bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 Overexpression and Doxorubicin in Adjuvant Chemotherapy for Resectable Breast Cancer
Authors: Moliterni Angela , Ménard Sylvie , Valagussa Pinuccia , Biganzoli Elia , Boracchi Patrizia , Balsari Andrea , Casalini Patrizia , Tomasic Gorana , Marubini Ettore , Pilotti Silvana , Bonadonna Gianni 
Published: January 2003

Purpose: Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2− tumors in terms of relapse-free survival (RFS) and overall survival (OS). Methods: Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors. Results: Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2− tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; CI, 0.32 to 1.16) than in HER2− patients (HR = 1.26). Conclusion: Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors.
Prognostic Significance of Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen in Metastatic Prostate Cancer: A Nested Study Within CALGB 9583
Authors: Halabi Susan , Small Eric J. , Hayes Daniel F. , Vogelzang Nicholas J. , Kantoff Philip W. 
Published: January 2003

Purpose: To determine whether reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating prostate-specific antigen (PSA)-positive cells is a prognostic factor for survival in hormone refractory prostate cancer and to validate the prognostic importance of this test in relation to other known prognostic factors. Patients and Methods: A single centralized laboratory received and analyzed whole blood for RT-PCR for PSA for a subset of patients enrolled on two Cancer and Leukemia Group B (CALGB) randomized trials (CALGB 9583 and CALGB 9480). Using 9583, a prognostic model was developed and an independent data set (CALGB 9480) was used to validate the fitted model. Results: Of 162 patients in 9583, 91 (56%) patients were negative for RT-PCR for PSA and 71 (44%) patients were positive. The median survival time was 21 months (95% confidence interval [CI], 18 to 27 months) for RT-PCR-negative patients compared with 11 months (95% CI, 8 to 15 months) for RT-PCR-positive patients (P ≤ .001). In multivariable analysis, the hazard ratio (HR) for death was 1.7 (95% CI, 1.2 to 2.4; P = .006) for positive RT-PCR patients compared with negative RT-PCR patients. A fitted model that incorporated RT-PCR for PSA and other factors was used to classify patients from 9480 into one of two risk groups: low or high. We observed good agreement between the observed and predicted survival probabilities for the two risk groups. Conclusion: RT-PCR to detect PSA-positive circulating cells is confirmed to be a significant prognostic factor of survival in patients with hormone refractory prostate cancer. This model could be used to stratify patients in randomized phase III trials.
Does Delay in Starting Treatment Affect the Outcomes of Radiotherapy? A Systematic Review
Authors: Huang Jenny , Barbera Lisa , Brouwers Melissa , Browman George , Mackillop William J. 
Published: January 2003

Purpose: The objective of this study was to synthesize what is known about the relationship between delay in radiotherapy (RT) and the outcomes of RT. Methods: A systematic review of the world literature was conducted to identify studies that described the association between delay in RT and the probability of local control, metastasis, and/or survival. Studies were classified by clinical and methodologic criteria and their results were combined using a random-effects model. Results: A total of 46 relevant studies involving 15,782 patients met our minimum methodologic criteria of validity; most (42) were retrospective observational studies. Thirty-nine studies described rates of local recurrence, 21 studies described rates of distant metastasis, and 19 studies described survival. The relationship between delay and the outcomes of RT had been studied in diverse situations, but most frequently in breast cancer (21 studies) and head and neck cancer (12 studies). Combined analysis showed that the 5-year local recurrence rate (LRR) was significantly higher in patients treated with adjuvant RT for breast cancer more than 8 weeks after surgery than in those treated within 8 weeks of surgery (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.21 to 2.16). Combined analysis also showed that the LRR was significantly higher among patients who received postoperative RT for head and neck cancer more than 6 weeks after surgery than among those treated within 6 weeks of surgery (OR = 2.89; 95% CI, 1.60 to 5.21). There was little evidence about the impact of delay in RT on the risk of metastases or the probability of long-term survival in any situation. Conclusion: Delay in the initiation of RT is associated with a decrease in LRR in breast cancer and head and neck cancer. Delays in starting RT should be as short as reasonably achievable.
Impact of Diabetes Mellitus on Outcomes in Patients With Colon Cancer
Authors: Meyerhardt Jeffrey A. , Catalano Paul J. , Haller Daniel G. , Mayer Robert J. , Macdonald John S. , Benson Al B. , Fuchs Charles S. 
Published: January 2003

Purpose: To determine the influence of diabetes mellitus on long-term outcomes and treatment-related toxicity among patients with curatively resected colon cancer. Patients and Methods: This study was a cohort study within a large, randomized adjuvant chemotherapy trial of 3,759 patients with high-risk stage II and stage III colon cancer treated between 1988 and 1992 throughout the United States. In the cohort, 287 patients were identified as having diabetes mellitus. With a median follow-up of 9.4 years, we analyzed differences in overall survival (OS) and colon cancer recurrence as well as treatment-related toxicity between patients with diabetes and those without diabetes. Results: At 5 years, patients with diabetes mellitus, compared with patients without diabetes, experienced a significantly worse disease-free survival (DFS; 48% diabetics v 59% nondiabetics; P < .0001), OS (57% v 66%; P < .0001), and recurrence-free survival (RFS; 56% v 64%, P = .012). Median survival was 6.0 years and 11.3 years for diabetics and nondiabetics, respectively. Compared with patients without a history of diabetes, those with diabetes had a 42% increased risk of death from any cause (P < .0001) and 21% increased risk for recurrence (P = .05) after adjustment for other predictors of colon cancer outcome. Treatment-related toxicities were similar between the two groups, although patients with diabetes experienced an increase in treatment-related diarrhea. Conclusion: Patients with diabetes mellitus and high-risk stage II and stage III colon cancer experienced a significantly higher rate of overall mortality and cancer recurrence, even after adjustment for other predictors of colon cancer outcome. These results underscore the need for further research to understand the mechanism that underlies this relation.
Dispositional Optimism Predicts Survival Status 1 Year After Diagnosis in Head and Neck Cancer Patients
Authors: Allison Paul J. , Guichard Christophe , Fung Karen , Gilain Laurent 
Published: January 2003

Purpose: The aim of this study was to investigate the hypothesis that, independent of other known prognostic factors, pessimistic head and neck (H&N) cancer patients have a greater risk of being dead 1 year after diagnosis than do optimistic patients. Patients and Methods: A prospective observational study design was used with a cohort of H&N cancer patients diagnosed during the period from March 1, 1997, to August 31, 1998, at the Centre Hospitalier Universitaire, Clermont-Ferrand, France. Dispositional optimism (DO) was evaluated at baseline using a French version of the Life Orientation Test translated and validated for this study. One-year survival status was collected on all subjects. The analysis of the hypothesized association between DO and 1-year survival was performed using multiple logistic regression analysis, controlling for other sociodemographic and clinical variables. Results: The sample size was 101 patients, representing all but one of those patients fitting the inclusion criteria who were diagnosed during the recruitment period. Of these, 51 were alive at 1 year after diagnosis, 45 were dead, and five were lost to follow-up. The multivariate analysis was performed on the data from the 96 subjects in whom 1-year survival status was known. Controlling for known predictors of H&N cancer survival, pessimistic subjects (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01 to 1.24) and those living alone (OR, 4.14; 95% CI, 1.21 to 14.17) were more likely than optimistic subjects and those living with others to be dead at 1 year. Conclusion: The results of this study of a cohort of French H&N cancer patients indicate that dispositional optimism predicts 1-year survival independent of other sociodemographic and clinical variables.
Phase II Trial of Systemic Continuous Fluorouracil and Subcutaneous Recombinant Interferon Alfa-2b for Treatment of Hepatocellular Carcinoma
Authors: Patt Yehuda Z. , Hassan Manal M. , Lozano Richard D. , Brown Thomas D. , Vauthey J. Nicolas , Curley Steven A. , Ellis Lee M. 
Published: January 2003

Purpose: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNα2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics. Patients and Methods: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d × 21 every 28 days) and subcutaneous (SC) rIFNα2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients. Results: The median ages of the patients were 63.5 and 19 years among HCC and FLHCC patients, respectively. Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients. Nine of 36 (25%; four of 28 [14%] HCC patients; five of eight [62.5%] FLHCC patients) patients in which a response could be assessed had a complete response (CR; one patient with FLHCC and no patients with HCC) or partial response (PR; eight patients [four HCC and four FLHCC patients]). Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation. One FLHCC patient also underwent resection without clear margins. Overall median survival was 19.5 months (95% confidence interval [CI], 11.2 to 27.8 months); median survival was 15.5 months (95% CI, 8.5 to 22.5 months) among HCC patients, and that of FLHCC patients was 23.1 months (95% CI, 10.3 to 35.9 months). Overall grade 3 or 4 toxicity included stomatitis (32.6%), fatigue (4.7%), and hematologic toxicity (9.3%). Conclusion: Continuous IV FU and thrice-weekly SC rIFNα2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease. This regimen has activity in HCC and can be tolerated even by cirrhotic patients.
Management and Outcome Differences in Supraglottic Cancer Between Ontario, Canada, and the Surveillance, Epidemiology, and End Results Areas of the United States
Authors: Groome Patti A. , O’Sullivan Brian , Irish Jonathan C. , Rothwell Deanna M. , Schulze Karleen , Warde Padraig R. , Schneider Ken M. , Mackenzie Robert G. , Hodson D. Ian , Hammond J. Alex , Gulavita Sunil P.P. , Eapen Libni J. , Dixon Peter F. , Bissett Randy J. , Mackillop William J. 
Published: January 2003

Purpose: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. Methods: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. Results: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P = .01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P = .40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P = .28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P = .10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P = .01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10−3). In stage III disease, the rates were 30% and 54%, respectively (P = .03), and in stage IV disease they were 33% and 64% (P = .002). Conclusion: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.
HER-2/neu Overexpression and Response to Oophorectomy Plus Tamoxifen Adjuvant Therapy in Estrogen Receptor-Positive Premenopausal Women With Operable Breast Cancer
Authors: Love Richard R. , Duc Nguyen Ba , Havighurst Thomas C. , Mohsin Syed K. , Zhang Qian , DeMets David L. , Allred D. Craig 
Published: January 2003

Purpose: Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment. We studied 282 patients participating in a randomized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry. Patients and Methods: Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used. Results: HER-2/neu overexpression was a negative prognostic factor for overall survival. In univariate analyses, in HER-2/neu-positive patients, the hazard ratio (HR) for disease-free survival (DFS) with adjuvant endocrine therapy was 0.37 (95% confidence interval [CI], 0.26 to 0.89); for HER-2/neu-negative patients, the corresponding HR for DFS was 0.48 (95% CI, 0.31 to 0.71). The overall survival (OS) data were HR=0.26 (95% CI, 0.07 to 0.92) and HR=0.68 (95% CI, 0.32 to 1.42) for HER-2/neu-positive and HER-2/neu-negative patients, respectively. In multivariate models, the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS, respectively. Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment. Conclusion: HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor–positive tumors.
Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non–Small-Cell Lung Cancer
Authors: Swinson Daniel E.B. , Jones J. Louise , Richardson Donna , Wykoff Charles , Turley Helen , Pastorek Jaromir , Taub Nick , Harris Adrian L. , O’Byrne Kenneth J. 
Published: January 2003

Purpose: To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non–small-cell lung cancer (NSCLC). Methods: Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained. Results: CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 μm, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CA IX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors. Conclusion: These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype.
A classification of FASTEX cyclones using a height‐attributable quasi‐geostrophic vertical‐motion diagnostic
Authors: Deveson A. C. L. , Browning K. A. , Hewson T. D. 
Published: January 2003

AbstractA systematic and objective procedure is developed for applying the simple cyclone classification scheme of Petterssen and Smebye. This method uses a height‐attributable solution of the quasi‐geostrophic ! equation to identify and quantify the relative importance of upper‐ and lower‐tropospheric forcing and also the time trend in the horizontal spacing of the forcing at these two levels. By applying this classification method to a sample of cyclogenesis events, during their maximum intensification stage, from the Fronts and Atlantic Storm‐Track EXperiment field experiment, the Type A and Type B scheme of Petterssen and Smebye is reproduced and extended to include a Type C. Type C consists of upper‐level dominated cyclones that form at high latitudes and in their initial stages resemble comma‐cloud‐type polar lows. Detailed examples of each of the three types are presented. Some cyclones can undergo more than one period of development and it is found that each development period can be classified as a different cyclogenesis category, A or B: these cyclones are classified as hybrid Type A=B. There is some evidence that cyclone forecast accuracy depends on cyclone type, thereby suggesting the potential for this method to be used to assign confidence levels for forecasts of cyclogenesis produced by numerical weather‐prediction models. Type B cyclones appear more difficult to predict, because their development depends, initially, on the interaction between significant features in the upper and lower troposphere. Copyright © 2002 Royal Meteorological Society. T. D. Hewson's contribution is Crown copyright.
The response of CAPE and CIN to tropospheric thermal variations
Authors: Parker D. J. 
Published: January 2003

AbstractIn the absence of moist convection, convective available potential energy (CAPE) and convective inhibition (CIN) both respond to changes in the thermal and humidity profiles of the atmosphere. It is shown that these changes can be understood in terms of a direct effect, involving changes in the profile in the absence of parcel changes, and an indirect effect involving changes in air‐parcel evolution in a developing convective boundary layer. Succinctly, low‐wave‐number (deep) changes in the thermal profile maximize the direct influence on CAPE while higher‐wave‐number (shallower, near‐surface) thermal changes maximize the direct influence on CIN. A simple estimate of the direct influence on CAPE, which is independent of the assumptions relating to choice of parcel ascent, is shown to give accurate results.The indirect influence comes about as a result of changes in the stability of the profile just above the inversion: the stability acts as a control on the entrainment of dry air into the boundary layer under conditions of surface heating, so that a boundary layer growing into a stable lower troposphere is more humid than one growing into a less stable profile, with significantly higher equivalent potential temperature. Thus, a profile of relatively high stability just above the inversion, typically exhibiting high CIN, will also tend to allow CAPE to build up in the boundary layer quite rapidly, through a suppression of the entrainment under conditions of surface heating and boundary‐layer growth. Thus it may be said that high CIN tends to lead to the accumulation of high CAPE even in the absence of convective downdraught feedbacks. Copyright © 2002 Royal Meteorological Society.
Mechanisms leading to singular‐vector growth for FASTEX cyclones
Authors: Montani A. , Thorpe A. J. 
Published: January 2003

AbstractCalculations of localized singular vectors (SVs) are performed using the European Centre for Medium‐Range Weather Forecasts prediction model and the dynamical properties responsible for the SVs' growth are investigated. Potential vorticity (PV) diagnostics are used to investigate the dynamical processes responsible for SV growth in terms of total energy and PV. The independent evolution of perturbations initially confined either in the lower or in the upper troposphere is considered in order to identify the more dynamically active regions within an SV. The extent to which balanced‐flow theory, valid in idealized models of non‐normal growth, can be applied during the evolution of SVs is also examined. It is found that the part of the SV located below 500 hPa plays a major role in the interaction processes between the perturbation and the basic‐state fields and is responsible for the SVs' energy growth. SVs are also shown to grow in terms of PV due to SV advection of the basic‐state PV horizontal gradients. Perturbations initially confined at low levels can propagate vertically more efficiently than those localized above 500 hPa and the interaction with the upper‐level basic‐state fields is much more effective, leading to PV growth. If SVs are calculated with the total‐energy norm, their initial state is found to be somewhat out of balance, because of a relative lack of amplitude in the vorticity component. During their evolution, SVs achieve a more balanced configuration. Copyright © 2002 Royal Meteorological Society.