Page 55 - ARNM-3-1

Advances in Radiotherapy
& Nuclear Medicine The novel index and osteoradionecrosis

(C-CRT) represents the current care standard. C-CRT such as tumor necrosis factor-α (TNF-α), interleukin-10
1,2
demonstrates significantly enhanced local control rates (IL-10), and vascular endothelial growth factor, which are
(>90%) and prolonged survival durations compared to crucial in tissue fibrosis. 16,22 Vascular thrombosis, hypoxia,
1
radiotherapy (RT). Nonetheless, a notable subset of patients and consequent fibrotic processes caused by radiation
subjected to this potent but potentially toxic treatment exposure can exacerbate localized damage by augmenting
modality may suffer from severe delayed complications, synthetic processes and the release of inflammatory
including persistent dysphagia necessitating feeding chemokines and cytokines such as IL-1, IL-6, hypoxia-
tubes, trismus, and osteoradionecrosis of the jaw (ORNJ). inducible factor-1 alpha (HIF-1α), insulin-like growth
Implementing more sophisticated intensity-modulated factor 2, and transforming growth factor-beta (TGF-ß). 23-26
RT (IMRT) protocols reduces the incidence rates of these Although the association between post-RT TEs and
complications to a certain extent; however, they cannot the increased incidence of ORNJ is well-documented,
eradicate them. 3-6 the effect of pre-RT TE remains uncertain. 27-30 However,
ORNJ is a debilitating long-term complication of a recent study conducted by our team revealed a notable
C-CRT in LA-NPC and other head-and-neck cancers. correlation between the occurrence of ≥4 pre-C-CRT TE
Its occurrence rate ranges from 2% to 22%, with over and substantially high ORNJ rates (3.3% vs. 19.1% for ≥4
29
70% of cases being identified within the initial 3 years TE; P = 0.003) in patients with LA-NPC. This finding
after C-CRT. 7-10 ORNJ can occur spontaneously, and underscores the potential significance of the level of
higher tumor stage, primary or nodal tumor invasion mandibular trauma, potentially rendering the irradiated
into the jaws, pretreatment alveolar surgery, non-IMRT jaw site more susceptible to ORNJ development. Based
techniques, tooth extractions (TEs) before and after on our previous findings, which indicated that high
treatment, and poor oral health are cited among the most pretreatment PIV levels ≥833 and ≥4 TE were strong
common risk factors. 7,11,12 The fibro-atrophic theory is predictors of ORNJ rates after C-CRT, we will attempt
the most appreciated explanation of ORNJ formation. to explore whether combining these specific parameters
According to this theory, the detrimental vascular changes could better stratify these patients into different ORNJ
in the bone, conjoined with endothelial changes or loss, risk groups. Consequently, this retrospective study aimed
cause an inflammatory response that results in hypoxia, to determine whether this hypothesis is valid for LA-NPC
hypervascularity, and hypocellularity. 11,13 This mediator- cohorts who received IMRT-based C-CRT.
induced inflammatory process is typically followed by
abnormally high fibroblastic activity and incompetent 2. Patients and methods
bone repair, resulting in bone necrosis, that is, ORNJ. 11-14 2.1. Patients
As inflammatory cells and mediators play important roles Data were collected from the institutional medical records
in ORNJ development, their potential use in predicting of 220 patients with LA-NPC who received comprehensive
the occurrence of ORNJ following RT or C-CRT warrants
further investigation. dental examinations and exclusive. C-CRT at the Dentistry
Clinics and the Department of Radiation Oncology of
Prognostic indexes, such as the pan- Baskent University between January 2011 and December
immune-inflammation value (PIV = 2022. The inclusion criteria were as follows: patients aged 18
[platelet×monocyte×neutrophil]÷lymphocyte]), combine – 80 years, confirmed squamous cell NPC histopathology,
different indicators from the whole blood count and have clinical and/or radiologic evidence of LA-NPC according
garnered considerable attention as a practical and indirect to the American Joint Committee on Cancer staging system
method of assessing the overall inflammation extent in the (8 edition), no previous systemic chemotherapy or RT,
th
body. The PIV is an exceptional composite biomarker accessible pre- and post-C-CRT panoramic radiographs,
15
that integrates lymphocytes, platelets, monocytes, and and complete blood count tests conducted before
neutrophils, objectively reflecting systemic inflammation C-CRT. This study excluded patients with mandibular
and immunological activity. High PIVs frequently tumor invasion, prior diagnosis of osteoradionecrosis
indicate persistent inflammation in individuals with (ORNJ), or those who had used steroids within 30 days
atherosclerosis, vascular occlusive diseases, and several preceding C-CRT. Patients presenting with active systemic
cancer. 16-19 In earlier research, 20,21 chronic systemic inflammatory conditions – including respiratory diseases,
inflammation has been linked to arthritis and venous rheumatologic diseases, viral hepatitis, nephritic disorders,
obstruction. Moreover, systemic inflammation has been confirmed immunosuppressive disorders, collagen vascular
connected to the activation of inflammatory mediators diseases, or other chronic inflammatory conditions –
generated by neutrophil granulocytes and thrombocytes, were also ineligible for participation. These criteria were

Volume 3 Issue 1 (2025) 47 doi: 10.36922/arnm.5799