Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer—A Risk Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Cohort
2.2. Eligibility Criteria
2.3. Multimodal Treatment Strategy
2.4. Radiotherapy Simulation, Contouring, and Planning
2.5. Statistical Analysis
2.5.1. Primary Variables
2.5.2. Variables Statistics
2.5.3. Secondary Variables
2.5.4. Risk Analysis and Logistic Model
3. Results
3.1. Patients
3.2. Therapy Modalities
3.3. Treatment-Related Adverse Events
3.4. Time Period to Maximum Drop of Leukocytes and Hemoglobin
3.5. Neutrophils and Platelets Drop
3.6. Hemoglobin Drop over the Course of Treatment
4. Discussion
4.1. Hematological Adverse Events
4.2. Clinical Adverse Events
4.3. Study Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviation
3D-CRT | 3D-conformal radiotherapy |
AE | Adverse event |
BMI | Body mass index |
CCRT | Concurrent chemoradiotherapy |
CHT | Chemotherapy |
CT | Computed tomography |
CTV | Clinical target volume |
CV | Cardiovascular |
DM | Diabetes mellitus |
DVH | Dose-volume histogram |
EBRT | External beam radiotherapy |
EF | Extended field |
GTV | Gross tumor volume |
HT | Hematological toxicity |
IMRT | Intensity-modulated radiotherapy |
OAR | Organ at risk |
OR | Odds-ratio |
OS | Overall survival |
PFS | Progression-free survival |
PTV | Planning target volume |
QoL | Quality of life |
RT | Radiotherapy |
RR | Risk-ratio |
UAIC | Uterine arterial interventional chemoembolization |
VMAT | Volumetric modulated arc therapy |
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Data Class | |
---|---|
1 | Clinical and Demographical |
2 | Pre-treatment tumor pathology features |
3 | Treatment modalities |
4 | Radiotherapy-related adverse events |
5 | Post-treatment characteristics |
Variable | Age (in yrs) | Weight (in kg) | BMI (in kg/m2) | |
---|---|---|---|---|
Mean | 54.19 | 69.47 | 26.33 | |
Range | 48 | 62 | 20.06 | |
Minimum | 28 | 40 | 15.63 | |
Maximum | 76 | 102 | 35.69 | |
Percentiles | 0.25 | 48.50 | 61.00 | 23.23 |
0.33 | 50.14 | 63.28 | 24.64 | |
0.50 | 53.00 | 70.00 | 26.56 | |
0.67 | 59.00 | 75.00 | 27.86 | |
0.75 | 62.50 | 76.00 | 28.90 | |
Variable | Value | N | % | |
High blood pressure and/or other CV diseases | Yes | 11 | 15.9 | |
No | 58 | 84.0 | ||
DM and/or obesity | Yes | 4 | 5.7 | |
No | 65 | 94.2 | ||
CV disease and DM or obesity combined | Yes | 10 | 14.4 | |
No | 59 | 85.5 | ||
Other diseases or immunity-related | Yes | 4 | 5.7 | |
No | 65 | 94.2 |
Characteristic | Value | N | % |
---|---|---|---|
Histopathological type | Squamous cell carcinoma | 53 | 94.6 |
Adenocarcinoma | 3 | 5.4 | |
Histopathological differentiation | G1 | 1 | 2.4 |
G2 | 24 | 58.5 | |
G3 | 16 | 39.0 | |
Presence of invaded lymph nodes | No | 27 | 46.6 |
Yes | 31 | 53.4 | |
Pre-treatment tumor (T) staging | T1a2 | 4 | 7.4 |
T1b | 2 | 3.7 | |
T1b1 | 1 | 1.9 | |
T1b2 | 1 | 1.9 | |
T1b3 | 1 | 1.9 | |
T2a | 36 | 66.7 | |
T2a2 | 6 | 11.1 | |
T2b | 3 | 5.6 | |
Pre-treatment nodal status (N) | Nx or N0 | 27 | 46.6 |
N1 | 26 | 44.8 | |
N2 | 5 | 8.6 | |
Pre-treatment AJCC Staging | Stage IB1 | 3 | 5.5 |
Stage IB2 | 1 | 1.8 | |
Stage IIB | 2 | 3.6 | |
Stage III | 20 | 36.4 | |
Stage IIIC1 | 7 | 12.7 | |
Stage IIIC2 | 17 | 30.9 | |
Stage IVA | 3 | 5.5 | |
Stage IVB | 2 | 3.6 |
Characteristic | Value | N | % |
---|---|---|---|
Chemotherapy | No chemotherapy | 1 | 1.8 |
Cisplatin | 52 | 92.9 | |
Carboplatin | 3 | 5.4 | |
NA | 13 | ||
Radiotherapy technique | 3D-CRT | 41 | 59.4 |
VMAT | 18 | 26.1 | |
Brachytherapy fractions | 0 | 4 | 5.8 |
2 | 45 | 65.2 | |
3 | 9 | 13.0 | |
4 | 1 | 1.4 | |
Duration (in weeks) of radiotherapy breaks | 0 | 49 | 82.5 |
1 | 5 | 8.8 | |
2 | 4 | 7.0 | |
4 | 1 | 1.8 |
Characteristic | Value | N | % |
---|---|---|---|
General | |||
Fatigue | No | 21 | 36.2 |
Yes | 37 | 63.8 | |
Unknown | 10 | ||
Genitourinary | |||
Dysuria | No | 41 | 70.7 |
Yes | 17 | 29.3 | |
Unknown | 10 | ||
Digestive | |||
Nausea and vomiting | No | 24 | 41.4 |
Yes | 34 | 58.6 | |
Unknown | 10 | ||
Diarrhea | No | 23 | 39.7 |
Yes | 35 | 60.3 | |
Unknown | 10 | ||
Hematological | |||
Anemia | No | 15 | 22.1 |
Yes | 53 | 77.9 | |
Thrombocytopenia | No | 43 | 63.2 |
Yes | 25 | 36.8 | |
Neutropenia | No | 39 | 57.4 |
Yes | 29 | 42.6 | |
Leukopenia | No | 23 | 33.8 |
Yes | 45 | 66.2 |
Variable | OR | 95%CI | p | RR | 95%CI |
---|---|---|---|---|---|
Neutropenia with a minimal neutrophils level ≤ 2.2; (VN: 2.0–7.7) (in 103/μL) during follow-up | |||||
Planned dose for pelvic region volume = 54 Gy | 6.82 | (1.15, 40.41) | 0.034 | 2.56 | (1.53, 4.29) |
Thrombocytopenia with a minimal platelets level ≤ 131.00; (VN: 150–400) (in 103/μL) during follow-up | |||||
Planned dose for pelvic region volume = 54 Gy | 6.67 | (1.22, 36.59) | 0.029 | 1.95 | (1.34, 2.83) |
Neutropenia during follow-up | |||||
Rectal V45 as planned within VMAT > 63.43% | 18.00 | (1.19, 271.46) | 0.037 | 5.26 | (2.86, 9.67) |
Bladder V50 as planned within VMAT > 10.69% | 16.50 | (1.09, 250.18) | 0.043 | 4.88 | (2.66, 8.93) |
Bowel V45 as planned within VMAT > 137.38 cc | 16.50 | (1.09, 250.18) | 0.043 | 4.88 | (2.66, 8.93) |
Maximum drop of leukocytes level in less than 35 days from RT initiation | |||||
Radiotherapy technique = 3D-CRT | 4.44 | (1.25, 15.82) | 0.021 | 1.94 | (1.00, 3.78) |
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 4.12 | (1.20, 14.14) | 0.025 | 1.75 | (1.04, 2.93) |
Planned dose for pelvic region volume = 54 Gy | 4.00 | (1.19, 13.50) | 0.025 | 1.75 | (1.02, 3.00) |
Variable | OR | 95%CI | p | RR | 95%CI |
---|---|---|---|---|---|
Maximum Hb variation > 2.50 g/dL | |||||
BMI > 23.23 kg/m2 | 8.68 | (1.01, 75.01) | 0.049 | 5.29 | (2.31, 12.14) |
Age > 53 yrs | 4.60 | (1.10, 19.22) | 0.036 | 2.99 | (1.84, 4.86) |
Radiotherapy technique 3D-CRT | 7.25 | (1.73, 30.38) | 0.007 | 4.13 | (2.63, 6.49) |
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 4.71 | (1.09, 20.47) | 0.038 | 3.26 | (1.95, 5.44) |
Per day maximum Hb variation rate > 0.03 g/dL/day | |||||
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 11.81 | (1.35, 103.04) | 0.025 | 1.49 | (1.31, 1.71) |
Planned dose for pelvic region volume = 54 Gy | 10.56 | (1.22, 91.01) | 0.032 | 1.48 | (1.30, 1.68) |
Per dose maximum Hb variation rate > 0.04 g/dL/Gy | |||||
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 10.50 | (2.00, 55.03) | 0.005 | 1.82 | (1.52, 2.19) |
Planned dose for pelvic region volume = 54 Gy | 8.82 | (1.71, 45.52) | 0.009 | 1.75 | (1.47, 2.07) |
Planned radiotherapy fractions > 28.00 fractions | 8.82 | (1.71, 45.52) | 0.009 | 1.75 | (1.47, 2.07) |
Per dose maximum Hb variation rate > 0.08 g/dL/fraction | |||||
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 8.89 | (1.69, 46.63) | 0.01 | 1.69 | (1.42, 2.00) |
Planned dose for pelvic region volume = 54 Gy | 7.60 | (1.47, 39.29) | 0.016 | 1.63 | (1.39, 1.91) |
Maximum Hb variation in less than 29 days from RT initiation | |||||
Planned dose for pelvic region volume = 54 Gy | 6.76 | (1.88, 24.29) | 0.003 | 2.85 | (1.27, 6.38) |
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 6.02 | (1.72, 21.10) | 0.005 | 2.61 | (1.24, 5.46) |
Maximum Hb variation in less than 35 days from the RT initiation | |||||
Planned dose for pelvic region volume > 50.40 Gy | 11.11 | (2.54, 48.66) | 0.001 | 5.32 | (3.25, 8.71) |
Total EQD2 > 66.1 Gy(CTV includes lomboaortic lymph nodes) | 8.00 | (1.86, 34.36) | 0.005 | 4.35 | (2.66, 7.11) |
Radiotherapy technique (1—VMAT, 2—3D-CRT) | 3.71 | (1.03, 13.46) | 0.035 | 2.36 | (1.65, 3.37) |
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Share and Cite
Marinescu, Ș.A.; Toma, R.-V.; Trifănescu, O.G.; Galeș, L.N.; Folea, A.R.; Sima, A.; Bîlteanu, L.; Anghel, R. Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer—A Risk Analysis. Cancers 2024, 16, 3032. https://doi.org/10.3390/cancers16173032
Marinescu ȘA, Toma R-V, Trifănescu OG, Galeș LN, Folea AR, Sima A, Bîlteanu L, Anghel R. Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer—A Risk Analysis. Cancers. 2024; 16(17):3032. https://doi.org/10.3390/cancers16173032
Chicago/Turabian StyleMarinescu, Șerban Andrei, Radu-Valeriu Toma, Oana Gabriela Trifănescu, Laurenția Nicoleta Galeș, Antonia Ruxandra Folea, Adrian Sima, Liviu Bîlteanu, and Rodica Anghel. 2024. "Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer—A Risk Analysis" Cancers 16, no. 17: 3032. https://doi.org/10.3390/cancers16173032