tbuckley/cabot-search huggingface dataset:
Dexamethasone as a means for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein and also for controlling oxaliplatin-induced hypersensitivity reactions.
Authors: Yoichiro Yoshida, Seiichiro Hoshino, Naoya Aisu, Hironari Shiwaku, Richiko Beppu, Syu Tanimura, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2012)

662 Background: With the recent development of XELOX therapy involving oral administration of drug preparations, etc., implantation of a CV port can be now avoided. However, vascular pain (pain in the peripheral veins) occasionally requires switching of the drip infusion route during XELOX therapy. Some investigators reported that addition of steroids to oxaliplatin drip infusion is useful in controlling vascular pain. However, the pharmacological use of steroids can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of oxaliplatin in this therapy is unknown because of lack of published data. This study was undertaken to evaluate the effectiveness of dexamethasone (DEX) in infusion solution containing oxaliplatin for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein. Methods: The study included 47 patients (33 males and 14 females; median age, 64) who received XELOX + bevacizumab for metastatic colorectal cancer without implantation of a CV port. In all the patients, oxaliplatin (130 mg/m 2 ) was administered in combination with DEX (6.6 mg) via the peripheral vein. Results: Vascular pain developed in 34 patients (72.3%), but it was transient. In only 1 of the 34 patients, the drip infusion route had to be switched to the opposite side because of vascular pain. No patients required CV port implantation. Grade 3 or higher hemotoxicity was noted in 14.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 21.2% of the patients. The response rate was 61.7%. Among 47 patients, no patients experienced hypersensitivity reactions to oxaliplatin. Conclusions: Addition of DEX to oxaliplatin drip infusion controlled vascular pain caused by the administration of oxaliplatin via the peripheral vein. The response rate to this therapy combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, ie, it does not affect the stability of oxaliplatin by elevating the pH. Furthermore, coinfusion of DEX to oxaliplatin may be a useful preventive method for oxaliplatin-induced hypersensitivity.
An optimized microRNA signature algorithm to predict clear cell renal cell carcinoma metastasis: A 265-case validation study using paraffin specimens.
Authors: Huiqing Wu, Xiwei Wu, Jennifer M Jin, Arthur X Li, Tommy Tong, Dongling Ma, Rebecca A. Nelson, Yuping Li, Sumanta K. Pal, Young S Kim, Ken Haberman, Jing Zhai, Clayton S. Lau, Chao Guo, Jeffrey J Wu, Wengang Chen, Bertram E. Yuh, Massimo D'Apuzzo, Wenzhe Li, Sharon Wilczynski
Journal: Journal of Clinical Oncology (2016)

612 Background: Clear cell renal cell carcinoma (ccRCC) metastasis is associated with a dismal prognosis. Early identification of patients at high or low risk of metastasis may help to guide appropriate treatment. There are currently no reliable clinico-pathologic and laboratory modalities for this purpose in a routine clinical setting. We previously performed a microarray study using frozen ccRCC specimens and identified dysregulation of 4 microRNAs (miRNAs), miR-10b, miR-139-5p, miR-130b and miR-199b-5p, to be highly associated ccRCC metastasis and prognosis. Methods: We established a training cohort including formalin-fixed paraffin-embedded (FFPE) specimens of localized (n = 13; pT1) and metastatic (n = 15; M1) ccRCCs. We measured the expression of the 4 miRNAs of the training cohort samples by quantitative RT-PCR, normalized with miR-24, one of the most stably expressed miRNAs in human renal tissue as we previously reported. Using the risk score method, we rebuilt a mathematical formula with cutoff points to predict a patient to be at high, low or equivocal risk of metastasis. We validated the signature in an FFPE test cohort of 265-case primary ccRCCs. We examined the signature performance and its correlation with the cancer-specific survival. Results: Multivariate logistic regression analysis showed the signature to be highly associated with ccRCC metastasis (OR 7.67, 95%Cl 2.80-21.09, p &lt; 0.0001), with the overall sensitivity and specificity of 80% and 76%. The sensitivities and specificities were 72% and 78%, 70% and 67%, and 78% and 75% for stage I, II or III patients, respectively. The signature predicted metastasis of small ccRCCs ( ≤ 4.0 cm), with the sensitivity of 60% and specificity of 77%. The overall positive and negative predictive values (PPV and NPV) were 61% and 89%. The area under the curve of ROC was 0.8. The signature was also found to be well correlated with worse cancer-specific survival (HR 3.06, 95%Cl 1.49-6.93, p &lt; 0.01). Conclusions: This optimized miRNA signature can reliably predict ccRCC metastasis and prognosis and may help to stratify patients for more appropriate therapies and suitable clinical trials.
Next-generation systematic reviews: prospective meta-analysis, individual-level data, networks and umbrella reviews
Authors: John Ioannidis
Journal: British Journal of Sports Medicine (2017)

Systematic reviews and meta-analyses have reached a critical point. Their success is solid and dreadful at the same time. They are widely considered the highest level of evidence. There are tens of thousands of systematic reviews already published, but their production is still increasing geometrically. The problem is that the majority of systematic reviews are flawed, misleading, redundant, useless or all of the above,1 and this applies to almost all medical fields, including sports and exercise medicine.

Part of the problem with systematic reviews stems from the poor, misleading primary evidence2 that authors try to synthesise and make sense of. However, if this were the only major problem, systematic reviews and meta-analyses would still be extremely useful. They could focus exactly on showing how flawed, misleading and useless this evidence is. This could lead to suggestions on how to improve research in the field. Instead, systematic reviews often sanctify results from poor studies, by making these seem even more statistically significant and (spuriously) conclusive. They can also compound the problems seen in the primary studies, if they are driven by reviewers and sponsors with conflicts of interest, financial or academic.

There are four types of ‘next-generation’ systematic reviews that may raise the bar and help shape a new generation of more reliable evidence synthesis: prospective meta-analysis, individual-level data, network meta-analyses and umbrella reviews. They are not necessarily brand new ideas, but in the current circumstances of uncontrollable overproduction and unchecked quality, they have a fresh opportunity for impact. This large-scale impact would have been unimaginable in the past due to constrains in access to data, limited availability of sophisticated methods and fewer opportunities for their application. None of these next-generation tools are bullet proof, but they hold promise and some distinct advantages. Their disadvantages also need to be …
JAK1 Genomic Alteration Associated With Exceptional Response to Siltuximab in Cutaneous Castleman Disease
Authors: Maulik Patel, Sadakatsu Ikeda, Susan R. Pilat, Razelle Kurzrock
Journal: JAMA Dermatology (2017)

Castleman disease (CD) is an ultrarare, interleukin-6 (IL-6)-driven lymphoproliferative disorder whose underlying molecular alterations are unknown. Siltuximab (anti-IL-6 antibody) is approved for treatment of this disease. To our knowledge, genomic sequencing of CD has not been reported.To investigate and identify molecular aberration(s) that help explain the exceptional response to siltuximab in a patient with cutaneous CD.This case study examines data from comprehensive genomic profiling (using targeted next-generation sequencing) of tissue from a patient with cutaneous CD who demonstrated an exceptional response to siltuximab treated at a National Cancer Institute-designated Comprehensive Cancer Center.Intravenous siltuximab 12 mg/kg every 3 weeks. Tissue from the patient was interrogated by next-generation sequencing (405 genes). Serum was evaluated for IL-6 levels by enzyme-linked immunoassay.Identification of pretreatment serum IL-6 levels and somatic variants that may explain the exceptional response to siltuximab in this patient with cutaneous CD.Patient pretreatment serum IL-6 levels were normal. Treatment with siltuximab resulted in a complete response lasting 7 years. Next-generation sequencing demonstrated a JAK1V310I missense mutation. Janus Kinase 1 (JAK1) is a crucial signaling component of the IL-6/IL-6 receptor/gp130 machinery. JAK1V310I may induce a conformation change with functional activation effect leading to enhanced sensitivity to the IL-6 ligand.Our observations suggest that a JAK1 alteration may explain the underlying biology of a patient's cutaneous CD, as well as the patient's exceptional response to siltuximab.
Dysregulation of interleukin 5 expression in familial eosinophilia
Authors: S. Prakash Babu, Y.‐Y. K. Chen, S. Bonne‐Annee, J. Yang, I. Maric, T. G. Myers, T. B. Nutman, A. D. Klion
Journal: Allergy (2017)

Familial eosinophilia (FE) is a rare autosomal dominant inherited disorder characterized by the presence of lifelong peripheral eosinophilia (>1500/μL). Mapped to chromosome 5q31-q33, the genetic cause of FE is unknown, and prior studies have failed to demonstrate a primary abnormality in the eosinophil lineage.
Laparoscopic distal gastrectomy for gastric cancer: Institutional experience with 38 consecutive patients and oncologic outcomes.
Authors: J. Ho, E. L. Kachikwu, R. A. Nelson, J. D. Ellenhorn
Journal: Journal of Clinical Oncology (2011)

145 Background: The application of laparoscopy in the surgical treatment of gastric cancer has become more popular in recent years. Most of the published series are from Asia and few report on survival. Our objective was to elucidate the safety, efficacy, and oncologic outcomes of laparoscopic distal gastrectomy in patients with gastric cancer. Methods: The medical records of all patients who underwent laparoscopic distal gastrectomy at City of Hope National Medical Center between 6/2005 and 8/2010 were retrospectively reviewed. Relevant data analyzed included patient demographics, operative parameters, complications, recurrence, and survival. Results: A total of 38 consecutive patients were identified. Thirty-four of the 38 patients had a diagnosis of gastric adenocarcinoma. Median age was 70 years (35-96). Median operative time was 379 min (228-583). Median EBL was 200 ml (10-900). Seventeen of the 38 laparoscopic distal gastrectomy cases employed robotic assistance in lymph node dissection. The median number of lymph node retrieval was 23.5. Twenty-two cases included D2 lymph node dissections, 14 cases were D1 dissections, and 2 cases involved D0 dissections. All intended D2 dissections had greater than 15 nodes retrieved. Median hospital stay was 6 days (3-39). Morbidity and mortality rates were 11% and 0%, respectively. Of the 34 patients with gastric adenocarcinoma, histological staging revealed 1 patient had stage 0 disease, 25 had stage I, 7 had stage II, and 2 had stage III. Median follow-up was 12 months (0.5 to 58). Cancer recurrence occurred in 2 patients (6%). The 3 year overall survival is 69% and disease specific survival is 90%. The median survival has not been reached. Conclusions: Laparoscopic distal gastrectomy is feasible and safe and can be performed in patients with gastric cancer with excellent surgical and oncologic outcomes. No significant financial relationships to disclose.
Preferential pathologic complete response (pCR) in HER-2 positive and triple-negative breast cancer to sequential FEC 100- docetaxel (T) neoadjuvant chemotherapy (NCT) in stage II-III operable breast cancer
Authors: P. Dubray, X. Durando, C. Abrial, M. Mouret-Reynier, B. Nayl, E. Thivat, P. Gimbergues, J. Achard, P. Chollet, F. Penault-Llorca
Journal: Journal of Clinical Oncology (2009)

e11502 Background: NCT is increasingly used for operable breast cancer to allow breast conservation. Our objective was to evaluate clinical and pathological response after sequential NCT of FEC 100-T. This chemotherapy is currently the reference in the adjuvant setting in France.In PACS 01 trial (Roche et al. J Clin Oncol, 2006) FEC followed by T significantly improved 5 years overall survival rates (90.7%) compared to 6 FEC 100 in node-positive breast cancer. However this combination has not yet been evaluated in NCT. Methods: 101 patients (pts) from February 2005 to September 2008 with stage II-III operable breast cancer received 3 cycles (c) of FEC 100 (epirubicin 100 mg/m 2 + 5-fluorouracil and cyclophosphamide 500mg/m 2 ) followed by 3 c of T (100mg/m 2 ) every 3 weeks. pCR was defined according to Chevallier's (Am J Clin Oncol, 1993) as level 1 and 2 and to Sataloff's classification (J Am Coll Surg, 1995) as grade A. A clinical, mammography and ultrasound breast evaluation was performed at baseline, after 3 or 4 c and before surgery. Results: Median age was 52.3 years [32–71]. Median diameter of the tumor was 42 mm [15–100]. 83 pts had a ductal, 14 a lobular, 3 ductal and lobular, 1 another carcinoma. 8.9% were grade I SBR, 58.4% grade II SBR, 28.7% grade III SBR and 4% unspecified. 74 (73.3%) tumors were HR+, 9(8.9%) Her-2 + and 18(17.8%) triple negative. Ultrasound objective response rate (ORR) was 66.3%: 6 pts had a complete response and 53 pts had a partial response. 77pts (76.2%) underwent breast-conserving surgery After the completion of NCT, complete histologic data were available for 92 pts. 10 (10.8%) achieved pCR using Chevallier's classification and 9 (9.8%) using Sataloff's classification. The pCR rate was superior in triple negative (4/12) and Her2+ (2/6) tumors than in patients with HR+/Her-2- according to Chevallier's classification (p=0.034) and to Sataloff's classification (p=0.014). Conclusions: Sequential NCT with FEC followed by T was active and significantly improved pCR in patients with triple negative and Her-2+ tumors without an anti-Her2 specific biological agent. Breast-conserving rate appeared satisfactory. No significant financial relationships to disclose.
Analysis of prognostic factors in advanced pancreatic cancer (APDAC) patients (pts) undergoing to first-line nab-paclitaxel (Nab-P) and gemcitabine (G) treatment.
Authors: Guido Giordano, Vanja Vaccaro, Eleonora Lucchini, Paola Bertocchi, Francesca Bergamo, Gianna Musettini, Matteo Santoni, Giovanni Lo Re, Elisa Giommoni, Marco Russano, Serena Campidoglio, Daniele Santini, Enrico Vasile, Stefano Cascinu, Vittorina Zagonel, Alberto Zaniboni, Davide Melisi, Michele Milella, Antonio Febbraro
Journal: Journal of Clinical Oncology (2015)

412 Background: Nab-P + G combination represents an optimal first line therapeutic option in APDAC. Actually we have no parameters to predict prognosis in pts receiving this regimen. Here we present data of a multicentre retrospective analysis evaluating prognostic impact of clinical or biological factors in a cohort of APDAC pts treated with Nab-P + G first line CT. Methods: Clinical records of 118 APDAC pts receiving first line Nab-P + G were retrospectively reviewed. Overall survival (OS) and progression free survival (PFS) were evaluated with Kaplan Meier method with 95% CI and curves were compared with log-rank test. Cox-regression model was applied to the data with univariate and multivariate approach. Variables included in analysis were age, gender, ECOG PS, primary tumor site, liver metastases, multiple metastatic sites, baseline CA19-9, bilirubin levels, neutrophil/lymphocyte ratio (NLR), CA19-9 decrease &gt; 50%, biliary stent and symptomatic disease. Results: Median age was 66 (37 - 83), M/F:65/53, ECOG PS 0/1/2: 51/46/21 respectively. 4 complete and 27 partial responses were observed with 26% response rate (RR). Median OS and PFS were 11 months (95% CI 9.58 – 12.41) and 7 months ( 95% CI 5.96 – 8.03) respectively. When considered at univariate analysis primary tumor location to the head, ECOG PS of 2, bilirubin levels higher than median and NLR ≥ 5 had a bad prognostic impact both on PFS and OS. Differently, CA19-9 decrease &gt; 50% was considered a positive prognostic factor for PFS and OS. Multivariate analysis confirmed the negative role of NLR ≥ 5 respect of PFS (HR 3.21; 95%CI 1.61 – 5.68, p = 0.002) and OS (HR 3.38; 95%CI 1.88 – 5.79, p = 0.001) and positive impact of CA19-9 decrease &gt; 50% on PFS (HR 0.37; 95% CI 0.11 – 0.68, p=0.006) and OS (HR 0.53; 95% CI 0.15 – 0.97, p=0.005), as independent prognostic factors. Conclusions: This analysis suggest that in APDAC pts receiving first line Nab-P + G, high NLR value (≥5) could be considered an easy detectable, independent parameter to predict poor outcomes in terms of PFS and OS. Furthermore CA19-9 reduction &gt; 50% from baseline may be, in absence of other clinical and molecular parameters, an early marker of good prognosis.
Which data for cabazitaxel (Cbz) from the real world? The safety experience from the Italian centres participating in the Expanded Access Programme (EAP).
Authors: Sergio Bracarda, Paolo Marchetti, Donatello Gasparro, Angela Gernone, Francesco Boccardo, Caterina Messina, Luca Gianni, Roberto Bortolus, Lucia Fratino, Giuseppe Fornarini, Giacomo Carteni, Marcello Tucci, Roberto Mazzanti, Tiziana Scotto, Andrea Martoni, Umberto Basso, Giuseppe Procopio, Franco Morelli, Rodolfo Mattioli, Giuseppe Di Lorenzo
Journal: Journal of Clinical Oncology (2013)

189 Background: A significant percentage of metastatic castration-resistant prostate cancer (mCRPC) patients (pts) progressing during or after a docetaxel (D) based therapy are candidates for additional effective treatments. Taxanes remain the mainstay of treatment for a wide range of tumours including mCRPC. Cabazitaxel, a next generation of taxane, was approved based on results from the TROPIC study (NCT00417079). Cbz plus prednisone (P) was associated with a higher overall survival than mitoxantrone (MTX) (15.1 vs 12.7 mo, HR=0.70; P&lt;0.0001). Moreover CbzP was associated with clinical benefits, better PFS, maintenance of ECOG PS, improved tumour and PSA response, longer time to tumour and PSA progression while pain control was similar to MTX. These clear benefits supported a global EAP. Methods: Here we report, the preliminary safety analysis of 165 pts entered in the study from 25 Italian centres between Jan and Nov 2011. Pts received Cbz 25 mg/m 2 (intravenous every 3 weeks) plus P 10 mg (oral daily). Results: Median age was 70 years (21.8% of the cases were ≥75 years); pts with PS 0-1=98.2%; median number of previous D cycles was 8; 30.8% received 450 ÷ 675 mg, 14.7% received 675 ÷ 900 mg and 28.2% received ≥ 900 mg of D. Median time from last D dose to first CbzP dose was 5 months including any other eventual chemotherapy treatment. 49.1% of the pts entered in this EAP because refractory to D (PD during or within 3 months since the last D administration), overall 72 % of pts had 2 or more met sites. At the time of this analysis approximately 50% of pts received 4 cycles. A total of 68 pts discontinued CbzP due to PD (38.2%), AEs related and not related (38.2)%, Investigator’s decision (2.9%) or other reasons (20.6%). The most common G 3/4 AEs were neutropenia (35.2%), leukopenia (17.6%), anaemia (5.5%) febrile neutropenia (4.2%); main non-haematological AEs were asthenia (4.8%) and fatigue (4.2%). Conclusions: This large analysis confirms a manageable safety profile of cabazitaxel in routine clinical practice. The safety profile showed in EAP study suggests cabazitaxel a safe and effective treatment option in mCRPC pts progressing during or after a docetaxel based therapy. Clinical trial information: NCT01254279.
Ultrasound Guided Core Biopsy of the Spleen in Lymphoma Diagnosis.
Authors: Fiona M. Miall, Adam D. Rye, Kim Krarup, Kevin P. West, W.S.R. Hew, Raman Tyagi, Matthew P.A. Lyttelton, Ben Kennedy, Gillian Thomas, Martin J.S. Dyer
Journal: Blood (2007)
Impact of dose-intensified daunorubicin in induction on patients with core binding factor acute myeloid leukemias
Authors: Y. Yamaguchi, N. Usui, N. Dobashi, O. Asai, S. Yano, T. Ichiba, H. Osawa, Y. Takei, Y. Ogasawara, T. Saito, M. Kobayashi
Journal: Journal of Clinical Oncology (2005)

6712 Background: The group of core binding factor (CBF) acute myeloid leukemias (AML) is defined by presence of the t(8;21) or the inv(16) and there is major agreement that high-dose Ara-C (HiDAC) may influence the outcome of those patients. In our institution, we tried two consecutive AML treatment trials including dose-intensified daunorubicin (DNR) in induction comparing to conventional treatments and without HiDAC based consolidation. Purpose: To investigate the impact of dose-intensified DNR in induction on patients with CBF AML, we retrospectively analyzed patients with AML who were treated by DC(T)P(III) or Double-7 therapy which were conducted in our institution from February 1985 and October 2001. Results: Twenty-four of 117 patients (median age, 45 y.o.; range, 17 to 63 y.o.; median PS, 1; range, 0 to 3; male: female, 15: 9) were identified CBF AML and they were assessable for this study. The median dose of DNR in induction was 280 (range, 200 to 400) mg/m2. Four patients underwent autologous PBSCT whose conditioning regimen included HiDAC after consolidation. The t(8;21) were identified in 18 patients (alone: 4, others: 14) and the inv(16) were in 6 patients (alone: 2, others: 4). Twenty-two (91.7%) patients achieved CR (t(8;21): 88.9%, inv(16): 100%). The 5-year disease-free survival and overall survival rates were 49.5% (t(8;21): 51.9%, inv(16): 41.7%) and 60.1% (t(8;21): 58.2%, inv(16): 66.7%). Six of 11 patients who relapsed or failed to the initial therapy received salvage therapy including HiDAC, but no one survived at the time when this data was calculated in those patients. Conclusions: The role of DNR or other anthracyclines for patients with CBF AML might be investigated as well as that of HiDAC. No significant financial relationships to disclose.