Diagnosis and Treatment of Soft Tissue Tumours: The Dutch Nationwide-Accepted Consensus

A reasonable number of soft tissue sarcomas arefound by chance. The reason is that general sur-geons are not familiar with these cancers and some-times do not realize that an `atypical lipoma’ or a`hernia of the muscle’ could be a soft tissue sar-coma. Whether these `whoops’ operations badlyin¯ uence the prognosis is uncertain, but it is certainthat de® nitive surgery can be very complex withincreased morbidity and frequently needed adjuvantradiotherapy.With this knowledge in mind, the Dutch Cooper-ative Group for Soft Tissue Tumours, founded in1991, recognized this important issue. The ® rstactivity involved organizing a nation-based consen-sus meeting. To achieve this goal all cancer centres(2), universities (6) and comprehensive cancer cen-tres (9) were asked to send representative partici-pants to prepare a draft report. On 29th October1993, after two-and-a-half-years and nine meetings,the text was open for discussion. Thereafter thede® nitive text was sent to all surgeons and to spe-cialists involved in soft tissue sarcoma treatment(ISBN 90-6910-164-5). A shorter version was pub-lished in the national general medical journal(


Introduction
A reasonable num ber of soft tissue sarcom as are found by chance. The reason is that general surgeons are not fam iliar w ith these cancers and som etimes do not realize that an`atypical lipom a' or à hernia of the m uscle' could be a soft tissue sarcom a. W hether these`w hoops' operations badly in¯uence the prognosis is uncertain, but it is certain that de® nitive surgery can be very com plex with increased m orbidity and frequently needed adjuvant radiotherapy.
W ith this knowledge in m ind, the D utch Cooperative Group for Soft Tissue T um ours, founded in 1991, recognized this im portant issue. T he ® rst activity involved organizing a nation-b ased consensus m eeting. T o achieve this goal all cancer centres (2), universities (6) and comprehensive cancer centres (9) were asked to send representative participants to prepare a draft report. O n 29th October 1993, after tw o-and-a-half-years and nine m eetings, the text was open for discussion. Thereafter the de® nitive text w as sent to all surgeons and to specialists involved in soft tissue sarcom a treatm ent . A shorter version was published in the national general m edical journal (N ed.Tijdsch.G eneesk 1995;139: 833± 7).
The original text is now published in this journal. T he intention is that this text, based on 28 m ain questions, can be helpful to those people who are also preparing a regional or national consensus. Alternatively this text could be encouraging those doctors with a special interest in soft tissue sarcom a to prepare such a consensus.

B asic questions
1: W hat order in diagnostics should be followed in patients presenting w ith a suspicious soft tissue tum our? 2: W hat conditions can be m ade for the preparation of pathology specimens and how to report the results? 3: W hat are the therapeutic possibilities of surgery, radiotherapy and chemotherapy in the treatm ent of prim ary soft tissue sarcom a?

D e® nition and classi® cation
1. Soft tissue sarcom as form a heterogeneous group of uncom mon tum ours with histopathological aspects of connective, muscle, fatty tissue or peripheral nerve tissue Soft tissue sarcom as include non-epithelial tum ours, excluding tum ours of the haematopoietic system , lym ph nodes, skeleton and central nervous system . H owever, tumours of the peripheral nerve system are classi® ed as soft tissue tum ours. C ontrary to other custom ary classi® cations, also non-epithelial tum ours of the internal organs such as the stom ach and uterus are discussed in this consensus text, since their diagnostics and treatm ent do not virtually differ from those occurring in other sites. Paediatric tum ours (age , 16) are disregarded because of their speci® c problem s.

C lassi® cation of soft tissue sarcom as according to Enzinger and W eiss 1 ' is currently most common
Prognosis of soft tissue sarcom as is determ ined by grade of m alignancy and histological typing. Over the years m any classi® cations have been proposed. C urrently, the classi® cation according to Enzinger and W eiss is used m ost, com prising in short: ® brosarcom a derm ato® brosarcom a protuberans The long-term cancer registration by the IKZ (C om prehensive Cancer C entre for South Holland) in Eindhoven show s no increase in the incidence of soft tissue sarcom as; however, it does show a signi® cant increase in the num ber of sm all tum ours and a decrease in the percentage of larger tum ours of unknown size.

Recognize an uncom mon tum ou r!
In a patient suspected of having a soft tissue tum our, a sarcoma should be assum ed until proof to the contrary; assessment of com plaints and growth speed and of local tum our growth, and regional and distant m etastases is necessary, including accurate assessm ent of tum our size (in cm) and involvem ent of surrounding structures. A fast-g rowing tum our (i.e. in som e weeks to m onths) or a tumour situated under the deep fascia should suggest a strong suspicion of a m alignancy. A solid consistency and an unusual localization should also alarm the clinician.
In case of the slightest suspicion of a m alignancy, surgical exploration of a soft tissue tum our should adhere to a num ber of rules. T he prognosis of soft tissue sarcom as at presentation depends on two factors only: local tum our extension (local and/or distant m etastasis), and the biological behaviour of the tum our, expressed as`grade of m alignancy' . T he latter prognostic factor cannot be in¯uenced; however, previous inexperienced m anipulation can indeed unfavo urably in¯uence the ® rst, hence complicating de® nitive treatm ent. Contam ination of nearby muscle groups or com partm ents by invasive exam ination necessitates involvem ent in the de® nitive treatment. Therefore, it is highly recomm ended that diagnostic im aging (for localization and staging) is perform ed prior to invasive diagnostics and particularly prior to biopsy.

D iagnostic imaging before every invasive examination
Im aging techniques that can be used are: conventional X -rays, ultrasound (us), M RI and/or C T. Bone scintigraphy and arteriography are not indicated, except in special situations that cannot be included in a protocol. O nly in exceptional cases can a probability diagnosis based on diagnostic im aging be m ade. U sually diagnostics start w ith conventional X -rays that can give an im pression of the extension of the tum our and of skeletal involvem ent. It can often differentiate the diagnosis of a prim ary soft tissue process betw een a primary osteosarcom a or a soft tissue tum our with skeletal in® ltration (e.g. in synovial sarcom a). Vascular calci® cations may indicate haem angioma. Ultrasound is a low-cost, fast and non-invasive m ethod to get a ® rst im pression of presence, localization and extension of a clinically diagnosed tum our. Sometimes the nature of the tum our can be further de® ned.
6. M RI is the most reliable method to assess localization and size of a soft tissue tum our, as well as involvement in several anatom ical compartm ents M agnetic resonance im aging (M RI) is a m ost reliable m ethod to de® ne exactly the localization and m acroscopic extension of the tum our. N ot only tum our size, but also involvem ent in several anatom ical com partm ents (m uscle groups, cortex, bone m arrow, neurovascular bundle, joint) can be accurately assessed. It is possib le to identify the tum our, the pseudocapsule and the reactive zone. Since tru-cut and surgical (open) biopsies cause reactive changes that are dif® cult to differentiate from tumour tissue by M RI. M RI should be perform ed prior to these invasive procedures. At least two T 1 and T2 w eighed perpendicular M RIs (e.g. in the transversal and sagittal directions) should be m ade.
CT is less reliable than M RI. C T is preferred in instances of an intra-abdom inal tum our, such as leiom yosarcom a of the stomach. In tum ours originating from m uscle and connective tissue, etc. CT is only indicated when M RI cannot be realized because of com pelling practical or patient-related reasons (claustrophobia, pacem aker, eye lens im plant).
In a num ber of cases, particularly benign diseases, a speci® c diagnosis can be m ade by M RI.

Since soft tissue sarcoma in general metastasizes prim arily to the lung, screening for lung metastases is a routine procedure in all patients with a soft tissue sarcoma
F or lung screening, conventional X-rays and CTthorax are used. Tim ing of X-thorax is not critical. It can be perform ed at the start of analysis (in case of a strong clinical suspicion), or alternatively after histologically diagnosing a soft tissue tum our. CT is indicated w hen histology shows a m alignant tum our, whereas X-thorax does not indicate the presence of lung m etastases.

Cytology is valuable in assessing a recurrent soft tissue tum our
C ytology is not the ® rst choice to diagnose a soft tissue tum our. W hen differentiation of a prim ary tum our betw een a soft tissue tum our, an epithelial tum our, a m elanom a or a lymphom a is suf® cient, cytology can generally be conclusive. In tumours surgically dif® cult to access, an ultrasound-guided cytological biopsy can be taken. T he biopsy site should be m arked. C ytological exam ination by a ® ne needle biopsy can be useful to assess recurrence or m etastasis of a known sarcoma. A tru-cut biopsy is indicated in tumours for which a cytological biopsy is inconclusive. For tissue obtained by tru-cut biopsy only a lim ited histopathological classi® cation and/or staging can be assesse d. By perform ing a tru-cut biopsy, a tissue cylinder is obtained directly from the tum our periphery, hence avoiding noninvolved m uscle groups. Specim ens obtained from the tum our centre often yield necrosis. The biopsy site is sutured; the suture rem ains in situ until de® nitive treatm ent.

A lso an incisional biopsy is aimed at a combined treatment of surgery and radiotherapy without unn ecessary mutilation
Except in sm all super® cial tumours the aim of surgical exploration should be kept in m ind: to obtain histopathological m aterial and not to be a de® nitive treatment for soft tissue sarcom a.
In perform ing an incisional biopsy, the follow ing guidelines should be followed: · avoid contam ination of other m uscles/m uscle groups or com partm ents as a result of in® ltration anaesthesia, tum our m anipulation, haem atoma and infection; · perform the biopsy by a longitudinal incision; · do not underm ine skin m argins; · take the biopsy from the tum our periphery (including the pseudo-capsule); · wash the wound with cytolytic¯uid (sterile water, D akin-¯uid); · perform accurate haemostasis; · when using a drain, do not release this through a separate drain hole; · use sterile instrum ents when closing the wound; · send fresh specim ens to pathology (eventually frozen sections, re:`representative m aterial?' ).

Send fresh soft tissue tum our specimens to pathology, indicating margins, grow th speed and previous treatment
In requesting a pathology review, the follow ing should be speci® cally recorded: · tum our localization (super® cial or deep) and in case of a biopsy, biopsy specimen or partial resection, and tumour sizes; · recurrence: yes or no; · previous treatment (if applicable).
T he resected tum our should be intact and fresh when handed to the pathologist. Surgical adequacy can then be judged best and before total ® xation tum our fragm ents can be rem oved for freezing purposes and separate ® xation for E M and other tests.
11. Pathology review is aimed at assessing a de® nitive, classifying diagn osis and at determining the extension of the soft tissue tum our, the extent of surgical adequacy in case of a malignancy, and prognostic factors in¯uencing treatment Pathology reviews and reports should include the following: · surgical nature (incisional biopsy, excisional biopsy, radical resection, etc.); · tum our sizes, preferably in three dim ensions, but m inim ally m entioning the largest diam eter; · surrounding tissues and involvem ent with the tum our (in® ltration: yes or no): skin, fascia, m uscle, fatty tissue, nerve, bone; · relation betw een the tum our and the resection lines, particularly the possible presence of m acroscopic disease in this area. M arks app lied by the surgeon to reconstruct the original position of the tumour in the body should be used here. Resection lines should be m arked, e.g. with Indian ink; · thickness of the cuff of normal tissue surrounding the tumour, with special attention for those sites indicated as non-radical resections (because of technical dif® culty). M uscle retraction can hinder judgement of treatm ent adequacy. It is very useful and som etimes necessary that the pathologist examines the m acroscopic specimen together with the surgeon. T he conclusions of this joint examination should be recorded in writing (schem atic drawing!); · tum our consistency and shape (clear m argins: yes or no; nodular), as w ell as its aspect in diam eter, especially colour, and presence and extension of m yxoid parts and necrosis; · non-radical resections based on m acroscopic observations and the m arks app lied by the surgeon. Fractions of these areas should be prepared as well and should be ® led such, preferably based on a schem atic drawing, that their origin can be reconstructed. F or m icroscopic diagnosis of the nature of the tum our a suf® cient num ber of tissue specim ens should be rem oved as w ell. As a guideline two fractions will be suf® cient for a tum our with m axim um diam eter up to 5 cm ; a tum our . 5 cm will need the num ber of fractions corresponding to half of the largest diam eter in centimetres. It is not particularly useful to prepare fractions from com pletely necrotic areas. H ow ever, necrosis should be m icroscopically assessed. Particularly, fractions should be prepared from Ð m acroscopically describedÐ areas with a deviating asp ect; · grading; · the conclusion should m inim ally include the following: (i) surgical nature (ii) localization (iii) previous treatment (if applicable) (iv) histological typing and grade (v) tumour size(s) (vi) data on treatment adequacy 12. Classi® cation in grades of malignancy and classifying diagnosis are equally important for soft tissue sarcoma prognosis T o de® ne prognostic correlations, grading and histological typing of soft tissue sarcom a are equally im portant. M ost publications appear to acknowledge prognostic value to histological typing, but in general this value disappe ars when in a m ultivariate analysis histological typing is tested as a variab le next to grading.
In this context it is striking that a generally accepted system exists for histologically typing these sarcom as, but not (as yet) for grading these m alignancies. From recent analysis it appears time and again that by m ultivariate analysis the number of m itoses, and the presence and am ount of necrosis are decisive for prognosis. T his also appears from a recently published EO RT C study on w hich the following classi® cation is based: · grade 1: , 4 m itoses per 2 m m 2 · grade 2: 4± 25 m itoses per 2 mm 2 · grade 3: . 25 m itoses per 2 m m 2 In tum ours that can locally be treated adequately, a 5-year survival can be expected for over 90% of grade 1 tumours, 6 70% for grade 2 tum ours and 6 45% for grade 3 tum ours. W e m ay assu m e that this system includes m alignant ® brous histiocytom a (M FH ), liposarcom a, leiom yosarcom a, ® brosarcom a, m alignant Schwannom a, and synovial sarcom a, together com prising . 86% of diagnosed sarcom as. In other sarcom as the grade of m alignancy should be estim ated based on histological typing. T his grading system excludes sarcom as of the internal organs. In the study on which this system is based, the presence or absence of necrosis m erely renders the possibility to divide grade/score 3 tum ours into two additional grades. In practice, no need appears to do this. N B: the number of m itoses cannot sim ply be used to differentiate between a benign (i.e. reactive) and a m alignant m esenchym al proliferation. Benign m esenchym al proliferations exist with a large number of m itoses.

Aggressive ® brom atosis and similar tum ours are treated as locally malign ant
Apart from sarcom as and benign tumours with only lim ited growth potential, a group of soft tissue tum ours can be distinguished with unlim ited growth potential, but without a risk for metastasis. T hese tum ours can be classi® ed as`locally m alignant' . Recurrence is due after inadequate local treatment. Since surgical treatment of a recurrence generally is m ore extensive and m ore m utilating, adequate local treatment is indicated ® rst.
For another group of tumours, histopathology cannot predict their clinical behaviour (such as probability of recurrence). This group is term ed tum ours of intermediate m alignancy' (according to Enzinger and W eiss). In these tumours the extent of surgery depends on considering both the disadvantages of locally adequate treatment and the possibility of adequately treating a recurrence.

Soft tissue sarcoma requires multidisciplinary treatment from the start. The team are acquainted with each other' s diagnostic and therapeutic possibilities
Surgery is the ® rst line of treatment for soft tissue tum ours. Conditions for proper surgical treatm ent are: · pre-operative staging (cTN M ); · pre-operative review with the consultant representing the hospital' s O ncology W orking Party (Com prehensive Cancer Centre); · preferably pre-operative assessm ent by a radiation oncologist; · preferably one adequate operation; · m arking of areas at risk and narrow m argins with titanium staples.

D irect prim ary excision only indicated for small super® cial soft tissue tum ours
Primary resection (excisional biopsy) should only be considered for very sm all ( , 3 cm) super® cial tum ours, for which surgery will not render functional loss. As in resection, also for these prim ary resections, wide m argins are required.
Radical resection is resection of the tum our en bloc including a cuff of norm al tissue of at least 2 cm. F or tum ours in® ltrating m uscular com partm ents com partm ental resection m ay be considered.
If radical resection implies sacri® cing the neurovascular bundle or bone, causing severe m orbidity, a com bined treatm ent of surgery and radiotherapy is preferred.
For retroperitoneal or head and neck lesions, radical resection w ill often be im possible for anatom ical reasons. A less radical resection and post-operative radiation will be the treatment of choice.

Surgical reports should completely describe all conclusions, anatom ical structures and areas at risk
T he surgical report should include the following: · operation, appro ach and vital structures; · a schem atic drawing of the resection, particularly indicating m argins and anatom ical structures; · areas at risk (narrow m argins); · haem oclips used as landm arks; · size of the tum our in centimetres; · reconstruction.

Inadequate surgery is preferably follow ed by reoperation, after consulting the Oncology Group
In case of inadequate resection, when clearance m argins show evidence of residual m acroscopic tum our (according to the surgical report/pathology conclusions), re-resection of the entire contam inated area should be performed if possible. If reresection is not possible, radiotherapy should be app lied.

Retroperitoneal sarcom a should be treated by a properly prepared radical resection, if possible follow ed by radiation to the tum our bed
Because of anatom ical reasons, radical resection som etimes im plies resection of surrounding structures as well, such as the colon, ureter, iliacal vessels, etc., with optional reconstruction. Preoperative review with the specialists in charge is strongly recom m ended. M argins often appear to be inadequate still. Therefore, treatment principally requires a com bined planning of surgery and radiotherapy.

After surgical treatment of retroperitonea l sarcom a the use of the om entum or a spacer should be considered to prevent radiation damage
T o apply a suf® cient radiation dose to the original tum our volum e, precautions should be taken to prevent irreversible sm all bowel radiation dam age, a long-term com plication. O ne of these precautions is retraction of the small bowel from the surgical area.

Radiotherapy is indicated after planned non-ra dical resection, when the resection margin is , 1 cm after ® xation, or after incom plete resection of the original surgical area
T he development of m egavoltage radiation equipm ent and m odern radiation techniques enables accurate radiation, hence sparing surrounding norm al tissues. In patients with a limited tum our process, post-operative adjuvant radiotherapy appears to reduce the risk of a local recurrence.
In this com bined treatm ent radiotherapy can be perform ed pre-operatively or post-operatively. Postoperative radiotherapy has been applied m ost. T he advantages of post-operative radiation over preoperative radiation are: · no delay of surgery; · no increased risk of post-op erative com plications; · optimal inform ation on the extent, m argins and histological aspects of the tum our, to determine the treatment volum e; · the radiation oncologist can inform him self of the exact tum our extent during surgery.
Post-operative radiotherapy is indicated for all G 3 tum ours and recurrences, even after radical surgery. In all other cases post-operative radiotherapy is indicated by the result of surgery: · after non-radical surgery, when reoperation is im possible or too m utilating; · after reoperation because of non-radical surgery, when the entire surgical area has not been rem oved; · after m arginal radical surgery (m argin , 2 cm [fresh specim en] or , 1 cm [after ® xation]); · in case of tum our contam ination (`spill' ) during surgery.
T he target area for post-operative radiotherapy includes the entire original tumour volum e, possible m icroscopic extension and areas possibly contam inated during resection (drain, haem atom a). To determ ine the target area a complete description of the surgical procedure and the pathology report, as w ell as pre-operative C T and/or M RI scans should be availab le to the radiation oncologist. Radiation m argins depend on tumour localization and extent.
Guidelines for determ ining the target area are: · In intracom partm ental tumours, the related com partm ent is considered the target area.
· M argins for extracompartm ental high-grade tumours (grades 2 and 3) are 7± 10 cm longitudinally from the original tum our, taking natural m argins into account. For low-grade tumours the m argin can be 5 cm . M argins should be wide, particularly in the direction of vessels and nerves and of fasc ia and m uscle ® bers. T ransversely, a m argin of at least 2 cm can be chosen, again taking into account natural m argins of anatom ical structures.
· In subcutaneous tum ours not in® ltrating the fasc ia and not situated near vessels and nerves, a margin of 5 cm around the original tumour w ill be suf® cient.
· For the booster dose the target area is the original tum our bed with a m argin of 2 cm. After a non-radical resection the highest dose is app lied to an area that is preferably m arked during surgery. T he m argin is determined by the treatment volum e, the total dose, and norm al tissue tolerance.
Radiation is generally perform ed using m ultiple m egavoltage photon beam s. A C T-scan in radiation position can be used to determine the treatm ent plan and to calculate the dose distribution. In case of radiotherapy of an extremity, beam directions should be chosen sparin g non-affe cted m uscle compartm ents and bone as m uch as possible. T he interosseous m embrane of the distal limb can serve as the m argin between the irradiated and the nonirradiated part of the extremity. Radiotherapy to the entire lim b periphery should be avoided as m uch as possible to preserve lym ph drainage. Haem oclips placed in the bottom and at the m argins of the surgical area can be useful to determ ine the treatm ent volum e. Patient positioning reproducibility m ay bene® t from proper patient ® xation in radiation position. T o this end, several m ethods are availab le. Radiotherapy to retroperitoneal or abdom inal sites m ay be dif® cult due to surrounding radiosensitive organs such as kidneys and bowel. Placing a spacer (either a tissue expander ® lled with saline or a silicone breast prosthesis) or a pedicled om entoplasty between the treatment volum e and these organs enables app lication of a higher radiation dosage.
IC RU dose recom m endations are 50 G y in 25 fractions in 5 weeks to the above treatment volum e, plus 10 Gy in 5 fractions applied similarly to the original tum our volum e, including the above-m entioned m argins.

Post-operative interstitial radiotherapy enables more accurate determination of the booster area and sparing of healthy tissues
W hen surgery is perform ed in a hospital with brachytherapy facilities, the radiation oncologist can, im m ediately following excision, insert loops in the original tum our area for post-operative interstitial application of an iridium booster dose using an afterloading system . T his approach requires intensive consultation between the surgeon and the radiation oncologist before the start of treatm ent. Preferably, the patient is also assesse d by the radiation oncologist before treatment. T echnique and dose of interstitial radiotherapy are presently studied.

D uring radiotherapy to an extremity and at least during 1 year thereafter physiotherapy is prescribed to prevent contractures
After high-dose radiotherapy som e ® brosis and skin discolouration is often seen. Severe com plications after radiotherapy m ay be: function im pairm ent due to ® brosis of m uscles and subcutaneous tissues; joint ankylosis; lym ph oedema; and vascular insuf® ciency due to vascular dam age. Also bone fractures due to irradiation are seen until long after treatment.
Accurate assessm ent of the radiation technique with sparin g of as m uch healthy tissue as possib le decreases the risk of these complications. After a com bined treatment of surgery and radiotherapy, long-term physiotherapy is highly important to preserve extremity function. T hese exercises, aimed at keeping m uscles and tendons at full length, should be done under the guidance of a physiotherapist and preferably after consulting a rehabilitation physician. T hey should be started prior to and during radiotherapy and be m aintained for 1± 2 years after treatm ent.

C hemotherapy for primary and metastasized soft tissue sarcom a is experimentally administered in trials
O nly three cytostatic drugs have proved to be effective in soft tissue sarcom a (adriam ycin, ifosfam ide and, to a lesser extent, D TIC). D ose± effect relations, com bined treatment schedules and the addition of growth factors are currently under investigation. System ic therapy is applied in trials only. Adjuvant chemotherapy in high-risk patients is not indicated as yet. The value of chemotherapy prior to radical surgery has not been assessed yet, nor when adm inistered intra-arterially in extremity lesions. Induction (neo-adju vant) chem otherapy is adm inistered in trials only.

Prior to resection of lung metastases a num ber of term s have to be met: (i) the primary tum our should be under control; (ii) exclusion of extrapulm onary metastases; (iii) no contra indications for pulm onary surgery
Soft tissue sarcom a usually m etastasizes prim arily to the lungs. Therefore, all patients w ith soft tissue sarcom a should be exam ined for lung m etastases. Since diagnosing lung m etastases is clinically relevant, chest X -ray is perform ed ® rst. A negative chest X -ray does not rule out lung m etastases and a C T-thorax should follow. Radical surgery of lung m etastases can accom plish cure or long-term complete rem ission. Lung function is extremely im portant in patients who had previous chem otherapy. T here should be no contraindications for pulm onary surgery.
Adequate patient selection can render a 5-year survival of 30± 40%. O ne factor is of utmost im portance: radical m etastectomy should be feasible. Prognosis after radical m etastectomy in grade 3 tumours seem s less favou rable than in grade 1 and grade 2 tum ours.
The choice betw een a sternotomy and a unilateral or bilateral thoracotom y strongly depends on localization and the num ber of m etastases.

E mbryonal soft tissue sarcomas in adults are treated as paediatric tum ours
Although the available separate studies do not show this num erically, analysis of a large num ber of publications using chemotherapy (doxorubicin 1 D TIC, or this com bination plus supplem entary endoxan and vincristin) shows no difference in response to chem otherapy in several histological types of soft tissue sarcom a. Em bryonal rhabdom yosarcoma in adults is an exception. The clinical behaviour of this subtype is som ewhat different: rather fast-g row ing, extensive haem atogenic m etastasis and a striking sensitivity to chem otherapy. W hereas chem otherapy for other histological subtypes renders response rates of 20± 40% , the response rates of embryonal rhabdom yosarcoma to chem otherapy is 80± 90% . In general, drugs such as vincristine and actinomycin have little effect on soft tissue sarcoma. H ow ever, these drugs do appear to be effective in embryonal rhabdom yosarcoma. Based on these data, it is recomm ended to treat em bryonal rhabdomyosarcom a analogous to paediatric tumours w ith chem otherapy, such as Ewing' s sarcom a and nephroblastom a.
26. If resection of a soft tissue sarcoma of the limb leads to amputation or severe morbidity, an isolated regional perfusion using TN F-a should be considered Regional isolated perfusion has been used as an alternative to am putation. This m ethod enables regional adm inistration of high doses of chem otherapy in soft tissue sarcom a of the lim bs without the risk of (lethal) toxicity. H owever, despite the use of different regim es the results are disappo inting regarding the choice of cytostatics as w ell as the app lication of hypertherm ia.
Tum our N ecrosis Factor-a (TN F-a ) is a cytokine with an acute and dram atic anti-tum our effect in anim al tumour m odels. Effective doses in anim als are m any times ( . 20 3 ) higher than the m axim um allowed dose in hum ans. System ic adm inistration of T N F-a in hum ans causes severe toxicity without reaching a signi® cant anti-tumour effect. Effective T N F-a levels can be reached in isolated regional perfusion of the lim bs.
The anti-tumour effect of T N F-a is probably based predom inantly on selective total destruction of tumour vessels. T his is illustrated by pre-and post-p erfusion angiographies, as well as by histopathological ® ndings. M elfalan has a strongly synergistic effect in com bination with T N F-a . T he tum ours usually react with acute softening, as an expression of m assive necrosis, follow ed by tum our regression, hence turning the tum our m obile and resectable.
In a m ulti-centre T N F study in Rotterdam (DD H CC), G roningen (University H ospital), Am sterdam (Antoni van Leeuwenhoek Hospital) and Lausanne (Centre Pluriform e d' Oncologie) patients with an irresectable soft tissue sarcom a of the lim b are treated.
An anatom ical or functional am putation can be prevented in 6 90% of the patients by perform ing an isolated perfusion, followed by a generally m inor resection of tumour rem nants, instead of am pu-tation or a m utilating com bination of m ajor resection and radiotherapy. Response percentages of soft tissue tum ours to T N F perfusion are im pressive: C R 44% , PR 53% and SD 3% . However, it has not (yet) rendered a bene® t in survival.

A ll patients with soft tissue tum ours are preferably treated in trials
Soft tissue tumours are uncomm on tumours with a large scale in histology and grading. Adequate local treatment reduces the risk of local recurrence to 10± 20%; however, 40% of patients with soft tissue tum ours w ill develop distant m etastases.
In order to get m ore insight in all tumours and to im prove the prognosis of patients with soft tissue tum ours, it is essential to participate in trials.

Rarity and diversity of soft tissue sarcom a and the uncertainties and complexity of the treatment argue for a national approach in documenting diagnostics, staging and treatment
Soft tissue sarcoma rarity is show n by the fact that the average surgeon and a pathologist see a few new cases only once every 2 years and once a year, respectively. Moreover, there is a diversity in localizations (for the surgeon) and in histological typing (for the pathologist).
N ational docum entation in this ® eld gives a unique opportunity to acquire a better insight into the behaviour, diagnostics and treatment of these tum ours. Large-scale studies have until now exclusively been perform ed in centres m eeting a selection of patients. It is of utmost im portance to start a larger databank than the current one used for cancer registration. Before ® ling the data, the m ain questions related to these tumours should be considered. once per year After 10-year diseasefree survival:

Follow-up
stop follow-up

C ontents of follow-up
Alw ays: historyÐ general and speci® c physical exam ination Every 6 m onths during the ® rst 2 years: C XR/yearly thereafter W hen indicated: C T-scan or M RI Indications for CT or M RI m ay be: · determining post-operative starting point in tum our areas dif® cult to exam ine, e.g.
(i) sarcom as of the head and neck (ii) retroperitoneal sarcom as (iii) sarcom as of pelvis and hip · follow-up of local control after doubtful radical surgery · in case of complaints or clinical suspicion.

A ppendix 2
TN M classi® cation (U ICC 1992, adults) T he TN M (Tum our, N ode, M etastasis) classi® cation is exclusively used in adults (m inim al age 16 years) and for histologically proven sarcom as.
M inim ally required procedures for assessing the T category: physical exam ination and im aging (M RI or C T-scan and/or ultrasound) of the primary tumour: