for treatment of NETs according to the tumor condition, including surgery as the first-line option, even in the metastasized tumors. Several palliative therapeutic options are used in nonresectable tumors, including chemotherapy and radionuclide therapy.[2]
A common property of NETs is overexpression of somatostatin receptors (SSTRs) leading to the establishment of alternative therapeutic option for these tumors, including radiolabeled somatostatin analogues.[3]
Peptide receptor radionuclide therapy (PRRT) is a very new treatment option, which includes systematic administration of radiolabeled somatostatin analogues with radiopharmaceuticals such as 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) to molecularly targeted malignant NETs. The results of several studies that have evaluated the clinical efficacy of PRRT with 177Lu-DOTATATE in NETs have shown the long-term survival for these patients.[1] [4] [5] Nevertheless, the PRRT approach is associated with few or reversible side effects in the kidney function and bone marrow, which are considered dose-limiting organs.[6]
Many studies have confirmed the promising results of 177Lu-labeled PRRT for treatment of these patients through gamma- and β-emission as a theranostic agent.[2] [7] [8] The purpose of this study was to evaluate the clinical efficacy and safety of PRRT with 177Lu-DOTATATE in patients with NETs and the effect of this therapy on the overall survival (OS) and quality of life (QOL).
#
Methods
Patient Characteristics
Sixteen patients (eight males and eight females) with pathologically verified NETs were included in this study from June 2017 to April 2020. The clinical characteristic and demographic data of patients were collected. The exclusion criteria were hemoglobin less than 8.0 g/dL, serum creatinine more than 150 μmol/L (1.7 mg/dL), creatinine clearance less than 50mL/minute, white blood cell count less than 2,000/millimeter2, platelet count less than 75,000/millimeter2, and total bilirubin greater than 3 times the upper limit of normal. The study protocol was explained to patients and written consent was obtained from them. The Ethical Committee of Bushehr University of Medical Sciences approved this study (Registration code: 345).
#
Pretreatment Imaging
Before PRRT, the expression of SSTRs was evaluated using 99mTc-octerotide scintigraphy or 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT). All images were reviewed by two nuclear medicine specialists. If lesions showed acceptable uptake of radiotracer (Krenning score ≥ 2) on 99mTc-octerotide scintigraphy and maximum standardized uptake value was higher than liver on 68Ga-DOTATATE PET/CT, the patient was scheduled for PRRT with 177Lu-DOTATATE.
#
Treatment
For PRRT, the patients were hospitalized in the dedicated theranostics center of the Department of Nuclear Medicine. The median amount of activity in each cycle was 5.5 GBq (range: 3.7–7.4). Commercial radiolabeled 177Lu-DOTATATE was obtained from Pars Isotope Co., Iran.
Before administration of 177Lu-DOTATATE, the probability of renal side effects was reduced by intravenous injection of amino acid solution (2.5% arginine and 2.5% lysine, 1 L) starting 30 minutes before infusion of the radiopharmaceutical. Then, the radiopharmaceutical was injected intravenously during approximately 20 minutes.
The time interval between treatment cycles was 6 to 8 weeks. The treatment was considered unsuccessful and subsequently stopped if there were complications such as severe hematological toxicities and cardiac problems, disease progression, or death, or if the patient was unable or unwilling to continue participation.
#
Posttreatment Imaging
For evaluation of radiotracer distribution, scintigraphy was performed 24 and 48 hours after PRRT. Images were acquired with a dual-head gamma camera (Vertex ADAC plus) equipped with a low-energy high-resolution collimator. Energy was set at 113 KeV with an energy window of 20%. The scan was performed in whole body anterior and posterior images. In the case of borderline abnormality, single-photon emission computed tomography—SPECT—images were performed to advance the detectability of lesions. All images were reviewed by two nuclear medicine specialists.
#
Response Evaluation
Tumor morphology and treatment response were evaluated through follow-up imaging including CT scan and magnetic resonance imaging every 6 to 8 weeks during treatment cycles as well as 3 and 6 months after the last treatment session and assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST).[9] According to the RECIST, response to treatment is classified into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Moreover, if available, some patients underwent 68Ga-DOTATATE PET/CT for follow-up in addition to anatomical imaging.
For evaluation of safety and toxicity of PRRT, blood analysis was performed monthly after administration of 177Lu-DOTATATE. Blood tests included hematology, renal function test (creatinine), and liver function test (aspartate aminotransferase and alanine aminotransferase).
PRRT-related toxicity was measured according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).
The Eastern Cooperative Oncology Group (ECOG) status performance was applied to estimate the patients' general condition in a scale of 0 (fully active) to 5 (dead). ECOG was assessed before each PRRT session and at least 3 months after the final treatment session in the follow-up visit for evaluation of any changes in the QOL.
Furthermore, OS was calculated as the time interval from the start of PRRT to death from any reason. In addition, progression-free survival (PFS) was calculated as the time from the initiation of treatment with 177Lu-DOTATATE until the first evidence of progression or relapse, or to death.
#
Data Collection and Statistical Analysis
Disease-related data were obtained from our hospital and another clinical department. Descriptive and categorical data are expressed as median and frequency, respectively. Chi-square test was used to analyze categorical variables. The Kaplan–Meier estimator and log-rank tests were applied to evaluate OS and the effect of multiple parameters on OS. Statistical analysis was performed using SPSS Statistics 21 (IBM Corporation, Somers, New York, United States). p-Values of less than 0.05 were considered significant.
#
#
Results
Patients
Sixteen NET patients including eight males and eight females were enrolled in this study. Nine cases (56%) were functional NET and seven cases (44%) were nonfunctional NET. The median age of the subjects was 60.5 years (range: 24–75). According to the medical history, three patients were hypertensive and four were diabetic. Of 16 patients, 12 were selected for PRRT according to 99mTc-octerotide scintigraphy and 4 according to 68Ga-DOTATATE PET/CT. The primary sites of NETs were the pancreas (8/16), gastrointestinal tract (5/16), and lungs (3/16). [Table 1] summarizes the patients' characteristics. The patients presented with metastases in the liver (13/16), lymph nodes (5/16), bone (1/16), kidney (1/16), and uterus (1/16). Of 16 patients, 10, 8, and 2 patients underwent surgery, chemotherapy, and radiotherapy, respectively. The median Krenning score was 3 (range: 3–4) according to the pretreatment imaging. The patients underwent PRRT with median cycles of 3.5 (range: 1–7) and median dose of 20.35 (range: 7.4 to 49.95 GBq).
Abbreviations: Ch, chemotherapy; DM, diabetes mellitus; F, female; GI, gastrointestinal; HT, hypertension; KS, Krenning Score; M, male; Rad, radiotherapy; Sur, surgery.
P: The patients underwent 68Ga-DOTATATE instead of 99mTc-octreotide scintigraphy for pretreatment evaluation of somatostatin receptor expression.
#
Response Rate
At the end of data collection, 11 (70%), 2 (12%), 1 (6%), and 2 (12%) patients had PR, CR, SD, and PD according to the RECIST, respectively. In addition to anatomical imaging, four patients underwent follow-up with 68Ga-DOTATATE PET/CT, which was consistent with the results of anatomical imaging. Three patients expired during or after the PRRT period. Of nine patients with functional NET, seven cases (78%) showed a reduction in symptoms. Before PRRT, the median ECOG and Karnofsky Performance Scale (KPS) values were 1.5 and 75, which significantly improved to 1 and 80 after PRRT, respectively (p < 0.05). According to the Kaplan–Meier test, the median OS was 23 months (95% confidence interval: 7.90–38.09; [Fig. 1]). Furthermore, the median PFS was 12.5 months (range: 3–35).


No significant association was found between the treatment response and other variables including baseline ECOG, sex, Krenning score, tumor site, metastases, previous therapy, number of PRRT cycle, total administered dose, and PRRT-related toxicity (p > 0.05). [Table 2] summarizes 177Lu-DOTATATE treatment profile and the treatment response in all patients.
Patient |
PRRT cycle |
Dose (GBq) |
ECOG (pre- and posttreatment) |
KPS (pre- and posttreatment) |
Response |
CgA (pre- and posttreatment) |
Toxicity |
Survival (months) |
PFS |
Alive |
---|---|---|---|---|---|---|---|---|---|---|
1 |
4 |
29.6 |
1/1 |
80/90 |
PR[a] |
–/9 |
Leucopenia (G1) Nephrotoxicity (G1) Anemia (G1) |
30 |
30 |
Yes |
2 |
5 |
27.75 |
2/1 |
60/80 |
PR |
−/− |
– |
35 |
35 |
Yes |
3 |
2 |
7.4 |
2/1 |
60/70 |
CR |
−/− |
– |
34 |
34 |
Yes |
4 |
5 |
37 |
1/0 |
90/100 |
PR |
946/24 |
Leucopenia (G2) Anemia (G2) Nephrotoxicity (G1) Thrombocytopenia (G1) |
24 |
24 |
Yes |
5 |
6 |
44.4 |
0/0 |
100/100 |
PR[a] |
73/34 |
Anemia (G1) |
25 |
20 |
Yes |
6 |
4 |
24.05 |
0/0 |
100/100 |
CR[a] |
72/26 |
Leucopenia (G2) |
23 |
23 |
Yes |
7 |
1 |
7.4 |
3/3 |
40/40 |
PD |
−/− |
Anemia (G1) |
3 |
3 |
No |
8 |
7 |
49.95 |
0/0 |
100/100 |
PR |
−/− |
Leucopenia (G1) Anemia (G2) |
15 |
15 |
Yes |
9 |
2 |
9.25 |
2/2 |
70/70 |
SD |
−/− |
Anemia (G2) Nephrotoxicity (G1) Thrombocytopenia (G1) |
6 |
4 |
No |
10 |
3 |
18.5 |
1/1 |
80/80 |
PR[a] |
−/− |
Leucopenia (G2) Anemia (G1) |
11 |
10 |
Yes |
11 |
5 |
22.2 |
1/1 |
80/80 |
PR |
−/− |
Anemia (G1) |
9 |
9 |
Yes |
12 |
5 |
22.2 |
3/1 |
60/80 |
PR |
−/− |
Leucopenia (G1) Anemia (G1) |
9 |
7 |
Yes |
13 |
3 |
13.32 |
2/1 |
70/80 |
PR |
−/− |
Anemia (G1) |
8 |
8 |
Yes |
14 |
2 |
7.4 |
0/0 |
100/100 |
PR |
−/− |
– |
9 |
9 |
Yes |
15 |
3 |
11.1 |
2/1 |
70/90 |
PR |
−/− |
– |
32 |
32 |
Yes |
16 |
2 |
11.1 |
3/3 |
50/50 |
PD |
−/− |
– |
12 |
8 |
No |
Abbreviations: CgA, chromogranin A; CR, complete response; ECOG, Eastern Cooperative Oncology Group; KPS, Karnofsky Performance Scale; PD, progressive disease; PFS, progression-free survival; PR, partial response; PRRT, peptide receptor radionuclide therapy; SD, stable disease.
a The patients performed follow-up 68Ga-DOTATATE PET/CT in addition to anatomical imaging, which was in correlation with anatomical imaging.
#
Side Effects
In evaluation of PRRT-related toxicity according to the CTCAE, three patients showed grade I and three patients had grade II leucopenia. Furthermore, three and seven patients had grade II and grade I anemia, respectively. Serum creatinine increased to grade I in three patients. In addition, two patients showed grade I thrombocytopenia ([Table 3]).
[Fig. 2] presents the outcome of PRRT in a patient with PR.


#
#
Discussion
The present study is a report of 4 years of experience with PRRT using 177Lu-DOTATATE in patients with NETs. The clinical efficacy and safety of PRRT were evaluated in 16 patients with NET.
In recent decades, after it was demonstrated that NETs could be detected with radiolabeled somatostatin analogues such as 68Ga-DOTATATE PET/CT and 99mTc-octreotide, PRRT was introduced as a therapeutic option for NETs, especially in patients who were refractory or progressive to conventional therapeutic modalities such as surgery, somatostatin analogue therapy, and chemotherapy. Since then, several studies have evaluated the clinical efficacy and safety of PRRT.[2] [3] [7] [8] [10] [11] [12] [13] A phase-three trial evaluated the efficacy and safety of 177Lu-DOTATATE therapy in advanced and progressive midgut NETs in comparison with somatostatin analogues therapy (control group), which resulted in an 18% response rate in the PRRT group in comparison to 3% in the control group. As for survival, 14 and 26 deaths occurred in the PRRT and control groups, respectively.[12] In another study, the efficacy of PRRT with 90Y- or 177Lu-DOTANOC as another somatostatin analogue was evaluated in patients with NET. The results showed moderate toxicity in 8/20 of the patients. In addition, of 20 patients that underwent PRRT, partial remission was seen in 5 patients, SD in 11 patients, and tumor progression in 4 patients.[2]
In the present study, of 16 evaluated patients, PR was found in 11 (70%), CR in 2 (12%), SD in 1 (6%), and PD in 2 (12%) patients according to the RECIST, indicating the favorable efficacy of PRRT for the treatment of patients with NET. Also, of nine patients with functional NET, seven cases (78%) showed a reduction in symptoms. In accordance with our results, Abou Jokh Casas et al reported that PRRT was effective in 69% of the patients with NETs. However, they reported progression too in 25% of the patients.[7] Kwekkeboom et al evaluated the effectiveness of PRRT using 177Lu-octreotide as a radiolabeled somatostatin analogue in patients with metastasized or inoperable endocrine gastroenteropancreatic tumors. The results showed CR in 2%, PR in 26%, minor response in 19%, SD in 35%, and PD in 18% of 131 treated patients.[3] In addition, they conducted another study to evaluate the efficacy of 177Lu-octreotide in a larger group of patients with gastroenteropancreatic NETs. The results showed that of 310 treated patients, CR was observed in 2%, PR in 28%, minor response in 16%, SD in 35%, and PD in 20% of the patients.[13] Our results were relatively in concordance with previous studies performed on resource-limited centers in India[8] and South Africa.[14] In a study performed in India by Danthala et al in evaluation of clinical efficacy of 177Lu-DOTATATE in patients with NETs, it has been showed that among 40 treated patients, 10 patients (25%) had a minimal response, 13 (32.5%) had a PR, and 9 (22.5%) had SD. PD was seen in 8 patients (20%), including 6 patients who died during or after the treatment period.[8] Vorster et al reported first results and experience with 177Lu-DOTATATE in patients with NETs in South Africa. They indicated that of 48 treated patients, 22 (46%) demonstrated SD, 20 (42%) demonstrated a PR, and 6 (12%) demonstrated PD.[14] It should be mentioned that these results compared favorably to chemotherapy reports in these patients. Previous studies showed PR and CR in less than 20% of the patients. In addition, PRRT showed a better outcome compared with chemotherapy in OS, duration of response, and toxicity.[15] [16] [17]
This study also evaluated the physical condition and QOL change of patients using KPS and ECOG scores. The results showed that KPS and ECOG improved significantly after treatment, indicating QOL improvement in the treated patients. Similarly, Khan et al evaluated the QOL of the patients with NETs that underwent PRRT using 177Lu-octreotide in different aspects including KPS. They reported that the overall QOL improved significantly after PRRT. In addition, they found that KPS improved significantly in patients who responded to PRRT and worsened in patients who progressed after PRRT.[18] In another study, QOL was assessed using the EORTC QLQ-C30 questionnaire—European Organization for Research and Treatment of Cancer core quality of life questionnaire-30—that was completed after each cycle of PRRT. The results showed a significant improvement in the overall QOL after PRRT. In analyzing specific aspects of the QOL, a significant improvement was found in emotional functioning, pain, and diarrhea.[19]
The median OS was 23 months in this study for all patients and death occurred in 18% (3/16) of the patients. In addition, the median PFS was 12.5 months (range: 3–35). There was no significant difference between OS and several baseline characteristics, which may be due to the small sample size and low number of events. Abou Jokh Casas et al reported that several factors could affect the OS after PRRT with 177Lu-DOTATATE in patients with metastatic NETs including toxicity in previous treatment, tumor grade, and presence of bone lesions.[7] Another study showed that in patients with grade 1 and 2 gastroenteropancreatic NET, PRRT resulted in a favorable response and long-term outcome, indicating that tumor grade is the most powerful predictive factor in OS.[20]
According to the CTCAE, approximately 75% of patients developed PRRT-related toxicity in this study. The most common toxicity was anemia that occurred in 10/16 patients including grade 2 in 3 and grade 1 in 7 patients. Leucopenia developed in six including grade 2 in three and grade 1 in three patients, grade 1 nephrotoxicity in two patients, and grade 1 thrombocytopenia in two patients. A study showed hematological toxicity in 38.8% of the patients during PRRT.[7] A multicenter study evaluated 450 patients with NETs and found that PRRT had rare serious adverse events including grade 3 leukopenia in 1.1% and grade 3 thrombocytopenia in 1.3% of the patients. Grade 4 thrombocytopenia was observed in only one patient in this study.[21]
This study had some limitations. The most important limitation was its small sample size and relatively short follow-up period. Therefore, to confirm the results, larger sample sizes and longer follow-ups are needed. Second, for more accurate decision-making, it is better to compare PRRT with other therapeutic methods such as chemotherapy and somatostatin analogues therapy, which was not possible in this study. Third, in addition to evaluation of treatment response with imaging modalities, it is better to measure chromogranin-A as a NETs marker.
#
Conclusion
In conclusion, since PRRT with 177Lu-DOTATATE in NETs has a favorable response rate and few adverse effects and improves the QOL, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.
#
#
Conflict of Interest
None declared.
Acknowledgments
The authors would like to thank colleagues at different units/departments for helping with data collection.
-
References
- 1 Yao JC, Hassan M, Phan A. et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26 (18) 3063-3072
- 2 Frilling A, Weber F, Saner F. et al. Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors. Surgery 2006; 140 (06) 968-976 , discussion 976–977
- 3 Kwekkeboom DJ, Teunissen JJ, Bakker WH. et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005; 23 (12) 2754-2762
- 4 Kwekkeboom DJ, Kam BL, van Essen M. et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer 2010; 17 (01) R53-R73
- 5 Gabriel M, Nilica B, Kaiser B, Virgolini IJ. Twelve-year follow-up after peptide receptor radionuclide therapy. J Nucl Med 2019; 60 (04) 524-529
- 6 Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer. Semin Nucl Med 2016; 46 (03) 225-238 PMID: 27067503
- 7 Abou Jokh Casas E, Pubul Núñez V, Anido-Herranz U. et al. Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. World J Gastroenterol 2020; 26 (13) 1513-1524
- 8 Danthala M, Kallur KG, Prashant GR, Rajkumar K, Raghavendra Rao M. (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India. Eur J Nucl Med Mol Imaging 2014; 41 (07) 1319-1326
- 9 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (02) 228-247
- 10 Bodei L, Cremonesi M, Ferrari M. et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008; 35 (10) 1847-1856
- 11 Forrer F, Uusijärvi H, Storch D, Maecke HR, Mueller-Brand J. Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med 2005; 46 (08) 1310-1316
- 12 Strosberg J, El-Haddad G, Wolin E. et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376 (02) 125-135
- 13 Kwekkeboom DJ, de Herder WW, Kam BL. et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26 (13) 2124-2130
- 14 Vorster M, Modiselle MR, Corbett CS, Lawal IO, Buscombe JR, Sathekge MM. First results and experience with PRRT in South Africa. World J Nucl Med 2018; 17 (02) 86-93
- 15 Bajetta E, Catena L, Procopio G. et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?. Cancer Chemother Pharmacol 2007; 59 (05) 637-642
- 16 Ducreux MP, Boige V, Leboulleux S. et al. A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas. Oncology 2006; 70 (02) 134-140
- 17 Ansell SM, Pitot HC, Burch PA, Kvols LK, Mahoney MR, Rubin J. A phase II study of high-dose paclitaxel in patients with advanced neuroendocrine tumors. Cancer 2001; 91 (08) 1543-1548
- 18 Khan S, Krenning EP, van Essen M, Kam BL, Teunissen JJ, Kwekkeboom DJ. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med 2011; 52 (09) 1361-1368
- 19 Marinova M, Mücke M, Fischer F. et al. Quality of life in patients with midgut NET following peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2019; 46 (11) 2252-2259
- 20 Ezziddin S, Attassi M, Yong-Hing CJ. et al. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med 2014; 55 (02) 183-190
- 21 Hörsch D, Ezziddin S, Haug A. et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: a multi-institutional registry study with prospective follow-up. Eur J Cancer 2016; 58: 41-51
Address for correspondence
Publication History
Article published online:
16 August 2022
© 2022. World Association of Radiopharmaceutical and Molecular Therapy (WARMTH). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Yao JC, Hassan M, Phan A. et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26 (18) 3063-3072
- 2 Frilling A, Weber F, Saner F. et al. Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors. Surgery 2006; 140 (06) 968-976 , discussion 976–977
- 3 Kwekkeboom DJ, Teunissen JJ, Bakker WH. et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005; 23 (12) 2754-2762
- 4 Kwekkeboom DJ, Kam BL, van Essen M. et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer 2010; 17 (01) R53-R73
- 5 Gabriel M, Nilica B, Kaiser B, Virgolini IJ. Twelve-year follow-up after peptide receptor radionuclide therapy. J Nucl Med 2019; 60 (04) 524-529
- 6 Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer. Semin Nucl Med 2016; 46 (03) 225-238 PMID: 27067503
- 7 Abou Jokh Casas E, Pubul Núñez V, Anido-Herranz U. et al. Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. World J Gastroenterol 2020; 26 (13) 1513-1524
- 8 Danthala M, Kallur KG, Prashant GR, Rajkumar K, Raghavendra Rao M. (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India. Eur J Nucl Med Mol Imaging 2014; 41 (07) 1319-1326
- 9 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (02) 228-247
- 10 Bodei L, Cremonesi M, Ferrari M. et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008; 35 (10) 1847-1856
- 11 Forrer F, Uusijärvi H, Storch D, Maecke HR, Mueller-Brand J. Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med 2005; 46 (08) 1310-1316
- 12 Strosberg J, El-Haddad G, Wolin E. et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376 (02) 125-135
- 13 Kwekkeboom DJ, de Herder WW, Kam BL. et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26 (13) 2124-2130
- 14 Vorster M, Modiselle MR, Corbett CS, Lawal IO, Buscombe JR, Sathekge MM. First results and experience with PRRT in South Africa. World J Nucl Med 2018; 17 (02) 86-93
- 15 Bajetta E, Catena L, Procopio G. et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?. Cancer Chemother Pharmacol 2007; 59 (05) 637-642
- 16 Ducreux MP, Boige V, Leboulleux S. et al. A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas. Oncology 2006; 70 (02) 134-140
- 17 Ansell SM, Pitot HC, Burch PA, Kvols LK, Mahoney MR, Rubin J. A phase II study of high-dose paclitaxel in patients with advanced neuroendocrine tumors. Cancer 2001; 91 (08) 1543-1548
- 18 Khan S, Krenning EP, van Essen M, Kam BL, Teunissen JJ, Kwekkeboom DJ. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med 2011; 52 (09) 1361-1368
- 19 Marinova M, Mücke M, Fischer F. et al. Quality of life in patients with midgut NET following peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2019; 46 (11) 2252-2259
- 20 Ezziddin S, Attassi M, Yong-Hing CJ. et al. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med 2014; 55 (02) 183-190
- 21 Hörsch D, Ezziddin S, Haug A. et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: a multi-institutional registry study with prospective follow-up. Eur J Cancer 2016; 58: 41-51



