HER2 positive rates are enriched amongst colorectal cancer brain metastases: a study amongst 1920 consecutive patients

Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation

Abstract

Background

Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients.

Patients and methods

Key inclusion criteria were: centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval (IFI) >3 months. TEMIRI (TMZ 150mg/sqm on days 1-5 plus irinotecan 100mg/sqm on days1,15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary endpoint was overall response rate (ORR). Exploratory translational analyses included MGMT immunoistochemistry (IHC) and methylBEAMing (MB).

Results

Between December 2014 and June 2017, 25 patients were enrolled. The primary endpoint was met, since 6 patients achieved a partial response (ORR 24%, 95% CI, 11%-43%). At a median follow-up of 15.6 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8 months, respectively. Only 4 (16%) patients had ≥ grade 3 adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0 months; HR = 0.29, 95%CI, 0.02-0.41; p = 0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy.

Conclusions

TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft tissue sarcomas

Abstract

Background

Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management.

Methods

A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated.

Results

CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72).

Conclusion

CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind^®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases

Publication date: Available online 2 June 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Mark D.P. Davis, Jeroen C.H. van der Hilst
A wide differential diagnosis must be considered in a patient presenting with urticarial plaques. Although acute and chronic urticaria are the commonest diagnoses, other differential diagnoses include polymorphous eruption of pregnancy, mast cell disorders, hypereosinophilic syndrome, urticarial vasculitis, pemphigoid, systemic lupus erythematosus, and autoinflammatory disease. This review will specifically address urticarial vasculitis and autoinflammatory syndromes. These entities represent contrasting examples of urticarial-like lesions resulting from either an adaptive immune complex–mediated mechanism (urticarial vasculitis) or an innate immune–mediated mechanism (autoinflammatory disorders), with differing therapeutic implications. In patients presenting with painful, persistent plaques that last more than 24 hours and resolve with bruising of the skin, consideration should be given to a diagnosis of urticarial vasculitis. A biopsy should be obtained to ascertain this diagnosis. In patients presenting with a persistent history of recurrent urticarial plaques associated with signs of systemic inflammation including fevers and elevated inflammatory markers (C-reactive protein [CRP]/serum amyloid A, leukocytosis, and negative connective tissue serologies), consideration should be given to autoinflammatory disorders: the 3 cryopyrin-associated periodic syndromes, Schnitzler syndrome, and familial cold autoinflammatory syndrome 2. Serum protein electrophoresis should be checked to rule out an underlying monoclonal gammopathy.

Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico

Publication date: Available online 2 June 2018
Source:Actas Dermo-Sifiliográficas
Author(s): P. Rodríguez-Jiménez, I. Mir-Viladrich, P. Chicharro, G. Solano-López, F.J. López-Longo, C. Taxonera, P. Sánchez-Martínez, X. Martínez-Lacasa, M. García-Gasalla, J. Dorca, M. Arias-Guillén, J.M. García-García, E. Dauden
El riesgo de infección por Mycobacterium tuberculosis se halla aumentado en los pacientes con enfermedades inflamatorias crónicas y en tratamiento inmunosupresor, en particular con terapia antifactor de necrosis tumoral α. La detección de la infección tuberculosa latente y el tratamiento preventivo dirigido a reducir el riesgo de progresión a tuberculosis activa es obligatoria en este grupo de pacientes. Este documento de consenso multidisciplinar actualiza la opinión de expertos y establece recomendaciones para el diagnóstico y tratamiento de la infección tuberculosa latente en estos pacientes, según los conocimientos actuales en terapias biológicas.Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.

Comparative study of Gram-negative bacteria response to solar photocatalytic inactivation

Abstract

Solar photocatalytic inactivation of Gram-negative bacteria with immobilized TiO₂-P25 in a fixed-bed reactor was modeled with simplified kinetic equations. The kinetic parameters are the following: the photocatalytic inactivation coefficient (k_d,QUV), the initial bacterial reduction rate (A) in the contact with the disinfecting agent, and the threshold level of damage (n) were determined to report the effect of Q_UV/TiO₂-P25 on bacterial cultivability and viability and to compare the response of bacterial strains to photocatalytic treatment. In addition, the integration of the reactivation coefficient (C_r) in the photocatalytic inactivation equation allowed evaluating the ability of bacterial reactivation after photocatalytic stress. Results showed different responses of the bacteria strains to photocatalytic stress and the ability of certain bacterial strains such as Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC4114 to resuscitate after photocatalytic treatment.