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Interventional Oncology

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Interventional Oncology

Image-guided percutaneous ablative therapies are potentially curative treatment options for liver cancer. They provide minimally invasive alternatives for patients with a few small metastases in accessible locations. While surgical resection of liver tumors remains the preferred treatment option as a result of better outcomes compared to interventional ablative approaches, fewer than 30% of patients are considered resectable.1  Minimally invasive interventional oncology procedures are often used as an option for treating tumors which cannot be resected by surgery or for tumors in patients who are poor candidates for surgery due to medical issues.

Potential interventional oncology procedures include both percutaneous and transarterial endovascular approaches which are used in the following settings:

Neoadjuvant setting (prior to surgery) –  treatment for unresectable tumors in patients with limited metastatic tumor burden or used to reduce the size of tumors to make them potentially resectable by surgery.

Adjuvant setting (following surgical resection of a tumor) – used in combination with chemotherapy to destroy any remnant tumor in select patients.

Salvage setting – for patients who have not been able to achieve successful treatment following chemotherapy.

Percutaneous ablative procedures

Percutaneous ablative techniques include both thermal and non-thermal approaches. Thermal approaches include heat-based procedures (radiofrequency and microwave ablation) and cold-based procedures (cryoablation). Irreversible electroporation is currently the only non-thermal ablative approach. Thermal ablative techniques have been shown to be effective in the local treatment of tumors which are <3 to 4cm in size and are associated with a low recurrence rate. Microwave ablation has replaced RFA due to the lack of a heat sink effect, as well as its speed and ease compared with RFA. The latest BCLC staging update recommends ablation for very early stage (BCLC-0) who are not candidates for liver transplant and early stage (BCLC-A) patients who have increased portal pressure or bilirubin and contraindications to liver transplant.2

Available percutaneous ablative procedures for HCC include:

Radiofrequency ablation (RFA) – is a minimally invasive procedure that uses electrical energy and heat to destroy cancer cells. A needle is inserted through the skin into the cancer tissue and the heat produces coagulation necrosis and subsequent cell death. While RFA is a simple, repeatable, standardized, lower risk procedure, it is limited by only having a small area of effectiveness since electrical impedance develops as the tissue boils and becomes charred. This insulates the tissue from the electrical signal and results in an effective area of only few millimeters. The effectiveness of RFA is also reduced when used near large blood vessels since this results in a heat sink effect where the heat is dissipated by the blood flowing through these vessels. Besides tumor location, other factors which impact the effectiveness of RFA include the size and number of tumors and the need for a large tumor-free margin.
Microwave ablation (MWA) – uses high frequency microwave energy to heat and kill cancer cells. A thin probe containing an antenna which emits microwaves is into the tumor. The probe produces intense heat that destroys tumor tissue via coagulation necrosis, often within 10 minutes. MWA has a number of advantages over RFA including faster heating over a larger area, shorter procedure time, no need for a grounding pad, resistance to the heat sink effect, and less pain. MWA has replaced RFA at many institutions due to the lack of a heat sink effect, as well as its speed and ease compared with RFA.

A recent systematic literature review and meta-analysis compared the efficacy and safety of MWA and radiofrequency ablation in the treatment of hepatocellular carcinoma.3  MWA was reported to have a lower rate of local tumor progression than RFA. There was no significant difference in the complete ablation rate between MWA and RFA for randomized controlled trials. No difference was seen in 1-year, 3-year, or 5-year overall survival rate or major complications between MWA and RFA for either randomized controlled trials or cohort studies. A separate systematic literature review and meta-analysis focused on the efficacy and safety of single- and multiple antenna MWA for the treatment of HCC and liver metastases.4 The overall complete ablation rate for MWA was 94.4%. The complete ablation rate for tumors >2 cm was 98.3% for multiple-antenna MWA versus 79.2% for single-antenna MWA. Multiple-antenna MWA group and single-antenna MWA group had similar local tumor progression-free (LTPF) rates with multiple antenna MWA reported to have a LTPF rate of 85.9%. Multiple- and single-antenna MWA had similar rates of complications and efficacy relative to one- and three-year overall survival.

Cryoablation –  Cryoablation causes rapid cooling of the target tissue, resulting in intracellular ice crystal formation that destroys organelle and cell membranes and induces membrane pore formation that disrupts the electrochemical gradient. Cellular tonicity is also disturbed, causing lethal transmembrane fluid shifts. If these changes do not cause immediate cell death, they often initiate apoptosis. The ability to visualize ice ball formation, the edge of which marks the 0°C isotherm, in cryoablation on several imaging modalities is a particular benefit.

While RFA and MWA have demonstrated effectiveness in the treatment of liver tumors, they are not ideal for treating lesions  near critical structures.5,6 Cryoablation is typically preferable for the treatment of tumors located near important anatomical structures due to the reduced risk of tissue damage beyond the area of tumor ablation necrosis.7 Additionally, the use of cryoablation avoid the heat sink effect observed with RFA and MWA which can also lead to ineffective ablation of perivascular tumors.

A recent systematic review and meta-analysis reported that cryoablation has a similar rate of local tumor progress and overall survival compared to RFA, but had a higher rate of complications, especially thrombocytopenia and renal impairment following microwave ablation.8

Irreversible electroporation (IRE) therapy – IRE is a nonthermal ablation technique that induces cell death by disrupting the electric potential gradient across cell membranes, leading to the formation of permanent nanopores through the plasma membrane, altering cellular transport and ultimately cell homeostasis.9 The procedure involves the delivery of a series of high voltage direct current electrical pulses between two electrodes placed within a target area surrounding the tumor. Since IRE is a nonthermal treatment, it has the advantage over thermal ablative treatments since the treatment zone can cross large blood vessels and bile ducts without damaging these vital structures.

Outcomes associated with the use of IRE for patients with HCC who were not candidates for resection or thermal ablative therapies because of a high risk of major complications have been reported.10 Complete ablation was achieved for 92% of tumors with a local tumor progression of 20% which were completely ablated. Only 5% of patients experience major complications with no complications related to bile duct injury.

Endovascular transarterial approaches provide an alternative treatment option for patients who are not candidates for surgical or percutaneous ablative procedures. Endovascular transarterial treatments use a minimally invasive approach and use image-guidance to deliver therapy into small hepatic arteries that provide the blood supply to the tumor in the liver. These procedures are performed in patients with liver cancer who are not candidates for surgical or percutaneous ablative procedures or for patients who are not responsive to therapy, have disease progression or toxicity to systemic chemotherapy. While these procedures are not curative, they can improve survival and improve quality of life.

 

Examples of endovascular transarterial procedures include:

  • Transarterial embolization (TAE) – TAE involves the placement of tiny particles made of gelatin beads or sponges into the small arteries of the liver and blocking the blood flow to the tumor. The beads are delivered through a catheter inserted through the femoral artery and guided to the liver. The therapy provides a local tumor treatment which does not block the blood supply to healthy liver tissue.
  • Transarterial chemoembolization (TACE) – TACE is similar procedure to TAE but also involves the local delivery of chemotherapy to the tumor while the blood supply is blocked. This reduces the risk of systemic side effects associated with chemotherapy and the drug remains for a longer period of time since the arteries remain blocked. TACE is frequently used for the treatment of patients with  intermediate-stage liver cancer with multi-nodular tumors who have preserved liver function. The 2022 BCLC update recommends TACE for down-staging tumors >3 cm in non-liver transplant patients and for patients bridging to a transplant with an anticipated with time of greater than 6 months.2
  • Drug-eluting bead transarterial chemoembolization (DEB-TACE)– DEB-TACE uses microspheres to precisely release local chemotherapy over time to the tumor. The beads are “loaded” with drugs and the therapy is delivered directly to the tumor, substantially reducing the concentration of the drug in the systemic circulation and decreasing the risk of side effects. A recent systematic review compared the safety and efficacy of TACE and DEB-TACE in the management of patients with unresectable HCC.11 The authors reported that while the adverse effect profiles of the two approaches were similar, the efficicay of DEB-TACE was superior to TACE in treating HCC and that DEB-TACE provides better survival and treatment response outcomes in certain patient populations.
  • Transarterial radioembolization (Yttrium 90 or Y90)– Y90 combines radiation therapy with embolization. Microscopic glass or resin microspheres are loaded with the radioisotope yttrium-90 (90Y) and injected into the hepatic artery. This enables the local delivery of radiation to the tumor, avoiding the complications associated systemic or local/regional radiation therapy. While the primary goal of Y90 therapy is to slow tumor growth and reduce cancer symptoms, it has also been used to reduce the size of tumors to enable surgical resection. Transarterial radioembolization has been demonstrated to be effective for the treatment of tumors with significant vascular invasion and large tumors which are greater >7 cm in diameter with disease control rates as high as 70% to 80%.12 Reported complications associated with Y90 therapy include radiation pneumonitis, pulmonary fibrosis, and post-radioembolization syndrome characterized by abdominal pain, fever, and nausea.13 A study compared Y90 therapy to SBRT reported no difference in disease-specific or overall survival between the two therapies.14

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References

  1. Delis SG, Dervenis C. Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease. World J Gastroenterol2008; 14: 3452–60.
  2. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681-693.
  3. Dou Z, Lu F, Ren L, Song X, Li B, Li X. Efficacy and safety of microwave ablation and radiofrequency ablation in the treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Medicine (Baltimore). 2022 Jul 29;101(30):e29321.
  4. Han Y, Zhao W, Wu M, Qian Y. Efficacy and safety of single- and multiple-antenna microwave ablation for the treatment of hepatocellular carcinoma and liver metastases: A systematic review and network meta-analysis. Medicine (Baltimore). 2022 Dec 23;101(51):e32304.
  5. Lencioni, R.; De Baere, T.; Martin, R.C.; Nutting, C.W.; Narayanan, G. Image-Guided Ablation of Malignant Liver Tumors: Recommendations for Clinical Validation of Novel Thermal and Non-Thermal Technologies-A Western Perspective. Liver Cancer2015, 4, 208–214.
  6. Benson, A.B.; Venook, A.P.; Al-Hawary, M.M.; Arain, M.A.; Chen, Y.-J.; Ciombor, K.K.; Cohen, S.; Cooper, H.S.; Deming, D.; Farkas, L.; et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.  Natl. Compr. Cancer Netw.2021, 19, 329–359.
  7. Wu, S.; Hou, J.; Ding, Y.; Wu, F.; Hu, Y.; Jiang, Q.; Mao, P.; Yang, Y. Cryoablation Versus Radiofrequency Ablation for Hepatic Malignancies: A Systematic Review and Literature-Based Analysis. Medicine2015, 94, e2252.
  8. Wu S, Hou J, Ding Y, Wu F, Hu Y, Jiang Q, Mao P, Yang Y. Cryoablation Versus Radiofrequency Ablation for Hepatic Malignancies: A Systematic Review and Literature-Based Analysis. Medicine (Baltimore). 2015 Dec;94(49):e2252.
  9. Xiao D, Yao C, Liu H, Li C, Cheng J, Guo F, Tang L. Irreversible electroporation and apoptosis in human liver cancer cells induced by nanosecond electric pulses. Bioelectromagnetics. 2013 Oct;34(7):512-20. doi: 10.1002/bem.21796. Epub 2013 Jun 6. PMID: 23740887.
  10. Sutter O, Calvo J, N’Kontchou G, Nault JC, Ourabia R, Nahon P, et al. Safety and efficacy of irreversible electroporation for the treatment of hepatocellular carcinoma not amenable to thermal ablation techniques: a retrospective single-center case series. 2017;284:877–886.
  11. Ayyub J, Dabhi KN, Gohil NV, et al. Evaluation of the Safety and Efficacy of Conventional Transarterial Chemoembolization (cTACE) and Drug-Eluting Bead (DEB)-TACE in the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review. Cureus. 2023 Jul 16;15(7):e41943.
  12. Wang EA, Broadwell SR, Bellavia RJ, Stein JP. Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma. J Gastrointest Oncol. 2017;8:266–278.
  13. Oladeru OT, Miccio JA, Yang J, Xue Y, Ryu S, Stessin AM. Conformal external beam radiation or selective internal radiation therapy-a comparison of treatment outcomes for hepatocellular carcinoma. J Gastrointest Oncol. 2016;7:433–440.
  14. Riaz A, Lewandowski RJ, Kulik LM, Mulcahy MF, Sato KT, Ryu RK, et al. Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J Vasc Interv Radiol. 2009;20:1121–1130.