Development of brain metastases in patients managed with non-curative thoracic radiotherapy for stage II/III non-small cell lung cancer

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Abstract

Background

This retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated.

Methods

Different baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed.

Results

The study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor.

Conclusion

The risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development.

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Most cited references 32

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The revised TNM staging system for lung cancer.

Thomas Crowley, Ramón Rami-Porta, P Goldstraw (2009)

The International Staging Committee (ISC) of the International Association for the Study of Lung Cancer (IASLC) collected 68,463 patients with nonsmall cell lung cancer and 13,032 patients with small cell lung cancer, registered or diagnosed from 1990 to 2000, whose records had adequate information for analyzing the tumor, node, metastasis (TNM) classification. The T, N, and M descriptors were analyzed, and recommendations for changes in the seventh edition of the TNM classification were proposed based on differences in survival. For the T component, tumor size was found to have prognostic relevance, and its analysis led to recommendations to subclassify T1 tumors into T1a ( 2 - 3 - 5 - 7 cm into T3. Furthermore, with additional nodules in the same lobe as the primary tumors, T4 tumors would be reclassified as T3; with additional nodules in another ipsilateral lobe, M1 as T4; and with pleural dissemination, T4 as M1. There were no changes in the N category. In the M category, M1 was recommended to be subclassified into M1a (contralateral lung nodules and pleural dissemination) and M1b (distant metastasis). The proposed changes for the new stage grouping were to upstage T2bN0M0 from stage IB to stage IIA, and to downstage T2aN1M0 from stage IIB to stage IIA and T4N0-N1M0 from stage IIIB to stage IIIA. The proposed changes better differentiate tumors of different prognoses.

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Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

H Strøm, R M Bremnes, S Sundstrøm … (2013)

Background: The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. Methods: Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. Results: Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05). Conclusion: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.

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Validation of the graded prognostic assessment for lung cancer with brain metastases using molecular markers (lung-molGPA)

Carsten Nieder, Mandy Hintz, Oliver Oehlke … (2017)

Background Many patients with brain metastases from non-small cell lung cancer have limited survival, while others survive for several years, depending on patterns of spread, EGFR and ALK alterations, among others. The purpose of this study was to validate a new prognostic model (Lung-molGPA) originally derived from a North American database. Patients and methods This retrospective study included 269 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status, histology, EGFR and ALK alterations was collected. The Lung-molGPA score was calculated as described by Sperduto et al. Results Median survival was 5.4 months. The score predicted survival in patients with adenocarcinoma histology and those with other types. For example, median survival was 3.0, 6.2, 14.7 and 25.0 months in the 4 different prognostic strata for adenocarcinoma. The corresponding figures were 2.4, 5.5 and 12.5 months in the 3 different prognostic strata for non-adenocarcinoma. Conclusions These results confirm the validity of the Lung-molGPA in an independent dataset from a different geographical region. However, median survival was shorter in 6 of 7 prognostic strata. Potential explanations include lead time bias and differences in treatment selection, both brain metastases-directed and systemically.

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Author and article information

Contributors

Carsten Nieder: carsten.nieder@nlsh.no

Journal

Journal ID (nlm-ta): Discov Oncol

Journal ID (iso-abbrev): Discov Oncol

Title: Discover Oncology

Publisher: Springer US (New York )

ISSN (Electronic): 2730-6011

Publication date (Electronic): 27 September 2024

Publication date PMC-release: 27 September 2024

Publication date Collection: December 2024

Volume: 15

Electronic Location Identifier: 495

Affiliations

[1 ]Department of Oncology and Palliative Medicine, Nordland Hospital, ( https://ror.org/01pj4nt72) 8092 Bodø, Norway

[2 ]Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, ( https://ror.org/00wge5k78) Tromsø, Norway

Article

Publisher ID: 1358

DOI: 10.1007/s12672-024-01358-6

PMC ID: 11436612

PubMed ID: 39331216

SO-VID: 102c1bec-5cf1-4622-aaf4-58c919bdb345

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 11 June 2024

Date accepted : 17 September 2024

Funding

Funded by: Open access funding provided by UiT The Arctic University of Norway (incl University Hospital of North Norway)

Funded by: UiT The Arctic University of Norway (incl University Hospital of North Norway)

Open Access :

Open access funding provided by UiT The Arctic University of Norway (incl University Hospital of North Norway)

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Keywords: cerebral metastases,radiation therapy,palliative treatment,predictive factors,hypofractionation

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Keywords: cerebral metastases, radiation therapy, palliative treatment, predictive factors, hypofractionation

Development of brain metastases in patients managed with non-curative thoracic radiotherapy for stage II/III non-small cell lung cancer

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Abstract

Background

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Conclusion

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Model Reduction of Parametrized Systems 2015

Most cited references 32

The revised TNM staging system for lung cancer.

Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

Validation of the graded prognostic assessment for lung cancer with brain metastases using molecular markers (lung-molGPA)

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