Comparative Study of Spinal Cord Toxicity from Dose Per Fraction Delivered to Cervical Spinal Cord in Head-and-neck Cancers by Volumetric-modulated Arc Therapy with Simultaneous Integrated Boost versus Three-dimensional Conformal Radiotherapy in a Murine Model.

AIM: To assess and compare the radiation-induced effects on the spinal cord of rats following fractionated irradiation with doses of 1.36 Gy and 2.0 Gy per fraction.

MATERIALS AND

METHODS

The risk of radiation-induced myelopathy and spinal cord tolerance represent the major dose-limiting factors during re-irradiation of head-and-neck cancers since spinal cord is exposed to maximum tolerance dose of 45 Gy in 1.8-2 Gy per fraction during first radiation treatment. However, modern radiotherapy techniques such as Volumetric-modulated Arc Therapy (VMAT) with simultaneous integrated boost (SIB) usually irradiate spinal cord with much less dose per fraction than 2 Gy per fraction of prescription dose. In this experimental study, the cervical spinal cord of male Wistar rats was irradiated to a total biologically effective dose of 120 Gy2 using different dose-per-fraction, control group was irradiated with 2 Gy per fraction for a total dose of 60 Gy/30F in 6 weeks while experimental group was given 1.36 Gy per fraction for a total dose of 70.72 Gy/52F in 10.5 weeks. The motor function including motor co-ordination and balance, locomotor activity was observed at 1, 3, and 5 months after the completion of radiation and was compared with baseline values.

RESULTS

Motor co-ordination and balance were preserved until the 3rd month in both control and experimental groups, with no significant difference from baseline (0 ± 0). Gradual functional deterioration became evident after 3 months and a significant decline was observed at 5 months in both groups, with a greater reduction in the control group (72 ± 2.4) compared to the experimental group (105 ± 2.8) (F = 367.9, P < 0.001). The decline was more pronounced in rats treated with 2 Gy per fraction than in those receiving 1.36 Gy per fraction. Locomotor activity declined progressively after irradiation in both groups. Baseline activity was 388.8 (control group) and 369.7 (experimental group). At 1 month, the control group showed a significantly greater reduction (180.2 ± 8.2) than the experimental group (272.5 ± 12.1), with a significant group and time interaction (F = 110.4, P < 0.001). This difference persisted at 3 months (control group: 130.2 ± 3.6; experimental group: 185.4 ± 4.8; F = 208.7, P < 0.001) and was most pronounced at 5 months (control group: 99.5 ± 1.7; experimental group: 147.4 ± 4.0; F = 610.9, P < 0.001).

CONCLUSIONS

This study demonstrates that fractionated irradiation of the spinal cord at 1.36 Gy per fraction, as commonly delivered during VMAT SIB, is less damaging in rats compared to the conventional 2 Gy per fraction used in three-dimensional conformal radiotherapy. Motor co-ordination and locomotor activity deterioration were more pronounced in the control group than in the experimental group. These findings suggest that smaller dose-per-fraction schedules may be well within the spinal cord tolerance, thereby potentially enabling safer re-irradiation scenarios.