Ambulatory Performance Status Research Articles

Clinical Impact of the Presence of a Diffuse Large B-Cell Lymphoma (DLBCL) Component in the Outcome of Untreated Patients with Follicular Lymphoma (FL)

Introduction: Histological transformation into an aggressive lymphoma, usually DLBCL, may occur during the follow-up of FL patients and determines a poor outcome. The presence of a DLBCL component in a FL (FL/DLBCL) is observed in some cases at diagnosis, usually being considered a transformation of a FL with a previously undetected indolent course. The clinical implications of this situation in terms of prognosis and treatment remain unclear. The aim of the present study was to analyze the clinicobiological characteristics and outcome of patients diagnosed with FL/DLBCL in the rituximab era, in comparison with patients diagnosed with pure FL or de novo DLBCL at the same period in a single institution.Patients and Methods: Eight hundred seventy eight patients sequentially diagnosed with either FL, DLBCL or FL/DLBCL between 2002 and 2015 ina single institution were included in the study. The histological distribution was as follows: FL grade 1, 2, 3a, 320 cases (140M/180F; median age, 58 years), FL 3b, 8 cases (4M/4F; median age, 66 years), DLBCL, 510 cases (275M/235F; median age, 65 years) and FL/DLBCL, 40 (16M/24F; median age, 65 years).According to institutional guidelines, the latter were treated as aggressive lymphomas, with no maintenance or further intensification. All FL/DLBCL biopsies were reviewed and the DLBCL component semiquantified. Cell of origin (COO) assessment by gene expression-based assay was determined in 127 cases and NOTCH1-2 mutational status in 216.Results: Main clinicobiological characteristics of the patients according to the histology are listed in the table. Compared to DLBCL cases, FL/DLBCL patients showed more frequently ambulatory performance status, primary nodal origin and advanced stage, with these features being closer to those of FL patients. On the contrary, FL/DLBCL patients had an intermediate position between FL and DLBCL cases regarding B-symptoms, bone marrow infiltration, hemoglobin and serum LDH levels. The proportion of DLBCL component in FL/DLBCL cases ranged from 5 to 95%, with no significant differences in the initial characteristics according to the proportion of DLBCL component. COO was determined in 11 FL/DLBCL, with 8 (73%) being GCB, 2 (18%) ABC, and 1 unclassified. Such distribution in 116 DLBCL with COO available was: 50 (43%) GCB, 50 (43%) ABC and 16 unclassified. NOTCH 1-2 was mutated in 4/39 (10%) FL/DLBCL, whereas this proportion was 1/41 (2%) FL and 11/136 (8%) DLBCL. All FL/DLBCL patients were treated as aggressive lymphoma with no intensification after front-line therapy. The proportion of primary refractoriness in FL/DLBCL patients was significantly higher than in FL and similar to that of DLBCL. Progression free survival (PFS) and overall survival (OS) are showed in the table and figure. Among the 40 FL/DLBCL cases, the amount of DLBCL component did not show prognostic impact, whereas the histological grade did (5-year OS FL grades 1-2-3a/DLBCL, 92% vs. FL grade 3b/DLBCL, 38%; p=0.001). In the different cohorts analyzed (FL+FL/DLBCL, FL+FL/DLBCL+DLBCL, and FL/DLBCL+DLBCL), FL/DLBCL histology did not show independent value for OS in multivariate analyses that included standard prognostic variables, namely, serum β2m and FLIPI or IPI scores. Sequential biopsies were available in 120 cases, with the following distribution according to the primary diagnosis: FL, 60 cases (at relapse: 37 FL and 23 DLBCL), FL/DLBCL, 6 cases (at relapse: 3 FL, 2 FL/DLBCL and 1 DLBCL), and DLBCL, 54 cases (at relapse: 4 FL and 50 DLBCL).Conclusion: Patients with FL/DLBCL, although infrequent, exists and have clinicobiological differentiated features compared to pure FL and DLBCL. When treated with standard immunochemotherapy their outcome is not worse than that of de novo DLBCL. Some clinicobiological characteristics suggest FL/DLBCL to be a specific category rather than a transformation from a FL; however, this warrants further biological studies. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Postoperative Ambulatory Performance Status Significantly Affects Implant Failure Rate Among Surgical Treatment Strategies in Patients With Proximal Femur Metastasis.

Surgical treatment strategies for proximal femur metastasis have been reported with mixed results. Little is known about risk factor for implant failure except for longer patient survival. Therefore, we determined whether implant survivorship differed among treatment strategies, as well as risk factors for implant failure. We retrospectively reviewed a consecutive 106 patients with proximal femur metastasis treated with prosthesis replacement (n=38), intramedullary nail (n=32), and dynamic hip screw (DHS) (n=36). Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky index were used to evaluate functional outcome. Patient characteristics and postoperative ambulatory performance status were assessed for their values in determining implant failure. Overall implant failure rate was 11.3% (12 of 106). Prosthesis replacement was related to better implant survivorship (P=0.041), without mechanical failures. On the contrary, 7 of the 10 implant failures in the fixation group were considered mechanical failures. Better postoperative ambulatory status (ECOG≤2) was a risk factor for implant failure (P=0.03). Notably, for patients with poor ambulatory status (ECOG≥3), implant survivorship was not different among choice of implants. In conclusion, prosthesis replacement would be a more durable option in the treatment of proximal femur metastasis. Postoperative ambulatory status could be an additional consideration. For patients with poor expected ambulatory performance status, fixation with intramedullary nail or DHS might be considered for a less technical demanding procedure.

Prognostic Significance of Ki-67 Expression in Extranodal NK/T Cell Lymphoma, Nasal Type: A Proposed Prognostic Index, KLABS Index.

Ki-67 is a nuclear antigen expressed by dividing cells, therefore, the percentage of Ki-67-positive cells reflects the proportion of tumor cells actively proliferating. However, the prognostic value of Ki-67 expression is still controversial in non-Hodgkin's lymphoma. Although a recent study in peripheral T-cell lymphoma showed a positive correlation with poor prognosis, the prognostic value of Ki-67 has never been studied in patients with extranodal NK/T cell lymphoma. Therefore, we performed this study to determine the value of Ki-67 expression in predicting prognosis and to propose a new prognostic model involving Ki-67 expression in patients with extranodal NK/T cell lymphoma. We studied 65 patients who were diagnosed with extranodal NK/T cell lymphoma from 1999 to 2005. All patients were treated with combination chemotherapy alone or followed by radiotherapy. We analyzed the percentage of Ki-67 expressing cells and determined its prognostic significance in terms of overall survival (OS) and disease-free survival (DFS). The immunohistochemical staining of Ki-67 was available for this study in fifty-five patients. The median age was 41 (range: 19 – 74 years), 89.1 percent of the patients (49/55) had an ambulatory performance status: Eastern Cooperative Oncology Group (ECOG) 0–1. Fifty-one patients presented as a localized disease: Ann Arbor stage I or II, and elevated level of serum lactate dehydrogenase (LDH) was observed in 14 patients. Thus, most patients showed the low or low-intermediate international prognostic index (IPI): low risk (74.5%, 41/55) or low intermediate risk (18.2%, 10/55). The percentage of Ki-67 expressing tumor cells was ranged from 5% to 95%, and the patients were separated into two groups: low Ki-67 (< 50%) versus high (≥ 50%). The patients in the high Ki-67 group had a shorter OS (95% CI 1.0-6.3, P = 0.046) and DFS (95% CI 1.1-5.5, P = 0.024) while the IPI failed to predict worse OS. Ki-67 expression could also predict the group with worse prognosis in 51 patients of low and low-intermediate IPI risk. Age, serum LDH, B symptoms, and tumor size were also associated with worse OS or DFS. Thus, based on the univariate and mutivariate analysis, we proposed a new prognostic index (KLABS index) with high Ki-67 expression, increased serum LDH, Age (≥ 60 years), presence of B symptoms, and bulky Size of tumors (≥ 10cm2) as follows: low risk, none or one of the above-mentioned factors; intermediate risk, presence of two factors; high risk, presence of three or more factors. This new index showed a high degree of correlation with survival outcomes in terms of OS and DFS (Figure A, B). This study demonstrated the prognostic significance of Ki-67 expression, and our new prognostic index may become a useful tool for predicting prognosis in extranodal NK/T cell lymphoma, nasal type. [Display omitted]

Venous sonography for the diagnosis of asymptomatic deep vein thrombosis in patients with cancer undergoing chemotherapy.

Early detection of asymptomatic deep vein thrombosis by venous sonography may identify patients who may benefit from anticoagulant therapy and thus may prevent morbidity and mortality associated with deep vein thrombosis. The aim of this study was to examine the prevalence of deep vein thrombosis by venous sonography in asymptomatic ambulatory patients with cancer undergoing chemotherapy and to evaluate the correlation between procoagulant activity and asymptomatic deep vein thrombosis. The study population included 62 patients (32 with lung cancer and 30 with lymphoma) receiving chemotherapy with an ambulatory performance status and without clinical evidence of deep vein thrombosis. Bilateral venous sonographic studies of the lower extremities were performed, covering the femoropopliteal venous system. The D-dimer level and acquired activated protein C resistance were determined in the patients and in 30 healthy control subjects. Sonographic evidence of deep vein thrombosis on the femoropopliteal axis was found in 0 (0%) of 62 patients (1-sided 95% confidence interval, 0%-4.8%). Acquired activated protein C resistance prevalence and D-dimer levels were increased in study patients compared with control subjects (34% versus 0%; P < .003; median, 0.72 versus 0.25 mg/L; P < .0001, respectively). Despite the procoagulant tendency, venous sonography did not detect asymptomatic deep vein thrombosis in patients with cancer undergoing chemotherapy. Thus, screening by venous sonography is not justified in this patient population.

Limited stage small cell lung cancer.

The management of limited stage small cell lung cancer begins with a firm pathologic diagnosis and careful staging. Patients with adequate pulmonary function, ambulatory performance status, and no evidence of metastatic disease outside a "tolerable" local radiotherapy volume should have consultation from both medical and radiation oncology disciplines for planning of integrated therapy. The chemotherapy prescription recommended is cisplatin plus etoposide at standard doses for four chemotherapy cycles. Thoracic irradiation should be administered concurrently with the first or second cycle of cisplatin and etoposide. Patients with complete response and excellent partial response should receive prophylactic cranial irradiation after completion of all chemotherapy.

Peripheral T-cell lymphomas: Initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification

Peripheral T-cell lymphomas (PTCL) account for about 10% of all lymphomas in Western countries. The aim of the present study is to analyze the initial characteristics and prognostic factors in a large series of PTCL patients. 174 patients (105 male/69 female; median age 61 years) were diagnosed with PTCL according to the R.E.A.L. Classification in nine Spanish institutions between 1985 and 1996. Cutaneous lymphomas and T-cell chronic lymphocytic/prolymphocytic leukemia were excluded from the study. Univariate and multivariate analyses were used to assess the prognostic value of the main initial variables. The distribution according to histology subgroup was: PTCL unspecified, 95 cases (54.4%); anaplastic large-cell Ki-l-positive (ALCL), 30 cases (17%); angioimmunoblastic T cell, 22 cases (13%); angiocentric, 14 cases (8%); intestinal T cell, 12 cases (7%), and hepatosplenic gamma delta T cell, one case (0.6%). As compared to the other types, ALCL presented more frequently in ambulatory performance status, without extranodal involvement, in early stage, normal serum beta 2-microglobulin (B2M) level and low-risk international prognostic index (IPI). Most patients were treated with adriamycin-containing regimens. The overall CR rate was 49% (69% for ALCL vs. 45% for other PTCL; P < 0.02). The risk of relapse was 48% at four years. Median survival of the series was 22 months (65 months for ALCL vs. 20 months for other PTCL; P = 0.03), with a four-year probability of survival of 38% (95% confidence intervals (95% CI): 28-48). In the univariate analysis, in addition to the histology, older age, poor performance status, presence of B-symptoms, extranodal involvement, bone marrow infiltration, advanced Ann Arbor stage, high serum LDH, high serum B2M, and intermediate- or high-risk IPI were related to poor survival. In the multivariate analysis the histologic subgroup (ALCL vs. other PTCL) (P = 0.02; response rate (RR): 4.3), the presence of B-symptoms (P = 0.02, RR: 2.2), and the IPI (low vs. high) (P = 0.04, RR: 2) maintained independent predictive value. When the analysis was restricted to the unspecified subtype, only IPI had independent prognostic value (P = 0.003; RR: 3.5). PTCL have adverse prognostic features at diagnosis, respond poorly to therapy and have short survival, with no sustained remission. ALCL constitutes a subgroup which responds better to therapy and has a longer survival.

Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2.

A database of 327 patients with advanced Renal Cell Carcinoma (RCC) has been analyzed in order to identify potential baseline prognostic factors predicting for survival, following recombinant Interleukin-2 treatment (rIL-2). All patients received a continuous infusion (CIV). Eligibility criteria were uniform across studies, and included patients with an ambulatory performance status (PS), measurable disease, no CNS metastases, and no major organ compromise. Multivariate analyses identified baseline PS (ECOG 0 vs. 1), time from diagnosis to treatment (DTI greater than 24 months vs. less than or equal to 24 months), and the number of metastatic sites (1 vs. greater than or equal to 2, where lung, bone and other sites are considered as separate sites) as important predictors for survival. Patients can be classified into 4 subgroups, which are a function of the number of risk factors present. Median survival for each subgroup is 28, 17, 10 and 5 months, respectively. The model was validated in an independent cohort of 125 patients with RCC treated with subcutaneous (s/c) rIL-2, and predicted for survival accurately. By determining in which risk group category patients may fall, treating physicians may be better equipped to decide on patient management. The model may also be of value in order to stratify patients in randomized clinical trials.

Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma

Data have been analysed for 327 patients with advanced renal cell carcinoma receiving a continuous infusion of recombinant interleukin 2 (rIL-2) alone (225 patients) or rIL-2 plus lymphokine activated killer (LAK) cells (102) on a normal oncology ward. Eligibility criteria were uniform across protocols, all patients having advanced progressive disease, but with an ambulatory performance status. The baseline characteristics of patients receiving rIL-2 alone did not differ significantly from those receiving LAK, with the exception that the LAK treated patients had a better performance status. Despite similar treatment intensity, toxicity was more severe in the patients receiving LAK. The addition of LAK did not lead to higher response rates or to prolonged response duration, progression-free survival or survival. This review confirms the activity of rIL-2 for the treatment of advanced renal cell carcinoma and demonstrates that the addition of LAK cells does not lead to increased efficacy.

A phase II trial of peg-L-asparaginase in the treatment of non-hodgkins lymphoma

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with Improved survival Included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoproteln levels. Patients living longer than 12 months fell Into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five “long-term” survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alphafetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively Indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum billrubin determination can identify those with some prospect of prolonged survival.

Evaluation of the clinical effectiveness of sperum CK-MB measurements on the dupont ACA for patients admitted to a coronary care unit

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with Improved survival Included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoproteln levels. Patients living longer than 12 months fell Into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five “long-term” survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alphafetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively Indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum billrubin determination can identify those with some prospect of prolonged survival.

Intracerebral metastases in solid-tumor patients: natural history and results of treatment.

In order to determine the natural history and results of treatment of intracerebral metastases in solid-tumor patients, the records of 191 patients with an antemortem diagnosis of intracerebral metastasis made during the period from August 1974 to November 1978 were reviewed. Malignancies included lung (122 patients), breast (26), unknown primary (16), melanoma (8), colorectal (6), hypernephroma (4), and others (12). Favorable prognostic factors included solitary brain metastasis (P less than 0.001), ambulatory performance status (P less than 0.001), symptoms of headache (P less than 0.001), or visual disturbances (P less than 0.02), and estrogen receptor positivity in breast cancer patients (P = 0.055). Poor prognostic factors included advanced age (P less than 0.04) and evidence of impaired consciousness, i.e., disorientation, lethargy, stupor, or coma (P less than 0.007). Median survival time after diagnosis of intracerebral metastasis was 3.7 months for the entire series. In those patients with a single intracerebral metastasis and minimal tumor burden, the type of treatment used had a significant impact on survival. Those cases treated with surgery and radiation had a median survival time of 9.7 months versus 3.7 months for those treated with radiation alone (P less than 0.02). When using a proportional hazard regression analysis to adjust for the three most important prognostic factors, treatment (surgery and radiation versus radiation alone) still appeared to be important. Intracerebral metastases were the immediate or contributing cause of death in 50% of the patients in this series. Patients at greater risk of dying of intracerebral metastases included those in whom the brain was the first site of distant metastasis, those with an intracerebral metastasis from an unknown primary site, and those whose presentation of malignancy was with symptoms of a brain metastasis. Although the therapeutic goal in intracerebral metastases is generally palliative, it appears that there are categories of cases that may benefit from more aggressive treatment.