Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma which is characterised by the transformation of specific cells in the mantle zone in the lymph nodes. Despite representing around 5-7% of all non-Hodgkin cases, MCL poses significant challenges due to its typically advanced stage at diagnosis and the complex nature of treatment. Radiation therapy plays a crucial role in managing various cancers like MCL, using high-energy radiation to damage the DNA of cancer cells and preventing them from proliferating and spreading. The use of radiation treatment in MCL treatment has been shown to be effective, particularly in certain clinical settings such as localised disease or with a combination of other treatments to help tackle more advanced cases. 

What is Mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a type of cancer that affects the lymphatic system, which is part of the body’s immune system. In MCL, a type of immune cell called B lymphocytes (or B cells) become mutated and begin to grow uncontrollably.¹ These abnormal B cells typically start in an area of the lymph nodes called the mantle zone¹, which play an important role in the immune response.

MCL is considered aggressive because it tends to grow and spread quickly to other parts of the body, including the bone marrow, spleen, and gastrointestinal tract. It is a relatively rare form of non-Hodgkin lymphoma, accounting for around 3-6% of cases.²

Causes 

The exact causes of MCL is not fully understood, but several factors and genetic abnormalities have been identified which contribute to its development.

• The most notable genetic abnormality associated with MCL is known as the t(11;14) translocation.³ This mutation causes the body to produce too much of a protein called cyclin D1, which helps cells to grow and divide³, which is a key aspect of cancer
• MCL may involve other genetic mutations which affect various pathways involved in cell growth, survival, and response to therapy, similar to many other types of cancers
• No specific environmental factors have been linked to MCL, however, exposure to certain chemicals, pesticides, or radiation has been thought to potentially increase the risk of developing lymphomas.
• MCL primarily affects older adults, with a median diagnosis age of 60, alongside the cancer mainly affects males²
• Disorders that weaken the immune system, such as certain autoimmune diseases, infections, or immunosuppressive therapies may increase the risk of developing MCL

Symptoms

The symptoms of MCL can vary widely, but they often reflect the aggressive nature of the disease and its tendency to spread to various parts of the body.⁴

• Swollen lymph nodes: painless swelling of lymph nodes in the neck, armpit, or groin is a common initial sign
• Fatigue: persistent tiredness and lack of energy, which can affect daily activities
• Unexplained weight loss: significant and unintentional weightloss over a short period of time
• Night sweats: excessive sweating during the night, often soaking clothing an bedding 
• Fever: recurrent or persistent fever without an obvious cause 
• Gastrointestinal symptoms: due to the frequent involvement of the gastrointestinal tract, symptoms can include nausea, vomiting, diarrhoea, abdominal pain, and bloating
• Loss of appetite: reduces desire to eat, which can contribute to weight loss
• Enlarged spleen: the spleen may become swollen, leading to discomfort or a feeling of fullness in the upper left abdomen
• Bone marrow involvement: this can result in low blood cell counts, causing symptoms like anaemia (leading to fatigue and pallor), increased risk of infections due to low white blood cell count, and easy bruising or bleeding due to low platelet count

Common treatment strategies for mantle cell lymphoma 

Chemotherapy 

Chemotherapy involves using powerful drugs to kill rapidly dividing cells, including cancer cells. These drugs circulate throughout the body, targeting cells that are in the process of dividing and multiplying.⁵ This makes chemotherapy effective against widespread disease, but it also affects healthy rapidly dividing cells, leading to side effects such as hair loss, nausea, and lowered blood cell counts.

Immunotherapy 

Immunotherapy makes use of the body’s immune system to recognise and attack cancer cells. This can involve using drugs called monoclonal antibodies, which attach to specific proteins on the surface of cancer cells, marking them for destruction by the immune system. Other forms of immunotherapy can boost the overall activity of the immune system or modify immune cells to better target cancer.⁶

Targeted therapy

Targeted therapy involves drugs that specifically target molecular changes or pathways that are essential for the survival and growth of cancer cells₇. Unlike chemotherapy, which affects all rapidly dividing cells, targeted therapy aims to interfere with specific proteins or genes in cancer cells, causing less damage to normal cells. This approach helps in minimising side effects and increasing effectiveness. 

Stem cell transplantation

Stem cell transplantation is a procedure used to replace damaged or destroyed bone marrow with healthy stem cells. It involves either: 

• Autologous transplantation: the patient’s own stem cells are collected, stored, and then reintroduced after intensive chemotherapy, which kills cancer cells but also destroys the bone marrow⁸
• Allogeneic transplantation: stem cells from a compatible donor are used. This can help generate a new immune response against cancer cells, known as the graft versus tumour effect. It also carries the risk of graft versus host disease, where the donor cells attack the patient’s healthy tissues⁹

Radiation therapy: mechanisms and techniques 

Radiation therapy, also known as radiotherapy, is a medical treatment that uses high-energy radiation to destroy or damage cancer cells. It works by targeting the DNA within the cancer cells, disrupting their ability to grow and divide. Radiation therapy can be delivered externally or internally, depending on the specific type of cancer and its location in the body

Mechanism of action 

Radiation therapy works primarily by damaging the DNA of cancer cells. Here’s how it typically functions:

• Ionisation - radiation delivers high-energy particles to the cancerous tissue. These particles ionise atoms along their path, creating ‘free radicals’ within the cells
• DNA damage: the free radicals generating by radiation disrupt the DNA structure in the cancer cells. This damage can interfere with the cells’ ability to replicate and repair themselves
• Cell death: cancer cells that sustain irreparable DNA damage undergo cell death, either directly during treatment or over time as they attempt to divide

Radiation therapy is designed to target specific areas of the body where cancer cells are present, minimising damage to surrounding healthy tissues. This precision is crucial in reducing side effects. 

Techniques of use 

Radiation therapy can be administered using different techniques, depending on the location, size and type of cancer being treated.

External beam radiation therapy (EBRT)

• Intensity-modulated radiation therapy (IMRT) uses computer-controlled X-ray beams to deliver precise doses of radiation to a tumour or specific area from multiple angles. This technique helps spare nearby healthy tissue
• Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to small tumours or localised areas, often in fewer sessions than traditional EBRT
• Image-guided radiation therapy (IGRT) incorporates imaging techniques such as CT scans or MRI to precisely target tumours, adjusting for any movement or changes in position during treatment 

Internal radiation therapy

This involves placing a radioactive source directly into or near the tumour. This allows for a higher dose of radiation to be delivered to the cancerous tissue while minimising exposure to surrounding healthy organs.

Radiosurgery 

This uses highly focused radiation beams to treat tumours in the brain or other areas of the body with minimal impact on nearby tissues. It is often used for small tumours or lesions that are difficult to reach with traditional surgery.

Radiation therapy in the context of mantle cell lymphoma 

Radiation therapy plays a specific role in the treatment of mantle cell lymphoma and is typically used in certain clinical scenarios to complement other types of treatment. Here’s how radiation therapy is utilised in the context of MCL:

• Localised disease control: radiation therapy is effective in treating localised areas of disease, especially when MCL is confined to specific lymph nodes or extranodal sites. It can be used to shrink or eliminate tumours, providing local disease control
• Consolidation therapy: after initial chemotherapy or in combination with chemotherapy, radiation therapy may be used as consolidation therapy. This approach aims to eradicate any disease which may remain and reduces the risk of relapse in patients who have achieved partial or complete remission with chemotherapy¹⁰
• Palliative treatment: in cases where MCL has spread to specific sites and causes symptoms such as pain or obstruction, radiation therapy can help alleviate these symptoms and improve quality of life
• Combined modality therapy: radiation therapy is sometimes integrated into a combined modality approach alongside chemotherapy, immunotherapy, or targeted therapy. This combined approach ais to maximise treatment effectiveness by targeting different aspects of the disease and improving overall outcomes¹⁰
• Reducing risk of CNS involvement: radiation therapy can be used prophylactically to reduce the risk of central nervous system (CNS) involvement in high-risk patients, although this is less common in MCL compared to other lymphomas¹¹

Disadvantages of radiation therapy for MCL

• Side effects: common side effects include fatigue, skin irritation, and localised hair loss. Depending on the treatment area, other side effects may include nausea, diarrhoea or difficulty swallowing¹²
• Damage to healthy tissue: despite advances in precision, radiation can still affect nearby healthy tissues, potentially causing long-term damage. For example, radiation to the chest can impact the lungs or heart, and abdominal radiation can affect the gastrointestinal tract
• Secondary cancers: there is a small risk that radiation therapy can lead to the development of secondary cancers later in life due to the exposure of healthy tissues to radiation¹³
• Limited use in widespread disease: radiation therapy is most effective for localised disease and may not be suitable for patients with widespread MCL. systemic therapies like chemotherapy and targeted therapy are generally more effective for extensive disease involvement
• Cumulative effects: for patients who have received previous radiation therapy or other cancer treatments, there can be cumulative effects that increase the risk of complications or exacerbate side effects
• Potential for acute toxicity: high doses of radiation or large treatment fields can cause acute toxicity, leading to more severe immediate side effect that may require medical management¹⁴

Summary 

• Mantle cell lymphoma (MCL) is a rare, aggressive cancer of the lymphatic system that originates in B lymphocytes found in the mantle zone
• Symptoms include swollen lymph nodes, fatigue and weight loss
• Radiation therapy destroys cancer cells by damaging DNA, meaning cancerous cells can no longer divide and spread
• This is useful in controlling disease without causing too much damage to surrounding healthy tissue, as well as consolidation after treatment and easing disease symptoms
• Risks include irritation, tissue damage and development of secondary cancers