tbuckley/cabot-search huggingface dataset:
Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D and doxorubicin. A report from the National Wilms Tumor Study (NWTS) Group
Authors: M. H. Malogolowkin, D. M. Green, C. Cotton, N. Breslow, E. Perlman, J. Miser, M. Ritchey, P. Thomas, M. Kletzel, P. F. Coccia
Journal: Journal of Clinical Oncology (2005)

8507 NWTS - 5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. 103 patients who relapsed after initial chemotherapy with vincristine, actinomycin D and doxorubicin, and radiation therapy were registered on stratum C of the NWTS-5 Relapse protocol. Twelve patients were not evaluable: 5 due to insufficient data, 6 due to major protocol violations and one for refusal of therapy. Among the 91 remaining patients, 14 with bilateral Wilms tumor at diagnosis, 1 who developed a contralateral relapse, and16 who did not achieve a complete response to the initial therapy were not included in this analysis. Relapse treatment included initial chemotherapy, followed by surgical excision, if feasible, and radiation therapy. Maintenance chemotherapy included alternating courses of the drug pairs of cyclophosphamide and etoposide and carboplatinum and etoposide. The median duration of follow-up of surviving patients was 3.44 years from registration on the relapse protocol. The most frequent toxicity was profound thrombocytopenia that contributed to one on-study death, and discontinuation of maintenance therapy for 12 patients. One patient developed acute myelogenous leukemia. These results demonstrate that approximately one-half of children with Wilms tumor who relapse after initial treatment with vincristine, actinomycin D, doxorubicin and radiation therapy can be successfully re-treated. Author Disclosure Site Number of Patients Number of Second Events 4-year EFS (%) Number of Deaths 4-year Survival (%) All 60 33 42.3 27 48.0 Operative bed lung other 7 6 14.3 4 38.1 Liver other 6 5 16.7 4 33.3 Abdomen or pelvis lung 6 5 16.7 5 0.0 Lung only 33 16 48.9 13 52.8 Lung and other 6 1 80.0 1 80.0 Other 2 0 - 0 - No significant financial relationships to disclose.
OC-103 The impact of low fodmap dietary advice and probiotics on symptoms in irritable bowel syndrome: a randomised, placebo-controlled, 2 × 2 factorial trial
Authors: H Staudacher, MC Lomer, JO Lindsay, PM Irving, K Whelan
Journal: Gut (2015)

<h3>Introduction</h3> Controlled trials using complete feeding diets have demonstrated that dietary restriction of fermentable carbohydrates (low FODMAP diet, LFD) reduces symptoms in patients with irritable bowel syndrome (IBS). However, a randomised, placebo controlled dietary advice trial has not been performed. Also, LFD has a negative impact on the gastrointestinal microbiota and the benefit of combining LFD with probiotics is unknown. This randomised controlled trial aimed to investigate the effect of LFD dietary advice with a probiotic on symptom response compared with a sham diet in patients with IBS. <h3>Method</h3> Adults with IBS referred to a secondary care dietetic service were screened for inclusion (n = 162). Eligible patients were randomised to LFD or sham (placebo) dietary advice and to the multi-strain probiotic VSL#3 or placebo for 4 weeks in a 2 × 2 factorial design. The sham (placebo) diet was designed to be equivalent in nutrients and FODMAP content to habitual diet. Outcome measures included the global symptom question (‘did you have adequate relief of your IBS symptoms over the last 7 days?’) and the validated IBS symptom severity scale (IBS-SSS, maximum score 500) at baseline and follow up. Statistical analysis was performed using logistic and linear regression. <h3>Results</h3> A total of 104 patients were recruited and 95 completed the study (63 females, 66%). There were 8 withdrawals (4 LFD, 4 sham) and 1 loss to follow up (sham). There was no significant interaction between diet (LFD/sham) and probiotic (VSL#3/placebo) for adequate relief or IBS-SSS. In the intention-to-treat analysis, a higher proportion of patients reported adequate relief at follow up in LFD (57%) versus sham (38%, p = 0.05; RR 1.51, 95% CI 0.99, 2.29) and for probiotic (57%) versus placebo (37%, p = 0.05, RR 1.52, 95% CI 0.99, 2.33). Mean IBS-SSS scores were significantly lower following the LFD versus sham (165.5 vs 231.8, p &lt; 0.001) but not different for probiotic versus placebo (196.9 vs 201.7, p = 0.75), after adjusting for baseline values. Subscores for IBS-SSS were significantly lower after LFD versus sham for days of pain (28.6 vs 44.7, p &lt; 0.001), distension (27.3 vs 41.6, p = 0.001) and satisfaction with bowel habit (40.7 vs 54.5, p &lt; 0.001). <h3>Conclusion</h3> This is the first randomised placebo-controlled trial evaluating the effect of LFD advice which demonstrates greater effectiveness compared with sham advice for IBS symptoms. The effectiveness of this probiotic is equivocal. Whether concomitant probiotic treatment is able to prevent the impact of LFD on the microbiota will be investigated. <h3>Disclosure of interest</h3> None Declared.
Human Renal Antigen Defined by a Murine Monoclonal Antibody2
Authors: Elda Tagliabue, Silvana Canevari, Sylvie Menard, Giuseppe Fossati, Andrea Balsari, Gabriella Delia Torre, Maria I. Colnaghi
Journal: JNCI Journal of the National Cancer Institute (1984)

Fusion of spleen cells from a mouse immunized with a surgical specimen of a human renal carcinoma with murine P3 myeloma cells resulted in the establishment of a hybridoma cell line that secreted a monoclonal antibody (MKi-1), of lgG1 subclass, which preferentially reacted on kidney crude membrane (CM) preparations. This monoclonal antibody was tested by solid-phase radioimmunometric assay and immunofluorescence (IF) on a panel of tumor cell lines and on CM preparations and cell suspensions from surgical specimens of normal and neoplastic tissues. In addition, cryosections of normal and cancer tissues of various histologic types were tested by IF. The expression of the MKi-1 antigen was limited to normal kidney epithelium, renal cancers, some areas in the pancreas, the apical region of some breast ducts, and a proportion (5–50%) of activated lymphocytes. Electron microscopic study by the immunoperoxidase technique on fixed sections from normal kidney showed that MKi-1 stained the brush border of almost all proximal tubules. The molecule recognized by MKi-1 was a single polypeptide chain with a molecular weight of 140,000.
Abstract 13435: Gender Differences in Impact of CYP2C19 Polymorphism on Risk of Coronary Artery Disease
Authors: Seiji Hokimoto, Tomonori Akasaka, Kazuko Nakagawa, Hisao Ogawa
Journal: Circulation (2014)

Background: Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. Specific CYPs, such as CYP2C9 and 2C19, localized in vascular smooth muscle and endothelium may contribute to the pathophysiology of cardiovascular diseases. The aim was to clarify whether CYP2C19 polymorphism would be associated with the development of coronary artery disease (CAD) as a disease-susceptibility gene independently of the conventional coronary risk factors. Methods: This study enrolled 723 patients with CAD (male 71%, 70yrs), and healthy subjects undergoing medical checkup (n=453) as control (male 69%, 53yrs). CAD was defined as definitive stable angina and acute coronary syndrome. We analyzed the incidence of CYP2C19 polymorphism for presence of CAD in all subjects and in the absence of diabetes, dyslipidemia, and chronic kidney disease (CKD) to minimize the influence of acquired and environmental coronary risk factors. CYP2C19 genotype was classified into 3 genotypes: (1) EM having normal function alleles, (2) IM having one loss-of-function (LOF) allele, and (3) PM having two LOF alleles. Results: The distribution of CYP2C19 genotype in total subjects between both groups was not different (EM, IM, PM: CAD; 34, 47, 19%: control; 32, 49, 19%). In the analysis of non-diabetes, non-dyslipidemia, and non-CKD status, there was no difference in incidence of CYP2C19 genotype between CAD (n=115) and control (n=194) groups (EM, IM, PM: non-risk CAD, 33, 46, 21%; non-risk control, 31, 52, 17%). When patients were stratified by gender, there was significant difference in distribution of CYP2C19 genotype between male and female in non-risk CAD patients (EM, IM, PM: male; 35, 50, 15%: female; 27, 36, 36%). In short, the PM frequency was significantly higher in female than in male (15% vs. 36%, P=0.011). Moreover, in females between CAD and control, incidence of PM was significantly higher in non-risk CAD patients than in non-risk control (36 vs. 14%, P=0.006), but not in male (16 vs. 19%, P=0.546). Conclusions: CYP2C19 PM status might be associated with the development of CAD. CYP2C19 polymorphism seems to have an important role in pathophysiology of atherosclerotic disease as a disease-susceptibility gene.
Lung cancer burden in Georgia by age, race, gender, poverty level, and rural/nonrural residence.
Authors: C. Robb, C. K. Smith, E. K. Smith, S. Wagner, J. Vena
Journal: Journal of Clinical Oncology (2010)

e12048 Background: Lung cancer, the leading cause of cancer mortality, poses a serious disease burden in the state of Georgia. The incidence of lung cancer deaths to Georgia residents from 2000-2007 was more than three times higher (34,225 deaths) than the next leading cause of cancer mortality, colon cancer (10,622 deaths) among this population. The population of Georgia is rapidly aging, so cancers affecting older adults such as lung cancer will likely increase in the next several decades. Race is also associated with variance in cancer rates due to genetic predisposition, environmental factors and/or lifestyles. Poverty levels influence access to health care and residence in urban or rural areas may determine health care access as well. This study examines the burden of lung cancer incidence and mortality in Georgia as related to age, gender, race, poverty level and urban/rural residence. Methods: We used 1998-2005 Georgia Comprehensive Cancer Registry data and Georgia Vital Statistics to examine lung cancer in Georgia. Results: We found a dramatic increase in lung cancer incidence in people age 60-plus vs. aged 21-59. Age-adjusted incidence rates of cancer in black men and white men were comparable, while white women were approximately 1.5 times more likely to have a lung cancer diagnosis than black women. Blacks were more likely to be diagnosed at a later stage than whites, affecting treatment options and outcome. Conversely, age-adjusted mortality rate for whites in rural areas was 11% higher than those in non-rural areas, while rural/non-rural residence had negligible impact on black mortality rates. As with incidence, there are differences young and old, for white and black men having worse lung cancer mortality rates in rural/non-MSA counties compared to urban/MSA Counties. This is not true for older women, who shows older late stage diagnosis in uban/MSA, and have higher mortality rates than their rural/Non-MSA counterparts. For all race-sex-stage groups except older women, regardless of stage, there is a trend of increased lung cancer mortality by poverty status of county. Conclusions: Details of these findings and implications for further research are discussed. No significant financial relationships to disclose.
Doctors in danger
Authors: Daniel Sokol
Journal: BMJ (2016)

There’s no obligation to stay, no matter the risk



In March 2011 the earth shook off the coast of Japan. The ensuing tsunami breached the walls of the Fukuyama Daiichi nuclear power plant, releasing vast quantities of radioactive material into the atmosphere. Hundreds of thousands of people evacuated the area. In a psychiatric hospital 35 km from Fukushima three of the six full-time doctors resigned and moved away. One explained, “I’m concerned about radiation because I’ve got a small child.”1

A feature of Ebola epidemics since 1976 has been the high death toll among clinicians and the tendency of local doctors and nurses to flee. In the recent outbreak in west Africa many foreign doctors returned home for safety reasons, leaving behind patients and local colleagues. So …
A comparison of lenalidomide/dexamethasone (RD) versus cyclophosphamide/lenalidomide/dexamethasone (CRD) versus cyclophosphamide/bortezomib/dexamethasone (CyborD) in newly diagnosed multiple myeloma (MM).
Authors: M. L. Khan, C. B. Reeder, S. Kumar, M. Lacy, D. E. Reece, K. M. Laumann, J. Mikhael, R. Fonseca, V. Rajkumar, A. K. Stewart
Journal: Journal of Clinical Oncology (2010)

8131 Background: Newly diagnosed MM patients (n = 150) were treated on 3 consecutive Phase II trials. Methods: RD (n = 34), CRD (n = 53) and CyborD (n = 63) were sequentially accrued (2004-2008) and analyzed for response and toxicity after 4 cycles of treatment and for progression free survival (PFS) and overall survival (OS) differences. Baseline parameters were balanced between trials except for ISS stage III (12%, 27% & 21% respectively). Median number of cycles delivered was higher for RD (8 vs. 5 vs. 4). Median age was 62 and 74 of the patients underwent stem cell transplantation. Risk profile by mSMART classification: high risk (N = 40) or standard risk (N = 89). Results: After 4 cycles of RD, CRD or CyborD, ≥ near complete response (nCR) was 13% vs. 2% vs. 47%, p<0.0001 and very good partial response was 38% vs. 30% vs. 67%, p = 0.0004. When all cycles of therapy were considered, ≥ nCR was 35%, 11% and 41%. PFS (median: 3.2 vs. 2.3 vs. 2.6 years, p = 0.35), and OS (2-year: 91% vs. 87% vs. 95%, p = 0.52) demonstrated no significant difference between regimens. Median PFS for all 150 patients regardless of regimen was 2.6 years. Transplantation status did not impact PFS (median: 3 vs. 2.3 years, p = 0.74) yet OS was superior in transplanted patients (3-year: 95% vs. 75%, p = 0.001). High risk mSMART patients had earlier relapse (2-year PFS: 50% vs. 70%, p = 0.03) than standard risk despite use of either lenalidomide or bortezomib. Reported grade 3 (59% vs. 74% vs. 41%, p = 0.002) and grade 4 (9% vs. 25% vs. 8%, p = 0.03) toxicities indicated CRD had more overall serious adverse events. Related neuropathy (any grade) was seen in 20%, 13% and 58% and thrombosis in 3%, 11% and 3%. Conclusions: CyborD demonstrates superior response rates and similar or less toxicity when compared to RD and CRD after 4 cycles. At this time improved early depth of response does not translate into different survival outcomes. High risk patients continue to relapse sooner with all regimens. Of encouragement 82% of patients treated with modern therapeutic approaches are alive at 4 years. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Celgene, Genzyme, Medtronic, Millennium, Ortho Biotech, Otsuka Celgene, Millennium, Ortho Biotech Biogen Idec, Celgene, Cylene, Genentech, Genzyme, Millennium, Onyx, Ortho Biotech Ortho Biotech
A pharmacogenetic UGT1A1 dose-escalation study for recurrent and refractory gynecologic cancer patients treated with combination therapy of irinotecan and cisplatin
Authors: M. Takano, M. Kato, T. Yoshikawa, J. Hirata, M. Takahashi, H. Yokota, N. Kino, T. Goto, R. Konno, H. Fujiwara
Journal: Journal of Clinical Oncology (2009)

e16536 Background: In addition to polymorphisms of UGT1A1*28, UGT1A1*6 has been recognized as a risk factor for severe irinotecal-related toxicities. We have conducted an UGT1A1 genotype-based dose-escalation study for recurrent and refractory gynecologic cancer patients (pts) treated with combination with irinotecan and cisplatin (CPT-P). Methods: Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancer, who received CPT-P; a course of therapy consisting of 40–80 mg/m 2 of irinotecan on days 1, 8, and 15 and 60 mg/m 2 of cisplatin on day 1, q4weeks. Polymorphisms of UGT1A1*28 and *6 were analyzed and the pts were categorized into three groups (wild-type, hetoro-type, and homo-type). Pharmacokinetics of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and platinums were analyzed according to the UGT1A1 genotyping. Results: During August 2008 and December 2008, 17 pts were enrolled in this study; 12 ovarian cancers and 5 uterine cancers. Genotypes of UGT1A1 were wild in 9 pts (53%), *28 in 4 pts (24%), *6 in 3 pts (18%), *6/*6 in 1 pt (6%). At the starting doses of irinotecan (60 mg/m 2 for wild-type and 40 mg/m 2 for hetero-/homo-type), dose limiting toxicities were observed in two of six wild-type cases and one of six hetero-type cases. Pharmacokinetic analyses revealed hetero-type cases were associated with lower area under time-concentartion curve (AUC) SN-38G to SN-38 (AUC SN-38G /AUC SN-38 ) compared with wild-type cases (p = 0.02), however, there was no significant difference of AUC SN-38 at the starting dose. Additionally, AUC of platinum was slightly higher in hetero-type cases in comparison with wild-type cases (p = 0.04). Pharmacokinetics of the drugs were similar between *28 and *6 cases. Conclusions: The present study indicated clinical significance of UGT1A1 genotyping upon pharmcokinetics of not only SN-38G/SN-38 but also platinum. In addition to UGT1A1*28, UGT1A1*6 was a key candidate to influence the pharmacokinetics of CPT-P regimen in gynecologic cancer patients. No significant financial relationships to disclose.
Toxicity of chemotherapy in elderly patients (&gt;75years old) with cancer
Authors: N. Pergantas, F. Matsiakou, G. F. Samelis, G. Zografos, A. Areovimata, P. Papakostas
Journal: Journal of Clinical Oncology (2005)

8282 Background: the use of chemotherapy in elderly patients (over 75 years-old) with cancer is a subject of controversy, regarding the toxicity and the tolerability of treatment in this population. Aim: The aim of our study is to consider the toxicity profile of chemotherapy in elderly patients with solid tumors. Materials and Methods: 44 patients (pts) with median age 78 (range 75 - 86) years, performance status 0 - 1 and histologicaly proved cancer (breast, colorectal, gastric, ovary, pancreas, bladder), received combination chemotherapy. The chemotherapeutic regimens included paclitaxel plus carboplatin (9 pts), irinotecan or Oxaliplatin plus Leucovorin and 5 - fluorouracil (24 pts), gemcitabine plus carboplatin (7 pts) and docetaxel plus gemcitabine (3 pts), in normal doses. Results: All 44 patients were evaluated for toxicity. Toxicities were as follows: grade IV toxicities: thrombocytopenia 1/44 (2%) pts, grade III toxicities: Alopecia 10/44 (23%) pts, leucopenia 2/44 (5%) pts, thrombocytopenia 1/44 (2%) pts, grade II toxicities: Anemia 19/44 (43%) pts, leucopenia 3/44 (7%) pts, thrombocytopenia 2/44 (5%) pts, peripheral neuropathy 4/44 (9%) pts. Twelve patients (27%) received GCSF prophilactically. No toxic death was reported. Conclusion: Chemotherapy in elderly patients (over 75 years - old) with different types of cancer is well tolerate and the toxicity profile is not different from the toxicity observed in younger patients. No significant financial relationships to disclose.
Combined Modality Therapy of Localized Gastric and Esophageal Cancers
Authors: Prajnan Das, Norio Fukami, Jaffer A. Ajani
Journal: Journal of the National Comprehensive Cancer Network (2006)

Gastric and esophageal cancers continue to be a significant health problem. The incidence of proximal gastric and distal esophageal cancers has been increasing, especially in white men. Gastric and esophageal cancers have high rates of locoregional and distant failure, resulting in poor overall survival. Therefore, patients with gastric and esophageal cancer may benefit from combined modality therapy. Adjuvant chemoradiation has been shown to improve survival in gastric and gastroesophageal cancers in a phase III trial. In esophageal cancer, most randomized trials have not shown a survival benefit for preoperative chemotherapy or chemoradiation, although these approaches are widely used. This article reviews the role of staging, surgery, and adjuvant and preoperative therapies in the management of localized gastric and esophageal cancers.
A single arm phase Ib study of RAD001 and sunitinib in patients with advanced renal cell carcinoma (RCC).
Authors: J. D. Turnbull, A. J. Armstrong, K. Morris, S. E. Yenser Wood, S. Voyles, Y. A. Fesko, D. J. George
Journal: Journal of Clinical Oncology (2010)

e15034 Background: RAD001 (Afinitor, Novartis), an oral inhibitor of mammalian target of rapamycin (mTOR), and sunitinib (Sutent, Pfizer), an oral inhibitor of VEGF/PDGF receptor tyrosine kinase signaling, are both USFDA approved and provide clinical benefit in patients with advanced RCC. We sought to determine the safety and preliminary efficacy of combination therapy with these agents in patients with advanced RCC. Methods: We conducted a phase Ib dose escalation trial of sunitinib and RAD001 in patients with advanced metastatic RCC. Prior nephrectomy was required, and prior radiation or chemotherapy other than VEGF/mTOR-based therapies was permitted. The primary endpoint was to determine the MTD/recommended phase 2 dose. Secondary endpoints included safety/tolerability, pharmacokinetics, and preliminary efficacy (response rates, PFS, OS) of the combination. Results: A total of 4 out of a planned 30 subjects were enrolled on this study (M:F= 2:2; mean age 52 yrs, 50% with KPS <80). The first three patients were enrolled on a 4+2 dosing schedule of daily sunitinib 50 mg and weekly RAD001 30 mg. Mean time on drug was 99 days (all subjects), with 2 subjects completing only 1 cycle. No partial responses were seen. Toxicities included 2/4 patients with G3 mucositis, 4/4 G3-4 thrombocytopenia, 1/4 G3 anemia, 1/4 G3 fatigue, 1/4 G3 dehydration, 1/4 G4 hypoglycemia. After dose reduction to 20 mg RAD001, 37.5 mg sunitinib, the first patient experienced G3 diarrhea and thrombocytopenia and was removed due to disease progression. The second patient was also dose reduced and maintained to cycle 5 where he experienced G3 hypophosphatemia and neutropenia and was removed from study. Due to multiple grade 3-4 toxicities, the protocol was amended to 2+1 dosing of sunitinib 37.5 mg and daily RAD001 5mg. The first patient on this new dose/schedule died from multi-organ failure with septic shock after 1 cycle of treatment. Consequently, the study was closed. Conclusions: Combined use of RAD001 and sunitinib is not well tolerated when used in combination, even at doses below the individual MTDs of each agent. PK data will be presented. Further comparative studies of other well tolerated VEGF and mTOR inhibitor combinations are warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis, Pfizer Novartis, Pfizer