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.     

Efficacy and safety of photodynamic therapy with temoporfin in curative treatment of recurrent carcinoma of the oral cavity and oropharynx

Therapeutic options for recurrent carcinoma of the upper aérodigestive tract (UADT) are limited. The prognosis of these tumours remains poor with significant rate of recurrence and a lower median survival time. Photodynamic therapy (PDT) is a relatively new therapeutic alternative which combines the use of a photosensitising agent and light to induce a cytotoxic effect on the tissues. This is a retrospective single-centre study carried out in patients with a recurrence of an oral cavity or oropharyngeal carcinoma or a second appearance of tumour in a previously irradiated area. There were no metastases in lymph nodes or other organs. Laser treatment was carried out 96 h after temoporfin (Foscan^®) injection. In our series we had 14 cases with a complete response, 1 partial response. Overall survival at 1 year was 72 % and 36 % at 5 years. Disease-specific survival at 1 year was 82 % and 45 % at 5 years. Recurrence-free survival at 1 year was 52 % and 34 % at 5 years. Side effects mainly described are pain in the area of illumination, well controlled. PDT with Foscan^® gives useful results in terms of survival and improvement in quality of life with few adverse events or severe complications. The fact that it has low toxicity and that treatment sessions can be repeated mean it should be considered in the therapeutic armamentarium for recurrent carcinoma of the UADT.     

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.     

Role of human papillomavirus in the development of head and neck squamous cell carcinomas

Objective To review the literature on the role of oncogenic human papillomaviruses (HPVs) in the carcinogenesis of the head and neck mucosa.

Material and Methods Molecular and epidemiological studies concerning the high-risk HPV types and their role in carcinogenesis in the head and neck region were screened.

Results Different studies revealed that: (i) 15–25% of head and neck squamous cell carcinomas (HNSCCs) are clonally associated with high risk HPV types (type 16); (ii) the oropharynx and particularly the tonsils are the most susceptible sites; (iii) patients with HPV-positive tumours present with more advanced stages of disease, are relatively younger, do not have extravagant tobacco and alcohol intake and seem to have a better survival; (iv) HPV-positive tumours are characterized by poor differentiation grade and a basaloid appearance; and (v) HPV-positive tumours exhibit integrated HPV DNA, wild-type p53, pRb downregulation and overexpression of p16^INK4A.

Conclusion Taken together, these data support the view that HPV-harbouring HNSCC can be considered a discrete tumour entity with, moreover, a favourable prognosis. Screening of patients, especially those with tonsillar cancers, for the presence of HPV may help to further optimize treatment protocols and to provide more accurate prognostic information.     

Photodynamic therapy in the treatment of multiple primary tumours in the head and neck,located to the oral cavity and oropharynx

Objectives: Multiple primary tumours are a common problem in the head and neck cancer patients. Curative surgery or radiotherapy of these tumours can be very mutilating or even impossible. This study aims at evaluating meta‐tetrahydroxy‐phenyl chlorin‐mediated photodynamic therapy for second or multiple primary tumours in the head and neck. Design: Retrospective study of all patients with second or multiple primary tumours treated by photodynamic therapy over a 10‐year period. Setting: All patients were treated in the Netherlands Cancer Institute, a tertiary referral centre for the head and neck cancer patients. Participants: A total of 27 patients with 42 the second or the multiple primary head and neck tumours were treated by photodynamic therapy (0.15 mg/kg meta‐tetrahydroxy‐phenyl chlorin). Main outcomes measures: Cure rates. Results: Twenty‐eight of 42 tumours were cured (67%). Cure rates for stage I or in situ disease were 85%versus 38% for stage II/III. Conclusions: Cure rates for photodynamic therapy of the multiple primary head and neck tumours were lower than previously described for first primaries, but were still very encouraging for this difficult patient population. The high cure rate obtained in stage I multiple primaries emphasises the importance of a meticulous follow‐up of patients treated for the head and neck cancer to detect new tumours at a curable stage.     

The increase in incidence of cancer of the tongue in the Nordic countries continues into the twenty-first century

Conclusions This study shows that heavy drinking is a risk factor for prolonged delay in presenting with head and neck cancer and for presenting with a large tumour in the head and neck region. Excessive smoking is only a risk factor for being diagnosed with a large tumour, although there is a weak association between smoking and prolonged diagnostic delay.

Objective It is reasonable to assume that prolonged delay in presenting with head and neck cancer is associated with an advanced stage of cancer at diagnosis. In this study we analysed the effects of drinking and smoking habits on diagnostic delay and the T stage of the tumour at diagnosis.

Material and methods A total of 427 patients with newly diagnosed head and neck carcinomas were eligible for this study. Of these, 306 (72%) actually participated: 134 (77%) with an oral tumour; 117 (69%) with a larynx tumour; and 55 (65%) with a pharynx tumour. Diagnostic delay was defined as a period of >30 days between the appearance of the first tumour-related symptoms and the first visit to a physician. T3–4 tumours were defined as advanced tumours. Drinking behaviour was classified into three types: light (0–2 drinks/day); moderate (3–4 drinks/day); and heavy (>4 drinks/day). Smoking habits were classified into 4 types: never; stopped; light (0–20 cigarettes/day); and heavy (>20 cigarettes/day).

Results Logistic regression showed that there were significantly more heavy than light drinkers [p=0.04; odds ratio (OR) 1.8; 95% CI 1.0–3.1] in the delay group than in the non-delay group. Light smokers showed a tendency towards prolonged delay (p=0.06; OR 2.2; 95% CI 1.0–5.0). Both heavy drinking (p=0.01; OR 2.0; 95% CI 1.2–3.6) and heavy smoking (p=0.03; OR 3.1; 95% CI 1.1–8.4) were risk factors for a patient to be diagnosed with a large tumour.     

The Netherlands Society for Oto-Rhino-Laryngology and Cervico-Facial Surgery

The following are the abstracts of the 174th meeting held in Amsterdam, 1-2 November 1991 The formation of endolymph in the inner ear Wound healing in the subglottis in relation to age Mandibular and soft tissue reconstruction using a free revascularized osteocutaneous fibula on behalf of the Cochlear Implant team (Nijmegen) Persistence of middle ear effusion after a recurrent episode of acute otitis media Biomarkers of early carcinogenesis in the head and neck The semi-implantable middle-ear hearing device (EORP): first results Experimental radioimmunotherapy of head and neck squamous cell carcinoma with ¹³¹I labelled monoclonal antibody E48 The voice after arytenoid adduction for unilateral vocal cord paralysis The importance of total laryngectomy for treatment of hypopharyngeal cancer Complications of rigid bronchoscopy in a pediatric hospital Neck dissection in T₂ squamous cell carcinoma of the anterior oral cavity: discontinuous or in-continuity? Amplification of oncogenes in human head and neck tumours The use of auricular cartilage as a graft material for the nose Two cases of inflammatory pseudotumour in the head and neck Rhinoplasty in patients with a cleft lip Effects of preoperative embolization on paragangliomas (glomus tumours) Defects in cellular immunity in patients with chronic infection of the upper airways: effects of treatment Inner ear vessels and their role in some cases of inner ear hearing loss Click-evoked otoacoustic emissions as a diagnostic parameter in patients with Ménière's disease New developments in Audiant implant hearing devices Amyloidosis of the nose; two case reports Results of a Cochlear Implant Programme 1988–1990 T. SPIES on behalf of the Cochlear Implant team (Nijmegen) Prevention of alcohol withdrawal delirium in patients with a head and neck tumour Otoscopic training for students and general practitioners using the Medical Image Schooling System (MISS) Sensitivity to methotrexate and new antifolates in seven human squamous carcinoma cell lines of the head and neck Tyrosine kinase activity in patients with head and neck tumours Kemp-echo in children with OME or middle ear ventilation tubes: a pilot study Patient information in general ENT practice Cartilage grafts in tip surgery     

Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice

Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systemically administered photo-sensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II® (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AIPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photo-sensitizer was 1.6 or 1.5, respectively. Administration of Pf-H (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm², 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.     

Non-squamous malignancy in lymph nodes: the occult primary

The present study presents 105 patients seen at a head and neck specialist clinic with a neck gland which subsequently proved to be a non-squamous malignancy. Of the 105 patients, 50 patients were eventually found to have a tumour in the head and neck region, 30 to have a distant primary and in 25 no primary site was ever found. The majority of patients were diagnosed in the clinic after careful examination and most of the remainder were diagnosed during endoscopy/biopsy. Chest radiography was the most useful investigation for diagnosing primary tumours of the lung. The 5-year-survival for the whole group of 105 patients was 28% (95% CI 17–39). The 5-year-survival for the head and neck primary tumour group was 44% (95% CI 25–60). The median survival of patients with a distant primary tumour was only a 6 months, there was one 5-year-survivor. The median survival for those in whom the primary was never discovered was 18 months. However, a reasonable proportion of these patients survived, five being alive at 5 years. The difference between survival for the three groups was statistically significant (P < 0.001). The most common histological type was undifferentiated/anaplastic tumours (37 out of 105) and this was followed by adenocarcinoma (33 out of 105). There was a significant difference in the survival between these two groups (χ²= 2.02, d.f. = 1, P= NS). Multi-variate analysis suggested that survival was better in the older age group and was affected by histology (P= 0.0093, P= 0.0332 respectively). The present study suggests that the treatment of patients in whom the primary site is eventually found to be in the head and neck region is rewarding with the same survival as a similar group of patients with squamous cell carcinoma. Sixty of the group of 105 patients had excision biopsies of the neck node and this did not affect survival.     

Development of novel radioresistant oral squamous cell carcinoma cell lines.

Objectives. Oral cancer is the most common head and neck cancer with an estimated 2 75 000 new cases in 2002.¹ Currently radiotherapy plays an important role in the management of oral cancer. Rates of radioresistance reported in the literature range from 19–53%.² This wide range of reported rates of radioresistance stems from variation in the definition of a radioresistant tumour. As all tumours in vivo posses a heterogeneous cell population, samples of tumour tissue taken for analysis cannot be guaranteed to have originated from a radioresistant subpopulation. These, and other factors, cause the discrepancy in resistance rates. This study aimed to address these issues by creating novel radioresistant cell lines. Method. Two oral cancer cell lines were studied. They were divided into two samples and cultured in identical conditions. Initial dose response curves and survival fractions were calculated for each at the outset of the study. One sample was then exposed to a course of fractionated radiotherapy at 4 Gy increments on a fortnightly basis whilst the other was cultured without exposure. Dose response curves were then constructed for the two daughter samples. Results. Each daughter cell line was found to survive doses of radiotherapy in excess of their parental counterpart. The LD₅₀ (lethal dose killing 50% of cells) was 5.85 Gy for the daughter cell line and 0.91Gy for the parental cells. Conclusions. We have created two radioresistant oral squamous cell carcinoma cell lines to allow further analysis to be performed on readily available proven radioresistant oral cancer cell lines. References 1 Parkin D.M., Bray F., Ferlay J. et al. (2005) Global Cancer Statistics, 2002. CA Cancer J Clin, 55, 74–108 2 Eckardt A., Barth E.L., Kokemueller H. et al. (2004) Recurrent carcinoma of the head and neck: treatment stratergies and survival analysis in a 20‐year period. Oral Oncology, 40, 427–32     

Randomized controlled trial comparing Merocel® and RapidRhino® packing in the management of anterior epistaxis*

Objectives: A prospective non‐blinded randomized controlled trial to compare the efficacy of Merocel^® and RapidRhino^® nasal packs in the treatment of anterior epistaxis. Methods: Fifty‐two consecutive participants admitted with anterior epistaxis refractory to digital pressure or nasal cautery were randomized to treatment using one or other of the nasal packs. Patients who required repacking because of continued bleeding, only the first packs were included in the analysis. Haemostatic properties of the packs were measured by grading bleeding during and after removal of the pack (0–4, where four is uncontrollable) and by noting if the nose was re‐packed or not. The difficulty of insertion and removal (graded 0–3 by clinician where 3 is the most difficult) and the participant's perception of discomfort (graded 0–10, where 10 is the worst pain) during insertion and removal of the pack were also measured. Results: For bleeding, the mean values for Merocel^® and RapidRhino^® during packing and after pack removal were not significant (P = 0.38 and 0.82 respectively). The mean values of patient discomfort on insertion were 6.9 and 5.0 (P = 0.01), and for discomfort on removal were 4.6 and 3.4 (P = 0.05) respectively. The mean values of insertion graded by the clinician were 1.7 and 0.9 (P = 0.0003), and for removal were 1.4 and 0.4 (P < 0.0001). Conclusions: RapidRhino^® and Merocel^® are equally effective in the control of anterior epistaxis but RapidRhino^® is significantly more comfortable for the patient and easier for the healthcare worker during insertion and removal.     

Light dosimetry in animal models: application to photodynamic therapy in otolaryngology

Photodynamic therapy (PDT) for treatment of head and neck cancer uses a photoactive compound that is illuminated with 630 nm (red) light. The effectiveness of PDT depends on the penetration of light into tissue that is both tissue and wavelength dependent. The characterization of the optical properties of an animal oral mucosa and skin has been done to determine the amount of light below these tissues available to be used for photodynamic therapy. The tissue absorbance of visible light from 400 nm to 700 nm has been determined in vitro for hamster check pouch mucosa and for athymic mouse skin. The pattern of absorbance is similar for both tissues and demonstrates greater transmission at the longer wavelengths. The diffuse transmittance of light in vivo for these animal models was measured with an interstitial fiberoptic probe. At 630 nm the diffuse transmittance for nude mouse skin averages 10% of the incident light energy, and that for the hamster mucosa almost 50% of the incident light energy.     

Low-dose dexamethasone with fosaprepitant and palonosetron to prevent cisplatin-induced nausea and vomiting in head and neck cancer patients

Abstract

Objective: To determine if a lower dose of dexamethasone can be used in combination with fosaprepitant and palonosetron for cisplatin-induced nausea and vomiting in head and neck cancer patients, we conducted a single-center, two-arm, cross-over comparison study.

Methods: Patients were randomly assigned to either standard dose dexamethasone group: intravenous 9.9?mg on day 1 and 6.6?mg on days 2–4 or low-dose dexamethasone group: intravenous 3.3?mg on days 1–4 for the first course and crossed over to the other treatment for the second course. The primary endpoint was complete response (CR) in the overall period.

Results: Twenty-five patients were screened for the study and 22 were evaluable. Eleven patients were randomly assigned to the standard dose dexamethasone group and 12 patients to the low-dose dexamethasone group. The CR rate in the overall period was 86% in the standard dose group and 73% in the low-dose group, showing no significant difference (p?=?.61).

Conclusion: The efficacy of low-dose dexamethasone with fosaprepitant and palonosetron was not inferior to that of the standard dose dexamethasone in the highly emetogenic cisplatin-based treatment for head and neck cancer patients.     

Adenoid cystic carcinoma of the head and neck

Adenoid cystic carcinoma has a long natural history but frequently proves fatal. The present study describes 108 patients with an adenoid cystic carcinoma of the head and neck seen over a 30-year period. Analysis of the data utilized both univariate and multivariate methods. Forty per cent of patients had tumours arising from the oral cavity and half of these were in the hard palate; 29% occurred in the major salivary glands; 41% of tumours were locally advanced at presentation and 11% had lymph node metastases at this time. The histological pattern was solid in 25%, cribriform in 40% and tubular in 20%. In addition, 15% of patients had a polymorphous low-grade adenocarcinoma and these were analysed separately. Primary site recurrence was more common in the presence of locally advanced tumours at presentation (T_3–4) (P = 0.0093). Only six patients had surgery with adjuvant radiotherapy. Six patients had no curative treatment, 21 had primary radiotherapy, 39 had local excision and 42 radical excision. The actuarial primary site recurrence rate was 100% at 30 years. The neck node recurrence rate was 23% at 15 years. Tumour specific survival was 40% at 20 years. Solid histology had a worse prognosis than other histological types (P = 0.0429) but those patients with polymorphous low-grade adenocarcinomas fared very well. Patients with tumours of the hard palate fared better than those patients with tumours at other sites (P = 0.0301). Early disease at the primary site (T_1–2) was a good prognostic sign (P = 0.0013). Patients with neck node metastases at presentation tended to do badly (P = 0.009).     

Pre‐treatment haemoglobin level predicts response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients

Objective: To investigate the prognostic value of the pre‐treatment haemoglobin level in patients with advanced squamous cell head and neck cancer treated with induction polychemotherapy. Design: Seventy‐two patients with advanced squamous cell head and neck cancer received primary combination chemotherapy consisting of docetaxel 75 mg/m² on day 1, cisplatin 100 mg/m² on day 1, and 5‐fluorouracil (5‐FU) 1000 mg/m²/day on days 1–4 (total dose 4000 mg/m²), repeated on days 1, 22 and 43 followed by chemoradiation. The data collected included pre‐treatment haemoglobin, response to treatment, disease‐free and overall survival. Results: The pre‐treatment haemoglobin level was found to be a significant predictor of response to induction chemotherapy (P = 0.01) and an independent predictor of overall survival [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58–1.03, P = 0.0001] and disease free survival (HR 2.09, 95% CI 1.41–3.09, P = 0.0001). Furthermore N‐stage was found to be a significant prognostic factor of overall survival (HR 9.24, 95% CI 6.90–21.34, P = 0.005). The Eastern Cooperative Oncology Group performance status scale was also found to be significant for disease free survival (HR 7.66, 95% CI 2.61–22.46, P = 0.003). Conclusion: In patients with advanced squamous cell head and neck cancer, the haemoglobin level prior to induction chemotherapy is significantly related to outcome including response and survival.     

Therapeutic effects of a new photosensitizer for photodynamic therapy of early head and neck cancer in relation to tissue concentration

Objective

Talaporfin sodium (Laserphyrin^®, Meiji Seika, Tokyo, Japan) is a second-generation photosensitizer developed in Japan. It is characterized by both mild and short-term skin photosensitivity. The objective of this study was to evaluate the efficacy and the pharmacokinetic characteristics in tumor tissues in patients with head and neck cancer.

Methods

(1) Four hours after administration intravenous injection of talaporfin sodium (40 mg/m²), 100 mg tissue specimens were taken from the central part of the tumor. The samples were analyzed by reverse phase liquid chromatography and concentrations were measured. (2) Four hours after intravenous injection of talaporfin sodium (40 mg/m²), we gave 60–150 J/cm² of 664 nm laser irradiation with a diode laser (PD laser, Panasonic, Japan). Biopsies were performed at 4 weeks and at 3 months after treatment and periodically thereafter to confirm the treatment efficacy of photodynamic therapy (PDT).

Results

Of the 14 patients who grope informed consent, more than 1 μg/g of talaporfin sodium was found in the tumor tissues in 13. Moreover, in 9 patients, tumor-to-normal-tissue ratios ranged from 2.32:1 to 5.69:1, which indicates that more than double the amount of talaporfin sodium was maintained within the tumor than in normal tissues. We have enrolled 22 patients with head and neck cancer with no clinically recognizable metastases after obtaining written informed consent to participate in this study. PDT using talaporfin sodium exhibited the equivalent efficacy to that of conventional PDT using hematoporphyrin derivative (HpD).

Conclusions

The results using a combination of talaporfin sodium and PD laser achieved a primary treatment outcome equivalent to that of conventional PDT. This method has also proven to be advantageous because of the reduced incidence of side effects such as photosensitivity and local edema.     

Diagnostic work-up and outcome of cervical metastases from an unknown primary

Conclusions. An intensive diagnostic work-up including ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) detects many unknown primary tumours, leads to a low emergence rate of primary tumours, and selects carcinoma of unknown primary with much more favourable results after neck dissection and postoperative radiotherapy. Objective. To investigate the optimal diagnostic approach and best treatment modality for rare head and neck cancer of unknown primary. Patients and methods. In a retrospective study, 69 patients admitted from 1987 to 2002 with cervical lymph node metastases without apparent primary were reviewed. Test characteristics of all diagnostic procedures were calculated. Disease-free and overall survival rates were calculated. Major prognostic factors were analysed univariately. Results. At the primary site FDG-PET showed the best sensitivity with 69% and the highest negative predictive value with 87%. Computed tomography and magnetic resonance imaging had a better specificity with 87% and 95%, respectively. The primary tumour was detected in 23 cases (33%). Frequent primary tumour origin was the palatine tonsil (n=8, 35%), base of the tongue (n=6, 26%) and lung (n=4, 17%). All patients with unknown primary were treated by neck dissection. Adjuvant radiotherapy was performed in 26 patients (57%), concurrent radiochemotherapy was performed in 12 patients (26%). The primary emergence rate was 7%. The 5-year overall survival rate was inferior in patients with detected primary in comparison with patients with unknown primary (22% versus 52%). Significant prognostic factors in case of unknown primary were M stage, smoking, alcohol consumption and tonsillectomy. Radiotherapy but not chemotherapy with carboplatin influenced the overall survival.     

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.     

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

Objective

Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100 mg/m² is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese.