Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer.

BACKGROUND: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825). METHODS: Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations. RESULTS: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. CONCLUSION: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.

Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.

BACKGROUND: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. METHODS: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.

A community needs assessment: the care needs assessment pack for dementia (CarenapD)--its development, reliability and validity.

OBJECTIVE: To develop and evaluate a multidisciplinary needs assessment tool for people with dementia living in the community and their carers. DESIGN: The measure was developed through applying a theory of need, generating content, consultation with potential users and refinement and evaluation. Validity was established incrementally through the development process. SETTING: The development and evaluation was conducted in a variety of settings, including multidisciplinary dementia community care teams, social work departments, day hospitals, and inpatient and residential care. PATIENTS: The evaluation included community patients with a formal diagnosis of dementia (N = 34) and consultation with a multidisciplinary group of potential users (N = 23). The development process included inpatients with a formal diagnosis of dementia (N = 157) and consultation with potential users (N = 170) from a range of professions including both health and social care. MEASURES: Interrater reliability was assessed using the kappa statistic. Social validity was estimated using a measure developed for this purpose as part of the development process. RESULTS: The evaluation of interrater reliability demonstrated that three-quarters of assessors agreed on at least 85% of items in the CarenapD. The kappa statistic demonstrated that agreement for 76.2% of items in the CarenapD was 'good' or better (ie kappa >0.75), for 12.4% of items it was 'fair' or 'moderate' (ie kappa 0.35-0.60) and for the remaining 12 (11.4%) items for which kappa could not be calculated there was low intra-item variance and high agreement (>90%). There was good evidence for social validity. CONCLUSIONS: The CarenapD is a reliable and valid multidisciplinary assessment of need for people with dementia living in the community and their carers.

Cutaneous sinus tracts of dental etiology.

Intermittently draining cutaneous sinus tracts in the area of the face and neck may be caused by chronic dental infection. Diagnosis of the cause may be challenging but is the key to successful therapy. Two cases of these uncommon lesions are presented; one involved a mandibular molar and the other a mandibular incisor. Nonsurgical endodontic treatment was performed. Healing was rapid and uneventful.

Garre's osteomyelitis of the mandible resolved by endodontic treatment.

A case of Garre's osteomyelitis of the mandible is presented. The occlusal radiographs are good examples of the redundant cortical layering of the bone (onion skinning) that is classically found with this phenomenon. The cause of this case was a necrotic pulp in a carious molar with a periapical radiolucent area. We believe this is the first reported case in which an odontogenic source of infection (carious tooth) was treated not by extraction but by endodontic therapy. During the year after the root canal filling, the periapical radiolucent area filled in with new bone and the bony expansion of the mandible was completely resolved.

Long-term study of pulp capping in monkeys with three agents.

The pulps of 40 permanent teeth of two monkeys were mechanically exposed and contaminated with adjacent saliva or plaque for 3 to 5 1/2 hours. The pulps were then capped with either Keflin (an antibiotic), Durelon (a polycarboxylate cement), or Dycal (a calcium hydroxide compound). Varnish and then amalgam were inserted. Each monkey received at least one dose of Procion red H-8BS vital dye. The teeth were extracted from one monkey 23 months after capping and from the other monkey 29 months after capping. Serial, decalcified, 7 mum-thick paraffin sections were prepared. Alternate slides were stained with hematoxylin ane eosin. Unstained sections were examined for Procion labeling, and selected slides were stained by the Brown-Brenn method for bacteria. Of 13 teeth capped with Keflin, only 4 responded satisfactorily. All of the Dycal and Durelon-capped pulps were successful at both time intervals. All of the Dycal-capped pulps showed complete bridging and no inflammation or pulp obliteration. Bridging was complete in only three of the Durelon-capped pulps. The findings of this study support the findings in our previous study3 and further substantiate the effectiveness of Dycal as a pulp-capping agent. The often-repeated claim that calcium hydroxide compounds exert a persistent stimulating effect on the pulp resulting in its eventual obliteration was not supported. Durelon is not recommended for pulp capping since the material apparently lacks an antibacterial effect and does not stimulate reparative dentinogenesis at the exposure site. The low rate of satisfactory responses of pulps capped with Keflin, as used, precludes its use of pulp capping.