ESTRO 2023

Session Item

Sunday

May 14

16:45 - 17:45

Plenary Hall

Lung

Co-Chair: Caroline Maguire, United Kingdom;

Chair: , Italy

Session Code: 2520

Session Type: Proffered Papers

Track: Clinical

16:55 - 17:05

Do patients with lung cancer and a genetic risk for rheumatoid arthritis have increased toxicity?

, United Kingdom

Presentation Number: OC-0608

Abstract

Abstract Title:

Do patients with lung cancer and a genetic risk for rheumatoid arthritis have increased toxicity?

Authors:

Alan McWilliam¹, Sarah Kerns², Deborah Marshall³, David Azria⁴, Jenny Chang-Claude⁵, Ananya Choudhury¹, Sara Gutiérrez-Enríquez⁶, Maarten Lambrecht⁷, Tiziana Rancati⁸, Dirk De Ruysscher⁹, Petra Seibold¹⁰, Chris Talbot¹¹, Ana Vega¹², Liv Veldeman¹³, Adam Webb¹⁴, Kathryn Banfill¹, Corinne Faivre-Finn¹, Barry Rosenstein¹⁵, Catharine West¹⁶

¹The University of Manchester, Division of Cancer Science, Manchester, United Kingdom; ²Medical College of Wisconsin, Radiation Oncology, Wisconsin, USA; ³Mount Sinai, Icahn School of Medicine , New York, USA; ⁴University Montpellier, Federation Universitaire d’oncologie radiothérapie d’Occitanie Méditerranée, Montpellier, France; ⁵German Cancer Research Centre, Division of Cancer Epidemiology, Heidelburg, Germany; ⁶Vall d’Hebron Barcelona Hospital Campus, Hereditary Cancer Genetics Group, Barcelona, Spain; ⁷Leuvens Kanker Instituut, Department of Radiotherapy-oncology, Leuven, Belgium; ⁸Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milian, Italy; ⁹Maastricht University Medical Center, Department of Radiation Oncology, Maastricht, The Netherlands; ¹⁰Germant Cancer Research Centre, Division of Cancer Epidemiology, Heidelburg, Germany; ¹¹University of Leicester, Leicester Cancer Research Centre, Leicester, United Kingdom; ¹²Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica,, Santiago de Compostela, Spain; ¹³Ghent University Hospital and Ghent University, Department of Radiation Oncology, Ghent, Belgium; ¹⁴University of Leicester, Department of Genetics and Genome Biology, Leicester, United Kingdom; ¹⁵Department of Radiation Oncology Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA; ¹⁶The University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom

Show Affiliations

Purpose or Objective

Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity.

Material and Methods

Data from 530 patients with lung cancer were available from the multicentre prospective REQUITE study. Germline DNA was genotyped using Illumina OncoArray-500K BeadChips and imputed using the 1000 Genomes Project Phase 3. PRS and weighted-PRS (wPRS) were calculated for RA (101 SNPs) and analysed as continuous variables and using a >90th percentile cut-off. Univariable and multivariable linear regression models analysed relationships with: 1) acute and late standardised total averaged toxicity (STAT) scores; and 2) individual toxicity end points. Acute toxicity was defined as max reported toxicity within 90 days of RT and late toxicity defined as max reported after 90 days for cough, dyspnoea, pneumonitis, dysphagia, and oesophagitis. Multivariable analyses included the following pre-selected adjustment variables: gender, age, smoking history, chemotherapy, forced expiratory volume (FEV), lung v20, oesophagus v35, prescription dose (biologically equivalent dose), and diagnosis of chronic obstructive pulmonary disease (COPD).

Results

No significant association was found between PRS or wPRS with acute or late STAT. Smoking history, (p=0.03), lung v20 (p=0.008), oesophagus v35 (p=0.02) and COPD (p=0.01) showed a significant association with STAT acute. Lung v20 (p=0.03), oesophagus v35 (p=0.01) and COPD (p < 0.01) were associated with STAT late. Patients with >90th percentile for PRS showed a beta coefficient of 0.17, p=0.06 associated with worse late STAT. Patients >90th percentile for wPRS showed no association with worse STAT late.

Analysing individual toxicity end points identified that patients >90th percentile for wPRS experienced significantly worse acute (coefficient 0.18, p=0.05) and late (coefficient 0.2, p = 0.03) oesophagitis. Smoking history (p=0.01), FEV (p=0.02) and COPD (p=0.05) increased risk of acute oesophagitis. FEV (p=0.02) and higher oesophagus v35 (p=0.03) were also significantly associated with worse late oesophagitis, table 2.

Conclusion

Patients with lung cancer who have a high genetic load for RA have an increased risk of acute and late oesophagitis. Results need to be further validated but suggest an actionable target for preferential oesophagus sparing in these patients.