tbuckley/cabot-search huggingface dataset:
Analysis of competing risks of causes of death and their variation over different time periods in Hodgkin disease
Authors: P. España, A. Sanchez, P. Espinosa, V. Massip, R. Perez-Maestu, M. Yebra, A. Hurtado, A. Hurtado, C. Maximiano, C. Salas, M. Provencio
Journal: Journal of Clinical Oncology (2007)

18528 Background: Hodgkin’s disease is put forward as a model of curable illness. However, long-term studies show an excessive mortality in relation to the general population. The only way for detecting these causes are the long-term follow-up clinical studies, even these long-term follow-ups may not be fully representative of current causes of death. Methods: All patients diagnosed with HD at the University Hospital “Clínica Puerta de Hierro” between 1967 and 2003 were included. The competing risks of causes of death and the vital situation were examined in three time periods. Three cohorts were compared: cohort A with patients treated before 1980, B with those treated 1981–1986 and C from 1986 on. Results: We studied 534 patients, with a median follow-up time of 9.1 years for the whole cohort. The 5, 15 and 20-year Kaplan-Meier survival estimates for all patients were 81%, 72% and 65%, respectively. At the close of the study, 337 (63.1%) were alive and 170 (31.8%) had died. In general, the most common cause was the progress of Hodgkin’s disease, followed by deaths due to a second tumor. By time periods, we found statistically significant differences between cohort A and the other two cohorts, with less LD and MC histology, fewer advanced stages and fewer combined treatments in the latter. Between cohorts B and C there were only differences in the histological results, with less LD and MC and increased NS in the latter. Survival was significantly worse in the first period than in the other two (p&lt;0.001) and in the three periods the main cause of death was tumor progression. Conclusions: The progression of Hodgkin’s disease is the main cause of death in all the periods studied. Over time a clear reduction in death related to the toxicity of treatments was seen. In the light of our results, the question is posed as to whether the survival and causes of death series for those patients treated since the 1970s are telling us about a real situation. Patients die now for reasons that are different from in the 1970s and this is important when planning preventive and clinical research activity. No significant financial relationships to disclose.
Impact of Genes Highly Correlated with <i>MMSET</i> Myeloma on the Survival of Non-<i>MMSET</i> Myeloma Patients
Authors: S. Peter Wu, Ruth M. Pfeiffer, Inhye E. Ahn, Sham Mailankody, Pieter Sonneveld, Mark van Duin, Nikhil C. Munshi, Brian A. Walker, Gareth Morgan, Ola Landgren
Journal: Clinical Cancer Research (2016)

The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined.We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients.Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways.MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. Clin Cancer Res; 22(16); 4039-44. ©2016 AACR.
Increased expression of chemokine receptors in inflammatory breast cancer: Implications for novel targeted therapies
Authors: N. Cabioglu, Y. Gong, N. Sneige, A. Sahin, A. M. Gonzalez-Angulo, C. Bucana, P. Morandi, G. Hortobagyi, M. Cristofanilli
Journal: Journal of Clinical Oncology (2005)

9655 Background: Inflammatory breast carcinoma (IBC) is the most aggressive form of primary breast neoplasm. Recent studies have suggested that expression of COX-2, and chemokine receptors CXCR4, and CCR7 might be associated with the metastatic behavior of breast cancer. We therefore investigated the expression of CXCR4, CCR7, and COX-2, along with that of the biomarker HER2-neu in primary IBC to evaluate expression patterns and prognostic implications. Methods: CXCR4, CCR7, and COX-2 were evaluated using paraffin-embedded tissue sections of breast cancers by immunohistochemical staining (IHC). HER2-neu amplification was assessed by FISH. All patients received multidisciplinary management including preoperative chemotherapy, surgery, and radiation according to our institutional protocols. Outcome data were correlated with the expression of the biomarkers. Results: Forty-six cases diagnosed with IBC between 1994 and 2002 were included in the study. The median age was 49.5 years (range 29–73). CXCR4 was expressed in 39% of cases (18/46), CCR7 expression was found in 30% (14/46), and HER-2 amplification was 53% (16/30), whereas only one patient’s tumor showed COX-2 positivity (2.3%). Fifty percent of the tumors either expressed CXCR4 and/or CCR7. Furthermore, CXCR4 expression was associated with HER2-neu amplification in 27% of cases (8/30). There was a significant correlation between CXCR4 and CCR7 expression (p=0.047), whereas no correlations were found between CXCR4 or CCR7 expression and ER, PR, or presence of high nuclear grade. At a median follow-up of 46 months (range, 1–98), 5-year overall and disease-free survival (OS and DFS) rates were 43% and 36%, respectively. The 5-year OS- and DFS-rates according to biomarker expression were: CXCR4- vs. CXCR4+ patients (OS, 51% vs. 30%, p=0.65; and DFS, 41% vs. 28%, p=0.50); CCR7- vs. CCR7+ patients (OS, 53% vs. 26%, p=0.19, and DFS, 39% vs. 29%, p=0.55). Comparison with non-IBC locally advanced breast cancer cases is ongoing. Conclusions: These results suggest that chemokine receptors CXCR4 and CCR7 are highly expressed in IBC. CXCR4 may represent a novel prognostic and therapeutic target for this aggressive form of primary breast cancer. No significant financial relationships to disclose.
High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer.
Authors: P J Cagnoni, Y Nieto, E J Shpall, S I Bearman, A E Barón, M Ross, S Matthes, S E Dunbar, R B Jones
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.
High incidence of new translocations in B-CLL detected by CD40L-enhanced cytogenetics (CEC): A new prognostic marker for infavorable survival outcome in patients with B-CLL
Authors: C. Mayr, C. Schoch, D. M. Kofler, R. Busch, M. Hallek, C.-M. Wendtner
Journal: Journal of Clinical Oncology (2004)

6561
Sequential chemotherapy and radiation for nasopharyngeal cancer: absence of long-term benefit despite a high rate of tumor response to chemotherapy.
Authors: I Tannock, D Payne, B Cummings, K Hewitt, T Panzarella
Journal: Journal of Clinical Oncology (1987)

Between April 1981 and December 1983, patients with locoregional carcinoma of the nasopharynx were treated with two courses of chemotherapy administered before radiation therapy. Chemotherapy consisted of methotrexate, bleomycin, and cisplatin, which were administered at 3-week intervals, and radiation therapy was scheduled to commence 3 weeks after the start of the second course. Forty-nine of 51 consecutive patients were treated; only one patient progressed on chemotherapy, and of 36 patients with measurable neck nodes, eight had complete and 19 had partial clearance (greater than 50% decrease in cross-sectional area) of these nodes when assessed before initiation of radiotherapy. Despite the high rate of tumor response (75%; 95% confidence limits, 59% to 91%), the actuarial survival and disease-free survival curves were almost identical to those recorded for a consecutive group of 140 historical controls of similar stage distribution treated with radiation alone. This chemotherapy provided a high rate of tumor remission, but did not appear to convey long-term benefit to patients when used before radiation therapy.
Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.
Authors: L J Ayash, A Elias, C Wheeler, E Reich, G Schwartz, R Mazanet, I Tepler, D Warren, C Lynch, R Gonin
Journal: Journal of Clinical Oncology (1994)

PURPOSE Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.
Stage I-II pediatric Hodgkin's disease: long-term follow-up demonstrates equivalent survival rates following different management schemes.
Authors: S S Donaldson, S J Whitaker, P N Plowman, M P Link, J S Malpas
Journal: Journal of Clinical Oncology (1990)

The results of treatment of 171 children with stage I-II Hodgkin's disease from two institutions with differing approaches to management have been analyzed. At the Stanford University Medical Center/Children's Hospital at Stanford (SUMC/CHaS), pathologic staging followed by extended-field radiation alone or involved-field radiation plus combination chemotherapy have been cardinal to the management policy. At St Bartholomew's Hospital/The Hospital for Sick Children at Great Ormond Street (Barts/GOS), clinical staging only has been used over the last 10 years, and involved/regional-field radiotherapy used as the treatment of choice rather than extended-field radiotherapy. Some children at each institution received combined modality therapy as primary management. Relapse among children with stage I disease was a more frequent occurrence in the Barts/GOS series than in the SUMC/CHaS group. However, the survival rates from the two centers are identical, 91% at 10 years. The following scientific-philosophic question is asked: Should one maximally stage and treat all children to increase the likelihood of a high freedom from relapse (FFR; cure) rate, or is it acceptable to minimize the initial staging and treatment, realizing that a proportion of patients will fail and require salvage/rescue therapy? With the awareness of morbidity from pathologic staging and aggressive treatment, and the favorable survival data reported from specialized centers using differing approaches, treatment strategies should be directed toward the long-term goal of cure of disease with maximal quality of life. A multidisciplinary management philosophy undertaken at a center with extensive experience in pediatric Hodgkin's disease is important to achieving this goal.
Bacterial airway colonization is not associated with increased procalcitonin in stable COPD
Authors: Daiana Stolz, Renaud Louis, Joachim Aerts, Tobias Welte, Alicia Lacoma, Wim Boersma, Kostantinos Kostikas, Francesco Blasi, Branislava Milenkovic, Cristina Prat, Janko Rakic, Lucas Boeck, Paola Castellotti, Gernot Rohde, Antoni Torres, Sabine Hertel, Sven Giersdorf, Michael Tamm
Journal: European Respiratory Journal (2012)

BACKGROUND:   Bacterial colonization of the airways hampers the utility of sputum microbiology at exacerbation of COPD. We hypothesize that, in contrast to exacerbation, circulating procalcitonin remains low in bacterial colonization in patients with stable COPD.   METHODS:   We prospectively evaluated 638 patients with stable COPD for ≥ 6 weeks, > 10 PY and GOLD II-IV seeking care in pulmonary tertiary hospitals in 8 European countries and included in the PROMISE cohort. Median observation time was 24 months.   RESULTS:   There were 393 patients (61.6%) reporting sputum production and 88 (22.4%) sputum purulence. At baseline, 251 (39.2%) provided sputum for analysis. Bacterial cultures of good quality sputum (n=183) grew potentially pathogenic bacteria in 55 cases (30.1%). The most common isolated pathogens were Pseudomonas aeruginosa (n=18), followed by Haemophilus influenzae (n=14), Streptococcus pneumoniae (n=11), Moraxella catarrhalis and Enterobacter species (n=10 each). As compared with those presenting negative sputum results, patients with positive sputum bacteriology were significantly older (p   CONCLUSION:   In contrast to acute exacerbation of COPD, procalcitonin values remain low in chronic bacterial airway colonization in stable COPD.
Potential Role of Phosphorylation as a Regulator of Aspartyl-(asparaginyl)-β-hydroxylase: Relevance to Infiltrative Spread of Human Hepatocellular Carcinoma
Authors: Diana L. Borgas, Jin-Song Gao, Ming Tong, Suzanne M. de la Monte
Journal: Liver Cancer (2015)

Abundant expression of aspartyl-(asparaginyl)-β-hydroxylase (AAH) correlates with infiltrative growth of hepatocellular carcinoma (HCC). Herein, we examine the role of phosphorylation in relation to AAH's protein expression, hydroxylase activity, promotion of cell motility, and activation of Notch signaling in human Huh7 hepatoma cells. Predicted glycogen synthase kinase-3β (GSK-3β) , protein kinase A (PKA), protein kinase C (PKC), and casein kinase 2 (CK2) phosphorylation sites encoded by human AAH cDNA were ablated by S/T&amp;#x2192;A site-directed mutagenesis using N-Myc-tagged constructs in which gene expression was controlled by a cytomegalovirus promoter. Functional consequences were assessed in transiently transfected Huh7 cells. Cells transfected with wildtype AAH had significantly increased AAH expression, catalytic activity, HES-1 expression, and directional motility relative to controls. Single phosphorylation site mutations in the C-terminus largely abrogated these effects and further inhibited catalytic activity relative to that in cells transfected with empty vector, whereas the effects of single point mutations within the N-terminus were more varied. In contrast, AAH cDNAs carrying multiple phosphorylation site mutations exhibited wildtype levels of AAH catalytic activity suggesting that the effects of AAH phosphorylation are complex and non-uniform. AAH expression and function can be modulated by direct phosphorylation of the protein. These findings suggest additional strategies for inhibiting infiltrative growth of HCC.
I Feel Witty, Oh So Witty
Authors: Donald A. Misch
Journal: JAMA (2016)

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Dose intensive chemotherapy for limited-stage (LS) small cell lung cancer (SCLC): A phase II study
Authors: K. Kubota, K. Yoh, S. Niho, K. Goto, H. Ohmatsu, T. Tamura, Y. Ohe, H. Kunitoh, I. Sekine, Y. Nishiwaki, N. Saijo
Journal: Journal of Clinical Oncology (2005)

7157 Background: Cisplatin plus etoposide (PE) and concurrent twice-daily (BID) thoracic radiotherapy (TRT) is a standard treatment for LS-SCLC. Dose intensive weekly regimen (CODE) with G-CSF is highly active in relapsed SCLC (J Clin Oncol 15:292,1997). Early administration of dose intensive, wide diversity regimen is an intriguing strategy for the treatment of LS-SCLC. The purpose of the phase II study was to evaluate safety and efficacy of sequential administration of CODE + G-CSF following concurrent PE and BID TRT. Methods: Treatment consisted of one induction cycle of cisplatin (C) 80 mg/m2 d 1 and Etoposide (E) 100 mg/m2 d 1–3. TRT 45 Gy was given 1.5 Gy bid 5d/week for 30 fractions concurrent with cycle 1. The CODE regimen started on week 5 and consisted of C 25 mg/m2 iv weekly for 6 wks, vincristine 1 mg/m2 iv wks 6, 8, and 10, doxorubicin 40 mg/m2 and E 80 mg/m2 X 3 days iv on wks 5, 7 and 9. 50{Unknown character “ÃéÂ¼”}g/ m2 of G-CSF was administered sc on the days when cytotoxic drugs were not given. Each patient had to fulfill the following criteria: histologically and/or cytologically documented SCLC, LS, ECOG PS 0, 1 or 2, age 74 years or younger, no prior treatment for SCLC, measurable or evaluable lesion, adequate organ functions. Results: Between Sep. 1997 and July 2001, 44 patients were enrolled. Forty-three patients are eligible and evaluable for safety and efficacy, including 36 male and 7 female, median age; 62 (range 41–74), 17 PS 0, 25 PS 1 and 1 PS 2. Overall response rate and complete response rate were 100% and 63%, respectively. The main toxicity was hematologic as follows: Grade 3/4 leukopenia in 21%/74%, anemia in 58%/26%, thrombocytopenia in 44%/5%. Two patients were deemed treatment related deaths due to pneumonitis. Thirty-nine patients started the CODE regimen and 37 (79%) patients completed 6 cycles of CODE. Median overall survival time was 33 months. Three-year and 5-year survival rate were 48% and 35%, respectively. Conclusions: PE and concurrent BID TRT followed by CODE+G-CSF is feasible with manageable toxicity and encouraging outcome has been demonstrated. Randomized trial comparing four cycles of PE and concurrent BID RT with this regimen is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb