tbuckley/cabot-search huggingface dataset:
Routine interval computed tomography in detecting new soft tissue disease in patients with androgen-independent prostate cancer (AIPC) and only bone metastasis
Authors: S. Wu, E. Jones, J. Gulley, P. Arlen, C. Chen, W. Figg, W. Dahut
Journal: Journal of Clinical Oncology (2006)

4621 Background: Bone is the most common metastatic site in AIPC and the only site of metastasis for many patients. However, some pts with only bone metastasis will eventually develop soft tissue disease. Thus many clinical trials include CT monitoring to exclude new soft tissue disease as the only manifestation of disease progression. The true incidence of the asymptomatic development of soft tissue metastases without PSA or bone scan progression is unknown. Here we have identified pts with bone metastasis only at the time of protocol enrollment. We analyzed their disease progression pattern to determine the utility of routine interval CT scans. Methods: We reviewed 100 pts with metastatic AIPC from three phase II clinical trials (docetaxel/thalidomide, docetaxel/vaccine, and ketoconazole/alendronate) between 1995 and 2004. Pts were assessed every 4 weeks with PSA measurement. CT and bone scans were performed 2 months after start of the trial and then at least every 3 months. Median follow-up time was 8 months (1–44 months). The pts with bone metastasis only were examined for the occurrence of soft tissue diseases by subsequent CT scans in association with bone scan and PSA. Results: Of 100 pts with metastatic AIPC, 33% had soft tissue disease alone or soft tissue and bone disease. 67% had no soft tissue involvement identified by CT but had bone metastasis revealed by bone scan. Of the pts with only bone metastasis, 3% (2 pts) developed new soft tissue disease. One pt developed new right illiac fossa lymphadenopathy after 8 months, and another a peri-rectal mass after 12 months. The one with new lymphadenopathy also had multiple new bone lesions identified by bone scan and PSA progression. The one with a peri-rectal mass had PSA progression and a palpable abnormality. Conclusions: The incidence of asymptomatic new soft tissue disease as the only manifestation of disease progression appears to be quite low in pts with only bone metastasis. Scheduled interval examination with CT to exclude new soft tissue disease does not appear to be warranted. CT scans should probably only be done at the time of disease progression shown by bone scan/PSA or when there are clinical signs or symptoms of new soft tissue disease. No significant financial relationships to disclose.
Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases
Authors: G. Miller, P. Biernacki, N. Kemeny, M. Gonen, R. Downey, W. R. Jarnagin, M. D’Angelica, Y. Fong, L. H. Blumgart, R. P. DeMatteo
Journal: Journal of Clinical Oncology (2007)

4059 Background: Surgical resection of isolated hepatic or pulmonary colorectal metastases prolongs survival in selected patients. However, the benefits of resection and appropriate selection criteria in patients who develop both hepatic and pulmonary metastases are ill-defined. Methods: Data were prospectively collected from 131 patients with colorectal cancer who underwent resection of both hepatic and pulmonary metastases over a 20-year period. Median follow-up was 6.6 years from the time of resection of the primary tumor. Patient, treatment, and outcome variables were analyzed using log-rank, Cox regression, and Kaplan-Meier methods. Results: The site of first metastasis was the liver in 65% of patients, lung in 11%, and both simultaneously in 24%. Multiple hepatic metastases were present in 51% of patients and multiple pulmonary metastases were found in 48%. Hepatic lobectomy or trisegmentectomy was required in 61% of patients while most lung metastases (80%) were treated with wedge excisions. Median survival from resection of the primary disease, first site of metastasis, and second site of metastasis was 6.9, 5.0, and 3.3 years, respectively. After resection of disease at the second site of metastasis, the 1, 3, 5, and 10 year disease-specific survival rates were 91, 55, 31 and 19%, respectively. An analysis of prognostic factors revealed that survival was significantly longer when the disease-free interval between the development of the first and second sites of metastases exceeded one year, in patients with a single liver metastasis, and in patients younger than 55 years. Conclusions: Surgical resection of both hepatic and pulmonary colorectal metastases is associated with prolonged survival in selected patients. Patients with a longer disease free interval between metastases and those with single liver lesions had the best outcomes. [Table: see text] No significant financial relationships to disclose.
Phase I/II double-blinded randomized study to determine the tolerability and efficacy of two different doses of lenalidomide (Len) in biochemically relapsed prostate cancer (BRPC) (M0) patients (pts).
Authors: D. Keizman, V. J. Sinibaldi, M. A. Carducci, S. R. Denmeade, C. G. Drake, R. Pili, E. S. Antonarakis, S. Hudock, M. Zahurak, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2010)

4554 Background: Preliminary data suggest that Len, an immunomodulatory agent and angiogenesis inhibitor, is active in prostate cancer. Aims: Evaluate the safety and efficacy of 6 months (mo) administration of 5 or 25 mg/day of Len. Methods: 60 noncastrate BRPC pts were stratified (PSADT, surgery/RT, prior ADT, Gleason) and randomized to oral Len at 5 (n=26) or 25 mg/day (n=34) given 3/4 weeks for 6 mo or until PSA progression (> 25% over baseline), clinical/radiographic progression or dose-limiting toxicity (tox). Disease status was evaluated at the end of every 6 mo cycle with scans and PSAs (collected/2 mo, assayed at 6 mo) and tox monthly. The proportion of pts with disease progression or dose limiting tox at 6 mo was compared between arms by chi-square test. Regression of the log PSA on the time of PSA measurement for each pt before and on study, was used to calculate pre and on study PSA slopes. The change in slope, on study slope minus pre study slope, was estimated for each pt and the mean changes for the two dose groups compared using a t-test. Results: Pre study parameters were balanced between arms. The occurrence of grade 3/4 tox was 11.5% with 5 mg and 29.4% with 25 mg, p=0.1, most commonly neutropenia (5 pts, all on 25 mg), venous thromboembolism (2 in each group), fatigue (2), skin rash (2). Mean (range) steady state Len plasma concentration (ng/ml) was 12.67 (6.1-19.2) versus 65.14 (24.3-106.0), p=0.01, for 5mg and 25mg respectively. Mean (range) follow up (mo) is 28.3±10.4 (12-41). A significant decrease in PSA slope favored the 25 mg (-0.172 vs. -0.033, p = 0.005) (Table). 50% and 44% of pts on 5 mg and 25 mg respectively, had PSA/scans progression at 6 mo. Currently 9 patients are still on study, 6 on 25 mg and 3 on 5 mg. Conclusions: Long-term Len treatment has acceptable tox, results in dose-dependent changes in PSA slope, and potentially delays progression of BRPC (M0). Randomized studies evaluating conventional disease endpoints should be performed. 5 mg 25 mg p value Mean (95% CI) pre-study PSA slope 0.16 (0.11 to 0.21) 0.18 (0.13 to 0.23) 0.55 Mean (95% CI) pre/post PSA slope −0.033 (−0.11 to 0.04) −0.172 (−0.24 to −0.11) 0.005 No significant financial relationships to disclose.
Evaluation of association between clinicopathologic characteristics of the disease and quality of life in cancer patients.
Authors: S. Kilickap, M. Erman, I. Celik, M. Hayran
Journal: Journal of Clinical Oncology (2010)

e19650 Background: Cancer is an important health problem because it is the second most common cause of mortality. Cancer and its treatment may influence health-related quality of life. Methods: In this study, we aimed to investigate quality of life and clinicopathological factors which may influence the quality of life in cancer patients who have been following at Hacettepe University Institute of Oncology. EORTC QLQ-C30 measurements were obtained from all patients with cancer. The associations between the quality of life score and demographical and clinical variables of the patients were evaluated. Results: A total of 1549 (F/M: 797/752) patients were analyzed. The median age was 54.5 (16-92) years. The most common cancer was breast cancer (21%). Poor performance status, family history of cancer, being an inpatient, to be under current therapy, advanced stage, and metastatic disease were significantly associated with poor quality of life score. For patients followed 1 year or less after the diagnosis, global quality of life score was significantly lower than those followed 3 years or more (p≤0.001). Quality of life score was higher in patients with no metastasis compared to in those with local or distant metastasis (respectively; 66.0±24.5 vs 58.8±25.9 vs 52.0±28.9; p≤0.001). Lower hemoglobin and serum albumin levels or leukopenia were also associated with poor quality of life. The association between quality of life score and gender, martial status, previous cancer history, and age were not significant. Global quality of life was higher in patients with gynecologic and colorectal cancer compared with the others. Conclusions: Global quality of life in patients with cancer is influenced by various clinicopathological features. No significant financial relationships to disclose.
Current trends in prophylactic cranial irradiation (PCI) for extensive-disease small cell lung cancer (EDSCLC): Results of a UK survey
Authors: N. Bayman, P. Lorigan, F. Blackhall, N. Thatcher, C. Faivre-Finn
Journal: Journal of Clinical Oncology (2008)

19040 Background: The EORTC 08993–22993 trial published in 2007 showed a survival benefit for PCI in patients who respond to initial systemic therapy for EDSCLC. This questionnaire-based study assesses the uptake of PCI in this setting in the UK. Methods: A 10 item questionnaire was sent to clinical oncologists involved in the treatment of small-cell lung cancer in 52 radiotherapy centres in the UK in December 2007. We asked if and when PCI became routine practice for the treatment of EDSCLC, the dose/fractionation regimens used, and if they had treated patients outside of the inclusion criteria for the EORTC trial. As a secondary point of interest we asked if patients were routinely treated with consolidation thoracic radiotherapy following systemic therapy for EDSCLC. Results: Completed questionnaires were returned from 39 centres (75.0% response). PCI is used in 89.7% of centres after a response to systemic therapy in EDSCLC. Before the results of the EORTC trial were available, 5 centres were routinely using PCI in this setting. 13 centres started using PCI after the results were presented at the 2007 ASCO annual meeting in June, and 16 centres began after the results were published in August 2007. The latest implementation of PCI in an oncology centre was in October 2007. No centre is treating more than 5 patients per month. The most common dose/fractionation regimens in use are 20 Gy/5 fractions (60%), 25 Gy/10 fractions (25.7%), and 30 Gy/10 fractions (28.6%). Of the centres using PCI for EDSCLC, 28.6% have treated patients over 75 years old despite these patients having been excluded from the EORTC trial, and 80% have treated patients with a World Health Organisation (WHO) performance status (PS) of 2. No centres have treated patients with WHO PS > 2. Consolidation thoracic radiotherapy is routinely given in 35.9% of centres. Most centres (79.5%) would be interested in taking part in a randomised controlled trial to assess the role of consolidation thoracic radiotherapy following systemic therapy in EDSCLC. Conclusions: Radiotherapy centres in the UK have been quick in the implementation of PCI in patients with EDSCLC. Most centres are following the EORTC trial protocol with respects to inclusion criteria and radiation dose/fractionation. No significant financial relationships to disclose.
A study of insulin resistance in moderate to severe obstructive sleep apnea in non diabetics and its response to nasal CPAP treatment
Authors: Archana Babu Rao, George Albert D. Souza, Sriram Sampath, Uma Subramanian Unni
Journal: European Respiratory Journal (2011)

Background: The effects of nasal continuous positive airway pressure (nCPAP) for obstructive sleep apnoea (OSA) on insulin resistance (IR) are not clear and have found conflicting results.

Aims and objectives: To evaluate IR in non diabetic patients with moderate to severe OSA and the effect of treatment with nCPAP on IR in these patients.

Method: 30 consecutively newly diagnosed patients with moderate to severe OSA were enrolled in the study. Samples of peripheral venous blood for measurement of glucose and insulin were collected after overnight fasting and IR was calculated by HOMA (Homeostasis model assessment) method. Patients were treated with nCPAP for 1month and HOMA IR was again measured.

Results: 30 OSA subjects,with a mean apnoea-hypopnoea index (AHI) of 80.46 [57.24] were included in the study. The HOMA IR (5.78) was significantly higher compared to normal south indian population. There was no positive correlation of HOMA IR with AHI. This may be due to the small sample size and IR attributable to OSA may be small and constant and not related to the severity. The HOMA IR was measured 1 month after use of CPAP. The HOMA IR significantly improved from 5.78 to 4.82 (p=0.024) after 1 month of treatment with nCPAP in OSA patients. There was also significant improvement in insulin levels from 21.75 to 19.39 (p=0.009).

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Conclusion: OSA is associated with an increase in IR which may be one of the reasons that OSA is a risk factor for coronary artery disease (CAD). Treatment with CPAP rapidly improves the insulin sensitivity in patients with OSA and thus may contributes to a reduction of cardiovascular risk in patients with moderate to severe OSA.

 [1]: pending:yes
Relapse after non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: early transplantation, use of an unrelated donor, and chronic graft-versus- host disease are protective
Authors: H Enright, SM Davies, T DeFor, X Shu, D Weisdorf, W Miller, NK Ramsay, D Arthur, C Verfaillie, J Miller, J Kersey, P McGlave
Journal: Blood (1996)
Histopathological grading of intracranial pediatric ependymomas
Authors: David Ellison, Catherine Godfraind, Mehmet Kocak, Dominique Figarella-Branger, Felice Giangaspero, Torsten Pietsch, Zhao Wei, Didier Frappaz, Maura Massimino, James Boyett, Richard Grundy
Journal: Neuro-Oncology (2008)
Changing pattern of invasive fungal infection in immunocompromised children: Experience at National Guard hospital, Jeddah, Saudi Arabia
Authors: T. M. Khattab, S. K. Felimban, A. A. Baothman, W. Jastaniah
Journal: Journal of Clinical Oncology (2008)

10046 Background: Invasive fungal infections (IFIS) are a common cause of morbidity and mortality in immunocompromised patients. Candida and Aspergillus are the most frequent pathogens. Increase incidence of IFIs due to increasing intensity of various chemotherapy regimens. Objectives: To study the pattern of IFIs at our institution, so we may modify local policies or implement new procedures to decrease incidence of IFIs. Methods: We retrospectively reviewed all children with hematological disease or solid tumour who developed IFIs during the course of their disease. We applied the criteria for definition of (IFIs) as developed by Ascioglu S. et al, CID 2002. We studied patients at 2 different era between 1993–2004 and 2004–2007 when a hipa filter fixed at our unit. The underlying diseases were (ALL) (n=411), (AML) (n=50), Lymphoma (n=104), solid tumors (n=248), Severe Aplastic Anemia (SAA) (=2) and others (n=44). Results: Sixty one patients 61/859 (7%), 36 were girls, aged 0.2–12 year (median 4) were diagnosed to have proven (n=49) or probable (n=12) IFIs. Before hepa filter Aspirgillus species were isolated in (26) patients, Candida (9) and Mucormycosis species (5) patient. After hepa filter, Asp.(3), Candida (16), undetermined (2). Sites of involvement were skin(n=12), lung(n=14), sinuses (n=8), and disseminated (n=27). 2 patients with disseminated candida required splenectomy. 14/61 (23%) patients presented at induction or relapse. Three patients with cutaneous IFIs required skin graft. Overall survival 33/61=54%, mortality due to IFIs 10/61=16% and due to resistant disease 18/61=30%. Conclusions: During this 15 year period 61/859 (7%) of immunocompromised children developed IFIs. Early antifungal therapy, surgical debridement for aspergillosis and mucormycosis and removal of central lines for candidiasis are essential for successful outcomes. Hipa filter decrease incidence of aspergillosis. No significant financial relationships to disclose.
Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against Podocytopathy
Authors: Sijie Zhou, Pei Wang, Yingjin Qiao, Yan Ge, Yingzi Wang, Songxia Quan, Ricky Yao, Shougang Zhuang, Li Juan Wang, Yong Du, Zhangsuo Liu, Rujun Gong
Journal: Journal of the American Society of Nephrology (2015)

Evidence suggests that the glycogen synthase kinase 3 (GSK3)–dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3 β (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3 β in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3 β mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3 β by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3 β -regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies.
Proteasome Inhibitor Does Not Affect the Function of Human Immune Systems: Effects on Dendritic Cells, T Lymphocytes and NK Cells.
Authors: Jooeun E. Bae, Tai Yu-Tzu, Teru Hidesima, Larence Catley, Xianfeng Li, Rao H. Prabhala, Ramesh B. Bachu, Robert Bertheau, Masood A. Shammas, Sushma Samala, Jeff Miller, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Natural History of Untreated Patients Who Had Metastatic Biliary Tract Cancer (Btc) with Good Performance Status (Ps)
Authors: A. Seo, J.H. Ji, H. Song, R.B. Kim, S.Y. Oh, H.Y. Lim, J.O. Park, S.H. Park, M.J. Kim, J.H. Kang, S. Lee, I.G. Hwang, J. Jang, H.J. Kim
Journal: Annals of Oncology (2014)
Cost-effectiveness of primary prophylaxis (PP) with colony-simulating factor (CSF) when compared with secondary prophylaxis (SP) in elderly patients with diffuse aggressive lymphoma undergoing curative chemotherapy
Authors: K. K. Chan, K. R. Imrie, S. M. Alibhai
Journal: Journal of Clinical Oncology (2007)

6558 Background: The 2006 ASCO guideline recommends PP with CSF for elderly patients with diffuse aggressive lymphoma, partially based on previous cost-minimization analyses showing that CSF saved costs when compared with no CSF by reducing hospitalization from febrile neutropenia (FN) when the risk of FN was &gt; 20%. However, these studies examined only one cycle of chemotherapy and did not account for costs of CSF in subsequent cycles, did not consider SP, and did not consider patients’ preferences. Methods: We conducted a cost-utility analysis to compare PP with SP in this setting using a Markov model for a time horizon of 8 cycles of chemotherapy with a government payer perspective. Costs were adjusted to 2006 $CAD. Ontario health economic data were used. The cost of hospitalization for FN was obtained from Ontario Case Costing Initiative. Data for efficacies of CSF, probabilities and utilities were obtained from published literature. Sensitivity analyses were conducted using a threshold of $100,000/QALY. Results: The base case costs for PP and SP were $22,077 and $17,641. The QALYs of PP and SP were 0.254 and 0.248. The incremental cost effectiveness ratio of PP to SP was $739,999/QALY. One-way sensitivity analyses showed that in order for PP to be cost-effective, the cost of hospitalization per episode of FN had to be &gt; $31,138 (i.e. 2.5 times &gt; base case), the cost of CSF per cycle had to be &lt; $896 (base case = $1,960), the risk of FN in the 1st cycle had to be &gt; 48% (base case = 24%), or the relative risk reduction of FN with CSF had to be &gt; 97% (base case = 41%). Our result was robust to all other cost, probability and utility variables. First order microsimulation showed that &lt; 17% of simulations were cost-effective. Conclusions: PP is not cost-effective when compared with SP for this population under most assumptions. PP only becomes attractive in places where the cost of hospitalization for FN is much more than that of Ontario, or the cost of CSF is under $896 per cycle. The costs of CSF and hospitalization in all cycles (instead of just one cycle) should be accounted for in any economic evaluation of CSF. Current guidelines recommending PP in this population should be revisited. No significant financial relationships to disclose.