tbuckley/cabot-search huggingface dataset:
The effect of comorbidity on participation in early phase cancer trials.
Authors: Ibrahim Sheriff, Henrik Møller, Jaya Ghosh, Aisyah Mohd Noor, Sophie Papa, James F. Spicer, Debashis Sarker
Journal: Journal of Clinical Oncology (2016)

2534 Background: The elderly, ethnic minorities and the socioeconomically deprived are underrepresented in oncology clinical trials, including early phase studies. Comorbid burden may contribute to this, but the impact of additional diagnoses on participation and outcome of early phase cancer trials has not been previously analysed. Methods: We evaluated data collected over an 8 year period from an early phase clinic at a UK cancer centre. Comorbid burden was evaluated using the Charlson Comorbidity Index (CCI). Data on age, ethnicity, socioeconomic status and ECOG performance status were also collected. Univariate and multivariate logistic and Cox regression analyses were performed to quantify the effect of CCI on trial enrolment, and overall survival of patients on trial. We hypothesised that comorbid burden influences these outcomes. Results: 681 patients were referred and included in this analysis. Of these, 230 patients went on trial (33.8%). CCI was significantly associated with increasing age (Pearson’s χ2 (10) = 19.02, P = 0.04) but not with socioeconomic or ethnic group. Trial enrolment and overall survival on trial was not affected by age, ethnicity or socioeconomic status. By contrast, patients with any significant comorbidity were less likely to be enrolled on a trial (CCI ≥ 2, adjusted odds ratio 0.27, p = 0.004, CI 0.11-0.66, compared to CCI = 0). CCI was not linked to overall survival on trial (CCI ≥ 2, adjusted hazard ratio 0.77, CI 0.32-1.84, compared to CCI = 0). Of the 451 patients who did not enrol on a trial, the main reasons for exclusion were patient choice in 98/451 (21.7%), poor ECOG performance status in 93/451 (20.6%) and ineligibility according to trial inclusion and exclusion criteria in 88/451 (19.5%). Comorbidity was directly cited as the reason for not enrolling in 21/451 patients (4.7%). Of these patients, 13/451 (2.9%) were excluded as their comorbidities rendered them ineligible for trial and 8/451 (1.8%) were excluded by clinician decision alone. Conclusions: Comorbidity affects the likelihood of enrolment on an early phase trial, but not overall survival once enrolled. These findings can further inform efforts to widen participation of underrepresented groups in early phase cancer trials.
Experience with single agent eribuln mesylate in extra cranial metastatic breast cancer.
Authors: Viveka Belathur Kalegowda
Journal: Journal of Clinical Oncology (2016)

e12524 Background: Single agent Eribulin has been used in management of metastatic breast cancer. We report our experience with Eribulin Mesylate(EM) in metastatic Breast Cancer patients in India. Methods: This is a single arm prospective study of thirty patients with metastatic Breast cancers with no intracranial metastasis irrespective of hormonal receptor status. Patients who had failed 3rd and 4th line chemotherapy and antiHer2 therapy were administered single agent Eribulin with standard approved doses over a median period of eight months. Time to progression and death were analyzed using Kaplan Meir analyses and correlation. Results: Overall median time to progression was 8 months with 63.3% of patients surviving.Hormone receptor status (Triple Negative vs ER/PR/Her 2 positivity) didn’t seem to influence time to progression in our study.However there was a trend for decrease in number of events (death) in those who received more cycles of chemotherapy ( > 3 cycles vs < 3 cycles) of EM (42.9% vs 31%) and ER/PR positive vs negative tumors (44.4% vs 25%) though not significant. Only minor adverse events such as grade 2/3 Neutropenia without febrile Neutropenia was seen in 12% of patients and grade 2/3 peripheral neuropathy in about 6% of patients. Conclusions: Preliminary results suggest that EM confers beneficial effects in breast cancer patients with acceptable minimal toxicity. EM is a feasible option for metastatic breast cancer patients who cannot afford anti-Her 2 therapies or have failed 2nd and 3rd line chemotherapies in India.
Blood flow restriction training: a novel approach to augment clinical rehabilitation: how to do it
Authors: Stephen D Patterson, Luke Hughes, Paul Head, Stuart Warmington, Christopher Brandner
Journal: British Journal of Sports Medicine (2017)

Strength training forms a pivotal part of rehabilitation. Heavy-load strength training (60%–70% one-repetition maximum (1RM)) has been traditionally prescribed to improve muscle strength, body mass and function,1 but may be unattainable and/or confer increased risk of adverse consequences in individuals with a musculoskeletal (MSK) impairment. The challenge faced by clinical practitioners is how to effectively and safely adapt training loads throughout rehabilitation.

In the past decade, research has proven that blood flow restriction (BFR) during light-load training (eg, 20%–30% 1RM) can produce significant gains in muscle strength and size in healthy populations, in contrast to non-BFR load-matched controls.2 In this novel training method, limb blood flow is restricted via a cuff throughout the contraction cycle and rest period. This results in partial restriction of arterial inflow to muscle, but, most significantly restricts venous outflow from muscle. Given the light-load nature and strengthening capacity …
Thoracic MRI is preferable for neuroblastoma
Authors: Kieran McHugh
Journal: BMJ (2017)

The picture used in print for the clinical update on neuroblastoma is out of date in a supposedly state-of-the-art review.1 It is a coronal CT (computed tomography) image of the chest and abdomen showing a large superior mediastinal neuroblastoma, probably in a young child.

As the authors correctly mention, ultrasonography …
High accumulation of metformin in colonic tissue of subjects with diabetes or metabolic syndrome.
Authors: Andrea De Censi, Juergen Burhenne, Walter E. Haefeli, Johanna Weiß, Wilfried Roth, Andrea Parodi, Michael Gnant, Thomas Bachleitner-Hofmann, Dominique Scherer, Neli Ulrich, Borut Štabuc, Marilena Petrera, Matteo Puntoni, Gianni Coccia, Laura Paleari
Journal: Journal of Clinical Oncology (2017)

1557 Background: Epidemiological studies consistently observed an association between metformin use in diabetic patients and decreased colon cancer incidence and mortality at clinical doses (1500-2250 mg day), corresponding to plasma levels of 0.003-0.045 mM. Preclinical models report much higher doses of metformin, ranging between 1 and 40 mM for in vitro and 0.006-0.145 mM for in vivo studies. A recent trial using a low dose of metformin (250 mg/day, Higurashi T et al. Lancet 2016;17:475) showed a 40% reduction of colorectal adenoma recurrence. We performed a pilot study to measure metformin in plasma and colonic tissue of subjects with diabetes or metabolic syndrome and to explore their correlation with different tissue biomarkers, including Ki-67, pS6k, a mTOR effector protein, and EGFR expression. Methods: We used LC-MS/MS to quantify metformin in plasma and colonic tissues from 13 volunteers with diabetes or metabolic syndrome undergoing screening colonoscopy. All patients had received metformin at 1000-1850 mg/day for a median of 6.5 yrs (range 2-15), except for one who served as untreated control. Tissue quantifications were performed on specimens derived from right and left colon biopsies with or without washing to exclude a potential contamination due to lumen accumulation by the drug. Biomarker assessment was performed by standard IHC assay. Results: The mean plasma metformin was 0.025 mM/L (range 5x10 -5 -0.017), whereas the colonic tissue was ~100 fold higher in right [0.39 mM/Kg (range 0.034-1.75)] and left colon [0.46 mM/Kg (range 5x10 -3 -1.86)]. There was no significant difference between washed and unwashed biopsies. No significant correlations were detected between metformin levels in plasma/tissue and tissue biomarkers. Conclusions: Metformin can attain ~100 fold higher colonic tissue levels than in plasma. These levels are in the range of a direct antitumor effect observed in in vivo preclinical models. A two-by-two clinical trial of metformin and aspirin in colon cancer patients is underway by our group to further elucidate independent and synergistic antitumor effects.
Treatment of high grade metastatic neuroendocrine tumor (mNET) with peptide receptor radionuclide therapy (PRRT): Retrospective analysis in a single referral center.
Authors: Tannaz Armaghany, Gelareh Vahdati, Sanjay Thamake, Mohammad Hamidi, Reza Amerinia, Ebrahim Delpassand
Journal: Journal of Clinical Oncology (2015)

e15175 Background: We retrospectively evaluated the efficacy of PRRT with 111 In-Octreotide (IN) or 117Lu-Octreotate (LU) in the treatment of high grade (HG) mNETS with a positive octreoscan image. Somatostatin analogues are used in the treatment (Tx) of low to intermediate grade NET patients. Somatostatin receptor expression (SRE) is seen in some of high grade NETs and this is the basis of PRRT. Methods: Charts of patients with SRE positive high grade mNETs who were treated with PRRT with either 111 In (IN) or 171Lu (LU) were reviewed. We used differentiation or Ki67 index > 20% for defining these patients. RECIST criteria was used to evaluate response. Patients were treated up to maximum of 4 PRRT cycles. Biological response was assessed by median SUV change of 3 target lesions by comparing baseline and the last repeated PET scan SUVs. This was reported as % of change in SUV in these lesions. Results: 17 patients were evaluable among 262 reviewed. Median age was 53. Ten patients had LU and 7 had IN. 9 patients had pancreatic NET primary, 4 GI NET , 1 lung, 1 prostate and 2 with unknown primary. PRRT was 1st line for 24%, second in 12%, third in 47% and 4thin 17% of patients 12 patients were followed up for a minimum of 12 months. Six had PRRT with LU and 6 with IN. Two out of six patients (33%) who received LU and three out of six patients (50%) who received IN had stable disease or partial response at 12 months. Two patients who received IN are alive without progression at their 18 and 68 months follow ups at the time of this report. The median progression free (MPFS) survival was 9.3 months for LU and 10.2 months for IN. MPFS was 12 months when both LU and IN was considered. Six patients had 30% SUV intensity reduction by PET/CT scan from average maximum SUV measured from 5.67 (baseline image) to 4.02 (last image). Conclusions: PRRT with LU or IN is a viable option for the Tx of HG mNETs that express sandostatin receptors. The median time to progression in our study is comparable to standard first line chemotherapy Tx. The Results of this study is limited by the small population size, patient selection and heterogeneity of primary origin. PRRT should be investigated further in the Tx of this condition. Clinical trial information: NCT01237457.
Accrual of older patients (pts) with breast cancer to Alliance systemic therapy trials over time: A151527.
Authors: Rachel A. Freedman, Drew K. Seisler, Jared C. Foster, Jacqueline M. Lafky, Gretchen Genevieve Kimmick, Aminah Jatoi, Hyman B. Muss, Harvey Jay Cohen, Jeanne S. Mandelblatt, Eric P. Winer, Clifford A. Hudis, Constance T. Cirrincione, Alvaro Moreno-Aspitia, Arti Hurria
Journal: Journal of Clinical Oncology (2016)

1024 Background: Despite increasing awareness of accrual challenges, it is unknown if accrual of older breast cancer pts to treatment trials has improved over time. Methods: We examined accrual of older pts to Alliance cooperative group, systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics for older (65+) vs. younger participants. To examine accrual trends, we modeled age as a function of time using logistic regression (+/- trials dedicated to older pts). Results: The table shows accrual dates and the numbers of older pts enrolled on each included trial. The proportion of enrolled pts aged 65+ significantly increased with time in adjuvant/neoadjuvant trials (odds ratios [OR] 1.04, 1.96, respectively; both p < .0001), but decreased slightly in metastatic trials (OR 0.98, p = .03). Similar trends were seen for pts aged 70+, but were statistically significant for adjuvant trials only (OR 1.05, p < .0001). Results after exclusion of trials dedicated to older pts will also be presented. Tumor subtypes were similar by age in neoadjuvant/metastatic trials but differed by age in adjuvant trials. Conclusions: Despite some increases in the overall proportion of older pts enrolling on studies over time, older patients remain under-represented in therapeutic trials. Novel strategies for accrual are critical if we want to meaningfully change the evidence-base for this growing number of pts. Support: UG1CA189823 Included trials. Trial Age 65+ N (%total) Age 70+ N (%total) Accrual ADJUVANT overall 2277 (15) 1099 (7) 1985-2010 CALGB 40101 468 (12) 177 (5) 06/02-07/10 CALGB 49907 633 (100) 415 (66) 06/02-12/06 N9831 301 (9) 126 (4) 05/00-04/05 CALGB 9741 162 (8) 54 (3) 10/97-03/99 CALGB 9344 182 (6) 55 (2) 05/94-04/97 NCCTG 89-30-52 381 (69) 225 (41) 01/91-04/95 CALGB 8541 150 (10) 47 (3) 01/85-03/91 NEOADJUVANT overall 407 (24) 252 (15) 2006-2012 CALGB 40603 40 (9) 10 (2) 07/09-08/12 CALGB 40601 25 (8) 10 (3) 02/09-02/12 Z1041 18 (6) 8 (3) 09/07-12/11 Z1031 324 (52) 224 (36) 01/06-01/09 METASTATIC overall (all CALGB) 624 (24) 321 (13) 1994-2011 40503 98 (25) 53 (13) 09/08-11/11 40502 166 (21) 81 (10) 11/08-11/11 40302 84 (28) 47 (16) 12/06-07/10 9840 149 (25) 87 (15) 09/98-11/03 9342 127 (27) 53 (11) 02/94-07/97
Complications après coagulation au plasma argon en endoscopie: résultats d'une enquête rétrospective multicentrique
Authors: A Boruchowicz, P Gower, H Coevoet, T Paupard, A Dewailly, F Guillemot, M Cassagnou, AB Marks, C Plane, P Bulois, C Gamblin, B Filoche
Journal: Endoscopy (2006)

L'électrocoagulation au plasma argon (APC) est utilisée en endoscopie pour le traitement des rectites radiques, des ectasies vasculaires antrales, des angiodysplasies, des ulcères hémorragiques, de l'obstruction des stents, des polypes et des résidus tissulaires après mucosectomie. La complication principale, la perforation, est considérée comme peu fréquente et pourrait être sous estimée avec 1 perforation observée au cours de 86séances pour le traitement d'angiodysplasies dans un travail récemment publié (1).
Safety and efficacy of eribulin in combination with gemcitabine in patients with advanced triple negative breast cancer.
Authors: Vasiliki Michalaki, Georgios Fragulidis, Ioannis Kondis, Eleni Karvouni, Nikolaos Dafnios, Antonia Kotsiou, Ioannis Vassiliou, Christos Papadimitriou
Journal: Journal of Clinical Oncology (2017)

e12578 Background: Triple negative breast cancer (TNBC) characterized by aggressive tumor behavior with very poor prognosis following progression after standard chemotherapeutic regimens.The combination of Gemcitabine, a nucleoside analogue, and eribulin a microtubule-targeting agent exhibited synergistic cytotoxic effects in pre-clinicall and clinical setting . Thus, eribulin combined with gemcitabine may synergistically induce tumor cell death, especially in tumors like TNBC. Based on this rationale, we conducted a phase II study evaluating this combination either in first- or in second-line treatment for advanced TNBC.Methods: Females with locally advanced or metastatic TNBC who had received previous chemotherapy , with an ECOG (PS) ≤ 1, and adequate hematological, renal and hepatic function. Patients received eribulin (1mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 until disease progression. CT scans were performed every 12 weeks. The main objective of this trial was to evaluate the overall response rate (ORR) and secondary were Feasibiliy, safety and clinical benefit rate (CBR ). Results: Thirty –two females (median age: 62 years, median ECOG performance status (PS) 1) were enrolled the study. The majority had visceral disease (78.5%). A median of 9 (range:4–18) treatment cycles was administered (69% of patients received ≥ 6 cycles), .All patients were evaluable for response. We did observe 12 partial responses for an overall response rate of 37.5% (95%CI,26.1-57.0). A stable disease was observed in 15 patients (46.8%). Clinical benefit, was observed in 21 patients (65.6%; 95%CI,48.1-76.6). The most common grade 3 or 4 toxicities were haematologic . The main grade 3 or 4 non-hematolgic toxicities were fatigue, diarrhoea, nausea and vomiting. Of the 32 patients in total 7 patients had dose reductions and 14 patients had dose delays. Conclusions: Resistance to current standard therapieslimits the available options for previously treated patients with metastatic TNBC and there is currently no preferred standard chemotherapy. This study demonstrated that the combination of eribulin and gemcitabine was efficacious, feasible and toxicity was generally manageable
Prospective evaluation of the crimper purse string device in carrying out intrathorasic oesophagogastric anastomosis
Authors: P Vassallo, B Gurney, PC Munipalle, YKS Viswanath
Journal: Endoscopy (2005)

Background: Anastomotic leakage following oesophago-gastrectomy is associated with high morbidity and mortality and can occur in 10–15% of these patients. This study assesses the usefulness of the crimper purse string device oesophagogastric anastomosis during 2-stage Oesophagectomy in a tertiary referral Upper GI centre.
Meta-analysis of hepatocellular carcinoma incidence in patients who have obtained a sustained virologic response after antiviral therapy for hepatitis C.
Authors: Ali Hosni, Tawnya Hansen, John S Sampalis, Yuxin Tu, Arlene Nugent
Journal: Journal of Clinical Oncology (2016)

1551 Background: Hepatitis C virus (HCV) is a risk factor for development of hepatocellular carcinoma (HCC). Patients (pt) with HCV can achieve a sustained virologic response (SVR; undetectable HCV RNA at least 12 weeks after the end of antiviral therapy), with a chance of decreasing disease burden. This meta-analysis aimed to determine the impact of SVR on the development of HCC by comparing the difference in HCC risk in HCV pt with SVR vs. non-SVR. Methods: A literature search (1980-2015) in EMBASE, MEDLINE, CCTR and Google Scholar was performed for inclusion and analysis of studies with HCV pt receiving anti-viral therapy in which HCC incidence was recorded in SVR and non-SVR groups. Study quality risk of bias was assessed using the Newcastle-Ottawa Scale. Statistical analysis included determination of the risk ratio (RR) through a random effects model on the incidence of HCC. Meta-regression analysis assessed the potential impact of cirrhosis on the RR. Results: Overall1095 articles were reviewed, of whom 37 studies were eligible for this analysis. Total sample size: 22,858 pt; median age range: 40-63 yr; median follow-up range: 2-13 yr; fibrosis/cirrhosis stage: non-cirrhotic (F0-2 stage) range: 0-86% and cirrhotic (F3-4 stage) range: 2-100%; antiviral therapy: interferon-based in 36 studies and direct acting antiviral drugs (DAAD) in 1 study; overall SVR vs. non-SVR rate: 48% vs. 52%; HCC incidence in SVR vs. non-SVR groups: 3.2% vs. 12.4%. The pooled RR of HCC incidence was 0.214 (95% CI, 0.168-0.273; p = 0.001) in favour of the SVR group with 78.6% reduction in the risk of developing HCC in SVR pt.On meta-regression analysis, cirrhosis (F3-4) significantly associated with the RR (adjusted RR: 0.245, p < 0.0001) and the reduction in the risk of HCC development changed to 75.5% in SVR cirrhotic pt. Conclusions: Obtaining SVR in HCV pt decreases the risk of developing HCC. New antiviral agents (DAAD) with potential SVR rate > 90% will eventually be effective in decreasing the incidence of HCC, and implementation of screening program for HCV, with treatment at earlier non-cirrhotic stage of the disease could have more protective effect against HCC development.
Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24
Authors: Shuji Ozaki, Masaaki Kosaka, Shingo Wakatsuki, Masahiro Abe, Yasuo Koishihara, Toshio Matsumoto
Journal: Blood (1997)

Abstract Multiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Alternative strategies are needed to solve these problems. To develop a new strategy, we have generated a monoclonal antibody (MoAb), which detects a human plasma cell-specific antigen, HM1.24. In this report, we evaluated the in vivo antitumor effect of unconjugated anti-HM1.24 MoAb on human myeloma xenografts implanted into severe combined immunodeficiency (SCID) mice. Two models of disseminated or localized tumors were established in SCID mice by either intravenous or subcutaneous injection of human myeloma cell lines, ARH-77 and RPMI 8226. When mice were treated with a single intraperitoneal injection of anti-HM1.24 MoAb 1 day after tumor inoculation, the development of disseminated myeloma was completely inhibited. In mice bearing advanced tumors, multiple injections of anti-HM1.24 MoAb reduced the tumor size and significantly prolonged survival, including tumor cure, in a dose-dependent manner. The proliferation of cultured human myeloma cells was inhibited in vitro by anti-HM1.24 IgG-mediated complement-dependent cytotoxicity, but not by the antibody alone. Moreover, spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells. These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias.