Post on 26-Mar-2015
NON METASTATIC NON METASTATIC OSTEOSARCOMA. EXPERIENCE OSTEOSARCOMA. EXPERIENCE
AT SKMCH & RC AT SKMCH & RC
ALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIMALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIM
SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND RESEARCH CENTRERESEARCH CENTRE
NON METASTATIC NON METASTATIC OSTEOSARCOMA. EXPERIENCE OSTEOSARCOMA. EXPERIENCE
AT SKMCH & RC AT SKMCH & RC
ALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIMALIA ZAIDI, AHSAN SHAMIM, WASILA SHAMIM
SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL AND RESEARCH CENTRERESEARCH CENTRE
BACKGROUNDBACKGROUND THE ROLE OF CHEMOTHERAPY IN THE THE ROLE OF CHEMOTHERAPY IN THE
TREATMENT OF OSTEOSARCOMA IS NOW TREATMENT OF OSTEOSARCOMA IS NOW WELL ESTABLISHED.WELL ESTABLISHED.
MOST CENTRES REPORT AN MOST CENTRES REPORT AN EFS > 60%EFS > 60% AND AND OS >70%OS >70% FOR NON-METASTATIC , EXTREMITY FOR NON-METASTATIC , EXTREMITY OSTEOSARCOMA. OSTEOSARCOMA.
THE PURPOSE OF THIS STUDY WAS TO THE PURPOSE OF THIS STUDY WAS TO ANALYZE TREATMENT OUTCOME FOR ANALYZE TREATMENT OUTCOME FOR OSTEOSARCOMA AT OUR HOSPITAL.OSTEOSARCOMA AT OUR HOSPITAL.
BETWEEN DECEMBER1994 AND APRIL 2004 , BETWEEN DECEMBER1994 AND APRIL 2004 , 278 PATIENTS <30 YRS AGE WERE 278 PATIENTS <30 YRS AGE WERE REGISTERED AT SKM WITH BONE TUMORS. OF REGISTERED AT SKM WITH BONE TUMORS. OF THESE 134 (48%) HAD OSTEOSARCOMA. THESE 134 (48%) HAD OSTEOSARCOMA.
MATERIALS AND METHODSMATERIALS AND METHODS
A RETROSPECTIVE OBSERVATIONAL STUDY.A RETROSPECTIVE OBSERVATIONAL STUDY.
INCLUSION CRITERIA:INCLUSION CRITERIA: INCLUDED ALL PATIENTS 30 YEARS OF AGE INCLUDED ALL PATIENTS 30 YEARS OF AGE AND YOUNGER WITH BIOPSY PROVEN AND YOUNGER WITH BIOPSY PROVEN OSTEOSARCOMA, REGISTERED AT SKM OSTEOSARCOMA, REGISTERED AT SKM BETWEEN 29/12/94 AND 30/04/04.BETWEEN 29/12/94 AND 30/04/04.
EXCLUSION CRITERIA EXCLUSION CRITERIA METASTATIC AT PRESENTATION. METASTATIC AT PRESENTATION. DID NOT COMPLETE TREATMENT AT DID NOT COMPLETE TREATMENT AT SKM.SKM.
MATERIALS AND METHODSMATERIALS AND METHODS
DATA COLLECTIONDATA COLLECTION INFORMATION WAS EXTRACTED FROM INFORMATION WAS EXTRACTED FROM
PATIENTS’ MEDICAL RECORDS.PATIENTS’ MEDICAL RECORDS. EVENT FREE SURVIVAL (EFS) WAS EVENT FREE SURVIVAL (EFS) WAS
CALCULATED FROM THE DATE OF CALCULATED FROM THE DATE OF DEFINITIVE SURGERY TO THE DATE OF DEFINITIVE SURGERY TO THE DATE OF RELAPSE, PROGRESSION, DEATH OR LAST RELAPSE, PROGRESSION, DEATH OR LAST FOLLOW UP. FOLLOW UP.
OVERALL SURVIVAL (OS) WAS OVERALL SURVIVAL (OS) WAS CALCULATED FROM THE DATE OF CALCULATED FROM THE DATE OF DIAGNOSIS TO DEATH OR LAST FOLLOW DIAGNOSIS TO DEATH OR LAST FOLLOW UP.UP.
STATISTICSSTATISTICS
EFS AND OS CURVES DERIVED EFS AND OS CURVES DERIVED USING THE ACTUARIAL LIFE METHOD USING THE ACTUARIAL LIFE METHOD ON THE SPSS STATISTICAL ON THE SPSS STATISTICAL PACKAGEPACKAGE..
TREATMENT OUTLINETREATMENT OUTLINE
NEOADJUVANT CHEMOTHERAPYNEOADJUVANT CHEMOTHERAPY
SURGERYSURGERY
ADJUVANT CHEMOTHERAPYADJUVANT CHEMOTHERAPY
FIRST LINE CHEMOTHERAPYFIRST LINE CHEMOTHERAPY
REGIMEN 1 :REGIMEN 1 :
CISPLATINCISPLATIN (100mg/m2 24-hour infusion) (100mg/m2 24-hour infusion) ADRIAMYCIN ADRIAMYCIN (25mg/m2 iv daily D1-D3 ). (25mg/m2 iv daily D1-D3 ).
TOTAL 6 CYCLES : 2 NEOADJUVANT & TOTAL 6 CYCLES : 2 NEOADJUVANT & 4 ADJUVANT4 ADJUVANT
FIRST LINE CHEMOTHERAPYFIRST LINE CHEMOTHERAPY
REGIMEN 2 :REGIMEN 2 :
CISPLATINCISPLATIN (100mg/m2 24-hour infusion) (100mg/m2 24-hour infusion) ADRIAMYCINADRIAMYCIN (25mg/m2 iv daily D1-D3 ). (25mg/m2 iv daily D1-D3 ). HDHD METHOTREXATEMETHOTREXATE (8gm/M2 for >12 years (8gm/M2 for >12 years
age & 12gm/M2 for <12 years) given on D22 age & 12gm/M2 for <12 years) given on D22 and D29 of each cycleand D29 of each cycle
TOTAL 6 CYCLES : 2 NEOADJUVANT & TOTAL 6 CYCLES : 2 NEOADJUVANT & 4 ADJUVANT4 ADJUVANT
SECOND LINE CHEMOTHERAPY SECOND LINE CHEMOTHERAPY
IFOSFAMIDEIFOSFAMIDE : : 3gm/M2 D1-D33gm/M2 D1-D3
ETOPOSIDEETOPOSIDE: 200mg/M2 D1- D3: 200mg/M2 D1- D3 HD METHOTREXATEHD METHOTREXATE : 8 – 12 gm/M2 D14 of : 8 – 12 gm/M2 D14 of each cycle.each cycle.
SURGERYSURGERY
AMPUTATIONAMPUTATION
LIMB SALVAGELIMB SALVAGE
RESULTSRESULTS
TOTAL PATIENTSTOTAL PATIENTS =134=134
PATIENTS EXCLUDEDPATIENTS EXCLUDED = 71= 71• METASTATICMETASTATIC = 35= 35• INCOMPLETE TREATMENT= 36INCOMPLETE TREATMENT= 36
ELIGIBLE PATIENTSELIGIBLE PATIENTS = 63= 63
RESULTSRESULTS
MEAN AGE=15.4 YEARSMEAN AGE=15.4 YEARS
AGE RANGE=8–28 YEARSAGE RANGE=8–28 YEARS
77.8% WERE77.8% WERE
<18 YEARS OF AGE <18 YEARS OF AGE
MALE =41MALE =41FEMALE =22FEMALE =22M : F =1.9 : 1M : F =1.9 : 1
Age (years)
27.525.022.520.017.515.012.510.07.5
Fre
quen
cy
20
10
0
Std. Dev = 4.34
Mean = 15.4
N = 63.00
SITE OF TUMOUR 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
RESULTSRESULTSCHEMOTHERAPYCHEMOTHERAPY
NEO-ADJUVANTNEO-ADJUVANTCISPLATIN + ADRIAMYCINCISPLATIN + ADRIAMYCIN N = 30N = 30CISPLATIN + ADRIAMYCIN + HD MTXCISPLATIN + ADRIAMYCIN + HD MTX N = 20N = 20NONENONE N = 13N = 13
ADJUVANTADJUVANTCISPLATIN + ADRIAMYCINCISPLATIN + ADRIAMYCIN N = 33N = 33
CISPLATIN + ADRIAMYCIN + HD MTXCISPLATIN + ADRIAMYCIN + HD MTX N = 30N = 30(SECOND LINE CHEMOTHERAPY)(SECOND LINE CHEMOTHERAPY) N = 12N = 12
NATURE OF SURGERYNATURE OF SURGERY
AmputationAmputation == 44 of 63 (70%)44 of 63 (70%)
Limb salvageLimb salvage == 19 of 63 (30%)19 of 63 (30%)
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
RESECTION ARTHRODESIS RESECTION ARTHRODESIS
OF KNEE = OF KNEE = 88
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
DIAPHYSEAL DIAPHYSEAL LESIONS-LESIONS-
SEGMENTAL SEGMENTAL RESECTION AND RESECTION AND
RECONSTRUCTION RECONSTRUCTION
= = 44
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
TICKHOFF-LINBERG TICKHOFF-LINBERG RESECTION OF THE RESECTION OF THE
SHOULDERSHOULDER = = 44
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
ENNEKING ENNEKING ARTHRODESIS ARTHRODESIS
SHOULDERSHOULDER = = 11
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
VAN NES VAN NES
ROTATIONPLASTYROTATIONPLASTY = = 11
LIMB SALVAGE PROCEDURE LIMB SALVAGE PROCEDURE
• ILIZAROV ILIZAROV
RECONTRUCTIONRECONTRUCTION = = 11
COMPLICATIONS OF TREATMENTCOMPLICATIONS OF TREATMENT
SERIOUS INFECTIONSSERIOUS INFECTIONSHEP. B WITH HEPATIC ENCEPHALOPATHY= 4 (6.3%)HEP. B WITH HEPATIC ENCEPHALOPATHY= 4 (6.3%)
GRAM NEGATIVE SEPTICAEMIA = 6 (9.5%)GRAM NEGATIVE SEPTICAEMIA = 6 (9.5%)
FUNGAL PNEUMONIA = 2 (3.2%)FUNGAL PNEUMONIA = 2 (3.2%)
CHEMOTHERAPY TOXICITYCHEMOTHERAPY TOXICITYCISPLATIN NEUROTOXICITY = 1 (1.5%)CISPLATIN NEUROTOXICITY = 1 (1.5%)
METHOTREXATE NEPHROTOXICITY = 2 (3.2%)METHOTREXATE NEPHROTOXICITY = 2 (3.2%)
ADRIAMYCIN CARDIOTOXICITY = 1 (1.5%)ADRIAMYCIN CARDIOTOXICITY = 1 (1.5%)
PSYCHOLOGICAL COMPLICATIONSPSYCHOLOGICAL COMPLICATIONSMAJOR DEPRESSION = 6 (9.5%)MAJOR DEPRESSION = 6 (9.5%)
COMPLICATIONS OF LIMB SALVAGE COMPLICATIONS OF LIMB SALVAGE SURGERYSURGERY
IMPLANT FAILURE REQUIRING REVISION IMPLANT FAILURE REQUIRING REVISION SURGERY 1 (5.2%)SURGERY 1 (5.2%)
IMPLANT EXPOSURE REQUIRING IMPLANT EXPOSURE REQUIRING SECONDARY PLASTIC SURGICAL SECONDARY PLASTIC SURGICAL RECONSTRUCTION 1 (5.2%)RECONSTRUCTION 1 (5.2%)
FOLLOWUPFOLLOWUP
MEAN FOLLOWUP WAS 32 MEAN FOLLOWUP WAS 32 26 26 months (Mean months (Mean 1SD) 1SD)
RANGE 3.6 TO 98.5 months RANGE 3.6 TO 98.5 months
OVERALL SURVIVALOVERALL SURVIVAL
Overall survival interval in months
100806040200
Su
rviv
al r
ate
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
DEATH2 * LOST Crosstabulation
Count
34 10 44
10 9 19
44 19 63
no
yes
DEATH2
Total
no yes
LOST
Total
60.4% of the patients were alive at 5 YEARS
EVENT FREE SURVIVALEVENT FREE SURVIVAL
Event free survival interval in months
100806040200
Su
rviv
al r
ate
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
.0
40% were event free at 5YEARS
EVENT * LOST Crosstabulation
Count
29 6 35
15 13 28
44 19 63
N
Y
EVENT
Total
no yes
LOST
Total
EFS ACCORDING TO THERAPY –RELATED EFS ACCORDING TO THERAPY –RELATED VARIABLESVARIABLES
Event free survival interval in months
100806040200
Su
rviv
al ra
te
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
.0
Necrosis
>90%
<90%
%age Necrosis%age Necrosis
<90% =44
>90% = 19
(P=0.8633)
EFS ACCORDING TO THERAPY –RELATED EFS ACCORDING TO THERAPY –RELATED VARIABLES VARIABLES
Event free survival interval in months
100806040200
Su
rviv
al r
ate
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
.0
Amputation/Salvage
Limb salvage
Amputation
Amputation Vs Limb SalvageAmputation Vs Limb Salvage
Limb salvage=19
Amputation = 44
(P =0.1895)
RESULTS SUMMARY RESULTS SUMMARY
OVERALL SURVIVAL 60.4% AT 5YRS.OVERALL SURVIVAL 60.4% AT 5YRS.EVENT FREE SURVIVAL 40% AT 5YRS.EVENT FREE SURVIVAL 40% AT 5YRS.NO OS DIFFERENCE BETWEEN GOOD NO OS DIFFERENCE BETWEEN GOOD AND BAD RESPONDERS TO INITIAL AND BAD RESPONDERS TO INITIAL CHEMOTHERAPY.CHEMOTHERAPY.NO OS DIFFERENCE BETWEEN LIMB NO OS DIFFERENCE BETWEEN LIMB SALVAGE AND ABLATION. SALVAGE AND ABLATION. TREATMENT WAS GENERALLY WELL TREATMENT WAS GENERALLY WELL TOLERATED.TOLERATED.
Literature ReviewLiterature Review
Sr. noSr. no JournalJournal AuthorAuthor Pat. No.Pat. No. F/upF/up EFS%EFS% OS%OS%
11 Ann of Oncol Ann of Oncol 8:765-771,19978:765-771,1997
Ferrari et alFerrari et al 127127 12 yrs12 yrs 46%46% 53%53%
22 Clin Ortho & Clin Ortho & Related Research Related Research 358:120-127,1999358:120-127,1999
Sluga et alSluga et al 133133 5 yrs5 yrs 67%67% 70%70%
33 J Clin Oncol J Clin Oncol 18:4016-4027 ,18:4016-4027 ,
20002000
Bacci et alBacci et al 164164 5 yrs5 yrs 63%63% 75%75%
44 The Oncologist, The Oncologist, 9:422-441, 2004.9:422-441, 2004.
Marina et alMarina et al Review Review articlearticle
5 yrs5 yrs
10 yrs10 yrs
74%74%
71%71%
DISCUSSIONDISCUSSION
LATE PRESENTATIONLATE PRESENTATION HIGH PERCENTAGE OF MACROMETASTASES HIGH PERCENTAGE OF MACROMETASTASES
AT PRESENTATION (35 OF 134 = 26%).AT PRESENTATION (35 OF 134 = 26%).LARGE NUMBER PATIENTS PRESENTING WITH LARGE NUMBER PATIENTS PRESENTING WITH
HUGE FUNGATING TUMOURS REQUIRING HUGE FUNGATING TUMOURS REQUIRING UPFRONT AMPUTATION.UPFRONT AMPUTATION.
DISCUSSIONDISCUSSION
LACK OF EDUCATION & AWARENESS LACK OF EDUCATION & AWARENESS HIGH TENDENCY FOR FAMILIES TO HIGH TENDENCY FOR FAMILIES TO
DISCONTINUE TREATMENT MIDWAY.DISCONTINUE TREATMENT MIDWAY. FAILURE TO CONTINUE REGULAR FOLLOW FAILURE TO CONTINUE REGULAR FOLLOW
UP IF THE PATIENT IS ALRIGHT POST UP IF THE PATIENT IS ALRIGHT POST TREATMENT.TREATMENT.
DISCUSSIONDISCUSSION
HIGH SYSTEMIC INFECTION RATE AND CO-HIGH SYSTEMIC INFECTION RATE AND CO-MORBIDITYMORBIDITY
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 = 1SEPTIC SHOCK = 1
FUNGAL PNEUMONIA = 1FUNGAL PNEUMONIA = 1
DISCUSSIONDISCUSSION
POSSIBILITY OF BIOLOGICALLY AGGRESSIVE POSSIBILITY OF BIOLOGICALLY AGGRESSIVE DISEASE?DISEASE?
44 OF 63 (70%) HAD <90% POST 44 OF 63 (70%) HAD <90% POST CHEMOTHERAPY NECROSIS.CHEMOTHERAPY NECROSIS.
4 OF 63 (6.3%) HAD DIAPHYSEAL LESIONS.4 OF 63 (6.3%) HAD DIAPHYSEAL LESIONS.
CONCLUSIONSCONCLUSIONS
• OUR RESULTS ARE COMPARABLE TO INTERNATIONAL OUR RESULTS ARE COMPARABLE TO INTERNATIONAL FIGURES THOUGH A MUCH LONGER FOLLOW UP (AT LEAST FIGURES THOUGH A MUCH LONGER FOLLOW UP (AT LEAST 10 YEARS) IS REQUIRED TO GET A MORE ACCURATE 10 YEARS) IS REQUIRED TO GET A MORE ACCURATE PICTURE.PICTURE.
• PATIENTS NEED TO BE STUDIED PROSPECTIVELY TO PATIENTS NEED TO BE STUDIED PROSPECTIVELY TO ENSURE MORE RELIABLE DATA.ENSURE MORE RELIABLE DATA.
• WE NEED TO ORGANIZE EDUCATIONAL CAMPAIGNS TO WE NEED TO ORGANIZE EDUCATIONAL CAMPAIGNS TO IMPROVE PUBLIC AND HEATH PERSONNEL AWARENESS IMPROVE PUBLIC AND HEATH PERSONNEL AWARENESS ABOUT TREATABLE NATURE OF THIS DISEASE IF CAUGHT ABOUT TREATABLE NATURE OF THIS DISEASE IF CAUGHT EARLY. EARLY.
• DESPITE LIMITATIONS OF WORKING IN A THIRD WORLD DESPITE LIMITATIONS OF WORKING IN A THIRD WORLD
TERTIARY CARE CENTRE, OUR PRELIMINARY RESULTS OF TERTIARY CARE CENTRE, OUR PRELIMINARY RESULTS OF LIMB SALVAGE SURGERY ARE HEARTENING (30%, NO LIMB SALVAGE SURGERY ARE HEARTENING (30%, NO STATISTICALLY SIGNIFICANT DIFFERENCE IN OUTCOME STATISTICALLY SIGNIFICANT DIFFERENCE IN OUTCOME COMPARED TO ABLATIVE SURGERY).COMPARED TO ABLATIVE SURGERY).