Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma

Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib- dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of anygrade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7

Competing risks methodology applied to the analysis of cancer therapy outcome

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

BTD Gene Mutations in Biotinidase Deficiency: Genotype-Phenotype Correlation

Objective: To identify the biotinidase (BTD) gene mutations in patients with biotinidase deficiency in our region; and to determine the phenotype-genotype correlations in the presence of clinical findings

Amino acid metabolism disorders and PAH gene mutations in Southeastern Anatolia Region

Objectives: Inborn errors of metabolism are generally autosomal recessive inherited disorders. The incidence and genetic features of neonatal metabolic disorders vary significantly by regions and populations. In this study, we aimed to determine the amino acid metabolism disorders and evaluate the genetic test results of these patients retrospectively

Effects of APOE, ACE, PICALM, and CYP2D6 Gene Variants on Alzheimer's Disease

Background: Alzheimer's disease is a multifactorial, neurodegenerative disease which is considered the most common cause of dementia. It is divided into two subtypes based on the age of onset: Early- Onset Alzheimer's Disease (EOAD) and Late-Onset Alzheimer's Disease ( LOAD)

Retrospective analysis of whole-body multislice computed tomography findings taken in trauma patients

Objectives: Using whole-body multislice computed tomography (MSCT) excessively or with irrelevant indications can be seen in many centers. The aim of this study was to analyze retrospectively the MSCT findings in trauma patients admitted to the emergency department. Methods: Records of the patients who have applied to the emergency department due to blunt trauma in a 12 month period and whose whole body MSCT images have been taken, were evaluated using the “Nucleus Medical Information System”. Results: The most frequent type of trauma was traffic accidents in 61.4%, falling down from the height in 22.4%, and motorcycle accidents in 11.4% of patients. Of the patients, 25.2% were discharged from the emergency, while 73.8% were hospitalized. At least one CT findings associated with trauma was present in 61.4% of our patients. Pathological findings in MSCT were most frequently detected in the head and face (35.3%) and thoracic (28.6%) regions, respectively. The most common finding in the head and face region was fractures. The most common pathological findings in the thoracic region were pulmonary contusion and rib fractures. A significant relationship was detected between trauma type and spinal MSCT result (p < 0.001). In a large percentage of the patients, MSCT findings were normal in the abdominal region and genitourinary system. Vertebral fractures were most frequently detected in the thoracolumbar region. Conclusions: In our study, our rate of negative CT was found to be 38.6%, which is a higher ratio compared to other studies conducte on this topic. Keywords: Emergency, Trauma, Whole-body multislice computed tomograph

Importance of patient, tumour and treatment related factors on quality of life in head and neck cancer patients after definitive treatment

The purpose of this study is to assess patient, tumour and treatment related factors on quality of life (QoL) outcomes of patients who received definitive or postoperative radiotherapy +/- A chemotherapy for head and neck (H&N) cancer. In this cross-sectional study, 110 H&N cancer patients were evaluated in follow-up visit and were asked to fill out the European Organisation for Research and Treatment of Cancer QoL Core Questionnaire (QLQ-C-30) and H&N Module (QLQ-H&N35). Patients were also graded for their late side effects using EORTC/RTOG scoring system. The QLQ C-30 and QLQ-H&N35 mean scores were compared using ANOVA analysis for these variables: age, gender, occupation, educational status, social security status, place of residence, tumour localization, clinical stage, comorbidity, Karnofsky performance score, treatment modality and side effects. Median follow-up was 29 (4-155) months. Tumour localization was significant factor affecting physical (P = 0.03), social (P = 0.01), cognitive (P = 0.002) functioning. Treatment modality had significant impact on the physical (P = 0.02) and cognitive scores (P = 0.008). Global QoL was affected significantly by disease stage (P = 0.01) and occupation (P = 0.01). The QLQ-H&N35 scores were found significantly higher in patients with moderate/severe late morbidity. Tumour localization and the treatment modality are the most important factors affecting the QoL of H&N cancer patients treated definitively

A Case of Enterobacter cloacae Meningitis Secondary to Urinary Tract Infection

WOS: 000464106200018Gram-negative bacterial meningitis can usually be seen in neonates and elderly patients, after head trauma or interventions such as prostate biopsy and brain surgery. Typical findings of acute bacterial meningitis such as fever, headache and meningeal irritation signs may not be observed, and mortality rate is high in these patients. In this report, we present a case of Gram-negative bacterial meningitis secondary to bacteremia probably due to urinary tract infection. The patient died despite appropriate antibiotic therapy. Central nervous system infection should be kept in mind especially when elderly patients with comorbid diseases do not respond to antibiotic treatment and changes in mental status develop