bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors.
Authors: Tirelli U , Errante D , Dolcetti R , Gloghini A , Serraino D , Vaccher E , Franceschi S , Boiocchi M , Carbone A 
Published: February 2017

PURPOSE To describe virologic, clinicopathologic, and therapeutic features of a large series of Italian patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS From November 1986 to March 1994, 114 cases were observed. The relationship between Epstein-Barr virus (EBV) and HD was determined by an in situ hybridization technique, immunostaining for EBV-encoded latent membrane protein-1 (LMP-1) expression, and Southern blotting. Twenty-six patients were included in a prospective study evaluating the combination of chemotherapy (CT) with zidovudine. RESULTS Combined approach on EBV study revealed that 14 (78%) of 18 patients were EBV-associated. An almost equivalent distribution of EBV subtypes was observed in EBV-carrying cases, indicating that in the HIV setting, type 2 EBV also may be pathogenetically involved in HD development. In comparing these 114 patients with our single-institutional series of 104 HIV-negative patients with HD, we observed at presentation a younger median age (29 v 38 years); a prevalence of males (90% v 56%); and a higher percentage of stage IV disease (52% v 15%), presence of B symptoms (77% v 35%), and extranodal disease (63% v 29%). The complete remission (CR) rate (58%) and median survival (13 months) of patients treated prospectively were similar to that of patients treated with standard CT regimens. The statistically significant favorable prognostic factors for survival being the following: achievement of CR, CD4+ count greater than 250/microL, and no prior diagnosis of AIDS at onset of HD. CONCLUSION Our virologic findings indicate that HIV-related HD is more closely associated with EBV than HD in the general population. The peculiar clinicopathologic findings, the role of some prognostic factors, and the possibility of cure of HIV-related HD have been demonstrated.
In vivo cell kinetics in head and neck squamous cell carcinomas predicts local control and helps guide radiotherapy regimen.
Authors: Corvò R , Giaretti W , Sanguineti G , Geido E , Orecchia R , Guenzi M , Margarino G , Bacigalupo A , Garaventa G , Barbieri M 
Published: February 2017

PURPOSE To determine whether pretherapy cell kinetics can predict local control for patients affected by head and neck squamous cell carcinomas (HN-SCCs) to be treated by primary radiotherapy and, moreover, guide to a choice between conventional and accelerated radiotherapy. PATIENTS AND METHODS Between 1989 and 1993, 83 patients with stage II to IV HN-SCC entered the study. Multiple primary tumor biopsies were obtained 6 hours after in vivo infusion of bromodeoxyuridine (BrdUrd). In vivo S-phase fraction labeling index (LI), duration of S phase (Ts), and potential doubling time (Tpot) were obtained by analysis of multivariate flow-cytometric data. Between April 1989 and January 1991, 49 patients were treated by conventional radiotherapy (70 Gy in 35 fractions over 7 weeks), whereas, afterwards, 34 patients entered an accelerated radiotherapy regimen with the concomitant boost technique (75 Gy in 40 fractions over 6 weeks). RESULTS Univariate analysis showed that, among patients treated by conventional radiotherapy, local control probability was affected by tumor stage (P = .02), Tpot (P < .001), and LI (P = .04). Similarly, among patients treated with accelerated radiotherapy, we found that local control probability was related to tumor stage (P = .03) and primary tumor site (P = .05). For the subgroup of patients with tumors characterized by fast growth (Tpot < or = 5 days), accelerated radiotherapy gave a better local control rate than conventional radiotherapy (P = .02). Cox multivariate analysis of the total number of patients showed that the only significant independent prognostic factors related to local control were tumor stage (P = .002) and Tpot (P = .004). Moreover, when the Cox analysis was restricted to the subgroup of patients treated with conventional radiotherapy, Tpot was the most significant factor to predict local outcome (P < .01). CONCLUSION Pretreatment tumor Tpot appears to be an important independent prognostic factor for local control of HN-SCC treated by primary radiotherapy.
Second malignant neoplasms following treatment for Wilm's tumor: a report from the National Wilms' Tumor Study Group.
Authors: Breslow N E , Takashima J R , Whitton J A , Moksness J , D'Angio G J , Green D M 
Published: February 2017

PURPOSE The study was undertaken to determine the incidence of second malignant neoplasms (SMNs) in patients treated for Wilms' tumor and demonstrate how the incidence varied with the initial treatment protocol. PATIENTS AND METHODS Between October 1969 and December 1991, 5,278 assessable patients were enrolled onto the National Wilms' Tumor Study (NWTS) and by the end of 1993 had contributed 39,461 person-years to a follow-up study. Expected numbers of second cancers were calculated by applying national incidence rates to person-years classified by age, sex, and calendar year. RESULTS Forty-three SMNs were observed, whereas only 5.1 were expected (standardized incidence ratio [SIR], 8.4; 95% confidence interval [CI], 6.1 to 11.4). Fifteen years after the Wilms' tumor diagnosis, the cumulative incidence of a SMN was 1.6% and increasing steadily. Abdominal irradiation received as part of the initial therapy increased the risk of a SMN (SIR, 1.43/10 Gy; 95% CI, 1.13 to 1.81). Doxorubicin potentiated the radiation effect. Among 234 patients who received doxorubicin and greater than 35 Gy of abdominal radiation, eight SMNs were observed, whereas only 0.22 were expected (SIR, 36; 95% CI, 16 to 72). Treatment for relapse further increased the SMN risk by a factor of 4 to 5. CONCLUSION These results demonstrate the importance of current efforts to limit the use of intensive chemotherapy and radiation therapy, which are now applied only to patients with the most aggressive disease. Continuing close surveillance of the great majority of Wilms' tumor patients who become long-term survivors is essential for early diagnosis of SMNs and other late sequelae of therapy.
Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study.
Authors: Bavinck J N , Tieben L M , Van der Woude F J , Tegzess A M , Hermans J , ter Schegget J , Vermeer B J 
Published: February 2017

PURPOSE The purpose of this study was to investigate the effect of acitretin on the development of keratotic skin lesions, and on squamous cell carcinomas and basal cell carcinomas in a group of renal transplant recipients. PATIENTS AND METHODS Forty-four renal transplant recipients with more than 10 keratotic skin lesions on the hands and forearms were enrolled onto a randomized, double-blind, placebo-controlled trial to test the possible skin cancer-preventing effect of a 6-month treatment with acitretin 30 mg/d. RESULTS No deterioration in renal function occurred in any of the 38 assessable patients treated. During the 6-month treatment period, two of 19 patients (11%) in the acitretin group reported a total of two new squamous cell carcinomas, compared with nine of 19 patients (47%) in the placebo group who developed a total of 18 new carcinomas (chi 2 = 6.27, P = .01). The relative decrease in the number of keratotic skin lesions in the acitretin group was 13.4%, as compared with a relative increase in the placebo group of 28.2% (difference, 41.6%; 95% confidence interval, 11.5 to 71.7). Most patients treated with acitretin had mild mucocutaneous side effects, but these were easily manageable. Some patients experienced mild hair loss. With the exception of three patients, no increase in serum cholesterol or triglyceride above pretreatment levels was observed, and liver function remained unchanged in all patients. CONCLUSION Acitretin 30 mg/d over 6 months had significantly more effect than placebo in the prevention of squamous cell carcinomas and reduced the occurrence of keratotic skin lesions in a group of renal transplant recipients with severe lesions. This effect was most pronounced in patients with a history of squamous cell carcinomas and basal cell carcinomas.
Phase I/II study of intermittent all-trans-retinoic acid, alone and in combination with interferon alfa-2a, in patients with epidemic Kaposi's sarcoma.
Authors: Bailey J , Pluda J M , Foli A , Saville M W , Bauza S , Adamson P C , Murphy R F , Cohen R B , Broder S , Yarchoan R 
Published: February 2017

PURPOSE A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added. RESULTS The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug. CONCLUSION Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.
Second solid malignancies after combined modality therapy for Hodgkin's disease.
Authors: Doria R , Holford T , Farber L R , Prosnitz L R , Cooper D L 
Published: February 2017

PURPOSE To determine the actuarial incidence (AI) and relative risk (RR) of second solid malignancies (SSM; solid tumors and non-Hodgkin's lymphoma) in patients with Hodgkin's disease who were treated with chemotherapy and adjuvant, low-dose radiation (combined modality therapy; CMT). PATIENTS AND METHODS From 1969 to 1983, 102 patients with previously untreated advanced Hodgkin's disease (group A) and 81 patients with recurrent disease after radiation (group B) were treated with CMT. Patients were observed for the development of solid tumors (ST) and non-Hodgkin's lymphoma (NHL), and the AI and RR were calculated. RESULTS Nearly half of the patients entering remission were observed for greater than 15 years. At 20 years, the AI for SSM was 12% in group A versus 41% in group B (P = .009). The overall RR for developing a ST in group A was 1.88 (not significant) versus 8.84 in group B (95% confidence interval, 5.3 to 15.4). The difference in the RR between groups A and B was significant (P < .001). The RR for developing NHL was significantly increased in both groups, but the difference between groups was not significant. CONCLUSION Previously untreated patients with advanced disease who were treated with CMT (group A) had a modest but not significant increase in the RR of ST; however, patients treated with CMT for recurrent disease (group B) had a highly significant increase in the RR of ST. Possible explanations for the increase in ST in group B include more cumulative radiation or a greater carcinogenic effect of chemotherapy in previously irradiated patients, but it also is possible that the increase is due to a longer follow-up time.
Phase I and clinical evaluation of a pharmacologically guided regimen of suramin in patients with hormone-refractory prostate cancer.
Authors: Eisenberger M A , Sinibaldi V J , Reyno L M , Sridhara R , Jodrell D I , Zuhowski E G , Tkaczuk K H , Lowitt M H , Hemady R K , Jacobs S C 
Published: February 2017

PURPOSE This phase I study was designed with the following objectives: (1) to describe the overall and dose-limiting toxicity (DLT) of suramin administered by intermittent short intravenous infusions until DLT or disease progression; (2) to determine the ability of an adaptive control with feedback (ACF) dosing strategy to maintain suramin plasma concentrations within a preselected range; (3) to develop a population model of suramin pharmacokinetics; and (4) to identify preliminary evidence of antitumor activity. PATIENTS AND METHODS Seventy-three patients with advanced, incurable, solid tumors (including 69 with hormone-refractory prostate cancer) received an initial 5- to 7-day daily loading treatment followed by intermittent infusions individually determined by ACF using a Bayesian algorithm and relying on population models of suramin pharmacokinetics. Treatment was given to three cohorts of patients based on target plasma suramin concentration ranges (peak, 30 minutes postsuramin, and trough on morning of the treatment day), as follows: cohort 1, 175 to 300 micrograms/mL (27 patients); cohort 2, 150 to 250 micrograms/mL (23 patients); and cohort 3, 100 to 200 micrograms/mL (23 patients). All patients were to receive suramin until DLT or disease progression. RESULTS The DLT was most commonly seen in cohort 1 and included a syndrome of malaise and fatigue, associated with weight loss, anorexia, and changes in taste. Other reversible toxicities were neurologic, renal, cutaneous, edema, lymphopenia and anemia, ophthalmologic, and alopecia. Forty of 67 assessable patients (60%) had a 50% reduction and 25 of 67 (37%) a 75% reduction in prostate-specific antigen (PSA) levels that lasted more than 4 weeks, seven of 18 (40%) had measurable responses, and 18 of 37 (49%) demonstrated major pain improvement. The overall times to disease progression and survival were 170 and 492 days, respectively. CONCLUSION We have characterized all toxicities with suramin in a pharmacologically guided phase I study designed to maintain plasma suramin concentrations of 100 to 300 micrograms/mL (cohorts 1 to 3). The incidence of grade 3 to 4 neurologic abnormalities was relatively low, particularly in cohorts 2 and 3 (100 to 250 micrograms/mL). Evidence of significant and durable antitumor activity was seen in all three cohorts.
Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.
Authors: Kelly W K , Scher H I , Mazumdar M , Pfister D , Curley T , Leibertz C , Cohen L , Vlamis V , Dnistrian A , Schwartz M 
Published: February 2017

PURPOSE The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity. PATIENTS AND METHODS Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydrocortisone plus suramin administered in the following manners: (1) a loading dose of suramin followed by a continuous infusion using an adaptive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric dosing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed using measurable-disease criteria, radionuclide scans, and posttherapy changes in prostate-specific antigen (PSA) levels. RESULTS Fifty-six patients were treated and plasma suramin concentrations were similar for each regimen. A partial response was observed in 4% (one of 28; 95% confidence interval, 0% to 18.4%) of patients with measurable disease, while 12% (six of 50; 95% confidence interval, 4.5% to 24.3%) had a greater than 80% decline in the baseline PSA level. The median duration of response was 12 months. No responses on radionuclide scans were seen. Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequential regimens, the frequency of renal insufficiency (P = .04) and coagulopathy (P < .0001) decreased, while transaminase elevations (P = .05) were more common using intermittent infusions (cohorts B and C) versus continuous infusion schedules (cohort A). CONCLUSION The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.
Preirradiation chemotherapy with carboplatin and etoposide in newly diagnosed embryonal pediatric CNS tumors.
Authors: Heideman R L , Kovnar E H , Kellie S J , Douglass E C , Gajjar A J , Walter A W , Langston J A , Jenkins J J , Li Y , Greenwald C 
Published: February 2017

PURPOSE We evaluated the clinical efficacy of preirradiation carboplatin (CARBO) and etoposide (VP-16) in 25 patients with newly diagnosed embryonal CNS tumors. PATIENTS AND METHODS Sixteen patients with high-risk medulloblastoma and nine with other embryonal tumors were treated with two daily doses of CARBO 350 mg/m2 and VP-16 100 mg/m2 (CARBO/VP) every 21 days for four cycles before standard craniospinal irradiation. Patients with disease progression (PD) before radiation therapy were additionally treated with intensive postirradiation cyclophosphamide (CYCLO) and vincristine (VINC). RESULTS Among 23 assessable patients, 48% (95% confidence interval, 27% to 69%) had a complete response (CR) or partial response (PR) to CARBO/VP; eight had PD. Among the subgroup of 15 assessable patients with medulloblastoma, 53% had a CR or PR (95% confidence interval, 27% to 79%) and five PD. The toxicity of CARBO/VP was predominantly hematologic; although grade IV neutropenia was common, only five episodes of febrile neutropenia occurred. Only thrombocytopenia was a more common toxicity than in other reported chemotherapy regimens; ototoxicity was less common than in cisplatin (CDDP) regimens. CONCLUSION The responses and survival associated with neoadjuvant CARBO/VP are similar to those with CDDP-containing and other neoadjuvant drug regimens. Although the rate of progression with this regimen may be higher than with similar CDDP-containing regimens, the numbers of patients in other published studies of these agents are too small to detect meaningful statistical differences. Future studies must balance the apparently comparable efficacy of CARBO and CDDP with their differing toxicities.
Impact of protracted venous infusion fluorouracil with or without interferon alfa-2b on tumor response, survival, and quality of life in advanced colorectal cancer.
Authors: Hill M , Norman A , Cunningham D , Findlay M , Watson M , Nicolson V , Webb A , Middleton G , Ahmed F , Hickish T 
Published: February 2017

PURPOSE The aim of this study was to investigate the effects of adding interferon alfa-2b (IFN) to protracted venous infusion fluorouracil (PVI 5-FU) from the start of treatment in patients with advanced colorectal cancer. PATIENTS AND METHODS Patients who attended our unit with histologically confirmed advanced colorectal cancer were randomized to receive either PVI 5-FU 300 mg/m2/d via Hickman line, and IFN 5 MU subcutaneously three times weekly, or PVI 5-FU alone. Treatment was given for a maximum of two 10-week blocks, with a 2-week gap for reassessment of all parameters. Quality of life (QL) was measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) pretreatment and every 6 weeks thereafter. RESULTS A total of 160 patients were randomized, with 155 eligible for assessment. Radiologic response was observed in 43 patients (28%): 17 of 77 (22%) in the 5-FU-plus-IFN arm (all partial responses [PRs]) and 26 of 78 (33%) in the 5-FU-alone group (complete responses [CRs] and 22 PRs) (difference not significant). Symptomatic improvement occurred in the majority of patients, and equally in both arms: 61% to 80% depending on the symptom. There was no significant difference between the two groups in failure-free survival (median, 161 v 193 days) or overall survival (median, 328 v 357 days). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .001), neutropenia (P = .04), mucositis (P = .008), and alopecia (P = .0002). There were no toxic deaths and few notable differences in QL between the two arms. CONCLUSION This study confirms that PVI 5-FU is effective in treating the symptoms associated with metastatic colorectal carcinoma, with only mild to moderate toxicity and maintenance of QL. IFN 5 MU three times weekly does not enhance these palliative benefits.
Prognostic value of size of lymph node metastases in patients with cutaneous melanoma.
Authors: Buzaid A C , Tinoco L A , Jendiroba D , Tu Z N , Lee J J , Legha S S , Ross M I , Balch C M , Benjamin R S 
Published: February 2017

PURPOSE To determine the prognostic significance of the size of the lymph node mass as measured by physical examination (PE) and of the size of the largest node measured by pathologic analysis (path) in patients with cutaneous melanoma and nodal metastases. PATIENTS AND METHODS The medical records of all patients with nodal metastases seen at The University of Texas M.D. Anderson Cancer Center from January 1, 1973 to December 31, 1989 were reviewed. Patient eligibility criteria included the following: (1) availability of data describing the nodal size either by PE or by path and the number of positive nodes; (2) no history of preoperative chemotherapy or radiotherapy; and (3) no history or presence of in-transit, satellite, local, or distant metastases. Eleven variables, including largest diameter of the nodal mass by PE and diameter of the largest node by path, were examined as potential prognostic factors for disease-free survival (DFS) and overall survival (OS). RESULTS Of 800 patients evaluated, 442 met the eligibility criteria and are the subjects of this study. In the univariate analysis, size of the nodal mass by PE was marginally significant for survival as a continuous variable (P = .045), but not as a categorical variable using a cutoff size of < or = 3 or more than 3 cm as indicated by the American Joint Committee on Cancer (AJCC) staging system (P = .61). Size of the largest node by path was not significant for survival. In the multivariate analysis, only the number of positive nodes (P < .001), age (P < .001), and tumor thickness (P < .001) were significant for survival. CONCLUSION Size of the nodal mass by PE and size of the largest node by path are not useful prognostic factors for survival and should be eliminated from the current staging system. More powerful and well-established prognostic factors, such as the number of positive nodes, should be considered for inclusion in staging.