Palliative radiotherapy near the end of life for brain metastases from lung cancer: a populationbased

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Palliative radiotherapy near the end of life for brain metastases from lung cancer: a populationbased analysis Roel Schlijper Fellow Radiation Oncology BC Cancer, Prince George

Disclosures No conflicts of interest

Learner centered objectives Learn basic principles of (brain) radiotherapy Understand the prognosis of lung cancer patients with brain metastases Discuss how to best select patients for brain radiotherapy

Radiation oncology Therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator.

Linear accelerator https://www.youtube.com/watch?v=pnakpexe dk0&feature=youtu.be

Radiation oncology

DNA damage DNA repair Difference between normal cell and cancer cell Fractionation of radiation dose

Radiation (dose) planning 4 field conventional 5 field conventional Arc Therapy

Radiation effects Local treatment Location Total dose Fraction dose Volume Local (side-)effect Tissue sensitive for RT? (Fraction) dose = (side- )effect Volume = side-effect

Radiation for brain metastases Indications Palliative vs. radical Whole-brain radiotherapy (WBRT) vs Stereotactic radiation (SRT)

WBRT vs. SRT WBRT Palliative treatment Volume = complete skull Also subclinical lesions Toxicity 5-10 fractions SRT Radical treatment Volume = metastasis Only treated lesions Less toxicity 1-3 fractions

Brain metastases in lung cancer 10% at time of diagnosis Large proportion of brain mets = lung primary Median survival 2.5-4.5 months Treatment impacts quality of life No difference WBRT vs optimal care SRT safe option for selected patients Pt selection is important

Getting back on topic

Goals Identify patients that died within 4 weeks and 90 days of start of radiotherapy Identify factors that predict which patients will not benefit from radiotherapy for brain metastases

Methods Database Patient characteristics Treatment characteristics Lung cancer patients in BC with brain metastases Treated with radiotherapy January 2014 December 2015 740 patients 826 courses of radiation

Patient characteristics 60% 50% Gender Age 40% 30% 20% 10% Male Female <50 50 - <60 60 - <70 70 - <80 80 0% Male Female Histology Other Small cell carcinoma NSCLC NOS Squamous cell carcinoma Histology Adenocarcinoma 0% 20% 40% 60% 80% 100%

Treatment characteristics ECOG performance score Initial systemic therapy Completion of radiotherapy Number of fractions Radiation technique Total radiation dose

Results 35% 30% 25% 20% 15% 10% 5% 0% ECOG performance score ECOG performance score Mortality 11% after 4 weeks 40% after 90 days Initial systemic treatment: 50% 95% completion rate 11% stereotactic radiation

Prognostic factors Factors predicting 4 week mortality after radiotherapy for brain metastases in lung cancer patients Initial systemic therapy lower risk >5 fractions lower risk Age 70 - <80 lower risk

Prognostic factors Factors predicting 90 day mortality after radiotherapy for brain metastases in lung cancer patients Higher age higher risk Squamous cell carcinoma higher risk Initial systemic therapy lower risk >5 fractions lower risk Stereotactic radiation lower risk

Discussion 4 week mortality: 11% 90 days mortality: 40% Important prognostic factors Initial systemic therapy >5 fractions of radiation Selection of patients important Our results possibly influenced by selection bias

Conclusions It s a matter of perspective Improve patient selection in future Who benefits from treatment? Better use of prognostic tools

Multivariate analysis 4 week mortality 95.0% C.I.for EXP(B) Odds Lower Upper Age continuous 1.066 0.98 1.16 Adenocarcinoma (reference) Squamous cell carcinoma 1.587 0.715 3.522 NSCLC NOS 1.307 0.604 2.83 Small cell lung cancer 1.28 0.634 2.585 Other histology 1.483 0.655 3.357 Initial systemic therapy 0.486 0.273 0.867 1-5 fractions conventional (reference) >5 fractions conventional 0.117 0.041 0.336 SRS / SFRT 0.579 0.148 2.266 Age <50 3.35 0.425 26.398 Age 50 - <60 1.063 0.39 2.897 Age 60 - <70 (reference) Age 70 - <80 0.365 0.139 0.961 Age 80 or higher 0.553 0.104 2.945

Multivariate analysis 90 day mortality 95.0% C.I.for EXP(B) Odds Lower Upper Age continuous 1.066 1.008 1.128 Adenocarcinoma (reference) Squamous cell carcinoma 2.077 1.109 3.89 NSCLC NOS 1.078 0.634 1.835 Small cell lung cancer 1.003 0.631 1.593 Other histology 1.447 0.744 2.817 Initial systemic therapy 0.486 0.34 0.693 1-5 fractions conventional (reference) >5 fractions conventional 0.25 0.161 0.386 SRS / SFRT 0.296 0.13 0.67 Age <50 2.566 0.648 10.157 Age 50 - <60 1.202 0.621 2.328 Age 60 - <70 (reference) Age 70 - <80 0.687 0.363 1.3 Age 80 or higher 0.671 0.2 2.247