Overview

Myxofibrosarcoma

Definition and characteristics

Myxofibrosarcoma is one type of soft tissue sarcoma or soft tissue cancer that tends to spread widely through the surrounding tissues, such as tissues supporting bones, muscles, and organs. This pattern causes the likelihood for surgeons to leave behind some cancer cells during surgery, which increases the risk of cancer recurrence in the same area.^1,2 Currently, the causes of this disease remain unclear and researchers are still trying to find more about the causes.²

Epidemiology and demographics

There were 4295 new cases of soft tissue cancer (sarcoma) in England from 2017 to 2019. Almost half of that can be survival from soft tissue sarcoma for 10 or more years data from 1996 to 2000.³ An average of 178 cases are being diagnosed with myxofibrosarcoma every year in the UK.² Moreover, myxofibrosarcoma is approximately one in twenty of all soft tissue cancers.² It is commonly found in the elderly, especially at the age of 60-80 years and occurs in people assigned male at birth more than people assigned female at birth.

Importance of understanding treatment options

Impact on patient outcomes

Current treatments for myxofibrosarcoma are involved in incorporating various types of therapy including surgery, radiation, and chemotherapy. However, it tends to explore personalised models to help guide treatment decisions and predict individual outcomes based on unique characteristics.⁴

Advances in treatment strategies

Recent studies are increasingly focusing on targeted therapy and immunotherapy as many clinical trials provided promising effective outcomes for myxofibrosarcoma.² Furthermore, newer approaches can better control the disease and improve the quality of life.

Diagnosis and grading

Diagnostic procedures

The diagnosis of myxofibrosarcoma is challenging because there is no specific marker to diagnose this disease and it is therefore based on external features of cells.

Imaging techniques

Imaging scans are to describe how much the growth of cancer cells extends to your body. Examples include CT scans, MRI and  PET scans.⁵

Biopsy

A biopsy is a process in which a technician takes a small piece of the growth cells to examine in a lab. Then, your doctor will examine whether your biopsy indicates myxofibrosarcoma.²

Grading

Tumour size and spread

Myxofibrosarcoma can be divided into three grades corresponding to how much the tumours have spread and the extent of the tumour-associated mortality.⁶ These include:

• The low grade indicates no sign of the tumour spreading
• The intermediate grade shows some development of the tumour spreading depending on the distance
• High-grade shows increased development of the tumour depending on the distance

Surgical treatment

In patients whose tumours localise or do not spread to other places, the first treatment recommended is to perform surgery which can be combined with radiotherapy. The objective of surgery is to remove the tumour cell as much as possible, although there is still a chance of myxofibrosarcoma coming back.^2,7

Types of surgical procedures

Wide local excision

The types of surgical procedures depend on the location of the tumour. Myxofibrosarcoma typically occurs in the arms or legs. Wide local excision is cutting the cancer area with the edge of surrounding healthy tissue in order to make sure that the cancer is completely removed.⁸

Amputation 

Amputation is to remove all or part of your legs. This will be considered only in severe cases.⁸

Surgical margins and reconstruction

Importance of clear margins

Making clear margins is important for lowering the risks of cancer recurrence in the same areas.⁸

Techniques for limb-sparing surgery

If myxofibrosarcoma tumours spread in the arms or legs, doctors will consider limb-sparing surgery. Limb-sparing surgery is to remove parts of cancer as much as possible whilst not affecting the whole arm or leg. This means your surgeon will make sure that your arms or legs are only minimally affected and their normal functions are maintained. In terms of removing cancers, this operation may require cutting a large area and including the edge area of healthy tissues called the margin.⁸

Reconstructive surgery options

Reconstructive surgery is an operation that reconstructs a part of a patient's body being operated or changed by previous surgery. The options consist of using free or rotational flaps and skin grafts.⁴

Radiation therapy

To make tumours smaller, radiotherapy may be administered using radiation. To remove all cancer cells, it may be given after surgery.² Radiation aims to destroy the genetic substances of tumour cells; however, healthy tissues can be affected.⁸

Role of radiation in treatment

Preoperative (neoadjuvant) radiation

The first management of myxofibrosarcoma is either surgery or radiotherapy. In some cases, extra treatment is given before the first treatment, called neoadjuvant therapy.⁹ Radiotherapy is used as a neoadjuvant therapy before surgery, which may decrease the risks of cancer relapse. However, neoadjuvant radiation may increase acute complications after surgery.¹⁰

Postoperative (adjuvant) radiation

Adjuvant radiation means giving radiation after surgery. The treatment typically takes 6 to 7 weeks on each weekday. Postoperative radiation will be given after wound healing as it can slow down the healing process.⁹ Adjuvant radiation can increase late side effects compared to neoadjuvant radiation.¹⁰

Techniques

External beam radiation therapy (EBRT)

External beam therapy (EBRT) uses high-energy or low-energy beams. The machine of EBRT will generate proton beams, and then the protons kill the cancer.¹¹ The beams are generated from outside of the body.

Intensity-modulated radiation therapy (IMRT)

Intensity-modulated radiation therapy (IMRT) delivers a high dose of radiation, shaping the target to closely match the cancer’s area.¹²

Side effects and management

Radiotherapy can cause a lot of side effects but it depends on the individual. Common side effects of radiotherapy are illustrated below:¹³

• Feeling hurt or sore on the skin - if you have soreness, you should wash and pat dry your skin, apply moisturiser regularly, and wear loose clothes to make you comfortable when moving
• Feeling tired or extremely tired - if you have tiredness, you should rest sufficiently or do low-impact exercises such as walking
• Hair loss - your hair will grow back after stopping treatment for 2 or 3 weeks; In the meantime, if you feel depressed, you can talk to your care team and they will provide you with support
• Sickness - talk to your care team, they will prescribe medications to ease this symptom

Chemotherapy

Chemotherapy is one of the standard treatments for various cancers which work by inhibiting or slowing the growth of cancer cells.

Indications for chemotherapy

1.  Metastatic myxofibrosarcoma is a stage of myxofibrosarcoma in which cancer cells spread to other areas in your body⁵
2.  High-grade tumours describe cancer cells that are growing and spreading more quickly and may need strong treatments.

Common chemotherapeutic agents

Doxorubicin

British cancer guidelines recommend that the first-line treatment of soft-tissue sarcoma spreading to other areas is doxorubicin alone or the combination of doxorubicin and ifosfamide.¹⁰ Doxorubicin kills cancers by inhibiting genetic substance synthesis such as DNA, leading to defects in DNA and cell death.¹⁴

Ifosfamide

Ifosfamide is inactive at first, which needs some process in the body to change to an active form. Its mechanisms induce cell death and increase free radicals, leading to DNA damage and stopping protein production.¹⁵

Efficacy and Side Effects

Response rates

The combination of doxorubicin and ifosfamide showed a good response in terms of increasing the possibility of surgery success and provided benefits in individual patients such as reducing some disturbing side effects.¹⁶ 

In a clinical trial, the doxorubicin/ifosfamide combination showed a higher length of time between cancer being cured and recurrence or progression-free survival (PFS) and improved overall response rates compared to doxorubicin alone. However, doxorubicin alone seemed to show fewer side effects from therapies.¹⁷

Management of chemotherapy-related toxicity

Side effects depend on the individual and adjuvant treatment. Some common side effects include:¹⁸

• Easily getting an infection - symptoms can be body temperature changing, or cold-like symptoms; you should contact your doctor if you have these symptoms
• Bleeding and discoloured spots on your skin - sometimes you may bleed from your nose or gums
• Anaemia
• Hair loss
• Loss of appetite
• Mouth and throat sore

Targeted therapy and immunotherapy

Emerging treatments

As the current treatments including surgery, chemotherapy, and radiation have a chance of cancer coming back and are associated with high side effects, researchers are trying to explore new treatments to reduce limitations, which are targeted therapy and immunotherapy.

Targeted therapies

Targeted therapies aim to directly and specifically destroy cancer cells, also referred to as biological therapies. They have different ways to work on tumours such as:⁸

• Stop or slow the growth of cancer cells
• Boost up the human immune system to kill cancer cells
• Inhibit blood vessel growth around cancer cells, which nurture cancer cells
• Attach with other treatments such as chemotherapy to lead the way to cancer cells
• Directly target cancer cells

Immunotherapies

Immunotherapy encourages your immune system to fight cancer cells.² Studies of Immunotherapy on myxofibrosarcoma are emerging as its promising potential.

Immune checkpoint blockade (ICB), one type of immunotherapies, has been showcased for its effectiveness in treating myxofibrosarcoma. On the surface of immune cells or cancer cells, there are immune checkpoint receptors which provide inhibitory effects. ICB blocks these receptors, leading to the enhancement of anti-tumour effects. In a recent clinical trial, patients with myxofibrosarcoma treated with an ICB called pembrolizumab showed partial responses to the treatment.¹⁹

What do you need to do after treatment?

After treatment, you still have follow-up appointments in order to:²

• Check your symptoms
• Examine signs of cancer coming back

Rehabilitation after treatment is necessary for recovery to normal daily life. This is because, after treatment, patients may have muscle weakness, be extremely tired or have problems with movement or normal functions.²⁰

Summary

Myxofibrosarcoma is one type of soft tissue sarcoma or cancer, however, its causes remain unclear. Therefore, current treatments including surgery, radiation, and chemotherapy are broad and not specific to the causes of cancer, leading to several side effects on healthy cells. Unfortunately, there is a high chance of cancer coming back, therefore, patients will require several follow-ups to check all signs of cancer recurrence. These leave room for future treatments such as targeted therapies and immunotherapies to improve these limitations.