International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Glioblastoma (GB) and x-ray-based radiation therapy are associated with lymphopenia, which worsens prognosis and impairs antitumor immunity. Proton therapy, with its dosimetric properties that spare healthy brain tissue, is an alternative to reduce radiotoxicity. This study examined the effects of brain irradiation with x-rays or protons on lymphopenia.

Methods and materials: We used GL261-tumor-bearing and tumor-free mice models to evaluate various lymphoid and myeloid cell populations after brain irradiation, assessing volume of brain irradiation, beam orientation, and lymphopenia onset timing via flow cytometry.

Results: In the GB mouse model, both tumor- and radiation-induced lymphopenia were evidenced. Severe lymphopenia, with a 50% depletion of CD45⁺CD3⁺ lymphocytes, CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell, CD3^-B220⁺ B cells, and CD45⁺CD11b⁺ myeloids, CD11b⁺Ly6C⁺ monocytes, and CD11b⁺Ly6G⁺ neutrophils, occurred as early as 12 hours after x-ray exposure in tumor-free mice. Myeloid subtypes recovered by day 2, whereas lymphocyte recovery was cell type dependent. The use of a lateral x-ray beam failed to alter circulating lymphocyte counts. Brain, cervical lymph nodes, and spleen immune cell quantification revealed a reduction in CD3⁺CD4⁺, CD3⁺CD8⁺ T and CD3^-B220⁺ B cells post-x-ray exposure. Protons caused a 15% decrease in circulating lymphocytes, with no change in myeloid cells. Proton exposure also reduced CD3⁺CD4⁺ T and CD3^-B220⁺ B cells in the cervical lymph nodes but did not affect the spleen. Plasma cytokine levels in the interleukin 1 and macrophage inflammatory protein families correlated with leucocyte changes following exposure to both particle types.

Conclusions: We describe that proton therapy resulted in less lymphopenia than proton radiation, and propose that the mechanism may be related to biological processes rather than solely decreased exposure of circulating lymphocytes. This may be used to guide the incorporation of immune therapy in GB.

Synopsis: Understanding how brain irradiation affects circulating immunity can inform strategies to improve brain tumor treatment. This involves combining irradiation with immunotherapy and adjusting clinical protocols to restore lymphocytes/boost antitumor T cells.

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.