Photodynamic therapy and the treatment of head and neck neoplasia

Objective: To present the theory, technique, and results of photodynamic therapy for the treatment of oral, laryngeal, and head and neck cancers. Study Design: Retrospective review of the literature of more than 500 patients with head and neck cancer treated with photodynamic therapy, as well as a retrospective review of the author's 107 patients treated with photodynamic therapy for head and neck neoplasia between 1990 and 1997. Methods: The literature was retrospectively reviewed, as were patient records, and tabulaled for age, sex, site, and staging of lesions, with special focus on post-photodynamic therapy treatment outcome, long-term disease-free survival, and complications. Results: Twenty-five patients with carcinoma in situ and T1 squamous cell carcinoma of the true vocal cord who underwent photodynamic therapy treatment for cure obtained a complete response after a single photodynamic therapy treatment. Only one patient has had recurrence to date, with a cure rate to 79-month follow-up of 95%. Twenty-nine patients with carcinoma in situ and T1 recurrent squamous cell carcinomas of the oral cavity and tongue were treated. All obtained a complete response after a single photodynamic therapy treatment; however, five patients developed local recurrence with follow-up to 70 months, for an 80% cure rate. A review of 217 patients with early squamous cell carcinomas of the head and neck treated with photodynamic therapy in the literature demonstrated an 89.5% complete response rate. The most common complication in these patients was limited prolonged skin photosensitivity without any permanent sequelae. Conclusions: Photodynamic therapy is effective for treating carcinoma in situ and T1 squamous cell carcinoma of the larynx and oral cavity and may be of benefit as an adjuvant intraoperative treatment of stages III and IV tumors of the head and neck in conjunction with surgery and radiation therapy to improve cure rates. Further controlled studies need to be performed to further demonstrate the effectiveness of photodynamic therapy and the treatment of head and neck cancers.     

Early vocal cord carcinoma in obese patients: A surgical lesion

Early epidermoid carcinoma of the vocal cord is treated successfully by radiation therapy with high 5-year survival rates, low morbidity, and preservation of excellent voice quality in most cases. Typically, surgery is reserved for salvage of radiation failure and provides overall 5-year survival rates of 98% and 90% for T1 and T2 lesions, respectively. The extremely obese patient, often with a short neck and excessive amounts of subcutaneous fat, is difficult for both radiotherapist and surgeon to diagnose and treat. The recent observation of an unusually high rate of radiotherapy failure in a cluster of obese patients with early vocal cord cancer called attention to this problem. Because the larynx is near the thoracic inlet in obese patients, they are not suitable for administration of radiotherapy by accurate opposed lateral portals. The patients reported herein were treated entirely with anterior oblique portals. Of the five obese patients who underwent primary radiation therapy for early vocal cord cancer, three developed recurrent disease (60%) and a fourth developed a severe perichondritis requiring tracheostomy. Two patients with recurrent disease were successfully salvaged with total laryngectomy, while the third patient refused surgery and died 2 years later. The sixth patient was treated by partial laryngectomy with imbrication reconstruction and is alive and without evidence of disease 2 years following surgery. Recurrence rates and complication rates following primary radiation therapy for early vocal cord cancer appear to be unacceptably high in obese patients treated with anterior oblique portals. Therefore, we recommend primary conservation laryngeal surgery for obese patients with early vocal cancer who cannot undergo “standard” radiotherapeutic techniques.     

Laser excision of early vocal cord carcinoma: indications, limitations, and precautions

Forty-six patients referred for laser surgery of early vocal cord carcinoma were treated by laser excisional techniques with or without radiotherapy. Mean follow-up was 3.5 years. There was a 90% rate of carcinoma control (18 of 20 patients) in patients with untreated mid-vocal cord T1 carcinomas without involvement of the anterior commissure or vocal process or deep muscle invasion. Larger, more invasive T1 vocal cord tumors (13 patients) had laser excision followed by radiotherapy without recurrence. Careful patient selection and accurate histopathologic evaluation are key elements for successful treatment.     

Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan<Superscript>®</Superscript>) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients

Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin and mucosa. After the injection of a photosensitising agent, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy tumour cells. From November 2003 to July 2007, a total of 35 patients with recurrent squamous cell carcinoma or secondary tumours of the head and neck region were treated with PDT at the German Armed Forces Hospital in Ulm. These patients had failed or found unsuitable for other treatments. Meta-tetrahydroxyphenylchlorin (mTHPC), known under the trade name of Foscan^®, was used as the photosensitising agent. Local control was achieved in 21 patients (60%) and partial remission in 10 patients (28.5%). Four patients (11.5%) did not respond to PDT treatment. The mean duration of overall survival was 401.45 (±321.2) days, median was 356 after the completion of treatment. The mean duration of recurrence-free survival was 327.7 (±131.1) days, median was 181 for patients with complete remission. None of the patient developed serious complications. Photodynamic therapy is an important treatment option for patients who present with recurrent carcinoma or secondary tumours of the upper aerodigestive tract and who have failed or unsuitable for other treatments. Due to the excellent treatment results that have been achieved so far, PDT may in the future also play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx.     

Laser therapy for T1 glottic carcinoma of the larynx

We treated 21 previously untreated T1 or tumor in situ squamous cell carcinomas of the true vocal cords by carbon dioxide laser excision. The mean follow-up was 42 months, with a range of 26 to 64 months. Recurrent vocal cord carcinomas, with an average interval to recurrence of 21 months developed in four patients. Three of the four recurrences involved the anterior portion of the true vocal cord, including the anterior commissure. One of the patients with recurrence was treated again with the laser, and the other three underwent radiotherapy. All four patients are alive and have retained their larynges. Laser excision of selected T1 and in situ carcinomas of the true vocal cords is a cost-effective and viable alternative to radiotherapy or more radical surgical therapy.     

Neuroendocrine tumor of the larynx. Small cell carcinoma

A 69-year-old patient diagnosed, in 1985, of squamous cell carcinoma of the right vocal cord (T1, N0, M0) was treated with cordectomy and radiotherapy. Eleven years later he presented with a larynx tumor of the glotto-subglottic region. Histopathological examination stated a small cells neuroendocrine tumor. We contribute with one new case to those rare laryngeal tumors, which we see often published in the specialty journals, probably due to the wide employed immunohistochemistry dyes.     

Results of treatment of 584 laryngeal cancers at the Ear-Nose-Throat Clinic of Marburg University

The results in the management of 460 vocal cord carcinomas and 124 supraglottic carcinomas are reported. Of the vocal cord carcinomas, 63.3% were diagnosed in the early Tis and T1 stage. Seventy-six tumors were resected endoscopically, 128 by laryngofissure and chordectomy. Not one of these patients has lost his life, larynx or voice. In bilateral tumors of the T1b category, 2 patients developed local recurrences and lost their larynx. Sixty-two carcinomas of the Tis, T1a and T1b categories were irradiated primarily. Two of these patients died and 14 underwent laryngectomy for local recurrence. In T2 carcinomas a 5-year cure rate of 87.5% was achieved by vertical partial resection. The 5-year cure rate after laryngectomy or laryngectomy with neck dissection for T2N0 and T2N+ carcinoma was 86.2% and 75.0% respectively. Most treatment failures were due to late metastases which could not be controlled. In T3 carcinomas with a 5-year cure rate of 71.4% (N0) and 70.0% (N+) respectively, treatment failures were also mainly seen in patients with N0 necks where we did not carry out a prophylactic neck dissection. Five-year survival rates for primary surgery in supraglottic T1-T4 carcinomas were 100%, 82.4%, 84% and 58.3%. The widely hel opinion that laryngeal carcinoma should only be subjected to surgery for irradiation failure can no longer be sustained. More patients lose their larynx or their life after irradiation of small carcinomas than after primary surgery. Furthermore, too many patients have to undergo two major cancer treatments (irradiation and salvage surgery). In larger carcinomas radiotherapy produces a lower survival rate and too many patients require two stressful cancer therapies. The number of retained larynges is not substantially higher than with primary surgery. Primary irradiation for selected cases should be part of every therapy concept that aims at an adequate and individual treatment of every patient.     

Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions

Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC). Thirty-two patients received laser therapy as their first therapy, whereas 11 patients had had previous radiation therapy for laryngeal carcinoma (n = 9) or CIS (n = 2). Recurrence after initial laser therapy necessitating re-treatment (a second laser treatment or radiotherapy) occurred in nine out of 32 patients (28 per cent), thus 23 (72 per cent) were maintained free of disease during the follow-up period. Besides the 32 patients without previous therapy, patients who had already undergone radiation therapy were also included in this study. In this group there were nine patients with SCC, one patient with CIS and one with dysplasia. They all underwent laser therapy. Four were free of disease during follow-up (36 per cent) and seven developed recurrences. Six (58 per cent of all patients with previous radiation therapy) underwent total laryngectomy.     

Predicting radioresistance in early glottic squamous cell carcinoma by DNA content

Nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types. Current data on the role of DNA content in head and neck carcinoma are conflicting and incomplete. To evaluate the role of DNA content in predicting radioresistance, 29 patients with T1N0M0 squamous cell carcinoma of the glottic larynx who had undergone uniform curative radiotherapy and whose clinical outcome was known had flow cytometric analysis for DNA content performed on their tumors with paraffin-embedded archival tissues. Five aneuploid lesions and 24 diploid lesions were identified. All aneuploid lesions occurred in radioresistant tumors. The probability of an aneuploid tumor failing radiotherapy was highly significant at p = .016. No DNA discordance was found in a sampling of half of the radioresistant lesions' pretreatment and recurrent specimens, for a 100% predictive value of moderate statistical power. On the basis of these findings, patients with aneuploid T1 glottic lesions should be referred for primary surgical therapy.     

Meta-tetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck

OBJECTIVE: Photodynamic therapy (PDT) is a relatively new treatment modality for various types of cancer, including cancer of the head and neck. The advent of the second-generation photosensitizers such as meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foscan; Scotia Pharmaceuticals, Stirling, Scotland), which are more effective and less phototoxic to the skin than their forerunners, now makes this treatment a feasible alternative to surgery or radiotherapy in specific cases. To evaluate the long-term outcome of this therapy for squamous cell carcinomas of the head and neck, we treated patients with PDT using mTHPC. DESIGN: Prospective study. SETTING: Tertiary cancer referral center. PATIENTS: Twenty-five patients with 29 T1-T2 N0 tumors of the oral cavity and/or oropharynx. INTERVENTION: Photodynamic therapy. MAIN OUTCOME MEASURE: Complete local tumor remission. RESULTS: The mean follow-up of the patients after treatment was 37 months. In 25 (86%) of 29 tumors, a complete remission of the primary tumor was obtained. In the 4 recurrences, salvage was achieved by conventional therapy. In none of the patients was any long-term functional deficit detected. CONCLUSIONS: This study confirms that PDT is a powerful treatment modality that could be considered as an alternative to surgery or radiotherapy in specific cases of head and neck cancer. The major advantage of PDT over these conventional therapies is the reduction in long-term morbidity. Radiotherapy or surgery could be reserved for salvage therapy in the event of a recurrence or second primary tumors.     

Mucoepidermoid cancer of the larynx. Case report and review of the literature]

Mucoepidermoid carcinoma (MEC) is classified among the salivary gland tumours and is most commonly found in the parotid gland. It rarely occurs in the larynx. There have been only 87 cases of laryngeal MEC reported in the literature. We report on an MEC of the vocal cord in a 75-year-old man, with a thickened right vocal cord without any loss of movement. The initial diagnosis was squamous cell carcinoma. One year after radiotherapy a tumour recurrence developed. Because the patient refused to laryngectomise, a tumour resection with the CO2 laser was performed twice. To date, the patient has been free from disease for more than five years. The true incidence of this type of neoplasm could be higher than is believed because of its frequent misdiagnosis as squamous cell carcinoma.     

Laryngeal structure following microcauterization.

This paper supports and reaffirms the objectives of contemporary laryngology in the treatment of cancer of this organmthese objectives are, first and foremost, the eradication of the tumor, and second, the preservation of function. A relatively recent contribution to the "state of the art" has been the development of the field of microlaryngology. The introduction of the surgical microscope has provided the laryngologist with better means to judge the type, localization and extent of neoplastic lesions. Reports indicate that superficial limited carcinomas of they larynx with good vocal cord mobility can be successfully treated by vocal cord stripping and/or radiotherapy. This paper presents the serious challenge posed by these limited tumors when they recur after radiotherapy. In a selected number of these patients radical surgery has been prevented by treating these recurrent tumors with the microcautery. Some of these patients, so treated, habe been free of disease for more than three years after their recurrent tumors were destroyed with the microcautery. During this time these patients have enjoyed adequate voices.     

Plattenepithelkarzinome im Kopf-Hals-Bereich

Introduction

Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin or mucous membranes. After the injection of a photosensitiser, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy the tumour cells.

Patients and methods

From November 2004 to February 2006, a total of 24 patients with recurrent or secondary tumours after squamous cell carcinoma of the head and neck were treated with PDT at the German Armed Forces Hospital in Ulm after other treatment options had failed. Meta-tetrahydroxyphenyl chlorin (mTHPC), known under the trade name of Foscan, was used as the photosensitising agent.

Results

Complete remission was observed in 12 patients (50%) and partial remission was seen in nine (37.5%). Three patients did not respond to treatment. The mean duration of overall survival was 305.7 days (±199.4) after completion of treatment. The mean duration of recurrence-free survival was 302.7 days (±144.9) for patients with complete remission. There were no serious complications.

Conclusions

Photodynamic therapy is an important treatment option for patients who develop recurrent or secondary tumours after squamous cell carcinoma of the upper aerodigestive tract and fail to respond to other treatments. In addition, PDT may play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx in the future.     

Return of vocal cord movement: an independent predictor of response to nonsurgical management of laryngeal cancers

OBJECTIVE: To determine whether return of vocal cord function after treatment of T2b/T3 laryngeal carcinoma is an independent prognostic factor for locoregional recurrence. STUDY DESIGN: A retrospective review of patients treated with radiation +/- chemotherapy between 2000 and 2005 for T2 with vocal cord paresis and T3 laryngeal carcinoma was conducted. METHODS: Only those patients obtained from the tumor registry with pre-and posttreatment video stroboscopies were included. Patients' charts were reviewed for local and regional recurrence after treatment. Fisher's exact test was used to determine significant association between recurrence and possible risk factors. RESULTS: Fourteen patients met the inclusion criterion. Six patients had T2 lesions with vocal cord paresis, and eight patients had T3 lesions. Fifty percent of patients with T2 and 75% of patients with T3 lesions had return of vocal cord function after treatment. Five of 14 patients did not have return of vocal cord function, and of these, 100% had locoregional recurrence. Of the nine patients who had return of vocal cord movement, none of the patients had recurrence. The proportion of recurrence was significantly higher for those whose vocal function did not return compared with the patients whose vocal function returned (100% vs. 0%, P < .01). CONCLUSION: The immobile vocal cord is associated with a worse prognosis and is therefore factored into the American Joint Commission on Cancer staging for laryngeal tumors. We show that vocal cord immobility is an independent prognostic factor of recurrence even after treatment and can predict treatment failure in T2 and T3 lesions of the larynx.     

Laryngeal adenocarcinoma, not otherwise specified, treated with carbon dioxide laser excision and postoperative radiotherapy.

Glandular carcinomas of the larynx are aggressive neoplasms that comprise less than 1% of all laryngeal malignancies. Adenocarcinoma, not otherwise specified, is the most common histologic type. The rarity of these lesions has prohibited clarification of definitive therapy. Traditionally, radical surgery is performed because of the usually high stage at presentation and the relative insensitivity to radiotherapy. A case of glottic T1 adenocarcinoma, not otherwise specified, is reported. The tumor presented clinically as a vocal fold granuloma. The treatment modalities included endoscopic excision with the carbon dioxide laser and postoperative radiotherapy. The patient has been followed up for 39 months without evidence of recurrence or metastases. The current literature is reviewed in regard to treatment of laryngeal glandular carcinomas.     

The results of radiation and surgical treatment of early vocal cord carcinoma (T1a, T1b)

Results of surgery treatment from the external access and radiotherapy in early, stage of vocal cords carcinoma were presented. Clinical material consisted of 94 cases with squamous cell carcinoma of vocal cords with stage T1a and T1b treated in Szczecin University Department of Otorhinolaryngology from 1987 to 1996. 51 cases were operated on (26 by chordectomy and 25 by frontolateral laryngectomy). Radiotherapy was applied in 43 patients. The 3 and 5 years' survival rate in the surgery group was 97% and after radiotherapy 88 to 80%. The functional results were also presented. It was concluded that the mode of treatment in early stages of vocal cord carcinoma should be individualized.     

Photofrin-mediated photodynamic therapy for treatment of aggressive head and neck nonmelanomatous skin tumors in elderly patients

OBJECTIVES/HYPOTHESIS: Aggressive nonmelanomatous skin tumors (basal cell carcinoma, squamous cell carcinoma, and Bowen's disease) of the head and neck often occur in Caucasian elderly patients because of prior history of radiation therapy for teenage acne and adenoid hypertrophy; severe solar-induced skin damage, basal cell nevus syndrome, and other genetic skin diseases; chemical carcinogen exposure; and drug-induced immunosuppression. In patients with large, multifocal recurrent tumors, standard therapy with acceptable cosmetic outcomes may be difficult. Photodynamic therapy (PDT) with photosensitizing agents selectively taken up by skin provides a primary or adjunct intraoperative option for treatment of this special group of cancer patients. STUDY DESIGN: Retrospective review. METHODS: Patients (age range, 60-92 y) were injected with 1.0 mg/kg PHOTOFRIN (dihematoporphyrin derivative) followed 60 hours later by intraoperative laser light activation. Light was delivered through microlens fiber by means of an argon dye laser at 630 nm at a light dose of 100 to 300 J/cm2 microlens delivery for PDT alone and 50 to 100 J/cm2 microlens delivery for tumor bed resection sites in the case of adjunct PDT combined with surgical resection. RESULTS: Twelve cases of aggressive recurrent nonmelanomatous cutaneous tumors of the head and neck were treated. Five patients received intraoperative PDT combined with surgical resection, including radical mastoidectomy, lateral temporal bone resection, partial maxillectomy with temporalis myofacial flap reconstruction, and wide local resection with secondary intention healing of exposed scalp wounds. Seven patients were treated with PDT alone for extensive multiple cutaneous lesions or wide-field primary or recurrent nonmelanomatous tumors. Ten patients achieved complete responses (follow-up, 6-60 mo) with excellent wound healing and cosmetic outcomes. CONCLUSIONS: PHOTOFRIN-mediated PDT is an excellent locoregional oncological modality for aggressive primary or recurrent basal cell carcinoma and squamous cell carcinoma, particularly in elderly patients who were previously treated with extensive Mohs microsurgery, surgical resection, and external-beam radiation therapy. Multiple repeat treatments are well tolerated, painless, without systemic morbidity, and amenable to local anesthesia or intravenous sedation for PDT alone, and wound healing and cosmetic outcomes are excellent.     

Vocal fold cancer

Ninety percent of vocal fold cancers take the form of squamous cell carcinoma. Since the 1980s, incidence in France has been constantly falling in males while increasing in females. The main risk factor is smoking, alcohol being less implicated than in other laryngeal or extralaryngeal locations. Vocal fold squamous cell carcinoma generally develops on healthy mucosa, although primary precancerous lesions such as leukoplakia or papillomatous keratosis are also frequent. The tumor usually originates in the non-lymphophilic mucosal free edge of the vocal fold then invades the various anatomic subunits of the larynx, acquiring lymph-node metastatic potential. Dysphonia is the first presenting symptom, initially caused by defective mucosal vibration and then by impaired mobility and finally fixation of the vocal fold. Extension, risk factor and pretreatment assessments are as in other upper-aerodigestive-tract cancer locations. The possibilities of laryngoscopic exposure and the tumor limits, however, need to be precisely determined if transoral resection is to be considered. For small tumors, surgery or exclusive radiation therapy can be suggested to the patient as part of an individual treatment plan, each having its advantages and drawbacks. Cutting-edge teams report 5-year local control rates of 85-95% in T1-class tumor and 60-90% in T2. Whatever the treatment option, smoking cessation, close surveillance and cardiovascular prevention enable screening of other oncologic locations and limit onset of the other pathologies implicated in most deaths.     

Clinical and histopathological considerations for the diagnosis and treatment of verrucous carcinoma of the larynx

Verrucous carcinoma of the larynx is quite distinct from well-differentiated squamous cell carcinoma has a characteristic morphology and specific clinical behavior. It accounts for approximately 1%-2% of all laryngeal carcinomas. However, difficulties are encountered clinically in separating verrucous carcinomas from keratoses, verruca vulgaris and squamous cell carcinomas with a verrucous appearance. Between 1962 and 1982, 1504 patients with squamous cell carcinomas of the larynx were diagnosed and treated by staff physicians in the Department of Otolaryngology--Head and Neck Surgery, Washington University in St. Louis. Fifteen of these patients (1%) had verrucous carcinomas. These cases were studied in order to clarify any diagnostic problems, trace the biologic behavior of the tumors and report the results of the treatment used. Of these 15 patients, we were able to follow up 8. The latter had been treated only with surgery and none of them had received radiotherapy. One death occurred, but the patient died of other causes and remained free of cancer. Reports in the literature describe a high rate of recurrence of verrucous carcinomas following radiotherapy with occasional anaplastic transformation of tumors. No patients in our series developed a metastasis in the neck, indicating that neck dissection is not justified for patients with these neoplasms even though clinically enlarged neck nodes may be present.     

Radiotherapy. The mainstay in the treatment of early glottic carcinoma

Early squamous cell carcinoma of the glottis may be effectively treated with surgery or radiation therapy. Controversy exists as to whether radiation therapy effects survival at the expense of vocal function by ultimately requiring more total laryngectomies for salvage of local tumor recurrence. This study reviewed the medical records of 185 patients with T1 or T2, NO invasive squamous cell carcinoma of the glottis treated with primary radiation therapy between 1969 and 1984. All patients were followed up for a minimum of 5 years after completion of therapy. One hundred sixty-one patients met the criteria for local control analysis. Radiation therapy controlled disease in 93% (105 of 113) of patients with T1 lesions and 73% (38 of 48) of those with T2 tumors. Ultimate control of disease for T1 and T2 lesions, including surgical salvage, was 111 (98%) of 113 and 44 (92%) of 48 patients, respectively. The rate of successful surgical salvage was 75% (T1) and 70% (T2). The T2 lesions with impaired vocal cord mobility or anterior commissure disease were identified as being at increased risk for recurrence after primary radiation therapy. Overall voice preservation was 90%. Our data demonstrate that radiation therapy effects disease-free survival rates that are comparable to those produced by surgery, without sacrificing voice. Although a small percentage of patients with selected early glottic lesions may be more effectively treated with primary conservation surgery, these data do not support a change in philosophy concerning primary treatment of early glottic cancer with radiation therapy.