bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient characteristics associated with high-risk methotrexate concentrations and toxicity.
Authors: Relling M V , Fairclough D , Ayers D , Crom W R , Rodman J H , Pui C H , Evans W E 
Published: February 2017

PURPOSE Following high-dose methotrexate (HD-MTX) treatment, delayed MTX elimination is an important problem because it necessitates increased leucovorin rescue and additional hospitalization for hydration and urinary alkalinization. Our purpose was to identify factors associated with high-risk MTX plasma concentrations (defined by plasma concentration > or = 1.0 mumol/L at 42 hours from the start of MTX) and with toxicity. PATIENTS AND METHODS Variables associated with MTX concentrations and toxicity were assessed in 134 children treated with one to five courses of HD-MTX (900 to 3,700 mg/m2 intravenously [i.v.] over 24 hours for a total of 481 courses) for acute lymphoblastic leukemia (ALL). RESULTS High-risk MTX concentrations, toxicity (usually mild mucositis), and delay in resuming continuation chemotherapy occurred in 106 (22%), 123 (26%), and 66 (14%) of 481 courses, respectively. Using a mixed effects model for repeated measures, high-risk MTX concentrations were significantly associated with a higher MTX area-under-the-concentration-time curve (AUC), low urine pH, emesis, low MTX clearance, low urine output relative to intake, use of antiemetics during the MTX infusion, and concurrent intrathecal therapy (all p values < .01). Clinical toxicities and delay in resumption of continuation chemotherapy due to myelosuppression were more common in those with high 42-hour MTX concentrations, despite increased leucovorin rescue for all patients with high-risk MTX concentrations. However, with individualized rescue, no patient developed life-threatening toxicity. A more aggressive hydration and alkalinization regimen for subsequent courses reduced the frequency of high-risk MTX concentrations to 7% of courses (13 of 183) (P = .0001), and the frequency of toxicity decreased to 11% of courses (P = .0074). CONCLUSION This study identified several clinical variables that influence MTX disposition that, when modified, can reduce the frequency of high-risk MTX concentrations and toxicity.
Transient acantholytic dermatosis in oncology patients.
Authors: Guana A L , Cohen P R 
Published: February 2017

PURPOSE To evaluate the characteristics of patients with cancer who have a previous history, concurrent episode, or subsequent appearance of transient acantholytic dermatosis (TAD). METHODS We report four oncology patients who developed TAD and review the 22 reports that have previously been published of individuals in whom TAD appeared either before, concomitant with, or after the diagnosis of their malignancy. RESULTS TAD was associated more frequently in patients with hematologic malignancies, especially acute and chronic myelogenous leukemia. It also appeared in patients with solid tumors, primarily those of the genitourinary organs. In almost all the cases, the onset of TAD was either concurrent or followed the discovery of malignancy. The TAD resolved completely, with or without treatment, in at least 20 patients in a median of 3 weeks. CONCLUSION TAD is a benign and temporary condition that may occur in patients with an internal malignancy. When the diagnosis of TAD is being considered, a lesional skin biopsy readily establishes histologic confirmation in a febrile patient with cancer who develops a new rash. TAD has been observed most frequently in oncology patients who have either myelogenous leukemia or carcinoma of the genitourinary organs. The appearance of TAD coincided with either the detection or the recurrence of malignancy in three individuals (12%). In the other 23 oncology patients, TAD was most likely secondary to either antineoplastic agents, excessive perspiration, fever, occlusive immobility, and/or ionizing or UV radiation.
Effect of a National Cancer Institute Clinical Alert on breast cancer practice patterns.
Authors: Johnson T P , Ford L , Warnecke R B , Nayfield S G , Kaluzny A , Cutter G , Gillings D , Sondik E , Ozer H 
Published: February 2017

PURPOSE This study evaluates the effect of the 1988 National Cancer Institute Clinical Alert regarding treatment of early-stage breast cancer on the patterns of treatment provided to patients. PATIENTS AND METHODS Data analyzed were collected from the hospital and outpatient records of 12,534 female patients with a primary diagnosis of breast cancer (stages I and II) initially diagnosed during the years 1983 through 1989. RESULTS Analyses revealed that the proportions of patients with a negative lymph node status diagnosed after the May 1988 Clinical Alert who received adjuvant treatment (tamoxifen and/or multidrug chemotherapy) were significantly greater than predicted from treatment trends established before the Alert's release. Proportions of patients with positive lymph node status receiving adjuvant therapy subsequent to the Alert's release, in contrast, did not fall outside the projected confidence intervals for that group. Additional analyses showed a significant effect of the Clinical Alert among several subgroups of node-negative patients. CONCLUSION Findings suggest that the Clinical Alert mechanism, followed by publication in the peer-reviewed scientific literature, is an effective way to communicate important research findings to practitioners in the community. However, the Alert mechanism is controversial and should be used judiciously to ensure its credibility.
Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer.
Authors: Passlick B , Izbicki J R , Kubuschok B , Nathrath W , Thetter O , Pichlmeier U , Schweiberer L , Riethmüller G , Pantel K 
Published: February 2017

PURPOSE This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). METHODS Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells. RESULTS Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005). CONCLUSION Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.
Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group.
Authors: Finlay J L , Boyett J M , Yates A J , Wisoff J H , Milstein J M , Geyer J R , Bertolone S J , McGuire P , Cherlow J M , Tefft M 
Published: February 2017

PURPOSE In a previous randomized trial, the addition of adjuvant chemotherapy to postoperative radiotherapy proved beneficial in the treatment of childhood high-grade astrocytomas. The present study tests the hypothesis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study. PATIENTS AND METHODS Between April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly diagnosed high-grade astrocytomas were eligible for this study, as determined by the treating institution's histopathologic diagnosis. Treatment consisted of postoperative local-field radiotherapy and adjuvant chemotherapy, either lomustine (CCNU), vincristine, and prednisone (control regimen) or eight-drugs-in-1-day chemotherapy (experimental regimen). Two cycles of postoperative preirradiation chemotherapy were administered in the experimental regimen. Patients were evaluated radiographically every 3 months after irradiation. RESULTS Eighty-five eligible patients were randomized to the control regimen and 87 to the experimental regimen. The progression-free survival (PFS) and overall survival (OS) at 5 years were 33% (SE = 5%) and 36% (SE = 6%), respectively. There was no statistical difference in outcome between the two chemotherapy regimens. In patients with confirmed diagnoses of anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM), anaplastic astrocytoma, greater than 90% resection, and nonmidline tumor location were characteristics predictive of an improved PFS. There was a difference in toxicity between the two chemotherapeutic regimens, with greater myelosuppression and hearing loss in the experimental regimen. Tumor recurrence occurred primarily within the primary tumor site. CONCLUSIONS There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone. Extent of tumor resection and histopathologic diagnosis are significant prognostic variables. The overall outcome for children with high-grade astrocytomas remains poor.
Results of the United Kingdom Children's Cancer Study Group first Wilms' Tumor Study.
Authors: Pritchard J , Imeson J , Barnes J , Cotterill S , Gough D , Marsden H B , Morris-Jones P , Pearson D 
Published: February 2017

PURPOSE The first United Kingdom Children's Cancer Study Group (UKCCSG) Wilms' Tumor Trial (UKW1) applied treatment regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria, seeking to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable-histology (UH) tumors with more intensive chemotherapy. PATIENTS AND METHODS Three hundred eighty-four consecutively diagnosed patients with Wilms' tumor were recruited from the 20 UKCCSG centers and Oslo, Norway, between January 1980 and June 1986. The regimen for stage I patients was vincristine (Vcr) only, while stage II patients received Vcr and dactinomycin (Act-D). Stage III patients received three-drug therapy and stage IV and UH patients four-drug regimens. Act-D was given as pulsed doses of 1.5 mg/m2 every 3 or every 6 weeks. No lung irradiation was used in stage IV patients. No randomized comparisons were attempted. End points were survival and event-free survival (EFS). RESULTS Survival at 6 years in FH patients was 96% for stage I, 93% for stage II, 83% for stage III, 65% for stage IV, and 50% for UH patients of all stages. CONCLUSION Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias.
Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome.
Authors: Kuzel T M , Roenigk H H , Samuelson E , Herrmann J J , Hurria A , Rademaker A W , Rosen S T 
Published: February 2017

PURPOSE To investigate the efficacy of combined topical therapy and systemic interferon alfa-2a in patients with mycosis fungoides (MF) and the Sézary syndrome (SS). PATIENTS AND METHODS Between December 1987 and April 1993, 39 patients with all stages of MF and SS were treated with combined phototherapy and systemic interferon alfa-2a as part of two institutional studies. The initial phase I study of 15 patients established the maximum-tolerated dose of interferon and has been previously reported. Subsequently, 24 patients have been entered onto a phase II trial. Long-term follow-up data are provided for both studies. RESULTS The median follow-up duration for the entire cohort is 28 months. Patients with all stages of disease were enrolled (stage IB, n = 14; IIA, n = 5; IIB, n = 6; III, n = 8; IVA, n = 5; IVB, n = 1). Thirty-four patients had received previous therapy. Overall, 36 of 39 patients achieved a complete response (CR; 62%) or partial response (28%) to therapy. The median response duration is 28 months (range, 1 to 64). Twenty-nine of 39 patients are alive, with a median survival duration of 62 months (range, 1 to 66). CONCLUSION Interferon alfa-2a combined with phototherapy is an effective, safe, durable therapy for MF and SS.
Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan.
Authors: Thom A K , Alexander H R , Andrich M P , Barker W C , Rosenberg S A , Fraker D L 
Published: February 2017

PURPOSE Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma. We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity. PATIENTS AND METHODS Nineteen patients with extremity melanoma (n = 16) or sarcoma (n = 3), underwent 90-minute ILP with TNF-alpha, interferon gamma (0.2 mg), and M (10 to 13 mg/L of limb volume) (TNF/IFN/M) (n = 12), or M alone (n = 7). Continuous intraoperative monitoring (CIM) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin. Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay. RESULTS Systemic leaks > or = 1% from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone. Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak (> or = 1%) and zero of six patients without a leak (< 1%). These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak (2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL, respectively; P < .05). All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 (IL-6) levels than in patients with M alone (12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL, respectively; P < .001). Intracellular adhesion molecule (ICAM), IL-8, and TNF-R levels were also increased after ILP with TNF/IFN/M. CONCLUSION ILP with TNF/IFN/M can be safely performed, as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit. Patients with a measured leak of > or = 1% develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks.
Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.
Authors: van der Zee A G , Hollema H , Suurmeijer A J , Krans M , Sluiter W J , Willemse P H , Aalders J G , de Vries E G 
Published: February 2017

PURPOSE To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.
All-trans retinoic acid pharmacokinetics and bioavailability in acute promyelocytic leukemia: intracellular concentrations and biologic response relationship.
Authors: Agadir A , Cornic M , Lefebvre P , Gourmel B , Jérôme M , Degos L , Fenaux P , Chomienne C 
Published: February 2017

PURPOSE This study investigated the in vitro pharmacologic behavior and disposition kinetics of all-trans retinoic acid (ATRA) in acute myeloid leukemic (AML) cells, their sensitivity to its differentiating effect, and the in vivo response of acute promyelocytic leukemia (APL) patients after therapy. PATIENTS AND METHODS Fresh leukemic cells from 14 AML patients (nine APL and five non-APL), were incubated in suspension culture in the absence or presence of 10(-6) mol/L ATRA. Intracellular ATRA concentration and ATRA metabolism was determined by high-performance liquid chromatography (HPLC). RESULTS Immediate uptake is observed with maximal intracellular levels (Cmax) achieved after 24 hours of incubation. At this time, ATRA levels were variable, ranging from 20 to 230 pmol/10(6) cells (median, 100 pmol/10(6) cells). Comparison of ATRA intracellular levels with the in vitro response of patients' cell samples as measured by the percentage of nitro blue tetrazolium (NBT)-positive cells after a 3-day incubation period allowed us to discriminate a group of APL patients (n = 6) with high Cmax (group A; median, 200 pmol/10(6) cells) and maximal differentiation at day 3 (median, 80%), and a group of patients (n = 8, three APL and five non-APL) with low Cmax (group B; median, 35 pmol/10(6) cells) and poor in vitro response (median, 40%; APL cases only). Interestingly, all APL patients, except one included in group A (rapid in vitro ATRA uptakers), achieved a complete remission. CONCLUSION These findings suggest that intracellular ATRA concentrations are determinant for ATRA response and should be taken into account when monitoring the efficacy of ATRA differentiation therapeutic trials in malignant disorders.
Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy.
Authors: Sonneveld P , de Ridder M , van der Lelie H , Nieuwenhuis K , Schouten H , Mulder A , van Reijswoud I , Hop W , Lowenberg B 
Published: February 2017

PURPOSE AND METHODS A prospective, randomized, multicenter phase III trial was performed to investigate the feasibility of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in elderly patients ( > or = 60 years) with advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy, and to compare the tolerance and efficacy of doxorubicin versus mitoxantrone (CHOP v CNOP). RESULTS Of 157 enrolled patients, 148 were eligible and 145 were assessable for response. Thirty-one percent of CNOP and 45% of CHOP patients completed six cycles without dose reduction. The cumulative normalized dose-intensity (NDI) was 92% with CHOP and 90% with CNOP after six cycles. The overall complete response (CR) rates were 49% and 31% in CHOP- and CNOP-treated patients, respectively (P = .03). Survival with CNOP was significantly worse as compared with CHOP (P = .03). Lymphoma-specific survival was significantly better in CHOP-treated patients (P = .034) At 3 years, 42% of CHOP and 26% of CNOP patients were alive. Additional unfavorable prognostic factors at diagnosis were high serum lactate dehydrogenase (LDH) level, bulky mass, and low performance status, but not age. The median disease-free intervals of complete responders were 27 (CHOP) and 15 (CNOP) months, respectively. Considering the complete group of patients, at 3 years 17% of CHOP and 13% of CNOP patients were alive and disease-free (P = .12). Common toxicity criteria (CTC) grade > or = 2 with CNOP and CHOP was not different. CONCLUSION CHOP is well tolerated in elderly patients with advanced intermediate- or high-grade NHL and its NDI is not seriously impaired. Treatment with CHOP (doxorubicin) results in better CR and survival rates than CNOP (mitoxantrone). CHOP should be recommended for elderly patients with high-risk NHL.