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Oncology- The Role of Unsealed Radionuclides in Oncology

4/4/2025

Oncology- The Role of Unsealed Radionuclides in Oncology
I. Nuclear Medicine in Oncology: The Big Picture
Nuclear medicine uses radioactive substances (radionuclides) to:

Localize tumors: Pinpoint the location of a cancerous growth.
Detect metastases: Identify cancer that has spread to other parts of the body.
Monitor treatment response & detect recurrence: Track how well treatment is working and identify any cancer that comes back.
Deliver targeted radiotherapy: Deliver radiation directly to cancerous cells.

II. Radiolabelled Tracers & Scintigraphy

Radiopharmaceuticals: These are the workhorses. They consist of a radionuclide (the radioactive part) attached to a ligand (a molecule that targets specific cells or tissues). Gamma rays emitted by the radionuclide are detected to create images.
Tumour detection mechanism: Radiopharmaceuticals concentrate in areas of abnormal biological activity, such as tumors, allowing visualization of these areas that are undetectable via cross-sectional imaging like CT or MRI.
Scintigraphy limitations: While scintigraphy offers functional information that CT and MRI lack, it provides less anatomical detail. Often, multiple imaging modalities are used together.
Common Radiopharmaceuticals:
- Iodine-123 (-131): Used for thyroid imaging and therapy.
- Thallium-201 (201Tl) & Gallium-67 (67Ga): Used for various imaging purposes.
- Technetium-99m (99mTc): An ideal radionuclide for imaging due to many favorable characteristics (details below).

III. Imaging Techniques

Gamma Cameras: Traditionally used for planar (2D) and whole-body scintigraphy.
Single-Photon Emission Computed Tomography (SPECT): Uses computer processing to generate cross-sectional (3D) images, offering improved sensitivity and localization compared to planar scintigraphy.
Positron Emission Tomography (PET): Uses positron-emitting radionuclides and provides quantitative tomographic images. Commonly used with 18F-fluorodeoxyglucose (FDG) to measure glucose metabolism in tumors, providing information about tumor vitality, cell turnover, and response to therapy.

IV. Specific Applications & Radionuclides
A. Bone Scintigraphy:

Radiopharmaceuticals: 99mTc-methylene diphosphonate (MDP) or 99mTc-hydroxymethylene diphosphonate (HDP).
Procedure: Injected 2-4 hours before imaging.
Sensitivity: High sensitivity (80-100%) for many cancers (breast, prostate, lung, etc.). Lower sensitivity (around 75%) for others (melanoma, small-cell lung cancer, etc.). "Cold" defects may indicate lesions lacking osteoblastic activity.

B. Thyroid Scintigraphy:

Radiopharmaceuticals: 131I, 123I, and 99mTc (pertechnetate).
131I advantages & disadvantages: Cheap and readily available, but has a long half-life and emits alpha particles, leading to significant radiation exposure.
123I advantages & disadvantages: Excellent imaging properties and shorter half-life but expensive.
99mTc: Trapped in the thyroid temporarily but not permanently incorporated.
Clinical indications: Evaluation of nodules and post-surgery follow-up for differentiated thyroid cancer.

V. Targeted Radiotherapy

Principles: Uses tumor-seeking radiopharmaceuticals. Ideal agents have high tumor-to-background ratios, long retention times in tumors, and emit radiation energetic enough for therapy but with limited penetration to minimize damage to healthy tissues.
Clinically useful radiopharmaceuticals: 131I, 89Sr, 32P, 186Re, 153Sm, 90Y.

A. Iodine-131 (131I) Therapy:

Uses: Treatment of thyrotoxicosis and differentiated thyroid carcinoma (ablation of remaining thyroid tissue after surgery, treatment of recurrent or metastatic disease).

B. 131I-Meta-iodobenzylguanidine (MIBG) Therapy:

Uses: Treatment of neural crest tumors (pheochromocytoma, neuroblastoma, paraganglioma, medullary thyroid carcinoma). Variable success rates (e.g., >50% for malignant pheochromocytoma).

C. Bone-Seeking Radiopharmaceuticals for Metastatic Bone Disease:

Mechanism: Mimic calcium or phosphate to accumulate in areas of high bone turnover (near metastases).
Examples: 89Sr (calcium analogue), 32P, 186Re, HEDP, and 153Sm (phosphate analogues).
89Sr: First systemic treatment for bone metastases in prostate cancer. Provides pain relief and delays disease progression in 75-80% of patients for 1-6 months. Myelosuppression (bone marrow suppression) is a side effect.
32P: Historically used for bone pain relief but limited by bone marrow toxicity.

D. Intracavitary Therapy:

Mechanism: Direct injection of radiopharmaceuticals into body cavities (pleural, pericardial, peritoneal, bladder, CSF, cysts) to target tumors locally, minimizing systemic exposure.
Radiopharmaceuticals: Colloids and monoclonal antibodies labeled with 32P, 90Y, or 131I.

VI. Monoclonal Antibodies (mAbs) in Radioimmunotherapy

Concept: Targeted delivery of radiation using antibodies specific to tumor cells.
Current status: Despite initial promise, radioimmunotherapy has faced numerous challenges and its future remains uncertain.

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Pathology-Intraoperative Radiotherapy (IORT)

4/4/2025

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Pathology-Intraoperative Radiotherapy (IORT)

I. Definition and Principle:

Intraoperative radiotherapy (IORT) delivers a single, high dose of external beam radiotherapy (EBRT) directly to exposed diseased tissue during surgery. This targeted approach aims to minimize radiation exposure to healthy surrounding tissues, reducing morbidity compared to conventional radiotherapy. The radiation source can be orthovoltage X-rays or electrons.

II. Advantages & Disadvantages:

Advantages:

Precise targeting of diseased tissue during surgery.
Reduced radiation damage to healthy tissues.

Disadvantages:

Requires specialized equipment in the operating room.
Increased radiation safety protocols and staff training needed.
Requires a radiation oncologist's presence during surgery.
Risk of significant radiation damage to adjacent normal tissues with a single large dose.
Limited long-term follow-up data.
Potential for inducing secondary malignancies (e.g., sarcomas), particularly in animal studies.
Complex treatment planning due to limited preoperative data on treatment volume.

III. Long-Term Effects and Risks:

Animal studies suggest that IORT doses up to 30Gy carry minimal long-term risk if radiosensitive structures (nerves, blood vessels, spinal cord, bowel) are shielded.
Nerve damage threshold: 20-25Gy, with a 6-9 month latency period.
Secondary malignancy risk: Animal studies (dogs) show a high incidence of sarcomas compared to other modalities. Further human data is needed to ascertain human risk.

IV. Specific Tumor Applications:

The effectiveness and safety of IORT varies across different tumor types:

Tumor Type	Findings
Rectal Cancer	May be beneficial in primary and recurrent cases.
Stomach/Esophagus	Doses up to 20Gy appear safe.
Bile Duct	Potential role in minimal residual disease.
Pancreas	Feasible, but no proven benefits yet.
Head & Neck Cancer	Safe, well-tolerated; encouraging results but limited data. May be helpful for minimal residual or recurrent disease.
Brain Cancer	Poor results.
Other Cancers	Potential benefits in some pediatric cancers, breast cancer, and soft tissue sarcomas.

V. Limitations and Future Directions:

Technical and logistical challenges limit widespread adoption.
Advances in conformal EBRT may reduce the advantage of IORT.
Conventional Conformal Radiotherapy (CRT) offers better reproducibility in setup, dosimetry, and fractionation.
Further research and clinical trials are needed to fully assess IORT's efficacy and safety profile. Current use is primarily limited to specialist centres.

VI. Key Concepts to Remember:

Targeted approach: IORT delivers radiation directly to the tumor during surgery.
Single high dose: A significant advantage but also a significant risk factor.
Limited long-term data: More research is needed to assess long-term effects and risks.
Tumor-specific efficacy: The success of IORT varies greatly depending on the type of cancer.
Technological limitations: Current technology and logistical challenges hinder widespread use.

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Oncology-Brachytherapy

4/3/2025

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Oncology-Brachytherapy
I. Definition and Indications:

Brachytherapy: Radiation therapy where sources are placed within or near the tumor. Crucially, precise tumor extent is vital because treatment targets a small volume, and missing the tumor (geographic miss) significantly increases recurrence risk. Accessibility for source insertion and removal, along with accurate source positioning, is also crucial.

II. Advantages:

High Localized Dose: Delivers a high dose to a small area, maximizing local tumor control while minimizing damage to surrounding normal tissue due to the sharp fall-off of radiation dose.
Short Treatment Duration (2-7 days): Uses low-dose-rate irradiation, leveraging the differing repair/repopulation rates of normal and malignant cells for enhanced therapeutic ratio. This also allows for reoxygenation of initially resistant hypoxic cells, increasing their radiosensitivity.
Compensation for Hypoxic Cells: Higher doses in the tumor center (near sources) help overcome the radioresistance of hypoxic cells often found in avascular/necrotic areas.
Irregular Tumor Treatment: Allows for treatment of irregularly shaped tumors by precise source placement, avoiding critical normal tissues.

III. Disadvantages:

Staff Radiation Exposure: γ-emitting sources expose staff to low but significant radiation. Afterloading techniques and low-energy radionuclides mitigate this risk.
Unsuitable for Large Tumors: Typically not suitable for large tumors; may be used as a boost after external beam radiotherapy (EBRT) and/or chemotherapy.
Accurate Source Positioning Crucial: Dose falls off rapidly (inverse square law), requiring precise source placement. This demands specialized skill and is not universally available.
Limited Treatment Volume: Surrounding structures (e.g., lymph nodes) are not irradiated.

IV. Types of Brachytherapy:

Intracavity: Radioactive material placed within body cavities (e.g., cervix, bronchus, esophagus, bile duct).
Interstitial: Radioactive material inserted into tissues (e.g., prostate, breast, head & neck, anal).
Surface: Radioactive material placed on the tumor surface (e.g., skin, eye).

V. Implant Types:

Manual Insertion: Should be avoided due to radiation hazards to staff.
Afterloading: Radioactive material loaded into pre-inserted applicators (needles, catheters). Reduces staff exposure significantly, allowing for optimal source placement.
- Manual Afterloading: Radioactive material manually loaded into applicators.
- Remote Afterloading: Machines (e.g., Selectron, Microselectron, Cathetron) control source placement, eliminating staff exposure. High-dose-rate remote afterloading often involves multiple outpatient fractions.

VI. Radionuclides:

γ Emitters:
- Radium: Obsolete; radon gas is a hazard.
- Cesium-137: Replaces radium; longer half-life (30 years), less penetrating γ rays.
- Iridium-192: Used in wires or seeds; flexible, advantages in interstitial brachytherapy; shorter half-life (74 days).
- Iodine-125: Used for permanent prostate implants; short half-life (59.6 days), low-energy γ rays allow for early discharge.
β Emitters: Primarily used in eye tumor treatment (strontium-90, ruthenium-106/rhodium-106 plaques).

VII. Dosimetry:

Treatment Planning Systems: Various systems (Paris system, Parker-Paterson, Quimby) are used to plan source distribution. The Paris system, common for iridium wire implants, uses parallel, equidistant wires. Computer calculations and graphs (Oxford cross-line curves) assist in dose calculation.
Dose Prescription: The basal dose rate (mean of minimum values between sources) is calculated. Treatment dose is prescribed to a reference dose line (often 85% of basal dose). Prescription points vary depending on the treatment type (e.g., Manchester A point for gynecological treatments). The ICRU Report 38 recommends reporting dose based on the volume enclosed by a 60Gy isodose line in gynecological treatments.

VIII. Future Developments:

3D Planning: Sophisticated 3D planning using CT or MRI scans for precise dose calculations.
Biological Effective Dose: Incorporating biological effects in dose calculations.
High-Dose-Rate Remote Afterloading: Continues to reduce staff exposure and improve treatment outcomes. High-dose-rate pulsed insertions are increasingly replacing continuous low-dose-rate implants for greater homogeneity.

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Oncology-Electron Beam Therapy

4/3/2025

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Oncology- Electron Beam Therapy
I. Electron Beam Therapy vs. Photon Radiotherapy
A. Fundamental Difference: Electron beams, unlike photons, possess charge. This leads to frequent interactions within tissue, resulting in a defined range of penetration and negligible dose beyond that range. Photons penetrate deeper.
B. Electron Beam Advantages:

Limited penetration: Ideal for superficial tumors, minimizing damage to underlying structures.
Negligible exit dose: Reduces radiation exposure to tissues beyond the target.
Superficial tumor treatment: Particularly useful for skin cancer, head and neck cancers, and breast cancer.
Reduced normal tissue dose: Minimizes damage to critical structures like the spinal cord and lungs.

C. Photon Beam Advantages:

Deep penetration: Suitable for deep-seated cancers.
Skin sparing: Delivers less radiation to the skin surface.
Easier beam matching: Facilitates precise treatment planning with crossfire techniques.

II. Production of Electron Beams

Linear Accelerators: Most radiotherapy facilities use linear accelerators to produce both X-ray and electron beams.
Beam Collimation: Due to significant air scattering, collimators (cones or trimmer bars) are used to shape the beam near the skin's surface. Further shaping can be achieved with lead apertures or lead sheets placed directly on the skin.

III. Dosimetric Characteristics of Electron Beams
A. Depth Dose Characteristics:

Dose buildup: The dose increases gradually to a maximum and then drops sharply to near zero at the practical range.
Practical Range (Rp): The depth at which the dose becomes negligible. Approximated by Rp ≈ E0 / 2. (E0 = incident beam energy in MeV)
Clinically Useful Range (d80): The depth where the dose falls to 80% of its maximum. Approximated by d80 ≈ E0 / 3.
Surface Dose: Significantly higher for electron beams than photon beams (85-95% of maximum dose, depending on energy).

B. Effect of Incident Energy: Higher incident energy (E0) leads to greater penetration depth. Common energies range from 6-15 MeV.
C. Beam Profile and Penumbra:

Larger Penumbra: Electron beams have a larger penumbra (area of dose falloff) than photon beams. A 10x10 cm² beam might only deliver a clinically useful dose to an 8x8 cm² area.
Abutment Challenges: The large penumbra makes combining electron and photon beams difficult, hindering uniform dose delivery across field junctions.

IV. Key Concepts to Remember

Charge and Interaction: Electrons' charge leads to their limited penetration and well-defined range.
Superficial vs. Deep: Electron beams are for superficial tumors, photons for deep-seated ones.
Penumbra: Electron beams have a larger penumbra than photon beams, affecting treatment planning.
Range Calculation: Understand the approximations for practical and clinically useful range based on incident energy.
Surface Dose: Electron beams have a higher surface dose than photon beams.

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Oncology-Recent Advances in External Beam Radiotherapy (EBRT)

4/3/2025

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Oncology-Recent Advances in External Beam Radiotherapy (EBRT)
I. Improved Accuracy and Precision
A. Volume Definition:

Past: Planning scans relied on diagnostic scanners, resulting in less precise tumor volume definition.
Present: High-resolution CT simulators are standard. 3D tumor volume definition is now accurate even for palliative treatments. Fusion of CT with MRI and PET scans further refines this for radical treatments.

B. Image-Guided Radiotherapy (IGRT):

Past: A 1cm margin was added to the Clinical Target Volume (CTV) to account for positioning errors. Megavoltage X-rays provided low-quality confirmation images.
Present:
- Electronic Portal Imaging Devices (EPIDs): Replaced port films, offering improved image quality. Online imaging corrects misalignments before treatment, while offline review identifies recurring setup errors.
- Intra-treatment Imaging: Precise tumor location is confirmed during treatment using:
  - Fiducial markers (e.g., gold seeds)
  - Ultrasound
  - Cone beam CT (mounted on the linear accelerator) for 3D online imaging.

II. Minimizing Radiation Exposure to Organs at Risk & Higher Tumor Doses
A. Inverse Planned Intensity-Modulated Radiotherapy (IMRT):

Mechanism: Computer optimization varies radiation beam intensity to meet dose constraints for healthy organs while delivering prescribed doses to the tumor (CTV and Gross Tumor Volume - GTV). This is achieved through:
- Step and shoot: Superimposing static uniform intensity segments.
- Dynamic MLC delivery: A shaped sliding window across the field.
- Tomotherapy: Multiple arcs with intensity modulated by dynamic MLCs.
Benefits: Reduced late effects on normal tissues with equivalent cancer control compared to conventional radiotherapy, particularly in prostate and head/neck cancers. Promising results in lung and gynecological cancers suggest it may replace 3D conformal radiotherapy (CRT) for many radical treatments.
Drawback: Significantly increases the workload of the physics team due to the extensive time (at least 2 hours per patient) required for meticulous volume definition.

B. Four-Dimensional (4D) Therapy Planning and Delivery:

Addresses the challenge of: Treating mobile structures (e.g., lung cancers moving with respiration).
Method: Links 4D CT planning (tumor volume defined at each respiratory phase) to treatment delivery during the expiratory phase for optimal coverage with minimal field size.

C. Stereotactic Radiotherapy:

Established for: Intracranial conditions (benign tumors, arteriovenous malformations).
Method: High precision (1-2mm) treatment of small lesions (<1cm3) using an external 3D coordinate system and stereotactic fixation. Typically uses 1-3 large fractions (12-20 Gy).
Recent expansion: Successful treatment of small malignancies in the brain, lung, and liver. IGRT facilitates accuracy in sites unsuitable for localization frames.

III. Key Terms & Concepts to Remember:

CTV: Clinical Target Volume
GTV: Gross Tumor Volume
EPID: Electronic Portal Imaging Device
IMRT: Intensity-Modulated Radiotherapy
MLC: Multileaf Collimator
IGRT: Image-Guided Radiotherapy
4D: Four-Dimensional (referring to respiratory gating)

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Oncology-External Beam Radiotherapy: Progress & Techniques

4/3/2025

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Oncology-External Beam Radiotherapy: Progress & Techniques
This study guide summarizes advancements in external beam radiotherapy, focusing on 3D planning and conformal treatment.
I. Three-Dimensional (3D) Radiotherapy Planning:

Revolutionizing Factor: The most significant advancement in the last 20 years is the integration of cross-sectional imaging (primarily CT scans) into radiotherapy planning. This shift enables:
- Accurate Target Definition: Precise delineation of tumors and critical structures.
- Precise Dose Calculation: More accurate determination of radiation dosage.
- True 3D Planning: Allows for:
  - Reduced Normal Tissue Damage: Minimizing harm to healthy tissue.
  - Increased Tumor Dose: Delivering higher radiation doses to the cancerous target.
  - Improved Therapeutic Index: Optimizing the balance between tumor control and side effects.

Key takeaway: 3D planning using CT scans significantly improves accuracy and allows for better treatment optimization, leading to improved outcomes.
II. Conformal Treatment and Multileaf Collimators (MLCs):

Goal: The primary goal of radiotherapy has always been to precisely conform the high-dose radiation to the target tumor while sparing surrounding healthy tissue.
Traditional Limitations: Until the 1990s, rectangular beams with limited blocking techniques resulted in unnecessary irradiation of normal tissue.
Advancements:
- Shaped Alloy Blocks: Improved conformation by manually placing shaped blocks to partially obstruct the radiation beam.
- Multileaf Collimators (MLCs): A significant advancement integrated into modern linear accelerators. MLCs allow for computer-controlled shaping of the radiation beam using numerous 0.5cm-wide leaves. This enables highly precise shaping of the radiation field.
Clinical Significance: By minimizing high-dose radiation to normal tissue, MLCs enable higher radiation doses to the tumor, potentially improving tumor control without increasing the risk of side effects (morbidity).

Key takeaway: MLCs are a crucial technology for conformal radiotherapy. They allow for precise shaping of the radiation beam, maximizing tumor dose while minimizing damage to healthy tissues. This improves the therapeutic ratio, aiming for better tumor control with fewer side effects.

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Oncology--External Beam Radiotherapy (EBRT)

4/3/2025

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Pathology-External Beam Radiotherapy (EBRT)
I. Types of EBRT
A. Superficial X-ray Therapy (80-300 kV): Used for superficial tumors (skin, ribs). Low-energy X-rays are generated by accelerating electrons in an X-ray tube, which then strike a tungsten anode causing bremsstrahlung radiation. Beam size is controlled by metal applicators.
B. Cobalt Teletherapy (Co-60): Uses gamma rays (1.25 MeV average energy) from Co-60 source for deeper tumors. Requires high source strength (around 350 TBq) for adequate dose rate.
C. Megavoltage Radiotherapy (4-20 MV): Most common method, using linear accelerators to produce high-energy X-rays. Offers advantages over Co-60: * Higher penetration * Higher dose rate * Better collimation (precise beam targeting)
D. Electron Therapy (4-20 MeV): Linear accelerators can also generate electron beams. These are suitable for superficial tumors, providing uniform treatment to a specific depth with a rapid dose fall-off beyond that depth. Depth of penetration depends on electron energy (e.g., 6 MeV ≈ 1.5 cm, 20 MeV ≈ 5.5 cm). Offers an alternative to kilovoltage X-rays for superficial tumors.
Limitations of Low-Energy X-ray Beams:

Unsuitable for deep-seated malignancies (thorax, abdomen, pelvis).
High skin dose.
Rapid dose fall-off with depth.
Higher bone dose compared to soft tissue.

II. Features of Megavoltage X-rays

High dose delivered at depth.
Maximum dose below the skin surface (skin-sparing effect).
Exponential dose fall-off with depth.
Sharp dose fall-off at beam edge (penumbra).
Beam shape modification via metal blocks or multileaf collimators.
Dose gradient creation using metal filters or wedges.
Treatment from any direction is possible.
Crossfire technique (2-4 beams) enhances target dose while sparing normal tissues.

III. EBRT Planning Process (Six Steps)
Step 1: Beam Dosimetry: Measuring the dose distribution pattern of each linear accelerator using an ionization chamber in a water tank. Calibration factors (output factors) are determined to calculate irradiation time for a specified dose.
Step 2: Planning Computer: Computer software uses measured beam data and algorithms to account for tissue density variations (often from CT scans) in dose calculations. Simpler planning can be done using tables or plots.
Step 3: Target Drawing: Defining the target volume to be irradiated. This includes: * GTV (Gross Tumor Volume): Visible tumor on imaging or clinical examination. * CTV (Clinical Target Volume): GTV plus surrounding tissue with potential microscopic tumor cells. * PTV (Planning Target Volume): CTV plus margins to account for setup uncertainties (patient positioning, organ movement, machine calibration). Critical organs (spinal cord, eyes, kidneys) are also defined.
Step 4: Dose Planning: Designing a treatment plan to uniformly irradiate the target while keeping critical organ doses within tolerance. Adjustable parameters include: * Patient position * Beam size & shape * Beam direction * Number of beams * Relative dose per beam (beam weight) * Wedging * Compensators
Step 5: Treatment Verification: Ensuring correct beam positioning and avoiding critical organ over-irradiation. Methods include: * Radiographs on a simulator. * Megavoltage radiographs or EPIDs (Electronic Portal Imaging Devices) during treatment. * In vivo dosimetry (thermoluminescence dosimeters) – the gold standard for radical treatments.
Step 6: Treatment Prescription and Delivery: The oncologist prescribes the dose, fractionation schedule, and beam configuration. This information is entered into the linear accelerator's computer system to control treatment delivery.

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Oncology-Radiotherapy Fractionation

4/3/2025

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Oncology- Radiotherapy Fractionation

I. Core Concepts:

Objective of Fractionation: To determine the optimal combination of total radiation dose (Gy), number of doses (fractions), and overall treatment time to effectively target cancer while minimizing damage to healthy tissues.
Linear Quadratic (LQ) Model: This model describes how tissues respond to radiation. Early-reacting tissues (e.g., skin) show a linear relationship between dose and damage (α component). Late-reacting tissues (e.g., spinal cord) exhibit a quadratic relationship, meaning damage increases disproportionately with dose (β component). The LQ model supports the use of many small fractions to minimize late-reacting tissue damage.

II. Fractionation Schedules:
Two main approaches exist:
A. Few Large Daily Fractions:

Advantages: Fewer patient visits, less resource consumption, faster tumor response, reduced tumor repopulation during treatment.
Disadvantages: Limits total safe dose, increases risk of late tissue damage, reduced reoxygenation potential (which improves radiotherapy effectiveness), often insufficient to eradicate all cancer cells.

B. Many Small Daily Fractions:

Advantages: Less severe acute reactions (due to longer treatment time), reduced late tissue damage, allows for higher total dose, maximizes reoxygenation, potentially eradicates all cancer cells, allows dose reduction if acute reactions are unexpectedly severe.
Disadvantages: Increased resource and patient demand, potential for tumor repopulation during prolonged treatment, prolonged acute reactions may require supportive care.

III. Tumor and Tissue Radiosensitivity:

Tumor Radiosensitivity: Varies widely. Some tumors (lymphoma, seminoma) are highly radiosensitive, requiring lower doses. Others (gliomas, sarcomas) are radioresistant.
Normal Tissue Tolerance Doses (2Gy per fraction): These are maximum doses before significant late damage occurs:
- Testis: 2 Gy
- Lens of the eye: 10 Gy
- Whole kidney: 20 Gy
- Whole lung: 20 Gy
- Spinal cord: 50 Gy
- Brain: 60 Gy
Inter-fraction Interval: At least 6 hours should separate fractions to allow for tissue repair. With once-daily fractionation, nearly all repair occurs before the next treatment.

IV. Advanced Fractionation Techniques:

Hyperfractionation: Delivers many small fractions (<2Gy) to increase total dose without increasing late tissue damage. May involve weekend treatments or multiple daily treatments.
Accelerated Radiotherapy: Shortens overall treatment time to reduce tumor repopulation during treatment. Often combined with hyperfractionation (e.g., ChaRT regimen). Example: ChaRT (Continuous Hyperfractionated Accelerated RadioTherapy) delivers 54 Gy in 1.5 Gy fractions three times daily for 12 days.

V. Treatment Intent and Regimen Selection:
A. Radical Radiotherapy (Curative Intent):

Goal: Highest tolerable dose for maximal cancer eradication.
Lower doses used for highly radiosensitive tumors or microscopic residual disease.
Multiple daily fractions (~2Gy) minimize late damage.
Significant acute toxicity is acceptable due to potential survival benefit.
Requires patient fitness for daily attendance.

B. Palliative Radiotherapy (Symptom Relief):

Goal: Quick symptom relief, may not impact survival significantly.
Lowest effective dose and fraction number are preferred.
Avoid prolonged acute damage; late effects may be irrelevant.
High-dose palliative radiotherapy may be appropriate in specific advanced cases with durable local disease control as a goal and reasonable life expectancy.

VI. Key Considerations for Studying:

Understand the LQ model: This is fundamental to understanding why fractionation is used.
Compare and contrast: Clearly differentiate between few large vs. many small fractions, highlighting advantages and disadvantages of each.
Know tolerance doses: These are crucial for safe treatment planning.
Understand advanced techniques: Grasp the principles behind hyperfractionation and accelerated radiotherapy.
Distinguish treatment intent: Recognize how treatment goals (radical vs. palliative) influence regimen selection.

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Oncology-Radiobiology of Normal Tissues

4/3/2025

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Oncology-Radiobiology of Normal Tissues

I. Mechanisms of Radiation Damage:

Apoptosis: Programmed cell death occurring within 24 hours of irradiation. Primarily affects specific cell types (e.g., some hematopoietic cells, salivary gland cells). Often clinically insignificant due to tissue redundancy and stem cell replacement.
Loss of Reproductive Capacity: Reduces the ability of cells to proliferate. The timing of damage manifestation depends on the tissue's cell renewal rate, leading to the distinction between acute and late effects. This is the predominant mechanism in most tissues.

II. Radiosensitivity:

Radiosensitivity varies greatly between tissues (see Table 1).

Radiosensitivity	Tissue
Highly Sensitive	Lymphocytes, Germ cells
Moderately Sensitive	Epithelial cells
Resistant	CNS, Connective tissue

Table 1: Radiosensitivity of Normal Tissues

III. Acute vs. Late Effects:

Acute Effects (within 8 weeks of treatment): Primarily affect rapidly proliferating tissues (skin, mucosa, hematopoietic system). Predominantly caused by loss of reproductive capacity, impacting cell replacement. Severity depends on total dose and treatment duration. Complete recovery is usually expected with properly selected treatment doses. Examples include erythema, desquamation, mucositis. The speed of recovery depends on stem cell survival.
Late Effects (months to years after treatment): Primarily affect slowly proliferating tissues (lung, kidney, heart, CNS, connective tissue). Severity depends on total dose and dose per fraction (smaller fractions offer protection). Recovery may be incomplete. Examples include fibrosis, telangiectasia, radiation pneumonitis, nephropathy, cardiomyopathy. Late effects are not always predictable from the severity of acute reactions.

IV. Specific Tissue Responses:

Skin: Acute – erythema, desquamation, ulceration (if severe). Late – atrophy, fibrosis, telangiectasia.
Oral Mucosa: Acute – erythema, ulceration. Late – dry mouth.
Gastrointestinal Tract: Acute – mucositis (oesophagitis, nausea/vomiting, diarrhoea, tenesmus). Late – ulceration, fibrosis, obstruction, necrosis.
Central Nervous System (CNS): No acute reaction. Late – demyelination (somnolence, Lhermitte's syndrome), radiation necrosis.
Lung: Acute – airway obstruction (with large single doses). Late – pneumonitis, fibrosis.
Kidney: No acute response. Late – nephropathy (proteinuria, hypertension, renal failure).
Heart: Late – pericarditis, cardiomyopathy, conduction blocks.

V. Normal Tissue Tolerance to Retreatment:

Some tissues (e.g., CNS) show significant recovery from subclinical radiation injury, allowing safe retreatment in certain circumstances.

VI. Carcinogenesis:

Radiation-induced DNA damage can lead to secondary malignancies (leukemias, solid tumors) years after exposure. The thyroid and breast are particularly susceptible, especially in childhood/young adulthood. This risk must be weighed against the risk of cancer recurrence.

VII. DNA Repair:

The body can repair some radiation-induced DNA damage. A minimum 6-8 hour gap between radiotherapy fractions is necessary for sufficient repair to prevent excessive normal tissue damage. Hereditary DNA repair defects can significantly increase the risk of severe normal tissue reactions to radiotherapy.

VIII. Hypoxia:

Hypoxic (oxygen-deficient) cells are less sensitive to radiation. Tumor hypoxia is common and can be aggravated by anemia. Tumor response and subsequent reoxygenation during fractionated radiotherapy can enhance tumor cell kill.

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Oncology -Radiation Oncology

4/3/2025

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Oncology -Radiation Oncology

I. Introduction to Radiation Oncology (Radiotherapy)

Definition: Treatment of malignant disease using ionizing radiation, primarily high-energy X-ray beams (External Beam Radiotherapy - EBRT).
Significance: Arguably the most important non-surgical cancer therapy, used in over 50% of cancer patients.

II. Historical Perspective: Key Milestones

This timeline highlights the evolution of radiotherapy techniques and understanding:

Year	Milestone	Significance
1896	Discovery of X-rays	Foundation of radiotherapy.
1898	Discovery of radium	Provided another source of ionizing radiation for treatment.
1899	Successful skin cancer treatment with X-rays	First documented successful cancer treatment using radiation.
1915	Cervical cancer treatment with radium implant	Introduction of brachytherapy (internal radiation therapy).
1922	Cure of laryngeal cancer with X-ray therapy	Demonstrated curative potential of external beam radiotherapy (EBRT).
1928	Roentgen defined as radiation exposure unit	Standardized radiation measurement.
1934	Dose fractionation principles proposed	Crucial development for optimizing treatment and minimizing side effects.
1950s	Radioactive cobalt teletherapy (1MV energy)	Advancement in technology for delivering radiation.
1960s	Megavoltage X-rays from linear accelerators	Significant improvement in radiation delivery precision and depth.
1990s	3D radiotherapy planning	Enhanced precision in targeting tumors.
2000s	IMRT, IGRT, Stereotactic radiotherapy	Advanced techniques for highly precise and targeted radiation delivery.

III. Mechanism of Action

Energy Absorption: X-rays passing through tissue cause ionization of molecules, producing fast-moving electrons and free radicals.
DNA Damage: The most crucial biological effect is DNA damage, including double-strand breaks. This damage leads to cell death, particularly in rapidly dividing cancer cells.
Unit of Dose: Gray (Gy) - energy absorbed per unit mass (J/kg).

IV. Fractionated Radiotherapy

Principle: Delivering radiation in small, daily doses (fractions) over several days or weeks.
Benefits:
- Preferential sparing of normal tissue: Allows higher total doses to be safely administered.
- Increased cancer cell kill: While minimizing damage to healthy tissue.
Mechanism: Allows normal tissue repair between fractions, while cancer cells, which often have impaired repair mechanisms, accumulate damage leading to their death.