High risk of myelodysplastic syndrome and acute myeloid leukemia after 177Lu-octreotate PRRT in NET patients heavily pretreated with alkylating chemotherapy

in Endocrine-Related Cancer

Dear Editor,

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare but seen with increasing incidence. Current medical options for the management of nonresectable GEP-NETs include somatostatin analogs, targeted therapies, chemotherapies, and radiological and radionuclide therapies.

Peptide receptor radionuclide therapy (PRRT) is a modern therapeutic approach using radionuclide combined with somatostatin analog peptide whose affinity with somatostatin receptors (SSRs) allows targeting disseminated tumor disease. According to the ENETS guidelines, PRRT is indicated for patients with nonresectable, progressive, grade 1 or 2 GEP-NETs with high uptake on SSR scintigraphy (Pavel et al. 2012). In a large retrospective study of 310 GEP-NETs, 46% had tumor response with 177Lu-octreotate therapy (Kwekkeboom et al. 2008) with good progression-free and overall survival. In addition, first results of the prospective randomized NETTER-1 trial comparing 177Lu-octreotate PRRT and octreotate LAR 60 mg have recently showed a median progression-free survival not reached at 25 and 8.4 months, respectively (Strosberg et al. 2015). PRRT is generally well tolerated, short-term side effects include mild fatigue, hematological and renal toxicity. Regarding longer term hematological side effects, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) was reported in 0.2–5.4% of the patients in large series (Kwekkeboom et al. 2008, Imhof et al. 2011, Sabet et al. 2013, Kesavan et al. 2014, Bodei et al. 2015). Here, we report a much higher occurrence of MDS or AML in a single-center experience in patients treated with 177Lutetium-octreotate at late disease stage, after alkylating-based chemotherapy.

Our study included all 20 consecutive patients treated with 177Lutetium-octreotate PRRT between January 2004 and January 2011 at our center. All patients had progressive metastatic GEP-NETs. PRRT was performed in the Department of Nuclear Medicine of the Erasmus Medical Center of Rotterdam (Rotterdam, the Netherlands) due to the unavailability of PRRT in France. This unavailability explained why relatively few patients received this treatment in our center, and generally after first-line chemotherapy. As defined in previous reports from Rotterdam’s team (Kwekkeboom et al. 2001), the radiochemical purity of 177Lu-octreotate was 88%, and then reached yield after addition of DTPA (diethylenetriaminepentaacetic acid) approached 99.99%. Patient medical records were reviewed to collect relevant data on demographics, tumor characteristics, surgery, treatments, and tolerability. A Student’s t-test was used to evaluate prognostic variables for the occurrence of therapy-related MDS or AML (t-MDS/AML).

Baseline clinical characteristics of the 20 patients are described in Table 1. Median follow-up from PRRT was 3.1 years (range 0.3–8.9). Treatment with 177Lu-PRRT consisted of four cycles of 7.5 GBq; 16 patients received the four full dose cycles (one of them received two additional cycles) and 4 received lower dose due to early hematological toxicity (one of them one cycle).

Table 1

Patients’ characteristics

Patient, age at diagnosisType of tumor, ENETS grade (G1/G2/G3)Treatments before PRRT: time interval from diagnosis, type of treatment (number of cycles), and responseHematological toxicities of each treatmentNumber of CT cycles and the time from the first cycle to PRRT (months)Bone metastases (localization)Bone metastases (metabolic burden)*PRRT: number of cycles, total dose (Gbq), and tumor response (CR/PR/SD/PD)AHT of PRRT, duration (months)DHT
N° 1, 45Pancreatic NET, G1S at 2 months: left pancreatectomy with complete resectionNone25, 121 monthsLeft ischial tuberosity and occipital part of the skullG24, 29.9, PRNoneYes
CT at 54 months: streptozotocin+adriamycin+interferon (9), PRG2 NE, G1 TH
TACE at 75 months: streptozotocin (3), SDNone
S at 115 months: liver transplantation None
CT at 116 months (adjuvant): 5-fluorouracile+streptozotocin (4), SDNone
RT at 160 months (hip and skull bones): clinical responseNone
CT at 163 months: 5-fluorouracil+streptozotocin (4), PDNone
CT at 170 months: FOLFIRI regimen (5), SDNone
N° 2, 54Pancreatic NET, G1CT at 4 months: 5-fluorouracil+streptozotocin (8), SDNone12, 47 monthsNoneG04, 29.9, CRG3 TH, G1 AN, 12 monthsYes
CT at 54 months: adriamycin+dacarbazine (4), SDNone
N° 3, 66Metastatic NET with unknown primary, G1CT at 6 months: 5-fluorouracil+streptozotocin (6), SDNone6, 15 monthsDisseminated metastases of the spine, sternum, ribs, and bony pelvisG44, 26.5, PRG3 NE, G4 TH, G1 AN, 12 monthsYes
N° 4, 50Gastric NET, G2TACE at 4 months: streptozotocin (4), PRNone12, 71 monthsThoracic vertebrae (second and seventh)G04, 30, CRG3 NE, G3 AN, G3 TH, 54 monthsYes
CT at 34 months: 5-fluorouracil+dacarbazine (4), SDNone
S at 48 months: liver transplantationNone
CT at 50 months (adjuvant): 5-fluorouracil+streptozotocin (4), SDNone
N° 5, 37Rectal NET, G2TACE at 2 months: streptozotocin (1), SDNone1, 6 monthsCervical vertebrae, left iliac wingG14, 25.75, PR G2 AN, G3 TH, G1 NE, 18 monthsNo
N° 6, 49Pancreatic NET, G2CT at 3 months: FOLFIRI regimen (10), PRNone19, 32 monthsTwo lumbar vertebrae, sacrumG21, 7.5, SDG4 AN, G4 TH, G4 NE, 5 monthsNo
CT at 22 months: etoposid+cisplatin (4), PDNone
CT at 25 months: sunitinib (5), SDG2 NE
N° 7, 68 Rectal NET, G2TACE at 3 months: streptozotocin (3), SDNone3, 11 monthsDisseminated metastases of the spine and ribsG36, 45, PRNoneNo
N° 8, 69Rectal NET, G2S at 1 month: rectal resection with coloanal anastomosisNone9, 21 monthsDisseminated metastases of the spine and ribsG34, 30, PRNoneNo
CT at 70 months: 5-fluorouracil+dacarbazine (8), SDNone
TACE at 83 months: Streptozotocin (1), PRNone
N° 9, 59Ileum NET, G1S at 1 month: right ileocolectomyNone4, 21 monthsNoneG04, 30, SDNoneNo
CT at 43 months: 5-fluorouracil+streptozotocin (4), PDNone
N° 10, 64Ileum NET, G1S at 1 month: segmentary resection of the ileum tumorNone0NoneG04, 30, PDNoneNo
N° 11, 61Pancreatic NET, G1None0NoneG04, 30, CRNoneNo
N° 12, 71 Pancreatic NETNone0NoneG04, 30, PRNoneNo
N° 13, 46Pancreatic NET, G2S at 2 months: cephalic duodenopancreatectomyNone0NoneG04, 30, PRNoneNo
N°14, 53Ileum NET, G2S at 1 month: segmentary resection of the ileum tumor None0Left scapula and right hipG24, 30, PRNoneNo
N° 15, 47Ileum NET, G1CT at 12 months: 5-fluorouracil+streptozotocin (2), SDNone2, 9 monthsNoneG04, 30, PRNoneNo
N° 16, 55 Colon NET, G1S at 1 month: resection of the primary tumorNone0One thoracic vertebraeG14, 30, CRNoneNo
N° 17, 26Duodenal NET, G2S at 1 month: cephalic duodenopancreatectomyNone8, 12 monthsDisseminated metastases of the spineG34, 30, SDNoneNo
CT at 8 months: adriamycin+streptozotocin (4), PDNone
CT at 15 months: FOLFIRI regimen+bevacizumab (4), PDNone
N° 18, 16Pancreatic NET, G1S at 1 month: left pancreatectomyNone6, 131 monthsSacrum and right hipG14, 30, PRNoneNo
S at 8 months: right hepatectomyNone
CT at 10 months (adjuvant): adriamycin+streptozotocin (6), SDNone
S at 51 months: liver resectionNone
N° 19, 31Anus NET, G2S at 1 month: abdo­minoperineal resectionNone4, 12 monthsNoneG04, 30, PRNoneNo
CT at 121 months: 5-fluorouracil+dacarbazine (4), PDNone
N° 20, 64Pancreatic NET, G2CT at 2 months: etoposid+cisplatin (6), SDG3 NE19, 18 monthsNoneG03, 22.5, PDNoneNo
CT at 10 months: FOLFIRI regimen (13), PRG2 NE

Abbreviations: AHT, acute hematological toxicity; AN, anemia; CR, complete response; CT, chemotherapy; DHT, delayed hematological toxicity; FOLFIRI, 5-fluorouracil+leucovorin+irinotecan; G1, grade 1; G2, grade 2; G3, grade 3; NE, neutropenia; NET, neuroendocrine tumor; PD, progressive disease; PR, partial response; PRRT, peptide receptor radionuclide therapy; RT, radiotherapy; S, surgery; SD, stable disease; TACE, tranzarterial chemoembolisation; TH, thrombopenia.

Tumor aggressiveness was evaluated according to the ENETS grade (Ki-67 proliferative index): G1, tumor with Ki-67 from 0 to 2%; G2, Ki-67 from 3 to 20%; G3, Ki-67 superior than 20%.

Bone involvement is graded according to the results of the OctreoScan. G0, no metastases; G1, 1–5 bone uptakes; G2, 6–10 bone uptakes; G3, more than 10 bone uptakes with disseminated spine involvement; G4, G3 and bone marrow involvement.

PPRT induced short-term thrombocytopenia, neutropenia, and anemia in 25, 15, and 10%, respectively. However, four (20%) patients developed delayed hematological toxicity with MDS or AML, diagnosed 30, 31, 54, and 70 months, respectively, after PRRT. All patients, before PRRT, had received prior chemotherapy containing an alkylating agent for 20, 12, 6, and 12 cycles, respectively. Three of the four patients (75%) had developed early hematological toxicity (grade 3–4 thrombocytopenia) during PRRT. At the time of MDS/AML diagnosis, the underlying tumor was active in three patients, and three had bone metastases. Three patients had MDS according to the WHO criteria (Della Porta et al. 2015), including refractory cytopenia with multilineage dysplasia in two cases, and refractory anemia with excess blasts type 2 in one case; the last patient had the WHO-defined AML (with, however, only 21% marrow blasts, i.e., partial blast infiltration very close to MDS diagnostic criteria). Karyotype showed monosomy 7 in three cases, with or without other chromosomal deletions, especially monosomy 5, and was not performed in the last patient.

Compared to other patients, the four patients who developed MDS or AML had received, prior to PPRT, more cycles of chemotherapy (mean: 13.8 vs 4.7, P=0.001) and more cycles of alkylating agents (mean: 12.5 vs 3.75, P=0.001), and had more frequently experienced early hematological toxicity (75 vs 13%, P=0.03) (Table 2). Two of the patients received supportive care only and two received azacitidine. Survival was 6, 2, 2, and 54 months, respectively. During the study period (2004–2011), 95 additional patients with GEP-NETs were treated with alkylating-based chemotherapy without subsequent PPRT at our center. Only one (1%) developed MDS.

Table 2

Prognostic factors of occurrence of MDS and AML in patients treated with PRRT

Patients who developed MDS/AML,n (%)Other patients,n (%)P-value
Total4 (20)16 (80)
Gender (F/M)3 (75)4 (25)0.16
Median age at diagnosis (years) (range)53.8 (45–66)51 (16–71)0.63
Mean number of cycles of previous chemotherapy (range) 13.8 (6–25)4.7 (0–19)0.001
Alkylating-based chemotherapy mean number of cycles (range)12.5 (6–20)3.75 (0–9)0.001
Bone metastases before PRRT3 (75)8 (50)0.39
Immunosuppressive treatment2 (50)0 (0)0.006
Mean dose of PRRT (GBq)2930.50.94
Mean number of cycles of PRRT440.97
Early hematological toxicity grade 3–43 (75)2 (13)0.03
Number of deaths4 (100)4 (29)
Cause of deaths: underlying tumor0 (0)4 (29)
MDS/AML4 (100)0 (0)

Abbreviations: AML, acute myeloid leukemia; F, female; M, male; MDS, myelodysplastic syndrome; PRRT, peptide receptor radionuclide therapy. Bold indicates significant values.

The high rate of MDS or AML (20%) we report in this limited series of 20 nonresectable NETs treated with 177Lu-PPRT after heavy pretreatment with chemotherapy is therefore much higher than in large published series of PRRT (Kwekkeboom et al. 2008, Imhof et al. 2011, Sabet et al. 2013, Kesavan et al. 2014, Bodei et al. 2015). This higher rate may be due to the fact that most of our patients had received chemotherapy and alkylating agents prior to PPRT, compared to previously published series of PPRT in metastatic NETs, where less than one-third of the patients had received chemotherapy before PRRT. Indeed, in our series, patients who developed MDS or AML had received more chemotherapy and more alkylating agents than other patients (P=0.001). Reasons why patients had received more chemotherapy prior to PRRT in our series probably include the fact that PPRT was until recently unavailable in France, requiring a partnership with centers abroad. Thus, PRRT was not a frontline therapy for metastatic GEP-NETs in France, where patients first received conventional systemic chemotherapy, targeted therapies, and transarterial chemoembolization.

In another study, about 65 patients receiving 177Lu-octreoate combined with capecitabine (n=28) or capecitabine and temozolomide (n=37), no MDS/AML was reported in the former group, but two (5.4%) cases were reported in the latter group (Kesavan et al. 2014). Temozolomide is an alkylating agent, further supporting our assumption that the risk of MDS/AML, very low with 177Lu-octreotate PRRT alone and possibly 177Lu-octreotate PRRT combined with nonalkylating chemotherapy, may be higher when 177Lu-octreotate PRRT is combined with alkylating agents.

The duration of follow-up in our series (3.1 years) cannot explain differences of MDS/AML rates compared with other studies: indeed, although three studies had shorter follow-up (1.6, 1.9, and 2.6 years) (Kwekkeboom et al. 2008, Imhof et al. 2011, Sabet et al. 2013), two other studies had similar or longer follow-up (3.0 and 4.2 years) (Kesavan et al. 2014, Bodei et al. 2015). Because of the known leukemogenic role of alkylating agents, we cannot exclude that MDS/AML in our series was a direct consequence of prior chemotherapy. Indeed, latencies before the first cycle of chemotherapy, and the diagnosis of the hematological malignancies were 12.6, 9.8, 3.8, and 10.4 years, respectively. It is well known that the maximum risk of MDS/AML ranges from 3 to 10 years after the myelotoxic treatment. However, the risk of MDS/AML in GEP-NETs treated with alkylating-based chemotherapy alone may be relatively small: during the study period (2004–2011), 95 additional GEP-NETs patients were treated with this approach without subsequent PPRT at our center, and only one (1%) developed MDS.

Other risk factors for MDS/AML, in our study, included early hematological toxicity after PPRT, observed in 3 of the 4 patients who subsequently developed MDS/AML, compared to only 2 of the 16 patients who did not develop MDS/AML. Platelet toxicity was also significantly related to development of secondary MDS or AML in a previous study (Bodei et al. 2015): close hematological monitoring therefore seems recommended in patients experiencing early hematological toxicity after PRRT. MDS and AML cases observed in this series were typical of those observed after alkylating agents or purine analogs. Indeed, they all had partial marrow blast infiltration (maximum 21%) and the three karyotyped patients had monosomy 7.

The impact of bone metastases in the occurrence of MDS/AML remained unclear, and it had no significant impact in our study (P=0.39). In a pilot study in 11patients with GEP-NETs and florid bone metastases (with advanced widespread metastatic bone disease) receiving PRRT (Sabet et al. 2014), a higher than usual rate of hematological toxicity was reported, with grade 3–4 reversible hematotoxicity of in 35% of the patients, but delayed hematological toxicity was not reported. In other studies, no statistical correlation between bone metastases after PRRT and the recovery of acute hematotoxicity or the subsequent occurrence of MDS/AML was seen (Sabet et al. 2013, Bergsma et al. 2015).

In conclusion, our study, although based on a limited number of patients, suggests a high occurrence of MDS/AML in patients with GEP-NETs treated with PRRT after previous chemotherapy with alkylating agents. The indication of PRRT should take into consideration the importance of previous chemotherapy. Exposure to alkylating agents should be avoided in patients with low-grade NET, who have a long survival expectancy and a significant likelihood of benefiting from PRRT, because it may compromise the safety and future applicability of this more effective therapy. Regular and prolonged monitoring of blood counts is mandatory, especially in patients experiencing early hematological toxicity after PRRT.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

References

  • BergsmaHKonijnenbergMWKamBLTeunissenJJKooijPPde HerderWWFranssenGJvan EijckCHKrenningEPKwekkeboomDJ2015Subacute haematotoxicity after PRRT with Lu-DOTA-octreotate: prognostic factors, incidence and course. European Journal of Nuclear Medicine and Molecular Imaging43453463. (doi:10.1007/s00259-015-3193-4)

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  • BodeiLKiddMPaganelliGGranaCMDrozdovICremonesiMLepenskyCKwekkeboomDJBaumRPKrenningEP .2015Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. European Journal of Nuclear Medicine and Molecular Imaging42519. (doi:10.1007/s00259-014-2893-5)

    • Search Google Scholar
    • Export Citation
  • Della PortaMGTuechlerHMalcovatiLSchanzJSanzGGarcia-ManeroGSoleFBennettJMBowenDFenauxP .2015Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia2915021513. (doi:10.1038/leu.2015.55)

    • Search Google Scholar
    • Export Citation
  • ImhofABrunnerPMarincekNBrielMSchindlerCRaschHMackeHRRochlitzCMuller-BrandJWalterMA2011Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. Journal of Clinical Oncology2924162423. (doi:10.1200/JCO.2010.33.7873)

    • Search Google Scholar
    • Export Citation
  • KesavanMClaringboldPGTurnerJH2014Hematological toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up. Neuroendocrinology99108117. (doi:10.1159/000362558)

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    • Export Citation
  • KwekkeboomDJBakkerWHKooijPPKonijnenbergMWSrinivasanAErionJLSchmidtMABugajJLde JongMKrenningEP2001[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. European Journal of Nuclear Medicine and Molecular Imaging2813191325. (doi:10.1007/s002590100574)

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  • KwekkeboomDJde HerderWWKamBLvan EijckCHvan EssenMKooijPPFeeldersRAvan AkenMOKrenningEP2008Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. Journal of Clinical Oncology2621242130. (doi:10.1200/JCO.2007.15.2553)

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    • Export Citation
  • PavelMBaudinECouvelardAKrenningEObergKSteinmullerTAnlaufMWiedenmannBSalazarR & Barcelona Consensus Conference participants2012ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology95157176. (doi:10.1159/000335597)

    • Search Google Scholar
    • Export Citation
  • SabetAEzziddinKPapeUFAhmadzadehfarHMayerKPoppelTGuhlkeSBiersackHJEzziddinS2013Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate. Journal of Nuclear Medicine5418571861. (doi:10.2967/jnumed.112.119347)

    • Search Google Scholar
    • Export Citation
  • SabetAKhalafFYong-HingCJSabetAHaslerudTAhmadzadehfarHGuhlkeSGrunwaldFBiersackHJEzziddinS2014Can peptide receptor radionuclide therapy be safely applied in florid bone metastases? A pilot analysis of late stage osseous involvement. Nuklearmedizin535459. (doi:10.3413/Nukmed-0614-13-08)

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    • Export Citation
  • StrosbergJWolinEChasenBKulkeMBushnellDCaplinMBaumRPMittraEHobdayTHendifarA .2015LATE BREAKING ABSTRACT: 177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: Results of the phase III NETTER-1 trial.European Journal of Cancer51 (S3) S710.

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References

  • BergsmaHKonijnenbergMWKamBLTeunissenJJKooijPPde HerderWWFranssenGJvan EijckCHKrenningEPKwekkeboomDJ2015Subacute haematotoxicity after PRRT with Lu-DOTA-octreotate: prognostic factors, incidence and course. European Journal of Nuclear Medicine and Molecular Imaging43453463. (doi:10.1007/s00259-015-3193-4)

    • Search Google Scholar
    • Export Citation
  • BodeiLKiddMPaganelliGGranaCMDrozdovICremonesiMLepenskyCKwekkeboomDJBaumRPKrenningEP .2015Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. European Journal of Nuclear Medicine and Molecular Imaging42519. (doi:10.1007/s00259-014-2893-5)

    • Search Google Scholar
    • Export Citation
  • Della PortaMGTuechlerHMalcovatiLSchanzJSanzGGarcia-ManeroGSoleFBennettJMBowenDFenauxP .2015Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia2915021513. (doi:10.1038/leu.2015.55)

    • Search Google Scholar
    • Export Citation
  • ImhofABrunnerPMarincekNBrielMSchindlerCRaschHMackeHRRochlitzCMuller-BrandJWalterMA2011Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. Journal of Clinical Oncology2924162423. (doi:10.1200/JCO.2010.33.7873)

    • Search Google Scholar
    • Export Citation
  • KesavanMClaringboldPGTurnerJH2014Hematological toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up. Neuroendocrinology99108117. (doi:10.1159/000362558)

    • Search Google Scholar
    • Export Citation
  • KwekkeboomDJBakkerWHKooijPPKonijnenbergMWSrinivasanAErionJLSchmidtMABugajJLde JongMKrenningEP2001[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. European Journal of Nuclear Medicine and Molecular Imaging2813191325. (doi:10.1007/s002590100574)

    • Search Google Scholar
    • Export Citation
  • KwekkeboomDJde HerderWWKamBLvan EijckCHvan EssenMKooijPPFeeldersRAvan AkenMOKrenningEP2008Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. Journal of Clinical Oncology2621242130. (doi:10.1200/JCO.2007.15.2553)

    • Search Google Scholar
    • Export Citation
  • PavelMBaudinECouvelardAKrenningEObergKSteinmullerTAnlaufMWiedenmannBSalazarR & Barcelona Consensus Conference participants2012ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology95157176. (doi:10.1159/000335597)

    • Search Google Scholar
    • Export Citation
  • SabetAEzziddinKPapeUFAhmadzadehfarHMayerKPoppelTGuhlkeSBiersackHJEzziddinS2013Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate. Journal of Nuclear Medicine5418571861. (doi:10.2967/jnumed.112.119347)

    • Search Google Scholar
    • Export Citation
  • SabetAKhalafFYong-HingCJSabetAHaslerudTAhmadzadehfarHGuhlkeSGrunwaldFBiersackHJEzziddinS2014Can peptide receptor radionuclide therapy be safely applied in florid bone metastases? A pilot analysis of late stage osseous involvement. Nuklearmedizin535459. (doi:10.3413/Nukmed-0614-13-08)

    • Search Google Scholar
    • Export Citation
  • StrosbergJWolinEChasenBKulkeMBushnellDCaplinMBaumRPMittraEHobdayTHendifarA .2015LATE BREAKING ABSTRACT: 177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: Results of the phase III NETTER-1 trial.European Journal of Cancer51 (S3) S710.

    • Search Google Scholar
    • Export Citation

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