tbuckley/cabot-search huggingface dataset:
Prescribing patterns for management of newly diagnosed squamous cancers of the head and neck (HNSCC) and opportunities to improve quality.
Authors: Arlene A. Forastiere, William A. Flood, Vlad Kozlovsky, Elaine Whyler, Evan W. Alley
Journal: Journal of Clinical Oncology (2014)

e17701 Background: Variability in prescribing and deviations from evidence-based (EB) standards contribute to the high cost of cancer care and affect quality. We sought to evaluate prescribing patterns for curative treatment of HNSCC in a commercially insured population of 1.8 million covered lives. Methods: The eviti web-based decision-support platform database of chemotherapy (CT) and radiation therapy (RT) treatment plans submitted for insurance pre-authorization between Feb 2011 and Nov 2013 was queried for analysis of patient characteristics and first line curative treatment of HNSCC. Results: A total of 902 individual RT and CT treatment plans were submitted constituting 426 pt episodes of curative treatment (single or multimodality); 414 had sufficient detail for analysis. Primary sites were: oral cavity(OC)- 53, oropharynx(OP)- 198, unknown- 19, larynx- 91, nasopharynx (NPC)- 27, other- 26; stage III/IV(M0) comprised 85%. Notably, only 9 of 414 pts were enrolled in a clinical trial. Approaches to definitive treatment by site were: OC-surgery + adjuvant RT +/- CT in 89% of pts, chemoradiation(CRT) 11%; OP & unknown primary: CRT 63%, surgery + adjuvant RT+/- CT 17%, RT alone 8.7%; larynx stage III/IV(M0)- CRT 73%, laryngectomy 17%, RT alone 10%; NPC- 92% of pts were prescribed the EB standard cisplatin/RT, 61% adjuvant cisplatin/5-FU, and 27% an induction regimen. CT regimens and variability: CRT was prescribed as definitive therapy in 215 pts. Single agent cisplatin prescribed in 63.7%, cetuximab 13.4%, carboplatin 8.8%, platinum + taxane 6.9%, other 6.9%. Induction CT was prescribed infrequently, total 69 pts of which 37 (53.6%) had T4 or N3 tumors. Combination taxane, cisplatin, 5-FU, the EB standard was prescribed in 57%. Conclusions: Too few HNSCC pts are enrolled in clinical trials. The treatment of NPC usually conforms to the level 1 EB standard. Single agent cisplatin (Level 1 EB) was prescribed for CRT in 64%, regimens with less evidence used in approx. 25% potentially over or under treat. When induction CT is prescribed, the EB regimen is often not used. Prescribing based on the highest level of evidence provides an opportunity to reduce variability and improve quality.
Role of metronomic capecitabine in advanced hepatocellular carcinoma.
Authors: Abdul Mateen, Allah Rakha Adil
Journal: Journal of Clinical Oncology (2014)

e15119 Background: Hepatocellular carcinoma is one of the top five cancers in countries where viral hepatitis is an endemic disease like Pakistan. Its incidence is rising continuously. Limited options are available for advanced stage disease in old and frail patients. These are intolerant to chemotherapy and biological therapy. Moreover, cost of biological therapy render their use limited in limited resource country. There is a desperate need for a treatment that is effective as well as minimal toxic to these patients so that quality of life is improved in this population. Methods: This study is aimed at testing the efficacy of low dose capecitabine (1000 mg daily in two divided doses) in newly diagnosed advanced hepatocellular carcinoma. Patients were planned to receive this treatment for three months followed by response assessment using ultrasound findings and alpha fetoprotein (AFP) levels compared to baseline findings. Various quality of life parameters including pain score, appetite, weight gain and performance status were also assessed. Results: Total of seventy patients were enrolled. Fifty five patients completed the treatment for three months and were available for evaluation. Two patients (3.6%) had complete response, twelve (21.8%) had partial response, nineteen (34.5%) had stable disease and twenty two (40%) had progressive disease. Thirty nine patients (70.9%) showed significant reduction in AFP levels. Pain score improved in forty two (76.4%) patients, appetite was increased in thirty seven patients (67.2%), weight was gained in twelve patients (21.8%) and performance status was improved in seventeen patients (30.9%). Six patients had one or more episode of grade 2 diarrhea, four patients developed encephalopathy and only one patients developed hand foot syndrome. Conclusions: Low dose continuous capecitabine is effective in advanced hepatocellular carcinoma with excellent tolerability and minimal toxicity.
C-MET expression as an independent prognostic marker in resected pancreatic ductal adenocarcinoma (PDAC): Proposition of a novel reliable immunostaining scoring method.
Authors: Cindy Neuzillet, Jerome Cros, Annemilai Tijeras-Raballand, Louis de Mestier, Armand De Gramont, Julien Moroch, Pierre Bedossa, Valerie Paradis, Alain Sauvanet, Jean-Baptiste Bachet, Philippe B. Ruszniewski, Eric Raymond, Anne Couvelard, Pascal Hammel
Journal: Journal of Clinical Oncology (2014)

e15200 Background: Activation of the HGF/c-Met pathway is involved in tumor-stroma interactions and PDAC cell invasiveness. Assessment of c-Met expression is a critical issue as Met inhibitors are under clinical development. We aimed to build a reliable score to assess c-Met expression in resected PDAC, meeting the following criteria: correlation with survival, reproducibility, and transposability on tissue microarrays (TMA). Methods: Patients with resected PDAC and no adjuvant chemotherapy were retrospectively selected. c-Met immunostaining was graded using a standard visual scale combining surface (S) and intensity (I) (standard SI) and a
‘To switch or not to switch’: the missing piece in the puzzle of biosimilar literature?
Authors: Marc Scherlinger, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2019)

To switch or not to switch': the missing piece in the puzzle of biosimilar literature?We read with great interest the paper from Glintborg and coauthors 'To switch or not to switch' reporting biosimilar etanercept switching in Denmark. 1 In the Danish Biologic (DANBIO) cohort, patient treated with originator etanercept (Enbrel) were informed of a mandatory switch to SB4.However, the 25 mg pen or a powder-based preparation of original etanercept (OE) were still available.At 1 year after this decision, the authors reported that only 79% of patients had switched to SB4 and 21% remained treated with the originator biologic.In westernised countries, biologics therapies take a high toll on healthcare systems.With their 20%-50% lower costs, biosimilars' wide diffusion are therefore a necessity in order to provide sustainable healthcare to patients with chronic inflammatory rheumatic diseases.][4][5] Two strategies for the use of biosimilars can be differentiated in patients already treated with an originator: mandatory switch or physician-patient shared decision.Physician-patient shared decision has been favored by rheumatology scientific societies, by an international consensus group and by patients association. 6-8Indeed, real-life studies reporting the acceptance of the switch from OE to SB4 in case of shared decision together with an optimised communication strategy have reported acceptance rates of 92%-99%. 9 10Outside an improved acceptance rate of physician-patient decision, there are reasonable evidence suggesting that forcing the switch on a patient is likely to increase the risk of nocebo effect, with negative effect on the patient and on physician-patient relationship (reviewed by Kravvaviti). 11This nocebo effect might, at best, mandate a reswitch to the originator, therefore, a failure of the switching strategy.In the worst case (if the originator is not available anymore), the patient will be switched to another (possibly originator) biologic, leading to an avoidable exhaustion of therapeutic options, a weakening of the patient-physician relationship and increased healthcare costs.Considering this body of evidence, we believe that Glintborg's study was the missing piece in the puzzle of the biosimilars literature, demonstrating that a mandatory switch is probably not the most efficient strategy for the wide diffusion of biosimilar in chronic rheumatic diseases and reinforcing the evidence of the necessity of a shared physician-patient decision as recommended by many.
Abstract 16869: Sodium Reduction, miRNA Profiling and Insights into Cardiovascular Phenotypes in Hypertensives
Authors: Li Chen, Fenjun He, Yanbin Dong, Gregory A Harshfield, Haidong Zhu
Journal: Circulation (2017)

Introduction: Sodium reduction has been shown to reduce blood pressure (BP) and the incidence of cardiovascular disease (CVD), while the underlying molecular mechanisms are still not clear. Emerging evidence suggest that miRNAs play an important role in CVD. Hypothesis: We aim to test the hypothesis that a reduction in sodium intake could induce changes in miRNA expression in hypertensives and those miRNA changes would be associated with improved BP, inflammation and kidney function. Methods: A whole genome miRNA next generation sequencing was carried out in paired serum samples selected from 10 black male untreated hypertensive subjects in a randomized double-blind crossover trial (slow sodium vs placebo while on low-sodium diet). Mixed-effects linear regression model was used to assess the differential expression between sodium and placebo tablets. Differentially expressed miRNAs were analyzed for enrichment by DIANA-miRPath v3.0. Mixed-effect model was used to examine the associations between changes i...
Recent developments in lymph node surgery for melanoma
Authors: A.C.J. Akkooi, A. Hayes
Journal: British Journal of Dermatology (2019)

There has been a historical emphasis on radical surgery both for the primary melanoma and for possible metastases within regional lymph nodes. This is because, in the absence of effective systemic therapy options, surgery was viewed as the only potential curative treatment. There are alternate hypotheses for the role of surgery in lymph node metastases in melanoma. Firstly, there is the ‘orderly progression’ of the metastatic process, initially through locoregional lymphatics to the regional lymph nodes, and subsequently to the second‐echelon lymph nodes and bloodstream. Therefore, early interruption of this process would in some way prevent further progression to distant visceral metastases and thereby improve overall survival (OS). The alternate hypothesis is that the development of metastatic disease within the locoregional lymph node(s) is an ‘indicator’ of metastatic potential and correlates with the development of distant metastases. However, removal of disease within lymph nodes at an early stage will not prevent the development of distant metastatic disease, which is governed by a complex interplay of the biology of the primary tumour and the host's innate defences.1 These two hypotheses are not mutually exclusive within a population of patients or indeed within an individual patient.
Association of EGFR exon 19 deletion and miRNA expression in lung adenocarcinomas.
Authors: Lixia Ju, Caicun Zhou
Journal: Journal of Clinical Oncology (2014)

e19140 Background: Epidermal growth factor receptor (EGFR) is frequently found to be activated by mutation in lung cancer. Though most patients with EGFR activating mutation response to EGFR-TKI, there are still about 30% patients showing no response. MiRNA expression is dysregulated in lung cancer, and miRNAs can regulate EGFR. So it is important to predict the candidate miRNAs that target EGFR mutation and to investigate the availability of these candidate miRNA regulators in lung cancer. Methods: In this study, we investigated the difference of miRNA expression in lung adenocarcinomas cell lines with EGFR exon 19 E746_A750 deletion (H1650 and PC-9) and wild-type EGFR (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual miRNAs were validated by RT-PCR assays. At last we detected the individual miRNAs expression in tumors of lung adenocarcinoma patients. Results: 1,732 miRNAs was evaluated. We found that miRNAs expression were different between these two groups. hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were upregulated and hsa-miR-4450 were downregulated in the mutated EGFR group. Then they were validated by RT-PCR assays. In 6 tumors with wild-type EGFR and 5 tumors with exon 19 deletion, RT-PCR assays show that hsa-miR-141-3p and hsa-miR-203 upregulated in the mutation group. Conclusions: It is suggested that there are different carcinogenic pathways for EGFR mutation tumors. Those miRNAs that associated EGFR mutation can be further explored for their application in target therapy and prognostics.
Meta-analysis of EGFR TKI as maintenance therapy in non-small cell lung cancer (NSCLC).
Authors: Lilian Martins Arruda, Felipe Melo Cruz, Waldec Jorge David, Auro Del Giglio
Journal: Journal of Clinical Oncology (2014)

e19081 Background: Maintenance therapy is defined as the continuation of a treatment after achieving a clinical response to platinum-based chemotherapy. The objective of this meta-analysis was to assess the effect of EGFR-TKI (gefitinib and erlotinib) as maintenance therapy in overall survival (OS) and progression free survival (PFS) in metastatic NSCLC. Methods: We conduct a systematic search in the PUBMED, EMBASE, LILACS and COCHRANE library databases for phase III trials with metastatic NSCLC patients who received EGFR-TKI as maintenance therapy. Patients should have received at least three cycles of first line platinum based chemotherapy followed by EGFR TKI or best supportive care immediately after the end of chemotherapy. We used STATA v. 12 for the statistical analysis. Results: Five studies including 2,263 patients were included in the pooled analysis. We observed a statistically significant improvement in OS (HR 0.83, 95% CI 0.77-0.90, p=0.0001, heterogeneity Q=0.54, p=0.97) and PFS (HR=0.61, 95% CI 0.49-0.76, p=0.0001, heterogeneity Q=53.3, p=0.001) favoring the EGFR-TKI arm. Exploring the heterogeneity for PFS by excluding the INFORM trial, the results turned to be homogenous with similar HR (0.68 95% CI 0.64-73, p=0.001, heterogeneity Q=1.94, p=0.58). All the studies enrolled patients with unselected EGFR mutation status. Only 516 patients (22.8%) had the EGFR mutation status known, 79 positive (mut) and 437 wild type (wt). The HR for PFS in mut patients was 0.13 (95% CI 0.07-0.21, p=0.0001) and in wt patients was 0.79 (95% CI 0.67-0.92, p=0.003). The EGFR TKI arm presented more grade 3-4 adverse events (elevated ALT/AST and skin rash). Conclusions: EGFR TKI maintenance therapy improves OS and PFS in unselected metastatic NSCLC patients. A larger benefit is observed, however, in EGFR mut patients. EGFR wt status should not contraindicate a trial of EGFR TKI maintenance in these patients.
Final overall survival (OS) results from a phase II study of pemetrexed (Pem) and cisplatin (Cis) with concurrent thoracic radiation (RT) after Pem-Cis induction in patients with unresectable locally advanced (LA) nonsquamous non-small cell lung cancer (NS-NSCLC).
Authors: Silvia Novello, Walburga Engel-Riedel, Monika Serke, Philippe Giraud, Carla Visseren-Grul, Sophie Ameryckx, Victoria Soldatenkova, Nadia Chouaki, Pilar Garrido
Journal: Journal of Clinical Oncology (2014)

7539^ Background: This single arm multicenter phase II study assessed the efficacy and safety of Pem-Cis induction chemotherapy (CT) followed by full-dose Pem-Cis + concurrent RT in patients (pts) with LA NS-NSCLC. The 1yr PFS rate (primary endpoint) was 51.3% (ECCO 2013), incidences of Grade (G)3/4 (esophagitis 12%, neutropenia 11%) and G1/2 toxicities were low during CT and CT+RT (ECCO 2013, WCLC 2013). Here we report the final results after 2yr follow-up. Methods: Pts with unresectable Stage IIIA/B NS-NSCLC (AJCC V6) and ECOG-PS 0-1 received 2 cycles of Pem 500/Cis 75mg/m2on Day (d)1, q21d. Pts who did not progress, with no residual neurological toxicity >G2, ECOG-PS 0-1 and lung V20<35% continued with 2 cycles of full dose Pem-Cis + concurrent RT (2Gy/fraction, 66Gy total). All pts received vitamin supplementation/dexamethasone prophylaxis as per Pem label. Results: Of 90 pts enrolled (all treated), 75 (83.3%) completed induction CT and started concurrent CT+RT (baseline for 90/75 pts: median age 61/62yrs, male 57%/53%, ECOG-PS 0 66%/65%, mean (SD) FEV 2.3(0.62)/2.3(0.59)L, adeno 90%/92%, Stage IIIA 36%/37%). Post discontinuation, 16.7% of pts had surgery, 26.7% RT, and 36.7% systemic CT. Median OS was 26.2mo (table). Tumor response rate (table) included 9 CRs (10.0%; 6 after surgery, 3 after CT-RT only), all were still progression-free at study end (CR for 3.8-19.6mo). Late toxicities included serious adverse events (SAE) related to study drug (3 pts: G3 leukopenia, G3 hypoacusis, G2 pulmonary embolism) and SAEs of radiation pneumonitis (2 pts: 1 G3, 1 G2). Conclusions: Pem-Cis induction CT followed by full-dose Pem-Cis and concurrent RT was effective (median OS 26mo), acute and late toxicity was manageable during both induction CT and concurrent CT+RT. Clinical trial information: NCT01000480. All pts (ITT) N=90 Started concurrent CT+RT (N=75) Kaplan-Meier estimate, months (95%CI) mPFs 10.6 (8.6, 17.3) 12.5 (9.6, 19.0) mOS 26.2 (16.7, n.e.) 30.0 (21.3, n.e.) Tumor response, % (95%CI) Response rate 60.0 (49.1, 70.2) 72.0 (60.4, 81.8) Disease control rate 77.8 (67.8, 85.9) 93.3 (85.1, 97.8)
Role of Single Agent and Combination Chemotherapy Strategies in Relapsed/Refractory Peripheral T-Cell Lymphoma: Results from the Complete Registry
Authors: Robert Stuver, Niloufer Khan, Marc Schwartz, Mark Acosta, Massimo Federico, Christian Gisselbrecht, Frederick Lansigan, Lauren C. Pinter-Brown, Barbara Pro, Andrei R. Shustov, Steven M. Horwitz, Francine M. Foss, Salvia Jain
Journal: Blood (2018)
Clinical significance of TILs subtypes in non-small cell lung cancer.
Authors: Kurt A. Schalper, Jason Brown, Joseph Francis McLaughlin, Roy S. Herbst, David L. Rimm
Journal: Journal of Clinical Oncology (2014)

8082 Background: Tumor infiltrating lymphocytes (TILs) are associated with better outcome in diverse neoplasms including non–small cell lung cancer (NSCLC). TILs are usually determined using subjective semi-quantitative methods. Studies suggest that TILs subtypes have independent roles and their contribution to prognosis remains unknown. Here, we measured TILs subtypes in NSCLC using objective methods and determined their relationship with clinico-pathologic characteristics and survival. Methods: Using the AQUA method of quantitative fluorescence, we measured the levels of CD3, CD8 and CD20 in 554 stages I-IV NSCLC represented in two tissue microarrays (YTMA79 n=204 and YTMA140 n=350). TILs subtypes were simultaneously measured in different tumor compartments using multiplexed immunofluorescence for epithelial tumor cells (cytokeratin), T lymphocytes (CD3), cytotoxic T cells (CD8), B lymphocytes (CD20) and nuclei (DAPI). Associations were determined using uni/multivariate analyses with per-unit adjustments. Results: In both NSCLC collections CD3, CD8 and CD20 signals showed a positive non-linear relationship (R=0.3-0.7, P<0.001). CD3 levels were not correlated with age, gender, smoking, tumor size, stage and histology. High levels of CD8 and CD20 (> median) were significantly associated with adenocarcinoma histology. Using proportional hazard models and continuous scores, CD3 and CD8 were significantly associated with longer survival in YTMA79 (HR=0.59 [CI:0.41-0.81] P=0.0003 for CD3 and HR=0.34 [CI:0.12-0.74] P=0.003 for CD8) and YTMA140 (HR=0.44 [CI:0.20-0.88] P=0.01 for CD3 and HR=0.437 [CI:0.20-0.81] P=0.007 for CD8). The contribution of CD20 was less pronounced (HR=0.86 P=0.05 and HR=0.93 P=0.29, respectively). In multivariate analysis, the prognostic effect of CD3 and CD8 were independent from age, tumor size, histology and stage. Conclusions: Increased CD3 and CD8 positive TILs are independent prognostic factors in NSCLC.Despite the positive relationship between TILs subtypes, only CD8 and CD20 show association with adenocarcinoma histology. Objective measurement of TILs subpopulations could be useful to predict response or monitor the off-target effect of anti-cancer immunostimulatory therapies.
Abstract #2799: Combination therapy with IMGN901 and lenalidomide plus low-dose dexamethasone is highly effective in multiple myeloma xenograft models
Authors: Kathleen Whiteman, Holly Johnson, Shanqin Xu, Jonathan Moreland, Veera Vyas, Laura Bartle, Olga Ab, Christina Carrigan, Jan Pinkas, Robert Lutz
Journal: Cancer Research (2009)

The CD56-binding antibody-maytansinoid conjugate IMGN901 is currently being evaluated in patients with CD56-positive multiple myeloma (MM). In preclinical studies, IMGN901 was found to be highly active as a single agent against MM xenograft models. Lenalidomide, used in combination with dexamethasone, is approved for the treatment of MM in patients who had received at least one prior therapy. More recent studies demonstrated that lenalidomide in combination with low-dose dexamethasone was highly active in newly-diagnosed MM patients. The activity of IMGN901 used in combination with lenalidomide plus low-dose dexamethasone (len/dex) was examined using human CD56-positive MM xenograft models. Immunodeficient mice bearing established subcutaneous human MM xenografts were treated with IMGN901 (150 µg/kg, days 1 and 8), len/dex (lenalidomide,100 mg/kg, days 1-5, 8-12; dexamethasone, 1.5 mg/kg, days 1 and 8) or the combination of these treatment regimens. Tumor volumes and body weights of mice in control and treatment groups were measured twice weekly. Satellite groups of tumor-bearing animals were treated in parallel, and at various time points during the treatment phase tumors were isolated for immunohistochemical analysis of markers of cell proliferation, apoptosis, and angiogenesis to investigate mechanisms of activity for the combination treatments. KI67 staining was performed to determine the tumor cell proliferative index. Cleaved caspase-3 and TUNEL staining was performed to assess apoptosis, and percent area staining for CD31 endothelial cell marker was determined to evaluate the anti-angiogenic activity of the monotherapies versus the IMGN901/len/dex triple combination. The combination of IMGN901 and len/dex demonstrated greater-than-additive anti-tumor activity in subcutaneous MM tumor xenografts as compared to treatment with either agent alone. Our preclinical results provide strong rationale supporting the clinical evaluation of IMGN901 in combination with lenalidomide plus low-dose dexamethasone for the treatment of patients with CD56-positive multiple myeloma.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2799.
Double Immune Checkpoint Inhibitor Blockade with Nivolumab and Ipilimumab with or without Azacitidine in Patients with Myelodysplastic Syndrome (MDS)
Authors: Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Koji Sasaki, Naval G. Daver, Elias J. Jabbour, Yesid Alvarado, Courtney D. DiNardo, Farhad Ravandi, Gautam Borthakur, Prithviraj Bose, Naveen Pemmaraju, Kiran Naqvi, Jorge E. Cortes, Tapan M. Kadia, Marina Y. Konopleva, Caitlin R. Rausch, Yvonne Gasior, Hagop M. Kantarjian
Journal: Blood (2018)
Abstract 14822: Aspirin Given Twice Daily Reduced the Platelet Reactivity More Than Once Daily in People With Type 2 Diabetes Without Cardiovascular Disease
Authors: Yihong Sun
Journal: Circulation (2013)

Background: In type 2 diabetes (T2DM), Aspirin at low doses has been established for secondary cardiovascular prevention, but as yet there is no definitive data showing primary cardiovascular preve...
APOBEC3B Is Induced By Activation of DNA Repair Pathway and Modulates the Survival and Treatment Response in Human Multiple Myeloma
Authors: Lijie Xing, Jiye Liu, Liang Lin, Shih-Feng Cho, Kenneth Wen, Tengteng Yu, Phillip Hsieh, Gang An, Lugui Qiu, Nikhil Munshi, Kenneth Anderson, Yu-Tzu Tai
Journal: Blood (2018)