Soft Tissue Sarcoma (incl. Liposarcoma) — treatment notes

18Soft Tissue Sarcoma (incl. Liposarcoma)

Snapshot. Rare malignant tumours of mesenchymal (connective) tissue — dozens of subtypes; extremity (thigh) is the commonest site. Grade (differentiation/mitoses/necrosis), not size alone, drives behaviour. Wide surgical excision with negative (R0) margins is the curative backbone; treatment beyond that is histology-driven — this is not one disease. Most metastasise to the LUNG — except myxoid liposarcoma, which spreads to EXTRApulmonary fat/bone (spine, retroperitoneum). Refer to a sarcoma centre — outcomes are volume/expertise-dependent; ideally before the first biopsy.

Workup

MRI of the primary (local extent) → core-needle biopsy FIRST — never shell out a mass blindly; plan the tract for later en-bloc resection · CT chest (lung = main met site; add spine/whole-body MRI if myxoid liposarcoma suspected — it doesn't go to lung) · grade by FNCLCC · subtype genetics: liposarcoma — MDM2/CDK4 amplification (well-/de-differentiated); myxoid liposarcoma — FUS-DDIT3 t(12;16), graded by round-cell % · germline: sarcoma is a core LI-FRAUMENI (TP53) tumour — young age, multiple primaries, or a Li-Fraumeni-spectrum family history (premenopausal breast, brain, adrenocortical, leukaemia) → germline TP53 testing + genetic counselling; ⚠ Li-Fraumeni patients are radiosensitive → minimise radiotherapy (radiation-induced second malignancy).

Treatment by setting

Setting	Treatment
LOCALISED most subtypes, resectable	Wide excision, R0 margins = mainstay Radiotherapy (pre- or post-op) for >5 cm / deep / high-grade to secure local control Adjuvant chemo (doxorubicin ± ifosfamide) is SELECTIVE high-grade / large only, modest benefit
WELL-DIFFERENTIATED LIPOSARCOMA atypical lipomatous tumour; extremity/trunk	Wide excision alone — essentially non-metastasising local recurrence is the real risk (drives re-excision), not systemic disease · no adjuvant chemo
RETROPERITONEAL mostly well-diff / dedifferentiated liposarcoma; local disease	Complete en-bloc (often multivisceral) resection at a specialist sarcoma centre the dominant prognostic factor Local recurrence — not distant spread — defines it → RE-RESECTION is the mainstay at each recurrence ⚠ Radiotherapy is controversial (STRASS) preop RT did not improve abdominal recurrence-free survival overall; a liposarcoma-subgroup / pooled signal supports it only in well-differentiated and G1–2 dedifferentiated liposarcoma, not G3 Systemic doxorubicin-based therapy is modest reserved for unresectable / metastatic disease
MYXOID LIPOSARCOMA FUS-DDIT3; low round-cell % = low-grade	Radiosensitive AND chemosensitive trabectedin particularly active Low-grade + R0 → surveillance only, no chemo ⚠ Surveillance must add spine / whole-body MRI chest CT alone misses fat / bone relapse
ADVANCED / METASTATIC	Doxorubicin-based (± ifosfamide) 1st line Leiomyosarcoma → doxorubicin + trabectedin → trabectedin maintenance (LMS-04) improved PFS and OS over doxorubicin alone Dedifferentiated liposarcoma → abemaciclib (SARC041) a CDK4/6 inhibitor; CDK4 is amplified in >90% of well-diff / dediff LPS — the first positive phase 3 in DDLS (median PFS ~10 vs 1.5 mo) Later lines by histology trabectedin (a marine-derived DNA-binding alkylator) · pazopanib (a VEGFR tyrosine kinase inhibitor — non-adipocytic only) · eribulin (a MICROTUBULE inhibitor — liposarcoma) · gemcitabine / docetaxel Resect isolated lung metastases (metastasectomy)

Watch

Biopsy BEFORE excision — unplanned "whoops" excisions worsen outcomes. Doxorubicin → cumulative cardiotoxicity (lifetime cap ~450–500 mg/m²; track dose + baseline LVEF); ifosfamide → haemorrhagic cystitis (give mesna) + encephalopathy. Myxoid liposarcoma metastasises to fat/bone, not lung — a chest-CT-only follow-up misses it. Abemaciclib → DIARRHOEA (early, dose-limiting — hold + loperamide), neutropenia, transaminitis, VTE risk. Cancer × transplant: a recent sarcoma needs oncology clearance + a cancer-free interval before transplant immunosuppression.