The use of virtual care rapidly increased during the COVID-19 pandemic and has persisted as a routine method of care delivery. Much of the literature on virtual care in oncology has focused on solid tumors, and little is known about its application in malignant hematology.We performed a retrospective review of patients with hematologic malignancies at Princess Margaret Cancer Centre from October 2019 to March 2021 to determine the use of virtual care during this period, cost-savings associated with virtual visits, and patient satisfaction. Patient satisfaction was assessed using the Your Voice Matters survey, a provincially administered survey to evaluate patient experience.Overall, 12.1% (1,122/9,295) of patients had a virtual visit during the study period (0% from October 2019 to February 2020, 36% from March to August 2020, and 30% from September 2020 to March 2021), of which 36% were in the lymphoma clinic and 46% were in the myeloma clinic. The mean two-way opportunity cost for an in-person visit was $168.00 CAD per person with public transit, and $120.40 CAD per person driving. Responses to the Your Voice Matters survey indicated that patients with a virtual visit reported that physical symptoms were discussed appropriately (mean 4.73/5), and were more likely to ask for a follow-up virtual visit compared with patients with in-person visits (mean 4.50/5 v 3.02/5, respectively; P < .01).These findings suggest that virtual care may be a feasible and well-received tool for delivering care to a substantial proportion of patients with hematologic malignancies, while enabling substantial cost-savings to patients.
<p>Predicting survival outcomes using cancer mutation concentration (CMC) at baseline and cycle 3 of pembrolizumab. CMC was determined using a tumor-informed bespoke approach across the trial cohort. At both baseline and cycle 3, patients were split into above- or below-median groups. Survival outcomes are shown, with hazard ratios and p-values adjusted for cohort using a Cox model. PFS analysis at cycle 3 excludes one patient who progressed before the collection of cycle 3 sample.</p>
<p>Increase in both ctDNA metrics identifies a subgroup with particularly poor outcome. Post-hoc analysis of ΔCSM and ΔCMC together demonstrates that a decrease in either metric was sufficient to result in significantly improved PFS and OS, whereas increase in both metrics identified a group with particularly poor outcomes. PFS analysis at cycle 3 excludes one patient who progressed before the collection of cycle 3 sample.</p>
<div>Abstract<p>Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.</p>Significance:<p>Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors.</p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-14-6-ITI" target="_blank">This article is featured in Selected Articles from This Issue, p. 897</a></i></p></div>
<div>Abstract<p>Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.</p>Significance:<p>Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors.</p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-14-6-ITI" target="_blank">This article is featured in Selected Articles from This Issue, p. 897</a></i></p></div>
<p>Multivariable analysis of OS and PFS using cancer mutation concentration (CMC) at baseline and cycle 3 of pembrolizumab. CMC was determined using a bespoke targeted approach across the trial cohort. At both baseline and cycle 3, patients were split into above- or below-median groups. Survival outcomes are shown in a multivariable analysis including cohort, PD-L1 expression, and tumor mutation burden (TMB).</p>
<p>Cancer-specific methylation (CSM) and fragment length scores (FLS) are moderately correlated. CSM and FLS scores were computed for each sample. Correlation testing between FLS and log-adjusted CSM was performed using Spearman's method.</p>
