tbuckley/cabot-search huggingface dataset:
Perioperative bevacizumab (Bev) containing chemotherapy for colorectal liver metastases
Authors: N. Bouganim, C. Ang, P. Kavan, P. Metrakos, W. H. Miller, G. Batist
Journal: Journal of Clinical Oncology (2008)

15073 Background: Colorectal liver metastases are potentially curable if treated aggressively. Liver resection with perioperative oxaliplatin based chemotherapy is effective. Adding Bev improves survival in metastatic colorectal cancer. The goals were to determine safety and efficacy of perioperative Bev and its impact on survival. Methods: In this single arm feasibility study, all patients (pts) with resectable liver disease eligible to receive Bev and chemotherapy were reviewed. Results: Thirty-one pts identified: 23 male, median age 56 years, ECOG < 2. Twenty-nine with synchronous liver metastases and 2 with late recurrent disease. All pts underwent perioperative Bev containing chemotherapy (Oxaliplatin based 24/31, CPT-11 7/31) and hepatectomy. Twenty-four received preoperative chemotherapy; all had postoperative chemotherapy. Median treatment duration pre and postoperatively was 3 and 6 months. Bev was discontinued 6 weeks before and restarted 8 weeks after surgery. Seven pts underwent staged liver resection. Overall response rate was 70% (22/31): 35% partial and 35% complete response, with a median follow up of 25months. No pts progressed prior to surgery. Overall survival rates at 12, 24, 36 and 48 months were: 100%, 89%, 80% and 77% respectively and 5 year median survival of 55%. Three pts relapsed 4, 5 and 12 months post treatment; 2 pts died (sepsis, disease progression). Grade 3/4 Bev related complications were seen in 4 pts (epistaxis, anaphylactic reaction, and hypertension), no postoperative complications. Conclusions: Bev containing chemotherapy and hepatectomy is well tolerated and effective in patients with colorectal liver metastases. Our 70% response rate is one of the highest reported, with only 3 pts progressing. Perioperative Bev containing chemotherapy seems to be justifiable in selected patients and warrants further investigation in phase III trials. No significant financial relationships to disclose.
Modulation of the Peritumoral Microenvironment by Cetuximab: A Window Pre-Operative Study in Patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Authors: S. Schmitz, M. Hamoir, H. Reychler, M. Magremanne, B. Weynand, R. Lhommel, F. Hanin, D. Rommel, N. Michoux, J.P. Machiels
Journal: Annals of Oncology (2012)
PTH-194 Palliative home parenteral nutrition (HPN) – tertiary gi oncology centre audit of practice
Authors: AS Charlesworth, J LeCouteur, S Newall, R White, S O’Sullivan, K Tocher, C Ferreira, M McCarthy, JM Dunn
Journal: Gut (2015)

<h3>Introduction</h3> The European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines state that “in intestinal failure (IF), long term PN should be offered if enteral nutrition is insufficient, expected survival due to tumour progression is longer than 2–3 months, it is expected that HPN can stabilise or improve performance status and quality of life and the patient desires this mode of nutrition support”. This study aims to review current practice in the prescribing patterns of palliative HPN, following publication of the guidelines. <h3>Method</h3> Retrospective casenote review of patients with cancer set up on HPN, between May 2011 and February 2015. GSTT is a tertiary GI oncology and regional IF centre. <h3>Results</h3> There were 12 patients (10 male, 2 female) set up on HPN, and one on Home IV fluids, within the 45 months period. One patient died awaiting HPN but had received PN at his local hospital prior to transfer. The majority of patients had primary GI cancer (12/13). The median age was 51 years (range 26–70 years). The total length of HPN was 1323 days, with a catheter related blood stream infection rate of 0.8/1000 catheter days. The median length on HPN was 86 days (range 1–310 days). Mortality is 62%, with a median of 37 days HPN (range 0–111 days). Chemotherapy was administered concurrently with HPN in 62%. There has been an increase in patient numbers, with 4 started in the first 3 years, and a further 9 patients set up over the last 9 months. This indicates a growing awareness and utilisation of palliative TPN. <h3>Conclusion</h3> The overall median length of HPN was 86 days, in keeping with the ESPEN guidelines of expected survival of longer than 60 days. We appear to be using HPN appropriately and are improving patient selection. There is anticipated increasing demand for HPN in the palliative setting, necessitating appropriate resource allocation regionally. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Bozetti F, Arends J, Micklewright A, <i>et al</i>. ESPEN guidelines on parenteral nutrition: non-surgical oncology. Clin Nutr. 2009;28:445–454
Classification of renal cell carcinoma (RCC) based on the expression of VEGF and its receptors on tumor cells and microvessels: Identification of subsets with distinct patterns of expression, microvessel density, and outcome
Authors: R. L. Camp, S. F. Siddiqui, W. K. Kelly, E. Uchio, H. M. Kluger
Journal: Journal of Clinical Oncology (2007)

15503 Background: The recent development of anti-angiogenic therapy for RCC has significantly improved the treatment of these often refractory tumors. However not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-Rs) to classify tumors. Methods: Tissue microarray analysis of 330 RCC (clear cell = 234, papillary = 46) was performed using a novel method of Automated Quantitative Analysis (AQUA) of VEGF and VEGF-Rs (R1, R2 &amp; R3) expression by fluorescent immunohistochemistry. The expression of VEGF and VEGF-Rs were separately quantitated within tumor cells, endothelial cells, and adjacent normal epithelium. Expression was recorded on a continuous scale and represents the average of two histocores. Results: VEGF and VEGF-Rs exhibited distinct expression patterns on tumor cells, tumor endothelium, and adjacent normal tissue. Within each component, expression of VEGF and its receptors was tightly correlated (all p-values &lt; 0.001). Although tumor cell expression of VEGF did not correlate with microvessel density (p- value = 0.1848), tumor cell expression of R1 and R2 were strongly and inversely correlated with microvessel density [p-values &lt;0.0001]. Unsupervised hierarchical clustering classified tumors according to the coordinated expression of VEGF and VEGF-Rs within the three tissue components - tumor (T), normal (N), and vessel (V). Tumors were classified into 5 clusters: 1) high T, N &amp; V; 2) low T, high N &amp; V; 3) high T, low N &amp; V; 4) low T, N &amp; V; and 5) high T &amp; N for R3 only. Of these, clusters 1 and 3 exhibited poor survival, whereas clusters 2 and 4 contained tumors with high vessel densities. The distribution of clear cell and papillary tumors was not significantly different between clusters. Conclusions: VEGF and its receptors exhibit a complex pattern of coordinated expression in RCC. Clustering of tumors based on VEGF and VEGF-R in tissue components may provide a prognostic assay as well as a means for determining which tumors will respond to what anti-angiogenic therapies. No significant financial relationships to disclose.
Pre-conceptions about cancer chemotherapy in non-cancer patients
Authors: S. B. Fleishman, L. B. Goldman
Journal: Journal of Clinical Oncology (2004)

6134 Background: When someone is advised that they have cancer and will need to undergo chemotherapy, their opinion about the effectiveness of chemotherapy and its side effects may have already been formed through information emanating from various external sources: personal experience or media information Methods: A questionnaire was distributed to non-cancer patients in the setting of a private practice physician office. Age, gender, religion, level of education and employment of respondents was determined. Most importantly, respondents were asked: AIf you had cancer and were told by your doctor that you needed chemotherapy, would you take it?“. Other questions sought to identify the sources of opinion or knowledge about chemotherapy from the media. The survey was offered to patients 18 years and older and completion was voluntary. Results: 181 responses were evaluated. In response to the question about agreeing to chemotherapy, 59.7% answered yes and 36.5% answered no. Differences in education, personal knowledge, source of influence, and opinions about chemotherapy were stratified between the yes and no respondents. There was no significant difference in the level of education between the groups. Movies, magazines, newspapers and the internet proved to have the greatest influence. Respondents who chose not to take chemotherapy generally listed fewer sources of outside influence than those who would undergo treatment. Of those who responded that they would choose to have chemotherapy, 77.8% knew someone personally who had cancer and 72.2% knew someone who had undergone chemotherapy. Of those who responded that they would not take chemotherapy, 51.1% of respondents knew someone who had cancer and 51% knew someone who had chemotherapy. Conclusions: Patients would choose to have chemotherapy more frequently based the decision on direct contact with someone who had cancer or chemotherapy than media information. Ultimately, an informed decision to take chemotherapy could be positively influenced by introducing newly diagnosed patients to veteran patients who have undergone similar treatment. No significant financial relationships to disclose.
Phase I/II trial of association of sorafenib in combination with temozolomide in patients with metastatic melanoma: Looking for predictive markers of efficacy.
Authors: C. Robert, N. Chaput, N. Lassau, A. Auperin, S. Koscielny, E. Hollville, V. Lazar, L. Lacroix, J. Soria, C. Mateus
Journal: Journal of Clinical Oncology (2010)

8552 Background: The poor activity of treatments (tt) against metastatic melanoma (MM) mainly relies in the absence of predictive markers of efficacy that could allow selection of responsive pts. This phase I/II clinical trial of sorafenib (S) + temozolomide (T) was done with an intense translational research program in order to evaluate both safety and efficacy and to identify early markers of treatment benefit. Methods: 63 pts with MM were included in the dose-escalating phase I (n = 15) and the phase II (n = 48). Sequential blood and tumor samples were harvested to study baseline parameters and intra-individual variations of biomarkers during the treatment. Tumor sequencing of 44 exons in 12 genes were done in 37 pts. CGH arrays, RNA expression profiling, immunostaining (P-ERK, P-MEK and Ki67) were performed at d0 and 21. Functional imaging using dynamic contrast enhanced ultrasonography (DCE-US) was performed at days 0, 7, 15, and every month. Results: 54 pts weretreated at the MTD: 400 mg of S bid and 150 mg/m2 of T every other week. Half of them had received ≥ 2 lines of prior chemotherapies and 37% had high LDH. Median number of cycles was 4 (1-22). Toxicity was manageable and required tt interruption for only 3 pts. On 49 evaluable pts, 4 had PR (8%), 19 SD (39%) and 26 PD (53%) for a treatment benefit in 47%. Six months PFS and overall survival rates were respectively 15.2% and 60.6%. DCE-US functional imaging parameters before treatment, at day 7 or day 15 were significantly associated with tt efficacy (OR or SD vs. PD) at 2, 4 or 6 months (p < 0.05). NKG2D ligand, soluble MICA, was found in 80% of pts with PR or SD vs. 3% of PD pts and was also significantly associated with clinical benefit (p < 0.05). On 37 tumors tested, mutations were found in BRAF (62%), STK11 (25%), NRAS (8%), TP53 (6%) CDKN2A (3%), CTNNB1 (3%) without correlation to clinical response. CGH array and RNA expression profiling results are pending. Conclusions: This study confirms the safety and efficacy of the association of S and T in pts with MM. Translational research identified early markers associated with treatment benefit that could allow selection of patients for more personalized and efficient treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Role of ADCC in the in vivo antitumor effects of zalutumumab, a human anti-EGF receptor antibody.
Authors: M. Overdijk, S. Verploegen, J. Van den Brakel, J. Lammerts van Bueren, G. Rigter, T. Vink, J. Van de Winkel, P. Parren, W. Bleeker
Journal: Journal of Clinical Oncology (2010)

e13102 Background: Zalutumumab (HuMax-EGFr, clone-2F8), a fully human IgG1 EGFR antibody, currently in phase III clinical trials, was previously demonstrated to have a dual mechanism of action. First, it blocks EGFR signaling by preventing ligand binding and inducing receptor downmodulation. This mechanism was found to be effective in established xenograft tumors at doses giving full receptor occupancy. Second, we observed in vitro induction of antibody-dependent cell-mediated cytotoxicity (ADCC), which was found to be already maximally active at very low, sub-saturating antibody concentrations. Because the contribution of ADCC to the antitumor effects of therapeutic cancer antibodies in solid tumors remains unclear we studied the importance of ADCC induction by zalutumumab in xenograft models. Methods: We prepared human EGFR antibodies with different functionalities for comparison with zalutumumab to: 1) clone 2F8-N297Q a mutant of zalutumumab, which has a nonfunctional Fc part regarding interaction with Fc receptors, 2) clone-018, a non-blocking human EGFR mAb, for which we observed ADCC in vitro as only mechanism of action and 3) clone-018-N297Q which displayed no in vitro activity. Results: Therapeutic treatment of established A431 tumor xenografts with these antibodies showed efficacy for zalutumumab and clone 2F8-N297Q only, indicating that blocking of signaling is crucial in this condition. In contrast, when given on the day of tumor induction, both zalutumumab and clone-018, but not clone-018-N297Q, were effective in preventing A431 tumor xenografts. In an experimental xenograft model, zalutumumab and clone 018 could completely prevent outgrowth of lung metastases, even when given at a low, nonsaturating dosing. Conclusions: Our experiments indicate that blocking of EGFR signaling is required for effectiveness of zalutumumab in established tumors, requiring doses giving full receptor occupancy. We conclude that induction of ADCC represents an additional, independent mechanism, which seems insufficient for reducing primary solid tumors, but is likely to have an important contribution in preventing metastases. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab Genmab Genmab
WARP - A multicentre prospective randomised controlled trial (RCT) of thrombosis prophylaxis with warfarin in cancer patients with central venous catheters (CVCs)
Authors: A. M. Young, G. Begum, L. J. Billingham, A. I. Hughes, D. J. Kerr, D. Rea, A. Stanley, A. Sweeney, K. Wheatley, J. Wilde
Journal: Journal of Clinical Oncology (2005)

LBA8004 Background: CVC-related thrombosis is a significant cause of morbidity and mortality in cancer patients. Prophylactic practice is varied. We report a large pragmatic RCT of thrombosis prophylaxis in cancer patients receiving chemotherapy via CVCs. The utility of warfarin and 2 dosing strategies was investigated. Methods: Patients, over 16 years old, with solid or haematological malignancies receiving chemotherapy via a CVC, with adequate haematological, hepatic and renal function and no contraindication to, or not currently on warfarin, were randomised according to clinicians’ prescribing practices: Uncertain indication - randomised to control vs warfarin (1mg or dose adjusted warfarin (DAW) to maintain INR between 1.5 and 2.0) Certain indication - randomised to 1mg warfarin vs DAW Patients were stratified by CVC insertion site, chemotherapy regimen and infusion duration. Analysis is on intention-to-treat and the primary endpoint is the number of radiologically proven CVC-related thrombotic events. Thrombosis rates will be compared using a test for proportions. The secondary endpoints of catheter longevity, toxicity and mortality will be investigated using chi-squared and logrank tests. The sample size was calculated to provide 90% power to detect a 10% difference in thrombosis rates between warfarin and no warfarin and 80% power to detect a 7% difference in the warfarin dose comparison (both 2p=0.05). Results: 1590 patients were randomised. In terms of the primary endpoint, patients are followed up for the duration of their CVC and the current median longevity is 105 days (inter-quartile range: 62 to 163). Conclusions: The results of WARP, whether showing benefit for warfarin or not, will impact on clinical practice internationally. No significant financial relationships to disclose.
Dopaminergic responsivity in alcoholism: trait, state, or residual marker?
Authors: M Dettling, A Heinz, P Dufeu, H Rommelspacher, K J Gräf, L G Schmidt
Journal: American Journal of Psychiatry (1995)

In order to classify neuroendocrine abnormalities in alcohol-dependent patients as trait, state, or residual markers, growth hormone (GH) secretion was assessed longitudinally.GH secretion, stimulated by the dopaminergic agonist apomorphine, was evaluated in 21 alcohol-dependent patients (16 men, five women) and 10 healthy comparison subjects (eight men, two women). The patients were tested during early withdrawal, after 8 days of abstinence, and after 3 months.Patients who relapsed within 3 months (N = 8) showed significantly less GH secretion in all neuroendocrine tests than did either the patients who abstained from ethanol consumption for 6 months (N = 13) or the healthy comparison subjects. The relapsers and abstainers did not differ significantly in any of their clinical or pathophysiological data, in the severity of their withdrawal symptoms, or in antecedent or concomitant illnesses associated with alcoholism.GH blunting appears to be a residual marker of clinical relevance in alcoholism.
Fertility-sparing management with progestin for young women with early-stage endometrial cancer and complex hyperplasia with atypia.
Authors: J. Park, H. Roh, W. Joo, H. You, D. Kim, J. Kim, Y. Kim, J. Nam
Journal: Journal of Clinical Oncology (2010)

5091 Background: To investigate the oncologic and reproductive outcomes of fertility-sparing management with progestin for young women with early-stage endometrial cancer (EC) and complex hyperplasia with atypia (CHA). Methods: This retrospective analsysis included 39 patients with early-stage EC and 17 patients with CHA who were treated conservatively with medroxyprogesterone acetate (MPA) or megestrol acetate (MA). Patients who received chemotherapy or pelvic radiation therapy were excluded. Oncologic and reproductive outcomes were analyzed. Results: The mean age of patients was 32 years (range, 24-40 years). Twenty eight patients were given a daily oral MPA (500 mg/day) and 17 patients were given a daily oral MA (160 mg/day). Pathologic complete response was observed in 13 or 17 patients with CHA (76%) and 30 of 39 patients with EC (77%). After median follow-up time of 42 months (range, 4-118 months), 11 of 33 patients who had complete response (33%) had recurrent disease. Nine patients tried again conservative management with progestin and five patients showed complete response. At the time of analysis, 23 patients attempted to conceive, 15 patients succeeded in pregnancy and 12 healthy babies were born. After completion of family planning, 4 patients underwent definitive surgical management including hysterectomy, bilateral salpingo-oophorectomy, and/or pelvic lymphadenecotmy. No one experienced progression to advanced-stage disease after fertility- sparing management. Conclusions: Fertility-sparing management with MPA or MA for young women with EC or CHA was safe and highly efficacious. The pregnancy outcomes were promising. However, because the significant portion of patients had a recurrent disease during follow-up period, a close surveillance and definitive surgical management after completion of family planning is required. No significant financial relationships to disclose.
Relapsed acute megakaryoblastic leukemia in Down syndrome (AMKL-DS) may be cured with chemotherapy alone, without stem cell transplantation (HSCT)
Authors: S. Jayabose, C. Sandoval, O. Levendoglu-Tugal, M. F. Ozkaynak
Journal: Journal of Clinical Oncology (2007)

17543 Background: Children with recurrent AMKL -DS have an extremely poor prognosis without HSCT. Methods: We report a case of a relapsed AMKL-DS cured with intensive chemotherapy alone, without HSCT. Results: A 19 month old boy with Down syndrome, who had transient leukemia as a newborn, developed AMKL-DS (GATA1 positive) and was treated with four cycles of CI-TAD: continuous infusion of cytarabine and daunorubicin, and oral thioguanine for four days, and intrathecal cytarabine; followed by two cycles of high dose cytarabine plus L-Asparaginase; and three weekly doses of intrathecal cytarabine. Although he achieved remission at the completion of first cycle of the induction chemotherapy, he relapsed within 6 weeks after the completion of therapy. He then received the following chemotherapy over the next six months: Cycle 1 and 2. High dose Ara-C ( 33. 3 mg/kg q 12 hours x 8 doses) on days 0 to 3 plus mitoxantrone 0. 4 mg/kg/day x 4 on days 3 to 6 Cycle 3. High dose Ara-C 33. 3 mg/kg q 12 hours x 8 doses Cycle 4 and 5 (FLAG): Fludarabine 0. 8 mg/kg/day x 4 plus Ara-C 67 mg/kg/d x 4 and G-CSF 10 mcg/kg/day x 4 all on days 0 to 3. He achieved complete remission after the 1 st cycle of chemotherapy, and underwent further cycles of chemotherapy while waiting for HSCT from an unrelated donor. But after the 5 th cycle of chemotherapy, he developed a pulmonary lesion of fungal etiology for which he received three months of therapy with liposomal amphotericin. Because of a persistent lung lesion on imaging, he was considered ineligible for HSCT, and no further therapy was given. His bone marrow aspirate after the 3rd cycle of therapy was negative for GATA1. He has been disease-free for 59 months after the completion of his last cycle of chemotherapy, and he is currently in good health without any evidence of pulmonary or cardiac dysfunction. Conclusions: Intensive chemotherapy alone, without HSCT, may be curative for relapsed AMKL- DS. No significant financial relationships to disclose.