NON METASTATIC OSTEOSARCOMA. EXPERIENCE AT SKMCH

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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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SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND
RESEARCH CENTRE, LAHORE, PAKISTAN.
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(No Transcript)
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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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BACKGROUND

• THE ROLE OF CHEMOTHERAPY IN THE TREATMENT OF
  OSTEOSARCOMA IS NOW WELL ESTABLISHED.
• MOST CENTRES REPORT AN EFS gt 60 AND OS gt70 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 lt30 YRS AGE WERE REGISTERED AT SKM WITH
  BONE TUMORS. OF THESE 134 (48) HAD OSTEOSARCOMA.
  

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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.

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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.

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STATISTICS

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

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TREATMENT OUTLINE

• NEOADJUVANT CHEMOTHERAPY
• SURGERY
• ADJUVANT CHEMOTHERAPY

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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

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FIRST LINE CHEMOTHERAPY

• REGIMEN 2
• CISPLATIN (100mg/m2 24-hour infusion)
• ADRIAMYCIN (25mg/m2 iv daily D1-D3 ).
• HD METHOTREXATE (8gm/M2 for gt12 years age
  12gm/M2 for lt12 years) given on D22 and D29 of
  each cycle
• TOTAL 6 CYCLES 2 NEOADJUVANT
• 4
  ADJUVANT

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SECOND LINE CHEMOTHERAPY

• IFOSFAMIDE 3gm/M2 D1-D3
• ETOPOSIDE 200mg/M2 D1- D3
• HD METHOTREXATE 8 12 gm/M2 D14 of
• each
  cycle.

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SURGERY

• AMPUTATION
• LIMB SALVAGE

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RESULTS

• TOTAL PATIENTS 134
• PATIENTS EXCLUDED 71
• METASTATIC 35
• INCOMPLETE TREATMENT 36
• ELIGIBLE PATIENTS 63

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RESULTS

• MEAN AGE15.4 YEARS
• AGE RANGE828 YEARS
• 77.8 WERE
• lt18 YEARS OF AGE
• MALE 41FEMALE 22M F 1.9 1

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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 3 4.8
PROXIMAL FEMUR 2 3.2
TIBIAL DIAPHYSIS 1 1.6
PROXIMAL ULNA 1 1.6
RIBS 1 1.6
TOTAL 63 100.0
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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

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NATURE OF SURGERY

• Amputation 44 of 63 (70)
• Limb salvage 19 of 63 (30)

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LIMB SALVAGE PROCEDURE

• RESECTION ARTHRODESIS
  OF KNEE 8

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LIMB SALVAGE PROCEDURE

• DIAPHYSEAL LESIONS-SEGMENTAL RESECTION AND
  RECONSTRUCTION
  4

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LIMB SALVAGE PROCEDURE

• TICKHOFF-LINBERG RESECTION OF THE SHOULDER
  4

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LIMB SALVAGE PROCEDURE

• ENNEKING ARTHRODESIS SHOULDER
  1

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LIMB SALVAGE PROCEDURE

• VAN NES ROTATIONPLASTY
  1

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LIMB SALVAGE PROCEDURE

• ILIZAROV RECONTRUCTION 1

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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)

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COMPLICATIONS OF LIMB SALVAGE SURGERY

• IMPLANT FAILURE REQUIRING REVISION SURGERY 1
  (5.2)
• IMPLANT EXPOSURE REQUIRING SECONDARY PLASTIC
  SURGICAL RECONSTRUCTION 1 (5.2)

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FOLLOWUP

• MEAN FOLLOWUP WAS 32 ? 26 months (Mean ? 1SD)
• RANGE 3.6 TO 98.5 months

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OVERALL SURVIVAL
60.4 of the patients were alive at 5 YEARS
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EVENT FREE SURVIVAL
40 were event free at 5YEARS
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EFS ACCORDING TO THERAPY RELATED VARIABLES
age Necrosis
(P0.8633)
lt90 44
gt90 19
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EFS ACCORDING TO THERAPY RELATED VARIABLES
Amputation Vs Limb Salvage
(P 0.1895)
Limb salvage19
Amputation 44
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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.

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Literature Review
Sr. no Journal Author Pat. No. F/up EFS OS
1 Ann of Oncol 8765-771,1997 Ferrari et al 127 12 yrs 46 53
2 Clin Ortho Related Research 358120-127,1999 Sluga et al 133 5 yrs 67 70
3 J Clin Oncol 184016-4027 , 2000 Bacci et al 164 5 yrs 63 75
4 The Oncologist, 9422-441, 2004. Marina et al Review article 5 yrs 10 yrs 74 71
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DISCUSSION

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

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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.

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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

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DISCUSSION

• POSSIBILITY OF BIOLOGICALLY AGGRESSIVE DISEASE?
• 44 OF 63 (70) HAD lt90 POST CHEMOTHERAPY
  NECROSIS.
• 4 OF 63 (6.3) HAD DIAPHYSEAL LESIONS.

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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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