Investigadores del UCLA Health Jonsson Comprehensive Cancer Center han validado una prueba que puede predecir con precisión qué pacientes con cáncer de próstata tienen un mayor riesgo de desarrollar efectos secundarios urinarios duraderos después de recibir radioterapia.
La prueba, llamada PROSTOX, es la primera de su tipo en utilizar microARNs para predecir la toxicidad de la terapia contra el cáncer. Podría ayudar a prevenir la carga de complicaciones a largo plazo al identificar a los pacientes con mayor riesgo antes de que comience el tratamiento.
En un estudio publicado en Clinical Cancer Research, una revista de la American Association for Cancer Research, el equipo de UCLA validó la capacidad de PROSTOX para predecir efectos secundarios urinarios a largo plazo, que pueden incluir dolor en el tracto urinario, sangre en la orina, aumento de la frecuencia de la micción y urgencia o incontinencia urinaria. Los investigadores también descubrieron que diferentes factores genéticos están relacionados con diferentes tipos de efectos secundarios, lo que refuerza la necesidad de enfoques más personalizados para el tratamiento.
A common problem patients may have after radiation is urinary side effects that can disrupt daily life, like frequent trips to the bathroom, pain, and an urgent need to go that doesn’t always come in time.
These side effects can happen right away (acute toxicity), much later (late toxicity), or start early and never go away (chronic toxicity). Even with the most advanced radiation techniques, some patients still develop these side effects, and it’s hard to know how they will respond to the stress of radiation.
In earlier work, Weidhaas and her team discovered that certain inherited genetic differences, especially in areas related to microRNAs, which help control how genes work, can predict how likely someone is to have these side effects. In partnership with MiraDx, the team used this information to develop the genetic test PROSTOX, which identifies 32 unique mirSNPs that are linked to radiation-related side effects and separates patients into low-risk and high-risk groups for developing serious long-term urinary side effects after SBRT. They found people in the high-risk group are about 10 to 12 times more likely to have problems.
In the new study, the researchers set out to confirm that PROSTOX works in a new group of 148 patients with prostate cancer receiving either MRI- or CT-guided SBRT from a phase III clinical trial at UCLA called MIRAGE. In addition, the team used machine learning, a type of artificial intelligence, to develop new models to predict acute and chronic urinary toxicity.
They confirmed that the test can successfully predict which patients will develop significant late urinary toxicity, regardless of whether the radiation was guided by MRI or CT. They also found that PROSTOX wasn’t influenced by other clinical factors, such as age or radiation dose, indicating that it detects an independent, genetic risk for toxicity.
The study also distinguished between two separate types of radiation-induced urinary side effects: chronic toxicity and late toxicity. Using genetic analysis, the team found these forms of toxicity have unique genetic signatures, suggesting they arise from different biological mechanisms.
Late toxicity seems connected to immune system dysfunction and long-term inflammation and chronic toxicity might be more affected by advanced technology, meaning better radiation techniques could help reduce these issues.
