Cancer care devours hours on the clock: travelling to the cancer centre, sitting in waiting rooms and dealing with adverse events and other problems, eat into the precious time a cancer patient has left – which, depending on the cancer and the stage, may not be long.
The problem has been termed “time toxicity”, and a growing number of oncologists suggests this should be discussed with patients when they consider treatment, particularly terminal patients.
People with advanced gastrointestinal cancer, for instance, can spend one of every four of their remaining days going back and forth between the hospital, said Dr Arjun Gupta, a gastrointestinal oncologist at the University of Minnesota, Minneapolis.
He said that’s enough to offset the improvement in survival – often around two to three extra months – patients with advanced solid tumours can expect with the latest treatments.
Lack of data
How patients spend their time while receiving treatment has been fairly well studied in cardiology and some other specialties, but the issue has only recently been gaining traction in oncology.
Perhaps the oncology field has been too busy incorporating “the marginal survival gains” from recent advances to pay much attention to the “everyday time demands of cancer care”, Gupta told Medscape Medical News.
“Overall, our community does not do a good job of acknowledging, quantifying, or weighing … the impact of time toxicity,” he and his colleagues write in a Journal of Clinical Oncology editorial.
They say this should change. Apart from discussing survival benefits, adverse events and out-of-pocket costs, patients should be told upfront about the time demands they can expect with various treatments so they can best weigh their options.
Opting for a more involved treatment isn’t necessarily wrong; rather, patients “should have the option to spend the time how they see fit”, said Dr Tim Brown, a haematology/oncology fellow at the University of Pennsylvania.
The problem in oncology is there has been very little research to quantify the time burdens of cancer care, so outside their own personal experience, oncologists don’t have much information to pass along to patients.
As a result, time toxicity remains “a very, very hidden cost of cancer care”, Gupta said.
An FDA mandate?
There are now plans to close the data gap. Gupta’s team is analysing completed clinical trials to estimate how much time patients spent on care-related activities. Analysis of the first trial is due to be published soon in the Journal of Clinical Oncology.
The team’s next step is to engage with co-operative groups to include time toxicity as a prospective endpoint in future studies.
Ultimately, Gupta would like to see the US Food and Drug Administration (FDA) require a measurement of time toxicity in cancer clinical trials. His team has proposed “days at home” as a metric that is easy to measure and understand.
“We’ve had generally very encouraging reactions to the idea from all stakeholders and, most importantly, patients and patient advocates,” he said.
"We are still in the early phases, but overall, we are building consensus in a body of work showing that it is possible to quantify time toxicity.
"We are making it more formalised…so (that) the science can move forward.”
Lessons from the loss of a loved one
Other groups are making similar moves. In a recent preprint publication, investigators led by Dr Vinay Prasad from the University of California, San Francisco, reviewed pivotal trials of 13 metastatic cancer drugs approved by the FDA from 2009–2022.
They found that patients in the investigative arms spent a median of an extra 16 hours monthly on trial-related activities compared with patients who received best supportive care. Of that time, 5.3 hours were spent travelling.
The extra time was spread over a minimum of 4-5 days a month. The calculation did not include time spent for infusions, since most of the drugs were taken orally, and it also did not include time spent on treating adverse events.
Across the trials, the median improvement in overall survival was just about two months.
Echoing what Gupta’s team is saying, Prasad and colleagues concluded that future trials “should prospectively assess actual time on care … and calculate actual home days gained”.
Similarly, a team from East Carolina University recently conducted a trial involving patients with locoregional pancreatic cancer who were treated with curative intent. The mean overall survival was 17.5 months, but the analysis showed that 11% of the patients’ days were spent in clinical encounters.
A proactive approach
A group of clinicians in Philadelphia is using a text-message app to save cancer patients time.
Co-investigator Dr Timothy Brown from the Penn Centre for Cancer Care Innovation at the University of Pennsylvania said they are using the app to survey patients for signs and symptoms of toxicity to immunotherapy. If patients report that they are doing well, the app lets them skip a routine check-up.
The team recently reported in JAMA Network Open that the approach is safe, with a 0% rate of false negatives. The next step is to study how much time patients save by using the app.
Regarding time toxicity, Brown says: “I think it’s really important to take a step back and make sure what we are proposing and prescribing for patients isn’t overly burdensome and is in line with their treatment goals. I think understanding time toxicity gives us another tool to do that.”
Study details
Estimation of time cost of anti-cancer drugs approved based on comparisons to best supportive care: a cross sectional analysis
Vinay Prasad, Timothée Olivier, Emerson Chen, Alyson Haslam.
Pre-print in MedRxiv on 22 June 2022
Background
Financial costs from cancer treatment are increasingly recognised, but what has historically been under-recognised is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BCS), with the assumption that without this drug, a patient could have been treated with observation, home palliative care or hospice services, with minimal time seeking medical care.
Methods
We searched all FDA approvals (2009 – March 2022) for randomised trials that used BCS as a treatment option for an anti-tumour drug in the metastatic setting and abstracted data on treatment related activities. We then estimated time spent on these activities using previously calculated times.
Results
Of the 13 drugs tested against BSC, nine studies demonstrated an improvement in median OS (median 2.1 months). The median monthly time spent for patients in the intervention arm of BSC trials was 15.8 hours.
Conclusion
Time is a valuable resource for people who have cancer, but especially for patients who may have few to no remaining treatment options, and yet, we found that patients can spend up to 16 hours in anti-cancer drug related activities per month.
Study details
Opportunity Costs of Surgical Resection and Perioperative Chemotherapy for Locoregional Pancreatic Adenocarcinoma
Szu-Aun Lim, Scarlett B. Hao, Breana Boyd, Anastasios Mitsakos, William Irish, Aidan M. Burke et al.
Published in Oncology Practice Vol 18
Purpose
Given the perioperative morbidity and intensity of multimodality treatment, patients with resected pancreatic ductal adenocarcinoma (PDAC) spend a substantial amount of time in clinical care. The primary aim was to determine total time spent in multimodality care for patients with locoregional PDAC.
Methods
A cohort study of all patients who underwent curative-intent resection for PDAC at a single-institution, tertiary care centre was performed (2015-2019). Exact times for all relevant visits were abstracted from the primary medical record, and travel time was calculated. Care time was divided into preoperative, surgical, radiation, and systemic therapy phases of care. Primary outcome measures were the percentage of total survival time (TST) and percentage of overall survival (OS) days spent in receipt of care.
Results
One hundred seven patients were included. Patients spent a median of 5.0% (interquartile range [IQR] 2.4%-10.1%) of TST and 11.0% (IQR, 5.7%-20.4%) of OS days in receipt of clinical care. Preoperative, surgical, radiation, and systemic therapy phases of care comprised a median of 0.9% (IQR, 0.4%-2.2%), 3.0% (IQR, 1.9%-6.8%), 4.4% (IQR, 3.6%-6.3%), and 10.0% (IQR, 6.2%-14.1%) of OS days. The median per-visit travel time was 60 minutes (IQR, 32-120), and the median cumulative travel time was 22.0 hours (IQR, 12.0-51.5). 12.1% (n = 13) and 7.8% (n = 4) of patients spent > 10% of TST in receipt of surgical and systemic therapy care, respectively.
Conclusion
Patients with locoregional pancreatic cancer spend a considerable percentage of their survival time in receipt of oncologic care. Further research to determine predictors of increased time burden is warranted to better inform shared decision making.
Study details
Accuracy of a Text Intervention to Minimize the Burden of Cancer Care Among Patients Treated With Immune Checkpoint Inhibitors
Erin M. Bange, Kerry Coughlin, Wenrui Li, et al
Published in JAMA Network Open on 29 August 2022
Introduction
Patients with cancer spend substantial time receiving cancer care1; thus, innovative strategies to decrease the time burden of cancer therapy are needed. The current care model consists largely of in-person visits to assess clinical status and treatment-related toxic effects. However many patients treated with immune checkpoint inhibitors (ICIs) do not experience toxic effects.2 We hypothesised that these patients without symptoms of ICI toxic effects could be accurately identified using a text message–based triage instrument and safely proceed to treatment, lessening the need for an in-person visit.
Methods
This single-centre, cross-sectional study evaluated the performance characteristics of a text message–based triage instrument to identify patient-reported ICI toxic effects, against the standard in-person clinician assessment documented in the electronic medical record. Patients were consecutively screened, and those who spoke English, were receiving single-agent ICI for a solid tumour, and had access to text messaging were approached for oral consent. Performance characteristics and number needed to text for 1 additional patient to avoid an office visit, were calculated with 95% CIs. The instrument contained 16 questions adapted from the National Cancer Institute’s Professional Common Terminology Criteria for Adverse Events and was administered once at a single point in time during their treatment course via secure text message 96 hours before the patient’s scheduled infusion. A positive response to any question (eg, score >0) was used to indicate toxic effects. Clinic notes were reviewed by 2 trained personnel (E.M. and T.J.B.) for the presence or absence of any grade of ICI toxic effect. Patient perspectives were quantified.
Results
Between October 1 and November 25, 2021, 70 patients were approached for consent. Of these, 50 enrolled and 45 patients completed the instrument. The median (IQR) age was 68 (60-72) years, 31 (62%) were male, and 44 (88%) were White. The median (IQR) ICI cycle number was 12.5 (4.0-23.0); most patients received either pembrolizumab (27 patients [54%]) or nivolumab (17 patients [34%]) for palliative management (37 patients [74%]) of genitourinary (15 patients [30%]), lung (13 patients [26%]), or skin (11 patients [22%]) cancers. Patients who completed the instrument were more likely to be younger (median [IQR] age, 67 [60-71] vs 76 [73-76] years) and male (30 patients [66%] vs 15 patients [33%]) than those who did not.
The prevalence of any documented ICI toxic effects in the electronic medical record was 57.8%. The instrument had 100% sensitivity (95% CI, 87%-100%) corresponding to a 0% false-negative rate, 47% specificity, and a negative predictive value of 100% (95% CI, 66%-100%). The number needed to text was determined to be 5 patients. Other accuracy parameters are presented in the Table. Visual impairment and limited access to a smartphone were common reported barriers to completion.
Journal of Clinical Oncology article – Time Toxicity of Cancer Treatment (Open access)
Medscape article – Time Toxicity: A 'Very Hidden' Cost of Cancer Care (Open access)
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