tbuckley/cabot-search huggingface dataset:
The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.
Authors: Naomi Hayashi, Goro Nakayama, Kiyoshi Ishigure, Hiroyuki Yokoyama, Toyohisa Yaguchi, Hiroshi Kojima, Kenji Tsuboi, Akihiro Ito, Tomohiro Deguchi, Masanori Sekiya, Chie Tanaka, Keisuke Uehara, Yuichi Ando, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2013)

e14552 Background: XELOX plus bevacizumab (BEV) is an established first line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty two patients (59%) were reintroduced oxaliplatin. After a median follow-up time of 24.2 months, median PFS was 13.4 months (95%CI: 11.7-15.1), median duration of disease control was 13.8 months (95%CI: 11.6-16.0) and median overall survival was 29.0 months (95%CI: 23.1-34.9). The response rate and disease control rate were 57.4% and 96.3% in the initial XELOX plus BEV therapy, 6.1% and 73.5% in Cape plus BEV maintenance therapy, and 0% and 72.4% in reintroduced XELOX plus BEV therapy. The incidence of neuropathy was 38% in initial therapy, 33% in maintenance therapy and 43% in reintroduced therapy. Conclusions: XELOX plus bevacizumab therapy with oxaliplatin stop-and-go strategy was feasible to maintain long disease control without increasing severe neurotoxicity in first-line treatment for mCRC. Clinical trial information: UMIN000006478.
Treatment patterns and outcomes in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC) treated in first line with bevacizumab (B) or cetuximab (C) containing regimens.
Authors: Arthur C. Houts, Sarika Ogale, Nicolas Sommer, Mark Stephen Walker
Journal: Journal of Clinical Oncology (2016)

550 Background: Patients with KRAS WT mCRC treated with B or C plus standard chemotherapy backbones had comparable outcomes in the Phase III CALGB 80405 trial; comparative effectiveness in a real-world community setting remains unknown. Methods: This retrospective study examined PFS and OS in a US community sample of adult, KRAS WT, mCRC patients treated 1 st line with B or C containing regimens. Medical records from the Vector Oncology and Affiliate Data Warehouse were used. Disease progression was determined from patient charts. OS was measured from start of 1 st line treatment until death; patients were censored at the last observed office visit. Results: B and C samples were comparable on patient characteristics (Table). Oxaliplatin-based and Irinotecan-based backbones were used more frequently with B and C, respectively. Median PFS and OS did not differ significantly between B and C, and were of similar magnitude as in CALGB 80405. In Cox models, number of metastatic sites was a significant predictor of PFS and OS, p &lt; 0.01. Outcomes did not differ significantly with different chemotherapy backbones. Conclusions: Consistent with CALGB 80405, 1st line PFS and OS for KRAS WT mCRC patients treated with B or C were comparable in this real-world analysis. Further analyses will focus on treatment sequences. [Table: see text]
Adverse effect of Bevacizumab; comparison between lung cancer versus colon cancer
Authors: Aya Nakaya, Takashi Yokoi, Shigeyoshi Iwamoto, Yoshitaro Torii, Yuichi Katashiba, Makoto Ogata, Takayasu Kurata, Madoka Hamada, Masanori Kon, Shosaku Nomura
Journal: Annals of Oncology (2015)
Treatment of dendritic cell sarcoma: 18-year experience at the MD Anderson Cancer Center.
Authors: Preetesh Jain, Keyur Patel, Carlos E. Bueso-Ramos, Jorge Enrique Romaguera, Luis Fayad, Larry W. Kwak, Nathan Hale Fowler
Journal: Journal of Clinical Oncology (2014)

8596 Background: Dendritic cell sarcomas (DCS) are rare tumors including follicular dendritic cell sarcoma (FDCS) and interdigitating cell sarcoma (IDCS). Typically DCS are difficult to diagnose and are associated with poor outcomes with standard therapy. Methods: This is a comprehensive retrospective analysis of 35 pts with confirmed diagnosis of DCS (FDCS n=31; IDCS n=4) treated at MDACC between 1995 and 2013. Pts were identified from an institution database and data was collected on the diagnosis, management and clinical outcomes of pts. Results: Median age at diagnosis was 50 yrs (range 17-74 yrs) and 58% were female. 60% pts presented with localized disease and 40% with systemic involvement. Abdomen was involved in 17/35 pts and the spleen (7/35) was the most common extranodal site. Bulky disease (> 5 cm) was noted in 21 pts. Nine pts had pre-existing or subsequent autoimmune disease. Common markers for FDCS were clusterin; EGFR, CD21, CD35 and CD23 in 94%, 87%, 89%, 77% and 63% samples. For IDCS, common markers included S-100 and CD68 in 100% and 75% pts. Molecular studies were performed in 2 pts who were negative for BRAF mutations. One pt had TP53 exon 8 and another PTEN mutation. Surgery followed by adjuvant chemotherapy was initial treatment in (23/35) and chemotherapy alone in (12/35) pts. Gemcitabine with taxanes and CHOP based regimens were most commonly used, and were associated with response rates of 86% and 60% respectively. Complete responses were rare. Median progression free and overall survival following systemic therapy was 41 and 59 months respectively. Pts with systemic presentation had inferior outcomes compared to those with localized disease. Conclusions: We present the largest single center report of pts with DCS. While detailed histopathological studies are necessary to define DCS, we identified several makers common to both FDC and IDCS. We observed higher responses with gemcitabine/docetaxel combinations compared to CHOP based therapy, but limited numbers make comparisons difficult and prospective studies are needed to define optimal treatment in this rare disease. Studies are currently underway at our institution to define the genomic profile in DCS and identify potential targets for therapy.
Whole-brain radiotherapy with concurrent fixed-dose daily temozolomide for brain metastases treatment: A randomized phase II trial.
Authors: C. Gamboa-Vignolle, O. G. Arrieta Rodriguez, T. Ferrari-Carballo
Journal: Journal of Clinical Oncology (2010)

2058 Background: Temozolomide (TMZ) a DNA alkylating agent crosses the blood brain barrier reaching therapeutic levels in brain; concurrent with whole-brain radiotherapy (WBRT) has been a treatment of brain metastases (BM). TMZ alone has been administered in advanced neoplasms at oral fixed-dose for 5 of every 7 days, at a maximum tolerated dose of 360 mg/d. Methods: This open label, randomized phase II trial, was designed with a type I error of 0.05 and power of 0.80. The primary aim was to find a difference in objective response rate (ORR) of 0.29 favorable to experimental arm (A). Patients (Pts) received TMZ at a fixed oral dose of 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday, before each one of 10 WBRT sessions, 30 Gy/2 weeks total dose, in arm A (without extra cycles of TMZ). In control arm (B) the same WBRT schedule only. Secondary aims were to compare BM progression-free survival (BMPFS), overall survival (OS), and systemic toxicity (AE) development. Eligibility criteria: both genders, previously untreated BM from solid neoplasms, CT or IRM diagnosed, life expectancy ≥ 12 weeks, KPS ≥ 50, adequate bone marrow, liver, and renal function. Extracranial metastases or primary tumor uncontrolled were allowed. Responses were confirmed according RECIST. Results: From Jan. 2006 to Sep. 2009 55 pts were enrolled, 28 into A and 27 into B. They were analyzed by intent-to treat. ORR was 78.6% (22/28) vs. 48.1% (13/27) for A vs. B, respectively (p = 0.019). Median of BMPFS was 11.8 (95% CI, 4.7-18.9) vs. 5.6 (95% CI, 4.9-6.2) months for A vs. B, respectively (p = 0.014). No difference was found in median OS. There was no acute neurologic toxicity. Lymphopenia G 3-4, was of 50% vs. 22.2% in A vs. B respectively. Also, leucopenia G3 in 1 patient; Thrombocytopenia G3 in 2 pts, G4 in 1 patient; G2 nausea/vomiting in 6 pts, and G3 in 1 patient were observed in A. There was no additional G3-4 EA in B. Conclusions: This scheme of WBRT plus TMZ was well tolerated, and resulted in significantly better local control of BM than WBRT alone, a phase III clinical trial is warranted. No significant financial relationships to disclose.
Multi-tiered Reorganization of the Genome during B Cell Affinity Maturation Anchored by a Germinal Center-Specific Locus Control Region
Authors: Karen L. Bunting, T. David Soong, Rajat Singh, Yanwen Jiang, Wendy Béguelin, David W. Poloway, Brandon L. Swed, Katerina Hatzi, William Reisacher, Matt Teater, Olivier Elemento, Ari M. Melnick
Journal: Immunity (2016)
An Optimized, Large Scale Generation and Validation of Aspergillus-Specific T Lymphocytes for the Management of Invasive Aspergillosis in Immunocompromised Patients
Authors: Anastasia Papadopoulou, Panayotis Kaloyannidis, Maria Alvanou, Joanne Kalogeropoulou, Achilles Anagnostopoulos, Evangelia Yannaki
Journal: Blood (2015)
P3-131: Mutations of EGFR and k–ras oncogene as predictors of tyrosinkinase inhibitors therapeutic outcome in NSCLC patients
Authors: Milos Pesek, Lucie Bene∫ová, Barbora Bel∫ánová, Franti∫ek Brùha, Petr Muken∫nabl, Dana Janèaoíková, Jana Krejèí, Marek Minárik
Journal: Journal of Thoracic Oncology (2007)
DIFFERENTIAL EXPRESSION OF PD-L1, PD1 AND CTLA4 RECEPTOR ACCORDING TO HISTOLOGY AND TUMOUR VS. SURROUNDING NON-MALIGNANT LUNG TISSUE IN NON-SMALL CELL LUNG CANCER: RNA SEQUENCING DATA
Authors: Dirk De Ruysscher, Els Wauters, Kobe Reynders, Johan Vansteenkiste, Herbert Decaluwe, Paul De Leyn, Kristiaan Nackaerts, Stéphanie Peeters, Christophe Dooms, Wim Janssens, Diether Lambrechts
Journal: Journal of Thoracic Oncology (2013)
Justice and Global Health Research
Authors: Sridhar Venkatapuram
Journal: The American Journal of Bioethics (2016)

One of the most interesting and knotty puzzles in global health justice can be found in Margaret Whitehead's decision tree for determining which health inequalities across human beings demand a social response. Whitehead argued that the subset of health inequalities that are avoidable, unnecessary, and unfair or unjust are health “inequities” (Whitehead 1990). While inequalities are value-free observations, inequities are moral bads that demand social action. While the effort is praiseworthy, I have argued elsewhere that many aspects of the health equity principles are problematic (Venkatapuram 2011). In particular, at the first step, a health inequality or impairment that is deemed unavoidable is moved outside of the scope of equity, ethics, and justice. In philosophy, it is often stated that a moral “ought implies can.” So if a disease/impairment is unpreventable or untreatable, there cannot be an ethical duty to prevent or mitigate a resulting health inequality. However, such a first cut would also dissipate any claims to or duties to conduct research on a disease/impairment that is currently unavoidable because we lack the knowledge about how to do so. A health inequality can also be unavoidable because there are not enough resources in a specific location to apply extant knowledge such as in many developing countries. Therefore, in relation to health and more, the prevailing view has been that moral claims and duties that cannot be immediately fulfilled are meaningless. Informed by his analyses of famines and Ronald Dworkin's account of rights, Amartya Sen offered a novel argument for a “meta-right”—a meta-right to x is a right to policies p(x) that genuinely aim to have the right to x realizable (Sen 1984). Sen's meta-right challenges Whitehead's first principle. When a health inequality is deemed unavoidable, a meta-right to health can still motivate both health sciences research and broader social and economic policies that aim toward realizing a right to health. That is why it is at the core of my argument for a human right to health or, more accurately, a meta-right to the meta-capability to be healthy.
Treatment or Monitoring for Early Prostate Cancer
Authors: Anthony V. D’Amico
Journal: New England Journal of Medicine (2016)

The "best" initial approach to early (low-risk or intermediate-risk)1 prostate cancer remains unknown. Specifically, does active monitoring with the use of prostate-specific antigen (PSA) testing as opposed to treatment lead to increased metastasis and death from prostate cancer? If yes, then which treatment, radical prostatectomy or radiation with or without short-term (3 to 6 months) androgen-suppression therapy, minimizes metastasis and death from prostate cancer?Hamdy and colleagues now report in the Journal the results of a randomized comparison of three of these four approaches after a median follow-up of 10 years,2 and Donovan and colleagues present data on patient-reported health-related . . .
Management of the patient with SVR
Authors: Norah A. Terrault, Tarek I. Hassanein
Journal: Journal of Hepatology (2016)

In the current era of therapy with direct-acting antiviral (DAAs) drugs, achievement of a sustained virological response (SVR) is achievable in ⩾90% of hepatitis C-infected patients. SVR benefits are well-recognized with reductions in rates of liver complications, hepatocellular carcinoma and mortality. Additional benefits include reduced morbidity related to extrahepatic and systemic manifestations of hepatitis C such as renal, dermatologic, and metabolic complications. However, not all patients will derive all of these benefits and monitoring for progression is necessary, especially in those with more advanced fibrosis. To maximize the health benefits of SVR, counseling patients on best means to maintain good liver health and prevent reinfection are also important.
Benefits and limitations of liquid biopsy in one patient’s clinical trial paradigm.
Authors: Jean-Francois Laes
Journal: Journal of Clinical Oncology (2016)

e23096 Background: Each cancer has its individual molecular and genetic fingerprints. Liquid biopsy tests are gaining ground within the industry and the oncology community and are considered as a viable alternative (or potential replacement) to traditional screening methods. Liquid biopsies are helpful to monitor the burden of the disease and identify mutations associated with resistances to targeted therapies. However, the comprehensive characterization of the resistant metastases remains necessary to adapt the treatment. Methods: 10 metastatic cancer patients have been sequenced for 409 genes at high coverage. In parallel IHCs targeting key pathways (mTOR, cell cycle, MAKP/ERK) have been performed. Based on those results different approved treatments were given to patients. They have then been monitored through liquid biopsies using specific markers coming from the initial tumor and a set of > 200 hotspots mutations related to resistance to targeted therapies. Results: For all patients, one or several variants have been found in the blood during the treatments leading to the conclusion of relapsing. All of those results have been confirmed by the oncologist; no false positive results reported. Over 5 patients, only one metastasis didn't schrink. A new biopsy was taken and a new profiling of NGS and IHCs was made. We reported common mutations at higher percentage (considered as driver mutations) but also new mutations associated with the same pathway than the one found in the first biopsy. We performed an new sequencing on those variants by increasing the coverage and found that some variants were present at very low percentage (confirming the heterogeneity of the tumor but still related to the same pathway). IHCs showed the same results but based on the NGS and the treatment, new hypothesis and new IHCs were performed leading to new possibilites of treatment. Conclusions: Thanks to a small cohort of patients with advanced metastatic tumors from different locations, we developed a personalized molecular passport combining the tumor profiling and its monitoring. This proof of concept trial demonstrated that characterization and evolution of a patient's tumor would help manage cancer as a chronic disease by being less invasive as possible.
再灌流療法における高速補正化TIMIフレームカウント(CTFC)は心筋損傷重症度を初期CTFCよりも正確に反映する
Authors: Matsuo Shusuke, Hinoi Toshihide, Tadehara Futoshi, Tomohiro Yasuyuki, Tsujiyama Shuji
Journal: Circulation (2007)
Reproductive Health as a Marker of Subsequent Cardiovascular Disease
Authors: JoAnn E. Manson, Teresa K. Woodruff
Journal: JAMA Cardiology (2016)

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UN urges broader access to drugs
Authors: Anne Gulland
Journal: BMJ (2016)

Drug companies and governments must do more to ensure access to drugs among the world’s poorest people, a United Nations report has urged.

The final report of the UN secretary general’s high level panel on access to medicines said that despite the improvements brought by medical innovation in the field of vaccines and antiretroviral drugs for HIV/AIDS over the past few decades, “millions of people continue to suffer and die from treatable conditions because of a lack of access to health technologies.”1

It said that investment in research and development (R&D) did not adequately …
CCDC26 Polymorphisms Are Differentially Expressed in Myeloid Malignancies with Mutant IDH1 Compared to Their IDH2R140-Mutated or IDH-Unmutated Counterparts
Authors: Terra L Lasho, Ayalew Tefferi, Animesh Pardanani, Christy Finke, Stephanie R Fink, Paul A Decker, Robert Jenkins
Journal: Blood (2011)
Microenvironmental Factors and The Role Of Tumor Necrosis Factor Receptor Type 1 (TNFR-1) In Chronic Lymphocytic Leukemia
Authors: Claudia Duerr, Angela Schulz, Sibylle Ohl, Thorsten Zenz, Stephan Stilgenbauer, Peter Lichter, Martina Seiffert
Journal: Blood (2013)
Improved topical delivery of tacrolimus: A novel composite hydrogel formulation for the treatment of psoriasis
Authors: Doris Gabriel, Thibault Mugnier, Herve Courthion, Ksanthi Kranidioti, Niki Karagianni, Maria C. Denis, Maria Lapteva, Yogeshvar Kalia, Michael Möller, Robert Gurny
Journal: Journal of Controlled Release (2016)
P1-171: Low risk subgroup identification in stage IB lung adenocarcinoma patients
Authors: Tetsuya Mizuno, Genichiro Ishii, Kanji Nagai, Junji Yoshida, Mitsuyo Nishimura, Takahiro Mochizuki, Osamu Kawai, Takahiro Hasebe, Atsushi Ochiai
Journal: Journal of Thoracic Oncology (2007)
Immunologic profiling of consensus molecular subtype (CMS) stratified colorectal cancer (CRC) primary and liver metastectomy specimens: Implications for immune targeting of proficient mismatch repair CRC.
Authors: Matthew Reilley, Jorge M Blando, Riham Katkhuda, David Menter, Padmanee Sharma, James Patrick Allison, Scott Kopetz, Dipen M. Maru, Michael J. Overman
Journal: Journal of Clinical Oncology (2016)

3520 Background: While checkpoint blockade therapy has shown promise in mismatch repair-deficient CRC, these represent a small fraction of overall cases. Limited data exists regarding the immune microenvironment of mismatch repair-proficient CRC, hindering efforts to develop novel immunotherapy treatments for the majority of CRC patients. Methods: Quantification of immune subsets was evaluated by immunohistochemical (IHC) analyses in 23 primary MSI tumors, 45 primary MSS tumors and 34 untreated liver metastatectomy (LM) specimens for both center of tumor (CT) and invasive margin (IM) regions. Immunologic data, tumor microsatellite status, and consensus molecular subtype (CMS) were evaluated for possible correlations. Results: In CT, we found average CD3, CD4 and CD8 T cell infiltrates to be 6%, 3%, and 2% respectively for LM vs 9%, 4% and 5% for MSI vs 7%, 4% and 4% for MSS. In IM, we found average CD3, CD4, and CD8 T cell infiltrates to be 24%, 11% and 12% for LM vs 29%, 16% and 18% for MSI vs 25%, 14% and 12% for MSS. Higher T cell infiltrates were found in IM as compared to CT (p < 0.01) and there were fewer CD8 T cell infiltrates found in metastases as compared to primary tumors (p < 0.01). We observed higher average frequency of CD68 macrophages in LM in both CT (26%) and IM (55%) as compared to MSI (CT = 21%; IM = 32%; p < 0.01) and MSS (CT = 18%; IM = 32%; p < 0.01). Average CT PD-L1 expression on tumor cells was higher in MSI (27%) vs MSS (9%) and LM (3%). We did not observe significant differences between LM, MSI and MSS for CD45RO and granzyme-B expression. Stratified by CMS subtypes, CD8 T cell infiltration (p < 0.01) and PD-L1 expression on tumor cells (p < 0.01) were significantly higher in CMS1 (immune subtype). CMS3 (metabolic subtype) demonstrated higher expression of ICOS in CT (p < 0.05) and OX40 (CT p = 0.05; IM p < 0.01) than other subtypes. Conclusions: Our findings support evidence for efficacy of PD-1/PD-L1 blockade in CMS1 and suggest that CMS3 CRC subtype may benefit from unique immunotherapy combinations. These findings have important implications for future immunotherapy approaches in CRC and merit further investigation.
The uncommon expression of B7 in gastrointestinal marginal zone B-cell lymphoma is associated with an absence of rearrangements and amplication of the B7 gene
Authors: A Driessen, J Dierlamm, Nadine Ectors, M Stul, Iwona Wlodarska, Anne Hagemeijer-Hausman, Christiane Peeters
Journal: Gut (1999)