Local Control in Ewing Sarcoma of the Chest Wall

Benedetta Bedetti

Andreas Ranft

Heribert Jürgens

Karsten Wiebe

Uta Dirksen

The story behind......

Is there a benefit from combined modality local treatment?Who needs additional radiotherapy?? Large Tumor ? Pre-Chemo Resection? Poor Response to Inductionchemotx? Shaved MarginWhat is an appropriate surgical procedure?

ewing@ukmuenster.de

CESS EURO E.W.I.N.G.- 99 cohort

198 patients

July 1998- April 2009

119 male (60 %), 79 female (40 %)

Age at diagnosis: 13,9 (0,5-60)

Localized disease only

Primary:134 Rib28 Scapula 23 Soft Tissue12 Clavicula1 Sternum

Cohort

Local treatment modalities

Surgery in 191 patients:

Surgery only (OP): 85 pts, 43 %Radiotherapy only (RT): 7 pts, 3,5 %OP + RT: 106 pts, 53,3%

130 complete en bloc resections81 reconstructions of the thoraxic wall

Local treatment modalities

5y-EFS (OP) = 0,75 (SE = ,07)5Y-EFS (RT) = 0,63 (SE = ,05)5y-EFS (OP+RT) = 0,65 (SE = ,07)

Recurrence Group OP+RT Group OP- Local 26 % 29,5 %- Systemic 53 % 41 %- Combined relapse 21 % 29,5 %

Years

Surv

ival

p=.233

Is there a group of patients that benefit from combined modality local treatment?

Tumorvolume < 200 ml Tumorvolume > 200 ml

OP= 39OP + RT = 60ALL= 995y-EFS (OP) = 0,56 (SE = ,05)5y-EFS (OP+RT) = 0,55 (SE = ,07)

OP = 44OP+ RT = 51ALL= 955y-EFS (OP) = 0,86 (SE = ,05)5y-EFS (OP+RT) = 0,73 (SE = ,07)

Years

Surv

ival

Surgical margin: R1&R2Surgical margin: R0

OP = 77OP + RT = 58ALL= 995y-EFS (OP) = 0,74 (SE = ,05)5y-EFS (OP+RT) = 0,62 (SE = ,07)

OP = 8OP + RT = 48ALL = 565y-EFS (OP) = 0,57 (SE = ,19)5y-EFS (OP+RT) = 0,64 (SE = ,07)

Years

Surv

ival

Good histological response Poor histological response

OP = 59OP + RT = 81ALL= 1405y-EFS (OP) = 0,75 (SE = ,07)5y-EFS (OP+RT) = 0,65 (SE = ,07)

OP = 8OP + RT = 20ALL= 285y-EFS (OP) = 0,46 (SE = ,07)5y-EFS (OP+RT) = 0,41 (SE = ,07)

Surv

ival

Years

Risk Factor N 3y-EFS 5y-EFS P valueSurgical Margins (n=191) 0.142- R0 135 73 % 69 % - R1 48 70 % 65. 5% - R2 8 43 % 43 % Histological tumor response (n=145) <0.001- Good 104 76 % 70 % - Poor 41 45 % 45 % Tumor size (n=194) 0.007- < 200 ml 95 79 % 79 % - >= 200 ml 99 63 % 55 % Not malignant pleural effusion (n=198) 0.041No 132 76 % 72 % Yes 66 60 % 56 % Local treatment (n=198) 0.233Radiotherapy 8 63% 63%Surgery 85 76% 75%Surgery & Radiotherapy 106 66% 65%

Univariate analysis

Multivariate analysis

• Tumor size (</>=200ml), • Surgical margins (R0/R1 and R2) • Pleura effusion• Local therapy modality (OP/OP&RT)

Poor histological response (Hazard Ratio=2.74; 95 %CI 1.54-4.89)

Complete versus partialresection of the affected rib

Unknown5Y-EFS complete resection= 0,63 (SE= ,07)5y-EFS partial resection = 0,65 (SE = ,06)

P=0.685

Complications after surgery Prosthetic Material N Complication NNon rigid 46 Pneumothorax after chest drain

removal7

- Gore Tex 28 Paralysis after surgery involving vertebra

1

- Prolene 5 Bleeding 1

- Vicryl 12 Anemia 2

- Biopatch 1 Pneumonia 1

Spontaneous pneumothorax 1

Rigid 5 Phrenic nerve paralysis 1

- Stratos 1 Subcutanous emphysema 2

- Marlex 4 Tension pneumothorax 2

Pleural effusion 3

Combined with or without muscular flap

20 Wound dehiscence 3

No Seroma 1

Late effect N Radiotherapy No Radiotherapy

Secondary malignancies 7 7

Thyroid cancer 3 1 2

AML 2 2 1

Tongue cancer 1 1

Colorectal cancer 1 1

Thoracic bone hypoplasia 3 3 1

Myelopathy 1 1 1

Heart /valular disease 6 3 3

Lung function impairment 14

Restricitive 11 5 6

Obstructive 3 2 1

Late effects

95 patients INT-0091 & POG 9354“The 5-year event-free survival was 56% (SE 7%) for the chest wall lesions compared with 64% (SE 2.4%) for the entire cohort of patients.”

Conclusions

• In patients with close margins additional radiotherapy seems recommended (small number of pts w/o additional RT)

• No added value in patients with other risk factors such as large tumorvolume, poor histological response

• Surgery should be done by an experienced team in the technique that seems appropriate

Münster Team

36 patients , St. Judes“The 15-year estimates of EFS and survival were 56.3% ± 11.2% and 65.6% ± 10.7%, respectively.” Five year EFS app. 65%.