Radiotherapy in Cancer Treatment

Radiotherapy Overview

• Radiotherapy is a cancer treatment that modulates the interaction between radiation and biological systems to increase its effectiveness.
• The goal is to enhance the therapeutic ratio, balancing tumor control with minimal toxicity to healthy tissues.

Learning Objectives

• Students will become familiar with cancer therapies, focusing on radiotherapy.
• They will understand the therapeutic ratio concept.
• They will grasp methods used to enhance the therapeutic ratio.

Quiz 1 Questions

• Identify and rank the three most effective anti-cancer treatments: Chemotherapy, Radiotherapy, Immunotherapy, Surgery, and Combined treatment.
• Is chemotherapy a local treatment? (No)
• Can radiotherapy be used to treat metastases? (Yes)
• Which anti-cancer treatments are non-toxic? (Radiotherapy, Immunotherapy, and Surgery)
• Enhancing the therapeutic index includes strategies to protect normal tissues. (True)

Local vs Systemic Treatments

• Radiotherapy and surgical therapy are local treatments targeting the diseased area directly.
• Chemotherapy, immunotherapy, and targeted therapies are systemic treatments that act on the whole body.

Enhancing the Therapeutic Ratio

• Balancing tumor control and toxicity is crucial.
• Strategies aim to protect normal tissue while maximizing tumor control.

Historical Context

• Victor Despeignes is a pioneer of radiotherapy with an early case study demonstrating tumor volume reduction through X-ray use (1896)
• Initial radiotherapy was limited to local effects and understanding of tissue reactions that might be caused by radiation
• Pierre Curie's experience with radiation-induced tissue damage helps frame the understanding of its effects on healthy tissue (1901)

Improvement of the Therapeutic Index

• Radioprotectors and radiosensitizers can improve the therapeutic index by modifying radiation sensitivity of tumor and normal tissue.
• Graphs demonstrate how these agents can lead to increased tumor control along a range of dosage while minimizing damage to normal tissues.

Improving the Therapeutic Ratio: Tools

• Biological and technological approaches are used to improve the therapeutic ratio.

Enhancing Tumor Killing

• Ways in which treatments improve tumor cell killing were discussed

Cancer Chemotherapy

• Drugs that target various stages of cellular growth and replication are discussed in the diagrams/visuals

Radiotherapy + Chemotherapy Combination

• Milestones in the usage of combined therapy were shown across the years with varying combinations and strategies.
• The usage of several chemotherapeutic drugs with each of the types of radiation therapy were covered

Cytotoxic Agents

• Cytotoxic agents enhance cell killing by altering DNA damage and repair pathways, enhancing apoptosis and cell death.

Cell-cycle Synchronization

• Different drugs have varying effects at different stages of the cell cycle.
• Synchronization can improve the effectiveness of radiotherapy and chemotherapy.

Biological Cooperation

• Radiotherapy can selectively kill hypoxic cells.
• Tumor heterogeneity, epigenetics, and hypoxia are key biological factors considered in treatments.
• Activation of signaling pathways and metabolic adaptations in cancer cells are discussed.

Quiz 2 Questions

• What are the targets of chemotherapy drugs? (Cell proliferation, cell cycle, tumor microenvironment, DNA damage/repair, cell signalling)
• Does combining radiotherapy and chemotherapy enhance anti-tumor efficacy? (True)
• Does combining radiotherapy and chemotherapy enhance normal tissue toxicity? (True)
• Which drugs target DNA repair? (Cisplatin, Mitomycin-C)

Radiation Oncology and Precision Medicine

• Radiotherapy, targeted therapies, and immunotherapy are discussed in combination.

Radiotherapy + Targeted Therapy

• Growth factor, signal transduction, hypoxia, cell cycle, and telomerase targeting are strategies that form part of the combination.

Radiotherapy + Immunotherapy

• Tumor microenvironment, immune cells, and abscopal effects are key components in the combination.

Quiz 3 Questions

• Do targeted drugs inhibit transduction pathways? (True)
• Are all targeted drugs antibodies? (False)
• Do targeted drugs have specific modes of action? (True)
• Do targeted drugs have off-target effects? (True)
• Can targeted drugs be combined with radiotherapy? (True)

Fractionated Radiotherapy

• Fractionated radiotherapy induces immune-mediated abscopal effects when combined with immune checkpoint inhibitors (e.g., CTLA4 antibodies).

3X8 Gy Dose and Volume

• Dose response curves and treatment strategies related to 3X8 Gy were noted

Normal Tissue Sparing

• Normal tissue response to irradiation is dose-rate dependent, but tumour response is not.
• High dose rate is crucial in minimizing normal tissue damage while maximizing tumour destruction.
• Strategies to enhance this balance are important

Fractionation and Enhanced Precision

• Detailed timeline of target volume, 2D/3D planning, stereo-RT, high-precision RT, and TomoTherapy improvements were noted

FLASH Radiotherapy

• FLASH-RT delivers radiation at extremely high doses in short pulses.
• The method can minimize side effects and enhance tumour treatment.
• The impact and rationale of using FLASH-RT was detailed.

FLASH-RT Clinical Trials

• FLASH-RT clinical trials utilize preclinical study technology and parameters.

Proton FLASH Radiotherapy

• A new study that compared high and low dose rates and addressed the efficacy and impact of the therapy technique

Dose and Volume

• Detailed information regarding dose, volume, and the imaging effects and/or changes were included across various time points post treatment

Late Effects

• FLASH-RT appears to reduce late toxicity in animal models and humans compared to conventional doses.

Future Directions

• More research is needed to fully assess the safety and effectiveness of FLASH-RT in clinical settings and for broader application.

Test your knowledge on radiotherapy's role in cancer treatment. This quiz covers key concepts such as therapeutic ratios, treatment tools, and strategies for enhancing tumor killing. Dive into the intricacies of combining radiotherapy with immunotherapy and targeted therapies.