Predictive Factor For Disease-free Survival Research Articles

Prognostic impact of p16 and PD-L1 expression in patients with oropharyngeal squamous cell carcinoma receiving a definitive treatment

AimsLimited information is available regarding the precise differences in the tumour immune microenvironment (TIM) of patients with human papilloma virus (HPV)-associated and non-HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Here, we...

Body weight loss after surgery affects the continuity of adjuvant chemotherapy for pancreatic cancer

BackgroundPostoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy.MethodsFifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis.ResultsUnivariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381–16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761–15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721–11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724–17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135–2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%.ConclusionsThe following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient’s prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.

Tubular and mucinous breast cancer: results of a cohort of 917 patients.

To analyze axillary lymph node involvement (ALNI) rate and survival for mucinous (MC) and tubular (TC) breast carcinomas considered being of very good prognosis and for which an axillary surgical exploration could be questioned. Our multicentric cohort consisted of 21,135 patients with clinically node-negative invasive breast cancer, without neoadjuvant therapy, between 1999 and 2013 in 10 French centers. ALNI rate and survival were analyzed according to patient and tumor characteristics. Our cohort consisted of 672 TC and 245 MC. Patients were older and tumor size greater for MC and pathologic factors were more pejorative. The rate of mastectomies and adjuvant chemotherapy was higher in the MC group. Axillary lymph node status was determined by SLNB alone in 71.2% of patients. ALNI rates were 17.9% and 18% for TC and MC, respectively. ALNI rate was lesser for MC (OR 0.503, p = 0.024) and greater in case of lympho-vascular invasion (OR 5.0, p < 0.0001) and for tumors >10 mm (OR 2.17, p = 0.042). Median follow-up was 58 months. The 5- and 7-year overall survival rates were 97.1% and 95% for TC, respectively; 92.3% and 91.2% for MC ( p = 0.043); 5- and 7-year disease-free survival rates were 97.9% and 97.2% versus 95.2 and 93.6% ( p = 0.041). Lympho-vascular invasion was the only predictive factor for overall survival (hazard ratio [HR] = 2.70)' grade 2 (HR = 10) and HR-negative (HR = 4.9) were the two predictive factors for disease-free survival. This study confirms the need for an axillary exploration for these tumors even for a tumor size <10 mm and a favorable prognosis.

Computer-aided Volumetry of Part-Solid Lung Cancers by Using CT: Solid Component Size Predicts Prognosis.

Purpose To investigate the relationship between the postoperative prognosis of patients with part-solid non-small cell lung cancer and the solid component size acquired by using three-dimensional (3D) volumetry software on multidetector computed tomographic (CT) images. Materials and Methods A retrospective study by using preoperative multidetector CT data with 0.5-mm section thickness, clinical records, and pathologic reports of 96 patients with primary subsolid non-small cell lung cancer (47 men and 49 women; mean age ± standard deviation, 66 years ± 8) were reviewed. Two radiologists measured the two-dimensional (2D) maximal solid size of each nodule on an axial image (hereafter, 2D MSSA), the 3D maximal solid size on multiplanar reconstructed images (hereafter, 3D MSSMPR), and the 3D solid volume of greater than 0 HU (hereafter, 3D SV0HU) within each nodule. The correlations between the postoperative recurrence and the effects of clinical and pathologic characteristics, 2D MSSA, 3D MSSMPR, and 3D SV0HU as prognostic imaging biomarkers were assessed by using a Cox proportional hazards model. Results For the prediction of postoperative recurrence, the area under the receiver operating characteristics curve was 0.796 (95% confidence interval: 0.692, 0.900) for 2D MSSA, 0.776 (95% confidence interval: 0.667, 0.886) for 3D MSSMPR, and 0.835 (95% confidence interval: 0.749, 0.922) for 3D SV0HU. The optimal cutoff value for 3D SV0HU for predicting tumor recurrence was 0.54 cm3, with a sensitivity of 0.933 (95% confidence interval: 0.679, 0.998) and a specificity of 0.716 (95% confidence interval: 0.605, 0.811) for the recurrence. Significant predictive factors for disease-free survival were 3D SV0HU greater than or equal to 0.54 cm3 (hazard ratio, 6.61; P = .001) and lymphatic and/or vascular invasion derived from histopathologic analysis (hazard ratio, 2.96; P = .040). Conclusion The measurement of 3D SV0HU predicted the postoperative prognosis of patients with part-solid lung cancer more accurately than did 2D MSSA and 3D MSSMPR. © RSNA, 2018.

OCA2 rs4778137 polymorphism predicts survival of breast cancer patients receiving neoadjuvant chemotherapy

BackgroundGenome-wide association study (GWAS) studies have showed that single nucleotide polymorphisms (SNPs) in OCA2 gene were associated with the survival of breast cancer patients treated with adjuvant chemotherapy. To further explain the association between OCA2 SNPs and breast cancer survival, we investigated the predictive value of rs4778137 located in OCA2 in local advanced breast cancer patients receiving neoadjuvant chemotherapy. Patients and methodsA case-cohort with 150 breast cancer patients was performed to evaluate the effects of the OCA2 rs4778137 on breast cancer survival. The association between rs4778137 genotypes and pathological complete response (pCR, defined that the postoperative pathology indicating no residual invasive breast cancer in the breast or the axillary lymph node) were analyzed. Logistic regression analysis was performed to identify the independent predictors of pCR. Survival was assessed by Kaplan-Meier method and Cox regression analysis according to the rs4778137 genotypes. ResultsThe differences between pCR and the rs4778137 genotypes were statistically significant (p < 0.05). The patients with genotype GG harbored a better disease-free survival (HR: 2.358, p = 0.000) and overall survival (HR: 1.578, p = 0.008) than the patients with genotype CC in rs4778137. The further Univariate and Multivariate survival analysis revealed that SNP rs4778137 was an independent predictive factor of disease-free survival (p = 0.000/p = 0.001) and overall survival (p = 0.006/p = 0.045). ConclusionThe OCA2 rs4778137 may be a predictor for the clinical response and survival in local advanced breast cancer patients who received neoadjuvant chemotherapy.

Endotherapy in case of relapse of neoplastic Barrett's esophagus after successful initial endoscopic resection.

Endotherapy in cases of neoplastic Barrett esophagus (BE) relapse after successful initial endoscopic management is commonly accepted, but few studies analyze this topic and also take into account the metachronous lesions. To evaluate the efficiency of endotherapy in the case of neoplastic BE relapse after successful complete endoscopic eradication of neoplastic BE and metaplastic BE. Retrospective review of medical records was collected in a computerized and prospective manner between 2000 and 2015, in a single tertiary care center. Recurrence was defined by histological presence of high-grade dysplasia or superficial adenocarcinoma at least 6months after the end of successful initial endotherapy. Eighteen patients were assessed (1F/17M). Delay between initial treatment and relapse was 16.6months (range 6-33). Endotherapy for relapse obtained a sustained and complete remission for 8/18 (44%) patients, with an average endoscopic follow-up of 28months. The complication rate of endotherapy was 6%. Surgical management was required in 33% (2 pT2N0M0, 2 pTisN0M0, 1 pTm2N0M0 and 1 pTm3N0M0) and salvage radiochemotherapy in 17% (3/18). One patient treated by 6 sessions of ER was considered as a failure given the multiple sessions of endotherapy. Multivariate analysis showed that length of BE (>5cm), late stenosis adverse events and the quality of vertical margin during initial ER are predictive factors for disease-free survival (p value<0.01, Hazard Ratio up to 0.076). Endotherapy could be a treatment for management of neoplastic BE relapse, but should be carefully used, with strict follow-up.

Post-resection recurrence of hepatocellular carcinoma in cirrhotic patients: Is thrombocytopenia a risk factor for recurrence?

PurposeLiver resection is the main treatment for hepatocellular carcinoma (HCC) patients with sufficient liver reserve. However, the long-term outcomes are dismal because the recurrence rate is high, especially in cirrhotic patients. The role of platelets as a predictive factor for HCC recurrence is still controversial. The aim of this study was to assess the influence of the preoperative platelet count on HCC recurrence after liver resection in patients with liver cirrhosis. Study designBetween 2004 and 2013, 233 HCC patients with pathologically proven liver cirrhosis underwent liver resection and were enrolled in this study. ResultsRecurrence occurred in 125 patients (53.6%), predominantly within the remnant liver (100 patients, 42.9%). The 1-, 3-, and 5-year disease-free survival (DFS) rates were 71.4%, 48.1%, and 40.5%, respectively. The predictive factors for DFS were analyzed with Cox's proportional hazard regression model. In the multivariable analysis, the preoperative platelet count (p = 0.021) and pT stage (p = 0.01) were the only significant independent predictors of HCC recurrence. The recurrence rate was clearly stratified by the preoperative platelet count. The optimal cut-off value of 135 × 103/μL on a receiver operating characteristic curve corresponded to the maximum sensitivity and specificity of prediction. The DFS of patients with low preoperative platelet counts was significantly worse than that of patients with high preoperative platelet counts (p = 0.006, log-rank test). ConclusionsThrombocytopenia is a significant predictor of HCC recurrence after liver resection in cirrhotic patients. However, the pathophysiological mechanism underlying this finding requires clarification.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases

Objective: To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion.Methods: Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS.Results: Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis.Conclusions: LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

Clinicopathologic and Prognostic Implications of Programmed Death Ligand 1 Expression in Thymoma

Programmed death ligand 1 (PD-L1) has been reported to be expressed in various malignancies and is considered to be a prognostic factor and an immunotherapeutic target. The aim of this study was to characterize PD-L1 expression in thymoma and determine statistical associations between this expression and clinical features. We reviewed formalin-fixed, paraffin-embedded tissue specimens from 82 thymoma cases accumulated at Kurume University, the majority of which achieved surgical complete resection. Expression of PD-L1 was evaluated by immunohistochemistry. Statistical associations between PD-L1 expression and clinicopathologic features were evaluated by using χ(2) test and Fisher's exact test. Disease-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test. Predictive factors for disease-free survival after complete resection were analyzed by using a Cox proportional hazards model in univariate and multivariate analysis. Overall, 44 thymoma cases (54%) revealed high PD-L1 expression. High PD-L1 expression was statistically associated with Masaoka stage III/IV disease (p = 0.043) and World Health Organization type B2 or B3 thymoma (p = 0.044). Disease-free survival after complete resection in high PD-L1 expression was significantly worse than that in low PD-L1 expression (p = 0.021), although there was no significant difference in overall survival (p = 0.957). Multivariate analysis also revealed high PD-L1 expression as an independent risk factor for recurrence (p = 0.008). Characterization of PD-L1 expression in thymoma should enable more effective clinical approaches, including prognostic stratification of patients and potential use of anti-PD-L1 antibody immunotherapy.

The prognostic value of clinical and pathologic features in nonmetastatic operable male breast cancer

Compared with female breast cancer, male breast cancer is a rare disease, and the relationship between clinical/pathologic features and prognosis is controversial, or even largely unknown. In this study, we performed a retrospective analysis using clinical and pathologic data from 109 nonmetastatic operable male breast cancer patients treated from January 1996 to December 2011 at Tianjin Medical University Cancer Institute and Hospital. Log-rank test showed that lower tumor stage, no lymph node involvement, and positive estrogen/progesterone receptor status were good predictors of both disease-free survival and overall survival on univariate analysis. However, hormonotherapy is only a good predictive factor of disease-free survival, and not of overall survival. In addition, based on a Cox proportional hazard regression model, only lymph node involvement, and estrogen/progesterone receptor status were statistically significant predictive factors on multivariate analysis. Our results demonstrated that although adjuvant systemic therapy is used extensively in male breast cancer patients and prognosis has improved over the last few decades, lymph node involvement, and estrogen/progesterone receptor status are still the most important prognostic factors. A prospective multi-center study with a larger sample size is urgently needed to further understand male breast cancer.

Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study)

We investigated the disease-free survival (DFS) of HER2-positive primary breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well as predictive factors for DFS and pathologic response. Data from 829 female patients treated between 2001 and 2010 were collected from 38 institutions in Japan. Predictive factors were evaluated using multivariate analyses. The 3-year DFS rate was 87 % [95 % confidence interval (CI) 85-90]. The pathologic complete response (pCR: ypT0/is + ypN0) rate was 51 %. The pCR rate was higher in the ER/PgR-negative patients than in the ER/PgR-positive patients (64 vs. 36 %, P < 0.001). Patients with pCR showed a higher DFS rate than patients without pCR (93 vs. 82 %, P < 0.001). Multivariate analysis revealed three independent predictors for poorer DFS: advanced nodal stage [hazard ratio (HR) 2.63, 95 % CI 1.36-5.21, P = 0.004 for cN2-3 vs. cN0], histological/nuclear grade 3 (HR 1.81, 95 % CI 1.15-2.91, P = 0.011), and non-pCR (HR 1.98, 95 % CI 1.22-3.24, P = 0.005). In the ER/PgR-negative dataset, non-pCR (HR 2.63, 95 % CI 1.43-4.90, P = 0.002) and clinical tumor stage (HR 2.20, 95 % CI 1.16-4.20, P = 0.017 for cT3-4 vs. cT1-2) were independent predictors for DFS, and in the ER/PgR-positive dataset, histological grade of 3 (HR 3.09, 95 % CI 1.48-6.62, P = 0.003), clinical nodal stage (HR 4.26, 95 % CI 1.53-13.14, P = 0.005 for cN2-3 vs. cN0), and young age (HR 2.40, 95 % CI 1.12-4.94, P = 0.026 for ≤40 vs. >40) were negative predictors for DFS. Strict pCR (ypT0 + ypN0) was an independent predictor for DFS in both the ER/PgR-negative and -positive datasets (HR 2.66, 95 % CI 1.31-5.97, P = 0.006 and HR 3.86, 95 % CI 1.13-24.21, P = 0.029, respectively). These results may help assure a more accurate prognosis and personalized treatment for HER2-positive breast cancer patients.

Results of salvage liver transplantation

Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n=28) was compared with PLT (n=198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group=72) compared to PLT (n=198). The five-year overall survival (OS) was 65.4% vs. 49.2% (P=0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P=0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P=0.003], alpha-foetoprotein (HR 1.002 P<0.001) and number of HCC nodules (HR 1.317 P=0.035), whereas viral hepatitis C positivity (HR 1.911 P=0.03) and outside Up-to-seven criteria (HR 2.652 P<0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n=72 including SLT plus LR group) and was 69.4% vs. 42.2% (P<0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P<0.001). Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.

The impact of p53 in predicting clinical outcome of breast cancer patients with visceral metastasis

In the study, we analyzed role of p53 in predicting outcome in visceral metastasis breast cancer (VMBC) patients. 97 consecutive VMBC patients were studied. P53 positivity rate was 29.9%. In the p53-negative group, median disease free survival (DFS), and time from primary breast cancer diagnosis to death (OS1), time from metastases to death (OS2) were 25, 42.5, and 13.5 months, respectively. In the p53-positive group, they were 10, 22, and 8 months, respectively. Statistically significant differences in DFS and OS1 were detected between the p53-negative and p53-positive subtypes. However, p53 appears to have no influence on OS2. In Cox regression analysis, p53 expression and TNM stage were predictive factors of DFS. In the multivariate analysis, p53 expression and the duration of DFS correlated with OS1, but not for OS2. Taken together, our data indicate p53 showing predicting role in OS1 for VMBC, but not for OS2.

Perioperative chemotherapy for resectable gastroesophageal cancer: A single-center experience

Multimodal treatment for locally advanced gastric cancer has been reported to improve disease-free survival when compared to surgery alone. We aimed to clarify the efficacy and safety of perioperative chemotherapy for locally advanced gastric cancer patients treated in daily clinical practice. Patients diagnosed with locally advanced gastric cancer were treated with perioperative chemotherapy and surgery. The primary end point was the complete resection (R0) rate. Secondary end points were disease-free survival (DFS), overall survival (OS), toxicity, radiological response rate, pathological response rate and downstaging rate. We also looked for prognostic and predictive factors for DFS, OS, pathological complete response and the R0 rate. Forty patients were found eligible for this retrospective analysis. At diagnosis, 52.5% of patients were classified as stage II and 47.5% were stage III. Forty percent of patients completed three preoperative cycles and three postoperative cycles. A tolerable toxicity related to chemotherapy was found. Thirty-nine patients underwent surgery: 80% reached a complete resection (R0), down-staging was detected in 57.5% and 17.5% had a pathologically complete response. The median time of disease-free survival was 34.05 months (95%CI 25.6-42.4), and the median time of overall survival was 39.01 months (95%CI 30.8-47.1). We found that the presence of comorbidities were independent predictive factors for the pathologic response, while the chemotherapy schedule and the clinical response could independently predict a complete resection. Our results support that perioperative chemotherapy for locally advanced gastric cancer can be safely delivered in daily clinical practice, obtaining an improvement of the pathologic response and the complete resection of gastric cancer.

P-0082 - Routine Use of Perioperative Chemotherapy for Resectable Gastroesophageal Cancer

Methods: Patients diagnosed with locally advanced gastric cancer were treated with perioperative chemotherapy and surgery in our institution. Perioperative chemotherapy schedules were selected by the oncologists according to each patient’s baseline characteristics and comorbidities. We obtained available clinical, radiological, surgical and pathological data for all patients analyzed. The primary end point was the complete resection (R0) rate. Secondary end points were disease-free survival (DFS), overall survival (OS), toxicity, radiological response rate, pathological response rate and downstaging rate. We also looked for prognostic and predictive factors for DFS, overall survival (OS), pathological complete response rate and the R0 rate. The study got the approval of the local Research Ethics Committee. Kaplan-Meier method and long-rank test were apply to univariate survival analysis. Multivariate analysis was performed. Cox regression and multiple linear regression analysis was applied when required. Results: Forty patients were found eligible for this retrospective analysis. The median follow-up period was 19 months (range 5.7-54.8). At diagnosis, 52.5% of patients were classified as stage II and 47.5% were stage III. The most common chemotherapy schedule used was a combination of epirubicin, cisplatin and capecitabine. Forty percent of patients completed three preoperative cycles and three postoperative cycles. A tolerable toxicity related to chemotherapy was found without any chemotherapy toxicity–related deaths. Thirty-nine patients underwent surgery: 80% reached a complete resection (R0), down-staging was detected in 57.5% and 17.5% had a pathologically complete response. The median time of disease-free survival was 34.05 months (IC95% 25.6-42.4) and the median time of overall survival was 39.01 months (IC95% 30.8-47.1). Pathological response, radiological response, perineural invasion and resection type were related to better disease-free survival (p0.001, p < 0.001, p0.001 and p < 0.001 respectively) and better overall survival (p0.001, p0.024, p < 0.001 and p0.002 respectively). However, the statistical significance was lost in the multivariate analysis. Predictive factors for pathological complete response in the univariate analysis were: vomiting at diagnosis (p0.0005), the presence of comorbidities (p0.0016) and radiological response (p0.004). Only the presence of comorbidities maintained statistical significance after the multiple linear regression analysis (p0.024). The resection type could be predicted by the chemotherapy schedule used (p0.014) and the clinical response (p0.048); these factors maintained significance after the multiple linear regression with p values of 0.029 and 0.025, respectively. Conclusion: Our results support that perioperative chemotherapy for locally advanced gastric cancer can be safely delivered in daily clinical practice, obtaining an improvement of the pathologic response and the complete resection of gastric cancer. We found that the presence of comorbidities were independent predictive factors for the pathologic response, while the chemotherapy schedule and the clinical response could independently predict a complete resection.

Number of involved lymph nodes is important in the prediction of prognosis for primary duodenal adenocarcinoma

BackgroundThe significance of lymph node involvement regarding the prognosis of primary duodenal adenocarcinoma remains controversial. This study aims to evaluate the prognostic accuracy of nodal metastasis using the seventh edition American Joint Committee on Cancer staging system in patients with primary duodenal adenocarcinoma. MethodsBetween 1993 and 2010, 36 patients who had undergone surgical resection for primary duodenal adenocarcinoma at the Kaohsiung Veterans General Hospital were retrospectively reviewed. ResultsThe median disease-free survival for all patients was 19 months and the median overall survival was 21 months. Lymph node metastases were found in 26 (72%) of the patients, and 14 patients (39%) patients had in excess of three positive lymph nodes (N2). Patients with N2 disease had significantly reduced overall survival, as compared to patients with three or fewer positive lymph nodes (N1; p = 0.036). In univariate analysis, factors including age >75 years, body weight loss, tumor size ≤4 cm, N2 disease and lymph node ratio >0.4 predicted shorter overall survival. Multivariate analysis demonstrated that N2 and lymph node ratio >0.4 are significant risk factors associated with overall survival (p = 0.026 and p = 0.042 respectively). N2 is also the only independent predictive factor for disease-free survival (p = 0.023). ConclusionSubdivision of metastatic lymph nodes into N1 and N2 improves predictive ability. The seventh edition American Joint Committee on Cancer staging system is applicable in the present study with regard to the prediction of the prognosis for primary duodenal adenocarcinoma.

Long-term results and prognostic factors of patients with cervical carcinoma treated with concurrent chemoradiotherapy

To evaluate the predictive factors of recurrence in cervical cancer treated with radical radiochemotherapy. A retrospective analysis of 56 women was performed. Response was assessed using the RECIST response. Overall survival and disease-free survival curves were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to analyse predictors of recurrence. Local recurrence was documented in 16 patients and distant metastases in 15. The Kaplan-Meier survival probabilities were 95.1 ± 6.4% at 3 years and 80.4 ± 13.1% at 5 years and the Kaplan-Meier curve values for disease-free survival were 60.3 ± 14.3% at 3 years and 53.0 ± 15.7% at 5 years. Thirty-five patients were alive and 21 patients died, 19 from metastatic disease and 2 from other causes. Complete response after chemoradiation therapy, squamous cell carcinoma and tumour size ≤ 4 cm were significantly associated with outcome. In the Cox regression model, tumour size > 4 cm (hazard ratio 7.48; 95% CI 2.71-20.6; p < 0.001) and partial response (hazard ratio 7.09; 95% CI 2.82-17.8; p < 0.001) were predictive factors for disease-free survival and partial response (hazard ratio 3.7; 95% CI 1.3-10.1; p < 0.001) and non-squamous cell carcinoma (hazard ratio 3.5; 95% CI 1.2-9.7; p < 0.001) were predictive factors for overall survival. Non-squamous histology and partial response were independent prognostic factors for overall survival and tumour size and partial response were independent prognostic variables for 5-year disease survival.

Vascular Reconstruction During Pancreatoduodenectomy for Ductal Adenocarcinoma of the Pancreas Improves Resectability but does not Achieve Cure

Combined vascular and pancreatic resection improves long-term survival of patients suffering from ductal adenocarcinoma of the pancreatic head. This study was designed to compare the results of surgical resection in patients with pancreatic cancer with or without vascular resection. Late 10-year disease-free survival was considered as an indicator of patients' disease cure. A total of 149 consecutive patients have undergone pancreatoduodenectomy without vascular resection (group 1: 82 patients), with isolated venous resection (group B: 67 patients), or with arterial and/or venous resection (group C: 8 patients). The duration of surgery and blood losses were significantly more important in groups B and C compared with group A; however, postoperative morbidity and mortality rates were similar. R1 resection was significantly more frequent in groups B (42%) and C (50%) compared with group A (13%; p=0.0002), but there were more advanced tumors in these groups, as demonstrated by a lower Karnowsky index, higher Ca 19-9 plasmatic level, greater tumor size, more advanced stage in the AJCC classification, and more tumor location in the uncinate process of the pancreas. Ten-year overall and disease-free survivals were significantly better in group A (19 and 20%) compared with group B (2.8 and 0%) and group C (0% and 0%). Multivariate analysis proved vascular resection and metastatic nodal status as being independent predictive factors of disease-free survival. Vascular resection combined to pancreatoduodenectomy for pancreatic cancer increases local resectability without increasing mortality and morbidity rates but does not improve patients' disease cure rate.

Inactivation of the MAL Gene in Breast Cancer Is a Common Event That Predicts Benefit from Adjuvant Chemotherapy

Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed hypermethylation in breast cancer cell lines and 69% of primary tumors analyzed compared with normal breast epithelial cells. Differential methylation between normal and cancer DNA was confined to the proximal promoter region. In a subset of breast cancer cell lines including T47D and MCF7 cells, promoter methylation correlated with transcriptional silencing that was reversible with the methylation inhibitor 5-aza-2'-deoxycytidine. In addition, expression of MAL reduced motility and resulted in a redistribution of lipid raft components in MCF10A cells. MAL protein expression measured by immunohistochemistry revealed no significant correlation with clinicopathologic features. However, in patients who did not receive adjuvant chemotherapy, reduced MAL expression was a significant predictive factor for disease-free survival. These data implicate MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy.

Prognostic value of the percentage of positive fragments in biopsies from patients with localized prostate cancer

To assess the prognostic value of the percentage of positive fragments (PPF) in biopsies from patients with localized prostate cancer (PCa) undergoing radical prostatectomy. During the period from March 1991 to November 2000, 440 patients were selected. Cases receiving neoadjuvant or adjuvant hormone therapy, or adjuvant radiotherapy, were excluded, as were cases presenting Gleason scores higher than 6 at biopsy. PPF was defined as the total number of fragments divided by the total number of biopsy fragments times 100. This variable was initially divided into categories from 0 to 25%, 25.1% to 50%, 50.1 to 75% and 75% to 100%. During the postoperative period, patients were assessed every 2 months for 1 year, then every 6 months for 5 years, and then yearly. Biochemical recurrence was defined as serum PSA higher than or equal to 0.4 ng/mL. Median follow-up was 60 months. One hundred and nine (24.8%) of the 440 patients under study had biochemical recurrence. In the univariate analysis, PPF significantly influenced disease-free survival (log-rank, p < 0.001), and patients with PPF between 75 and 100% presented a risk of a biochemical recurrence of the disease 3 times higher than patients with PPF between 0 and 25% (p < 0.001). After the Cox regression analysis, both serum PSA (p = 0.001) and PPF (p < 0.001) showed to be independent predictive factors for disease-free survival following surgery. PPF measurement in biopsy is a simple and practical method, which should be routinely used as a predictive factor for biochemical recurrence in patients with PCa presenting Gleason scores between 2 and 6.