Johan Reizenstein

Electroporation Therapy of Skin Cancer in the Head and Neck Area

BACKGROUND Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent. OBJECTIVE To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin. MATERIALS AND METHODS Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow‐up period was 24 months and included biopsies after 8 weeks. RESULTS In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow‐up period CONCLUSION Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer. Genetronics, Inc. provided financial support for this study and has paid Dr. L. Lofgren an honorarium for work at investigator meetings.

Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma The ARTSCAN study

BACKGROUND AND PURPOSE Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. MATERIALS AND METHODS Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. CONCLUSION Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.

The quality assurance process for the ARTSCAN head and neck study – A practical interactive approach for QA in 3DCRT and IMRT

AIM This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.

Electroporation therapy for T1 and T2 oral tongue cancer

Abstract Conclusion: Electroporation therapy appears to be a safe treatment achieving excellent local tumor control and very good functional results in our study and it should be further clinically evaluated. Objectives: The objectives of this study were to assess local tumor control, survival, and effects on speech and eating after treatment of tongue cancer with electroporation therapy, a new local therapeutic modality. In this approach intracellular accumulation of a chemotherapeutic agent is achieved by using a locally applied electrical field. Methods: Fifteen patients with primary T1 and T2 oral tongue cancer were treated with electroporation therapy with intratumorally administered bleomycin. Postoperative radiotherapy was performed when the tumor infiltration was 5 mm or more. The follow-up time was 24 months for the surviving patients and 20.4 months overall. The effects on eating and speech were assessed using the PSS-HN scale and voice recordings. Results: No local recurrence was recorded in any patient during the follow-up. Three patients died, two from progressive regional disease. Of the 12 surviving patients, 2 patients had regional recurrence and 10 patients including the 5 patients treated with EPT alone were tumor-free both locally and regionally at the last follow-up. The functional outcome for speech and eating were very good.

Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma – The ARTSCAN trial

BACKGROUND AND PURPOSE This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. MATERIAL AND METHODS Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, N0 glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1Gy+2Gy per day, 5days/week for 4.5weeks, total dose 68Gy) and conventional fractionation (CF) (2Gy per day, 5days/week for 7weeks, total dose 68Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. RESULTS There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p=0.75). LRC at 5years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p=0.99). The estimated cancer specific survival (CSS) at 5years was 62.2% (AF) and 63.3% (CF) (p=0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16- tumours. CONCLUSION This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.

Impact of age at diagnosis on prognosis and treatment in laryngeal cancer.

The aims of this study were to analyze how age affects treatment and treatment outcome, and to determine whether tumor characteristics differ between different age groups with laryngeal cancer.

Long-term follow-up in patients treated with curative electrochemotherapy for cancer in the oral cavity and oropharynx

Abstract 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.

Electrochemotherapy - possible benefits and limitations to its use in the head and neck region.

Abstract 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.

A national approach for automated collection of standardized and population-based radiation therapy data in Sweden.

PURPOSE To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. MATERIALS AND METHODS The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. RESULTS The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA®, Mosaiq®, Eclipse™, and Oncentra® is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. CONCLUSIONS An infrastructure for structured and automated prospective collection of syntactically interoperable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.

Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.

BACKGROUND AND PURPOSE Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. MATERIAL AND METHODS 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. RESULTS The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. CONCLUSION In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.