tbuckley/cabot-search huggingface dataset:
Genomic profiling using targeted ultra-deep next-generation sequencing for prediction of treatment outcome after concurrent chemoradiation: Results from the German ARO-0401 trial.
Authors: Inge Tinhofer, Volker Budach, Volker Endris, Albrecht Stenzinger, Wilko Weichert
Journal: Journal of Clinical Oncology (2014)

6002 Background: Genomic profiling using next-generation sequencing (NGS) has provided novel insights in the genomic landscape of squamous cell carcinoma in the head and neck region (SCCHN). This is the first report on its application within a phase III trial of concurrent chemoradiation in locally advanced SCCHN. Methods: Between 2004 and 2008, 364 patients with stage IV SCC of the oro- or hypopharynx were treated with hyperfractionated accelerated radiotherapy with cisplatin/5-FU or mitomycin C/5-FU. From 174 patients (48%) FFPE samples could be collected. HPV DNA PCR and p16 immunohistochemistry were carried out. From 106 cases (29%) targeted NGS was possible. Based on previous reports an SCCHN panel was designed comprised of 224 exons from 53 genes (mean coverage 3000-fold, minimum 370-fold). Only non-synonymous germline and somatic single-nucleotide polymorphisms (SNP) with an allele frequency of >5% were considered. SNP were classified according to a damage-score prediction algorithm. Kaplan-Meier-analysis, log-rank test and multivariate Cox regression analysis were performed. Results: The most frequent germline/somatic SNP were found in TP53 (total 94%, disruptive mutations 22%) followed by FAT1, PCDH15, KDR, PDGFRA and NOTCH1 (14%), with disruptive mutations in TP53 and NOTCH1 being almost mutually exclusive. Disruptive mutations in TP53 were significantly associated with an HPV-negative status and correlated with reduced OS (HR 0.37, 95% CI 0.21-0.65, p=0.0005) and PFS (HR 0.39, 95% CI 0.23-0.69, p=0.001). In contrast, NOTCH1 mutations were not related to HPV status, were significantly associated with improved OS (HR 2.4, 95% CI 1.1-5.7, p=0.039) and showed a trend to improved PFS (HR 2.1, 95% CI 0.9-5.1, p=0.07). Disruptive mutations in TP53 and NOTCH1 remained significant after correction for smoking, HPV and treatment. Conclusions: Targeted NGS revealed three SCCHN subgroups with distinct outcomes after chemoradiation. As discriminative factors we identified HPV, NOTCH1 and disruptive TP53 mutations. The functional relevance of NOTCH1 mutations for radio-/chemosensitivity remains to be determined.
Brain metastasis as initial presentation of non-small cell lung cancer.
Authors: Abdulrahman Ali Alshehri, Manish Monga, Sijin Wen
Journal: Journal of Clinical Oncology (2014)

e19152 Background: Brain metastasis in patients with cancer is a predictor of poor prognosis. Metastasis to brain is identified upon initial diagnosis in approximately 10% of the patients with non-small cell lung cancer (NSCLC). Methods: A retrospective analysis for a period of 3 years identified 45 patients with confirmed radiological and or histopathological diagnosis of NSCLC with brain metastasis, clinical, treatment and outcome data was collected. Kaplan-Meier method and log-rank test were used in the survival analysis. Results: Twenty-three patients (51%) had brain as the only site of metastatic disease;19 patients (42%) underwent brain metastasis resection; 33 patients (73%) received Radiation treatment (12 received gamma knife radiotherapy). Median survival for 45 patients was 4.5 months (95%CI: 3.6 - 9.8). Twenty-three patients received palliative chemotherapy and all patients received platinum based doublet agents. Various combination of chemotherapy agents used including pemetrexed, gemcitabine, paclitaxel , docetaxel . Combination of platinum and pemetrexed was superior to other platinum based regimen combinations with median survival of 12.2 versus 4.5 months (p=0.003). Smaller primary lung lesion correlated with better survival, the median survival for T1/T2 lesions was 7.2 months versus 3.6 months for T3/T4 lesions (p = 0.017). Median survival in patients who received chemotherapy was 8.7 months compared to 3.0 months in patient who did not receive chemotherapy(p < 0.0001), Patient who received chemotherapy and radiation therapy showed a better median survival of 7.5 months compared to 2.2 months in patients who received radiation therapy only (p<0.0001). There was no difference in survival in patients with brain as the only site of metastasis versus patients with brain and other site(s) of metastasis, median survival was 4.5 versus 4.2 months (p = 0.288). Conclusions: Patients with synchronous brain metastases from non-small cell lung cancer have poor prognosis. Pemetrexed based combination chemotherapy seems to improve overall survival, this finding needs to be confirmed in a prospective study. Improved understanding about the genomics of lung cancer metastasis to brain will lead to improved therapeutic options.
Non-sugar sweeteners: lack of evidence that they help to control weight
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

There is no compelling evidence that non-sugar sweeteners improve health or help people to lose weight, a review of published studies has found.

Many people are eating foods and drinks that contain non-sugar sweeteners rather than sugar in the belief that these are healthier, and although several non-sugar sweeteners are approved, the evidence about their potential benefits and harms is often limited and conflicting, according to European researchers reporting in The BMJ .1

To understand these potential benefits and harms better they analysed 56 studies comparing no intake or lower intake of non-sugar sweeteners with higher intake in healthy adults and children. Of these studies, …
Role of hnRNP K and Interacting mRNAs in Pathogenesis of AML with 9q Deletion
Authors: Kerstin Rahn, Isabel Naarmann-de Vries, Yvonne Sackmann, Felicitas Klein, Antje Ostareck-Lederer, Dirk Ostareck, Edgar Jost, Ali T Abdallah, Bernd Denecke, Lin Gan, Gerhard Ehninger, Tim H Brümmendorf, Gernot Marx, Christoph Rollig, Christian Thiede, Martina Crysandt
Journal: Blood (2018)
Adalimumab treatment for psoriasis – safety in numbers
Authors: C. Ryan
Journal: British Journal of Dermatology (2019)

Linked Article: Leonardi et al. Br J Dermatol 2019; 180:76–85. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Accelerated Knee Osteoarthritis Is Characterized by Destabilizing Meniscal Tears and Preradiographic Structural Disease Burden
Authors: Jeffrey B. Driban, Julie E. Davis, Bing Lu, Lori Lyn Price, Robert J. Ward, James W. MacKay, Charles B. Eaton, Grace H. Lo, Mary F. Barbe, Ming Zhang, Jincheng Pang, Alina C. Stout, Matthew S. Harkey, Timothy E. McAlindon
Journal: Arthritis & Rheumatology (2018)

Objective To determine whether accelerated knee osteoarthritis ( KOA ) is preceded by, and characterized over time by, destabilizing meniscal tears or other pathologic changes. Methods We selected 3 sex‐matched groups of subjects from the first 48 months of the Osteoarthritis Initiative, comprising adults who had a knee without KOA (Kellgren/Lawrence [K/L] radiographic grade &lt;2) at baseline. Subjects in the accelerated KOA group developed KOA of K/L grade ≥3, those with typical KOA showed increased K/L radiographic scores, and those with no KOA had the same K/L grade over time. An index visit was the visit when the radiographic criteria for accelerated KOA and typical KOA were met (the no KOA group was matched to the accelerated KOA group). The observation period was up to 2 years before and after an index visit. Radiologists reviewed magnetic resonance ( MR ) images of the index knee and identified destabilizing meniscal tears (root tears, radial tears, complex tears), miscellaneous pathologic features (acute ligamentous or tendinous injuries, attrition, subchondral insufficiency fractures, other incidental findings), and meniscal damage in &gt; 2 of 6 regions (3 regions per meniscus: anterior horn, body, posterior horn). In addition, bone marrow lesions ( BML s) and cartilage damage on MR images were quantified. Linear mixed regression models were performed to analyze the results. Results At 1 year before the index visit, &gt;75% of adults with accelerated KOA had meniscal damage in ≥2 regions (odds ratio 3.19 [95% confidence interval 1.70–5.97] versus adults with typical KOA ). By the index visit, meniscal damage in ≥2 regions was ubiquitous in adults with accelerated KOA , including 42% of subjects having evidence of a destabilizing meniscal tear (versus 14% of subjects with typical KOA ). These changes corresponded to findings of larger BML s and greater cartilage loss in the accelerated KOA group. Conclusion Accelerated KOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in &gt; 2 regions, and also characterized by the presence of large BML s and greater cartilage loss.
Prediction of CAR T-Related Toxicities in R/R DLBCL Patients Treated with Axicabtagene Ciloleucel Using Point of Care Cytokine Measurements
Authors: Rawan Faramand, Hiroshi Kotani, Dylan Morrissey, Bin Yu, Frederick L. Locke, Michael D. Jain, Julio C. Chavez, Xuefeng Wang, Asmita Mishra, Christina A Bachmeier, Renier J. Brentjens, Sarah Yoo, Jae H. Park, Marco L. Davila
Journal: Blood (2018)
Prognosis of Patients with Waldenström Macroglobulinemia: A Simplified Model
Authors: Saurabh Zanwar, Jithma Prasad Abeykoon, Stephen M. Ansell, Angela Dispenzieri, Morie A. Gertz, David J Inwards, Thomas E. Witzig, Martha Q. Lacy, Thomas M. Habermann, David Dingli, Francis K. Buadi, Ronald S. Go, Wilson I Gonsalves, Eli Muchtar, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar, Prashant Kapoor
Journal: Blood (2018)
Cisplatin- and carboplatin-related ototoxicity in children with cancer in a Turkish pediatric oncology center.
Authors: Nurdan Tacyildiz, Hilal Cengiz, Gulhis Deda, Can Ates, Suna Yilmaz, Gulsan Yavuz, Emel Unal, Handan Dincaslan, Gulsah oktay Tanyildiz
Journal: Journal of Clinical Oncology (2014)

e21028 Background: Cysplatin (CsP) and carboplatin (CP) are chemotherapeutic agents used in the treatment of many childhood cancers but hearing loss (HL) may be limiting side effect. We aimed to asses relation between HL, total CsP and CP dosage, concomitant crainal radiotherapy (RT) and aminoglycoside (AG) usage in our childhood cancer patients (pts). Methods: Thirty two pts (mean age 10.14, range: 0.8 to 18 years), who were planned to be receive CsP and CP, were included in this prospective study. Pts who met study criteria (mainly retinoblastoma pts under 2 years old age treated with CP or bone sarcoma pts older than 2 years treated with CsP) and are found to be normal by autoscopic examination were evaluated with tonal audiometry (evaluated according to Brock staging system), brain stem auditory evoked potential (BAER) and transient evocaid autoacustic emission (TEOAE) tests. Statistical analysis was performed with SPSS-15 version. Results: Nine pts (%28,1) received CsP, and 18 pts (56,3%) recevied CP alone, while 5 patients (15,6%) received both. 15 pts out of 32 (53,5%) were found to have hearing loss (HL) at any level. HL was detected in 9 patients (64%) out of 14 who were treated with CsP either alone or with CP. Five of these patients (55,5%) were in HL changing from moderate to heavy. CP was used in 23 patients either alone or with combination with CsP which 9 of them (39%) hadhearing loss at any level. 3 pts with cumulative dosage of CysP 400mg/m2or higher were detected to have bilateral or unilateral stage 3 HL. AG usage was very rare in pts that under treatment of Platins so there was no related HL. In addition, HL in older age group was higher than younger probably due to more CsP based chemotherapy (CT) protocols of them. One patient who was treated with both CP and RT also found to have hearing loss. The incidence of autotoxicity in patients who were treated with cranial RT was found to be 40%. Improved HL in 3 patients after bone-marrow transplantation was an interesting observation. Conclusions: Pts who will be treated with CyP and CP should be evaluated by audiologically before and after the treatment, the ones with heavy hearing loss should be recommended hearing aids.
The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology
Authors: Wilfried Mullens, Kevin Damman, Veli‐Pekka Harjola, Alexandre Mebazaa, Hans‐Peter Brunner‐La Rocca, Pieter Martens, Jeffrey M. Testani, W.H. Wilson Tang, Francesco Orso, Patrick Rossignol, Marco Metra, Gerasimos Filippatos, Petar M. Seferovic, Frank Ruschitzka, Andrew J. Coats
Journal: European Journal of Heart Failure (2019)
Predictor factors in laser thermal therapy for recurrent head and neck cancer.
Authors: Marcos B. Paiva, Michael Bublik, Dan J. Castro, Michael Masterman-Smith, Marilene B. Wang, Joel A. Sercarz
Journal: Cancer Research (2006)

5329  Squamous cell carcinoma of the head and neck occurs frequently worldwide with more than 500,000 new cases projected annually. Once recurrent after primary treatment, survival rates for head and neck cancers are very poor. Management of recurrent head and neck cancer is a seldom reported but a common clinical dilemma. Only a small subset of patients are candidates for potentially curative surgery. Chemotherapy alone provides only limited palliation with no long term survivors, and reirradiation in most cases is unfeasible because of local toxicity. Experience is accumulating using laser-induced thermal therapy (LITT) for treatment of recurrent, unresectable head and neck cancers leading to favorable results and apparent long-term efficacy in some cases. In this study, we review our results on 104 patients with recurrent head and neck cancer that were treated by LITT . Best results were seen in oral cavity tumors where average survival was 20.3 months (10.7-30mo; 95%CI) compared to neck (avg.=14.4 months, 7.5-20.7mo; 95%CI) and other tumor sites (avg.=18 months, 13.8-22.3mo; 95%CI). Tumor regrowth was not seen after treatment for an average of 47 days with significant palliation of symptoms observed in most of these patients. Therapy response was inversely related to initial tumor volume and was dependent on both histology and growth rate. Smaller slow growing tumors and more differentiated tumors were palliated successfully with a better local therapy response rate than poorly differentiated and rapidly dividing malignancies. The results of LITT in recurrent head and neck cancer and the prognostic factors predicting outcome in this patient population are also reviewed.
Clinical practice use of panitumumab combined with chemotherapy in patients with wild-type <i>RAS</i> metastatic colorectal cancer.
Authors: Holger Frithjof Hebart, Jiri Tomasek, Tibor Csõszi, Reija Koukakis, George Kafatos, Anja Kuhn, Katja Björklöf, Tomas Buchler
Journal: Journal of Clinical Oncology (2018)

852 Background: This study aimed to understand panitumumab (pmab) use in clinical practice for patients with wild-type RAS metastatic colorectal cancer (mCRC), in first-line (1L) with FOLFOX or second-line (2L) with FOLFIRI following fluoropyrimidine-based chemotherapy (excl. irinotecan). Methods: This is a combined analysis of two observational, non-interventional prospective cohort studies conducted in Germany/France (2012-2016) and Bulgaria/Czech Republic/Hungary (2013-2016). Results: Results are presented in the order of 1L FOLFOX (n = 332) followed by 2L FOLFIRI (n = 94). Patients received a median of 10 and 11.5 pmab infusions. The median duration of pmab exposure was 5.7 and 6.9 months (note that 53 and 10 patients continued pmab use after study end). The unadjusted overall response rate (complete or partial response) was 42% and 29%, based on 45% and 44% of patients with available response data post-baseline. In the 1L setting, resectability was achieved in 9%, not achieved in 42%, and unknown in 48%. Hospitalizations were reported for 100% and 99%, mostly cancer-related visits such as scheduled anticancer treatment (e.g. chemotherapy/pmab administrations), tumor assessment visits, or interventions; 93% in both groups reported outpatient, 66% and 60% inpatient visits. Conclusions: Overall, the study results show that treatment patterns and clinical efficacy of pmab in routine clinical practice were comparable to randomized controlled trials (RCTs). The ADR/SADR skin toxicity events are lower than expected based on findings from RCTs, however, similar findings have been shown in a previous observational study. More investigation is required to understand the reason for this.[Table: see text]
Impact of body image in the quality of life of university students according to nutritional status
Authors: J. A. D. B. Campos, W. R. Silva, B. G. Martins, J. Maroco
Journal: Psychotherapy and Psychosomatics (2015)

State Univ Julio de Mesquita Filho, Dept Food & Nutr, Fac Pharm Araraquara, Sao Paulo, Brazil
Long-term follow-up of a 10-year single-center experience with high-dose pharmacokinetics-directed intravenous busulfan in combination with cyclophosphamide and etoposide as preparative regimen for intermediate- and high-grade non-Hodgkin lymphoma.
Authors: Neha R Patil, Donna E. Salzman, William P. Vaughan
Journal: Journal of Clinical Oncology (2014)

e19521 Background: High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is indicated for patients with Non-Hodgkin Lymphoma (NHL) recurring after or resistant to primary therapy. Busulfan (Bu) based regimens are commonly used. At University of Alabama at Birmingham we have been using a regimen of the intravenous formulation of Bu (IVBu) since its FDA approval in April 1999. AHSCT patients have been treated with a regimen of pharmacokinetics directed (PK) Bu together with cyclophosphamide and etoposide (IVBuCyE). We here report the long term follow up of this experience. Methods: Between April 1999 and November 2009, 69 consecutive transplant eligible patients with intermediate or high risk NHL ranging in age from 19 to 74 with a median age of 54 were treated with a IVBu “test dose” of one 60 mg vial adjusting the remaining doses to achieve an exposure of 20,000 uMol-min total Bu AUC followed by Cy (2.5 g/m2) and E (1800 mg/m2). Results: The average hospital stay was 25 days. There were 2 patient deaths prior to hospital discharge (sepsis and heart failure) and 3 additional deaths within the 100 day post-transplant period*. At a minimum follow-up of 3 years the overall survival and disease free survival were 59% and 56%, respectively, for patients less than 54 years of age and 57% and 54%, respectively, for patients more than 54 years of age. The 100 day mortality, 1 year mortality, overall survival and relapse-free survival were similar in regardless of age (p value 0.5). Conclusions: PK directed Bu and CyE regimen followed by AHSCT resulted in 58% 3 year overall and disease free survival in intermediate or high risk NHL patients. Survival outcomes were similar regardless of patient age at the time of transplant. Diffuse large B-ell lymphoma (n=40) Follicular Llymphoma (n=15) Mantle cell lymphoma (n=14) 100-day mortality* 2 (5%) 2 (13%) 1 (7%) 100-day - 1-year mortality 8 (20%) 4 (26%) 1 (7%) 3-year overall survival 63% 47% 57% 3-year relapse-free survival 60% 46% 50% *Causes of 100-day mortality Intracranial hemorrhage, disease Heart failure, sepsis Sepsis
Acalabrutinib in Patients with Relapsed/Refractory (R/R) and High-Risk, Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL)
Authors: Clare C. Sun, Pia Nierman, Inhye E. Ahn, Janet Valdez, Jennifer Lotter, Susan Soto, Sarah E. M. Herman, Todd Covey, Ahmed Hamdy, Raquel Izumi, Dongmei Liu, Priti Patel, Adrian Wiestner
Journal: Blood (2018)
Prospective evaluation of echocardiography and serum biomarkers as predictors of cardiotoxicity in patients with breast cancer treated with anthracyclines, taxanes, with/without trastuzumab.
Authors: Jorge soler Lopez, Ramon De Las Penas, Leticia De avila, Maria De Julian, Maria Arnal, Eduardo Martinez-De Duenas, Santiago Olmos, Angela Lopez-Rodriguez, Javier Munarriz, Ana Peset, Alejandro Cortell, Candela Rodriguez, Angel Solloso
Journal: Journal of Clinical Oncology (2014)

e20686 Background: To evaluate whether echocardiographic parameters and serum biomarkers may predict early cardiac dysfunction in patients treated with taxanes, anthracyclines with / without trastuzumab (T). Methods: A prospective study in patients with early breast cancer adjuvant anthracyclines, taxanes with / without T, if HER2 positive, in which a complete cardiac evaluation including echocardiography and serum biomarkers (Troponin-I, BNP, Ca 12.5) at baseline, at 6 and 12 months (baseline, 3, 6, 9 and 12 months in patients treated with T). Cardiac event was defined as: CHF NYHA III / IV with an absolute value of LVEF <50% and reduced LVEF ≥ 10% or asymptomatic decrease in LVEF ≥ 10% (overall <50%). Patients with LVEF <50% at baseline were excluded. Results: Up to November 2013 were included 204 patients, of the 250 planned. With a median age of 53 years, of which 62.7% were treated with Trastuzumab. There were only 11 cardiac events (3 of them CHF NYHA III / IV), including 6 treated with T. No significant differences in cardiac parameters, or serum biomarkers analyzed were found. The study is closed. Conclusions: The results show a low incidence of cardiac toxicity (probably by appropriate patient selection and treatment given). None of the echocardiographic variables nor serum biomarkers has been useful in predicting cardiac events.
Correlation of APC, CYP3A4, and ESR2 expressions in locally advanced rectal cancer with the pathologic response of preoperative concurrent CAPOX/RT.
Authors: Ekaphop Sirachainan, Chomporn Sitathanee, Sith Phongkitkarun, Weerapat Suwanthanma, Noppadol Larbcharoensub, Narumol Trachu, Somthawin Lukrak, Kanit Sumboonnanonda
Journal: Journal of Clinical Oncology (2014)

e14610 Background: Capecitabine and 5-FU showed similar response rate in preoperative concurrent chemoradiotherapy in locally advanced rectal cancer. CAPOX demonstrated substantial benefit in advanced colorectal cancer. The molecular predictive factors of preoperative concurrent CAPOX/RT in locally advanced rectal cancer have never been investigated. Methods: We conducted a phase II study to determine the efficacy and predictive factors of preoperative concurrent CAPOX-RT in locally advanced rectal cancer (cT3-4 or N+). Capecitabine 1,650 mg/m2/day was taken on day 1-14 and 22-35 of RT. Oxaliplatin 50 mg/m2was administered on day 1, 8, 22 and 29 of RT. The radiation dose to the pelvis was 45 Gy/25 fractions with a boost dose of 5.4 Gy/3 fractions. The total dose to the tumor bed was 50.4 Gy/28 fractions. Pelvic MRI was done preoperatively. Patients underwent surgery between 4-6 weeks after completion of radiotherapy. mRNA of pretreatment and post treatment tumors were analyzed for gene expressions using RT² Profiler PCR Arrays. Overall survival and gene expression patterns were correlated with Dworak tumor regression grade (TRG). Results: Twenty patients have been enrolled. Fifty five percent weremale. All patients had clinical T3 N positive disease, except one had T4 disease. One patient refused surgery after pre-operative treatment. Response rate was evaluated in 20 patients. Clinical response rate was 90% (cCR 55%). Dworak TRG 1-2 and 3-4 were detected in 36.8% and 63.2% respectively. Most patients received adjuvant chemotherapy. Four patients developed recurrent disease and finally expired. Three-year disease-free survival and overall survival was 67.7% and 68.9 %, respectively. No three-year overall survival difference between patients with various Dworak TRG was found (TRG 1-2, 54.5% vs TRG 3-4, 100% respectively, p=.149). Pre-treatment tumor APC, CYP3A4, and ESR2 overexpressions were more commonly detected in patients with Dworak TRG 3-4 than TRG 1-2 (5.04, 5.28 and 4.51 fold respectively). Conclusions: Dworak TRG could not be prognostic factor. APC, CYP3A4, and ESR2 expressions are potential predictive factors of preoperative concurrent CAPOX/RT in locally advanced rectal cancer.