(P 21) YOUNG ADULTS WITH NONMETASTATIC OPERABLE OSTEOSARCOMA TREATED PERIOPERATIVELY WITH METHOTREXATE, DOXORUBICIN AND CISPLATIN SCHEDULE, SINGLE INSTITUTION REPORT

Objective: Osteosarcoma has its peak incidence in adolescents and young adults (AYA) between 16 and 30 years however this young group of patients is underrepresented in clinical trials and in analyses concerning survival prognosis. Treated with three or more drug schedules (including Methotrexate-MTX, Doxorubicin and Cisplatin; MAP) designated for children, AYA do not have the same outcomes and reliable prognostic markers providing relevant estimation of prognosis.

Methods: Treated in our department and eligible for the analysis were patients (pts): in the age of 18-30 inclusively, diagnosed with non-metastatic high-grade operable skeletal osteosarcoma, received at least one dose of methotrexate preoperatively as a part of MAP schedule. Data on patient, disease, treatment and survival characteristics were retrospectively collected. OS (overall survival) and DMFS (distant metastases free survival) for the analyzed group were calculated using “R” software.
Survival predictions using validated Koichi Ogura’s Nomogram of 2015 and Ziege Liu’s Nomogram of 2023 were carried out for each patient based on the variables included in nomograms. We looked at pts in our dataset who had an event during the follow-up and compared their data with those with worse prognosis according to nomograms but with better outcomes in our cohort. We took under consideration variables additional to those included in nomograms such as: clinical stage, presence of positive lymph nodes, dosages of chemotherapeutics (given pre- and postoperatively), osteosarcoma histology and alkaline phosphatase concentration at the treatment start. Descriptive statistics was performed due to a small sample size.

Results: Eligibility criteria were met by 16 pts treated between 2018-2023. Two of them were excluded due to the ongoing treatment. Median age was 22 (range: 19-25). Most of the pts were males (64%). Extremity was a primary tumor site in 71% of pts, while other were axial locations (rib, clavicle or pelvis). Three pts (21%) had pathological fracture. The most common stage by AJCC (The American Joint Committee on Cancer) was IIB (64%). With a median follow up of 42.3 months (range 7.9-60) we have observed relapses in two pts and one death.
All pts received doxorubicin plus cisplatin pre and postoperatively, 28.6% (4) of pts did not receive MTX postoperatively, 78.6% (11) received all 4 doses of MTX preoperatively. There were no treatment-related deaths. Nobody relapsed during the treatment. One patient with no evidence of a disease during follow-up developed myelodysplastic syndrome 31 months after the end of treatment.
Calculated 3-year OS and DMFS rates in our cohort were 87.5% (95% CI: 0.673-1) and 82.1% (95% CI: 0.621-1), respectively.
Estimated mean of 3-yr OS for our pts by Liu's nomogram'23 was 69% and by Ogura’s nomogram’15 was 82%. Mean 3-yr DMFS estimated by Ogura’s nomogram’15 was 63%. Estimated mean for 3-yr OS and for DMFS in our pts according to Ogura’s and Liu’s nomograms were lower than actual calculated for the entire cohort.
We have observed that the deceased patient in our cohort did not have the worst survival prediction according to Liu’s and Ogura’s nomograms. Patients with better outcomes despite worse nomogram predictions for 3-yr OS in comparison to the deceased patient had: higher doxorubicin and cisplatin dosages per m2 for perioperative treatment, higher MTX dose per m2 per cycle preoperatively and lower clinical stage by AJCC, lower alkaline phosphatase concentration (less than 2.5 times the upper limit) and none lymph nodes involved.

Conclusion: Our findings, similarly to other studies, indicate that osteosarcoma in adolescents and young adults is not consistent with established prognostic factors for survival in other age groups. Distinctive analysis of prognostic factors in AYA group and nomograms created for them exclusively are needed. Statistical justification of possible impact on survival of such variables as: doxorubicin and cisplatin dosages per m2 for perioperative treatment, MTX dose per m2 per cycle preoperatively, alkaline phosphatase concentration of more than 2.5 times the upper limit at start and lymph node involvement is needed in much larger cohort and is planned for the future.