bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.
Authors: Wendt T G , Grabenbauer G G , Rödel C M , Thiel H J , Aydin H , Rohloff R , Wustrow T P , Iro H , Popella C , Schalhorn A 
Published: February 2017

PURPOSE A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.
Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.
Authors: Zucali R , Mariani L , Marubini E , Kenda R , Lozza L , Rilke F , Veronesi U 
Published: February 2017

PURPOSE The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.
Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer.
Authors: Lindley C , Vasa S , Sawyer W T , Winer E P 
Published: February 2017

PURPOSE To evaluate the quality of life (QOL) of breast cancer patients who survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal therapy and to characterize relationships between QOL and patient physical symptoms, sexual function, and preferences regarding adjuvant treatment. PATIENTS AND METHODS Eighty-six patients who had completed systemic adjuvant therapy for early-stage breast cancer between 1988 and 1991 were surveyed by written questionnaire and telephone interview. Sociodemographic information was obtained for each patient, and patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS) Short Form 36 (SF-36), a series of questions regarding sexual function, and a survey about preferences for adjuvant therapy in relation to possible benefit. RESULTS The mean FLIC score among all patients was 138.3 (+/- 12.2), which suggests a high level of QOL. The reported frequency of moderate to severe symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%), and local numbness at the site of surgery (22.1%) occurring with greatest frequency. Patients reported a wide range of sexual difficulties. Preference assessment showed that more than 65% of patients were willing to undergo 6 months of chemotherapy for a 5% increase in likelihood of cancer cure. CONCLUSION Self-rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was generally favorable. Less than one third of patients reported moderate to severe symptoms. Selected aspects of sexual function appeared to be compromised. The majority of patients indicated a willingness to accept 6 months of chemotherapy for small to modest potential benefit.
Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression.
Authors: Adachi M , Taki T , Konishi T , Huang C I , Higashiyama M , Miyake M 
Published: February 2017

PURPOSE The transmembrane-4 superfamily (TM4SF) is a recently discovered family of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63 have been reported to modulate tumor progression or metastasis. In this study, we investigated the relationships between these three genes, MRP-1, KAI1, and ME491, in patients with non-small-cell lung cancers (NSCLCs). Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs. PATIENTS AND METHODS One hundred seventy-two patients up to stage IIIB NSCLC underwent radical surgery during the period of January 1991 through June 1994. Using a quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we studied the expression of MRP-1, KAI1, and ME491 genes in these patients. RESULTS We found that 109 patients (63.4%) had MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors. Conversely, all 172 patients expressed ME491. No relationship was found between MRP-1 expression and KAI1 expression. We classified these patients into three groups. The 36 patients who were positive for both MRP-1 and KAI1 were defined as group A; the 79 patients with reduced expression of either MRP-1 or KAI1 were defined as group B, and the remaining 57 patients with reduced expression of both MRP-1 and KAI1 were defined as group C. This new classification was correlated with nodal status, tumor status, and pathologic stage (P = .0056, P = .0003, and P < .0001, respectively). In NSCLC patients, the 5-year survival rate of group A patients was significantly better than that of group B patients and much better than that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P < .0001). Cox multivariate regression analysis showed that this new classification in NSCLCs was a significant prognostic factor, as was the nodal status (P < .0001). CONCLUSION Our results suggest that a low MRP-1 and KAI1 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that the evaluation for MRP-1 and KAI1 expression may identify node-negative lung cancer patients who are at high risk for early disease recurrence, and thus need intensive adjuvant therapy.
Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.
Authors: Pantel K , Passlick B , Vogt J , Stosiek P , Angstwurm M , Seen-Hibler R , Häussinger K , Thetter O , Izbicki J R , Riethmüller G 
Published: February 2017

PURPOSE Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer. PATIENTS AND METHODS At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery. RESULTS Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038). CONCLUSION Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.
Is the survival of melanoma patients receiving polyvalent melanoma cell vaccine linked to the human leukocyte antigen phenotype of patients?
Authors: Hoon D S , Okamoto T , Wang H J , Elashoff R , Nizze A J , Foshag L J , Gammon G , Morton D L 
Published: February 2017

PURPOSE An allogeneic polyvalent melanoma cell vaccine (PMCV) has been shown to be efficacious in improving overall survival of patients with malignant melanoma in a phase II clinical setting. The PMCV consists of three allogeneic melanoma cell lines. The objectives of the study were to determine (1) whether the survival of melanoma patients who received PMCV was related to the patient's human leukocyte antigen (HLA) class I phenotype matching the HLA class I phenotype of the PMCV, and (2) whether PMCV clinical efficacy was correlated to melanoma patients with a particular HLA phenotype(s). MATERIALS AND METHODS PMCV was given to 69 melanoma patients with American Joint Committee on Cancer (AJCC) stage I to IV disease status. The PMCV and patients lymphocytes were typed for HLA-A and -B. A correlation was made between the HLA expression of PMCV lines and the HLA of patients to their survival status. A second correlation was made between the HLA of patients and survival independent of the PMCV HLA phenotype. RESULTS Patients whose HLA phenotype (A3/11 and B7/44) matched the PMCV lines had a better overall survival (P < .029). Analysis of HLA expression of patients independent of PMCV HLA to survival showed that HLA-A25 phenotype patients had a significantly better overall survival (P = .006). HLA-B35 patients had a poorer survival outcome (P = .019). CONCLUSION The studies indicate that overall survival following PMCV treatment in melanoma patients significantly correlates with their HLA phenotypes. These correlations may be related to the host immune response to the PMCV or due to differences in the clinical course of melanoma in patients with different HLA types.
Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team.
Authors: Dezube B J , Von Roenn J H , Holden-Wiltse J , Cheung T W , Remick S C , Cooley T P , Moore J , Sommadossi J P , Shriver S L , Suckow C W , Gill P S 
Published: February 2017

PURPOSE Angiogenesis is a major component of Kaposi's sarcoma (KS) and a critical process in tumor growth. The present study was designed primarily to test the toxicity and pharmacokinetics (PK) of the angiogenesis inhibitor TNP-470 and secondarily to evaluate tumor response in patients with early AIDS-related KS. PATIENTS AND METHODS Patients with AIDS-related KS were required to have cutaneous disease with > or = 5 measurable lesions and no evidence of pulmonary, symptomatic gastrointestinal, or acutely life-threatening KS. Thirty-eight patients received TNP-470 by weekly intravenous infusion over 1 hour at one of six dose levels for up to 24 weeks. RESULTS The dose levels tested included 10, 20, 30, 40, 50 and 70 mg/m2. Median CD4 count was 24 cells/microl (range, 0 to 460). Fourteen patients (36%) had > or = 50 cutaneous lesions and 19 (49%) had oral lesions. Adverse events included neutropenia (n = 2), hemorrhage (n = 3), and urticaria (n = 1). PK studies showed wide interpatient and intrapatient variability. Elimination half-life values were short (range, 0.01 to 0.61 hours). Seven patients (18%) achieved a partial response. The median time to partial response was 4 weeks (range, 2 to 25), and the median duration of response was 11 weeks (range, 3 to 26+). CONCLUSION TNP-470, administered as a weekly, 1-hour infusion to patients with early AIDS-KS is well-tolerated at doses up to and including the highest dose tested. Tumor responses were observed in a substantial number of cases and occurred at various dose levels. TNP-470 should be evaluated further in patients with AIDS-KS as a single agent and in combination with other biologic response modifiers in early disease or after initial response to cytotoxic chemotherapy.
Phase I and pharmacokinetic trial of aminopterin in patients with refractory malignancies.
Authors: Ratliff A F , Wilson J , Hum M , Marling-Cason M , Rose K , Winick N , Kamen B A 
Published: February 2017

PURPOSE Aminopterin (AMT) is a potent folate analog that is no longer in routine clinical use. Because of laboratory data that suggests improved metabolism of AMT versus methotrexate (MTX) in lymphoblasts, we developed a phase I trial to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of AMT. PATIENTS AND METHODS Twenty patients with refractory malignancies were treated. The starting dose of AMT was 2.5 mg/m2 every 12 hours for two doses weekly: the dose of AMT was decreased and leucovorin (LV) rescue was added after the DLT was observed. Pharmacokinetics were performed after both intravenous (i.v.) and oral AMT administration. RESULTS Mucosal toxicity was dose-limiting and resulted in the need for a dose reduction (dose level 2: AMT 2 mg/m2 every 12 hours for two doses weekly) and, subsequently, the addition of scheduled LV rescue (dose level 3: AMT 2 mg/m2 every 12 hours for two doses followed by LV 5 mg/m2 orally every 12 hours for two doses, starting 24 hours after the second dose of AMT). The mean areas under the curve (AUC) for the i.v. (n = 14) and oral (n = 13) doses were 1.20 +/- 0.09 (SE) and 1.05 +/- 0.14 micromol x h/L respectively. The half-life was 3.64 +/- 0.28 hours and the oral bioavailability in 12 matched subjects was 83.5% +/- 8.3%. One patient with endometrial adenocarcinoma achieved a complete response (CR) and remains on therapy at 11+ months. Seven patients had stable disease (SD) for 8 weeks or greater, which included one patient with a metastatic nerve sheath tumor who was stable for 9 months. CONCLUSION We conclude that AMT has good oral bioavailability and that, when given on a q12 hour x two weekly schedule, the MTD is 2 mg/m2 with delayed LV rescue.
Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.
Authors: Gamelin E , Boisdron-Celle M , Delva R , Regimbeau C , Cailleux P E , Alleaume C , Maillet M L , Goudier M J , Sire M , Person-Joly M C , Maigre M , Maillart P , Fety R , Burtin P , Lortholary A , Dumesnil Y , Picon L , Geslin J , Gesta P , Danquechin-Dorval E , Larra F , Robert J 
Published: February 2017

PURPOSE A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. PATIENTS AND METHODS Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. RESULTS A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. CONCLUSION Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.
Nucleolar organizer region counts predict complete remission, remission duration, and survival in adult acute myelogenous leukemia patients.
Authors: Pich A , Chiusa L , Audisio E , Marmont F 
Published: February 2017

PURPOSE The analysis of the nucleolar organizer regions (AgNORs) was performed in patients with acute myelogenous leukemia (AML) to verify the role of cell proliferation in predicting complete remission (CR) and survival. MATERIALS AND METHODS Bone marrow biopsies from 40 adult patients with AML were stained with the argyrophilic method. The mean AgNOR number (AgNOR count) was calculated for each case. After induction therapy, patients who achieved CR received intensive consolidation; two underwent autologous and four allogeneic bone marrow transplantations (BMT). RESULTS The mean AgNOR count for the whole series was 6.6 (SD = 1.35); it was higher in CR patients than in resistant ones (P = .02). The median duration of CR was 26 months for patients with an AgNOR count greater than 6.6, but only 6 months for those with lower counts (P = .01). Sixteen patients who achieved a CR relapsed and 14 reached a second CR; the median duration of second CR was 16 months for patients with AgNOR count greater than 6.6, but only 5 months for those with lower counts (P = .01). The median survival time for the whole series was 14 months, with 30% of patients alive and in continuous CR at 103 months. Survival was longer for patients with an AgNOR count greater than 6.6 (33 months) than for those with lower counts (6 months; P = .0009). In multivariate analysis, when CR was excluded from the model, AgNOR count appeared as an independent prognostic variable (P = .005). CONCLUSION AgNOR analysis is a suitable method to assess cell proliferation in bone marrow biopsies and can predict CR, remission duration, and survival in AML patients.
Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.
Authors: Zinzani P L , Pileri S , Bendandi M , Buzzi M , Sabattini E , Ascani S , Gherlinzoni F , Magagnoli M , Albertini P , Tura S 
Published: February 2017

PURPOSE In the last few years, the search for new biologic markers in high-grade non-Hodgkin's lymphomas has provided important results. In particular, soluble CD30 (sCD30) levels were elevated in most patients with Hodgkin's disease (HD) and anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS From September 1988 to October 1993, treatment was completed in 70 previously untreated patients with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkin's-like subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and after induction polychemotherapy in all patients; in addition, the initial sCD30 levels were compared with those obtained from 50 stage-matched patients with HD. RESULTS Pretreatment levels of sCD30 were highly elevated in the stage-matched group of HD patients compared with healthy controls; median sCD30 levels in patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively, than in patients with HD. The sCD30 level normalized on achievement of complete response (CR). The risk of lower relapse-free survival was associated with bulky disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower overall survival was associated with advanced stage and pretreatment levels of sCD30 in both univariate and multivariate analysis. CONCLUSION The results of this study suggest that sCD30 is a specific prognostic indicator of the risk for lower complete response rate and relapse-free expectancy for patients with ALCL.