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

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Presentation on theme: "NON METASTATIC OSTEOSARCOMA. EXPERIENCE AT SKMCH & RC ALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIM SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND RESEARCH CENTRE."— Presentation transcript:

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

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

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

12 SECOND LINE CHEMOTHERAPY IFOSFAMIDE : 3gm/M2 D1-D3 ETOPOSIDE: 200mg/M2 D1- D3 ETOPOSIDE: 200mg/M2 D1- D3 HD METHOTREXATE : 8 – 12 gm/M2 D14 of each cycle. each cycle.

13 SURGERY AMPUTATION LIMB SALVAGE

14 RESULTS TOTAL PATIENTS=134 PATIENTS EXCLUDED= 71 METASTATIC= 35 METASTATIC= 35 INCOMPLETE TREATMENT= 36 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 <18 YEARS OF AGE MALE =41 FEMALE =22 M : F =1.9 : 1

16 SITE OF TUMOUR SITEFREQUENCYPERCENTAGE DISTAL FEMUR2946.0 PROXIMAL TIBIA1320.6 PROXIMAL HUMERUS69.5 FIBULA46.4 DISTAL TIBIA34.8 FEMORAL DIAPHYSIS34.8 PROXIMAL FEMUR23.2 TIBIAL DIAPHYSIS11.6 PROXIMAL ULNA11.6 RIBS11.6 TOTAL63100.0

17 RESULTS CHEMOTHERAPYNEO-ADJUVANT CISPLATIN + ADRIAMYCINN = 30 CISPLATIN + ADRIAMYCIN + HD MTXN = 20 NONEN = 13 ADJUVANT CISPLATIN + ADRIAMYCINN = 33 CISPLATIN + ADRIAMYCIN + HD MTXN = 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 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 <90% =44 >90% = 19 (P=0.8633)

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

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 JournalAuthor Pat. No. F/upEFS%OS% 1 Ann of Oncol 8:765-771,1997 Ferrari et al 127 12 yrs 46%53% 2 Clin Ortho & Related Research 358:120-127,1999 Sluga et al 133 5 yrs 67%70% 3 J Clin Oncol 18:4016-4027, 2000 Bacci et al 164 5 yrs 63%75% 4 The Oncologist, 9:422-441, 2004. Marina et al Review article 5 yrs 10 yrs 74%71%

34 DISCUSSION LATE PRESENTATION HIGH PERCENTAGE OF MACROMETASTASES AT PRESENTATION (35 OF 134 = 26%). HIGH PERCENTAGE OF MACROMETASTASES AT PRESENTATION (35 OF 134 = 26%). LARGE NUMBER PATIENTS PRESENTING WITH HUGE FUNGATING TUMOURS REQUIRING UPFRONT AMPUTATION. 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. HIGH TENDENCY FOR FAMILIES TO DISCONTINUE TREATMENT MIDWAY. FAILURE TO CONTINUE REGULAR FOLLOW UP IF THE PATIENT IS ALRIGHT POST TREATMENT. 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 6 DEATHS (31.5%) WERE DUE TO INFECTIONS HEPATITIS B WITH HEPATIC HEPATITIS B WITH HEPATIC ENCEPHALOPATHY = 4 ENCEPHALOPATHY = 4 SEPTIC SHOCK = 1 SEPTIC SHOCK = 1 FUNGAL PNEUMONIA = 1 FUNGAL PNEUMONIA = 1

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