tbuckley/cabot-search huggingface dataset:
Vemurafenib and ipilimumab: A promising combination?
Authors: Jessica Cecile Hassel, Sophia Lee, Frank Meiss, Friedegund Elke Meier, Antonia Dimitrakopoulou-Strauss, Dirk Jaeger, Alexander Enk
Journal: Journal of Clinical Oncology (2015)

e20075 Background: The purpose of combining targeted agents and immunotherapy is to achieve a good response with a chance of long-term tumor control. Methods: Between April 2012 and December 2013, ten patients with metastatic melanoma were treated with a combination treatment of vemurafenib and ipilimumab as an individual treatment decision after detailed information and giving written informed consent. Results: All the patients had advanced symptomatic disease, seven with elevated serum lactate dehydrogenase levels and six with brain metastases on MRI. After clinical improvement under vemurafenib monotherapy (median 11.5 weeks), four cycles of ipilimumab were administered additionally. Combination treatment was tolerated well, with only two patients developing ≥ grade 3 elevation of transaminases; this was asymptomatic and resolved on cessation of BRAF inhibitor treatment. Staging 12 weeks after initiation of ipilimumab revealed partial response for five patients, stable disease for two, and disease progression for three. Of the seven patients with disease control we stopped vemurafenib for five, to determine whether ipilimumab treatment led to disease control. Two revealed progressive disease in the next staging 2 months later, and received vemurafenib again, but for three the disease was controlled for at least a year, and two are still in partial remission without any further treatment. Progression-free survival was a median of 8.0 months (95% CI 4.8–11.2), overall survival was 13.0 months (95% CI 5.0–21.0), and four patients are still alive. Conclusions: The combination of vemurafenib and ipilimumab was well-tolerated by our cohort, and clinical outcome for advanced melanoma patients was promising. This treatment combination should be re-evaluated in larger clinical trials.
A randomized controlled trial to evaluate the effect of a new skincare regimen on skin barrier function in those with podoconiosis in Ethiopia
Authors: J. Brooks, S.J. Ersser, F. Cowdell, E. Gardiner, A. Mengistu, P.J. Matts
Journal: British Journal of Dermatology (2017)

Podoconiosis affects an estimated 3 million people in Ethiopia with a further 19 million at risk. Volcanic soil and pathogens enter skin breaches in the feet causing inflammation, lymphoedema and hyperkeratosis. There is no robust evidence on optimal podoconiosis skincare regimens to improve skin barrier function (SBF). To evaluate the effectiveness of a new, low‐cost, evidence‐based intervention to improve SBF in the lower limbs of those with podoconiosis. A randomized controlled trial (NCT02839772) was conducted over 3 months in two podoconiosis clinics (n = 193). The intervention comprised 2% (v/v) glycerine added to a reduced volume of soaking water. The control group received the current skincare regimen. Primary outcome measures were transepidermal water loss (TEWL) and stratum corneum hydration (SCH) at four specific sites on the lower limbs. Improvement in SBF was observed in both groups across all measurement sites and time points, although this was significantly greater in the experimental group. TEWL reduced in both groups at all sites. For example, on top of the foot the estimated group difference in TEWL at visit 4 was 1·751 [standard error (SE) = 0·0390] in favour of the experimental group [t = 3·15, degrees of freedom (df) = 189·58, P = 0·002, 95% confidence interval (CI) 0·066–2·85], indicating a greater reduction in TEWL in the experimental group. Similarly, at the same site the estimated group difference in SCH at visit 4 was −2·041 (SE = 0·572) in favour of the experimental group (t = −3·56, df = 186·74, P < 0·001, 95% CI −3·16 to −0·91), indicating a greater increase in SCH in the experimental group. There were also significantly greater reductions in odour, number of wounds and largest foot circumference in the experimental vs. the control group. The addition of 2% (v/v) glycerol to a reduced volume (83% reduction) of soaking water significantly improved SBF.
Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism
Authors: Saikumari Y. Krishnaiah, Gang Wu, Brian J. Altman, Jacqueline Growe, Seth D. Rhoades, Faith Coldren, Anand Venkataraman, Anthony O. Olarerin-George, Lauren J. Francey, Sarmistha Mukherjee, Saiveda Girish, Christopher P. Selby, Sibel Cal, Ubeydullah ER, Bahareh Sianati, Arjun Sengupta, Ron C. Anafi, I. Halil Kavakli, Aziz Sancar, Joseph A. Baur, Chi V. Dang, John B. Hogenesch, Aalim M. Weljie
Journal: Cell Metabolism (2017)
Autologous bone marrow (BM) stem cell transplantation into infarcted myocardium –A pilot study
Authors: S. Mohanty, L. Kumar, P. Venugopal, B. Airan, R. Narang, A. K. Bisoi, K. K. Talwar
Journal: Journal of Clinical Oncology (2004)

6667 Background: BM stem cells have ability to differentiate into cardiac myocytes, smooth muscle cells and endothelial cells when injected into the myocardium after ischemic injury. Methods:21 patients of myocardial infarct (confirmed on stress thallium SPECT and trans-thoracic echocardiography) undergoing CABG (coronary artery bypass grafting) were studied. During CABG, BM was harvested in heparinised syringes by sternal aspirate. BM mononuclear cells (MNC) were separated using Ficoll density gradient centrifugation. At the end of the CABG, MNC were injected in and around the region of myocardial scar in 19 patients. In 2 patients stem cells were implanted through infarct related artery by coronary angioplasty. Results:The mean age of the 21 patients was 50.57years (SD =7.07) with male: female ratio of 19:2. The mean volume of BM collected was 35.33ml (SD =8.6) with a cell count of 1.3 x 107/ml (SD =2 x107). Viability of the MNC was 99% (checked by Trypan blue dye exclusion test). The MNC morphology was also seen under the light microscope by Giemsa staining and the average percentage of MNCs was 89.28 (SD=1.7). CD 34+ cells were enumerated by flowcytometry in 5 patients only, and the mean count was 0.95% (SD = 0.54). The MNCs were finally suspended in normal saline and a mean of 38+9 infarct sites were injected with 0.25ml /site. The average number of cells injected per site was 3.2 x 106. There was no adverse effect of the procedure (immediate, in-hospital or at a mean follow-up of 5.9 months + 2.8 mo). Specifically, there were no deaths and no significant ventricular arrhythmias on 24 hour holter monitoring. Initial follow-up information is currently available for the first 8 patients. There was improvement in New York Heart Association functional class (from 2.67+0.82 to 1.5+ 0.55; p=0.02) and left ventricular ejection fraction (from 30+ 13% to 42+ 10%; p=0.04). Three and 6 months follow-up data (invasive and non-invasive) is being acquired. Conclusions:This pilot study has indicated the potential safe use of the hematopoietic stem cells for repair of myocardium. No significant financial relationships to disclose.
The impact of young age on outcome in colon cancer
Authors: C. Truong, S. Kempton, S. Lum, J. W. Morgan, J. H. Wong, S. Roy-Chowdhury
Journal: Journal of Clinical Oncology (2009)

4075 Background: The early age of diagnosis (&lt;40 years) of colon cancer (CC) is generally considered to be associated with a particularly grave prognosis. Our objective was to determine the prognostic relevance of young age on outcome in CC. Methods: Retrospective cohort study from Region 5 of the California Cancer Registry (R5 CCR). Survival by Kaplan- Meier with significance assessed by log-rank test, T-test and Chi Square where appropriate. Results: Between January 1,1994 and December 31, 2003 10,730 patients with CC were diagnosed in R5 CCR. The patients ranged in age from 18–103 years (mean 71.1 years). Two hundred fourteen patients (2%) were 40 years of age or younger. The mean age of young patients was 34.6 years (range 18–40) and for old patients 71.3 years (range 41–103). The mean number of nodes examined were 18.5 in the young CC patient and 18.4 in the remainder of CC patients. There was no significant difference in the anatomic sub-site of the primary between younger and older CC patients (p=0.43). Young patients presented with more advanced primary tumors (T4 18.7% vs. 11.6%, p=0.03), more frequently with more extensive nodal involvement (N+ (54.4% vs. 40.2%, p&lt;0.0001), and more frequently with distant metastatic disease (M1 25.7% vs. 18.3%, p=0.005). Despite these adverse characteristics, young patients had a significantly better disease specific survival (DSS) compared to their older counterparts (5 year survival 70.1% vs. 62.3%, p=0.02). Young patients had a suggestion of improved DSS compared to older patients in Stage I disease (5 yr DSS 96.0% vs. 90.5%, p=0.34) with more certain evidence of improved DSS in Stage II (5 yr DSS 94.8% vs. 79.9%, p=0.02), Stage III (5 yr DSS 73.4% vs. 57.2%, p=0.01) and most profoundly in Stage IV (5 yr DSS 20.1% vs. 0.08%, p=0.002). Conclusions: Despite adverse characteristics at diagnosis, young CC patients have a better DSS than their older counterparts. This is in contrast to the generally held opinion that young CC patients fare worse. This may reflect the ability of young CC patients to accept and tolerate more intense and aggressive therapies. No significant financial relationships to disclose.
Histological and perioperative outcomes of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced germ cell turmors – A single center experience.
Authors: Achim Lusch, Martin Zaum, Christian Winter, Ruediger Krauspe, Klaus Grabitz, Peter Albers
Journal: Journal of Clinical Oncology (2015)

e15557 Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is standard of care for patients (pts) with non-seminomatous germ cell tumors. Aim of this analysis is an update of histological findings, complications and necessity of adjunctive procedures in the era of modern perioperative care from a large single-center cohort. Methods: Our single center database was evaluated for perioperative outcomes of 295 pts with 312 PC-RPLNDs. 193 pts received surgery after 1st line chemotherapy (CTX), 48 pts after 1stor subsequent conventional salvage CTX, and 70 pts after high-dose (HD) salvage CTX. Results: Mean age was 34 yrs and mean residual tumor size was 3 cm (1-25). Mean OR time was 235 min (90-510) and mean intra-operative blood loss was 1246 cc (0-15000). 36% of pts needed blood transfusions. In 21.2% of cases a significant vascular injury was seen: aorta (8.6%), v. cava (10.2%), and others like renal vein (2.9%). Caval and aortic replacement was performed in 24 (7.7%) and 7 (2.9%) of the cases, respectively. Adjunctive surgical procedures, like nephrectomy, partial liver resection, and vertebral resection were performed in 36 (11.5%), 30 (9.6%), and 12 (3.8%) of cases, respectively. Complications by Clavien-Dindo: Grade I: 27% (incl. postoperative hematoma and lymphocele), Grade II: 36% (incl. blood transfusion); Grade III: 2.6%; Grade III b: 2.6%; Grade IV a: 1%; Grade V: 0.3%. Overall Clavien-Dindo grade > III complications: 6.5%. Final histology revealed vital cancer in 36/193 (18.6%) after 1st line CTX, 10/48 (20.8%) after conventional salvage, and 35/70 (51.4%) after salvage HD-CTX. Predominant vital cancer histology after HD-CTX was embryonal cancer and yolk sac tumor. Conclusions: In every 2nd pt after salvage HD-CTX and in every 5th patient after 1st line or conventional salvage CTX PC-RPLND revealed vital cancer. Frequent adjunctive surgical procedures, such as vascular interventions with possible aortic and caval resection are common ( > 25%). This type of surgery requires a complex multidisciplinary approach and should be performed in experienced tertiary referral centers only.
Efficacy and safety of bevacizumab combined with capecitabine in progressive, metastatic well-differentiated digestive endocrine tumors (BETTER study).
Authors: Emmanuel Mitry, Thomas Walter, Eric Baudin, Jean-Emmanuel Kurtz, Philippe Ruszniewski, Sophie Dominguez, Leila Bengrine-Lefevre, Guilaume Cadiot, Sandrine Kraemer, Michel Ducreux
Journal: Journal of Clinical Oncology (2012)

4071 Background: Neuroendocrine digestive tumors are highly vascularized neoplasms known to express the vascular endothelial growth factor (VEGF). We assessed the activity of bevacizumab (Bv), a monoclonal antibody directed against VEGF combined with capecitabine (CAP). Methods: In this multicenter, open-label, non-randomized, two-group phase II trial, one group assessed Bv (7.5 mg/m² on d1/3 weeks) combined with CAP (1,000 mg/m 2 twice daily, orally d1-14, resumed on day 22). Eligible patients (pts) had progressive, metastatic well-differentiateddigestive tract endocrine tumors (WHO 2000 classification), ECOG-PS ≤2, Ki 67 index &lt; 15%, no prior systemic chemotherapy and acceptable organ functions. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival, response rate, safety and quality of life. Pts were treated for a minimum of 6 months and study duration was 24 months. Results: From Jun 2007 to Oct 2009, 49 pts were enrolled, 26 (53.1%) were men; median age 60.3 years (41.2-82.3); ECOG-PS was 0/1 in 46 (93.9%) pts. Primary tumor site was: small intestine 40 (81.6%) pts, caecum 3 (6.1%), rectum 4 (8.2%) and stomach 2 (4.1%). Ki-67 proliferative index was 0-2% in 17 (35.4%) pts, 3-4% in 14 (29.2%), 5-9% in 13 (27.1%), 10-14% in 4 (8.3%) Metastatic sites were liver: 46 (93.9%) pts, lymph nodes: 24 (49.0%), peritoneum 23 (46.9%). Median treatment duration was 13.8 months; median number of cycles was 19. At 24 months, median PFS was 23.4 months [95%CI: 13.2; not reached] based on 26 events. PFS rate at 18 months was 55%. Tumor control rate was 87.8% (n=43) including partial response in 9 (18.4%) pts and stable disease in 34 (69.4%) pts. Survival rate at 24 months was 85%, median overall survival was not reached, 8 patients died. CTC grade 3/4 Adverse Events (AEs) occurred in 41 (83.7%) pts, mainly digestive 14 (28.6%) pts. Main G3/4 Bv targeted AE was hypertension in 15 (30.6%) pts. Conclusions: In this chemotherapy resistant tumor, the combination of capecitabine and bevacizumab, assessed in a phase II study, shows such encouraging results that this combination may become a reference in the medical treatment of ileal NET.
Polyglutamine-Expanded Huntingtin Exacerbates Age-Related Disruption of Nuclear Integrity and Nucleocytoplasmic Transport
Authors: Fatima Gasset-Rosa, Carlos Chillon-Marinas, Alexander Goginashvili, Ranjit Singh Atwal, Jonathan W. Artates, Ricardos Tabet, Vanessa C. Wheeler, Anne G. Bang, Don W. Cleveland, Clotilde Lagier-Tourenne
Journal: Neuron (2017)
DNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury
Authors: Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
Journal: Kidney International (2017)
Evaluation of thoracic stereotactic body radiation therapy (SBRT) for stage IV non-small cell lung cancer (NSCLC).
Authors: Charles Eric Wooten, Adam Joel Taylor Smith, Jason M Edwards, Susanne M. Arnold, Ronald McGarry
Journal: Journal of Clinical Oncology (2014)

e19093 Background: Thoracic SBRT in patients with stage IV non-small cell lung cancer (NSCLC) has the potential to improve overall survival (OS) by controlling the most likely sites of relapse and delaying disease progression, as is the case with treatment of oligometastasis. We hypothesized that thoracic control with SBRT can improve OS for select patients with stage IV NSCLC. Methods: A retrospective review was performed of all stage IV NSCLC patients treated with SBRT from January 2007 through July 2013. Patients had total of ≤ 5 sites of oligometastasis. All patients received SBRT to a thoracic site. Patients were commonly treated with a biological equivalent dose ≥ 100. Results: 23 patients were treated to a total of 30 thoracic sites with SBRT. Median age was 63 (43 – 91) and median follow up after SBRT was 12.0 months for all patients. The 1, 2 and 3 year actuarial OS rates were 86.7%, 45.7% and 22.8% respectively. Median OS was 24 months for all patients. Median survival of 8 patients who received systemic therapy with consolidation to all oligometastatic sites was 36 months. Advanced T stage at diagnosis, number of thoracic sites treated, systemic therapy, treatment of all oligometastatic sites and Karnofsky performance status > 80 were associated with improved OS. Only two patients were found to fail locally. Grade 3 toxicity was limited to a single instance of pneumonitis. Conclusions: Thoracic SBRT for oligorecurrent, oligometastatic and residual disease in stage IV NSCLC was associated with favorable OS for select patients when compared to historical controls. Receiving consolidative therapy to all known sites of disease in conjunction with systemic therapy was predictive for substantially greater OS. Thoracic cytoreduction to appropriate patients with stage IV NSCLC is associated with improvement in OS.
A phase I/II study of Xcellerated T Cells after autologous peripheral blood stem cell transplantation in patients with multiple myeloma
Authors: I. M. Borrello, R. Vij, R. A. Vescio, T. G. Martin, D. Siegel, J. R. Berenson, F. Janmohamed, M. Bonyhadi, R. J. Berenson, M. W. Frohlich
Journal: Journal of Clinical Oncology (2004)

2540 Background: Previous studies have demonstrated an association between survival & lymphocyte recovery following autologous transplantation (Porrata et al., Blood 2001). We have initiated a trial in the transplant setting to evaluate the activity of T cells activated and expanded ex vivo with the Xcellerate Process, which uses anti-CD3 and anti-CD28 antibody coated magnetic beads. Methods: Following induction therapy, patients undergo leukapheresis to collect peripheral blood mononuclear cells for the Xcellerate Process. Patients then undergo stem cell mobilization and collection, followed by high dose melphalan (200 mg/m2). Three days following peripheral blood stem cell infusion, patients receive 50–100 x 109 Xcellerated T Cells. Results: 36 patients have been treated with median f/u of 143 days post transplant (range 10–353). Using a new bioreactor process instituted during the trial, T cells expanded 268 ± 101 fold (mean + SD), with 93.6 ± 0.8 x 109 cells infused, & final product 98.5 + 2.3% T cells (n = 19). There have been no Grade 3 or 4 acute infusional toxicities. Days of neutropenia and thrombocytopenia have been 5 (3–43) and 4 (0–88) respectively [median (range)] . Lymphocyte recovery has been rapid, with counts reaching > 500/mm3 generally within 1–2 days following T cell infusion. Historically, lymphocyte recovery to > 500/mm3 usually does not occur for 3 or more weeks post-transplant. The T cell repertoire measured 25 days following T cell infusion demonstrates a more normal pattern than prior to T cell infusion (n = 5). This is in contrast to the severe skewing of T cell receptor diversity normally seen in myeloma patients following autologous stem cell transplantation (Mariani et al, BJH 2001). In 24 patients with median f/u of 135 (45–270) days, preliminary results demonstrate 13% CRs, 42% VGPRs, 33% PRs, and 13% with PD, using the pre-induction M-protein as reference. Conclusions: Xcellerated T Cell therapy leads to rapid lymphocyte recovery and appears to restore a normal T cell receptor repertoire. Additional follow-up is needed to determine if this will translate to improved clinical outcomes. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcyte Therapies, Inc. Xcyte Therapies, Inc. Xcyte Therapies, Inc.
Treatment patterns among patients with higher-risk myelodysplastic syndromes in a real-world setting: Electronic medical record (EMR)-based data.
Authors: Bruce Jeffrey Dezube, Jill Bell, Aaron Galaznik, Eileen Farrelly, Marlo Blazer, Brian S. Seal, Huai-Che Shih, Michael Eaddy
Journal: Journal of Clinical Oncology (2017)

247 Background: Treatment decisions in MDS are based on a prognostic scoring system that divides pts into five distinct risk categories (NCCN 2016). Treatment guidelines for HR MDS pts include hypomethylating agents (HMAs) alone (azacitidine &amp; decitabine), high-intensity induction chemotherapy (IC), &amp; stem cell transplant (SCT) alone or after HMAs. Limited information is available on how these recommendations are applied in practice. This study evaluated the real-world treatment of HR MDS pts. Methods: Newly diagnosed HR MDS pts who were ≥18 years old &amp; initiated first-line therapy (1LT) were retrospectively identified from a large United States EMR database between 1/1/2008 &amp; 7/31/2015. As complete cytogenetics were not available in the database, HR was based on: ICD coding: ≥1 inpatient claim with an HR MDS ICD-9/10 code (ICD-9 code: 238.73; ICD-10 codes: D46.20, D46.21, D46.22), or ≥2 outpatient claims with an MDS ICD-9/10 code, or an adapted HR MDS algorithm (NCCN Guidelines in Oncology for MDS v.1.2016; Greenberg, et al. Blood. 2012;120:2454-65; Schanz et al. J Clin Oncol. 2012;30:820-9). The first MDS claim served as the index date. 1LT was defined as an MDS-specific treatment initiated on or after the index date. Pts were followed until death, progression to acute myeloid leukemia (AML), loss to follow-up, or end of study (9/30/2015). Results: 720 newly diagnosed HR MDS pts were identified; of these, 229 (32%) pts received MDS-specific treatment. Median time to treatment was 22 days (interquartile range [IQR]: 10, 74). HMAs were the most common agents in the 1LT with 60% (n= 138) &amp; 24% (n=54) receiving azacitidine &amp; decitabine, respectively. Lenalidomide was used in 7.4% of pts (n=17), 4.8% received SCT alone (n=11), &amp; 3.9% (n=9) received IC. At median follow-up of 9.4 months (IQR: 4.3, 18.4), 38% (n=86) died &amp; 28% (n=63) progressed to AML. Conclusions: Despite guidelines, most HR MDS pts in a real-world setting were not treated with MDS-specific treatment. Among treated pts, 1LT with HMAs &amp; azacitidine predominated. Subsequent research is needed to understand reasons for lack of treatment.