International Journal of Radiation Oncology Biology Physics最新文献

Background: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiotherapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients.

Methods: Cancer patients receiving thoracic RT (2019-2022) were prospectively enrolled at [Anonymized for Review]. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and up to 12 months post-RT. TL was measured using quantitative PCR, and multi-pathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation (FM-HCR) assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve.

Results: Pre-RT TL decreased with age (0.44% lower per year, 95% CI: 0.12%, 0.77%) and advanced cancer stage (6.87% lower per step increase of stage, 95% CI: 3.45%, 10.16%). Radical RT was associated with telomere shortening (3.7% lower, 95% CI: 0.27%, 7.07%) in PBMCs, detectable up to 6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8oxoG repair capacity mediating 12.8% of RT-induced TL shortening.

Conclusions: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared to static measures. Further studies are needed to fully determine the clinical utility of TL.

Purpose: Stereotactic magnetic resonance imaging-guided adaptive radiation therapy (SMART) has emerged as a treatment for localized prostate cancer with excellent acute toxicity outcomes. However, long-term outcomes have not been reported. This study reports on long-term outcomes of SMART for prostate cancer in a single institution.

Methods and materials: We included consecutive patients with localized prostate cancer treated with SMART in an institutional prospective database comprising all risk categories. Treatment was delivered in 5 fractions of 7.25 Gy with daily online adaptation, preferably within 2 weeks. Acute and late toxicity as well as biochemical recurrences were routinely assessed during follow-up. Biochemical recurrence was defined by Phoenix criteria (prostate-specific antigen nadir + 2), and local, regional, or distant recurrence was confirmed by PSMA PET-CT imaging.

Results: From 2016-2021, 464 patients were analyzed. Median age was 72 years (range, 50-89) and the majority of patients had intermediate (50.0%) or high (44.8%) risk prostate cancer based on EAU guidelines. Acute gastrointestinal and genitourinary toxicity grade ≥2 rates were 5.2% and 19.8%, and cumulative late gastrointestinal and genitourinary toxicity grade ≥2 rates were 0.2% and 6.5%, respectively. After a median follow-up of 48.8 months (IQR, 36.3-63.5), 76 recurrences (16.4%) were recorded, most occurred in the high-risk group. Estimated 5-year freedom from biochemical or clinical failure for low-, intermediate-, and high-risk subgroups was 100% (95% CI, 100-100), 77.7% (95% CI, 68.2-84.7) and 74.9% (95% CI, 66.2-81.7), respectively. Incorporation of diagnostic imaging in tumor staging improved risk stratification and led to corresponding rates of 100% (95% CI, 100-100), 85.5% (95% CI, 76.6-91.2), and 71.6% (95% CI, 63.2-78.4).

Conclusions: In this large cohort of patients with prostate cancer treated with SMART, acute and late toxicity was low. Biochemical and clinical control for high-risk patients was lower than for low- and intermediate-risk patients. Improved staging refines risk classification, guiding treatment intensification such as dose escalation in high-risk patients.