PIOC is a rare malignancy that may develop from the remnants of odontogenic epithelium and is located within bone without demonstrable evidence of a primary carcinoma in oral or sinusal mucosa 9. Due to the rarity of primary intraosseous carcinoma, few studies and related clinical data are available for this disease, which prompt us to sought to investigate the prognostic factors and treatment of primary intraosseous carcinoma. In previous studies, swelling, pain, and pyorrhea after tooth extraction and cyst enucleation were the main complaints at the initial diagnosis of PIOC. The most common clinical manifestation of PIOC is swelling, pain, facial asymmetry, and diffuse distension of the jaws 10. Half of the patients in our cohort presented with facial masses and pain, which is consistent with previous reports.
In the 1960s, the 5-year OS of primary intraosseous carcinoma, known as intra-alveolar epidermoid carcinoma at that time, was reported to be 30-40% by Shear et. al.11. Huang et. al. reported a 2-years OS of 69.8% and a 5-year OS of 36.3% for 39 patients with PIOC 12. Similar findings have been reported by Xu and others 8,13,14. In our cohort, the 2-year OS and 5-year OS of PIOC are 60.7% and 38.5% respectively, which are close to previous reports. A definite diagnosis of PIOC at early stage is often challenging resulting in poor prognosis, based on unobvious symptoms and difficulty to distinguish squamous cell carcinoma of surface mucosal origin and other odontogenic carcinomas which warrants early diagnosis and treatment.
Histologically, these tumors are squamous cell carcinomas which range from well differentiated to poorly differentiated lesions. In present study, patients with well differentiated tumors had better OS (46.2% vs. 16.7%) and PFS (46.2% vs. 0%, P = 0.01) than those with poorly differentiated tumors, which was consistent with previous studies 8,13.
PICO is considered to have infiltrated into the mandible, surgical procedures included resection of the lesion mass, partial or total removal of the upper / lower jaws, and radical or select cervical lymph node dissection to ensure that the tumor is thoroughly excised 8,15. Surgical intervention is currently the first choice for this disease, and 89.3% of patients received surgical. It has been reported that patients with positive lymph nodes had a lower 2-year OS compared to those with negative lymph nodes 13. Whereas in the present study, patients with negative lymph nodes (N0) had an OS of 55.6% and those with positive lymph nodes (n1-3) had an OS of 36.8%.
PIOC is an aggressive disease that tends to locally recurrent and metastases distantly. Nowadays the staging system and treatment guideline for PIOC still remain uncertain although we used American Joint Committee on Cancer (AJCC) classification for oral cancer in this study which was not perfect enough. Meanwhile the specific treatment guidelines for PIOC are not available yet, Naruse et al. believe that the treatment of PIOSCC should be similar with that of at least stage T3N0 oral cancer 14. In addition to surgical treatment, other recommended treatments according to National Comprehensive Cancer Network (NCCN) guidelines include radiotherapy, chemotherapy, targeted treatment etc. Recent studies have shown that appropriate adjuvant treatment can achieve the lowest local recurrence and ensure a better survival 16. Chen et al. concluded that postoperative radiotherapy should be given to patients with i. positive operative margins, ii. tumor involvement of adjacent soft tissues, iii. metastatic neck nodes, and iv. partial excision of the primary tumor 17. Alotaibi O et al. reported that patients with PIOC who received adjuvant radiotherapy after surgery had better survival, demonstrating the effectiveness of adjuvant therapy after surgery 18. However Xu et al. believed that patients treated by surgery alone had a better survival rate than those who were treated with combined chemoradiotherapy, because the latter cohort of patients had more aggressive tumor and higher clinical and pathological stage of the tumor 8, Some studies also believe that whether adjuvant radiotherapy or chemotherapy after surgery has no significant statistical difference in the OS 19
In the present study, 6 patients who received surgical treatment alone, had an OS of 16.7%. The other 19 patients who were treated with radiotherapy and/or chemotherapy after surgery had an OS of 52.6%, which is significantly higher than that in patients who underwent surgery alone. The result showed that radiotherapy could significantly improve the survival rate of patients. Patients with tumor-free surgical margins and received adjuvant radiation had a higher survival rate (64.3% vs 33.3%) compared with those who received a radical radiotherapy. This may be associated with a lighter adverse effect of radiotherapy. It’s the first time to report that radiotherapy can improve the survival for the patient with PIOC of the jaw with data to back it up. The reason for the differences among these studies may be that the number of patients included in some studies using radiotherapy or chemotherapy was too small, which failed to yield positive results. Moreover, patients in some of the studies received chemoradiotherapy in an insufficient dose, which made patients being unable to benefit from chemoradiotherapy and suffering increased toxic side effects. This study confirmed the indispensable role of surgical treatment in the management of PIOC patients and also emphasized that radiotherapy plays an irreplaceable role in the treatment of PIOC.
In the treatment of advanced squamous cell carcinoma of the head and neck, targeted therapy has become a routine treatment, which can shrink the tumor mass and kill micro tumor metastases, at the same time, it can reduce the dose of chemotherapy drugs to achieve better efficacy with fewer side effects20. Studies on PIOC targeted therapy are rarely reported. In our cohort, two patients were administrated nimotuzumab and one patient took cetuximab. The role of targeted therapy in PIOC needs further investigation because of the small size of sample.