Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients

Background: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet.Patients and methods: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS).Results: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P = 0.03), lymph nodal involvement (P = 0.002), and PML expression (P = 0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P = 0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P = 0.003) and the only statically significant prognostic factor for OS (P = 0.009).Conclusions: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.     

Expression of nuclear FIH independently predicts overall survival of clear cell renal cell carcinoma patients

AimThe hypoxia inducible factor (HIF) pathway plays an important role in sporadic clear cell renal cell carcinoma (ccRCC) by stimulating processes of angiogenesis, cell proliferation, cell survival and metastases formation. Herein, we evaluate the significance of upstream proteins directly regulating the HIF pathway; the prolyl hydroxylases domain proteins (PHD)1, 2 and 3 and factor-inhibiting HIF (FIH), as prognostic markers for ccRCC.MethodsImmunohistochemical marker expression was examined on a tissue microarray containing tumour tissue derived from 100 patients who underwent nephrectomy for ccRCC. Expression levels of HIF, FIH and PHD1, 2 and 3 were correlated with overall survival (OS) and clinicopathological prognostic factors.ResultsHIF-1α was positively correlated with HIF-2α (p < 0.0001), PHD1 (p = 0.024), PHD2 (p < 0.0001), PHD3 (p = 0.004), FIH (p < 0.0001) and VHL (p = 0.031). HIF-2α levels were significantly associated with FIH (p < 0.0001) and PHD2 (p = 0.0155). Mutations in the VHL gene, expression variations of HIF-1α, HIF-2α and PHD1, 2, 3 did not show a correlation to OS or clinicopathological prognostic factors. Tumour stage, grade, diameter, metastastic disease and intensity of nuclear FIH were significantly correlated to OS in univariable analysis (p = 0.023). Low nuclear FIH levels remained a strong independent prognostic factor in multivariable analysis (p = 0.009).ConclusionThese results show that low nuclear expression of FIH is a strong independent prognostic factor for a poor overall survival in ccRCC.     

Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer

Background: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs.Patients and methods: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of ≥3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS).Results: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), ≥65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS.Conclusion: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.     

The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma

Background: Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients’ survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC.Materials and methods: One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients’ survival.Results: The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan–Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013).Conclusions: The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.     

The prognostic value of erythrocyte polyamines in the preoperative evaluation of patients with renal cell carcinoma

IntroductionPolyamines, spermine and spermidine, are ubiquitous polycationic structures, which are essential for cell proliferation and differentiation. We tested whether spermine and spermidine could improve the prognostic ability of six established preoperative predictors of cancer-specific mortality (CSM) after partial or radical nephrectomy for renal cell carcinoma (RCC).Materials and methodsOverall, 385 patients with clinical stages T_1–3, M_0–1 RCC were treated with radical or partial nephrectomy at a single institution between 1990 and 2007. Kaplan–Meier plots depicted CSM after stratification according to spermine and spermidine levels (dichotomised to above and below the median value). Univariable and multivariable Cox regression models tested the prognostic ability of continuously coded spermine and spermidine levels in preoperative CSM predictions. Covariates consisted of pre-treatment T stage, M stage, age, gender and symptom classification.ResultsThe 5-year CSM-free survival of patients with spermine levels ?4.5 and >4.5 nmol/8 × 10⁹ erythrocytes were, respectively, 79.5% and 65.0%. Similarly, the 5-year CSM-free survival of patients with spermidine levels ?9.0 and > 9.0 nmol/8 × 10⁹ erythrocytes were, respectively, 81.1% and 63.7%. In multivariable analyses addressing CSM after surgery, both spermine (p ? 0.002) and spermidine (p ? 0.001) achieved independent predictor status and improved the accuracy of established preoperative CSM predictors by 2.1% (p < 0.001).ConclusionsCirculating polyamine levels may significantly improve the prognostic value of established determinants of CSM in patients with RCC of all stages prior to nephrectomy. External validation of our findings is required prior to implementation in clinical practice.     

Kallikrein 10 (KLK10) methylation as a novel prognostic biomarker in early breast cancer

Background: We evaluated the prognostic significance of KLK10 exon 3 methylation in patients with early-stage breast cancer since it has been shown to have a significant impact on biological characteristics of breast tumors.Materials and methods: Using methylation-specific PCR, we evaluated the specificity of KLK10 methylation in 10 breast tumors and matching normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and in a testing group of 35 patients. The prognostic significance of KLK10 methylation was validated in an independent cohort of 93 patients.Results:KLK10 was not methylated in normal breast tissues and fibroadenomas while it was in 5 of 10 breast tumors and in 1 of 10 matching normal tissues. In the testing group of 35 patients, KLK10 methylation was detected in 70.0% of patients who relapsed (P = 0.001) and in 77.8% of patients who died (P = 0.025). In the independent cohort, 53 of 93 (57.0%) patients were found positive for KLK10 methylation. During the follow-up period, 24 of 93 (25.8%) patients relapsed and 19 of 93 (20.4%) died. Disease-free interval (DFI) and overall survival (OS) were significantly associated with KLK10 methylation (P = 0.0025 and P = 0.003). Multivariate analysis revealed that KLK10 methylation was an independent prognostic factor for DFI and OS.Conclusion:KLK10 exon 3 methylation provides important prognostic information in early breast cancer patients.     

Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: A multicentre,single-arm,phase 2 trial

BackgroundWe performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results.MethodsPatients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m² in addition to CHOP every 3 weeks for a total of six cycles.ResultsForty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n = 16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n = 10), angioimmunoblastic T-cell lymphoma (AITL, n = 8), ALK-negative anaplastic large-cell lymphoma (ALCL, n = 6), cutaneous T-cell lymphoma (CTCL, n = 5) and hepatosplenic T-cell lymphoma (n = 1). Thirty patients achieved complete response (CR, 65%) and the overall response rate was 76% (35/46). Although the CR rate of ENKTL was only 30% (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87% of overall response rate (ORR) (26/30) and 73% of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47% and 35%, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy.ConclusionsThe combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.     

Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators

BackgroundMortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome.MethodsPrimary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test.ResultsThe CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10^–6).ConclusionsThe CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.     

Absolute lymphocyte count is a novel prognostic indicator in extranodal natural killer/T-cell lymphoma,nasal type

Background: Extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a heterogeneous entity with poor survival, requiring risk stratification in affected patients. We proposed absolute lymphocyte count (ALC) as a new prognostic factor in ENKL.Patients and methods: We retrospectively analyzed 128 patients newly diagnosed with ENKL. Independent prognostic factors of survival were determined by Cox regression analysis.Results: Patients with low ALC (<1.0 × 10⁹/l) at diagnosis tended to have more adverse clinical features. Patients with high ALC (≥1.0 × 10⁹/l) at diagnosis had better overall survival (OS; P < 0.0001) and progression-free survival (PFS; P<0.0001), and achieved higher complete remission rates (P=0.001). Multivariate analysis with known prognostic factors showed that ALC, B symptoms and advanced stage were independent predictors for OS and PFS. Using the International Prognostic Index, Prognostic Index for Peripheral T-cell lymphoma unspecified, or Korean Prognostic Index for nasal NK/T-cell lymphoma, the majority of patients were in the low-risk category (with no or one adverse factor). ALC was helpful to differentiate the low-risk patients with different survival outcomes (P < 0.0001).Conclusions: Our data suggest that ALC at diagnosis is a novel, powerful predictor of prognosis in ENKL. Immune status at diagnosis might have an important influence on survival in patients with ENKL.     

Incidence of brain metastases in renal cell carcinoma treated with sorafenib

Background: This retrospective study evaluated the incidence of brain metastases in a subgroup of patients with metastatic renal cell carcinoma (RCC) who were randomly assigned to receive sorafenib, an oral multikinase inhibitor (400 mg b.i.d.), versus placebo in the phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET).Patients and methods: Patients enrolled in TARGET at two centres (Institut Gustave Roussy, Villejuif, France, n = 85; Central Clinical Hospital of Military Medical Academy, Warsaw, Poland, n = 54) made up the current subgroup, who were retrospectively evaluated for the incidence of brain metastases during follow-up. The association between treatment (sorafenib versus placebo) and occurrence of brain metastases was evaluated by univariate analysis.Results: The overall incidence of brain metastases in patients receiving sorafenib was 3% (2 of 70 patients) compared with 12% (8 of 69 patients) in patients receiving placebo (P < 0.05). The incidence of brain metastases was also significantly lower in the sorafenib group after 1 (P = 0.0447) and 2 years (P = 0.005) of treatment compared with the placebo group.Conclusions: In this subpopulation, sorafenib may reduce the occurrence of brain metastases. Antiangiogenic therapy, such as sorafenib, could be an effective preventive therapy for brain metastases in advanced RCC.     

The role of postoperative radiotherapy (PORT) in pulmonary large cell neuroendocrine carcinoma (PLCNEC)

PurposeTo assess the long-term survivals and related prognostic indicators of patients with pulmonary large cell neuroendocrine carcinoma (PLCNEC), and determine the prognostic value of post-operative radiotherapy in PLCNEC.Materials and methodsPatients diagnosed with PLCNEC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in our study. Cox proportional hazard model was used to evaluate the factors related to overall survival (OS). Propensity score matching analysis (PSM analysis) was used to balance the variables differences between postoperative radiotherapy (PORT) and non-PORT groups.ResultsA total of 701 postoperative cases were identified, with the median follow-up time of 23 months. The 3- and 5-year OS were 50.7%, and 41.2%, respectively. Multivariate analysis revealed that stage I (P < 0.001), age < 65 years old (P < 0.001), chemotherapy (P < 0.001) were independent favorable prognostic factors. There is no significant difference in survival between patients with or without postoperative radiotherapy (PORT) after PSM analysis (P = 0.489). No survival benefit in favor of PORT were displayed, even when subgroups were deeply analyzed.ConclusionsAge, stage, and chemotherapy were significantly associated with OS of patients with resected PLCNEC. However, PORT after resection did not improve long-term outcome of PLCNEC patients.     

Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced-stage squamous cell carcinoma of the larynx and hypopharynx

BackgroundMetabolic tumor volume (MTV) of ¹⁸F-FDG PET/CT is a volumetric measurement of tumor cells with increased ¹⁸F-FDG uptake. We evaluated the prognostic value of MTV in patients with locoregionally advanced laryngeal and hypopharyngeal cancer.Patients and methodsWe evaluated 81 patients with advanced-stage squamous cell carcinoma of the laryngohypopharynx who underwent ¹⁸F-FDG PET/CT between January 2004 and September 2009. Clinicopathologic factors and MTV were analyzed for their association with locoregional control (LRC) and overall survival (OS).ResultsThe 3-year LRC and OS for all patients were 70.9 and 78.7%, respectively, with a median follow-up of 40.4 months (range 24.5–90.1). In univariate analyses, MTV, primary site, and primary treatment strategy were associated with both LRC and OS (P < 0.05). On multivariate analysis, MTV was an independent prognostic factor for both LRC [P = 0.018; HR = 3.141, 95% confidence interval (CI) = 1.175–8.399] and OS (P = 0.008; HR = 3.758, 95% CI = 1.415–9.982). Primary site was also a significant prognostic factor for LRC (P = 0.047).ConclusionPretreatment MTV is an independent prognostic factor in patients with locoregionally advanced squamous cell carcinoma of the larynx and hypopharynx.     

A new prognostic model using absolute lymphocyte count in patients with primary central nervous system lymphoma

PurposePrimary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma (NHL). Absolute lymphocyte count (ALC) has been suggested to have a prognostic value in several subtypes of NHL. We evaluated the prognostic significance of clinical factors, including ALC, in patients with PCNSL to develop a new prognostic model.MethodsWe analysed prognostic factors, including ALC, at diagnosis in 81 PCNSL patients receiving high-dose methotrexate-based therapy.ResultsThe median ALC at diagnosis was 1210 × 10⁶/L (range, 210–3610), with lymphopenia (≤875 × 10⁶/L) being detected in 27 (33.3%) patients. In the multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) >1 (hazard ratio [HR] 3.18, P = 0.003), age >50 years (HR 4.23, P = 0.012), and lymphopenia at diagnosis (HR 2.83, P = 0.008) remained independent prognostic factors for low overall survival (OS). Lymphopenia was also a significant prognostic factor for progression-free survival (HR 3.17, P = 0.001). By means of a new three-factor prognostic model using ECOG PS >1, age >50 years, and presence of lymphopenia, with 1 point assigned to each factor, we successfully classified the patients into three risk groups: low (0 and 1), intermediate (2), and high (3). The 5-year OS rates of the patients in the low-, intermediate-, and high-risk groups were 74.3%, 21.7%, and 12.5%, respectively (P < 0.001).ConclusionsLow ALC is a useful indicator of poor prognosis in patients with PCNSL. The proposed three-factor model should be validated in large-scale studies.     

Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study

Background: Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS).Materials and methods: A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence.Results: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance.Conclusions: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.     

NK/T-Cell Lymphomas: Pathobiology, Prognosis and Treatment Paradigm

The current World Health Organization (WHO) classification includes two types of natural killer (NK)-cell lymphomas: extranodal NK/T-cell lymphoma, nasal type (ENKL), and aggressive NK-cell leukemia (ANKL). These diseases are mostly endemic to East Asia and Latin America. The Epstein-Barr virus (EBV) is usually detected in tumor cells, suggesting that EBV plays an important role in lymphomagenesis. At the site of origin, ENKL can be divided into two major subtypes: nasal and extranasal diseases. The advanced disease presentation, highly aggressive clinical course, and poor prognosis of the latter are analogous to ANKL. It is well known that P-glycoprotein, which is a product of the multi-drug resistance (MDR1) gene, is expressed on neoplastic cells of ENKL or ANKL. This is a major cause of the refractoriness of malignant lymphoma to conventional chemotherapeutic regimens containing anthracycline. Recent studies, however, have identified that L-asparaginase-containing regimens, such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase and etoposide), are effective for ENKL. Considering the myelotoxicity of SMILE, its use in the treatment of ANKL needs some modifications, but this treatment scheme is promising in improving the prognosis of NK-cell lymphomas.     

CXC chemokine receptor 2 is associated with postoperative recurrence and survival of patients with non-metastatic clear-cell renal cell carcinoma

BackgroundAberrant CXC chemokine receptor 2 (CXCR2) expression has been shown to promote angiogenesis and proliferation in renal cell carcinoma (RCC). Our current study aims to evaluate the prognostic significance of CXCR2 in patients with non-metastatic clear-cell renal cell carcinoma (ccRCC).MethodsWe retrospectively enrolled 375 patients with non-metastatic ccRCC undergoing nephrectomy at Zhongshan Hospital, Fudan University between 2003 and 2008. The cohort was split into a training set (n = 184) and a validation set (n = 191). CXCR2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated.ResultsCXCR2 expression was significantly associated with tumour size (P = 0.036 and P = 0.016, respectively) and Fuhrman grade (P = 0.009 and P = 0.001, respectively) in the training and validation sets. Moreover, high CXCR2 expression indicated poor overall survival (OS) (P < 0.001 and P = 0.001, respectively) and recurrence-free survival (P < 0.001 and P < 0.001, respectively) in the training and validation sets. The incorporation of CXCR2 into the T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, CXCR2 expression was identified as an independent adverse prognostic factor for survival (P < 0.001) and recurrence (P < 0.001). A predictive nomogram was generated with identified independent prognosticators to assess patient recurrence-free survival at 5 and 10 years.ConclusionsCXCR2 is a potential independent adverse prognostic biomarker for recurrence and survival of patients with non-metastatic ccRCC after nephrectomy.     

When do we need central nervous system prophylaxis in patients with extranodal NK/T-cell lymphoma,nasal type?

Background: The incidence and risk factors of central nervous system (CNS) invasion is still unclear in extranodal natural killer (NK)/T-cell lymphoma, nasal type.Patients and methods: We analyzed 208 patients to study the clinical features and outcomes of CNS disease in extranodal NK/T-cell lymphoma.Results: Twelve patients (5.76%, 12/208) experienced CNS disease during treatment or follow-up period (median 11.62 months, range 0.2–123.2 months). The clinical variables associated with CNS disease were Ann Arbor stage III/IV (15.87%, P <0.001), regional lymph node involvement (10.41%, P = 0.006), group III/IV of NK/T-cell lymphoma prognostic index (NKPI; 10.20%, P = 0.003), high/high–intermediate international prognostic index (9.30%, P = 0.072) and extra-upper aerodigestive primary sites (9.75%, P = 0.008). In multivariate analysis, NKPI retained the strongest statistical power to predict CNS disease (P = 0.007, relative risk 9.289, 95% confidence interval 1.828–47.212) in extranodal NK/T-cell lymphoma.Conclusions: Despite extranodal NK/T-cell lymphoma frequently involves paranasal sinus, a routine CNS evaluation and prophylaxis do not seem to be necessary in NKPI group I or II patients due to a very low incidence. Nevertheless, CNS prophylaxis should be considered in NKPI groups III and IV.     

A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy

Background: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response).Methods: Two hundred and twenty-one stage II–III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis.Results: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 ≥15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 ≥15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 ≥15%), and (iii) high risk (nodal positivity and Ki-67 ≥15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042).Conclusions: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.     

Clinical significance of survivin and VEGF mRNA detection in the cell fraction of the peripheral blood in non-small cell lung cancer patients before and after surgery

PurposeThe aim of this study was to evaluate the predictive and prognostic value of peripheral blood survivin and VEGF mRNA expression levels in non-small cell lung cancer (NSCLC) patients.Patients and methodsFifty-eight patients with stage I-IIIA NSCLC who underwent surgical resection were enrolled in this study. Thirty-six patients with benign lung disease (BLD) entered this study as control group. Quantitative real-time PCR was used to detect survivin and VEGF mRNA levels in the cell fraction of peripheral blood in NSCLC patients before and after surgery and BLD patients. The relationship between blood survivin and VEGF mRNA levels and patients clinicopathologic parameters and prognostic factors were investigated.ResultsThe levels of survivin and VEGF mRNA were decreased significantly after surgery in NSCLC patients (P = 0.024 and P = 0.012 respectively). Tumor recurrence was significantly more frequent in NSCLC patients with survivin and VEGF mRNA positivity postoperation than in patients without (P = 0.003 and P = 0.006, respectively). Patients with survivin or VEGF mRNA positivity postoperation had markedly shorter disease-free survival (DFS) and overall survival (OS) than patients without (P = 0.023 and P = 0.016 for survivin; P = 0.031 and P = 0.025 for VEGF, respectively). Multivariate analysis showed that survivin positivity preoperation (P = 0.026, P = 0.041, respectively) and postoperation (P = 0.003, P = 0.005, respectively) and VEGF mRNA positivity postoperation (P = 0.007, P = 0.009, respectively) were independently associated with DFS and OS.ConclusionAlthough the levels of surviving and VEGF mRNA were decreased significantly after surgery, postoperative detections of survivin and VEGF mRNA by quantitative real-time PCR could be used as tools to monitor tumor recurrence and predict prognosis.     

Exclusive radiotherapy for primary squamous cell carcinoma of the vagina

PurposeTo retrospectively analyze results of external beam therapy (EBT) with brachytherapy (BT) for primary vaginal squamous cell carcinoma (PVSCC).Materials and methodsFrom 1970 to 2001, 91 patients were included. FIGO stages were: I (29%), II (38%), III (29%) and IVa (4%). EBT delivered a median total dose of 50 Gy to the pelvis. BT was performed with a customized intra-vaginal applicator and in 36% of applications combined endocavitary and interstitial BT. ICRU Report 38 parameters were reported.ResultsThe 5-year cause specific survival (CSS) rates were: 83% for stage I, 76% for stage II, 52% for stage III, and 2 of the 4 stage IVa patients died 9 and 36 months after treatment. The 5-year pelvis control rates were: 79% for stage I and II and 62% for stage III. Recurrences as a first event were local only in 68% of cases, nodal only in 10%, metastatic only in 13% and combined in 9%. In multivariate analysis: stage (I and II versus II and IV), response to EBT (evaluated at BT), and the number of BT applications were statistically significant for CSS. Grade 2–3 toxicities were as follows (Franco-Italian Glossary): rectum (n = 3), sigmoid colon and small bowel (n = 8), bladder (n = 5), ureter (n = 4) and vagina (n = 13). Anterior location of the tumor increased bladder toxicity (p = 0.01) and total reference air kerma was higher in patients who experienced grade 2–3 urinary or digestive toxicity (p = 0.03).ConclusionEBT with BT is an effective treatment for patients with stage I–II PVSCC. The incidence and severity of late toxicity were relatively low. Recent advances in the treatment of cervix carcinoma emphasize the need for concomitant radio-chemotherapy in stages III–IV and the use of MRI for treatment planning.