non-Hodgkin Lymphoma Overall Survival Research Articles

Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma.

Increased microvascular density correlates with more advanced disease and unfavorable overall survival in non-Hodgkin lymphoma (NHL), suggesting that angiogenesis is important for disease progression. However, studies of anti-angiogenic agents in NHL patients, have generally not shown favorable outcomes. The aim of this study was to investigate whether plasma levels of a subset of angiogenesis-associated proteins are increased in indolent B-cell derived NHL (B-NHL) and to investigate whether the levels differ between patients with asymptomatic versus symptomatic disease. Plasma levels of growth differentiation factor 15 (GDF15), endostatin, matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), long pentraxin 3 (PTX3), and galectin 3 (GAL-3) were measured by ELISA in 35 patients with symptomatic indolent B-NHL, 41 patients with asymptomatic disease, and 62 healthy controls. Bootstrap t-tests were used to assess the relative differences in biomarker levels between groups. Group differences were visualized using a principal component plot. Mean plasma endostatin and GDF15 levels were significantly higher in symptomatic and asymptomatic lymphoma patients than in controls. Symptomatic patients had higher mean MMP9 and NGAL than controls. The finding of increased plasma endostatin and GDF15 in patients with asymptomatic indolent B-NHL suggests that increased angiogenic activity is an early event in indolent B-NHL disease progression.

Abstract B58: Sunlight exposure and overall survival in melanoma, colon cancer, and non-Hodgkin's lymphoma

Abstract Background: Sunlight exposure is a major source of vitamin D, which is thought to inhibit tumor growth as well as enhance the efficacy of chemotherapy. Accumulating evidence suggests sunlight exposure is associated with prognosis of several cancers through vitamin D related or other unknown biological pathways. We hypothesized that, due to variation in Vitamin D receptors as well as potential variation in underlying biological mechanisms across different tissues, the protective effect of sunlight exposure on overall survival may vary across cancer types. Methods: A retrospective cohort study was conducted at Moffitt Cancer Center, Florida, to evaluate sunlight related factors in association with overall survival of three different cancers. Cases included patients with pathologically confirmed primary colon cancer (n=380), primary non-Hodgkin's lymphoma (NHL) (n=311) and primary melanoma (n=1364), who were treated at Moffitt Cancer Center from 2007 through 2012. At their first visit to Moffitt, patients completed an electronic questionnaire including information on demographics, past medical history, current symptoms, and a variety of lifestyle risk factors that can impact prognosis of cancer. Questions related to sunlight exposure included history of blistering sunburn, history of sunbed, sunlamp or tanning bed use, frequency of sunburns and other risk factors for skin cancer. Data on vital status were obtained from Moffitt's cancer registry. Cox proportional hazards ratios were estimated to determine the association of sun exposure related factors with overall survival, adjusting for confounders. Analyses were further stratified by stage at diagnosis. Results: History of blistering sunburns was associated with 52% significantly improved overall survival among NHL cases (HR=0.48, 95% CI=0.23-0.97), after adjusting for age and stage at diagnosis. While no association was observed between history of sunburns and survival of NHL cases with early stage at diagnosis, 63% improved overall survival was observed among cases with advanced stage disease (HR=0.37, 95% CI=0.17-0.84). Although not significant, history of sunbed use was associated with 50% (HR=0.50, 95% CI=0.07-3.69) improved overall survival among NHL cases. No significant associations were observed between history of sunburn or history of sunbed use and survival of colon cancer and melanoma. Conclusion: Sunlight exposure may be an important predictor of overall survival in NHL but not in colon cancer and melanoma and may be related to protective effect of increased Vitamin D levels. The protective effect of sunlight exposure may differ by stage at diagnosis in patients with NHL. Additional research should be conducted to further investigate biological pathways, with a focus on Vitamin D, which may explain these findings. Citation Format: Shalaka S. Hampras, Vernon K. Sondak, David Shibata, Samir M. Dalia, Dana E. Rollison. Sunlight exposure and overall survival in melanoma, colon cancer, and non-Hodgkin's lymphoma. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B58.

Dietary intake of fruits and vegetables and overall survival in non-Hodgkin lymphoma

In a cohort of 301 patients with non-Hodgkin lymphoma (NHL), we examined whether the pre-diagnostic consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with overall survival (OS). Proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. A total of 91 deaths occurred in the patient cohort over a median follow-up period of 8.2 years. No association with OS was detected for a dietary pattern characterized by high intakes of fruits, vegetables and starch; fruit intake; vegetable intake; or nutrient intake in patients diagnosed with overall NHL, follicular lymphoma or diffuse large B-cell lymphoma. Higher intakes of carotene-rich vegetables (HR = 0.4 [0.2–1.0]; ptrend = 0.05) and α-carotene (HRT3 vs. T1 = 0.4 [0.2–0.9]; ptrend = 0.03) were associated with better OS among ever smokers. Overall, our data suggest that the intake of fruits and vegetables prior to diagnosis is not associated with OS in patients with NHL.

The Impact of Cigarette Smoking On Overall Survival in Non-Hodgkin Lymphoma

AbstractAbstract 5100 Introduction:Smoking has been suggested as a potential risk factor for the development of non-Hodgkin lymphoma (NHL). However, the prognostic impact of smoking in patients with NHL has not been well studied and may have important implications regarding outcome. Methods:In a population-based cohort of 308 NHL patients diagnosed between 1999 and 2002, we examined the association between cigarette smoking habits prior to NHL diagnosis and overall survival (OS). Multivariable Cox proportional hazards models adjusted for age, gender, and education were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all NHL, and for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Measurements of smoking included categories for smoking status, pack-years of smoking, years of smoking, daily number of cigarettes smoked, and years since quitting smoking. Continuous exposures for cigarette smoking were also examined with potential non-linear relations tested using restricted cubic splines. We conducted subgroup analyses adjusting for established clinical and prognostic variables. Results:In the patient cohort, a total of 96 deaths occurred over a median follow-up period of 8. 2 years. For all NHL cases, current smokers had worse survival (HR=1. 8 [1. 0–3. 1], ptrend=0. 07, for risk of all-cause mortality) when compared to never smokers. The inferior survival was also associated with pack-years of smoking (HR=1. 5 [0. 9–2. 4], ptrend=0. 12, for >30 pack-years) and smoking duration (HR=1. 5 [0. 9–2. 3], ptrend=0. 13, for >30 years). Smoking remained an independent predictor of OS after adjustment for initial treatment, stage at diagnosis and the presence of B symptoms: HR=2. 6 [1. 1–6. 3], ptrend=0. 03, for current smokers; HR=2. 4 [1. 1–5. 6], ptrend=0. 03, for patients with >30 pack-years of cigarette smoking; and HR=2. 5 [1. 2–5. 5], ptrend=0. 02, for patients smoking longer than 30 years. Among former smokers, a shorter interval from quitting to diagnosis was associated with worse survival (per 5 years of quitting cigarette smoking, HR=0. 9 [0. 8–1. 0], ptrend=0. 06). The associations with cigarette smoking and OS were stronger for FL than for DLBCL. In analyses stratified by age at diagnosis, the associations for current smokers (HR=3. 7 [1. 5–9. 2], ptrend=0. 01), daily number of cigarettes smoked (HR=2. 8 [1. 0–7. 5], ptrend=0. 04), and years of cigarette smoking (HR=3. 0 [1. 1–8. 3], ptrend=0. 04) were stronger for patients diagnosed at <60 years of age. The risk estimates for smoking with OS did not depart from unity among those diagnosed at ≥ 60 years of age. The associations between cigarette smoking and OS were similar for men and women. Conclusion:Our data suggest that cigarette smoking prior to diagnosis is associated with inferior OS in NHL patients. The reduction in survival is most prominent for patients diagnosed at <60 years of age and for those with FL. Among former smokers, greater time from cessation of smoking to diagnosis may improve OS. Further research examining the impact of smoking cession on OS among NHL patients is warranted. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma

AbstractClinical trials have demonstrated that rituximab improves overall survival in non-Hodgkin lymphoma (NHL), except in mantle cell lymphoma (MCL). We used Surveillance Epidemiology and End Results (SEER)–Medicare data to compare survival in older MCL patients who began chemotherapy with or without rituximab within 180 days of diagnosis. Patients were followed from diagnosis (January 1999 to December 2005) until death or the end of observation (December 2007). Medicare administrative and claims data were used to identify the date and cause of death and the immunochemotherapy regimen. Of 638 patients, the mean age at diagnosis was 75 years, 75% had stage III/IV disease, 67% had extranodal involvement, and 64% received rituximab. The average length of first-line treatment was 21 weeks, with no difference between the 2 groups (P = .76). Median survival was 27 months for chemotherapy alone, compared with 37 months for chemotherapy plus rituximab (P < .001). In multivariate analysis of 2-year survival, rituximab plus chemotherapy was associated with lower all-cause (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.41-0.82; P < .01), and cancer-specific (HR 0.56; 95% CI 0.37-0.84; P < .01) mortality. Results were similar when using the entire observation period, propensity score analysis, and limiting chemotherapy to CHOP/CHOP-like. We conclude that first-line chemotherapy including rituximab is associated with significantly improved survival in older patients diagnosed with MCL.

High serum angiogenin at diagnosis predicts for failure on long-term treatment response and for poor overall survival in non-Hodgkin lymphoma

Background Angiogenin is a potent inducer of angiogenesis. We prospectively evaluated the prognostic significance of serum angiogenin from 204 consecutive non-Hodgkin lymphoma (NHL) patients diagnosed and treated in a single institution. Methods Serum angiogenin, VEGF, and bFGF concentrations at diagnosis were determined using a quantitative sandwich enzyme immunoassay technique. Kaplan–Meier survival curves were compared by the log-rank test. Multivariate survival analyses were performed using the parametric model of Weibull and the non-parametric proportional hazards model of Cox. Results Patients with a high serum angiogenin at diagnosis (>median; 401 ng/ml) had significantly lower 5-year survival rate than those with a low (⩽median) angiogenin (42% versus 63%, respectively; P = 0.0073). Serum angiogenin provided additional information to the International Prognostic Index (IPI) identifying a subgroup (serum angiogenin >median and IPI > 1) with very poor prognosis (5-year survival 19%, P < 0.0001). In receiver operating characteristic (ROC) analyses the accuracy of the IPI to correctly classify patients with favourable or poor survival was improved from fair to good by complementing the IPI with serum angiogenin concentration. With patients who initially achieved complete response (CR) after chemotherapy, a high angiogenin at diagnosis (>median; relative risk (RR) 2.38; P = 0.0077) and an advanced tumour stage (III–IV; RR 2.41; P = 0.0087) were the only independent predictors for patients with unfavourable outcome although first responding well to therapy. Conclusions We conclude that elevated serum angiogenin surfaced as an independent predictor for failure in long-term treatment response and for poor overall survival in a series of 204 NHL patients, and might thus also complement the IPI in identifying the patients with particularly aggressive and/or treatment resistant disease.

Smoking, Obesity and Overall Survival in Non-Hodgkin Lymphoma (NHL): A Population-Based Study.

Background: Several studies suggest that smoking and obesity may increase the risk of developing NHL, but the impact of these factors on survival is relatively unexplored. One recent population-based Italian study found that smoking may negatively impact overall survival.Methods: We evaluated the association of body mass index (BMI) and cigarette smoking on overall survival in 1,286 patients who participated in a population-based case-control study conducted through the Surveillance, Epidemiology, and End Results (SEER) cancer registries in Detroit, Iowa, Seattle and Los Angeles. BMI (on 1189 participants) and a smoking history (on 471 participants) were obtained through in-person interviews. Histology, stage, presence of B symptoms, first course of therapy, date of last follow-up, and vital status were derived from linkage to registry databases at each study site in the spring of 2005. Hazard Ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models, while adjusting for demographic and clinical factors.Results: The median age at diagnosis was 58 years (range: 16 – 74), and the most common histologies were DLBCL (33%), follicular (25%), SLL/CLL (12%), marginal zone (9%), mantle cell (4%) and Peripheral T-cell (3%). The median BMI was 26.6 (range: 16.2 – 47.3), and 26% of patients were classified as obese (i.e. BMI >30). Of patients with a smoking history, 47% had never smoked, 19% were active smokers at diagnosis, and 34% were former smokers. No significant differences were observed between those with and without tobacco use data in terms of primary lymphoma characteristics. Overall survival (OS) was defined as time from diagnosis to death due to any cause. Median follow-up on all living patients was 58 months (range: 4 – 78), and 333 patients had died. When BMI was assessed as a continuous measure, it was borderline significantly associated with OS (p=0.050). An indicator of whether or not BMI > 30 was also significantly associated with OS (HR=1.30; 95% CI: 1.01 – 1.68; p=0.042). Ever vs. never smokers also exhibited a survival disadvantage (HR=1.66; 95% CI: 1.12 – 2.44; p=0.011). When broken down further, former smokers who had smoked for >10 years (HR=1.61; 95% CI: 1.02 – 2.52; p=0.039) and current smokers (HR=1.79; 95% CI: 1.07 – 3.02; p=0.028) were at a survival disadvantage over those who had never smoked. When both smoking and BMI status were included in the model, only the indicator of being a current smoker remained statistically significant (p=0.031), with a trend toward decreased survival for former smokers who had smoked >10 years (p=0.061) and those with BMI >30 (p=0.058).Conclusions: NHL patients who smoke or are obese had a poorer overall survival. These observations warrant further investigation, including whether interventions for smoking cessation or weight loss can impact NHL survival.