What Happens Inside the Body During Radiation Therapy

The Physics of a Therapeutic Beam: Photons, Electrons, Protons, and Precision

Radiation therapy begins as a choreography of particles and waves. Clinical machines accelerate particles to high energies, then deliver beams measured in gray (Gy), where 1 Gy equals 1 joule of energy absorbed per kilogram of tissue. The practical goal is simple but demanding: deposit enough energy in tumor cells to stop their ability to reproduce, while limiting energy to nearby healthy tissue. That balance is pursued through careful planning, image guidance, and choices among different beam types, each with distinct depth and dose characteristics.

Photons (high‑energy x‑rays) are the workhorse for deep tumors because they penetrate through the body, depositing dose along their path with a gradual falloff. Electrons are useful for superficial targets—skin and shallow tissues—because their energy drops sharply after a short range. Protons travel differently: they release most of their energy at a particular depth (the Bragg peak), allowing planners to sculpt dose that rises inside the tumor and tapers beyond it. Each approach is tailored to tumor location, size, and sensitivity.

Planning stitches physics to anatomy. A planning CT maps the patient’s geometry; planners contour targets and risk organs, then optimize beam angles, shapes, and intensities. Modern collimation can segment a beam into many tiny “leaves,” shaping dose with millimeter attention. Fractionation—delivering treatment in daily portions, commonly around 1.8–2 Gy per session—exploits biology (more on that later) and allows normal tissues to repair between visits. Total prescribed doses vary by disease and intent, often ranging from a few Gy for palliation to 60–70 Gy for certain curative courses.

It helps to picture dose as a heat map that must fit the tumor like a glove without singeing nearby organs. Image guidance before each session checks alignment to account for setup variation and internal motion from breathing or digestion. The tools are precise, but the body moves; margins around the target are intentionally added to ensure coverage, then refined with motion management techniques when needed.

At a glance, different beams trade penetration for precision:

– Photons: versatile depth, gradual exit dose; suitable for many deep sites.
– Electrons: shallow penetration; focused on surface or near-surface lesions.
– Protons: concentrated dose at set depths; helpful next to sensitive structures.

Energy Meets Biology: Ionization, Free Radicals, and DNA Damage Cascades

Once a beam enters tissue, physics hands the baton to chemistry. Charged particles and high‑energy photons interact with atoms and molecules, causing ionizations—small jolts that rip electrons free. About two‑thirds of the biological effect for low‑LET radiation (like photons and electrons) arises indirectly: energy splits nearby water molecules, generating short‑lived but potent reactive oxygen species, including hydroxyl radicals. These radicals diffuse nanometers—the scale of DNA—and damage nucleic acids, proteins, and membranes.

DNA is prime real estate in this story. The most consequential lesions are double‑strand breaks (DSBs), where both strands in the helix snap near one another. Single‑strand breaks and base modifications are common too, and while cells repair many of them efficiently, unrepaired or misrepaired DSBs are strongly linked to cell death or malfunction. High‑LET radiation (such as heavier ions) creates dense clusters of damage that are harder to fix; in contrast, low‑LET tracks seed damage more sparsely.

Oxygen matters because it “fixes” radical‑induced damage into lasting lesions—a concept reflected in the oxygen enhancement ratio. Well‑oxygenated tumor regions are therefore more radiosensitive than hypoxic pockets. Clinically, fractionation can help reoxygenate tumors between daily treatments as blood flow and cellular turnover change local conditions. Meanwhile, cell cycle position also tunes sensitivity: cells are generally more vulnerable in late G2 and M phases than in S phase, where DNA repair machinery runs hot.

Think of a treatment session as a flurry of micro‑events: in a cubic millimeter of tissue, millions of ionizations carve tracks only nanometers wide, yet collectively tip the scales of cellular fate. The dose is macroscopic—measured in Gy—but the consequences are microscopic, unfolding across femtoseconds for ionization, milliseconds for radical chemistry, and hours to days for biological responses.

Key takeaways on energy-to-damage links:

– Indirect action dominates for photons/electrons via water radiolysis and radicals.
– Double‑strand DNA breaks carry the highest stakes for survival.
– Oxygen makes damage “stick,” while hypoxia can blunt effect.
– Sensitivity waxes and wanes with the cell cycle stage.

Cell Decisions Under Stress: Repair Pathways, Checkpoints, and Tumor Biology

After the chemical spark, cells face a decision tree governed by sensors, repair crews, and internal brakes. Damage sensors recruit repair complexes to DNA, and the cell activates checkpoints at G1/S and G2/M to pause the cycle. Two main double‑strand break repair routes take center stage: non‑homologous end joining (NHEJ), a quick but sometimes error‑prone method that ligates ends, and homologous recombination (HR), a more precise template‑based process favored in S/G2 when a sister chromatid is available. The balance between these pathways shapes whether a cell survives with integrity, accumulates mutations, or fails to divide.

Outcomes vary:

– Successful repair and cell cycle restart: the cell lives to function another day.
– Apoptosis: programmed cell death removes damaged cells cleanly.
– Mitotic catastrophe: the cell enters division with unresolved damage and fails.
– Senescence: the cell exits the cell cycle, remaining metabolically active but non‑dividing.

Tumors and normal tissues do not play by the same rules. Many cancers harbor defects in checkpoints or HR components, making them more reliant on faster, error‑prone pathways; this can heighten radiosensitivity or alter how they accumulate lethal errors across fractions. Conversely, some tumors contain quiescent or hypoxic cells that are relatively resistant on a given day, only to become more vulnerable as reoxygenation and reassortment occur between sessions. This is where the classic “four Rs” of radiobiology connect to the clinic: repair (of sublethal damage in normal tissues), reassortment (cells moving into more sensitive phases), repopulation (cells dividing between fractions), and reoxygenation (improved oxygen supply to previously hypoxic tumor zones).

Clinicians harness these principles through fractionation schedules and dose per fraction choices. Many curative regimens use daily fractions around 1.8–2 Gy to promote normal tissue repair while cumulatively overwhelming tumor cells’ imperfect repair capacity. In certain settings, higher dose per fraction schedules can be used to exploit specific radiobiologic vulnerabilities, though this demands careful protection of nearby organs.

Under the hood, a cell’s fate is not just a coin toss—it’s a weighted vote informed by DNA integrity, redox balance, checkpoint fidelity, and microenvironmental cues. When therapy works as intended, the tumor’s clonogenic cells (those capable of indefinite division) are eliminated across the course, even if some non‑clonogenic cells persist for a time.

Beyond the Cell: Tissue Microenvironment, Vessels, and Immune Cross‑Talk

Zooming out to the tissue level reveals a landscape shaped by blood vessels, connective matrix, nerves, immune cells, and resident stem cells. Radiation perturbs this ecosystem in staged ways. In the short term, endothelial cells lining blood vessels can become leaky, shifting local oxygen and nutrient delivery. Cytokines such as interleukins and TGF‑β rise and fall over days to weeks, orchestrating inflammation and repair. Fibroblasts respond by modifying the extracellular matrix; depending on dose and organ, this can restore architecture or, later, lead to fibrosis and stiffness.

Immune effects are not a side note—they can be central. When irradiated tumor cells die, they release antigens and danger signals that can prime dendritic cells and recruit T cells. This process, sometimes dubbed immunogenic cell death, helps the immune system “see” the tumor more clearly. Pathways like cGAS‑STING can be triggered by cytosolic DNA fragments, amplifying type I interferon signals. In some patients, immune activation in and around the irradiated site correlates with better local control; rarely, effects beyond the field (the so‑called abscopal phenomenon) have been observed.

Different organs reflect these dynamics with their own signatures. The gut’s fast‑turnover lining may become inflamed quickly yet often heals rapidly once therapy ends. The lung, with delicate alveoli and capillaries, can show early inflammation that in a subset of cases evolves into later‑stage fibrosis if cumulative dose to large volumes is high. Salivary glands are sensitive, with dryness tied to dose delivered to glandular tissue; careful planning aims to spare portions where feasible. In the brain, white matter changes and vascular responses can develop slowly, again tied closely to dose and volume.

Consider these tissue‑scale patterns:

– Early phase (days–weeks): vascular leakiness, cytokine surges, transient inflammation.
– Intermediate (weeks–months): remodeling of matrix and partial functional recovery.
– Late (months–years): risk of fibrosis or chronic changes if high dose reached sensitive structures.

The throughline is dose distribution over space and time. By shaping beams to conform around targets and by fractionating dose, planners try to tap into tissues’ capacity for coordinated repair while minimizing the conditions that set the stage for lasting change.

Sensations and Side Effects: Acute vs. Late Changes and How the Body Protects Itself

What patients feel is the macro expression of the micro events above. Acute effects arise in tissues with rapid cell turnover or high inflammatory sensitivity. Fatigue is common and multifactorial: a mix of immune signaling, modest metabolic shifts, and the daily routine of treatment. Skin in the beam path may redden, warm, or itch as basal cells and microvessels react. In the mouth and throat, mucositis can make swallowing uncomfortable; in the abdomen, temporary nausea or bowel changes may appear. Most of these calm down after sessions end as epithelial layers repopulate and inflammatory cues quiet.

Late effects emerge more slowly and are closely linked to total dose, dose per fraction, and the volume of normal tissue exposed. They may involve subtle changes—stiffness from fibrosis, reduced gland function, or altered sensation. These risks are managed proactively through careful planning constraints that cap how much dose organs receive. For example, heart and lung regions near chest targets are given strict limits; in the head and neck, salivary glands and swallowing structures receive particular attention. Motion management (breath‑holding or gating) and image guidance help keep dose off critical areas by ensuring the plan matches anatomy each day.

Patients can support their bodies’ defenses in simple, evidence‑aligned ways:

– Gentle skincare in the beam area, avoiding harsh friction or extreme temperatures.
– Balanced nutrition and hydration to fuel repair and maintain weight.
– Light, regular activity—like short walks—to combat fatigue and preserve function.
– Clear communication with the care team about symptoms so adjustments and supportive medicines can be considered.

Acute versus late is not just a timeline; it reflects tissue biology. Rapidly dividing surfaces feel radiation’s presence early; slower, structural tissues declare their response later. Both are influenced by how precisely the dose fits the target and how generously normal tissue is spared. The overall aim is durable tumor control with side effects that are manageable and temporary where possible, anchored by planning discipline and the body’s own capacity to heal.