Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Multidisciplinary Management
3.2. Baseline Prognostic Characterization
3.3. Watchful Waiting
3.4. Follow-Up of Radically Resected NENs
3.5. Therapeutic Strategies
3.6. Informed Consent for RLT
3.7. Dosimetry of RLT
3.8. Management of Patients with Comorbidities
3.9. Management of Therapy with SSA during RLT
3.10. Evaluation of Tumor Response (Morphological vs. Functional and Clinical) after RLT
3.11. Follow-Up after RLT
3.12. Off-Label Use of RLT
3.13. Approach to Patients with Bone Metastases
3.14. Role of Patient-Reported Outcomes in Management
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Statement | |
---|---|
1. Multidisciplinary discussion | A network among “tumor boards” working on NEN patients is advisable NEN-dedicated multidisciplinary teams should adopt the same main criteria independently of local experience. |
2. Initial prognostic characterization | Initial prognostic characterization should be based on clinical information (functioning/non-functioning, performance status, comorbidity), histopathology (differentiation and grading), and morphological and functional imaging. There is no recommended definition of disease at high risk after radical surgery across NEN primary diseases. |
3. Watchful waiting | A watchful waiting strategy is generally not recommended in locally advanced/metastatic patients. |
4. Follow-up of radically resected NENs | Follow-up should be patient-tailored in patients with NEN after radical surgery and should include a panel of conventional tests, including circulating markers, plus a list of optional instrumental tests, chosen based on the characteristics of the tumor and patient. A patient-tailored long term follow-up strategy is still lacking and needs to be defined. The timing should be modulated on the basis of prognostic parameters, while strongly taking into account safety issues related to potentially invasive exams. |
5. Therapeutic strategies | There is poor evidence regarding a specific sequence or integration of various treatments in NENs. The therapeutic strategy with sequence and type of treatments should be decided in a tumor board considering the characteristics of the patient, literature data, and regulatory aspects. |
6. Informed consent for RLT | A standard informed consent form for RLT should be used. Informed consent should include specific information about the purpose, mode of execution, risk-benefit balance, and potential for early and late side effects, allowing optimization of communication about the risks, benefits, and possible alternative options, to provide the same level of information within all institutions. |
7. Dosimetry of RLT (for therapy) | Dosimetry evaluation should be recommended to prevent potential risks to bone marrow and kidney function to provide data to clinicians, especially in patients with long survival expectancy. |
8. Management of patients with comorbidities | Comorbidities not representing an absolute contraindication to RLT (i.e., severe hypertension, brittle diabetes, functioning tumors, concomitant meningioma, etc.) should require specific protocols. |
9. Management of therapy with SSA during RLT | SSA therapy should be continued during the entire course of RLT. Dosage may be adjusted in case of functioning tumors. |
10. Evaluation of response (morphological vs. functional and clinical) after RLT | Assessment of tumor response after RLT should carefully consider both morphological and functional imaging. However, the timing of imaging should be correlated with characteristics of the individual tumor. |
11. Follow-up after RLT | Follow-up should be patient-tailored and include morphological (CT and/or MRI) and/or functional (PET/CT with radiolabeled somatostatin analogs and/or FDG) imaging and biomarkers, chosen based on the characteristics of the tumor. The timing should be modulated based on prognostic parameters, while strongly considering safety issues. It is suggested to intercalate morphological and functional imaging to reduce the patient’s irradiation dose given the very long follow-up. |
12. Off-label use of RLT | Alternative schedules, means of administration, indications other than approved, and rechallenge should be limited to specific clinical studies. |
13. Approach to patients with bone metastases | Bone involvement with appropriate imaging techniques must be carefully assessed in patients with a metastatic NEN to identify those at risk of skeletal-related events. |
14. Role of PROs in management | Patient-reported outcomes (PROs) should be considered as a critical endpoint of benefit. Thus, guidelines should consider PROs, pointing out that their lack may have a bearing on the ultimate recommendation. |
Study | Number of Patients | Initial RLT | Re-Treatment RLT | PFS (Months) | 95% CI |
---|---|---|---|---|---|
Sabet et al., 2014 [72] | 33 | 177Lu-DOTATATE | 177Lu-DOTATATE | 13.0 | 9.0–18.0 |
Severi et al., 2015 [70] | 26 | 90Y-DOTATOC | 177Lu-DOTATATE | 9.0 | 5.0–17.0 |
Vaughan et al., 2018 [69] | 47 | 177Lu-DOTATATE or 90Y-DOTATOC | 177Lu-DOTATATE or 90Y-DOTATOC | 17.5 | 11.0–23.8 |
Baum et al. [71] | 470 | 177Lu-DOTATATE or 90Y-DOTATOC | 177Lu-DOTATATE or 90Y-DOTATOC | 11.0 | 9.4–12.5 |
Van der Zwal et al., 2019 [68] | 168 | 177Lu-DOTATATE | 177Lu-DOTATATE | 14.6 | 12.4–19.6 |
Rudisile S et al., 2019 [67] | 32 | 177Lu-DOTATATE | 177Lu-DOTATATE | 6.0 | 0.0–16.00 |
Combination Partner | ORR (%) | OS (Months) | PFS (Months) | SAE (%) | Reference |
---|---|---|---|---|---|
SSA | 37 | NR | 48 | 3% hepatoxicity | [52,53,65] |
Capecitabine | 24–30 | NR | 31 | 15% hematotoxicity | [87,88] |
CAPTEM | 53–70 | NR | 22–48 | 6% hematotoxicity | [76,77,78] |
5-FU | 25 | NR | - | - | [89] |
Everolimus | 44 | NR | 63 at 2 years | 100% hematotoxicity | [79] |
EBRT | 0 | NR | 108 | - | [90] |
Liver Embolization | |||||
(90Y) | 16 | 42–68 | - | 50% liver enzyme elevation | [83,84,91] |
(166Ho) | 43 | - | 10% abdominal pain | ||
Dual RLT (177Lu/90Y) | 42 | 66–127 | - | 2% MDS | [63,85,86] |
(177Lu/225Ac) | - | 7% hematotoxicity | |||
MIBG (131I) | 0 | - | 33% thrombocytopenia | [92] |
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Bartolomei, M.; Berruti, A.; Falconi, M.; Fazio, N.; Ferone, D.; Lastoria, S.; Pappagallo, G.; Seregni, E.; Versari, A. Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise. Cancers 2022, 14, 2501. https://doi.org/10.3390/cancers14102501
Bartolomei M, Berruti A, Falconi M, Fazio N, Ferone D, Lastoria S, Pappagallo G, Seregni E, Versari A. Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise. Cancers. 2022; 14(10):2501. https://doi.org/10.3390/cancers14102501
Chicago/Turabian StyleBartolomei, Mirco, Alfredo Berruti, Massimo Falconi, Nicola Fazio, Diego Ferone, Secondo Lastoria, Giovanni Pappagallo, Ettore Seregni, and Annibale Versari. 2022. "Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise" Cancers 14, no. 10: 2501. https://doi.org/10.3390/cancers14102501