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Current Oncology Reports
Published in: Current Oncology Reports 6/2021

01-06-2021 | Brachytherapy | Interventional Oncology (DC Madoff, Section Editor)

Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy

Authors: Florentine E.F. Timmer, Bart Geboers, Sanne Nieuwenhuizen, Evelien A.C. Schouten, Madelon Dijkstra, Jan J.J. de Vries, M. Petrousjka van den Tol, Tanja D. de Gruijl, Hester J. Scheffer, Martijn R. Meijerink

Published in: Current Oncology Reports | Issue 6/2021

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Abstract

Purpose of Review

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC.

Recent Findings

Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials.

Summary

The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results.
Literature
1.
2.
Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v56–68.PubMedCrossRef
3.
4.
Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16(7):1727–33.PubMedCrossRef
5.
•• Ruarus AH, Vroomen L, Geboers B, van Veldhuisen E, Puijk RS, Nieuwenhuizen S, et al. Percutaneous Irreversible Electroporation in Locally Advanced and Recurrent Pancreatic Cancer (PANFIRE-2): a multicenter, prospective, single-arm, phase II study. Radiology. 2019:191109 This is the largest prospective trial to date on percutaneous IRE for LAPC patients, thus holding valuable data on the potential of the technique. They demonstrated survival after diagnosis of 17 months and after treatment of 9.6 months.
6.
Scheffer HJ, Vroomen LG, de Jong MC, Melenhorst MC, Zonderhuis BM, Daams F, et al. Ablation of locally advanced pancreatic cancer with percutaneous irreversible electroporation: results of the phase I/II PANFIRE study. Radiology. 2017;282(2):585–97.PubMedCrossRef
7.
• Leen E, Picard J, Stebbing J, Abel M, Dhillon T, Wasan H. Percutaneous irreversible electroporation with systemic treatment for locally advanced pancreatic adenocarcinoma. J Gastrointest Oncol. 2018;9(2):275–81 This is the largest (retrospective) series on percutanous IRE for LAPC patients, simultaneously demonstrating the longest survival outcomes (27 months after treatment).PubMedPubMedCentralCrossRef
8.
Liu B, Zhou T, Geng J, Zhang F, Wang J, Li Y. Percutaneous computed tomography-guided iodine-125 seeds implantation for unresectable pancreatic cancer. Indian J Cancer. 2015;52(Suppl 2):e69–74.PubMedCrossRef
9.
Liu F, Tang Y, Sun J, Yuan Z, Li S, Sheng J, et al. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2012;7(7):e40847.PubMedPubMedCentralCrossRef
10.
van Veldhuisen E, Vroomen LG, Ruarus AH, Derksen TC, Busch OR, de Jong MC, et al. Value of CT-guided percutaneous irreversible electroporation added to FOLFIRINOX chemotherapy in locally advanced pancreatic cancer: a post hoc comparison. J Vasc Interv Radiol. 2020;31(10):1600–8.PubMedCrossRef
11.
Narayanan G, Hosein PJ, Beulaygue IC, Froud T, Scheffer HJ, Venkat SR, et al. Percutaneous image-guided irreversible electroporation for the treatment of unresectable, locally advanced pancreatic adenocarcinoma. J Vasc Interv Radiol. 2017;28(3):342–8.PubMedCrossRef
12.
Xu K, Niu L, Mu F, Hu Y. Cryosurgery in combination with brachytherapy of iodine-125 seeds for pancreatic cancer. Gland Surgery. 2013;2(2):91–9.PubMedPubMedCentral
13.
Geboers B, Ruarus AH, Nieuwenhuizen S, Puijk RS, Scheffer HJ, de Gruijl TD, et al. Needle-guided ablation of locally advanced pancreatic cancer: cytoreduction or immunomodulation by in vivo vaccination? Chin Clin Oncol. 2019;8(6):61.PubMedCrossRef
14.
Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity. 2013;39(1):74–88.PubMedCrossRef
15.
Marabelle A, Andtbacka R, Harrington K, Melero I, Leidner R, de Baere T, et al. Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT). Annals of Oncology. 2018;29(11):2163–74.PubMedCrossRefPubMedCentral
16.
D’Onofrio M, Crosara S, De Robertis R, Butturini G, Salvia R, Paiella S, et al. Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results. Technol Cancer Res Treat. 2017;16(3):285–94.PubMedCrossRef
17.
Carrafiello G, Ierardi AM, Fontana F, Petrillo M, Floridi C, Lucchina N, et al. Microwave ablation of pancreatic head cancer: safety and efficacy. J Vasc Interv Radiol. 2013;24(10):1513–20.PubMedCrossRef
18.
Ierardi AM, Biondetti P, Coppola A, Fumarola EM, Biasina AM, Alessio Angileri S, et al. Percutaneous microwave thermosphere ablation of pancreatic tumours. Gland Surg. 2018;7(2):59–66.PubMedPubMedCentralCrossRef
19.
Vogl TJ, Panahi B, Albrecht MH, Naguib NNN, Nour-Eldin N-EA, Gruber-Rouh T, et al. Microwave ablation of pancreatic tumors. Minimally Invasive Therapy & Allied Technologies. 2018;27(1):33–40.CrossRef
20.
Dunki-Jacobs EM, Philips P, Martin RC 2nd. Evaluation of resistance as a measure of successful tumor ablation during irreversible electroporation of the pancreas. J Am Coll Surg. 2014;218(2):179–87.PubMedCrossRef
21.
Belfiore MP, Ronza FM, Romano F, Ianniello GP, De Lucia G, Gallo C, et al. Percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in locally advanced pancreatic cancer: our preliminary experience. Int J Surg. 2015;21(Suppl 1):S34–S9.PubMedCrossRef
22.
Månsson C, Brahmstaedt R, Nilsson A, Nygren P, Karlson BM. Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy. Eur J Surg Oncol. 2016;42(9):1401–6.PubMedCrossRef
23.
Zhang Y, Shi J, Zeng J, Alnagger M, Zhou L, Fang G, et al. Percutaneous irreversible electroporation for ablation of locally advanced pancreatic cancer: experience from a Chinese institution. Pancreas. 2017;46(2):e12–e4.PubMedCrossRef
24.
Sugimoto K, Moriyasu F, Tsuchiya T, Nagakawa Y, Hosokawa Y, Saito K, et al. Irreversible electroporation for nonthermal tumor ablation in patients with locally advanced pancreatic cancer: initial clinical experience in Japan. Internal medicine (Tokyo, Japan). 2018;57(22):3225–31.PubMedCentralCrossRef
25.
Mansson C, Brahmstaedt R, Nygren P, Nilsson A, Urdzik J, Karlson BM. Percutaneous irreversible electroporation as first-line treatment of locally advanced pancreatic cancer. Anticancer Res. 2019;39(5):2509–12.PubMedCrossRef
26.
Flak RV, Stender MT, Jensen TM, Andersen KL, Henriksen SD, Mortensen PB, et al. Treatment of locally advanced pancreatic cancer with irreversible electroporation-a Danish single center study of safety and feasibility. Scand J Gastroenterol. 2019;54(2):252–8.PubMedCrossRef
27.
Zhongmin W, Yu L, Fenju L, Kemin C, Gang H. Clinical efficacy of CT-guided iodine-125 seed implantation therapy in patients with advanced pancreatic cancer. European radiology. 2010;20(7):1786–91.PubMedCrossRef
28.
Yang M, Yan Z, Luo J, Liu Q, Zhang W, Ma J, et al. A pilot study of intraluminal brachytherapy using (125)I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice. Brachytherapy. 2016;15(6):859–64.PubMedCrossRef
29.
Lv WF, Lu D, Xiao JK, Mukhiya G, Tan ZX, Cheng DL, et al. The side effects and complications of percutaneous iodine-125 seeds implantation under CT-guide for patients with advanced pancreatic cancer. Medicine (Baltimore). 2017;96(52):e9535.PubMedPubMedCentralCrossRef
30.
Liu X, Yang X, Zhou G, Chen Y, Li C, Wang X. Gemcitabine-based regional intra-arterial infusion chemotherapy in patients with advanced pancreatic adenocarcinoma. Medicine (Baltimore). 2016;95(11):e3098.PubMedPubMedCentralCrossRef
31.
Rosemurgy AS, Ross SB, Vitulli PL, Malek R, Li J, Agah R. Safety Study of Targeted and localized intra-arterial delivery of gemcitabine in patients with locally advanced pancreatic adenocarcinoma. J Pancreat Cancer. 2017;3(1):58–65.PubMedPubMedCentralCrossRef
32.
• Aigner KR, Gailhofer S, Selak E, Aigner K. Intra-arterial infusion chemotherapy versus isolated upper abdominal perfusion for advanced pancreatic cancer: a retrospective cohort study on 454 patients. J Cancer Res Clin Oncol. 2019;145(11):2855–62 This large retrospective study compared two chemotherapy infusion techniques (IAIC and UAP), including 174 LAPC patients. They demonstrated that IAIC was able to achieve survival outcomes of 8 months.PubMedPubMedCentralCrossRef
33.
Qiu B, Zhang X, Tsauo J, Zhao H, Gong T, Li J, et al. Transcatheter arterial infusion for pancreatic cancer: a 10-year National Cancer Center experience in 115 patients and literature review. Abdom Radiol (NY). 2019;44(8):2801–8.PubMedCrossRef
34.
Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nature reviews Cancer. 2014;14(3):199–208.PubMedCrossRef
35.
Mehta A, Oklu R, Sheth RA. Thermal ablative therapies and immune checkpoint modulation: can locoregional approaches effect a systemic response? Gastroenterol Res Pract. 2016;2016:9251375.PubMedPubMedCentralCrossRef
36.
Bang JY, Sutton B, Hawes RH, Varadarajulu S. EUS-guided celiac ganglion radiofrequency ablation versus celiac plexus neurolysis for palliation of pain in pancreatic cancer: a randomized controlled trial (with videos). Gastrointest Endosc. 2019;89(1):58–66.e3.PubMedCrossRef
37.
Casadei R, Ricci C, Pezzilli R, Serra C, Calculli L, Morselli-Labate AM, et al. A prospective study on radiofrequency ablation locally advanced pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2010;9(3):306–11.PubMed
38.
Girelli R, Frigerio I, Salvia R, Barbi E, Tinazzi Martini P, Bassi C. Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer. Br J Surg. 2010;97(2):220–5.PubMedCrossRef
39.
Girelli R, Frigerio I, Giardino A, Regi P, Gobbo S, Malleo G, et al. Results of 100 pancreatic radiofrequency ablations in the context of a multimodal strategy for stage III ductal adenocarcinoma. Langenbecks Arch Surg. 2013;398(1):63–9.PubMedCrossRef
40.
Cantore M, Girelli R, Mambrini A, Frigerio I, Boz G, Salvia R, et al. Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma. Br J Surg. 2012;99(8):1083–8.PubMedCrossRef
41.
Frigerio I, Girelli R, Giardino A, Regi P, Salvia R, Bassi C. Short term chemotherapy followed by radiofrequency ablation in stage III pancreatic cancer: results from a single center. J Hepatobiliary Pancreat Sci. 2013;20(6):574–7.PubMedCrossRef
42.
Paiella S, Butturini G, Frigerio I, Salvia R, Armatura G, Bacchion M, et al. Safety and feasibility of irreversible electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. Digestive Surgery. 2015;32(2):90–7.PubMedCrossRef
43.
Fegrachi S, Walma MS, de Vries JJJ, van Santvoort HC, Besselink MG, von Asmuth EG, et al. Safety of radiofrequency ablation in patients with locally advanced, unresectable pancreatic cancer: a phase II study. Eur J Surg Oncol. 2019;45(11):2166–72.PubMedCrossRef
44.
Crinò SF, D’Onofrio M, Bernardoni L, Frulloni L, Iannelli M, Malleo G, et al. EUS-guided radiofrequency ablation (EUS-RFA) of solid pancreatic neoplasm using an 18-gauge needle electrode: feasibility, safety, and technical success. J Gastrointestin Liver Dis. 2018;27(1):67–72.PubMedCrossRef
45.
Arcidiacono PG, Carrara S, Reni M, Petrone MC, Cappio S, Balzano G, et al. Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer. Gastrointest Endosc. 2012;76(6):1142–51.PubMedCrossRef
46.
Scopelliti F, Pea A, Conigliaro R, Butturini G, Frigerio I, Regi P, et al. Technique, safety, and feasibility of EUS-guided radiofrequency ablation in unresectable pancreatic cancer. Surg Endosc. 2018;32(9):4022–8.PubMedCrossRef
47.
Ruarus A, Vroomen L, Puijk R, Scheffer H, Meijerink M. Locally advanced pancreatic cancer: a review of local ablative therapies. Cancers (Basel). 2018;10(1):16.PubMedCentralCrossRef
48.
Fegrachi S, Besselink MG, van Santvoort HC, van Hillegersberg R, Molenaar IQ. Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review. HPB (Oxford). 2014;16(2):119–23.PubMedCrossRef
49.
Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations-boosting the anticancer immune response. J Immunother Cancer. 2017;5(1):78.PubMedPubMedCentralCrossRef
50.
den Brok MH, Sutmuller RP, Nierkens S, Bennink EJ, Frielink C, Toonen LW, et al. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. Br J Cancer. 2006;95(7):896–905.CrossRef
51.
Haen SP, Gouttefangeas C, Schmidt D, Boss A, Clasen S, von Herbay A, et al. Elevated serum levels of heat shock protein 70 can be detected after radiofrequency ablation. Cell Stress Chaperones. 2011;16(5):495–504.PubMedPubMedCentralCrossRef
52.
Wan J, Wu W, Huang Y, Ge W, Liu S. Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α. Oncol Rep. 2016;36(2):659–68.PubMedPubMedCentralCrossRef
53.
Nijkamp MW, van der Bilt JD, de Bruijn MT, Molenaar IQ, Voest EE, van Diest PJ, et al. Accelerated perinecrotic outgrowth of colorectal liver metastases following radiofrequency ablation is a hypoxia-driven phenomenon. Ann Surg. 2009;249(5):814–23.PubMedCrossRef
54.
Gao S, Pu N, Yin H, Li J, Chen Q, Yang M, et al. Radiofrequency ablation in combination with an mTOR inhibitor restrains pancreatic cancer growth induced by intrinsic HSP70. Ther Adv Med Oncol. 2020;12:1758835920953728.PubMedPubMedCentralCrossRef
55.
Rozenblum N, Zeira E, Bulvik B, Gourevitch S, Yotvat H, Galun E, et al. Radiofrequency ablation: inflammatory changes in the periablative zone can induce global organ effects, including liver regeneration. Radiology. 2015;276(2):416–25.PubMedCrossRef
56.
• Giardino A, Innamorati G, Ugel S, Perbellini O, Girelli R, Frigerio I, et al. Immunomodulation after radiofrequency ablation of locally advanced pancreatic cancer by monitoring the immune response in 10 patients. Pancreatology. 2017;17(6):962–6 This study published the first clinical results of RFA-induced immune response in LAPC patients. They demonstrated that RFA increased CD4+ and CD8+ T-cells, while mainainting stable Treg numbers.PubMedCrossRef
57.
Lubner MG, Brace CL, Hinshaw JL, Lee FT. Microwave tumor ablation: mechanism of action, clinical results, and devices. Journal of Vascular and Interventional Radiology. 2010;21(8, Supplement):S192–203.PubMedPubMedCentralCrossRef
58.
59.
Ahmad F, Gravante G, Bhardwaj N, Strickland A, Basit R, West K, et al. Renal effects of microwave ablation compared with radiofrequency, cryotherapy and surgical resection at different volumes of the liver treated. Liver Int. 2010;30(9):1305–14.PubMedCrossRef
60.
61.
Li J, Chen X, Yang H, Wang X, Yuan D, Zeng Y, et al. Tumour cryoablation combined with palliative bypass surgery in the treatment of unresectable pancreatic cancer: a retrospective study of 142 patients. Postgrad Med J. 2011;87(1024):89–95.PubMedCrossRef
62.
Song ZG, Hao JH, Gao S, Gao CT, Tang Y, Liu JC. The outcome of cryoablation in treating advanced pancreatic cancer: a comparison with palliative bypass surgery alone. J Dig Dis. 2014;15(10):561–9.PubMedCrossRef
63.
Niu L, He L, Zhou L, Mu F, Wu B, Li H, et al. Percutaneous ultrasonography and computed tomography guided pancreatic cryoablation: feasibility and safety assessment. Cryobiology. 2012;65(3):301–7.PubMedCrossRef
64.
Shao Q, O’Flanagan S, Lam T, Roy P, Pelaez F, Burbach BJ, et al. Engineering T cell response to cancer antigens by choice of focal therapeutic conditions. Int J Hyperthermia. 2019;36(1):130–8.PubMedCrossRef
65.
den Brok MHMGM, Sutmuller RPM, Nierkens S, Bennink EJ, Frielink C, Toonen LWJ, et al. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. British Journal of Cancer. 2006;95(7):896–905.CrossRef
66.
Chapman WC, Debelak JP, Wright Pinson C, Washington MK, Atkinson JB, Venkatakrishnan A, et al. Hepatic cryoablation, but not radiofrequency ablation, results in lung inflammation. Ann Surg. 2000;231(5):752–61.PubMedPubMedCentralCrossRef
67.
Shibata T, Suzuki K, Yamashita T, Takeichi N, Mark M, Hosokawa M, et al. Immunological analysis of enhanced spontaneous metastasis in WKA rats following cryosurgery. Anticancer Res. 1998;18(4a):2483–6.PubMed
68.
69.
Takaki H, Imai N, Thomas CT, Yamakado K, Yarmohammadi H, Ziv E, et al. Changes in peripheral blood T-cell balance after percutaneous tumor ablation. Minim Invasive Ther Allied Technol. 2017;26(6):331–7.PubMedCrossRef
70.
Sabel MS, Su G, Griffith KA, Chang AE. Rate of freeze alters the immunologic response after cryoablation of breast cancer. Ann Surg Oncol. 2010;17(4):1187–93.PubMedCrossRef
71.
White SB, Zhang Z, Chen J, Gogineni VR, Larson AC. Early immunologic response of irreversible electroporation versus cryoablation in a rodent model of pancreatic cancer. J Vasc Interv Radiol. 2018;29(12):1764–9.PubMedCrossRef
72.
Geboers B, Scheffer HJ, Graybill PM, Ruarus AH, Nieuwenhuizen S, Puijk RS, et al. High-voltage electrical pulses in oncology: irreversible electroporation, electrochemotherapy, gene electrotransfer, electrofusion, and electroimmunotherapy. Radiology. 2020;295(2):254–72.PubMedCrossRef
73.
Vogel JA, Vroomen LGPH, Srimathveeravalli G. The effect of irreversible electroporation on blood vessels, bile ducts, urinary tract, intestines, and nerves. In: Meijerink MR, Scheffer HJ, Narayanan G, editors. Irreversible electroporation in clinical practice. Cham: Springer International Publishing; 2018. p. 81–94.CrossRef
74.
Yang PC, Huang KW, Pua U, Kim MD, Li SP, Li XY, et al. Prognostic factor analysis of irreversible electroporation for locally advanced pancreatic cancer-a multi-institutional clinical study in Asia. Eur J Surg Oncol. 2020;46(5):811–7.PubMedCrossRef
75.
Kwon JH, Chung MJ, Park JY, Lee HS, Hwang HK, Kang CM, et al. Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population. Acta Radiol. 2020;284185120917118.
76.
Martin RC 2nd, Kwon D, Chalikonda S, Sellers M, Kotz E, Scoggins C, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg. 2015;262(3):486–94 discussion 92-4.PubMedCrossRef
77.
Kluger MD, Epelboym I, Schrope BA, Mahendraraj K, Hecht EM, Susman J, et al. Single-institution experience with irreversible electroporation for T4 pancreatic cancer: first 50 patients. Annals of surgical oncology. 2016;23(5):1736–43.PubMedCrossRef
78.
Lambert L, Horejs J, Krska Z, Hoskovec D, Petruzelka L, Krechler T, et al. Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience. Neoplasma. 2016;63(2):269–73.PubMed
79.
Vogel JA, Rombouts SJ, de Rooij T, van Delden OM, Dijkgraaf MG, van Gulik TM, et al. Induction chemotherapy followed by resection or irreversible electroporation in locally advanced pancreatic cancer (IMPALA): a prospective cohort study. Ann Surg Oncol. 2017;24(9):2734–43.PubMedCrossRef
80.
Yan L, Chen YL, Su M, Liu T, Xu K, Liang F, et al. A single-institution experience with open irreversible electroporation for locally advanced pancreatic carcinoma. Chin Med J (Engl). 2016;129(24):2920–5.PubMedPubMedCentralCrossRef
81.
Simmerman E, Chung J, Lawson A, Kruse E. Application of irreversible electroporation ablation as adjunctive treatment for margin enhancement: safety and efficacy. J Surg Res. 2020;246:260–8.PubMedCrossRef
82.
Belfiore G, Belfiore MP, Reginelli A, Capasso R, Romano F, Ianniello GP, et al. Concurrent chemotherapy alone versus irreversible electroporation followed by chemotherapy on survival in patients with locally advanced pancreatic cancer. Med Oncol. 2017;34(3):38.PubMedCrossRef
83.
He C, Huang X, Zhang Y, Cai Z, Lin X, Li S. Comparison of survival between irreversible electroporation followed by chemotherapy and chemotherapy alone for locally advanced pancreatic cancer. Front Oncol. 2020;10:6.PubMedPubMedCentralCrossRef
84.
Xu K, Chen Y, Su J, Su M, Yan L. Irreversible electroporation and adjuvant chemoradiotherapy for locally advanced pancreatic carcinoma. J Cancer Res Ther. 2020;16(2):280–5.PubMedCrossRef
85.
•• Zhao J, Wen X, Tian L, Li T, Xu C, Wen X, et al. Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer. Nature Communications. 2019;10(1):899 This was the first pre-clinical study in mice combining IRE with immune checkpoint inhibitors. They achieved promising durable results using this combination treatment, whilst either as monotherapy only demonstrated marginal improvement compared to the controls.PubMedPubMedCentralCrossRef
86.
• Scheffer HJ, AGM S, Geboers B, LGPH V, Ruarus A, de Bruijn B, et al. Irreversible electroporation of locally advanced pancreatic cancer transiently alleviates immune suppression and creates a window for antitumor T cell activation. Oncoimmunology. 2019;8(11):1652532 Along with Pandit et al., the first clinical results of IRE-induced immune response in LAPC patients. The results demonstrated a transient alleviation of an immunesuppressive state, with elevation of CD4+PD1+ and CD8+PD1+ T-cells and a decrease in Tregs.PubMedPubMedCentralCrossRef
87.
• Pandit H, Hong YK, Li Y, Rostas J, Pulliam Z, Li SP, et al. Evaluating the regulatory immunomodulation effect of irreversible electroporation (IRE) in pancreatic adenocarcinoma. Ann Surg Oncol. 2019;26(3):800–6 Along with Scheffer et al., the first clinical results of IRE-induced immune response in LAPC patients. Their results demonstrate an inverse correlation of Tregs with time after IRE treatment.PubMedCrossRef
88.
Gai B, Zhang F. Chinese expert consensus on radioactive <sup>125</sup>I seeds interstitial implantation brachytherapy for pancreatic cancer. Journal of Cancer Research and Therapeutics. 2018;14(7):1455–62.PubMedCrossRef
89.
Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 2007;14(7):1237–43.PubMedCrossRef
90.
Zou YP, Li WM, Zheng F, Li FC, Huang H, Du JD, et al. Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer. World J Gastroenterol. 2010;16(40):5104–10.PubMedPubMedCentralCrossRef
91.
Li CG, Zhou ZP, Jia YZ, Tan XL, Song YY. Radioactive (125)I seed implantation for locally advanced pancreatic cancer: a retrospective analysis of 50 cases. World J Clin Cases. 2020;8(17):3743–50.PubMedPubMedCentralCrossRef
92.
Y-f L, Z-q L, Y-s Z, Dong L-m, Wang C-y, S-m G, et al. Implantation of radioactive 125I seeds improves the prognosis of locally advanced pancreatic cancer patients: a retrospective study. Journal of Huazhong University of Science and Technology [Medical Sciences]. 2016;36(2):205–10.CrossRef
93.
Wang H, Wang J, Jiang Y, Li J, Tian S, Ran W, et al. The investigation of 125I seed implantation as a salvage modality for unresectable pancreatic carcinoma. J Exp Clin Cancer Res. 2013;32(1):106.PubMedPubMedCentralCrossRef
94.
Zheng Z, Xu Y, Zhang S, Pu G, Cui C. Surgical bypass and permanent iodine-125 seed implantation vs. surgical bypass for the treatment of pancreatic head cancer. Oncol Lett. 2017;14(3):2838–44.PubMedPubMedCentralCrossRef
95.
Jia SN, Wen FX, Gong TT, Li X, Wang HJ, Sun YM, et al. A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers. Int J Radiat Biol. 2020;96(3):383–9.PubMedCrossRef
96.
Carvalho HA, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo). 2018;73(suppl 1):e557s.CrossRef
97.
Fujiwara K, Saung MT, Jing H, Herbst B, Zarecki M, Muth S, et al. Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer. Journal for ImmunoTherapy of Cancer. 2020;8(2):e000351.PubMedPubMedCentralCrossRef
98.
Liu W, Song QK, Xing BC. A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases. Int J Colorectal Dis. 2015;30(8):1091–102.PubMedCrossRef
99.
Sodergren MH, Mangal N, Wasan H, Sadanandam A, Balachandran VP, Jiao LR, et al. Immunological combination treatment holds the key to improving survival in pancreatic cancer. J Cancer Res Clin Oncol. 2020;146(11):2897–911.PubMedPubMedCentralCrossRef
100.
Galluzzi L, Humeau J, Buqué A, Zitvogel L. Kroemer G. Nature Reviews Clinical Oncology: Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors; 2020.
101.
Michelakos T, Cai L, Villani V, Sabbatino F, Kontos F, Fernández-Del Castillo C, et al. Tumor microenvironment immune response in pancreatic ductal adenocarcinoma patients treated with neoadjuvant therapy. J Natl Cancer Inst. 2020.
102.
Fransen MF, van der Sluis TC, Ossendorp F, Arens R, Melief CJM. Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell–dependent tumor eradication and decreases risk of toxic side effects. Clinical Cancer Research. 2013;19(19):5381–9.PubMedCrossRef
103.
Fransen MF, Schoonderwoerd M, Knopf P, MGM C, LJAC H, Kneilling M, et al. Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI Insight. 2018;3(23).
104.
Francis DM, Manspeaker MP, Schudel A, Sestito LF, O’Melia MJ, Kissick HT, et al. Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy. Science Translational Medicine. 2020;12(563):eaay3575.PubMedCrossRefPubMedCentral
105.
Marabelle A, Tselikas L, de Baere T, Houot R. Intratumoral immunotherapy: using the tumor as the remedy. Annals of Oncology. 2017;28:xii33–43.PubMedCrossRef
106.
Hemminki O, dos Santos JM, Hemminki A. Oncolytic viruses for cancer immunotherapy. Journal of Hematology & Oncology. 2020;13(1):84.CrossRef
107.
• Hirooka Y, Kasuya H, Ishikawa T, Kawashima H, Ohno E, Villalobos IB, et al. A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer. BMC Cancer. 2018;18(1):596 One of the first clinical studies publishing on intra-tumoral injection of an oncolytic virus in combination with erlotinib and gemcitabine in LAPC patients, concluding its safety (SAE 20%), with PFS of 6.3 months and OS of 15.5 months.PubMedPubMedCentralCrossRef
108.
Nguyen KG, Vrabel MR, Mantooth SM, Hopkins JJ, Wagner ES, Gabaldon TA, et al. Localized interleukin-12 for cancer immunotherapy. Frontiers in Immunology. 2020;11:2510.CrossRef
109.
Bortolanza S, Bunuales M, Otano I, Gonzalez-Aseguinolaza G, Ortiz-de-Solorzano C, Perez D, et al. Treatment of pancreatic cancer with an oncolytic adenovirus expressing interleukin-12 in Syrian hamsters. Mol Ther. 2009;17(4):614–22.PubMedPubMedCentralCrossRef
110.
Sandin LC, Eriksson F, Ellmark P, Loskog ASI, Tötterman TH, Mangsbo SM. Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo. Oncoimmunology. 2014;3(1):e27614.PubMedPubMedCentralCrossRef
111.
Krieg AM. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene. 2008;27(2):161–7.PubMedCrossRef
112.
Schmidt J, Welsch T, Jäger D, Mühlradt PF, Büchler MW, Märten A. Intratumoural injection of the toll-like receptor-2/6 agonist ‘macrophage-activating lipopeptide-2’ in patients with pancreatic carcinoma: a phase I/II trial. Br J Cancer. 2007;97(5):598–604.PubMedPubMedCentralCrossRef
113.
Mills BN, Connolly KA, Ye J, Murphy JD, Uccello TP, Han BJ, et al. Stereotactic body radiation and interleukin-12 combination therapy eradicates pancreatic tumors by repolarizing the immune microenvironment. Cell Rep. 2019;29(2):406–21.e5.PubMedPubMedCentralCrossRef
114.
• JSS N, Ray P, Hayashi T, Whisenant TC, Vicente D, Carson DA, et al. Irreversible electroporation combined with checkpoint blockade and TLR7 stimulation induces antitumor immunity in a murine pancreatic cancer model. Cancer Immunol Res. 2019;7(10):1714–26 This study built on the design of Zhao et al., combining IRE with immune checkpoint inhibitors and an intra-tumoral TLR-7. This triple treatment improved treatment responses and resulted in elimination of untreated concomitant metastases.CrossRef
115.
Lin M, Alnaggar M, Liang S, Wang X, Liang Y, Zhang M, et al. An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer. Oncotarget. 2017;8(60):101795–807.PubMedPubMedCentralCrossRef
116.
• Pan Q, Hu C, Fan Y, Wang Y, Li R, Hu X. Efficacy of irreversible electroporation ablation combined with natural killer cells in treating locally advanced pancreatic cancer. Journal of BUON : official journal of the Balkan Union of Oncology. 2020;25(3):1643–9 This clinical study demonstrated the significantly superior overall response rate of LAPC patients (n = 92) treated with IRE + NK cells, compared to sole IRE.
117.
•• Lin M, Zhang X, Liang S, Luo H, Alnaggar M, Liu A, et al. Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients. Signal Transduction and Targeted Therapy. 2020;5(1):215 This is the first clinical study combining IRE with γδ T cells in LAPC patients (n = 62). Patients were randomized to receive IRE alone (n = 32) or IRE + γδ T cells (n = 30), the latter group achieving longer progression-free (8.5 vs. 11 months) and overall survival (11 vs. 14.5 months).PubMedPubMedCentralCrossRef
Metadata
Title
Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy
Authors
Florentine E.F. Timmer
Bart Geboers
Sanne Nieuwenhuizen
Evelien A.C. Schouten
Madelon Dijkstra
Jan J.J. de Vries
M. Petrousjka van den Tol
Tanja D. de Gruijl
Hester J. Scheffer
Martijn R. Meijerink
Publication date
01-06-2021
Publisher
Springer US
Published in
Current Oncology Reports / Issue 6/2021
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-021-01057-3

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