Osteosarcoma in pediatric patients and young adults: a single institution retrospective review of presentation, therapy, and outcome

Abstract

Background. Little is known about how cumulative chemotherapy delivery influences the poorer outcome observed in young adult (YA, 18-40 years) versus pediatric (<18 years) osteosarcoma patients. Here, we retrospectively examined differences in presentation, therapy, including cumulative chemotherapy dose, and outcome in YA and pediatric patients. Methods. We reviewed 111 cases of high-grade osteosarcoma at Moffitt Cancer Center between 1988 and 2012. Presentation factors, therapies, and survival were compared between YA and pediatric cohorts. Results. The cohorts were equivalent with respect to metastatic status, gender, tumor size, tumor site, and histological subtype. We found that the YA patients tended to have poorer histologic response to neoadjuvant chemotherapy measured by necrosis with 55% and 35% of pediatric versus YA patients responding favorably (P = 0.06). Only 39% of YA patients achieved the typical pediatric dose of methotrexate, doxorubicin, and cisplatin. These patients had a 3-year EFS of 76% (CI 53-100%) versus 47% (CI 26-69%; P = 0.09) in those who received less chemotherapy. Conclusion. Age continues to be a prognostic factor in osteosarcoma. Our study suggests that presentation factors are not associated with prognosis, while poorer response to chemotherapy and lower cumulative dose of chemotherapy delivered to YA patients may contribute to poorer outcomes.

Figure 1

Patient cohorts (pediatric and YA). Of the 83 patients included in our analysis, 14 had metastatic disease at diagnosis, and 26 patients went on to have recurrence.

Figure 2

The YA cohort received less chemotherapy than the typical pediatric regimen. (a) Heat map for the YA cohort's chemotherapy regimen, with each column representing 1 patient. The green squares indicate that the patient received the typical dose according to pediatric osteosarcoma protocols. The red squares indicate that the patient received fewer doses than the typical pediatric dose. Asterisks (∗) indicate patients who progressed on primary therapy. Light green box indicates patient who received etoposide/ifosfamide instead of cisplatin. (b) Percentage of patients in the YA cohort that received each dose of chemotherapy. The black bars indicate the typical dose of each drug for pediatric patients. The percentages shown indicate the percentage of patients in the YA cohort that received less than the typical dose.

Figure 3

Localized disease outcomes for pediatric and YA cohorts demonstrate better overall survival in pediatric cohort and improved 3-year EFS for MAP+ YA patients. (a) Five-year overall survival of patients with localized disease in the pediatric and YA cohort (P = 0.05). (b) Three-year EFS for pediatric cohort and YA cohort (P = 0.73). (c) Three-year EFS of YA patients who received less chemotherapy than the typical pediatric regimen (MAP−) compared to YA patients who received the typical pediatric regimen (MAP+) (P = 0.09). (d) Three-year EFS of YA MAP− patients compared to YA MAP+ patients. Patients who had recurrence during primary MAP therapy were removed (P = 0.17).