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.

Isolated inverting papilloma of the sphenoid sinus.

OBJECTIVES/HYPOTHESIS: Primary inverting papilloma of the sphenoid sinus is rare. We present a case of inverting papilloma with isolated involvement of the sphenoid sinus and discuss the incidence, clinical presentation, radiographic features, histological findings, and management of patients with this disease. STUDY DESIGN: Case report. METHODS: The medical records, films, and pathology slides of a patient with isolated inverting papilloma of the sphenoid sinus seen at University of California Los Angeles Medical Center were reviewed. The clinical presentation, radiographic features, histopathological findings, treatment, and outcome of the case were examined. RESULTS: A single case of inverting papilloma with isolated involvement of the sphenoid sinus is presented. Headache and diplopia were the presenting complaints, as is often seen with other isolated sphenoid sinus lesions. Endoscopic intranasal sphenoid sinusotomy was performed, and no evidence of recurrent disease has been seen after 6 months of follow-up. CONCLUSIONS: Isolated inverting papilloma of the sphenoid sinus is a rare phenomenon. In contrast to the vast majority of cases that present with nasal complaints (i.e., unilateral nasal obstruction, epistaxis) because of involvement of the lateral nasal wall, the clinical presentation of inverting papillomas confined to the sphenoid sinus is often nonspecific and insidious, with visual deficits being the predominant feature. Nevertheless, functional endoscopic intranasal sphenoidotomy remains an effective mode of treatment for patients with these lesions.

The role of intratumoral therapy with cisplatin/epinephrine injectable gel in the management of advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. DESIGN: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. SETTING: Tertiary referral centers in North America and Europe. PATIENTS: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. INTERVENTION: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. MAIN OUTCOME MEASURES: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. RESULTS: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P<.001). Tumor response and patient benefit were significantly correlated (P=.006): 47% (17/36) of patients with target tumor responses achieved a rigorously defined benefit based on a prospectively selected treatment goal vs 15% (22/142) of nonresponders. CONCLUSION: Cisplatin/epinephrine injectable gel reduces tumor burden, ameliorates tumor symptoms, and provides a new therapeutic option for treating patients with squamous cell carcinoma of the head and neck.

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.

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.

Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America.

BACKGROUND: The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were < or =20 cm(3); most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. DOSE: 0.25 mL CDDP/epi gel/cm(3) tumor volume. TREATMENTS: < or =6 weekly intratumoral injections in an 8-week period. PRIMARY OUTCOMES: target tumor response and symptom relief. RESULTS: During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p <.001). Responses occurred within a median of four treatments (range, 2-6) and were durable (median, 95 days; range, 34-168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p =.036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3-12 weeks. Renal and hematologic toxicities were rare. CONCLUSIONS: This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors.