Marcos B. Paiva

End results of a prospective trial on elective lateral neck dissection vs type III modified radical neck dissection in the management of supraglottic and transglottic carcinomas

Either modified type III radical neck dissection (MRND) or lateral neck dissections (LNDs) are considered valid treatments for patients with laryngeal carcinoma with clinically negative neck findings (N0). The object of this prospective study was to compare complications, neck recurrences, and survival results of elective MRND and LND on the management of laryngeal cancer patients.

Hypericin: A New Laser Phototargeting Agent for Human Cancer Cells†‡

Laser activation of anthracycline‐related drugs combines chemotherapy with photoablation for improved treatment. Hypericin, a structurally related anthraquinone, was tested for laser activation and cytotoxicity in human cancer cells. Viability of P3 squamous cell carcinoma cells incubated with 1 to 20μg/mL hypericin was reduced by more than 95% after 1 minute exposure at 4°C to an argon laser (514 nm, 5 W), a KTP‐532 laser (532 nm, 5 W), or a 20‐A xenon lamp. Viability was reduced over 90% in six human carcinoma, sarcoma, and melanoma cell lines by this combined treatment, but only trace toxicity was seen after separate exposure to hypericin or light alone. These results show that hypericin is a sensitive agent for phototherapy of human cancer cells in vitro and indicate that this drug may be useful for tumor targeting via minimally invasive imaging‐guided laser fiberoptics.

Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy.

Tissue uptake and biodistribution of hypericin was measured in rabbits and in nu/nu mice xenografted with P3 human squamous cell carcinoma to assess the value of this dye as an in vivo sensitizer for laser photoinactivation of solid tumors. Hypericin has absorption maxima at 545 and 590 nm with a fluorescence emission peak at 640 nm in ethanol. Dye uptake after intravenous injection was tested at 4 and 24 hours in rabbit tissues by ethanol extraction and quantitative fluorescence spectrophotometry. Maximum dye levels were seen at 4 hours in most vascular organs with lung having fivefold higher uptake than spleen followed by liver, blood, and kidney. Mice were examined after 2, 4, 6, 8, and 24 hours and after 3 and 7 days for dye uptake. The peak concentration of hypericin in murine organs was reached at 4 hours with uptake per gram of tissue as follows: lung>spleen>liver>blood>kidney>heart>gut>tumor>stomach>skin>muscle>brain. Elimination of hypericin was rapid in most murine organs with residual dye under 10% of maximum by 7 days compared to 25% to 30% retention for the squamous cell tumors and several normal tissues. These results suggest that hypericin may be a useful photosensitizer for KTP/532 laser interstitial therapy of human cancer.

Intratumoral hypericin and KTP laser therapy for transplanted squamous cell carcinoma.

Objectives/Hypothesis To test intratumoral photodynamic therapy (IPDT) as a new treatment for squamous cell carcinoma in a preclinical tumor model.

Palliative laser therapy for recurrent head and neck cancer : A phase II clinical study

Objectives: Laser therapy is becoming a more precise, minimally invasive alternative for tumor ablation. Recent reports confirm successful palliation of pain and functional disabilities in patients with advanced deep carcinoma of the head and neck using interstitial laser phototherapy (ILT). Study Design, Patients, and Methods: The current study describes an ongoing Phase II trial of neodymium/yttrium‐aluminum‐garnet (Nd:YAG) laser therapy for palliation of advanced head and neck cancer. A total of 40 advanced cancer patients have been entered into this protocol (25 men and 15 women). Results: Nineteen of these patients had no evidence of recurrence after ILT with an average follow‐up of 11 months (range, 2 to 24 mo). Currently, 19 of these patients are alive, 14 with tumor remission and six with persistent disease. A total of 79 tumor sites received ILT with 43 (54.5%) completely ablated. Stratified by tumor site, ILT led to a complete response in 21 of 24 in the oral cavity, eight of 28 neck tumors, four of 10 in skin, and 10 of 17 in other sites. The procedure was well tolerated in most cases and was repeated at intervals in patients with residual disease or recurrences for a total of 118 laser treatments (average, 2.95 treatments per patient). Conclusions: The results suggest that ILT can be performed safely and repeated as needed, and may be less costly than conventional surgery for head and neck cancer. However, additional follow‐up is needed to obtain convincing evidence of long‐term therapeutic benefits.

Dynamic MRI-guided interstitial laser therapy: A new technique for minimally invasive surgery

Interstitial laser therapy (ILT) is a promising therapeutic technique in which laser energy is delivered percutaneously to various depths in tissue. In this study, the authors compared high‐speed magnetic resonance imaging (MRI) of ILT in tissues during treatment with post‐treatment histopathologic specimens. The use of 5‐second MRI scans allowed detection of thermal damage by the 1064‐nm neodym‐ium:yttrium‐aluminum‐garnet laser in ex vivo liver and brain tissues. These tissues were treated by ILT with 20 W of laser output for 5 to 30 seconds via a 600‐μm fiberoptic inserted 1 cm into the specimens at a power density of 7 kW/cm2 at the tip of the bare fiber.

Anthrapyrazoles and Interstitial Laser Phototherapy for Experimental Treatment of Squamous Cell Carcinoma

Interstitial laser therapy (ILT) is an effective palliative treatment for advanced head and neck cancer, but recurrence often is seen at the margin. The objective of the current study was to test combined drug and laser therapy as an experimental approach for improved treatment of human squamous cell carcinoma (SCCA). Human SCCA tumor transplants were grown in nude mice and injected with the photosensitive anthrapyrazole CI‐941 before ILT. Intralesional drug injections alone at levels ranging from 60 to 1200 μg/gm of tumor induced a growth delay at the higher doses, but recurrence was seen in all 35 tumors tested. SCCA tumor transplants injected with 240 μg/gm CI‐941 followed after 4 hours by ILT with the KTP532 laser led to a complete response rate of 72% (21/29) compared with 45% (13/29) for ILT alone. Laser chemotherapy was a significant improvement compared with ILT when partial and complete responses were combined (P < 0.03). The results provide preclinical evidence that laser chemotherapy may become a useful minimally invasive treatment for advanced squamous cell carcinoma of the head and neck.

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.

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA‐SO‐P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.

Cisplatinum and interstitial laser therapy for advanced head and neck cancer: A preclinical study

Direct intratumor injection of cisplatinum (CDDP) and laser therapy were tested for improved treatment of squamous cell carcinoma (SCCA).