soft tissue sarcoma

Soft tissue sarcoma

Soft tissue Sarcomas Group together all malignant tumours developed at the expense of the extra-skeletal supportive connective tissue, such as adipose, muscular, vascular, fibrous, and peripheral nervous system tissues.

Soft tissue sarcomas are rare cancers, occurring in children as well as in adults. They can occur at any place in the body. The diagnosis and management of soft tissue sarcomas, as with visceral or bony sarcomas, is a matter for highly specialized teams from the outset of management.

Epidemiology
Soft tissue sarcomas are rare cancers. In France, their annual incidence is 3.6 for 100 000 inhabitants and they represent 1% of cancers. 4 000 new cases are diagnosed each year in France1.

Risk Factors
The only risk factors for known soft tissue sarcomas are exceptional genetic diseases and exposure to certain toxic substances.

The major genetic diseases likely to cause sarcomas are neurofibromatosis type I, Li-Fraumeni syndrome, Gardner syndrome and Werner syndrome.

Exposures to toxic substances likely to cause sarcomas are:

Accidental or medical irradiation.
Exposure to certain Industry2 products (chlorophenol, dioxin, vinyl chloride).
Exposure to certain viruses.
Diagnosis
The main symptom of soft tissue sarcoma is the more or less rapid onset of a mass or swelling that can develop throughout the body. The distribution of soft tissue sarcomas is suivante3:

Upper or lower limbs: 49%
Trunk: 40% (17% located in the thorax, 9% in the retroperitoneal tumor, 8% in the pelvis and 6% in the rest of the abdomen)
Head and neck: 11%
The diagnosis is very difficult given the scarcity of this type of cancer. It is very often after the removal of a mass of unknown nature, taken for a benign tumor, that the diagnosis is posed. The problem is that the initial quality of surgery is an essential element in the management of Sarcomas.

However, some elements evoke the malignant nature of the tumor: the depth in relation to the superficial fascia, the speed of growth and the size of the TUMEUR4. Pain is still a bit of a discriminating element. Ultrasound or X-ray may help to suspect diagnostic5 but remain insufficient in the initial balance sheet. The scanner and MRI seem of équivalent6 interest.

Initial support recommendations
In order to improve the management, the European Society of Medical Oncology (ESMO) has published, as of 2004, recommendations, regularly put in JOUR7. These international recommendations include:

The need for initial imaging adapted before any treatment i.e. CT in case of deep thoraco-abdominal localization or an MRI in case of thoraco-abdominal parietal localization, on limbs, head or neck.

The need for a large-caliber coaxial percutaneous biopsy (14G minimum) under radiological control prior to any treatment (surgical resection from the outset, in bulk and without tumor intrusion being only in the adult an alternative to the biopsy In the case of superficial lesions less than 3 cm).

The need for a proofreading anatomopathologic by an expert.

The need for a discussion in a multidisciplinary expert meeting the case of any patient with an unexplained mass of soft tissues more than 3 cm if it is superficial or whatever its size if it is deep or if it occurs In a child under the age of 18, before any treatment.

Pathology

The diagnosis is made either to the anatomopathologic analysis of the resection's operating room or to a biopsie8.

Sarcomas are malignant tumours developed at the expense of supporting tissues (mesenchymal tumor). The histological type obviously depends on the nature of the tissue from which the tumor developed. If sarcoma develops at the expense of a greasy tissue, it will be a liposarcoma, if it comes from a striated muscle it is a rhabdomyosarcoma.

The Anatomopathologic reference classification of soft tissue sarcomas is that of the World Health Organization (WHO) updated in 20129. It lists benign and malignant tumours of soft tissues in 12 large classes subdivided into 113 histological subtypes. This classification is based on optical microscopy arguments with a complement of immunohistochemical analysis. For some patients, no differentiation line is clearly identifiable and specific molecular anomalies found in half of the cases allowing an objective classification. Soft tissue sarcomas can now be categorized into five major molecular categories: translocation sarcomas, activator-mutation sarcomas, inhibitory mutation sarcomas, sarcomas with simple amplifications and sarcomas with complex genomic anomalies.

The anatomopathologic classification alone does not provide enough information to determine the treatments. Several systems for the degradation of tumor aggression have been proposed since the first embroidery work in 1939. The most accurate, the most reproducible and the most predictive is the rank of the National Federation of Cancer Control Centres (FNCLCC), described by Trojani in 1984.

The histological grade of the FNCLCC10

Differentiation

Score 1: Sarcoma resembling a normal tissue

Score 2: Sarcoma with a certain histological diagnosis

Score 3: Embryonic sarcomas, Synovialosarcomes, epithelioid sarcomas, light cell sarcomas, soft-parted sarcomas, undifferentiated sarcomas, and sarcomas for which the histological type is uncertain

mitotic Index

Score 1:0 at 9 mitoses for 10 fields

Score 2:10 at 19 mitoses for 10 fields

Score 3: More than 19 mitoses for 10 fields

Tumor necrosis

Score 1: No necrosis

Score 2: Less than 50% tumor necrosis

Score 3: More than 50% tumor necrosis

The ranks

Grade 1: Sum of scores: 2 to 3

Grade 2: Sum of scores: 4 to 5

Grade 3: Sum of scores: 6 to 8

Beyond the intrinsic characteristics of the tumor, a collection of information related to the extension of the disease allows to classify the disease according to the size and extension of the primitive tumor, lymph node invasion And the presence of metastasis.

Classification (AJCC/UICC 2010) 11

T (tumor)

T1: Tumor of 5 cm or less in its largest diameter

T1A: Superficial tumor

T1B: Deep tumor

T2A: Superficial tumor, which respects the superficial fascia

T2B: Deep tumor, which reaches the superficial fascia or extends beyond (retroperitoneal, mediastinal and pelvic sarcomas are considered to be profound tumors).

N (regional adenopathies)

N0: Absence of invaded ganglion

N1: Ganglionic intrusion

M (remote metastases)

M0: Absence of metastasis

M1: Remote Metastasis

Treatment

The treatment of soft tissue sarcomas is a highly specialized care, and this is possible even before the first biopsy sampling. Unfortunately, many sarcomas are unexpectedly discovered after resection and, despite a later specialized care, with a loss of chance in terms of healings and complications12.

Complex multimodal treatment is often necessary. It depends on many factors such as the histological tumor type, the presence of remote metastases, the location and tumor size, the progression rate, the age and general condition of the patient, and the previous and adapted treatments. The 3 treatments available are surgery, radiotherapy and chemotherapy.

The surgery

Adequate and complete surgical resection is the cornerstone of the curative treatment of non-metastatic soft tissue sarcomas. Its planning is complex and depends on many factors. Management in an expert centre decreases the risk of local relapse in limb soft tissue sarcomas and improves survival rates in nerve block soft tissue sarcomas. The deficiencies of an inappropriate initial surgery are never caught up by complementary treatment, with sometimes dramatic consequences such as death or amputation.

The rate of amputation in the management of primitive tumors is now less than 1% in the expert centres, in particular through advanced techniques such as isolated limb perfusion. In advanced forms, surgery can be performed with symptomatic sight. In France, the clinical Reference network for sarcomas-GIST-Desmoid (NetSarc [Archive]) guarantees a suitable surgical management within its 26 expert centres.

Radiation therapy

Radiotherapy can be administered in pre-operative or post-operative order to decrease the recidivism rate. It can also be administered exclusively when a local tumor is not accessible to surgery.

Chemotherapy

Pre-operative chemotherapy (known as neoadjuvant), based on anthracyclines, can be used for high grade tumours, extremities or trunk walls, to facilitate surgical action. Post-operative chemotherapy is not a standard.

Chemotherapy is the reference treatment for locally advanced or metastatic soft tissue sarcomas. The most active and first-line drugs in this area are doxorubicin, ifosfamide, and dacarbazine. They can be given as monotherapy exclusively or in combination.

Since 2007, Trabectidine is a drug available for patients with metastatic soft tissue sarcoma, after failure of doxorubicin or ifosfamide-based treatment, or in the case of contraindications to these two drugs. Depending on the histological subtype of sarcomas other medications can be administered, preferentially for leiomyosarcomas, such as paclitaxel for Angiosarcomas. Finally, pazopanib (multi-kinase inhibitor, targeted molecular therapeutics for VEGF receptors) also has a marketing authorisation (AMM) for the treatment of soft tissue sarcomas (excluding liposarcomes) from the 2nd Metastatic line.

Peri-operative chemotherapy at surgery is not a standard in the treatment of soft tissue sarcomas and should be discussed in an expert multidisciplinary consultation meeting in the field of SARCOMES13.

Certain soft tissue sarcomas carrying a specific mutation may undergo targeted therapy, in the image of gastrointestinal stromal tumours (GIST) whose C-kit activator mutation is the target of several inhibitors of Tyrosinekinases, with spectacular results and median survival over 7 years in MÉTASTATIQUE14 situation. Imatinib, sunitinib, and Regorafenib have a MDA in the treatment of GISTs in 1st, 2nd and 3rd metastatic line. New drugs are being developed in this area.

Prognosis

The most important prognostic factors in the treatment of soft tissue sarcomas are the quality of initial management, the metastatic or non-metastasized nature of the disease, the histological subtype of sarcoma, and the grade according to FNCLCC.

In metastatic conditions, the median of global survival oscillates between 3 and 27 months depending on these factors and the response to TRAITEMENTS15. At an earlier stage, proper surgery, properly combined with other therapeutic modalities (radiotherapy, chemotherapy) reduced the local recidivism rate to less than 20% in limb sarcomas and nerve block sarcomas. The rate of patients who will develop metastases at a distance after surgery is 21%, regardless of the tumoral16 type.

Networks and structuring of the support of soft tissue sarcomas in France

Rare cancers pose specific problems directly related to their rarity. Patients suffering from it suffer in addition to a long diagnostic wandering, an increased risk of mistaken diagnosis and therefore inadequate treatment. Few repositories are available. Access to certain complex treatments is restricted to only a few establishments. An organization of support at a national level helps to limit these problems. In the field of soft tissue sarcomas, France has two national networks labelled by the National Cancer Institute (CNIB) operating in parallel.

The reference network for the pathology of soft tissue sarcomas and Viscera (RRePS): It is a national grouping of expert pathologists whose objective is to systematize the anatomopathologic double reading of all rare malignant tumours of which All new cases of sarcoma developed in soft tissues or viscera (https://rreps.sarcomabcb.org/home.htm).

The clinical reference network for sarcomas-GIST-Desmoid (NetSarc [Archive]) is a group of physicians (oncologists, surgeons, radiologists and radiotherapists) who are responsible for the definition of management recommendations of patients, the organisation of a recourse activity, the coordination of research, the participation in an epidemiological watch, the structuring of a care chain and training. Its organisation is based on 3 national coordinating centres (Institut Bergonié in Bordeaux, Centre Léon Bérard in Lyon and Gustave Rousse in the City of France) in close collaboration with a network of 23 expert centres covering the national territory.