NON METASTATIC OSTEOSARCOMA. EXPERIENCE AT SKMCH & RC

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 • ADJUVANT CHEMOTHERAPY

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 ). • HDMETHOTREXATE (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: 3gm/M2 D1-D3 ETOPOSIDE: 200mg/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 =41FEMALE =22M : F =1.9 : 1

16. SITE OF TUMOUR

17. RESULTS CHEMOTHERAPY NEO-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

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).

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