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Adverse Prognostic Factor (adverse + prognostic_factor)
Kinds of Adverse Prognostic Factor Selected AbstractsSafety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007Paul G. Richardson Summary Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age ,65 years) and high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34,40% vs. 13,19%), including complete response rate (5,8% vs. 0,1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged ,65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma. [source] Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myelomaCANCER, Issue 15 2010Long-term follow-up Abstract BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n = 27) or unrelated donor (n = 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010. © 2010 American Cancer Society. [source] Aberrant methylation of GTPase regulator associated with the focal adhesion kinase (GRAF) promoter is an adverse prognostic factor in myelodysplastic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2010Jun Qian No abstract is available for this article. [source] Malignant fibrous histiocytoma of the sinonasal tractHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2009Cheng-Ping Wang MD Abstract Background Sinonasal malignant fibrous histiocytoma (MFH) is rare. Methods Twenty-five patients were registered with a diagnosis of sinonasal MFH at our hospital in the past 30 years. Clinical data were retrospectively reviewed. Results Eight tumors were primary MFH and 17 tumors were post-irradiated MFH, located within the radiation field for previous nasopharyngeal carcinoma. Twenty-one tumors originated from the maxillary sinus, 3 from the nasopharynx, and 1 from the nasal cavity. Twenty-three patients underwent surgery but only 12 tumors were removed completely. The 5-year overall and disease-free survival rates were 25.1% and 21.5%, respectively. Multivariate analyses showed that previous radiation was the only adverse prognostic factor for disease-free survival (p = .045). The 5-year disease-free survival rates of primary MFH and post-irradiated MFH were 72.9% and 0%. Conclusion In this series, post-irradiated MFH was more common than primary MFH. The prognosis of post-irradiated MFH is poor, whereas primary MFH is fair. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Expression, regulation, and function of ,V integrins in hepatocellular carcinoma: An in vivo and in vitro studyHEPATOLOGY, Issue 2 2002Mimoun Nejjari The expression of ,V integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of ,V integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of ,V integrins in hepatocellular carcinoma. We first analyzed the expression of ,V integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. ,V integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 ,V-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study ,V integrin regulation and function. HepG2 and Hep3B cells expressed ,V integrin chain and used ,V,1 and ,V,5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) , and transforming growth factor (TGF) , significantly increased the expression levels of ,V integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an ,V integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor. [source] An abnormal nonhyperdiploid karyotype is a significant adverse prognostic factor for multiple myeloma in the bortezomib era,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Daryl Tan Multiple myeloma is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several high-risk features of myeloma, the validity of conventional risk-stratification and prognostication systems needs to be reevaluated. We study the survival data of 261 previously untreated myeloma patients managed at our institution, where bortezomib became available from 2004 for the treatment of relapse disease. Patient and disease characteristics, and survival data were evaluated overall, and with respect to bortezomib exposure. Overall, the international staging system (ISS), metaphase karyotyping and interphase fluorescence in situ hybridization (FISH) were discerning of survival outcomes, where the median for the entire cohort was 5.2 years. However, when stratified by bortezomib exposure, only metaphase karyotyping was still discriminating of long-term prognosis. The presence of an abnormal nonhyperdiploid karyotype overrides all other clinical and laboratory parameters in predicting for a worse outcome on multivariate analysis (median survival 2.6 years, P = 0.001), suggesting that bortezomib used at relapse is better able to overcome adverse risk related to high tumor burden (as measured by the ISS) than adverse cytogenetics on conventional karyotyping. Metaphase karyotyping provides additional prognostic information on tumor kinetics where the presence of a normal diploid karyotype in the absence of any high-risk FISH markers correlated with superior survival and could act as a surrogate for lower plasma cell proliferation. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Outcome of 122 pregnancies in essential thrombocythemia patients: A report from the Italian registryAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Lorella Melillo Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P < 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%, P = 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%, P = 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013,0.846, P = 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%, P = 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17,32.61; P = 0.038). No outcome concordance between first and second pregnancies was found (P = 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Impact of bowel obstruction at the time of initial presentation in women with ovarian cancerBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2010JA Rauh-Hain Objective, To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women. Design, Retrospective cohort study. Setting, Dedicated gynaecological oncology service of a large tertiary institution. Population, Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction). Methods, Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. Main outcome measures, Progression-free survival (PFS) and overall survival (OS). Results, Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction. Conclusions, Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer. [source] Relapse prediction in acute myeloid leukaemia patients in complete remission using WT1 as a molecular marker: development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervalsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Hans Beier Ommen Summary We hypothesized that Wilms tumour 1 gene (WT1) expression levels in acute myeloid leukaemia (AML) patients might have predictive value and reveal molecular relapse kinetics. WT1 level was determined at diagnosis, during therapy and post-therapy follow-up in 89 patients who reached first complete remission (CR1) (952 samples, median 8 samples/patient, range 2,38). CR1 bone marrow (BM) WT1 level above normal (based on 39 healthy donors) was an independent adverse prognostic factor regarding both disease-free survival [hazard ratio (HR) 4·46, P = 0·001] and overall survival (HR 2·62, P = 0·019). By grouping 34 BM and 99 peripheral blood (PB) complete remission samples in monthly intervals prior to clinical relapse, disease development was delineated and a simple mathematical model constructed, that allowed for the prediction of relapse detection rates (RDRs) as well as median times [tms] from WT1 positivity to clinical relapse. BM sampling was required to obtain RDRs above 93% and tms above 67 d. Acceptable RDRs and tms (81% and 44 d, respectively) could be acquired by bimonthly PB sampling. In conclusion, CR1 WT1 expression is an independent prognostic factor in AML. According to our model, BM is superior for relapse prediction, but PB samples are useful when shorter sampling intervals are possible. [source] Time to disease recurrence in basal-type breast cancers,CANCER, Issue 21 2009Effects of tumor size, lymph node status Abstract BACKGROUND: Basal-like breast cancers are a subgroup of breast cancers defined by the absence of staining for estrogen-receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) and by positive staining for the cytokeratins (CKs) expressed in the myoepithelial cells of the ducts and lobules (CK5/CK6, CK14) and for epidermal growth factor receptor (EGFR). This class of tumors has an unusually aggressive course, and it is not clear whether conventional prognostic factors for breast cancers also predict outcome for patients who have the basal phenotype. METHODS: A panel of 962 breast cancers was stained for 5 markers (ER, PR, HER-2/neu, CK5/CK6, and EGFR). The patients were followed for clinical outcomes for up to 15 years from diagnosis, and the rates of distant disease recurrence and death were compared by tumor size (,2 cm or >2 cm) and by lymph node status within the subgroups of women with basal and nonbasal cancers. RESULTS: Of the 962 women with breast cancer, 116 cancers were basal (12%), 845 were nonbasal (88%), and 1 could not be classified as either basal or nonbasal and was excluded. In total, 426 tumors measured ,2 cm (45%), and 530 tumors measured >2 cm (55%). Among women with nonbasal cancers, large tumor size was an adverse prognostic factor. Among women with basal cancers, a transient adverse effect of size on disease recurrence was observed; however, after 10 years, mortality rates were equal for women with small tumors and women with large tumors. CONCLUSIONS: Among women with basal breast cancers, the long-term prognosis was similar for women with large tumors and women with small tumors. However, women with large basal tumors appeared to develop recurrent disease sooner. Cancer 2009. © 2009 American Cancer Society. [source] Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromesCANCER, Issue 5 2008Elias Jabbour MD Abstract BACKGROUND Approximately 15,000 new cases of myelodysplastic syndromes (MDS) are expected in the United States each year. METHODS The mainstay for the management of myelodysplastic syndromes (MDS) is supportive therapy with red blood cell (RBC) transfusions to improve the patient's quality of life. RBC transfusions enable adequate tissue oxygenation and increase hemoglobin levels, improve fatigue, and improve the physical and intellectual activity of patients. Up to 90% of patients with MDS will receive RBC transfusions during the course of their disease, and many will become chronically dependent on transfusions to manage their anemia. These transfusions lead to an accumulation of excess iron that, in turn, can develop into a condition known as iron overload, causing clinical consequences like hypertransaminasemia and cirrhosis, dilated cardiomyopathy, and progressive dysfunction of the endocrine glands. RESULTS Studies in patients with MDS have indicated that iron overload because of RBC transfusions was an independent, adverse prognostic factor for overall survival (OS) and leukemia-free survival (LFS): OS and LFS were significantly shorter in transfusion-dependent patients with MDS than in those who were not transfusion dependent. CONCLUSIONS Although the National Comprehensive Cancer Network guidelines for the treatment of patients with MDS recommend the use of RBC transfusions as supportive care, they further recommend that the iron burden of transfused patients be monitored regularly and that iron chelation therapy be considered to maintain serum ferritin levels of <1000 ng/mL. Cancer 2008. © 2008 American Cancer Society. [source] Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcomaCANCER, Issue 10 2006Tsukasa Sotobori M.D. Abstract BACKGROUND There have been several recent reports that Wilms tumor gene (WT1) mRNA is overexpressed in many types of neoplasms, and those results suggested that WT1 has oncogenic properties. The objective of the current study was to evaluate the prognostic significance of WT1 mRNA expression in patients with soft tissue sarcoma. METHODS Levels of WT1 mRNA expression were examined by quantitative, real-time reverse transcriptase-polymerase chain reaction analysis in frozen tissue samples from 52 patients with soft tissue sarcoma. Various clinicopathologic factors were analyzed along with the disease-specific survival rate for correlations with WT1 mRNA expression levels. RESULTS The levels of WT1 mRNA expression in a variety of soft tissue sarcomas were significantly greater compared with the levels in normal soft tissue samples (P = .0212). No significant correlation was observed between the level of WT1 mRNA expression and clinicopathologic factors, including gender, age, primary tumor site, tumor depth, tumor size, histologic grade, and distant metastasis at initial presentation. The disease-specific survival rate for patients with high WT1 mRNA expression levels was found significantly poorer compared with the rate for patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate analysis indicated that a high WT1 mRNA expression level was an independent, adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P = .0488). CONCLUSIONS WT1 mRNA expression level can serve as a potent prognostic indicator in soft tissue sarcoma patients. Cancer 2006. © 2006 American Cancer Society. [source] Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of boneCANCER, Issue 5 2002Richard B. Wilder M.D. Abstract BACKGROUND Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29,77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30,70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS Median follow-up was 7.8 years (range, 1.0,25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level. Cancer 2002;94:1532,7. © 2002 American Cancer Society. DOI 10.1002/cncr.10366 [source] Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients,CYTOMETRY, Issue 3 2010Sergio Matarraz Abstract A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34+ cells and/or other major subsets of CD34, cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping. Methods: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease. Results: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low- versus high-grade cases. The most informative prognostic factors included the number of CD34+ cells, presence of aberrant CD34,/CD117+ precursors, decreased mature neutrophils and CD34, erythroid precursors, and increased numbers of CD36,/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival. Conclusions: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival. © 2010 Clinical Cytometry Society [source] Effectiveness of selective neck dissection in the treatment of the clinically positive neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2008FRCS ORL-HNS, Rajan S. Patel MBChB Abstract Background. The aim of this work was to determine whether or not patients treated with therapeutic selective neck dissection for head and neck squamous cell carcinoma were oncologically disadvantaged compared with those having comprehensive procedures. Methods. The study involves a retrospective review of 232 therapeutic neck dissections with a minimum of 2 years follow-up. Results. Patients having selective neck dissection had fewer adverse prognostic factors compared with patients having comprehensive dissection (pN2/3, p = .001; and extracapsular spread, p = .001). There were trends toward improved control in the dissected neck (96% vs 86%, p = .06), and disease-specific survival (59% vs 43%, p = .06) following selective neck dissection. Disease-specific survival for all patients was adversely affected by pN classification (p <.001) and extracapsular spread (p <.001). Conclusions. Patients undergoing aggressive neck surgery had more extensive disease. Selective neck dissection can be used to effectively treat clinically positive nodal disease in selected patients. © 2008 Wiley Periodicals, Inc. Head Neck 2008 [source] Outcome of treatment for advanced cervical metastatic squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2005Jonathan Clark FRACS Abstract Background. Patients with advanced cervical metastases from mucosal squamous cell carcinoma have a poor prognosis because of their high risk of regional and distal failure. This study aims to evaluate the outcomes of patients with clinical N2 or N3 disease managed with surgery and postoperative radiotherapy. Methods. From a comprehensive computerized database, 181 entered patients who had neck dissection for N2 or N3 disease between 1988 and 1999 were evaluated. The mean age was 62 years, and minimum follow-up was 3 years. Results. A total of 233 neck dissections were performed in 181 patients, including 163 comprehensive and 70 selective dissections. Postoperative radiotherapy was given in 82% of cases. The local control rate was 75% at 5 years, and control of disease in the treated neck was achieved in 86%. Macroscopic extracapsular spread (ECS) significantly increased regional recurrence (p = .001). Adjuvant radiotherapy significantly improved neck control (p = .004) but did not alter survival. Patients with ECS (both microscopic and macroscopic) who received radiotherapy had a significantly better survival than did patients with ECS who did not receive radiotherapy. Disease-specific survival for the entire group was 39% at 5 years. By use of multivariate analysis, macroscopic ECS and N2c neck disease were independent adverse prognostic factors for survival (p = .001). Conclusions. Despite a high rate of control in the treated neck, the poor survival (39%) in this patient group indicates that adjuvant therapeutic strategies need to be considered. © 2004 Wiley Periodicals, Inc. Head Neck27: 87,94, 2005 [source] Tenascin-C in primary malignant melanoma of the skinHISTOPATHOLOGY, Issue 4 2004S Ilmonen Aims :,To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. Methods and results :,The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04,7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. Conclusions :,In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases. [source] Practical questions in liver metastases of colorectal cancer: general principles of treatmentHPB, Issue 4 2007Héctor Daniel González Abstract Liver metastases of colorectal cancer are currently treated by multidisciplinary teams using strategies that combine chemotherapy, surgery and ablative techniques. Many patients classically considered non-resectable can now be rescued by neoadjuvant chemotherapy followed by liver resection, with similar results to those obtained in initial resections. While many of those patients will recur, repeat resection is a feasible and safe approach if the recurrence is confined to the liver. Several factors that until recently were considered contraindications are now recognized only as adverse prognostic factors and no longer as contraindications for surgery. The current evaluation process to select patients for surgery is no longer focused on what is to be removed but rather on what will remain. The single most important objective is to achieve a complete (R0) resection within the limits of safety in terms of quantity and quality of the remaining liver. An increasing number of patients with synchronous liver metastases are treated by simultaneous resection of the primary and the liver metastatic tumours. Multilobar disease can also be approached by staged procedures that combine neoadjuvant chemotherapy, limited resections in one lobe, embolization or ligation of the contralateral portal vein and a major resection in a second procedure. Extrahepatic disease is no longer a contraindication for surgery provided that an R0 resection can be achieved. A reverse surgical staged approach (liver metastases first, primary second) is another strategy that has appeared recently. Provided that a careful selection is made, elderly patients can also benefit from surgical treatment of liver metastases. [source] Multidrug resistance in haematological malignanciesJOURNAL OF INTERNAL MEDICINE, Issue 5 2000P. Sonneveld Abstract. Sonneveld P (University Hospital Rotterdam , Dijkzigt, The Netherlands). Multidrug resistance in haematological malignancies (Internal Medicine in the 21st Century). J Intern Med 2000; 247: 521,534. The development of refractory disease in acute myeloid or lymphoblastic leukaemias (AML, ALL) and multiple myeloma (MM) is frequently associated with the expression of one or several multidrug resistance (MDR) genes. MDR1, MRP1 and LRP have been identified as important adverse prognostic factors in AML, T-ALL and MM. Recently, it has become possible to reverse clinical multidrug resistance by blocking P-glycoprotein-mediated drug efflux. The potential relevance of these reversal agents of MDR and potential new approaches to treat refractory disease are discussed. [source] Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myelomaCANCER, Issue 15 2010Long-term follow-up Abstract BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n = 27) or unrelated donor (n = 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010. © 2010 American Cancer Society. [source] Metastatic melanoma to lymph nodes in patients with unknown primary sitesCANCER, Issue 9 2006Janice N. Cormier M.D., M.P.H. Abstract BACKGROUND The natural history of metastatic melanoma in lymph nodes in the absence of a known primary site (MUP) has been defined poorly; thus, treatment guidelines for patients with MUP are not clear-cut. METHODS The authors conducted a retrospective analysis of consecutive patients with melanoma (from 1990 to 2001) who underwent surgical resection for melanoma metastatic to regional lymph nodes. Among those patients, 71 patients with MUP and 466 control patients who had regional lymph node metastases of similar stage with a known primary site were identified. Associations between clinicopathologic factors and survival were estimated by using the Cox proportional hazards model. RESULTS After they underwent lymph node dissection, patients with MUP were classified with N1b disease (47%), N2b disease (14%), or N3 disease (39%). With a median follow-up of 7.7 years, the 5-year and 10-year overall survival rates were 55% and 44%, respectively, for patients with MUP, compared with 42% and 32%, respectively, for the control group (P = .04). In multivariate analyses, age 50 years or older, male gender, and N2b or N3 disease status were identified as adverse prognostic factors, and MUP was identified as a favorable prognostic factor (hazard ratio, 0.61; 95% confidence interval, 0.42,0.86; P = .006) for overall survival. CONCLUSIONS The relatively favorable long-term survival of patients with MUP in the current study suggested that patients with MUP have a natural history that is similar to (if not better than) the survival of many patients with Stage III disease. Therefore, patients with MUP should be treated with an aggressive surgical approach with curative intent and should be considered for Stage III adjuvant therapy protocols. Cancer 2006. © 2006 American Cancer Society. [source] Disease biology rather than age is the most important determinant of survival of patients , 60 years with acute myeloid leukemia treated with uniform intensive therapyCANCER, Issue 10 2005Vikas Gupta M.D. Abstract BACKGROUND The objectives of the current study were to evaluate the outcome of patients , 60 years with acute myeloid leukemia (AML) treated uniformly with high-dose daunorubicin containing induction and modified high-dose cytosine arabinoside containing postremission therapy, and to identify factors predictive of complete disease remission (CR) and survival. METHODS Between 1998 and 2002, the authors treated 117 newly diagnosed patients (acute promyelocytic leukemia excluded) with AML , 60 years (median, 67 years; range, 60,82 years). Karyotype (Medical Research Council classification) at diagnosis was categorized as good risk (n = 3), intermediate risk (n = 69), adverse risk (n = 26), and suboptimal/not done (n = 19). A normal karyotype was seen in 41 patients and 40 (34%) had secondary AML. RESULTS The outcome of induction included the following: CR, 62 (53%); early death, 5 (4%); death during hypoplasia, 14 (12%); and resistant disease, 36 (31%). The 3-year event-free (EFS) and overall survival (OS) rates were 9% (95% confidence interval [95% CI], 3,16%) and 17% (95% CI, 9,29%), respectively. In a univariate analysis, cytogenetics, lactate dehydrogenase level, leukocyte count, and performance status were the significant factors for EFS and OS. Age was not a significant prognostic factor for either CR or survival. In a multivariate model, adverse-risk cytogenetics, previous history of myelodysplastic syndrome or antecedent hematologic disorder, and high leukocyte count (> 30 × 109/L) were independent adverse prognostic factors for survival. The impact of adverse karyotype on EFS and OS was time dependent and was observed after 50 and 150 days, respectively. CONCLUSIONS The authors concluded that candidacy for intensive therapy in older patients should be based on biologic features of disease and fitness, rather than on age. Cancer 2005. © 2005 American Cancer Society. [source] Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck,CANCER, Issue 10 2004An analysis of two Eastern Cooperative Oncology Group randomized trials Abstract BACKGROUND The current study was conducted to identify prognostic factors and report the characteristics of long-term survivors in patients with recurrent or metastatic carcinoma of the head and neck who were treated with cisplatin-based combination chemotherapy in two randomized, Phase III trials conducted by the Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395). METHODS The authors analyzed prognostic factors for response and survival by combining data from the E1393 trial, which compared cisplatin plus paclitaxel at two dose levels, with data from the E1395 trial, which compared cisplatin plus paclitaxel with cisplatin plus 5-fluorouracil (5-FU), using logistic regression and Cox regression models. RESULTS A total of 399 eligible patients were included. The median follow-up was 4.7 years. The 1-year overall survival (OS) rate for all patients was 32%, the median OS was 7.8 months, and the objective response rate was 32%. On multivariate analysis, the following were found to be independent unfavorable predictors of objective response: weight loss of > 5%, an ECOG performance status of 1 (vs. 0), residual disease at the primary tumor site, a primary tumor site other than the oropharynx, prior radiation therapy (RT) (P = 0.056), and well/moderate tumor cell differentiation (P = 0.067). Independent unfavorable prognostic factors for OS were weight loss, an ECOG performance status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in the oral cavity or hypopharynx, and prior RT. The following were found to be independent unfavorable prognostic facotrs for time to disease progression: well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary tumor, and prior RT. Patients with , 2 adverse prognostic factors were reported to have a median OS of 1 year, whereas patients with 3,5 adverse prognostic factors were found to have a median OS of 0.5 years (P < 0.0001). Forty-nine patients (12%) survived for , 2 years and 6 patients were alive at 5 years. Two-year survivors were more likely to have achieved an objective response to chemotherapy, have poor tumor cell differentiation, be white, have an ECOG performance status of 0, and have received no prior RT. CONCLUSIONS Clinical parameters and tumor cell differentiation appear to be strong pretreatment predictors of outcome in patients with carcinoma of the head and neck and should be considered in the design of future randomized trials. A small percentage of patients with recurrent head and neck carcinoma can achieve long-term survival. Cancer 2004. © 2004 American Cancer Society. [source] | ||||||||||||||||||||||