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2017 ; 475
(3
): 842-850
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A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The
Birmingham Classification
#MMPMID27138473
Jeys LM
; Thorne CJ
; Parry M
; Gaston CL
; Sumathi VP
; Grimer JR
Clin Orthop Relat Res
2017[Mar]; 475
(3
): 842-850
PMID27138473
show ga
BACKGROUND: Chemotherapy response and surgical margins have been shown to be
associated with the risk of local recurrence in patients with osteosarcoma.
However, existing surgical staging systems fail to reflect the response to
chemotherapy or define an appropriate safe metric distance from the tumor that
will allow complete excision and closely predict the chance of disease
recurrence. We therefore sought to review a group of patients with primary
high-grade osteosarcoma treated with neoadjuvant chemotherapy and surgical
resection and analyzed margins and chemotherapy response in terms of local
recurrence. QUESTIONS/PURPOSES: (1) What predictor or combination of predictors
available to the clinician can be assessed that more reliably predict the
likelihood of local recurrence? (2) Can we determine a better predictor of local
recurrence-free survival than the currently applied system of surgical margins?
(3) Can we determine a better predictor of overall survival than the currently
applied system of surgical margins? METHODS: This retrospective study included
all patients with high-grade conventional osteosarcomas without metastasis at
diagnosis treated at one center between 1997 and 2012 with preoperative
chemotherapy followed by resection or amputation of the primary tumor who were
younger than age 50 years with minimum 24-month followup for those still alive. A
total of 389 participants matched the inclusion criteria. Univariate log-rank
test and multivariate Cox analyses were undertaken to identify predictors of
local recurrence-free survival (LRFS). The Birmingham classification was devised
on the basis of two stems: the response to chemotherapy (good response = ? 90%
necrosis; poor response = < 90% necrosis) and margins (< 2 mm or ? 2 mm). The
5-year overall survival rate was 67% (95% confidence interval [CI], 61%-71%) and
47 patients developed local recurrence (12%). RESULTS: Intralesional margins
(hazard ratio [HR], 9.9; 95% CI, 1.2-82; p = 0.03 versus radical margin HR, 1)
and a poor response to neoadjuvant chemotherapy (HR, 3.8; 95% CI, 1.7-8.4; p =
0.001 versus good response HR, 1) were independent risk factors for local
recurrence (LR). The best predictor of LR, however, was a combination of margins
? 2 mm and a less than 90% necrosis response to chemotherapy (Birmingham 2b HR,
19.6; 95% CI, 2.6-144; p = 0.003 versus Birmingham 1a; margin >2 mm and more than
90% necrosis HR, 1). Two-stage Cox regression model and higher Harrell's C
statistic demonstrate that the Birmingham classification was superior to the
Musculoskeletal Tumor Society (MSTS) margin classification for predicting LR
(Harrell's C statistic Birmingham classification 0.68, MSTS criteria 0.59). A
difference in overall survival was seen between groups of the Birmingham
classification (log-rank test p < 0.0001), whereas the MSTS margin system was not
discriminatory (log-rank test p = 0.14). CONCLUSIONS: Based on these
observations, we believe that a combination of the recording of surgical margins
in millimeters and the response to neoadjuvant chemotherapy can more accurately
predict the risk of local recurrence than the current MSTS system. A multicenter
collaboration study initiated by the International Society of Limb Salvage is
recommended to test the validity of the proposed classification and if these
findings are confirmed, this classification system might be considered the
standard practice in oncology centers treating patients with osteosarcomas and
allow more effective communication of margin status for research. LEVEL OF
EVIDENCE: Level IV, prognostic study.
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