tbuckley/cabot-search huggingface dataset:
An open-label, multi centre, phase II, non-comparative trial of ZD1839 monotherapy in chemotherapy-naive patients with stage IV or stage III non-operable non-small cell lung cancer (NSCLC)
Authors: M. Reck, U. Gatzemeier, E. Bucholz, C. G. Gahlemann, C. Manegold
Journal: Journal of Clinical Oncology (2005)

7098 Background: Second- or third-line gefitinib (IRESSA) monotherapy is active and well tolerated in patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to determine the efficacy and safety of gefitinib as monotherapy in chemotherapy-naïve patients with good performance status (PS). Methods: Chemotherapy-naïve patients who had PS 0–2 with histologically confirmed, non-operable, stage III/IV NSCLC were enrolled. Patients received gefitinib 250 mg/day until disease progression. To ensure that the best available treatment was not withheld for an undue length of time, tumors were assessed by X-ray at weeks 3 and 9, and by computed tomography every 6 weeks following start of treatment. Results: 58 out of 59 patients were evaluable: Histology: Adeno carcinoma (CA) (32); bronchioalveolar CA (10); squamous cell CA (8); large cell CA (4); other (4). Median age: 67 years (range 41–84). Smoking history: current 33%, former 48%, never 19%. PS 0/1/2: 10%;66%,24%. Response: complete response (CR; n=1; 2%), partial response (PR; n=2; 3%), stable disease (SD; n=23; 40%); progressive disease (PD; n=28; 48%). Median progression free survival to date: 52 days. 14 patients are still undergoing treatment. There were no therapy-related serious adverse events. Grade 3 toxicities were rash 1,7%, nausea 1,7%, fatigue 6,9%, cough 3,4%, pain 1,7%. Conclusions: Gefitinib as first-line monotherapy has activity in patients with advanced NSCLC, with clinical benefit (CR+PR+SD) observed in 45% (26/58) of patients. Due to the favorable tolerability profile, gefitinib should be investigated further in controlled, randomized studies in those patients who are unable to tolerate, or who refuse, chemotherapy. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Longitudinal quality of life (QoL) and quality adjusted survival (QAS) in a randomised controlled trial (RCT) comparing bolus (24 weeks) vs. protracted venous infusion (PVI 12 weeks) 5-FU as adjuvant chemotherapy for colorectal cancer (CRC)
Authors: A. R. Norman, I. Chau, T. Iveson, M. Hill, T. Hickish, F. Lofts, D. Jodrell, P. Shellito, J. Oates, D. Cunningham
Journal: Journal of Clinical Oncology (2004)

3625 Background: QoL is infrequently assessed in RCTs of adjuvant therapy for CRC. This analysis aims to assess QoL and QAS in patients receiving adjuvant 5-FU for stage II and III CRC according to treatment arm, age, gender and primary tumour location. Methods: We performed a multicentre RCT in which 801 patients were randomised to 6 months of bolus 5-FU/leucovorin (n=404) or 12 weeks of PVI 5-FU (n=397). QoL was assessed by EORTC QoL core 30 questionnaire before randomisation, during treatment and follow-up to a maximum of 5 years. QAS analysis was performed by integrating the product of the grouped QoL and the survival function. P-values <0.01 were considered significant. Results: Between 1993 and 2003, 9,607 questionnaires were returned. There was significant difference in the deterioration of QoL scores at week 2 with bolus 5-FU compared to PVI 5-FU, coinciding with toxicity peak during the first cycle. Following week 12, global QoL recovered to baseline when PVI 5-FU was stopped but this was delayed with bolus 5-FU until completion at week 24. QoL scores significantly improved in both arms during follow-up (p<0.001) and reached a plateau by year 1. Females and rectal cancer patients had significantly worse baseline QoL scores. QoL improved significantly in patients aged <70 during follow-up whereas patients >= 70 only returned to baseline. The changes from baseline QoL by sex, age and primary tumour locations followed the same general trends as treatment arms. There was no significant differences in QAS between treatment arms, although patients with stage III and performance status 1–2 had significantly worse QAS. Conclusions: 12 weeks of adjuvant PVI 5-FU was associated with significantly better QoL during treatment and faster time to recovery compared to bolus 5-FU. No significant financial relationships to disclose.
Evaluation of pro-angiogenic and pro-coagulant activity of irradiated and non irradiated stored blood used in transfusion practice
Authors: M. Mandel, R. Yeskaraev, A. Achiron, R. Weitzen, T. Livnat, G. Harari, J. Baram, A. Inbal
Journal: Journal of Clinical Oncology (2004)

9710 Background: Side effects of blood transfusion may be associated with infusion of bioactive substances. It has been previously reported that increase in pro-angiogenic and pro-coagulant parameters was observed in plasma of patients transfused with blood and platelet concentrates, respectively. Irradiation of cellular blood components is currently the only acceptable method for prevention of transfusion-associated GVHD. The aim of this study was to evaluate the pro-angiogenic and pro-coagulant potential of stored non-irradiated and irradiated blood. Methods: Ten units of whole blood, 4 of them irradiated at day 7 of storage (2500 rad), were studied. VEGF, thrombin antithrombin complex (TAT), prothrombin fragments 1+2 (F1+2) and endostatin were measured. K and LDH served as parameters of hemolysis. Results: An increase in VEGF was observed with increase in storage time (p by ANOVA = 0.016 and 0.018 for non irradiated and irradiated units, respectively). An increase was more pronounced in irradiated units (p<0.001). No difference in the endostatin level was observed throughout the study (p = 0.259 and 0.326 by ANOVA for non irradiated and irradiated units, respectively). A statistically significant increase in F1+2 and TAT was observed only in stored irradiated units (p= 0.013 for F1+2 and 0.0109 for TAT by ANOVA) with significant difference between the non-irradiated and irradiated units (p = 0.001 for each F1=2 and TAT). Similarly, a significant increase in thrombin generation in irradiated units was observed using a different method (Thromb Haemost 2000; 83:589). An increase in hemolytic parameters was observed in all the units regardless of irradiation (p=0.007 and 0.002 for K in non-irradiated and irradiated units, respectively; p=0.003 and <0.001 for LDH in non-irradiated and irradiated units, respectively). Conclusions: 1. Storage of blood is associated with an increase in pro-angiogenic factor -VEGF with further rise in its levels by irradiation. 2. Storage of irradiated blood is associated with an increase in thrombin generation resulting in potential pro-coagulant activities of the transfused units. No significant financial relationships to disclose.
Minimal arm lymphedema after breast conservation therapy
Authors: V. Bar Ad, A. Cheville, N. Amin, J. Booty, L. J. Solin, E. E. Harris
Journal: Journal of Clinical Oncology (2006)

10527 Background: Arm lymphedema (ALE) is a serious consequence of the treatment for breast carcinoma. The objective of the current retrospective study was to analyze the time-course of minimal ALE after breast conservation treatment for early stage breast cancer. Methods: The study cohort was drawn from consecutive stage I or II patients who underwent breast conservation therapy including axillary staging followed by radiation. During follow up assessments after treatment, measurements of arm circumference were frequently performed at regular intervals, for clinically evident swelling of the arm or for complaints of swelling of the arm. ALE was documented in 274 of 1861 (15%) patients. 109 patients, 6% of overall group, and 40% of the patients with lymphedema, presented with minimal ALE, defined as a difference of 2 cm or less between the affected and unaffected arms. Results: The median age of patients was 54 years. The median interval to develop ALE was 1 year. The median follow up was 11 years. Among all 109 patients with minimal grade ALE at the time of ALE diagnosis, 21%, 13% and 14% of the patients progressed to more severe grades of lymphedema after 1,3 and 5 years of follow-up, respectively (See table). 40% of the patients with minimal grade ALE received therapy for lymphedema. Despite treatment for minimal grade ALE, 37% of treated patients progressed to more severe grades of lymphedema at 1 year follow up, and 24% progressed at 3 and 5 years follow up. Conclusions: Minimal ALE after breast conservation therapy, including axillary staging, developed in 6% of stage I or II breast cancer patients. Minimal ALE has the potential to progress to more severe grade of ALE. Despite treatment for lymphedema for minimal grade ALE, some patients still progressed to more severe grades of lymphedema. [Table: see text] No significant financial relationships to disclose.
Use of lymphoscintigraphic patterns to predict nodal status in SLNB.
Authors: T. Chang
Journal: Journal of Clinical Oncology (2010)

e11067 Background: In approximately 80% of breast cancer patients, the hottest sentinel lymph nodes (SLNs) can be used to predict nodal metastasis. We investigate the reliability of using these nodes to represent true SLN's with different lymphoscintigraphic patterns in breast cancer. Methods: SLN biopsies for T(1-2)N(o) breast cancer were performed on 467 patients. Lymphoscintigraphic patterns were divided into three groups by the number of draining routes using blue dye and radiocolloid and whether the hottest nodes were the first nodes in the channel. Results: The hottest SLNs detected 78 of 87 (90%) cases of SLN metastasis in the 399 patients with successful labeling of both blue dye and radiocolloid in their SLNs. False-negative rates were 0% (single-channel, first node), 58% (multi- channel, first node), and 71% (zero-channel, 0 hottest nodes) (FNR: SingleChanl versus ZeroChanl, P=0.005 and SingleChanl versus MultiChanl, P=0.037; Fisher's exact test). Conclusions: We recommend a preoperative lymphoscintigram to distinguish the subset of breast-cancer patients with a single draining channel and whose hottest node is the first node, in whom hottest nodes can be used to predict SLN metastasis. No significant financial relationships to disclose.
A phase II trial of lapatinib and capecitabine for patients with refractory advanced colorectal adenocarcinoma.
Authors: D. J. Frank, N. K. LoConte, W. Brooks, K. Kim, D. Mulkerin, W. R. Schelman, A. Jumonville, K. D. Holen
Journal: Journal of Clinical Oncology (2010)

e14092 Background: Patients with metastatic colorectal cancer (mCRC) who have progressed after first-line therapy portend a poor prognosis. EGFR inhibitors have been proven effective as second-line therapy and beyond in mCRC. Capecitabine (C) is an approved regimen for the treatment of mCRC and the combination of C and lapatinib (L), a pan-EGFR inhibitor, has been evaluated in 9 phase II studies and a phase III study in women with breast cancer. C+L is effective in breast cancer but has been less effective in other solid tumors. This study was done in part with the Wisconsin Oncology Network (WON). Methods: Eligible patients had progressed on or within six months of prior 5-FU, oxaliplatin or irinotecan based therapy. Prior use of cetuximab or panitumumab was allowed. K-ras mutational analysis was not a part of the protocol. Patients were treated with L 1,250 mg po daily and C 2,000 mg/m2 po divided bid for days 1-14 of 21 day cycle. The primary endpoint was response rate. Secondary endpoints include toxicity, overall survival (OS) and disease-free survival (DFS). A 2-stage Simon Optimal design was used in which 2 or more partial or complete responses were needed in the first 18 patients to enroll an additional 21 patients; accrual was not held to assess for response in the first 18 patients. Results: 29 patients were enrolled, 100% ECOG 0-1, 55% male, 24% rectal cancer, mean age 60.4 years, and mean of 3 prior therapies. Grade 3 toxicities (41%) included diarrhea, infection, small bowel obstruction, mucositis, fatigue, anorexia, hand/foot syndrome and vomiting. There were no grade 4 or 5 toxicities. Median OS was 6.8 months (95% CI 3.5-10.6) and median DFS was 2.1 months (95% CI 2.1-3.5). There were no partial responses, however one patient underwent subsequent metastatectomy. 20 patients had received prior EGFR inhibitors. Conclusions: C + L is not an effective regimen as second line therapy in patients with mCRC. The role of k-ras status in the efficacy of this combination is unknown. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Efficacy of Intraperitoneal and Intravenous Administration of Antitumor Drugs in Rats with Peritoneal Carcinomatosis
Authors: Vladimir Bespalov, Ekaterina Vyshinskaya, Galina Kireeva, Olesya Belyaeva, Alexandr Stukov, Irina Vasilyeva, Alexandr Semenov, Alexey Belyaev
Journal: Annals of Oncology (2014)
Phase II prime/boost vaccination using poxviruses expressing PSA in hormone dependent prostate cancer: Follow-up clinical results from ECOG 7897
Authors: H. L. Kaufman, W. Wang, J. Manola, R. S. Dipaola, Y.-J. Ko, C. J. Sweeney, T. Whiteside, J. Schlom, G. Wilding, L. M. Weiner
Journal: Journal of Clinical Oncology (2005)

4501 We have previously reported the initial results of a Phase II clinical trial evaluating the feasibility of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human PSA in patients with hormone-dependent prostate cancer. 64 eligible patients with biochemical progression after local therapy were randomly assigned to three treatment arms: (A) fowlpox-PSA (rF-PSA) by intramuscular injection every six weeks for four doses, (B) rF-PSA for three doses followed by vaccinia-PSA (rV-PSA) given by intradermal injection, or (C) rV-PSA followed by three rF-PSA vaccines. Vaccination was well tolerated without evidence of autoimmunity. Our initial analysis was conducted at a median follow-up of 19.1 months and demonstrated that 45.3% of men were free of PSA progression and 78.1% were free of clinical progression with a trend favoring arm C. The patients enrolled on this trial have been followed for PSA response and clinical outcome and we now report data with a median follow-up of 50 months. The median time to PSA progression is 9.2 and 9.1 months for arms A and B respectively, compared to 18.2 months for arm C (rV-PSA prime and rF-PSA boost; p=0.15 by Log Rank Test). The median time to clinical progression has still not been reached for any treatment group with 80% of men in arms A and B free of disease progression compared to 90% of men in arm C free of clinical progression (p=0.73 by log rank test). These results suggest that men with hormone-dependent prostate cancer and a rising PSA may derive long-term clinical benefit from vaccinations with poxviruses expressing PSA. A trend in PSA and clinical response favoring patients receiving a prime vaccination with rV-PSA followed by booster immunizations with rF-PSA appears to persist at 50 months median follow-up. Collectively, these results establish the feasibility of a poxvirus vaccine strategy for men with early hormone-dependent prostate cancer recurrences, and support future phase III studies. No significant financial relationships to disclose.
Determinants of functional disability in stage IV breast cancer
Authors: A. L. Cheville, J. Basford, A. Troxel, A. Kornblith
Journal: Journal of Clinical Oncology (2009)

9567 Background: Functional disability degrades cancer patients' quality of life, exhausts caregivers and incurs significant expense yet little is know of the factors that contribute to disablement or whether the impact of these factors differs across functional domains. Better understanding of the influence that symptoms, physical impairments, and disease characteristics exert on disablement is needed in order to develop service delivery models that preserve function. Methods: To identify factors that influence functional performance in community dwelling people with stage IV breast cancer we conducted a cross-sectional study in a tertiary medical center outpatient cancer clinic. A consecutive sample of 163 community-dwelling patients with stage IV breast cancer were administered self- and clinician-rated functional metrics covering multiple domains including overall functioning, mobility, and self care. Self report measures included the Medical Outcomes Study Physical Function Subscale (PF-10) and the Older Americans Resource Study (OARS) Activities of Daily Living (ADL) and Instrumental ADL (IADL) subscales, and clinician report measures included the Karnofsky Performance Scale (KPS) and the Functional Independence Measure (FIM) Total and Mobility scores. Pain and mental health were assessed through administration of the Brief Pain Inventory (BPI) and Mental Health Inventory-17 (MHI-17), respectively. Electronic medical record review provided cancer-related and demographic information. The presence of physical impairments was determined through a comprehensive musculoskeletal and neurological physical examination including the 6 minute walk test. Linear and ordinal logistic regression models were constructed with function metrics as dependent variables. Results: Total number of physical impairments, BPI scores, and the presence of pleural effusions were highly significant in all models (p&lt;0.01). Exertional intolerance and age were associated with PF-10 and OARS-ADL scores (p&lt;0.01), while the presence of a pre-morbid disability was associated compromised mobility. Conclusions: Potentially remediable factors; pain intensity, cumulative impairment burden and pleural effusions, degrade all functional domains in patients with stage IV breast cancer. No significant financial relationships to disclose.
Immune responses to vaccines delivered by encapsulation into and/or adsorption onto cationic lipid-PLGA hybrid nanoparticles
Authors: Lanxia Liu, Pingchuan Ma, Hai Wang, Chao Zhang, Hongfan Sun, Chun Wang, Cunxian Song, Xigang Leng, Deling Kong, Guilei Ma
Journal: Journal of Controlled Release (2016)
The BMJ requires data sharing on request for all trials
Authors: E. Loder, T. Groves
Journal: BMJ (2015)

Background: A robust and stable phylogenetic framework is a fundamental goal of evolutionary biology. As the third largest insect order following by Diptera and Coleoptera in the world, lepidoptera (butterflies and moths) play a central role in almost every terrestrial ecosystem as the indicators of environmental change and serve as important models for biologists exploring questions related to ecology and evolutionary biology. However, for such charismatic insect group, the higher-level phylogenetic relationships among its superfamilies are still poorly unresolved. Results: we increased taxon sampling among Lepidoptera (40 superfamilies and 76 families contained 286 taxa) and filtered the unqualified samples, then acquired a series of large amino-acid datasets from 69,680 to 400,330 for phylogenomic reconstructions. Using these datasets, we explored the effect of different taxon sampling on tree topology by considering a series of systematic errors using ML and BI methods. Moreover, we also tested the effectiveness in topology robustness among the three ML-based models. The results showed that taxon sampling is an important determinant in tree robustness of accurate lepidopteran phylogenetic estimation. Long-branch attraction (LBA) caused by site-wise heterogeneity is a significant source of bias given rise to topologies divergence of ditrysia in phylogenomic reconstruction. Phylogenetic inference showed a most comprehensive framework by far to reveal the relationships among lepidopteran superfamilies, but limited by taxon sampling, it could only represent the current understanding of the lepidopteran tree of life. The relationships within the species-rich and relatively rapid radiation Ditrysia and especially Apoditrysia remain poorly unresolved, which need to increase taxon sampling and adopt lineage-specific genes for further phylogenomic reconstruction. Conclusions: The present study further expands the taxon sampling of lepidopteran phylogeny and provides a potential phylogenomic foundation for further understanding its current higher-level relationships.
PWE-067 Recessively inherited non-polyposis colorectal cancer: genotype and phenotype
Authors: K J Monahan, K Pack, C Cummings, H J W Thomas, I P M Tomlinson
Journal: Gut (2010)

<h3>Introduction</h3> Patients diagnosed before 50 years of age have a likely strong genetic or environmental aetiological factor. There is good evidence from population studies1 that recessive inheritance is common in young colorectal cancer patients. <h3>Methods</h3> A cohort of 133 colorectal cancer patients without multiple polyps or a family history of dominant inheritance were diagnosed under the age of 50 years. They were identified and recruited from the Bobby Moore database in the Family Cancer Clinic, St Mark9s Hospital, Harrow. MYH was screened for germline mutations. As these patients fulfilled Bethesda criteria they were tested for hereditary non-polyposis colorectal cancer (HNPCC) by microsatellite instability analysis and immunohistochemistry of mismatch repair proteins. Immunohistochemistry was also performed on β-catenin and P53. Loss of heterozygosity of the APC locus at 5q21–22 was tested using a set of microsatellite markers. Sequencing was used to identify somatic mutations in KRAS and BRAF. <h3>Results</h3> Forty-four patients (33%) had cancers proximal to the splenic flexure, 79 (59%) distal and had 11 (8%) synchronous colorectal cancers. Thirty-seven patients (28%) had an affected sibling and 33 (25%) patients had a second-degree relative with cancer at any site. The median age of diagnosis of colorectal cancer was 39 years (range 14–49 years of age). Twenty-six patients (20%) were found to harbour sequence variation in the MYH gene but none of these variants were likely to be pathogenic, and there was no difference in the frequency of these compared to a control group of 50 patients. Eighty percent of tumours were found to be microsatellite stable. 20/30 cancers had nuclear localisation of β-catenin and 21/30 had nuclear localisation of P53 antibodies on immunohistochemistry. Loss of heterozygosity of the APC locus at 5q21–22 was present in 14/30 cases. Thus Wnt pathway activation is likely by over half of this group of cancers. Four cancers had BRAF V600E mutations and five had KRAS codon 12 or 13 mutations. <h3>Conclusion</h3> In a cohort of 133 young colorectal cancer patients without multiple polyps, most tumours demonstrated Wnt pathway activation and other somatic changes consistent with the classical adenoma-to-carcinoma sequence. Germline mutations in the colorectal neoplasia predisposition gene MYH appear to be rare events in such patients. The majority of recessive inheritance in young patients is probably caused by mutations in unknown predisposition genes.