bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin‐based chemotherapy for diffuse large B‐cell lymphoma in elderly patients
Authors: Lee Keun‐Wook , Kim Dae‐Young , Yun Tak , Kim Dong‐Wan , Kim Tae‐You , Yoon Sung‐Soo , Seog Heo Dae , Bang Yung‐Jue , Park Seonyang , Kook Kim Byoung , Kyeong Kim Noe 
Published: December 2003

AbstractBACKGROUNDAlthough many studies of elderly patients with non‐Hodgkin lymphoma have focused on the dose intensity of chemotherapy, few studies have restricted the histologic inclusion criteria such that only patients with diffuse large B‐cell lymphoma (DLCL) are considered. In the current study, treatment outcomes for elderly patients (age ≥ 60 years) were analyzed, with emphasis on the dose intensity of doxorubicin.METHODSBetween 1994 and 2000, 195 patients with DLCL were treated initially with doxorubicin‐based chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, vincristine, bleomycin, doxorubicin, procarbazine, and prednisone). Of these patients, 70 were aged 60 years or older.RESULTSElderly patients had poorer treatment outcomes than did young patients (5‐year survival, 30% vs. 57%;P< 0.001); however, elderly patients who received doxorubicin at dose intensities ≥ 10 mg/m2per week (n= 25) had outcomes (5‐year survival, 52%) that were comparable to those of young patients. Among prognostic factors, only International Prognostic Index score (P= 0.022) and dose intensity of doxorubicin (P= 0.039) were found to have significant effects on the overall survival of elderly patients. When the reasons for doxorubicin dose reduction in 45 elderly patients who ultimately received doxorubicin at dose intensities < 10 mg/m2per week were analyzed, it was found that 20 patients received reduced doses from the start of treatment because of their old age alone; these dose reductions in the 20 cases resulted in poorer treatment outcomes.CONCLUSIONSElderly patients with DLCL who received doxorubicin at dose intensities ≥ 10 mg/m2per week had treatment outcomes that were comparable to those of young patients; however, physician bias associated with patient age was found to be related to unnecessary dose reductions. Efforts to maintain doxorubicin dose intensities ≥ 10 mg/m2per week and more objective standards for the selection of elderly patients capable of tolerating doxorubicin‐based regimens are required. Cancer 2003;98:2651–6. © 2003 American Cancer Society.
Prophylactic oophorectomy
Authors: Schlosshauer Peter W. , Cohen Carmel J. , Penault‐Llorca Frederique , Miranda Carlos R. , Bignon Yves‐Jean , Dauplat Jacques , Deligdisch Liane 
Published: December 2003

AbstractBACKGROUNDThe tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia‐associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium.METHODSMorphologic features and immunohistochemical expression patterns of CA‐125, Ki‐67, p53, E‐cadherin, and Bcl‐2 were evaluated in 21 normal ovaries, 31 ovaries that were removed prophylactically for increased carcinoma risk, and 7 ovarian papillary serous carcinomas. Representative slides from formalin‐fixed, paraffin‐embedded tissue blocks were submitted to immunohistochemical staining and were evaluated independently by three gynecologic pathologists. For statistical analyses, Fisher exact tests, multivariate analyses, Spearman rank correlation coefficients, Wald statistics, Kruskal–Wallis tests, and Mann–Whitney tests were used. Immunohistochemical staining results were correlated with morphologic findings.RESULTSThe authors found progressive increases in reactivity with the lowest expression in normal ovarian epithelium, stronger expression in epithelium from prophylactically removed ovaries, and the highest expression in carcinomas for Ki‐67 and p53. A similar trend was observed for CA‐125. Positivity for Ki‐67 and p53 was seen predominantly in the epithelium of inclusion cysts and deep invaginations, including those areas that had been identified as hyperplastic or dysplastic on routine hematoxylin and eosin‐stained sections.CONCLUSIONSThe current results suggest biologic/molecular evidence for the existence of preneoplastic changes in ovarian surface epithelium and support the previously proposed concept of ovarian dysplasia. Subtle morphologic alterations of the ovarian epithelium may be biologically significant. Cancer 2003;98:2599–606. © 2003 American Cancer Society.
Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma
Authors: Rasiah Kris K. , Stricker Phillip D. , Haynes Anne‐Maree , Delprado Warick , Turner Jennifer J. , Golovsky David , Brenner Phillip C. , Kooner Raji , O'Neill Gordon F. , Grygiel John J. , Sutherland Robert L. , Henshall Susan M. 
Published: December 2003

AbstractBACKGROUNDIn the current study, the authors sought to further stratify the prognosis of patients with Gleason score (GS) 7 prostate carcinoma. They assessed the influence on outcome of a predominant poorly differentiated Gleason pattern (primary Gleason pattern [GP] 4) and/or a coincident small focus of poorly differentiated tumor of higher grade (tertiary GP 5).METHODSThe authors studied 412 patients (mean postoperative follow‐up, 33 months) with GS 7 tumors treated with radical prostatectomy at a single Australian campus between November 1989 and December 2002. The chi‐square test, Kaplan–Meier method, and Cox proportional hazards analyses were used to evaluate the correlation between primary GP 4 and tertiary GP 5 with the occurrence of adverse pathologic features and disease recurrence.RESULTSIn this cohort, 307 patients (75%) had primary GP 3 tumors, 105 (25%) had primary GP 4 tumors, and 17 (2.3%) had a tertiary element of high‐grade tumor (GP 5). Patients with primary GP 4 tumors displayed higher rates of seminal vesicle involvement and extraprostatic extension and, along with patients with tertiary GP 5, had significantly shorter times to disease recurrence. Univariate analysis demonstrated that primary GP 4 (P = 0.0003) and tertiary GP 5 (P < 0.0001) were strong predictors of disease recurrence. Primary GP 4 (P = 0.0122) remained an independent predictor of disease recurrence on stepwise multivariate analysis.CONCLUSIONSPrimary GP 4 tumors represented an aggressive subset of GS 7 prostate carcinomas. Primary GP was an easily accessible and clinically relevant predictor of disease recurrence in patients with GS 7 prostate carcinoma. Cancer 2003;98:2560–5. © 2003 American Cancer Society.
Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma
Authors: Leibovich Bradley C. , Han Ken‐ryu , Bui Matthew H. T. , Pantuck Allan J. , Dorey Frederick J. , Figlin Robert A. , Belldegrun Arie 
Published: December 2003

AbstractBACKGROUNDThe objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy.METHODSThe medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin‐2 (IL‐2)‐based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid‐stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease‐specific survival was estimated using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival.RESULTSThe median follow‐up was 3.2 years (range, 0.2–9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low‐risk, intermediate‐risk, and high‐risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low‐risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high‐risk group had 1% survival at 1 year and no survivors at 3 years.CONCLUSIONSIn patients with metastatic RCC who were treated with nephrectomy and IL‐2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials. Cancer 2003;98:2566–75. © 2003 American Cancer Society.
Quantitative alterations in nuclear structure predict prostate carcinoma distant metastasis and death in men with biochemical recurrence after radical prostatectomy
Authors: Khan Masood A. , Walsh Patrick C. , Miller M. Craig , Bales Wesley D. , Epstein Jonathan I. , Mangold Leslie A. , Partin Alan W. , Veltri Robert W. 
Published: December 2003

AbstractBACKGROUNDMicroscopic histologic grade has been the best predictor of prostate carcinoma (PCa) progression in men after surgical therapy. The ability to predict accurately, at the time of surgery, which patients are likely to develop metastatic PCa would enable optimization of disease management with adjuvant therapy. The authors assessed the ability of pathologic, nuclear morphometric, and chromatin parameters to predict metastatic PCa progression and/or death in 227 men with biochemical recurrence and long‐term follow‐up after undergoing radical prostatectomy.METHODSMultivariate logistic regression (LR) was used to calculate quantitative nuclear grade (QNG) solutions using the variances of 60 nuclear morphometric descriptors (NMDs) of nuclear size, shape, DNA content, and chromatin organization that predicted distant metastasis and/or PCa‐specific death. An LR model also was generated to predict this outcome using a combination of pathologic variables and the best QNG solution. Cox proportional hazards models were generated, and Kaplan–Meier plots were used to display three risk groups based on pathology, QNG, and a combination of these variables.RESULTSA multivariate LR model using pathology retained lymph node (LN) status, seminal vesicle status, and prostatectomy Gleason score, yielding an area under the curve–receiver operator characteristic (AUC‐ROC) of 75% with an accuracy of 59% at 90% sensitivity. The best QNG solution used the variance of 25 NMDs, yielding an AUC‐ROC of 84% and an accuracy of 70% at 90% sensitivity. The combined pathology‐QNG model retained LN status, prostatectomy Gleason score, and QNG, yielding an AUC‐ROC of 86% with an accuracy of 76% at 90% sensitivity. The Cox proportional hazards models produced the following significant univariate and multivariate hazard ratios: QNG, 3.5 and 2.9, respectively; LN, 2.7 and 1.8, respectively; and prostatectomy Gleason score, 2.8 and 2.1, respectively.CONCLUSIONSAlterations in the structure of tumor nuclei measured by computer‐assisted image analysis were strong predictors of PCa progression and death in men with long‐term follow‐up who had biochemical recurrence after undergoing radical prostatectomy. QNG solutions can serve as a new supplemental biomarker for accurate prediction of PCa progression at the time of surgery. Cancer 2003;98:2583–91. © 2003 American Cancer Society.
Correlation of bcl‐2 and p53 expression in primary breast tumors and corresponding metastatic lymph nodes
Authors: Arun Banu , Kilic Gokhan , Yen Charles , Foster Barbara , Yardley Denise , Gaynor Richard , Ashfaq Raheela 
Published: December 2003

AbstractBACKGROUND.The p53 tumor suppressor gene product participated in G1 cell cycle arrest or cell death. Loss of function was associated with poor outcome in patients with breast carcinoma. bcl‐2 prevented apoptosis induced by c‐myc or growth factor deprivation. High bcl‐2 expression in breast tumor tissue specimens appears to be associated with favorable prognostic factors. However, Bcl‐2 and p53 expression in primary tumor tissue specimens versus metastatic lymph node specimens in breast carcinoma has not been studied. The current study compared Bcl‐2 and p53 expression in primary breast carcinoma tissue specimens with Bcl‐2 and p53 expression in axillary lymph node specimens.METHODS.Primary breast tumor and corresponding axillary metastatic lymph node tissue specimens were obtained from 60 patients with breast carcinoma. They were evaluated for the presence of Bcl‐2 and p53 expression by immunohistochemistry using standard methods.RESULTS.Bcl‐2 expression in primary tumor tissue specimens (53%) was correlated with Bcl‐2 expression in metastatic lymph node specimens (50 %; Pearson correlation = 0.656). p53 expression in primary tumor specimens (72%) was correlated with p53 expression in metastatic lymph node specimens (60 %; Pearson correlation = 0.800). A significant inverse correlation also was found between p53 and Bcl‐2 expression in primary breast tumor tissue specimens (Pearson correlation = −0.310).CONCLUSIONS.The current study suggested that Bcl‐2 and p53 expression in axillary metastatic lymph node specimens is correlated with Bcl‐2 and p53 expression in the primary tumor tissue specimens. The prognostic and predictive value of Bcl‐2 and p53 expression in axillary lymph node metastasis in patients with breast carcinoma needs to be further evaluated in larger trials with longer follow‐up. Cancer 2003;98:2554–9. © 2003 American Cancer Society.
Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules
Authors: Taïeb Julien , Bonyhay Luminita , Golli Lamia , Ducreux Michel , Boleslawski Emmanuel , Tigaud Jean‐Marie , de Baere Thierry , Mansourbakht Touraj , Delgado Marie Anna , Hannoun Laureut , Poynard Thierry , Boige Valerie 
Published: December 2003

AbstractBACKGROUNDNew therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine‐oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC.METHODSTwenty‐one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX‐1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX‐2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred.RESULTSAll patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13–26%), including 3 patients in the GEMOX‐1 group and 1 patient in the GEMOX‐2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression‐free survival was 5 months, and the median overall survival was 12 months. Fifty‐four percent of patients in the GEMOX‐1 group and 50% of patients in the GEMOX‐2 group had received previous systemic chemotherapy or cisplatin‐based chemoembolization. Grade 3–4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX‐1 vs. GEMOX‐2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3–4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX‐1 and in 7 patients and 1 patient receiving GEMOX‐2.CONCLUSIONSGemcitabine‐oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX‐1 regimen was tolerated better than the GEMOX‐2 regimen. Currently, the GEMOX‐1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC. Cancer 2003;98:2664–70. © 2003 American Cancer Society.
A two‐arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas
Authors: Trent Jonathan C. , Beach Jennifer , Burgess Michael A. , Papadopolous Nicholas , Chen Lei L. , Benjamin Robert S. , Patel Shreyaskumar R. 
Published: December 2003

AbstractBACKGROUNDThe authors conducted a two‐arm Phase II study of temozolomide to determine its efficacy and toxicity in patients with soft tissue sarcomas (STSs) who had received, had refused, or were not eligible for standard chemotherapy with doxorubicin and ifosfamide (Arm 1) and in patients with gastrointestinal stromal tumors (GISTs; Arm 2). Patients with GIST were eligible regardless of prior therapy before imatinib was available.METHODSSixty patients were enrolled in the current study, 19 of whom had GISTs and 41 of whom had other STSs. The patients received temozolomide at a dose of 85 mg/m2 orally for 21 days followed by 7 days without treatment. Standard radiographic imaging after every two cycles was used to assess the treatment response.RESULTSOf the 39 patients in Arm 1, there was 1 complete response and 1 partial response of 39 evaluable patients, for a total response rate of 5% (95% confidence interval, 0–12%). The responses lasted 7 months and 8 months, respectively. In Arm 2, there was no response in 17 patients. The disease was stable in 22% of the patients with GISTs and 33% of the patients with other STSs. The median overall survival time was 26.4 months in patients with GISTs and 11 months in patients with other STSs. The median time to disease progression was 2.3 months in patients with GISTs and 3.3 months in patients with other STSs. Grade 3 and Grade 4 adverse effects (according to National Cancer Institute Common Toxicity Criteria) were rare and included fatigue (eight patients), anemia (six patients), constipation (four patients), neutropenia (four patients), and thrombocytopenia (four patients).CONCLUSIONSThe data from the current study suggest that temozolomide is well tolerated but has only minimal efficacy and a limited role in the treatment of patients with STSs. Cancer 2003;98:2693–9. © 2003 American Cancer Society.
Complications in long‐term survivors of Ewing sarcoma
Authors: Fuchs Bruno , Valenzuela Richard G. , Inwards Carrie , Sim Franklin H. , Rock Michael G. 
Published: December 2003

AbstractBACKGROUNDMultimodality treatment has dramatically improved the outcome of patients with Ewing sarcoma. However, there appears to be little information concerning treatment‐related complications in patients who are long‐term survivors.METHODSForty‐one patients with Ewing sarcoma who were treated between 1960–1980 and who survived the disease by at least 20 years were included in the current study. In a retrospective analysis, all complications related to the multimodality treatment of Ewing sarcoma were assessed.RESULTSThe patient group was comprised of 17 men and 24 women, with a mean age at the time of presentation of 16.8 years (range, 5–51 years). Approximately 20% of the lesions were located in the pelvis. All but 9 patients (78%) received chemotherapy as part of their treatment. The overall follow‐up period averaged 25 years (range, 20–36 years). All except 1 patient were alive at the time of final follow‐up, with the latter patient dying of radiation‐induced secondary malignancy after 33 years. Only 17 patients (41%) were found to be free of any complication. These included metastases, local recurrence, secondary malignancies, pathologic fractures, and radiation‐associated and chemotherapy‐associated morbidities.CONCLUSIONSAlthough the patients in the current study were treated successfully in terms of surviving an aggressive tumor, the high complication rate in this group of long‐term survivors is noteworthy and indicates that long‐term follow‐up should be mandatory. Cancer 2003;98:2687–92. © 2003 American Cancer Society.DOI 10.1002/cncr.11891
Potential gains from CO2 trading in the EU
Authors: Svendsen Gert Tinggaard , Vesterdal Morten 
Published: December 2003

AbstractA new Green Paper from the European Commission on emissions trading foresees the setting up of a CO2 trading system within the EU for the energy sector. Because any such international environmental agreement is self‐enforcing, the participants must have an economic net gain from joining the proposed system. Our contribution is therefore to follow the Green Paper proposal and investigate whether member countries and the largest industrial boilers in the electricity sector actually will receive significant net gains from CO2 trade in the European Union rather than undertaking domestic actions solely. We show, based on the PRIMES model, that a full CO2 emission trading system between Annex B countries suggests overall cost savings of the order of 40% compared with a situation with no trading at all between member states. A tradable CO2 permit scheme with comprehensive coverage of emissions within the EU could reduce the total abatement costs by 32% compared with a system with no trading. In comparison, a Community‐wide system containing only the electricity and steam sector would reduce the total abatement costs by 13% only. Though a tradable CO2 permit market for the power and steam sector can provide significant gains from trading, these gains can be almost four times higher than for a trade system that includes all sectors in the EU. Thus, the electricity and steam sector is a fit target group as starting point, but in the longer run the system must be organized in a way that provides opportunities for other sectors to ‘opt in’ over time. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
The EU Water Framework Directive: part 1. European policy‐making and the changing topography of lobbying
Authors: Kaika Maria , Page Ben 
Published: December 2003

AbstractThis paper is a history of the making of the European Union's Water Framework Directive (WFD). It will be followed by a second paper, which analyses the relationship between the innovations of the WFD and a range of different interest groups. This directive is of particular interest to commentators on EU policy‐making because it was created through the co‐decision process, in which the Council of Ministers and the European Parliament have joint influence over the final text. Following substantive differences in position between the two bodies the WFD was finalized through a conciliation process in June 2000. This change in the practice of European decision‐making has allowed non‐governmental organizations new opportunities to participate in water policy‐making and to have a greater influence on EU directives. It is argued that the environmental lobby has adapted swiftly to these changes and used them to considerable advantage in pursuit of its own goals. The passage of the legislation between 1998 and 2000 is described, paying careful attention to who participated in the process of amending the draft directive and what major amendments were made. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.