bluuebunny/crossref_metadata_2025 huggingface dataset:
The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era
Authors: Korshunov Andrey , Golanov Andrey , Sycheva Regina , Timirgaz Valery
Published: March 2004

BACKGROUND

Ependymomas account for 3–5% of all intracranial malignancies and occur most often in children and young adults. These neoplasms continue to generate considerable controversy with regard to their rational clinical management. It has been shown that the histologic classification of ependymoma is a significant predictor of clinical outcome in patients with ependymoma.

METHODS

Ependymomas from 258 patients who underwent microsurgery at a single institution were evaluated histologically to elucidate the prognostic utility of a recently proposed grading scheme. Pathologic and clinical data then were compared using univariate and multivariate analyses.

RESULTS

Increasing grade of ependymoma malignancy was found to be associated strongly and independently with worse clinical outcomes in terms of both event‐free survival and overall survival. The effect of radiotherapy also was found to be related to histologic grade and was more beneficial for patients who had anaplastic ependymomas and had undergone complete tumor removal.

CONCLUSIONS

The application of a uniform diagnostic criteria for grading ependymomas highlighted the key role of tumor histology in clinical outcome in a cohort of patients who were treated in the microsurgical era. The recently proposed grading scheme is likely to be practically useful, reproducible, and clinically applicable. Cancer 2004. © 2004 American Cancer Society.
Optimism and survival in lung carcinoma patients
Authors: Schofield Penelope , Ball David , Smith Jennifer G. , Borland Ron , O'Brien Peter , Davis Sidney , Olver Ian , Ryan Gail , Joseph David
Published: March 2004

BACKGROUND

It is popular belief that the psychologic response to a diagnosis of cancer influences survival in patients with cancer; however, research has produced contradictory results. In this prospective study, the authors investigated the relation between pretreatment levels of optimism and survival in patients with nonsmall cell lung carcinoma (NSCLC).

METHODS

Two hundred four patients who were participating in a randomized trial that compared accelerated and conventional radiotherapy with and without carboplatin chemotherapy were asked to complete two questionnaires assessing optimism. The first assessment was just prior to commencing treatment and the second assessment took place after completing treatment. Survival was measured from the date of randomization to the date of death. Surviving patients were followed until February 8, 2001.

RESULTS

The pretreatment questionnaire was completed by 179 patients, and 148 of those patients completed the posttreatment questionnaire. There was a small but significant reduction in optimism scores after treatment (P = 0.005). There was no association noted between pretreatment optimism and progression‐free survival (P = 0.52, unadjusted; P = 0.22, adjusted for Eastern Cooperative Oncology Group performance status and patient age), nor was there an association noted between pretreatment optimism and overall survival (P = 0.36, unadjusted; P = 0.19, adjusted for disease stage).

CONCLUSIONS

There was no evidence that a high level of optimism prior to treatment enhanced survival in patients with NSCLC. Encouraging patients to “be positive” only may add to the burden of having cancer while providing little benefit, at least in patients with NSCLC. Cancer 2004. © 2004 American Cancer Society.
Frequency and risk factors for meningioma in clinically healthy 75‐year‐old patients
Authors: Krampla Wolfgang , Newrkla Stephan , Pfisterer Wolfgang , Jungwirth Susanne , Fischer Peter , Leitha Thomas , Hruby Walter , Tragl Karl Heinz
Published: March 2004

BACKGROUND

The prevalence of clinically silent intracranial tumors in specific populations is poorly researched. It is known that, in advanced age groups, the number of clinically manifest meningiomas constitute a small proportion of the actual number of cases. The goals of the current study were to determine the frequency of asymptomatic patients with meningioma in advanced age and to identify risk factors for meningiomas in this population.

METHODS

Between May 2000 and November 2002, 532 probands from a specifically defined geographic area of Vienna who were age 75 years underwent a magnetic resonance imaging scan of the brain and were evaluated for the presence of a space‐occupying mass. All probands were examined clinically and neurologically as well as by a neuropsychiatrist. The patients' medical histories were carefully documented with regard to previous diseases, medication, and lifestyle, as were their laboratory reports. The collected data were correlated and similarities among subjects with meningioma were determined.

RESULTS

Nine meningiomas that were unknown until the time of investigation were observed among the 318 women included in the trial (corresponding to a calculated prevalence of 2800/100,000 clinically silent meningiomas in 75‐year‐old women). No tumors were found among men. Associated clinical changes or deficits were not observed in any subject. Apart from advanced age and female gender, no other accepted or well known risk factors were observed in the tumor patients.

CONCLUSIONS

Clinically quiescent meningiomas in the elderly female population were more common than was believed to be the case to date. Known and influenceable risk factors were found to be less important than age and gender. The high frequency of this lesion should be considered when deciding on the treatment of patients with incidentally discovered, clinically quiescent meningiomas. Cancer 2004. © 2004 American Cancer Society.
Quality of colon carcinoma pathology reporting
Authors: Wei Jeffrey T. , Miller Eric A. , Woosley John T. , Martin Christopher F. , Sandler Robert S.
Published: March 2004

BACKGROUND

In 1996, the Association of Directors of Anatomic and Surgical Pathology (ADASP) published recommendations for colon carcinoma reporting. Since this publication, no study has evaluated physician practice in relation to these recommendations. The objectives of the current study were to describe pathology reporting for colon carcinoma, evaluate potential variations in reporting, and identify areas for improvement.

METHODS

Data were obtained from a population‐based study of incident colon carcinoma in 33 counties in North Carolina between 1997 and 2000. All subjects with surgically resected colon carcinoma of tumor stage T2–T4 with available surgical pathology reports were eligible for inclusion in the current analysis. The authors reviewed pathology reports for adherence to recommendations of the ADASP.

RESULTS

Four hundred thirty‐eight pathology reports were included for analysis. Adherence to ADASP recommendations was < 90% for descriptions of how specimen was received (68%), how specimen was identified (71%), macroscopic depth of penetration (82%), appearance of serosa adjacent to tumor (50%), and status of residual bowel (73%). All other criteria were reported in > 90% of patients. Teaching hospital and contract pathology laboratories had greater adherence to recommendations, compared with community hospital laboratories. Hospitals with the highest colon carcinoma case volume demonstrated greater adherence to recommendations, compared with low‐volume hospitals.

CONCLUSIONS

Pathology reports were effective in communicating most pertinent findings from surgically resected colon carcinoma specimens. Omissions of some critical characteristics did occur, however, and significant variability in reporting existed based on laboratory affiliation and hospital case volume. Cancer 2004. © 2004 American Cancer Society.
Fractionated low‐dose radiotherapy after myeloablative stem cell transplantation for local control in patients with high‐risk neuroblastoma
Authors: Bradfield Scott M. , Douglas James G. , Hawkins Douglas S. , Sanders Jean E. , Park Julie R.
Published: March 2004

BACKGROUND

The optimal administration of radiotherapy for patients with high‐risk neuroblastoma (NB) currently is undefined in the context of modern therapy using myeloablative chemotherapy with autologous stem cell rescue (hematopoietic stem cell transplantation [HSCT]).

METHODS

The authors conducted a retrospective review of the records of 21 consecutive patients with high‐risk NB to assess local control and toxicity of external beam radiotherapy (XRT). Therapy included multiagent induction chemotherapy and delayed surgical resection, consolidation of HSCT and local XRT, and 13‐cis‐retinoic acid maintenance therapy. XRT was delivered to the primary site, using postchemotherapy volumes, and to initial metastatic sites with 1–2 cm margins to 2100 centigrays (cGy) using 14 fractions administered once daily.

RESULTS

Four of 21 patients did not receive XRT due to toxic death (n = 2), disease progression before XRT (n = 1), or parental refusal (n = 1). The median time to XRT post‐HSCT was 54 days. Thirteen patients received a second peripheral blood stem cell infusion after completing XRT. Twelve of the 14 patients who received XRT post‐HSCT and for whom toxicity data were available had Grade 3–4 acute toxicities, including gastrointestinal toxicity (n = 8), hematologic toxicity (n = 9), and infection (n = 1). Nonrecurrent long‐term toxicities included prolonged nutritional deficiency (n = 9) and leg‐length discrepancy (n = 1). Tumors recurred in 7 of 21 patients (5 of 17 patients who received radiotherapy), either within a radiation field (n = 1) or at distant nonirradiated sites (n = 6). The estimated local failure rate was 7% (95% confidence interval [95% CI], 0–14%), with a 2‐year event‐free survival rate of 48% (95% CI, 26–70%).

CONCLUSIONS

Post‐HSCT, fractionated XRT to 2100 cGy was a tolerable and effective treatment for patients with high‐risk NB, and minimal recurrences were observed at designated XRT sites. Cancer 2004. © 2004 American Cancer Society.
Estimation of an optimal radiotherapy utilization rate for melanoma
Authors: Delaney Geoff , Barton Michael , Jacob Susannah
Published: March 2004

BACKGROUND

Radiotherapy is not used commonly in the treatment of patients with malignant melanoma. The benchmark optimal radiotherapy utilization rates for melanoma are largely unknown, despite the fact that melanoma is a very common cancer.

METHODS

To develop an evidence‐based benchmark for the optimal proportion of patients with melanoma who should receive radiotherapy, the authors reviewed major treatment guidelines for melanoma. A radiotherapy decision tree was constructed showing the clinical features of melanoma patients for whom radiotherapy was indicated based on evidence. The proportions of melanoma patients with indications for radiotherapy were obtained from epidemiologic data and were used to calculate the optimal proportion of melanoma patients who should receive radiotherapy.

RESULTS

The proportion of patients with melanoma for whom radiotherapy is indicated at some point in their illness, according to the best available evidence, was calculated at 23% of all melanoma patients. The utilization rates of radiotherapy for melanoma recorded in actual practice were 13% in New South Wales, 6% in data from the American College of Surgeons, and 1% according to Surveillance, Epidemiology, and End Results data.

CONCLUSIONS

Strategies for implementing the evidence‐based guidelines are recommended to overcome the shortfall in the use of radiotherapy in the treatment of patients with melanoma. Cancer 2004. © 2004 American Cancer Society.
Recurrence‐free survival rates after external‐beam radiotherapy for patients with clinical T1–T3 prostate carcinoma in the prostate‐specific antigen era
Authors: Khuntia Deepak , Reddy Chandana A. , Mahadevan Arul , Klein Eric A. , Kupelian Patrick A.
Published: March 2004

BACKGROUND

The objective of the current study was to report biochemical recurrence–free survival (bRFS) rates among men with T1–T3 prostate carcinoma who were treated with external‐beam radiotherapy (RT) at the Cleveland Clinic Foundation (Cleveland, OH).

METHODS

In total, 1352 patients were identified between 1987 and 2000 with a minimum follow‐up of 1 year (median follow‐up, 55 months; range, 12–189 months). The median radiation dose was 74.0 grays (Gy) (range, 63.0–83.0 Gy). The median radiation doses for patients who received < 68.0 Gy (n = 201), 68.0–72.0 Gy (n = 373), and ≥ 72.0 Gy (n = 778) were 66.6 Gy, 70.0 Gy, and 78.0 Gy, respectively. The RT techniques used were standard RT in 41% of patients, 3‐dimensional conformal RT in 34% of patients, and intensity‐modulated RT in 25% of patients. Androgen‐deprivation (AD) therapy lasting ≤ 6 months was administered to 34% of patients.

RESULTS

The 5‐year and 7‐year bRFS rates were 63% and 59%, respectively. On multivariate analysis, T classification (P < 0.001), pretreatment prostate‐specific antigen level (P < 0.001), biopsy Gleason score (P = 0.001), radiation dose (P < 0.001), and year of therapy (P < 0.001) were independent predictors of biochemical failure. Age, race, AD therapy, and RT technique did not predict for biochemical failure. For patients with low‐risk tumors, the 5‐year bRFS rates for those who received RT doses of ≤ 68.0 Gy, 68.0–72.0 Gy, and ≥ 72.0 Gy were 52%, 82%, and 93%, respectively (P < 0.001); for patients with intermediate‐risk tumors, the respective 5‐year bRFS rates were 27%, 51%, and 83% (P < 0.001); and for patients with high‐risk tumors, the respective 5‐year bRFS rates were 21%, 29%, and 71%, respectively (P < 0.001).

CONCLUSIONS

The most significant therapeutic factor affecting bRFS rates after RT was radiation dose, rather than AD therapy use or radiation technique. Cancer 2004. © 2004 American Cancer Society.
Intestinal expression of mutant and wild‐type progastrin significantly increases colon carcinogenesis in response to azoxymethane in transgenic mice
Authors: Cobb Stephanie , Wood Thomas , Ceci Jeffrey , Varro Andrea , Velasco Marco , Singh Pomila
Published: March 2004

BACKGROUND

The authors recently reported that transgenic mice (hGAS) expressing pharmacologic levels of progastrin (PG) (> 10 nM to 100 nM) exhibited increased susceptibility to colon carcinogenesis in response to azoxymethane (AOM). It is not known whether PG functions as a cocarcinogen at the concentrations observed in patients with hypergastrinemia (∼1.0 nM).

METHODS

The authors generated transgenic mice that overexpressed either wild‐type (wtPG) or mutant (mtPG) human PG in the intestinal mucosa using the murine fatty acid binding protein (Fabp) promoter. Fabp‐PG mice and their wild‐type littermates were treated with AOM, and their colons were examined for preneoplastic (aberrant crypt foci [ACF]) and neoplastic (adenomas [Ads] and adenocarcinomas [AdCas]) lesions after 2 weeks and 6 months of treatment.

RESULTS

ACF and tumors were significantly more common (by a factor of ∼2) in colon specimens from both Fabp‐wtPG mice and Fabp‐mtPG mice relative to wild‐type mice. It is noteworthy that the multiplicity of ACF and the total number of small and large Ads and AdCas were significantly greater in colon specimens from Fabp‐PG mice compared with colon specimens from wild‐type mice, irrespective of gender.

CONCLUSIONS

The results of the current study suggest that at concentrations (∼1.0 nM) far lower than the ones observed in hGAS mice, PG functions as an equally potent cocarcinogen and significantly increases the risk of colon carcinogenesis in response to AOM. Thus, PG may represent a clinically relevant target molecule in patients with hypergastrinemia or colon carcinoma. Cancer 2004. © 2004 American Cancer Society.
Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis
Authors: Hao Xishan , Sun Baocun , Hu Limei , Lähdesmäki Harri , Dunmire Valerie , Feng Yumei , Zhang Shi‐Wu , Wang Huamin , Wu Chunlei , Wang Hua , Fuller Gregory N. , Symmans W. Fraser , Shmulevich Ilya , Zhang Wei
Published: March 2004

BACKGROUND

Metastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step in the metastatic process.

METHODS

To gain insight into the molecular events that underlie breast carcinoma metastasis, the authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and metastases after screening for enrichment of tumor cells. Statistical analysis identified genes that are expressed at elevated or decreased levels in metastases relative to the corresponding primary tumors. Multidimensional scaling analysis indicated that in terms of expression levels, primary tumors were tightly clustered, whereas metastases exhibited a greater spread; this finding points to the more heterogeneous nature of metastases. Among the differentially expressed entities were the invasion‐ and tissue modeling–related genes IGFBP5, fibronectin, and MMP2; the cell cycle regulatory gene cyclin D1; other genes, such as enolase 2; and an expressed sequence tag similar to angiopoietin 1. To validate and extend these initial findings, the authors constructed a tissue microarray consisting of 100 primary malignancies paired with their lymph node metastases. Antibodies for the IGFBP‐5, fibronectin, MMP‐2, cyclin D1, and MDM‐2 proteins were used to stain tissue array sections.

RESULTS

Consistent with microarray data, statistically significant overexpression of IGFBP‐5, down‐regulation of cyclin D1, and unchanged MDM‐2 levels were observed in metastatic tumor cells. Nonetheless, although fibronectin and MMP2 mRNA expression levels were decreased in many metastasis specimens, expression levels of the corresponding proteins in the extracellular matrix were elevated in most metastases. Decreased expression of fibronectin and MMP2 in lymph node metastases was further confirmed by real‐time polymerase chain reaction assays performed on five additional specimen pairs.

CONCLUSIONS

The results of the current study suggest that extracellular matrix protein expression and nuclear gene expression are associated via a negative‐feedback regulatory mechanism. Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process. Cancer 2004. © 2004 American Cancer Society.
Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors
Authors: Tzika A. Aria , Astrakas Loukas G. , Zarifi Maria K. , Zurakowski David , Poussaint Tina Young , Goumnerova Liliana , Tarbell Nancy J. , Black Peter McL.
Published: March 2004

BACKGROUND

In vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors.

METHODS

MR spectroscopic imaging examinations were performed on 27 children with neuroglial brain tumors during therapy on a 1.5‐Tesla MR system. Normalized rTBV values were measured in 11 of 27 patients. Each examination was rated as stable or progressive by clinical and imaging criteria.

RESULTS

The percent change in normalized choline (Cho) was significantly greater in patients who had progressive examinations compared with patients who had stable examinations (P = 0.03). The percent change in Cho/N‐acetylaspartate (Cho/NAA) was significantly higher in patients who had progressive outcomes (n = 18 patients) compared with patients who had stable outcomes (n = 32 patients; P < 0.001; sensitivity, 0.89; specificity, 0.88) and was identified as the most important prognostic indicator of tumor progression by logistic regression (likelihood ratio test, 33.4; P < 0.001). The odds of tumor progression were approximately 55 times greater for patients who showed at least a 20% change in Cho/NAA. rTBV distinguished between progressing and stable tumors (P = 0.03), and Cho/NAA and rTBV values showed interaction to predict the probability of a progressing clinical outcome.

CONCLUSIONS

The percent change in Cho/NAA by proton MR spectroscopic imaging, assisted by rTBV, was useful in predicting tumor progression in children with brain tumors. Cancer 2004. © 2004 American Cancer Society.
Expression of regenerating gene I in gastric adenocarcinomas
Authors: Dhar Dipok Kumar , Udagawa Jun , Ishihara Shunji , Otani Hiroki , Kinoshita Yoshikazu , Takasawa Shin , Okamoto Hiroshi , Kubota Hirofumi , Fujii Toshiyuki , Tachibana Mitsuo , Nagasue Naofumi
Published: March 2004

BACKGROUND

Regenerating gene I (REG) was identified as a growth factor for pancreatic islet beta cells. Enhanced REG expression was observed during the healing of gastric mucosa. REG expression was observed in various tumors including gastric carcinoma, but to the authors' knowledge, the correlation between REG expression and clinicopathologic characteristics and patient prognosis have not been evaluated.

METHODS

The REG messenger RNA level was analyzed by Northern blot analysis and localization was performed by in situ hybridization and immunohistochemistry in gastric adenocarcinoma specimens. The correlations between REG expression and clinicopathologic features and survival of the patients were analyzed.

RESULTS

Of the 68 patients studied, 24 (35%) were positive for REG. There was a significant consistency in the intensity and localization of REG transcript and protein expressions. REG expression was enhanced in advanced T classification tumors and in tumors that were not well differentiated. A significant number of metastatic lymph nodes were present in REG‐positive tumors. Overall and disease‐free survival were found to be poor for patients with REG‐positive tumors. REG expression was reported to be an independent predictor of overall patient survival.

CONCLUSIONS

Determination of REG expression may help to identify aggressive gastric tumors and to tailor appropriate therapy for patients with REG‐positive tumors. Cancer 2004. © 2004 American Cancer Society.
Restaging surgery for women with borderline ovarian tumors
Authors: Fauvet Raffaèle , Boccara Joëlle , Dufournet Charlotte , David‐Montefiore Emmanuel , Poncelet Christophe , Daraï Emile
Published: March 2004

BACKGROUND

The purpose of the current study was to examine the surgical management of women with borderline ovarian tumors and the adequacy of initial staging according to the guidelines of the International Federation of Gynecology and Obstetrics; to evaluate the impact of restaging operations; and to identify risk factors for initial understaging.

METHODS

In a retrospective French multicenter study, 54 of 360 women with borderline ovarian tumors underwent a restaging operation. After excluding women with initial complete staging (n = 62), epidemiologic, surgical, and histologic parameters and risk of recurrence were compared between women who underwent restaging (n = 54) and those who did not (n = 244).

RESULTS

One hundred fifty (41.6%) of 360 women underwent intraoperative histologic examination, which led to the diagnosis of a borderline tumor in 97 cases (64.7%). Thirty‐seven (38.1%) of these 97 women had undergone complete initial staging procedures. A restaging operation was performed for 54 women. A lower median age and a higher rate of conservative treatment were noted in the group that underwent restaging. Eight (14.8%) of the 54 women who underwent restaging had their tumors upstaged: 7 of the 41 cases initially diagnosed as Stage IA tumors were upstaged to Stage IB (n = 3) or to Stage IIA, IIB, IIIA, or IIIC (n = 1 for each); in the eighth case, a Stage IC tumor was upstaged to Stage IIIA. Upstaging tended to be more common in women with serous borderline tumors (P = 0.06) and in women who underwent cystectomy (P = 0.08). There was no difference in recurrence rates according to whether a restaging operation was performed. The recurrence rates after conservative and radical treatment were 15.6% (25 of 160) and 4.5% (9 of 200), respectively (P < 0.001).

CONCLUSIONS

Women who initially were diagnosed with Stage IA disease and who had serous borderline tumors or underwent cystectomy appeared to derive the most benefit from restaging surgery. Nonetheless, the indications for restaging surgery remain controversial, as no difference in recurrence rate was observed between women who underwent restaging and those who did not. Cancer 2004. © 2004 American Cancer Society.
Comparison of plasma Epstein–Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma
Authors: Shao Jian‐Yong , Li Yu‐Hong , Gao Hong‐Yi , Wu Qiu‐Liang , Cui Nian‐Ji , Zhang Li , Cheng Gang , Hu Li‐Fu , Ernberg Ingemar , Zeng Yi‐Xin
Published: March 2004

BACKGROUND

Serologic measurement of antibodies to Epstein–Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group.

METHODS

Real‐time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme‐linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non‐NPC tumors, and in 47 control individuals.

RESULTS

The median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non‐NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers ≥ 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers ≤ 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC.

CONCLUSIONS

The results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor. Cancer 2004. © 2004 American Cancer Society.
Gemcitabine and docetaxel as front‐line chemotherapy in patients with carcinoma of an unknown primary site
Authors: Pouessel Damien , Culine Stéphane , Becht Catherine , Ychou Marc , Romieu Gilles , Fabbro Michel , Cupissol Didier , Pinguet Frédéric
Published: March 2004

BACKGROUND

The current study was performed to evaluate the efficacy and toxicity of a noncisplatin‐based chemotherapy regimen combining gemcitabine and docetaxel as front‐line chemotherapy for patients with carcinoma of an unknown primary site.

METHODS

Patients were to receive intravenous gemcitabine at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 and docetaxel at a dose of 75 mg/m2 over 1 hour on Day 8 in an outpatient setting. The schedule was repeated every 3 weeks for a maximum of 6 cycles.

RESULTS

Thirty‐five patients were assessable for response and survival. One complete and 13 partial responses were observed. The overall response rate was 40% (95% confidence interval, 28–52%). The median time to disease progression was 2 months (range, 1–4 months). The median overall survival time was 10 months (range, 0–32 months). Toxicity was reported to be manageable.

CONCLUSIONS

The combination of gemcitabine and docetaxel was found to be active in patients with carcinomas of an unknown primary site. However, the overall outcome of these patients remains poor and novel treatment approaches are required. Cancer 2004. © 2004 American Cancer Society.
Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: Who benefits?
Authors: Zang Rong‐Yu , Li Zi‐Ting , Tang Jie , Cheng Xi , Cai Shu‐Mo , Zhang Zhi‐Yi , Teng Nelson N.
Published: March 2004

BACKGROUND

This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression‐free interval ⩾ 3 months.

METHODS

One hundred seventeen patients with relapsed EOC after a clinical complete remission duration ≥ 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan–Meier method, and statistical comparisons were performed using log‐rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model.

RESULTS

The median patient age at the time of relapse was 53 years (range, 20–78 years). The median survival was 22 months and the estimated 5‐year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to ≥ 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured ≤ 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. ≤ 1 cm [P = 0.1211], ≤ 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1–2 cycles vs. 3–5 cycles [P = 0.0144]; 1–2 cycles vs. ≥ 6 cycles [P < 0.0001]; and 3–5 cycles vs. ≥ 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106).

CONCLUSIONS

SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted ≥ 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy. Cancer 2004. © 2004 American Cancer Society.
Genetic alterations in early‐stage pulmonary large cell neuroendocrine carcinoma
Authors: Hiroshima Kenzo , Iyoda Akira , Shibuya Kiyoshi , Haga Yukiko , Toyozaki Tetsuya , Iizasa Toshihiko , Nakayama Toshinori , Fujisawa Takehiko , Ohwada Hidemi
Published: March 2004

BACKGROUND

Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high‐grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC).

METHODS

Twenty‐two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically.

RESULTS

LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites.

CONCLUSIONS

Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. Cancer 2004. © 2004 American Cancer Society.
A randomized clinical trial of energy conservation for patients with cancer‐related fatigue
Authors: Barsevick Andrea M. , Dudley William , Beck Susan , Sweeney Carole , Whitmer Kyra , Nail Lillian
Published: March 2004

BACKGROUND

The efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment.

METHODS

A randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n= 200) or the control intervention (n= 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow‐up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance.

RESULTS

A repeated‐measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group–by‐time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F2,544= 4.5;P= 0.01). The intervention was not associated with changes in overall functional performance.

CONCLUSIONS

Individuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management. Cancer 2004. © 2004 American Cancer Society.
Neutral and Cationic Methylaluminium Complexes of 2‐Anilinotropone Ligands: Synthesis, Characterization, and Reactivity toward Ethylene
Authors: Pappalardo Daniela , Mazzeo Mina , Montefusco Pasquale , Tedesco Consiglia , Pellecchia Claudio
Published: March 2004

Some new aluminium complexes bearing bidentate monoanionic 2‐anilinotroponate ligands have been synthesized and characterized. Reaction of 2‐(2,6‐diisopropylanilino)tropone or 2‐(perfluoroanilino)tropone with AlMe3 (1 equiv.) gave, by methane elimination, compounds [2‐(2,6‐diisopropylanilino)tropone]AlMe2 (1) and [2‐(perfluoroanilino)tropone]AlMe2 (2), respectively, as yellow solids. Reaction of 1 with 1 equiv. of the ligand furnished, by protodealumination of a second Al−CH3 bond, the [2‐(2,6‐diisopropylanilino)tropone]2AlMe derivative 3. The structure of 3 has been determined by single‐crystal X‐ray diffraction, showing a five‐coordinate aluminium atom with a distorted trigonal‐bipyramidal geometry. Compounds 1 and 3 underwent methyl abstraction reactions with B(C6F5)3; the resulting cationic species was trapped in the presence of THF in dichloromethane solution. The reactivity of the synthesized compounds in ethylene polymerisation has also been explored. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis, Structure and Magnetic Properties of a μ‐Carboxylato‐Bridged Ferromagnetic Trinuclear Copper(II) Complex with Lariat Tetraazacrown Ether as Ligand
Authors: Ma Shu‐Lan , Zhu Wen‐Xiang , Gao Song , Guo Qian‐Ling , Xu Miao‐Qiong
Published: March 2004

Four o‐toluic acid pendant groups have been attached to a tetraaza crown ether to prepare the novel tetraazamacrocyclic ligand H4L, 4,7,13,16‐tetrakis(2‐carboxybenzyl)‐1,10‐dioxa‐4,7,13,16‐tetraazacyclooctadecane. The trinuclear copper(II) complex of the ligand, [Cu3L·2H2O]2+·2NO3−·2H2O, has been newly synthesized, and its subsequent structural characterization has revealed that it consists of three CuII cores with a isosceles triangular array and that there is a twofold rotation axis that passes through the Cu2 center. The complex contains two symmetry‐related CuN2O3 cores in a distorted square‐pyramidal geometry and one CuO4 core in a distorted square‐plane geometry. The two μ‐bidentate syn‐anti carboxylate groups bridge Cu1 with Cu2, and Cu1A with Cu2. The trinuclear copper(II) complex units are connected in a one‐dimensional zigzag chain via μ‐H2O−NO3−‐bridged hydrogen bonds. Variable‐temperature susceptibility measurements (2−300 K) reveal a ferromagnetic coupling, Ja = 8.08 cm−1, between the μ‐carboxylato‐bridged Cu1 and Cu2, or Cu1A and Cu2, and a weak antiferromagnetic interaction, Jb = −0.40 cm−1, between Cu1 and Cu1A. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis, Structure and Characterizations in Solid State and Solution of Dinuclear Pentacoordinated FeII and MnII Complexes and of a Linear Tetranuclear FeIII Complex Obtained with the Ligand N,N,N′,N′‐Tetrakis[(6‐methyl‐2‐pyridyl)methyl]propane‐1,3‐diamine
Authors: Balland Véronique , Anxolabéhère‐Mallart Elodie , Banse Frédéric , Rivière Eric , Bourcier Sophie , Nierlich Martine , Girerd Jean‐Jacques
Published: March 2004

Two neutral complexes [(L634M)Fe2Cl4]·2H2O·2CHCl3 (1) and [(L634M)Mn2Cl4]·CH3CN (2) have been synthesized {L634M = N,N,N′,N′‐tetrakis[(6‐methyl‐2‐pyridyl)methyl]propane‐1,3‐diamine} and their molecular structures established by X‐ray crystallography. Both structures are similar, with each metal center in a trigonal‐bipyramidal environment. No magnetic coupling is observed between the metal centers. UV/Vis spectra and cyclic voltammograms were recorded in CH2Cl2 and CH3CN solutions. Both complexes are stable in CH2Cl2, whereas only 2 is stable in CH3CN. On the contrary, 1 is in equilibrium with another FeII species in CH3CN. When this last solution is aerated, monocrystals of the neutral linear tetranuclear complex [(L634M)Fe4(μ‐O)3Cl6]·2CH3CN (3) can be isolated. Its structure is unusual with two FeIII ions pentacoordinate and the two others tetracoordinate with only chloro ligands and oxo bridges. The magnetic properties reveal that two consecutive metal centers are strongly antiferromagnetically coupled. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Carbonylation of Platinum(II) Organometallic Complexes with Bis(phosphanyl) Monosulfides − Crystal Structures of [κ2P,S‐{Ph2CH2P(S)Ph2}Pt(CH3)(Cl)] and [κP,μ‐κS‐{Ph2CH2CH2P(S)Ph2}Pt‐(CH3)]2[BF4]2
Authors: Mastrorilli Piero , Nobile Cosimo F. , Suranna Gian P. , Fanizzi Francesco P. , Ciccarella Giuseppe , Englert Ulli , Li Qi
Published: March 2004

The neutral complexes of formula [κ2P,S‐(dppmS)Pt(CH3)(Cl)] (1) and [κ2P,S‐(dppeS)Pt(CH3)(Cl)] (2) [dppmS = Ph2PCH2P(S)Ph2, dppeS = Ph2P(CH2)2P(S)Ph2] have been synthesised and characterised. Reaction of 1 and 2 with AgBF4 carried out in CH3CN or CH3CN/CH2Cl2 affords the corresponding monomeric cationic complexes [κ2P,S‐(dppmS)Pt(CH3CN)(CH3)][BF4] (3) and [κ2P,S‐(dppeS)Pt(CH3CN)(CH3)][BF4] (4). Complexes 3 and 4 partially dissociate in CD2Cl2, giving, in the case of 3, the asymmetric dimer {[κ2P,S‐(dppmS)](CH3)Pt{κP,μ‐κS‐(dppmS)}Pt(CH3)(CH3CN)][BF4]2 (5), and, in the case of 4, the symmetrical sulfur‐bridged dimer [κP,μ‐κS‐(dppeS)Pt(CH3)]2[BF4]2 (6). Pure 6 can be obtained by heating 4 under vacuum. Exposing CD2Cl2 solutions of the cationic complexes 3 and 4 to CO at ambient conditions brings about the formation of the monomeric methyl carbonyl complexes [κ2P,S‐(dppmS)Pt(CO)(CH3)][BF4] (CO trans to P, 7a) and [κ2P,S‐(dppeS)Pt(CO)(CH3)][BF4] (CO trans to P, 8a), which slowly transform into their CO cis to P isomers 7b and 8b, respectively. The single‐crystal X‐ray diffraction studies of 1·CD2Cl2 and 6·2CD2Cl2 are reported. Mass spectrometric analyses with APCI and ESI interfaces were also performed for all new complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Predicted Structures of the New Pnictides HfMQ in Contrast to ZrMQ (M = Ti, V; Q = P, As)
Authors: Derakhshan Shahab , Dashjav Enkhtsetseg , Kleinke Holger
Published: March 2004

The new pnictides HfTiP, HfTiAs and HfVAs have been prepared through arc‐melting. These arsenides form the predicted structures with (distorted) TiAs4 and VAs4 tetrahedra, while the structures of both Zr analogs (ZrTiAs and ZrVAs) are comprised of TiAs4 and VAs4 square planes, respectively. These differences stem from significant differences in the metal atom substructures. On the other hand, HfTiP and ZrTiP are isostructural. These variations were predicted by utilizing a structure map for metal‐rich pnictides and chalcogenides M2Q (M = valence‐electron poor transition metal, Q = pnicogen or chalcogen) presented in the year 2000. The HfMQ structure is stabilized by strong Hf−Q, M−Q and M−M bonds, and to a minor extent by Hf−Hf and Hf−M bonding interactions. All three new Hf1−δM1+δQ phases exhibit significant phase ranges. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A Series of Transition Metal Bis(dicyanobenzenedithiolate) Complexes [M(dcbdt)2] (M = Fe, Co, Ni, Pd, Pt, Cu, Au and Zn)
Authors: Alves Helena , Simão Dulce , Cordeiro Santos Isabel , Gama Vasco , Teives Henriques Rui , Novais Horácio , Almeida Manuel
Published: March 2004

A series of new M[(dcbdt)2]−z complexes of the dicyanobenzodithiolate (dcbdt) ligand with a range of transition metals (M = Co, Pd, Pt, Cu, Au and Zn) in different oxidation states (z = 0.4, 1, 2) were prepared as their nBu4N salts and characterised by X‐ray diffraction, cyclic voltammetry, EPR and static magnetic susceptibility. Their properties are discussed in comparison with the Ni and Fe analogues described by us recently. The structures of these complexes belong to four distinct groups: i) the ZnII compound 10 is triclinic P$\bar 1$
with the metal in a tetrahedral coordination geometry; ii) other MII complexes [M = Pt (8), Pd (7), Co (3) and Cu (5)] are monoclinic C2/m, and are isostructural with the NiII analogue, presenting a perfectly planar square geometry; iii) the CoIII compound 4 is triclinic P$\bar 1$
, and isostructural with the Fe and Ni analogues, with a strong dimerisation of the M(dcbdt)2 units and the metal in a square‐pyramidal coordination geometry; iv) the MIII salts with M = Au (2), Cu (6) and Pt (9) are monoclinic P21/c and the complexes are arranged as pseudo‐dimers. The EPR and static magnetic‐susceptibility measurements show that the CoII (3), CuII (5), PtIII (9) and CoIII (4) complexes are paramagnetic corresponding to an S = 1/2 state, except for CoIII, which is in a high‐spin S = 1 configuration. The solid state EPR spectra of the CoII compound presents a hyperfine structure typical of the I = 7/2 59Co. The temperature dependence of the paramagnetic susceptibility of the PtIII compound follows a singlet‐triplet model with a dimer antiferromagnetic coupling, J, of 984 K. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
(Nitrido)ruthenium(VI) and ‐osmium(VI) Complexes with Catecholate Auxiliaries: Synthesis, Structure, and Conversion into a (Phosphoraniminato)osmium(V) Complex
Authors: Fang Guo‐Su , Huang Jie‐Sheng , Zhu Nianyong , Che Chi‐Ming
Published: March 2004

Treatment of [NnBu4][MVINCl4] (where M = Ru, Os) with catechol (H2Cat) and 3,5‐di‐tert‐butylcatechol (H2DBCat) in the presence of 2,6‐dimethylpyridine (2,6‐Me2Py) gave [NnBu4][MVIN(Cat)2] (where M = Ru 1a, Os 1b) and [2,6Me2PyH][MVIN(DBCat)2] (where M = Ru 2a, Os 2b), respectively, in 75−90 % yields. Reaction of 2b with triphenylphosphane afforded the (phosphoraniminato)osmium(V) complex [OsV(NPPh3)(DBCat)2(PPh3)] (3) in 90 % yield. X‐ray crystal structure determinations on 1a, 1b and 3 reveal M≡N distances of 1.603(4) and 1.641(8) Å (for 1a and 1b, respectively) and an Os−N(NPPh3) distance of 2.077(3) Å (for 3). The C−O distances in the three complexes range from 1.341(4) to 1.374(7) Å, indicating that the coordinated catecholate ligands adopt the catecholate(2−) state, rather than the semiquinonate(1−) or quinone states. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis, Structural Characterisation and Reactivity of New Dinuclear Monocyclopentadienyl Imidoniobium and ‐tantalum Complexes − X‐ray Crystal Structures of [{Nb(η5‐C5H4SiMe3)Cl2}2(μ‐1,4‐NC6H4N)], [{Ta(η5‐C5Me5)Cl2}2(μ‐1,4‐NC6H4N)] and [{Ta(η5‐C5Me5)(CH2SiMe3)2}2(μ‐1,4‐NC6H4N)]
Authors: Antiñolo Antonio , Dorado Iván , Fajardo Mariano , Garcés Andrés , López‐Solera Isabel , López‐Mardomingo Carmen , Kubicki Marek M. , Otero Antonio , Prashar Sanjiv
Published: March 2004

The preparation of a family of dinuclear monocyclopentadienyl imidoniobium and ‐tantalum complexes was achieved by two different synthetic routes. The diimido complexes [{M(Cp′)Cl2}2(μ‐1,i‐NC6H4N)] [Cp′ = η5‐C5H4SiMe3, M = Nb, i = 4 (1); Cp′ = η5‐C5H4SiMe3, M = Nb, i = 3 (2); Cp′ = η5‐C5H4SiMe3, M = Nb, i = 2 (3); Cp′ = η5‐C5Me5, M = Nb, i = 4 (4); Cp′ = η5‐C5Me5, M = Nb, i = 3 (5); Cp′ = η5‐C5H4SiMe3, M = Ta, i = 4 (6); Cp′ = η5‐C5H4SiMe3, M = Ta, i = 3 (7)] were prepared by the reaction of one equivalent of the trichloro precursor [{MCl3}2(μ‐1,i‐NC6H4N)] (M = Nb, Ta, i = 4, 3 or 2) with two equivalents of either C5H4(SiMe3)2 or C5Me5(SiMe3). Complexes 1−7 can also be prepared by the reaction of two equivalents of [MCp′Cl4] (Cp′ = η5‐C5H4SiMe3, M = Nb, Ta; Cp′ = η5‐C5Me5, M = Nb, Ta) with one equivalent of the corresponding aniline compound, N,N,N′,N′‐tetrakis(trimethylsilyl)‐1,4‐, ‐1,3‐, or ‐1,2‐phenylenediamine, respectively. The synthesis of [{Ta(Cp′)Cl2}2(μ‐1,i‐NC6H4N)] [Cp′ = η5‐C5Me5, i = 4 (8); Cp′ = η5‐C5Me5, i = 3 (9)] was only successful with the second preparative method. The reaction of 1, 2 and 8 with alkylating reagents gave the corresponding tetraalkyl derivatives, [{M(Cp′)R2}2(μ‐1,i‐NC6H4N)] [Cp′ = η5‐C5H4SiMe3, M = Nb, R = Me, i = 4 (10); Cp′ = η5‐C5H4SiMe3, M = Nb, R = CH2SiMe3, i = 4 (11); Cp′ = η5‐C5H4SiMe3, M = Nb, R = CH2Ph, i = 4 (12); Cp′ = η5‐C5H4SiMe3, M = Nb, R = Me, i = 3 (13); Cp′ = η5‐C5H4SiMe3, M = Nb, R = CH2SiMe3, i = 3 (14); Cp′ = η5‐C5H4SiMe3, M = Nb, R = CH2Ph, i = 3 (15); Cp′ = η5‐C5Me5, M = Ta, R = Me, i = 4 (16); Cp′ = η5‐C5Me5, M = Ta, R = CH2SiMe3, i = 4 (17); Cp′ = η5‐C5Me5, M = Ta, R = CH2Ph, i = 4 (18)]. The alkylated complexes with other stoichiometries, [{M(Cp′)(Me)(X)}2(μ‐1,4‐NC6H4N)] [Cp = η5‐C5H4SiMe3, M = Nb, X = Cl (19); Cp = η5‐C5H4SiMe3, M = Nb, X = NMe2 (20); Cp = η5‐C5Me5, M = Ta, X = Cl (21)], were also prepared. The molecular structures of complexes 1, 8 and 17 were determined by single‐crystal X‐ray diffraction studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)