Significance For Disease-free Survival Research Articles

Hepatic artery lymph node relevance in periampullary tumors: A retrospective analysis of survival outcomes.

The Periampullary area comprehends a heterogeneous and complex structure with different histological tissues. Surgical standards include the peripancreatic regional lymphadenectomy, and during pancreatoduodenectomy (PD) the hepatic artery lymph node HALN(8a) is dissected. We aimed to describe the prognostic significance of the HALN(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) in a specific cohort of patients in limited economic and social conditions. A retrospective study was conducted based on a prospective database from the HPB department of patients who underwent pancreaticoduodenectomy (PD) due to periampullary tumors during 2014-2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HALN(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis was used. 111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). The positive rate of the HALN(8a) node was 21.62%. The Median OS time was 25.5 months, and the median DFS time was 13,8 months. Positive HLAN(8a) node, the cutoff of lymph node ratio resection (LNRR), and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p = 0.04 HR = 2.1; p = 0.02 HR = 0.4 CI 95%). In this series of PD, OS was reduced in patients with HALN(8a) compromise in patients with pancreatic cancer, however without statistical significance in DFS. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.

Hepatectomy strategy for T2 gallbladder cancer between segment IVb and V resection and wedge resection: A propensity score-matched study

BackgroundLiver resection is recommended for T2 gallbladder cancer, but the optimal hepatectomy strategy remains controversial. We aimed to assess the safety and effectiveness of segment IVb and V resection versus wedge resection in patients with T2 gallbladder cancer. MethodsThis is a retrospective multicenter propensity score-matched study in China. Overall survival, disease-free survival, perioperative complications, and hospital length of stay were used to evaluate safety and effectiveness. ResultsThere are a total of 512 patients. 112 of 117 patients undergoing segment IVb and V resection were matched to 112 patients undergoing wedge resection. After matching, segment IVb and V resection demonstrated no statistical difference in overall survival (hazard ratio, 0.970 [0.639–1.474]; P = .886), but significance in disease-free survival (hazard ratio, 0.708 [0.506–0.991]; P = .040). Patients with incidental gallbladder cancer (hazard ratio, 0.390 [0.180–0.846]; P = .019), stage T2b (hazard ratio, 0.515 [0.302–0.878]; P = .016), and negative lymph nodes status (hazard ratio, 0.627 [0.406–0.991]; P = .043) were associated with improved disease-free survival after segment IVb and V resection, but not in wedge resection. However, perioperative complications occurred more frequently after segment IVb and V resection (28.5% vs 9.1%, P < .001) along with the longer hospital length of stay (17.3 vs 10.2 days, P < .001). Notably, patients with jaundice (odds ratio, 4.053 [1.361–12.23]; P = .013), undergoing laparoscopic resection (odds ratio, 2.387 [1.059–4.484]; P = .028) or surgeon performing per the first 10 segment IVb and V resections (odds ratio, 2.697 [1.035–6.998]; P = .041), were the independent risk factors for perioperative complications in the segment IVb and V resection group. ConclusionT2 gallbladder cancer patients undergoing segment IVb and V resection rather than wedge resection have an improved disease-free survival, especially for incidental gallbladder cancer or hepatic-sided (T2b) gallbladder cancer. However, high rates of perioperative complications and longer hospital length of stay after segment IVb and V resection indicated that surgeons must rely on their own surgical skills and the patient profile to decide the optimal hepatectomy strategy.

The prognostic significance of magnetic resonance imaging (MRI) following neoadjuvant concurrent chemoradiation (NCCR) in patients with locally advanced rectal adenocarcinoma (LARA).

e15166 Background: In patients with locally advanced rectal adenocarcinoma (LARA), the response to neoadjuvant concurrent chemoradiation (NCCR) correlates with long-term outcomes. Neoadjuvant rectal (NAR) score ([5 ypN - 3 (cT - ypT) + 12]2/9.61) is a novel short-term surrogate endpoint for disease free survival (DFS) and Overall survival (OS). The prognostic significance of magnetic resonance imaging (MRI) findings following NCCR is yet to be explored. Here, we evaluated the agreement between post NCCR MRI yT and yN and pathological ypT and ypN. In addition, we calculated the post NCCR MRI NAR (mNAR) score using the MRI yT and yN ([5 yN - 3 (cT - yT) + 12]2/9.61) and explored its prognostic significance. Methods: Between 2014 and 2018, all patients with LARA were identified. Among those, 43 patients received NCCR, had post NCCR MRI and underwent surgical resection. Weighted Kappa was used to measure the agreement between post NCCR MRI yT and yN and pathological ypT and ypN. Paired t-test was used to compare the means between NAR and mNAR scores. NAR and mNAR scores were classified as low ( &lt; 8), intermediate (8-16) and high ( &gt; 16). DFS and OS were analyzed using Kaplan-Meier curves. Results: In our cohort, the agreement was slight between post NCCR MRI yT and Pathological ypT (p = 0.111), and fair between post NCCR MRI yN and pathological ypN (0.278). The mean NAR score was 16 and the mean mNAR score was 20 (p = 0.0079). Low-intermediate and high NAR scores were seen in 31 (72%) and 12 (28%) patients respectively. However, low-intermediate and high mNAR scores were seen in 20 (47%) and 23 (53%) patients respectively. The median DFS in patients with low-intermediate and high NAR scores was not reached and 30 months (p = 0.00063) respectively. The median OS in patients with low-intermediate and high NAR scores was not reached and 40 months (p = 0.00056) respectively. The median DFS in patients with low-intermediate and high mNAR scores was not reached in both groups (p = 0.058). The median OS in patients with low-intermediate and high mNAR scores was not reached in both groups (p = 0.15). Conclusions: Post NCCR MRI yT and yN had slight and fair agreements with ypT and ypN respectively. In our cohort, there was a difference between NAR and mNAR. NAR demonstrated prognostic significance for DFS and OS, while mNAR did not at the time of analysis.

Prognostic factors for intrathyroidal papillary carcinomas - a multivariate analysis

Aim: to examine prognostic significance of patient-related, tumor-related and treatment-related factors for intrathyroidal papillary thyroid carcinomas (PTC), via multivariate analysis. Material and methods. This study included 153 patients with intrathyroidal PTCs (pT1/pT2/pT3) surgically treated in our Institution during two-decade period. Patients with locally invasive tumors (pT4) and initial distant metastases (M1) were excluded. Parameters of interest were: gender (male; female), age ( 45 years), tumor size (pTNM classification WHO 1984), multifocality (no; yes), histological type of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of lymphonodal metastases (pN1a; ipsilateral-pN1b; contralateral-pN1b; total), surgery extent (total thyroidectomy; total thyroidectomy with lymphonodal dissections). Univariate and multivariate analysis of all parameters was performed in order to distinguish factors of significance for disease-free survival (DFS) and cancer-specific overall survival (cs-OS). Results. In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2% died due to PTC. Univariate analysis distinguished older age, male gender, tumors over 4cm in diameter, multifocality and poorly differentiated PTC-types as unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor multifocality was unfavorable prognostic factor for both DFS and cs-OS. Independent prognostic factors for intrathyroidal PTCs, based on Cox multivariate analysis, were multifocality and gender for DFS, and multifocality and age at diagnosis for cs-OS. Conclusions. Prognostic factors define risk groups within population of differentiated PTCs providing timely, adequate treatment and opportunity for longer quality life of patients with PTCs.

Prognostic factors for intrathyroidal papillary carcinomas – a multivariate analysis

Aim: to examine prognostic significance of patient-related, tumor-related and treatment-related factors for intrathyroidal papillary thyroid carcinomas (PTC), via multivariate analysis.Material and methods. This study included 153 patients with intrathyroidal PTCs (pT1/pT2/pT3) surgically treated in our Institution during two-decade period. Patients with locally invasive tumors (pT4) and initial distant metastases (M1) were excluded. Parameters of interest were: gender (male; female), age (&lt;=45; &gt;45 years), tumor size (pTNM classification WHO 1984), multifocality (no; yes), histological type of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of lymphonodal metastases (pN1a; ipsilateral-pN1b; contralateral-pN1b; total), surgery extent (total thyroidectomy; total thyroidectomy with lymphonodal dissections). Univariate and multivariate analysis of all parameters was performed in order to distinguish factors of significance for disease-free survival (DFS) and cancer-specific overall survival (cs-OS).Results. In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2% died due to PTC. Univariate analysis distinguished older age, male gender, tumors over 4cm in diameter, multifocality and poorly differentiated PTC-types as unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor multifocality was unfavorable prognostic factor for both DFS and cs-OS. Independent prognostic factors for intrathyroidal PTCs, based on Cox multivariate analysis, were multifocality and gender for DFS, and multifocality and age at diagnosis for cs-OS.Conclusions. Prognostic factors define risk groups within population of differentiated PTCs providing timely, adequate treatment and opportunity for longer quality life of patients with PTCs.

Prognostic Influence of Pre-Operative C-Reactive Protein in Node-Negative Breast Cancer Patients

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02–1.07) and OS (P = 0.036, HR = 1.03, 95% CI = 1.00–1.06), whereas a trend was observed for MFS (P = 0.111). In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR = 1.01, 95% CI = 1.00–1.07) as well as OS (P = 0.023, HR = 1.03, 95% CI = 1.00–1.06), independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6%) patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman's rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and prognosis in breast cancer.

Prognostic value of pretreatment hemoglobin level in patients with early cervical cancer

ObjectiveThe purpose of this study is to investigate the prognostic role of pretreatment anemia in patients with early cervical cancer who underwent radical hysterectomy.MethodsIn this study, we retrospectively enrolled patients with early cervical cancer (International Federation of Obstetrics and Gynecology stage IB to IIA) who were treated at Samsung Medical Center, Seoul, Korea, from 1996 to 2007.ResultsWe retrospectively enrolled 805 patients. Median pretreatment hemoglobin (Hb) level was 12.8 g/dL (4.0-16.9) in all patients. Ninety-ninth out of 805 patients had pretreatment anemia (12.3%). Pretreatment anemia was significantly associated with large tumor size, advanced clinical stage, and parametrial invasion. In multivariate analysis, higher pretreatment Hb entailed better prognostic significance in disease free survival (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.078-0.99) but not in overall survival (HR, 0.94; 95% CI, 0.80-1.10).ConclusionIn conclusion, we found that the negative association between pretreatment Hb level and tumor size and the impact of anemia before treatment on disease free survival adjusted for other factors including clinical stage and pathological findings in early stage cervical cancer.

Prognostic significance of cytosolic phospholipase A2 expression in patients with colorectal cancer

PurposeCyclooxygenase-2 is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Cytosolic phospholipase A2 (cPLA2), also, have been suggested to be related to the carcinogenesis of CRC. The aim of this study was to investigate cPLA2 expression and its relationship with prognostic significance in CRC.MethodsEighty-eight patients with colorectal cancer who underwent curative surgery were enrolled in this study. cPLA2 was examined in 88 primary CRCs by immunohistochemistry and we compared their expression with clinicopathologic findings, recurrence and survival in patients with CRC.ResultsThe expression of cPLA2 was positive in 54.5% (48/88). The expression of cPLA2 was not correlated with clinicopathologic parameters. However, cPLA2 expression was significantly related with vascular endothelial growth factor expression. Kaplan-Meier analysis didn't show any clinical significance in disease-free survival and overall survival according to cPLA2 expression.ConclusionThese results suggest that cPLA2 expression was not associated with the prognosis of CRC. However, further large-scale studies are needed to clarify the prognostic effect of cPLA2 in CRC.

Validation of FOXA1 as a Prognostic Marker in Breast Cancer in a Large Population-Based Tissue Microarray.

Abstract FOXA (Forkhead box protein A) proteins play major roles in development and differentiation. However, recently, FOXA1 has been identified to play a role in controlling nearly 50% of estrogen receptor target genes and has been deemed as a 'pioneer factor'. It is believed to have a dual role in breast cancer: (1) growth promotion by coactivating ERα and (2) growth inhibition by regulating factors like p27Kip1 and E-cadherin. We studied the expression of FOXA1 in a population based tissue microarray of 4,046 invasive breast cancer cases with a median follow- up of 12.4 years using immunohistochemistry and studied its correlation with estrogen receptor and other clinicopathological variables. The percent positivity (P) and intensity (I) of nuclear FOXA1 expression were multiplied to generate a numerical score (S = P × I) that ranged from 0 to 30. Scores between 0 and 3 were defined as low FOXA1 expression and 4 to 30 were defined as high FOXA1 expression. Variable FOXA1 expression was noted in the 3581 interpretable tumors: none (10.6%), weak (3.5%), moderate (19.3%) and strong (55.1%). High level of FOXA1 expression (FOXA1 score greater than 3) was seen in nearly 86% of the tumors. FOXA1 expression correlated positively with ER (p&amp;lt; 0.0001), PR (p&amp;lt; 0.0001), E-cadherin (p&amp;lt;0.0001), age (p&amp;lt; 0.0001) and negatively with basal subtype (p&amp;lt; 0.0001), Ki67 (p&amp;lt;0.0001), tumor size (p&amp;lt; 0.0001) and tumor grade (p&amp;lt;0.0001). Univariate analyses showed small tumor size (T1 tumors), low grade (Grade I), node negative disease, absence of lymphovascular invasion, ER, PR, Her2, cyclin D1 and Ki67 as independent predictors of better overall survival. Patients with Luminal A subtype breast cancers had better overall survival than those with non-Luminal A subtype breast cancers. FOXA1 is found to be a significant predictor of breast cancer specific survival (p=0.012) and locoregional relapse free survival (p=0.0001). However, FOXA1 did not reach statistical significance for disease free survival (p=0.110) and distant relapse free survival (p=0.147). When stratified by molecular subtypes using IHC, FOXA1 did not show any trend for overall survival. In those treated with tamoxifen, low FOXA1 expression was associated with poor overall survival (p&amp;lt;0.0001). In a subset of ERα-positive breast cancer cases, FOXA1 was a significant predictor of breast cancer specific survival (p=0.012). To summarize, FOXA1 expression in ERα-positive breast cancer is of prognostic significance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2130.

Quantitative risk stratification and individual comprehensive therapy for invasive bladder cancers in China

To evaluate the risk factors for invasive bladder cancer and to develop a predictive model for the improvement of individual comprehensive therapy for invasive bladder cancers. The records of 356 patients with invasive bladder cancer, operated on at three Chinese medical institutes, were reviewed. The Cox proportional hazards regression model was used to assess the clinical and pathological variables affecting disease-free survival (DFS). The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). PI was used to categorize the patients into different risk groups. Kaplan-Meier survival curves followed with log-rank test were plotted to compare the difference. Tumor configuration (RR = 1.60, P = 0.01), multiplicity (RR = 1.41, P = 0.04), histological subtype (RR = 2.13, P < 0.01), tumor stage (RR = 2.50, P < 0.01), tumor grade (RR = 2.35, P < 0.01), node status (RR = 2.48, P < 0.01), and neoadjuvant chemotherapy (RR = 0.46, P = 0.02), had independent prognostic significance for DFS. PI = 0.47 x (configuration) + 0.34 x (multiplicity) + 0.76 x (tumor histological subtype) + 0.92 x (stage) + 0.86 x (grade) + 0.91 x (node status) - 0.79 x (neoadjuvant chemotherapy). The range of PI was -0.32 to 6.52, which was equally divided into three risk groups with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.01). Meanwhile, the patient's probability of survival could be calculated by PI. Seven factors (tumor configuration, multiplicity, histological subtype, tumor stage, tumor grade, node status, neoadjuvant chemotherapy) affect the prognosis after radical cystectomy (RC) for invasive bladder cancer. PI can be used to optimize the individual comprehensive therapy. Given fewer perioperative complications, fast recovery from surgery and relatively satisfactory quality of life, ureterocutaneostomy, and ileal conduit are suitable for the patients with short expected life spans.

Evaluation of the prognostic significance of human kallikrein 8 protein expression levels in advanced ovarian cancer by using automated quantitative protein analysis

5581 Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 8 (hkl8) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Materials and Methods: A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of kallikrein 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time of the cohort was 34.35 months. One hundred twenty six of 150 cases had sufficient tissue for AQUA analysis. There was association between tumor mask hk8 protein expression levels and clinicopathological variables including grade (p=0.0011), residual disease (p=0.0063),clinical response to chemotherapy (p=0.0346). In univariate survival analysis there was a correlation between hk8 tumor mask expression and 5 years progression-free survival. Low hk8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterized prognostic variables, tumor hkl8 expression level retained its prognostic significance for disease free survival (95%CI: 0.341–1.027, p=0.0468). Conclusions: Human Kallikrein 8 is an adverse prognostic factor in patients with ovarian cancer.The possibilities that hK8 may be suitable candidate as diagnostic, prognostic marker and therapeutic target merit further investigation. No significant financial relationships to disclose.

Prognostic significance of cyclooxygenase-2 (COX-2) expression in young Korean patients with invasive breast carcinoma

829 Background: The proportion of early-onset breast carcinoma is high in Korea. We evaluated COX-2 expression, roles of prognostic significance and association with other clinicopathologic parameters in Korean patients with early-onset, invasive breast carcinoma. Methods: Paraffin embedded tissue samples were selected from 175 Korean patients with invasive breast carcinoma, at the age 45 or younger. The patients had undergone curative surgery between 1993 and 2002 and received adjuvant therapy according to clinicopathologic status and median follow-up was 58 months. Samples were immunohistochemically stained with antibodies to COX-2 and the expression was then related to clinicopathologic parameters and follow-up data. Results: COX-2 expression was detected in 58 of the 175 (33.1%) invasive carcinoma studied. COX-2 positivity was correlated with tumor size, axillary lymph node status and estrogen receptor negativity (p<0.05). The 5-year disease free survival for patients with COX-2 negative and positive staining were 87.0% and 69.0%, respectively (p=0.0167). In a multivariate analysis, expression of COX-2 was of borderline significance for disease free survival (relative risk, 2.09; 95% confidence interval, 0.95–4.60), adjusting for tumor size, histologic grade, number of positive lymph node, hormone receptor status, and patients age. Conclusions: Our data suggest that COX-2 expression may play an important role in the progression of Korean patients with early-onset breast carcinoma. No significant financial relationships to disclose.

Zonal location of prostate cancer: significance for disease-free survival after radical prostatectomy?

Objectives To analyze the zonal location of prostate cancer as a possible predictive feature of progression-free survival after radical prostatectomy. Methods Prostate cancers were divided into three groups according to the percentage of cancer volume (70% or more, 31% to 69%, and 30% or less) located in the transition zone (TZ). In a total of 307 patients, 5-year progression-free probabilities were estimated for different clinical and pathologic tumor characteristics using the Kaplan-Meier method. With emphasis on the percentage of cancer volume located in the TZ, univariate and multivariate analyses were performed to calculate their prognostic significance in predicting progression-free probability. Results Prostate cancer with 70% or more, 31% to 69%, and 30% or less of the cancer volume in the TZ was found in 17.3%, 6.8%, and 75.9% of the patients, respectively. Patients with tumors with 70% or more of the cancer volume in the TZ had a significantly (log-rank P = 0.0402) greater rate of biochemical cure than those with 30% or less (82.1% versus 66.2%). The increasing percentage of cancer volume located in the TZ was significantly ( P = 0.0258) associated with a greater progression-free probability in univariate analysis, but did not retain independent significance ( P = 0.5748) in multivariate analysis. Instead, pathologic stage ( P <0.0001), lymph node involvement ( P = 0.0189), and Gleason score on prostatectomy specimen ( P = 0.0023) were independent prognosticators. Conclusions The location of prostate cancer in the TZ was associated with a greater overall biochemical cure rate after radical prostatectomy. However, it was not an independent prognosticator on multivariate analysis. Therefore, the knowledge about zonal location of prostate cancer offers no advantage over the well-established prognostic factors in predicting disease recurrence.

Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-d-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy

In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P =.01) and DFS (42% v 79%, P =.005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

Favorable Impact of Virological Response to Highly Active Antiretroviral Therapy on Survival in Patients with AIDS-related Lymphoma

We have retrospectively studied the influence of highly active antiretroviral therapy (HAART) on the outcome of AIDS-related lymphomas (ARL) as well as the possible influence of the virological response to HAART on complete response (CR) rate and survival in our series of ARL treated with CHOP. Two groups of patients were studied: (1) 44 patients who did not take HAART when the lymphoma was diagnosed, and (2) 26 patients treated with HAART concomitantly and after chemotherapy. There were 4 (9%) women in group 1 versus 11 (42%) in group 2 (P =0.01), and serum lactate dehydrogenase (LDH) level was lower in group 2. The response rate to CHOP was higher in group 2 patients (15 out of 23, 65%) than in those of group 1 (16 out of 44, 36%) (P =0.025). The factors associated with improvement of CR in the multivariate analysis were the administration of HAART (P =0.004) and International Prognostic Index (IPI) score ≤ 2 (P =0.006). Among group 2 patients, those with a virological response to HAART and with IPI score ≤ 2 had better response rate to chemotherapy (odds ratios 9.3 and 11.8, respectively). The median (95% CI) overall survival (OS) for group 1 patients was 7 (3-11) months, whereas it has not been reached for group 2 (P =0.002). The only parameters influencing OS in the multivariate analysis were HAART (0.003), as a protective factor and IPI score>2 (P =0.015) with negative influence. Among patients treated with HAART, those with virological response had higher OS probability (P =0.004), whereas those with IPI score>2 had an unfavorable prognosis (P =0.014). The only variable with statistical significance for disease free survival (DFS) in the univariate and multivariate analyses was HAART (P =0.0168 and P =0.028, respectively). We conclude that HAART is an independent prognostic factor for CR attainment, OS and DFS in patients with ARL treated with CHOP. Those patients with virological response to HAART had a better survival.

Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors.

Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood. Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.) The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained. Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical significance for disease free survival. Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.