Current Status of Gastroenteropancreatic Tumor Management

September 1, 2002
Irvin M. Modlin, MD, PhD

Oncology, ONCOLOGY Vol 16 No 9, Volume 16, Issue 9

Gastroenteropancreatic tumors, although relatively rare, present management problems that may last many years, in comparison with the usually more aggressive adenocarcinomas whose management may encompass a far briefer span of time. In general, 50% of such tumors are insulinomas, while gastrinomas comprise 25%, and nonfunctional tumors 20% VIPomas and glucagonomas are the predominant lesions of the remaining 5%. Clinical diagnosis is usually made on the presence of the classical symptom complex. In uncertain circumstances or covert presentations, the critical diagnostic biochemical test is plasma chromogranin A as well as measurement of the specific peptide.

Gastroenteropancreatic tumors, although relatively rare,present management problems that may last many years, in comparison with theusually more aggressive adenocarcinomas whose management may encompass a farbriefer span of time. In general, 50% of such tumors are insulinomas, whilegastrinomas comprise 25%, and nonfunctional tumors 20% VIPomas and glucagonomas are the predominant lesions of the remaining 5%.Clinical diagnosis is usually made on the presence of the classical symptomcomplex. In uncertain circumstances or covert presentations, the criticaldiagnostic biochemical test is plasma chromogranin A as well as measurement ofthe specific peptide.

Localization of the lesion is best undertaken by111In-pentetreotide imaging (OctreoScan, Mallinkrodt Imaging), althoughinsulinomas may occasionally not be identifiable in 111In-pentetreotide becausethey are somewhat less likely to express somatostatin receptors. Intraoperativelocalization of impalpable lesions still remains a problem because the adequategamma probe collimators are unavailable. For solitary lesions, surgicalresection is still the ideal therapy. The majority of lesions, however, havespread, and in such instances, alternative therapy is required. This mayinclude, but is not limited to, resection, cytoreduction, hepatictransplantation, chemotherapy, chemoembolization, biotherapy, and symptomatictreatment with octreotide LAR depot (Sandostatin LAR Depot).

Formal liver resection appears to be of marginal benefitunless lesions are lobe-specific, and outcome usually reflects surgicaltechnique rather than the nature of the tumor itself. Hepatic cytoreductionincluding cryoablation, and more recently thermoablation, has gainedprominence.[1-3] Current data suggest no major advantage to this technique, andthermoablation poses some danger if structures such as bile ducts or majorvessels are compromised. Chemoembolization is significantly less invasive, canbe repeated, and appears as efficacious although no rigorous comparisons areavailable.[4] Liver transplantation has been of marginal benefit in highlyselected situations, but inadequate data exist to support its formalintroduction into a therapeutic strategy.[5]

A wide variety of cytotoxics have been utilized withextremely modest outcome, and all are associated with significant side effectsthat seriously decrease quality of life.[4,6] More recent agents studied includeetoposide, paclitaxel, and gemcitabine (Gemzar), although insufficient data areavailable to determine their final utility. Octreotide LAR depot currentlyappears to be among the most promising therapeutic strategies. It may also beadvantageously used alone or in combination with surgery or chemoembolization.[7]Of note is the fact that octreotide LAR depot may be useful in the management ofgastrinoma patients and may be capable of inhibiting the development of gastriccarcinoids in individuals with the MEN-1 syndrome.[8,9]

Biotherapy using interferon may be useful in unresponsivepatients, although its toxicity remains a concern. Although interferon hassignificantly more side effects than octreotide LAR depot, a combination therapyof the two agents has yielded early promising data. Octreotide LAR depot is alsoan important adjunct to surgery in that it decreases postoperative biliary andpancreatic complications and reduces symptoms. Of particular interest is the useof octreotide-associated radioisotopic therapy.[10,11] The initial use of indiumhas been promising, and although yttrium appears to be more effective, it hasbeen more often associated with renal problems. Current studies with thelutetium isotope are considered even more promising, but insufficient experiencerenders a final conclusion premature at this time.

Overall, the best gastroenteropancreatic management strategy involves tumorcytoreduction followed by symptom relief using octreotide LAR depot and specifictumor ablation, using the least invasive technique possible.

References:

1. Chung MH, Pisegna J, Spirt M, et al: Hepatic cytoreductionfollowed by a novel long-acting somatostatin analog: A paradigm for intractableneuroendocrine tumors metastatic to the liver. Surgery 130:954-962, 2001.

2. Siperstein AE, Rogers SJ, Hansen PD, et al: Laparoscopicthermal ablation of hepatic neuroendocrine tumor metastases. Surgery122:1147-1154, 1997; discussion 1154-1155.

3. Bilchik AJ, Sarantou T, Foshag LJ, et al: Cryosurgicalpalliation of metastatic neuroendocrine tumors resistant to conventionaltherapy. Surgery 122:1040-1047, 1997.

4. Faiss S, Scherubl H, Riecken EO, et al: Drug therapy inmetastatic neuroendocrine tumors of the gastroenteropancreatic system. RecentResults Cancer Res 142:193-207, 1996.

5. Dousset B, Houssin D, Soubrane O, et al: Metastaticendocrine tumors: is there a place for liver transplantation? Liver Transpl Surg1:111-117, 1995.

6. Schott M, Scherbaum WA, Feldkamp J: Drug therapy ofendocrine neoplasms. Part II: Malignant gastrinomas, insulinomas, glucagonomas,carcinoids and other tumors. Med Klin 95:81-84, 2000.

7. Claure RE, Drover DD, Haddow GR, et al: Orthotopic livertransplantation for carcinoid tumour metastatic to the liver: Anestheticmanagement. Can J Anaesth 47:334-337, 2000.

8. Angeletti S, Corleto VD, Schillaci O, et al: Single doseof octreotide stabilize metastatic gastro-entero-pancreatic endocrine tumours.Ital J Gastroenterol Hepatol 31:23-27, 1999.

9. Shojamanesh H, Gibril F, Louie A, et al: Prospective studyof the antitumor efficacy of long-term octreotide treatment in patients withprogressive metastatic gastrinoma. Cancer 94:331-343, 2002.

10. Waldherr C, Pless M, Maecke HR, et al: Tumor response andclincial benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J NuclMed 43:610-616, 2002.

11. Waldherr C, Pless M, Maecke HR, et al: The clinical value of[90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment ofneuroendocrine tumours: A clinical phase II study. Ann Oncol 12:941-945, 2001.