Patient-Reported Outcome Measures Used in Routine Care Predict for Survival at Disease Progression in Patients With Advanced Lung Cancer

BackgroundPatient-reported outcome (PRO) measures have been increasingly implemented in routine care to aid in clinical decision-making. However, the prognostic value of PRO measures as a tool for decision making is not easily interpreted by clinicians. Our aims were to explore the prognostic value of PRO measures at disease progression and the changes in PRO measures between treatment start (baseline) and disease progression.Patients and MethodsSince 2014, patients with lung cancer have completed an electronic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and LC-13 before every outpatient visit at the Department of Oncology, Hospital Unit West, Jutland, Denmark. The patients’ responses were used in routine care. Patients receiving palliative antineoplastic treatment were eligible for analysis if the questionnaire had been completed at the initiation of first-line treatment and at disease progression. The prognostic value of the scores was evaluated using a Cox proportional hazard model. A P value < .01 was considered statistically significant.ResultsA total of 94 screened patients were included. At disease progression, survival could be predicted from the absolute score of the global health scale, 3 functional scales (physical, role, emotional), and 7 symptom scales (fatigue, pain, dyspnea, hemoptysis, lung cancer dyspnea, chest pain). In addition, changes in hemoptysis, dysphagia, dyspnea, and chest pain predicted for survival at progression.ConclusionPRO measures used in routine care can provide clinicians with relevant prognostic information about patients with lung cancer at disease progression. These results show the potential value of PRO measures when used in clinical decision-making.     

Capillary electrophoretic analysis of fragment length polymorphism in ribosomal markers of Cryptosporidium from humans

Cryptosporidium oocyst DNA samples (n=80) from humans with cryptosporidiosis in Australia and the UK were characterized genetically and categorized by capillary electrophoretic (CE) analysis of part of the small subunit gene (pSSU; approximately 300bp) and second internal transcribed spacer (pITS-2; approximately 230bp) of nuclear ribosomal DNA. The amplicons were heat denatured and subjected to capillary electrophoresis in LPA matrix (Amersham) in a MegaBACEtrade mark 1000 system (Amersham). The chromatograms captured were stored electronically and then analysed using MegaBACEtrade mark Fragment Profiler software. Using reference DNA control samples representing Cryptosporidium hominis and Cryptosporidium parvum, particular peaks in the profiles were defined for their specific identification and differentiation. The two species could be readily differentiated based on their profile in the pSSU, the peak differences being associated with a nucleotide difference of <1.7%. While no variation was detectable in the pSSU profiles within each species, significant intraspecific variability in the positions of peaks in the pITS-2 chromatograms was displayed. For the 80 samples subjected to CE analysis of the pITS-2, four different genetic variants (genotypes) were detected within C. hominis and seven within C. parvum. Based on CE analysis of either pSSU and pITS-2 amplicons, it was readily possible to detect both species in 'mixed samples'. This CE method is time- and cost-effective, and may find applicability as a tool for the high throughput analysis of oocyst DNA samples for epidemiological surveys and for the monitoring of cryptosporidiosis outbreaks.     

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09–1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26–1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of ?1.06 min (?1.80 to ?0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.     

Outcomes of research biopsies in phase I clinical trials: the MD anderson cancer center experience

Background.

Research biopsies are crucial for exploring the impact of novel agents on putative targets. The current study assesses the safety and success rate associated with performing such biopsies.

Methods.

We reviewed the medical records of 155 consecutive patients who had one or more research biopsies as part of a phase I trial from September 2004 to October 2009.

Results.

Of 281 research biopsies performed, 118 were paired before and after treatment biopsies (total = 236 biopsies). The most common sites of biopsy were superficial lymph node (19.9%), followed by liver (16.4%), and then soft tissue (15.7%). Ultrasound-guided biopsies were the most frequent type (53.7%). Among 142 patients who consented for mandatory biopsy, 86.6% had the biopsy performed, compared with 4.4% of 911 patients offered a biopsy on an optional basis (p < .0001). Biopsy was obtained most frequently on industry-sponsored trials; lack of funding on nonindustry trials was the most common reason that biopsies were not obtained. Of 281 single biopsies, only 4 (1.4%) had complications: pneumothorax requiring chest tube placement (n = 2), infection requiring admission (n = 1), and arrhythmia with hypotension (n = 1). All but one biopsy was successful in obtaining tissue. No deaths were attributable to biopsy.

Conclusions.

Our experience demonstrates that research biopsies in early phase clinical trials are safe (1.4% risk of serious complications), and a higher percentage of patients underwent mandatory biopsies (86.6%) compared with that of the patients with optional biopsies (4.4%).     

Interaction of MLL amino terminal sequences with menin is required for transformation

Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. Both wild-type MLL and MLL fusion proteins interact with the tumor suppressor menin and with the Hoxa9 locus in vivo. Here, we show that MLL sequences between amino acids 5 and 44 are required for interaction with menin and for the transformation of hematopoietic progenitors. Blocking the MLL-menin interaction by the expression of a dominant negative inhibitor composed of amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, suggesting that targeting this interaction may be an effective therapeutic strategy for leukemias with MLL rearrangements.