Osteosarcoma of the Upper Extremities: A National Analysis of the US Population

Discussion

To our knowledge, this is the largest study to determine the incidence of osteosarcomas of the upper extremities in the US population. Osteosarcoma of the hand and wrist is very rare; however, we found a higher incidence (0.9%) than previous studies. Okada et al. (4) reported an incidence of 0.18% for osteosarcoma of the hand from 1,681 patients with skeletal osteosarcomas, while Anninga et al. (5) found an incidence of 0.5% out of 2,488 osteosarcoma cases. The higher incidence of osteosarcoma of the hand and wrist in our study may be due to the larger sample size.

Regarding patient characteristics in those with osteosarcoma of the upper extremities, we did not find the typical bimodal distribution according to age. Mirabello et al. (3) found a peak in the incidence of patients between 0 and 24 years, and a second peak in patients aged 60 years or older. Moreover, our study found that osteosarcomas of the upper extremities tended to appear more often in white men. Previous studies have described that osteosarcomas appear more frequently in white men when they are older, in contrast to osteosarcomas diagnosed at younger ages that are more often in black men (3, 9).

In addition, our study found that patients in Academic/Research programs were more frequently diagnosed with osteosarcoma of the upper extremities compared to other programs. We believe that this finding may correspond to a higher suspicion for the disease and ability to perform laboratory and imaging tests for diagnosis in academic programs (10). Another explanation may be due to the symptoms that may overlap with other conditions. Osteosarcoma presents with variable dull pain and tenderness that may last several months and suddenly becomes more severe, but as the presentation usually is after a recent history of trauma, its diagnosis may be delayed (11).

Osteosarcomas follow different histologic patterns. According to the predominant type of matrix (osteoid, cartilage, or collagen), they are classified into osteoblastic, chondroblastic and fibroblastic (12). In long bone osteosarcomas, the osteoblastic type predominates and has the worse prognosis (13). In our study, we found that the most common histology type in the upper extremities was osteosarcoma NOS, which included osteogenic and osteoblastic types. Although we could not distinguish the most frequent between these two types of osteosarcoma, we were able to determine that histology type does not differ according to location of osteosarcoma.

The most common location of osteosarcomas in the upper extremities was the forearm, arm, and shoulder. The humerus accounts for 10% to 15% of all the cases of osteosarcoma, and it is considered the third most common location of primary osteosarcoma, (7) after the distal femur and proximal tibia (14). The proximal humerus is the most common location of osteosarcoma in the upper extremities, followed by the radius, ulna, metacarpals, and phalanges (15).

Negative prognostic factors for osteosarcoma survival include high grade, large tumor size, location in limbs, and presence of metastasis at time of presentation (16). Our study described the frequency of the prognostic factors in patients with osteosarcomas of the upper extremities. Most patients presented with high-grade tumors larger than 8 cm and without metastasis to lymph nodes or lungs.

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Figure 1.

Ten-year overall survival according to location in the upper extremities.

Conventional treatment for osteosarcomas consists of a combination of surgery and chemotherapy (17). Surgical options include limb salvage and amputation. Although, there is controversy regarding the use of these procedures, both treatments are still being performed as the objective of both is complete resection of the tumor (18). Our study found that most of the patients with osteosarcomas of the upper extremities underwent complete excision of the tumor with limb salvage and chemotherapy. Limb salvage surgeries include resection and reconstruction of the limb, providing a safe treatment for patients with high-grade osteosarcoma (19). Development of new schemes of chemotherapy has prevented distant metastasis, controlling invasion, reducing the size of primary tumors and improving survival (2). Regarding other types of treatment, we found that a lower number of patients underwent radiotherapy. This could be due to the late disease stage found in some of these patients. Radiotherapy is recommended for patients with osteosarcoma that presents with inaccessible lesions, for those refusing surgery, or for whom surgical resection is not possible, and represents an alternative therapy to control the local tumor in the extremities (20).

When tumor characteristics were compared, we only found statistical difference in the grade of tumor. The lower risk of high-grade tumors in the hand and wrist suggests better prognosis and less aggressiveness compared to osteosarcomas of the forearm, arm, and shoulder. However, 10-year OS demonstrated no statistical difference between these two locations, possibly due to a similar proportion of patients with the same prognostic factors in both locations. The 10-year OS of osteosarcoma of the upper extremities in the US population has not been described before. Colding-Rasmussen et al. (21) identified a 46% 10-year OS in patients with appendicular osteosarcomas in Denmark. This result is close to the 10-year OS of 51% in patients with osteosarcoma of the upper extremities in the US found in our study.

As a retrospective study, a few limitations of this NCDB study should be noted. In particular, our results were dependent on the information compiled in the NCDB, which was not always complete. In an effort to obtain the most accurate results possible, we excluded missing information that would have affected the models. Furthermore, the histology classification was also database-dependent, and the category ‘osteosarcoma NOS’ included different histology types. However, we were still able to determine the most frequent histology types. Despite these limitations, we believe this study reports a valuable analysis of the demographics and tumor characteristics of patients with osteosarcoma of the upper extremities. These findings determine the character of the disease and underscore the importance of prompt diagnosis.

In conclusion, this study identified that osteosarcomas of the upper extremities were more commonly located in the forearm, arm, and shoulder, with high-grade tumors larger than 8 cm and absence of metastasis. Most patients underwent surgery with limb reconstruction and chemotherapy. In addition, although osteosarcomas in the hand and wrist were less likely to be high grade compared with osteosarcomas located in the forearm, arm, and shoulder, we found no difference in the 10-year OS between the two locations. This study highlights the importance of the characteristics of osteosarcoma in the upper extremities that would help to better approach the disease.