Comment on “Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma” (DOI: 10.1159/000527261)

We were very interested in the study by Tufano-Sugarman and colleagues, which compared clinical and radiologic features of osteonecrosis to those of recurrent or advancing cancer [1]. Nineteen patients with clinical and/or radiological suspicion of osteoradionecrosis (ORN) after radiotherapy (RT) for head and neck squamous cell carcinoma were included in the study. Patients were divided into three categories based on their definitive diagnosis: ORN, recurrent or persistent squamous cell carcinoma, and indeterminate. The authors defined the indeterminate group as patients who died before a confirmatory biopsy. The statistical outcomes revealed that the clinical presentation or radiological characteristics, the median time between treatment and the start of symptoms, the dosage and type of RT, and the time between treatment and symptom onset were not linked to the diagnosis. On the basis of the results, the authors concluded that the clinical and radiological features of ORN and cancer had a substantial degree of overlap. In addition, it was emphasized that symptoms occurring within 6 months of the conclusion of chemoradiotherapy should be regarded as indications of recurrence or progression of cancer, not as ORN. Although the data may provide valuable information about the current challenges in obtaining an accurate ORN diagnosis, we have three concerns about the study’s findings.

First, previous studies demonstrated that the required mean mandibular dose for ORN development was frequently higher than 60 Gy and that the V50–V60 (volume of the mandible receiving 50 or 60 Gy or more) was also critical [2]. The current analysis results indicate that the dose administered to the mandible in ORN patients was 62.14 Gy, as opposed to 57.7 Gy in cancer patients. Hence, it is reasonable to suspect ORN in the group with the highest mean mandibular dose if there is a significant dosage disparity. In this regard, V50–V60 or another study-specific volumetric cutoff may also help identify cases of ORN with a high probability. However, neither a volumetric cutoff nor the locations of hot-spot areas in the mandible or how they relate to ORN sites were disclosed. Despite the lack of these data, it still seems reasonable to infer that the 60 Gy critical cutoff for ORN development would be exceeded in cases where the mean mandibular RT dose was 62.14 Gy, as opposed to 57.83 Gy in cases of recurrent or progressive cancer.

Second, ORN is defined as irradiated bone that failed to heal within 3 months without evidence of persistent, recurrent, or metastatic cancer [4]. This definition clearly states that exposing the bone to RT is a prerequisite for an ORN diagnosis. However, in the current study, bisphosphonates were administered in 2 cases. Thus, it will be impossible to determine if the necrotic bone or clinical findings are consistent with bisphosphonate-related osteonecrosis of the mandible or an actual ORN [5]. Moreover, even though pathological confirmation is the gold standard for detecting recurrent illness [6], two of the so-called ORN patients were not biopsied; therefore, it may be invalid to include these 2 cases in the ORN group.

And third, the authors reported that two ORN instances were identified at month zero. But, according to the literature, ORN is a late-stage RT complication frequently diagnosed 8–19 months after RT completion [7]. Therefore, month zero is too soon to make a definitive ORN diagnosis. Although previous dental extractions, mandibular surgery, or bisphosphonate use may have coincidentally led to the development of osteonecrosis [9], not ORN, no detailed information about these issues is provided, which could help determine the exact cause of osteonecrosis in these 2 patients. Consequently, the missing information should be supplied to determine the precise cause of the osteonecrosis: true ORN as opposed to traumatic or medication-related osteonecrosis.