Comprehensive Study Notes on Sarcoma

Sarcoma Overview

  • Sarcomas are tumors that arise in the connective tissues of the body, including:

    • Fat

    • Blood vessels

    • Nerves

    • Bones

    • Muscles

    • Deep skin tissues

    • Cartilage

  • Sarcomas are categorized into two main groups:

    • Soft tissue sarcomas (STS)

    • Bone sarcomas

  • These tumors originate from a variety of sites but exhibit similar pathology, clinical findings, and behavior.

  • Epidemiological statistics indicate that 40% of STS arise in the upper and lower limbs, while 10% of trunk sarcomas occur in the retroperitoneum and 20% in the chest or abdominal wall.

Epidemiology

  • In Australia:

    • Sarcomas are classified as less than 1% of all cancers.

    • Approximately 1,600 new cases of STS are diagnosed annually.

    • About 500 new cases of bone sarcomas are diagnosed annually.

Common Types of Soft Tissue Sarcomas
In Adults:

  • Undifferentiated pleomorphic sarcoma (UPS)

    • Aggressive with high rates of local recurrence and metastasis

    • Predominantly affects individuals aged 50-70 years

  • Leiomyosarcoma

    • Malignant smooth muscle tumor, commonly found in limbs, abdomen, and uterus

  • Liposarcoma

    • Arises from fat cells, typically found in trunk, limbs, and abdomen

  • Angiosarcoma

    • Arises from blood or lymphatic vessels; previous radiotherapy is a risk factor, with a median latency of 10 years.

  • Malignant peripheral nerve sheath tumor

    • Develops in the lining of nerves, often in deep tissues of arms, legs, and trunk

  • Fibrosarcoma

    • Develops in the fibrous tissues of the body, mainly in limbs, skin, and trunk

  • Gastrointestinal stromal tumor

    • Commonly originates in the digestive tract, prevalent in people aged 50-80.

  • Kaposi’s sarcoma

    • Caused by a virus, notably affecting those with compromised immune systems (e.g., AIDS), commonly impacting skin, mouth, and internal organs.

In Children:

  • Rhabdomyosarcoma

    • Aggressive sarcoma from skeletal muscles; most common in children under 10 but can also occur in older individuals.

  • Synovial sarcoma

    • Malignant tumor around joints and tendons; primarily seen in children and young adults.

Common Locations of STS

  • Extremities:

    • Commonly affected by liposarcoma and malignant fibrous histiocytoma.

  • Retroperitoneum:

    • Primarily affected by liposarcoma and leiomyosarcoma.

  • Gastrointestinal stromal tumors are usually located in visceral areas.

Aetiology

  • The etiology of sarcomas is primarily unknown, but several genetic and environmental factors are implicated:

    • Inherited disorders: retinoblastoma, neurofibromatosis, tuberous sclerosis, familial adenomatous polyposis, Li–Fraumeni syndrome, Werner syndrome, nevoid basal cell carcinoma syndrome.

    • Prior radiation therapy for different cancers (e.g., breast cancer, lymphoma).

    • Exposure to chemicals (thorium dioxide, vinyl chloride, arsenic).

    • Chronic lymphoedema in arms or legs.

    • Lifestyle factors such as smoking, diet, and exercise are not risk factors.

Presentation and Symptoms

  • STS may present with locally advanced disease, particularly intra-abdominal sarcomas which can grow to large sizes.

  • Common symptoms include:

    • Growing lump under the skin (often painless or painful)

    • Pain

    • Breathing difficulties in cases of chest involvement

  • Specific symptoms associated with gastrointestinal stromal tumors:

    • Hematochezia (blood in stools, black tarry stools)

    • Abdominal pain

    • Abdominal swelling

    • Nausea and vomiting

    • Loss of appetite or feeling full quickly

    • Weight loss and fatigue

    • Difficulty swallowing (for oesophageal tumors)

Diagnosis

  • The diagnosis involves several steps:

    • Physical examination

    • Imaging modalities:

    • X-ray,

    • CT scans,

    • MRI (preferred due to soft tissue contrast),

    • PET scans,

    • Bone scans,

    • Liver ultrasound

    • Biopsy is critical for histological confirmation; needle core biopsy is sufficient in 90% of cases.

    • A full blood count and liver function test may also be conducted.

Staging and Grading

  • The American Joint Committee on Cancer (AJCC) uses the TNM classification system for staging:

    • Tumors are graded considering histological subtype, degree of necrosis, and mitotic index.

    • Low-grade tumors have well differentiation, few mitoses, and no necrosis.

    • Tumors larger than 5 cm have a higher likelihood of local recurrence and distant metastasis.

AJCC TNM Staging System for Soft Tissue Sarcomas (UICC 2009)

  • Stage IA: T1a, N0, M0 (low grade, superficial, <5 cm)

  • Stage IB: T1b, N0, M0 (low grade, deep, >5 cm)

  • Stage IIA: T1a, N0, M0 (high grade, superficial)

  • Stage IIB: T2b, N0, M0 (high grade, deep)

  • Stage III: T2b, N1, M0 (high grade, any T)

  • Stage IV: Any T, Any N, M1 (distant metastases)

Treatment

  • Multidisciplinary team (MDT) management is crucial, involving surgery, chemotherapy, and radiation therapy:

    • Historically, amputation was common but has shifted.

    • Limb-sparing surgery and radiotherapy now provide comparable survival rates with slightly higher recurrence rates.

    • Previously thought to be radioresistant; now recognized as radiosensitive.

Surgical Considerations

  • Surgery is primary; if margins are clear (≥2cm), a 90% 5-year survival is expected.

  • Surgery extent depends on:

    • Tumor site

    • Stage

    • Histological grade

    • Resection includes all skin and subcutaneous tissues close to the tumor and any prior excision sites.

Amputation Criteria

  • Indicated for:

    • High morbidity risk from radical radiotherapy

    • Distal limb tumors where amputation may be more functional

    • Recurrent disease not amenable to limited resection or radiotherapy.

Post-operative Radiation Therapy Indications

  • Necessary under certain conditions:

    • Limb-conserving surgeries

    • Following gross residual tumors or insufficient excision margins

    • Higher grade histology (grade 2 or 3)

    • Tumors ≥5 cm, particularly those deep to fascia.

Benefits and Risks of Pre-operative RT

  • Benefits:

    • Smaller treatment volumes

    • Less aggressive surgery due to possible tumor regression

    • Reduced surgical contamination

    • No delay to radiation start

    • More effective biological impact.

  • Risks:

    • Increased chance of post-radiation surgical complications

    • Lack of precise pathological description due to changes from RT.

Treatment Techniques

  • Radiotherapy depends on tumor location:

    • Techniques used include 3D conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT).

  • Careful planning is necessary due to the often large target volumes for STS.

  • Treatment planning aims to minimize radiation to surrounding healthy tissues to avoid lymphedema and other complications.

Dose Response and Treatment Protocols

  • For sarcomas, standard prescriptions include:

    • Pre-operative radiation therapy: 50-50.4 Gy in 25-28 fractions over 5-5.5 weeks.

    • Post-operative radiation therapy:

    • For negative margins: 50 Gy in 25 fractions, with a phase 2 of 10 Gy in 5 fractions.

    • For positive margins: phase 1 of 50 Gy in 25 fractions, phase 2 of 16 Gy in 8 fractions, or as required for aggressive margins.

Chemotherapy Considerations

  • Chemotherapeutics such as doxorubicin and ifosfamide have response rates above 20% for STS.

  • Some trials show slight improvements in recurrence-free survival and overall survival with combination therapies.

  • Generally reserved for metastatic disease since preoperative chemotherapy lacks clear evidence supporting its efficacy.

Bone Sarcomas Overview

  • Bone sarcomas can be classified as benign or malignant, with malignant types being termed sarcomas.

  • Significant genetic and environmental factors are involved in their etiology, including:

    • Inherited disorders such as Bloom syndrome, retinoblastoma, and Li–Fraumeni syndrome.

    • Past treatments, including radiation and alkylating agents.

Primary Bone Tumors

  • Rare, accounting for <0.2% of total malignancies.

  • Most common types include:

    • Chondrosarcoma: Primarily in adults; most frequent primary bone tumor, with a mean age of 60 years.

    • Osteosarcoma: Most common in pediatrics, typically occurring in long bones, particularly knees, with a peak incidence in ages 10-30.

    • Ewing Sarcoma: Frequently found in pelvis, chest wall, and long bones; prevalent in ages 10-20.

Prognostic Factors for Bone Sarcomas

  • Factors influencing prognosis include tumor location, histological grade, patient age and gender, and response to preoperative chemotherapy.

Treatment and Management Implications

  • Chondrosarcomas are primarily treated through surgical resection, and chemotherapy is not usually effective.

  • Osteosarcoma treatment involves a multi-modal approach, emphasizing neoadjuvant chemotherapy followed by resection.

  • Ewing Sarcoma treatment integrates surgery, chemotherapy, and radiation.

Side Effects and Complications

  • Acute side effects include:

    • Skin reactions

    • Mucositis

    • Neutropenia

  • Late effects can manifest as growth delays, scoliosis, and increased susceptibility to infections or fractures.

Summary

  • Sarcoma represents a complex and multifaceted cancer group, necessitating interdisciplinary management approaches and careful treatment planning to optimize patient outcomes.