CSI irradiation is a challenging treatment, not only due to the age of the patients but also because of the many challenges of its practical realization. During the planning of 3D conformal radiotherapy it is a difficult task to align the whole cranial irradiation with the field treating the spine, and to align the spine fields with each other. The cranial field is usually covered by two lateral fields, while the spine fields consist of single posterior fields. The development of the so called ”hot spots”, dose inhomogeneities increases at the points of alignment, thus, the risk of overdosing increases8 − 11. Sebestyén et al. demonstrated the technique utilized at their institute for avoiding overdosing, on 8 patients. By using segments in the field, no overdosed areas developed at the points of field alignment12. This may be reduced by using the intensity modulate technique (IMRT)13. Kuster et al., using the IMRT technique, managed to decrease inhomogeneous dose distribution, they increased the coverage of the target area and the protection of the organs at risk14.
With the further advancements in the radiotherapeutic techniques and the planning options and with the volumetric arc therapy (VMAT) becoming more and more widespread, the need emerged for studying how much more gentle is this treatment modality compared to the conventional stationary field IMRT treatment. Rolina et al analyzed the plans of 10 patients. They were able to improve the coverage of the target area by using the VMAT technique, however, this did not result in significant differences. No remarkable differences were seen in terms of the dose exposures of the organs-at-risk between the two techniques15. These results were supported by other studies conducted at other institutes16 − 18. In the study of the SIOP-E-BTG group, the same cases were sent to 15 institutes for planning, in order to compile the best 3D-CRT, IMRT, VMAT and Proton therapeutic plans. The modern radiotherapeutic techniques resulted in the improvement of the dose conformity and the dose homogeneity compared to 3D-CRT. The dose exposure of organs-at-risk also improved, however, significant differences were only obtained with the proton therapy19.
Hideghéty et al. assessed the benefits and disadvantages of prone and supine patient positioning with 12 patients. No differences were seen regarding dose homogeneity, and coverage. However, supine position was more advantageous in terms of patient comfort and easier treatment realization. While using this positioning, general anesthesia of the patients became avoidable and due to the better stability of this position we achieved better reproducibility during online verification compared to applying prone patient positioning.
The side effects of the treatment can be acute or delayed. In the current study we essentially dealt with the acute side effects, and we were looking for an explanation for their development. In the study of St. Claire, during the use of IMRT and other modern techniques, the dose limits of organs-at-risk were not approached compared to the 3D-CRT, thus, according to their opinion, the side-effects may decrease21. During the prospective study of Cox conducted between 2010 and 2014, the acute side effects were analyzed in 10 patients. During the treatments, gastrointestinal side effects occurred predominantly, such as vomiting and diarrhea. However, these side effects are well tolerable with appropriate supportive care, unlike the much more therapy resistant alopecia and headache22. As an effect of the dose modulation during the IMRT treatment, the dose delivered towards the abdominal organs is well controllable, therefore, the side effects are also more tolerable14. In the HIT91 study, according to the description of Kortman et al.treatment interruptions became necessary due to the occurrence of myelosuppressive side-effects. Notable (> grade 3) myelosuppression was seen at 35% of the patients who received chemotherapeutic regimens before and after their radiotherapy, and at 19.3% of patients who received maintenance therapy only. The hematological side-effect was prolonged especially in young adults. With the elimination of the direct field, the dose of the sternum - being an organ-at-risk - was successfully reduced by 57% using the IMRT treatment23. This was supported by our results as well, as the dose of sternum was 2299/1156 cGy. We demonstrated the safety of the rotating field arc radiation therapy, and no remarkable myelosuppressive side-effects were observed.
Bone marrow suppression as an acute side effect is typical during the treatment. Sung Zong-Wen outlined in his work that a large area of tissue is affected by a relatively low dose during the VMAT treatment. In addition, the main side effect in the treated patients was hematological toxicity, which did not exceed the decrease beyond the Grade (Gr) 3 value24. Wong et al. observed hematological toxicity with the following magnitude in 14 patients during VMAT treatment. Leukopenia Gr 2: 11%, Gr 3: 26%, Gr 4: 63%, Anemia Gr 2: 89%, Thrombocytopenia Gr 1–2: 16%, Gr 3: 26%, Gr 4: 37%25. Kumar et al. conducted a study involving 4 institutes between 2011 and 2014, and they analyzed the hematological causes of therapy discontinuation in 52 patients. Treatment was discontinued if a grade 2 side-effect developed, and, it was continued upon the appearance of grade 1 side-effects. The irradiation of the spine had to be interrupted at 73.1% of the patients, for which the cause was leukopenia in 92% of the cases, it was thrombocytopenia in 2.6% of the cases, and both were responsible in 5.3% of the cases26. In our study, we encountered milder side effects both in the 3D conformal arm and in the IMRT/ARC arm.
According to Fossati et al., a decrease in the development of delayed side effects can be observed in the case of the IMRT treatment, which include cardiac side-effects and hypothyroidism. However, with increasing doses, no additional delayed toxicities can observed regarding the lungs, kidneys, testicles, uterus and ovaries. For the final evaluation of the delayed side effects of the IMRT treatment we still do not possess enough data, due to the relatively short follow-up period. It may be noted at this point that IMRT carried out with arc irradiation has a benefit over the 3D conformal technique in the protection of the hypothalamus and the hippocampus, considering that the IMRT treatment provides better dose homogeneity. However, further observation is necessary according to Bernier et al.28. Further evaluation of our data is necessary for the assessment of the delayed side effects.
Salloum et al. processed mortality and morbidity data from patients treated with medulloblastomas between 1970 and 1999, thus these data covered three decades. The median time from diagnosis was 21 years at the 1311 enrolled patients. The 15-year mortality rates were 23.2% and 12.8% in patients treated in the 70 s and 90 s, respectively. Mortality rates due to recurrences were 17.7% and 9.6%, respectively. However, the rate of a second tumor was higher in patients treated with multiple modalities in the 90 s (56.6% vs. 39.9%). It was also indicated that patients, who have been treated due to highrisk medulloblastomas had a greater need for services aiding learning29. Altogether, the role of advancing and developing techniques was highlighted, and we also set a similar objective in our study. Similarly good results were achieved during the follow-up of our patients with the use of these advanced techniques.