Dipresentasikan Oleh : dr. Ardean Bernandito Pembimbing : dr.

Kunta Setiaji SpB (K) Onk

Introduction
Treatment for desmoid tumours (deep fibromatoses) has been

modelled on that for low-grade soft tissue sarcomas.

Desmoids tumours are usually not life-threatening. Treatment efficacy is difficult to evaluate because of the

unpredictable behaviour of desmoids.

The management of desmoid tumours should be reassessed. Treatment should be different from that for sarcomas and other

cancers.

Introduction
The role of surgery in treating desmoids has therefore been

questioned.
Some authors now suggest a wait-and-see policy in selected

cases.
The aim of this research is to analyse the natural history of a

series of desmoid tumours identify clinical variables the prognostic factors better treatment outcomes.

Patients and methods

Long-term follow-up (median 123 months) of a series of 106

treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome.
Patients treated or followed-up at our centre for desmoid

tumours from 1976 - 2007 were included

The Union Internationale Contre le Cancer (UICC) residual

disease classification (R) was used to assess quality of surgery

Last follow-up was December 2007.

Patient and methods

Functional impairment was classified as absent, moderate

(compensated by treatment) or major (disability or pain not compensated by treatment).

Tumour growth patterns were analysed by calculating : The intervals between the date of first event or treatment

and date of first recurrence or progression ( time to first recurrence); The intervals between the first and the last tumoural events before stabilisation or regression ( time to progression); and The intervals between last progression and final follow-up ( stable period).

Patient characteristics

Treatment policy
During the 32-year period, various treatments were available.

Primary tumours without complementary treatment Surgery

was advised
When the tumours were deemed to be inoperable, a first-line

medical treatment was delivered (SERMs, especially tamoxifen, non-steroidal anti-inflammatory drugs (NSAIDs), inhibitors (antiCox2) in the last decade, imatinib mesylate in the last 3 years, interferon and chemotherapy). Whenever possible, surgery was performed secondarily.
In recurrent tumours, re-excision followed by radiotherapy was

proposed

Treatments
Number of patients : 106 patients 92 patiens ( 63 primary and 29 recurrent ) Excision 14 patiens ( 6 primary and 8 recurrent ) Biopsy /no

excision 23 patients ( 7 initially and 16 after recurence ) radiotherapy at a median dose of 50 Gy 11 patients ( 5 primary and 6 recurent ) chemotherapy 44 patients (20 primary and 22 recurrent ) various medical treatments

Outcomes
47

patients remained with some functional impairment ( 28 Moderate and 19 Major ) At a median follow-up of 123 months (range : 3 - 482 months) : 1 patient had died of treatment consequences (a postoperative vascular rupture after surgery for a recurrent mesenteric desmoid ) 10 had died of other causes (DOC ) 24 patients were alive with disease (AWD) 71 were alive without evidence of disease (NED)

Result : variabels influencing outcomes

Primary vs recurrent desmoids
The female/male ratio was 2.8/1 vs. 1.2/1 in primary vs recurrent

presentations a higher risk of recurrence in men than in women Completeness of surgery was better in primary than in recurrent disease After complete resection (R0 + R1 + Rx) local recurrence was 9/58 in primary disease and 14/25 in recurrent disease Functional impairment was less frequent after treatment for primary tumours than for recurrent tumours (32% vs. 68%). The proportion of surviving patients with no disease/remaining disease was higher in the primary than in the recurrent group

Result : Prefential Tumour Locations

Result : Gender
There were 71 women and 35 men, giving a sex ratio 2/1.
Women were younger than men (median age 39 vs 44

years), had more primary tumours (72% vs. 51%) and had tumours preponderantly located in the trunk walls and pelvic girdle Residual disease (R2 or biopsy only) after surgery in primary or recurrent disease occurred in 10/71 women and in 13/35 men.
Finally, 55 women remained without evidence of disease

vs 16 men.

Result : Tumor Growth patterns

Results : Type of resection

Results : Type of resection

Local recurrence (LR) after complete resection(R0 + R1 +

Rx) occurred in 23/83 patients. There was LR in 2/22 patients after resection R0 and in 19/56 patients after resection R1 ( p < 0.05 according the Chi2 test) This nearly fourfold difference in LR after resections R0 or R1 did not translate into a significant difference in outcome at final follow-up with 19/22 and 43/56 patients NED, respectively. No significant difference in overall survival was seen between patients having complete resection (83) or not (23) with 73 and 22 patients alive, respectively

Results : Number of surgeries

Results : Radiotherapy
7 patients underwent radiotherapy initially, including

3 after incomplete surgery 6 of them had a recurrence, 5 patients were NED, 2 AWD. Functional impairment 6 patients and was major in 3 of them. 16 patients had radiotherapy at recurrence 6 of them had a recurrence ( 12 patients were NED, 3 AWD and 1 patient died of other causes) . Functional impairment 12 patients and was major in 4 of them. In total, 12/23 patients a recurrence after radiotherapy and 18/ 23 functional impairments consecutive to multiple treatments including radiotherapy.

Results : FAP Linked desmoids

3 patients had a confirmed APC gene mutation indicating

an FAP-linked desmoid, 7 patients had unconfirmed suspicion of FAP and 8 a possible FAP. There were more mesenteric tumours in the first two groups (4/10) and a longer median period of tumour progression (48 months) than in the general population. Functional impairment occurred in 5/18 patients, similar to functional results in the general population. Major functional impairments in 4 patients all were due to repetitive treatments and their complication

Result :
Desmoids typically evolved actively over a median period of 3

years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17 months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy.

Decision-making acording to tumour presentation

Decisions should be based on the treatment benefit/risk ratio

and on tumour presentation.

Primary lower girdle and trunk wall tumours in women seem to

benefit most from surgery. The recommended surgey fullthickness trunk wall excision with or without mesh repair.

Primary upper girdle and trunk wall tumours wait and see

policy before deciding on treatment, When a tumour remains quiescent and asymptomatic surgery may be an option. Painful or rapidly growing tumour medical treatment, preferably including NSAIDs or antiCox2s

 Locally

advanced desmoids and in popliteal and mesenteric locations Surgery should be avoided Wait-and-see and standard medical treatments should be proposed first. Apart from recurrent abdominal wall tumours in women, where repeat surgery can be helpful, intensifying treatment with repeated surgery or radiotherapy appears deleterious in recurrent desmoids observation or medical treatment. Location is an essential factor when deciding on treatment options.

Conclusion :
The long-term follow-up in this series suggests that

desmoid tumours stabilise over time and can eventually regress in some cases, after an active phase of development lasting an average of 3 years. Surgery could re-activate the tumour process, hence prolonging the active phase. A wait-and-see policy is the best for evaluating the rapidity of growth. Treatment options should take into account tumour presentations with a view to relieving symptoms but not to eradicating the tumour at all costs. Treatment associations and new targeted therapies should be evaluated.

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