tbuckley/cabot-search huggingface dataset:
A phase II pilot study of weekly docetaxel, cisplatin, and 5-fluorouracil in metastatic gastric cancer.
Authors: K. Okutur, F. Dane, M. Ilhan, S. Seber, T. Korkmaz, K. Aydin, M. Bozkurt, E. Namal, N. S. Turhal, G. Demir
Journal: Journal of Clinical Oncology (2010)

e14589 Background: Docetaxel, cisplatin and 5-fluorouracil (DCF) regimen have the best response rate and survival advantage for patients (pts) with metastatic gastric cancer (MGC). However, the 3-week schedules of DCF were associated with significant grade 3-4 toxicity. Two phase I study has been showed that weekly administration of DCF regimen could achieve equivalent dose intensity as 3-week schedule regimen with a tolerable toxicity profile, mainly a decreased incidence of grade 3-4 neutropenia or leukopenia. The aim of this study was to evaluate the efficacy and toxicity of weekly DCF regimen in pts with MGC. Methods: The eligibility criteria were as follows; 1) histologically confirmed metastatic gastric cancer with measurable lesion, 2) ECOG PS ≤ 3, 3) age ≥ 18, 4) adequate bone marrow, liver, renal and cardiac functions, 5) no prior chemotherapy. Pts were treated with weekly 1hour-infusion of docetaxel 25 mg/m2, 30 minutes infusion of cisplatin 25 mg/m2, and 24 hour continue infusion of 5-fluorouracil 1,000 mg/m2 for 3 consecutive weeks every 4 weeks. The primary end-point was response rate (RR) confirmed by RECIST. Toxicity evaluated by National Cancer Institute-Common Toxicity Criteria. Results: Twenty pts were enrolled. Nine pts were male and eleven female. Median age was 65 yr (40-85). ECOG PS were as follows; 0-1 (13 pts), 2 (5 pts) and 3 (2 pts). Thirteen pts had metastatic lymph nodes, 9 hepatic metastases, 8 peritoneal carcinomatosis: 2 ovarian metastases, 1 lung metastases, 1 bone metastases, 1 pancreatic metastases and, 1 adrenal metastases. All pts were evaluable for response and toxicity analysis. A total of 70 chemotherapy cycles were administered. One complete response and 7 partial responses were achieved, for an overall RR of 40%. Five pts (25%) had stable disease and 7 (35%) progressed on therapy. There was any grade 4 toxicity, grade 3 toxicity was observed in 4 pts (20%); grade 3 neutropenia and nausea (1 patient), grade 3 nausea (1 patient), grade 3 fatigue (1 patient), and grade 3 diarrhea (1 patient). Conclusions: Even if the study is still ongoing (a planned accrual up to 50 patients), weekly DCF seems to an active regimen with a good toxicity profile for pts with MGC. No significant financial relationships to disclose.
Surgery in patients with metastatic or recurrent gastrointestinal stromal tumor (GIST) upon best response or limited progression following imatinib therapy
Authors: U. Ronellenfitsch, C. Mussi, E. Wardelmann, J. Jakob, E. Fumagalli, E. Tamborini, S. Pilotti, P. Reichardt, P. Hohenberger, A. Gronchi
Journal: Journal of Clinical Oncology (2008)

10555 Background: Indication and best timing of surgery for metastatic and recurrent GIST treated with imatinib are not clearly established. This study assesses long-term outcome for patients resected either upon clinical response or focal progression. Methods: We analyzed 80 patients who underwent surgery for metastatic or recurrent GIST after imatinib therapy between July 2002 and October 2007. Patients were divided into those with surgery at best clinical response (group A, n=49) and those with surgery at focal progression of a single lesion (group B, n=31). Median follow-up was 26 months from surgery and 47 months from imatinib onset. Primary endpoints were progression- free survival (PFS) and disease-specific survival (DSS). Secondary endpoint was surgical morbidity. Multivariate Cox regression was carried out for PFS and DSS. Results: In group A, 17 patients (34.7%) showed progression after a median of 16 postoperative months and 69 months after starting imatinib. 2-year PFS/DSS from surgery was 64.4%/97.6%. 5-year DSS from imatinib onset was 82.9%. In group B, 19 patients (61.3%) showed progression after a median of 8 postoperative months and 44 months after starting imatinib therapy. 2-year PFS/DSS from surgery was 9.7%/69.5% and 5-year DSS from imatinib onset 67.6%. Surgical morbidity occurred in 13 patients (16.3%). Uni- and multivariate analyses in both groups did not show significant associations between primary tumor site, specific c-kit or PDGFR-A mutations, histological regression, completeness of resection and PFS/DSS. Joint Cox regression of both groups confirmed a significantly shorter PFS and DSS in group B after adjustment for the named tumor characteristics. Conclusions: Our retrospective data show that long-term outcome is better for patients in whom resection of recurrent or metastasized GIST is achieved upon best clinical response to imatinib. We were not able to show a significant influence of specific tumor characteristics on outcomes, probably due to low power of our analyses. Surgery-related morbidity was acceptable. Evidence from prospective randomized trials is needed to fully assess the benefit and determine indications and best timing of surgery for metastatic or recurrent GISTs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis
FOrMAT: Feasibility of a molecular characterization approach to treatment of patients (pts) with advanced gastrointestinal (GI) tumors.
Authors: Sing Yu Moorcraft, David Gonzalez de Castro, David Cunningham, Brian A Walker, Sanna Hulkki Wilson, Javier Diez Perez, Clare Peckitt, Andrew Wotherspoon, Ruwaida Begum, Nicola Valeri, Marco Gerlinger, Chiara Braconi, Sheela Rao, David Watkins, Ian Chau, Naureen Starling
Journal: Journal of Clinical Oncology (2015)

TPS227 Background: The molecular characteristics of a pt’s tumour can determine their suitability for treatment with targeted drugs. Several molecular alterations are only seen in a small percentage of pts and so it is often necessary to screen many pts to identify those who may benefit from targeted therapies. Testing each pt for multiple biomarkers is also increasingly important. Targeted next generation sequencing (NGS) can rapidly interrogate tumours for actionable genetic aberrations and therefore facilitate a personalised treatment approach. FOrMAT aims to assess the feasibility of delivering validated NGS results (to accredited standards) in a clinically meaningful timeframe and how this could be adopted into routine clinical practice in the United Kingdom’s National Health Service. Methods: FOrMAT (ClinicalTrials.gov identifier NCT02112357) is a single-centre translational study in pts with locally advanced/metastatic GI tumours (including gastroesophageal, pancreatic, biliary tract and colorectal). Targeted capture sequencing is performed on archival or fresh biopsy samples to detect mutations, copy number variations and translocations in 45 genes which have prognostic, predictive or pharmacogenomic significance or are targets in current/upcoming clinical trials. Results are discussed by a Sequencing Tumour Board to establish if a pt is potentially suitable for a targeted therapy (e.g. within another clinical trial, as part of standard of care or via a compassionate access program). Changes to pts’ treatment are not mandated. The primary endpoint is the percentage of pts in whom a currently actionable molecular alteration was detected. Secondary endpoints include evaluation of the time required to obtain sequencing results. Blood samples will be collected at baseline and at the time of each tumour response assessment for analysis of molecular markers, including ctDNA and microRNA. Pts may also consent to optional biopsies for exploratory research into tumour heterogeneity and development of pt-derived organoids. The study aims to recruit 200 pts over 2 years. Recruitment started in February 2014 and to date 56 pts have been recruited. Clinical trial information: NCT02112357.
Fresh tissue harvest and histopathologic processing of uveal melanoma specimens: Implications for basic research and patient care
Authors: D. Gombos, W. H. Klein, G. N. Fuller, C.-A. Mao, A. K. El-Naggar, J. E. Lee, R. Banay, G. Lozano, B. Esmaeli
Journal: Journal of Clinical Oncology (2005)

7535 Background: To determine the impact of immediate harvest of fresh uveal melanoma at the time of enucleation on subsequent histopathologic assessment of the enucleated specimen in patients with uveal melanoma. Fresh uveal tissue harvest is necessary to analyze transcript expression via DNA microarrays. Methods: We conducted a prospective nonrandomized trial in patients with uveal melanoma who underwent primary enucleation at our institution between January 2002 and April 2004. In each case, the enucleated globe was transilluminated to permit accurate delineation of the location of the tumor. The globe was then transected away from the tumor site, and uveal melanoma cells (representing less than half of the tumor mass) were harvested prior to formalin fixation of the rest of the ocular specimen. The harvested tissue was frozen within 30 minutes after enucleation and was stored for future DNA, RNA, and protein extraction. Results: Eleven patients were eligible for the study, and all 11 chose to participate and underwent harvest of fresh uveal melanoma. In all 11 patients, the fresh tissue harvest did not compromise the ability of the ocular pathologist to comment on the usual prognostic features of uveal melanoma, such as tumor type and grade, presence of extrascleral extension, and involvement of the ocular microvasculature. Conclusions: Immediate harvest of fresh uveal melanoma can be performed at the time of enucleation without compromising histopathologic assessment of the specimen. Fresh frozen uveal melanoma can be used for future DNA, RNA, and protein extraction. The extracted material can be used for assessing somatic mutations, transcript analysis and protein expression. No significant financial relationships to disclose.
Phylogenetic relationships among Japanese, rhesus, Formosan, and crab-eating monkeys, inferred from restriction-enzyme analysis of mitochondrial DNAs.
Authors: K Hayasaka, S Horai, T Gojobori, T Shotake, K Nozawa, E Matsunaga
Journal: Molecular Biology and Evolution (1988)

Mitochondrial DNA (mtDNA) polymorphisms in four species of macaques, i.e., Japanese monkey (Macaca fuscata), rhesus monkey (M. mulatta), Formosan monkey (M. cyclopis), and crab-eating monkey (M. fascicularis), were analyzed to study phylogenetic relationships. When 17 restriction enzymes of 6-bp recognition were used, 42-49 sites were observed in the samples. The estimated number of nucleotide substitutions per site among Japanese, rhesus, and Formosan monkeys ranges from 0.0318 to 0.0396, and that between the crab-eating monkey and the other monkeys from 0.0577 to 0.0653. These findings suggest that the crab-eating monkey diverged from the other three approximately 1.5-3.0 Myr before the present (Mybp) and that the Japanese, rhesus, and Formosan monkeys diverged approximately 0.9-1.8 Mybp, although the branching order cannot be determined conclusively.
Bosutinib Apears to be Safe, with Low Cross Intolerance, in Patients Treated in 4th Line. Results of the Spanish Compassionate Use Program
Authors: Valentín García-Gutiérrez, Begoña Maestro, Alejandra Martinez-Trillo, Jose Luis Lopez Lorenzo, Maria Luisa Martin Mateos, Alberto Alvarez, Ana Iglesias Pérez, Andrés Romo Collado, Angeles Fernandez, Guiomar Bautista, Angeles Portero, Beatriz Cuevas, Concepción Ruiz, Esperanza Romero, Fernando Ortega, Isabel Mata, José Tallón, Maria del Carmen García Garay, María José Ramirez Sánchez, Natalia de las Heras, Pilar Giraldo, Sabela Bobillo, José María Guinea, Guillermo Deben, Sandra Valencia, Ana Sebrango, Concepción Boqué, Juan Luis Steegmann
Journal: Blood (2014)
A phase II study of cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin (Myocet), and prednisone plus rituxmab (R-COMP) in elderly patients with diffuse large B-cell lymphoma (DLBCL)
Authors: M. Federico, D. M. Caballero, E. Thiel, S. Bologna, M. J. S. Dyer, S. Luminari
Journal: Journal of Clinical Oncology (2006)

17506 Background: The majority of patients (pts) with diffuse large B-cell lymphoma (DLBCL) are elderly and may have limited tolerance to intense chemotherapy. Myocet has an improved therapeutic index in comparison to doxorubicin, resulting in less myelosuppresion, lower GI toxicity and reduced risk of cardiotoxicity. The aim of this study was to assess the efficacy and safety of the R-CHOP modified by replacing doxorubicin with Myocet (R-COMP) in pts ≥ 60 years with newly diagnosed, advanced DLBCL. Methods: Sample size was defined with the level of no interest P 0 = 40% of CRs and the level of interest P 1 = 60% of CRs. After assessment of the first 25 evaluable pts accrual continued to 75 pts, sample size estimated to include 66 evaluable pts. R-COMP regimen: d1 every 3 wks Myocet 50 mg/m 2 , cyclophosphamide 750 mg/m 2 , vincristine 1.4 mg/m 2 (max. 2 mg), rituximab 375 mg/m 2 (d3 C1, d1 thereafter) and prednisone 100 mg/d d1–5. After 3 cycles pts with an objective response received 5 additional cycles. Results: Between Oct 2002 and Apr 2005, 75 pts were registered. This analysis includes the first 51 evaluable pts: median age was 71 (60–83); 56% of pts had an intermediate or high risk IPI score (≥ 3); median LVEF at baseline was 60% (50–89). Relative dose intensity was 89.8%. Median treatment of 8 cycles (1–8). Thirty-four pts (67%) achieved CR (95% CI = 51, 5–79,3) and 10 pts (20%) PR; Five percent of cycles were delayed and 9% were dose reduced due to toxicity. Toxicity: Grade (G) 3–4 neutropenia in 22% of cycles (52% of pts), febrile neutropenia in 3% of cycles (12% of pts), G 3–4 thrombocytopenia in 2 cycles, one episode of neutropenic sepsis, mucositis and related infections in 1% of the cycles each. Median final LVEF was 60% (40–79). Four pts were withdrawn due to decrease in LVEF. One pt had acute pulmonary oedema (considered related to the drug in absence of other reasons). No pts had congestive heart failure related to study drug. Conclusions: The R-COMP regimen is a well-tolerated and effective treatment for aggressive NHL in elderly pts. Both, the general tolerability and the low incidence of cardiac events warrants further studies in order to confirm the clinical benefit of R-COMP in elderly population. [Table: see text]
Comparison of Neoplasms in Six Sources of Rats
Authors: William F. Mac Kenzie, F. M. Garner
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Comparison of Neoplasms in Six Sources of Rats Get access William F. Mac Kenzie, William F. Mac Kenzie Lt. Colonel, USAF, VC Veterinary Pathology Division, Armed Forces Institute of Pathology, Washington, D.C. 20306 Search for other works by this author on: Oxford Academic PubMed Google Scholar F. M. Garner F. M. Garner Colonel, VC, USA, Retired Veterinary Pathology Division, Armed Forces Institute of Pathology, Washington, D.C. 20306 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1243–1257, https://doi.org/10.1093/jnci/50.5.1243 Published: 01 May 1973 Article history Received: 05 September 1972 Accepted: 01 February 1973 Published: 01 May 1973
The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer.
Authors: L E Rutqvist, B Cedermark, T Fornander, U Glas, H Johansson, B Nordenskjöld, S Rotstein, L Skoog, A Somell, T Theve
Journal: Journal of Clinical Oncology (1989)

The relationship between hormone receptor status and the effect of adjuvant tamoxifen in early breast cancer remains controversial. This article presents the results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy in postmenopausal patients. During 1976 to 1984, 1,407 patients were included in the study. Of these, 427 (30%) had high-risk tumors (pN + or pT greater than 30 mm) and were included in a concurrent randomized comparison of postoperative radiotherapy versus adjuvant polychemotherapy. The mean follow-up time was 61/2 years. Tamoxifen improved the recurrence-free survival (RFS) (P less than .01), but the overall survival difference in favor of the tamoxifen-allocated patients was not significant. Data on estrogen (ER) and progesterone receptor (PgR) content were available in 750 patients. Their mean follow-up time was 41/2 years. The effect of tamoxifen was significantly related to ER level (P less than .01). No benefit with tamoxifen was observed among ER-negative patients. The relation to PgR level was of borderline significance (P = .06). Multivariate analysis indicated that most of the interaction between treatment and receptor content was explained by the interaction with ER (P less than .01). The PgR status appeared to modify the effect of tamoxifen among the ER-positive patients and the greatest effect was observed among patients who were positive for both receptors. However, the additional predictive information provided by the PgR assay did not help to identify an unresponsive subgroup of patients.
Randomized phase III trial of high-dose interferon alfa-2b (HDI) for 4 weeks induction only in patients with intermediate- and high-risk melanoma (Intergroup trial E 1697) .
Authors: S. S. Agarwala, S. J. Lee, L. E. Flaherty, M. Smylie, R. F. Kefford, W. E. Carson, G. Cohen, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2011)

8505 Background: To assess the benefit of 4 weeks of HDI compared with observation (obs) in relation to the relapse free survival (RFS) and overall survival (OS) of patients (pts) with resectable intermediate and high-risk melanoma Methods: Pts with intermediate and high-risk melanoma defined as T3 (AJCC 6th ed. >Breslow thickness 1.5mm (AJCC 7th ed. >2.0mm) or any thickness with microscopically positive node disease (N1a-N2a) were randomized to receive postoperative adjuvant Interferon (IFN) alfa2b 20 MU/m2/day for 5 days/week X 4 weeks or observation. Primary endpoints of the trial were RFS and OS. A sample size of 1420 pts was chosen to detect a 15% relative increase in the median time-to-event for those not cured and a 7.5% absolute increase in the cure rate with 88% power at a 5% level of significance, using a two-sided log-rank test. Results: Between December 1998 and October 2010, 1150 pts were enrolled – 581 assigned to HDI and 596 to obs. The breakdown of stage at entry was as follows: T2N0: 22%, T3N0: 45%, T4N0: 14%, T1-4, N1a-2a:19%. Primary ulceration was present in 36% of pts. A third interim analysis of this trial was carried out in August 2010 with RFS data in 838 and OS data in 1091 pts. The 234 RFS events correspond to 69.0% information time, while the 134 OS events correspond to 74% information time. Median RFS for Obs was 7.3 years (95% CI 5.3, 9.8; n=413) while for IFN, RFS was 6.8 years (95% CI 5.1, 9.0; n=425). The 5-year survival rate for OBS was 0.85 (95% CI .81, .89; n=535) while for IFN induction-only the 5-year survival rate was 0.82 with (95% CI .78, .86; n=556). Accrual to the trial has therefore been terminated. Conclusions: Adjuvant HDI induction with only 4 weeks therapy neither improved RFS nor OS over observation for pts with intermediate and high-risk melanoma. This trial supports the importance of HDI treatment duration and argues that the approved 1 year Interferon regimen of induction followed by maintenance remains the standard of care for pts with T4N0 or node positive disease.
Prospective comparison of running injuries between shod and barefoot runners
Authors: Allison R Altman, Irene S Davis
Journal: British Journal of Sports Medicine (2015)

Background Advocates of barefoot running suggest that it is more natural and may be a way to minimise injury risk. In contrast, opponents believe shoes are needed to adequately cushion and support the foot. However, to date, there have been no prospective studies of injury patterns in barefoot and shod runners. The purpose of this study was to compare the incidence and rate of injuries between shod and barefoot runners. Methods A prospective survey was conducted over the course of a year among 201 (107 barefoot and 94 shod) adult runners. Information regarding injuries and mileage was logged monthly using a custom, web-based database program. The number of injured runners, number of injuries per runner and injury rates were compared between habitual barefoot and habitual shod runners. Both musculoskeletal and plantar surface injuries were assessed. Results Statistically fewer overall, diagnosed, musculoskeletal injuries/runner were noted in the barefoot group. However, injury rates were not statistically different between groups due to significantly less mileage run in the barefoot group. As expected, barefoot runners sustained a statistically greater number of injuries to the plantar surface of the foot. The descriptive analysis suggests a greater number of calf injuries, but lower number of knee and hip injuries in the barefoot group. Additionally barefoot runners reported less plantar fasciitis than the shod group. Conclusions Barefoot running is associated with fewer overall musculoskeletal injuries/runner, but similar injury rates. A larger scale cohort is needed to more accurately assess differences in individual injuries between these two groups.
Abstract P103: Kidney Function and Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Takeki Suzuki, Sunil K Agarwal, Rajat Deo, Nona Sotoodehnia, Morgan Grams, Elizabeth Selvin, Hugh Calkins, Wayne Rosamond, Gordon Tomaselli, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2015)

Introduction: Individuals with chronic kidney disease (CKD), particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, data for the full-spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. Methods: We investigated the associations of baseline eGFRs using either serum creatinine, cystatin C (CysC), or both (eGFRcr, eGFRcr-cys, and eGFRcys), CysC itself, and β 2 -microglobulin (B2M) with SCD through 2001 among 13,070 blacks and whites participants at the second visit (1990-92) of the community-based ARIC Study. Cox regression models were used to quantify the associations of kidney function and different markers of kidney filtration with SCD after the adjustment for potential confounders. The cohort was divided into 5 groups based on clinical CKD Stages as well as quartiles. Results: Over a median of 11 years of follow-up, 205 participants developed SCD (1.4 cases per 1000 person-years). Low eGFR was independently associated with SCD risk: for example, HR for eGFR 30-44 vs ≥90 ml/min/1.73m 2 was 3.97 (95%CI 1.57-10.03) with eGFRcr; HR 6.96 (3.56-13.61) with eGFRcr-cys; and HR 5.47 (2.97-10.09) with eGFRcys. Of note, when eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When we compared all kidney markers based on their quartiles, B2M demonstrated the strongest association with SCD ( Table ). Qualitatively consistent results were observed across clinical and demographic subgroups. Conclusion: Kidney function was independently and robustly associated with SCD in the community, particularly when CysC or B2M were taken into account as filtration markers. These results may suggest the importance of kidney function for SCD risk evaluation and the value of novel filtration markers beyond eGFRcr in association with SCD.