How can we optimise concurrent chemoradiotherapy for inoperable stage III non-small cell lung cancer?

Bayman, N.; Blackhall, Fiona; McCloskey, P.; Taylor, Paul D.; Faivre-Finn, Corinne

doi:10.1016/j.lungcan.2013.11.017

Cited by 35 publications

(36 citation statements)

References 91 publications

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“…RTOG 9410 has highlighted that dose escalation delivered over a standard overall radiotherapy time does not improve OS. The benefits of dose escalation might be realized when overall radiotherapy time is reduced to mitigate accelerated tumor repopulation while advanced radiotherapy techniques are utilized to reduce dose to OARs and thus widening the therapeutic window (31). Therefore, the long overall radiotherapy time and serious toxicity might account for the failure of dose escalation (74 Gy) in RTOG 0617.…”

Section: Discussionmentioning

confidence: 99%

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

Huang

Chen

et al. 2016

J. Thorac. Dis.

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Background:The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. Methods: Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). Results: The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One-and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One-and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant prognostic factors for both OS and PFS. Multivariate analysis indicated that PS and radiotherapy technique were independent prognostic factors of OS and PS was independent prognostic factor of PFS. Conclusions: Hypofractionated chemoradiotherapy via HT can shorten the radiotherapy time without increasing treatment-related toxicity. The preliminary findings are that OS and PFS can be improved by hypofractionated chemoradiotherapy via HT for patients with stage III NSCLC.

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Section: Discussionmentioning

confidence: 99%

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

Huang

Chen

et al. 2016

J. Thorac. Dis.

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“…Cancer relapse after radiotherapy and chemotherapy is the essential reason for reduced survival (6). Previously, efforts have focused on investigating the cells and mechanisms involved in the resistance and later virulence of lung cancers after therapeutic treatments (7,8). Recent theories in cancer research consider the existence of cell populations with stem cell-like properties in many cancer types (9,10).…”

Section: Introductionmentioning

confidence: 99%

miR-17-92/p38α Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression

2016

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Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. Here we report that the lung stem cell marker Lgr6 becomes enriched in non-small cell lung cancer (NSCLC) cells during malignant progression. Lgr6 þ NSCLC cells displayed self-renewal and differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested that a defective repression of the miR-17-92 gene cluster was responsible for evolution of a selection for outgrowth of Lgr6 þ NSCLC cells. High levels of expression of miR-19 family members were found to target and downregulate levels of p38a kinase, providing a specific survival signal for Lgr6 þ cells as mediated by increased Wnt/ß-catenin activity. Our results identify a specific stem-like cell population in NSCLC with increased malignant potential, the elucidation of which may enable earlier prognosis and possibly the development of more effective targeted treatments. CancerRes; 76(13); 4012-22. Ó2016 AACR.

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“…Radiotherapy is an integral part in almost all treatment schedules for lung cancer (4). Despite an initial remission after the start of treatment, a relapse is frequently observed after which the tumor can no longer be treated effectively (5).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

Nagel

Walsum

Buijze

et al. 2015

Molecular Cancer Therapeutics

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Lung cancer is the most common cancer worldwide and on top of that has a very poor prognosis, which is reflected by a 5-year survival rate of 5% to 15%. Radiotherapy is an integral part of most treatment regimens for this type of tumor, often combined with radiosensitizing cytotoxic drugs. In this study, we identified many genes that could potentially be exploited for targeted radiosensitization using a genome-wide siRNA screen in non-small cell lung cancer (NSCLC) cells. The screen identified 433 siRNAs that potentially sensitize lung cancer cells to radiation. Validation experiments showed that knockdown of expression of Forkhead box M1 (FOXM1) or microtubuleassociated serine/threonine kinase-like (MASTL) indeed causes radiosensitization in a panel of NSCLC cells. Strikingly, this effect was not observed in primary human fibroblasts, suggesting that the observed radiosensitization is specific for cancer cells. Phosphoproteomics analyses with and without irradiation showed that a number of cell-cycle-related proteins were significantly less phosphorylated after MASTL knockdown in comparison to the control, while there were no changes in the levels of phosphorylation of DNA damage response proteins. Subsequent analyses showed that MASTL knockdown cells respond differently to radiation, with a significantly shortened G 2 -M phase arrest and defects in cytokinesis, which are followed by a cell-cycle arrest. In summary, we have identified many potential therapeutic targets that could be used for radiosensitization of NSCLC cells, with MASTL being a very promising and druggable target to combine with radiotherapy.

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How can we optimise concurrent chemoradiotherapy for inoperable stage III non-small cell lung cancer?

Cited by 35 publications

References 91 publications

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

miR-17-92/p38α Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

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