bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer.
Authors: Ryberg M , Nielsen D , Skovsgaard T , Hansen J , Jensen B V , Dombernowsky P 
Published: February 2017

PURPOSE To evaluate the influence of cumulative dose, dose-intensity, single-dose level, and schedule of epirubicin on the risk of developing congestive heart failure (CHF) in patients with advanced breast cancer. PATIENTS AND METHODS Four hundred sixty-nine consecutive anthracyline-naive patients with metastatic breast cancer were included. Only patients with cardiac failure according to New York Heart Association (NYHA) function class II or more were recorded as having CHF. For each patient, the following were calculated: the cumulative dose of epirubicin, mean dose-intensity (cumulative dose of epirubicin/duration of treatment), and single-dose level (cumulative dose of epirubicin/number of injections). RESULTS Thirty-four patients (7.2%) developed CHF. The cumulative risk of cardiotoxicity was 4% at 900 mg/m2 and increased exponentially to 15% at 1,000 mg/m2. Irradiation against the mediastinum and thoracic spine increased the risk of CHF (P=.025), but dose-intensity, single-dose level, and schedule had no influence on the risk of developing CHF. Age, previous adjuvant irradiation (to the left or right hemithorax), and previous chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) were not risk factors. The median time to onset of CHF following the last dose of epirubicin was 57 days (range, 0 to 853). Among patients with CHF, 13 (38.2%) died of cardiac failure. The median survival time for all patients with CHF was 162 days (range, 0 to +1,957). Previous irradiation directly against the heart increased the risk of death due to cardiac failure and decreased the median survival time to 125 days (range, 0 to 336). CONCLUSION The present large retrospective study of 469 patients substantiates previous results concerning the cardiotoxicity of epirubicin. A significantly increasing risk of CHF in patients who receive cumulative doses greater than 950 mg/m2 was established. The future recommended maximum cumulative dose of epirubicin should be 900 mg/m2 in patients with metastatic breast cancer. Previous irradiation against the heart leads to an increased risk of developing CHF with an accelerated course to death, which indicates an additive cardiotoxic effect of irradiation and epirubicin.
Detection of recurrent or persistent nasopharyngeal carcinomas after radiotherapy with 18-fluoro-2-deoxyglucose positron emission tomography and comparison with computed tomography.
Authors: Kao C H , ChangLai S P , Chieng P U , Yen R F , Yen T C 
Published: February 2017

PURPOSE The effectiveness of positron emission tomography (PET) with 1 8-fluoro-2-deoxyglucose (FDG) for detecting suspected recurrence of nasopharyngeal carcinomas (NPC) was evaluated and compared with computed tomography (CT). PATIENTS AND METHODS FDG-PET studies were performed on 36 NPC patients 4 months after radiotherapy. The images were interpreted visually and quantitatively by calculating standardized uptake values (SUVs). RESULTS The sensitivity, specificity, and accuracy of visually interpreted FDG-PET images, for differentiation of recurrent or persistent NPC from benign lesions, were 100%, 96%, and 97%, respectively. Cases with recurrent or persistent NPC (1.6 to 5.8) had significantly higher SUVs than cases with benign lesions (0.8 to 1.5). The sensitivity, specificity, and accuracy of CT for detecting recurrent or persistent NPC were 72%, 88%, and 83%, respectively. CONCLUSION FDG-PET is a better tool than CT for the detection of recurrent or persistent NPC. Either visual interpretation or SUV can be used to differentiate benign lesions from recurrent or persistent NPC.
Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases.
Authors: Pirzkall A , Debus J , Lohr F , Fuss M , Rhein B , Engenhart-Cabillic R , Wannenmacher M 
Published: February 2017

PURPOSE Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) > or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.
Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.
Authors: Joensuu H , Holli K , Heikkinen M , Suonio E , Aro A R , Hietanen P , Huovinen R 
Published: February 2017

PURPOSE We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS Patients in the single-agent arm (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2 three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m2 every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger than 50. RESULTS An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agent arm. No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments were compared or when survival was calculated from the beginning of the second-line therapy. CONCLUSION Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL as compared with those treated with CEF followed by MV.
Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.
Authors: Pui C H , Rubnitz J E , Hancock M L , Downing J R , Raimondi S C , Rivera G K , Sandlund J T , Ribeiro R C , Head D R , Relling M V , Evans W E , Behm F G 
Published: February 2017

PURPOSE To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis. RESULTS CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements. CONCLUSION Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.
Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.
Authors: Khouri I F , Romaguera J , Kantarjian H , Palmer J L , Pugh W C , Korbling M , Hagemeister F , Samuels B , Rodriguez A , Giralt S , Younes A , Przepiorka D , Claxton D , Cabanillas F , Champlin R 
Published: February 2017

PURPOSE Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.
Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.
Authors: Thiede C , Alpen B , Morgner A , Schmidt M , Ritter M , Ehninger G , Stolte M , Bayerdörffer E , Neubauer A 
Published: February 2017

PURPOSE Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. PATIENTS AND METHODS Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. RESULTS Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. CONCLUSION In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.
Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review.
Authors: Kushner B H , Cheung N K , Kramer K , Heller G , Jhanwar S C 
Published: February 2017

PURPOSE To assess treatment-related myelodysplasia/leukemia (t-AML) in neuroblastoma patients by a review of the Memorial Sloan-Kettering Cancer Center (MSKCC) data and the literature. PATIENTS AND METHODS We studied 380 previously untreated and treated MSKCC patients. Low-risk patients received no cytotoxic therapy. High-risk patients received the N4, N5, or N6 regimens. Dosing per cycle and cumulative dosing of leukemogenic agents peaked with N6, which included four cycles of cyclophosphamide 4,200 mg/m2 and doxorubicin 75 mg/m2, plus three cycles of cisplatin 200 mg/m2 and etoposide 600 mg/m2. We reviewed the literature. RESULTS t-AML occurred in six MSKCC patients, which included three of 53 patients in whom the only chemotherapy consisted of N6, and three patients treated for relapsed or refractory neuroblastoma; no case of leukemia emerged among the 50 low-risk patients. Four cases were found incidentally in routine follow-up bone marrow tests. The 36-month cumulative incidence of t-AML in the N6 cohort was 7% (95% confidence interval, 0 to 15). Published data parallel the MSKCC experience in that t-AML after neuroblastoma was once rare but has become less so since the mid-1980s, when the intensified use of topoisomerase-II inhibitors and alkylators first gained wide acceptance and produced better response rates and longer survival. CONCLUSION Neuroblastoma itself is not associated with a host susceptibility to leukemia. However, current neuroblastoma treatment programs that use high-dose cyclophosphamide, cisplatin, and topoisomerase-II inhibitors may entail a considerable risk for t-AML. The incidence of t-AML in neuroblastoma patients may be underestimated because treatment and clinical factors can mask its presence. Efforts to devise effective but less leukemogenic treatment for neuroblastoma or to truncate leukemogenic therapy, eg, by exploiting molecular techniques for the early identification of complete remission, are warranted.
Current use of bisphosphonates in oncology. International Bone and Cancer Study Group.
Authors: Body J J , Bartl R , Burckhardt P , Delmas P D , Diel I J , Fleisch H , Kanis J A , Kyle R A , Mundy G R , Paterson A H , Rubens R D 
Published: February 2017

PURPOSE The purpose of this article is to review the recent data on bisphosphonate use in oncology and to provide some guidelines on the indications for their use in cancer patients. DESIGN The group consensus reached by experts on the rationale for the use of bisphosphonates in cancer patients and their current indications for the treatment of tumor-induced hypercalcemia and metastatic bone pain in advanced disease and for the prevention of the complications of multiple myeloma and of metastatic bone disease are reviewed. RESULTS Bisphosphonates are potent inhibitors of tumor-induced osteoclast-mediated bone resorption. They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect. Intravenous bisphosphonates exert clinically relevant analgesic effects in patients with metastatic bone pain. Regular pamidronate infusions can also achieve a partial objective response by conventional International Union Against Cancer criteria and enhance the objective response rate to chemotherapy. In breast cancer, the prolonged administration of oral clodronate 1,600 mg daily reduces the frequency of morbid skeletal events by more than one fourth, whereas monthly pamidronate infusions of 90 mg for only 1 year in addition to chemotherapy reduce by more than one third the frequency of all skeletal-related events. The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half. CONCLUSION Bisphosphonate use is a major therapeutic advance in the management of the skeletal morbidity caused by metastatic breast cancer or multiple myeloma, although many questions remain unanswered, notably regarding the optimal selection of patients and the duration of treatment.
Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer.
Authors: Köhne C H , Schöffski P , Wilke H , Käufer C , Andreesen R , Ohl U , Klaasen U , Westerhausen M , Hiddemann W , Schott G , Harstick A , Bade J , Horster A , Schubert U , Hecker H , Dörken B , Schmoll H J 
Published: February 2017

PURPOSE To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer. PATIENTS AND METHODS Patients (n = 236) with progressive, measurable disease were randomized to three groups and received FU 2,600 mg/m2 as a 24-hour continuous infusion (CI) weekly for 6 weeks with 2 weeks rest (FU24h) and LV 500 mg/m2 as a 2-hour infusion before FU or IFN 3 x 10(6) U subcutaneously 3 times weekly or both. Treatment continued until progressive disease or unacceptable toxicity was observed. Pairs of treatment arms were analyzed sequentially to detect equivalence or a 25% difference in response rates. RESULTS The rate of objective remission in patients who received FU24h/LV (44%; 40 of 91) was significantly higher than in patients who received FU24h/IFN (18%; 16 of 90; P < .05). The response rates of patients who received FU24h/LV versus FU24h/LV/IFN (27%; 13 of 49) were statistically equivalent. Significant differences were observed for time to tumor progression (TTP) (FU24h/LV, 7.1 months; FU24h/IFN, 3.9 months; FU24h/LV/IFN, 6.3 months; global P value < .009) and survival (16.6 months, 12.7 months, 19.6 months, respectively; global P value < .04). Unpredictable and life-threatening toxicity in the FU24h/LV/IFN arm required dose reduction of FU to 2,000 mg/m2/day and early stoppage of this arm. Toxicity was manageable in patients who received both FU24h/LV (grade 3 to 4 diarrhea, 21%) and FU24h/IFN (grade 3 to 4 diarrhea, 15%). CONCLUSION Response rate, TTP, and overall survival were superior for LV-containing regimens compared with IFN modulation alone. The addition of IFN to high-dose infusional FU plus LV offers no advantage and may increase toxicity. The regimen of high-dose infusional FU24h/LV warrants further evaluation in patients with metastatic colorectal cancer.
Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.
Authors: Ogunbiyi O A , Goodfellow P J , Herfarth K , Gagliardi G , Swanson P E , Birnbaum E H , Read T E , Fleshman J W , Kodner I J , Moley J F 
Published: February 2017

PURPOSE Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.