Role of nitric oxide in predicting radiotherapy-related side effects in patients with cervical cancer
Year 2025,
Volume: 38 Issue: 3, 215 - 220, 10.10.2025
Dilek Gül
,
Hazan Özyurt
,
Özlem Gümüştekin Bülbül
,
Alpaslan Mayadağlı
Abstract
Objective: To assess whether serum nitric oxide (NO) levels can predict radiation-induced side effects in cervical cancer patients
undergoing pelvic radiotherapy (RT).
Patients and Methods: Twenty participants diagnosed with locally advanced-stage cervical cancer were included. Weekly blood
samples were analyzed for NO levels. Genitourinary (GU), lower gastrointestinal (LGI), and upper gastrointestinal (UGI) toxicities
were graded weekly. Two separate analyses were conducted based on initial NO levels either categorized as NO-low and NO-high or
the mean NO ratios (NOR) recorded before and after RT. Lastly, the mean clinical symptoms (grade < 2 versus grade ≥ 2) at the end of
RT were correlated with the mean NO values.
Results: Serum NO levels increased significantly from baseline (p = 0.001). No significant differences in toxicity were found when
comparing mean NOR values before and after RT. Symptomatic patients (grade ≥ 2) exhibited higher NO levels at week 5 for GU and
LGI toxicities. Baseline NO levels did not consistently predict the severity of side effects.
Conclusion: Serum NO levels increased significantly during RT. No definitive correlation with toxicity severity and NO levels were
observed. Further studies require to clarify the potential of NO as a biomarker for predicting RT-induced side effects.
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oxide in patients with nasopharyngeal carcinoma. Int Forum
Allergy Rhinol 2023;13:1982-1986. doi: 10.1002/alr.23161.
Year 2025,
Volume: 38 Issue: 3, 215 - 220, 10.10.2025
Dilek Gül
,
Hazan Özyurt
,
Özlem Gümüştekin Bülbül
,
Alpaslan Mayadağlı
References
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Hunsberger KS, Tewari KS, Monk BJ, Chase DM. Standard
of care treatment for stage IVB cervical cancer: A systematic
review and meta-analysis. Gynecol Oncol 2024 191: 259-64.
doi: 10.1016/j.ygyno.2024.10.023.
-
Franco I, Viswanathan AN. Radiation oncology management
of stage III and IVA cervical carcinoma. Int J Gynecol Cancer
2022 32:231-8. doi: 10.1136/ijgc-2021-002491.
-
Maduro JH, Pras E, Willemse PH, de Vries EG. Acute
and long-term toxicity following radiotherapy alone or in
combination with chemotherapy for locally advanced cervical
cancer. Cancer Treat Rev 2003 29:471-88. doi: 10.1016/s0305-
7372(03)00117-8.
-
Damast S, Jeffery DD, Son CH, et al. Literature review of
vaginal stenosis and dilator use in radiation oncology. Pract
Radiat Oncol 2019 9:479-91. doi: 10.1016/j.prro.2019.07.001.
-
Lawrie TA, Green JT, Beresford M, et al. Interventions to
reduce acute and late adverse gastrointestinal effects of
pelvic radiotherapy for primary pelvic cancers. Cochrane
Database Syst Rev 2018 1:CD012529. doi: 10.1002/14651858.
CD012529.pub2.
-
Gandhi AK, Sharma DN, Rath GK, et al. Early clinical outcomes
and toxicity of intensity modulated versus conventional pelvic
radiation therapy for locally advanced cervix carcinoma: a
prospective randomized study. Int J Radiat Oncol Biol Phys
2013 87:542-8. doi: 10.1016/j.ijrobp.2013.06.2059.
-
Aryankalayil M, Bylicky MA, Chopra S, et al. Biomarkers
for biodosimetry and their role in predicting radiation
injury. Cytogenet Genome Res 2023 163:103-9. doi:
10.1159/000531444.
-
Vorotnikova E, Rosenthal RA, Tries M, Doctrow SR, Braunhut
SJ. Novel synthetic SOD/catalase mimetics can mitigate
capillary endothelial cell apoptosis caused by ionizing
radiation. Radiat Res 2010 173:748-59.
-
Aktan F. iNOS-mediated nitric oxide production and its
regulation. Life Sci 2004 75: 639-53, 2004.
-
Guerrero T, Martinez J, McCurdy MR, Wolski M, McAleer
MF. Elevation in exhaled nitric oxide predicts for radiation
pneumonitis. Int J Radiat Oncol Biol Phys 2012;82:981-8. doi:
10.1016/j.ijrobp.2010.08.041.
-
Chen GG, Lee TW, Xu H, et al. Increased inducible nitric
oxide synthase in lung carcinoma of smokers. Cancer 2008;
11: 372–81. doi: 10.1002/cncr.23166.
-
Basudhar D, Somasundaram V, de Oliveira GA, et al. Nitric
oxide synthase-2-derived nitric oxide drives multiple
pathways of breast cancer progression. Antioxid Redox Signal
2017; 26: 1044-58.
-
Naidu MS, Suryakar AN, Swami SC, Katkam RV, Kumbar
KM. Oxidative stress and antioxidant status in cervical cancer
patients. Indian J Clin Biochem 2007;22:140-4. doi: 10.1007/
BF02913333.
-
McCurdy MR, Wazni MW, Martinez J, McAleer MF, Guerrero
T. Exhaled nitric oxide predicts radiation pneumonitis in
esophageal and lung cancer patients receiving thoracic
radiation. Radiother Oncol 2011;101:443-8. doi: 10.1016/j.
radonc.2011.08.035.
-
Corbeau A, Heemsbergen WD, Kuipers SC, et al. Predictive
factors for toxicity after primary chemoradiation for
locally advanced cervical cancer: A systematic review. Int
J Radiat Oncol Biol Phys 2024 119:127-42. doi: 10.1016/j.
ijrobp.2023.11.010.
-
Moore DH. Cervical cancer. Obstet Gynecol 2006 107:1152-
61. doi: 10.1097/01.AOG.000.021.5986.48590.79.
-
Oken MM, Creech RH, Tormey DC, et al. Toxicity and
response criteria of the Eastern Cooperative Oncology Group.
Am J Clin Oncol 1982 5:649-55.
-
Trotti A, Byhardt R, Stetz J, et al. Common toxicity criteria:
version 2.0. an improved reference for grading the acute
effects of cancer treatment: impact on radiotherapy. Int J
Radiat Oncol Biol Phys 2000 47:13-47. doi: 10.1016/s0360-
3016(99)00559-3.
-
Gao Y, Luo T, Huang D, et al. Construction of a checkpoint
inhibitor-related pneumonia diagnostic model based on
exhaled nitric oxide: a prospective observational study. Transl
Lung Cancer Res 2025;14:1740-55. doi: 10.21037/tlcr-2024-
1085.
-
Ho YT, Lee TJ, Chang PH, Fu CH. Post-irradiation nasal nitric
oxide in patients with nasopharyngeal carcinoma. Int Forum
Allergy Rhinol 2023;13:1982-1986. doi: 10.1002/alr.23161.