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V.K. Lam
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-029 - Obesity Is Associated with Long-Term Improved Survival in Definitively Treated Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) (ID 2958)
09:30 - 17:00 | Author(s): V.K. Lam
- Abstract
Background:
Limited studies suggest that obese patients (pts) with NSCLC paradoxically have improved survival. However, characterization of factors influencing Body Mass Index (BMI) at disease presentation and the impact that it may have on outcomes in NSCLC patients remains incomplete. We evaluated the prognostic effect of BMI in a retrospective cohort treated for LA-NSCLC (AJCC 7[th] edition stage III).
Methods:
From January 2000 to December 2010, 311 consecutive LA-NSCLC pts were definitively treated at our institution with chemotherapy and radiotherapy ± surgery. Radiation was most commonly administered with concurrent chemotherapy. After excluding pts for whom pre-treatment BMI was not available, we evaluated 291 pts who were stratified into four BMI groups based on World Health Organization criteria: underweight (< 18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), and obese (>= 30 kg/m2). Kaplan-Meier survival analysis was performed with log-rank test-for-trend. Cox proportional hazards modeling was used for univariate and multivariate analyses.
Results:
Baseline characteristics were similar between obese and normal weight pts (Table 1). Median survival was 17 months (mo), 19 mo, 23 mo, and 29 mo for each BMI group respectively. A trend for improved survival with increasing BMI was highly significant (P=0.009) and persisted even when underweight cases were excluded, suggesting that the survival benefit is not driven by unfavorable prognostic factors in the underweight cases. There was a sustained 31% to 58% reduction in mortality of obese relative to normal weight pts (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Additionally, there was no correlation between BMI and smoking pack-years, even when underweight pts were excluded. (correlation coefficient 0.033 [95% CI 0.09 – 0.15, P=0.59]). Table 1: Baseline Characteristics of Study Cohort Figure 1
Conclusion:
In this retrospective study of definitively treated LA-NSCLC patients, obese pts had significantly improved survival relative to normal weight pts. This favorable prognostic effect was independent of stage and was significantly more durable than previously reported in advanced NSCLC patients. Additionally, the putative relationship between BMI and smoking history was not observed in this cohort. These new findings suggest that the protective effect of obesity in NSCLC is not solely due to short-term treatment effects or decreased smoking exposure. We plan to investigate additional parameters such as histology, chemoradiation course, subsequent surgery, and metformin use to further clarify the role of obesity in survival of NSCLC pts.
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P1.03-030 - Marital Status Is Strongly Prognostic and Associated with More Favorable Nutritional Status in Locally Advanced Non-Small Cell Lung Cancer (ID 2390)
09:30 - 17:00 | Author(s): V.K. Lam
- Abstract
Background:
We updated our previous analysis demonstrating marital status is prognostic in stage III NSCLC. We hypothesized that married patients have more favorable nutritional or immunologic status than unmarried patients as a potential mechanism for this survival advantage.
Methods:
Between January 2000 and December 2010, 268 patients with stage III NSCLC received definitive chemotherapy and radiation therapy, with or without surgery at our institution. All had complete demographic, diagnosis, treatment, lab, and survival data. A Kaplan-Meier method estimated overall survival and we applied the log-rank test to compare mortality between groups. Multivariable analysis of prognostic factors was conducted using the Cox proportional hazards model. We tested the interaction between marital status and pre-treatment body mass index (BMI), albumin, white blood count, absolute neutrophil count, absolute lymphocyte count and calculated neutrophil-lymphocyte ratio (NLR).
Results:
More married patients presented with stage IIIA (rather than IIIB) disease (58% vs. 46%, P=0.03), had a PS 0 (57% vs. 36%, P<0.001), were white (69% vs. 43% (P<0.001) and lived in higher median income areas ($45,646 vs. $38,331, P<0.001) than non-married patients. There was no difference in tobacco history or diagnosis age between married and unmarried patients. After adjusting for stage, PS, race, and median household income, the hazard ratio for any-cause mortality in married patients was 0.59, 95% CI (0.45, 0.78), P<0.001. Median OS for married vs. unmarried patients was 28 (23, 34) vs. 16 (13, 19) months (P<0.001). Contrary to other reports, the reduction in mortality associated with being married was similar in males, 45%,and females 43%, with the test for interaction in a multivariable Cox model being non-significant (P=0.38). Figure 1 We also found married status was associated with higher median, 25[th], and 75[th] percentile BMI (26.3 vs. 23.8; 23.3 vs. 20.6, and 30.8 vs. 28.4, respectively; P=0.014) and albumin (3.7 vs. 3.6; 3.4 vs. 3.1; and 4.0 vs. 3.8, respectively; P=0.001).
Conclusion:
Marital status is an important predictor of survival in stage III NSCLC and appears to offset the disadvantage of higher stage disease. Our results suggest one mechanism for this may be married patients have more favorable nutritional status evidenced by higher BMI and albumin. We did not find an association between marital status and immunologic status in our analysis. Future studies that evaluate how social support impacts nutritional status prior to therapy may lead to interventions to target vulnerable populations. Marital status may be an important stratification factor in clinical trials.
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P1.06 - Poster Session/ Screening and Early Detection (ID 218)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.06-003 - Low-Dose CT Lung Cancer Screening in the Community: A Prospective Cohort Study Incorporating a Gene-Based Lung Cancer Risk Test (ID 879)
09:30 - 17:00 | Author(s): V.K. Lam
- Abstract
Background:
Following the publication of the National Lung Screening Trial (NLST) results in 2011, CT screening for lung cancer is now widely recommended in the US. However concerns remain with regards to patient selection according to risk level and overdiagnosis.Moreover adherence outside screening trials is typically about 50-60% and has been shown to be highly dependent on an individual's risk perception. This feasibility study explores the relevance of gene-based data on lung cancer risk assessment and adherence to screening, in a pilot screening program.
Methods:
This feasibility study was initiated in 2010 prior to NLST results being published. Following local media-based advertising, 157 current or former smokers (>50 years old with ≥20 pack year history), volunteered for lung cancer risk assessment and CT screening (using the IELCAP protocol). Participants were followed up for a mean of 2.4 years.At baseline CT screening, participants were assigned their lung cancer risk category according to a published and prospectively validated gene-based risk algorithm. This algorithm combines clinical risk variables with risk genotypes, derived from analysis of 20 risk single nucleotide polymorphisms (SNPS), to derive a composite lung cancer risk score categorised as moderate, high or very high.
Results:
SNP genotype results contributed to overall lung cancer risk in 88% of participants compared to the contribution from age = 68%, family history of lung cancer = 29% and self reported chronic obstructive pulmonary disease =15%. The SNP genotype results were the sole basis of risk in 18% of participants and contributed to risk in a further 70% of participants (total 88%). Adding SNP scores to the clinical risk score re-assigned screening participants into different risk categories in 28% (44/157) of participants (Figure 1). Importantly, timely adherence to the CT screening protocol was two-fold greater in those with a very high risk score compared to the high and moderate risk categories (71% vs 52% vs 52% respectively, OR =2.3, P<0.05). Figure 1
Conclusion:
In this feasibility study of a pilot community-based CT screening program we found gene-based risk assessment was of interest to all screening volunteers. As part of risk assessment, personalised SNP data made the greatest contribution to overall assignment of lung cancer risk in association with established clinical variables and significantly improved screening adherence. We conclude that gene-based risk stratification helps assign lung cancer risk and appears to improve adherence to screening.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-082 - Pathological Response with Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Use in Advanced Non-Small Cell Lung Cancer (ID 2156)
09:30 - 17:00 | Author(s): V.K. Lam
- Abstract
Background:
Angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) are among the most common medications in the treatment of hypertension and diabetes. These drugs are under evaluation as a means to mitigate radiation pneumonitis/fibrosis likely mediated by anti-inflammatory and endothelial effects. Their collateral impact on oncological outcomes is unknown. We retrospectively evaluate the effect of ACEi and ARB usage on pathological response during preoperative platinum-based concurrent chemoradiotherapy (CCRT) with high-dose radiotherapy (≥59.4 Gy) in a cohort of patients with stage III non-small cell lung cancer (NSCLC).
Methods:
Between June 2000 and December 2009, 79 patients with stage III NSCLC (AJCC 7[th] ed.) were treated with preoperative CCRT at our institution. Data on ACEi/ARB usage during CCRT and pathological response was available for 72 patients. The primary end-point was pathological complete response (pCR), in both the primary site and involved lymph nodes. X[2] analysis was to assess distribution of categorical variables, Kaplan-Meier survival analysis with log rank test for univariate and Cox regression multivariate (age, gender, race, stage, RT dose and chemotherapy regimen) analysis of overall survival (OS) and freedom-from recurrence (FFR) was performed.
Results:
The median age at diagnosis was 56 years (range, 38-78) with 56% males, 74% Caucasians and 96% smokers. Stage distribution was IIIA (72%), IIIB (28%), T1/2 (54%), T3/4 (46%), N0/1 (14%) and N2/3 (86%). The median radiation dose was 66.6 Gy (range 59.4-69.6 Gy) with the most common CCRT regimen being carboplatin-paclitaxel (54%). At a median follow up of 3.8 years for all patients and 6.8 years for surviving patients, the median OS and FFR of the entire cohort were 4.9 years (95% Confidence Interval (CI): 3.5-6.5) and 3.1 years (95% CI: 1.3-4.9), respectively with overall pCR rate of 44%. During CCRT, 11 patients (15%) were taking ACEi/ARB and 61 patients (85%) were not taking ACEi/ARB. No statistical differences were seen in the distribution of baseline variables between the two cohorts. None of the patients developed acute radiation pneumonitis in the time interval between radiotherapy completion and surgery (median 55 days; range, 33-105 days). The pCR rate without and with ACEi/ARB was 46% vs 36% (p=0.56). The median FFR without and with concurrent ACEi/ARB use was 3.1 years vs. not reached, p = 0.35, while the corresponding median OS values were 4.8 years and 5.5 years, p = 0.59, respectively. On multivariate analysis, an improved OS was associated with younger age (HR: 0.39, 95%CI: 0.2-0.8, p<0.01), an improved FFR was associated with lower stage (HR: 0.3, 95%CI: 0.15-0.76, p<0.01) and Caucasian race (HR=0.37, 95% CI: 0.15-0.88, p=0.02), with no impact of ACEi/ARB use on either outcome.
Conclusion:
The use of ACEi/ARB did not have any apparent influence the rates of pCR in this small cohort of advanced stage NSCLC patients treated with trimodality therapy following preoperative platinum-based CCRT with high-dose radiotherapy. As the role of these drugs in mitigating radiation pneumonitis continues to be evaluated, simultaneous assessment of lack of a negative impact on disease outcomes needs to be validated in larger, prospective analyses.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-058 - Neutrophil-Lymphocyte Ratio (NLR) as a Prognostic Marker in Locally Advanced Non-Small Cell Lung Cancer (LANSCLC) (ID 2404)
09:30 - 17:00 | Author(s): V.K. Lam
- Abstract
Background:
NLR is a measure of systemic inflammation which appears prognostic in localized and advanced NSCLC. Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesize that low NLR measured at diagnosis is associated with improved overall survival (OS) in patients with LANSCLC.
Methods:
Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery at our institution between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline patient demographic data and pre-treatment absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method and the logrank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used to adjust for other prognostic factors in a multivariable analysis. Distributions of NLR in subgroups were compared using the Mann-Whitney U test. All P-values are 2-tailed.
Results:
NLR was a highly prognostic factor for overall survival (p<0.0001). Median survival [95% CI] for the first, second, third and fourth quartile groups of the population distribution of NLR were 27 months [19-36], 28 months [22-34], 22 months [12-31] and 10 months [8-12], respectively. NLR correlated with race, gender, stage and performance status. Even after adjusting for stage (IIIA vs. IIIB), NLR remained predictive of overall survival (p=0.001). Figure 1 Figure 2
Conclusion:
To our knowledge, this is the first large series evaluating NLR as a prognostic indicator in LANSCLC. Pre-treatment NLR is strongly associated with OS in LANSCLC. NLR is an inexpensive biomarker which is significantly prognostic even after adjusting for race, gender and stage. It can be easily utilized at the time of LANSCLC diagnosis to help predict life expectancy. As an indicator of inflammatory response, it should be explored in the context of immunomodulatory therapy.
