1. NON METASTATIC OSTEOSARCOMA. EXPERIENCE AT SKMCH & RC
ALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIM
SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND RESEARCH CENTRE

2. SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL
AND RESEARCH CENTRE, LAHORE, PAKISTAN.

4. NON METASTATIC OSTEOSARCOMA. EXPERIENCE AT SKMCH & RC
ALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIM
SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND RESEARCH CENTRE

5. BACKGROUND
THE ROLE OF CHEMOTHERAPY IN THE TREATMENT OF OSTEOSARCOMA IS NOW WELL ESTABLISHED.
MOST CENTRES REPORT AN EFS > 60% AND OS >70% FOR NON-METASTATIC , EXTREMITY OSTEOSARCOMA.
THE PURPOSE OF THIS STUDY WAS TO ANALYZE TREATMENT OUTCOME FOR OSTEOSARCOMA AT OUR HOSPITAL.
BETWEEN DECEMBER1994 AND APRIL 2004 , 278 PATIENTS <30 YRS AGE WERE REGISTERED AT SKM WITH BONE TUMORS. OF THESE 134 (48%) HAD OSTEOSARCOMA.

6. MATERIALS AND METHODS A RETROSPECTIVE OBSERVATIONAL STUDY.
INCLUSION CRITERIA: INCLUDED ALL PATIENTS 30 YEARS OF AGE AND YOUNGER WITH BIOPSY PROVEN OSTEOSARCOMA, REGISTERED AT SKM BETWEEN 29/12/94 AND 30/04/04.
EXCLUSION CRITERIA METASTATIC AT PRESENTATION DID NOT COMPLETE TREATMENT AT SKM.

7. MATERIALS AND METHODS DATA COLLECTION
INFORMATION WAS EXTRACTED FROM PATIENTS’ MEDICAL RECORDS.
EVENT FREE SURVIVAL (EFS) WAS CALCULATED FROM THE DATE OF DEFINITIVE SURGERY TO THE DATE OF RELAPSE, PROGRESSION, DEATH OR LAST FOLLOW UP.
OVERALL SURVIVAL (OS) WAS CALCULATED FROM THE DATE OF DIAGNOSIS TO DEATH OR LAST FOLLOW UP.

8. STATISTICS
EFS AND OS CURVES DERIVED USING THE ACTUARIAL LIFE METHOD ON THE SPSS STATISTICAL PACKAGE.

9. TREATMENT OUTLINE NEOADJUVANT CHEMOTHERAPY SURGERY

10. FIRST LINE CHEMOTHERAPY
REGIMEN 1 :
CISPLATIN (100mg/m2 24-hour infusion)
ADRIAMYCIN (25mg/m2 iv daily D1-D3 ).
TOTAL 6 CYCLES : 2 NEOADJUVANT &
4 ADJUVANT

11. FIRST LINE CHEMOTHERAPY
REGIMEN 2 :
CISPLATIN (100mg/m2 24-hour infusion)
ADRIAMYCIN (25mg/m2 iv daily D1-D3 ).
HD METHOTREXATE (8gm/M2 for >12 years age & 12gm/M2 for <12 years) given on D22 and D29 of each cycle
TOTAL 6 CYCLES : 2 NEOADJUVANT &
4 ADJUVANT

12. SECOND LINE CHEMOTHERAPY
IFOSFAMIDE : gm/M2 D1-D3
ETOPOSIDE: mg/M2 D1- D3
HD METHOTREXATE : 8 – 12 gm/M2 D14 of
each cycle.

13. SURGERY
AMPUTATION
LIMB SALVAGE

14. RESULTS TOTAL PATIENTS =134 PATIENTS EXCLUDED = 71 METASTATIC = 35
INCOMPLETE TREATMENT= 36
ELIGIBLE PATIENTS = 63

15. RESULTS MEAN AGE=15.4 YEARS AGE RANGE=8–28 YEARS 77.8% WERE
<18 YEARS OF AGE
MALE =41 FEMALE =22 M : F =1.9 : 1

16. SITE OF TUMOUR SITE FREQUENCY PERCENTAGE DISTAL FEMUR 29 46.0
PROXIMAL TIBIA 13
20.6
PROXIMAL HUMERUS 6
9.5
FIBULA 4
6.4
DISTAL TIBIA 3
4.8
FEMORAL DIAPHYSIS
PROXIMAL FEMUR 2
3.2
TIBIAL DIAPHYSIS 1
1.6
PROXIMAL ULNA
RIBS
TOTAL 63
100.0

17. RESULTS CHEMOTHERAPY NEO-ADJUVANT ADJUVANT
CISPLATIN + ADRIAMYCIN N = 30
CISPLATIN + ADRIAMYCIN + HD MTX N = 20
NONE N = 13
ADJUVANT
CISPLATIN + ADRIAMYCIN N = 33
CISPLATIN + ADRIAMYCIN + HD MTX N = 30
(SECOND LINE CHEMOTHERAPY) N = 12

18. NATURE OF SURGERY Amputation = 44 of 63 (70%)
Limb salvage = 19 of 63 (30%)

19. LIMB SALVAGE PROCEDURE
RESECTION ARTHRODESIS OF KNEE = 8

20. LIMB SALVAGE PROCEDURE
DIAPHYSEAL LESIONS-SEGMENTAL RESECTION AND RECONSTRUCTION = 4

21. LIMB SALVAGE PROCEDURE
TICKHOFF-LINBERG RESECTION OF THE SHOULDER = 4

22. LIMB SALVAGE PROCEDURE
ENNEKING ARTHRODESIS SHOULDER = 1

23. LIMB SALVAGE PROCEDURE
VAN NES ROTATIONPLASTY = 1

24. LIMB SALVAGE PROCEDURE
ILIZAROV RECONTRUCTION = 1

25. COMPLICATIONS OF TREATMENT
SERIOUS INFECTIONS
HEP. B WITH HEPATIC ENCEPHALOPATHY= 4 (6.3%)
GRAM NEGATIVE SEPTICAEMIA = 6 (9.5%)
FUNGAL PNEUMONIA = 2 (3.2%)
CHEMOTHERAPY TOXICITY
CISPLATIN NEUROTOXICITY = 1 (1.5%)
METHOTREXATE NEPHROTOXICITY = 2 (3.2%)
ADRIAMYCIN CARDIOTOXICITY = 1 (1.5%)
PSYCHOLOGICAL COMPLICATIONS
MAJOR DEPRESSION = 6 (9.5%)

26. COMPLICATIONS OF LIMB SALVAGE SURGERY
IMPLANT FAILURE REQUIRING REVISION SURGERY 1 (5.2%)
IMPLANT EXPOSURE REQUIRING SECONDARY PLASTIC SURGICAL RECONSTRUCTION 1 (5.2%)

27. FOLLOWUP MEAN FOLLOWUP WAS 32  26 months (Mean  1SD)
RANGE 3.6 TO 98.5 months

28. OVERALL SURVIVAL
60.4% of the patients were alive at 5 YEARS

29. EVENT FREE SURVIVAL
40% were event free at 5YEARS

30. EFS ACCORDING TO THERAPY –RELATED VARIABLES
%age Necrosis
(P=0.8633)
<90% =44
>90% = 19

31. EFS ACCORDING TO THERAPY –RELATED VARIABLES
Amputation Vs Limb Salvage
(P =0.1895)
Limb salvage=19
Amputation = 44

32. RESULTS SUMMARY OVERALL SURVIVAL 60.4% AT 5YRS.
EVENT FREE SURVIVAL 40% AT 5YRS.
NO OS DIFFERENCE BETWEEN GOOD AND BAD RESPONDERS TO INITIAL CHEMOTHERAPY.
NO OS DIFFERENCE BETWEEN LIMB SALVAGE AND ABLATION.
TREATMENT WAS GENERALLY WELL TOLERATED.

33. Literature Review Sr. no Journal Author Pat. No. F/up EFS% OS% 1
Ann of Oncol 8: ,1997
Ferrari et al
127
12 yrs
46%
53% 2
Clin Ortho & Related Research 358: ,1999
Sluga et al
133
5 yrs
67%
70% 3
J Clin Oncol 18: ,
2000
Bacci et al
164
63%
75% 4
The Oncologist, 9: , 2004.
Marina et al
Review article
10 yrs
74%
71%

34. DISCUSSION LATE PRESENTATION
HIGH PERCENTAGE OF MACROMETASTASES AT PRESENTATION (35 OF 134 = 26%).
LARGE NUMBER PATIENTS PRESENTING WITH HUGE FUNGATING TUMOURS REQUIRING UPFRONT AMPUTATION.

35. DISCUSSION LACK OF EDUCATION & AWARENESS
HIGH TENDENCY FOR FAMILIES TO DISCONTINUE TREATMENT MIDWAY.
FAILURE TO CONTINUE REGULAR FOLLOW UP IF THE PATIENT IS ALRIGHT POST TREATMENT.

36. DISCUSSION HIGH SYSTEMIC INFECTION RATE AND CO-MORBIDITY
6 DEATHS (31.5%) WERE DUE TO INFECTIONS
HEPATITIS B WITH HEPATIC
ENCEPHALOPATHY = 4
SEPTIC SHOCK = 1
FUNGAL PNEUMONIA = 1

37. DISCUSSION POSSIBILITY OF BIOLOGICALLY AGGRESSIVE DISEASE?
44 OF 63 (70%) HAD <90% POST CHEMOTHERAPY NECROSIS.
4 OF 63 (6.3%) HAD DIAPHYSEAL LESIONS.

38. CONCLUSIONS
OUR RESULTS ARE COMPARABLE TO INTERNATIONAL FIGURES THOUGH A MUCH LONGER FOLLOW UP (AT LEAST 10 YEARS) IS REQUIRED TO GET A MORE ACCURATE PICTURE.
PATIENTS NEED TO BE STUDIED PROSPECTIVELY TO ENSURE MORE RELIABLE DATA.
WE NEED TO ORGANIZE EDUCATIONAL CAMPAIGNS TO IMPROVE PUBLIC AND HEATH PERSONNEL AWARENESS ABOUT TREATABLE NATURE OF THIS DISEASE IF CAUGHT EARLY.
DESPITE LIMITATIONS OF WORKING IN A THIRD WORLD TERTIARY CARE CENTRE, OUR PRELIMINARY RESULTS OF LIMB SALVAGE SURGERY ARE HEARTENING (30%, NO STATISTICALLY SIGNIFICANT DIFFERENCE IN OUTCOME COMPARED TO ABLATIVE SURGERY).

39. LAHORE IS WAITING
TO WELCOME YOU ALL