**8. Prognostic factors**

Unfortunately, regardless of the treatment regimen, survival of patients afflicted with osteosarcomas of the head and neck remains poor.

While there are several single and multicenter studies reported, population data are scarce and controversial. On a literature review by Mendehall et al. [6] in 2011, overall survival shows a very wide range among the different series, going from 24 to 86% at 5 years. In Smith et al. [8] NCDB study with 496 patients, the 5-year diseasespecific survival was reported to be 59.7%, for patients who were diagnosed with HNOS between 1985 and 1991. Similarly, in Lee et al. [9] cohort of the SEER tumor registry, with 541 patients, the 5-year overall and disease-specific survival were 52% and 62%, respectively, and the 10-year overall and disease-specific survival were 35% and 54%, respectively, with a median overall survival of 8 years.

Both of this large series report multiple patient, tumor, and treatment factors that were associated independently with a significantly worse survival. These risk factors included: skull or facial bone sites (vs. mandible); age older than 60 years; tumor size >6 cm; osteoblastic/NOS histology; high histological grade; advanced stage at presentation; nonsurgical initial therapy; and the presence of residual disease after surgical resection [8, 9].

Different series confirm the finding that mandibular tumors appear to have a better prognosis than maxillary tumors, showing significant difference in the metastatic rate and local recurrence [8, 9, 16]. The median overall survival for osteosarcoma of the mandible has been reported to be 10.4 years vs. 6.3 years for osteosarcoma of the skull/facial bones, including the maxilla [9]. This may be due to a greater metastatic potential in more vascularized sites such as the maxilla and skull base and/or to a more economical resection in these areas, compared with the mandible, with smaller oncologic safety margins, given the greater anatomic complexity and proximity to vital structures. Maxillary tumors show greater rate of positive margins [16]. In any case, this observation emphasizes the need for greater therapeutic consideration.

Age is another factor named repeatedly by different authors to impact survival, generally 60 years and older. Advanced age could affect by an age-dependent T-lymphocyte depletion, an intolerance to the cytotoxic effects of chemotherapy, a higher propensity to development of metastatic disease, or differences in management based on age [9].

In addition, a tumor size, histology, and grade have also shown to impact survival. Of note, osteoblastic OS has evidenced worse overall survival [8], and fibroblastic and chondroblastic osteosarcoma had the best prognosis of histological subtypes,

### *Perspective Chapter: Osteosarcomas of the Head and Neck DOI: http://dx.doi.org/10.5772/intechopen.107456*

while osteosarcoma in Paget disease had a particularly poor outcome with an overall survival not longer than 6 months [9].

Histological Grade has been proved to impact severely on survival, thus is now taken into account for staging [8, 9, 16, 39]. Within the NCDB [8], patients with low-grade HNOS tumors showed a 74% 5-year survival rate, compared with 42% for patients with high-grade tumors. Ha et al. [21] also noted a marked discrepancy in survival for patients with high-grade versus low-grade HNOS tumors, with a difference at 5 years of nearly 60%. However, on the SEER tumor registry [9], the multivariate analysis found that grade was not considered to be and independent significant determinant of survival, which could perhaps be explained by the high percentage of cases defined to be unknown.

On another hand, treatment has shown to impact dramatically patients' outcome, and surgical resection has been found to improve 5-year overall and disease-specific survival [8, 9, 16]. Complete surgical resection with wide margins has been reported as the most significant prognostic factor in HNOS [6, 13, 15]. It is reasonable to state that patients with HNOS who are not candidates for surgical resection because of advanced disease or notable comorbidities at presentation may bias the survival advantage seen in the different cohorts. However, according to Smith et al. [8], patients who did not undergo surgical therapy had a markedly worse survival with a 5-year overall survival of 21.7% compared with 74.7% for patients treated with surgery alone and 71.3% surgery plus chemotherapy.

Finally, prognosis follows a dynamic course that has been and will continue to change as the best treatment approach for these patients becomes clearer. In a study by Granowski-LeCornu et al. [16], where patients with OS of the jaw were treated from 1967 to 1991 where compared with patients treated from 1992 to 2009, this second group had better prognosis than patients in the earlier treatment group (overall 5-yeral survival rate of 77% vs. 52%). They discuss that this could be explained by several factors favoring the latter group, such as better imaging, both CT and MRI, allowing for earlier diagnosis, thus, smaller tumors at diagnosis and better treatment planning. Also, more sophisticated reconstructive techniques allow wider ablative procedures and better chance of achieving clear margins.

For more recent HNOS patients, we now offer improved diagnostic tools, more aggressive treatment, and better surveillance. The role of neoadjuvant chemotherapy remains to be elucidated and may perhaps, added to all this other factors, continue to improve prognosis.
