Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity.Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G2-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes.Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX).Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues.
A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.
In this unique historic period afflicted by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, radiation therapy treatments cannot be delayed or suspended. We report the case of a 73-year-old woman with recently diagnosed extensive-stage small cell lung cancer with metastatic liver and bone lesions. A SARS-CoV-2 test was performed upon hospital admission and was negative. After 5 days she underwent radiation therapy on T6 and T11 with single fractions of 8 Gy each. Before treatment a cone beam computed tomography (CBCT) scan was performed to check the setup of the patient. Some suspected lung areas of ground glass opacities (GGOs) were clearly visible in the CBCT without any counterpart in the previous computed tomography (CT) simulation scan 3 days before. A new high-quality chest CT scan confirmed the previously suspected GGOs. The exam revealed multiple bilateral areas of subpleural GGOs, which are the primary findings on CT scan in the early phases of coronavirus disease 2019 (COVID-19) lung infection, in addition to pleural effusions, a finding that may occur as a complication of COVID-19. The patient then urgently repeated the SARS-CoV-2 test, which was positive and confirmed the infection. In conclusion, daily CBCT can be effective for early detection of COVID-19 lung disease in asymptomatic or mildly symptomatic patients.
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