Comorbidity is an issue of growing importance due to changing demographics and the increasing number of adults over the age of 65 with cancer. The best approach to the clinical management and decision-making in older adults with comorbid conditions remains unclear. In May 2015, the Cancer and Aging Research Group in collaboration with the National Cancer Institute and National Institute on Aging met to discuss the design and implementation of intervention studies in older adults with cancer. A presentation and discussion on comorbidity measurement, interventions, and future research was included. In this article we discuss the relevance of comorbidities in cancer, examine the commonly used tools to measure comorbidity, and discuss the future direction of comorbidity research. Incorporating standardized comorbidity measurement, relaxing clinical trial eligibility criteria, and utilizing novel trial designs are critical to developing a larger and more generalizable evidence base to guide the management of these patients. Creating or adapting comorbidity management strategies for use in older adults with cancer is necessary to define optimal care for this growing population.
PURPOSE: For patients with cancer who are older than 65 years, the 2018 ASCO Guideline recommends geriatric assessment (GA) be performed. However, there are limited data on providers’ practices using GA. Therefore, ASCO’s Geriatric Oncology Task Force conducted a survey of providers to assess practice patterns and barriers to GA. METHODS: Cancer providers treating adult patients including those ≥ 65 years completed an online survey. Questions included those asking about awareness of ASCO’s Geriatric Oncology Guideline (2018), use of validated GA tools, and perceived barriers to using GA. Descriptive statistics and statistical comparisons between those aware of the Guideline and those who were not were conducted. Statistical significance was set at P < .05. RESULTS: Participants (N = 1,277) responded between April 5 and June 5, 2019. Approximately half (53%) reported awareness of the Guideline. The most frequently used GA tools, among those aware of the Guideline and those who were not, assessed functional status (69% v 50%; P < .001) and falls (62% v 45%; P < .001). Remaining tools were used < 50% of the time, including tools assessing weight loss, comorbidities, cognition, life expectancy, chemotherapy toxicity, mood, and noncancer mortality risk. GA use was two to four times higher among those who are aware of the Guideline. The most frequent barriers for those who reported being Guideline aware were lack of resources, specifically time (81.7%) and staff (77.0%). In comparison, those who were unaware of the Guideline most often reported the following barriers: lack of knowledge or training (78.4%), lack of awareness about tools (75.2%), and uncertainty about use of tools (75.0%). CONCLUSION: Among providers caring for older adults, 52% were aware of the ASCO Guideline. Some domains were assessed frequently (eg, function, falls), whereas other domains were assessed rarely (eg, mood, cognition). Guideline awareness was associated with two to four times increased use of GA and differing perceived barriers. Interventions facilitating Guideline-consistent implementation will require various strategies to change behavior.
Background Most animals and plants have more than one set of chromosomes and package these haplotypes into a single nucleus within each cell. In contrast, many fungal species carry multiple haploid nuclei per cell. Rust fungi are such species with two nuclei (karyons) that contain a full set of haploid chromosomes each. The physical separation of haplotypes in dikaryons means that, unlike in diploids, Hi-C chromatin contacts between haplotypes are false-positive signals. Results We generate the first chromosome-scale, fully-phased assembly for the dikaryotic leaf rust fungus Puccinia triticina and compare Nanopore MinION and PacBio HiFi sequence-based assemblies. We show that false-positive Hi-C contacts between haplotypes are predominantly caused by phase switches rather than by collapsed regions or Hi-C read mis-mappings. We introduce a method for phasing of dikaryotic genomes into the two haplotypes using Hi-C contact graphs, including a phase switch correction step. In the HiFi assembly, relatively few phase switches occur, and these are predominantly located at haplotig boundaries and can be readily corrected. In contrast, phase switches are widespread throughout the Nanopore assembly. We show that haploid genome read coverage of 30–40 times using HiFi sequencing is required for phasing of the leaf rust genome, with 0.7% heterozygosity, and that HiFi sequencing resolves genomic regions with low heterozygosity that are otherwise collapsed in the Nanopore assembly. Conclusions This first Hi-C based phasing pipeline for dikaryons and comparison of long-read sequencing technologies will inform future genome assembly and haplotype phasing projects in other non-haploid organisms.
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