local control in ewing sarcoma of the chest wall benedetta bedetti andreas ranft heribert jürgens...

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%.