**7. Treatment alternatives**

Overall, HNOS are rare tumors that present unique treatment challenges. Due to its infrequency, most studies on the subject are retrospective analyses of small cohorts that utilize multiple treatment modalities, thus most treatment strategies are dictated by the existing knowledge of OS in long bones, and a variety of approaches are being applied without a standardized method of comparing relative outcomes and an answer for which the optimal treatment modality remains inconclusive.

Moreover, as stated before, HNOS has major differences from OS in the rest of the body, which could mean the need for a different treatment approach. HNOS presents at an older age than OS of long bones, has a lower metastatic potential, but a markedly higher rate of local recurrence.

Nevertheless, surgery remains the cornerstone of treatment, and negative margins the main prognostic factor and the only way to ensure locoregional control.

### **7.1 Surgery**

The impact of impact of surgical treatment on 5-year disease-specific survival is dramatic and was evidenced on the analysis of the NCDB [8], where patients who did not undergo surgical therapy had a markedly worse survival. Patients who underwent surgery alone and surgery plus chemotherapy demonstrated similar 5-year survival rates (74.7% and 71.3%, respectively). In comparison, nonsurgical therapy resulted in a 21.7% 5-year survival [8].

However, surgical success in these patients represents a real challenge, as ensuring negative margins can be difficult, because of the anatomical complexity of the region, tumor resections are occasionally incomplete. Local recurrences and intracranial invasion have long been reported as the major causes of treatment failure due to incomplete neoplasm resection.

Furthermore, in addition to the presence of noble structures surrounding the tumor and the significant rate of irresectability that we can find in these fast-growing tumors, the lack of consensus on what we define as "adequate margins," "close margins," or "insufficient margins" also poses a problem. Obtaining disease-free resection margins is of course imperative, to avoid the risk of local recurrence; however, adequate margins of several centimeters, usually required for long bone OS, are often not achievable on HNOS since resecting few millimeters more often means endangering pivotal functional structures, with a noticeable decrease in the patients' quality of life.

Of course, this may vary by tumor subsite, and the rationale and surgical treatment planning will depend on the location. It has been documented that mandibular tumors have a significantly higher chance of achieving a wide negative margin, probably because these tumors are detected earlier than in other bones of the skull/ face and because larger resections can be performed with less damage to surrounding noble structures and with better chances of functional reconstruction [7, 16].
