gms | German Medical Science

In advanced tumours of the anterior skull base it is imperative to reach local tumour control in order to enhance survival rates and quality of life for patients. Currently surgical resection with negative histological margins followed by postoperative radiotherapy is the established therapy.

Nevertheless locally recurrent tumour is observed frequently and diminishes the chance for cure in these patients. Recurrence is caused by tumour cells left behind after surgery, which have had time to divide in the period leading to the start of postoperative radiotherapy. Remaining cancer cells are often so numerous that even with the highest possible doses of radiation, and despite concomitant chemotherapy it is difficult to prevent local recurrence.

During surgery it may be possible to define close surgical margins, however it is from these sites where later visible tumour recurrence may develop. With intraoperative radiotherapy (IOERT) it is possible to apply a single dose of irradiation which is high enough to prevent division of remaining tumour cells, or at least contain the number of cells at low levels thus preventing local recurrence.

Prerequisite for the best possible therapy is a multidisciplinary team effort under the guidance of the ENT surgeon. Only if surgical resection can limit the remaining number of tumour cells, can intraoperative radiotherapy be capable of enhancing tumour control by the aforementioned mechanism. Elaborate surgical techniques allow total tumour resection in advanced anterior skull base lesions with invasion of orbit, dura, lacrimal apparatus or fossa infratemporalis. In these cases, endoscopic approaches are usually not possible. Open techniques are chosen to enable R0 tumour resection, proven by frozen section histology. These open techniques allow the possibility of intraoperative radiotherapy using a plexiglass-cone adapted by size in the tumour bed area. By using defined doses of electron energy, radiation can be adapted to a well defined volume depth of tissue. Sensitive tissues, like the eye-ball, optic nerve, parts of the brain and other structures can be spared from irradiation by plexiglass-blocks, which are introduced and fixed within electron tubes. The entire intraoperative radiotherapy procedure takes an additional time of about 30 minutes, which is usually possible to perform during a surgery, lasting 4 to 12 hours.

The surgical procedures which are used and which enable IOERT, consisted in our series of midfacial degloving, subfrontal, facial translocation and midfacial swing approaches. A total of 18 patients with advanced primary and recurrent tumours of the anterior skull base were operated and treated with IOERT between January 2001 and October 2004. These patients were part of a group of thirty patients, all with advanced tumours of the whole skull base. The other 12 patients had lesions not situated at the anterior skull base and therefore surgical approaches from the side including various Fisch techniques were used.

We wish to discuss here the 18 patients of the anterior skull base because in this group the majority had a primary tumour resection. In the group of the other 12 patients the majority had recurrent tumours, several times not even first, but multiple recurrences and therefore, in this group therapy has to be seen as palliative.

In 12 of the 18 patients in our series, tumour resection, IOERT, and postoperative radiotherapy were performed , in one patient with a pT2 primary tumour no postoperative radiotherapy was given, in 5 patients with recurrent tumours, an attempt of curative resection with IOERT, but without postoperative radiation was done. All surgical procedures were performed in a dedicated operating room with an integrated linear accelerator at the University Clinic for Radiotherapy and Radio-Oncology

After tumour resection an intraoperative dose between 8 and 10 Gray was applied in all 18 Patients. There were no acute side effects regarding of the performance of IOERT in despite of the long duration of the surgical procedures necessary in these patients. In order to improve the visualization and application of the dose in the surgical area, a dedicated treatment planning system, which allows the scanning of irregular surfaces and the correction of monitor units of the linear accelerator was developed and used thus achieving an additional quality of treatment. Another improvement consisted of the use of the above described plexiglass blocks, which can shield sensitive structures.

During intraoperative radiotherapy all medical staff except the patient were outside the operating room. Anaesthesia was remotely controlled by monitors. An interruption of radiation would have been possible at any time during the procedure if there would have been any sign of worsening of vital functions, or of equipment malfunction. After a median follow-up time of 15.25 months 10/18 patients are alive: 8 without recurrent tumour and 2 alive with recurrences, one inside and one outside the IOERT field. The patient with recurrent tumour inside the IOERT field one year after the procedure was operated primarily with a T4 recurrence, 2 years after surgery and postoperative radiotherapy of an advanced sinunasal cancer. At the time of tumour recurrence there was also evidence of lung metastases in the PET-scan and thorax-CT. Two patients died because of metastases of their primary tumour, two because of metastases of a second malignancy (kidney cancer and pancreatic carcinoma). One patient succumbed due to a second head & neck malignancy (oropharynx), in one patient with paranasal sinus cancer intracerebral recurrence developed outside the IOERT field and the patient died 25 months after IOERT. Two patients succumbed for intercurrent disease (sepsis, myocardial infarction) 1 and 9 months after IOERT respectively. No patient died because of treatment failure within the IOERT field.

Out of 13 patients with primary tumour, all 6 patients who died, did so because of metastases of the primary tumour (3), or metastases of a second cancer (2), or because of second cancer (1). One of the patients with primary tumour is alive with tumour recurrence outside the IOERT field of a maxillary cancer 15 months after first surgery (recurrence in frontal sinus). Six patients with primary tumour are alive without disease.

Two of the five patients with recurrent tumour at the time of IOERT died, one intercurrent because of sepsis one month after the second resection of skull base metastases of a kidney cancer, and the other because of myocardial infarction 9 months after the fifth recurrence of a skin cancer which had grown into the skull base. Three of the patients with recurrent tumours are alive, two without evidence of disease, 52 and 18 months after IOERT, one patient with locally recurrent tumour and lung metastases one year after IOERT will have chemotherapy and further radiotherapy as a palliative treatment.

In published literature the most common reason (more than 50%) for treatment failure in advanced tumours of the anterior skull base is the inability to control the tumour locally. In an attempt to enhance therapy, 18 patients with primary and recurrent cancer of the skull base were treated with surgical tumour resection and intraoperative radiotherapy. First analysis shows us that local treatment failure occurred only in a minority of patients and in none of the cases this was the reason for a fatal outcome. One third of the patients died because of metastatic disease and second cancer. Future direction of therapy has to be aimed at better systemic therapy in order to further improve treatment outcome. Nevertheless, the high local tumour control rate within the IOERT field (surgical field) is very encouraging and we will continue to use this treatment modality in our patients with advanced anterior skull base tumours.