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: Background and purposeTo evaluate the potential role and mechanism of docetaxel plus flavopiridol in modulating radiosensitivity in vitro and in vivo.: Patients and methodsIn vitro. H460 human lung carcinoma cells were treated with docetaxel (10 nM for 1 h, at t=0 h)→radiation (0–5 Gy, at t=6 h)→flavopiridol (120 nM for 24 h, at t=8 h). Colony forming ability was measured to assess the modulation of sensitivity. Cell cycle redistribution was measured by flow cytometric analysis using propidium iodide. Percent apoptosis was also measured by flow cytometric analysis using 7-amino-actinomycin D staining. In vivo. H460 cell xenografts were used in nude mice. Tumors were grown subcutaneously on the flank, then treated with docetaxel (2.5 mg/kg, at t=0 h)→radiation (2 Gy, at t=6 h)→flavopiridol (1.25 mg/kg, at t=8 h) for 5 consecutive days. Tumor growth delay was then measured and compared with the control group.: ResultsDocetaxel plus flavopiridol enhanced the effect of radiation. The maximum radiopotentiation and apoptosis were observed when the cells were treated with the sequence of docetaxel→radiation→flavopiridol both in vitro and in vivo. Flavopiridol and docetaxel induced G1 and G2/M arrest, respectively.: ConclusionsThis study shows that docetaxel plus flavopiridol enhances the effects of radiation in vitro and in vivo. Our data suggest that the mechanism of radiopotentiation by combining flavopiridol and docetaxel involves an enhancement of apoptosis and changes of cell cycle by docetaxel and flavopiridol. [Copyright &y& Elsevier]

Background and purpose: To evaluate a semisynthetic epothilone B, BMS-247550, as a potential radiosensitizer in vitro and in vivo.Materials and methods: Human NCI-H460 lung cancer cells were treated with either BMS-247550 or paclitaxel and in combination with radiation at multiple doses for different time periods. Surviving fractions were then analyzed using a clonogenic assay. Cell cycle redistribution by BMS-247550 was measured with propidium iodide and flow cytometry. Percent apoptosis was also measured using 7-amino-actinomycin D staining with flow cytometry. For in vivo studies, the H460 xenograft model was used in athymic nude mice. Tumors were treated with BMS-247550 (5 mg/kg) i.p. injection on days 0, 2, and 4 and/or radiation (2 Gy/day, days 0–4).Results: The in vitro radiation dose enhancement ratios (DER) of 1-h BMS-247550 and paclitaxel were 2.03 and 1.34, respectively. Treatment with BMS-247550 enhanced the G2/M block and induced apoptosis; whereas in combination with radiation, the induction of apoptosis was additive. BMS-247550 in combination with radiation in vivo enhanced the tumor growth delay when compared with either drug or radiation alone.Conclusions: These results demonstrated that BMS-247550 could enhance the effects of radiation in human lung cancer cells both in vitro and in vivo and that a G2/M block and increased apoptosis might be possible explanations for the enhancement. [Copyright &y& Elsevier]

• Neutrophil-lymphocyte ratio and absolute neutrophil count were identified as potential predictors for severe RILI. • Association with severity of interstitial lung disease and severe RILI. • Patients who developed severe RILI had dismal prognosis. This study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. The study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil–lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6–114) months. Among 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. Pretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI. [ABSTRACT FROM AUTHOR]