Significant Predictors Of Worse Survival Research Articles

Abstract 14172: Impact of Sex on Survival With Preserved Neurologic Function Following Out-of-Hospital Cardiac Arrest

Introduction: Females experience worse survival than males following out-of-hospital cardiac arrest (OHCA). Proposed explanations include previous observations that females less often have an initial shockable rhythm or a witnessed arrest and less often receive bystander CPR. Methods: We utilized a prospective, population-based registry of patients experiencing OHCA responded to by EMS from 2011-2015. We included patients 18 years or older who were admitted to the hospital. Univariate comparisons were performed with chi-squared test for categorical variables and t-test for age. Additional analysis compared outcomes stratified by age > 50 years as a surrogate for menopausal status. A multivariate logistic regression model was constructed to evaluate the independent association of sex with outcomes. The primary outcome was survival to hospital discharge with Modified Rankin Score (MRS) ≤3. Results: Of 13,651 patients, 4894 were female and 8757 were male. The average age was 65 years for females and 64.2 years for males (P=0.005). Females were less likely than males to arrest in a public location (13% vs 27%; P <0.001), have bystander witnessed arrest (48% vs 57%; P <0.001), receive bystander CPR (44% vs 49%; P <0.001), have an initial shockable rhythm (29% vs 48%; P <0.001), have achieved ROSC upon ED arrival (76% vs 78%; P=0.014), have an ED arrival time less than 30 minutes from dispatch call (10% vs 12% P=0.008). Among males, 27% had a favorable outcome compared to 16% of females (P <0.0001). Among individuals of age ≤ 50 years, 31% of males and 26% of females had a favorable outcome (P= 0.004). Among those of age > 50 years, 26% of males and 14% of females had a favorable outcome (P <0.0001). After adjustment for differences in age and presentation, female sex was found to be independently associated with lower rates of survival with intact neurologic function (OR 0.79, 95% CI 0.71-0.89, P =0.0001). Conclusions: Compared to males, females have less favorable OHCA presentations and worse survival to hospital discharge with preserved neurologic function. However, even after adjustment for the differences in presentation, female sex remains a significant predictor of worse survival with preserved neurologic function.

Relative Sarcopenia With Excess Adiposity Predicts Survival After Transjugular Intrahepatic Portosystemic Shunt Creation.

OBJECTIVE. The purpose of this study was to assess the impact of relative sarcopenia with excess adiposity on mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS. In this single-institution retrospective study, patients underwent abdominal CT scans within 100 days before or 30 days after TIPS creation. Subcutaneous and visceral adipose tissue and muscle were segmented at the L3 vertebral level. Relative sarcopenia with excess adiposity was defined as the lowest sex-specific quartile of muscle area divided by muscle plus adipose. Dates of death, liver transplantation, TIPS occlusion, and hepatic encephalopathy (HE) after TIPS creation were identified. Mortality was evaluated using competing risks survival analysis. Number of HE episodes and time to first episode were analyzed using negative binomial regression and competing risks survival analysis, respectively. RESULTS. A total of 141 patients (91 men; mean age, 56 years) were included in this study. In univariate analyses, Model for End-Stage Liver Disease (MELD) score (hazard ratio [HR], 1.09 per point; CI, 1.05-1.13; p < 0.001) and relative sarcopenia with excess adiposity (HR, 2.70; CI, 1.55-4.69; p < 0.001) were significant risk factors for shorter survival after TIPS. In multivariate analysis, both MELD score (HR, 1.09; CI, 1.03-1.15; p = 0.003) and relative sarcopenia with excess adiposity (HR, 2.65; CI, 1.56-4.51; p < 0.001) were significant predictors of worse survival. The C-index at 30 days was 0.71 for MELD score, 0.72 for relative sarcopenia with excess adiposity, and 0.80 for a model including both. There was no association between relative sarcopenia with excess adiposity and number of HE episodes (incidence rate ratio, 1.08; CI, 0.49-2.40; p = 0.84) or time to first HE episode (HR, 0.89; CI, 0.51-1.54; p = 0.67). CONCLUSION. Relative sarcopenia with excess adiposity is a risk factor for mortality after TIPS and contributes additional prognostic information beyond MELD score.

Predictors of quality of care and survival in a three-state cohort of locally advanced cervical cancer patients and development of a predictive model to identify women at risk of incomplete treatment.

To expand our prior statewide analysis of care distribution for locally advanced cervical cancer in Virginia to include 2 more states and to develop a tool for predicting quality of care. Complete treatment was defined as receiving chemotherapy (CT), brachytherapy (BT), and external beam radiotherapy.State cancer registry databases yielded a three-state cohort of 3197 women diagnosed with locally advanced cervical cancer from 2000 to 2013. A logistic regression evaluated predictors for receipt of BT, CT, and high (2-3 modalities received) versus low (0-1 modalities received) quality care. A Cox proportional hazards models determined predictors of survival. Finally, a predictive model was developed and preliminarily validated using our cohort.Only 35.3% of the cohort received complete treatment and only 57.3% received BT. Significant predictors of lower odds of receiving high quality care varied by state but included: 66+ age at diagnosis as compared to 18 to 42, 42 to 53, or 53 to 66; cancer stage IVA as compared to IIIx, IIx, or IB2; public insurance with supplement as compared to private; treatment at a low volume facility; and closer distance quintiles to a high volume treatment center as compared to the furthest quintile. Significant predictors of worse survival varied by state but included: low quality score (0-1 modalities received); 2000 to 2004 or 2005 to 2009 year of diagnosis as compared to 2010 to 2013; 66+ age at diagnosis as compared to 18 to 42, 42 to 53, or 53 to 66; cancer stage IVA as compared to IIIx, IIx, or IB2; treatment at a low volume facility; and unmarried/unknown marital status as compared to married. Our treatment quality prediction tool included age, age, treatment at high volume facility, and cancer stage and demonstrated 78.2% sensitivity and a 62.9% specificity.Only 35.3% of patients received complete guidelines-concordant treatment. Additionally, in 2/3 states it appeared that BT usage may have decreased during the study period. Our predictive model may help identify patients/regions at risk of receiving low quality care to target interventions aimed at improving cervical cancer treatment quality and survival.

Clinical predictors and outcome implications of early readmission in lung transplant recipients

The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients. We conducted a retrospective cohort study of lung transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination. The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259-2.470). Even for patients with no documented perioperative complication, readmission rates were still >35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients. Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation.

Basal Cell Adenocarcinoma of the Major Salivary Glands: A Population-Level Study of 509 Cases

Objectives/Hypothesis We sought to better characterize patient, tumor, and long-term survival characteristics of basal cell adenocarcinoma (BCAC) of the major salivary glands with the National Cancer Database (NCDB). Study Design Retrospective database review of the NCDB (1998–2012). Methods We retrospectively reviewed the NCDB for all cases of major salivary gland BCAC with histologic code 8147/3. Relevant demographic, tumor, and survival variables were extracted and analyzed. COX multivariate regression was performed to identify prognosticators. Results Out of 36,224 major salivary gland cancers in the NCDB, we found 509 cases of BCAC (1.4%), 88% of which were in the parotid glands, 11.2% in the submandibular glands, and 0.8% in the sublingual glands. Age at diagnosis ranged from 18 to 92 years (average 64). No gender preference was found (50.7% male). Most tumors were 2 to 4 cm in size (47.3%). Regional (11.9%) and distant metastasis (1.8%) were uncommon. Overall survival at 5 and 10 years was 79% and 62%, respectively. Although numerous variables were found to significantly impact survival on univariate regression analysis, only age ≥ 65 (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.56–4.19; P < 0.001) and high primary tumor (T)-stage (HR 1.85; 95% CI, 1.16–2.95; P = 0.010) remained significant prognosticators in our multivariate model. For high T-stage disease, surgery with radiation had significantly better survival than surgery alone. Conclusion Basal cell adenocarcinoma is a rare salivary malignancy with a good prognosis. Regional and distant metastasis were uncommon. Radiation with surgery may help for higher T-stage disease. Old age and high T-stage were significant predictors of worse survival. Level of Evidence 4. Laryngoscope, 2015

Basal cell adenocarcinoma of the major salivary glands: A population-level study of 509 cases.

We sought to better characterize patient, tumor, and long-term survival characteristics of basal cell adenocarcinoma (BCAC) of the major salivary glands with the National Cancer Database (NCDB). Retrospective database review of the NCDB (1998-2012). We retrospectively reviewed the NCDB for all cases of major salivary gland BCAC with histologic code 8147/3. Relevant demographic, tumor, and survival variables were extracted and analyzed. COX multivariate regression was performed to identify prognosticators. Out of 36,224 major salivary gland cancers in the NCDB, we found 509 cases of BCAC (1.4%), 88% of which were in the parotid glands, 11.2% in the submandibular glands, and 0.8% in the sublingual glands. Age at diagnosis ranged from 18 to 92 years (average 64). No gender preference was found (50.7% male). Most tumors were 2 to 4 cm in size (47.3%). Regional (11.9%) and distant metastasis (1.8%) were uncommon. Overall survival at 5 and 10 years was 79% and 62%, respectively. Although numerous variables were found to significantly impact survival on univariate regression analysis, only age ≥ 65 (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.56-4.19; P < 0.001) and high primary tumor (T)-stage (HR 1.85; 95% CI, 1.16-2.95; P = 0.010) remained significant prognosticators in our multivariate model. For high T-stage disease, surgery with radiation had significantly better survival than surgery alone. Basal cell adenocarcinoma is a rare salivary malignancy with a good prognosis. Regional and distant metastasis were uncommon. Radiation with surgery may help for higher T-stage disease. Old age and high T-stage were significant predictors of worse survival. 4. Laryngoscope, 126:1086-1090, 2016.

Abstract 859: Impact of obesity in melanoma outcomes: Analysis of data from a multinational randomized controlled sentinel lymph node trial

Abstract Introduction: In the United States and around the world, obesity rates have been rising. While rates of some cancers are higher in the obese population, the data related to melanoma incidence is conflicting. Furthermore, the impact of obesity on outcomes in melanoma is unknown. We aim to discern the impact of rising body mass index (BMI) on survival and surgical outcomes in melanoma. Methods: The first Multicenter Selective Lymphadenectomy Trial (MSLT-I) is a multinational randomized controlled trial evaluating the role of sentinel lymph node biopsy in melanoma. We queried this prospective trial database for all patients with height and weight data at the time of enrollment into the trial. Patients were stratified by BMI as obese (BMI ≥30) or not obese (BMI&amp;lt;30). Patient age, sex, Breslow thickness, and lymph node status were assessed for their impact on melanoma specific survival (MSS) and surgical complications. Pathologic data and primary site data were also analyzed with regards to obesity. Results: A total of 1,839 patients were included in the analysis, 741 from the observation group (OBS, no sentinel lymph node biopsy), and 1098 from the sentinel node group (SLN). 376 patients (20%) were obese and 1,463 (80%) were not. MSS at 5 years was 88.8% (±1.7) for obese patients and 82.2% (±1.0) for non-obese patients (p = 0.0512, univariate). A small minority of patients were underweight (n = 27, 1.5%, BMI &amp;lt; 18.5) and they experienced a trend towards worse survival than obese patients (5-yr MSS 79.0% ±8.4). We assessed BMI in a multivariable analysis as a continuous and categorical variable and found a consistent direct association with MSS (for BMI ≥30: HR 0.69 [0.52-0.91], p = 0.010). Multivariable analysis identified decreased BMI, male sex, older age, thicker Breslow level, lymphatic spread, and ulceration as significant predictors of worse survival. Despite a trend towards increased local complications in the obese (23.1% vs. 20.5%, p = 0.267), there was no significant difference in rate of complications based on BMI. The distribution of primary melanoma sites was not different among obese and non-obese populations and there was no difference in pathologic variables (Breslow thickness, ulceration, regression, number of lymph nodes excised, or presence of tumor infiltrating lymphocytes). Conclusions: In this prospective trial database, obesity offers a protective effect on survival without a significantly increased rate of complications. Future studies may look for obesity-related factors and mechanisms to explain the improved outcomes. Citation Format: Daniel D. Kirchoff, Gary B. Deutsch, Stacey L. Stern, Simon Lavotshkin, Delphine J. Lee, Leland J. Foshag, Mark B. Faries. Impact of obesity in melanoma outcomes: Analysis of data from a multinational randomized controlled sentinel lymph node trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 859. doi:10.1158/1538-7445.AM2015-859

Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy for Stage I Non-Small Cell Lung Cancer

Pulmonary function tests predict respiratory complications after lobectomy. We evaluated the impact of pulmonary function measurements on long-term survival after lobectomy for stage I non-small cell lung cancer. The relationship between percent predicted forced expiratory volume in 1 second (FEV1) and percent predicted diffusing capacity of the lung for carbon monoxide (Dlco) and overall survival for patients who underwent lobectomy without induction therapy for stage I (T1-2N0M0) non-small cell lung cancer from 1996 to 2012 was evaluated using the Kaplan-Meier approach and a multivariable Cox proportional hazard model. During the study period, 972 patients (mean Dlco 76 ± 21, mean FEV1 73 ± 21) met inclusion criteria. Perioperative mortality was 2.6% (n = 25). The 5-year survival of the entire cohort was 60.1%, with a median follow-up of 43 months. The 5-year survival for patients with percent predicted FEV1 stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.1%, 59.3%, 52.5%, and 53.4%, respectively. The 5-year survival for patients with percent predicted Dlco stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.2%, 63.4%, 44.2%, and 33.1%, respectively. In multivariable survival analysis, both larger tumor size (hazard ratio 1.15, p = 0.01) and lower Dlco (hazard ratio 0.986, p < 0.0001) were significant predictors of worse survival. The association of FEV1 and survival was not statistically significant (p = 0.18). Survival after lobectomy for patients with stage I non-small cell lung cancer is impacted by lower Dlco, which can be used in the risk and benefit assessment when choosing therapy.

Outcomes of hepatectomy for hepatocellular carcinoma with bile duct tumour thrombus

BackgroundHepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy. MethodsA retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio. ResultsThirtyseven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child–Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), enbloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5year overall survival (38.5% versus 34.6%, P = 0.59) and 5year diseasefree survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and postoperative complication were significant predictors for worse survival whereas BDTT was not. DiscussionA major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and longterm survival is possible after radical surgery.

Palliative care in patients with ovarian cancer and bowel obstruction.

Malignant bowel obstruction (MBO) is usually a pre-terminal event in patients with ovarian cancer. However, because of the lack of data in literature, decisions around surgical intervention, non-resectional procedures, or medical treatment of MBO in patients with ovarian cancer cannot be lightly undertaken. We analyzed medical and surgical procedures, performance status, nutritional status, cachexia, and their prognostic value in this group of patients. We retrospectively selected all consecutive patients with recurrent ovarian cancer who received medical or surgical treatment for MBO between October 2008 and January 2014 at the Academic Department of Gynecological Oncology of Mauriziano Hospital of Turin (Italy). We found 40 patients: 18 of them underwent medical treatment and 22 of them were submitted to surgery. In the group of surgery, the hospitalization was shorter (p 0.02), the pain reduction was more effective (p 0.001), the number of chemotherapy lines was higher (p 0.03), and re-obstruction was more rare (p 0.02). Between the two groups, we did not find any differences in post-palliation episodes of vomit (p 0.83), type of diet (p 0.34), ability to return home (p 0.72), and death setting (p 0.28). Median survival after palliation was longer in the group of surgery (p 0.025). Cachexia, low performance status, and poor nutritional status were significant predictors of worse survival after MBO, independently by the treatment. Surgery has to be considered in patients without serious contraindications; otherwise, a medical protocol, including antisecretory drugs, is the standard of care in frail patients.

The ART Score Is Not Effective to Select Patients for Transarterial Chemoembolization Retreatment in an Italian Series

Background: The ART score (a point score for the assessment of retreatment with transarterial chemoembolization, TACE) has been recently developed in Austria to differentiate patients who may benefit from multiple sessions of TACE for hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to test the validity of the ART score in an Italian study cohort. The secondary aims were to evaluate overall survival (OS) and clinical determinants of improved survival in patients treated with multiple TACE sessions. Methods: The ART score and the clinical outcome of 51 consecutive patients with HCC submitted to multiple TACE sessions from April 2002 to December 2009 were retrospectively analyzed. Results: Median OS was 26.0 months (95% confidence interval 18.4-33.6) with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty-three patients had an ART score of 0-1.5 and in 18 it was ≥2.5, but in our patient series, the ART score was not found to be a predictor of survival (p = 0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0 months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9: 26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between the first and second TACE (absent vs. + 1 point vs. + ≥2 points: 27.0 vs. 4.0 vs. 5.0 months; p < 0.001) were statistically related with survival. At multivariate analysis, only Child-Pugh score increase remained a significant predictor of worse survival (p = 0.001, hazard rate = 11.6). Conclusions: The ART score was not found to work as an objective tool to guide TACE retreatment in our Italian patient series, only the Child-Pugh score increase was an independent predictor of a shorter survival.

Aggressive and minimally invasive surgery for pulmonary metastasis of sarcoma

Pulmonary metastasectomy has become a standard approach for sarcoma, but uncertainty remains regarding risk factors that accurately assess postoperative prognosis and can be used to guide surgical decision making. We identified 145 patients who underwent 204 consecutive pulmonary metastasectomies for sarcomabetween 1996 and 2009, and examined 174 complete resections in 118 patients. Predictors included surgical procedure, number/size of lesions, repeat resection, intervals to metastasis and to recurrence, chemotherapy, sarcoma subtype, distribution of pulmonary and extrapulmonary metastasis, and patient age/sex. Survival estimates were based on Kaplan-Meier analysis and compared using a log-rank test. Predictors were compared using univariate and multivariate Cox proportional hazards modeling. Among patients undergoing R0 resections, median survival was 35 months (95% confidence interval, 22-60 months), with 3-, 5- and 10-year survival of 48%, 42%, and 31%, respectively. The number or size of lesions did not influence survival. Metastasis synchronous to the primary tumor, but not disease-free interval, was a significant predictor of worse survival on single variable and adjusted modeling (hazard ratio, 3.0; 95% confidence interval, 1.4-6.6; P=.005); the presence of extrapulmonary metastasis and a need for anatomic resection were also likely predictors (P=.06 and P = .07). Recurrence of pulmonary metastasis was not associated with a reduction in survival if completely resected, and a more aggressive and less invasive surgical approach during the later half of the study period was not associated with a significant decline in survival. Evolving surgical practice may allow an increasingly aggressive approach to pulmonary sarcoma metastasis, which may be facilitated by increased use of a minimally invasive approach.

Racial and ethnic disparities in presentation, treatment, and outcomes for minority populations with diagnosis of lung cancer.

e17540 Background: There are differences in the presentation, treatment and outcome of lung cancer patients (pts), based on ethnicity, however there are not enough publications regarding these issues. Methods: Registry data on 2,255 pts with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated during last 10 years (2002-2011) at Memorial Health Care System was obtained. The main objective of the study was to evaluate differences in lung cancer survival according to ethnicity. Chi-square was used to compare distribution of tumor stage. Survival curves were compared using log-rank test for each of the tumor stages. Adjusted hazard ratios (AHR) and 95% confidence intervals (95% CI) were reported based on the results of a multivariate Cox regression model for overall survival (OS) with adjustment for gender, age at diagnosis, race, stage and health insurance. Results: A total of 1940 pts (86%) had the diagnosis of NSCLC, the rest were SCLC. There were 1170 (52%) females. Non-Hispanic whites (NHW) were 1,791 pts (79%), Hispanics (H) 266 (12%) and African-American (AA) 149 (7%). Fifty eight percent of patients had stage III/IV at diagnosis. 2054 of the pts were insured (91%). There was a significant difference in age at diagnosis among H (66.5 y), AA (64.4y) and WNH (69.5y). The probability of being diagnosed at a late stage (IIIB/IV) was two times higher among AA compared to NHW (OR= 1.77, P&lt;0.05) or H (OR = 1.67, p&lt;0.05). There was no survival difference between NSCLC and SCLC (19m vs. 16m). Females with NSCLC lived significantly longer than males (Adjusted Hazard ratio (AHR= 1.14 p&lt;0.01). The same was true for SCLC (AHR = 1.43 p &lt; 0.01). Significant predictors for worse survival for patients with NSCLC were: older age at diagnosis (AHR = 1.01, p&lt;0.001), male gender (AHR=1.12, p&lt;0.05) and late stage at diagnosis (AHR=2.27, p&lt;0.001). Insurance and ethnicity were not significant predictors of of survival. Conclusions: There are significant disparities in presentation and outcomes among minority patients with lung cancer. We will further evaluate if other social or genetic factors can explain these disparities.

Microvascular invasion does not predict long-term survival in hepatocellular carcinoma up to 2 cm: reappraisal of the staging system for solitary tumors.

Excellent long-term outcomes have been reported recently for patients with small (≤2cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2cm. In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2cm) and patients with tumors larger than 2cm was analyzed. In patients with small HCC, long-term survival was not affected by MVI (p=0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p<0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95% confidence interval (CI) 1.27-1.99; p<0.001), elevated alpha-fetoprotein (HR 1.41; 95% CI 1.11-1.8; p=0.005), and higher histologic grade (HR 1.29; 95% CI 1.01-1.64; p=0.04) were significant predictors of worse survival in patients with HCC larger than 2cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups-HCC≤2, >2cm without MVI, and HCC>2cm with MVI-significant between-group survival difference was observed (p<0.0001). Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs.>2cm).

A morpho-molecular prognostic model for hepatocellular carcinoma

Background:Hepatocellular carcinoma (HCC) is the third common cause of cancer-related deaths and its prognostication is still suboptimal. The aim of this study was to establish a new prognostication algorithm for HCC.Methods:In all, 13 biomarkers related to the etiopathogenesis of HCC were evaluated by immunohistochemistry using tissue microarrays containing 121 primary HCC resection cases, and validated in subsequent cohort of 85 HCC cases. The results were compared with Affymetrix Gene Chip Human Genome U133Plus microarray data in a separate cohort of 228 HCC patients.Results:On immunohistochemical evaluation and multivariate Cox regression analysis p53, alpha fetaprotein (AFP), CD44 and CD31, tumour size and vascular invasion, were significant predictors for worse survival in HCC patients. A morpho-molecular prognostic model (MMPM) was constructed and it was a significant independent predictor for overall survival (OS) and relapse-free survival (RFS) (P<0.000). The OS and RFS of HCClow was higher (104 and 78 months) as compared with HCChigh (73 and 43 months) (P<0.0001for OS and RFS). Hepatocellular carcinoma patients with higher stage (III+IV), >5 cm tumour size, positive vascular invasion and satellitosis belonged to HCChigh group. The validation group reproduced the same findings. Gene expression analysis confirmed that 7 of the 12 biomarkers were overexpressed in >50% of tumour samples and significant overexpression in tumour samples was observed in AFP, CD31, CD117 and Ki-67 genes.Conclusion:The MMPM, based on the expression of selected proteins and clinicopathological parameters, can be used to classify HCC patients between good vs poor prognosis and high vs low risk of recurrence following hepatic resection.

Liver Transplantation for Hepatic Metastases of Neuroendocrine Pancreatic Tumors: A Survival-Based Analysis

Liver transplantation (LT) has been accepted as a treatment in selected cases of neuroendocrine tumors (NETs) with hepatic metastases. A systematic review of the literature was conducted to evaluate long-term patient survival in the instances of LT for pancreatic NET. Univariate and multivariate regression analyses and survival analysis were performed. Fifty-three clinical studies were screened. Data from 20 studies encompassing 89 transplanted patients were included in the study. Most primary tumors were endocrine pancreatic tumors (n=69), with gastrinomas representing the most frequent diagnosis (n=21). There were 61 functioning pancreatic NET. Simultaneous LT and pancreatic NET resections were performed in 45 instances. Cumulative 1-, 3-, and 5-year survival was 71%, 55%, and 44%, respectively, with a calculated mean survival of 54.45±6.31 months. Vasoactive intestinal peptide (VIPomas) had the best overall survival. Recurrence-free survival at 1, 3, and 5 years was 84%, 47%, and 47%, respectively. Recipient age more than or equal to 55 years (P=0.0242) and simultaneous LT-pancreatic resection (P=0.0132) were found to be significant predictors of worse survival by both univariate and multivariate Cox proportional hazard analyses. A scoring system was developed, with prognostic points assigned as follows: age more than or equal to 55 years:age less than 55 years=1:0 points and simultaneous LT-pancreatic resection:LT alone=1:0 points. This stratification delineated three separate population samples corresponding to patients with scores of 0, 1, and 2, respectively. The calculated 5-year survival for scores 0, 1, and 2 was 61%, 40%, and 0%, respectively (P=0.0023). Despite the limitations of this retrospective analysis, good results can be achieved even for pancreatic NET primaries if the above-proposed scoring system is applied.

The impact of pathological fractures on therapy outcome in patients with primary malignant bone tumours

The primary objective of this study was to investigate the implications of pathological fractures on therapy outcome in patients with primary malignant bone tumours and to determine whether limb salvage can be safely performed. A retrospective analysis of 447 patients with primary malignant bone tumours, treated between 1985 and 2005, was performed. Multivariate Cox regression analysis was used to investigate the influence of pathological fractures and further independent variables on survival rate. In 52 of the 447 patients, the primary malignant bone tumour was complicated by a pathological fracture. These fractures were more common in malignant fibrous histiocytoma (MFH) of the bone and in the tumour stages IIa/b and III. Ablative surgery was performed in ten patients and limb salvage surgery in 42 patients. The mortality risk for patients with pathological fractures was significantly increased by a factor of 1.82 (p = 0.015), and overall duration of survival was significantly lower in the fracture group, with a median of 6.2 years (p < 0.00001). In univariate and multivariate analysis, fracture, higher tumour stages and resection margins remained a significant predictor of worse survival. Overall survival, rate of local recurrence and distant metastases were not affected by the type of surgical treatment selected; there was no difference between the patients who underwent limb salvage and those who underwent an amputation. Pathological fracture in patients with primary malignant bone tumours is a predictor of worse survival and significantly increases mortality risk. Reconstructive surgery did not influence the survival rate, showing that limb salvage therapy is safe when adequate resection margins are achieved.

The Effect of treatment on survival in patients with advanced laryngeal carcinoma

Over the last 2 decades, survival from laryngeal cancer has decreased. We sought to identify factors associated with decreased survival in laryngeal cancer. Patients diagnosed with laryngeal squamous cell carcinoma from 1985 to 2002 were retrospectively reviewed. A total of 451 patients met study criteria. Five-year survival rates were 85% for stage I, 77% for stage II, 51% for stage III, and 35% for stage IV disease. Survival for patients with stage I-III disease was similar for patients treated operatively or nonoperatively (P = .4). However, patients with stage III disease treated nonoperatively had worse survival with radiation alone (XRT) compared to chemoradiation (CR) (P = .006). Patients with stage IV disease had significantly better survival with surgery (49%) than CR (21%) or XRT alone (14%) (P < .0001). Analysis by primary tumor stage demonstrated that survival for T1-T3 disease was independent of treatment modality (P = .2); however, for T4 patients, operative treatment was associated with significantly better survival (55%) than CR (25%) or XRT (0%) (P < .0001). Proportional hazards models confirmed significantly worse survival for stage IV, T4, N2 or N3 disease, and nonoperative treatment. For T4 disease, after controlling for nodal status, nonoperative treatment was the only significant predictor of worse survival. Primary surgical treatment is associated with improved survival for patients with stage IV disease and specifically T4 primary tumors. These data suggest that the observed national decrease in survival from laryngeal cancer may be due to a shift toward nonoperative treatment in that subset of patients with advanced primary disease.

Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor.

Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma. The prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S-phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c-erbB-2, p53, and bcl-2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs). The median duration of survival was 17.8 months (95% confidence interval, 15.2-21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl-2 expression, together with c-erbB-2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl-2 expression were significant predictors of worse survival (P < 0.05). In addition to traditional risk factors, bcl-2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting.

Gender and other survival predictors in patients with metastatic melanoma on Southwest Oncology Group trials.

Some studies have suggested that women with metastatic malignant melanoma have a better survival rate than men. However, little is known about the effect of gender on survival in combination with other clinical variables and treatment variables. Thus, an analysis of 813 eligible patients from 15 consecutive Southwest Oncology Group (SWOG) Phase II or III trials evaluating chemotherapy or chemoimmunotherapy for metastatic melanoma was performed. A multivariate Cox regression model was used. Poor performance status (P < 0.001), more organ sites with metastases (OSM) (P < 0.001), liver involvement (P < 0.001), and nonliver visceral involvement (P = 0.01) were highly significant predictors of worse survival, whereas the disease free interval (P = 0.08) had borderline significance. After adjustment for all factors, there was no difference in overall survival between men and women (P = 0.19). Women had a longer disease free interval (P = 0.003) and fewer OSM (P = 0.004) at study registration than men. The current study found that performance status, OSM, and type of visceral involvement were independent predictors of survival in patients with metastic malignant melanoma and should be used as stratification factors in future Phase III trials. However, the current study also found that gender did not appear to be a significant independent predictor of survival for this stage of disease. A longer disease free interval from initial diagnosis and fewer OSMs may partly explain the improved outcome reported for women in selected trials. The study concluded that further investigation of the biologic differences at early stage diagnosis should be undertaken to determine whether women truly have a different pace of disease progression and a different metastatic pattern.