Purpose: Radiation therapy (RT), by using ionizing radiation (IR), destroys cancer cells inducing DNA damage. Despite several studies are continuously performed to identify the best curative dose of IR, the role of dose-rate, IR delivered per unit of time, on tumor control is still largely unknown. Materials and methods: Rhabdomyosarcoma (RMS) and prostate cancer (PCa) cell lines were irradiated with 2 or 10 Gy delivered at dose-rates of 1.5, 2.5, 5.5 and 10.1 Gy/min. Cell-survival rate and cell cycle distribution were evaluated by clonogenic assays and flow cytometry, respectively. The production of reactive oxygen species (ROS) was detected by cytometry. Quantitative polymerase chain reaction assessed the expression of anti-oxidant-related factors including NRF2, SODs, . Annexin V and caspase-8, -9 and -3 activity were assessed to characterize cell death. Senescence was determined by assessing b-galactosidase (SA-b-gal) activity. Immunoblotting was performed to assess the expression/ activation of: i) phosphorylated H2AX (c-H2AX), markers of DNA double strand breaks (DSBs); ii) p19 Kip1/Cip1 , p21 Waf1/Cip1 and p27 Kip1/Cip1 , senescence-related-markers; iii) p62, LC3-I and LC3-II, regulators of autophagy; iv) ATM, RAD51, DNA-PKcs, Ku70 and Ku80, mediators of DSBs repair. Results: Low dose-rate (LDR) more efficiently induced apoptosis and senescence in RMS while high dose-rate (HDR) necrosis in PCa. This paralleled with a lower ability of LDR-RMS and HDR-PCa irradiated cells to activate DSBs repair. Modulating the dose rate did not differently affect the antioxidant ability of cancer cells. Conclusion:The present results indicate that a stronger cytotoxic effect was induced by modulating the dose-rate in a cancer cell-dependent manner, this suggesting that choose the dose-rate based on the individual patient's tumor characteristics could be strategic for effective RT exposures.
Aim: To report the long-term results after definitive chemoradiotherapy (CRT) for anal carcinoma, using consistent time-to-event endpoints. Methods and Materials: Anal carcinoma patient charts were reviewed. All patients received definitive CRT. Overall survival (OS), local failure-free survival (LFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and anal dysfunction-free survival (ADFS) were estimated. Results: In total, 65 patients were included. CRT was well tolerated, with only 24.6% grade ≥3 acute toxicity. Overall, the 5-year OS, LFFS, LRFFS, and DMFS were 75.3, 60.2, 74.2, and 66.2%, respectively. Early complete clinical response and tumor stage at diagnosis were the strongest predictors of OS (p = 0.04) and local failure (p = 0.03), respectively. Conclusions: In the treatment of anal cancers, excellent ADFS and OS, and valid LFFS, LRFFS, and DMFS can be achieved with definitive CRT. Adequacy of time-to-event endpoints is paramount.
Context. Post-operative clinical and biochemical hypocalcemia is a common complication of thyroid surgery and the correlation with incidental parathyroidectomy (IP) remains controversial.Objective. To evaluate the incidence of IP during TT, its correlation to early post-surgery hypocalcemia, and its potential risk factors.Patients and Methods. 77 consecutive patients submitted to thyroid surgery between January 2018 and December 2019. Demographic, clinical, biochemical, surgical and histopathological factors were assessed. Statistical multivariate analysis was performed to identify the risk of IP.Results. IP was evident in 22 (28.5%) patients who underwent TT, TT with lymph node dissection of the central compartment (CLND) and reoperation for previous hemithyroidectomy with CLND. Early symptomatic hypocalcemia 24 hours after TT was demonstrated in 12/22 (54.5%) patients, with PTH value of <14pg/mL in 7/12 (58.3%) patients, and in 6 of these 7 patients (85.7%) the PTH value was <6.3pg/mL. In 5/22 (22.7%) patients the IP was associated with biochemical hypocalcemia <8.4mg/dL, and in 5/22 (22.7%) patients anatomical damage was not associated with a reduction in plasma calcium levels. The severity of early post-op hypocalcemia was not correlated with the number of parathyroid glands left in situ. The multivariate analysis did not show statistically significant values between the clinical-pathological variables and increased risk of IP.Conclusions. No IP clinical-pathological risk factors have been identified during thyroid surgery. In all cases of TT, with or without CLND, the meticulous identification of the parathyroid glands, whose incidental removal is frequently associated with clinical and biochemical hypocalcemia, is recommended.
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