Preoperative thrombocytosis predicts poor survival in patients with glioblastoma

Thrombocytosis, which is defined as a platelet count greater than 400 platelets/nl, has been found to be an independent predictor of shorter survival in various tumors. Release of growth factors from tumors has been proposed to increase platelet counts. Preoperative platelet counts and other clinical and hematological parameters were reviewed from the records of 153 patients diagnosed between 1999 and 2004 with histologically confirmed glioblastoma in order to evaluate the prognostic significance of preoperative thrombocytosis in these patients. The relationship between thrombocytosis and survival was initially analyzed in all patients regardless of further therapy. Univariate log-rank tests showed that the median survival time of 29 patients with preoperative thrombocytosis (19%) was significantly shorter (4 months; 95% confidence interval [95% CI], 3-6 months) compared to 124 patients with normal platelet counts (11 months; 95% CI, 8-13 months; p = 0.0006). Multivariate analysis (Cox proportional hazards model) confirmed preoperative platelet count, age, prothrombin time, and activated partial thromboplastin time to be prognostic factors of survival (all p < 0.05). In a subset of patients (only operated patients with radiation therapy with or without additional chemotherapy), survival was likewise significantly shorter when preoperative thrombocytosis was diagnosed (6 months; 95% CI, 4-12 months) compared to patients with normal platelet count (13 months; 95% CI, 11-15 months; p = 0.0359). In multivariate analysis, age, platelet count, preoperative prothrombin time, and degree of tumor resection retained significance as prognostic factors of survival (all p < 0.05). The results of our study demonstrate preoperative thrombocytosis to be a prognostic factor associated with shorter survival time in patients with glioblastoma.     

Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

BACKGROUND: The objective of the current study was to determine the significance of sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma (RCC). METHODS: Patients with metastatic RCC were included in this study and were categorized according to sarcomatoid differentiation. RESULTS: Patients with sarcomatoid differentiation had more aggressive tumor characteristics than those without sarcomatoid differentiation. After immunotherapy, the median progression-free survival was 9.0 months (95% confidence interval [CI] 1.4-52.7) for patient without sarcomatoid differentiation and 3.2 months (95% CI 0.4-42.9) for patients with sarcomatoid differentiation, respectively (P=0.0001). The median overall survival was 22.2 months (95% CI 3.2-75.4) and 10.0 months (95% CI 0.7-60.1) in both groups. When comparing patients with sarcomatoid differentiation, there was no significant difference of overall survival in the immunotherapy group and the no immunotherapy group. Multivariate Cox proportional hazards model analysis showed that T stage (Hazard ratio [HR] 1.71; 95% CI 1.07-2.74; P=0.024), sarcomatoid differentiation (HR 2.18; 95% CI 1.30-3.66; P = 0.003), and the number of metastasis sites (HR 1.81; 95% CI 1.14-2.88; P=0.012) were independent predictors of progression-free survival. Sarcomatoid differentiation and the number of metastasis sites were independent prognostic predictors of overall survival. The estimated relative risks of sarcomatoid differentiation and the number of metastasis sites were 2.83 (95% CI 1.49-5.40; P=0.002) and 2.31 (95% CI 1.29-4.16; P=0.005), respectively. CONCLUSIONS: Our findings suggest that sarcomatoid differentiation is an important prognostic factor for immunotherapy in metastatic RCC.     

Expression parameters of the inhibitors of apoptosis cIAP1 and cIAP2 in renal cell carcinomas and their prognostic relevance

The expression of the inhibitor of apoptosis (IAP) family members cIAP1 and cIAP2 have been shown to be altered in various cancer entities. This study was done to characterize the tumor-related expression profile of cIAP1 and cIAP2 in patients with renal cell carcinomas (RCC) and to evaluate its potential predictive value after curative resection. Expression of cIAP1 and cIAP2 was analyzed by real-time RT-PCR in RCC and corresponding normal tissue samples obtained from a cohort of 127 RCC patients (median follow-up: 48 months) undergoing surgical treatment. Expression data was correlated to histopathological variables and outcome. Overexpression of cIAP1 and cIAP2 occurred in most RCC specimens (p < 0.001), but 20% of the patients had lower cIAP levels in malignant than in normal tissue. The cIAP1 expression correlated with the tumor stage, levels being higher in pT1 tumors than in advanced pathological stages (p = 0.002). Decreased cIAP1 expression in RCC relative to paired normal samples predicted an abbreviated time to recurrence (hazard rate 2.96; 95% CI: 1.23-7.09) and tumor-specific survival (hazard rate 2.78; 95% CI: 1.22-6.38) irrespective of the tumor stage and grade. The prognostic effect of cIAP1 was most pronounced in patients with pT3 disease (log rank test p = 0.001). The results of uni- and multivariate analysis suggest a prognostic value of cIAP1 expression for RCC patients, downregulation indicating an aggressive, potentially lethal phenotype.     

Preoperative Serum Carcinoembryonic Antigen,Carbohydrate Antigen19-9 and Carbohydrate Antigen 125 as Prognostic Factors for Recurrence-free Survival in Colorectal Cancer

Objective: Colorectal cancer (CRC) is among the most common malignancies worldwide. Understanding CRCprognosis at the initial diagnosis is very important for therapeutic strategy selection. This study was conductedto evaluate the prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonicantigen (CEA) and carbohydrate antigen 125 (CA125) for predicting 5-year recurrence-free survival (RFS) inCRC patients. Methods: Preoperative serum CA19-9, CEA and CA125 levels were detected by C12 proteinchip diagnostic system in 103 patients with CRC, and their correlations with the 5-year RFS were analyzed.Results: Patients with positive preoperative serum CA19-9, CEA and CA125 had higher 5-year recurrent rates(75.0% vs 41.0%, 65.6% vs 39.4%, and 87.5% vs 44.2% respectively, all p<0.05), and reduced median RFS (14vs 35 months, 20 vs 36 months, and 4 vs 35 months respectively, all p<0.05) compared with patients negative forcorresponding tumor marker (TM). The median RFS was 59 months (95% CI 28.9-89.1 months) with negativeTMs, 14 months (95% CI 4.5-23.5) for 1~2 positive TMs, and 4 months (95% CI 2.4-5.6) for all 3 positive TMs.Patients with simultaneously positive serum CA19-9, CEA and CA125 had the highest recurrence rate (100%)and the shortest RFS (median 4 months). Univariate analysis showed that stage and the preoperative singleTM or combined TMs correlated with RFS, whereas multivariate Cox regression model analysis revealed onlystage and preoperative serum status of CEA+CA19-9+CA125 to be independent prognostic factors. Conclusion:Preoperative serum CA19-9+CEA+CA125 can be used an independent prognostic factor for CRC 5-year RFS.     

The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma

BACKGROUND: Prognostic nomograms are used increasingly in clinical trials and to guide surveillance for patients with renal cell carcinoma (RCC). An elevated erythrocyte sedimentation rate (ESR) reportedly has been associated with a poor prognosis among patients with RCC, but the ESR is not incorporated into existing nomograms. Hence, the current study was conducted to expand on prior observations pertaining to the ESR as a prognostic indicator in patients with RCC. METHODS: The authors identified 3008 patients who underwent nephrectomy for RCC between 1970 and 2002. Disease-specific survival was estimated using the Kaplan-Meier method, and its association with the ESR and other clinical and pathologic features was evaluated using Cox proportional hazards regression analysis. RESULTS: A preoperative ESR was available for 1075 patients (35.7%), 501 of whom (46.6%) exhibited an elevated ESR, including 437 of 881 patients (49.2%) with clear cell RCC, 41 of 134 patients (30.6%) with papillary RCC, and 20 of 48 patients (41.7%) with chromophobe RCC. An elevated ESR was associated with adverse clinical, laboratory, and pathologic profiles for all three histologic subtypes. The risk ratios (RRs) and 95% confidence intervals (95% CIs) for death because of clear cell RCC, papillary RCC, and chromophobe RCC for patients with an elevated ESR were 3.6 (95% CI, 1.1-1.9), 3.8 (95% CI, 1.4-10.6), and 10.3 (95% CI, 1.2-89.5), respectively. The association between an elevated ESR and death from clear cell RCC persisted even after multivariate analysis (RR of 1.5; 95% CI, 1.2-2.0). CONCLUSIONS: An elevated ESR in patients with RCC suggested the presence of aggressive disease and poorer outcomes after surgical treatment. For patients with clear cell RCC, the ESR provided useful information above and beyond traditional prognostic algorithms, and it may be valuable for preoperative prognostication.     

Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α, and tegafur-uracil: a single-institution experience

BACKGROUND: The objective of the current study was to determine the efficacy and safety of very low-dose interleukin-2 (IL-2), interferon (IFN)-alpha, and tegafur-uracil for patients with unresectable renal cell carcinoma (RCC), metastatic RCC, or both. Clinical prognostic factors were also investigated. METHODS: Fifty consecutive patients underwent a 3-week treatment cycle of IL-2 (0.7 x 10(6) Japanese reference units [JRU])/person on days 1-3 weekly), IFN-alpha (3 x 10(6) international units/person, on days 1-5 weekly), and tegafururacil (300 mg/person daily). RESULTS: The median follow-up after treatment initiation was 11.3 months. A median of three (range, 1-20) treatment cycles was administered. Of 47 eligible patients, 4 had a treatment response (3 complete responses and 1 partial response; objective response rate, 8.5%). The median progression-free and overall survivals were 8.3 months (95% confidence interval [CI], 5.5-10.9 months) and 38.8 months (95% CI, 27.8-49.7 months), respectively. Only 8 patients had grade III/IV toxicities. Two parameters, i.e., the absence of a previous nephrectomy and a low hemoglobin level, were identified as independent factors predictive of poor survival. Patients with low or intermediate risk (presence of none or one of the two prognostic factors) had a durable median survival exceeding 30 months. High-risk patients with both risk factors had rapid disease progression despite treatment. CONCLUSION: While the effectiveness of this immunochemotherapy resulted in a limited antitumor response, low-and intermediate-risk patients with metastatic RCC seemed likely to have a survival benefit. Patient selection is essential to enhance treatment efficiency and avoid useless treatment for high-risk patients.     

Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.     

Characteristics of metastasis as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

AIMS AND BACKGROUND: This study aimed to evaluate the significance of characteristics of metastasis as prognostic factors in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 148 patients who had received immunotherapy were included in the study. Patients were categorized in various ways according to the characteristics of metastasis, including a synchronous metastasis group (n = 77) vs a metachronous metastasis group (n = 71), and a solitary metastasis group (n = 93) vs a multiple metastases group (n = 55). RESULTS: In the synchronous and metachronous metastasis groups, median progression-free survival was 4.3 months (95% confidence interval [CI] 2.9-5.7) and 11.1 months (95% CI 6.7-15.5), respectively (P = 0.004). Median overall survival was 17.1 months (95% CI 9.5-24.7) and 54.8 months (95% Cl 38.371.3) in the two groups (P = 0.019). In the solitary and multiple metastasis groups, median progression-free survival was 11.0 months (95% CI 6.6-15.5) and 3.9 months (95% CI 2.6-5.2), respectively (P <0.001). Median overall survival was 55.2 months (95% CI 50.7-59.7) and 15.6 months (95% CI 10.9-20.3) in the two groups (P <0.001). Multivariate Cox proportional hazards model analysis using the clinical variables showed that T stage (P = 0.026), number of metastatic sites (P = 0.009) and time to metastasis (P = 0.019) were independent predictors of progression-free survival. Using the same variables, only the number of metastatic sites was an independent prognostic predictor of overall survival (P = 0.014). CONCLUSIONS: Our findings suggest that the time to metastasis and the number of metastases are important prognostic factors in metastatic RCC.     

Preoperative serum albumin is an independent prognostic predictor of survival in ovarian cancer

Ovarian cancer is associated with high mortality due to asymptomatic nature of the disease and advance stage at presentation. In advanced stages, it is associated with cachexia and ascites leading to malnutrition. Nutritional status of a patient with cancer has been well known to be associated with survival and can be assessed by level of albumin in blood. Therefore, in this study, we sought to determine preoperative serum albumin as prognostic predictor of survival in patients with ovarian cancer. Preoperative serum albumin was determined in 235 patients undergoing surgery for ovarian cancer at Royal Derby Hospital. The prognostic predictive value of serum albumin, along with other prognostic markers was then analysed using univariate and multivariate analyses. Low serum albumin was associated with poor survival (P < 0.001) in patients with ovarian cancer. There was an inverse correlation between serum albumin levels and survival with lower levels having poor survival. Patients with serum albumin levels of <25 g/l had a median survival of 4.8 months (95% CI 0-13.1 months), whilst levels >35 g/l were associated with median survival of 43.2 months (95% CI 11.6-20.9). Serum albumin (P < 0.001) retained its significance as an independent predictor of poor survival on Cox's multivariate regression analysis along with Age (P < 0.001) and FIGO stage (P < 0.001). Serum albumin can be used as an independent prognostic predictor of survival in patients with ovarian cancer.     

Predictors of Survival in Patients Undergoing Surgery for Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus

IntroductionSurgical resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is a complex procedure with significant morbidity. Patient selection is critical to determining whether the benefits of the procedure outweigh the risks. In this study, we identified and stratified the risk factors that were associated with overall survival (OS) and recurrence-free survival (RFS) in patients undergoing surgical resection of RCC with IVC thrombus.MethodsWe identified all patients with RCC with IVC tumor thrombus (stages cT3b and cT3c) who had undergone radical nephrectomy with tumor thrombectomy between December 1, 1993 and June 30, 2009. Kaplan-Meier method was used to estimate OS and RFS. Cox proportional hazards models were used to determine the association between risk factors and OS. Patients were stratified into 3 groups based on the number of risk factors present at diagnosis.ResultsTwo hundred twenty-four patients were included in the study. A total of 45.3% of patients had metastasis at presentation, 84.5% had cT3b, and 90.2% had clear cell RCC. cT3c, cN1, and cM1 were significantly associated with the risk of death. Group 1 patients (0 risk factors) had a median OS duration of 77.6 months (95% CI 50.5-90.4), group 2 (1 risk factor) 26.0 months (95% CI 19.5-35.2), and group 3 (≥2 risk factors) 8.9 months (95% CI 5.2-12.9; P < .001).ConclusionsStratification of patients with RCC and IVC thrombus by risk factors allowed us to predict survival duration. In patients with ≥2 risk factors, new treatment strategies with preoperative systemic therapy may improve survival.     

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors

A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml(-1), high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l(-1). In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26-4.16), poor performance status: 1.73 (1.15-2.62), age: 1.02 (1.003-1.043), a high serum NSE level: 1.72 (1.11-2.68), neurological symptoms: 1.63 (1.05-2.54), and a low serum sodium level: 2.99 (1.17-7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation.     

Long-Term Response to Sunitinib Therapy for Metastatic Renal Cell Carcinoma

BackgroundSunitinib achieves objective response and prolongs progression-free survival (PFS) in patients with metastatic renal cell carcinoma (RCC). A subset of patients achieves long-term responses. The characteristics of patients who achieved long-term response (defined as patients achieving ongoing complete response [CR] or remaining progression free for > 18 months while receiving sunitinib) are reported.Patients and MethodsA database of 186 patients treated with sunitinib alone (n = 89) or in combination (n = 97) in 9 clinical trials was reviewed; all had 1 year or more follow-up from sunitinib start to data cutoff for analysis. Median PFS was 10.8 months (95% CI, 8.3-13.3); median overall survival (OS) was 30.4 months (95% CI, 21.5-36.8 months) for the 186 patients. Thirty-four patients were identified as long-term responders because they either had durable CR or remained progression free while receiving sunitinib for > 18 months.ResultsBest response for 34 long-term responders was CR in 3 patients, partial response (PR) in 24 patients, and stable disease in 7 patients. The median duration of sunitinib therapy was 24.9 months (range, 18.1-73.9 months). The median PFS among the long-term responders was 17.4 months (95% CI, 7-29.9 months) at a landmark PFS analysis performed after 18 months from treatment start. Univariate analysis from the 186 patients identified bone metastasis, lung metastasis, and intermediate/poor risk groups as adverse prognostic factors for long-term response.ConclusionSunitinib achieves long-term response in a subset of patients with metastatic RCC. Lack of bone metastasis or lung metastasis and good MSKCC risk status may predict long-term response.     

Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study

Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1–27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7–16.4) months at a median follow-up time of 61.8 (95% CI: 16.2–97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.     

Population characteristics and prognostic factors in metastatic non-small-cell lung cancer: a Fox Chase Cancer Center retrospective

PURPOSE: With the increasing use of magnetic resonance imaging and positron emission tomography for staging non-small-cell lung cancer (NSCLC), the demographics, performance status (PS), and distribution of metastases at diagnosis in this patient population are changing. We therefore reassessed the prognostic implications of baseline clinical variables in the modern era. PATIENTS AND METHODS: We retrospectively evaluated the charts of 172 consecutive, unselected patients aged 41-89 years (median, 62 years) with stage IV NSCLC monitored at the Fox Chase Cancer Center, a tertiary referral center, between October 2000 and August 2003. Cox proportional models were used to conduct univariate and multivariate analyses of baseline prognostic factors. RESULTS: Median age was 62 years; 79% of patients were PS 0/1 at first presentation. Fifty-six percent had single organ metastasis; 35% had brain metastases (one third had a solitary brain metastasis). Overall median survival was 10.4 months (95% CI, 8.1-13.6 months). The 1-, 2-, 3-, and 4-year survival rates were 44.2% (95% CI, 36.7%-51.4%), 21.9% (95% CI, 16%-28.3%), 11.6% (95% CI, 7.3%-17%), and 7.8% (95% CI, 4.2%-12.8%), respectively. On multivariate analysis, statistically significant negative prognostic factors included PS > or = 2 (hazard ratio [HR], 1.9 [95% CI, 1.1-3.28]), serum albumin of < or = 3 g/dL (HR, 1.7 [95% CI, 1.1-2.76 g/dL]), and metastases to > 1 organ (HR, 1.6 [95% CI, 1.03-2.3]). Brain, bone, and liver metastases were not found to be independent predictors of survival. CONCLUSION: The most important prognostic determinants were PS, baseline albumin, and number of metastatic sites. Incidence of brain metastases at presentation in this population was higher than usually described. Survival rates in this cohort equal or exceed contemporary figures observed in Eastern Cooperative Oncology Group advanced NSCLC trials.     

Body mass index and survival in patients with renal cell carcinoma: A clinical‐based cohort and meta‐analysis

Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, we analyzed a large cohort of patients with RCC and undertook a meta‐analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow‐up through 2008. Patients were grouped according to BMI (kg/m²): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese ≥25. We estimated survival using the Kaplan–Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer‐specific survival (CSS) with adjustment for covariates. We performed a meta‐analysis of BMI and OS, CSS and recurrence‐free survival (RFS) from all relevant studies using a random‐effects model. The 5‐year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45; 95% CI: 0.29–0.68) and CSS (HR = 0.47; 95% CI: 0.29–0.77] in obese patients than in normal weight patients. The meta‐analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43–0.76), CSS (HR = 0.59; 95% CI: 0.48–0.74) and RFS (HR = 0.49; 95% CI: 0.30–0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.     

Clinical prognostic factors in 1277 patients with neuroblastoma: results of The European Neuroblastoma Study Group 'Survey' 1982-1992

In 1982 the European Neuroblastoma Study Group (ENSG) established a prospective registry for patients with newly diagnosed neuroblastoma ('The ENSG Survey'). Clinical information was collected primarily to: (a) establish an ENSG database; and (b) investigate prognostic factors in neuroblastoma. This paper summarises the results of the survey. By 1992, 1277 patients with a median age of 26 months (range: 0-289 months), gender ratio of 1.19 M:F had been registered from 30 centres. The median follow-up of survivors is 9.7 years (range: 1-14 years). Overall 5-year survival (S) is 45% (95% CI 42-48%), and event-free survival (EFS) is 43% (95% CI 40-45%). For both survival and EFS the key established prognostic factors, stage and age, are highly significant (P<0.001). In particular, patients under 1 year of age at diagnosis, whatever the disease stage, had a more favourable prognosis than older patients; stage 2 (EFS 93% (95% (CI 85-97) versus 76% (95% CI 67-86), P=0.02), stage 3 (EFS 91% (95% CI 82-96) versus 52% (95% CI 44-60), P<0.001) and stage 4 (EFS 59% (95% CI 48-69) versus 16% (95% CI 13-19), P<0.001). Multivariate analysis established that the anatomical location of the primary tumour (i.e. abdominal versus other sites) and primary tumour volume also conferred a statistically significant difference. In stage 4 disease the 20% of patients without demonstrable bone marrow involvement had a more favourable prognosis than those with infiltrated marrow (EFS 36% (95% CI 13-19) versus 16% (95% CI 29-45), P<0.001). Urine catecholamine metabolite levels (raised versus normal), histology (ganglioneuroblastoma versus neuroblastoma) and gender had no significant effect on outcome after stage and age were accounted for. 5-year survival following first relapse is only 5.6% (95% CI 2.8-8.4). This ENSG Survey provides secure data for future comparisons with new prognostic factors and treatment programmes.     

Prognosis of hypercalcemia in aerodigestive tract cancers: study of 136 recent cases

Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002-January 2004). Hypercalcemia was defined by calcemia level above 2.55 mmol/l. Univariate analysis for prognosis was performed with Mann-Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18-86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2-553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2-553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07-6.82), age inferior to 50 (OR=2.67 CI 95% 1.23-5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8-11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73-17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99-13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02-10.52), male gender (OR=38.22 CI 95% 12.2-89), calcemia level superior to 2.7 mmol/l (OR=3.08 CI 95% 1.42-6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01-4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.     

Serum YKL-40 and colorectal cancer

YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion.     

CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials

In a multivariate analysis of 154 patients receiving chemotherapy, baseline CA19-9 was an independent prognostic factor for overall survival (OS) (HR 1.8; 95% CI: 1.3-2.5, P = 0.0004). The 1-year OS was 19 and 46%, respectively, for patients with a baseline CA19-9 above or below the median value. A fall of 20% in CA19-9 level from baseline was an independent prognostic factor for OS (HR 1.9; 95% CI: 1.1-3.4, P = 0.019).     

Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers

BACKGROUND: A standard concept for the integration of surgery into the chemotherapy-based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers. METHODS: The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin-based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow-up of 74 months (range, 24-207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753-64.553; P = 0.043 and P = 0.016, respectively; log-rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log-rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516-fold (95% CI, 1.786-87.781) and 9.311-fold (95% CI, 1.796-48.256), respectively. CONCLUSIONS: Salvage surgery in patients with high serum tumors markers resulted in long-term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long-term disease free status.