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.

• Accelerator-based BNCT systems (NeuCure, nuBeam, NeuPex): Boron neutron capture therapy used to need a nuclear reactor. These hospital-sized accelerators make the neutron beam instead, and in 2020 Japan approved the first one, with its boron drug, for head and neck cancers that have come back or cannot be removed.
• Acupuncture for dry mouth after head and neck radiotherapy: Radiotherapy to the head and neck can permanently dry the mouth. A randomised trial in the United States and China found that acupuncture given during radiotherapy reduced dry mouth a year later compared with standard care, an effect that needs confirming.
• Adaptive radiotherapy (online replanning): Re-shaping the treatment plan to the anatomy of the day, using the images taken on the treatment couch, so the dose follows a shrinking tumour or a moving bladder.
• 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.
• Biology-guided radiotherapy (RefleXion X1, SCINTIX): A radiotherapy machine with PET detectors built in: the tumour's own radioactive tracer signal tells the beam where to fire, hundreds of times a second, so moving tumours and several metastases can be tracked and treated without external markers.
• 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.
• Bowel function after pelvic radiotherapy: New bowel symptoms after radiotherapy to the prostate, cervix, womb, bladder or rectum are common and are often treated as something to live with. They usually have several separate and treatable causes, and a trial showed that working through them with a written algorithm, delivered by a nurse or a gastroenterologist, improved symptoms more than a self-help booklet.
• Brachytherapy: Brachytherapy places a radioactive source directly inside or next to the tumour.
• C-arm medical linear accelerators (TrueBeam, Versa HD and others): The standard radiotherapy machine: an electron accelerator in a rotating arm that makes high-energy X-rays or electron beams, shapes them with moving metal leaves, and takes a CT of the patient before each dose. Most people who have radiotherapy are treated on one.
• Carbon-ion synchrotrons and facilities: Carbon ions are twelve times heavier than protons, so every clinical facility uses a synchrotron ring tens of metres across and fixed or huge rotating beamlines. Only about a dozen centres exist, in Japan, Germany, Italy, Austria, China, South Korea and Taiwan.

• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · A cancer with a visible precursor, and the first proof that finding it early saves lives (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Total mesorectal excision, and radiotherapy before the operation (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Chemotherapy after the operation, and how small the benefit is when the nodes are clear (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · The screening programmes, and the discovery that uptake is the whole game (current)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Antibodies, and the two things that decide whether they work (current)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · The genome, the subtypes and the hypermutated sixth (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · The cause is named, and cancer epidemiology is invented to name it (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Cytotoxic chemotherapy, and the ceiling it hit (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · EGFR, ALK, and the invention of precision oncology in solid tumours (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Low-dose computed tomography earns its place, and chest radiography loses its (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Immunotherapy, and the trouble with PD-L1 as a gate (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Stage III, and treatment moving to either side of the operation (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Two viruses, found because lymphoma is the cancer you can get hold of (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · How little is enough: the Hodgkin de-escalation programme begins (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Reading the genes, and the twenty years it took to make that useful (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Everything that failed to beat R-CHOP, and the one thing that did (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · The scan after two cycles, and what it is good for (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Indolent lymphoma: how long to treat, and the two-year mark that splits the disease (current)
• 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)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · From X-rays to conformal beams (historic)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · Modulation, image guidance and fewer fractions (historic)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · Radiation plus drugs: what worked and what did not (current)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · Particles, magnets and adaptation (current)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · Doing less: fewer visits and fewer treatments (current)
• Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH · FLASH, arcs, upright and new particles (emerging)

• VISION (phase 3, n=861): Overall survival: 15.3 months vs 11.3 months, HR 0.62
• EORTC 26981 / NCIC CE.3 (Stupp trial) (phase 3, n=575): Overall survival: 14.6 months vs 12.1 months, HR 0.63
• NRG Oncology RTOG 0521 (phase 3, n=612): Overall survival at 4 years: 93% vs 89%, HR 0.69
• Intergroup 0096 (Turrisi): twice-daily versus once-daily thoracic radiotherapy (phase 3, n=417): Overall survival at 5 years: 26% vs 16%
• CROSS (phase 3, n=366): Overall survival: 49.4 months vs 24 months, HR 0.68
• RTOG 94-08 (phase 3, n=1,979): Overall survival at 10 years: 62% vs 57%, HR 1.17

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).

• NCI: Radiation therapy to treat cancer: https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy