bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Comparison of Combination Chemotherapy With Etoposide, Bleomycin, and Either High-Dose or Standard-Dose Cisplatin in Children and Adolescents With High-Risk Malignant Germ Cell Tumors: A Pediatric Intergroup Study—Pediatric Oncology Group 9049 and Children's Cancer Group 8882
Authors: Cushing Barbara , Giller Roger , Cullen John W. , Marina Neyssa M. , Lauer Stephen J. , Olson Thomas A. , Rogers Paul C. , Colombani Paul , Rescorla Frederick , Billmire Deborah F. , Vinocur Charles D. , Hawkins Edith P. , Davis Mary Margaret , Perlman Elizabeth J. , London Wendy B. , Castleberry Robert P. 
Published: June 2004

Purpose To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.
Small-Cell Carcinomas of the Gastrointestinal Tract: A Review
Authors: Brenner Baruch , Tang Laura H. , Klimstra David S. , Kelsen David P. 
Published: June 2004

Purpose To improve our understanding of the entity of small-cell carcinoma (SmCC) of the gastrointestinal (GI) tract. Methods A MEDLINE search was done, using the terms “small cell carcinoma” or “oat cell carcinoma” combined with “gastrointestinal” or with any of the GI sites, for the period 1970 to 2003. The 138 eligible reports identified in this way were reviewed for clinical data. Results To date, approximately 544 cases of GI SmCC have been reported. The disease represents 0.1% to 1% of all GI malignancies, with the esophagus being the most common primary site. A majority of patients present with overt distant metastases. Systemic symptoms are common; ectopic hormonal secretion may occur. By light microscopy, GI SmCCs are essentially indistinguishable from primary pulmonary SmCC. The presence of non-SmCC components is common. Data from molecular analysis of the disease has identified some similarities to pulmonary SmCC. Chemotherapy represents the main treatment option, with modest impact on survival. In locoregional disease, the literature suggests that treatment be initiated using chemoradiotherapy and then, if metastatic disease is still excluded, surgical resection be considered. The disease is highly aggressive, and survival is in the range of several weeks for untreated patients and of 6 to 12 months for those receiving therapy. Conclusion SmCC of the GI tract is a rare and lethal disease. Although there are many similarities to pulmonary SmCC, some differences between the two entities are suggested. While chemotherapy can achieve significant palliation, surgery may have a potential impact on long-term survival of patients with locoregional disease.
Comparison of the Informed Consent Process for Randomized Clinical Trials in Pediatric and Adult Oncology
Authors: Simon Christian M. , Siminoff Laura A. , Kodish Eric D. , Burant Christopher 
Published: June 2004

Purpose To compare the informed consent processes for phase III pediatric and adult oncology clinical trials in view of the critical importance of human subjects protection in both pediatric and adult cancer care. Findings are discussed in terms of the opportunities for improving pediatric and adult oncology informed consent. Patients and Methods A total of 219 subjects are reported on. Adult oncology patients made up 36.1% (n = 79) of the sample. Pediatric surrogates made up the remaining 63.9% (n = 140). Subjects in both studies were observed and audiotaped in conversation with their oncologists, and interviewed afterwards. Comparisons between the adult and pediatric subjects were done using χ2 statistics and t tests. Results Differences between the pediatric and adult informed consent processes were found. Adult oncology decision makers were, on average, more fully informed and more actively engaged by their oncologists. Pediatric decision makers were, however, given more information about survival/cure, randomization, and voluntariness. Comprehension difficulties were more frequent among pediatric decision makers. Suggestions for improvement are made in view of the differences between adult and pediatric oncology research environments. Conclusion Ongoing efforts to improve the ethical framework of clinical cancer research need to take into account the key differences between pediatric and adult oncology informed consent. More research needs to be done to explore the differences between adult and pediatric informed consent processes in oncology.
Combined-Modality Therapy With Gemcitabine and Radiotherapy As a Bladder Preservation Strategy: Results of a Phase I Trial
Authors: Kent Elizabeth , Sandler Howard , Montie James , Lee Cheryl , Herman Joseph , Esper Peg , Fardig Judith , Smith David C. 
Published: June 2004

Purpose We conducted a phase I trial of gemcitabine given twice weekly with concurrent radiotherapy in patients with muscle-invasive bladder cancer. Patients and Methods Eligible patients underwent maximal transurethral resection of their bladder tumors followed by twice-weekly infusion of gemcitabine with 2 Gy/d concurrent radiotherapy to the bladder, for a total of 60 Gy over 6 weeks. The starting dose of gemcitabine was 10 mg/m2 with subsequent dose levels of 20, 27, 30, and 33 mg/m2. The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy. Secondary end points included assessment of toxicity associated with combined-modality therapy and initial assessment of the rate of bladder preservation. Results Twenty-four patients were enrolled and 23 were assessable for toxicity and response. No significant toxicity was demonstrated at the 10 or 20 mg/m2 twice-weekly doses. Dose-limiting toxicity (DLT) occurred in two of three patients treated at 33 mg/m2. Intermediate dose levels of 27 and 30 mg/m2 were then evaluated. The MTD of gemcitabine was 27 mg/m2. The DLT was systemic, manifested as an elevation in liver function tests, malaise, and edema. Fifteen of 23 patients (65%) are alive with bladders intact and no evidence of recurrent disease at a median follow-up of 43 months. Conclusion Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated. The MTD of gemcitabine is 27 mg/m2. There is a high rate of bladder preservation in this selected group of patients.
Liposome-Encapsulated Doxorubicin in Combination With Standard Agents (cyclophosphamide, vincristine, prednisone) in Patients With Newly Diagnosed AIDS-Related Non-Hodgkin's Lymphoma: Results of Therapy and Correlates of Response
Authors: Levine Alexandra M. , Tulpule Anil , Espina Byron , Sherrod Andy , Boswell William D. , Lieberman Robert D. , Nathwani Bharat N. , Welles Lauri 
Published: June 2004

Purpose To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. Patients and Methods Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. Results Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm3 (range, 19/mm3 to 791/mm3). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P = .027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. Conclusion Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.
Colorectal Cancer Screening Knowledge, Attitudes, and Beliefs Among Veterans: Does Literacy Make a Difference?
Authors: Dolan Nancy C. , Ferreira M. Rosario , Davis Terry C. , Fitzgibbon Marian L. , Rademaker Alfred , Liu Dachao , Schmitt Brian P. , Gorby Nicolle , Wolf Michael , Bennett Charles L. 
Published: June 2004

Purpose To evaluate whether lower literacy is associated with poorer knowledge and more negative attitudes and beliefs toward colorectal cancer screening among veterans without recent colorectal cancer screening. Patients and Methods Three hundred seventy-seven male veterans, age 50 years and older, who had not undergone recent colorectal cancer screening, were surveyed about their knowledge, attitudes, and beliefs regarding colorectal cancer screening. Patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine, an individually administered screening test for reading. Results Thirty-six percent of the 377 men had an eighth grade literacy level or higher. Men with lower literacy were 3.5 times as likely not to have heard about colorectal cancer (8.8% v 2.5%; P = .006), 1.5 times as likely not to know about screening tests (58.4% v 40.9%; P = .0001), and were more likely to have negative attitudes about fecal occult blood testing (FOBT), but not about flexible sigmoidoscopy. Specifically, men with lower literacy skills were two times as likely to be worried that FOBT was messy (26.7% v 13.3%; P = .008), 1.5 times as likely to feel that FOBT was inconvenient (28.7% v 18%; P = .05), and four times as likely to state they would not use an FOBT kit even if their physician recommended it (17.9% v 4.0%; P = .02). Conclusion Limited literacy may be an overlooked barrier in colorectal cancer screening among veterans.
Outcomes of a Randomized Trial of Hyperfractionated Cranial Radiation Therapy for Treatment of High-Risk Acute Lymphoblastic Leukemia: Therapeutic Efficacy and Neurotoxicity
Authors: Waber Deborah P. , Silverman Lewis B. , Catania Lori , Mautz William , Rue Montse , Gelber Richard D. , Levy Donna E. , Goldwasser Meredith A. , Adams Heather , Dufresne Annie , Metzger Victoria , Romero Ivonne , Tarbell Nancy J. , Dalton Virginia Kimball , Sallan Stephen E. 
Published: June 2004

Purpose We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT. Patients and Methods Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol. Results Eight-year event-free survival (± SE) was 80% ± 3% for children randomly assigned to CFX and 72% ± 3% for HFX (P = .06). Overall survival was 85% ± 3% for CFX and 78% ± 3% for HFX (P = .06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P = .99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P < .05). Conclusion HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia.
Docetaxel Versus Docetaxel Plus Cisplatin As Front-Line Treatment of Patients With Advanced Non—Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Trial
Authors: Georgoulias Vassilis , Ardavanis Alexandros , Agelidou Athina , Agelidou Maria , Chandrinos Vassilis , Tsaroucha Emilia , Toumbis Michael , Kouroussis Charalambos , Syrigos Konstantinos , Polyzos Aristidis , Samaras Nikolaos , Papakotoulas Pavlos , Christofilakis Charalambos , Ziras Nicolaos , Alegakis Athanasios 
Published: June 2004

Purpose To compare the overall survival (OS) of patients with advanced non–small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone. Patients and Methods Chemotherapy-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m2 on day 1, cisplatin 80 mg/m2 on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 μg/m2/d on days 3 to 9) or D (n = 152; 100 mg/m2 on day 1 without rhG-CSF) every 3 weeks. Results The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P = .004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P = .200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P = .580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P = .0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P = .0001), diarrhea (P = .007), neurotoxicity (P = .017), and nephroroxicity (P = .006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P = .098). Conclusion DC regimen resulted in a higher response rate but without improvement in median time to tumor progession or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.
Tumor Karyotype Predicts Clinical Outcome in Colorectal Cancer Patients
Authors: Bardi Georgia , Fenger Claus , Johansson Bertil , Mitelman Felix , Heim Sverre 
Published: June 2004

Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.
Tree-Based Model for Breast Cancer Prognostication
Authors: Banerjee Mousumi , George Julie , Song Eun Young , Roy Anuradha , Hryniuk William 
Published: June 2004

PurposeTo define prognostic groups for recurrence-free survival in breast cancer, assess relative effects of prognostic factors, and examine the influence of treatment variations on recurrence-free survival in patients with similar prognostic-factor profiles.Patients and MethodsWe analyzed 1,055 patients diagnosed with stage I-III breast cancer between 1990 and 1996. Variables studied included socioeconomic factors, tumor characteristics, concurrent medical conditions, and treatment. The primary end point was recurrence-free survival (RFS). Multivariable analyses were performed using recursive partitioning and Cox proportional hazards regression.ResultsThe most significant difference in prognosis was between patients with fewer than four and those with at least four positive nodes (P < .0001). Four distinct prognostic groups (5-year RFS, 97%, 78%, 58%, and 27%) were developed, defined by the number of positive nodes, tumor size, progesterone receptor (PR) status, differentiation, race, and marital status. Patients with fewer than four positive nodes and tumor ≤ 2 cm, PR positive, and well or moderately differentiated had the best prognosis. RFS in this group was unaffected by type of adjuvant therapy (P = .38). Patients with at least four positive nodes and PR-negative tumors had the worst prognosis, and those treated with tamoxifen plus chemotherapy had the best outcome in this group (P = .0001). Among patients in the two intermediate-risk groups, those treated with tamoxifen or a combination of tamoxifen and chemotherapy had the best outcome.ConclusionLymph node status, PR status, tumor size, differentiation, race, and marital status are valuable for prognostication in breast cancer. The prognostic groups derived can provide guidance for clinical trial design, patient management, and future treatment policy.
Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial
Authors: Xiong Henry Q. , Rosenberg Arthur , LoBuglio Albert , Schmidt William , Wolff Robert A. , Deutsch John , Needle Michael , Abbruzzese James L. 
Published: June 2004

Purpose To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer. Patients and Methods Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m2 for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks. Results Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%). Conclusion Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.
A Role for Kisspeptins in the Regulation of Gonadotropin Secretion in the Mouse
Authors: Gottsch M. L. , Cunningham M. J. , Smith J. T. , Popa S. M. , Acohido B. V. , Crowley W. F. , Seminara S. , Clifton D. K. , Steiner R. A. 
Published: June 2004

Abstract
Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.