Researchers Use Laser Against Head and Neck Cancer

laser-induced thermal therapy
Experimental technique combines localized chemotherapy and laser applications to make treatment less invasive and completely remove tumors (photo: Leo Ramos/ Pesquisa FAPESP magazine)

To offer advanced cancer patients a treatment that is less aggressive than conventional therapy, researchers at the Federal University of São Paulo (UNIFESP) in Brazil are experimentally applying an innovative technique in the institution’s outpatient clinic that uses infrared light to remove solid head and neck tumors.

Introduced and refined by UNIFESP’s Otolaryngology & Head and Neck Surgery Department under the aegis of the FAPESP-funded Thematic Project “Combination of cisplatin and laser thermal therapy for head and neck cancer”, the technique consists of tumor thermal ablation – evaporation of water from the cellular compartment of solid lesions, resulting in the elimination of tumoral tissue – applied in parallel with intratumoral injections of the chemotherapy drug cisplatin.

“This outpatient practice enables us to improve certain morbid conditions in the patient, such as bleeding, pain due to tumor compression, local infection and odor, that affect quality of life in an advanced disease,” said Marcos Bandiera Paiva, who brought the technique to Brazil after 20 years of research at the University of California Los Angeles (UCLA), where more than 500 patients have successfully undergone the procedure to date.

Known as laser-induced thermal therapy (LITT), the technique is used at UCLA for thermal ablation of brain, breast, lung and prostate tumors. With support from FAPESP, the treatment has been enhanced by local injections of the chemotherapy drug cisplatin in conjunction with LITT, an innovation compared with the treatment administered to patients in the US, which consists only of LITT.

The advantage of combining cisplatin with LITT lies in its broader scope. The maximum levels of energy during tumor removal are observed in the central area of the tumor, which is subjected to temperatures in excess of 100°C, while the edges are treated at subtherapeutic levels, with the laser at 40°C-60°C, permitting recurrence of tumor growth. Injections of cisplatin on the tumor’s perimeter favor localized tumor eradication – according to Paiva, this is because the toxicity of cisplatin increases when it is heated on the edges of the tumor during laser application.

“The heat exacerbates the drug’s capacity to penetrate the cell membranes,” Paiva said. “Tumor cells are made more permeable to cisplatin, increasing the toxicity of local chemotherapy and leading to more effective tumor eradication.”

Unlike radiotherapy, which has sufficient energy to ionize atoms and molecules, damaging healthy cells and affecting genetic material, the outpatient procedure used at UNIFESP can be repeated after a three-week interval, guaranteeing better results and even complete removal of the tumor.

Protocol

Patients who may be candidates for the treatment are first screened. Among those eligible are individuals who have not responded to conventional treatment, such as systemic chemotherapy or radiotherapy, and cannot undergo surgery. Their clinical condition must be good enough to safely receive general anesthesia.

“The technique introduces the innovative concept of a minimally invasive procedure using intratumoral injections of high doses of chemotherapy concurrently with local hyperthermia. This is an experimental palliative treatment for local control of the disease in selected patients. A cure isn’t guaranteed, but the treatment does considerably improve specific symptoms,” Paiva said.

“The treatment also offers a certain amount of hope for patients because as a localized technique, it could be associated with innovative systemic therapies for head and neck cancer, such as the administration of cetuximab.”

Approved in 2010 by ANVISA, Brazil’s National Health Surveillance Agency, cetuximab is a monoclonal antibody with a more targeted action – in this case, as an inhibitor of epidermal growth factor receptors (EGFRs). Cetuximab binds to these receptors, turning off the signal that causes cells to divide. This reduces the invasion of normal tissue by malignant cells and stops the cancer from spreading to new areas. The drug also inhibits the capacity of malignant cells to repair the damage caused by chemotherapy or radiotherapy.

The researchers continue to pursue ways of refining LITT as an outpatient procedure, including possible applications in the treatment of other diseases.

“We’ve shown that treatment of tumor edges in patients with advanced head and neck cancer combined with local injections of cisplatin and followed by LITT for thermal ablation isn’t toxic, improves quality of life and is effective,” Paiva said. “The technique can be enhanced to benefit even more people. For example, connecting an optical fiber to a laser can give us surgical access to any lesion in the human body to apply a minimally invasive outpatient technique that reduces the cost to the national health system.”