tbuckley/cabot-search huggingface dataset:
Interim data for ACT III: Phase II trial of PF-04948568 (CDX-110) in combination with temozolomide (TMZ) in patients (pts) with glioblastoma (GBM).
Authors: R. Lai, L. D. Recht, D. A. Reardon, N. Paleologos, M. D. Groves, M. R. Rosenfeld, S. Meech, T. A. Davis, D. Pavlov, J. H. Sampson
Journal: Journal of Clinical Oncology (2010)

2014 Background: EGFRvIII is a constitutively activated mutation of EGFR, not expressed in normal tissues but expressed in GBM and other neoplasms. PF-04948568, a vaccine consisting of 13 amino acids unique to EGFRvIII, conjugated to keyhole limpet hemocyanin (KLH), has been coadministered intradermally with GM-CSF for the treatment of GBM. An initial single-arm phase II study conducted at Duke University and MDACC demonstrated tolerability and encouraging clinical activity. Subsequently a U.S., multicenter, randomized, open-label phase IIb/III study (ACT III) was initiated. Methods: Pts with gross total resection of newly diagnosed, EGFRvIII+ve GBM and successful completion of standard RT with concurrent TMZ, were eligible for enrollment. PF-04948568 was administered every other week x 3 prior to starting maintenance TMZ and monthly thereafter on day 21 of each TMZ cycle, until disease progression. Primary endpoint was progression-free rate (PFR) at 5.5 months from first vaccination. Results: 81 pts were enrolled (65 receiving PF-04948568). The trial was amended to a single arm design when 14/16 pts randomized to the control arm (standard of care alone) declined further participation after notification of treatment assignment. Interim efficacy data on the first 40 pts treated with PF-04948568 are reported. 28/40 pts were alive and progression free at 5.5 months (PFR [95% CI] = 70% [53.5;83.4]). Local injection site reactions were the most common treatment-related AE's and were reported in the majority of patients. Reversible hypersensitivity reactions (all grades) occurred in 5% of pts with one reaction being reported as serious and requiring discontinuation of PF-04948568. Conclusions: Vaccination with PF-04948568 was well tolerated in combination with maintenance TMZ in pts with newly diagnosed, fully resected GBM. PFR of 70% at 5.5 months reported from this multicenter experience is similar to that reported from the previous Duke/MDACC trial. Difficulties retaining control arm pts in this open label US trial, suggest that additional study of the vaccine would require a placebo controlled trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celldex Therapeutics, Pfizer Celldex Therapeutics, Pfizer Celldex Therapeutics Celldex Therapeutics, Pfizer
Audit of child protection procedures in an A&amp;E department
Authors: P O Brennan, M J Bannon, Y H Carter, J E Porter
Journal: BMJ (1998)

Editor—Sidebotham and Pearce’s audit of child protection procedures in an accident and emergency department should raise general awareness that children in any such departments need special consideration.1 It should also raise specific awareness that non-accidental injury often presents to accident and emergency departments. 

It is interesting that the nurses seem to have been given the job of scoring the risk factors for abuse in this study and that the doctors were given the job of auditing nurse practice. All accident and emergency staff should be informed and aware of the possibility of non-accidental injury, although the checking system would be carried out more efficiently if it was the responsibility of one clearly identified individual, in this case the initial assessment nurse. 

The accident and emergency department at Sheffield Children’s Hospital has a system of amalgamating a child’s notes so that every previous attendance to the department can be checked at each new attendance. In accident and emergency one does not have the benefit that general practitioners have of having known the child and family over a period. Every clue to the child’s health and lifestyle is needed to put the current attendance in context. 

There has long been an alerting system not only for children officially on the child protection register but also for families who have caused concern to other health professionals such as paediatricians, health visitors, and general practitioners. Family problems such as alcoholism and substance abuse have an impact on children and their care. With the modern practice of working with parents and registering as few children as possible for as short a time as possible, there are many children and families who need extra assessment, care, and support when children are not officially registered. 

I believe that there are even broader and more subtle considerations when trying to define a child at risk. The paediatric influence in accident and emergency departments would be best served by increasing the number of accident and emergency consultants with a special interest in paediatrics or at least by having a paediatrician linked closely to each department.
Enrollment of lung cancer patients on clinical trials at an NCI comprehensive cancer center
Authors: V. L. Keedy, L. Horn, A. Hayes, B. Spencer, G. Garcia, N. Campbell, A. Sandler, D. Carbone, D. H. Johnson
Journal: Journal of Clinical Oncology (2009)

6633 Background: Enrollment of cancer patients (pt) in clinical trials is considered essential in order to improve cancer care. However, cancer clinical trials participation remains low. Understanding barriers to pt enrollment is necessary to overcome this problem. Previous reports have identified pt age, race, and ethnicity, disease stage, performance status (PS) and relationship with their health care provider as factors that can influence the enrollment of pts in clinical trials. Methods: We conducted a retrospective review of the charts of all lung cancer pts seen in the Thoracic Oncology Clinic at Vanderbilt Ingram Cancer Center between November 2005 and November 2008. A total of 1075 lung cancer pts were seen. Results: 577 charts (of a planned 1075) have been audited to date. Pt demographics: median age = 64 yrs; male = 54%; Caucasian = 92%, African American = 4%, and Asian = 1%; NSCLC = 80%, SCLC = 17%. Male pts were more likely than females to be eligible for a clinical trial (p = 0.056). A study protocol was available for 57% of pts; 52% of pts proved eligible; 36% were entered into a study (11% total population). Significantly more protocols were available for NSCLC pts compared to pts with SCLC (p ≤ 0.001); there was also a non-significant trend towards higher enrollment of eligible NSCLC pts. There was no difference in eligibility between ethnicity; the percentage of eligible pts enrolling on trials was similar between Caucasian &amp; African American pts (46% and 43%); no Asian pts were enrolled. The most common reasons for not enrolling included a preference for treatment closer to home (29%), patient refusal (19%), PS (19%), and co-morbidities (17%). The distance pts traveled was inversely correlated with likelihood of study participation. Conclusions: A total of 11% of lung cancer pt evaluated in our Thoracic Oncology Clinic were enrolled in clinical trials. Our data suggest additional strategies are needed to attract minority groups, increase enrollment of women and pts with comorbidities and poor PS. Travel distances influence pt willingness to participate in clinical trials. Strategies are needed to overcome this factor. No significant financial relationships to disclose.
Determining incidence and predictors of deep vein thrombosis in patients with non-small cell lung cancer
Authors: D. Levi, V. Tagalakis, V. Cohen, J. Agulnik, G. Kasymjanova, D. Small
Journal: Journal of Clinical Oncology (2006)

7159 Background: The risk of deep vein thrombosis (DVT) among patients with non-small cell lung cancer (NSCLC) has not been well studied. We conducted a retrospective cohort study of patients with NSCLC to determine the incidence of DVT and characterize predictors of DVT in NSCLC patients. Methods: The pulmonary oncology database of the SMBD-Jewish General Hospital contains prospectively collected clinical data on all lung cancer patients followed in the pulmonary oncology clinic since January 1, 1997. We identified all consecutive patients with a histologically confirmed new diagnosis of NSCLC between January 1, 1997 and December 31, 2004 and determined the occurrence of an objectively defined DVT. Data on age, gender, NSCLC type and stage, Eastern Cooperative Oncology Group (ECOG) performance status, exposure to surgery and chemotherapy, and death was collected and compared among patients with DVT and patients without DVT. Results: Of the 493 NSCLC patients included in the cohort for a total of 634 person-years, 67 (13.6%) patients developed an objectively confirmed DVT. We calculated an incidence rate of 110 cases (95% confidence interval (CI) 80, 130) per 1000 person-years. Risk factors associated with occurrence of DVT were advanced stage (p = 0.0006) and male sex (p = 0.04). A multivariable regression analysis adjusted for recent surgery and performance status showed that advanced stage (Rate ratio 2.55, 95% CI 1.33–4.89) and male sex (Rate ratio 1.75, 95% CI 1.03–2.94) were independent predictors of DVT. Age, type of NSCLC, and chemotherapy did not predict DVT. The risk of dying was 1.7-fold increased (Hazard Ratio 1.73, 95% CI 1.29–2.32, adjusted for age, sex, stage, surgery, performance status, and date of lung cancer diagnosis) among patients with DVT compared to patients without DVT. Conclusions: Our results show a high incidence of DVT in NSCLC patients and that advanced stage and male sex are important predictors of DVT. Moreover, NSCLC patients with DVT have a 1.7 fold increased risk of dying than patients without DVT. Confirmation of our results by prospective studies may provide the necessary evidence for targeted use of prophylactic anticoagulants in NSCLC patients to prevent development of DVT and improve related survival. No significant financial relationships to disclose.
Do all patients with HER2-positive gastric/GEJ cancer benefit from trastuzumab?
Authors: Jun Ho Yi, Jung Hun Kang, In Gyu Hwang, Hee Kyung Ahn, Soonil Lee, Do Hyoung Lim, Young-Woong Won, Jun Ho Ji, Hyo Song Kim, Sun Young Rha, Sung Yong Oh, Kyung Eun Lee, Taekyu Lim, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Se Hoon Park
Journal: Journal of Clinical Oncology (2015)

185 Background: Trastuzumab-based chemotherapy became the standard option for patients with HER2 (+) metastatic gastric cancer after ToGA study. However, the OS benefit was not found in Asian and diffuse-type cancer patients. The aim of the current study is to analyze whether Asian ethnicity or poorly differentiated histology (PDH) affects the clinical outcomes of patients who were treated with trastuzumab-based chemotherapy. Methods: We collected the medical records of the patients with HER2 (+) (IHC3+ or IHC2+&amp;FISH+) gastric/GEJ cancer who were treated with trastuzumab-based chemotherapy. The ORR, PFS, and OS were compared according to the patients’ clinicopathologic features and data from ToGA trial. Results: From March 2012 to June 2014, data of 163 Asian patients from 11 institutes in South Korea were collected. The median age was 60 (range 27-85) and the male:female ratio was 116 (71.2%):47 (28.8%). 157 (96.3%) had stomach cancer and 6 (3.7%) had GEJ cancer. Fourteen (8.6%), 62 (38.0%), 71 (43.6%) and 11 (6.7%) patients had well, moderately, poorly differentiated tubular adenocarcinoma (TAC) and signet ring cell carcinoma (SRC), respectively. The ORR was 52.7% (86/163) which is similar to that of the ToGA trial. (47%) The median PFS was 9.8 months (95% CI 8.6 – 11.0 and the median OS was 18.5 months. (95% CI 16.5 – 20.5) These numerical data are slightly better than those of the ToGA trial. (PFS, 6.7 months; OS, 16.0 months) Next, we investigated if PDH (poorly differentiated TAC + SRC) affected on clinical outcomes. The ORR (50.0% vs. 56.6%, p = 0.408) and the PFS (8.8 months vs. 11.2 months, p = 0.109) were slightly inferior in PDH patients but still, they were better than that of the ToGA trial. The median OS was significantly shorter for PDH patients (14.1 months vs. 19.0 months, p = 0.046). Conclusions: While subset analysis of ToGA trial has demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asian ethnicity and poorly differentiated histology, our real world data suggested that even in Asian and patients with PDH, trastuzumab-based chemotherapy is associated with improved clinical outcomes in patients with HER2 (+) gastric cancer.
Retreatment with trastuzumab after progression on lapatinib-based therapy in heavily pretreated HER2-positive metastatic breast cancer: A monoinstitutional experience.
Authors: S. Spazzapan, D. Crivellari, S. Tumolo V, A. Russo
Journal: Journal of Clinical Oncology (2010)

1082 Background: Continuing trastuzumab (T) in association with a different cytotoxic agent (CA) is a common practice in metastatic breast cancer (MBC) showing progression on T plus chemotherapy. Lapatinib plus Capecitabine (L-X) is another option in that setting. Little data is available about the efficacy of retreatment with T after L. Preclinical data(Scaltriti et al, 2009) suggest the possibility of a further response to T after L. Methods: From April 2007 to March 2009, we treated 58 HER2-positive MBC patients (pts) who had developed progression after antracycline, taxane, and T-based regimens with L-X as part of an expanded access program and thereafter with commercial drug. Of these 58 pts, 21 were retreated, at progression on L-X, with T combined with a different CA (mostly gemcitabine). The outcome of these 21 pts was retrospectively evaluated. Results: The median number of treatment lines, including the adjuvant setting, was 5 (ranging from 2 to 8). The median duration of previous T treatment (given alone or with chemotherapy) was 16 months (range, 6-57 months). T was generally combined with a CA not previously used, mostly gemcitabine (12 pts, 57 %) and vinorelbine (6 pts, 28%). Other drugs were used in 3 pts (14%). The median time to progression after first line T plus CA was 12 months, after L-X it was 7.5 months and after retreatment with T it was 4.5 months. No severe toxicities occurred. Clinical benefit (CB) (defined as complete remission plus partial remission plus stable disease lasting for at least 6 months) with T retreatment was noted in 10 pts (48%). 2 pts are still on treatment. Conclusions: This is a favorably selected population of HER2-positive pts responding to sequential targeted therapies. However, the previous chemotherapy treatment was very substantial. Our data suggest that T can be used in association with a different CA after T and L-X without significant toxicity and still with an encouraging CB rate. These data may be supportive of the Scaltriti hypothesis. No significant financial relationships to disclose.
Dasatinib or high-dose imatinib for patients with chronic myelogenous leukemia chronic-phase (CML-CP) resistant to standard- dose imatinib: 2-year follow-up data from START-R
Authors: P. H. Rousselot, T. Facon, R. Paquette, E. Bleickardt, D. Dejardin, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2008)

7012 Background: Resistance to imatinib is a well-recognized problem in CML-CP. Dasatinib is 325-fold more potent than imatinib against BCR-ABL in vitro is effective in imatinib-resistant CML patients. Prior to dasatinib, imatinib dose escalation to 800 mg/day was the primary option for resistance to standard-dose imatinib. Methods: In this global Phase II study, 150 patients (pts) with CML-CP resistant to imatinib 400–600 mg/d were randomized 2:1 to dasatinib 70 mg BID (n=101) or imatinib 800 mg/d (n=49). The primary endpoint of the study was major cytogenetic response (MCyR) at 12 wks. Crossover was permitted for confirmed progression, lack of MCyR at 12 wks, or intolerance despite dose reduction. MCyR rates at 12 weeks were 36% vs 29%; p=0.4025. Two-year follow-up is now presented. Results: With a minimum follow-up (LPFV to database closure) of 24 mos, MCyR rates were (53% vs 33%, p=0.017) for pts receiving dasatinib and high-dose imatinib, respectively; the difference being attributable to complete cytogenetic responses (44% dasatinib vs 18% imatinib, p=0.0025). Major molecular responses (MMR) were also more frequent with dasatinib (29% vs 12%, p=0.028). Duration of MCyR was greater with dasatinib; 90% of dasatinib pts maintained MCyR at 18 mos vs 74% of imatinib pts. Analysis of progression-free survival at 24 mos favored dasatinib (86% vs 65%, p=0.0012); results were consistent irrespective of the prior imatinib dose received (400 mg/d, p=0.0562; 600 mg/d, p=0.0033). Time to treatment failure also favored dasatinib (proportion of pts without failure at 24 mos: 59% vs 18% p<0.0001). Grade 3–4 non-hematologic toxicity was minimal for both treatment groups. Grade 3–4 cytopenia was more frequent with dasatinib. Discontinuation attributable to toxicity occurred in 22% of pts receiving dasatinib and 20% treated with imatinib. Conclusions: With an extended follow-up of 24 mos, the overall benefit-risk assessment favors dasatinib over high-dose imatinib in CML-CP pts with resistance to 400–600 mg imatinib. The current labelled dose of 100 mg QD was approved based on a subsequent Phase III dose optimization study which showed comparable efficacy with improved tolerability compared with 70 mg BID. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb, Novartis
Testosterone kinetics in the first cycle of intermittent androgen deprivation (IAD) for men with localized or biochemical relapse (BR) of prostate cancer (PC)
Authors: R. Gulati, E. Y. Yu, D. Telesca, P. Jiang, R. B. Montgomery, S. Tam, K. J. Russell, P. S. Nelson, R. B. Etzioni, C. S. Higano
Journal: Journal of Clinical Oncology (2008)

5134 Background: Patients (pts) with localized PC or BR treated with androgen deprivation therapy (ADT) eventually become androgen independent (AI) and die. We previously defined a model that correlates first cycle IAD PSA nadir and duration off treatment (OFF) with time to AI and death in 53 pts (abstract 5146 ASCO ’07). We now report data on a larger number of evaluable pts and include the analysis of testosterone (T) kinetics. Methods: Eligible pts had histologic diagnosis of PC, no evidence of metastasis by bone and CT scan, and at least 2 consecutive rising PSAs 2 weeks apart. Pts were treated with 9 months of leuprolide acetate and anti-androgen then ADT was stopped. Monthly PSA and T levels were tracked until PSA reached 1 ng/mL if prostate removed or 4 ng/mL if prostate intact, at which time ADT was resumed as before in a new cycle. Pts were treated until AI, defined as 2 rises in PSA while on ADT with castrate T levels (< 0.5 ng/mL). Results: 74 of 102 pts were evaluable for analysis. The previously reported model associating first cycle PSA nadir and duration OFF values with time to AI and death was confirmed with this larger sample size. Low risk patients (PSA nadir < 0.1 ng/mL and OFF duration > 40 weeks) significantly differed from high risk patients (PSA nadir > 0.1 ng/mL and/or duration OFF < 40 weeks) in terms of time to progression to AI (p=0.0006) and death (p=0.003). Higher baseline T (n=40, of whom 14 became AI and 12 died) was associated with shorter duration OFF (p<0.02) but not with time to AI (p=0.72) or death (p=0.52). First on treatment T nadir (n=40) was not associated with time to AI or death. Higher T at end of first OFF relative to baseline T (n=39) was associated with longer time to AI (p=0.04) and death (p=0.04). Conclusions: PSA nadir and duration OFF define PC patients at low and high risk for progression to AI and death while on IAD. While there is theoretical concern that pts who have suboptimal T nadir may be at higher risk to develop AI, this was not observed in this series. The biological explanation for why a higher ratio of T at end of first OFF to T at baseline is associated with longer time to AI and death is not clear. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Improvement of patency rate in heparin-coated small synthetic vascular grafts. Commentary
Authors: B. H. Walpoth, R. Rogulenko, E. Tikhvinskaia, S. Gogolewski, T. Schaffner, O. M. Hess, U. Althaus, H. L. Lazar
Journal: Circulation (1998)

Background-Graft thrombosis and intimal hyperplasia represent the major causes of graft failure. Heparin has been shown to have a beneficial effect on long-term patency and on prevention of intimal hyperplasia. Thus, the purpose of the present study was to evaluate the effect of heparin coating on patency rate and intimal hyperplasia in small synthetic vascular grafts. Methods and Results-Two synthetic grafts (expanded polytetrafluoroethylene [ePTFE], and polyurethane) with and without heparin coating were implanted in the infrarenal aorta (diameter, 2 mm) of 40 Whistar rats. Animals survived 8 weeks after implantation. Graft patency, intimal thickness, and percentage of diameter stenosis were determined by light microscopy at the proximal respectively distal anastomosis and in the middle of the graft. Uncoated grafts showed a patency rate of 70% for ePTFE and 60% for polyurethane grafts. Heparin-coated grafts showed a patency rate of 100% for ePTFE and 90% for polyurethane grafts. Intimal hyperplasia was observed in all grafts mainly at the anastomosis site. Intimal wall thickness and percentage of stenosis were significantly more pronounced in the polyurethane than ePTFE grafts (P<0.01). Heparin coating significantly reduced overall graft thrombosis (P<0.05) but had no significant effect on intimal hyperplasia. Conclusions-Small grafts show a high rate of graft thrombosis and an enhanced intimal hyperplasia, ePTFE grafts show significantly less intimal hyperplasia and percentage of stenosis than polyurethane grafts. Heparin coating significantly reduced graft thrombosis but had no significant effect on intimal hyperplasia. Thus, heparin coating seems to be beneficial for graft patency, and ePTFE appears to be superior to polyurethane as graft material.
Dissimilar Respiratory and Hemodynamic Responses In TRALI Induced by Stored Red Cells and Whole Blood Platelets.
Authors: John-Paul Tung, John F Fraser, Maria Nataatmadja, Adrian G Barnett, Kathryn I Colebourne, Kristen M Glenister, Anna Y Zhou, Peter Wood, Christopher C Silliman, Yoke Lin Fung
Journal: Blood (2010)