bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunocytoma: A Retrospective Analysis From St Bartholomew's Hospital—1972 to 1996
Authors: Papamichael D. , Norton A. J. , Foran J. M. , Mulatero C. , Mathews J. , Amess J. A.L , Bradburn M. , Lister T. A. , Rohatiner A. Z.S. 
Published: February 2017

PURPOSE: To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. PATIENTS AND METHODS: One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. RESULTS: Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P < .01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P = .01). A comparison of the three IMC subgroups showed that there was a trend (P = .06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. CONCLUSION: Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.
Characteristics and Outcome of Children With Beckwith-Wiedemann Syndrome and Wilms’ Tumor: A Report From the National Wilms Tumor Study Group
Authors: Porteus Matthew H. , Narkool Patricia , Neuberg Donna , Guthrie Katherine , Breslow Norman , Green Daniel M. , Diller Lisa 
Published: February 2017

PURPOSE: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms’ tumor (WT). We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. METHODS: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. RESULTS: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P = .0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P = .02), a trend not seen in the non-BWS patients. CONCLUSION: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller tumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate.
Sequence Effect of Epirubicin and Paclitaxel Treatment on Pharmacokinetics and Toxicity
Authors: Venturini Marco , Lunardi Gianluigi , Del Mastro Lucia , Vannozzi Maria Ornella , Tolino Giuseppina , Numico Gianmauro , Viale Maurizio , Pastrone Ilaria , Angiolini Catia , Bertelli Gianfilippo , Straneo Manuela , Rosso Riccardo , Esposito Mauro 
Published: February 2017

PURPOSE: Sequence-dependent clinical and pharmacokinetic interactions between paclitaxel and doxorubicin have been reported. Some data have shown an influence of paclitaxel on epirubicin metabolism, but no data are available about the effect of diverse sequences of these drugs. We investigated whether reversing the sequence of epirubicin and paclitaxel affects the pattern or degree of toxicity and pharmacokinetics. PATIENTS AND METHODS: Patients receiving epirubicin 90 mg/m2 by intravenous bolus followed by paclitaxel 175 mg/m2 over 3-hour infusion or the opposite sequence every 3 weeks for four cycles were eligible. Toxicity was recorded at nadir. Pharmacokinetic data were evaluated at the first and the second cycle and were correlated with toxicity parameters. RESULTS: Thirty-nine consecutive stage II breast cancer patients were treated. Twenty-one patients received epirubicin followed by paclitaxel (ET group), and 18 received the opposite sequence (TE group). No significant difference in nonhematologic toxicity was seen. A lower neutrophil and platelet nadir and a statistically significant slower neutrophil recovery was observed in the TE group. Area under the concentration-time curve (AUC) of epirubicin was higher in the TE group (2,346 ng/mL · h v 1,717 ng/mL · h; P = .002). An inverse linear correlation between epirubicin AUC and neutrophil recovery was also observed (P = .012). No difference was detected in paclitaxel pharmacokinetics. CONCLUSION: Our results support a sequence-dependent effect of paclitaxel over epirubicin pharmacokinetics that is associated with increased myelotoxicity. Because schedule modifications of anthracyclines and paclitaxel can have clinical consequences, the classical way of administration (ie, anthracyclines followed by paclitaxel) should be maintained in clinical practice.
Quantitative Bone Single-Photon Emission Computed Tomography for Prediction of Pain Relief in Metastatic Bone Disease Treated With Rhenium-186 Etidronate
Authors: Israel Ora , Keidar Zohar , Rubinov Rafael , Iosilevski Galina , Frenkel Alex , Kuten Abraham , Betman Lise , Kolodny Gerald M. , Yarnitsky David , Front Dov 
Published: February 2017

PURPOSE: To calculate radiation doses of rhenium-186 (186Re) etidronate in painful bone metastases using quantitative bone single-photon emission computed tomography (SPECT) and to determine the threshold dose for predicting pain relief. We also wanted to determine whether technetium-99m (99mTc) methylene diphosphonate (MDP) concentrations predict radiation doses of 186Re etidronate in painful lesions. MATERIALS AND METHODS: Forty-eight patients with breast and prostate cancer were evaluated. Patients received therapeutic doses of 186Re etidronate. The area under the pain over time curve (AUPC) was measured for 8 weeks after treatment. Response was calculated as the percentage of change in AUPC. Quantitative bone SPECT (QBS)–measured concentration of 186Re etidronate was used for calculating radiation doses. Receiver operating characteristics curve analysis determined the radiation dose threshold that best separated responders from nonresponders. SPECT-measured concentration of 186Re etidronate in the urinary bladder was correlated with its concentration in the voided urine. Concentration of 99mTc MDP was compared with radiation doses to painful metastases. RESULTS: The radiation dose threshold was 2.10 Gy. For a decrease of 50% in the AUPC, the positive predictive value (PPV) of this value was 75% and the negative predictive value (NPV) was 88%. For a decrease in pain of 33%, the PPV was 84% and the NPV was 81%. In prostate cancer patients only, the PPV was 81% and the NPV was 92%. The correlation between in vivo/in vitro measured urine concentration was 0.90. The correlation between 99mTc MDP concentration and radiation doses of 186Re etidronate was 0.92. CONCLUSION: QBS-measured radiation doses of 186Re etidronate in painful metastases are a good predictor of pain relief. Bone SPECT using 99mTc MDP predicts radiation doses delivered by 186Re etidronate.
Phase I and Pharmacokinetic Trial of Gemcitabine in Patients With Hepatic or Renal Dysfunction: Cancer and Leukemia Group B 9565
Authors: Venook Alan P. , Egorin Merrill J. , Rosner Gary L. , Hollis Donna , Mani Sridhar , Hawkins Michael , Byrd John , Hohl Raymond , Budman Daniel , Meropol Neal J. , Ratain Mark J. 
Published: February 2017

PURPOSE: To ascertain if hepatic or renal dysfunction leads to increased toxicity at a given dose of gemcitabine and to characterize the pharmacokinetics of gemcitabine and its major metabolite in patients with such dysfunction. PATIENTS AND METHODS: Adults with tumors appropriate for gemcitabine therapy and who had abnormal liver or renal function tests were eligible. Patients were assigned to one of three treatment cohorts: I—AST level less than or equal to two times normal and bilirubin level less than 1.6 mg/dL; II—bilirubin level 1.6 to 7.0 mg/dL; and III—creatinine level 1.6 to 5.0 mg/dL with normal liver function. Doses were explored in at least three patients within each cohort. Gemcitabine and its metabolite were to be measured in the blood in all patients. RESULTS: Forty patients were assessable for toxicity. Transient transaminase elevations were observed in many patients but were not dose limiting. Patients with AST elevations tolerated gemcitabine without increased toxicity, but patients with elevated bilirubin levels had significant deterioration in liver function after gemcitabine therapy. Patients with elevated creatinine levels had significant toxicity even at reduced doses of gemcitabine, including two instances of severe skin toxicity. There were no apparent pharmacokinetic differences among the three groups or compared with historical controls. CONCLUSION: If gemcitabine is used for patients with elevations in AST level, no dose reduction is necessary. Patients with elevated bilirubin levels have an increased risk of hepatic toxicity, and a dose reduction is recommended. Patients with elevated creatinine levels seem to have increased sensitivity to gemcitabine, but the data are not adequate to support a specific dosing recommendation.
Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non–Small-Cell Lung Cancer
Authors: Khuri Fadlo R. , Lotan Reuben , Kemp Bonnie L. , Lippman Scott M. , Wu Hong , Feng Lei , Lee J. Jack , Cooksley Catherine S. , Parr Bianca , Chang Evelyn , Walsh Garrett L. , Lee Jin S. , Hong Waun K. , Xu Xiao-Chun 
Published: February 2017

PURPOSE: Retinoids are pivotal in the growth and differentiation of certain epithelial tissues, interacting with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors. RAR-beta mRNA is undetectable by in situ hybridization (ISH) in 50% of non–small-cell lung cancers (NSCLC). RAR-β may suppress tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-β gene in stage I NSCLC is a prognostic factor of a poor clinical outcome. PATIENTS AND METHODS: We retrospectively analyzed RAR-β mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available. RESULTS: One hundred fifty-six patients who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha mRNA (used as a control to assess RNA degradation) and who had adequate follow-up could be evaluated. RAR-β mRNA expression was undetectable in 51 patients, weakly positive in 64 patients, and strongly positive in 41 patients. Overall survival of the 41 patients with strongly positive RAR-β was significantly worse than for the 115 patients with weak or absent RAR-β (P = .045). CONCLUSION: Unexpectedly, strong RAR-β expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.
Tamoxifen Should be Cost-Effective in Reducing Breast Cancer Risk in High-Risk Women
Authors: Smith Thomas J. , Hillner Bruce E. 
Published: February 2017

PURPOSE: To estimate the cost-effectiveness of tamoxifen in the prevention of breast cancer. PATIENTS AND METHODS: Clinical trial results of National Surgical Adjuvant Breast Program P−1 compared tamoxifen versus placebo in the prevention of breast cancer, and direct medical care costs were estimated from the Agency for Health Care Policy and Research and local sources. The base estimate of effectiveness included all women on the trial. RESULTS: For every 100 women treated for 5 years, 1.665 expected cancers would not be detected. If breast cancer death is fully prevented by this strategy, then the cost-effectiveness of tamoxifen compared with no intervention is $8,479 per additional year of life gained. If lifetime prevention of the risk of death from breast cancer exceeded 17%, then the cost-effectiveness ratio would be less than $50,000 per year of life gained (a common benchmark). CONCLUSIONS: Tamoxifen for breast cancer prevention should be cost-effective under nearly all circumstances. Its use will require additional resources because it is not cost saving, but it fits within accepted guidelines.
New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia
Authors: Socié Gérard , Curtis Rochelle E. , Deeg H. Joachim , Sobocinski Kathleen A. , Filipovich Alexandra H. , Travis Lois B. , Sullivan Keith M. , Rowlings Philip A. , Kingma Douglas W. , Banks Peter M. , Travis William D. , Witherspoon Robert P. , Sanders Jean , Jaffe Elaine S. , Horowitz Mary M. 
Published: February 2017

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P < .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell–depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.
Effect of Adjuvant Tamoxifen on the Endometrium in Women With Breast Cancer: A Prospective Study Using Office Endometrial Biopsy
Authors: Barakat R.R. , Gilewski T.A. , Almadrones L. , Saigo P.E. , Venkatraman E. , Hudis C. , Hoskins W.J. 
Published: February 2017

PURPOSE: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved. PATIENTS AND METHODS: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study. In this study, office endometrial biopsies (EMBs) were obtained during the initiation of tamoxifen and at 6-month intervals for a 2-year period. Three subsequent annual EMBs were recorded for each patient, amounting to a 5-year surveillance. RESULTS: One hundred fifty-nine patients with a median age of 50 years were entered onto study. Patients were assessable if EMBs were performed at least 1 year after the initiation of tamoxifen treatment. Nine patients (5.7%) were considered protocol violations. The remaining 111 assessable patients underwent a total of 635 EMBs (mean, 5.8 EMBs), with a median surveillance time of 36 months. Eighty-two (12.9%) of the 635 biopsies revealed tissue insufficient for diagnosis. Fourteen patients (12.6%) underwent dilation and curettage (D&C) for an abnormal EMB, persistent bleeding, or for evaluation of adnexal masses at the time of laparoscopy. Findings at D&C included complex hyperplasia (n = 1), abnormal histiocytes (n = 1), simple hyperplasia (n = 2), polyps (n = 4), endocervical polyp (n = 1), and decidualization (n = 2). Three D&Cs were negative. Three patients have undergone hysterectomy. CONCLUSION: EMB was used to monitor the endometrium in the majority (95%) of breast cancer patients on tamoxifen in this trial, but the utility of routine EMB for screening in tamoxifen-treated women seems limited.
In Vivo Cytoreduction Studies and Cell Sorting–Enhanced Tumor-Cell Detection in High-Risk Neuroblastoma Patients: Implications for Leukapheresis Strategies
Authors: Faulkner Lawrence B. , Garaventa Alberto , Paoli Antonella , Tintori Veronica , Tamburini Angela , Lacitignola Laura , Veltroni Marinella , Piccolo Maria Serena Lo , Viscardi Elisabetta , Milanaccio Claudia , Tondo Annalisa , Spinelli Serena , Bernini Gabriella , De Bernardi Bruno 
Published: February 2017

PURPOSE: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis. PATIENTS AND METHODS: Anti-GD2 immunocytochemistry (sensitivity, 1 in 105 to 106 leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-GD2 immunomagnetic enrichment step was used to enhance tumor-cell detection. RESULTS: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-GD2 immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 107 to 108 leukocytes). CONCLUSION: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered.
Abnormalities of Chromosome Bands 13q12 to 13q14 in Childhood Acute Lymphoblastic Leukemia
Authors: Heerema Nyla A. , Sather Harland N. , Sensel Martha G. , Lee Mei K. , Hutchinson Raymond J. , Nachman James B. , Reaman Gregory H. , Lange Beverly J. , Steinherz Peter G. , Bostrom Bruce C. , Gaynon Paul S. , Uckun Fatih M. 
Published: February 2017

PURPOSE: Little is known about nonrandom deletions of chromosome bands 13q12 to 13q14 (13q12–14) in acute lymphoblastic leukemia (ALL). We determined the prognostic significance of cytogenetically identified breakpoints in 13q12–14 in children with newly diagnosed ALL treated on Children’s Cancer Group protocols from 1988 to 1995. PATIENTS AND METHODS: Breakpoints in 13q12–14 were identified in 36 (2%) of the 1,946 cases with accepted cytogenetic data. Outcome analysis used standard life-table methods. RESULTS: Seventeen patients (47%) with an abnormal 13q12–14 were classified, according to the National Cancer Institute (NCI), as poor risk, and 15 patients (42%) were standard risk; four (11%) were infants less than 12 months of age. Eight cases had balanced rearrangements of 13q12–14, 27 patients had a partial loss of 13q, and one had both a partial gain and a partial loss. The most frequent additional abnormalities among these patients were an abnormal 12p, a del(6q), a del(9p), a 14q11 breakpoint, and an 11q23 breakpoint. Nineteen patients were pseudodiploid, 10 were hyperdiploid, and seven were hypodiploid. Patients with an abnormal 13q12–14 had significantly worse event-free survival than patients lacking such an abnormality, with estimates at 6 years of 61% (SD = 14%) and 74% (SD = 1%), respectively (P = .04; relative risk = 1.74). Overall survival, however, was similar for the two groups (P = .25). The prognostic effect of an abnormal 13q was attenuated in a multivariate analysis adjusted for NCI risk status and ploidy (P = .72). CONCLUSION: Aberrations of 13q12–14 may contribute to leukemogenesis of childhood ALL and confer increased risk of treatment failure but are associated with other poor-risk features.
Large-Cell Lymphoma Arising in the Mediastinum in Children and Adolescents Is Associated With an Excellent Outcome: A Children’s Cancer Group Report
Authors: Lones Mark A. , Perkins Sherrie L. , Sposto Richard , Kadin Marshall E. , Kjeldsberg Carl R. , Wilson John F. , Cairo Mitchell S. 
Published: February 2017

PURPOSE: Large-cell lymphoma (LCL) arising in the mediastinum (LCL-M) is a heterogeneous group of non-Hodgkin’s lymphoma (NHL) that includes B-cell lymphomas as well as T-cell lymphomas, including anaplastic LCL. LCL-M is well recognized in young adults but is less well characterized and infrequent in children and adolescents. METHODS: A retrospective review of Children’s Cancer Group therapeutic studies for nonlymphoblastic lymphomas (CCG-551, CCG-503, CCG-552, and CCG-5911) identified 20 patients with LCL-M, representing 7.2% of all LCLs classified by central pathology review. RESULTS: The patients ranged in age from 4 to 19 years (median, 12.5 years; mean, 12 years); 55% of the patients were male. Although a variety of chemotherapy regimens were used, response was excellent, with all 20 patients (100%) achieving a complete response. Four patients (20%) experienced relapse locally or in distant sites including brain and kidney. One patient died of sepsis during therapy. For the 20 patients with LCL-M, the product-limit estimated 5-year event-free survival (EFS) and 5-year overall survival (OS) rates are 75% ± 10% and 85% ± 8%, respectively. For disseminated LCLs (192 cases), the EFS and OS rates were 50% ± 4% and 63% ± 4%, respectively, which differ significantly from the those of the LCL-M cases (EFS, P = .025; OS, P = .034). The 5-year EFS and OS rates for patients with localized LCL (67 cases) were 92 ± 3% and 97 ± 2%, respectively. CONCLUSION: LCL-M is a heterogeneous group of NHLs that makes up approximately 7.2% of LCL in children and adolescents. Response to therapy and OS in this young age group seems excellent and superior to that of disseminated LCLs but inferior to that of other localized LCL. Future studies of LCL-M will evaluate short intense chemotherapy administered without radiation therapy.