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Laser Laboratory
Laser Laboratory
Research Projects
Under the direction of Marcos Paiva, MD, PhD, the primary objective of the Laser Lab is to combine intratumor injections of chemotherapy with laser interstitial thermal therapy (LITT) for palliative treatment of head and neck cancer. Laboratory research has resulted in a series of innovative publications that broadens the concept of tumor palliation based on thermal denaturation of malignant cells to include anti-cancer drug activation in tumors by laser energy. Other research interests include photodynamic therapy in head and neck cancer, as well as clinical assessment on the impact of minimal invasive palliative procedures in quality of life of cancer patients. Dr. Paiva is also the principal investigator for the National Institute of Health (NIH) funded project "Combined Minimally Invasive Treatment for Cancer" which initiated clinical testing of laser and chemotherapy for palliation of recurrent head and neck cancer.
Members
Principal Investigator: Marcos Paiva, MD, PhD
Clinical Application
Head and neck squamous cell carcinoma (SCCA) is the sixth most common cancer worldwide and has a 60% recurrence rate within 5 years after surgical excision, radiation therapy, or chemotherapy.(1,2) Recurrent or advanced head and neck cancer is a common clinical dilemma, since recurrent disease is incurable.(1-5) At UCLA we have developed laser induced-/interstitial thermal therapy (LITT) in a stepwise fashion (Phase I-II) to palliate patients with advanced and recurrent head and neck tumors as an alternative to more radical surgery.(6-8) Our team has treated approximately 500 patients with recurrent head and neck cancer by LITT, and is among the most experienced medical centers in the country using Nd:YAG laser therapy for palliation of recurrent head and neck cancer. Although LITT procedures are safe, feasible, and can extend survival, margin recurrence is seen in many cases, particularly for palliation of advanced obstructing cancers of the gastrointestinal and bronchial tracts by endoscopic recanalization.(9-14) More effective treatment should be possible by combined therapy.(15-18) During LITT high photothermal laser energy levels are delivered to the area of maximum obstruction inducing irreversible coagulative changes while lower levels to the tumor margin. Reversible hyperthermic damage in the tumor margins frequently leads to tumor recurrence requiring additional laser application for tumor eradication. (10,12,13,19)
In an attempt to improve tumor response after LITT for recurrent head and neck cancer, this investigator has been involved in translational studies exploring ways to couple chemotherapy with laser ablation as an adjunct strategy to eliminate regrowth in the periphery of LITT treatment sites.(10,20,21) Recent studies with human SCCA transplant models combining injections of cisplatinum in a gel vehicle (CDDP/gel) with LITT encourages us to further develop this novel minimally invasive combined therapy in our pursuit to successfully eradicate recurrent head and neck cancer.(10,18-26)
Additional Information and Future of Translational Study
We propose a less invasive and potentially more effective regional therapy approach by topical administration of CDDP/gel as an intra-operative adjunct to LITT ablation for treatment of recurrent head and neck tumors.(20, 22-24) In the past these patients were treated at UCLA either by LITT (Phase II study) or by CDDP/gel (Phase III trials) as part of a multi-center Phase III study.(12,25,27) Both of these palliative methods show clear evidence of tumor regression in some patients, but eventual margin recurrence is seen in the majority of cases.(10,12,25) An obvious next step is to combine intratumor CDDP/gel injections with LITT for enhanced therapy in the tumor margins and further improve cancer treatment.(28)
Our team has treated approximately 500 patients with recurrent head and neck cancer by LITT, and is among the most experienced medical centers in the country using Nd:YAG laser therapy for palliation of recurrent head and neck cancer. Although LITT procedures are safe, feasible, and can extend survival, margin recurrence is seen in many cases. Laboratory results discussed above demonstrated the proof of principle on the potential to improve laser thermal therapy by local injections of a chemotherapeutic agent in an animal model, a concept that is currently undergoing translational studies for clinical application.(29,30) Expanding the same concept, Vogl and colleagues, the most experienced group in liver LITT, has recently proposed a combination of chemoembolization and LITT for liver tumors with promising results.(31,32) These studies show a strong translational potential not only for head and neck but for other accessible inoperable primary and/or recurrent tumors of the chest wall, breast, liver, prostate and colon, as a minimally invasive and low cost treatment.
References
1. Carvalho AL, Nishimoto IN, Califano JA, et al. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005;114:806-16.
2. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30.
3. Correa AJ, Burkey BB. Current options in management of head and neck cancer patients. Med Clin North Am 1999;83:235-46, xi.
4. Forastiere A, Koch W, Trotti A, et al. Head and neck cancer. N Engl J Med 2001;345:1890-900.
5. Goodwin WJ, Jr. Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? Laryngoscope 2000;110:1-18.
6. Castro DJ, Saxton RE, Soudant J, et al. Minimally invasive palliative tumor therapy guided by imaging techniques: the UCLA experience. J Clin Laser Med Surg 1994;12:65-73.
7. Paiva MB, Blackwell KE, Saxton RE, et al. Palliative laser therapy for recurrent head and neck cancer: a Phase II clinical study. Laryngoscope 1998;108:1277-83.
8. Paiva MB, Blackwell KE, Saxton RE, et al. Nd:YAG laser therapy for palliation of recurrent squamous cell carcinomas in the oral cavity. Lasers Surg Med 2002;31:64-9.
9. Castro D, Calcaterra T, Saxton R, et al. Ultrasound guided minimally invasive therapy for recurrent head and neck cancer. Oper Tech Otolaryngol Head Neck Surg 1995;5:259-66.
10. Paiva MB, Saxton RE, VanderWerf QM, et al. Cisplatinum and interstitial laser therapy for advanced head and neck cancer: a preclinical study. Lasers Surg Med 1997;21:423-31.
11. Paiva M, Saxton R, Elashoff R, et al. Palliative laser induced thermal-therapy for recurrent head and neck cancer in a phase ll clinical study. Journal of Investigative Medicine 2002;50:176.
12. Joffee S, Tajiri H, Oguro Y, et al. Laserthermia: A new method of interstitial local hyperthermia using the contact Nd:Yag laser. Radiol Clinic of North AM 1989;27:611-20.
13. Feyh J, Gutmann R, Leunig A, et al. MRI-guided laser interstitial thermal therapy (LITT) of head and neck tumors: progress with a new method. J Clin Laser Med Surg 1996;14:361-6.
14. Mueller-Lisse UG, Heuck AF, Thoma M, et al. Predictability of the size of laser-induced lesions in T1-Weighted MR images obtained during interstitial laser-induced thermotherapy of benign prostatic hyperplasia. J Magn Reson Imaging 1998;8:31-9.
15. Al-Sarraf M. Treatment of locally advanced head and neck cancer: historical and critical review. Cancer Control 2002;9:387-99.
16. Adelstein DJ. Recent randomized trials of chemoradiation in the management of locally advanced head and neck cancer. Curr Opin Oncol 1998;10:213-8.
17. Weisman RA, Robbins KT. Management of the neck in patients with head and neck cancer treated by concurrent chemotherapy and radiation. Otolaryngol Clin North Am 1998;31:773-84.
18. Saxton RE, Paiva MB, Lufkin RB, et al. Laser photochemotherapy: a less invasive approach for treatment of cancer. Semin Surg Oncol 1995;11:283-9.
19. Anzai Y, Lufkin RB, Saxton RE, et al. Nd: YAG interstitial laser phototherapy guided by magnetic resonance imaging in an ex vivo model: dosimetry of laser-MR-tissue interaction. Laryngoscope 1991;101:755-60.
20. Paiva MB, Saxton RE, Letts GA, et al. Interstitial laser photochemotherapy with new anthrapyrazole drugs for the treatment of xenograft tumors. J Clin Laser Med Surg 1995;13:307-13.
21. Graeber IP, Paiva MB, Eshraghi AA, et al. Anthrapyrazoles and interstitial laser phototherapy for experimental treatment of squamous cell carcinoma. Laryngoscope 1998;108:351-7.
22. Paiva MB, Graeber IP, Castro DJ, et al. Laser and cisplatinum for treatment of human squamous cell carcinoma. Laryngoscope 1998;108:1269-76.
23. Graeber IP, Eshraghi AA, Paiva MB, et al. Combined intratumor cisplatinum injection and Nd:YAG laser therapy. Laryngoscope 1999;109:447-54.
24. Chung PS, Kim HG, Rhee CK, et al. Anticancer effect of combined intratumor cisplatin injection and interstitial KTP laser therapy on xenografted squamous cell carcinoma. J Clin Laser Med Surg 2003;21:23-7.
25. Paiva M, Saxton R, Blackwell K, et al. Combined cisplatinum and laser thermal therapy for palliation of recurrent head and neck tumors. Diag Ther Endoscop 2000;6:133-40.
26. Clayman GL, Dreiling LK. Injectable modalities as local and regional strategies for head and neck cancer. Hematol Oncol Clin North Am 1999;13:787-810, viii.
27. Castro DJ, Sridhar KS, Garewal HS, et al. Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America. Head Neck 2003;25:717-31.
28. Paiva MB, Bublik M, Castro DJ, et al. Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer. Photomed Laser Surg 2005;23:531-5.
29. Paiva MB, Graeber IP, Castro DJ, et al. Laser and cisplatinum for treatment of human squamous cell carcinoma. Laryngoscope 1998;108:1269-76.
30. Paiva MB, Bublik M, Castro DJ, et al. Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer. Photomed Laser Surg 2005;23:531-5.
31. Vogl TJ, Trapp M, Schroeder H, et al. Transarterial chemoembolization for hepatocellular carcinoma: volumetric and morphologic CT critreia for assessment of prognosis and therapeutic success - results from a liver transplantation center. Radiology 2000;214:349-57.
32. Vogl TJ, Naguib NN, Nour-Eldin NE, et al. Review on transarterial chemoembolization in hepatocellular carcinoma: Palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol 2008; Oct 1 pub ahead of print. 
