bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Adjuvant Chemotherapy and Radiation Therapy for Colorectal Cancer in a Population-Based Cohort
Authors: Ayanian John Z. , Zaslavsky Alan M. , Fuchs Charles S. , Guadagnoli Edward , Creech Cynthia M. , Cress Rosemary D. , O’Connor Lilia C. , West Dee W. , Allen Mark E. , Wolf Robert E. , Wright William E. 
Published: March 2003

Purpose: Randomized trials have demonstrated that adjuvant chemotherapy improves survival for patients with stage III colon cancer and that chemotherapy combined with radiation therapy improves survival for patients with stage II or III rectal cancer. This population-based study was designed to assess use of these treatments in clinical practice. Patients and Methods: From the California Cancer Registry, we identified all patients diagnosed during 1996 to 1997 with stage III colon cancer (n = 1,422) and stage II or III rectal cancer (n = 534) in 22 northern California counties. To supplement registry data on adjuvant therapies and ascertain reasons they were not used, we surveyed physicians or reviewed office records for 1,449 patients (74%). Results: Chemotherapy rates varied widely by age from 88% (age < 55 years) to 11% (age ≥ 85 years), and radiation therapy varied similarly. Adjusting for demographic, clinical, and hospital characteristics, chemotherapy was used less often among older and unmarried patients, and radiation therapy was used less often among older patients, black patients, and those initially treated in low-volume hospitals. Adjusted rates of chemotherapy varied significantly (P < .01) among individual hospitals: 79% and 51%, respectively, at one SD above and below average (67%). Physicians’ reasons for not providing adjuvant therapy included patient refusal (30% for chemotherapy, 22% for radiation therapy), comorbid illness (22% and 14%, respectively), or lack of clinical indication (22% and 45%, respectively). Conclusion: Use of adjuvant therapy for colorectal cancer varies substantially by age, race, marital status, hospital volume, and individual hospital, indicating opportunities to improve care. With enhanced data on adjuvant therapies, population-based registries could become a valuable resource for monitoring the quality of cancer care.
Combined Intraperitoneal and Intravenous Chemotherapy for Women With Optimally Debulked Ovarian Cancer: Results From an Intergroup Phase II Trial
Authors: Rothenberg Mace L. , Liu P.Y. , Braly Patricia S. , Wilczynski Sharon P. , Hannigan Edward V. , Wadler Scott , Stuart Gavin , Jiang Caroline , Markman Maurie , Alberts David S. 
Published: March 2003

Purpose: The median survival time for women with optimally debulked adenocarcinoma of the ovary treated with intravenous (IV) chemotherapy is 41 to 52 months, and the 2-year survival rate is 65% to 70%. Recent studies evaluating intraperitoneal (IP) chemotherapy have reported a median survival time of 49 to 63 months and 2-year survival rates of 70% to 80%. This phase II trial was undertaken to evaluate the feasibility of and 2-year survival rate achieved by the combination of IP paclitaxel, IP cisplatin, and IV paclitaxel in women with optimally debulked, stage III ovarian cancer. Patients and Methods: Treatment consisted of paclitaxel 135 mg/m2 IV over 24 hours on days 1 to 2, cisplatin 100 mg/m2 IP on day 2, and paclitaxel 60 mg/m2 IP on day 8 administered every 21 days for six cycles. Results: In 68 assessable women with optimal stage III ovarian cancer, the 2-year survival rate was 91%, and the median survival time was 51 months. The 2-year disease-free survival rate was 66%, and median disease-free survival time was 33 months. Ninety-six percent of all patients experienced at least one grade 3 to 4 adverse event during therapy, with the most common events being neutropenia (79%), nausea (50%), vomiting (34%), and fatigue/malaise/lethargy (24%). Seventy-one percent of patients completed all six cycles of IV/IP therapy as planned. Conclusion: Combined IV and IP chemotherapy with cisplatin and paclitaxel is associated with a very promising 2-year survival rate in women with optimally debulked ovarian cancer. The ultimate impact of this approach on overall survival requires further evaluation in a randomized trial setting.
Positron Emission Tomography Is Superior to Computed Tomography Scanning for Response-Assessment After Radical Radiotherapy or Chemoradiotherapy in Patients With Non–Small-Cell Lung Cancer
Authors: Mac Manus Michael P. , Hicks Rodney J. , Matthews Jane P. , McKenzie Allan , Rischin Danny , Salminen Eeva K. , Ball David L. 
Published: March 2003

Purpose: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non–small-cell lung cancer (NSCLC). Patients and Methods: Seventy-three patients with NSCLC underwent [18F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. Results: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P < .0001). Conclusion: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.
PCR-Detectable Nonneoplastic Bcl-2/IgH Rearrangements Are Common in Normal Subjects and Cancer Patients at Diagnosis but Rare in Subjects Treated With Chemotherapy
Authors: Ladetto Marco , Drandi Daniela , Compagno Mara , Astolfi Monica , Volpato Federica , Voena Claudia , Novarino Anna , Pollio Berardino , Addeo Alfredo , Ricca Irene , Falco Patrizia , Cavallo Federica , Vallet Sonia , Corradini Paolo , Pileri Alessandro , Tamponi Giacomo , Palumbo Antonio , Bertetto Oscar , Boccadoro Mario , Tarella Corrado 
Published: March 2003

Purpose: To assess whether nonneoplastic Bcl-2/IgH rearrangements act as a confounding factor in the setting of minimal residual disease analysis by evaluating their incidence in a panel of lymphoma-free subjects, including cancer-free donors and chemotherapy-naive and chemotherapy-treated cancer patients. Patients and Methods: A total of 501 nonlymphoma subjects have been assessed: 258 cancer-free patients and 243 patients with malignancies other than lymphoma, 112 of whom were chemotherapy-naive. Patients were primarily assessed by nested polymerase chain reaction (PCR), followed by real-time quantitative PCR if they scored positive. In addition, six initially PCR-positive cancer-free donors were prospectively reassessed by qualitative and quantitative PCR after 30 and 60 days. Results: The overall incidence of Bcl-2/IgH positivity was 9.6%, with a median number of 11 rearrangements per 1,000,000 diploid genomes (range, 0 to 2,845 rearrangements), as assessed by real-time PCR. The incidence was similar in healthy subjects and cancer patients at diagnosis (12% and 12.5%; P = not significant). In contrast, the incidence of this translocation was only 2.3% in chemotherapy-treated patients (P < .001). In addition, three initially PCR-positive cancer-free donors showed persistence of their rearrangements when assessed after 30 and 60 days. Conclusion: The low incidence of nonneoplastic Bcl-2/IgH rearrangements following chemotherapy provides further evidence of the prognostic role of persistent PCR-positivity in the posttreatment molecular follow-up of follicular lymphoma patients.
Long-Term Neurological Outcome of Childhood Brain Tumors Treated by Surgery Only
Authors: Sønderkær Signe , Schmiegelow Marianne , Carstensen Henrik , Nielsen Lars Bøgeskov , Müller Jørn , Schmiegelow Kjeld 
Published: March 2003

Purpose: To evaluate the pattern of neurological late effects in patients who have received surgery only for a brain tumor in childhood and to identify possible risk factors for neurological sequelae. Patients and Methods: The medical, histologic, and operative records were reviewed for 65 consecutive patients operated for a benign brain tumor from 1970 to 1997, and all patients were re-examined after a median length of follow-up of 10.7 years. Thirty-four patients had posterior fossa tumors, 22 patients had cerebral hemisphere tumors, and nine patients had midline tumors. Results: At the time of follow-up, 20 patients (31%) had no neurological deficits, 22 patients (34%) had minor deficits that did not interfere with their daily life activities, and 23 patients (35%) had moderate or severe deficits such as severe ataxia, spastic paresis, seriously reduced vision, or epilepsy with more than two seizures per year. Fourteen of the 31 patients (45%) registered with ataxia preoperatively had recovered fully. Six of seven patients had persistence of a pre- or postoperatively developed hemiparesis. Thirteen of 23 patients had persistence of cranial nerve deficits that developed second to surgery. Fifty-five percent of the 18 patients with seizures at diagnosis were seizure-free at follow-up. At follow-up both ataxia and hemiparesis were significantly more frequent among females (P = .02 and P = .03, respectively). Conclusion: In patients who received operation as the only treatment for their brain tumor, there was a good chance of total or partial recovery of preoperative and postoperative neurological deficits, although only one third of the patients will have no long-term neurological deficits.
Participation of Patients 65 Years of Age or Older in Cancer Clinical Trials
Authors: Lewis Joy H. , Kilgore Meredith L. , Goldman Dana P. , Trimble Edward L. , Kaplan Richard , Montello Michael J. , Housman Michael G. , Escarce José J. 
Published: March 2003

Purpose: Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation. Patients and Methods: We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly. Results: Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P < .001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%. Conclusion: The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient.
Phase II and Pharmacodynamic Study of the Farnesyltransferase Inhibitor R115777 as Initial Therapy in Patients With Metastatic Pancreatic Adenocarcinoma
Authors: Cohen Steven J. , Ho Linus , Ranganathan Sulabha , Abbruzzese James L. , Alpaugh R. Katherine , Beard Mary , Lewis Nancy L. , McLaughlin Susan , Rogatko André , Perez-Ruixo Juan J. , Thistle Amanda M. , Verhaeghe Tom , Wang Hao , Weiner Louis M. , Wright John J. , Hudes Gary R. , Meropol Neal J. 
Published: March 2003

Purpose: R115777 is a selective nonpeptidomimetic inhibitor of farnesyltransferase (FTase), one of several enzymes responsible for posttranslational modification that is required for the function of p21ras and other proteins. Given that RAS mutations are nearly universal in pancreatic cancer and R115777 demonstrated preclinical activity against pancreatic cell lines and xenografts, this phase II study was undertaken to determine its clinical activity and effect on target proteins in patients with measurable metastatic pancreatic adenocarcinoma. Patients and Methods: Twenty patients who had not received prior therapy for metastatic disease were treated with 300 mg of R115777 orally every 12 hours for 21 of 28 days. Inhibition of FTase activity in peripheral-blood mononuclear cells was measured using a lamin B C-terminus peptide as substrate. Western blot analysis was performed to monitor farnesylation status of the chaperone protein HDJ-2. Results: No objective responses were seen. Median time to progression was 4.9 weeks, and median survival time was 19.7 weeks. The estimated 6-month survival rate was 25%, with no patients progression-free at 6 months. Grade 3/4 toxicities were liver enzyme elevation, anemia, neutropenia, thrombocytopenia, fatigue, nausea/vomiting, rash, and anorexia. FTase activity (mean ± SD) decreased by 49.8% ± 9.8% 4 hours after treatment on day 1 and 36.1% ± 24.8% before treatment on day 15. HDJ-2 farnesylation (mean ± SD) decreased by 33.4% ± 19.8% on day 15. Conclusion: Although treatment with R115777 resulted in partial inhibition of FTase activity in mononuclear cells, it did not exhibit single-agent antitumor activity in patients with previously untreated metastatic pancreatic cancer.
End Points and United States Food and Drug Administration Approval of Oncology Drugs
Authors: Johnson John R. , Williams Grant , Pazdur Richard 
Published: March 2003

Purpose: To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years. Materials and Methods: The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed. Results: The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs. Conclusion: End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002.
Pentostatin and Cyclophosphamide: An Effective New Regimen in Previously Treated Patients With Chronic Lymphocytic Leukemia
Authors: Weiss Mark A. , Maslak Peter G. , Jurcic Joseph G. , Scheinberg David A. , Aliff Timothy B. , Lamanna Nicole , Frankel Stanley R. , Kossman Steven E. , Horgan Denise 
Published: March 2003

Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs. Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/m2. Seventeen patients received cyclophosphamide 600 mg/m2, and six patients received cyclophosphamide 900 mg/m2. Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy. Results: The cyclophosphamide 900 mg/m2 dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m2 as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy. Conclusion: Pentostatin 4 mg/m2 with cyclophosphamide 600 mg/m2 is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL.
Improving the Care of Patients With Regard to Chemotherapy-Induced Nausea and Emesis: The Effect of Feedback to Clinicians on Adherence to Antiemetic Prescribing Guidelines
Authors: Mertens Wilson C. , Higby Donald J. , Brown David , Parisi Regina , Fitzgerald Janice , Benjamin Evan M. , Lindenauer Peter K. 
Published: March 2003

Purpose: To evaluate the effect of performance and outcomes feedback on adherence to clinical practice guidelines regarding chemotherapy-induced nausea and emesis (CINE). Methods: Institutional CINE clinical practice guidelines were developed based on American Society of Clinical Oncology guidelines. Consecutive administrations of moderately/highly emetogenic chemotherapy were assessed for errors. Baseline statistical process control (SPC) charts were created and mean errors per administration were calculated. Prospective SPC charts were used to measure the effect of guideline development and distribution, a visiting lecturer, and ongoing feedback regarding compliance with guidelines employing SPC charts. Patients were surveyed regarding the extent and severity of CINE for 5 days postadministration. These outcomes were then shared with physicians. Results: Baseline compliance was poor (mean, 0.87 omissions per chemotherapy administration), largely because of inadequate adherence to recommendations for delayed CINE management. Most patients experienced delayed nausea, particularly on day 3 postchemotherapy. Physician prescribing performance did not undergo sustained improvement despite guideline development or distribution, a lecture by a visiting expert, or sharing of adherence data with clinicians. Once patient outcomes were shared, physicians accepted the need for compliance and instituted nurse practitioner antiemetic prescribing, with almost complete compliance and concurrent measurable reduction in day 3 nausea. SPC charts documented improvements in both outcomes. Conclusions: SPC charts effectively monitor ongoing compliance and patient symptoms and represent appropriate outcome measurement and change facilitation tools. However, physician participation in guideline development and evidence of poor compliance alone did not improve prescribing performance. Only evidence of patient CINE experience coupled with noncompliance improved results.
Detection of Clinically Significant, Occult Prostate Cancer Metastases in Lymph Nodes Using a Splice Variant-Specific RT-PCR Assay for Human Glandular Kallikrein
Authors: Shariat Shahrokh F. , Kattan Michael W. , Erdamar Sibel , Nguyen Cuong , Scardino Peter T. , Spencer David M. , Wheeler Thomas M. , Slawin Kevin M. 
Published: March 2003

Purpose: To compare the detection of human glandular kallikrein 2 (hK2) mRNA expression in archival lymph nodes with disease progression, the development of prostate cancer metastases, and mortality in patients undergoing radical prostatectomy for locally advanced nonmetastatic prostate cancer. Patients and Methods: We evaluated total RNA extracted from fixed, paraffin-embedded, histopathologically normal pelvic lymph nodes, removed at radical prostatectomy, from 199 pT3N0 prostate cancer patients (150 extraprostatic extension only; 49 seminal vesicle involvement) for hK2-expressing cells using a novel reverse transcriptase polymerase chain reaction (RT-PCR)/hK2 assay. Cumulative incidence functions and Cox proportional hazards analyses were performed. Results: Forty patients (20%) had positive results, 80 patients (40%) had negative results, and 79 patients (40%) had equivocal results. RT-PCR/hK2 status was not associated with any pathologic characteristics (P > .05). In postoperative multivariable models, the RT-PCR/hK2 result was associated with prostate cancer progression (P = .001), development of distant metastases (P = .001), and prostate cancer–specific survival (P = .005). In patients experiencing biochemical progression (n = 33), RT-PCR/hK2 status was a predictor of failure to respond to salvage radiotherapy (P = .002). Conclusion: RT-PCR/hK2 can detect biologically and clinically significant occult prostate cancer metastases in histopathologically normal lymph nodes. In patients with locally advanced prostate cancer, RT-PCR/hK2 is strongly associated with prostate cancer progression, failure following salvage radiation therapy, development of clinically evident metastases, and prostate cancer–specific mortality after surgery.