Teaching pack: Radiation Therapy

External beam radiation has moved from 2D fields to intensity-modulated, image-guided, stereotactic, and particle (proton, carbon) therapy. Adaptive and MR-guided delivery, ultra-high dose rate FLASH, and combination with immunotherapy are the frontier. Radiopharmaceuticals deliver radiation systemically to a molecular target.

• AI auto-contouring and adaptive planning: Software that draws organs and tumours on scans automatically, saving hours per patient and making daily plan adaptation practical.
• Boron neutron capture therapy: In boron neutron capture therapy a boron drug accumulates in tumour cells, then a neutron beam makes only those cells explode from inside.
• Brachytherapy: Brachytherapy places a radioactive source directly inside or next to the tumour.
• Carbon-ion therapy: Heavier charged particles that kill even radiation-resistant tumours, available at only a handful of centres worldwide.
• FLASH radiotherapy: Delivering an entire dose in under a second, which in animals spares healthy tissue while still killing the tumour.
• Hyperthermia: Hyperthermia heats tumours to 40-43 °C to make radiation and chemotherapy work better.
• IMRT / IGRT (modern external beam): Radiation shaped precisely to the tumour and checked with daily imaging, sparing surrounding organs.
• Intraoperative radiotherapy (IORT): Giving a single large dose of radiation directly to the tumour bed during surgery, with normal organs moved out of the way; used mainly in breast cancer as an alternative to weeks of external radiotherapy.
• Lattice and GRID radiotherapy: Deliberately treating a big tumour unevenly, with a lattice of very high dose peaks inside it, instead of a uniform dose.
• Magnetic nanoparticle hyperthermia: Magnetic nanoparticle hyperthermia injects iron-oxide nanoparticles into a tumour and heats them from outside with an alternating magnetic field.

• Radical oncology: what could change the war by 2035 · Ideas already being tested against a control arm (current)
• Radical oncology: what could change the war by 2035 · Living drugs, logic gates, and designed proteins reach decision points (emerging)
• Radical oncology: what could change the war by 2035 · Radiation and radiopharmaceuticals get a second act (emerging)
• Radical oncology: what could change the war by 2035 · Monitoring becomes continuous and selection becomes spatial (emerging)
• Radical oncology: what could change the war by 2035 · Writing to the genome and the epigenome inside a tumour (speculative)
• Radical oncology: what could change the war by 2035 · Treating the soil rather than the seed (speculative)

• VISION (phase 3, n=831): Overall survival: 15.3 months vs 11.3 months, HR 0.62
• EORTC 26981 / NCIC CE.3 (Stupp trial) (phase 3, n=573): Overall survival: 14.6 months vs 12.1 months, HR 0.63
• CROSS (phase 3, n=366): Overall survival: 49.4 months vs 24 months, HR 0.68
• KEYNOTE-A18 / ENGOT-cx11 / GOG-3047 (phase 3, n=1,060): Progression-free survival at 24 months: 68% vs 57%, HR 0.7
• PORTEC-3 (phase 3, n=660): Overall survival at 5 years: 81.4% vs 76.1%, HR 0.7
• PSMAddition (phase 3, n=1,144): Radiographic progression-free survival: Updated HR 0.67; OS HR 0.80, immature

1. What did the VISION trial show?
   Answer

   177Lu-PSMA-617 plus standard care improved overall survival (15.3 vs 11.3 months, HR 0.62) in PSMA-positive metastatic castration-resistant prostate cancer after ARPI and taxane.
2. What is FLASH radiotherapy?
   Answer

   Delivering a full radiation dose in under a second at ultra-high dose rates (>40 Gy/s), which spares normal tissue in animal models; first-in-human trials (FAST-01/02, Varian) show feasibility but the clinical benefit is unproven.
3. What is brachytherapy and where is it essential?
   Answer

   Placing a radioactive source directly inside or next to the tumour; essential in cervical cancer, used in prostate (seeds or HDR), breast, skin, and eye melanoma.
4. What is the difference between lutetium-177 and actinium-225 as therapeutic isotopes?
   Answer

   177Lu emits beta particles (range 1-10 mm, crossfire helps bulky heterogeneous tumours, marrow toxicity, 6.7-day half-life); 225Ac emits alpha particles (range 50-100 µm, very high energy, oxygen-independent clustered DNA damage, good for micrometastases, daughter redistribution and supply constraints).