Unfavorable Prognosis Factor Research Articles

Expression of BCL10 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

This study used an immunohistochemical technique to examine the expression of BCL10 in 93 specimens of oral squamous cell carcinoma (OSCC) and 21 specimens of normal oral mucosa (NOM). We found a significant correlation between the higher mean BCL10 labeling index (LI) and OSCCs at the tongue, with larger tumor size, with positive lymph node metastasis, with more advanced clinical stages, or with recurrence (all p-values=0.000). Positive lymph node metastasis (p=0.044) and BCL10 LI>50% (p=0.037) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. The Kaplan-Meier curve showed that OSCC patients with a BCL10 LI>50% had a significantly poorer cumulative survival than those with a BCL10 LI<50% (log-rank test, p<0.00001). We conclude that the BCL10 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

Comparison of clinicopathological features and operative prognosis of gastric carcinoma complicated with Krukenberg tumor and with pelvic peritoneal dissemination

To compare the clinicopathological characters and operative prognosis of gastric cancer complicated with Krukenberg tumor and with pelvic peritoneal dissemination. Thirty-nine female cases of gastric carcinoma with pelvic metastasis were treated operated on between August 1994 and March 2006. Among them, 18 cases were complicated with Krukenberg tumor and 21 cases with pelvic peritoneal dissemination. The clinicopathological characters in the two groups were recorded and compared and the operative prognosis were analyzed. There was no significant difference in age, tumor location and size, hepatic metastasis, organic encroachment, infiltration degree, positive lymph nodes, differentiated degree, tissue typing, Borrmann typing, value of carcinoembryonic antigen between the two groups (P > 0.05). The rate of P3 (peritoneal dissemination) in the cases of Krukenberg tumor (44.4%) was significantly lower than that in pelvic peritoneal dissemination group (85.7%) (P < 0.01), whereas the focal resection rate (77.8%) and multi-organ dissection rate (55.6%) were significantly higher than in pelvic peritoneal dissemination (38.0%, 23.8%) (P < 0.05). The mean survival of all cases was 12.6 months. The mean survival in the patients with Krukenberg tumor and pelvic peritoneal dissemination was 20.5, 15.0 months, respectively (P < 0.05). The mean survival of total focal resection, palliative focal resection, non-focal resection was 19.9, 12.5 and 5.7 months, respectively (P < 0.01). Non-focal resection, pelvic peritoneal dissemination, P3 of peritoneal implantation, hepatic metastasis, organic encroachment, total gastric cancer were unfavorable prognosis factors for all cases. Compared with pelvic peritoneal dissemination, the gastric cancer with Krukenberg tumor is associated with more limited peritoneal dissemination, higher resection rate and better prognosis. Focal resection can improve the prognosis.

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 +/- 6 days after the event. IRA was patent in 61 patients and occluded in 40. Overall MTHFR 677TT frequency was 22%. Patients with MTHFR 677TT homozygosis had higher prevalence of occluded IRA (73%) versus those with MTHFR 677CT/CC genotype (30%, P < 0.001); MTHFR 677TT genotype predicted independently the risk of IRA occlusion with a specificity of 90% (odds ratio 3.8, 95% confidence interval 1.1-9.1; P = 0.03). Moreover, patients with occluded IRA and MTHFR 677TT genotype had the highest homocysteine levels (21 +/- 7.6 micromol/l vs. < or =14.9 +/- 3.8 micromol/l; P = 0.011). In patients with AMI, MTHFR 677TT homozygosis is independently associated with a persistently occluded IRA after thrombolysis. This finding may have pathophysiological and therapeutic implications for recanalization strategies in patients with AMI.

Reply to the Letter to the Editor from Oudejans et al

In Response:We appreciate the comments in the letter by Oudejans et al. about whether the presence of CTLs is a favorable or unfavorable factor for prognosis in diffuse large B-cell lymphoma (1, 2). Whereas the studies by their group (2, 3) and others (4) find that a high percentage of CTLs are associated with poor outcome, there are also other studies besides our own showing that high numbers of CD8+ T cells in diffuse large B-cell lymphoma may be associated instead with superior survival (5, 6). The tissue site distribution of diffuse large B-cell lymphoma in each study is likely one explanation of the different results. For example, 46% of cases in our study were extranodal, and there was a trend toward different patterns of T-cell distribution (and tumor prognosis) in those cases compared with the nodal tumors.However, we agree that the study methodologies can also affect the result, including particular immunostaining protocols, antibodies used, method of quantitation, and selection of analyzed areas. In our study, we counted the absolute granzyme B+ cells in areas of most dense intratumoral infiltration, expressed as cell number per high-power field. In contrast, Oudejans' group randomly selected tumor areas using an automatic scanning stage and expressed the granzyme B+ cells as the percentage of granzyme B+ cells divided by the total CD3+ cells. These different methods can yield different results even in the same study. For example, in the article by Riemersma et al. (3), the absolute number of granzyme B+ cells in diffuse large B-cell lymphoma of the central nervous system/brain was lower than that in skin and nodal tumors, but the percentage of CTLs (number of granzyme B+ cells / number of CD3+ cells) showed the reverse result.We would also emphasize that the interaction between the immune system and diffuse large B-cell lymphoma is complex, with differential T-cell and dendritic cell responses. In our study, we hypothesized that the cooperative action of infiltrating dendritic cells and CTLs in a subset of diffuse large B-cell lymphoma may contribute to a favorable prognosis by boosting dendritic cell–associated T-cell immunity. Whether this immunotherapy strategy can be used to boost responses in diffuse large B-cell lymphoma remains to be determined empirically. In view of the current progress, however, it may be clinically feasible in the near future (7).

Subcellular Localization of Activated Leukocyte Cell Adhesion Molecule Is a Molecular Predictor of Survival in Ovarian Carcinoma Patients

Currently available clinicopathologic prognostic factors are imperfect predictors of clinical course in advanced-stage epithelial ovarian cancer patients. New molecular predictors are needed to identify patients with higher risk of relapse or death from disease. In a retrospective study, we investigated the prognostic impact of activated leukocyte cell adhesion molecule (ALCAM) expression in epithelial ovarian cancer. We analyzed the effect of cell-anchorage loss on ALCAM cellular localization in vitro and assessed ALCAM expression by immunohistochemistry in a series of 109 well-characterized epithelial ovarian cancer patient samples. Chi-square test, Kaplan-Meier method, and Cox proportional hazard analyses were used to relate ALCAM cellular localization to clinical-pathologic parameters and to overall survival (OS) rate. Loss of epithelial ovarian cancer cell anchorage was associated both in vitro and in vivo with decreased ALCAM membrane expression. In vivo, ALCAM was localized to cell membrane in normal surface ovarian epithelium, whereas in 67% of the epithelial ovarian cancer samples, membrane localization was decreased or even lost, and the molecule was mainly expressed in cytoplasm. Median OS in this group of patients was 58 months, whereas a median OS was not yet reached in patients with ALCAM membrane localization (P = 0.036, hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.1 to 3.5). In a multivariate Cox regression model including all the available clinicopathologic variables, loss of ALCAM membrane expression was an independent factor of unfavorable prognosis (P = 0.042, HR = 2.15, 95% CI: 1.0 to 4.5). Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer patients and might help to identify patients who could benefit from more frequent follow-up or alternative therapeutic modalities.

Expression of RCAS1 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

This study used an immunohistochemical technique to examine the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs) increased significantly from NOM (12+/-5%) through mild OED (31+/-13%), moderate OED (44+/-17%), and severe OED (56+/-18%) to OSCC samples (68+/-20%, p<0.001). A significant correlation was found between the higher mean RCAS1 LI and OSCCs with larger tumor size (p=0.001), positive lymph node metastasis (p<0.001), or more advanced clinical stages (p<0.001). Positive lymph node metastasis (p=0.0073) and RCAS1 LI > or = 60% (p=0.048) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a RCAS1 LI > ot = 60% had a significantly poorer cumulative survival than those with a RCAS1 LI<60% (log-rank test, p=0.0113). We conclude that the expression of RCAS1 is an early event in oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

Subclinical Rejection in the Initial Postoperative Period in Small Intestinal Transplantation: A Negative Influence on Graft Survival

Subclinical rejection (SCR) is a known entity in various solid organ transplants but not in intestinal transplantation. The purpose of this study is to characterize the presence and effect of SCR in small intestinal transplantation (Itx). A total of 151 patients who underwent Itx and maintained a functioning graft for at least 3 months after Itx were investigated. The clinicopathological characteristics associated with a SCR episode within 3 months after Itx were analyzed. Cox regression with the landmark method (the landmark time being 3 months after Itx) was used for the analyses of overall graft survival and cause-specific hazard rate of SCR. A total of 2744 small intestinal transplant biopsies within 3 months after Itx were available for retrospective evaluation; 171 cases (6.2%) were determined as SCR and 78 patients (51.7%) experienced SCR episode within 3 months after Itx. Adult patients were associated with a significantly higher occurrence of a SCR episode (P=0.001). Overall graft survival at 5 years posttransplant for patients experiencing SCR within 3 months posttransplant and for patients without SCR was 37.2% and 60.2%, respectively (P=0.009). Cause-specific hazard rate analysis showed that a SCR episode was associated with a significantly higher hazard rate of death due to infection (P=0.005). A SCR episode in the initial postoperative period of Itx is a significant factor for unfavorable graft prognosis, likely representing alloimmune injury ultimately resulting in patient morbidity due to infection.

Analysis of Molecular Pathological Factors of Unfavorable Prognosis for Young Cervical Cancer Patients

The aim of this study was to explore the molecularpathological characteristics of cervical cancer inwomen aged below 35, disclose the factors that indicatethe unfavorable prognosis, and provide some useful targetsfor improving therapeutic outcome. Patients andMethods: 64 cases of pathological data originating fromcervical cancer patients aged below 35 served as the studygroup to perform a retrospective research, and pathologicaldata from 90 cases of cervical cancer patients beyondage 35, who underwent treatment during the same time,were selected at random as the reference group. Immunohistochemistryand quantified image analysis were utilizedto detect synchronously the protein expression differenceof survivin and p27 between the 2 groups. Results: Thetotal 5-year survival rate of the study group was 65.6%compared to 84.4% in the reference group, while thelymph node metastasis rate was 25% compared to 12.2%in the reference group. Both differences were statisticallysignificant (p < 0.05). Survivin expression is much greaterin the study group than in the reference group (p < 0.05);there is no statistical difference of the p27 expression betweenthe 2 groups (p > 0.05), but p27 expression is relatedto lymph node metastasis. Conclusion: Younger femalepatients have a worse prognosis than older ones, and survivinexpression is associated with poor prognosis. Targetingthese molecular factors may lead to a hopeful biomedicaltherapy to improve the prognosis of young femalecervical cancer patients.

Risk Factors for Recurrence and Unfavorable Prognosis in Patients with Stage I Non-small Cell Lung Cancer and a Tumor Diameter of 20 mm or Less

The purpose of this study was to identify risk factors for disease recurrence and unfavorable prognosis after surgical resection for stage I non-small cell lung cancer in patients with tumor diameters of < or =20 mm. One hundred sixty-three patients who had pathologic stage I non-small cell lung cancer with tumor diameters < or =20 mm and who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. The relationships between clinicopathologic factors and clinical outcomes, including recurrence and survival, were then examined. The clinicopathologic factors examined in this study were age, sex, smoking status, preoperative serum carcinoembryonic antigen level, pathologic tumor size, histologic subtype, histologic grade, and visceral pleural invasion. Among the clinicopathologic factors that were examined, the histologic grade of the carcinoma status was significantly related to a high risk of recurrence when analyzed using univariate (p = 0.01) and multivariate analyses (p = 0.049). Regarding survival, patients with poorly differentiated carcinomas showed a significantly unfavorable overall survival (p < 0.001), disease-specific survival (p = 0.003), and disease-free survival (p = 0.002) compared with patients with well-/moderately differentiated carcinomas according to univariate analyses. A Cox proportional hazards model indicated that a poorly differentiated carcinoma status was the only independent factor for an unfavorable overall survival (p = 0.02), disease-specific survival (p = 0.046), and disease-free survival (p = 0.04). Poor differentiation of tumor was the only risk factor for recurrence and an unfavorable prognosis for stage I non-small cell lung cancer patients with tumor diameters of < or =20 mm.

P3-233: Risk factors for recurrence and unfavorable prognosis in patients with stage IA non-small-cell lung cancer and a tumor diameter of 20mm or less

P3-233: Risk factors for recurrence and unfavorable prognosis in patients with stage IA non-small-cell lung cancer and a tumor diameter of 20mm or less

Expression of hypoxia‐inducible factor‐1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Background: Overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers.Methods: This study examined the expression of HIF‐1α in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry.Results: We found that the mean nuclear HIF‐1α labeling indices (LIs) increased significantly from NOM (9 ± 6%) through mild OED (25 ± 18%), moderate OED (41 ± 27%), and severe OED (42 ± 22%) to OSCC samples (55 ± 23%, P &lt; 0.001). A significant correlation was found between the higher mean nuclear HIF‐1α LI and OSCCs with larger tumor size (P &lt; 0.001), regional lymph node metastasis (P &lt; 0.001), or more advanced clinical stages (P &lt; 0.001). Only larger tumor size (P = 0.002) and nuclear HIF‐1α LI ≥ 60% (P = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan–Meier curve showed that OSCC patients with a nuclear HIF‐1α LI ≥ 60% had a significantly poorer cumulative survival than those with a nuclear HIF‐1α LI &lt; 60% (log‐rank test, P = 0.022).Conclusions: We conclude that the expression of HIF‐1α is an early event in oral carcinogenesis. The nuclear HIF‐1α LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

Concurrent chemoradiotherapy and adjuvant chemotherapy with Topotecan for patients with glioblastoma multiforme

The prognosis for patients with glioblastoma multiforme remains poor. Phase II studies, meta-analyses and a phase III study show that concurrent chemoradiotherapy has an advantage over irradiation alone. In this study the effectiveness of concurrent chemoradiotherapy with Topotecan and an adjuvant chemotherapy with Topotecan was investigated. Forty-two patients with predominantly unfavourable prognosis factors were included in the study and treated as follows: hyperfractionated accelerated radiotherapy (2x1.75Gy to 45.5 + 12.25 Gy (RP)) with a concurrent, continuous infusion of Topotecan (0.5 mg/m(2)/d, days 1-21). On day 28 the adjuvant chemotherapy (three courses) was begun according to the same scheme. Haematological toxicities were 13/42 (30%) grade III leucopenia, 2/42 (4%) grade IV, as well as 5/42 (10%) grade III thrombopenias and 1/42 (2%) grade IV. 30/42 (71%) patients showed improvement or stabilisation of an existing neurological symptomatic complex. The median time to progression was 7.2 (+/- 0.8) months, the median total survival was 10 (+/- 1.2) months, the 2 year survival rate 4.7 (+/- 0.3)%. Prognostic factors were age, surgical radicality, performance status and the tumour volume before therapy. Concurrent chemoradiotherapy and an adjuvant chemotherapy with Topotecan is feasible at acceptable toxicity levels also for patients with a moderate performance status. The patients benefit from the improvement of the clinical symptomatic complex and, even with unfavourable prognosis factors, have a higher median survival in comparison to data published on similar groups of patients given only radiotherapy.

Expression of E-Cadherin, β-Catenin, and CD-44v6 cell adhesion molecules in Primary Tumors and Metastases of Colorectal Adenocarcinoma

Immunohistochemical analysis of the expression of E-cadherin, beta-catenin, and CD-44v6 proteins was carried out for evaluating the metastatic potential of colorectal cancer cells. Specific features of expression, distribution, and interactions of adhesive molecules in primary tumors of the large intestine and their metastases in the liver and lymph nodes were studied. Reduction and complete absence of E-cadherin expression were much more often observed in patients with colorectal cancer with metastases in the liver than in patients without metastases. Cytoplasmic immunoreactivity and nuclear translocation of beta-catenin were increased in more than 80% cases with colorectal adenocarcinoma with metastases. These changes in the expression of E-cadherin and beta-catenin in tumor cells can be regarded as factors of unfavorable prognosis of colorectal cancer. No significant relationship between expression of CD-44v6 protein and metastatic potential of cancer cells was detected.

0543 Afro-descendants as a predictive factor for unfavorable clinical prognosis in patients with multiple sclerosis

0543 Afro-descendants as a predictive factor for unfavorable clinical prognosis in patients with multiple sclerosis

Androgen receptor (AR) expression is an independent unfavorable prognostic factor in gastric cancer.

To investigate the expression of sex steroid receptors in gastric cancer and to correlate their tumor expression profile with the clinicopathological parameters and overall survival of the patients. Immunohistochemical methodology was employed in formalin-fixed paraffin-embedded sections from 86 patients with gastric carcinoma. Monoclonal antibodies against androgen (AR), estrogen (ER), and progesterone (PR) receptors were used. Survival rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazards model. Fifteen (17.4%) cases of gastric adenocarcinomas were positive for AR, two (2.3%) were positive for PR and three (3.5%) were positive for ER. Significantly higher AR expression was found in tumors with metastases to lymph nodes (P = 0.03). Patients with AR-positive tumors (AR+) had worse prognosis than (AR-) patients (median survival 9 months vs 24 months, P = 0.03). Patients with AR- and heat shock protein 27 (HSP27)-positive tumors (AR+/HSP27+) had a median survival of 6 months, whereas (AR-/HSP27-) patients had a median survival of 42 months (P = 0.017). Multivariate analysis revealed that AR expression and UICC stage were independent factors of unfavorable prognosis (P = 0.037 and P = 0.0055, respectively). Identification of AR-positive gastric carcinomas in gastric biopsies may warrant a more aggressive therapeutic approach and anti-androgen or AR-targeted agents may represent a novel strategy in tackling this devastating malignancy.

Suppressing HER2/neu-Mediated Cell Transformation by Transcriptional Repressors

Breast and ovarian cancer are two of the leading causes of death for women in the United States. HER2/neu overexpression is an unfavorable prognosis factor associated with low patient survival rate of multiple cancer types including breast and ovarian cancer. Downregulation of the HER2/neu gene expression in cancer cells has been shown to be a useful strategy to significantly reverse the malignant characteristics induced by HER2/neu overexpression. It is possible that HER2/neu overexpression can be repressed through inhibiting the promoter activity of the gene. We have identified a number of potent transcriptional regulators, including the adenovirus type 5 E1A, the SV40 large T antigen, and the ets family member PEA3, and have tested their activity to repress HER2/neu overexpression. Ectopic expression of these transcriptional regulators resulted in downregulation of the HER2/neu promoter activity and reversed the transformed phenotype of the cancer cells in vitro. These observations were followed by a series of studies to investigate whether these HER2/neu repressors could act therapeutically as tumor suppressor genes for cancers overexpressing HER2/neu. The results of these preclinical studies clearly indicated that transcriptional repressors, which downregulate HER2/neu overexpression, can be an effective regimen for cancer treatment in a gene therapy format combined with an appropriate gene delivery system such as the cationic liposome DC-Chol or replication-deficient adenovirus vector. Our results have demonstrated that these delivery systems can effectively transfer the therapeutic genes into the cancer cells in vivo and lead to significant suppressive effects on tumor growth. Furthermore, tumor-free survival rate of treated animals is increased dramatically using nontoxic doses, compared with animals without the treatment. A great body of evidence has revealed the potential of using transcriptional repressors to suppress HER2/neu overexpression and abolish tumor growth. Thus, suppression of oncogenic gene expression using transcription factors can be a novel field for cancer treatment and prevention.

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients.

Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis. © 1999 Cancer Research Campaign

Vitamin D Analogs, Leukemia and WAF1

Vitamin D compounds induce differentiation of human leukemic cells and have potential for the treatment of leukemia. In this review we summarize some of the basic mechanisms underlying the action of vitamin D compounds. A variety of vitamin D analogues were synthesized until now, some of which have enhanced antileukemic activity and a decreased propensity to cause hypercalcemia. Most actions of vitamin D compounds are mediated by nuclear receptors. In vivo, vitamin D binding protein interacts with free vitamin D compounds. Both in normal and leukemic cells, vitamin D compounds cause a differentiation to monocytes and macrophages. A variety of genes are regulated by vitamin D compounds. Recently, the cell cycle inhibitory gene p21/WAF-1/CIP-1 was characterized. The expression de novo of WAF-1 in blasts of acute myelogenous leukemia is an independent factor of unfavorable prognosis. In HL-60 leukemic cells treated with vitamin D analogs, WAF-1 can be induced by nano- or picomolar concentrations of vitamin D analogs and correlates with the induction of a differentiated phenotype. When vitamin D analogs are combined in-vitro with retinoids, an irreversible differentiation is observed. Clinical trials of vitamin D analogs are indicated in the situation of minimal residual disease and in combination with standard chemotherapy.

Primary therapy of metastatic prostate carcinoma with depot gonadotropin-releasing hormone analogue goserelin versus estramustine phosphate

Objective. To determine if initial chemo-hormone therapy (estramustine phosphate) of metastatic prostate carcinomas can lengthen the period until progression, compared with hormone treatment (goserelin) alone? The time to progression, side effects and prognostic factors were assessed. Methods. The prospective phase III study (11 86 until V 91) involved 243 patients randomized consecutively in two groups. Progress was assessed according to NPCP criteria. Results. The following prognostic factors were established to be significant: metastatic status, metastatic bone pain, alkaline phosphatase and performance status. No difference was observed between the two methods of treatment in time to progression. However on stratifying according to groups with the same prognostic factors, progression in the high risk group occurred at a later stage during treatment with estramustine than during pure hormone treatment. The quality of life was clearly more heavily restricted by side effects from estramustine. Conclusions. Thus, when comparing these treatments, there were no statistically significant differences. Patients in the high risk groups with unfavorable prognosis factors benefitted from the chemo-hormone treatment with estramustine phosphate.

Novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) before radical radiotherapy in localized stages (I-IIIA) of Hodgkin's disease

A novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) was scheduled to reduce the toxicity of chemotherapy and to improve its application in treatment of Hodgkin's disease. This combination followed a previous regimen given every 15 days (EBVP I) by the same cooperative group. EPVP II is given every 21 days with increased dosage and increased intensity of epirubicin. This regimen was given to 100 consecutive patients with favourable or unfavourable limited-stage disease (clinical stages I-IIIA) excluding very favourable stages I and II and stages IIIB and IV. Such patients first received three injections of EBVP II and were then radically irradiated; those with unfavourable prognosis factors received three subsequent injections of EBVP II. The present analysis reports the early results of such treatment and considers particularly toxicity and the obtention of complete remission, which is preeminent for a cure. EBVP II was given in full dosage in 99% of the primary set of three injections. The main toxicity was alopecia and to a lesser degree nausea and vomiting and veinitis. Complete remission was obtained in 76 patients before radiotherapy and in 20 others after radiotherapy. With a median follow-up of 30 months 1 patient died from Hodgkin's disease, 9 are alive after relapse and 90 with no evidence of disease. This treatment appears to be as efficient as previous chemotherapy, well tolerated and particularly easy to give. It deserves further comparison with other proved regimens taking into consideration the survival and quality of life of patients.