
Presenter: Melsew.A
COR2
Moderater: Dr Matheos .A
Clinical oncologist and inernist
Osteosarcoma

 A case of a Patient
 Clinical Presentation
 Standard work up
 Principles of management
 Prognostic factors
 Follow up
 Case Critics
Outlines of presentation

 A 50 years old male and camera man patient come
from AA presented with falling down accident of 3
days duration from standing position
 3 months prior to his accident he has left leg pain
and swelling .
 Otherwise he has no medical illness ,and trauma hx
 He has no hx of irradiation
 He has no cough
 He is refered from menilik hospital
MRN 549475

 GA ;acutely sick looking in pain
 VS BP 140/70,PR 114
 Msk;posterior long leg gutter and 4x5cm swelling inside
gutter
 ASST:left tibia pathologic fracture
 PLAN :was to do left leg x ray,CXR,MRI of left leg,OFT
 ON 28/4/2011
 On 10/5/2011
 Incisional biopsy and external fixation was done
P/E
ON 28/4/2011

 Hx :same
 ECOG1
 V/S: stable
 HEENT:pink conjuctiva and NIS
 P/E :there is 5x4cm hard immobile mas on left distal
tibia
In our OPD

 CBC:normal
 Abdominopelvic U/S:normal
 OFT:normal
 Chest CT:normal
Investigations





 ASST:High grade conventional osteosarcoma
 Plan :Neoajuvant cisplatin and adriamycine
 Mid cycle evaluation for surgery and then ajuvant
cisplatin and adriamycin
Cont..

Question ???

 Most patients present with localized pain in the
affected bone.
 Pain is usually of several months duration and may
wax and wane.
 There may be associated soft tissue swelling or a
palpable mass.
 Some patients present with pathologic fracture.
 Osteosarcoma has a predilection for involvement of
the metaphysis of long bones.
Clinical Presentation

 The most common site of involvement is the knee
(distal femur or proximal tibia), followed by the
proximal humerus, mid and proximal femur, and
then other bones.
 Although most patients have micrometastatic
disease at the time of presentation, only 10% to 20%
of patients present with clinical evident macro
metastases.
 The lung is the most common site of metastatic
involvement, followed by bone.
Cont..

Diagnostic Evaluation



Staging Systems


Management principles


 Types:
 Fine needle aspiration
 Core needle biopsy
 Open incisional biopsy
Biopsy

 Surgery
 Chemotherapy
 radiotherapy
Treatments of OS

 The mainstay of surgical management is the
complete en bloc resection of tumor.
 The extent of surgery have dramatically evolved
over time, with an emphasis on more conservative,
limb-sparing resections with maintenance of
function rather than amputation.
 Neoadjuvant chemotherapy has played an important
role in this evolution
Surgery

 For extremity lesions, limb preservation is preferred
and can be accomplished in the majority of cases.
 Retrospective studies have shown equivalent results
of limb-sparing surgery and amputation as long as
adequate margins can be achieved
cont.,…

 1
JBJS Classics
227 patients
From26 institutions
Limbs paring
Procedure
73disarticulati
on of the hip
39
above-the
knee
amputation
115
LR
9
7.8%
SUR
67
58%
Met
65
56%
LR
0
0%
SUR
21
53%
MET
21
53%
LR
8
10%
SUR
40
54.7%
MET
43
58.9
%
PEPTS
local
recurrence
Metastasis
survival
after a median length of follow-up of 5.5years

 The Kaplan-Meier estimates of the percentage of
patients who survived and the percentage of patients
without recurrent disease showed no difference
among the three surgical groups (Mantel-Cox test
statistic: p = 0.8)
 It appears that, compared with above-the-knee
amputation or disarticulation of the hip, the use of a
limb salvage procedure for osteosarcoma of the
distal end of the femur did not shorten the disease-
free interval or compromise long-term survival.
Cont.…

 However, not all patients are candidates for more
conservative surgery .
 Axial tumors, although much less common, pose a
particular challenge because achieving complete
surgical resection can be difficult.
Cont…

 Pelvic tumors typically require a hemipelvectomy
for en bloc resection.
 Some patients can undergo resection of the
hemipelvis with preservation of the extremity .
 This has a better functional outcome compared to an
external hemipelvectomy, also referred to as a
hindquarter amputation
Cont..



 compromise between amputation and limb salvage
 most commonly used for osteosarcomas of the distal
femur in skeletally immature patients
 It is a procedure where the neurovascular structures
and distal aspect of the limb (leg) are retained
Rotationplasty

 For functional purposes, the distal segment is turned
180 degrees so that the ankle joint functions as a knee
joint,
 thus converting an above-knee to a below-knee
amputation in order for prosthetic use to be
maximized
Cont…



 Contraindications to limb-sparing surgery include;
 nerve or vascular encasement,
 presence of large, biopsy-related hematoma,
 And pathologic fracture.
 Reconstructive options include use of allografts,
endoprostheses, and occasionally rotationplasty
Cont..

 In the absence of chemotherapy, 80% to 90% of
patients will subsequently develop distant
metastases.
 Chemotherapy thus plays an important role for all
patients with intermediate- and high-grade tumors
 Eilber et al. reported on 59 patients with
nonmetastatic osteosarcoma
 randomized to surgery followed by observation
versus adjuvant chemotherapy
chemotherapy


Eilber et al.
To determine the role of
chemotherapy
59 patients of conventional
high grade
osteosarcoma
32 received
MAP,and
BCD
.27 No chemo
DFS
55%
OS
80%
DFS
20%
OS
48%
(P < .01).
PEPTS
OS,DFS
At a median follow-up of 2 years

 At a median follow-up of 2 years, there was a
statistically significant improvement in both disease-
free and overall survival in those who received
adjuvant chemotherapy.



 Link et al. reported similar results in a group of 36
patients with nonmetastatic, high-grade
osteosarcoma randomized to observation versus
adjuvant chemotherapy after primary surgery.
 Disease-free survival at 2 years was 66% with
chemotherapy and 17% with observation (P < .001).
Cont..


Link et al
36 patients
To see effect of ajuvant
multiagent chemo
18
Received
chemo
18 No
chemo
RFS at 2y
66%
RFS at 2 year
17%
P<0.001
At a median follow-up of 2
years
PEPTS
RFS


neoadjuvant
chemotherapy

 The concept of neoadjuvant chemotherapy arose in
conjunction with evolving surgical techniques
striving for limb-preserving procedures and
improved functional outcomes.
 This led to a randomized clinical trial by the
PediatricOncology Group (POG8651).
neoadjuvant
chemotherapy

 Advantages of neoadjuvant chemotherapy: -
 regression of the primary tumor, making a successful
limb salvage operation easier.
 may decrease the spread of tumor cells at the time of
surgery
 Effectively treating micrometastases at the earliest
time possible.
 It avoid tumor progression, which may occur during
any delay before surgery.
Cont…


POG-8651
106 Patients
55 patients
immediate
surgery
45 patients
neoajuvant
chemo
Regimen
MA ,and BCD
6
excluded
Limb
salvage
surgery 55%
DFS at 5 yrs
69%
Limb salvage
surgery 50%
DFS at 5
yrs
61%
P= .8
PEPTS
Limbsalv
age
surge
DFS


 The optimal choice of chemotherapy and
administration schedule remains a subject of active
research
The optimal choice of
chemotherapy

 phase 3 randomised, controlled trial.
 Consenting patients with newly diagnosed,
resectable, high-grade osteosarcoma aged 40 years
or younger were eligible for randomisation
EURAMOS-1


EURAMOS-1
2260 patients
325 sites in 17 countries
to see IE effect in poor
responders
1642
Good
response
neoajuvant
MAP
618
Poor to MAP
310 to
receive
MAP
308 to
receive
MAPIE
Median
follow-up
was 62.1
months
EFS
55%
EFS
53%P = .69
PEPTS
OSDFS



 Final results were unfortunately negative with
neither ifosfamide and etoposide nor interferon
showing improved event free survival.
 For the poor response group, at 62 months median
follow-up, 3- year event-free survival was 55% for
MAP and 53% MAP + IE (P = .69).
 For the good response group, at 44 months median
follow-up, 3-year event-free survival was 74% for
MAP and 77% MAP with interferon (P = .214
Cont..



EOI
407 patients with operable,
non-metastatic
osteosarcoma
PEPTS
OS,PFS
16
patients
excluded
199 patients
Receive 18
week of AC
192 patients
Receive PREOP MAV
,POSTOP,BCD,MAP
OS
65%
PFS
47%
OS
65%
PFS
47%
at median of 3 years




Chemotherapy in older
patients
GAETANOBACCI.ET AL
53 patients
aged between 40
and 60 years
Cisp
+ad
m
29
patients
Received
surg,neoa
juvant
chemo
24
patients
Received
surgery
alone
PEPTS
EFS,OSa good
histologic
response
received the
same two
drugs
poor response
ifosfamide
and etoposide
were added to
cisplatin and
adriamycin.



 Operative resection is the only potentially curative
treatment for patients with thoracic metastases from
osteogenic sarcoma.
 Following resection, adjuvant chemotherapy can
improve disease-free survival and decrease the
burden of metastatic pulmonary disease.
 Resection of pulmonary metastases should always be
part of a combined modality approach
Role of metastatectomy

 Surgical margins; Negative surgical margins (defined as
at least 1 cm in bone with 2–5 cm recommended)
 Therefore, limb salvage is recommended when adequate
surgical margins can be achieved
 tumor responsiveness are directly associated with local
recurrence:
 In patients with marginal resections and with tumor
necrosis less than 90% after preoperative chemotherapy,
local recurrence has been reported as high as 30%
Prognostic factores

 Stage at diagnose
 tumor volume
 old age,
 sex,
 and possibly p-glycoprotein expression
Cont.…


Follow up

 Good documentation
 Proper work up with available set up except
ALP,LDH
 EXTERNAL fixation ??
 Proper treatment planning
Case critics

 Edward Pérez 7th ed.
 Devita 11th ed.
 Uptodate 2018
 NCCN 2019
 Google
References

 .

osteosarcoma locally advanced

  • 1.
     Presenter: Melsew.A COR2 Moderater: DrMatheos .A Clinical oncologist and inernist Osteosarcoma
  • 2.
      A caseof a Patient  Clinical Presentation  Standard work up  Principles of management  Prognostic factors  Follow up  Case Critics Outlines of presentation
  • 3.
      A 50years old male and camera man patient come from AA presented with falling down accident of 3 days duration from standing position  3 months prior to his accident he has left leg pain and swelling .  Otherwise he has no medical illness ,and trauma hx  He has no hx of irradiation  He has no cough  He is refered from menilik hospital MRN 549475
  • 4.
      GA ;acutelysick looking in pain  VS BP 140/70,PR 114  Msk;posterior long leg gutter and 4x5cm swelling inside gutter  ASST:left tibia pathologic fracture  PLAN :was to do left leg x ray,CXR,MRI of left leg,OFT  ON 28/4/2011  On 10/5/2011  Incisional biopsy and external fixation was done P/E ON 28/4/2011
  • 5.
      Hx :same ECOG1  V/S: stable  HEENT:pink conjuctiva and NIS  P/E :there is 5x4cm hard immobile mas on left distal tibia In our OPD
  • 6.
      CBC:normal  AbdominopelvicU/S:normal  OFT:normal  Chest CT:normal Investigations
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
      ASST:High gradeconventional osteosarcoma  Plan :Neoajuvant cisplatin and adriamycine  Mid cycle evaluation for surgery and then ajuvant cisplatin and adriamycin Cont..
  • 12.
  • 13.
      Most patientspresent with localized pain in the affected bone.  Pain is usually of several months duration and may wax and wane.  There may be associated soft tissue swelling or a palpable mass.  Some patients present with pathologic fracture.  Osteosarcoma has a predilection for involvement of the metaphysis of long bones. Clinical Presentation
  • 14.
      The mostcommon site of involvement is the knee (distal femur or proximal tibia), followed by the proximal humerus, mid and proximal femur, and then other bones.  Although most patients have micrometastatic disease at the time of presentation, only 10% to 20% of patients present with clinical evident macro metastases.  The lung is the most common site of metastatic involvement, followed by bone. Cont..
  • 15.
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22.
      Types:  Fineneedle aspiration  Core needle biopsy  Open incisional biopsy Biopsy
  • 23.
      Surgery  Chemotherapy radiotherapy Treatments of OS
  • 24.
      The mainstayof surgical management is the complete en bloc resection of tumor.  The extent of surgery have dramatically evolved over time, with an emphasis on more conservative, limb-sparing resections with maintenance of function rather than amputation.  Neoadjuvant chemotherapy has played an important role in this evolution Surgery
  • 25.
      For extremitylesions, limb preservation is preferred and can be accomplished in the majority of cases.  Retrospective studies have shown equivalent results of limb-sparing surgery and amputation as long as adequate margins can be achieved cont.,…
  • 26.
      1 JBJS Classics 227patients From26 institutions Limbs paring Procedure 73disarticulati on of the hip 39 above-the knee amputation 115 LR 9 7.8% SUR 67 58% Met 65 56% LR 0 0% SUR 21 53% MET 21 53% LR 8 10% SUR 40 54.7% MET 43 58.9 % PEPTS local recurrence Metastasis survival after a median length of follow-up of 5.5years
  • 27.
      The Kaplan-Meierestimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8)  It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease- free interval or compromise long-term survival. Cont.…
  • 28.
      However, notall patients are candidates for more conservative surgery .  Axial tumors, although much less common, pose a particular challenge because achieving complete surgical resection can be difficult. Cont…
  • 29.
      Pelvic tumorstypically require a hemipelvectomy for en bloc resection.  Some patients can undergo resection of the hemipelvis with preservation of the extremity .  This has a better functional outcome compared to an external hemipelvectomy, also referred to as a hindquarter amputation Cont..
  • 30.
  • 31.
  • 32.
      compromise betweenamputation and limb salvage  most commonly used for osteosarcomas of the distal femur in skeletally immature patients  It is a procedure where the neurovascular structures and distal aspect of the limb (leg) are retained Rotationplasty
  • 33.
      For functionalpurposes, the distal segment is turned 180 degrees so that the ankle joint functions as a knee joint,  thus converting an above-knee to a below-knee amputation in order for prosthetic use to be maximized Cont…
  • 34.
  • 35.
  • 36.
      Contraindications tolimb-sparing surgery include;  nerve or vascular encasement,  presence of large, biopsy-related hematoma,  And pathologic fracture.  Reconstructive options include use of allografts, endoprostheses, and occasionally rotationplasty Cont..
  • 37.
      In theabsence of chemotherapy, 80% to 90% of patients will subsequently develop distant metastases.  Chemotherapy thus plays an important role for all patients with intermediate- and high-grade tumors  Eilber et al. reported on 59 patients with nonmetastatic osteosarcoma  randomized to surgery followed by observation versus adjuvant chemotherapy chemotherapy
  • 38.
      Eilber et al. Todetermine the role of chemotherapy 59 patients of conventional high grade osteosarcoma 32 received MAP,and BCD .27 No chemo DFS 55% OS 80% DFS 20% OS 48% (P < .01). PEPTS OS,DFS At a median follow-up of 2 years
  • 39.
      At amedian follow-up of 2 years, there was a statistically significant improvement in both disease- free and overall survival in those who received adjuvant chemotherapy.
  • 40.
  • 41.
  • 42.
      Link etal. reported similar results in a group of 36 patients with nonmetastatic, high-grade osteosarcoma randomized to observation versus adjuvant chemotherapy after primary surgery.  Disease-free survival at 2 years was 66% with chemotherapy and 17% with observation (P < .001). Cont..
  • 43.
      Link et al 36patients To see effect of ajuvant multiagent chemo 18 Received chemo 18 No chemo RFS at 2y 66% RFS at 2 year 17% P<0.001 At a median follow-up of 2 years PEPTS RFS
  • 44.
  • 45.
  • 46.
      The conceptof neoadjuvant chemotherapy arose in conjunction with evolving surgical techniques striving for limb-preserving procedures and improved functional outcomes.  This led to a randomized clinical trial by the PediatricOncology Group (POG8651). neoadjuvant chemotherapy
  • 47.
      Advantages ofneoadjuvant chemotherapy: -  regression of the primary tumor, making a successful limb salvage operation easier.  may decrease the spread of tumor cells at the time of surgery  Effectively treating micrometastases at the earliest time possible.  It avoid tumor progression, which may occur during any delay before surgery. Cont…
  • 48.
      POG-8651 106 Patients 55 patients immediate surgery 45patients neoajuvant chemo Regimen MA ,and BCD 6 excluded Limb salvage surgery 55% DFS at 5 yrs 69% Limb salvage surgery 50% DFS at 5 yrs 61% P= .8 PEPTS Limbsalv age surge DFS
  • 49.
  • 50.
      The optimalchoice of chemotherapy and administration schedule remains a subject of active research The optimal choice of chemotherapy
  • 51.
      phase 3randomised, controlled trial.  Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation EURAMOS-1
  • 52.
      EURAMOS-1 2260 patients 325 sitesin 17 countries to see IE effect in poor responders 1642 Good response neoajuvant MAP 618 Poor to MAP 310 to receive MAP 308 to receive MAPIE Median follow-up was 62.1 months EFS 55% EFS 53%P = .69 PEPTS OSDFS
  • 53.
  • 54.
  • 55.
      Final resultswere unfortunately negative with neither ifosfamide and etoposide nor interferon showing improved event free survival.  For the poor response group, at 62 months median follow-up, 3- year event-free survival was 55% for MAP and 53% MAP + IE (P = .69).  For the good response group, at 44 months median follow-up, 3-year event-free survival was 74% for MAP and 77% MAP with interferon (P = .214 Cont..
  • 56.
  • 57.
      EOI 407 patients withoperable, non-metastatic osteosarcoma PEPTS OS,PFS 16 patients excluded 199 patients Receive 18 week of AC 192 patients Receive PREOP MAV ,POSTOP,BCD,MAP OS 65% PFS 47% OS 65% PFS 47% at median of 3 years
  • 58.
  • 59.
  • 60.
      Chemotherapy in older patients GAETANOBACCI.ETAL 53 patients aged between 40 and 60 years Cisp +ad m 29 patients Received surg,neoa juvant chemo 24 patients Received surgery alone PEPTS EFS,OSa good histologic response received the same two drugs poor response ifosfamide and etoposide were added to cisplatin and adriamycin.
  • 61.
  • 62.
  • 63.
      Operative resectionis the only potentially curative treatment for patients with thoracic metastases from osteogenic sarcoma.  Following resection, adjuvant chemotherapy can improve disease-free survival and decrease the burden of metastatic pulmonary disease.  Resection of pulmonary metastases should always be part of a combined modality approach Role of metastatectomy
  • 64.
      Surgical margins;Negative surgical margins (defined as at least 1 cm in bone with 2–5 cm recommended)  Therefore, limb salvage is recommended when adequate surgical margins can be achieved  tumor responsiveness are directly associated with local recurrence:  In patients with marginal resections and with tumor necrosis less than 90% after preoperative chemotherapy, local recurrence has been reported as high as 30% Prognostic factores
  • 65.
      Stage atdiagnose  tumor volume  old age,  sex,  and possibly p-glycoprotein expression Cont.…
  • 66.
  • 67.
  • 68.
      Good documentation Proper work up with available set up except ALP,LDH  EXTERNAL fixation ??  Proper treatment planning Case critics
  • 69.
      Edward Pérez7th ed.  Devita 11th ed.  Uptodate 2018  NCCN 2019  Google References
  • 70.