2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Endoprosthetic vs. “Condyle-Sparing” Intercalary Allografts for Distal Femoral Osteosarcoma: A Comparison of Long- Term Follow-up Timothy B. Rapp, M.D., Loyola University Medical Center Melissa Zimmel, Northwestern University Ernest U. Conrad III, M.D., University of Washington Presented by Dr. Conrad at the Connective Tissue Oncology Society Annual Meeting, November 2004 Montreal, Canada

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Reconstructive Options Endoprosthetic replacement  10-year implant survival ~70%  Concern over bone stock long term Osteoarticular allografts  Knee instability  Allograft complications “Condyle-Sparing” intercalary allografts  Preserves native knee joint  Allograft complications

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service ALLOGRAFT: HISTORICAL Mankin JBJS 1997  104 intercalary allografts for malignancy, retrospective 84 % “successful”84 % “successful” Overall salvage rate 92%Overall salvage rate 92% Local recurrence 9%Local recurrence 9% Survival for high grade tumors 60%Survival for high grade tumors 60% High non-union rate 28%High non-union rate 28% Deep infection rate 12%Deep infection rate 12% Outcome not affected byOutcome not affected by Age, gender, anatomical site, length of graft Outcome adversely affected byOutcome adversely affected by Infection, fracture, stage of lesion, use of chemotherapy Mankin H, JBJS, 79-A 1997

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Distal Femur- Bone Allograft: Osseous Union??

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service REVISIONS=50% !? REVISIONS=50% !? NOT 25-30% NOT 25-30% AND AND 15 YR OLD PT. 15 YR OLD PT. Age 25/35/?? Age 25/35/?? or Age20/25/30? or Age20/25/30? LIMB SALVAGE REVISIONS?

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Overall “Implant Survival “ Adults vs Children (N=88)

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service LIMB SALVAGE “HYPOTHESIS” CONDYLE SPARING GRAFT SUPERIOR TO IMPLANT ?

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service “MATCHED REVIEW” OF OSTEOSARCOMA OF THE DISTAL FEMUR

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service CRITERIA:OSTEOSARCOMA- DISTAL FEMUR -GRAFTS vs JOINTS  ISSUES:  ADEQUATE OSSEOUS MARGIN (vs SOFT TISSUE)  ALLOGRAFT vs DISTAL FEMUR

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service MethodsMethods IRB Approved review of Allografts and Implants SARCOBASE + Chart Review  Survival  Local recurrence  Surgical complications/revisions Functional Assessment  Modified MSTS/SF-36 Careful X-ray Review

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service ALLOGRAFTS- OVERALL N=80/73 N=80/73 Mean age= 28 yrs Mean age= 28 yrs Mean F/U= 5.3yrs Mean F/U= 5.3yrs Site=Femur/tibia/pelvis Site=Femur/tibia/pelvis 42/22/16% 42/22/16% Grafts= NTC Grafts= NTC

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service OVERALL ALLOGRAFT- RESULTS RADIOGRAPHIC REVIEW= “ NONUNION”=39% “ NONUNION”=39% DELAYED UNION=10% DELAYED UNION=10% TIME TO UNION= 14.6mos TIME TO UNION= 14.6mos OTHER: OTHER: FRACTURE= 5% FRACTURE= 5% INFECTION= 5% INFECTION= 5% REVISION=40% REVISION=40%

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Allografts: New Fixation Techniques vs Immunologic -Biologic Graft Issues

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service IMPLANTS- OVERALL REVIEW N= N=88 AGE= 9-86 yrs mn=33yrs AGE= 9-86 yrs mn=33yrs Pediatric age =31/88 Pediatric age =31/88 Follow-up=70 mos Follow-up=70 mos Anatomic=Femur/Tibia Anatomic=Femur/Tibia =61/27 =61/27 FunctionalAssess=MSTS FunctionalAssess=MSTS /SF 36 /SF 36

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Radiographic Outcome Xrays scored in 3 major categories  Continuous cement mantle (2mm)  No lucencies > 1mm  Cortical bridging from bone to collar Mean xray score 75/100 Lower “cement mantle” and “lucency” scores associated with pain and the need for revision “Bone bridging” did not correlate with revision status!

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Statistical Methods Patient and prosthetic survivorship curves by Kaplan-Meier method Student t tests to compare radiographic groups

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service OVERALL IMPLANT RESULTS RADIOGRAPHIC: RADIOGRAPHIC: “ Aseptic Loosenening”=19% “ Aseptic Loosenening”=19% Other: Other: Implant Failure= 12.5% Implant Failure= 12.5% Revision=55% Revision=55% Major=40.6% Minor=59.4% Major=40.6% Minor=59.4% Pediatric Prox Tibia p=0.029 Pediatric Prox Tibia p=0.029

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Overall Complications=50% --Knee stiffness: 10 pts Overall Complications=50% --Knee stiffness: 10 pts Deep infection: 7 pts Superficial wound: 6 pts Nerve palsy: 7 pts Bushing failure: 6 pts Stem fracture: 5 pts Patella instability: 4 pts DVT/PE: 3 pts MAJOR vs MINOR COMP’S Overall Implant Complications

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service GOOD NEWS-BAD NEWS ! PEDIATRIC SURVIVAL IS BETTER THAN PEDIATRIC SURVIVAL IS BETTER THAN IMPLANT SURVIVAL !? ( “GOOD RESULT “= GOES SKIING ?? ) GOES SKIING ?? )

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Clinical Outcome SF-36  8 standard categories assessed Physical functioning, Role Physical functioning, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental HealthPhysical functioning, Role Physical functioning, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health  Knee implant population scores lower than general U.S. population in each category, but NOT statistically significant Differed most in physical function and bodily pain categoriesDiffered most in physical function and bodily pain categories

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Results -”Matched” Distal Femur Allograft vs Implant 45 patients between treated for a distal femoral (meta-diaphyseal) osteogenic sarcoma  All patients received neoadjuvant chemotherapy 27 patients- “condyle-sparing” allograft  Average age 18.1 years  Average follow-up 6.5 years 18 patients - primary endoprosthesis  Average age 13.8 years  Average follow-up 6.4 years

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service SurgicalResults-Matched Series “Condyle-Sparing” Allografts (n=27)  Ten (37%) patients revised to endoprosthesis Average 3.5 years after original allograftAverage 3.5 years after original allograft Eight cases due to allograft/host non-unionEight cases due to allograft/host non-union  Average of 3.3 revision procedures/pt Bone grafting/screw or nail exchangeBone grafting/screw or nail exchange  Two deep infections (both eventually converted to implant)  One amputation for local recurrence Endoprosthesis (n=18)  Four (22%) patients revised Average 4.8 years after index procedureAverage 4.8 years after index procedure  Average of 1.1 revision procedures/pt  Three deep infections  One amputation for pain/stiff

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Oncologic Results-Matched Series Overall Survival 84%  Four deaths in allograft group  Three deaths in endoprosthesis group Local Recurrences  Two in allograft group (avg. 15 months after surgery)  One in endoprosthesis group (five months after surgery) Surgical Osseous Margins  Allograft=2.7cm(prox)+1.5cm(distal) ave bone margin  Endoprosthesis=3.1cm(prox)=2.6cm(distal-jt) ave margin

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Functional Results-Matched Series Functional Results-Matched Series Pain  Allografts (n=17): No narcotics  Endoprosthesis (n=18): One patient required occasional narcotics Walking Aids  Allografts: Two patients using canes, one uses crutches for long distance  Endoprosthesis: One patient using cane, one uses crutches for long distance ROM  Allografts: One flexion contracture (10º); average motion arc 105º  Endoprosthesis: Three contractures (avg. 15º); avg. motion arc 110º Strength  Allograft: Four patients with 4/5, otherwise 5/5  Endoprosthesis: Three patients with 4/5, otherwise 5/5

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Clinical Outcome SF-36  8 standard categories assessed Physical functioning, Role Physical functioning, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental HealthPhysical functioning, Role Physical functioning, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health  Knee implant population scores lower than general U.S. population in each category, but NOT statistically significant Differed most in physical function and bodily pain categoriesDiffered most in physical function and bodily pain categories MSTS=63% GOOD + EXC / Grafts= Implants “TESS” IS BETTER ?

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service GOOD NEWS-BAD NEWS ! PEDIATRIC PT. SURVIVAL IS BETTER THAN PEDIATRIC PT. SURVIVAL IS BETTER THAN IMPLANT SURVIVAL ORTHOPAEDIC CHALLENGE ORTHOPAEDIC CHALLENGE

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Discussion-Matched Endoprosthesis vs. “Condyle-Sparing” Allografts: Tumor control -similar  Survival  Local recurrence Final Functional - Similar??  Pain meds, walking aids, strength, ROM Higher Failure Rate in Allografts REVISION RATE=37 vs 22% (GRAFTS vs yrs

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service LIMB SALVAGE- FUTURE? Endoprosthesis  FOCUS ON 10 YR RESULTS +PATTERNS OF FAILURE  ISOLATE +IMPR0VE REVISION SCENARIO  CONSIDER NEW STEM FIXATION IN CHILDREN  FOCUS ON CAUSES OF FAILURE “Condyle-sparing” allografts  CLEARLY HAVE HIGHER FAILURE RATE-EARLY(5YRS)  EMPHACIZE FIXATION TECH’S  CLOSE BUT CAUTIOUS BONY MARGIN  TIME TO UNION=14 months  ALLOGRAFT BIOLOGY IN THE FUTURE? ALL LIMB SALVAGE PATIENTS ARE DONE ON “PROTOCOL”

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service THANK YOU

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Thank you for your attention! Research supported by educational grants from Stryker Howmedica Osteonics, Inc. and Zimmer, Inc.

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Thank You

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service

Allograft Overall Allograft group overall (n=?) Non-union=40% Delayed union= Sepsis=6% Tumor Recurrence=5%

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Implant Overall Implant group overall (n=88) “Implant survival”  At five years=71%  At ten years=59% Infection=7% Aseptic Loosening=19%

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service Overall Implant Survival Rate Adults vs. Children (N=88)

2004 Connective Tissue Oncology SocietyUniversity of Washington Musculoskeletal Tumor Service “LIMB SALVAGE “ They do well ? BEWARE THE SUBTLETIES !!