Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH

Founded by Marie Curie; a leader in breast cancer, radiotherapy, and proton therapy.

Brachytherapy places a radioactive source directly inside or next to the tumour.

The original targeted radiotherapy: thyroid cells soak up iodine, so radioactive iodine destroys leftover thyroid tissue and metastases while sparing everything else.

Radiation shaped precisely to the tumour and checked with daily imaging, sparing surrounding organs.

Radiation shaped precisely to the tumour and checked with daily imaging, sparing surrounding organs.

Very high, very precise radiation doses in 1-5 sessions that can ablate a tumour like surgery.

Giving radiotherapy in fewer, bigger daily doses (fractions) so a course takes one to three weeks instead of five to seven, with equal cure and side effects for many cancers. Convenience, cost and machine capacity all improve.

Settled the radiotherapy schedule debate in limited-stage disease: neither schedule was superior, so twice-daily 45 Gy remains standard and once-daily is an acceptable alternative.

The software that calculates exactly how radiation beams should be shaped and checks the machine delivered it.

Varian is the largest radiotherapy equipment maker and is running the first human FLASH proton trials.

Elekta is the Swedish radiotherapy company behind Unity, the leading MR-linac, and Gamma Knife.

RaySearch makes the vendor-neutral RayStation treatment planning system, strong in proton and adaptive planning, with machine-learning planning tools.

Made a year of immunotherapy after chemoradiation the standard for stage III lung cancer, with a survival benefit that held at five years.

A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.

Adding immunotherapy to curative chemoradiation for locally advanced cervical cancer improved both control and survival, the first such advance in two decades.

For stage III lung cancers with an EGFR mutation, a targeted pill after chemoradiation cut progression by more than 80%.

Six weeks of cheap, generic chemotherapy before standard chemoradiation cut deaths by 40%, an advance usable anywhere in the world.

The trial that made chemotherapy plus radiation before surgery the standard for oesophageal cancer; the survival gain was still there ten years later.

Adding chemotherapy to radiation after surgery helped women with high-risk endometrial cancer, especially those whose tumours have a broken p53 gene.

Adding a PD-L1 blocker to curative chemoradiation did not help, the first of several such failures in head and neck cancer.

A promising phase 2 drug that sensitises tumours to radiation made things worse in phase 3, a reminder that early wins in this disease often do not replicate.

Attempts to give HPV-positive throat cancer patients less radiation fell short: the standard dose remained better, so de-escalation is not yet routine.

The only chemotherapy proven to extend life in glioblastoma, given during and after radiation. It works best when the tumour has switched off a repair gene called MGMT.

The 2005 trial that set the treatment every glioblastoma patient still receives. Nothing has replaced it in twenty years.

Radiation using protons, which stop inside the tumour instead of passing through, so tissue behind it gets no dose.

The Christie is Europe's largest single-site cancer centre and the UK's first NHS proton therapy centre.

Harvard's largest hospital; leaders in lung cancer targeted therapy, proton therapy, and ctDNA research.

IBA is the largest supplier of proton therapy equipment.

Mevion makes compact single-room proton therapy systems.

Heavier charged particles that kill even radiation-resistant tumours, available at only a handful of centres worldwide.

Mayo Clinic's Florida campus, building North America's first carbon-ion therapy facility alongside proton therapy and a cancer vaccine programme.

The MR-linac is a radiation machine with an MRI inside it, so the plan is adjusted to where the tumour is that very day.

Elekta is the Swedish radiotherapy company behind Unity, the leading MR-linac, and Gamma Knife.

RefleXion Medical makes the first PET-guided radiotherapy system, which uses the tumour's own emissions to steer the beam.

Software that draws organs and tumours on scans automatically, saving hours per patient and making daily plan adaptation practical.

Limbus AI provides AI auto-contouring for radiotherapy, FDA-cleared and used across hundreds of centres.

TheraPanacea is a Paris AI company whose ART-Plan does auto-contouring and synthetic CT in radiotherapy.

Short courses of radiation, often a single treatment, to relieve pain from bone metastases, stop bleeding, open blocked airways or protect the spinal cord. Among the most cost-effective treatments in cancer.

One radiotherapy session relieves bone pain as well as ten, according to many trials, yet most patients still get the longer course. Making one session the default would spare patients trips and free machines.

Proved that most people with small, low-risk thyroid cancers can skip radioactive iodine after surgery without any increase in recurrence.

This trial asked whether children with average-risk medulloblastoma could safely receive less radiation. Shrinking the boost to the tumour bed was safe; cutting the dose to the whole brain and spine in young children was not, so 23.4 Gy remains the floor for most.

Small-cell lung cancer spreads to the brain so often that doctors used to irradiate the whole brain pre-emptively. Regular MRI scans are now challenging that practice.

Giving radiotherapy in five larger doses over one week instead of 15-25 smaller doses is proven safe for breast and prostate cancer and could treat three times as many patients on the same machines.

Instead of guessing from HPV status who can get less radiation, measure the virus DNA in blood during treatment and reduce dose only when it clears fast.

Delivering an entire dose in under a second, which in animals spares healthy tissue while still killing the tumour.

THERYQ is a French company building FLASH radiotherapy machines that deliver a whole dose of radiation in a fraction of a second using very high energy electron beams, an approach that in animal studies damaged healthy tissue less while still controlling tumours.

Varian is the largest radiotherapy equipment maker and is running the first human FLASH proton trials.

Using very fast electrons instead of photons or protons: a possible way to deliver FLASH-speed radiation to deep tumours from a compact machine.

Rotating the proton beam continuously around the patient instead of firing from a few fixed angles, to spread the entrance dose and sharpen the target dose.

Leo Cancer Care builds radiotherapy equipment that treats patients sitting upright instead of lying down, so the beam can stay fixed and the room, machine and building can be far smaller and cheaper.

P-Cure makes a compact proton therapy system in which the patient sits upright in a rotating chair in front of a fixed beam, so the treatment fits inside an ordinary radiotherapy room instead of a purpose-built multi-storey building.

In boron neutron capture therapy a boron drug accumulates in tumour cells, then a neutron beam makes only those cells explode from inside.

TAE Life Sciences is developing boron neutron capture therapy, in which a boron drug collects in cancer cells and a hospital-based neutron beam then triggers a tiny nuclear reaction inside those cells to destroy them while sparing nearby healthy tissue.

Neutron Therapeutics makes a compact particle accelerator that produces the neutron beam needed for boron neutron capture therapy, a form of radiotherapy that targets cancer cells one at a time, so hospitals no longer need a nuclear reactor to offer it.

Deliberately treating a big tumour unevenly, with a lattice of very high dose peaks inside it, instead of a uniform dose.

Nanoparticles that turn ordinary radiotherapy X-rays into a much bigger dose exactly where they sit.

Hyperthermia heats tumours to 40-43 °C to make radiation and chemotherapy work better.

Radiation can alert the immune system, but too big a single dose destroys the very alarm signal it creates. Picking the right dose and schedule may be free extra benefit.

The radiopharmaceutical roadmap runs eighty years from radioactive iodine for thyroid cancer to alpha-emitting drugs for prostate and neuroendocrine cancers, with isotope supply as the limiting factor.

Attaching a radioactive atom to an antibody, so an ADC's targeting is used to deliver radiation instead of chemotherapy.

Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage.

Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes.

Radical oncology is a horizon map of the wilder ideas in cancer, sorted by how close they are to mattering, with the reason each one might never arrive.

Surgery and radiotherapy cure more people than drugs do, but attract a fraction of the research investment.

Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce.

The number of people with cancer is rising faster than the workforce trained to treat them.

A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.

Countries buying radiotherapy machines one at a time pay high prices and get poor service. A single global buyer negotiating for dozens of machines a year could cut prices and demand long-term support.

Governments and donors should buy guaranteed working hours from radiotherapy vendors, with remote monitoring and regional spare-parts depots, instead of buying machines that then sit broken.

Hospitals without enough physicists could upload scans to a shared planning centre, where AI drafts the treatment plan and remote experts finish and check it within a day.

Medical physicists, who keep radiotherapy machines accurate and safe, are scarcer than oncologists in many countries. Remote quality checks with local technologists could let one physicist safely oversee several machines.

Cervical cancer cannot be cured by external radiotherapy alone; it needs internal radiation, which many hospitals lack. A cheaper internal-radiation unit using a long-lived source could be placed in every regional centre.