Radiation Therapy: How It Works, Types, and Side Effects

Radiation therapy is the use of high-energy ionizing radiation to damage the DNA inside cancer cells, preventing them from dividing and causing them to die. It is one of the most important and widely used treatments in oncology — more than half of all cancer patients receive radiation therapy at some point during their care, either as a primary treatment, in combination with surgery or chemotherapy, or to relieve symptoms.

Unlike chemotherapy, which circulates throughout the bloodstream to reach cancer cells anywhere in the body, radiation therapy is a local and regional treatment: it targets a specific area, making it particularly effective for tumors confined to one site, for treating tissue where cancer has been surgically removed, or for ablating a defined number of metastatic sites. This article covers how radiation therapy works, the different delivery techniques available today, how treatment is planned, and how side effects are prevented and managed. For an overview of how radiation fits within all treatment options, see the cancer treatment options guide.

97.6% 3-year primary tumor control for inoperable early-stage lung cancer with SBRT (RTOG 0236)

42.9% vs. 33.4% 5-year overall survival: durvalumab + CRT vs. CRT alone for Stage III unresectable NSCLC (PACIFIC trial)

28.4% vs. 14.3% Pathologic complete response: short-course RT + chemo vs. long-course CRT for rectal cancer (RAPIDO trial)

5 fractions Ultra-hypofractionated whole-breast RT (26 Gy over 1 week) non-inferior to 5-week course at 5 years (FAST-Forward trial)

How Radiation Therapy Works — Radiobiology

Radiation therapy deposits energy in tissue through ionization — removing electrons from atoms. This process creates reactive oxygen species (primarily hydroxyl radicals from water molecules) that cause double-strand DNA breaks, the most lethal form of DNA damage. Single-strand breaks are repaired efficiently by both normal and cancer cells; double-strand breaks are far harder to fix.

Cancer cells are particularly vulnerable because they divide more rapidly (placing them more often in vulnerable cell cycle phases) and because they typically have defective DNA repair pathways — the same mutations that drive cancer growth impair their ability to recover from radiation. Normal cells with intact repair mechanisms recover between treatment sessions, which is why radiation is almost always given in multiple fractions rather than as a single large dose.

The 4 Rs of Radiobiology

Repair: Normal cells repair sublethal radiation damage between fractions more effectively than cancer cells — fractionation exploits this differential
Repopulation: Both tumor and normal cells divide between fractions; overall treatment time must balance against tumor repopulation
Redistribution: Radiation kills cells in radiosensitive phases (G2/M); surviving cells redistribute to more sensitive phases before the next fraction
Reoxygenation: Hypoxic tumor cells are up to 3× more radioresistant than oxygenated cells; after radiation kills well-oxygenated cells, previously hypoxic cells reoxygenate — increasing the effect of subsequent fractions

Fractionation and the α/β Ratio

The α/β ratio describes how sensitive a tissue is to fraction size. Tumors with a low α/β ratio (prostate ~1.5–2 Gy; breast ~3–4 Gy) are more sensitive to larger fractions — making them ideal candidates for hypofractionation (fewer, larger fractions), which delivers equivalent or superior tumor control with equivalent or reduced late toxicity. Tumors with a high α/β ratio (~10 Gy; head and neck carcinomas) are relatively insensitive to fraction size, and conventional fractionation (1.8–2 Gy/fraction) is appropriate.

This radiobiology is why modern prostate cancer treatment now uses 5 SBRT fractions rather than 39–40 conventional fractions, and why whole breast irradiation is routinely completed in 15 fractions rather than 25.

Types of Radiation Therapy

IMRT / VMAT

Computer-optimized external beam; modulates thousands of beamlets to sculpt dose around the tumor. Standard for H&N, prostate, gynecologic, lung, and rectal cancers. VMAT delivers same dose in 3–10 min via rotating arc.

SBRT / SABR

3–5 high-dose fractions with stereotactic precision. 97.6% tumor control for early lung cancer (RTOG 0236); non-inferior for prostate (PACE-B); 5-yr OS 42.3% vs. 17.7% for oligomets (SABR-COMET).

Stereotactic Radiosurgery (SRS)

Single-fraction intracranial treatment. Gamma Knife (brain mets, AVM); CyberKnife. NCCTG N0574 (JAMA 2016): SRS alone vs. SRS + WBRT — no OS difference; WBRT worsens cognition. SRS alone now preferred for 1–3 brain mets.

Proton Therapy

Bragg peak: maximum dose at target depth, near-zero beyond. Reduces dose to distal normal tissue. Established benefit: pediatric tumors, base of skull, uveal melanoma. Not uniformly superior to IMRT for adult solid tumors.

Brachytherapy

Internal radioactive sources. LDR: permanent prostate seeds (I-125/Pd-103). HDR: temporary Ir-192 catheter for cervical cancer boost, breast APBI, endometrial. GEC-ESTRO: brachytherapy boost superior to EBRT-only for cervical cancer.

IGRT + Adaptive (MR-Linac)

Daily cone beam CT corrects for organ motion and setup variation before each fraction. MR-linac (Elekta Unity, ViewRay MRIdian) enables daily MRI-guided replanning — particularly valuable for H&N and abdominal tumors.

SBRT and Oligometastatic Disease

The SABR-COMET trial (Palma DA et al., *Lancet* 2019; 5-year update 2020) randomized patients with 1–5 metastatic sites to SABR (stereotactic ablative radiotherapy) versus palliative standard of care. At 5 years, overall survival was 42.3% vs. 17.7% — a potential paradigm shift suggesting that eliminating all identifiable metastatic sites with ablative RT may be curative in some patients with limited metastatic disease. This finding has generated multiple ongoing confirmatory trials. For more on the minimally invasive approach of SBRT, see the minimally invasive cancer treatment guide.

The Brain Metastasis Standard: SRS vs. WBRT

NCCTG N0574 (Brown PD et al., JAMA 2016)

213 patients with 1–3 brain metastases randomized to SRS alone vs. SRS + whole-brain radiation therapy (WBRT). Result: no overall survival difference, but WBRT significantly worsened cognitive function at 3 months (52.4% vs. 23.7% cognitive deterioration rate) and reduced quality of life. SRS alone is now the preferred standard for patients with 1–3 brain metastases with adequate PS — WBRT reserved for diffuse disease or leptomeningeal involvement.

Radiation Planning — From Simulation to Treatment

Every radiation therapy course begins with a CT simulation — a dedicated CT scan acquired with the patient in the exact treatment position, using custom immobilization devices: thermoplastic masks for head/neck and brain tumors; stereotactic body frames for SBRT; wing boards or breast boards for breast cancer. For lung and liver SBRT, 4D-CT captures tumor motion through the entire breathing cycle.

The radiation oncologist then defines treatment volumes based on the ICRU reporting framework:

GTV (Gross Tumor Volume): Macroscopic tumor visible on imaging (CT, MRI, PET)
CTV (Clinical Target Volume): GTV + margin for microscopic extension beyond what imaging shows
ITV (Internal Target Volume): CTV + internal motion margin (breathing, organ filling)
PTV (Planning Target Volume): ITV + setup uncertainty margin for daily positioning variation

The medical physicist creates the treatment plan through computer optimization — selecting beam angles, modulating intensity, and meeting dose constraints for Organs At Risk (OARs):

Spinal cord: maximum dose ≤45–50 Gy
Parotid glands (H&N RT): mean dose ≤26 Gy to preserve salivary function
Lung: V20Gy ≤30% (percentage of lung receiving ≥20 Gy) to limit pneumonitis risk
Rectum (prostate RT): V70Gy ≤20% to reduce late bleeding risk

After plan approval via Dose-Volume Histogram (DVH) review, treatment begins. Each daily visit takes 15–30 minutes total — the radiation beam is on for only 2–5 minutes. IGRT imaging confirms positioning before each fraction.

Cancer Type	Fractionation Schedule	Key Evidence
Head & neck	70 Gy / 35 fr (conventional, once daily)	RTOG 91-11: concurrent CRT superior larynx preservation
Breast (whole breast)	40 Gy / 15 fr OR 26 Gy / 5 fr	START B (15 fr) 10-yr equivalent; FAST-Forward (5 fr) 5-yr non-inferior
Prostate (SBRT)	36.25 Gy / 5 fr (every other day)	PACE-B: 5-yr DFS 95.8% vs. 94.8% conventional
Lung Stage I (SBRT)	54 Gy / 3 fr OR 50 Gy / 5 fr	RTOG 0236: 97.6% 3-yr primary control
Stage III NSCLC (CRT)	60–66 Gy concurrent with chemo	PACIFIC: 5-yr OS 42.9% with durvalumab consolidation
Rectal cancer (SCRT)	25 Gy / 5 fr → systemic chemo → surgery	RAPIDO: pCR 28.4% vs. 14.3% long-course CRT
Cervical cancer	45–50.4 Gy + weekly cisplatin → brachy boost	GEC-ESTRO: brachy boost superior to EBRT-only
Brain mets (SRS)	15–24 Gy / 1 fr (Gamma Knife / CyberKnife)	NCCTG N0574: SRS alone preferred; WBRT worsens cognition

radiation therapy linear accelerator IMRT cancer treatment — A linear accelerator (linac) delivers IMRT radiation therapy — computer-optimized beams sculpt dose around the tumor while protecting nearby structures.

Radiation Combined with Other Cancer Treatments

Radiation therapy is rarely used alone — it is most commonly integrated with chemotherapy (concurrent chemoradiation), surgery, or immunotherapy to achieve superior outcomes.

Concurrent Chemoradiation (CRT)

Cisplatin is the most widely used radiosensitizer. Its mechanism: cisplatin impairs cancer cells’ ability to repair radiation-induced DNA double-strand breaks, increasing cell kill beyond either treatment alone. Key concurrent CRT regimens:

Head and neck SCC: Cisplatin 100 mg/m² every 3 weeks × 3 (or weekly 40 mg/m²) concurrent with 70 Gy; RTOG 91-11 showed superior larynx preservation with concurrent vs. sequential chemotherapy-then-RT or RT alone
Cervical cancer: Weekly cisplatin 40 mg/m² concurrent with 45–50.4 Gy EBRT → intracavitary brachytherapy boost; standard of care since the 1999 NCI clinical announcement across five simultaneous trials
Stage III unresectable NSCLC: Concurrent CRT (carboplatin + paclitaxel weekly or cisplatin + etoposide) followed by 12 months durvalumab (PACIFIC trial): 5-year OS 42.9% vs. 33.4%; median OS 47.5 months vs. 29.1 months
Rectal cancer: Capecitabine or 5-FU concurrent with 45–50.4 Gy (long-course); or short-course 25 Gy/5 fractions followed by FOLFIRINOX → surgery (RAPIDO: pCR 28.4% vs. 14.3%)

Radiation After Surgery

Post-operative radiation reduces local recurrence by treating microscopic residual disease. Key applications:

Breast-conserving surgery (lumpectomy): whole breast RT achieves equivalent long-term survival to mastectomy (NSABP B-06)
Post-mastectomy RT (PMRT): standard when ≥4 lymph nodes involved, T3/T4 tumor, or positive margins
Prostate: salvage RT to prostate bed after radical prostatectomy for biochemical failure

For more on how radiation integrates with surgical decisions and the combined modality approach, see the cancer surgery guide. See also the cancer treatment overview for how all modalities work together.

Side Effects of Radiation Therapy

Radiation side effects divide into acute effects (during treatment and up to 90 days after — reflect rapidly dividing normal cell injury; generally reversible) and late effects (more than 90 days after treatment, sometimes years later — reflect vascular damage and fibrosis; may be permanent).

Acute Side Effects by Site

Contact Your Team Immediately For:

Fever during radiation therapy (may signal infection in a compromised patient); severe difficulty swallowing or breathing; chest pain or severe shortness of breath developing after thoracic radiation (possible radiation pneumonitis); persistent rectal bleeding or inability to urinate after pelvic radiation.

Head and neck: Oral mucositis (painful mouth sores, peaks at weeks 3–5 of a 7-week course); xerostomia (dry mouth — IMRT parotid-sparing at mean dose ≤26 Gy significantly reduces this); dysphagia (swallowing exercises during treatment preserve function); skin dermatitis
Breast: Radiation dermatitis (redness, skin irritation, and moist desquamation in skin folds; gentle washing and aqueous creams); fatigue (graded exercise recommended by ACSM)
Thoracic: Radiation pneumonitis (cough, dyspnea developing 1–6 months after thoracic RT; prevented by keeping V20Gy <30%; treated with prednisone 60 mg/day × 6-week taper); esophagitis during concurrent CRT
Pelvis: Acute radiation proctitis (loose stools, urgency, rectal bleeding — resolves within weeks after RT); urinary symptoms during prostate RT (frequency, urgency, dysuria — managed with alpha-blockers)
Brain: Cerebral edema (dexamethasone during WBRT); fatigue; hair loss only within the radiation field

Late Radiation Effects

Xerostomia: Permanent salivary gland damage from high-dose H&N RT; IMRT parotid sparing reduces grade 2+ xerostomia significantly
Radiation fibrosis: Progressive fibrosis in irradiated soft tissue — lung fibrosis, breast tissue changes, limb lymphedema with nodal RT
Osteoradionecrosis: Mandibular bone necrosis after H&N RT >60 Gy — precipitated by dental extraction; require dental clearance before RT; treated with hyperbaric oxygen and surgical debridement
Brain radiation necrosis: Occurs in ~5% after radiosurgery; bevacizumab reduces MRI changes and neurologic symptoms; advanced MRI (perfusion, spectroscopy) and PET distinguish from tumor recurrence
Hypothyroidism: Common after neck irradiation; annual TSH monitoring recommended indefinitely
Cardiac effects: Late coronary artery disease after left-sided breast RT and mediastinal RT (Hodgkin lymphoma); modern techniques (deep inspiration breath-hold, cardiac-sparing IMRT) minimize cardiac dose
Secondary malignancy: Small but real risk (~0.2% at 10 years); higher concern in younger patients and larger treatment volumes

Frequently Asked Questions

What is radiation therapy and how does it work?

Radiation therapy uses high-energy ionizing radiation — photons (X-rays, gamma rays), protons, or charged particles — to damage the DNA inside cancer cells. When cancer cell DNA is damaged through double-strand breaks, the cells cannot divide and eventually die. Normal cells repair radiation-induced DNA damage more effectively than cancer cells, which is why radiation therapy is delivered in fractions — multiple smaller doses allow normal tissue to recover between treatments while cancer cells accumulate lethal damage. The treatment may be delivered externally (from a machine outside the body), internally (brachytherapy, where radioactive sources are placed inside the body), or both. According to the National Cancer Institute, radiation therapy is used to treat nearly every type of solid tumor and some hematologic malignancies.

What is the difference between SBRT and conventional radiation therapy?

Conventional radiation therapy delivers 1.8–2 Gy per fraction over 25–39 sessions (5–8 weeks). SBRT (stereotactic body radiotherapy) delivers 6–20 Gy per fraction in 3–5 sessions — a dramatically higher dose per fraction requiring submillimeter accuracy. SBRT’s biologically effective dose is substantially higher, making it ablative: more like destroying the tumor than gradually shrinking it. RTOG 0236 showed 97.6% 3-year primary tumor control with lung SBRT for inoperable early-stage disease. SBRT is appropriate for tumors that can be precisely defined on imaging and are away from critical structures — early-stage lung, liver, prostate, spine, and limited metastatic sites. Conventional fractionation remains preferred for large tumors, tumors adjacent to bowel or optic nerves, and sites where hypofractionation hasn’t been adequately validated in randomized trials.

Does radiation therapy hurt?

The radiation beam itself is completely painless — you cannot feel it, hear it, or see it during treatment. A treatment session feels no different from lying still for a standard X-ray. What patients experience over time is the tissue response: radiation dermatitis (skin redness and soreness within the treatment field), mucositis (mouth sores for head and neck RT), esophagitis, or proctitis — these develop over weeks during the course and peak 2–3 weeks after completion, then resolve over the following weeks. Side effects are entirely site-specific: a prostate cancer patient will not experience mouth sores; a head and neck patient will not experience rectal symptoms. Your radiation oncology team will prescribe specific medications (mouth rinses, topical creams, anti-inflammatory drugs, pain medications) for the side effects expected from your specific treatment site.

What are the most common side effects of radiation therapy?

Side effects depend entirely on which part of the body is treated. Common acute effects include fatigue (nearly universal regardless of site), skin reaction within the radiation field, and site-specific tissue effects: mucositis and xerostomia for head and neck RT; radiation dermatitis for breast RT; radiation proctitis and urinary urgency for pelvic RT; radiation pneumonitis (1–6 months after thoracic RT). Late effects include xerostomia (permanent after high salivary gland doses without IMRT parotid sparing), soft tissue fibrosis, osteoradionecrosis (jaw bone) in the setting of high head and neck doses, and at very long follow-up, a small risk of secondary malignancy and cardiac effects (with left-sided breast or mediastinal RT). According to the ASTRO patient guide, most acute side effects resolve within 2–4 weeks of completing radiation therapy.

How long does a radiation therapy course last?

Duration varies widely based on cancer type, treatment intent, and fractionation schedule: curative head and neck treatment takes 7 weeks (35 fractions, daily Monday–Friday); whole breast RT now takes 3 weeks (15 fractions, START B) or just 1 week (5 fractions, FAST-Forward); prostate SBRT takes 1.5–2 weeks (5 fractions on alternating days); lung SBRT takes 1–2 weeks (3–5 fractions); palliative RT for pain or bleeding may be given in 1–5 fractions over 1 week; cervical cancer treatment takes 5–6 weeks of external beam plus 4–5 brachytherapy sessions. Each daily visit to the radiation center takes 15–30 minutes total — the beam is actually on for only 2–5 minutes. Most of the visit time is spent on IGRT setup verification and positioning.

Can radiation therapy cure cancer?

Yes — radiation therapy achieves cure in many settings. Stage I–II non-small cell lung cancer treated with SBRT achieves greater than 90% local control in patients who cannot undergo surgery. Localized prostate cancer treated with EBRT or brachytherapy has long-term cure rates equivalent to surgery. Early nasopharyngeal cancer achieves ~80–90% local control with cisplatin plus RT. Early Hodgkin lymphoma is cured in approximately 95% of patients with combined chemotherapy and RT. Lumpectomy plus radiation achieves the same long-term overall survival as mastectomy for early breast cancer (NSABP B-06). In Stage III unresectable NSCLC — historically considered incurable — concurrent chemoradiation followed by durvalumab (PACIFIC trial) now achieves 5-year overall survival of 42.9%. Radiation also contributes to cure as part of combined modality treatment, reducing local recurrence risk after surgery in breast cancer, rectal cancer, cervical cancer, and sarcoma.

Timmerman R et al. — RTOG 0236 (SBRT for inoperable early NSCLC); JAMA 2010
Brand DH et al. — PACE-B (prostate SBRT vs. conventional RT); Lancet Oncology 2019
Palma DA et al. — SABR-COMET (SABR for oligometastatic disease); Lancet 2019; 5-yr update 2020
Brown PD et al. — NCCTG N0574 (SRS vs. SRS + WBRT for brain mets); JAMA 2016
Antonia SJ et al. / Spigel DR et al. — PACIFIC (durvalumab after CRT for Stage III NSCLC); NEJM 2017; JCO 2022
Haviland JS et al. — START B (40 Gy/15 fr breast hypofractionation); Lancet Oncology 2013
Murray Brunt A et al. — FAST-Forward (26 Gy/5 fr breast); Lancet 2020
Bahadoer RR et al. — RAPIDO (short-course RT + chemotherapy for rectal cancer); Lancet Oncology 2021
Pötter R et al. — GEC-ESTRO (brachytherapy boost for cervical cancer); Radiotherapy & Oncology 2011
National Cancer Institute — Radiation Therapy to Treat Cancer
ASTRO — RT Answers — Patient Information

This article is for educational purposes only and does not constitute medical advice. Discuss all radiation therapy decisions with your radiation oncology team.