Douglas S. Hawkins, Kristy Seidel, Mark Krailo, Leo
Mascarenhas, Paul Meyers, Neyssa Marina,
Ernest U. Conrad
Connective Tissue Oncology Society
November 2008

 498 patients in INT-0133 OS CT trial
 BMI breakdown:



Low BMI (<10%): 73 patients (14.7%)
Middle BMI (10-94%): 382 patients (76.7%)
High BMI (>95%): 43 patients (8.6%)
 Complications:






Any: 76 patients (15.3%)
Wound slough: 52 patients (10.5%)
Infection: 15 patients (3.0%)
Hematoma:
Thrombosis:
Hemorrhage:
15 patients (3.0%)
6 patients (1.2%)
4 patients (0.8%)
23. September - Sitzung der
EGF Bert Uwe Drechsel

 Wound slough or infection:

Low BMI: 14 patients (19.2%) OR=2.0 (p=0.04)


Middle BMI:
High BMI:
40 patients (10.5%) Reference
7 patients (16.3%) OR =1.7 (p=0.25)
 Thrombosis:



Low BMI:
Middle BMI:
High BMI:
0 patients (0%) OR=1.4 (p=1.0)
3 patients (0.8) Reference
3 patients (7.0%) OR=9.4 (p=0.03)
23. September - Sitzung der
EGF Bert Uwe Drechsel

 Low BMI at study entry for patients with localized osteosarcoma receiving neoadjuvant chemotherapy is associated with an increased risk of wound infection or wound slough after delayed definitive surgery
 Future studies should evaluate whether correction of malnutrition reduces the risk of surgical complication
23. September - Sitzung der
EGF Bert Uwe Drechsel

 This study measured BMI at start of Rx – did you look at change in BMI as a more potent cause of problems – eg the underweight child who loses weight?
 Were wound problems related to toxicity of chemotherapy?
23. September - Sitzung der
EGF Bert Uwe Drechsel

Simon Jordan, Peter Goldstraw, Elizabeth Belcher, Ambrus Szántho,
Jeremy Whelan*, Beatrice Seddon*, Maria Michelagnoli*,
Anna Cassoni*, Sandra Strauss*, Michelle Scurr + , Frank Saran + ,
Ian Judson + , George Ladas
Royal Brompton Hospital, London, United Kingdom;
*University College Hospital, London, United Kingdom;
+ Royal Marsden Hospital, London, United Kingdom
Royal Brompton Hospital Pulmonary Metastasectomy for Sarcoma

 Prolonged survival following pulmonary metastasectomy is well documented. However, the presence of a pleural effusion raises concerns as to the suitability of aggressive treatment. The prognostic significance of such effusions has not been addressed.
 Retrospective assessment of 105 consecutive patients operated on by a single surgeon undergoing pulmonary metastasectomy for sarcomatous disease between 01/01/95 and 31/03/2007 was undertaken. Kaplan-Meier methods, Log-rank test and Cox regression models were utilised to compare survival.
Royal Brompton Hospital Pulmonary Metastasectomy for Sarcoma

 105 patients underwent 157 metastasectomy procedures. Operative mortality was 0%. Operative mortality was 51.7% at 5 years and 46.7% at 10 years. A pleural effusion was present pre-operatively in
11 of 105 patients. In 7 patients the effusion was haemorrhagic. The presence of a pleural effusion, did not affect prognosis (HR 1.44 (CI: 0.61-3.4, p=0.408)). Moreover, a haemorrhagic pleural effusion did not influence survival (HR 1.49 (CI: 0.53-4.17, p=0.447)). We suggest that the presence of a pleural effusion should not preclude patients from undergoing pulmonary metastasectomy.
Patients at risk
105 57 34 27 16 11 10 6 4 2
Figure. 1.
Overall survival following lung metastasectomy in sarcoma patients .
Royal Brompton Hospital Pulmonary Metastasectomy for Sarcoma

 Was surgical technique any different for patients with a pleural effusion?
 Did the surgeon find pleural metastases more commonly in these cases?
 If a pleural metastasis was found ‘stuck’ to the chest wall – was the chest wall resected ‘en bloc’?
Royal Brompton Hospital Pulmonary Metastasectomy for Sarcoma

Survey: Mangement of Pulmonary Metastatic Osteosarcoma
D. Carrle, S. Bielack – COSS Stuttgart
Background:
Evidence:
1. Detection: No perfect imaging method
2. Treatment: Complete surgical resection of all malignant leseions in osteosarcoma
Lack of evidence:
Practical diagnostic and therapeutic aspects of management.
Purpose:
Survey to determine current practice of experts in the field.
Method:
Postal survey addressing 17 representatives from international study groups and selected institutions.
Results:
Response rate:
94%
Items
Initial staging at 1 st presentation:
1. Use of CT-Thorax
2. Additional use of Chest-X-Ray
Yes
16/16
12/15

Items
3. Lesion sized > 5 cm:
4. Lesion sized < .5 cm:
5. Routine follow-up: insufficient to distinguish malignant from benign lesion
Use of CT-Thorax
6. Suspicious lesion on CT: Open Thoracotomy as next step
7. At thoracotomy: sufficient to distinguish malignant from benign lesion
8. Unilateral disease:
9. „Disappearing“ lesions under chemotherapy:
Manual exploration routinely recommended
Bilateral exploration?
Surgery?
Yes
12/15
15/15
10/16
13/16
16/16
11/16
8/16
Conclusion:
Survey amongst experts in the field: generates new (1, 6) or substantiate (3, 4, 7) existing evidence (  Level
5, °D) exposes controversies in some areas (5, 8, 9).
Prospective studies needed - Join SAREZ/ TranSaRNet Consortium
(Sarcoma Registry)!

• Unilateral disease – bilateral exploration - what is hit rate for finding abnormalities
• Role of better imaging for the 5mm nodules? ? PET
• What happens to cases of disappearing mets?

Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: A report from the Children's Oncology
Group
AJ Chou, ES Kleinerman, MD Krailo, Z Chen, DL Betcher, JH
Healey, EU Conrad, H Nadel, ML Nieder, J Sato, MA Weiner, RJ
Wells, RB Womer, PA Meyers, on behalf of the Children’s
Oncology Group


21 patients with OS + mets at diagnosis
Randomized to chemo


A - Ad/Cisplat/HDMTX + MTPE
B - Ad/Cisplat/HDMTX/Ifos + MTPE

Results: Overall Survival
Survival by Randomized Regimen
0 5
Year
10 15
Regimen
A-
A+
B-
B+
Survival by MTP Assignment
0 5
Year
10 15
Assigned MTP
Yes
No

Conclusions


Predictors of poor outcome

Race (Hispanic worse)



Gender (males worse)
Non-pulmonary sites of disease
High alkaline phosphatase, LDH
− Number of pulmonary nodules did not appear to predict poor outcome  ? Significance ? Explanation
The pattern seen in the metastatic cohort was similar to the non-metastatic cohort with the same reduction in the relative risk of death associated with the addition of L-
MTP-PE to conventional chemotherapy, but the improvement did not reach conventional levels of statistical significance

Qqqqqqq



HELIOS Klinikum Berlin-Buch
Sentinel node biopsy in soft tissue sarcoma of the extremities. A singlecenter experience
Dimosthenis Andreou
S. Fehlberg, C. Tiedke,
S. Richter, D. Pink, P.-U. Tunn
HELIOS Klinikum Berlin-Buch – Department Tumororthopädie, Sarkomzentrum Berlin-Brandenburg Dimosthenis Andreou

Sentinel node biopsy in soft tissue sarcoma of the extremities - Results
• a series of 22 consecutive patients with synovial sarcoma (n=17), clear cell sarcoma (n=2), epithelioid sarcoma (n=2) and rhabdomyosarcoma
(n=1) underwent a sentinel node biopsy
• 2 positive, 1 false negative and 24 negative sentinel nodes were identified
• at least one sentinel was detected in each patient
• no biopsy-related complications were observed
HELIOS Klinikum Berlin-Buch – Department Tumororthopädie, Sarkomzentrum Berlin-Brandenburg Dimosthenis Andreou

Sentinel node biopsy in soft tissue sarcoma of the extremities - Discussion
• up to date there is no validated, non-invasive method to assess regional lymph node status in patients with soft tissue sarcoma
• SN-biopsy can be successfully and safely applied
• further prospective studies are required to determine the clinical relevance and the prognostic significance of SN-biopsy in soft tissue sarcoma
HELIOS Klinikum Berlin-Buch – Department Tumororthopädie, Sarkomzentrum Berlin-Brandenburg Dimosthenis Andreou

Qqqqqq…
• Which were the +ve cases?
• Was there any clinical or radiological suspicion in those?
• Did it alter management?
• Is it cost effective?
HELIOS Klinikum Berlin-Buch – Department Tumororthopädie, Sarkomzentrum Berlin-Brandenburg Dimosthenis Andreou

Ruggieri P., Ussia G., Bosco G., Angelini A., Montalti M.,
Pala E., Biagini R., Mercuri M.
Department of Orthopedics, University of Bologna, Istituto Ortopedico Rizzoli

28 cases (1986-2006)
• retrospective study
• age range: 4 – 68 ys. (mean age 30)
• mean follow-up 9.6 ys. ( min.2- max.22 )
• No lung metastases at dx., no multicentric GCTs
• Neurologic deficits at presentation 43%
• Stage 3 GCT 89%
• Previous treatment elsewhere in 4 cases
• S 1 was involved in 82% of the cases (23/28)

Surgical treatment: intralesional excision in 28 cases
• Surgical approach:
- Anterior and posterior 14 cases
- Posterior 13 cases
- Anterior 1 cases (death after 14 day of surgery)
• Radiotherapy (adjuvant) in 20 cases, average dose
43.5 Gy
(min.36- max.70 Gy)
• Preoperative selective arterial embolization in 22 cases:
- 2 times in 2 cases
- 1 time in 20 cases
• Local adjuvants in 17 cases: phenol (16), liquid nitrogen (3)
- 14 cases phenol
- 1 case liquid nitrogen
- 2 cases both

• 24 cases NED
• Local Recurrence in 3 cases ( 2 NED1, 1 DOD with radio-induced sarcoma)
• 1 DOD with postoperative massive pulmonary embolism
• Overall mortality 7.1% (2/28)
• Perioperative mortality 3.6% (1/28)
• Overall LR rate 11% (3/27):
- 1 LR/7 cases with surgery only (14%)
- 2 LR/20 cases with surgery and radiotherapy (10%)
Radio-induced sarcoma 5% (1/20)
No lung metastases
Postoperative neurologic deficit 48%
CONCLUSIONS: recommended treatment is surgical excision with local adjuvants, without radiotherapy pietro.ruggieri@ior.it

• Some reports suggest embolisation itself may cure many of these patients…..
• How control bleeding if no embolisaton?
• What is follow up for RT treated patients?
• How many neurologically worse after surgery than before?
• Do you foresee any role for biphosphonates / denosumab in these cases?

THE CLINICAL AND FUNCTIONAL OUTCOME FOR
RADIATION-INDUCED SOFT-TISSUE SARCOMA IN ADULTS
Soha Riad, Anthony Griffin, Ginger Holt, Cindy Wong, Joel Werier, Robert Turcotte,
Peter Ferguson, Benjamin Deheshi, Brian O’Sullivan, Jay Wunder
Musculoskeletal Oncology Unit, Mount Sinai, Vanderbilt Medical Center, McGill
University Health Center, Ottawa Hospital-General Campus, Departments of
Radiation Oncology and Surgical Oncology, Princess Margaret Hospital, University
Health Network, The University of Toronto
Purpose:

To compare the clinical and functional outcome of patients with radiation-induced soft tissue sarcomas
(RI-STS) to those with primary extremity soft-tissue sarcoma.
Diagnosis
MFH
Angiosarcoma
Liposarcoma
STS-Osteosarcoma
Leiomyosarcoma
NOS
Methods:

Retrospective data from 4 centers were collected for
RI-STS cases treated from 1989-2004.

33 patients with median age of 54.5 years
Median period from irradiation of primary cancer to RI-
STS was18 years (3-56 years).

4/31 patients had positive resection margins.

42% of RI-STS developed a systemic relapse and
24% developed a local recurrences
45
40
35
30
25
20
15
10
5
0
Rhabdomyosarcoma
Malignant Peripheral
Nerve Sheath
Tumour
Percentage (%)
33.3
15.2
12.1
12.1
9.1
9.1
6.1
3.0
LR of Original
Cancer
LR of Sarcoma Node mets of
Sarcoma
Type of Relapses
Systemic mets of Sarcoma


RI-STS 5-year overall survival was 39% compared to 72% for the Other STS group.
 14 patients had postoperative functional assessment using TESS and MSTS1987 scores; mean 83
(61-100), 27 (17-33) respectively, compared to 86 (13-
100), 30 (14-35) for the Other
STS population.
Overall Survival comparison for Grade 3 RI-STS vs. Other Grade 3 STS groups
1.0
0.8
Conclusions
 Patients with RI-STS have a poor prognosis due to high local and systemic recurrence rates.
 Limb salvage and negative margins were obtainable for most of the RI-STS group.
 Good functional results are possible for these patients.
 Novel systemic treatments are necessary to help improve their oncologic outcomes.
0.6
Other STS Group
0.4
p = 0.0002
RI-STS Group
0.2
0.0
p = > 0.00001
0 24 48 72 96
MONTHS
120 144 168 192






What most the common site
What was the most common primary
In how many did you feel there may be a ‘field change’ rather than a single focus
Could you use further RT in any?
Chemotherapy?

The Functional Consequence of Femoral Nerve Resection in the Thigh
Kevin B. Jones* † , Soha Riad*, Anthony M. Griffin*, Benjamin Deheshi*, Robert S. Bell*, Peter C. Ferguson*, Jay S. Wunder*
*University Musculoskeletal Oncology Unit, Mount Sinai and Princess Margaret Hospitals, University of Toronto.
† Sarcoma Services, Huntsman Cancer Institute and the Department of Orthopaedic Surgery, University of Utah.
Findings
•
10 patients retrospectively identified from a prospective sarcoma database had undergone complete femoral nerve ablation during soft tissue sarcoma resection.
•
Compared to sciatic nerve resection patients, a non-nerve-involved thigh sarcoma control group, and a gender-matched control group, TESS, MSTS1987, and MSTS1993 trended toward worse outcomes among the 10 patients with femoral nerve resection. Statistical significance was not reached.
• 6 of the 10 patients suffered a total of 8 fractures following complete femoral nerve resection, many in the contralateral limb, due to frequent falls.

The Functional Consequence of Femoral Nerve Resection in the Thigh
Kevin B. Jones* † , Soha Riad*, Anthony M. Griffin*, Benjamin Deheshi*, Robert S. Bell*, Peter C. Ferguson*, Jay S. Wunder*
*University Musculoskeletal Oncology Unit, Mount Sinai and Princess Margaret Hospitals, University of Toronto.
† Sarcoma Services, Huntsman Cancer Institute and the Department of Orthopaedic Surgery, University of Utah.
Relevance
• Sciatic nerve resection in the thigh changed from a categorical indication for amputation to an undertaking compatible with limb salvage when functional outcomes were carefully studied.
•
In contrast, it appears that the functional morbidity of femoral nerve resection may have been under-estimated in the absence of nerve-specific outcomes data, perhaps because complete extensor power ablation is somewhat commonly associated with distal femur resection and reconstruction in the sarcoma world, but the effects are there mitigated by implant hyperextension.
•
Functional outcomes, as well as fall-preventive interventions, following femoral nerve resection for soft tissue sarcoma merit further attention and study, as do other nerve-specific functional outcomes.

• Did any of the patients have a brace?
• Did any have a tendon graft?
• Anyone know a good reconstruction following excision of the femoral nerve?

.
G. Bosco, A. Bosco, G. Paone, E. Pala,T. Calabrò,
P. Ruggieri
Department of Orthopedics, University of Bologna, Istituto Ortopedico Rizzoli

Injection of metilprednisolone acetato in treatment of the eosinophilic granuloma of bone
50 cases (Jan 1994 - Dec 2004)
31 - 19
Age: 9.7 yrs (min 2 – max 60)
Site: Lower limb 17
Upper Limb 12
Pelvis
Spine
11
4
Multiple localizations 6 *
Follow up: 36.7 months (min 3 - max 94)
*all pts. received systemic therapy (Vinblastin+Prednisone)
2 had previous Prednisone local injection

Injection of metilprednisolone acetato in treatment of the eosinophilic granuloma of bone
40 pts. healed with a single injection mean time to radiografic healing
->
9 months
One Months Five Months
steroids injection effective in single bone lesions
no further injections if at 3 mos. positive X rays changes
multiple lesions require systemic treatment

• How many Eosinophilic granulomas Rx in the same time period without steroid injection?
• How many healed without injection?
• What are indications for steroid injection?