A presentation for rapid review of sarcoma for post graduate general surgery residents.

2. MAI  NACT
MAID  Mesna, Adriamycin, Ifosfamide, Dacarbazide

3. Soft tissue sarcomas
Nabin Paudyal

4. Epidemiology of Soft Tissue Sarcoma
(STS):
• STS comprises over 60 neoplasms originating from various tissues, affecting
a wide age range.
• Tissue types of STS origin include skeletal muscle, adipose cells, blood and
lymphatic vessels, connective tissue, and peripheral nerves.
• Clinical behaviors of mesodermal tumors range from benign lipomas to
aggressive neoplasms like metastatic angiosarcoma.
• STS is relatively rare, with 12,020 estimated new cases and 4,740 estimated
deaths in 2014.
• While STS represents 1% of cancer incidence in the U.S., it accounts for 2%
of cancer-related deaths.
• Diagnosing STS can be challenging due to its rarity, as many non-neoplastic
conditions can mimic STS.

5. Core Concepts in STS:
• Large series show that extremity and trunk STS are more common
than intraperitoneal and retroperitoneal STS.
• Proximal limbs, particularly the thigh, are frequently affected by
extremity STS.
• The age at diagnosis is closely linked to the histologic STS subtype.
• Certain STS subtypes, like rhabdomyosarcoma, hemangioma,
neurofibroma, and alveolar sarcoma, predominantly affect children
and young adults.[@RNA]
• While most STS cases occur sporadically, documented causes
include germline mutations, radiation exposure, and environmental
factors.

6. Germline Mutations:
1.Neurofibromatosis Type 1 (NF1):
1. An autosomal dominant condition caused by mutations of the NF1 gene on chromosome
17q11.2.
2. NF1 codes for neurofibromin, a tumor suppressor of the ras oncogene signaling pathway.
3. Associated with the development of malignant peripheral nerve sheath tumors (MPNST),
schwannomas, gliomas, and other tumors.
2.Li-Fraumeni Syndrome:
1. A rare autosomal dominant disorder caused by mutations of the TP53 gene on chromosome
17p13.1.
2. TP53 codes for p53, a tumor suppressor protein.
3. Increases the risk of various malignant neoplasms, including breast cancer, STS, adrenocortical
carcinoma, brain cancer, and more.
4. Patients exhibit different phenotypes based on the types of mutations.
3.Familial Adenomatous Polyposis and Gardner Syndrome:
1. An autosomal dominant disorder caused by mutation of the APC gene on chromosome 5q21-
q22.
2. APC codes for a tumor suppressor protein that inhibits β-catenin's nuclear localization.
3. Results in colonic polyps and may lead to extracolonic manifestations, such as desmoid tumors,
epidermoid cysts, and osteomas.

7. • Radiation:
• Radiation exposure is associated with an increased long-term risk of STS
development, particularly at the periphery of the radiation field.
• Main STS subtypes linked to prior radiation exposure include unclassified
pleomorphic sarcoma, angiosarcoma, leiomyosarcoma, fibrosarcoma, and
MPNST. [@PALM]
• Patients treated for childhood cancers requiring radiation therapy
may develop STS in a dose-dependent manner, typically 11.8 years
later.
• Stewart-Treves syndrome is characterized by angiosarcoma development
following postmastectomy lymphedema and radiation therapy.
• Carcinogens:
• Hepatic angiosarcoma is related to carcinogenic substances like
Thorotrast, polyvinyl chloride, and arsenic.
• Thorotrast, a thorium-based intravenous contrast agent used between
1930 and 1955, leads to hepatic angiosarcoma diagnosis 20 to 30 years
after exposure.
• Prolonged exposure to polyvinyl chloride, a common form of plastic, is
associated with hepatic angiosarcoma development.

8. • Gene Fusions and Molecular Testing:
• Gene fusions are significant driver mutations in various STS subtypes, with
diagnostic and therapeutic potential.
• Molecular analysis, including gene fusions and additional platforms, plays
a crucial role in the diagnosis and treatment of STS.
• Platforms like Complex INdex in SARComas (CINSARC) may predict
metastasis-free survival and prognosis more effectively than histologic
grade.
• CINSARC is a platform where 67 genes are assessed and metastasis free survival is
assessed.

9. Staging and Grading in Soft Tissue
Sarcoma (STS):
• Tumor Grade:
• In the American Joint Committee on Cancer (AJCC) staging system for STS, tumor grade is an
essential parameter.
• Two widely applied grading systems are the French Fédération Nationale des Centres de
Lutte Contre le Cancer (FNCLCC) system and the National Institutes of Health (NIH)
system.
• The FNCLCC system is preferred and involves scoring based on three categories: tumor
differentiation, rate of mitoses, and amount of tumor necrosis.
• The FNCLCC system is found to be superior in estimating the risk of distant metastasis and
survival compared to the NIH system.
• Tumor Staging:
• The eighth edition AJCC staging system for STS has separate staging definitions for various
anatomic sarcoma locations: head and neck, trunk and extremities, abdomen and visceral
organs, and the retroperitoneum.
• It maintains separate schemas for specific STS subtypes, such as gastrointestinal stromal tumor
(GIST), Kaposi sarcoma, and dermatofibrosarcoma protuberans (DFSP).

12. • Tumor Size:
• The eighth edition AJCC staging system defines tumor categories based on size. T1 tumors are 5
cm or less, T2 tumors are >5 to ≤10 cm, T3 tumors are >10 to ≤15 cm, and T4 tumors are >15 cm.
• The superficial versus deep anatomic designation with respect to the investing fascia has
been eliminated.
• Visceral and retroperitoneal STS has lower disease-specific survival, primarily driven by distant
metastasis in visceral STS and local recurrence risk in retroperitoneal STS.
• Lymph Node Involvement: {lymph Rape}
• Regional lymph node involvement is uncommon in STS (2% to 10%).
• Most common STS subtypes undergoing lymphadenectomy for nodal metastases include
angiosarcoma, rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, epithelioid sarcoma,
clear cell sarcoma, and liposarcoma. [@ CL-RAPE]
• Sentinel lymph node dissection has been proposed but is generally inaccurate and has not been
successfully applied in STS.
• Nomograms:
• To better estimate prognosis in STS patients, nomograms have been developed.
• Over 13 different nomograms have been published for STS, addressing various oncologic
outcomes such as local recurrence and overall survival.
• Nomograms are reported to provide more accurate prognostication than traditional staging
systems and can impact patient care.
• The proliferation of nomograms may influence future editions of traditional staging systems.

14. Clinical Evaluation and Staging in Soft
Tissue Sarcoma (STS):
• Clinical Presentation:
• Common clinical presentation of STS includes a painless
mass, often without prior evaluation.
• Common mimicking diagnoses include hypertrophic scar, myositis
ossificans, hematoma, or cyst.
• Small, superficial, and mobile masses separate from vital structures
may be resected with wide gross margins, while tumors close to vital
structures should be referred to specialized centers.
• Preoperative biopsy may be unnecessary in some cases, as it can lead
to incorrect non-STS diagnoses, nonideal biopsy site placement, and
treatment delays.

15. • Oncologic Staging Indications:
• Larger or complex lesions.
• Indications for preoperative imaging and biopsy include situations where
• the extent of the mass can't be determined through physical examination
• suspected neurovascular involvement
• suspicion of regional or distant metastasis
• need for surgery with potential significant functional deficit
• suspicion of unresectability or questionable surgical margins at presentation.
• Imaging and Biopsy:
• MRI is generally considered the most informative imaging modality for trunk and
extremity STS.
• A chest CT scan is recommended, as lung metastasis is common.
• Biopsy methods include fine-needle aspirate, image-guided core needle biopsy, and
incisional biopsy.
• Core biopsy planning should incorporate the biopsy trajectory into the forthcoming
surgical resection volume.
• When core needle biopsy attempts are nondiagnostic, incisional biopsy may be
necessary, planning the incision to include the entire biopsy trajectory.

17. • Multidisciplinary Evaluation:
• A multidisciplinary team at a high-volume STS center, with representatives
from various fields, discusses the case to assess treatment modalities and
their sequence for each patient.
• Postoperative Surveillance:
• Due to the risk of recurrence, close postoperative surveillance is essential.
• Physical examinations should occur every 3 to 6 months for 2 to 3 years,
followed by every 6 months for the next 2 years, and then annually.
• Regular radiographic surveillance of the chest, abdomen, and pelvis is
recommended. The modality and frequency should be individualized to the
patient and tumor characteristics.
• A shorter imaging frequency may be appropriate for patients with close
surgical margins or particularly ominous histologic types.
• High-volume STS centers are associated with better outcomes,
including reduced residual disease at re-resection, lower mortality
rates, higher rates of limb preservation, and improved overall
survival.