Introduction

Proton therapy or proton beam therapy is a novel treatment option for many cancers including brain tumours, breast cancer, gastrointestinal cancer, lymphoma, sarcoma, head and neck cancer, liver cancer, lung cancer and more.¹

Although, it is not applicable to all cancer treatments because it is expensive as compared to other traditional treatments and limited data available on safety and efficacy. Proton therapy uses high-energy protons (+ve charged particles) to treat cancer; It can be used as a single therapy or in combination with other therapies i.e. chemotherapy or surgery.¹

Gastrointestinal(GI) cancer is one of the most common types of cancer globally, among all types more than 25% represent GI cancer and 33.3% death incidence.² In GI cancer, abnormal cell growth appears on different parts of the GI tract which include the oesophagus, stomach, colon, rectum and anus. The most common symptoms a person can experience are abdominal pain, nausea, vomiting, decreased appetite, weight loss, heartburn and indigestion. Treatment of GI cancer involves surgery, chemotherapy, radiation therapy and proton therapy.³

The treatment of gastrointestinal cancer with proton therapy shows promising results. It enhances patient compliance and reduces the potential side effects and complications. Proton therapy delivers targeted beams of proton to specific organs and kills cancerous cells.⁴

Further we will discuss in this review, the mechanism, benefits and clinical applications of proton therapy.

Principle of proton therapy

Proton therapy is a type of radiation therapy and it works by damaging the structure of DNA in tumor cells and destroying it. It releases a high beam of protons; these are positively charged particles and have a distinct property named as bragg peak, which means before the beam of radiation ends it is deeply deposited at the targeted site that allows precise delivery of radiation to the tumour cells and therefore, causing no or less damage to nearby healthy tissues or cells.⁵

Proton therapy vs traditional radiation therapy

Proton therapy is an expensive procedure but it is safer and more effective than conventional radiation therapy. Traditional radiation therapy releases X-ray or high beams of photons rather than protons to kill the cancerous cells and its radiation is not limited to targeted cells or tissues. This can cause more damage to surrounding healthy cells.⁶

Advantages of proton therapy

• Proton therapy has an ability to target only tumour cells. This means it has the benefit of protecting surrounding cells
• Target delivery of radiation prevents the spreading of cancer to other organs
• It is a painless and precise treatment, having fewer side effects than traditional treatment
• Children and young adults benefit more from proton therapy as their normal tissues are developing fast⁷

Side effects of proton therapy

The side effects of proton therapy depend upon the type and location of cancer. Some side effects may occur at an early stage of treatment while some side effects may appear later on after months or years of treatment, both are mentioned below:⁸

Early side-effects: nausea, vomiting, diarrhoea, alopecia (hair loss), headache, tiredness, dryness of skin, difficulty in swallowing, urine incontinence.⁸

Late side-effects: swelling on different body parts, infertility, changes in the brain and spinal cord.⁸

Proton therapy in gastrointestinal cancers

Nearly 156000 patients are diagnosed with different types of GI cancers each year in the US. Most of the time surgery is the first choice of therapy but treatment with radiation and chemotherapeutic drugs can also be employed according to the patient's condition.⁹ Radiation therapy has more critical outcomes in GI cancer as it damages the surrounding organs due to high doses of radiation. On the other hand, chemotherapy can also show some complications.

Proton therapy gives promising result in treating GI cancer because precise dose distribution and targeted delivery can protect nearby organs.⁹

According to recent research treatment of GI cancers with proton therapy shows fewer side effects, delays complications and improves treatment compliance.⁹

Types of GI cancer treated with proton therapy

It can treat different types of gastrointestinal cancer and these are:

• Esophageal cancer
• Gastric/Stomach cancer
• Liver cancer
• Pancreatic cancer
• Bile duct cancer
• Rectal and anal cancer⁹

Indications for proton therapy in GI cancer

The main treatment of GI cancer or tumor is the removal of a tumour from the body part however in some cases when there is a high risk in removing the tumor; proton therapy is the best option because it is effective in treating GI cancer and it has less side effects on nearby organs but 

There are some conditions for using proton therapy as treatment; it is used only in those cancers which have not spread to other body organs and proton therapy is combined with chemotherapeutic drugs to treat cancer.¹⁰

Clinical evidence to support proton therapy

Some clinical data are currently available that support proton therapy:

• A number of studies have shown better control of disease and low risk of mortality with proton therapy as compared to traditional radiation therapy. Due to its less adverse effects and prevent the destruction of healthy tissues it is recommended in childhood cancer¹¹
• It also has promising results in treating brain tumours because of its reduced adverse effect on cognitive dysfunction
• Some retrospective studies show reduced toxicities and better disease control with proton therapy in cases of oesophageal cancer
• A randomised trial of liver cancer has shown exceptional results in treating liver carcinoma, particularly for large tumours¹¹
• Head and neck cancer are challenging to treat with traditional radiation because of its complex structure but it shows promising results with proton therapy
• Skull and sinonasal cancers require a high dose of radiation without causing harm to nearby organs or tissues and it is not achieved through traditional radiation therefore, in this scenario proton therapy is more effective¹¹

Challenges and limitations

Despite having successful clinical trials and studies showing positive results of proton therapy, it also has some challenges and limitations.¹¹

Limited availability of proton therapy facilities, limited clinical access and an insufficient number of centres are present for providing proton therapy. It requires more time to plan the treatment and advance technology for the delivery system. As time passes technology advances and proton therapy requires advancements in its structure that give better precision and dose distribution and manufacturers will also work on it. Another challenge that limits the use of proton therapy is highly expensive therapy not everyone can afford the treatment.¹¹

Future direction for use and research

Future research is still going on to understand the development, physical and biological aspects of proton therapy and compare it with traditional radiation therapy. Moreover, a report in a peer literature review shows that it reduces the occurrence of toxicity in breast and prostate cancer.

However, as time passes new advancements in the field of oncology give new indications of proton therapy.¹² Targeted therapy and immunotherapy produce remarkable effects on patients they are treating and even higher doses of radiation can be given by proton therapy which is not possible in traditional therapy.

It can also show a reduced death rate and toxic effects related to disease and therapy. Cancer patients are living their lives longer with reduced adverse effects. Increasing availability of centres, and cost-effective single rooms; all these facilities can make easy access to proton therapy without delaying the treatment. Thus, more patients can get proton therapy and cancer will be cured.¹²

FAQs

How long does proton radiation present in your body?

Proton radiation has a very short life span, it enters your body and targets the tumour cells to prevent spreading to surrounding tissues which is why it has reduced adverse effects.

Which element is used in proton therapy?

An accelerator is used in proton therapy and it works by breaking the hydrogen atom and separating electrons from protons, protons release the energy.

How many times does a proton therapy require?

It requires 5 to 35 treatment sessions depending on the patient's condition and type of cancer.

Summary 

Proton therapy is an advanced treatment option for cancer, using high-energy proton beams to destroy the structure of DNA and cure cancer. Although it is not applicable to treat all types of cancer, certain cancers including breast cancer, prostate cancer, types of GI cancer, lymphomas, sarcomas, head and neck cancer give promising results when treated with proton therapy.

It has less toxic effects and decreases morbidity and mortality rates. Moreover, it has a target delivery system and dose precision which can protect nearby healthy organs from the hazardous effects of radiation. The data of safety and efficacy of proton therapy is limited but multiple studies show its effectiveness in different types of cancers still future research is continuing to make proton therapy more accessible to patients.