Background: Electrochemotherapy (ECT) is a cancer treatment modality where the intracellular accumulation of chemotherapeutic agents is enhanced by an applied electrical field.

Aims/Objectives: To evaluate the long-term efficacy, safety and functional outcome after ECT treatment in high-risk non-melanoma skin cancer (NMSC) with curative intent.

Materials and methods: Seven patients with SCC or BCC in the head and neck area were treated with ECT with intratumoral bleomycin administration.

Results: Five patients were cured by ECT as a mono-modality treatment after a median 10-year follow-up period. Two patients had recurrences and/or persisting tumors after treatment that required salvage surgery and radiotherapy. In two patients, the eye was spared with no visual impairment. In another patient, full facial nerve function was spared.

Conclusions: ECT can be a curative as well as an organ and function-sparing mono modality treatment in high-risk NMSC.

Background: The five Nordic countries with a population of 27 M people form a rather homogenous region in terms of health care. The management of head and neck cancer is centralized to the 21 university hospitals in these countries. Our aim was to gain an overview of the volume and role of transoral robotic surgery (TORS) and to evaluate the need to centralize it in this area as the field is rapidly developing.

Materials and Methods: A structured questionnaire was sent to all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic countries having an active programme for TORS in December 2017.

Results: The total cumulative number of performed robotic surgeries at these 10 Nordic centers was 528 and varied between 5 and 240 per center. The median annual number of robotic surgeries was 38 (range, 5-60). The observed number of annually operated cases remained fairly low (<25) at most of the centers.

Conclusions: The present results showing a limited volume of performed surgeries call for considerations to further centralize TORS in the Nordic countries.

Conclusion: Electrochemotherapy (ECT) is an efficacious treatment. It should, however, be used with some caution in the treatment of head and neck cancer.

Objectives: To assess local tumor control, safety, survival, and functional outcome after treatment of cancer in the head and neck region with ECT.

Methods: Four patients with primary T2 cancer of the oral cavity or oropharynx and one patient with a metastasis of renal cancer in the masseter muscle were treated with ECT with intratumorally administered bleomycin. Control biopsies were carried out 2 months after treatment. Postoperative radiotherapy was performed based on tumor T-stage and the depth of tumor infiltration. Serious adverse events and treatment malfunctions were recorded. The follow-up time was 24 months for the surviving patients and 20 months overall. The PSS-HN scale was used to assess the functional outcome.

Results: No local recurrence was recorded in any patient during the follow-up. However, only one patient was treated with ECT alone. There were four serious adverse events: one nearly lethal bleeding, two cases of osteoradionecrosis, and a fistula. One patient died from distant metastasis. The other patients were tumor-free both locally and overall at 24 months. The median functional outcome in all parameters was worse 1 year after treatment.

Aim: Electrochemotherapy (ECT) is a new cancer treatment modality that uses electroporation to potentiate chemotherapeutic agents, especially bleomycin. ECT causes both a direct toxic effect and an anti-vascular effect. The aim of the present study was to investigate a possible selective effect of ECT on the survival of fibroblasts, endothelial cells (HUVEC) and two squamous cell carcinoma cell lines (CAL-27 and SCC-4).

Materials and Methods: Cells were electroporated using two bleomycin concentrations. The survival rate was assessed 1, 2, 3 and 4 days after treatment, by two different assays.

Results: The survival rate of the fibroblasts was statistically significantly higher than the other cell lines at day 4. The HUVEC survival rate was statistically significantly lower than the other cell types at day 1 after electroporation-alone.

Conclusion: A selective survival effect after ECT was observed in vitro, supporting the anti-vascular effect seen in vivo.

Conclusion: ECT can be a safe curative mono modality treatment, especially in tongue cancer. The future role for ECT in head and neck cancer needs to be further investigated.

Introduction: Electrochemotherapy (ECT) is a cancer treatment modality that uses electroporation to increase the intracellular accumulation of hydrophilic chemotherapeutic drugs, especially bleomycin.

Objectives: To report the 5-year local tumor control, safety of treatment and survival after ECT, and the 1-year quality-of-life (QoL) data.

Materials and methods: Nineteen patients with primary head and neck cancer were included and treated with ECT with curative intent. All except one patient had squamous cell carcinoma (SCC). Radiotherapy (RT) was performed in all patients with SCC and tumor infiltration ‡5 mm. The EORTC H&N 35 questionnaire was used at baseline and 12 months after treatment. The Wilcoxon signed rank test and McNemar’s test were used for paired data and Mann Whitney U-test and Fishers exact test were used for independent data (sub-group comparison).

Results: There were no local recurrences in the follow-up period. Thirteen patients were treated with adjuvant RT. The six patients that were treated with ECT alone were tumor-free and alive 5 years after treatment. There was one serious adverse event reported; aspiration after treatment of a tongue base tumor. The tumor-specific 5-year survival was 75%. The QoL outcome 1 year after ECT showed a significant increase in problems with senses (taste, smell), speech, mouth opening and xerostomia. The QoL outcome also showed worse outcome in the smoking patients regarding speech, in the patients receiving adjuvant RT regarding mouth dryness and swallowing and in the patients with non-tongue oral cavity cancer regarding need for painkillers.

Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments.

Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs.

Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice.

Photodynamic therapy, PDT, is a method to diagnose and treat cancer. In PDT a sensitizer is administered to the patient and this sensitizer is accumulated in tumors. If the sensitizer-containing tumor is subjected to a laser of a specific wavelength the tumor is fluorescing allowing diagnostics. If other wavelengths are used a process involving reactive oxygen species and singlet oxygen is started and the tumor cells are killed. This process thus requires oxygen as well.

This thesis investigates how UV-induced damage of the skin and different physiological factors of the skin influences the uptake of 5- aminolevulinic acid, ALA, and its conversion to the active sensitizer protoporphyrin IX, PpIX. It shows that UV-induced damage affects both the uptake and production of PpIX. UV-induced damage lowers the PpIX produced after ALA application both if the damage is acute and in chronically UV-affected skin.

The PpIX production differs inter and intra individually. When looking how different physiological factors affect the PpIX production after topically applied ALA the thesis shows that an increase of temperature increases the production. No correlation between the formation of PpIX and the density of hair follicles was found and a weak correlation was seen comparing the epidermal and total dermal thickness and PpIX production

The thesis also shows how PDT is used in treating laryngeal malignancies. It shows that it is possible to cure laryngeal tumors (both squamous cell carcinomas and sarcomas) using PDT primarily, and that the cure rate as well as outcome of voice and patient safety is comparable to the conventional treatment modalities.

PDT can also be used as a function and organ sparing treatment for recurring laryngeal cancers, both squamous cell carcinomas and sarcomas.

Formation of protoporphyrin IX (PpIX) after topical application of 5-aminolevulinic acid (ALA) and its hexylester derivative (ALA-Hex) was studied on healthy human skin. Temperature, density of hair follicles, epidermal and skin thickness were measured on the application sites. The skin temperature was found to be the strongest determinant for PpIX formation. The PpIX fluorescence increase was about 25% per degree Celsius. Formation of PpIX was found to be independent of the density of hair follicles. A weak correlation was found between the PpIX fluorescence and the thickness of epidermis and skin. Sun exposure seems to reduce the production of PpIX slightly.

The skin of nude mice was exposed to erythemogenic doses of UV radiation, which resulted in erythema with edema. An ointment containing 5-aminolevulinic acid (ALA) was topically applied on mouse and human skin. Differences in the kinetics of protoporphyrin accumulation were investigated in normal and UV-exposed skin. At 24 and 48 h after UV exposure, skin produced significantly less protoporphyrin IX (PpIX) than skin unexposed to UV. Human skin on body sites frequently exposed to solar radiation (the lower arm) also produced less PpIX than skin exposed more rarely to the sun (the upper arm). It is concluded that UV radiation introduces persisting changes in the skin, relevant to its capability of producing PpIX from ALA. The observed differences in ALA-induced PpIX fluorescence may be the result of altered penetration of ALA through the stratum corneum or altered metabolizing ability of normal and UV-exposed skin (or both).

Background and purpose: To evaluate the long time outcome with regard to local tumour control, side effects and quality of life of a combined pulsed dose rate (PDR) boost and hyperfractionated accelerated external beam radiotherapy (EBRT) for primary base of tongue (BOT) cancers.

Patients and methods: Between 1994 and 2007 we treated 83 patients, median age 60 (38-82) years, with primary T1-T4 BOT cancers. Seven patients (8 %) were T1-2N0 (AJCC stage I-II) and 76 (92 %) patients were T1-2N+ or T3-4N0-3 (AJCC stage III-IV). The mean estimated primary tumour volume was 15 (1-75) cm³.  EBRT was given with 1.7 Gy twice daily to 40,8 Gy to primary tumour and bilateral neck lymph nodes in 2.5 weeks. A PDR boost of 35 Gy and a neck dissection in clinical node positive cases was performed 2-3 weeks later. The patients were followed for a median of 54 (2-168) months.

Results: The 2-, 5- and 10-years rates of actuarial local control were 91 %, 89 % and 85 %, overall survival 85 %, 65 % and 44 %, disease free survival 86 %, 80 % and 76 % respectively. The regional contral rate was 95 %. Six patients (7 %) developed distant metastases. Analysis of dosimetry showed a mean treated volume of 58 cm³.  In a review of late complications we found 11 (13 %) minor and 4 (5 %) major soft tissue necroses and 6 (7 %) osteoradionecroses. The patients median subjective SOMA/LENT scoring at last follow up was; grade 0 for pain and trismus, grade 1 for dysphagia and taste alteration and grade 2 for xerostomia. Global visual-analog-scale (VAS) scoring of quality of life was 8.

Conclusions: Local and regional tumour control rate was excellent in this treatment protocol. The data support that PDR boost is at least as effective as published continuous low dose rate (CLDR) results.