SIOP‑HRMB is an international clinical trial for children, young people, and adults who have high‑risk medulloblastoma, a type of brain tumour.

At the moment, treatment for high‑risk medulloblastoma is difficult. Only about 60% of patients are cured, and those who survive often experience long‑term side effects, especially from radiotherapy. These side effects can affect learning, memory, balance, hearing, and overall quality of life.

The aim of the trial is to improve survival while also reducing long‑term side effects as much as possible.

How the Trial Works

The trial has two stages, each with a randomised choice between different treatment options. “Randomised” means a computer chooses the treatment group, not the doctors or patient. This helps ensure the results are fair and reliable.

1. First part: Choosing the type of radiotherapy treatment

Before this, all patients receive two courses of induction chemotherapy, which is the first step in treating the tumour.

Then, patients are randomly placed into one of three radiotherapy strategies:

Option A — Conventional Radiotherapy

The standard approach used in most hospitals today.

Option B — HART (Hyperfractionated‑Accelerated Radiotherapy)

Similar to standard radiotherapy, but:

• treatment is given twice a day,

• over a shorter period,

• with a slightly higher total dose.

This aims to treat the tumour more intensively while still trying to keep side effects manageable.

Option C — High‑Dose Chemotherapy + Conventional Radiotherapy

Patients receive:

• a high dose of a chemotherapy drug called thiotepa,

• followed by conventional radiotherapy.

Because high‑dose chemotherapy can damage the bone marrow, patients first have their own stem cells collected from their blood earlier in treatment. After the high‑dose chemotherapy, these stem cells are given back to help their bone marrow recover more quickly.
This approach aims to intensify treatment without adding more radiotherapy‑related side effects.

2. Second part: Choosing the maintenance chemotherapy

After radiotherapy, patients move to the next stage of treatment, where they are again randomised into one of two maintenance chemotherapy options:

Option A — Standard Multi‑Drug Chemotherapy

This is the current standard treatment and includes:

• cisplatin

• vincristine

• lomustine

• cyclophosphamide

It is given in 8 cycles and involves combinations of these medicines. Although it is effective, it can cause significant side effects and has never been formally compared in a randomised trial before.

Option B — Temozolomide Only

A single chemotherapy drug taken by mouth for 6 cycles.
There is evidence suggesting that temozolomide may work as well as, or possibly better than, the standard treatment but with fewer side effects.

What the Trial Hopes to Achieve

• Improve survival rates for patients with high‑risk medulloblastoma

• Reduce long‑term side effects, especially those linked to radiotherapy

• Find the most effective and safest radiotherapy approach

• Understand whether simpler chemotherapy (temozolomide) can replace more intensive multi‑drug treatment

• Overall, help patients live longer and with better quality of life

Patient in this study may receive photon therapy at their local radiotherapy centre, or proton therapy in Manchester or London.