Clinical approach and Radiotherapy principles.pptx

CLINICALAPPROACH TO CANCER
PATIENTS AND PRINCIPLES OF
RADIOTHERAPY
Presenter: Omayido Jesse Esabu
Fellow: Dr. Odala Friday
Facilitators: Dr. Kibudde Solomon
Dr. Kavuma Awusi
4th
/08/2025

Outline on approach to cancer patients
• Definition
• History taking
• Physical examination
• Investigations
• Modalities of treatment
• Follow up
• Supportive care
• Role of multidisciplinary approach to management

Definition
Cancer is a group of more than 100 different diseases that are characterized
by uncontrolled cellular growth, local tissue invasion, and distant metastases
Etiology
• Carcinogenesis
A cancer, is thought to develop from a cell in which the normal mechanisms
for control of growth and proliferation are altered.
Two major genes are involved in carcinogenesis and these are :
• Oncogenes
• Tumor suppressor genes

Global Cancer Observatory by Ferlay J. et al.. (2024)

History taking
Identify risk factors, symptoms, and possible cancer types.
 Chief Complaint: Duration, nature (e.g., lump, bleeding, pain).
 Symptom Analysis: Constitutional symptoms (fever, weight loss, night sweats).
 Past Medical History: Chronic diseases (e.g., HIV, hepatitis), previous cancer.
 Family History: Hereditary cancers (e.g., BRCA in breast/ovarian cancer).
 Social History:
o Smoking, alcohol, occupational exposure (asbestos,).
o Lifestyle (diet, physical activity).
 Drug History: Prior chemo, immunosuppression, hormone use.
Gynecologic/ Obstetric History (for female patients): Menstrual history, pregnancies, contraceptive
use, Pap smear history

Physical examination
Evaluate for signs of cancer, metastasis, and patient fitness for treatment.
 General examination: Vital signs, performance status (ECOG), pallor,
cachexia, lymphadenopathy,jaundice
 Local examination: Palpation of mass, size, mobility, tenderness, skin
changes
 Regional lymph nodes: Evaluation of draining nodes
 Systemic exam: chest, abdomen, neurological status to detect
metastases

Investigations
• Establish diagnosis, stage cancer, and assess fitness for therapy.
Laboratory Tests:
• CBC, LFTs, RFTs, tumor markers (e.g., PSA, CA-125, AFP)
Imaging:
• X-ray, Ultrasound, CT, MRI, PET scan for staging
• Bone scan (for bony metastases)
Histopathology:
• Biopsy (FNAC, core, excisional)
• Immunohistochemistry and molecular markers
Genetic testing:
• BRCA, EGFR depending on cancer type

Modalities of treatment
Apply individualized, evidence-based treatments.
A. Surgery
 Curative (early-stage cancers).
 Palliative (e.g., obstruction).
 Diagnostic (biopsy).
B. Chemotherapy
 Neoadjuvant (before surgery).
 Adjuvant (after surgery).
 Palliative (advanced disease).
Side effects: Neutropenia, nausea, mucositis.

Modalities cont.…
C. Radiotherapy
 External beam, brachytherapy.
 Curative or palliative.
Side effects: Skin burns, mucositis, fatigue.
D. Targeted Therapy
 Monoclonal antibodies (trastuzumab, rituximab).
 Tyrosine kinase inhibitors (imatinib, erlotinib).

Modalities cont…
E. Immunotherapy
 Checkpoint inhibitors (nivolumab, pembrolizumab).
 Adoptive T-cell therapy
F. Hormonal Therapy
 Tamoxifen, aromatase inhibitors (breast).
 Androgen deprivation (prostate).

Follow up
Monitor for recurrence, complications, and quality of life.
Follow-Up Strategies:
 Interval-based: Every 3–6 months for 2 years, then annually.
 Monitoring tools: Imaging, tumor markers, physical exam.
 Assessment:
o Recurrence or metastasis.
o Late side effects (cardiomyopathy, secondary malignancies).
 Rehabilitation: Speech therapy, physiotherapy, occupational therapy.

Supportive care
 Pain management: WHO analgesic ladder.
 Nutritional support: Supplements, enteral feeding.
 Psychological support: Counseling, psychiatric care.
 Palliative care: Symptom control, hospice care.
 Infection prevention: Neutropenic precautions.
 Social and spiritual support: Support groups.

Role of multidisciplinary approach to management
Goal: Collaborative, patient-centered decision-making.
Team Members:
 Medical, radiation oncologists,surgeons.,Pathologists, radiologists, palliative care team,
nurses, social workers.
Benefits:
 Comprehensive care plans.
 Evidence-based and individualized treatment.
 Coordinated care and better communication.
 Improved patient satisfaction and outcomes.

Multi disciplinary team Functions:
 Tumor board meetings.
 Joint decision-making.
 Continuous re-evaluation of care

Principles of radiotherapy
Contents
1. Introduction
2. Radiobiology and MOA
3. Techniques
4. Treatment process

• Radiotherapy (RT), or radiation therapy, is a clinical modality that uses
ionizing radiation to control or kill malignant cells.
• The principles are rooted in radiobiology, physics, and clinical
oncology.

Mechanism of Action
DNA Damage: Ionizing radiation damages cancer
cells primarily by causing damage to their DNA.
This can be:
• Direct Action ≈ 15%: The radiation directly
ionizes atoms within the DNA molecule,
leading to breaks in the sugar-phosphate
backbone, hydrogen bonds
• Indirect Action ≈ 85% : More common for
X-rays and gamma rays.
• Radiation ionizes water molecules within
the cell, producing highly reactive free
radicals (e.g., hydroxyl radical, •OH).
• The free radicals then diffuse to and
damage DNA
Cell Death: Extensive DNA damage that is unrepaired or
mis-repaired, leads to cell death through several
mechanisms:
• Mitotic Catastrophe: Cells attempt to divide with
damaged chromosomes, leading to lethal errors
during mitosis. This is the predominant mode of
cell death for many cancer cells after irradiation.
• Apoptosis: Programmed cell death of damaged
cells
• Senescence: Irreversible cell cycle arrest
• Autophagy: organelles and proteins degraded by
lysosomes.

Clinical approach and Radiotherapy principles.pptx

The 6 R's of Radiobiology (Fractionation):
Multiple small doses (fractions) over several weeks rather than a single large dose.
Exploits biological differences between tumor cells and normal surrounding tissues
• Repair: Normal tissues generally have a greater capacity to repair sublethal DNA damage between
fractions than tumor cells. Fractionation allows time for this repair in normal tissues.
• Reassortment (Redistribution): Cells vary in radiosensitivity throughout the cell cycle (M and G2 phases
are most sensitive; late S phase is most resistant).
• Repopulation: Both tumor cells and normal cells can proliferate during a course of RT.
• Reoxygenation: Tumors often contain hypoxic regions, more radioresistant (2-3 times) than well-
oxygenated cells. As the tumor shrinks, some previously hypoxic regions may become reoxygenated,
thus more sensitive to subsequent fractions.
• Radiosensitivity: The intrinsic sensitivity of cells to radiation varies. This inherent difference can be
exploited, although it's less influenced by fractionation itself.
• Reactivation of the Immune Response: Radiation can induce immunogenic cell death, releasing tumor
antigens. This can stimulate the host's immune system to recognize and attack cancer cells

Therapeutic Ratio:
The goal of RT is to maximize tumor control
probability (TCP) while minimizing normal
tissue complication probability (NTCP).
The "therapeutic ratio" is the balance
between these two outcomes.
Techniques and fractionation schedules are
designed to widen this ratio

• External Beam Radiotherapy (EBRT): Radiation is delivered from a machine outside the body,
typically a linear accelerator (LINAC).
• 3D Conformal Radiotherapy (3D-CRT): Uses CT imaging to create a 3D tumor model, allowing
radiation beams to be shaped to match the tumor's dimensions.
• Intensity-Modulated Radiotherapy (IMRT): An advanced form of 3D-CRT where the intensity of
each radiation beam is modulated, allowing for highly conformal dose distributions that spare
adjacent normal tissues more effectively.
• Volumetric Modulated Arc Therapy (VMAT): A form of IMRT where the LINAC rotates around the
patient, delivering radiation continuously while the beam shape and intensity change.
• Stereotactic Radiotherapy (SRT): Delivers very high doses of radiation to small, well-defined
targets in a few fractions.
• Stereotactic Body Radiotherapy (SBRT) or Stereotactic Ablative Radiotherapy (SABR) for
extracranial sites.
• Stereotactic Radiosurgery (SRS) for intracranial sites, often in a single fraction.
• Particle/Hadronic Therapy: Uses high energy particles like protons, neutrons. Protons deposit
most of their energy at a specific depth (Bragg peak), with minimal exit dose, potentially
reducing dose to normal tissues beyond the target.

Cont…
• Brachytherapy (Sealed Radiotherapy): Radioactive sources are placed directly into or near the
tumor.
• Intracavitary: Sources placed in body cavities (e.g., cervix, uterus).
• Interstitial: Sources implanted into tissues (e.g., prostate).
• Can be Low Dose Rate (LDR) or High Dose Rate (HDR).
• Systemic Radioisotope Therapy (Radiopharmaceutical Therapy): Radioactive drugs are
administered orally or intravenously, which then travel through the body to target cancer cells
(e.g., iodine-131 for thyroid cancer, Lutetium-177 for prostate cancer).

Consultation: Patient evaluation, discussion of treatment options.
Simulation (CT Simulation): Patient is immobilized in the treatment position, and a CT scan acquired to
create a 3D model for planning.
Contouring: The radiation oncologist defines the GTV, CTV, PTV, Organs at Risk (OARs) are also
delineated.
Treatment Planning: Medical physicists and dosimetrists use specialized software to design beam
arrangements and calculate dose distributions to achieve the prescribed dose to the PTV while
minimizing dose to OARs.
Quality Assurance (QA): The treatment plan is verified before delivery.
Treatment Delivery: Radiation is delivered according to the plan, typically daily for several weeks.
Follow-up: Monitoring for response and side effects.

Volume definitions
• Gross tumor volume(GTV); is the primary tumor or other tumor mass shown
by the clinical exam or imaging.
• Clinical target volume(CTV); contains GTV when present and/or subclinical
microscopic disease that has to be eradicated to cure the tumour
• Planning target volume(PTV); denotes the CTV and includes margins for
geometric uncertainties. Also accounts for variations in treatment setup and
other anatomic motion during Rx
• Organ motion/ internal margin; accounts for variations of motion of different
organs

Volume definitions
• Treated volume; this is the volume of tissue that is planned to receive a
specified dose and is enclosed by the isodose surface corresponding to
that dose level e.g 95%
• Conformity index; the ratio of PTV to the treated volume and indicates
how well the PTV is covered by the treatment while minimizing dose to
normal tissues
• Irradiated volume; this is the volume of tissue that is irradiated to a dose
considered significant in terms of normal tissue tolerance & is dependent
on Rx technique used
• Organs at risk (OAR); critical normal tissues who radiation sensitivity may
significantly influence Rx planning.

Toxicity:
• Acute Effects: Occur during or shortly after treatment (e.g., skin
redness, fatigue, mucositis). Generally reversible.
• Late Effects: Occur months to years after treatment (e.g., fibrosis,
secondary malignancies, organ dysfunction). Can be permanent.

Scoring systems
• ECOG Performance Status (or WHO/Zubrod score):
• Scale: 0 to 5
• ECOG 0-1, sometimes 2 are generally eligible for more intensive, curative-intent
radiotherapy regimens, often combined with chemotherapy.
• Patients with poor performance status (ECOG 3-4) may only be candidates for palliative
radiotherapy with shorter, less toxic regimens, or no radiotherapy
• Karnofsky Performance Status (KPS):
• Scale: 100 down to 0 , in decrements of 10.
• Similar to ECOG, gauges a patient's fitness for treatment.
• A KPS ≥70 is often a threshold for more aggressive therapies.

References
 National Comprehensive Cancer Network (NCCN) Guidelines
 WHO Cancer Management Guidelines
 DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology
 UpToDate articles on cancer management
 Basic oncology text book , second edition
 Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A,
Soerjomataram I, Bray F (2024). Global Cancer Observatory:
 Radiopedia
 Principles and Practice of Radiotherapy the techniques in Thoracic. Gokhon O., Vgur S.,Ekan T.
Springer International publishing Switzerland 2016

Clinical approach and Radiotherapy principles.pptx

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