Response after neoadjuvant chemotherapy for pancreatic neuroendocrine tumors

BS Makayla A. Slaby,; BA Kaitlyn F. Nimmer,; MD Naveen M. Kulkarni,; Giacinto, DO Brian J. Di; MD Tamara Giorgadze,; MD Kathleen K. Christians,; MD Michael Holt,; MD Douglas B. Evans,; MD Alexandria T. Phan,; MD Callisia N. Clarke; MS

doi:10.1530/endoabs.108.C47

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Endocrine Abstracts (2024) 108 C47 | DOI: 10.1530/endoabs.108.C47

NANETS2024 17th Annual Multidisciplinary NET Medical Symposium NANETS 2024 Clinical - Surgery/Applied Pathology (9 abstracts)

Response after neoadjuvant chemotherapy for pancreatic neuroendocrine tumors

Makayla A. Slaby, BS¹, Kaitlyn F. Nimmer, BA¹, Naveen M. Kulkarni, MD², Brian J. Di Giacinto, DO², Tamara Giorgadze, MD³, Kathleen K. Christians, MD³, Michael Holt, MD², Douglas B. Evans, MD¹, Alexandria T. Phan, MD⁴, Callisia N. Clarke MD & MS¹

Author affiliations

¹Division of Surgical Oncology in the Department of Surgery, Medical College of Wisconsin, Milwaukee; ²Department of Radiology, Medical College of Wisconsin, Milwaukee; ³Department of Pathology, Medical College of Wisconsin, Milwaukee; ⁴Division of Hematology and Oncology in the Department of Medicine, Medical College of Wisconsin, Milwaukee

Background: Neoadjuvant therapy (NAT) has been widely employed in PDAC to downsize tumors. However, data to support the routine use of NAT in advanced PNET is limited. This study aims to investigate the overall response rate (ORR) of cytotoxic NAT in advanced PNET.

Methods: We performed a retrospective review of patients with PNETs who underwent NAT followed by surgical resection at a high-volume tertiary cancer center from January 2009 to August 2023. Demographic and clinicopathologic characteristics were evaluated. ORR was defined as ≥ 30% reduction in serum Chromogranin A (CgA) or hormone level in functional-PNET, partial radiographic response per RESIST v1.1 criteria, and/or tumor downgrading after NAT. Secondary endpoints were progression free survival (PFS) and overall survival (OS).

Results: This cohort of 34 patients had a median follow-up of 42 months (IQR 18-99). 25 (74%) patients had metastatic disease at presentation (Table 1.). 26 (76%) patients received neoadjuvant CAPTEM, 2 (6%) received Everolimus, 2 (6%) received Etoposide+Cisplatin, 2 (6%) received Streptozotocin+5-FU+Leucovorin, 1 (3%) received Sunitinib, and 1 (3%) received Bevacizumab.23 (68%) underwent resection of all visible lesions. 11 (32%) underwent cytoreductive surgery with >70% debulking. 18 (53%) had progression of disease after resection with a median PFS of 33 months (IQR 5-43). Median OS of the cohort was not reached. 3 (9%) patients died due to disease (median resection to death was 58 months). ORR after NAT for the entire cohort was 76% (26 patients). 20 (59%) showed a response by serum biomarker, 10 (29%) by reduction in tumor grade, and 9 (26%) by RESIST criteria. 4 (12%) patients showed response by all 3 criteria; they all received CAPTEM.

Table 1. Study Cohort Demographic and Clinicopathological Characteristics
Cohort Characteristics	n = 34(%)
Median Age, yrs(IQR)	56(45-63)
Sex
Male	15(44%)
Female	19(56%)
Race
White	31(91%)
Black	2(6%)
Other	1(3%)
Ethnicity
Non-Hispanic	32(94%)
Hispanic	2(6%)
Tumor Grade
G1	8(23%)
G2	21(62%)
G3	5(15%)
Surgical Procedure for primary tumor
Distal Pancreatectomy	21(62%)
Pancreatoduodenectomy	9(26%)
Total Pancreatectomy	4(12%)
Median largest primary tumor Size, cm(IQR)	5.0(3.4-8.0)
Primary Tumor Margin
R0	23(68%)
R1	11(32%)
Nodal Metastasis
N0	11(32%)
N1	23(68%)
Distant Metastasis
M0	9(26%)
M1	25(74%)
Liver	20(59%)
Multiple sites	5(15%)
Neoadjuvant Cytotoxic Regimen
CAPTEM	26(76%)
Streptozotocin, 5-FU, Leucovorin	2(6%)
Everolimus	2(6%)
Bevacizumab	1(3%)
Sunitinib	1(3%)
Etoposide, Cisplatin	2(6%)

Conclusions: For advanced PNETs, NAT was associated with an ORR of 76%. NAT allowed for surgical resection in patients with advanced metastatic disease and provided durable PFS and OS.

ABSTRACT ID28692