Negative Prognostic Factor For Survival Research Articles

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi‐centric lymphoma

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance.

Development of radiation pneumopathy and generalised radiological changes after radiotherapy are independent negative prognostic factors for survival in non-small cell lung cancer patients

Background and purposeTo investigate the risk factors for radiation pneumopathy (RP) and survival rate of non-small cell lung cancer patients with RP and generalised interstitial lung changes (gen-ILC). Material and methodsA total of 147 consecutive patients receiving curative radiotherapy were analysed. RP was graded according to Common Terminology Criteria for Adverse Events v. 3. Computed tomography images were assessed for the presence of gen-ILC after radiotherapy. Univariate and multivariate analyses were performed to identify significant factors. ResultsMedian follow-up was 16.2months (range 1.4–58.6). Radiological changes after radiotherapy were confined to high dose irradiation volume in 111 patients, while 31 patients developed gen-ILC. Dosimetric parameters and level of C-reactive protein before radiotherapy were significantly associated with severe RP. Development of gen-ILC (p=0.008), as well as severe RP (p=0.03) had significant negative impact on patients’ survival. These two factors remained significant in the multivariate analysis. ConclusionsSevere radiation pneumopathy and generalised radiographic changes were significant independent prognostic factors for survival. More studies on pathophysiology of radiation induced damage are necessary to fully understand the mechanisms behind it.

The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer.

e15123 Background: Vascular endothelial growth factor receptor 2 (VEGFR-2) is considered a prognostic factor and treatment target for metastatic colorectal and ovarian cancer. Peritoneal Carcinomatosis (PC) from appendiceal cancer is a rare malignancy, treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), for which tumor histology, completeness of cytoreduction (CC), and lymph node (LN) status are predictors of survival. We hypothesize that high VEGFR-2 expression is a negative prognostic factor for survival in patients with PC from appendiceal cancer. Methods: A retrospective study of a prospective database was conducted in 127 patients with PC from appendiceal cancer who underwent CRS/HIPEC. Surgical specimens from a total of 59 patients were tested to identify “high” vs. “low” VEGFR-2 expression. Patients were divided into 2 groups: high VEGFR-2 expressers and low VEGFR-2 expressers. Patients’ outcomes and survival were analyzed. Results: There were 26 males and 33 females. Mean age was 51 years. Mean follow up of high and low expressers was 25.1 and 26.6, respectively (p = 0.806). At follow up, 33 (70%) of high expressers were alive and 14 (30%) deceased, while 11 (92%) of low expressers were alive and 1 (8%) deceased. Overall recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers and did not correlate with survival or outcome. OS for high expressers was 90.5%, 59.8, and 47.1% at 1-, 3-, 5-years (p = 0.133) respectively, while OS for low expressers was 91.7% at 1-, 3-, and 5-years. Conclusions: There is a trend toward better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. However, follow up is short and a larger number of patients is needed to confirm this trend and possibly correlate a high expression of VEGFR-2 to poorer outcomes and decreased survival in PC of appendiceal origin.

Impact of wait times on survival of women with uterine cancer.

5586 Background: Reducing cancer wait times have been a priority investment for Cancer Care Ontario since 2005. Our objective was to determine whether wait time from histologic diagnosis of uterine cancer to time of definitive surgery by hysterectomy impacted on all cause survival. Methods: Cases were identified in the Ontario Cancer Registry using ICD-09 codes 179 and 182. Excluded were women without histologic/cytologic confirmation of cancer prior to surgery, with no definitive surgery, or with wait times of ≤14 days or >2 years. Survival was calculated using the Kaplan-Meier method from the day of hysterectomy. Factors were evaluated for their prognostic ability on survival using Cox proportional hazards regression. Wait time was evaluated as a continuous variable and dichotomized at selected cutpoints in the univariable analyses and in a multivariable model adjusting for significant patient factors identified using forward stepwise selection. Results: The final study population included 8,744 women. 51.9% had surgery by a gynaecologist and 69.9% had endometrioid adenocarcinoma. The optimal model is shown below. Multivariable analysis of factors prognostic for survival. Longer wait times remained a statistically significant negative prognostic factor for survival regardless of definition, univariably (p<0.002) and multivariably after adjusting for other significant factors (p<0.001). The final multivariable model is shown. 5-year (95%CI) survival for women with more than 12 week wait times was 61.4 (57.8-64.8)% versus 71.9 (69.9-73.8)% for women with less than 6 week wait time. Conclusions: The longer a woman waits from diagnosis of uterine cancer to definitive surgery negatively impacts her overall survival. [Table: see text]

KRAS gene mutation status and sensitivity to pemetrexed: A retrospective analysis.

e19154 Background: KRAS is the most frequently mutated oncogene (25%) in lung adenocarcinoma. KRAS mutations are a negative prognostic factor for survival. Recent phase II trial with a MEK inhibitor has shown promising efficacy albeit at the cost of higher adverse events. Preclinical work by Moran et al showed that antifolate therapies like pemetrexed decrease KRAS gene expression in KRAS wild type and KRAS mutant but do not do so in KRAS mutant amplified cells. Targeted therapies for EGFR, ALK and ROS1 have increased the survival for lung adenocarcinoma expressing these actionable targets. No therapies are yet approved for KRAS mutant subsets. Hence therapeutic strategies that target this cohort represent an unmet medical need. Methods: We reviewed data from patients (pts) in our thoracic oncology clinic with stage IIIB and stage IV lung adenocarcinoma with KRAS mutation positive tumours who received pemetrexed either during induction or maintenance therapy. Pt characteristics including age, sex, race, smoking history, KRAS mutation subtype and overall survival were analyzed. Results: Between April 2010 and October 2012 we treated 154 pts with stage IIIB and stage IV lung adenocarcinoma. Of these 154 pts we found 34 patients with KRAS mutation positive tumours. 10 pts out of 34 pts with KRAS mutation positive tumours received pemetrexed during induction or maintenance therapy and were analyzed further. Median age 63. 60% females. 90% Caucasians. 90% were smokers. KRAS 12C mutation was found in 2 pts, KRAS 12V in 4, KRAS 12A in 3 and KRAS 13A in 1 pt. 4(40%) patients died. Median overall survival (OS) in the KRAS 12C, 12V, 12A and 13A was 14, 9.5, 10 and 12 months respectively. Conclusions: The median OS in published series is 15.4, 14, 8 and 7 months in the KRAS 12C, 12V, 12A and 13A cohorts respectively (Rosell et al). Our analysis found that pts with KRAS 12C, 12A and 13A mutation had a survival advantage with pemetrexed therapy as compared to pts with KRAS 12V mutation. Thus this retrospective study supports the concept that KRAS mutation status affects sensitivity to antifolate therapy (pemetrexed).

Abstract 1374: Influence of radiation target volume on circulating lymphocyte counts in patients with malignant glioma receiving radiation therapy and temozolomide.

Abstract Introduction: Treatment induced lymphopenia (TRL) is an independent negative prognostic factor for survival in patients with malignant glioma (MG). Radiation therapy (RT) is a likely contributor to TRL through the irradiation of circulating lymphocytes. Previous modeling studies suggested that RT target volume (PTV) would not have an appreciable impact on total lymphocyte count (TLC) at the end of RT given the large PTVs in patients with MG. In this study, we attempted to validate the model by studying % changes in total lymphocyte count (TLC) during brain RT in patients with MG. Methods: This was an IRB-approved retrospective chart review study. All patients received 59.4-60Gy given in 1.8-2Gy daily fractions with concurrent temozolomide (TMZ; 75 mg/m2). Data on baseline patient characteristics were collected along with data on weekly TLC obtained through the clinical laboratory and data on PTV obtained from the RT planning system (Pinnacle®). Pearson correlation was used to test the relationship between PTV size and TLC after RT. Results: This study included 63 patients, 30 (45%) female and 37 (55%) male. Median age was 58 years (range 22-79 years). Median baseline KPS was 90 (range 30-100). Most patients (n=58; 87%) had GBM. Gross total resection was performed in 25 patients (37%), subtotal resesction in 34 (50%) and biopsy in 8 (12%). Median PTV size was 337 cm3 (range 103-879 cm3). Median baseline lymphocyte count was 1230 cells/uL (range, 331-4790). Median lymphocyte counts decreased during and after the course of treatment. Median TLCs during the last week of RT/TMZ, one month after RT/TMZ, and two months after RT/TMZ were 730 cells/uL (range 84-2270), 910 cells/uL (range 331-4790), and 820 cells/uL (range 183-1900), respectively. PTV was not correlated with % decrease in the lymphocyte count at the end of treatment nor at one or two months after completing treatment (r = 0.005, 0.11, and 0.16; p = 0.99, 0.42, and 0.27, respectively). There was no significant difference in mean PTV size among patients who developed grade 3-4 lymphopenia compared with those who did not. Conclusions: Brain radiation induces lymphopenia which is progressive over the course of therapy. PTV size was not correlated with lymphocyte count at the end of treatment nor with the risk of developing grade 3-4 lymphopenia. Although modeling predicts that differences in PTV size may impact lymphocyte counts very early in treatment or when very small PTVs are used, it is unlikely that changing PTV size will have a major effect on lymphocyte counts given a six-week course to a large field such as is used in malignant glioma. These conclusions may not apply to patients treated with very small PTVs or with only a few RT fractions (i.e., stereotactic radiosurgery). Alternative strategies are needed to prevent or treat lymphopenia in patients receiving protracted RT courses to a large target volume. Citation Format: Susannah Yovino, Eric Ford, Prakash Ambady, Stuart Grossman, Lawrence Kleinberg, Xiaobu Ye. Influence of radiation target volume on circulating lymphocyte counts in patients with malignant glioma receiving radiation therapy and temozolomide. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1374. doi:10.1158/1538-7445.AM2013-1374

CD4/CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy

BackgroundThough traditionally regarded as immunosuppressive, radiotherapy may also stimulate immune cells and facilitate an anti-tumor immune response. We therefore aimed to explore the prognostic significance of immune cell markers in non-small cell lung cancer (NSCLC) patients treated with postoperative radiotherapy (PORT). MethodsIn addition to demographic and clinicopathological information, tumor tissue samples were collected and tissue microarrays (TMAs) were constructed from 55 patients with stage I-IIIA NSCLC who received PORT. Tumor and stromal expression of CD1a+, CD3+, CD4+, CD8+, CD20+, CD56+, CD68+, CD117+ and CD138+ cells, as well as M-CSF and CSF-1R, was assessed by immunohistochemistry. ResultsIn univariate analysis, high co-expression of CD4+ and CD8+ T lymphocytes as well as high expression of CD1a+ dendritic cells in the tumor stroma correlated with improved disease-specific survival (DSS). In multivariate analysis patients with stromal ↓CD4/↓CD8 expression had a hazard ratio of 21.1 (CI95% 3.9–115.6, P<0.001) when compared to those with ↑CD4/↑CD8 expression. ConclusionsStromal ↓CD4/↓CD8 expression was an independent negative prognostic factor for survival in NSCLC patients receiving PORT, indicating a highly detrimental prognosis.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study

As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Expression of Girdin in Human Colorectal Cancer and Its Association with Tumor Progression

Girdin is crucial for cellular motility in cancer cell lines and for metastasis in a mouse model. Its expression has been demonstrated in a range of cancers by a few studies and was a prognostic factor in a subset of patients. The aim of this study was to investigate the relationship of Girdin expression to clinicopathologic factors in terms of the progression of colorectal cancers and patient survival. This study is a retrospective review of immunohistochemical and clinicopathologic data. This study was conducted at a tertiary care hospital/referral center in South Korea. Tissue microarrays were made from surgical biopsies of 298 patients with colorectal cancer diagnosed between November 1996 and August 2007. Patients were included in the study if their survival time was known and if well-preserved surgical biopsy specimens were available. The primary outcomes measured were Girdin expression and its association in tumor progression and patient survival. Positive staining for Girdin was observed in samples from 66 of 242 patients (27.3%). Expression of Girdin was significantly associated with tumor-node-metastasis stage (p = 0.036), liver metastasis (p = 0.025), and metastases involving the liver and other organs (p = 0.009). However, Girdin expression did not correlate significantly with the overall survival of patients and was not a significant negative prognostic factor for survival by univariate or multivariate analyses. The number of investigated patients and the number of cases with positive staining for Girdin were rather small for the multivariate analysis. The inclusion time frame is long and includes other surgical and medical improvements, which influence a patient's survival. The expression of Girdin is related to tumor metastasis but not to survival in human colorectal cancers.

Hypoxia-related molecules HIF-1α, CA9, and osteopontin

A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas. HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry. Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028). Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma

Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p < 0.001), lymphovascular invasion (p = 0.022) and poor survival with an estimated 5-year CSS probability of 54% for tumors with nuclear expression of survivin vs. 73% for those without nuclear expression of survivin (hazard ratio = 2.19; 95% confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67%, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.

MiR34s in Normal and Malignant B-Cells: miR34A Plays a Dominant Role in Normal B-Cells, and aggressive Diffuse Large B-Cell Lymphoma Carry Combined Lesions of TP53, MIR34A, and MIR34B/C

AbstractAbstract 296 Background:In diffuse large B-cell lymphoma (DLBCL), a number of studies have shown that dual disruption of the p16/Rb and the ARF/p53 pathway, e.g. deletion of the INK4A/ARF locus, are negative prognostic factors for survival. Molecular studies have shown that the p53-miR34 axis may be another link between the ARF/p53 pathway and the p16/Rb pathway. In a complex circuit, p53 promotes transcription of MIR34A and MIR34B/C, and the miR34s' in turn act as mediators of p53 signaling. In addition, miR34s' have been shown to inhibit MYC and several proto-oncogens that counteract the p16/Rb tumor suppressor pathway. These observations place the miR34s' at the center of cell cycle and apoptosis regulation, and loss of miR34 expression has been associated with adverse response to therapy in several tumor types. In CLL it has been suggested that miR34A expression is a surrogate marker for TP53 disruption and the MDM2 SNP309 GG genotype, both associated with a poor prognosis. Design and methods:In CD19+ B-cells isolated from healthy donors (PBL-B) and reactive lymph nodes, the expression of the –5p and –3p species of miR34A, miR34B, and miR34C was analysed by qRT-PCR using LNA-based primers from Exiqon that discriminate the individual miR34 members. Histone H3K4 and H3K27 methylation status at the MIR34A and MIR34B/C promoters was analyzed by ChIP. In 120 newly diagnosed DLBCLs we studied the combined status of TP53 mutations, MIR34A and MIR34B/C promoter DNA methylation, and the MDM2SNP309 GG genotype using a panel of PCR based methods. Results:We initially determined the expression of the individual miR34 family members in PBL-B and in reactive lymph nodes. While miR34A-5p was expressed at low levels in normal PBL-B, no expression of miR34A-3p, miR34B-5p, miR34B-3p, miR34C-5p, and miR34C-3p was observed. In reactive lymph nodes the expression of miR34A-5p was induced in average 70 fold (P<0.001), while no significant induction was observed for the rest of the investigated miRs, including the homologous miR34B-5p and miR34C-5p. No promoter DNA methylation was observed in PBL-B, but ChIP experiments showed a relative enrichment for the bivalent H3K4me3/H3K27me3 silencing mark at the MIR34B/C promoter.In 100 of the 120 (83%) DLBCLs one or more of the investigated genes carried (epi)-genomic alterations including TP53 mutations: 20(17%), MIR34A methylation: 34(28%), MIR34B/C methylation: 93(78%) and the MDM2 SNP309 GG-genotype 11(9%). All but one of the MIR34A methylated cases also had methylation of MIR34B/C. Seven cases carried combined TP53 mutation and methylation of both MIR34A and MIR34B/C. A borderline inferior overall survival for patients carrying TP53 mutations was found (p=0.058), while none of the other parameters influenced survival. However, the 7 cases with concomitant mutation of TP53 and methylation of both MIR34A and MIR34 B/C had a median survival of 14 months (p=0.02). In a DLBCL-cell line with concomitant TP53 mutation and methylation of both MIR34A and MIR34B/C, miR34s' were upregulated by 5-aza-2'deoxycytidine (5-aza-CdR). Conclusions:In normal B-cells miR34A seems to play a dominant role over miR34B/C, however in DLBCL the concomitant DNA methylation of MIR34B/C in the MIR34A methylated cases suggest they may compensate for each other. Our results suggest that in DLBCL the p53-miR34 axis is not linear, and that the TP53, MIR34A and MIR34B/C “triple-hit” DLBCLs may represent more aggressive lymphomas that may benefit from treatment with 5-aza-CdR. This is, to the best of our knowledge, the first study to address these issues in a large sample of diagnostic DLBCL cases. Disclosures:No relevant conflicts of interest to declare.

Occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic cancer

The aim of this study was to test the hypothesis that occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic adenocarcinoma. Real-time RT-PCR analysis of CEA, EGFR and hTERT transcript levels was used to identify occult tumour cells in peritoneal lavage samples from 96 pancreatic cancer patients. We found significant association between CEA expression levels in peritoneal lavage and clinical stage. We also found that EGFR transcript levels were higher in peritoneal lavage samples from patients with high grade tumours than in samples from patients with low grade tumours. Detection of CEA and/or EGFR occult tumour cell markers in the peritoneal lavage was associated with significantly shorter overall survival and increased hazard ratio for disease recurrence. The results show that the presence of occult tumour cells in peritoneal lavage is a negative prognostic factor for survival in pancreatic cancer patients, and that detection of occult tumour cells using PCR-based methods can identify patients with advanced disease for whom radical surgery is likely to have little benefit.

Erlotinib and Bevacizumab in Newly Diagnosed Performance Status 2 or Elderly Patients With Nonsquamous Non–Small-Cell Lung Cancer, a Phase II Study of the Hoosier Oncology Group: LUN04-77

BackgroundPoor PS is a negative prognostic factor for survival and a risk factor for treatment-related toxicity with standard platinum-doublet chemotherapy for advanced NSCLC. A phase II study combining erlotinib and bevacizumab for treatment of recurrent NSCLC showed encouraging efficacy and acceptable toxicity. Patients and MethodsThis single-arm phase II study evaluated erlotinib and bevacizumab as first-line therapy for newly diagnosed nonsquamous advanced NSCLC patients with Eastern Cooperative Oncology Group PS ≥ 2 or age 70 or older. Only patients eligible for bevacizumab per label were enrolled. Patients received erlotinib 150 mg orally daily and bevacizumab 15 mg/kg intravenously on day 1 every 21 days for up to 6 cycles. The primary end point was the rate of nonprogressive disease at 4 months (alternative hypothesis > 60%). ResultsTwenty-five patients were enrolled, with median age 77 years (range, 52-90 years), 44% female, 20% never- or remote-smokers. Ninety-two percent of patients enrolled had PS of 2 per investigator assessment. The rate of nonprogressive disease at 4 months was 28%. There were no complete responses, 1 patient achieved a partial response, and 11 patients (44%) experienced stable disease as best response. Rash, fatigue, and diarrhea were the most common toxicities. ConclusionThe combination of erlotinib and bevacizumab had insufficient activity in the absence of known activating epidermal growth factor receptor gene mutations to warrant study in newly diagnosed elderly or poor PS patients with nonsquamous NSCLC.

Tumor Size and Diabetes Are the Most Important Pre-Operative Prognostic Factors Influencing Survival After Pancreaticoduodenectomy in Pancreas Cancer Patients

Context The median survival in resected pancreatic ductal adenocarcinoma (PDAC) is about two years. However, a considerable percentage of patients die within the first year after resection. Objective The aim of this study was to evaluate pre-operative factors predicting a short survival after pancreatico­duodenectomy (PD) for PDAC. Methods One hundred consecutive patients undergone PD for PDAC without in-hospital mortality from October 2006 to July 2010 were retrieved from our prospective database. The cohort was divided by survival into short term (≤12 months: group A) and long term (>12 months: group B) survivors and evaluated regarding pre-operative factors including age, weight loss, BMI, tumor size and proximity (no contact-contact) to the portal/mesenteric vein (PV/SMV). Results No significant differences were found between group A (n=27) and group B (n=73) regarding mean age (68±2 vs . 66±1 years; P=0.3), weight loss (87% vs . 85%; P=1.0), BMI (24±0.6 kg/m 2 vs . 24±0.5 kg/m 2 ; P=0.7) or adjuvant treatment. Group A had bigger tumors (35±2 mm vs . 29±1 mm; P=0.01) but no significant difference in proximity of the tumor to the PV/SMV (contact: A 67% vs . B 49%; P=0.2) or venous resections. Group A had more frequently pre-operative diabetes (33% vs . 9.6%; P=0.01) compared to group B. Conclusion Tumor size and pre-operative diabetes seems to be important negative prognostic factors for survival after PD for PDAC.

Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy.

Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.

Is Lymph Node Dissection Required in Pulmonary Metastasectomy for Colorectal Adenocarcinoma?

The aim of this study was to clarify the clinical outcome and significance of mediastinal lymph node dissection (LND) during pulmonary resection of metastases from colorectal adenocarcinoma. A retrospective chart review was performed. Between April 1985 and December 2009, 518 patients underwent 720 pulmonary metastasectomies for metastatic colorectal adenocarcinoma. Relevant factors were analyzed with the χ2 or Fisher exact test and the Mann-Whitney test. Survival and lymph node (LN) recurrence-free period after pulmonary metastasectomy were analyzed with Kaplan-Meier and Cox proportional hazards methods. The overall 5-year and 10-year survival rate after pulmonary metastasectomy were 47.1% and 27.7%, respectively. The only significant prognostic factor for survival after pulmonary metastasectomy was mediastinal LN metastasis (p=0.047 in univariate and 0.0028 in multivariate analysis); 199 patients did not undergo LND, 279 patients underwent LND that were negative, and 40 patients underwent LND that contained 1 or more positive mediastinal LN for metastases. The sensitivity of positron emission tomographic scan for detecting mediastinal LN metastases was only 35%. Although long-term survivors were present, systematic LND was not a significant factor for prolonged survival (p=0.26) in the positive LND group. Mediastinal LN metastases are a significant negative prognostic factor for survival after pulmonary metastasectomy for metastatic colorectal cancer. Computed tomography and positron emission tomography based imaging, as well as preoperative carcinoembryonic antigen levels have poor sensitivity for detecting malignant mediastinal LN in this setting. Systematic mediastinal LND should be performed for prognostic purposes during pulmonary metastasectomy for colorectal metastases.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal poorly differentiated neuroendocrine carcinoma: The NORDIC NEC study.

4015 Background: Gastrointestinal poorly differentiated neuroendocrine carcinoma (GI-NEC) are aggressive tumors with Ki-67&gt;20% and usually metastatic at diagnosis. Knowledge about GI-NEC is limited. We retrospectively reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Methods: Epidemiological, biochemical, histopathological, treatment and survival data were registered for advanced GI-NEC patients diagnosed during 2000-2009 at 12 Nordic university hospitals. Results: 305 patients were included. Palliative chemotherapy was given to 252 patients, median survival was 11 months. Response rate to 1st-line chemotherapy was 31%, 33% had stable disease. Ki-67&lt;55% was by ROC analyses the best cut-off value concerning correlation to response rate. Response rate to platinum-based chemotherapy was lower in patients with Ki-67&lt;55% (14% vs.44%, p&lt;0.001). Response rate for 84 patients given 2nd-line chemotherapy was 18%, whereas 33% achieved SD. The most important negative prognostic factors for survival were poor performance status, primary colorectal tumors, and elevated baseline platelets or lactate dehydrogenase (LDH) levels. Patients with Ki-67&lt;55% had longer median survival (15 months) than patients with Ki-67&gt;55% (10 months) (p&lt;0.001). Survival and response rates did not differ between the different platinum chemotherapy schedules (cisplatin-based vs. carboplatin-based) or morphology subtypes. 53 patients received best supportive care only with a median survival of 1 month. Conclusions: This is, to our knowledge, the largest study reporting patient and tumor characteristics, treatment and survival in advanced GI-NEC. Performance status, location of primary tumor and blood levels of platelets and LDH were the strongest prognostic factors for survival. Patients with Ki-67&lt;55% had significantly longer survival than patients with higher Ki-67, but were less responsive to platinum-based chemotherapy. Our data indicate that to consider all GI-NEC as one single disease entity may not be correct.

Tumor Cell Expression of Heat Shock Protein (HSP) 72 is Influenced by HSP72 [HSPA1B A(1267)G] Polymorphism and Predicts Survival in Small Cell Lung Cancer (SCLC) Patients

The inducible heat shock protein (HSP)72 plays a central role in antitumor immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients with advanced and metastatic small cell lung cancer (SCLC) by immunohistochemistry and HSP72 [HSPA1B A(1267)G] polymorphism was determined. HSP72 expression of SCLC cells was significantly decreased in GG as compared to cells of AA or AG genotype patients, and was associated with significantly shorter survival in GG patients as compared to carriers of the A allele. Decreased HSP72 expression of SCLC cells associated with HSP72 GG genotype is a negative prognostic factor for survival in SCLC patients.

Clinical outcome of extragonadal germ cell tumors: Retrospective analysis at a single institution in Japan.

345 Background: Extragonadal germ cell tumors (EGGCT) are very rare and account for only 2% to 5% of all malignant germ cell neoplasms. Although multimodality treatment, including cisplatin-based chemotherapy and postchemotherapy surgery, has improved the prognosis of patients with EGGCT, few findings are available for these tumors. We therefore performed a retrospective analysis of Japanese patients with EGGCT. Methods: We performed a retrospective review of the medical records of 34 male patients ranging in age from 18 to 62 years (median age, 30 years) treated at our institution between 1982 and 2010. Fifteen patients (44%) had primary mediastinal EGGCT, 16 patients (47%) had primary retroperitoneal EGGCT, and three patients (9%) had primary mediastinal and retroperitoneal EGGCT. Results: Twenty-six patients (76%) had nonseminomatous EGGCT, and eight patients (24%) had seminomatous histology. Surgical procedures were performed in five patients (15%) as induction treatment. Three of them had seminomatous histology and were continuously disease-free after adjuvant chemotherapy. Twenty-nine patients (85%) had received cisplatin-containing regimen as induction therapy. Twenty-three patients underwent post–chemotherapy surgery, and 14 of them (60%) had residual viable malignant cells. On univariate analysis, nonseminomatous EGGCT (P&lt;0.01) and resistance to cisplatin (lack of achievement of CR/PRm- by induction chemotherapy; P&lt;0.01) were identified as negative prognostic factors for survival. Twenty of 34 patients (59%) were alive without disease, and 13 patients with nonseminomatous histology died of disease progression. The overall 10-year survival rate for all patients was 53%. Conclusions: Patients with seminomatous EGGCT have a very good prognosis, while nonseminomatous histology and resistance to cisplatin were found to be negative prognostic factors.