Laser-induced Interstitial Thermal Therapy for Liver Metastases

Summary and conclusions

SBU’s appraisal of the evidence

Laser-induced thermotherapy is a non-surgical method for treating tumors in solid organs. The method is experimental and considered primarily in treating patients with liver metastases¹ when surgery is not an option.

• It is uncertain whether or not laser-induced thermotherapy extends life in patients with liver metastases. Comparative studies are lacking. Studies published to date show that this treatment method can ablate metastases, and that risks associated with the procedure are minor. However, the beneficial effects of metastases ablation, in terms of symptoms and quality of life, has not been demonstrated in the literature.
• Use of the method should be limited to controlled trials. This implies, eg, that patients must be informed about the different treatment options and the scientific evidence available at the time.

Technology and target group

Colorectal cancer and breast cancer are two of the most common cancer types in Sweden – annually affecting approximately 6 000 and 7 000 people, respectively. These cancers frequently metastasize to the lungs and the liver. Surgery may be the best available treatment option for metastases involving the liver in, eg, colorectal cancer, and in some cases surgical intervention is curative. However, the disease often spreads as tumors metastasize, resulting in a high risk for the appearance of metastases in multiple organs. In many cases surgery is not feasible due to the extent of the metastases or their location, or because the patient’s general condition does not allow surgical intervention.

Several non-surgical techniques are available that aim to destroy tumor tissue in a way that is as gentle as possible for patients. One such method is laser-induced interstitial thermal therapy (LITT), also called laser-induced thermotherapy. LITT directs laser light through thin optical fibers to target a well-defined area and destroy the tumor. Some form of imaging technology, eg, magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound is used in positioning the fibers. Laser light delivers a high level of energy that heats and destroys tissue. The procedure involves a local anesthetic and takes 1 to 2 hours to perform, including preparation.

LITT is considered to be one of several alternatives for treating liver metastases when surgery, for various reasons, is not an option. An estimated 60 to 80 percent of all patients with liver metastases are not candidates for surgery. Annually in Sweden, approximately 600 to 700 patients with liver metastases from colorectal or breast cancers would be candidates for LITT. However, this estimate is highly uncertain.

Although LITT was originally developed to cause cell death locally, it has been suggested that laser therapy might also have favorable effects on patients’ immune defense. The hypothesis is that treatment could promote greater immune defense against tumors, and that the patient’s immune system could detect and destroy cancer cells hiding in the body. Hence, the treatment would have curative potential.

Primary questions

• Does treatment with laser-induced thermotherapy extend survival in patients with liver metastases?
• Can laser-induced thermotherapy destroy liver metastases? Does the treatment have any effects on symptoms or quality of life?
• Is there any evidence for immunologically induced treatment effects?
• Is the method safe? What side effects or complications are associated with the method?
• What does the method cost? What is the method’s cost-effectiveness?

Patient benefit

The assessment included four studies that investigated LITT in treating liver metastases, primarily from colorectal cancer and breast cancer. All of the studies were case-series without control groups. These studies included approximately 1 000 patients in total.

Whether or not LITT extends survival in patients with liver metastases is uncertain (insufficient scientific evidence ). Studies published to date have reported average survival of 2 to 4 years after treatment with LITT. The studies show that the method can destroy local metastases (limited scientific evidence ), and the risks for complications and side effects are minor. However, the literature does not show whether patients benefit in terms of symptoms and quality of life after ablation of metastases. We found no clinical studies of sufficient size that addressed the potential immunological effects of LITT.

It is conceivable that the method may be appropriate in palliative treatment of liver metastases in cases where surgery is not an option. Use of the method should be limited to the context of controlled trials. This implies, eg, that patients must be informed about the different treatment options and the evidence available at the time. Furthermore, it is important to offer this treatment option primarily to patients who are candidates for curative surgery.

Economic aspects

Laser-induced thermotherapy requires the acquisition of laser light sources, accessibility to appropriate imaging modalities (eg, MRI), and single-use products such as optical fibers. A Medilas Fibertom 5100-laser (Dornier, Germany) is estimated to cost approximately SEK 450 000 (USD 65 000). The approximate average cost for a LITT treatment is estimated at approximately SEK 50 000 (CAD 7 000). Treatment costs depend on factors such as the number and size of tumors.

We were unable to identify any literature addressing the cost-effectiveness of LITT. Since the evidence currently available does not enable an appraisal of the method’s effectiveness, it is not possible to determine its cost-effectiveness.

Footnote

¹ Metastases in the liver that originate from another primary tumor.

Four levels are used in grading the strength of the scientific evidence on which conclusions are based:
Strong scientific evidence (). Based on high- or medium-quality studies containing no factors that weaken the overall judgment.
Moderately strong scientific evidence (). Based on high- or medium-quality studies containing isolated factors that weaken the overall judgment.
Limited scientific evidence (). Based on high- or medium-quality studies containing factors that weaken the overall judgment.
Insufficient scientific evidence (). The evidence base is insufficient when scientific evidence is lacking, the quality of available studies is low, or studies of similar quality are contradictory.

SBU Alert is a service provided by SBU in collaboration with the Medical Products Agency, the National Board of Health and Welfare, and the Swedish Association of Local Authorities and Regions.

References

1. Socialstyrelsen. Cancer i siffror 2009 – Populärvetenskapliga fakta om cancer. Stockholm: Socialstyrelsen; 2009. ISBN 978-91-89446-36-6.
2. Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997;15(3):938-46.
3. Gannon CJ, Curley SA. The role of focal liver ablation in the treatment of unresectable primary and secondary malignant liver tumors. Semin Radiat Oncol 2005;15(4):265-72.
4. Bown SG. Phototherapy in tumors. World J Surg 1983;7(6):700-9.
5. Ma Y, Kepp O, Ghiringhelli F, Apetoh L, Aymeric L, Locher C, et al. Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin Immunol 2010;22(3):113-24.
6. Zerbini A, Pilli M, Penna A, Pelosi G, Schianchi C, Molinari A, et al. Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res 2006;66(2):1139-46.
7. Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150(3):195-203.
8. Hoe AL, Royle GT, Taylor I. Breast liver metastases – incidence, diagnosis and outcome. J R Soc Med 1991;84(12):714-6.
9. Zinser JW, Hortobagyi GN, Buzdar AU, Smith TL, Fraschini G. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987;5(5):773-82.
10. Pech M, Wieners G, Freund T, Dudeck O, Fischbach F, Ricke J, et al. MR-guided interstitial laser thermotherapy of colorectal liver metastases: efficiency, safety and patient survival. Eur J Med Res 2007;12(4):161-8.
11. Christophi C, Nikfarjam M, Malcontenti-Wilson C, Muralidharan V. Long-term survival of patients with unresectable colorectal liver metastases treated by percutaneous interstitial laser thermotherapy. World J Surg 2004;28(10):987-94.
12. Mack MG, Straub R, Eichler K, Söllner O, Lehnert T, Vogl TJ. Breast cancer metastases in liver: laser-induced interstitial thermotherapy – local tumor control rate and survival data. Radiology 2004;233(2):400-9.
13. Mack MG, Straub R, Eichler K, Engelmann K, Zangos S, Roggan A, et al. Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases. Abdom Imaging 2001;26(4):369-74.
14. Shanbhogue AK, Karnad AB, Prasad SR. Tumor response evaluation in oncology: current update. J Comput Assist Tomogr 2010;34(4):479-84.
15. Vogl TJ, Straub R, Eichler K, Söllner O, Mack MG. Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy – local tumor control rate and survival data. Radiology 2004;230(2):450-8.
16. Vogl TJ, Straub R, Zangos S, Mack MG, Eichler K. MR-guided laser-induced thermotherapy (LITT) of liver tumours: experimental and clinical data. Int J Hyperthermia 2004;20(7):713-24.
17. Wiksell H, Schässburger KU, Janicijevic M, Leifland K, Löfgren L, Rotstein S, et al. Prevention of tumour cell dissemination in diagnostic needle procedures. Br J Cancer 2010;103(11):1706-9.
18. Wietzke-Braun P, Schindler C, Raddatz D, Braun F, Armbrust T, Nolte W, et al. Quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy for non-resectable liver metastases of colorectal cancer. Eur J Gastroenterol Hepatol 2004;16(4):389-95.
19. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85(5):365-76.
20. Sercarz JA, Bublik M, Joo J, Paiva PB, Areco KN, Brandalise MH, et al. Outcomes of laser thermal therapy for recurrent head and neck cancer. Otolaryngol Head Neck Surg 2010;142(3):344-50.
21. Bublik M, Sercarz JA, Lufkin RB, Masterman-Smith M, Polyakov M, Paiva PB, et al. Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy. Laryngoscope 2006;116(8):1507-11.
22. Vogl TJ, Wissniowski TT, Naguib NN, Hammerstingl RM, Mack MG, Münch S, et al. Activation of tumor-specific T lymphocytes after laser-induced thermotherapy in patients with colorectal liver metastases. Cancer Immunol Immunother 2009;58(10):1557-63.
23. Ivarsson K, Myllymäki L, Jansner K, Stenram U, Tranberg KG. Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response. Br J Cancer 2005;93(4):435-40.
24. Canadian Agency for Drugs and Technologies in Health (CADTH). Using Lasers to Destroy Liver Tumours. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2006. Health Technology Update 2006, Issue 3. ISSN 1715-5541 (print).
25. Lars-Erik Eriksson, Clinical Laserthermia Systems AB, January 2011, personal communication.
26. Haraldsdóttir KH, Ivarsson K, Götberg S, Ingvar C, Stenram U, Tranberg KG. Interstitial laser thermotherapy (ILT) of breast cancer. Eur J Surg Oncol 2008;34(7):739-45.