tbuckley/cabot-search huggingface dataset:
Acute interstitial pneumonitis following adjuvant tamoxifen therapy
Authors: S. Ahmed, R. K. Shahid
Journal: Journal of Clinical Oncology (2009)

e11637 Background: Tamoxifen is a serum estrogen receptor modulator that is widely used in the treatment of women with breast cancer and has a low incidence of serious side-effects. Although hypersensitivity reactions to tamoxifen have rarely been described, to our knowledge acute lung toxicity has not previously been reported. Objective: To report an unusual case of acute interstitial pneumonitis in a patient with early stage breast cancer treated with tamoxifen. Results: A 66 year old post-menopausal woman with past medical history of type 2 diabetes mellitus, and hypertension noted a lump in the right breast. An excision biopsy revealed 9 mm moderately differentiated invasive ductal carcinoma. Lymph nodes were not involvd by the tumor. The tumor cells were positive for estrogen and progesterone receptors and were negative for ErbB-2 over expression. The post operative course was complicated by wound infection treated with combination of clindamycin and ciprofloxacin. The patient was recommended adjuvant tamoxifen. Her other medication were metformin, valsartan, calcium and vitamin D. One week after the commencement of tamoxifen she noted increasing dyspnea, cough, and intermittent fever. X-ray chest showed bilateral lung infiltrates. She was hospitalized and treated with broad spectrum antibiotic. The patient condition deteriorated. She developed acute respiratory failure requiring intubation and mechanical ventilation. Tamoxifen was discontinued. A CT scan of chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was performed which was negative for infection. An open lung biopsy was done which showed focal diffuse alveolar damage consistent with interstitial pneumonia. No evidence of an infective agent, malignancy, or granuloma was noted. The patient was treated with high dose steroid. She gradually recovered and was discharge to home with normal lung function. Conclusions: Drug-induced lung injuries are usually idiosyncratic reactions and occur in an unpredictable manner. The presence of a temporal relationship between the lung injury and tamoxifen administration, a rapid clinical improvement after discontinuation of the drug, and absence of other causes strongly implicated tamoxifen as a potential cause of acute lung injury. No significant financial relationships to disclose.
Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.
Authors: D J Bloomfield, M D Krahn, T Neogi, T Panzarella, T J Smith, P Warde, A R Willan, S Ernst, M J Moore, A Neville, I F Tannock
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.
Preliminary Results of a Randomized Radiotherapy Dose-Escalation Study Comparing 70 Gy With 78 Gy for Prostate Cancer
Authors: Alan Pollack, Gunar K. Zagars, Lewis G. Smith, J. Jack Lee, Andrew C. von Eschenbach, John A. Antolak, George Starkschall, Isaac Rosen
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial. PATIENTS AND METHODS: A total of 305 stage T1 through T3 patients were randomized to receive 70 Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months. RESULTS: One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P = .058). Multiple-covariate Cox proportional hazards regression showed that the study randomization was an independent correlate of FFF, along with pretreatment PSA, Gleason score, and stage. The patients who benefited most from the 8-Gy dose escalation were those with a pretreatment PSA of more than 10 ng/mL; 5-year FFF rates were 48% and 75% (P = .011) for the 70-Gy and 78-Gy arms, respectively. There was no difference between the arms (∼80% 5-year FFF) when the pretreatment PSA was ≤ 10 ng/mL. CONCLUSION: A modest dose increase of 8 Gy using conformal radiotherapy resulted in a substantial improvement in prostate cancer FFF rates for patients with a pretreatment PSA of more than 10 ng/mL. These findings document that local persistence of prostate cancer in intermediate- to high-risk patients is a major problem when doses of 70 Gy or less are used.
Cystic Neoplasms of the Pancreas
Authors: Rohit Chandwani, Peter J. Allen
Journal: Annual Review of Medicine (2015)

Cystic neoplasms of the pancreas are being identified at an increasing frequency largely due to the increased use of abdominal cross-sectional imaging. These neoplasms represent a heterogeneous group of tumors with various genetic alterations, molecular features, and risks of malignancy. Despite the use of high-resolution radiographic studies, endoscopic evaluation, cyst fluid analysis, and novel molecular diagnostics, many of these lesions remain difficult to classify without operative resection. These diagnostic challenges are coupled with an improving but limited understanding of the natural history of these neoplasms. Treatment of pancreatic cystic neoplasms therefore remains controversial but consists largely of a selective tumor-specific approach to surgical resection. Future research remains necessary to better discriminate the biological behavior of these tumors in order to more appropriately select patients for operative intervention.
Microbial markers and the development of asthma in childhood: A birth cohort study
Authors: Anne M. Karvonen, Anne Hyvärinen, Helena Rintala, Matti Korppi, Leea Keski-Nisula, Sami Remes, Jussi Lampi, Aino Nevalainen, Juha Pekkanen
Journal: European Respiratory Journal (2011)

Background:  Early-life exposure to environmental microbial agents may be associated with a development of asthma.   Objective:  To determine the effect of microbial exposure at homes in early age on the risk of asthma.   Methods:  A birth cohort of 396 children was followed-up with questionnaires until the age of 5 years. Collection of living room floor dust samples and home inspection for moisture damage were performed before the age of 1 year. Concentrations of 3-hydroxy fatty acids (3-OH FAs), muramic acid, ergosterol and quantitative polymerase chain reaction (qPCR) for two bacterial genera and six fungal species, genera or groups were determined from house dust.   Results:  The associations between early microbial exposure and occurrence of doctor-diagnosed asthma were mainly seen with concentrations of 3-OH FAs, qPCR for  Mycobacterium  and  Wallemia sebi , and amount of dust. Significant interaction was observed between major moisture damage in home and 3-OH FAs ( p=0.006 ). In addition, there was a suggestion ( p≤0.15 ) that 3-OH FAs and qPCR for  Mycobacterium  were inversely associated with asthma especially among non-farm children.   Conclusion:  The study results suggest that microbial markers may represent different types of microbial exposure in different environments e.g. living on a farm or in a moisture damaged house. The source and variety of microbial exposures should be better taken into account in future studies on the development of asthma.
Multicenter Phase II Study of Fludarabine Phosphate for Patients With Newly Diagnosed Lymphoplasmacytoid Lymphoma, Waldenström's Macroglobulinemia, and Mantle-Cell Lymphoma
Authors: James M. Foran, Ama Z.S. Rohatiner, Bertr Coiffier, Tiziano Barbui, Stephen A. Johnson, Wolfgang Hiddemann, John A. Radford, Andrew J. Norton, Susan M. Tollerfield, Martin P. Wilson, T. Andrew Lister
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenström's macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced-stage disease and are incurable with standard alkylator-based chemotherapy. A phase II trial was undertaken to determine the activity of F-AMP in patients newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996, 78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m 2 /d for 5 days, every 4 weeks) until maximum response, plus two further cycles as consolidation. The primary end point was response rate; secondary end points included time to progression (TTP), duration of response, and overall survival (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow-up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma; the median duration of response was 2.5 years. The median survival has not yet been reached. There was no significant difference in the duration of response or OS between patients with different histologies; TTP was shorter in patients with MCL (P = .015). Myelosuppression was relatively common, and the treatment-related mortality (TRM) was 5%, mostly associated with pancytopenia and infection. CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is low, and the TRM is relatively high. Its role in combination chemotherapy remains to be demonstrated.
Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph11The authors have no proprietary interest in the Heidelberg Retina Tomograph.
Authors: Mark R Lesk, George L Spaeth, Augusto Azuara-Blanco, Silvana V Araujo, L.Jay Katz, Annette K Terebuh, Richard P Wilson, Marlene R Moster, Courtland M Schmidt
Journal: Ophthalmology (1999)
Early diagnosis of small airway disease
Authors: Evangelia Daniil, Georgios Kaltsakas, Sofia-Antiopi Gennimata, Anastasios Palamidas, John Jordanoglou, Nikolaos G. Koulouris
Journal: European Respiratory Journal (2012)

Inflammatory changes in the peripheral airways of smokers are detected even when “normal” spirometry is still present, indicating that early structural damage in the small airways develop before the diagnosis of overt COPD is established. There are several tests, as FEF25-75%, slope of phase III, and effective time (Thorax 1980; 35: 375-378) and its variations, advocated to early detect small airways disease and discriminate between smokers and non-smokes. However, it is not clear which of the aforementioned tests is the “best” for early detection of small airways disease. We studied 30 (15 men) Caucasian subjects (10 never smokers, 10 smokers with normal spirometry, and 10 COPDers in GOLD I), aged (mean±SD) 52±14 y with FVC%pred=111±12, FEV1%pred=98±14, FEV1/FVC%=73±10. All smokers had smoking history more than 10 pack-years. Simple spirometry, the slope of phase III (ΔN2/l), and the effective time at the 60-70% part of the forced vital capacity of the lung (TEFFp7) were measured. The FEF25-75%%pred (64±29) was abnormal in 16/30 subjects. The ΔN2/l%pred (192±150) was abnormal in 14/30 subjects. TEFFp7%pred was 155±88 and was abnormal in 17/30. Multiple linear regression analysis showed that TEFFp7%pred is more appropriate, among the tests performed, for discriminating smokers from never smokers (p=0.008). In conclusion, TEFFp7 appears to be a sensitive test for the early detection of small airway disease.
Place of short-term androgen deprivation therapy in intermediate-risk prostate cancer treated with radiotherapy: A phase III trial.
Authors: Abdenour Nabid, Nathalie Carrier, Eric Vigneault, Luis Souhami, Céline Lemaire, Marc-André Brassard, Boris Bahoric, Robert Archambault, François Vincent, Thu-Van Nguyen-Huynh
Journal: Journal of Clinical Oncology (2015)

5 Background: The place of short term androgen deprivation therapy (STADT) in combination with radiation therapy (RT) for patients with intermediate risk prostate cancer (IRPC) remains controversial. The purpose of this prospective, randomized trial was to compare outcomes between patients with IRPC treated with different doses of RT with or without STADT, (PCS III trial, Clinical Trials.gov, NCT00223145). Methods: From December 2000 to September 2010, 600 patients with IRPC were randomized to 6 months of STADT and two levels of prostate RT doses of 70 (arm 1) or 76 Gy (arm 2) versus prostate dose-escalated RT alone at 76 Gy (arm 3). STADT consisted of bicalutamide and gosereline for six months. RT (2 Gy per fraction) started four months after the beginning of STADT. Biochemical failure and disease-free survival (DFS) were primary end-points, with overall survival (OS) as secondary endpoint. DFS and OS rates were estimated with Kaplan-Meier and compared with log rank test and Cox regression. Results: Patient’s characteristics were well balanced among the 3 arms (median age 71 years, median PSA 10 ng/ml, median Gleason score 7). At a median follow-up of 75.4 months, biochemical failure occurred in 84 (14%) patients (arms 1 to 3: 12.5%, 8.0%, 21.5%) with statistical difference between arm 1 and 3 (p = 0.023) and arm 2 and 3 (p &lt; 0.001). There was no significant difference between arm 1 and 2. A total of 113 (19%) patients had died with only 6 deaths (1%) attributed to prostate cancer. The 5-/10-year DFS rates were 93%, 97.5% and 86%, and 77%, 90% and 64.5%, respectively. Significant differences in DFS between the treatment arms were observed at 5 years but at 10 years it was observed only between arm 1 and 3 (p=0.01) and arm 2 and 3 (p&lt;0.001). The 5-/10-year OS rates were 91%, 95% and 93%, and 64%, 70% and 78%, respectively. There was no statistical difference in OS between arms at 5 and 10 years. Conclusions: In patients with IRPC, the use of STADT in association with RT, even at lower doses, leads to a superior biochemical control and DFS as compared to dose-escalated RT alone. These outcomes did not translate into an improved OS. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145.
Lung clearance index is a reliable and sensitive measure of airways disease in bronchiectasis
Authors: Stephen Rowan, Judy Bradley, Madeleine Ennis, Alex Horsley, Nicholas Bell, Per Gustafsson, Joseph Stuart Elborn
Journal: European Respiratory Journal (2012)

Introduction: In bronchiectasis (BE), there is a need for a sensitive outcome measure that is responsive to interventions, particularly in those with mild disease. FEV1 is insensitive to small airways disease and is often within normal range in BE. Lung clearance index (LCI) is a measure of ventilation inhomogeneity derived from multiple breath washout (MBW). Objective: To assess intra and inter-visit repeatability of LCI and determine the relationship between FEV1 and LCI in stable BE.  Methods: Inclusion criteria: HRCT diagnosis of BE within 5 years; clinically stable (>4 weeks no infective symptoms); no features of CF. Participants attended for 2 visits, 2 weeks apart. At each visit they performed MBW in triplicate, using 0.2% SF6 and a modified InnocorTM device. LCI was derived from the mean of at least 2 acceptable washouts. Spirometry was performed to ATS/ERS standards.  Results: 30 patients (14M/16F) attended for 2 visits. The mean (SD) age was 56.6 (14) yrs. Mean (SD) FEV1 % predicted was 84.8 (20.7), range (40-117). Mean (SD) LCI was 9.2(1.7) on visit 1 and 9.3(1.9) on visit 2 (normal   Conclusions: This is the first report of LCI in BE. LCI has good intra and inter-visit repeatability. Across a range of FEV1 there is a strong relationship between LCI and FEV1. LCI is a more sensitive test of lung function than FEV1 and FEF25-75, and is abnormal in the majority of people with BE who have a normal FEV1.
An Inborn Variation In The Anaplastic Lymphoma Receptor Tyrosine Kinase Gene (ALK) Increases Risk Of MAF (Musculoaponeurotic Fibrosarcoma Oncogene Homolog) High Expressing Myeloma
Authors: Annette Juul Vangsted, Stephen Erickson, Naveen Sanath Kumar, Elizabeth Ann Coleman, Erming Tian, Julia Goodwin, Joshua Epstein, Owen Stephens, Bart Barlogie, Christoph Heuck
Journal: Blood (2013)
Importance of continued testicular suppression in hormone-refractory prostate cancer.
Authors: C D Taylor, P Elson, D L Trump
Journal: Journal of Clinical Oncology (1993)

PURPOSE Patients in whom prostate cancer progresses despite testicular androgen ablation are generally said to have cancers that have become resistant to hormonal maneuvers. If androgen suppression has been pharmacologic, this therapy is often stopped before consideration of other systemic treatments. This exploratory study sought clinical correlates of experimental evidence that there may be substantial acceleration of tumor growth after cessation of androgen suppression. MATERIALS AND METHODS A retrospective multivariate analysis was performed on survival data for 341 patients treated on four clinical trials of secondary therapy for hormone-refractory prostate cancer. Factors included in the model were recent weight loss, age, performance status, disease site (soft tissue v bone-dominant), prior radiotherapy, and continued androgen suppression v discontinued exogenous endocrine therapy. RESULTS Recent weight loss, age, performance status, and disease site were important prognostic factors for survival duration in hormone-refractory prostate cancer. Correcting for these factors, continued testicular androgen suppression was also an important predictor of survival duration in all data sets examined. CONCLUSION This retrospective study showed a modest advantage in survival duration for men with hormone-refractory prostate cancer who continued to receive testicular androgen suppression. The hypothesis that continued hormonal maneuvers can still affect survival in this group warrants examination in prospective trials.
Efficiency of nebulised therapy in preventive maintenance of bronchial stump insufficiency after pneumonectomy
Authors: Shuhrat Hudaybergenov, Georgy Pahomov, Rustem Hayaliev, Ortikali Irisov, Otabek Eshonhodzhaev, Ezoz Rizaev
Journal: European Respiratory Journal (2011)

Introduction:  Introduction for preventive maintenance COPD nebulised therapy (NT) promotes the high local activity of inhalated remedies.   Purpose:  To value efficiency of NT in preventive maintenance of bronchial stump insufficiency (BSI) after pneumonectomy (PE).   Material and methods:  The interesting results were received at study of the influence accompanying pathology on frequency of development BSI after PE. The frequent diseases were COPD and heart-vascular pathology. So from 390 patients in 207 (53,1%) accompanying COPD was revealled, on background which after PE in 36 (17,4%) patients was noted development of BSI. In turn, amongst 183 (46,9%) patients without accompanying COPD this complication was noted only in 2,7% of the cases. That is to say, presence of COPD raised the risk of the development BSI more then in 6 once.   Results:  Introduction NT has allowed in the main group to reduce the risk of the intensification COPD to 16,1% after PE on the left and 17,2% after PE on the right, and frequency of the development of BSI on background accompanying COPD decreased to 3,2% and 6,9% accordingly. In the main group accompanying COPD was revealled in 60 patients (61,2%), activation after operation was noted in 10 (16,7%) patients, but development of BSI only in 3 patients, that has formed 5,0%.   Findings:  Introduction of NT for preventive maintenance COPD promotes not only reliable improvement of the factors of breathing frequency (P
Association between activities related to routes of infection and clinical manifestations of melioidosis
Authors: C. Lim, S.J. Peacock, D. Limmathurotsakul
Journal: Clinical Microbiology and Infection (2015)

We sought associations between route of infection by Burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast Thailand using bivariate multivariable logistic regression models. Activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. Our study suggests that route of infection is one of the factors related to clinical manifestations of melioidosis.