Prognostic significance of cytokine modulation in non-small cell lung cancer

Increased production of immunosuppressive interleukin-10 (IL-10) by non-small cell lung cancer (NSCLC) and increased serum IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in whole blood cell cultures of NSCLC-patients. We now analyzed the influence of IL-2 secretion on survival in NSCLC-patients and the influence of IL-10 on IL-2 secretion. The correlation of the IL-2 producing ability of whole blood cells in response to PHA in 90 NSCLC-patients at the time of diagnosis to survival was calculated by Crit-level, the Kaplan-Meier method and the log-rank test. With a cut-off value of IL-2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with a p-value of 0.014. In the group with high and low IL-2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically-treated patients the difference in survival was significant with a p-value of 0.011. In 14 patients with surgical resection of the tumor and high IL-2 at diagnosis and 19 patients with surgical resection, but low IL-2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL-2 in whole blood cell cultures from healthy individuals was inhibited in a dose-dependent manner upon addition of IL-10. Taken together, suppression of IL-2 secretion has prognostic significance for survival of NSCLC-patients and may be mediated by tumor-derived IL-10.     

Alterations of routine blood tests in adult patients with soft tissue sarcomas: Relationships to cytokine serum levels and prognostic significance

Background:It has been reported that malignancy is oftenaccompanied by hematological alterations and that such alterations maycorrelate with poor prognosis. It has also been demonstrated thatseveral cytokines may be synthesized by many malignant tumors and thatelevated serum levels of some cytokines are associated with changes inblood cell counts in cancer patients. However, so far little is knownabout the prognostic significance and mechanism of hematological changesin soft tissue sarcomas. The aim of the study was to evaluate theroutine blood tests of disturbances in patients with malignantsoft-tissue tumors prior to treatment and to correlate these resultswith selected cytokine serum levels, clinicopathological features of thetumors and patient survival. Patients and methods:145patients (75 males, 70 females; mean age 49.97 ± 16.9 yrs) withhistologically confirmed soft tissue sarcomas before treatment wereenrolled into the study. In all these patients we evaluated routineblood tests (hemoglobin level HGB, white blood cell count WBC, plateletcount PLT, white blood cell differential count–neutrocyte countNE, lymphocyte count LY, monocyte count MN, eosinophile count EO) andserum levels of 13 cytokines and soluble cytokine receptors (IL-6, IL-8,IL-10, TNF, G-CSF, M-CSF, bFGF, VEGF, IL-1ra, sIL-2R, sIL-6R, TNFRI, TNF RII) – ELISA method. Peripheral blood samples from 50healthy volunteers served as control. Statistical analysis was performedusing Kolmogorov–Smirnov and Mann–Whitney U-tests,² test (P < 0.05), whereappropriate. For survival analysis the Kaplan–Meier method,log-rank test and multivariate Cox analysis were applied. Results:Alterations of at least one of the standard bloodtests were found in 43.4% of all cases. The most frequentalterations were: neutrophilia (28.3% of cases), leukocytosis(27.6%), decreased HGB (25.5%), monocytosis (19.3%)and thrombocytosis (14.5%); they correlated strongly withelevated serum levels of several cytokines and soluble cytokinereceptors (particularly: sIL-2R, IL-6, IL-8, M-CSF, VEGF, TNF RI, TNFRII) (P < 0.001). Lymphocytopenia(LY < 1.0) found in 10.3% of patients correlatedstrongly with increased serum levels of IL-6, sIL-2R, TNF RI. Inparallel, we found a significant difference in serum levels of 11of 13 cytokines (IL-1ra, sIL-2R, IL-6, IL-8, IL-10, TNF RI, TNF RII,TNF, M-CSF, bFGF, VEGF) (P < 0.001) in softtissue sarcoma patients compared to healthy controls. Hematologicalalterations were significantly more frequent in patients with advancedtumors. In multivariate analysis we found no prognostic significance ofany of the routine blood tests in soft tissue sarcoma patients. Conclusion:The results of this study demonstrate thathematological alterations, which occur in over 40% of soft tissuesarcoma cases, are found more frequently in patients with advancedtumors. Strong correlations between the occurrence of hematologicalabnormalities and elevated serum levels of several cytokines and solublecytokine receptors, suggest that the former may develop as a result ofcytokine misbalance frequently detected in soft tissue sarcoma patients.However, the results of routine blood tests alone are no independentprognostic factor for survival of soft-tissue sarcoma patients.     

Selective suppression of cytokine secretion in patients with small-cell lung cancer

BACKGROUND: Whether or not cytokine secretion is impaired in patients withsmall-cell lung cancer (SCLC), is unknown. We therefore investigatedwhether cytokine secretion by immunocompetent cells may be suppressedin patients with SCLC PATIENTS AND METHODS: We determined cytokine secretion by lymphocytes and monocytesin whole blood cell cultures from 58 patients with SCLC, 95patients with non-small-cell lung cancer (NSCLC), 10 patientswith nonmalignant lung disease and from 44 normal healthy individualsby using an enzyme-linked immunosorbent assay (ELISA) specificfor the different cytokines measured. RESULTS: Compared to normal controls, immunocompetent cells from patientswith SCLC secreted significantly lower amounts of IL-2, IFN     

Serum vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in small cell lung cancer

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.     

Carcinoid tumors: Analysis of prognostic factors and survival in 301 patients from a referral center

Background: Little is known about factors related to prognosis in patientswith carcinoid disease. In this study we have tried to identify such factors.Patients and methods: We have evaluated 301 consecutive carcinoid patients(256 midgut, 39 foregut and six hindgut) referred during 15 years for medicaltreatment with respect to tumor distribution, hormone production, prognosticfactors and survival.Results: Survival was significantly shorter in midgut carcinoid patientswith 5 liver metastases or with high levels of urinary5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. Byunivariate analysis, these variables together with the presence of carcinoidsyndrome were related to a higher risk of dying. In multivariate analyses,performed in the 71 patients with full information on all variables, advancedage and plasma chromogranin A > 5000 µg/l were independent predictorsof overall survival.Conclusions: Poor prognostic factors for midgut carcinoid patients weremultiple liver metastases, presence of carcinoid syndrome and high levels ofthe tumor markers studied. In this study the only independent predictors ofbad prognosis in midgut carcinoid patients were advanced age, which howeveris inherently related to overall survival, and plasma chromogranin A >5000µg/l. Thus, chromogranin A may prove to be an important prognosticmarker for patients with carcinoid tumors.     

Neuron-specific enolase and response to initial therapy are important prognostic factors in patients with small cell lung cancer

Purpose

The prognostic factors for the survival of small cell lung cancer (SCLC) patients are still widely debated. The aim of this study was to identify the clinical features and prognostic factors in SCLC patients.

Methods

A retrospective study was conducted on SCLC patients who were treated in our hospital between July 2010 and July 2015. Comparison of overall survival (OS) was performed using the Kaplan–Meier method. Prognostic factors for OS were identified by multivariate Cox regression models.

Results

A total of 523 patients with complete data and ECOG 0-2 were enrolled in our study. A total of 383 patients (73.2%) were diagnosed with ES-SCLC (extensive-stage SCLC) and 140 patients (26.8%) were diagnosed with LS-SCLC (limited-stage SCLC). In all patients, early disease stage, good ECOG, normal neuron-specific enolase (NSE), thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation, good response to initial therapy were independent favorable prognostic factors for OS, along with gender, age, CEA and CA125. In LS-SCLC patients, normal NSE, normal CEA, good response to initial therapy and surgery were independent favorable prognostic factors for OS. In ES-SCLC patients, good ECOG, normal NSE, thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation and good response to initial therapy were independent favorable prognostic factors for OS. Remarkably, NSE and response to initial therapy were independent prognostic factors for OS in all SCLC patients, LS-SCLC patients and ES-SCLC patients.

Conclusion

The normal NSE and good response to initial therapy predicted a better survival for SCLC patients, regardless of disease stage.

     

Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor

OBJECTIVES: Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). METHODS: Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were referred to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. RESULTS: Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. CONCLUSIONS: Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.     

The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer

Background:

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment.

Methods:

We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital.

Results:

In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS.

Conclusions:

NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.     

Prognostic value of circulating tumor cells’ reduction in patients with extensive small-cell lung cancer

Objectives

Circulating tumor cells (CTCs) have been hypothesized to be a prognostic factor in small-cell lung cancer (SCLC), and different cutoffs have been proposed to identify patients at high risk. We assessed the prognostic value of CTCs in patients with extensive SCLC.

Materials and methods

CTCs were assessed with the CellSearch system in 60 extensive SCLC patients. CTC count at baseline or after one cycle of chemotherapy (cycle-1) or as change after chemotherapy were analyzed separately. Primary outcome was overall survival. The accuracy of prognostic role was assessed by Harrell's c-index. “Optimal” cutoffs were derived by bootstrap resampling to reduce the overfitting bias; accuracy improvement was estimated by calculating the difference of c-indexes of models including clinical variables with or without CTCs.

Results

CTCs were identified in 90% (54/60) of patients at baseline, in which CTC count ranged from 0 to 24,281. CTC count was strongly associated with the number of organs involved. The prognostic accuracy was only marginally increased by the addition to clinical information of “optimal” CTC cutoffs at baseline and after cycle-1. Conversely, a reduction of CTC count higher than 89% following chemotherapy significantly improved prognostic accuracy (bootstrap p-value = 0.009) and was associated with a lower risk of death (HR 0.24, 95% CI 0.09–0.61). When previously proposed cutoffs were applied to our cohort, they showed only marginal improvement of the prognostic accuracy.

Conclusion

CTCs have useful prognostic role in extensive SCLC, but only the change of CTC count after the first cycle of chemotherapy provides clinically relevant information. Previously reported CTC cutoffs were not prognostic in our cohort of patients.     

Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma

Background Interleukin-18 (IL-18), a cytokine produced by macrophages, is capable of inducing T-lymphocyte synthesis of interferon- (IFN-). In this study, for the first time, the serum concentration of IL-18 and its significance as a prognostic indicator was evaluated in patients with epithelial ovarian cancer.Methods The serum IL-18 level was measured by an enzyme-linked immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8 healthy controls. Relationships between the IL-18 level and clinicopathological features were examined by univariate and multivariate analyses.Results The median serum IL-18 level in the ovarian cancer patients was 229.6pg/ml, and the level was significantly elevated compared with that in the normal controls (151.3pg/ml; P 0.01). No significant correlations were detected between the IL-18 level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate analysis, overall survival was shown to be affected by IL-18 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-18 serum levels, while confirming the role of previously established prognostic variables, such as performance status, stage, and residual tumor.Conclusion This study showed that IL-18 serum levels were elevated in ovarian cancer patients and were correlated with overall survival, although they were shown not to be an independent prognostic factor.     

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

Background:

Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients.

Methods:

Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS).

Results:

Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide.

Conclusion:

Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment.     

Interleukin-33 Expression does not Correlate with Survival of Gastric Cancer Patients

The aim of the study was to investigate IL-33 expression in gastric cancer (GC) and its association with the clinical characteristics and the prognosis. IL-33 protein in tumor and corresponding adjacent tissues were detected by immunohistochemistry in 179 GC patients and clinical features plus prognostic value were analyzed via Pearson’s chi-square test and Kaplan–Meier test in Cox proportional hazards model, respectively. IL-33 protein levels were significantly lower in tumor tissues than adjacent tissues (29.05% vs. 78.77%, χ ²  = 89.05, P < 0.001). The positive rate of IL-33 in the ulcerative type group was the lowest among all groups (P < 0.05). IL-33 levels were correlated with age (P = 0.025) and invasion depth (P = 0.030) while not significantly associated with the overall survival of GC patients. IL-33 expression is associated with age and invasive depth of GC patients but not an independent risk factor of prognosis.     

Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie.

PURPOSE: Few clinical prognostic factors have been identified for patients with metastatic renal cell carcinoma (MRCC), and no biomarker is known in this disease. Several endogenous cytokines have demonstrated interesting and significant correlations with survival in these patients. Our objective was to analyze the prognostic value of circulating vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and interleukin-6 (IL-6). PATIENTS AND METHODS: Serum levels of IL-6, IL-10, and VEGF were measured in patients with MRCC. Their prognostic value for response to treatment and progression-free and overall survival was evaluated. Pretreatment samples were obtained from 138 patients of a large randomized multicentric trial. Endogenous cytokine levels were determined using immunoassays. Univariate and multivariate analyses were performed to evaluate the prognostic value of each factor further controlled by an internal validation test. Threshold values for serum IL-6 and VEGF were determined using the quartile method. RESULTS: Serum IL-6 was detectable in 70% of the patients. IL-10 and VEGF were elevated in 8% and 71% of the patients, respectively. None of these circulating factors was correlated with response to treatment. IL-10 was not significantly correlated with progression-free or overall survival. Despite significant correlation with survival, VEGF was not an independent prognostic factor in the multivariate analysis. Finally, IL-6 was significantly correlated with progression-free survival and overall survival, and has prognostic value for overall survival. CONCLUSION: Circulating IL-6 level appears to be an important independent prognostic factor in patients with MRCC; if confirmed in further studies, it could be considered for treatment decisions in these patients.     

Lack of interleukin-10 expression could predict poor outcome in patients with stage I non-small cell lung cancer

PURPOSE: Interleukin-10 (IL-10) may play an important role in controlling tumor growth and metastasis. Some reports have shown that IL-10 can be a potent inhibitor of tumor growth, but others suggest that IL-10 expression by the tumor is an adverse prognostic factor. Because normal bronchial epithelial cells constitutively produce IL-10, we decided to test the prognostic value of IL-10 in a well-defined population of patients with stage I non-small cell lung cancer (NSCLC) treated in a single institution. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed IL-10 expression in specimens from 138 patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available. RESULTS: IL-10 expression was retained (IL-10 labeling index > or = 10%) in 94 patients (68.1%) and lost in 44 patients (31.9%). The duration of overall, disease-specific, and disease-free survival in the 44 patients lacking IL-10 expression was worse than in the 94 patients with IL-10 expression (P = 0.08, 0.02, and 0.05, respectively; Log-rank test). Interestingly, IL-10 expression was observed more frequently in tumors with squamous cell histology than in tumors of other histological subtypes (P = 0.04; chi(2) test). Multivariate analysis confirmed the independent prognostic value of IL-10 expression for disease-specific survival (P = 0.04). CONCLUSION: Lack of IL-10 expression by the tumor was associated with a significantly worse outcome of early stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.     

Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis

BACKGROUND: Cytokines have been implicated in diverse processes that are relevant to pancreatic carcinoma, including cachexia, asthenia, and tumor growth. The objective of this study was to examine the association between serum levels of proinflammatory and antiinflammatory or angiogenic cytokines and the outcomes of patients with pancreatic carcinoma. METHODS: Serum cytokine levels were measured by enzyme-linked immunosorbent assay from 51 patients with pancreatic carcinoma and from 48-62 healthy volunteers. Cytokine levels were compared with disease manifestations and overall survival. RESULTS: Circulating levels of vascular endothelial growth factor, tumor necrosis factor alpha, interleukin-1alpha (IL-1alpha), and IL-1beta were not elevated significantly in patients with pancreatic carcinoma, but levels of IL-6, IL-8, IL-10, and IL-1 receptor antagonist (IL-1RA) were elevated significantly (P <0.05). Cytokine levels were dichotomized based on an analysis of null Martingale residuals. Patients who had IL-6 levels > 5.2 pg/mL or IL-10 levels >9.8 pg/mL had significantly worse survival compared with patients who had lower IL-6 or IL-10 levels (P <0.05). IL-8 levels were not associated with survival differences. Patients who had IL-1RA levels <159 pg/mL had significantly worse survival compared with patients who had higher IL-1RA levels (P <0.05). Higher IL-6, IL-10, and IL-8 levels were associated with poor performance status and/or weight loss. In multivariate analysis, only T4 tumors and high IL-6 levels were selected as independent prognostic factors for poor survival. CONCLUSIONS: Circulating levels of several cytokines were high in patients with pancreatic carcinoma, and their association with weight loss and poor performance status suggested that they may be involved in these disease manifestations. Furthermore, serum cytokine levels, in particular IL-6, may be a useful prognostic marker.     

Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC)

In this study, we evaluated the clinical usefulness of ProGRP and NSE for diagnosis and prognosis of small-cell lung cancer (SCLC). Serum levels of ProGRP and NSE were determined in 108 healthy subjects, 103 patients with benign pulmonary diseases, 142 with non-small cell lung cancer (NSCLC), and 114 with SCLC. Sensitivity of ProGRP in diagnosis of SCLC was significantly higher than that of NSE (64.9 vs. 43.0%, P < 0.001). The difference was substantial in patients with limited disease (56.5 vs. 20.3%, P < 0.001). However, 11 of 40 SCLC patients with normal levels of serum ProGRP (27.5%) showed elevated levels of serum NSE. In the SCLC patients receiving chemotherapy, the CR rate in patients with elevated NSE levels was significantly lower than in patients with normal levels of NSE (18.5 vs. 61.7%, P < 0.001). Elevation of both ProGRP and NSE was a poor prognostic factor, and patients with elevated levels of either ProGRP or NSE showed shorter survival than those without. From multivariate analysis, NSE was found to have a greater effect on survival of SCLC patients than ProGRP. These findings indicate that ProGRP is more sensitive than NSE for diagnosis of SCLC, while NSE is superior to ProGRP as a prognostic factor. In conclusion, both ProGRP and NSE are useful tumor markers and they have a complementary role for each other in diagnosis and prognosis of SCLC.     

Evaluation of the Simplified Comorbidity Score (Colinet) as a prognostic indicator for patients with lung cancer: A cancer registry study

Introduction

A Simplified Comorbidity Score (SCS) provided additional prognostic information to the established factors in patients with non-small cell lung cancer lung cancer. We undertook this analysis to test the prognostic value of the SCS in a population-based study.

Patients and methods

Retrospective survey of all Victorians diagnosed with lung cancer in January–June 2003, identified from the Victorian Cancer Registry.

Results

There were 921 patients, with data available for 841 (91.3%). Median age was 72 years (range 30–94) and 63.1% were male. A tissue diagnosis was made for 89.9%, of which 86.6% were non-small cell (NSCLC), and 13.4% small cell carcinoma (SCLC). Comorbidities on which the SCS is based were distributed: cardiovascular 54.6%; respiratory 38.9%; neoplastic 19.9%; renal 4.6%; diabetes 11.7%; alcoholism 5.5%; and tobacco 83.1%.In patients with NSCLC, higher SCS score (>9) was associated with increasing stage, ECOG performance status, male sex, increasing age, tobacco consumption and not receiving treatment. Using Cox regression, survival was analysed by SCS score after adjusting for the effect of age, sex, cell type (NSCLC, SCLC, no histology), ECOG performance status and stage for all patients and then restricted to NSCLC. As a continuous or dichotomous (≤ or >9) variable, SCS was not a significant prognostic factor for all patients or when restricted to NSCLC.

Conclusion

In this retrospective analysis of population based registry patients, SCS did not provide additional prognostic information in patients with lung cancer. ECOG performance status may be a substitute for the effect of comorbidity.     

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.     

Autoimmunity resulting from cytokine treatment predicts long-term survival in patients with metastatic renal cell cancer.

PURPOSE: In patients undergoing cytokine therapy, systemically applied interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) have been reported to induce thyroid dysfunction as well as thyroid autoantibodies. We analyzed the correlation of thyroid autoimmunity with HLA phenotype, various other autoimmune parameters, and patient survival. PATIENTS AND METHODS: For this purpose, antithyroglobulin autoantibodies, antimicrosomal thyroid autoantibodies, thyroglobulin receptor autoantibodies, thyroid dysfunction, and multiple clinical parameters were determined in 329 unselected patients with metastatic renal cell cancer before and after systemic IL-2 and IFN-alpha2 therapy. For statistical analysis, we used both univariate and multivariate Cox proportional hazards models and the two-tailed Fisher's exact test. RESULTS: Antithyroglobulin autoantibodies and antimicrosomal thyroid autoantibodies were detected in 60 patients (18%); positive autoantibody titers of various other autoimmune parameters were statistically unrelated. The presence of thyroid autoantibodies was correlated with prolonged survival (P<.0001). There was a statistically significant difference in frequencies of HLA-Cw7 expression between thyroid autoantibody-positive and -negative patients (P< or =.05), and the Cw7 expression was associated with prolonged overall survival (P = .009). CONCLUSION: The evaluation of thyroid autoantibodies during cytokine therapy could be a useful prognostic marker for patients with renal cell carcinoma who benefit from cytokine treatment. IL-2- and IFN-alpha2-induced tumor control and prolonged survival may require breaking of immunologic tolerance against self-antigens.     

Alternating triple therapy for the treatment of intermediate grade and immunoblastic lymphoma

Background: CHOP is currently considered the gold standard of treatmentfor intermediate grade lymphomas. We designed a new regimen known as ATT(alternating triple therapy) which uses three non-cross resistantcombinations in alternating sequence for nine cycles.Materials and methods: This is a phase II clinical trial with comparisonto CHOP/CMED historical controls using prognostic factors. The tumor scoresystem was used to evaluate the results of this trial. Two hundredsixty-eight eligible patients who had one or more of the following adversefeatures: bulky disease, elevated LDH or >1 extranodal site wereanalyzed. Outcome measures consist of survival and failure free survival.Results: At a median follow-up of 32 months, there was no statisticallysignificant difference in survival for those with favorable prognosticfactors (tumor score 2). However, there was a statistically significantdifference in favor of ATT for those with unfavorable tumor scores. When weexamined the failure-free survival of those with unfavorable tumor scores,we again observed a superiority for the ATT regimen over CHOP/CMED but theopposite was true for those with favorable tumor scores. We also found astatistically significant difference in favor of the ATT regimen whencompared with CHOP/CMED for patients 60 years old with a tumor score3, while no advantage was found for those >60 years.Conclusions: ATT appears more effective but only for patients <60 yearsold with unfavorable tumor scores. In those older than 60 years with favorabletumor score, CHOP/CMED appears superior. ATT might be an adequate regimen foryoung patients with poor prognostic features while CHOP/CMED might be a betterchoice for those with good prognosis irrespective of age. For those >60years with unfavorable tumor scores neither ATT or CHOP/CMED were adequatetreatment. Because of the phase II nature of this study, these conclusionsshould be considered as hypotheses which require prospective testing.