JOA Clinical Practice Guidelines for Soft-Tissue Tumors
In March 2022, the Japanese Orthopaedic Association (JOA) published clinical practice guidelines for the management of soft-tissue tumors. [36] Recommendations included the following.
Diagnosis and initial management
Genetic testing for pathologic diagnosis is recommended, subject to conditions.
For malignant soft-tissue tumors, computed tomography (CT) is suggested to explore distant metastases; positron emission tomography (PET)-CT is suggested both before and after treatment.
For soft-tissue tumors ≥5 cm, preoperative biopsy is suggested; for tumors ≤ 2 cm, excisional biopsy is permissible, subject to conditions.
Surgical treatment
For atypical lipomatous tumors of the extremity or the superficial location of the trunk, marginal excision is suggested over wide excision.
For malignant soft-tissue tumors, wide excision is suggested; for those with image-based findings of infiltration, a surgical margin that addresses the infiltration is suggested. Use of an ultrasonic scalpel to control bleeding is suggested.
Chemotherapy
For operable high-grade malignant soft-tissue tumors, perioperative adjuvant chemotherapy (ChT) is recommended, subject to conditions.
For infantile fibrosarcoma, perioperative ChT is recommended, subject to conditions.
For synovial sarcoma during childhood or adolescence, perioperative ChT is not recommended, subject to conditions.
Radiation therapy
For malignant soft-tissue tumors, perioperative adjuvant radiation therapy (RT) is suggested; neither preoperative nor postoperative irradiation can be considered superior to the other as adjuvant RT.
Treatment of advanced or difficult conditions
For malignant soft-tissue tumors with distant metastases, excision of the primary tumor and the metastatic tumors is suggested.
For locally recurring malignant soft-tissue tumors, wide excision of the tumor together with scarring from the previous surgery is suggested.
For unresectable advanced and/or recurrent malignant soft-tissue tumors, drug therapy is suggested; doxorubicin monotherapy is recommended as first-line treatment.
For unresectable malignant soft-tissue tumors, particle-beam RT is suggested.
For elderly patients with malignant soft-tissue tumors for which wide excision is indicated, avoidance of marginal excision plus RT is suggested.
ESMO/EURACAN/GENTURIS Clinical Practice Guidelines for Soft-Tissue and Visceral Sarcoma
In November 2021, guidelines for the management of soft-tissue and visceral sarcomas were published by the European Society for Medical Oncology (ESMO), the European Reference Network for Rare Adult Solid Cancers (EURACAN), and the European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS). [37] Recommendations included the following.
Local/locoregional disease
For all patients with an adult-type, localized soft-tissue sarcoma (STS), standard treatment is surgery (en-bloc wide excision with R0 margins) by a surgeon specifically trained in the treatment of STSs.
For high-grade (G2-3) lesions, standard treatment is wide excision with RT. The order of administration varies, but there is a shift toward preoperative RT, especially when preservation of a critical structure is a goal. RT can be omitted only after multidisciplinary discussion.
Options for limb-preserving surgery include (1) ChT, RT, or both; (2) isolated limb perfusion; and (3) regional hyperthermia combined with ChT.
For patients at high risk of death, adjuvant/neoadjuvant anthracycline-ifosfamide (AI) ChT for at least three cycles is an option; neoadjuvant ChT with regional hyperthermia is another individualized option.
Advanced disease
For metachronous (disease-free interval ≥1 y), resectable lung metastases without extrapulmonary disease, standard treatment is surgery if complete excision of all lesions is feasible.
Standard ChT is based on anthracyclines as first-line treatment. Multiagent ChT with adequate-dose AI or dacarbazine may be the treatment of choice, particularly in subtypes sensitive to ifosfamide or dacarbazine, when a tumor response is felt to be potentially advantageous and patient performance status is good. Gemcitabine-docetaxel is not generally recommended as first-line therapy.
Imatinib is standard medical therapy for dermatofibrosarcoma protuberans.
Neurotrophic tyrosine receptor kinase (NTRK) inhibitors are standard treatment for advanced NTRK-rearranged sarcomas; they can also be considered preoperatively, when cytoreduction can improve morbidity and function.
Trabectedin is an option for advanced STS in second and further lines of treatment.
Pazopanib is an option for nonadipogenic STS in second and further lines of treatment.
Eribulin is an option in patients with liposarcomas.
Dacarbazine-gemcitabine or gemcitabine-docetaxel is an option for doxorubicin-pretreated patients.
Special presentation and entities
For retroperitoneal sarcoma (RPS), standard treatment is surgical resection en bloc with adherent organs. For primary low- or intermediate-grade retroperitoneal liposarcoma, neoadjuvant RT has shown signs of efficacy. Intraoperative/postoperative RT is of no proven value in RPS. The role of adjuvant/neoadjuvant ChT has not been established.
For localized uterine leiomyosarcoma, endometrial stromal sarcoma, and undifferentiated endometrial sarcoma, standard local treatment is en-bloc total hysterectomy. Adjuvant RT is not recommended.
For newly diagnosed primary desmoid-type fibromatosis (DF) without life-threatening presentations, active surveillance is the first-line strategy. For progressing DF, the strategy must be individualized and may consist of continuation of active surveillance, systemic therapies, or local therapies.
NCCN Clinical Practice Guidelines for Soft-Tissue Sarcoma
In May 2018, the National Comprehensive Cancer Network (NCCN) released clinical practice guidelines for soft-tissue sarcoma (STS). [38]
STS of extremities, superficial trunk, or head and neck
Imaging studies should include cross-sectional imaging to provide details about tumor size and contiguity to nearby visceral structures and neurovascular landmarks. The panel recommends MRI with contrast, with or without CT with contrast. Other imaging studies such as CT angiography and plain radiography may be warranted in selected circumstances.
Surgery
The goal of surgery for patients with STS of extremities should be functional limb preservation, if possible, within the realm of an appropriate oncologic resection. Limb-sparing surgery is recommended for most patients with STS of extremities to achieve local tumor control with minimal morbidity. Amputation may improve local control in patients who might not be candidates for limb-sparing surgery and should be considered with patient preference, or if the gross total resection of the tumor is expected to render the limb nonfunctional.
When external-beam RT (EBRT) is used, sophisticated treatment planning with intensity-modulated RT (IMRT), tomotherapy, and/or proton therapy can be used to improve therapeutic effect. RT is not a substitute for definitive surgical resection with negative margins, and re-resection to negative margins is preferable.
The usual dose of preoperative RT is 50 Gy in 1.8-2.0 Gy per fraction. If the patient has not previously received RT, one could attempt to control microscopic residual disease with postoperative RT if re-resection is not feasible. If wide margins are obtained, postoperative RT may not be necessary. For patients treated with preoperative RT followed by surgery, the guidelines recommend consideration of observation in addition to postoperative RT boost for patients with positive margins.
The recommended EBRT boost doses are 16 to 18 Gy for microscopic residual disease and 20 to 26 Gy for macroscopic residual disease. Brachytherapy boosts should be delivered several days after surgery, through catheters placed at surgery, with doses of 16 to 26 Gy for low-dose-rate (LDR) brachytherapy and 14 to 24 Gy for high-dose-rate (HDR) brachytherapy, based on the margin status. Alternatively, IORT (10-12.5 Gy for microscopic residual disease and 15 Gy for gross residual disease) can be delivered immediately after resection to the area at risk, avoiding the uninvolved organs.
For patients who have not received preoperative RT, the postoperative choices include EBRT (50 Gy irrespective of surgical margins in 1.8–2.0 Gy per fraction), intraoperative RT (IORT; 10-16 Gy followed by 50 Gy EBRT), or brachytherapy. The guidelines recommend 45 Gy LDR brachytherapy or HDR equivalent for patients with negative margins. LDR brachytherapy (16-20 Gy) or HDR equivalent is recommended for patients with positive margins followed by EBRT. EBRT after IORT or brachytherapy is delivered to the target volume to a total dose of 50 Gy, after surgical healing is complete (3-8 weeks).
For patients treated with postoperative EBRT, the guidelines recommend an additional EBRT boost (unless prior IORT) to the original tumor bed based on the margin status (10-16 Gy for negative surgical margin; 16-18 Gy for microscopic residual disease; and 20-26 Gy for grossly positive margins). However, many institutions are no longer giving a boost after preoperative RT to patients who have widely negative margins, based on local control rates approaching 95% with preoperative RT at 50 Gy and negative margins. The panel also emphasizes that RT is not a substitute for suboptimal surgical resection, and re-resection is preferred for patients with positive surgical margins.
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CT-guided needle biopsy of high-grade soft tissue sarcoma arising in left hemipelvis. CT artifact from needle can be seen in upper right corner of image as needle enters lesion just anterior and medial to dome of left hip joint. Image courtesy of Howard A Chansky, MD.
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MRI is used to demonstrate involvement of critical structures by tumor. This recurrent, high-grade soft tissue sarcoma in posterior calf abuts tibial nerve and posterior tibial vessels. Extensive reactive zone surrounds structures. Patient was treated with below-knee amputation. Image courtesy of Howard A Chansky, MD.
Tables
Benign Soft-Tissue Tumors |
Characteristic Cytogenetic Events |
Frequency |
Benign schwannoma |
Monosomy 22 |
50% |
Desmoid tumor |
Trisomy 8 |
25% |
|
Deletion of 5q |
10% |
Lipoblastoma |
Rearrangement of 8q |
>25% |
Lipoma, solitary |
Rearrangement of bands 12q14-15 |
75% |
|
Rearrangement of 6p |
10% |
|
Deletion of 13q |
10% |
Uterine leiomyoma |
t(12;14)(q15;q24) |
20% |
|
Deletion of 7q |
15% |
|
Trisomy 12 |
10% |
Malignant Soft-Tissue Tumors |
Characteristic Cytogenetic Events |
Frequency |
Clear cell sarcoma |
t(12;22)(q13;q12) |
>75% |
Dermatofibrosarcoma protuberans |
Ring chromosome 17 |
>75% |
Ewing sarcoma |
t(11;22)(q24;q12) |
95% |
Extraskeletal myxoid chondrosarcoma |
t(9;22)(q31;q12) |
50% |
Liposarcoma, myxoid |
t(12;16)(q13;p11) |
75% |
Liposarcoma, well differentiated |
Ring chromosome 12 |
80% |
Alveolar rhabdomyosarcoma |
t(2;13)(q35;q14) |
80% |
Synovial sarcoma |
t(X;18) |
95% |
Stage Groupings |
Tumor Grade |
Primary Tumor |
Regional Lymph Node Involvement |
Distant Metastasis |
Stage IA |
GX, G1 |
T1 |
N0 |
M0 |
Stage IB |
GX, G1 |
T2 |
N0 |
M0 |
Stage IIA |
G2, G3 |
T1 |
N0 |
M0 |
Stage IIB |
G2 |
T2 |
N0 |
M0 |
Stage III |
G3 Any G |
T2 Any T |
N0 N1 |
M0 M0 |
Stage IV |
Any G | Any T | Any N | M1 |
