The analysis of quality of life of patients with glioblastoma after adjuvant radiation therapy

ABSTRACT


Relationship with academic programs, plans and themes
The work was performed as a part of the planned research project of State Institution «Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine» «Investigation of the effectiveness of adjuvant immunotherapeutic and radiotherapeutic technologies in the complex treatment of malignant glial brain tumors», state registration number No. 0119U03900, applied, implementation term 2020-2022, led by Doctor of Medical Sciences, Professor O.Ya.Glavatskyi.

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Wilcoxon test showed a statistically significant decrease in QoL in the domain of insomnia (р = 0.000733) in SRT group and in the domain of fatigue (р = 0.016813) in HRT group.When comparing the results of the third and the second survey (12 vs. 6 months), the H0 hypothesis for all the studied parameters of QoL (GHS, insomnia, and fatigue) was rejected in both SRT and HRT groups (p ≤ 0.017 with the Bonferroni correction).When comparing the results of the third and the first survey (12 vs. 3 months), a statistically significant decrease in QoL in all studied parameters of QoL was observed: GHSS (р = 0.000078); fatigue (р = 0.000294); insomnia (р = 0.000318).The comparison of the results of these surveys in SRT group showed a statistically significant decrease of QoL in GHSS (р = 0.004650) and fatigue (p = 0.017938), with the level of statistical significance getting closer to the set critical value considering the Bonferroni correction.The intergroup analysis according to the Mann-Whitney U test showed a statistically significant advantage of HRT over SRT in all studied parameters of QoL in three subsequent surveys (p < 0.05).The ρ-test confirmed these data: HRT group patients had better parameters of QoL than SRT group patients over the whole period of the follow-up.Conclusions.The analysis of QoL according to the results of three subsequent surveys 3, 6, and 12 months after RT according to the GHSS, domains of insomnia and fatigue of the EORTC QLQ-C30 demonstrated a decrease in QoL of patients in both SRT and HRT groups.At the same time, a statistically significant advantage of HRT group over SRT group in all studied parameters of SRT was observed when the results of three subsequent surveys were compared.The proposed regimen of HRT for patients with primarily diagnosed GB may be considered an acceptable alternative to SRT in view of impact on QoL.
Сучасні технології прецизійного, висококонформного підведення дози, суттєво мінімізуючи променеву токсичність, надають можливість оптимізувати стандартні режими ПТ.В свою чергу, це призводить до більш широкого використання скорочених за трива-Glioblastoma (GB) is a primary malignant brain tumor that belongs to the most aggressive types of human cancers [1].More than 90% of patients with GB die within 5 years, with a median overall survival (OS) of 12-15 months [2].Taking into consideration an extremely poor prognosis for GB, searching for more effective therapeutic strategies for patients with this disease remains an urgent need.At the same time, increasing survival without maintaining the patient's quality of life (QoL) cannot be considered successful treatment [3].Radiation therapy (RT) is one of the main treatment methods for patients with GB that has demonstrated positive impact on survival in numerous studies [4,5].
Modern techniques of high-precision and highconformal dose delivery allow standard regimens of RT to be optimized by significantly minimizing radiation toxicity.Consequently, it leads to a wider use of shortened RT courses, in particular, hypofractionated RT (HRT) in patients with brain malignancies [6][7][8].Today HRT is considered a possible alternative to standard regimens of RT under the condition of comparability of oncological results, QoL, and radiation toxicity [9][10][11].Recent studies are strongly focused on the analysis of the results of HRT in patients with GB primarily in regard to its impact on survival [12][13][14].However, there is still a limited number of publications that deal with analysis of QoL in view of HRT of neuro-oncology patients.
Our study is concerned particularly with this issue and describes the results of the analysis of QoL after SRT and HRT in patients with primarily diagnosed GB.
Patient inclusion criteria for the study were: -men and women ≥18 years; -pathomorphologically confirmed diagnosis of GB (WHO grade 4 diffuse glioma); -patients with GB who received a course of adjuvant radiation treatment according to the standard (total dose 60.0 Gy in 30 fractions over 6 weeks) or the hypofractionated (total dose 52.5 Gy in 15 fractions over 3 weeks) regimens; -life expectancy >3 months; -informed voluntary written consent to receive treatment; willingness and ability to adhere to the procedures of the study and further follow-up.
Patient exclusion criteria for the study were: -age less than 18 years; -absence of pathomorphological verification of diagnosis of GB (WHO grade 4 diffuse glioma); -patients with GB who did not receive adjuvant RT or who were treated with any other treatment regimen than SRT (total dose 60.0 Gy in 30 fractions over 6 weeks) or HRT (total dose 52.5 Gy in 15 fractions over 3 weeks); -unwillingness to participate in the study, unsatisfactory compliance.
According to extent of surgical resection, the total cohort, SRT and HRT groups were divided the following way: removal of the tumor along the perifocal zone (gross total resection) -82 (51.6%), 23  In 15 (9.4%) patients of the total cohort (10 (6.3%) patients of HRT group and 5 (3.1%) patients of SRT group), adjuvant RT was performed in monoregimen without chemotherapy (CT).Accordingly, combined chemoradiation adjuvant treatment was used in the majority of the patients of the studied cohort -144 (90.6%) patients, most of who received alkylating CT (temozolomide) -125 (78.6%).The other 19 (12.0%) patients received nitrosourea-based CT (PCV).
In SRT and HRT groups, 38 (77.6%) out of 49 patients and 87 (79.1%) out of 110 patients received temozolomide and 6 (12.3%) out of 49 patients and 13 (11.8%)out of 110 patients received PCV, respectively.All the patients who underwent CT had no contraindications to it.

Design of the study of QoL
The study of QoL of patients with GB after adjuvant RT was performed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30 version 3.0) [15], whose informative value has already been proved in numerous studies [16][17][18][19].
The patient survey about Global Health Status (GHS) and domains of insomnia and fatigue (symptom points) was conducted three times subsequently during checkup examinations in postradiation period according to the follow-up plan 3, 6, and 12 months after cessation of RT (further referred to as the first, the second, and the third survey).
All scales and values are measured in points from 0 to 100.The higher the score on the GHS scale, the higher the level of QoL, and vice versa, the higher the score on the symptom scale, the higher the level of clinical symptoms.The total score was calculated from raw scores according to the recommendations on the EORTC QLQ-C30 scoring.
The statistical analysis of QoL parameters was performed separately for each group (SRT and HRT), comparing the results of the first, second, and third survey (intragroup analysis), as well as between SRT and HRT groups as comparison of independent groups with a different number of examinations for each period of the follow-up (intergroup analysis).
We used the Friedman test, which is a nonparametric analogue to the repeated measures ANOVA dispersion analysis.In addition, aposterior pairwise check of differences in three subsequent surveys 3, 6 and 12 months after RT was performed using the nonparametric Wilcoxon signed-rank test with the Bonferroni correction for critical level of statistical significance for this study.
The H0 hypothesis, which was tested using the Friedman test, was that the data of three subsequent surveys were samples from one universal set, i.e., the differences between the three surveys were entirely coincidental.
We used the nonparametric Mann-Whitney U test in the group analysis on the comparison of the results of the surveys between SRT and HRT groups.It is a nonparametric statistical test used for calculating difference between two independent samples according to the value of any parameter.
In descriptive statistics, the Kruskal-Wallis ANOVA & Median test and the Pearson's χ2 test were used for testing the intergroup distribution homogeneity of quantitative and relative values, respectively.
In all statistical tests, the critical level of statistical significance was set at αcrit = 0.05, considering the respective Bonferroni corrections for the Wilcoxon's signed-rank test.
Primary data collection and preparation were done in MS Excel, statistical calculations were performed using STATISTICA 64 v.12.5.192.0Windows NT 6.2 software for statistical data analysis.
Результати проведеного вище статистичного аналізу ГСЗ за EORTC QLQ-C30 щодо трьох послідовних опитувань пацієнтів групи СПТ та ГПТ проілюстро-During the postradiation follow-up period, the total number of times the patients were surveyed about QoL according to the GHS scale and domains of insomnia and fatigue symptoms was 239.Among them, the patients from SRT group were surveyed 85 times and the patients from HRT group -154 times.During the first survey (3 months after cessation of RT), 34 (69.4%)patients in SRT group and 74 patients (67.3%) in HRT group were surveyed; during the second survey (6 months after RT), 30 (61.2%) patients in SRT group and 48 (43.6%) patients in HRT group were surveyed; during the third survey (12 months after RT), 21 (42.9%)patients in SRT group and 32 (29.1%) patients in HRT group were surveyed.
At the first stage of statistical analysis, QoL of patients of the studied sample was calculated separately in SRT and HRT groups (intragroup analysis), i.e., the data obtained in SRT and HRT groups in three subsequent surveys according to GHS and domains of insomnia and fatigue according to the EORTC QLQ-C30 were analyzed separately.
According to the results of statistical calculations according to the Friedman test, the H0 hypothesis about three subsequent surveys that represent GHS according to the EORTC QLQ-C30 in patients from SRT group should be rejected: Friedman ANOVA and Kendall Coeff. of Concordance ANOVA Chi Sqr.(N = 21, df = 2) = 20.57143;p = 0.00003; Coeff. of Concordance = 0.48980; Aver.rank r = 0.46429.
At the same time, the results of this statistical analysis for HRT group also allow the H0 hypothesis about three subsequent surveys that represent GHS according to the EORTC QLQ-C30 in patients from SRT group to be rejected: Friedman ANOVA and Kendall Coeff. of Concordance ANOVA Chi Sqr.(N = 32, df = 2) = 39.03529;p = 0.00000; Coeff. of Concordance = 0.60993 Aver.rank r = 0.59734.
The results of the abovementioned statistical analysis of GHS according to the EORTC QLQ-C30 in three subsequent surveys of patients from SRT and HRT groups Thus, according to the results of the abovementioned statistical calculations, the H0 hypothesis about three subsequent surveys about the symptoms of fatigue and insomnia according to the EORTC QLQ-C30 is rejected with respective level of statistical significance for this study.
Figure 2 shows that the symptoms of fatigue in both SRT and HRT groups tend to worsen 12 months after therapy, compared to the second as well as the first survey.It can also be seen that this effect develops more rapidly in HRT group, although it does not reach the level of negative assessment as in the respective survey in SRT group (55 points vs. 78 points).
Figure 3 also shows that the results of the survey about the symptoms of insomnia in SRT group after 12 months are practically the same as the results of the first survey (after 3 months).However, in HRT group, there is a tendency toward worsening, compared to the results of the second as well as the first survey.Nevertheless, similarly to the symptoms of fatigue, the results do not reach the level of negative assessment as in the respective survey in SRT group (31 points vs. 67 points).
Taking into consideration the abovedescribed assumptions about changes in medians of the analyzed parameters of QoL (Fig. 1-3), it is important to note that these assumptions may be considered statistically significant conclusions according to the set critical level α during the intragroup analysis using the Wilcoxon test and during the intergroup comparison of SRT and HRT groups using the Mann-Whitney U test as described below.
The next stage of the intragroup study of the parameters of QoL in SRT and HRT groups was conducting a statistical analysis using the Wilcoxon test for pairwise comparison of the results of the first against the second survey; the second against the third survey; the first against the third survey in SRT and HRT groups separately.
The results of this statistical analysis are given in Table 2.
Thus, compared to the second assessment, QoL statistically significantly differs in the third assessment for all studied parameters (GHS, insomnia, fatigue) in both SRT and HRT groups according to the Wilcoxon signed-rank test for linked samples considering the Bonferroni corrections.
The comparison of the results of the first and the third survey in HRT group showed statistically significant difference in all the studied parameters of QoL: GHS, fatigue, insomnia.
In SRT group, the first and the third survey statistically significantly differed in GHS (p = 0.004650).However, the comparison of the results of the first and the third survey in this group demonstrated p-value = 0.017938

Note:
for accepting/rejecting the H0 hypothesis, the Bonferroni correction with α = 0.017 was used.
Український which was close to the critical value α = 0.017 for rejecting/accepting the H0 hypothesis, taking into consideration the Bonferroni correction.For insomnia, distributions of the first and the third survey in SRT group did not differ statistically significantly (p = 0.833936).Thus, the results of statistical calculations according to the Wilcoxon's test allow the conclusion to be made that the most significant difference was observed between the second and the third survey in both groups.There was the least difference between the first and the second survey, and statistically significant difference in SRT group was observed only in the domain of insomnia, whereas in HRT group -only in the domain of fatigue.
The results of the comparison of the first and the third survey are interesting because they indicate the presence of statistically significant difference in all the studied parameters of QoL in HRT group, as shown in Table 2.
At the same time, the results of the comparison of the first and the third survey in SRT group are not similar to those in HRT group: there is statistical difference in GHS (p = 0.004650); there is no statistical difference in insomnia (p = 0.833936); in the domain of fatigue, the level of statistical significance (p = 0.017938), which was close to the critical value α = 0.017 for rejecting/accepting the H0 hypothesis, taking into consideration the Bonferroni correction, was observed.
The abovementioned results of statistical testing also allow the statistical significance of the assumptions about the intragroup comparison of the tendencies of QoL parameters that are illustrated in Fig. 1-3 to be confirmed.
Thus, we described the results of the intragroup study and set statistical significance for the respective results of the comparison of the tendencies of QoL parameters in patients after RT.
Consequently, the next stage of the study was an intergroup analysis of SRT and HRT groups, which made it possible to compare QoL of patients of these groups according to the respective periods of surveys using the Mann-Whitney U test.Testing H0 hypothesis according to the Mann-Whitney U test allows us to make conclusions about the statistical significance of the discovered intergroup tendencies of the parameters of QoL described above.
The results of the calculation of the Mann-Whitney U test statistics for comparing QoL between SRT and HRT groups demonstrated statistically significant difference (p < αcrit) in all the studied parameters of QoL (GHS, fatigue, insomnia) at all stages of the study with the set critical level of statistical significance.
We also used an additional statistical analysis with ρ parameter [21].This parameter is a nonparametric measure of overlap between two distributions that can take a value from 0 to 1.Both extreme values present a complete division of distributions, whereas ρ = 0.5 means a complete overlap.However, two distributions that significantly differ according to the Mann-Whitney U test may have almost identical medians (the «average» patient of the first group does not differ from the «average» patient from the second group).Nevertheless, if the value of ρ parameter in this case is, for example, 0.7 in favor of group 1, it indicates the fact that all the patients of group 1 prevail over all the patients of group 2. рівень статистичної значущості p-value = 0,017938, що наближується до критичного значення α = 0,017 для відхилення/прийняття гіпотези Н0, враховуючи корекцію Бонферроні.Для безсоння розподіли першого і третього опитування у групі СПТ статистично значуще не розрізнялись (р = 0,833936).
This method was chosen for statistical analysis, as it allowed statistical significance of the abovementioned assumptions about the tendencies of the parameters of QoL, which prevailed at each of the stages of the survey, to be assessed.
The results of statistical calculations of the difference between SRT and HRT group in the studied parameters of QoL at different stages of the survey according to the ρ parameter (a nonparametric measure of overlap between two distributions) demonstrated that HRT group had better parameters at all stages of the survey in all the studied parameters of QoL (GHS, fatigue, insomnia).When interpreting this result, we took into consideration the feature of QoL scoring for the GHS scale and domains of symptoms (fatigue and insomnia), respectively.Thus, the higher the score on the GHS scale, the higher the level of QoL; on the contrary, the higher the score on the symptom scale, the higher the level of expression of clinical symptoms.
The box-and-whisker plot analysis is given below for illustrating and interpreting the abovementioned results of the comparison between SRT and HRT groups in all studied parameters of QoL for the first and the last (third) survey (Fig. 4-6).The assessment of QoL of neuro-oncology patients attracts attention of an increasingly greater number of scientists because it is considered an important criterion for making clinical decisions about effectiveness of a certain type of treatment.
The modern approaches to analyzing QoL, particularly using the EORTC QLQ-C30, make it possible to quantitatively assess parameters, which show various aspects of subjective perception of the patient's state in the context of a certain disease (from functional limitation to the degree of life satisfaction).and the group of hypofractionated radiation therapy (Hypo RT).Median -median, 25-75% -interquartile range, Min -Max -minimum and maximum value Thus, QoL is not considered an overcomplicated and amorphous term by doctors anymore.It is an effective tool for clinical decision-making with analytical evidential basis [23,24].The comparison of different types of treatment according to the results of the assessment of QoL allows the most optimal therapy to be chosen, given that there is no significant difference in survival and toxicity of compared methods.
The results of the survival analysis of the patients of this cohort (SRT and HRT groups) are described in detail in a different publication [25].Statistical calculations did not show an advantage in survival, depending on the type of radiation treatment used.The median overall survival (OS) in SRT and HRT groups was 15.0 (95% CI 14.1-17.1)and 16.5 (95% CI 14.1-18.8)months, respectively (logrank test; p = 0.06757).According to the time period before onset of progression, SRT and HRT groups did not differ practically: in SRT group, the median progression-free survival (PFS) was 9.0 (95% CI 9.0-10.0)months; in HRT group, the median PFS was 9.0 (95% CI 8.0-10.0)months (logrank test; p = 0.43374).
Прикладом такого аналізу є нещодавня публікація Baviskar, Y. та співавт.(2023), що демонструє результати ІІ фази проспективного клінічного випробування, метою якого було вивчити довгострокові результати ЯЖ та виживання пацієнтів з несприятливим прогнозом гліоми високого ступеня злоякісності, які отримували паліативну ГПТ (СВД 35 Гр за 10 фракцій протягом 2 тижнів) [28].Оцінювання ЯЖ However, the analysis of QoL during the 12-month postradiation period of the follow-up showed an advantage of a shorter treatment regimen (HRT) according to the studied parameters of the EORTC QLQ-C30: GHS, fatigue, insomnia.The intragroup analysis demonstrated statistically significant difference between the parameters of QoL within one group when comparing the results of three subsequent surveys (the Friedman test) and allowed us to conduct a pairwise comparison of the results of the survey (6 vs. 3 months; 12 vs. 3 months) in groups separately according to the Wilcoxon signedrank test for linked samples, considering the Bonferroni correction.The most significant difference in QoL parameters in SRT and HRT groups was observed in the pairwise comparison of the second against the third survey, the least significant -in the comparison between the first and the second survey (Table 2).
It should be mentioned that the central tendency of QoL within the group demonstrates a gradual deterioration of QoL over time, which is represented by GHS and fatigue during the follow-up period, with lower intensity of these negative changes in HRT group, compared to SRT group.
QoL represented by fatigue practically returns to the results of the first survey in SRT group 12 months after RT.However, in HRT group, there is a tendency toward worsening during the follow-up period despite the fact that, similarly to fatigue, the results do not reach the level of negative assessment, which is characteristic of the respective survey in SRT group.
The comparison of the studied parameters of QoL in SRT and HRT groups using the Mann-Whitney U test demonstrated the presence of statistically significant difference at all stages of the survey and showed an advantage in QoL according to the median value in HRT patients.Taking into consideration the features of this statistical test that allows independent groups to be compared, interpretation of its results may be the following: an advantage in QoL of the «average» patient of HRT group over the «average» patient of SRT group was observed.
To confirm the advantage in the parameters of QoL of one of the studied groups, the analysis with ρ-test was used.This test makes it possible to compare all the patients in the group, i.e., the whole distribution.It was found that all patients in HRT group dominated in the analyzed parameters of QoL over SRT group.
It should be mentioned that the number of publications that are concerned with the analysis of QoL of patients with malignant gliomas after hypofractionared RT remains limited.
Hypofractionated regimens of RT in patients with primarily diagnosed glioblastoma are recommended as standard treatment for elderly patients and/or patients with unfavorable prognosis, as well as in progression (recurrence) of the tumor [26,27].Therefore, the aspect of QoL in view of radiation treatment in glioblastoma is the most studied particularly in these clinical variants.
Найбільш повно це питання розкрито в нещодавній публікації, співавторами якої є потужна група провідних світових нейроонкологів.Це мультицент-using the QLQ-C30 and its additional BN20 brain tumor module.The authors demonstrated that the shortened course of palliative HRT in patients with unfavorable prognosis for malignant glioma was associated with stable and/or improved parameters of QoL.After the palliative course of HRT, statistically significant improvement was observed in such domains, as fatigue (p = 0.032), dyspnea (p = 0.042), and movement dysfunction (p = 0.036) over time.Thus, the authors demonstrated that the hypofractionated treatment regimen proposed by them should be considered as the one associated with certain clinical benefits, namely the positive impact on QoL of the patients with unfavorable prognosis for malignant glioma.
However, Arakawa Y. et al. ( 2022) emphasize in their publication that is concerned with the choice of an optimal treatment strategy for elderly patients with GB that chronological age should not exclude the possibility of multimodal treatment, as well as provision of satisfactory QoL in case of the increase in survival.The authors also state that although the combination of HRT and chemotherapy with temozolomide after the surgery has become a recommended treatment for elderly patients with GB, some problems remain unsolved, namely the issue of the number of fractions and dose regimen of RT that would ensure the best parameters of QoL and survival [29].
In 2021, Melo S. M. et al. published a meta-analysis that described four randomized clinical trials about studying QoL when using HRT in elderly patients with primarily diagnosed GB [30].Because of the fact that QoL was studied using different methods and at different points of time (only two studies used QLQ-C30 and BN20), it is difficult to summarize the results of the performed analysis.It is worth emphasizing that among the clinical trials analyzed in this metaanalysis, there are ones that are regarded as the most significant in neuro-oncology in recent decades.It indicates that the leading world experts have been already certain for some time about the importance of adding parameters of QoL as endpoints of clinical trials.
At the same time, the factor of QoL plays a significant role in determining optimal treatment strategy in progression of malignant glioma because there is no consensus about standard treatment of these patients and the studies aimed at developing more effective therapeutic strategies are still in progress [31,32].For example, Maitre P. et al. studied QoL and everyday life activity of patients after repeated treatment of recurrence/progression of gliona [33].According to the authors' analysis, QoL assessed according to QLQ-C30 and BN20 remains stable and is accompanied with improvement in everyday life activity according to the modified Barthel index after repeated high-dose treatment of progression of glioma.
Nevertheless, other authors deepen discussion on the clinical importance of QoL analysis in neuro-oncology patients and think over whether the enhancement of symptoms and deterioration of QoL are associated with the tumor progression [34].
This issue is described in most detail in a recent publication written by a powerful group of the leading world neuro-oncologists.It is a multi-centre study that includes a numerous cohort of 5539 patients with gliomas (64% of them have GB), in who QoL during the PFS period was analyzed and the factors associated with QoL deterioration were determined using QLQ-C30 До основних обмежень нашої роботи слід віднести обмежений термін спостереження та кількості пацієнтів у групі стандартного фракціонування, відсутність даних щодо ЯЖ перед опроміненням та даних, які були б отримані за допомогою інших шкал and BN20 [35].It was established that almost half (47%) of the patients experienced deterioration of healthrelated QoL during the PFS period.Only the level of functional ability was associated with deterioration of QoL at the statistically significant and clinically significant level.Apart from the functional ability, several other factors, including elderly age, male sex, and diagnosis of GB, were independently associated with deterioration of certain QoL scales.However, the degree of deterioration was not considered statistically significant.It was determined that treatment was not independently associated with deterioration of QoL during the PFS period.Nevertheless, the use of some treatment methods apart from RT was associated with statistically significant but not clinically significant deterioration of QoL, namely chemotherapy and the combination of chemotherapy with angiogenesis inhibitors were associated with deterioration of physical functioning at the statistically significant but not clinically significant level.
This study is vitally important for neuro-oncologists because it researches the issue of whether there is a possibility to maintain QoL of patients with glioma during the PFS period on a numerous cohort of patients using powerful methods of statistical analysis.It was determined which exact social demographic and clinical factors were independently associated with deterioration of QoL during the PFS period.An important conclusion is the fact that the treatment was not directly independently associated with deterioration of QoL of the patients during the PFS period.It was noted that «the time before deterioration of QoL» (this term excludes tumor progression as an event and thus depicts the possible impact of unfavorable effects on QoL in a better way) was longer than «survival without deterioration of QoL» (this term includes deterioration of QoL, tumor progression, or death of the patient) in the overwhelming majority (85-92%) of the patients included in analysis of the clinical trials.It indicates the importance of glioma progression as a key event that leads to deterioration of QoL.
The abovementioned data prove that the analysis of QoL is an essential part of the assessment of treatment results of patients with GB and is more widely implemented in modern neuro-oncology studies.Consequently, our study is concerned with currently important problems of modern neuro-oncology and radiation oncology.
We performed an intragroup and an intergroup statistical analysis of QoL parameters for SRT and HRT groups that demonstrated the changes of studied parameters of QoL over time during the postradiation period and showed the advantage of hypofractionated treatment regimen in the studied cohort, i.e., patients with GB who received HRT had statistically significantly higher QoL according to the studied parameters, namely GHS scale and domains of fatigue and insomnia.
The main limitations of our study are the limited follow-up period, the limited number of patients in the group of standard fractionation, and the absence of data on QoL before treatment and the data that would be received using other scales of the EORTC QLQ-C30.We believe that further studies on the analysis of QoL of neuro-oncology patients are of great importance.Враховуючи вищезазначене, отримані нами результати можна вважати такими, що підтверджують доцільність більш широкого застосування гіпофракційних режимів ПТ у пацієнтів з ГБ.Оскільки вони демонструють відсутність переваги стандартного режиму ПТ як в онкологічних результатах [25], так і щодо збереження ЯЖ. treatment, particularly different regimens of hypofractionation (for example, medium-intensity hypofractionation against ultrahypofractionation/stereotactic radiosurgery), volume of irradiation target, localization of the area of irradiation in the brain, degree of radiation load on critical structures of the brain.An interesting thing is determination of certain clinical features/symptoms of «prodrome» of deterioration of QoL in early postradiation period, especially in cases when QoL significantly deteriorates in late postradiation period, and how it is associated particularly with radiation load.It would allow «risk patients» to be distinguished based on deterioration of QoL in postradiation period and measures of QoL preservation for patients with GB after aggressive multimodal treatment to be improved.
Taking into consideration the abovementioned information, the results that we obtained could be considered as the ones that confirm the relevance of a wider use of hypofractionated regimens of RT in patients with GB because they demonstrate the absence of advantage of the standard regimen of RT in both oncological results [25] and preservation of QoL.
In SRT group, statistical difference in QoL between the last and the first survey (12 vs. 3 months) was observed according to the GHS scale and domain of fatigue.
The separate analysis of SRT and HRT groups showed that the most significant deterioration of QoL in both groups was observed when comparing the results of the third and the second survey (12 vs. 6 months).Statistically significant difference was observed for all the studied parameters of QoL.
The least significant difference in QoL in both groups was observed when comparing the second and the first survey (6 vs. 3 months): in SRT group, a statistically significant decrease in QoL according to the domain of insomnia was observed, in HRT group -according to the domain of fatigue.
The analysis of QoL according to the results of three subsequent surveys 3, 6, and 12 months after RT according to the GHSS, domains of insomnia and fatigue of the EORTC QLQ-C30 demonstrated a decrease in QoL of patients in both SRT and HRT groups.At the same time, a statistically significant advantage

Перспективи подальших досліджень Prospects for further research
Якість життя є важливим чинником прийняття клінічних рішень.Тому в нейроонкології зростає актуальність досліджень, що присвячені аналізу якості життя пацієнтів із Quality of life is an important factor for clinical decision-making.Therefore, the relevance of neuro-oncology studies concerned with analysis of quality of life of patients with brain tumors

1
State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine 2 State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine», Kharkiv, Ukraine 3 Educational and Research Institute for Applied System Analysis of the National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute» of the Ministry of Education and Science of Ukraine, Kyiv, Ukraine