Toward Precision Radiotherapy: The Role of RSI and GARD in Personalized Treatment

Radiotherapy has long been a cornerstone in cancer treatment, yet its application often follows a one-size-fits-all approach. This standardization can limit effectiveness and increase side effects because tumors and patients vary widely in their response to radiation. The French Society for Radiation Oncology (SFRO) has recently taken a significant step toward changing this by endorsing two genomic tools—the Radiosensitivity Index (RSI) and the Genome-based Adjusted Radiation Dose (GARD)—in their 2025 guidelines. These tools offer a promising path to truly personalized radiotherapy, where treatment is tailored to the unique biology of each tumor.

Understanding Radiosensitivity and Its Importance

Radiosensitivity refers to how susceptible cancer cells are to damage from radiation. Tumors with high radiosensitivity respond well to lower doses, while radioresistant tumors may require higher doses for effective control. Traditionally, radiation doses have been standardized, often based on tumor type and stage, without considering individual tumor biology. This approach can lead to under-treatment or overtreatment, affecting patient outcomes and quality of life.

The SFRO’s recognition of RSI and GARD marks a shift toward integrating genomic data into clinical decision-making. These tools predict tumor radiosensitivity, enabling oncologists to adjust radiation doses more precisely.

What is the Radiosensitivity Index (RSI)?

The Radiosensitivity Index is a genomic signature derived from the expression of specific genes linked to radiation response. It provides a score that estimates how sensitive a tumor is to radiation. A lower RSI score indicates higher radiosensitivity, suggesting that the tumor may respond well to standard or even reduced radiation doses. Conversely, a higher RSI score points to radioresistance, signaling the need for dose escalation or alternative strategies.

RSI has been validated across multiple cancer types, including breast, lung, and head and neck cancers. Its ability to stratify patients based on tumor biology helps avoid unnecessary toxicity and improves the chances of tumor control.

How GARD Enhances Dose Personalization

While RSI predicts radiosensitivity, the Genome-based Adjusted Radiation Dose (GARD) translates this information into actionable treatment plans. GARD combines the RSI score with the planned radiation dose to calculate a personalized radiation dose that maximizes tumor control while minimizing harm to normal tissues.

For example, two patients with the same cancer type but different RSI scores might receive different radiation doses based on their GARD values. This approach moves beyond fixed dosing schedules, allowing treatment intensity to be guided by the tumor’s genetic profile.

Clinical Evidence Supporting RSI and GARD

The SFRO’s 2025 guidelines classify RSI and GARD as supported by Level II evidence. This means there is strong clinical data from well-designed studies backing their use in dose personalization. Several retrospective and prospective studies have demonstrated that using these tools can improve treatment outcomes:

• Patients with low RSI tumors showed better local control and survival rates when treated with standard doses.

• Patients with high RSI tumors benefited from dose escalation guided by GARD, reducing recurrence rates.

• Incorporating these models helped reduce radiation-induced toxicity by avoiding overtreatment in radiosensitive tumors.

  
  

These findings suggest that RSI and GARD can refine radiotherapy plans, balancing efficacy and safety.

Practical Implications for Oncologists and Patients

Implementing RSI and GARD in clinical practice requires genomic testing of tumor samples, which is increasingly accessible with advances in molecular diagnostics. Oncologists can use these tools to:

• Identify patients who may need higher or lower radiation doses.

• Avoid unnecessary side effects by tailoring dose intensity.

• Combine radiotherapy with other treatments based on tumor biology.

• Improve patient counseling by providing personalized risk-benefit information.

  
  

For patients, this means treatments that are more likely to be effective and less likely to cause severe side effects, improving overall quality of life during and after therapy.

Challenges and Future Directions

Despite promising results, some challenges remain before RSI and GARD become standard care worldwide:

• Integration into routine clinical workflows requires education and infrastructure.

• Cost and reimbursement policies for genomic testing must be addressed.

• Combining radiosensitivity data with other biomarkers could further enhance personalization.

  
  

The SFRO’s endorsement is a critical milestone that encourages further research and adoption of these tools.

Summary

The SFRO’s 2025 guidelines highlight the Radiosensitivity Index and Genome-based Adjusted Radiation Dose as valuable tools for personalizing radiotherapy. By predicting tumor response to radiation, these models allow oncologists to tailor doses to each patient’s tumor biology. This approach promises to improve treatment outcomes, reduce side effects, and move cancer care closer to precision medicine.

Clinicians and researchers should consider incorporating RSI and GARD into practice and trials to refine radiotherapy further. Patients stand to benefit from treatments designed specifically for their unique cancer profiles, marking a new era in radiation oncology.

For those interested, the full open-access SFRO paper is available here: Tumour and normal tissue radiosensitivity: update — SFRO 2025 recommendations.