Skoujoensen2188

Patients with altered expression of signature genes have increased risk of death and enhanced cervical lymph node involvement. The identified SAES can be utilized as a novel predictor of increased disease aggressiveness and poor outcome in smoking-associated HNSCC.The ALK inhibitors are promising therapeutic agents against lung cancer harboring ALK fusion genes and are currently under development up to the third generation. However, its therapeutic effects are reported to be affected by differences in ALK variants and co-occurrent mutations. Materials and Methods; We experienced an autopsy case of an ALK-positive lung cancer patient who showed primary resistance to three generations of ALK inhibitors. The poor survival time of the case was 14 months. To reveal the mechanism of primary resistance to three generations of ALK inhibitors, we performed next generation sequencing for 12 specimes obtained from an autopsy with covering whole exons of 53 significantly mutated, lung cancer-associated genes and amplicon-based target RNA sequenceing for the ALK fusion gene. The NGS analysis revealed a rare variant.3 of ALK fusion, in which 30 bp of base was inserted at the end of ALK intron.19 and was associated with EML exon.6 [E6_ins30A20] and a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. Structural analysis of the fusion protein ALK [E6_ins30A20] showed no interferance with the binding of ALK inhibitors to the kinase domain. RZ-2994 The NGS analysis of primary and metastatic lesions obtained from an autopsy revealed a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. The constitutive activation of PI3K-Akt signal by PIK3CA E542K mutation occurred downstream of ALK signaling pathway, could lead to primary resistance to ALK inhibitors in all generations.

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).

Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).

Patients received monotherapy based on 5-FU (n=1068), a cytotoxic doublet (n=395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n=727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0-1 (OR 2.57; 95% CI [1.16, 5.73]; p=0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p=0.02), alkaline phosphatase>300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p<0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p=0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80-0.96]; p=0.004).

ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.

ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.

Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations existbetween its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them.

Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P<0.0001) whilst increasing diarrhoea severity (P=0.0007) and treatment-related mortality (P=0.0045). Importantly, thte the acute and chronic complications caused by disruption of the gastrointestinal microenvironment. Translation of this new knowledge should focus on stabilising and strengthening the gut microbiome before chemotherapy and developing new microbial approaches to accelerate recovery of the mucosa. By controlling the depth and duration of mucosal injury, secondary consequences of gastrointestinal toxicity may be avoided.

The Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire is a validated patient-reported outcome measure (PROM) capturing the impacts of vaginal symptoms in postmenopausal women.

We aimed to psychometrically validate the German version of the DIVA questionnaire.

Data was collected online and by paper-pencil. We ran confirmatory factor analyses to confirm the a priori four-factor structure of the DIVA. Internal consistency was calculated using Cronbach's alpha. Correlations with other outcome measures such as the Patient Health Questionnaire-4 (PHQ-4), the SF-12 SOEP (socio-economic panel) version and self-created anchor questions were calculated regarding convergent validity. Known groups regarding age, home country and disease severity were analyzed. Test-retest reliability after 1 week and responsiveness after 4 weeks were only descriptively assessed due to low sample sizes.

The DIVA questionnaire, the Menopause Rating Scale (MRS II), the PHQ-4 and the SF-12 SOEP version were the main outcome measures.