**8.5 Cytotoxic chemotherapies**

Much of the focus on treatment over the past half century has been on the use of conventional cytotoxic agents such as streptozocin [99] and temozolomide [100]. Sunitinib and everolimus are approved for use in PNETs (**Table 11**).

## **8.6 Peptide receptor radionuclide therapy (PRRT)**

Majority of neuroendocrine tumors show increased level expression of somatostatin receptors (SSRs) 2 and 5 on the tumor cell surface and it forms the basis


#### **Table 12.**

*Various retrospective studies have been conducted on PRRT.*

of not only functional imaging but also tumor directed therapies like somatostatin analogues [111]. Beyond somatostatin analogues, PRRT, which is described as peptide receptor radioligand therapy or targeted radiotherapy using radiolabeled somatostatin analogs is emerging as an effective treatment modality in metastatic, well-differentiated, grade 1 and 2 GEP-NET [112]. Yttrium, a high-energy β particle emitter and Lutetium, a β and γ particle emitter with lower tissue penetration are most commonly studied radioligands [113] (**Table 12**).

131I-metaiodobenzylguanidine (131I-MIBG) therapy has shown promise in in MIBG positive metastatic neuroendocrine tumors, in addition to radiolabeled somatostatin analogs [121].

The toxicities associated with PRRT include myelosuppression and nephrotoxicity, both of which are reversible, acute pain due to radiation edema and nausea and vomiting, associated with the use of amino acids to reduce the risk of nephrotoxicity and very rarely myelodysplastic syndrome.

## **9. Prognosis**

Depends upon Metastatic spread, large tumor size, and hormonal hypersecretion as well as gender, age, and histopathological high-grade, Ki67 (**Table 13**).


#### **Table 13.**

*5-year relative survival rates for pancreatic NET [8].*
