tbuckley/cabot-search huggingface dataset:
Serum carcinoembryonic antigen (CEA) levels and prognosis in early and advanced non-small cell lung cancer (NSCLC).
Authors: S. Cedres Perez, I. Nuñez, M. Longo, P. Martínez, E. Rodríguez Checa, M. Cazorla, E. Felip
Journal: Journal of Clinical Oncology (2010)

e21054 Background: The usefulness of tumor markers in NSCLC is not well defined. High levels of CEA are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is yet to be defined. The aim of the study is to analyze the prognostic value of basal level of CEA in unselected NSCLC patients. Methods: 320 NSCLC patients diagnosed in our institution between April 2004 and March 2009 were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology, clinical stage and brain metastases. Overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. The cutoff value of serum CEA level was 5 ng/mL. Results: Baseline patients characteristics: median age 63 (30-82 years), males 84.4%, stage I: 7.2%, II: 6.3%, III: 33% and IV 53%; squamous carcinoma 23.8%, adenocarcinoma 39.7%, large cell carcinoma 19.4% and undifferentiated carcinoma 15%. High levels of CEA were detected in 179 (56.5%) patients. Significant higher levels of CEA at baseline were present in adenocarcinoma (p = 0.03) and patients with advanced disease (p = 0.01) but not difference according sex or brain metastases were detected. After a follow-up of 9.7 months, 256 patients relapsed and 202 patients had died. In the 275 patients with advanced disease, the PFS was 5.3 months vs 7.4 months for patients with high and normal CEA (p = 0.011) and the OS 10.0 months vs 14.0 months in patients with high and normal CEA (p = 0.085). In early stages (I-II) the DFS was 14.2 vs 20.3 months (p = 0.141) and OS 35 vs 47.7 months (p = 0.045) for patients with high and normal CEA. In the multivariate analysis only high levels of CEA, histology and stage were significant correlated with worse prognostic. Conclusions: In our analysis, high levels of CEA at baseline are correlated with worse survival in stage I-IV NSCLC patients. No significant financial relationships to disclose.
Ulcerative keratitis in gatrointestinal stromal tumor patients treated with perifosine
Authors: B. Esmaeli, J. Trent, L. Espandar, E. Hatef, S. K. Kim, D. Song
Journal: Journal of Clinical Oncology (2007)

19664 Background: Perifosine is a novel, oral, alkylphospholipid with antiproliferative properties attributed to Akt inhibition. We describe the ocular findings in 5 patients enrolled in phase I/phase II trials of perifosine in combination with imatinib for treatment of advanced GIST. Methods: The medical records of 5 patients who developed peripheral ulcerative keratitis while receiving perifosine and imatinib were retrospectively reviewed. Results: 1 man and 4 women ranged in age from 43 to 72 (median, 57 years). The ocular symptoms included redness, irritation, tearing, photophobia and a gradual decrease in vision. Slit lamp biomicroscopy in each case revealed a peripheral, paralimbal, ring-shaped, superficial stromal infiltration and ulcerative keratitis (UK), reminiscent of the autoimmune keratitis in conditions such as rheumatoid arthritis. The best corrected visual acuity in the affected eye(s) ranged from 20/25 to 20/300 (median 20/70). The UK was unilateral in 3 and bilateral in 2 patients; it was NCI grade II in all. All 6 patients had imatinib-resistant metastatic GIST and had continued on the highest dose of imatinib tolerated and initiated therapy with perifosine 100 mg daily or 900 mg weekly. Time from start of perifosine therapy to diagnosis of UK ranged from 1 to 3 months (median, 2). A combination of topical steroids, topical antibiotics and lubricating drops were used to manage UK. In the first 3 patients, UK was initially treated with topical antibiotics without improvement, but subsequently improved significantly once topical steroids were added. In 5 of 6 patients, the visual acuity improved with this regimen. Conclusions: UK may occur as a side effect of perifosine and shares features of autoimmune forms of keratitis. It is possible that imatinib in combination with perifosine is contributing to this toxicity. Topical steroids improve the signs and symptoms of UK and early treatment with topical steroids may lessen the potential risk of permanent corneal scarring and visual loss. The visual loss associated with perifosine can be reversible with close monitoring and judicious use of topical steroids, topical antibiotic coverage, and lubrication. No significant financial relationships to disclose.
A phase I study of XL228, a potent IGF1R/AURORA/SRC inhibitor, in patients with solid tumors or hematologic malignancies
Authors: D. C. Smith, C. Britten, D. O. Clary, L. T. Nguyen, P. Woodard, H. I. Hurwitz
Journal: Journal of Clinical Oncology (2009)

3512 Background: XL228 is a protein kinase inhibitor targeting IGF1R, the AURORA kinases, FGFR1–3, ABL and SRC family kinases. It is being evaluated in a phase 1 trial in patients (pts) with advanced malignancies. Methods: XL228 is administered as weekly 1-hour IV infusions. Cohorts of pts with refractory solid tumors or lymphoma are evaluated for determination of the maximum tolerated dose, pharmacokinetics, and pharmacodynamic effects using FDG-PET, signal pathway analysis in tumor and normal tissue biopsies, and plasma marker analysis. MTD expansion cohorts will include pts with multiple myeloma and colorectal cancer. Results: Thirty-six pts have been treated at doses ranging from 0.45 to 8.0mg/kg. The maximum administered dose was defined as 8.0mg/kg as a result of the dose limiting toxicities of Grade (Gr) 4 neutropenia, and Gr 3 neutropenia requiring dose skipping. XL228 is generally well tolerated; one serious adverse event of drug-related Gr 3 vomiting has been observed. Common drug-related adverse events include Gr 1 nausea, fatigue, decreased appetite, and flushing, and Grade 1–2 hyperglycemia (fasting) lasting up to 4 hours post- infusion. XL228 exposure was approximately dose-proportional; the mean terminal half-life (t 1/2, z ) ranged from 27 to 54 hours. Low accumulation was observed after weekly administration. Protein phosphorylation measurements in skin, hair, and blood samples demonstrate inhibition of IGF1R, SRC and FGFR1 signaling by XL228, including reductions in hair follicle phospho-IGF1R and phospho-FAK1 of 39% and 42%, respectively, in a pt dosed at 5.4mg/kg. Evidence of clinical activity includes one non-small cell lung cancer pt with an unconfirmed partial response (confirmation pending) and 9 additional pts (of 30 evaluable) with stable disease (SD) lasting &gt;3 months, including a small cell lung cancer pt on study for 13.3+ months after failing carboplatin/etoposide. For pts with SD, the median time on study is currently 5.9 months (range 3.3+ to 13.3+). Conclusions: XL228 is generally well tolerated and has shown encouraging preliminary clinical and pharmacodynamic activity. [Table: see text]
Minimally increased risk of cerebrovascular occlusive disease or intracerebral hemorrhage in patients on bevacizumab treatment and association with intracerebral malignancies
Authors: Y. Oh, S. Wallace, S. Taylor, R. S. Herbst, S. M. Lippman, D. D. Karp, D. J. Stewart
Journal: Journal of Clinical Oncology (2008)

14507 Background: Bevacizumab (Bv) and other VEGF/VEGFR-targeting agents have become useful therapies for cancer and are active against primary and metastatic central nervous system malignancies (CNSM). Its use in patients with brain metastases, however, has been largely avoided over concerns for precipitating intracerebral hemorrhage (ICH) and also an increased risk of thromboembolic disease. We report here a retrospective analysis of ICH and cerebrovascular infarct (CVA) incidences in CNSM patients who received Bv-based treatment. Methods: Using institutional billing and pharmacy databases we reviewed the electronic records of 149,421 patients treated at the University of Texas M. D. Anderson Cancer Center between 9/1/02 and 8/31/06. CNSM were diagnosed in 6674 patients. The first 13,088 cancer patients without CNSM were analyzed as a control group. The prevalence of CNSM, treatment with Bev, and ICD-9 codes for CVD, cerebral infarcts, and ICH, and their temporal relationships were compared and analyzed by Yates Corrected Chi-square test. Results: 1,360 patients received Bv therapy; of these 179 had CNSM. The prevalence of ICH among those with CNSM whether they receved Bv or not (4.5% vs 4.4%, p=0.887). Prior radiotherapy had been given to 4 of 8 patients who developed ICH after Bv treatment. In Bev-treated patients, ICH prevalence was higher in those with CNSM than in those without (4.5% vs 0.9%, p=0.0006). In those not receiving Bv, ICH prevalence was lower in those with CNSM than in those without (4.4% vs 5.8%, p<0.0001). The prevalence of CVA was increased in CNSM by Bv treatment (0.5% to 1.7%, p=0.095). In non-CNSM patients, Bv treatment compared to no Bv treatment was associated with lower CVA prevalence (0.1% vs 1.6%, HR 0.06, p=0,0001) and lower ICH prevalence (0.9% vs. 5.8%, HR 0.16, p<0.0001). Conclusions: In CNSM patients treatment with Bv does not appear to increase the risk of ICH, and despite an increase in CVA prevalence, the risk was not statistically significant. Bv-based therapy carries no appreciable increase in cerebrovascular risk in patients with CNSM. In patients without CNSM, those selected for Bv therapy had markedly lower cerebrovascular risk than those who were not. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech
The penetrance of HFE-associated hemochromatosis as assessed by clinical evaluation and liver biopsy in subjects identified by health checks, family screening or population screening
Authors: L. W. Powell, J. L. Dixon, G. A. Ramm, G. J. Anderson, V. N. Subramaniam, D. M. Purdie, D. G. Hewett, J. W. Searle, L. M. Fletcher, D. H. Crawford, H. Rodgers, T. L. Khoo, J. A. Cavanaugh, M. L. Bassett
Journal: Hepatology (2004)
Diethylhexyl Phthalate
Journal: Environmental Health Perspectives (1997)

We treated KunYangOan (KYD) in SD rats in order to examine the protective effect against cell damage induced by diethylhexyl phthalate (DEHP). KYD reduced DEHP toxicity by increasing the function of immune cell numbers, weight increase of spleen, red blood cells, HB, and HCT content, sperm number and mobility, resulting in improving reproductive function by judging from the recovery of testosterone content. Interestingly, the hormone change of testosterone by KYD significantly recovered the decreased its level. Taken together, these results suggest that KYD specifically affect the reproductive function induced by DEHP, an endocrine disruptor.
Patupilone in chemotherapy-pretreated patients with advanced colorectal cancer (CRC) receiving nutritional support and intensive diarrhea management: A phase I multicenter trial
Authors: E. Casado, J. Tabernero, B. Melichar, J. Bridgewater, J. Bennouna, J. Delord, M. Sopala, I. Sklenar, W. Cheung, A. Johri
Journal: Journal of Clinical Oncology (2006)

3593 Background: In previous clinical studies, a positive effect was noted in patients with CRC heavily pretreated with chemotherapy who received the novel microtubule stabilizer patupilone (EPO906; epothilone B) once-weekly or q3wk; however, susceptibility to diarrhea was high and response rates were modest. This dose-escalation trial examined the safety/efficacy of 3 patupilone regimens in chemotherapy-pretreated patients with CRC who received nutritional support and intensive diarrhea management. Methods: Patients with histologically confirmed CRC, without ileo- or colostomy or history of abdominal/pelvic irradiation, and who relapsed or were refractory after ≤4 prior chemotherapy regimens received nutritional support, intensive diarrhea management if needed, and patupilone as IV bolus q3wk or 1-or 5-day continuous IV (CIV) q3wk at doses of 6–10 mg/m 2 . Additional inclusion criteria: ≥1 measurable lesion; age ≥18 years; WHO performance status &lt;2; no hepatic, renal, or hematologic impairment. Nutritional supplementation: ω-3 fatty acids, pre- and probiotics, antisecretory factor, and glutamine. Diarrhea management: appropriate clinical care, loperamide, opium tincture, codeine, and octreotide. Dose escalation was per protocol following a 3+3 design. The primary objective of this trial was to determine the maximum tolerated dose of the 3 patupilone treatment schedules in these patients. Results: Forty-four patients were enrolled: bolus, n = 22; 5-day CIV, n = 3; 1-day CIV, n = 19. Mean age 58.8 years; 95% Caucasian; 54% men. In the 5-day CIV arm, enrollment was closed at the 6.5-mg/m 2 dose level since 2 dose-limiting toxicities (severe diarrhea) were reported. With bolus and 1-day CIV, the current doses are 10 and 9 mg/m 2 , respectively. The most common adverse events in the 43 patients evaluable for safety were diarrhea (70%), asthenia (23%), and nausea (21%). Grade 3 diarrhea occurred in 9 patients (21%). Overall response: 4 partial responses and 13 stable disease. Conclusions: Preliminary results suggest that patupilone monotherapy administered q3wk + intensive diarrhea management may prove beneficial in patients with CRC who progressed after 2–3 chemotherapy regimens. [Table: see text]
SP0191 Live Attenuated Vaccines in Rheumatic Diseases
Authors: R. Thomas
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Adult and paediatric patients with rheumatic diseases may be immunodeficient due to treatment with high-dose corticosteroids, immunosuppressive drugs such as cyclophosphamide or biologics. The diseases themselves may also lead to immune compromise. In view of the paucity of evidence, it is generally recommended that live attenuated vaccines – including BCG, MMR, VZV, yellow fever, cholera and oral poliomyelitis - be avoided in patients with rheumatic diseases on immunosuppressive regimens. Where possible, such vaccines should be given before commencing immune suppression. I will review the available evidence along with evidence of exacerbation of infections in patients treated with immunosuppressive regimens including biologics. I will also consider potential alternative strategies for treatment of rheumatic disease which avoid systemic immune suppression. <h3>Disclosure of Interest</h3> R. Thomas Grant/Research support from: R&amp;D collaboration with Janssen for RA immunotherapy <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6193
Effect of clinical stage on survival outcome in patients with pathological stage I gastric cancer.
Authors: Masanori Tokunaga, Rie Makuuchi, Yuichiro Miki, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2015)

178 Background: Patients with clinical stage (cStage) II or III gastric cancer are possible candidates for neoadjuvant chemotherapy. In this situation, contamination of pathological stage (pStage) I patients, for whom gastrectomy without adjuvant chemotherapy is a standard treatment of care, is a problem. However, it is unclear whether survival outcome in patients with cStage II-III / pStage I gastric cancer is as good as that of patients with cStage I / pStage I disease. The aim of the present study is to clarify the effect of clinical stage on survival outcome in patients with pStage I gastric cancer. Methods: The present study included 558 patients with pStage I gastric cancer who underwent gastrectomy between 2002 and 2006 at Shizuoka Cancer Center, Japan. Clinicopathological characteristics were investigated, and survival outcome was compared between cStage I and cStage II-III. In addition, we investigated the effect of other clinical factors, including clinically diagnosed tumor depth (cT) and nodal status (cN), on survival outcome. Results: The present retrospective cohort includs 368 male and 190 female patients, with median age of 64 years Five-year survival rate (5ysr) was significantly worse in cStage II-III (84.2%) than in cStage I (95.5%, p=0.003). 5ysr was also worse in cT2-4 (86.6%) than in cT1 (96.3%, p&lt;0.001). On the contrary, clinical nodal status did not affect survival outcome of pStage I patients. Conclusions: cT and cStage affected survival outcomes of patients with pStage I gastric cancer. Patients who are preoperatively diagnosed with advanced disease have worse survival outcomes and can be candidates for neoadjuvant chemotherapy.
Incidence of hypersensitivity reactions (HSRs) to albumin-bound paclitaxel (ABI) in patients (pts) with a history of HSR to cremophor-based paclitaxel (P).
Authors: J. P. Timoney, D. McGuffy, D. DeRitis, E. Tyler, J. Sumka, M. Pozotrigo, V. Bhatt, A. Chan, N. T. Sklarin
Journal: Journal of Clinical Oncology (2011)

2566 Background: ABI is a cremophor-free formulation of paclitaxel which has been reported to have a lower incidence of HSRs. A retrospective evaluation was performed to determine the incidence of HSRs to ABI in pts with a history of HSRs to P. Methods: A query of the institutions medication database was performed to identify pts who received ABI during the evaluation period 2/05 - 5/09. A waiver of authorization was obtained to review the medical records. Results: At the discretion of the physician, 69 pts were switched to ABI following an HSR to P. Cancer diagnoses were 92% breast and 8% lung. The median age was 50 years and 92% were female. All pts who experienced an HSR to P had received premedication with corticosteroids, histamine 1 and histamine 2 antagonists. Pts’ HSRs to P were grade 3 (1%), grade 2(74%) and grade 1 (25%) according to CTCAE 4 .03. The most common manifestations of HSRs to P were flushing 50%, shortness of breath 20%, chest tightness 18% and lower back pain 17%. The most common treatments to HSRs from P were stopping the infusion 81%, diphenhydramine IV (53%), hydrocortisone IV (30%) and dexamethasone IV (14%). Following the initial HSR to P, 30% of pts were rechallenged with P where 67% were able to complete the infusion at a slower rate while 33% developed a grade 1 or 2 HSR upon rechallenge. Of the 69 pts switched to ABI, 64 (93 %) did not experience a subsequent HSR. Twenty two (68%) of pts did not receive any premedication prior to the ABI challenge. Of the 5 pts who experienced an HSR to ABI, 2 were grade 1 and 3 were grade 2. Two of the five ABI HSR pts had been premedicated prior to the ABI challenge. The most common manifestations of HSRs to ABI were flushing and rash. Four of the 5 pts experienced the HSR during or immediately following the first dose of ABI. Four of these 5 pts were re-challenged with ABI and all 4 continued to receive further treatment courses after the reaction manifestations resolved. Conclusions: The majority of pts with a history of grade 1 or 2 HSR to P could receive ABI without developing an HSR. Of those who reacted to ABI, reactions were tolerable and most were able to be re-challenged and continue treatment with ABI.
What is the role of F-18 FDG PET within randomized multicenter clinical trials for multi-modality treatment of non-small cell lung cancer stage III?
Authors: M. Schmuecking, C. P. Schneider, J. Soeldner, J. Leonhardi, N. Presselt, M. Scheithauer, R. P. Baum, K. M. Mueller, T. G. Wendt, R. Bonnet
Journal: Journal of Clinical Oncology (2005)

7182 Background: To evaluate the role of F-18 FDG PET within clinical trials for staging, therapy management, molecular radiation treatment planning (MRTP), early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 98 patients with NSCLC are analyzed prospectively in an ongoing multicenter randomized trial (LUCAS-MD). Methods: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. Neoadjuvant treatment for every patient: 2–3 cycles of chemotherapy with paclitaxel/carboplatin and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel/carboplatin) followed by surgery. Randomization: early vs. late chemoradiation. Staging: PET in addition to CT and/or MRI after randomization. Second PET after completion of neoadjuvant therapy. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histological regression grade (RG) and correlation with PET for PT and each LN. Statistical analyses: Wilcoxon-, chi-square-, Mantel-Haenszel-test, Kaplan-Meier-method, multivariate Cox-regression. Results: Upstaging in 8/98 patients due to distant metastases. Downstaging in 2/98. Complete vs. incomplete metabolic remission after 36 months: 79% vs. 30% (p=0,0035). RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 36 months: 77% vs. 25% (p=0,0081). Multivariate Cox-analysis for SUV: p>0,05. Statistical power of the tests: 70% so far. Due to PET findings, the planning target volume for MRTP was reduced substantially in 22%, increased in 10%. Conclusions: Integration of PET in clinical trials enables a more accurate MRTP and therapy management (10% stage migration). Histological regression grade correlates well with metabolic remission as detected by PET. F-18 FDG PET may predict (long term) therapeutic outcome in stage III NSCLC. No significant financial relationships to disclose.