tbuckley/cabot-search huggingface dataset:
Pulmonary hypertension (PH) in patients (pts) with CML treated with tyrosine kinase inhibitors (TKIs).
Authors: S. Gaballa, A. Al-Kali, H. Kantarjian, E. Jabbour, A. Quintas-Cardama, M. Ayoubi, G. Borthakur, S. M. O'Brien, J. E. Cortes
Journal: Journal of Clinical Oncology (2010)

6597 Background: TKIs are the current standard therapy for patients with CML. Fluid retention and pleural effusions have been reported in pts treated with TKIs, particularly with dasatinib. Although TKIs have been shown to reverse PH in animal models, there have been some reports of development of reversible PH with dasatinib. Methods: We conducted a retrospective analysis on 401 CML pts in CP who were treated with TKIs (imatinib, dasatinib or nilotinib) as initial therapy for CML and had a transthoracic echocardiogram done (TTE) at some point during the course of therapy. PH was diagnosed if the patient had an estimated right ventricular systolic pressure (RVSP) of 35 mm Hg or greater. Secondary causes of PH (systolic or diastolic dysfunction on TTE, chronic obstructive pulmonary diseases [COPD], obstructive sleep apnea [OSA] and pulmonary embolism) were investigated during chart review. Results: Twenty pts had at least one TTE; median age 57 years, 46% males. Six pts (30%) received nilotinib 400 mg BID, 4 (20%) pts imatinib (400 mg; n = 1, 600 mg; n = 1 and 800 mg daily; n = 2), and 10 (50%) pts received dasatinib (dose between 40 mg to 140 mg daily). Five (25%) pts had coronary artery disease, 9 (45%) pts had systemic hypertension, 2 (10%) pts had COPD and 3 (15%) pts had OSA. Thirteen pts had serial TTE to compare the progression of PH including 6 (7%) who had a TTE prior to starting TKI. Among these 13 pts with serial TTE, 7 had rising RVSP with one patient having mild global hypokinesia, another with diastolic dysfunction and another with OSA. Four of those 7 patients had normal RVSP on their TTE prior to starting therapy. Five other pts had improvement in the RVSP on serial TTE, 4 of them with systemic hypertension. Two of those 5 pts had elevated RVSP on their TTE prior to starting therapy. One pt had no change. Eleven pts had pleural effusions (7 dasatinib, 3 imatinib, 1 nilotinib) associated with PH. Conclusions: TKI therapy is occasionally associated with development of PH, but RVSP may improve spontaneously in some pts. A prospective study is needed to further investigate the relationship between TKIs and the development of PH. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis
Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I-II non-Hodgkin's lymphomas.
Authors: P Mauch, R Leonard, A Skarin, D Rosenthal, S Come, J Chaffey, S Hellman, G Canellos
Journal: Journal of Clinical Oncology (1985)

A retrospective analysis of 144 patients with stage I-II non-Hodgkin's lymphoma (NHL) treated between June 1968 and December 1980 was performed. Patients were staged by bone marrow biopsy, chest radiography, blood chemistries, and either bipedal lymphangiography, computerized axial tomography, or surgical exploration of the abdomen. Patients were subclassified by extent of disease; minimal disease was defined as less than 10 cm and involved one or two contiguous sites, while patients with disease exceeding these limitations were considered to have extended stage I-II disease. Treatment consisted of radiation therapy (RT) alone in 74 patients and 70 patients were treated with chemotherapy with or without RT. Combination chemotherapy in patients with diffuse undifferentiated (DU) or diffuse histiocytic (DH) lymphoma resulted in a significantly higher 6-year survival as compared to patients treated with RT alone. For minimal disease DU/DH patients, the 6-year survival with chemotherapy +/- RT was 96% as compared to 61% with RT alone (P = .03). For extended disease DU/DH patients the 6-year survival with chemotherapy +/- RT was 56% as compared with 18% with RT alone (P = .003). This survival advantage from the initial use of chemotherapy was not seen in any of the other histologic subgroups.
Preliminary experience with 11C-acetate and positron emission tomography (PET) in prostate cancer
Authors: P. Manente, G. Vicario, F. Chierichetti, G. Liessi, S. Bissoli
Journal: Journal of Clinical Oncology (2005)

4680 Background: Imaging of relapses and metastases in prostate cancer is an open field in nuclear medicine and radiological examinations.Traditional FDG (fluorodeoxyglucose) PET is poorly sensitive especially for local recurrence. Prostate normal cells undergo malignant transformation loosing their capability of citrate production:this alteration leads to an increased turnover of acetate.Aim of our study was to evaluate 11C-acetate as a potentially good marker for in vivo imaging. Methods: We examined 33(mean age 66 years) patients with previous prostate cancer submitted to surgery (31) and brachitherapy (2).19 out of them were on anti-androgen therapy.PSA values ranged from 0.5 to 21.9 and Gleason scale was from 4 to 9.PET was performed by a CT/PET scanner starting acquisition 5 min after injection of 555 MBq of 11C-acetate. Results: Reconstructed images (coronal, sagittal and axial planes) were examined by a nuclear physician and a radiologist trained,respectively, in PET and CT. CT/PET was positive for relapse in 19 cases where we found 11 local relapses,8 abdominal nodal sites of metastases (from one to five),5 bone metastatic lesions (spread in 2 patients),1 brain lesion. 14 examinations were completely negative for tumor relapse.In the positive cases PSA ranged from 3,93 to 21,9 but it was 1.0 in the patient with brain lesion. In negative patients PSA values were comprised from 0.5 to 1.78. Final diagnosis was assessed by surgery in 2 and by clinical and instrumental evaluations.In 2 patients with negative CT/PET,local tumor recurrence was proved by MRI (FN).All positive examinations had a final diagnosis of relapse. Conclusions: From our preliminary data, 11C-acetate is sensitive to detect prostate recurrence when PSA is increased even if we did not find a relevant correlation between the number of metastases and PSA values:the case presenting 21.9 had three sites of abdominal nodes and a patient whose PSA was 8.55 showed spread bone and nodal metastases. PSA values seems not useful to decide proper treatment.Even if further data are needed,11C-acetate may be a better marker to assess the extension of disease and CT/PET is a worthful mean,for surgical purpose too,to localize the sites of relapse. No significant financial relationships to disclose.
Routine interim disease assessment in patients undergoing induction chemotherapy for acute myeloid leukemia: Can we do better?
Authors: Germán Campuzano‐Zuluaga, Yehuda Deutsch, Matthew Salzberg, Alexandra Gomez, Fernando Vargas, Roy Elias, Deukwoo Kwon, Mark Goodman, Offiong F. Ikpatt, Jennifer R. Chapman, Justin Watts, Francisco Vega, Ronan Swords
Journal: American Journal of Hematology (2015)

The presence of >5% blasts at "day 14" (D14), in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) is problematic. It is unclear if a second course of chemotherapy for early persistent disease will alter outcome in these patients. We conducted a retrospective study of AML patients undergoing induction chemotherapy where diagnostic, interim (around day 14), and recovery (days 21-42) bone marrow (BM) evaluations were available for review. Of the 113 patients included in the final analysis, 99 (87.6%) achieved CR at hematologic recovery. At D14, 90 patients (79.6%) had <5% blasts and of these, 87 (96.7%) ultimately achieved CR. At D14, Twenty-three (20.4%) patients had residual leukemia (>5% blasts). Of these, 11 (47.8%) received a second course of chemotherapy (double induction [DI]) and 12 (52.2%) were observed until count recovery (single induction [SI]). No significant difference in CR rates was observed between these two groups (58.3% DI group vs. 45.5% SI group, P value = 0.684). In our analysis, D14 BM evaluation did not uniformly identify patients with primary induction failure. To unequivocally determine the value of a D14 marrow assessment in AML, prospective studies in the context of large cooperative group trials are required. Considering our findings and similar reports from others, we propose that D14 marrow assessment should be individualized, and that other factors, such as cytogenetics and early peripheral blood blast clearance should be considered, to identify patients most likely to benefit from interim disease assessment during AML induction therapy.
Fragmentation of the Nucleus in Rous Sarcoma Virus-Infected Chick Embryo Cells. II. Structural and Metabolic Studies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Warren Levinson
Journal: JNCI Journal of the National Cancer Institute (1970)

Structural and metabolic studies were designed to obtain additional information as to the nature of the nuclear fragmentation process in Rous sarcoma virus-infected chick embryo cells. No obvious alterations in the fragmented nuclei could be seen in electron micrographs, and the amount of DNA in the fragmented nuclei was similar to that in normal-shaped nuclei. The maximum percentage of cells with fragmented nuclei was approximately 10%, even with a multiplicity of infection of 1. Infected cultures passaged 7 times contained 10% of cells with fragmented nuclei, which indicated either survival or continued formation of these cells. Autoradiographic studies demonstrated that thymidine, uridine, and leucine incorporation was the same or greater in cells with fragmented nuclei as in cells with normal nuclei. Exposure of infected cells to bromodeoxyuridine enhanced the formation of fragmented nuclei.
An On-Site Audit of the South African Trial of High-Dose Chemotherapy for Metastatic Breast Cancer and Associated Publications
Authors: Raymond B. Weiss, Geraldine G. Gill, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The randomized study reported by Bezwoda et al of high-dose chemotherapy (HDC) for treatment of metastatic breast cancer was audited on site to verify the study results. Additional published studies were reviewed to determine whether they had been subject to the required institutional oversight. PATIENTS AND METHODS: Ninety patients were reported to have been randomized and treated on this trial. A log of the names, hospital numbers, entry dates, and regimen received had been provided by the principal investigator. A search of more than 15,000 sets of medical records available from two Johannesburg hospitals was performed to locate records for as many of these 90 patients as possible. Standard auditing techniques were used. Additional clinical trials published by Bezwoda were compared against the minutes of the University of the Witwatersrand Committee for Research on Human Subjects to verify review and approval. RESULTS: Records for only 61 of the 90 patients could be found. Of these 61, only 27 had sufficient records to verify eligibility for the trial by the published criteria. Of these 27, 18 did not meet one or more eligibility criteria. Only 25 patients appeared to have received their assigned therapy temporally associated with their enrollment date, and all but three of these 25 received HDC. The treatment details of individual patients were at great variance from the published data. Nine other trials reported by Bezwoda were not reviewed or approved by the appropriate institutional committee despite statements to the contrary in the publications. CONCLUSION: The multiple publications of this study do not report verifiable data, and nine other publications coauthored by the principal investigator contain at least one major untrue statement.
Staging with FDG-PET/CT influences stage-specific survival in non small cell lung cancer (NSCLC)
Authors: Kaja Zimmermann, Simone Tönnies, Daniel Misch, Christian Boch, Nicolas Schoenfeld, Gregor J. Förster, Jens Kollmeier, Torsten Bauer
Journal: European Respiratory Journal (2011)

Background:  Fluorodeoxyglucose (FDG)-PET/CT has a high sensitivity (89-100%) and reasonable specificity (79-95%) for the diagnosis of NSCLC. Currently it is mainly used in preoperative staging. In approximately 15% of these cases, it leads to the diagnosis of metastatic disease that was neither clinically suspected nor seen in conventional imaging. It may be assumed that integrating these cases in the palliative stage IV group, has an influence on overall survival.   Aim:  To compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients where conventional imaging procedures were performed.   Methods:  We analyzed the OS of all patients diagnosed in 2009 (n=254), 96/254 (38%) patients were staged with PET/CT and 158/254 (62%) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics.   Results:  Patient in the PET/CT group (65±11) were younger than in the CT group (68±10 years; p = 0.008). The median OS of all patients was 246 (range: 217 – 275); 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) in the CT group (p = 0.001).   Conclusion:  FDG-PET/CT staging leads to earlier recognition of stage IV NSCLC patients and thus longer survival times. To what extend a selection bias for age and/or clinical condition may have influenced our results, needs to be discussed.
Retrospective analysis of the role of adjuvant chemotherapy and microRNAs expression in resected cholangiocarcinomas (CCAs)
Authors: M. Ghidini, F. Trevisani, M. Fassan, L. Cascione, J.C. Hahne, A. Lampis, I.H. Cheong, A. Scarpa, C. Vicentini, A. Zerbi, G. Torzilli, M. Roncalli, L. Rimassa, N. Valeri, A. Santoro, C. Braconi
Journal: Annals of Oncology (2015)
Community acquired and health-care associated pneumonia : should we own follow guidelines?
Authors: Maria Carrabba, Marina Zarantonello, Cinzia Hu, Giovanna Fabio
Journal: European Respiratory Journal (2012)

Treatment of healthcare-associated pneumonia (HCAP) according to published guidelines recommend initial broad-spectrum antibiotics and de-escalation based on culture results.  This study aims to investigate the in-hospital and 30-day mortality and LOS in both CAP and HCAP non-immunocompromised (NIC) and HCAP immunocompromised (IC) related to the empirical antibiotic therapy started at admission, before microbiological data availability.  All patients admitted to a university tertiary care hospital in Milan with a diagnosis of pneumonia from 2005 to 2011 were prospectical enrolled. CAP, HCAP and immunocompromised were identified on the basis of the existing criteria. Therapies of two periods (T1: 2005-2007 and T2: 2010-2011) have been compared.  Ongoing Results  A total of 275 patients, 135 HCAP, were included in the analysis. T1 accounted for 240 CAP, 40 HCAP-NIC and 80 HCAP-IC. T2 (partial results) accounted for 20 CAP, 4 HCAP-NIC, 11 CAP-IC.  During T1, culture positive were 23.3% and culture negative 55%. The majority of CAP was started with monotherapy (51.7%), while the most of HCAP with dual-therapy (NIC 45%, IC 41.3%). Triple-therapy was addressed for 9.2% of CAP, 12.5% of HCAP-NIC and 25.0% of HCAP-IC.  During T2, culture positive were 17.1% and culture negative 80%. The majority of CAP and HCAP-IC started a dual-therapy (55% and 54.5%), while 50% of HCAP-NIC had a monotherapy. Triple-therapy was started in 5% of CAP, 25% of HCAP-NIC and 18.2% of HCAP-IC.  In CAP of both periods none of the patients treated with triple-therapy died, and there were no differences for mortality between mono and dual-therapy. HCAP with dual therapy had less mortality than both monotherapy and triple-therapy.
Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer
Authors: Elisabeth Brambilla, Gwénaël Le Teuff, Sophie Marguet, Sylvie Lantuejoul, Ariane Dunant, Stephen Graziano, Robert Pirker, Jean-Yves Douillard, Thierry Le Chevalier, Martin Filipits, Rafael Rosell, Robert Kratzke, Helmut Popper, Jean-Charles Soria, Frances A. Shepherd, Lesley Seymour, Ming Sound Tsao
Journal: Journal of Clinical Oncology (2016)

Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer.A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non-small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set.Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points).Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non-small-cell lung cancer.
Spinal reirradiation using the Cyberknife-preliminary efficacy from a single institution
Authors: J. A. Haas, M. R. Witten, J. R. Matera, E. P. Montchal, J. A. Brown, M. Brisman, N. Epstein, J. Lauritano, K. Episcopia, A. J. Katz
Journal: Journal of Clinical Oncology (2008)

2059 Background: Spinal cord tolerance to prior radiation is a major limiting factor in reirradiating patients with spine metastases that have relapsed or progressed in a prior treated field due to concerns about toxicity. The accepted total tolerance dose of the spinal cord is approximately 5,000 cGy in conventional fractionation (180 cGy/day). This dose is reported to cause a 5% risk of myelitis. Methods: 13 consecutive patients who had received prior external beam radiation to the spine and who were subsequently retreated with Cyberknife radiosurgery in 2005–2006 were reviewed. The radiation dose to the spinal cord and cauda equina given during the external beam and Cyberknife treatments were measured. The doses were also converted into 180 cGy equivalent doses using alpha/beta corrections and were also measured. Local control as measured by pre and post treatment imaging is reported. Results: The median follow up was 9.1 months. The median external beam dose to the spinal cord was 3,811 cGy. The median fraction size was 238 cGy. The median prescribed dose using the Cyberknife for retreatment was 2,030 cGy. The median dose per fraction using the Cyberknife was 500 cGy. The median dose to 5% of the spinal cord (D05) from the Cyberknife was 1171 cGy. The median dose to the spinal cord converted to 180 cGy/day equivalent from the prior external radiation was 4,228 cGy. The median dose to the D05 of the spinal cord from the Cyberknife converted to 180 cGy/day equivalent was 1,641 cGy. The median total cumulative dose to the spinal cord from both external beam and Cyberknife was 5,171 cGy. The median total cumulative dose to the spinal cord from both external beam and Cyberknife converted to 180 cGy/day equivalent was 5,889 cGy. Local control was achieved in 13/13 patients (100%) No patients suffered from treatment related complications from the retreatment of the spinal cord. Conclusions: Cancer patients with recurrent or progressive disease after prior external beam radiation can be safely retreated using the Cyberknife. Cyberknife radiosurgery provides local control and minimal risk of radiation induced myelopathy during the patient's lifetime. Cyberknife should be considered a safe treatment option for retreating patients who have relapsed or progressed in the treated spine after prior external beam radiation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Accuray
Cetuximab Relative Dose Intensity (Rdi) in Recurrent/Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (Scchn): First Observational Prospective Study in Unselected Patients (Direct Trial)
Authors: J. Guigay, F. Peyrade, B. Petre-Lazar, F. Mornex, P. Ceruse, L. Digue, A. Berrier, M. Degardin, M. Alfonsi, X. Artignan, L. Cals, S. Faivre, E. Vuillemin, F. Rolland, A. Timochenko, E. Babin, A. Prevost, O. Romano, E. Chamorey, C. Le Tourneau
Journal: Annals of Oncology (2014)
Association of high symptom burden with oral oncolytic agents.
Authors: Jane Alcyne Severson, Emily Mackler, Bernard Marini, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2014)

177 Background: Increasing numbers of cancer patients are being treated with oral oncolytics. This change represents a shift from frequent direct observation during intravenous therapy to periodic observation and increased necessity for improved monitoring and self-care management. Despite this shift, patients are at risk to develop many of the same chemotherapy-associated symptoms and toxicities. We sought to understand the symptom burden associated with use of oral oncolytics. Methods: Michigan Oncology Quality Consortium (MOQC) sponsored a quality improvement initiative focused on improving oral oncolytic care. Eight oncology practices participated. Patients were assessed with a modified Edmonton Symptom Assessment System (ESAS) prior to each outpatient visit. A total of 537 surveys were analyzed. 13 measures were categorized into mild (0 to 3), moderate (4 to 6), and severe (7 to 10) symptom burden. Results: Overall, the average ESAS symptom score was mild in 81% of patients, moderate in 13% of patients, and severe in 6% of patients. These average scores, however, obscure the significant burden in select ESAS domains. For example, 39% of patients categorized their overall well-being as being moderate/severely affected; 38% of patients felt they were moderate/severely fatigued, and 21% indicated moderate/severe neuropathy symptoms. Notably, 118/537 (24%) of the assessments had 4 or more symptoms rated moderate to severe. Conclusions: Patients taking oral oncolytics experience significant symptom burden that impacts quality of life. Intolerance of oral oncolytics may lead to adherence issues, potentially affecting expected outcomes. Given the prevalence of symptoms and potential for toxicity, self-care strategies to improve early recognition and treatment of symptoms by patients taking oral oncolytics are necessary. [Table: see text]