bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia
Authors: Aversa Franco , Terenzi Adelmo , Carotti Alessandra , Felicini Rita , Jacucci Roberta , Zei Tiziana , Latini Paolo , Aristei Cynthia , Santucci Antonella , Martelli Maria Paola , Cunningham Isabel , Reisner Yair , Martelli Massimo F. 
Published: February 2017

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.
Pharmacokinetic Study of Single Doses of Oral Fludarabine Phosphate in Patients With “Low-Grade” Non-Hodgkin's Lymphoma and B-Cell Chronic Lymphocytic Leukemia
Authors: Foran James M. , Oscier David , Orchard Jennifer , Johnson Stephen A. , Tighe Mary , Cullen Michael H. , de Takats Philippa G. , Kraus Christian , Klein Marcus , Lister T. Andrew 
Published: February 2017

PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with “low-grade” non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the “conventional” treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyl-adenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cmax. The linear increase in mean AUC(0-24h) by factors of 1.36 ± 0.22 (mean ± SD) and 1.72 ± 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.
Review of the Efficacy of Individualized Chemotherapy Selected by In Vitro Drug Sensitivity Testing for Patients With Cancer
Authors: Cortazar Patricia , Johnson Bruce E. 
Published: February 2017

PURPOSE: The purpose of this study is to review the potential efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing (DST) compared with empiric regimens for patients with cancer. METHODS: MEDLINE and CANCERLIT were searched for articles published (in English) about prospective clinical trials in which patients were treated with chemotherapy that was selected with the use of in vitro DST. RESULTS: We identified 12 prospective studies that examined the benefit of chemotherapy selected by DST. Five hundred six patients (33%) were treated with chemotherapy that was selected with the use of in vitro DST. The mean response rate for patients treated with in vitro–selected therapy was 27% (range, 10% to 100%; n = 12 studies) compared with 18% (range, 0% to 100%; n = 7 studies) for patients treated with empiric therapy. Five studies (only one randomized) evaluated the impact of chemotherapy selected by in vitro DST on patient survival. Three studies showed that survival was 1 to 4 months longer for the 238 patients treated with empiric chemotherapy compared with that of the 65 patients treated with chemotherapy that was selected by in vitro testing. Two nonrandomized studies showed that survival was 4 or 19 months longer for 27 patients treated with chemotherapy selected by in vitro testing compared with that of 80 patients who were treated with empiric chemotherapy. CONCLUSION: Only one third of patients entered in prospective trials of in vitro DST were actually treated with an in vitro best regimen. The response rates seem to be better with in vitro selected chemotherapy regimens than with empiric regimens, but the impact on survival has not been adequately addressed.
Health-Related Quality of Life in Men With Metastatic Prostate Cancer Treated With Prednisone Alone or Mitoxantrone and Prednisone
Authors: Osoba David , Tannock Ian F. , Ernst D. Scott , Neville Alan J. 
Published: February 2017

PURPOSE: A combination of mitoxantrone plus prednisone is preferable to prednisone alone for reduction of pain in men with metastatic, hormone-resistant, prostate cancer. The purpose of this study was to assess the effects of these treatments on health-related quality of life (HQL). PATIENTS AND METHODS: Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone. Those who received prednisone alone could have mitoxantrone added after 6 weeks if there was no improvement in pain. HQL was assessed before treatment initiation and then every 3 weeks using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ-C30) and the Quality of Life Module–Prostate 14 (QOLM-P14), a trial-specific module developed for this study. An intent-to-treat analysis was used to determine the mean duration of HQL improvement and differences in improvement duration between groups of patients. RESULTS: At 6 weeks, both groups showed improvement in several HQL domains, and only physicalfunctioning and pain were better in the mitoxantrone-plus-prednisone group than in the prednisone-alone group. After 6 weeks, patients taking prednisone showed no improvement in HQL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P = .009), four functioning domains, and nine symptoms (.001 < P < .01), and the improvement (> 10 units on a scale of 0 to100) lasted longer than in the prednisone-alone group (.004 < P < .05). The addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (.001 < P < .003). CONCLUSION: Treatment with mitoxantrone plus prednisone was associated with greater and longer-lasting improvement in several HQL domains and symptoms than treatment with prednisone alone.
Postmenopausal Hormone Replacement Therapy: Effect on Diagnosis and Outcome in Early-Stage Invasive Breast Cancer Treated With Conservative Surgery and Radiation
Authors: Fowble Barbara , Hanlon Alexandra , Freedman Gary , Patchefsky Art , Kessler Howard , Nicolaou Nicos , Hoffman John , Sigurdson Elin , Boraas Marcia , Goldstein Lori 
Published: February 2017

PURPOSE: To compare the pretreatment characteristics and outcome of postmenopausal women with stage I-II breast cancer treated with conservative surgery and radiation who had a history of hormone replacement therapy (HRT) with those who had never received HRT. MATERIALS AND METHODS: From 1979 to 1993, 485 postmenopausal women underwent excisional biopsy, axillary dissection, and radiation for stage I-II breast cancer. The median follow-up was 5.9 years. One hundred forty-one patients reported a history of HRT. The median length of use was 5 years. Three hundred forty-four patients reported no history of HRT. RESULTS: Statistically significant differences between the two groups were observed for median age (HRT 60 years v no HRT 64 years; P = .0009), median weight (HRT 142 lbs v no HRT 152 lbs; P = .004), clinical tumor size ≤ 2 cm (HRT 77% v no HRT 66%; P = .02), and the use of re-excision (HRT 62% v no HRT 49%; P = .01). The method of detection by mammogram only (HRT 52% v no HRT 42%; P = .06) was of borderline statistical significance. The HRT patients had a statistically significant increased cumulative incidence of ipsilateral breast tumor recurrence (8% v 2%; P = .02), a statistically significant decreased cumulative incidence of distant metastases (HRT 6% v no HRT 17%; P = .01), and a borderline statistically significant improvement in cause-specific survival at 10 years (HRT 92% v no HRT 86%; P = .07). Postmenopausal women with a history of HRT did not have an increased risk of contralateral breast cancer or second non–breast cancer malignancy. CONCLUSION: This study failed to identify an adverse effect of HRT on breast cancer mortality in patients with stage I-II disease treated with conservative surgery and radiation.
Expression and Prognostic Significance of Metalloproteinases and Their Tissue Inhibitors in Patients With Small-Cell Lung Cancer
Authors: Michael M. , Babic B. , Khokha R. , Tsao M. , Ho J. , Pintilie M. , Leco K. , Chamberlain D. , Shepherd F. A. 
Published: February 2017

PURPOSE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. RESULTS: Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P = .043). Significant factors for survival were tumor stage (P = .0021); weight loss (P = .013); and high tumor cell expression of MMP-3 (P = .077), MMP-11 (P = .031), and MMP-14 (P = .019). MMP and TIMP expression did not differ significantly between stages. CONCLUSION: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.
Comparison of Lumbar and Shunt Cerebrospinal Fluid Specimens for Cytologic Detection of Leptomeningeal Disease in Pediatric Patients With Brain Tumors
Authors: Gajjar Amar , Fouladi Maryam , Walter Andrew W. , Thompson Stephen J. , Reardon David A. , Merchant Thomas E. , Jenkins Jesse J. , Liu Aiyi , Boyett James M. , Kun Larry E. , Heideman Richard L. 
Published: February 2017

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P = .0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P = .011). Analysis of the subset of patients with embryonal tumors showed similar results (P = .0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.
Insufficient Effectiveness of 5-Hydroxytryptamine-3 Receptor Antagonists Due to Oral Morphine Administration in Patients With Cisplatin-Induced Emesis
Authors: Shoji Akira , Toda Mariko , Suzuki Kaneo , Takahashi Hiroshi , Takahashi Kenichi , Yoshiike Yasuhiro , Ogura Takashi , Watanuki Yuji , Nishiyama Harumi , Odagiri Shigeki 
Published: February 2017

PURPOSE: To compare the effect of 5-hydroxytryptamine-3 (5HT3) receptor antagonists in cancer patients receiving chemotherapy including cisplatin (CDDP), with or without sustained-release oral morphine (MS Contin; Shionogi Co, Osaka, Japan). PATIENTS AND METHODS: We retrospectively studied 58 lung cancer patients given chemotherapy including at least 50 mg/m2 CDDP with 5-HT3 receptor antagonists between January 1996 and December 1997. Number of vomiting episodes, average porportions of hospital-supplied meals consumed (0 to 100%, as an index of appetite), and nausea severity scores (0 to 2 points, subjective patient judgment) were compared between oral morphine–administered (+) and morphine-free (−) groups. RESULTS: Sixteen morphine(+) and 42 morphine(−) cases were used. In cases of acute emesis (within 24 hours after CDDP injection), morphine(+) and morphine(−) groups were significantly different in number of vomiting episodes (1.25 and 0.14, respectively; P < .0001), appetite (58.13% and 90.24%; P < .0001), and nausea severity scores (1.63 and 0.62; P < .0001). In delayed-emesis cases (24 to 120 hours after CDDP), these groups differed significantly in number of vomiting episodes (1.94 and 0.43, respectively; P = .0001), appetite (23.13% and 52.08%; P < .0001), and nausea severity (1.38 and 0.91; P = .009). There were no significant differences in sex, age, anticancer drugs concurrent with CDDP, CDDP dose, corticosteroid administration, clinical stage, or type of 5-HT3 antagonist. CONCLUSIONS: These data suggest that morphine can markedly reduce the effectiveness of 5-HT3 receptor antagonists in patients receiving chemotherapy that includes CDDP. These results require confirmation by reinvestigation of clinical data on the efficacy of 5-HT3 receptor antagonists and by extensive prospective analyses.
Development and Testing of a Visit-Specific Patient Satisfaction Questionnaire: The Princess Margaret Hospital Satisfaction With Doctor Questionnaire
Authors: Loblaw D. Andrew , Bezjak Andrea , Bunston† Terry 
Published: February 2017

PURPOSE: To develop a psychometrically sound patient-satisfaction-with-physician questionnaire that can be used in an outpatient oncology setting. PATIENTS AND METHODS: The questionnaire was developed by a four-step process involving a total of 277 cancer patients. The item-generation process utilized input from 95 oncology outpatients, three medical researchers, and the relevant literature. Items were tested by 70 of the above patients. Initial item reduction was achieved by input from another eight patients. Factor analysis and validity testing used data derived from a different group of 174 oncology outpatients. Convergent validity was tested by correlating the Princess Margaret Hospital Patient Satisfaction with Doctor Questionnaire (PMH/PSQ-MD) with Rubin et al's Physician subscale of the Patient's Viewpoint Questionnaire (PS-PVQ) and Smith et al's Patient-Doctor Interaction Scale (PDIS). Divergent validity was tested by comparing these questionnaires with Spitzer's quality of life (QOL) questionnaire. RESULTS: The final PMH/PSQ-MD is a 29-item self-administered questionnaire with four response categories and a “does not apply” category. Four domains were confirmed by factor analysis: (1) information exchange, (2) interpersonal skills, (3) empathy, and (4) quality of time. The questionnaire has an overall Cronbach's alpha of 0.97; the values for each domain are, respectively, 0.92, 0.90, 0.88, and 0.88. The PMH/PSQ-MD correlated well with both the PDIS and the PS-PVQ (P < .001 for both). Divergent validity was confirmed with Spitzer's QOL questionnaire. CONCLUSION: The PMH/PSQ-MD is an outpatient satisfaction questionnaire specific to the patient-physician interaction that has shown excellent internal consistency, is feasible, and has strong support for validity in this oncology population.
Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry for the Evaluation of HER-2/neu in Breast Cancer
Authors: Jacobs Timothy W. , Gown Allen M. , Yaziji Hadi , Barnes Melissa J. , Schnitt Stuart J. 
Published: February 2017

PURPOSE: To compare fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in the determination of HER-2/neu status of breast cancers. MATERIALS AND METHODS: FISH and IHC for HER-2/neu were performed on formalin-fixed paraffin sections of 100 consecutive invasive breast cancers. FISH was performed at Beth Israel Deaconess Medical Center, Boston, MA, using the Oncor/Ventana INFORM kit (Ventana Medical Systems, Tucson, AZ; formerly sold by Oncor, Inc, Gaithersburg, MD) in a laboratory certified as proficient in this procedure. IHC was performed at PhenoPath Laboratories, Seattle, WA, using a polyclonal antibody to the HER-2/neu protein. FISH and IHC were analyzed in a blinded fashion, and the results were then compared. Procedure and interpretation times and reagent costs for FISH and IHC were also compared. RESULTS: HER-2/neu was amplified by FISH in 26% of cases, and 23% were HER-2/neu–positive by IHC. FISHand IHC were both assessable in 90 cases. Concordance between FISH and IHC results was seen in 82 of these cases (91%, P < .001). The FISH procedure required more technologist time and more interpretation time per case for the pathologist than IHC. Reagent costs were substantially higher for FISH than for IHC. CONCLUSION: There is a high level of correlation between FISH and IHC in the evaluation of HER-2/neu status of breast cancers using formalin-fixed paraffin-embedded specimens. Although the choice of which assay to use should be left for individual laboratories to make based on technical and economic considerations, our results may make it difficult to justify the routine use of FISH for determination of HER-2/neu status in breast cancer.
Phase I Trial of Twice-Weekly Gemcitabine and Concurrent Radiation in Patients With Advanced Pancreatic Cancer
Authors: Blackstock A. William , Bernard Stephen A. , Richards Frederick , Eagle Kaye S. , Case L. Douglas , Poole Michael E. , Savage Paul D. , Tepper Joel E. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m2 by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m2 increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2 given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m2 dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m2 produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.