bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescence In Situ Hybridization on Peripheral-Blood Specimens Is a Reliable Method to Evaluate Cytogenetic Response in Chronic Myeloid Leukemia
Authors: Le Gouill Steven , Talmant Pascaline , Milpied Noël , Daviet Axelle , Ancelot Michèle , Moreau Philippe , Harousseau Jean-Luc , Bataille Régis , Avet-Loiseau Hervé 
Published: February 2017

PURPOSE: To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH. RESULTS: The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r = .98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r = .97). CONCLUSION: Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.
Role of Isolated Locoregional Recurrence of Breast Cancer: Results of Four Prospective Studies
Authors: Schmoor Claudia , Sauerbrei Willi , Bastert Gunter , Schumacher Martin ,   for the German Breast Cancer Study Group
Published: February 2017

PURPOSE: We evaluated the effect on future prognosis of an isolated locoregional recurrence (ILRR) after the primary diagnosis of breast cancer. Using data from four prospective studies of the German Breast Cancer Study Group, we investigated factors influencing prognosis after ILRR and defined a simple classification of patients into groups with different prognoses. PATIENTS AND METHODS: From 1983 to 1989, 2,746 patients were recruited into four studies comparing different treatments in primary breast cancer. After a median follow-up time of 8 years, 337 patients developed an ILRR as the first event. The influence of ILRRs on disease progression was examined. The effects of different prognostic factors on progression-free survival (PFS) and overall survival after ILRR were analyzed after a median follow-up time of 4.5 years. RESULTS: ILRRs increased the risk with respect to distant recurrence and death. After ILRR, 185 events occurred with respect to the PFS end point, and 171 patients died. Primary nodal status, tumor grade, estrogen receptor status of the primary tumor, and length of the disease-free interval (DFI) until the time of the ILRR had a significant prognostic impact. CONCLUSION: Determinants of prognosis after the ILRR should be taken into account for designing future risk-adapted clinical studies for these patients. Risk strata can be defined by a simple classification scheme based on primary nodal status and DFI.
Drug Interactions in Palliative Care
Authors: Bernard Stephen A. , Bruera Eduardo 
Published: February 2017

PURPOSE: This review of drug interactions in palliative care examines the relevant literature in this area and summarizes the information on interactions of drugs, nutrients, and natural products that are used in the palliative care setting. Particular emphasis is placed on describing the newer information on the cytochrome P450 (CYP) system and the interactions of opioids, antidepressants, and the antitussive, dextromethorphan.METHODS: We performed a search of the MEDLINE database of the time period from 1966 until April 1998, using medical subject headings such as the names of selective serotonin reuptake inhibitors and other relevant medications in palliative care. Literature reviewed included both human and animal articles as well as non-English literature. Bibliographies of these articles and the personal libraries of several palliative care specialists were reviewed. Software developed by The Medical Letter—The Drug Interaction Program was also used.RESULTS: Drug interactions can be categorized in several ways. Drug-drug interactions are the most well known and can be kinetic, dynamic, or pharmaceutical. Pharmacokinetic interactions can involve CYP 2D6, which acts on drugs such as codeine and is responsible for its conversion to morphine. Poor metabolizers, either genotypic or due to phenocopying, are at risk for undertreatment if not recognized. Pharmacodynamic interactions with dextromethorphan may produce serotonin syndrome.CONCLUSION: Drug interactions are important in palliative care as in other aspects of medicine. These interactions are similar to those seen in other areas of medical care but have significant consequences in pain management. Failure to recognize these interactions can lead to either overdosing or undertreatment.
Early Detection of Relapse by Hypermetaphase Fluorescence In Situ Hybridization After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia
Authors: Seong Chy-Myong , Giralt Sergio , Kantarjian Hagop , Xu Jingping , Swantkowski Jolynn , Hayes Kimberley , Glassman Armand B. , Khouri Issa , Korbling Martin , Thall Peter , Siciliano Michael J. , Champlin Richard E. 
Published: February 2017

PURPOSE: Standard G-band cytogenetic analysis (CG) provides information on approximately 25 metaphases for monitoring the presence of Philadelphia chromosome positive (Ph+) cells in chronic myelogenous leukemia (CML) patients, making the detection of a low frequency of Ph+ cells problematic. The purpose of this study was to improve the detection of a low frequency of Ph+ cells. PATIENTS AND METHODS: We combined fluorescence in situ hybridization (FISH) with long-term colcemid exposure, capturing several hundred metaphases in bone marrow cultures (hypermetaphase FISH [HMF]). Using probes that identify Ph+ cells, HMF was compared with CG analysis in the follow-up evaluations of 51 patients with CML at various time points after allogeneic bone marrow transplant (BMT). RESULTS: Thirty-five patients never showed the presence of Ph+ cells by either method. In four patients, high frequencies of Ph+ cells were detected by both methods. In the remaining 12 patients, Ph+ cells were detected by HMF at time points after BMT when they were not detected by CG. In seven of the 12 patients, low but statistically significant frequencies of Ph+ cells (0.37% to 5.20%) were detected 3 months or later after BMT, and when no intervention was initiated, all seven patients later relapsed. Based on those data, an eighth patient with mixed chimerism and a similar HMF-detected Ph+ frequency (1.8% at 27 months after BMT) was reinfused with donor lymphocytes and achieved remission with 0% Ph+ cells studied by HMF (up to 50 months after BMT). Ph+ cells detected by HMF but not by CG less than 3 months after BMT disappeared on later examination in two of four patients. After detection of Ph+ cells by HMF only, the median time to cytogenetic progression (detection of Ph+ cells by CG) was 101 days. CONCLUSION: The results demonstrate the ability of HMF to detect low but clinically relevant levels of leukemic cells not detected by CG in transplant patients. The data indicate that HMF can detect low levels of Ph+ cells before standard cytogenetics at a time that may be useful in monitoring disease status and planning clinical interventions.
Alpha Hemolytic Streptococcal Infection During Intensive Treatment for Acute Myeloid Leukemia: A Report From the Children’s Cancer Group Study CCG-2891
Authors: Gamis Alan S. , Howells William B. , DeSwarte-Wallace Joetta , Feusner James H. , Buckley Jonathan D. , Woods William G. 
Published: February 2017

PURPOSE: Past reports indicate that alpha hemolytic streptococcal (AHS) organisms are a common cause of infection among acute myeloid leukemia (AML) patients. This study was intended to ascertain the population incidence and rate (infections per 100 patient-days of treatment) of AHS and to identify associated risk factors. PATIENTS AND METHODS: Patients (n = 874 with 151,350 days of risk) enrolled on the Children’s Cancer Group (CCG) protocol for newly diagnosed AML, CCG-2891, which randomly assigned intensity of induction and intensification, were prospectively evaluated for infectious complications. RESULTS: AHS occurred in 21% of patients, was primarily blood borne (86%), made up 21% of bacteremic infections, and had a recurrent incidence of 31% during subsequent therapy. AHS was more often life-threatening (59%) than other infections (41%) (P = .001). AHS rates increased with age less than 10 years (odds ratio [OR], 2.0; P = .007), intensively timed induction (OR, 1.8 to 1.9; P = .02), and high-dose cytarabine intensification (OR, 3.7; P < .0001). Among all courses, the greatest incidence (19%) and rate (0.41) were associated with the use of high-dose cytarabine. Gastrointestinal toxicity correlated significantly with AHS bacteremia (P < .01). Infection with AHS resulted in increased hospital days (P = .0001). Only among bone marrow transplant patients were overall survival (OR, 2.8; P = .0001) and disease-free survival (OR, 2.1; P = .008) decreased after AHS bacteremia. CONCLUSION: This study, the first to prospectively examine AHS incidence among uniformly treated patients in multiple institutions, established that as the intensity of AML therapy has increased, so has the rate of AHS. Young children, those with previous AHS bacteremias, and those receiving high-dose cytarabine are at particularly high risk of AHS bacteremia.
Loss of Heterozygosity at 1p36 Independently Predicts for Disease Progression But Not Decreased Overall Survival Probability in Neuroblastoma Patients: A Children’s Cancer Group Study
Authors: Maris John M. , Weiss Matthew J. , Guo Chun , Gerbing Robert B. , Stram Daniel O. , White Peter S. , Hogarty Michael D. , Sulman Erik P. , Thompson Patricia M. , Lukens John N. , Matthay Katherine K. , Seeger Robert C. , Brodeur Garrett M. 
Published: February 2017

PURPOSE: To determine the independent prognostic significance of 1p36 loss of heterozygosity (LOH) in a representative group of neuroblastoma patients. PATIENTS AND METHODS: Diagnostic tumor specimens from 238 patients registered onto the most recent Children’s Cancer Group phase III clinical trials were assayed for LOH with 13 microsatellite polymorphic markers spanning chromosome band 1p36. Allelic status at 1p36 was correlated with other prognostic variables and disease outcome. RESULTS: LOH at 1p36 was detected in 83 (35%) of 238 neuroblastomas. There was a correlation of 1p36 LOH with age at diagnosis greater than 1 year (P = .026), metastatic disease (P < .001), elevated serum ferritin level (P < .001), unfavorable histopathology (P < .001), and MYCN oncogene amplification (P < .001). LOH at 1p36 was associated with decreased event-free survival (EFS) and overall survival (OS) probabilities (P < .0001). For the 180 cases with single-copy MYCN, 1p36 LOH status was highly correlated with decreased EFS (P = .0002) but not OS (P = .1212). Entering 1p36 LOH into a multivariate regression model suggested a trend toward an independent association with decreased EFS (P = .0558) but not with decreased OS (P = .3687). Furthermore, allelic status at 1p36 was the only prognostic variable that was significantly associated with decreased EFS in low-risk neuroblastoma patients (P = .0148). CONCLUSION: LOH at 1p36 is independently associated with decreased EFS, but not OS, in neuroblastoma patients. Determination of 1p36 allelic status may be useful for predicting which neuroblastoma patients with otherwise favorable clinical and biologic features are more likely to have disease progression.
Stereotactic Single-Dose Radiation Therapy of Liver Tumors: Results of a Phase I/II Trial
Authors: Herfarth Klaus K. , Debus Jürgen , Lohr Frank , Bahner Malte L. , Rhein Bernhard , Fritz Peter , Höss Angelika , Schlegel Wolfgang , Wannenmacher Michael F. 
Published: February 2017

PURPOSE: To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS: Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm3 (range, 1 to 132 cm3). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS: Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION: Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.
Treatment of Orbital Rhabdomyosarcoma: Survival and Late Effects of Treatment—Results of an International Workshop
Authors: Oberlin Odile , Rey Annie , Anderson James , Carli Modesto , Raney R. Beverley , Treuner Joern , Stevens Michael C.G. ,   the Intergroup Rhabdomyosarcoma Study Group,,   the Italian Cooperative Soft Tissue Sarcoma Group, and,   the German Collaborative Soft Tissue Sarcoma Group
Published: February 2017

PURPOSE: Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS: A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS: At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION: These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.
Effect of Endocrine Treatment on Sexuality in Premenopausal Breast Cancer Patients: A Prospective Randomized Study
Authors: Berglund Gunilla , Nystedt Marianne , Bolund Christina , Sjödén Per-Olow , Rutquist Lars-Erik 
Published: February 2017

PURPOSE: To study the sexual effects of the 2-year adjuvant goserelin (Zoladex [Zeneca AB, Södertälje, Sweden]) alone, tamoxifen alone, and Zoladex and tamoxifen in combination (ZT) versus no adjuvant endocrine therapy among premenopausal breast cancer patients with or without chemotherapy in a controlled clinical trial (a European multicenter trial: Zoladex in Premenopausal Breast Cancer Patients). PATIENTS AND METHODS: This prospective study examined several aspects of sexuality through the use of self-administered questionnaires, which were completed by patients at seven points of assessment for 3 years after randomization. RESULTS: Patients treated with chemotherapy had a higher level of sexual dysfunction than did patients who received no systemic treatment. The addition of endocrine treatment did not alter this result. In contrast, among patients who did not receive chemotherapy, Zoladex and ZT produced a significantly higher level of dysfunction from 1 to 2 years after inclusion, as compared with those who received no endocrine treatment. Tamoxifen alone did not produce side effects. After termination of endocrine treatment, sexual dysfunction began to diminish. Those with chemotherapy had high and frequently increasing levels of dysfunction even after 2 to 3 years of independent of endocrine treatment. Zoladex had a negative effect on sexual fear, which was reduced by the addition of tamoxifen. CONCLUSION: Zoladex increased sexual dysfunction during treatment among patients without chemotherapy, but the disturbances of sexual functioning were reversible. The use of adjuvant chemotherapy was associated with continued sexual problems, even at 3 years after randomization.
Psychosocial Characteristics of Individuals With Non–Stage IV Melanoma
Authors: Trask Peter C. , Paterson Amber G. , Hayasaka Satoru , Dunn Rodney L. , Riba Michelle , Johnson Timothy 
Published: February 2017

PURPOSE: Melanoma is the fastest growing solid tumor among men and women and accounts for 79% of skin cancer–related deaths. Research has identified that distress is frequently associated with a diagnosis of cancer and may slow treatment-seeking and recovery, increasing morbidity and even mortality through faster disease course. Given that the 5-year survival rates for individuals with melanoma are determined primarily by the depth and extent of spread, distress that interferes with seeking treatment has the potential to be life-threatening. PATIENTS AND METHODS: The current study was designed to identify levels of distress present in individuals seeking treatment at a large, Midwestern, multidisciplinary melanoma clinic. It also focused on determining the quality of life, level of anxiety, and coping strategies used by individuals with melanoma before treatment. Given that the course of treatment and outcome for patients with stage IV disease is vastly different from that of patients with stages I to III disease, they were excluded from the study. RESULTS: Results indicated that most individuals who are presenting to a melanoma clinic do not report a clinically significant level of distress. However, there is some variability in this, with 29% of patients reporting moderate to high levels of distress. Moreover, analyses suggest that distressed individuals are more likely to use maladaptive coping strategies, such as escape-avoidance coping, and to have poorer quality of life. CONCLUSION: Although most individuals do not present with significant levels of distress, a significant minority are distressed and rely more heavily on coping strategies that do not benefit them. Such individuals would likely benefit most from psychological intervention.
Phase I/II Trial of the Multidrug-Resistance Modulator Valspodar Combined With Cisplatin and Doxorubicin in Refractory Ovarian Cancer
Authors: Baekelandt Mark , Lehne Gustav , Tropé Claes G. , Szántó István , Pfeiffer Per , Gustavssson Bengt , Kristensen Gunnar B. 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose (MTD) of doxorubicin when given in combination with cisplatin and the multidrug-resistance (MDR) modulator valspodar and the remission rate induced by this combination in patients with platinum- and anthracycline-resistant ovarian cancer. PATIENTS AND METHODS: Fifty-nine patients who had failed prior platinum- and anthracycline-based chemotherapy were enrolled. During the dose-finding phase, patients received a loading dose of valspodar (1.5 or 2 mg/kg) via 2-hour intravenous (IV) infusion on day 1 and continuous IV infusion (CIVI) of valspodar (2, 4, or 10 mg/kg/d) over 3 days. Doxorubicin (starting from 20 up to 50 mg/m2) and cisplatin (50 mg/m2) were administered via 15- to 20-minute IV infusions on day 3. During the efficacy phase, patients received at least two treatment cycles unless toxicity was unacceptable, and responding patients and those with stable disease received four to six cycles. RESULTS: All patients completed at least one cycle of combined treatment. The MTD of doxorubicin was determined to be 35 mg/m2 when administered with valspodar at 2 mg/kg loading dose and 10 mg/kg/d CIVI plus 50 mg/m2 cisplatin. At these doses, valspodar blood concentrations known to reverse MDR in vitro were reached in all patients. Valspodar was well tolerated at all dose levels. Dose-limiting toxicities of the combination were primarily hematologic and included febrile neutropenia and prolonged leucopenia. The addition of valspodar to the treatment did not worsen cisplatin-related toxicity. Among 33 patients treated at the MTD for doxorubicin, one (3%) had a complete response, and four (12%) had a partial response. An additional seven patients experienced a stabilization of their previously progressive disease. The survival rates at 6 and 12 months were 59% and 19%, respectively. CONCLUSION: Valspodar can be safely coadministered with doxorubicin and cisplatin. Although the regimen used in this trial produced renewed responses in patients with heavily pretreated, refractory ovarian cancer, the value of valspodar in reversing resistance mediated by P-glycoprotein remains to be determined.