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How variations of treatment time affect the safety/efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. Due to the relative simplicity of treatment planning for trigeminal neuralgia (TN) this question has been addressed in a group of these patients. Using the concept of biologically effective dose (BED) the effect of the two key variables, dose and treatment time have been taken into account.METHODS A retrospective analysis was carried out on 408 TN cases, treated between 1997 and 2010. Treatment involved the use of a single 4 mm iso-center. If conditions allowed, the iso-center was placed at a median distance of 7.5 mm from the emergence of the trigeminal nerve from the brain stem. Effects were assessed in terms of the incidence of the complication, hypoesthesia, or in terms of efficacy, the incidence of 'pain free' after 30 days and at 1 and 2 years. These responses were evaluated with respect to both the physical dose and the biological effective dose (BED), the latter using a bi-exponential repair model. RESULTSRe-evaluation showed that the prescription doses, at the 100% iso-dose, varied between 75 and 97.9 Gy, delivered over 25 -135 min. The relationship between physical dose and the incidence of hypoesthesia was not significant; the overall incidence being approximately 20%. However, there was a clear relationship between BED and the incidence of hypoesthesia, the incidence increasing from < 5% after a BED of ~1800 Gy 2.47 to 42% after ~2600 Gy 2.47 . Efficacy, in terms of freedom from pain, was approximately 90%, irrespective of the BED (1550-2600 Gy 2.47 ) at 1 and 2 years. There was a suggestion from the data that 'pain free' status developed more slowly at lower BED values.CONCLUSION These results strongly suggest that safety/efficacy may be better achieved by prescribing a specific BED instead of a physical dose. A dose/time to BED conversion table has been prepared to enable iso-BED prescriptions. This finding may dramatically change dose-planning strategies in the future. This concept needs to be validated in other indications where more complex dose-planning is required.

Radiosurgery (RS) treatment times vary, even for the same prescription dose, due to variations in the collimator size, the number of iso-centres/beams/arcs used and the time gap between each of these exposures. The biologically effective dose (BED) concept, incorporating fast and slow components of repair, was used to show the likely influence of these variables for Gamma Knife patients with Vestibular Schwannomas. Two patients plans were selected, treated with the Model B Gamma Knife, these representing the widest range of treatment variables; iso-centre numbers 3 and 13, overall treatment times 25.4 and 129.6 min, prescription dose 14 Gy. These were compared with 3 cases treated with the Perfexion(®) Gamma Knife. The iso-centre number varied between 11 and 18, treatment time 35.7 - 74.4 min, prescription dose 13 Gy. In the longer Model B Gamma Knife treatment plan the 14 Gy iso-dose was best matched by the 58 Gy2.47 iso-BED line, although higher and lower BED values were associated with regions on the prescription iso-dose. The equivalent value for the shorter treatment was 85 Gy2.47. BED volume histograms showed that a BED of 85 Gy2.47 only covered ∼65% of the target in the plan with the longer overall treatment time. The corresponding BED values for the 3 cases, treated with the Perfexion(®) Gamma Knife, were 59.5, 68.5 and 71.5 Gy2.47. In conclusion BED calculations, taking account of the repair of sublethal damage, may indicate the importance of reporting overall time to reflect the biological effectiveness of the total physical dose applied.

The linear-quadratic (LQ) model for fractionated external beam therapy has been modified by previous authors to include the effects due to an exponentially decaying dose rate. However, the LQ model has now been extended to include a general time varying dose rate profile, and the equations can be readily evaluated if an exponential radiation damage repair process is assumed. These equations are applicable to radionuclide directed therapy, including brachytherapy. Kinetic uptake data obtained during radionuclide directed therapy may therefore be used to determine the radiobiological dosimetry of the target and non-target tissues. Also, preliminary tracer studies may be used to pre-plan the radionuclide directed therapy, provided that tracer and therapeutic amounts of the radionuclide carrier are identically processed by the tissues. It is also shown that continuous radionuclide therapy will induce less damage in late-responding tissues than 2 Gy/fraction external beam therapy if the ratio of the maximum dose rate and the sublethal damage repair half-life in the tissue is less than 1.0 Gy. Similar inequalities may be derived for beta-particle radionuclide directed therapy. For example, it can be shown that radionuclide directed therapy will induce less damage to slowly repopulating tissue than 2 Gy/fraction external beam therapy for the same total dose if the maximum percentage initial uptake in tissue is less than 0.046%/g or 0.23%/g for an injected activity of 50 mCi of 90Y or 131I, respectively.