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W. Xu
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O01 - Prognostic and Predictive Biomarkers I (ID 94)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:T. Mitsudomi, V. Gregorc
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Auditorium, Level 1
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O01.01 - Genetic polymorphisms of inflammatory and DNA repair pathways, radiation-related esophagitis and pneumonitis in definitive chemoradiation treated non-small cell lung cancer patients. (ID 2997)
10:30 - 12:00 | Author(s): W. Xu
- Abstract
- Presentation
Background
The benefits of concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC) are tempered by treatment toxicity. Germline genetic variants have been associated with intrinsic radiosensitivity and radiotoxicity in various cancer settings. We investigated whether variants in genes involved in inflammation response and DNA repair pathways independently influence radiation-induced phenotypes of esophagitis and pneumonitis. From 19 candidate genes, 52 polymorphisms, directed by literature and by tagging procedures, were systematically selected for assessment. The candidate genes were involved in DNA repair (double-strand breaks, homology directed, nucleotide excision) and pro/anti-inflammatory signaling. The this investigation sought to evaluate the association of genetic sequence markers for two clinically significant radiation-induced toxicities - esophagitis and pneumonitis – seen in NSCLC patients treated with a curative intent.Methods
From 312 patients treated at PMCC between 2005-12, a training cohort was defined consisting of 92 definitive concurrent chemoradiation/radiation-treated NSCLC patients with genotype information on the 52 polymorphisms. A second, validation cohort consisted of 209 patients. Multivariate logistic regression was performed for each polymorphism of interest, adjusting for known clinical and dosimetric prognostic factors on the dichotomized outcomes of radiation esophagitis (Grades 0-2 vs 3-5) and pneumonitis (Grades 0-1 vs 2-5). The CTCAEv4.03 grading criteria were used. Additive genetic models were used for genetic association analysis. In the training set, genetic variants, genotyped by IlluminaGoldenGate, with p<=0.05 were identified for validation; HWE was set at p>0.01, a criteria met by all polymorphisms with statistical significance.Results
In the combined training and validation datasets, 63% were males, with median age of 65 years. Specifically in the training dataset, 65% were male, with median age of 62, median mean lung doses of 15.9, median max esophageal dose of 67.1 and median V20 of 27.6. For esophagitis, the final models were adjusted for concurrent chemotherapy, V20 and max esophageal dose. Five genetic variants linked to TNF and IL6 were significantly associated with outcome (each using wild-type genotype as reference) (Table 1). For pneumonitis, the final models adjusted for V20 and smoking status. Eight genetic variants found within four genes (ATM, BRCA2, IL1alpha, IL1RN) were associated with significant pneumonitis (Table 1).ESOPHAGITIS Function / Pathway Gene refSNP OR 95% CI P value pro-inflammatory cytokine TNF rs3093662 3.54 1.9-10.6 0.02 pro-inflammatory cytokine TNF rs3093664 3.42 1.2-10.2 0.03 pro-inflammatory cytokine TNF rs3093665 4.95 1.2-21.1 0.03 anti-inflammatory cytokine IL6 rs1800797 2.53 1.0-6.2 0.04 anti-inflammatory cytokine IL6 rs1800795 2.45 1.0-5.9 0.046 PNEUMONITIS Function / Pathway Gene refSNP OR 95% CI P value double-strand break repair ATM rs664143 2.67 1.3-5.6 0.01 double-strand break repair ATM rs664677 2.37 1.2-4.7 0.01 homology-directed repair BRCA2 rs1799955 2.59 1.3-5.3 0.01 homology-directed repair BRCA2 rs1801406 2.42 1.2-4.8 0.01 homology-directed repair BRCA2 rs1799943 2.09 1.0-4.2 0.04 anti-inflammatory cytokine IL1alpha rs17561 2.63 1.2-5.7 0.01 anti-inflammatory cytokine IL1alpha rs2856863 2.60 1.1-5.9 0.02 anti-inflammatory cytokine IL1RN rs3087263 0.17 0.04-0.8 0.04 Conclusion
In our 92 patient training set, genetic variations in TNF and IL6 are associated with radiation esophagitis, while genetic variations in ATM, BRCA2, IL1alpha and IL1RN are associated with pneumonitis. Results from the 209 patients in the validation dataset will be presented at the meeting (A.H. and G. L are co-senior authors).Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O24 - Cancer Control and Epidemiology III (ID 134)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:N. Van Zandwijk, P. Yang
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside 103, Level 1
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O24.05 - The impact of body mass index on survival in stage 3 and 4 lung cancer (ID 663)
16:15 - 17:45 | Author(s): W. Xu
- Abstract
- Presentation
Background
Obesity has been shown to be an adverse prognostic factor in several cancers, including breast, colorectal, endometrial, ovarian, pancreatic and prostate. However, studies of body mass index (BMI) and outcomes in lung cancer are lacking. Understanding the clinical impact of body weight on cancer outcomes is important given the high prevalence of obesity globally. We retrospectively evaluated the distribution of BMI at diagnosis and its effects on survival in stage 3 and 4 lung cancer patients.Methods
1,121 patients with stage 3 or 4 lung cancer from a single institution were analyzed. Clinicopathologic data were collected retrospectively. Adjusted hazard ratios (aHR) for overall survival (OS) and progression-free survival (PFS) were generated by Cox regression for each BMI (kg/m[2]) category (underweight: <18.5, normal: 18.5-24.9, overweight: 25.0-29.9, obese: ≥30), after adjusting for age, gender, Charlson Comorbidity Index, performance status (PS), clinical stage and treatment regimen.Results
In this cohort (n=1,121), the frequencies of stage 3A, 3B and 4 lung cancers were 35%, 32% and 33%, respectively. There were 633 (57%) adenocarcinomas, 238 (21%) squamous cell carcinomas, 38 (3%) small cell lung cancers, and 210 (19%) other histologies. Patients had variable BMI: 82 (7%) underweight, 550 (49%) normal weight, 333 (30%) overweight, 156 (14%) obese. Being overweight/obese was associated with older age (p=0.002) and stage 3A disease (p=0.001); underweight patients were more likely current smokers (p<0.001). OS was significantly decreased with age ≥65, males, PS 2-3, stage 4, and lack of systemic treatment (p<0.001). Median OS in underweight, normal weight, overweight and obese patients were 14, 23, 24 and 26 months, respectively. Compared with BMI ≥18.5, being underweight was associated with significantly poorer OS (aHR 1.33, 95% CI 1.01-1.77, p=0.045), but not PFS (aHR 1.12, 95% CI 0.86-1.46, p=0.414). The magnitude of this association was greatest among those aged less than 65 years (aHR 1.57, 95% CI 1.11-2.22, p=0.011).Conclusion
In stage 3 and 4 lung cancer, being underweight at diagnosis is associated with significantly poorer OS, especially in patients younger than 65 years of age. Lower BMI is mostly observed in current smokers, while above normal BMI is seen in older patients and stage 3A disease. Unlike other malignancies, obesity does not increase mortality in this population. The BMI-survival relationship in lung cancer requires further study.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.22 - Poster Session 1 - Epidemiology, Etiology (ID 166)
- Event: WCLC 2013
- Type: Poster Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.22-011 - Assessment of the accuracy and reliability of health related behavioural data obtained from patient-reported surveys (PRS) compared with electronic patient records (EPR) in lung cancer patient population (ID 2948)
09:30 - 16:30 | Author(s): W. Xu
- Abstract
Background
Cigarette smoking, alcohol consumption and presence of co morbidities are important factors that affect health status and mortality in patients diagnosed with lung cancer. While the gold standard for presence or absence of co-morbidities is EPR, the gold standard for obtaining accurate data pertaining to health-related behaviours is by PRS. The purpose of this study is to ascertain, whether in the absence of patient self-reported data, health related behavioural data pertaining to cigarette smoking and alcohol consumption abstracted from EPR provides an accurate and reliable surrogate.Methods
731 lung cancer patients completed a PRS pertaining to information on their lifetime tobacco use, alcohol consumption and whether or not they had been diagnosed with certain co-morbid conditions. Relevant smoking, alcohol consumption and co-morbidity data was collected independently from EPR. Kappa coefficient analysis was used to assess the agreement.Results
Results can be seen in Table 1. Ever/never status for smoking showed almost perfect agreement (k=0.95) between PRS and EPR and surpassed all other health behavioural measures and all co-morbidity agreement values. The calculation of pack-years from EPR and PRS showed substantial agreement (k=0.77); However, categorizing the smoking status into current/ former / never, resulted in only moderate agreement (k=0.47). Alcohol ever/ never status agreement was moderate (0.44) with high sensitivity (0.90) but low specificity (0.50). The lung related co-morbidities like emphysema (k=0.41) and chronic bronchitis (k=0.28) showed fair agreement but with substantial missing data through EPR.Table 1 Health Behaviour N Missing Data in EPR Agreement (k) 95% CI (P value) Se Sp Smoking (E/N) 709 0 0.95 (0.79, 0.89) 0.995 0.94 Smoking (Pkyrs)* 606 81(11%) 0.77 P<0.0001 Smoking (C/F/N)** 705 4(0.5%) 0.47 (0.41, 0.51) Alcohol (E/N) 575 150(20.5%) 0.44 (0.36, 0.52) 0.9 0.5 Comorbidity Emphysema 589 126(17.2%) 0.41 (0.33, 0.49) 0.41 0.95 Chronic Bronchitis 601 94(12.8%) 0.28 (0.19, 0.37) 0.39 0.88 *Spearman correlation coefficient **Weighted kappa Conclusion
In the absence of PRS data, EPR provides a reliable surrogate for ever/ never smoking status and moderately reliable for lifetime smoking exposure in this lung cancer population. However current/ former/ never smoking status and ever/ never alcohol status cannot be reliably ascertained from medical records. Missing EPR data related to smoking pack years, alcohol consumption and lung co-morbidities is concerning and suggests more systematic or synoptic reporting by physicians would improve opportunities for research
