Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood
Abstract
:1. Introduction
2. Materials and Methods
Statistical Data Processing
3. Results
3.1. Comparative Characteristics According to Endocrine Anomalies
3.2. Comparative Characteristics of ECHO Data in Patients after CSR and CR
3.3. Comparative Characteristics of the Main Clinical and Demographic Indicators in Patients after CR and CSR
3.4. Comparison of the Physical Performance Indicators in Patients after Oncological Treatment in Childhood and Healthy Individuals
3.5. Independent Predictors of Reduced Physical Performance and Ventilation Efficiency
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Value |
---|---|
Age at the time of diagnosis, years | 13.6 ± 4.3 |
Mean time after diagnosis, years | 7.9 ± 5.3 |
Mean time after the end of treatment, years | 6.9 ± 5.4 |
Pathological diagnosis, n (%): | |
- Medulloblastoma | 25 (52.1) |
- Astrocytoma | 5 (10.4) |
- Germinomas | 8 (16.7) |
- Primitive tumors | 3 (6.2) |
- Other types of tumors | 7 (14.5) |
Hormonal abnormalities, n (%): | 39 (81.3) |
- Somatotropin insufficiency | 32 (66.7) |
- Hypocorticism | 25 (52.1) |
- Hypothyroidism | 28 (58.3) |
- Hypogonadism | 28 (58.3) |
Previous treatment, n (%): | |
- Cx | 43 (89.6) |
- RT | 48 (100) |
- Gamma knife | 1 (2.1) |
- Surgery | 40 (83.3) |
Combination treatment, n (%): | |
- Surgery + Cx + RT | 37 (77.1) |
- Cx + RT | 6 (12.5) |
- Surgery + RT | 3 (6.3) |
- RT | 2 (4.2) |
Antitumor agents, n (%): | |
- Carboplatin | 3 (6.4) |
- Cisplatin | 31 (64.6) |
- Etoposide | 11 (22.9) |
- Ifosfamide | 6 (12.6) |
- Cyclophosphamide | 6 (12.6) |
- Temodal | 9 (18.7) |
- Lomustin | 28 (58.3) |
- Vincristine | 29 (60.4) |
- Cytosar | 1 (2.1) |
Mean number of chemotherapy cycles, n | 9.1 ± 6.9 |
Mean effective dose of RT depending | |
on the area of exposure, Gy: | |
TCD | 32.9 ± 9.9 |
TCSD | 33.9 ± 3.6 |
3D conformal RT-CSA | 35.2 |
3D conformal RT boost | 60.0 |
3D conformal RT—metastases | 40.0 |
TTBD | 50.2 ± 9.7 |
PCFTD | 58.1 ± 13.9 |
Dose for metastases | 36.4 ± 18.0 |
Parameter | Main Group (n = 48) |
---|---|
Men, n (%) | 20 (42) |
Height, cm | 162.5 ± 12.9 |
Bodyweight, kg | 59.3 ± 17.7 |
Body mass index, kg/m2 | 22.0 ± 4.2 |
Smokers, n (%) | 1 (2.1) |
Mean BP, mm Hg | 75.8 ± 8.8 |
Heart rate at rest, bpm | 81.3 ± 12.7 |
Total cholesterol, mmol/L | 5.4 ± 1.3 |
LDL cholesterol, mmol/L | 3.2 ± 1.0 |
HDL cholesterol, mmol/L | 1.5 ± 0.5 |
Triglycerides, mmol/L | 1.2 ± 0.6 |
Dyslipidemia *, n (%) | 27 (56) |
Parameter | Patients after Cranial Radiation Therapy (n = 8) | Patients after Craniospinal Radiation Therapy (n = 40) | p-Value |
---|---|---|---|
LVEF, % | 62.0 ± 5.7 | 64.4 ± 4.6 | 0.406 |
VTI, % | 19.5 ± 2.9 | 17.9 ± 2.4 | 0.104 |
GLS, % | 20.7 ± 1.0 | 19.1 ± 3.1 | 0.659 |
ESV, mL | 19.8 ± 11.1 | 20.3 ± 8.7 | 0.954 |
EDV, mL | 63.7 ± 24.2 | 60.7 ± 17.6 | 0.853 |
LA, mL | 33.4 ± 12.2 | 33.9 ± 10.2 | 0.843 |
RA, mL | 24.2 ± 7.6 | 23.4 ± 7.2 | 0.540 |
RV, cm | 2.4 ± 0.3 | 2.5 ± 0.4 | 0.974 |
E | 90.6 ± 13.3 | 90.5 ± 18.7 | 0.947 |
A | 60.0 ± 17.5 | 59.5 ± 14.1 | 0.881 |
E/A | 1.5 ± 0.4 | 1.5 ± 0.3 | 0.839 |
TAPSE, cm | 1.9 ± 0.2 | 1.9 ± 0.2 | 0.818 |
E/E’med | 7.5 ± 4.3 | 7.6 ± 5.0 | 0.971 |
Parameters | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 |
---|---|---|---|---|---|
Type of tumor | Germinoma | Medulloblastoma | Germinoma | Medulloblastoma | Anaplastic ependymoma |
Type of treatment | Surgery + Cx + RT | Surgery + Cx + RT | Cx + RT | Surgery + Cx + RT | Surgery + Cx + RT |
RT, Gy | total cranial dose—56.1 Gy, spinal dose—47.1 Gy, tumor bed dose—77.5 Gy | craniospinal dose 35 Gy, posterior cranial fossa, total dose 55 Gy | total cranial dose—24 Gy, tumor bed dose—54 Gy | total cranial dose—31 Gy, spinal dose—32 Gy, tumor bed dose—49 Gy | total cranial dose—35 Gy, spinal dose—35 Gy, posterior cranial fossa, total dose—55 Gy |
Cx | Platinum drugs, alkaloids, alkylating drugs | Platinum drugs, alkylating drugs | Platinum drugs, alkaloids | Platinum drugs, alkaloids, alkylating drugs | Platinum drugs, alkylating drugs |
Indicators of physical performance | Reduced VO2 peak 20, 9 mL × min−1 × kg % VO2 peak 52%, AT 11.2 mL × min−1 × kg | Reduced VO2 peak—13 mL × min−1 × kg % VO2 peak—28%, AT—12.2 mL × min−1 × kg | Reduced VO2 peak—11.3 mL × min−1 × kg % VO2 peak—20%, AT—8.8 mL × min−1 × kg | Reduced VO2 peak—16.7 mL × min−1 × kg % VO2 peak—37%, AT—13.4 mL × min−1 × kg | Reduced VO2 peak 25.5 mL × min−1 × kg % VO2 peak—74%, AT—15.1 mL × min−1 × kg |
Changes in ECHO parameters | TAPSE—1.6, VTI—12%, EF—54% | TAPSE—1.6, VTI—14%, EF—66%, GLS—16% | TAPSE—1.7 VTI—14%, EF—51% | TAPSE—1.4, VTI—13.4%, EF—55%, GLS—12.5% | Calcification of the aortic valve |
Parameter | Patients after Cranial Radiation Therapy (n = 8) | Patients after Craniospinal Radiation Therapy (n = 40) | p-Value |
---|---|---|---|
Age, years | 21.7 ± 4.4 | 21.7 ± 4.4 | 0.946 |
Age, years (min–max) | 18–30 | 16–33 | |
Men, n (%) | 4 (50) | 18 (45) | 0.999 |
Height, cm | 161.1 ± 13.8 | 162.7 ± 12.9 | 0.694 |
Weight, kg | 62.8 ± 17.8 | 58.6 ± 17.8 | 0.471 |
Age at the time of treatment, years | 13.3 ± 2.9 | 12.1 ± 4.2 | 0.674 |
Time after treatment, years | 6.9 ± 5.2 | 7.1 ± 5.3 | 0.797 |
Surgery, n (%) | 4 (50) | 36 (90) | 0.018 |
Cx, n (%) | 7 (87.5) | 36 (90) | 0.999 |
Cx courses, n | 10.4 ± 12.4 | 8.8 ± 5.6 | 0.307 |
Total tumor bed dose, Gy Min–max, Gy | 57.4 ± 2.9 54.0–60.0 | 51.9 ± 12.1 30.0–75.6 | 0.311 |
Total cranial dose, Gy Min–max, Gy | 36.0 ± 15.8 24.0–54.0 | 35.5 ± 10.4 24.0–55.0 | 0.599 |
Mean BP, mm Hg | 81.3 ± 8.3 | 74.8 ± 8.5 | 0.073 |
Heart rate at rest, bpm | 74.0 ± 10.1 | 82.7 ± 12.7 | 0.067 |
Parameter | Patients after Cranial Radiation Therapy (n = 8) | Patients after Craniospinal Radiation Therapy (n = 40) | p-Value |
---|---|---|---|
AT, mL × min−1 × kg | 14.8 ± 3.1 | 14.5 ± 3.6 | 0.999 |
VO2 peak, mL × min−1 × kg | 22.5 ± 4.5 | 19.4 ± 6.5 | 0.305 |
TSH, µIU/mL | 1.1 ± 1.3 | 2.7 ± 1.9 | 0.022 |
FSH, mIU/mL | 3.9 ± 3.7 | 9.2 ± 11.9 | 0.089 |
Prolactin, µIU/mL | 248.1 ± 204.4 | 333.2 ± 218.6 | 0.314 |
Cortisol, nmol/L | 259.1 ± 177.1 | 400.1 ± 164.9 | 0.094 |
GH, mIU/L | 1.4 ± 1.3 | 1.7 ± 1.8 | 0.617 |
ACTH, pmol/L | 3.7 ± 1.7 | 5.7 ± 3.5 | 0.283 |
IGF-1, ng/mL | 201.6 ± 130.2 | 131.2 ± 64.9 | 0.131 |
Parameter | Main Group (n = 48) | Control Group (n = 20) | p-Value |
---|---|---|---|
VO2 peak, mL × min−1 × kg | 19.8 ± 6.4 | 30.3 ± 5.8 | <0.0001 |
VO2 peak reduced, n (%) | 30 (62.5) | 5 (25) | <0.0001 |
VO2 peak, % of normal | 50.6 ± 16.8 | 85.8 ± 11.4 | <0.0001 |
Anaerobic threshold/ mL × min−1 × kg | 14.5 ± 3.7 | 16.4 ± 3.9 | 0.315 |
Anaerobic threshold reduced, n (%) | 23 (47.9) | 5 (25) | 0.204 |
METs | 7.1 ± 2.6 | 8.9 ± 1.5 | 0.003 |
Reduced exercise tolerance, n (%) | 23 (47.9) | 5 (25) | 0.003 |
PetCO2 rest, mm Hg | 26.5 ± 4.8 | 28.8 ± 5.4 | 0.3001 |
PetCO2 rest less 34 mm Hg, n (%) | 43 (89.5) | 17 (85) | 0.295 |
PetCO2 peak, mmHg | 36.3 ± 5.2 | 40.6 ± 4.0 | 0.009 |
PetCO2 peak less 34 mm Hg, n (%) | 18 (37.5) | 2 (10) | 0.010 |
VE/VCO2, % | 29.9 ± 5.1 | 23.6 ± 3.6 | 0.044 |
VE/VCO2 elevated, n (%) | 26 (54.2) | 1 (5) | <0.0001 |
Outcome | Possible Predictors | Value | Indicators|t|-Statistics | F-Statistics | p |
---|---|---|---|---|---|
Reduced tolerance, METs 1 | Younger age at the start of treatment | 0.145 | 2.165 | 4.686 | 0.035 |
Reduced PetCO2 at rest 2 | Higher total cranial dose | 0.042 | 3.089 | 9.543 | 0.003 |
Reduced PetCO2 at load 2 | Higher total cranial dose | 0.041 | 2.804 | 7.972 | 0.007 |
Reduced CO2 ventilatory equivalent 3 | Higher total cranial dose Higher dose on the tumor bed | 0.037 0.027 | 3.193 4.317 | 10.19 18.64 | 0.002 <0.0001 |
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Novikova, A.; Poltavskaya, M.; Pavlova, M.; Chomakhidze, P.; Bykova, A.; Potemkina, N.; Chashkina, M.; Fashafsha, Z.Z.A.; Mesitskaya, D.; Gogiberidze, N.; et al. Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood. J. Clin. Med. 2024, 13, 3045. https://doi.org/10.3390/jcm13113045
Novikova A, Poltavskaya M, Pavlova M, Chomakhidze P, Bykova A, Potemkina N, Chashkina M, Fashafsha ZZA, Mesitskaya D, Gogiberidze N, et al. Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood. Journal of Clinical Medicine. 2024; 13(11):3045. https://doi.org/10.3390/jcm13113045
Chicago/Turabian StyleNovikova, Alena, Maria Poltavskaya, Maria Pavlova, Petr Chomakhidze, Aleksandra Bykova, Nadezhda Potemkina, Maria Chashkina, Zaki Z. A. Fashafsha, Dinara Mesitskaya, Nana Gogiberidze, and et al. 2024. "Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood" Journal of Clinical Medicine 13, no. 11: 3045. https://doi.org/10.3390/jcm13113045
APA StyleNovikova, A., Poltavskaya, M., Pavlova, M., Chomakhidze, P., Bykova, A., Potemkina, N., Chashkina, M., Fashafsha, Z. Z. A., Mesitskaya, D., Gogiberidze, N., Levshina, A., Giverts, I., Shchekochikhin, D., & Andreev, D. (2024). Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood. Journal of Clinical Medicine, 13(11), 3045. https://doi.org/10.3390/jcm13113045