13 research outputs found

    Multimodality treatment of locally advanced squamous cell carcinoma of the oesophagus: A comprehensive review and network meta-analysis

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    Background Surgery is the mainstay of treatment for oesophageal squamous-cell carcinoma (OSCC) but with poor results. Attempts to improve patient outcome have been made by introducing chemotherapy (CT), radiotherapy (RT), or both (CRT). However, randomized comparisons for all these strategies are not always available. Patients and methods We conducted an extensive literature search for studies comparing surgery with multimodality treatment (i.e. [neo-]adjuvant CT or RT or CRT or definitive CRT). Network meta-analysis was performed in a Bayesian framewor and node-split models were built to assess inconsistency. Results Twenty-five trials including a total of 3866 OSCC patients were included. Neoadjuvant CRT was associated with the most robust survival advantage across different multimodality treatment options (HR 0.73; 95% credible interval [CrI] 0.63â\u80\u930.86). Definitive CRT was also significantly more effective than surgery but with greater uncertainties (HR 0.62; 95%CrI 0.41â\u80\u930.96). Neoadjuvant CT (HR 0.90; 95%CrI 0.76â\u80\u931.07) and adjuvant CRT (HR 1.00; 95%CrI 0.70â\u80\u931.40) are associated with a non-significant benefit. Conclusions To date, neoadjuvant CRT seems to represent the best approach to maximize the benefit of a multimodality approach

    Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with Nivolumab in the Italian NSCLC expanded access programme.

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    Abstract Background The incidence of any and of severe grade immune-related adverse events (irAEs) with second-line Nivolumab (N) monotherapy is 26% and 6% respectively. While potentially serious and even fatal, in the absence of appropriate therapy, such events might be an indicator of the activation of the immune system and, potentially, of efficacy. Methods We collected the records of 1.959 NSCLC patients (pts) including those with Squamous (S) and non-Squamous (non-S) histology, treated with N in the Italian expanded access programme and we recorded the appearance of any and of severe grade irAEs. We then retrospectively searched for potential correlations between this type of toxicity and efficacy parameters by using cox regression analysis. Results A total of 1.585 and 374 pts had non-S and S cell carcinoma respectively and 57% received N as second-third line of therapy. Overall 342 (17.8%) developed an irAE of any grade. We observed that pts developing any grade irAE achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to pts who did not. IrAEs correlate with clinical outcomes in both non-S and S histology. At multivariate analysis the development of an irAE remained an independent indicator of N efficacy (HR 1.44[95% CI: 1.22-1.71] p < 0.0001). Conclusions This is the first report performed in a large series of Caucasian NSCLC pts showing that the activation of the immune system induced by N and documented by the appearance of irAEs correlates with outcome. A careful management of pts with such an event could lead to a maximum clinical benefit

    Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program

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    Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9–7.1] vs 3.0 [95% CI: 2.8–3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5–19.9] vs 9.4 [95% CI: 8.4–10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22–1.71] p < 0.0001)
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