Curative Radiotherapy for Non-small Cell Lung Cancer: Practice Changing and Changing Practice?

McDonald, Fiona; Senan, Suresh; Faivre-Finn, Corinne; Hatton, Matthew

doi:10.1016/j.clon.2019.07.025

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…In addition, there was a large regional variation in the percentage of patients receiving curative intent treatment from 8-80% ( 10 ). It has been suggested that the centres offering a greater proportion of patients curative intent treatment may have better access to optimal radiotherapy planning techniques and image guided treatment ( 20 ). Indeed, in the Royal College of Radiologists (RCR) published consensus statements for radiotherapy for lung cancer, it is recommended that patients receiving radical radiotherapy are planned with advanced techniques such as IMRT or VMAT ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer

et al. 2022

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BackgroundLung cancer survival remains poor. The introduction of Intensity-Modulated Radiotherapy (IMRT) allows treatment of more complex tumours as it improves conformity around the tumour and greater normal tissue sparing. However, there is limited evidence assessing the clinical impact of IMRT. In this study, we evaluated whether the introduction of IMRT had an influence on the proportion of patients treated with curative-intent radiotherapy over time, and whether this had an effect on patient survival.Materials and MethodsPatients treated with thoracic radiotherapy at our institute between 2005 and 2020 were retrospectively identified and grouped into three time periods: A) 2005-2008 (pre-IMRT), B) 2009-2012 (selective use of IMRT), and C) 2013-2020 (full access to IMRT). Data on performance status (PS), stage, age, gross tumour volume (GTV), planning target volume (PTV) and survival were collected. The proportion of patients treated with a curative dose between these periods was compared. Multivariable survival models were fitted to evaluate the hazard for patients treated in each time period, adjusting for PS, stage, age and tumour volume.Results12,499 patients were included in the analysis (n=2675 (A), n=3127 (B), and n=6697 (C)). The proportion of patients treated with curative-intent radiotherapy increased between the 3 time periods, from 38.1% to 50.2% to 65.6% (p<0.001). When stage IV patients were excluded, this increased to 40.1% to 58.1% to 82.9% (p<0.001). This trend was seen across all PS and stages. The GTV size increased across the time periods and PTV size decreased. Patients treated with curative-intent during period C had a survival improvement compared to time period A when adjusting for clinical variables (HR=0.725 (0.632-0.831), p<0.001).ConclusionIMRT was associated with to more patients receiving curative-intent radiotherapy. In addition, it facilitated the treatment of larger tumours that historically would have been treated palliatively. Despite treating larger, more complex tumours with curative-intent, a survival benefit was seen for patients treated when full access to IMRT was available (2013-2020). This study highlights the impact of IMRT on thoracic oncology practice, accepting that improved survival may also be attributed to a number of other contributing factors, including improvements in staging, other technological radiotherapy advances and changes to systemic treatment.

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Section: Discussionmentioning

confidence: 99%

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer

et al. 2022

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“…Non-small cell lung cancer (NSCLC) accounts for approximately 85-90% and remains one of the leading causes of mortality worldwide 1 . Besides surgery, chemotherapy as well as targeted therapy, radiotherapy represents a main strategy when used alone or combined with other adjuvant treatment 2 . However, the basic or gradually resistance of cancer cells to ionizing radiation often leads to failure of therapy 3 , 4 .…”

Section: Introductionmentioning

confidence: 99%

Sirt3 Promoted DNA Damage Repair and Radioresistance Through ATM-Chk2 in Non-small Cell Lung Cancer Cells

et al. 2021

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Objective: Radiotherapy is an indispensable approach for lung cancer, especially for non-small cell lung cancer (NSCLC) with high incidence and mortality. However, cellular resistance to ionizing radiation often results in failure in treatment. In this study, we aimed to investigate the role of Sirt3 in radiotherapy on NSCLC. Materials and Methods: Resected samples from 80 pairs of lung cancer was used to prepare tissue array and Sirt3 was stained with immunochemical method. Cell survival as well as apoptosis assay were used to determine the cellular radiosensitivity. Moreover, DNA damage was evaluated by using γ-H2AX foci. Finally, an in situ lung cancer model to test the radiosensitivity in vivo. Results: Sirtuin 3 (Sirt3) was found upregulated in NSCLC cell lines, as well as lung cancer tissues compared with normal tissues. Knockdown of Sirt3 significantly increased radiation-induced cell apoptosis, and increased cell survival efficacy. In contrast, Sirt3 overexpression promoted radioresistance in lung cancer cells. Sirt3 knockdown also aggravated the G2/M cell cycle arrest caused by irradiation. Furthermore, Sirt3 was found to be critical for the activation of ATM-Chk2 pathway upon irradiation. Finally, our in vivo model showed that targeting Sirt3 significantly sensitized lung cancer to radiotherapy. Conclusion:In conclusion, our findings identified a significant role of Sirt3 in radioresistanct of NSCLC, which provides novel mechanism as well as target for radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Sirt3 Regulates Radioresistance of Non-small Cell Lung Cancer through ATM-Chk2 Pathway

Cao

Chen

Huang

et al. 2020

Preprint

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With high incidence and mortality, non-small cell lung cancer (NSCLC) represent 85-90% in all lung cancer patients. In addition to surgery and chemotherapy, radiotherapy is an indispensable approach for cancer treatment. However, cellular resistance to ionizing radiation often results in failure in treatment. In this study, we aimed to investigate the role of Sirt3 in radiotherapy on NSCLC. Briefly, survival as well as apoptosis assay were used to determine the cellular radiosensitivity, and an in situ lung cancer model to test the radiosensitivity in vivo. Firstly, our data show that Sirt3 is upregulated in NSCLC cell lines, as well as tissues compared with normal tissues. Then we generated Sirt3 knockdown cells and overexpression cells and found that Sirt3 knockdown increased radiosensitivity, while Sirt3 overexpression caused resistance. Sirt3 knockdown also aggravated the G2/M cell cycle arrest caused by irradiation. Furthermore, Sirt3 was found to be critical for the activation of ATM-Chk2 pathway upon irradiation. Finally, our in vivo model showed that targeting Sirt3 significantly sensitized lung cancer to radiotherapy. In conclusion, our findings identified a significant role of Sirt3 in radioresistanct of NSCLC, which provides novel mechanism as well as target for radiotherapy.

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Curative Radiotherapy for Non-small Cell Lung Cancer: Practice Changing and Changing Practice?

Cited by 4 publications

References 14 publications

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer

Sirt3 Promoted DNA Damage Repair and Radioresistance Through ATM-Chk2 in Non-small Cell Lung Cancer Cells

Sirt3 Regulates Radioresistance of Non-small Cell Lung Cancer through ATM-Chk2 Pathway

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