chondrosarcoma of the pelvis prognostic factors and survival analysis at 10-20 years

Chondrosarcoma of the Pelvis

Prognostic Factors and Survival

Analysis at 10-20 Years

Matthew J. Seidel, MD

Patrick P. Lin, MD

Valerae O. Lewis, MD

Christopher P.Cannon, MD

Alan W. Yasko, MD

Literature

Author/Yr #Pts Follow-up 10-Yr Surv Pelvic only?

Comment

Pring 2001 64 12 yr med97% (gr1), 75%(gr2), 14%(DD)

YFew High-Grade (1-gr 3, 7-DD)

Berg 2001 69 13 yr mean 67% NNot all resected; sacrum, spine included

Mochizuki 2000

135 3.9 yr mean 65% NShort f/u, data by stage, sacrum included

Ozaki 1997 31 5.5 yr med 45% YShort f/u, small #pts, data by stage

Sheth 1996 67 9.6 yr med -- YRecurrent tumors included

Goal of Study

• Define long-term oncologic outcome and prognostic factors for chondrosarcoma arising in the pelvic bones

Study Design

• Pelvic chondrosarcoma • Surgically treated with curative intent• Minimum 5 year f/u for living patients

– 5 year potential f/u for deceased patients

• Exclusion:– Sacral epicenter– Recurrent presentation– Metastatic presentation– Prior resection/surgery (other than biopsy)

Data Collection

• Retrospective medical record review including operative, pathology, and radiology reports– Demographics

– Tumor grade, size, location, physical characteristics

– Surgical type and margins

– Timing and location of local recurrence and metastasis

• Long-term data from clinical follow-up, phone call, or letter

Statistics

• Kaplan-Meier survival– Disease-specific survival

– Local recurrence-free survival

– Distant relapse-free survival

• Log rank (determine difference between KM curves)

• Chi-square or Fisher’s exact test

101 Patients

• Collection period: 1948-2000

• Follow-up: 5 to 45 years– Overall median 6 year

follow-up

– Living patients: median 13 year follow-up

• 31 female, 70 male

Overall Survival

• Status At Last Follow-up– 41 NED

– 1 AWD

– 45 DOD

– 13 DOC

– 1 DUC

Grade

• 34 Low

• 24 Intermediate

• 27 High

• 16 Dedifferentiated

Epicenter

• Ilium: 57

• Pubis: 24

• Acetabulum: 10

• Ischium: 10

Tumor Characteristics

• Mean Size: 18.5 cm– Range 3 to 25 cm

• Extra-osseous extension in 91 (90%)

Surgical

• Surgery Type– Amputation: 37– Limb salvage: 64

• Surgical Margins– Negative: 56– Positive: 42– Not Specified: 3

Disease-Specific Survival

5-Year 10-year 20-Year

Low 88% 85% 72%

Intermediate 70% 45% 45%

High 42% 39% 35%

Disease-Specific Survival

5-Year 10-year 20-Year

Low 88% 85% 72%

Intermediate 70% 45% 45%

High 50% 45% 38%

DD31%(15 mo)

31% ---

DSS: Prognostic VariablesVariable Prognostic P-value

Dedifferentiated Y <.0001

High Grade Y .0001

Cross Midline Y .0004

Displace Bladder Y .001

Local Recurrence Y .007

Intermediate Grade Marginal .07

Size >=10 cm Marginal .08

Amputation (vs. LSS) Marginal .08

Extra-osseous extension

N .11

Positive Margin N .13

Epicenter N .45

Effect of LR On DSS

• Significant decrease in survival for patients with LR

• P=.007

Follow-up (months)

6005004003002001000

Survival

1.0

.8

.6

.4

.2

0.0

No LR

LR

Effect of LR On DSSLow Grade

• Significant survival difference

• P=.003

Effect of LR On DSS Intermediate Grade

• Marginal significance• P=.08

Effect of LR On DSSHigh Grade

• Not Significant • P=0.42

Results – Local Recurrence

• 35 Local Recurrences– Mean time 29 months– Range 3 to 120 months

• 91% (32/35) occurred within five years• 3 Local Recurrence after five years

– 84 months (low-grade)– 108 months (intermediate-grade)– 120 months (low-grade)

Results – Local Recurrence

• 68% of LR (23/34) associated with positive resection margins

Negative Margin

(56)

Positive Margin

(42)

LR 10 (17.9%) 23 (54.8%)P=.002

No LR 46 (82.1%) 19 (45.2%)

Local Recurrence-Free Survival

5-Year 10-year 20-Year

Low 73% 66% 66%

Intermediate 49% 37% 37%

High 63% 63% 63%

LR – Prognostic VariablesVariable Prognostic P-Value

Positive Margin Y .0002

Cross Midline Y .007

Displace Bladder Y .001

Size >= 10cm Marginal .06

Pubis Epicenter Marginal .06

Non-Pubis Epicenter N .12

High-Grade N .19

Extra-osseous extension N .25

Dedifferentiated N .35

Surgery (Amp vs LSS) N .91

Results - Metastasis

• 28 Metastasis– Mean time 22 months– Range 1-114 months

• Location– Lung most common (27)– Other locations: liver (4), brain (2), spine (2),

kidney (1), heart (1), pericardium (1), humerus (1), lymph node (1), scalp (1)

Results - Metastasis

• 93% (26/28) metastasis occurred in first four years

• Two metastasis occurred after four years– 74 months (low-grade; LR at 23, 36, 41

months)– 114 months (intermediate-grade; LR at 108

months)

Results - Metastasis

• 26/28 (93%) DOD at last follow-up– Median time 9 months

• 2/28 (7%)– DOC (1): NED 5 years after wedge resection at 24 mo

– AWD(1): alive 4 years, wedge resection pending

• Metastasis has a significant negative effect on DSS (p<.0001)

Distant Relapse-Free Survival

5-Year 10-year 20-Year

Low 91% 88% 88%

Intermediate 76% 61% 61%

High 51% 46% 46%

DR-Prognostic Variables

Variable Prognostic (Y/N) P-Value

Amputation Y .0004

Dedifferentiated Y .002

High-Grade Y .002

Displaced Bladder Y .02

Size >= 10 cm Marginal .08

Local Recurrence N .19

Positive Margin N .30

Extra-osseous extension N .43

Cross Midline N .55

Location N .68

Study Limitations

• Diminishing number of patients at 20 years– 39% >10 yr f/u– 17% >20 yr f/u

• Changes in mode and quality of radiographic imaging over study period

• Vagaries of histological grading

• Limited long-term radiographic imaging

Conclusions

• Long term follow-up data show LR or metastasis can occur beyond five years

• No first LR or metastasis was seen after 10 years

Conclusions

• Local Recurrence has a significant negative effect on long term survival – Most pronounced for low and intermediate

grade tumors.

• Metastasis overwhelmingly resulted in death

Conclusions

• Significant prognostic factors at late follow-up are unchanged from short-term follow-up data– Disease-specific survival– Local recurrence-free survival– Distant relapse-free survival

Conclusions

• Evidence-based post-operative surveillance strategy should include at least 10 year follow-up after initial resection