Radiation Therapy for Cancer: Mechanism, Techniques, and Treatment Course

How Radiation Therapy Works

Ionizing radiation (X-rays, gamma, protons, electrons) damages DNA → cell death or reproductive failure. Cancer cells have impaired repair vs. normal cells.

Mechanisms of Cell Kill

• Direct: Radiation hits DNA → strand breaks (single/double).
• Indirect (predominant): Radiation ionizes water → free radicals (OH•) → DNA damage.
• Death pathways: Mitotic catastrophe (failed division), apoptosis, senescence, autophagy.

Fractionation Rationale

• Total dose divided into daily fractions (1.8-2 Gy typical).
• Allows normal tissue repair (sublethal damage repair, repopulation, reoxygenation, redistribution).
• Therapeutic ratio = tumor control / normal tissue complication.

Modern Delivery Techniques

Technique	Description	Advantage
3D-CRT	Shaped beams from multiple angles	Conforms to target, spares organs
IMRT	Modulated beamlets per field	Highly conformal, dose painting
VMAT/RapidArc	Continuous arc with modulation	Faster, less integral dose
SBRT/SRS	1-5 high-dose fractions	Ablative for small targets
Proton Therapy	Bragg peak (no exit dose)	Superior sparing, pediatric, base of skull
Brachytherapy	Sealed sources inside/near tumor	Steep dose fall-off (prostate, GYN, breast)

Treatment Planning

1. Simulation (CT ± MRI/PET).
2. Target delineation (GTV, CTV, PTV) + OARs.
3. Dose prescription, constraints, optimization.
4. QA, verification, delivery.

Radiosensitivity

• High: Lymphoma, germ cell, small cell Ca, pediatric.
• Low: Melanoma, sarcoma, renal cell, glioma (but still treated).
• Modified by hypoxia, cell cycle, genetic factors (TP53, ATM).

Side Effects

• Acute: Inflammation (dermatitis, mucositis, enteritis), fatigue.
• Late: Fibrosis, vascular damage, second malignancy (rare), organ dysfunction.

Multidisciplinary team: radiation oncologist, medical physicist, dosimetrist, therapists, nurses.