Intratumor cisplatin nephrotoxicity in combined laser-induced thermal therapy for cancer treatment.

INTRODUCTION: Thermal ablation of tumors by Nd:YAG laser has been growing as a multidisciplinary subspecialty defined as laser-induced thermal therapy (LITT), and has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent cancer. Previous studies have shown that adjuvant chemotherapy can potentiate laser thermal ablation of tumors leading to improved palliation in advanced cancer patients. OBJECTIVE: Evaluate nephrotoxicity by early markers of renal function in treating head and neck cancer using intra-tumor injections of cisplatin combined with laser-induced thermal therapy (CDDP-LITT). METHODS: Nine patients with recurrent head and neck tumors were treated by CDDP-LITT in order to determine nephrotoxicity related to this synergistic association. Among the tests requested to detect early were creatinine, magnesium, creatinine clearance, serum urea-BUN, type I urine, and proteinuria at 24 hours. RESULTS: Twelve recurrent tumors in nine patients were treated by CDDP-LITT. Pain was the major complaint (four patients), while other symptoms included dysphagia, dyspnea, bleeding, and difficulties in chewing. Fifteen laser procedures were performed and maximal CDDP dose was 50 mg. None of the markers for nephrotoxicity showed changes at these levels of CDDP intra-tumor injections. CONCLUSION: This initial experience with (CDDP-LITT) indicates both safety and therapeutic potential for palliation of advanced head and neck cancer. However, safety and feasibility must be confirmed by longer follow-up and further escalation of CDDP doses in a Phase I study to determine maximum tolerated dose (MTD) and demonstrate tangible benefits for patients. Lasers Surg. Med. 49:756-762, 2017. © 2017 Wiley Periodicals, Inc.

Update on laser photochemotherapy: an alternative for cancer treatment.

Although major progress has been made in surgery, radiation, and chemotherapy for the treatment of malignancy during the last 20 years, there has been little improvement in the survival of patients with recurrent or advanced head and neck cancer. Because of the ease and accessibility for surgery and their loco-regional biological behavior, head and neck cancers serve as an ideal model to test combined laser energy delivered via interstitial fiberoptics and chemotherapeutic agents activated by photo-thermal energy as an alternative, less invasive treatment for cancer. A number of investigators have shown that anthracyclines and cisplatin are likely candidates for light or heat activation in cancer cells. Maximum tolerated dose followed by photochemical and thermal activation via laser fiberoptics can improve treatment by sensitizing tumor response. The higher intratumor drug levels compared to systemic drug administration along with laser activation should also reduce systemic toxicity. In this article the authors analyze the concept of combining anti-cancer drugs and laser therapy and review the clinical application. In summary, the literature available suggests photochemotherapy with currently approved drugs and lasers may soon become an attractive alternative for cancer treatment.

Outcomes of laser thermal therapy for recurrent head and neck cancer.

OBJECTIVE: To review the outcomes of a phase II study using laser-induced thermal therapy (LITT) as a palliative treatment for 106 patients with recurrent head and neck tumors. STUDY DESIGN: Retrospective study. SETTING: Tertiary hospital in the United States. SUBJECTS AND METHODS: The primary endpoints were tumor response and survival. Prognostic values were assessed by the Kaplan-Meier method. RESULTS: The best results were seen in oral cavity tumors, in which mean survival was 29.1 months, as compared to neck tumors (mean 14.4 +/- 6.9 months; range 7.5-20.7 months; with a 95% confidence interval). Further analysis showed that clinical factors such as gender, smoking, and alcohol use were not indicators of poor prognosis, whereas neck disease and tumor stage at first treatment were relevant factors. CONCLUSION: In this study, 40 out of 106 patients treated by LITT remained alive at the end of our follow-up, and a complete response was seen in 24 (22.6%) patients. The highest response rate was seen in oral cavity tumors, which suggests that tumor location at this site may be a predictor of favorable outcome with LITT.

Laser-induced thermal therapy and cisplatin for recurrent head and neck cancer: a case characterized by an unusually long disease-free survival.

Recurrent squamous cell carcinoma after major surgery and microvascular reconstruction with a free-flap transfer is difficult to handle via conventional treatment methods. Based on our experience with laser-induced thermal therapy for recurrent head and neck tumors, we explored an aggressive treatment protocol using laser thermal ablation with concurrent cisplatin chemotherapy as a minimally invasive option for the treatment of a patient with recurrent squamous cell carcinoma of the neck who had previously undergone a reconstructive free-flap transfer. Because of the very favorable outcome we observed in this patient with this combined treatment modality, we report this case, and we review some aspects of the treatment proposed. The remarkable survival of this patient suggests that the combination of laser-induced thermal therapy and chemotherapy warrants further investigation as an alternate treatment for patients with recurrent head and neck cancer.

Retention of intratumor injections of cisplatinum in murine tumors and the impact on laser thermal therapy for cancer treatment.

Recent studies using murine models of human squamous cell carcinoma (SCCA) have revealed a significant improvement in survival and cure rate of animals transplanted with human SCCA when treated with a combination of intratumor injections of chemotherapy and laser induced thermal therapy (LITT). These preliminary results suggest that this novel combination therapy may lead to improved clinical response compared to either treatment modality alone. Using a murine model of human SCCA we investigated two different modes of intratumor injection of cisplatin: a sustained-release cisplatin gel implant (CDDP/gel) versus cisplatin in solution (CDDP) at varying doses (range 1-3 mg/ml). In addition, we tested CDDP/gel combined with LITT. Results showed optimal drug concentration (30-300 nM) at tumor margins up to 4 h after injection of CDDP/gel implant compared to 3 nM at 5 min after injection with CDDP solution. Combined CDDP/gel and laser therapy significantly decreased tumor volume (P<0.05), with recurrence in only 25% of animals tested, compared to 78% tumor regrowth after LITT alone. These results suggest that laser chemotherapy may be an effective treatment for head and neck SCCA.

Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy.

OBJECTIVES: Laser-induced thermal therapy (LITT) for cancer is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, and so on) is directly applied into a tumor at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real- or "near" real-time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. The objective of this study is to report UCLA's experience using UTZ monitoring of Nd:YAG laser thermal ablation of malignant cervical adenopathy in a phase II study. STUDY DESIGN: The authors conducted a retrospective study of patients treated at a tertiary medical center. METHODS: Forty-seven patients with a total of 55 neck tumors were treated on an outpatient basis in the operating room using UTZ for image-guided laser interstitial thermal therapy. Laser energy was delivered through an SLT Nd:YAG laser powered at 30 W (power density: 2,200 J/cm). RESULTS: Eleven patients had a complete response ranging from 5.5 to 90 months (mean, 22.1 months). Based on the findings of this study, it was possible to show that proximity to the carotid artery was the most relevant factor in projecting patient survival. Patients' individual treatment analysis and final outcome are further discussed. CONCLUSIONS: LITT ablation of malignant cervical adenopathy was considered safe and feasible. No intraoperative complications occurred. Further development of this technique applying laser energy delivery to mathematical imaging models should lead to more effective tumor palliation as an alternative to surgery.

Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer.

OBJECTIVE: The aim of this work was to report initial findings on the clinical application of intratumor injection of cisplatin in a gel (CDDP/gel) combined with laser-induced thermal therapy (LITT) for cancer treatment in a single patient with advanced stage disease. BACKGROUND DATA: LITT with the neodymium:yttriumaluminum- garnet (Nd:YAG) laser via fiberoptics is a precise, minimally invasive alternative for thermoablation of unresectable or recurrent head and neck neoplasms, but recurrence is often seen at the treatment margins. Combining intratumor chemotherapy with interstitial laser should be most effective using drugs with thermally enhanced toxicity, such as cisplatin. The CDDP/gel therapeutic implant was expected to retain a higher concentration of cisplatin in the tumor margins for improved LITT treatment of the patient presented. METHODS: In this case report, the cisplatin dose was 0.25 mL gel/cm(3) tumor volume (20 mg of CDDP) followed by LITT (Nd:YAG laser, 50 W, PD = 2,200 J/cm(2)) after the chemotherapy session. RESULTS: The patient responded with local tumor eradication, and no signs of systemic toxicity were observed related to this therapy. However, the patient developed progressive metastatic disease in the lungs and died 2.5 months later. CONCLUSIONS: This is a report of a patient with an accessible solid tumor who was treated with intratumor injection of CDDP/gel followed by LITT, which proved to be feasible. Based on preclinical evidence obtained at UCLA and the results of this study, we are encouraged to continue our refinement of LITT combined with chemotherapy for cancer treatment.

Nd:YAG laser therapy for palliation of recurrent squamous cell carcinomas in the oral cavity.

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the outcome of laser photo-thermoablation for palliation of recurrent squamous cell tumors of the oral cavity. STUDY DESIGN/PATIENTS AND METHODS: Seventeen patients were treated with the Nd:YAG laser (power output was 50 W) delivered through a curved oral handpiece. RESULTS: Ten patients are alive, 7 with tumor remission, and 3 with persistent disease with an average follow-up of 16 months (range = 2-36). A total of 29 tumor sites received laser treatment with 17 (58%) completely ablated. Stratified by tumor site Nd:YAG treatment led to complete local response in 8/10 buccal mucosa, 2/5 retromolar trigone, 2/2 tongue, 2/5 gingiva, 1/2 floor of mouth, 2/4 hard palate. CONCLUSIONS: Nd:YAG laser treatment of recurrent oral cavity squamous cell carcinoma can be performed safely and repeated as needed to achieve tumor palliation. However, extended follow-up may be needed before convincing evidence of long-term therapeutic benefits is obtained.