Time toxicity among older patients with cancer treated with palliative systemic therapy.

PURPOSE: The time toxicity of anticancer therapy, defined as days spent with healthcare contact during treatment, represents a critical but understudied outcome. This study aims to quantify time toxicity among older patients with cancer receiving palliative systemic treatment. METHODS: All patients aged ≥ 65 years with metastatic cancer receiving cytotoxic chemotherapy, immunotherapy, or targeted therapy at a single center in Mexico were selected from a prospective patient navigation cohort. Patients completed a baseline assessment, including the G8 screening and quality of life measures. Physical healthcare contact days within the first 6 months were extracted from medical records and divided by days alive during the same period. Beta regression models were used to identify predictors of time toxicity. RESULTS: We identified 158 older patients (median age 71 years); 86% received cytotoxic chemotherapy. Seventy-three percent had an impaired G8 score and were considered vulnerable/frail. Six-month overall survival was 74%. Within the first 6 months, patients spent a mean of 21% (95% confidence interval (CI) 19-23%) of days with healthcare contact. Concurrent radiotherapy (odds ratio (OR) 1.55; 95%CI 1.21-1.97), cytotoxic chemotherapy versus targeted therapy (OR 1.64; 95%CI 1.13-2.37), and an impaired G8 (OR 1.27; 95%CI 1.01-1.60) were associated with increased time toxicity. CONCLUSION: Older adults with metastatic cancer spend 1 in 5 days with healthcare contact during treatment, with a higher burden of time toxicity for patients receiving radiotherapy or cytotoxic chemotherapy and those with potential frailty. These findings underscore the importance of informing patients about their expected healthcare contact days within the context of a limited life expectancy.

Patients' considerations of time toxicity when assessing cancer treatments with marginal benefit.

BACKGROUND: Effective techniques for eliciting patients' preferences regarding their own care, when treatment options offer marginal gains and different risks, is an important clinical need. We sought to evaluate the association between patients' considerations of the time burdens of care ("time toxicity") with decisions about hypothetical treatment options. METHODS: We conducted a secondary analysis of a multicenter, mixed-methods study that evaluated patients' attitudes and preferences toward palliative-intent cancer treatments that delayed imaging progression-free survival (PFS) but did not improve overall survival (OS). We classified participants based on if they spontaneously volunteered one or more consideration of time burdens during qualitative interviews after treatment trade-off exercises. We compared the percentage of participants who opted for treatments with no PFS gain, some PFS gain, or who declined treatment regardless of PFS gain (in the absence of OS benefit). We conducted narrative analysis of themes related to time burdens. RESULTS: The study cohort included 100 participants with advanced cancer (55% women, 63% age > 60 years, 38% with gastrointestinal cancer, and 80% currently receiving cancer-directed treatment. Forty-six percent (46/100) spontaneously described time burdens as a factor they considered in making treatment decisions. Participants who mentioned time (vs not) had higher thresholds for PFS gains required for choosing additional treatments (P value .004). Participants who mentioned time were more likely to decline treatments with no OS benefit irrespective of the magnitude of PFS benefit (65%, vs 31%). On qualitative analysis, we found that time burdens are influenced by several treatment-related factors and have broad-ranging impact, and illustrate how patients' experiences with time burdens and their preferences regarding time influence their decisions. CONCLUSIONS: Almost half of participating patients spontaneously raised the issue of time burdens of cancer care when making hypothetical treatment decisions. These patients had notable differences in treatment preferences compared to those who did not mention considerations of time. Decision science researchers and clinicians should consider time burdens as an important attribute in research and in clinic.

Mitigating time toxicity in lymphoma and multiple myeloma.

The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. For example, time toxicity may influence the choice of chemoimmunotherapy versus lenalidomide-rituximab in follicular lymphoma. In myeloma, it may inform the optimal dosing schedule for proteasome inhibitors and bisphosphonates. In both malignancies, varying time toxicity profiles are a key distinction between chimeric antigen receptor T-cell therapies and bispecific antibodies. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and in clinical trials. Throughout the review, we highlight strategies to lower the time toxicity of therapies in lymphoma and myeloma without compromising their efficacy or patient safety.

Reporting time toxicity in prospective cancer clinical trials: A scoping review.

PURPOSE: This review aimed to assess the measurement and reporting of time toxicity (i.e., time spent receiving care) within prospective oncologic studies. METHODS: On July 23, 2023, PubMed, Scopus, and Embase were queried for prospective or randomized controlled trials (RCT) from 1984 to 2023 that reported time toxicity as a primary or secondary outcome for oncologic treatments or interventions. Secondary analyses of RCTs were included if they reported time toxicity. The included studies were then evaluated for how they reported and defined time toxicity. RESULTS: The initial query identified 883 records, with 10 studies (3 RCTs, 2 prospective cohort studies, and 5 secondary analyses of RCTs) meeting the final inclusion criteria. Treatment interventions included surgery (n = 5), systemic therapies (n = 4), and specialized palliative care (n = 1). The metric "days alive and out of the hospital" was used by 80% (n = 4) of the surgical studies. Three of the surgical studies did not include time spent receiving ambulatory care within the calculation of time toxicity. "Time spent at home" was assessed by three studies (30%), each using different definitions. The five secondary analyses from RCTs used more comprehensive metrics that included time spent receiving both inpatient and ambulatory care. CONCLUSIONS: Time toxicity is infrequently reported within oncologic clinical trials, with no standardized definition, metric, or methodology. Further research is needed to identify best practices in the measurement and reporting of time toxicity to develop strategies that can be implemented to reduce its burden on patients seeking cancer care.

Financial Toxicity, Time Toxicity, and Quality of Life in Multiple Myeloma.

BACKGROUND: Patients with multiple myeloma (MM) may be on therapy for years, which can lead to financial toxicity (FinTox) or time toxicity (TimeTox). The prevalence, predictors, and quality of life (QOL) impacts of FinTox and TimeTox during different phases of MM treatment have not been characterized. PATIENTS AND METHODS: We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. FinTox+ was defined as a COST-FACIT score <23, TimeTox+ as MM-related interactions (including phone calls) ≥1x weekly or ≥1x monthly in-person among far-residing patients, QOL using PROMIS Global Health, and functional status using patient-reported Karnofsky performance status (KPS). RESULTS: Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ predictors included annual income (P < .01) and out-of-pocket costs (P < .01). TimeTox+ predictors included disease status (P < .001), caregiver status (P = .01), far-residing status (P < .001), and out-of-pocket costs (P = .03). FinTox+ was associated with a clinically meaningful decrease in mental QOL, while TimeTox+ patients were more likely to have KPS ≤ 80. CONCLUSIONS: In our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. FinTox+ was associated with decreased mental health, while TimeTox+ was associated with worse performance status. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development.

Consuming Patients' Days: Time Spent on Ambulatory Appointments by People With Cancer.

BACKGROUND: In qualitative work, patients report that seemingly short trips to clinic (eg, a supposed 10-minute blood draw) often turn into "all-day affairs." We sought to quantify the time patients with cancer spend attending ambulatory appointments. METHODS: We conducted a retrospective study of patients scheduled for oncology-related ambulatory care (eg, labs, imaging, procedures, infusions, and clinician visits) at an academic cancer center over 1 week. The primary exposure was the ambulatory service type(s) (eg, clinician visit only, labs and infusion, etc.). We used Real-Time Location System badge data to calculate clinic times and estimated round-trip travel times and parking times. We calculated and summarized clinic and total (clinic + travel + parking) times for ambulatory service types. RESULTS: We included 435 patients. Across all service day type(s), the median (IQR) clinic time was 119 (78-202) minutes. The estimated median (IQR) round-trip driving distance and travel time was 34 (17-49) miles and 50 (36-68) minutes. The median (IQR) parking time was 14 (12-15) minutes. Overall, the median (IQR) total time was 197 (143-287) minutes. The median total times for specific service type(s) included: 99 minutes for lab-only, 144 minutes for clinician visit only, and 278 minutes for labs, clinician visit, and infusion. CONCLUSION: Patients often spent several hours pursuing ambulatory cancer care on a given day. Accounting for opportunity time costs and the coordination of activities around ambulatory care, these results highlight the substantial time burdens of cancer care, and support the notion that many days with ambulatory health care contact may represent "lost days."

Trajectory of Healthcare Contact Days for Veterans With Advanced Gastrointestinal Malignancy.

How and where patients with advanced cancer facing limited survival spend their time is critical. Healthcare contact days (days with healthcare contact outside the home) offer a patient-centered and practical measure of how much of a person's life is consumed by healthcare. We retrospectively analyzed contact days among decedent veterans with stage IV gastrointestinal cancer at the Minneapolis Veterans Affairs Healthcare System from 2010 to 2021. Among 468 decedents, the median overall survival was 4 months. Patients spent 1 in 3 days with healthcare contact. Over the course of illness, the percentage of contact days followed a "U-shaped" pattern, with an initial post-diagnosis peak, a lower middle trough, and an eventual rise as patients neared the end-of-life. Contact days varied by clinical factors and by sociodemographics. These data have important implications for improving care delivery, such as through care coordination and communicating expected burdens to and supporting patients and care partners.

Cancer Treatment Closer to the Patient Reduces Travel Burden, Time Toxicity, and Improves Patient Satisfaction, Results of 546 Consecutive Patients in a Northern Italian District.

Background and Objectives: The distance to cancer facilities may cause disparities by creating barriers to oncologic diagnosis and treatment, and travel burden may cause time and financial toxicity. Materials and Methods: To relieve travel burden, a program to deliver oncologic treatment closer to the patient was initiated in the district of Piacenza (Northern Italy) several years ago. The oncologic activities are performed by oncologists and by nurses who travel from the oncologic ward of the city hospital to territorial centres to provide cancer patient management. This model is called Territorial Oncology Care (TOC): patients are managed near their home, in three territorial hospitals and in a health centre, named "Casa della Salute" (CDS). A retrospective study was performed and the records of patients with cancer managed in the TOC program were analysed. The primary endpoints were the km and time saved, the secondary endpoints: reduction of caregiver need for transport and patient satisfaction. Results: 546 cancer patients managed in the TOC program from 2 January 2021 to 30 June 2022 were included in this study. Primary endpoints: median km to reach the city hospital: 26 (range 11-79 km) median time: 44 min (range 32-116); median km to reach the territorial clinicians in the TOC program: 7 (range 1-35 km), median time: 16 minutes (range 6-54), p < 0.001. Secondary endpoints: 64.8% of patients who needed a caregiver for the city hospital could travel alone in the TOC program and 99.63% of patients were satisfied. Conclusions: The results of this retrospective study highlight the possibility of treating cancer patients near their residence, reducing travel burden and saving time.

Time toxicity associated with early phase clinical trial participation.

BACKGROUND: Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. PATIENTS AND METHODS: A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. RESULTS: A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. CONCLUSIONS: Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Contact Days Associated With Cancer Treatments in the CCTG LY.12 Trial.

BACKGROUND: When cancer treatments have similar oncologic outcomes, the number of days with in-person healthcare contact (""contact days'') can help contextualize expected time use with each treatment. We assessed contact days in a completed randomized clinical trial. PATIENTS AND METHODS: We conducted a secondary analysis of the CCTG LY.12 RCT that evaluated 2-3 cycles of gemcitabine, dexamethasone, and cisplatin (GDP) vs. dexamethasone, cytarabine, and cisplatin (DHAP) in 619 patients with relapsed/refractory lymphoma prior to stem cell transplant. Primary analyses reported similar response rates and survival. We calculated patient-level "contact days" by analyzing trial forms. The study period was from assignment to progression or transplant. Days without healthcare contact were considered "home days''. We compared measures of contact days across arms. RESULTS: The study period was longer in the GDP arm (median 50, vs. 47 days, P = .007). Contact days were comparable in both arms (median 18 vs 19, P = 0.79), but home days were higher in the GDP arm (median 33 vs 28, P < .001). The proportion of contact days was lower in the GDP arm (34%, vs. 38%, P = .009). The GDP arm experienced more contact days related to planned outpatient chemotherapy (median, 10 vs. 8 days), but the DHAP arm experienced many more inpatient contact days (median, 11 vs. 0 days). CONCLUSIONS: Measures of time use, such as contact days, can be extracted from RCTs. In LY.12, despite comparable oncologic outcomes, GDP was associated with fewer contact days. Such information can guide decision-making for patients with hematological cancers, who already face significant healthcare contact.

The unequal burden of time toxicity.

Many cancer treatments impose large time investments on patients. We have termed these time burdens 'time toxicity' and have urged their consideration as adverse events of treatment. Here, we discuss time toxicity measures while considering inequitable access to healthcare, time as a resource, and patterns of time toxicity.

The least costly pharmacy for cancer supportive care medications over time: the logistic toxicity of playing catch up.

PURPOSE: No single pharmacy in an urban zip code is consistently the least expensive across medications. If medication prices change differently across pharmacies, patients and clinicians will face challenges accessing affordable medications when refilling medications. This is especially pertinent to people with cancer with multiple fills of supportive care medications over time. We evaluated if the lowest-priced pharmacy for a formulation remains the lowest-priced over time. METHODS: We compiled generic medications used to manage nausea/vomiting (14 formulations) and anorexia/cachexia (12 formulations). We extracted discounted prices in October 2021 and again in March 2022 for a typical fill at 8 pharmacies in Minneapolis, Minnesota, USA (zip code 55,414) using GoodRx.com. We examined how prices changed across formulations and pharmacies over time. RESULTS: Data were available for all 208 possible pharmacy-formulation combinations (8 pharmacies × 26 formulations). For 172 (83%) of the 208 pharmacy-formulation combinations, the March 2022 price was within 20% of the October 2021 price. Across pharmacy-formulation combinations, the price change over time ranged from - 76 to + 292%. For 12 (46%) of the 26 formulations, at least one pharmacy with the lowest price in October 2021 no longer was the least costly in March 2022. For one formulation (dronabinol tablets), the least expensive pharmacy became the most expensive, with an absolute and relative price increase of a fill of $22 and 85%. CONCLUSION: For almost half of formulations studied, at least one pharmacy with the lowest price was no longer the least costly a few months later. The lowest price for a formulation (across pharmacies) could also change considerably. Thus, even if a patient accesses the least expensive pharmacy for a medication, they may need to re-check prices across all pharmacies with each subsequent fill to access the lowest prices. In addition to safety concerns, directing medications to and accessing medications at multiple pharmacies can add time and logistic toxicity to patients with cancer, their care partners, prescribers, and pharmacy teams.