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Failure-free Survival (failure-free + survival)
Selected AbstractsPrognostic factors in advanced stage Hodgkin's lymphoma: the significance of the number of involved anatomic sitesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2001T.P. Vassilakopoulos Abstract:Background: Advanced Hodgkin's lymphoma (HL) is curable by conventional chemotherapy in 60,70% of patients. The pretreatment identification of a sizeable subgroup of patients with sufficiently low failure-free survival (FFS) to be eligible for investigational treatment is necessary. Objectives: To determine the prognostic significance of the number of involved sites (NIS) in patients with advanced HL and its relationship to the International Prognostic Score (IPS). Methods: A retrospective review of patients with advanced HL, defined as Ann Arbor stage (AAS) IB, IIB, III or IV, treated with anthracycline-based regimens. The end-point was FFS. Results: We identified 277 patients with a median age of 32 yr (14,78), 57% of whom were males. AAS was I in 4% of patients, II in 29%, III in 38% and IV in 29%. B-symptoms were recorded in 81%. Most patients had nodular sclerosis (64%) and mixed cellularity (26%) histology. IPS was ,3 in 44% of 242 evaluable patients. The NIS was ,5 in 32% of the patients and 20% of all patients had both ,5 involved sites and IPS ,3. The 10-yr FFS was 67%, being 76% vs. 50% for patients with ,4 vs. ,5 involved sites (P < 0.0001). The NIS (, 5), AAS IV and anemia were independent predictors of FFS in multivariate analysis. The NIS remained significant along with IPS, when the latter was included in the analysis. Patients with ,5 involved sites and IPS ,3 had 10-yr FFS overall, and relapse-free survival of 41%, 45% and 49%, respectively. Conclusions: The NIS was associated with FFS in advanced HL, was independent of IPS, and led to the identification of a sizeable subgroup of patients with 10-yr FFS of approximately 40%. This factor should be evaluated during the development of prognostic systems. [source] RM2 antigen (,1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Seiichi Saito Abstract Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, ,1,4-GalNAc-disialyl-Lc4, defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and ,4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern ,4, high Gleason score (,8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer. © 2005 Wiley-Liss, Inc. [source] Clinical verification of the superiority of the current International Union Against Cancer staging criteria in an Australian population of patients with nasopharyngeal carcinomaJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2004J Corry Summary The purpose of this study is to assess the prognostic abilities of the fourth and fifth edition International Union Against Cancer (UICC) staging systems for nasopharyngeal carcinoma (NPC) in Australian patients. All patients planned for curative treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. There were 181 patients eligible for this study. The median follow up was 7.6 years. Histological subgroups were World Health Organization (WHO) 1 (23), WHO 2 (12), and WHO 3 (146). Presentation with stage IV disease was 83% by UICC fourth edition staging and 34% by UICC fifth edition staging. The 5 years failure-free survival (FFS) rates for stage 1, 2, 3 and 4 disease by the fourth edition was 77, 100, 93, and 49% respectively,and by the fifth edition was 85, 76, 57 and 36%, respectively. The 5 years overall survival (OS) for stage 1, 2, 3, and 4 disease by the fourth edition was 77, 100, 100 and 61%; respectively, and by the fifth edition was 85, 82, 67 and 53%, respectively. Stage 4 patients by the fourth edition were reclassified as stages 2, 3 and 4 by the fifth edition with hazard ratios of 0.77, 1.01 and 1.79, respectively. In multifactor analysis, the fifth edition staging system was significantly related to FFS and OS after allowing for the fourth edition (FFS: P = 0.002; OS: P = 0.005), but the fourth edition was not significantly related to FFS or OS after allowing for the fifth edition (FFS: P = 0.96; OS: P = 0.96). This study confirms the prognostic superiority of the fifth edition UICC staging system over the fourth edition staging system in an Australian NPC population. [source] Dose-intensified treatment of Burkitt lymphoma and B-cell lymphoma unclassifiable, (with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) in young adults (<50 years): A comparison of two adapted BFM protocols,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Sudhir Tauro The chemotherapy dose-intensity in two adapted German BFM paediatric protocols (BFM 90 and NHL 86) was compared in contemporaneously treated adults <50 years with Burkitt lymphoma and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (collectively referred to as BL). In BFM 90, primary prophylaxis with Granulocyte-colony-stimulating factor was used, postinduction treatment was started at granulocytes ,0.5 × 109/L (,1.0 × 109/L in NHL 86) with a higher mean methotrexate dose (2.9 g/m2/cycle, n = 23; 1.6 g/m2/cycle in NHL 86, n = 22, P < 0.001). Intervals between consecutive treatment-cycles were shorter in BFM 90 (P < 0.001) with no additional toxicity. However, the two-year failure-free survival with BFM 90 (82%) was similar to that achieved with NHL 86 (72%, P = 0.33). We conclude that BFM 90 enables safe intensification of therapy in young adults with BL compared to NHL 86, but registry-based studies are required to further evaluate the antineoplastic effects and cost-effectiveness of the two therapeutic approaches. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Influence of methotrexate exposure on outcome in patients treated with MBVP chemotherapy for primary central nervous system lymphomaBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2010Hélène Blasco WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Although treated using the same high-dose methotrexate (HD-MTX)-based multiagent chemotherapy, patients with primary central nervous system lymphoma (PCNSL) have significant differences in outcome. However, little information has been published about factors influencing outcome in PCNSL. As it is known that the pharmacokinetics of MTX vary considerably between subjects leading to different exposure in patients receiving the same dose, it is important to evaluate its role in response to chemotherapy. WHAT THIS STUDY ADDS This study is the first to evaluate the exposure,response relationship in patients treated with MBVP chemotherapy. We found that patients who were early non-responders to MBVP chemotherapy had poor survival, whatever the salvage regimen. Tumour response at early evaluation was not associated with MTX pharmacokinetics and increasing the dose would probably not improve results. AIMS Although the standard treatment for primary central nervous system lymphoma (PCNSL) consists of three cycles of MBVP (methotrexate, BCNU, VP16, methylprednisolone) and radiotherapy, early failure of treatment may require modification of the treatment. However, our understanding of the outcome in such patients and of the factors involved in early failure of treatment is poor. In addition to known prognostic factors, we evaluated the influence of methotrexate (MTX) exposure on the response to MBVP chemotherapy in patients treated for PCNSL after the first two cycles. METHODS We retrospectively analyzed all patients with PCNSL treated with the MBVP regimen over the previous 10 years. Clinical, personal data and known prognostic factors were studied. The parameters of MTX exposure were estimated using a population pharmacokinetic approach with NONMEM. Objective response (OR), overall survival (OS) and failure-free survival (FFS) were evaluated in all patients. RESULTS Thirty-seven patients were studied. We observed lower FFS and OS (0.49 years) in patients who were not able to receive the planned treatment (group 1, n= 12) than in those who received three cycles (8.04 years) (group 2, n= 25). Known prognostic factors were comparable in both groups, but mean dose of MTX and mean AUC tended to be lower in patients who failed prematurely or showed no response after two cycles. CONCLUSIONS We found that patients who were early non-responders to MBVP chemotherapy had poor survival, without major influence of MTX exposure. It is thus probably unlikely that increasing the dose of MTX would improve outcome. [source] High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2009Mars B. Van't Veer Summary Mantle cell lymphoma (MCL) has a dismal outcome when treated with conventional chemotherapy. This single arm phase 2 study evaluated intensive consolidation treatment of patients with newly diagnosed MCL up to the age of 65 years, responsive to R-CHOP (rituximab, cyclophosphamide, oncovin, adriamycin, prednisolone). Endpoints for evaluation were toxicity, failure-free survival (FFS) and overall survival (OS). Eighty-seven patients were treated with three cycles of R,CHOP. Sixty-six patients responded to R-CHOP with at least a partial response, 62 continued protocol treatment with high-dose cytarabine (Ara-C; 2000 mg/m2, bid. over 4 d) and 61 patients received rituximab and stem cell harvest, followed by BEAM (carmustine, etoposide, Ara-C, melphalan) and autologous stem cell rescue. Non-haematological toxicity, grades III and IV, was seen in 8% of the patients after R-CHOP, in 22% after high-dose Ara-C and in 55% after BEAM. The overall response rate was 70% (complete response rate 64%, partial response rate 6%), FFS and OS at 4 years were 36 ± 7% and 66 ± 6%, respectively. The FFS and OS at 4 years from the evaluation after BEAM in the 61 R-CHOP responsive patients was 46 ± 9% and 79 ± 7%, respectively. In conclusion, high-dose Ara-C and BEAM with stem cell rescue in newly diagnosed MCL patients responsive to R-CHOP is a manageable treatment with respect to toxicity. This regimen leads to long-term, but probably not durable, remissions. [source] High serum levels of B-lymphocyte stimulator are associated with clinical,pathological features and outcome in classical Hodgkin lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2007C. Tecchio Summary B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical-pathological features and outcomes. Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean ± standard error 4493·9 ± 264·9 pg/ml vs. 2687·0 ± 200·9 pg/ml; P < 0·0001). Levels above the median value (4242·0 pg/ml) were associated with age ,45 years (P = 0·042), advanced stages of disease (P = 0·005), systemic symptoms (P = 0·014) and extranodal involvement (P = 0·009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88·6% as compared to 65·1% of those with levels above the median (P = 0·009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0·046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target. [source] Anthracycline-fludarabine-containing regimens with or without rituximab in the treatment of patients with advanced follicular lymphoma,CANCER, Issue 9 2009Stefano Luminari MD Abstract BACKGROUND: Recent experience has suggested that there has been a stepwise improvement in the survival outcomes of patients who have follicular lymphoma with the introduction of new treatment options. In the current study, the authors report the results of 2 subsequent phase 2 trials of 238 previously untreated patients. METHODS: In a trial of bleomycin, epidoxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP) plus fludarabine, mitoxantrone, and dexamethasone (FND), 144 patients received 2 BACOP treatments followed by 4 FND treatments. In a trial of BACOP plus fludarabine and rituximab (FR), 94 patients received 3 BACOP treatments followed by 4 FR treatments. RESULTS: The complete remission (CR) rate for BACOP/FND was 62%. After a median follow-up of 60 months, the failure-free survival (FFS) and overall survival (OS) rates at 4 years were 53% and 77%, respectively. The CR rate for BACOP/FR was 79%. After a median follow-up of 36 months, the FFS and OS rates at 4 years were 56% and 97%, respectively, which were significant compared with the CR and OS rates achieved with BACOP/FND. Twenty-five of 42 bcl -2-positive patients attained a molecularly negative CR and had improved FFS. No significant differences were observed between the 2 trials in the percentage of infections or neutropenia. CONCLUSIONS: The CR and OS rates achieved with BACOP/FR were better, and overall toxicity did not increase. Furthermore, patients who received rituximab had a better FFS compared with patients who received chemotherapy alone. Finally, although conclusions between nonrandomized groups may depend on differences in observed and unobserved prognostic features, the current results suggested that the addition of rituximab to anthracycline-fludarabine,containing regimens have a favorable effect on the prognosis of patients with advanced follicular lymphoma. Cancer 2009. © 2009 American Cancer Society. [source] Proliferation predicts failure-free survival in mantle cell lymphoma patients treated with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabineCANCER, Issue 5 2009Mar Garcia MD Abstract BACKGROUND: It has been demonstrated that the tumor proliferation index has prognostic significance in patients with mantle cell lymphoma (MCL). Patients in most of studies, however, have been treated with relatively traditional chemotherapy regimens. At the authors' institution, patients with MCL received an aggressive chemotherapy regimen: rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabine (R-hyper-CVAD). METHODS: The authors assessed the proliferation rate of MCL using immunohistochemistry and an antibody specific for Ki-67 in 71 untreated patients who subsequently received R-hyper-CVAD. The study group included 59 patients who had classic MCL and 12 patients who had the blastoid variant of MCL. RESULTS: For the entire study group and for the group of patients with classic MCL, a proliferation index of >20% Ki-67-positive cells was correlated significantly with shorter failure-free survival. There was no correlation between the proliferation index and overall survival. CONCLUSIONS: The current results indicated that the proliferation index in patients with MCL predicted prognosis in those who uniformly received the R-hyper-CVAD chemotherapy regimen. Cancer 2009. © 2009 American Cancer Society. [source] Clinical implications of nodal marginal zone B-cell lymphoma among Japanese: study of 65 casesCANCER SCIENCE, Issue 1 2007Masaru Kojima To clarify the clinical presentation and outcome of nodal marginal zone B-cell lymphoma (NMZBL), 65 Japanese patients with this disease were studied and compared with the published literature from western countries. The clinical findings of our 65 cases were similar to those of their cases in some aspects: (1) 58% of the patients were >60 years old (median age, 64 years); (2) there was a slight female predominance; (3) 90% of the patients exhibited asymptomatic lymphadenopathy in the head and neck area; (4) only a minority of patients had B symptoms (6%) and poor performance status (8%); and (5) only 5% of patients were positive for M-protein. However, the 65 patients in this series exhibited relatively longer 5-year overall survival (85%) and failure-free survival (60%) than the NMZBL series published in western literature, suggesting that NMZBL should be classified as indolent lymphoma. Moreover, based on the histological findings, we further classified four histological subtypes as follows: (1) splenic type (n = 7); (2) floral type (n = 9); (3) mucosa-associated lymphoid tissue (MALT) type (n = 29); and (4) diffuse large B-cell lymphoma (DLBCL) + MALT type (n = 20). DLBCL + MALT type exhibited significantly poorer 5-year overall survival than the splenic variant. The recognition of DLBCL + MALT type appears important. No API2,MALT1 fusion transcript was detected in any of the 14 cases examined. (Cancer Sci 2007; 98: 44,49) [source] |