Telemedicine and Cancer Care: Barriers and Strategies to Optimize Delivery.

ABSTRACT: Telemedicine holds the potential to transform cancer care delivery and optimize value, access, and quality of care. A transformed regulatory environment coupled with the need to continue medical care despite operational limitations led to the rapid expansion of telemedicine in cancer care during the COVID-19 pandemic. Its utilization has since varied, and it has faced significant challenges. In this review, we will explore the state of telemedicine in cancer care delivery, the challenges it faces, and strategies to enhance its successful implementation.

The association between telemedicine, advance care planning, and unplanned hospitalizations among high-risk patients with cancer.

BACKGROUND: Despite the widespread implementation of telemedicine, there are limited data regarding its impact on key components of care for patients with incurable or high-risk cancer. For these patients, high-quality care requires detailed conversations regarding treatment priorities (advance care planning) and clinical care to minimize unnecessary acute care (unplanned hospitalizations). Whether telemedicine affects these outcomes relative to in-person clinic visits was examined among patients with cancer at high risk for 6-month mortality. METHODS: This retrospective cohort study included adult patients with cancer with any tumor type treated at the University of Pennsylvania who were newly identified between April 1 and December 31, 2020, to be at high risk for 6-month mortality via a validated machine learning algorithm. Separate modified Poisson regressions were used to assess the occurrence of advance care planning and unplanned hospitalizations for telemedicine as compared to in-person visits. Additional analyses were done comparing telemedicine type (video or phone) as compared to in-person clinic visits. RESULTS: The occurrence of advance care planning was similar between telemedicine and in-person visits (6.8% vs. 6.0%; adjusted risk ratio [aRR], 1.25; 95% CI, 0.92-1.69). In regard to telemedicine subtype, patients exposed to video encounters were modestly more likely to have documented advance care planning in comparison to those seen in person (7.5% vs. 6.0%; aRR, 1.48; 95% CI, 1.03-2.11). The 3-month risk for unplanned hospitalization was comparable for telemedicine compared to in-person clinic encounters (21% vs. 18%; aRR, 1.06; 95% CI, 0.81-1.38). CONCLUSIONS: In this study, care delivered by telemedicine, compared to in-person clinic visits, produced comparable rates of advance care planning conversations without increasing hospitalizations, which suggests that vulnerable patients can be managed safely by telemedicine.

Patient headache questionnaires can improve headache diagnosis and treatment in children.

OBJECTIVE: To examine trends in diagnosis of headache and migraine in a large pediatric neurology cohort, and test whether an electronic health record (EHR)-integrated headache questionnaire can increase specificity of diagnosis and likelihood of prescribing migraine treatment. BACKGROUND: Under-diagnosis of migraine contributes to the burden of disease. As we founded our Pediatric Headache Program in 2013, we recognized that the proportion of patients with headache who were given a diagnosis of migraine was much lower than expected. METHODS: We developed a patient headache questionnaire, initially on paper (2013-2014), then in an electronic database (2014-2016), and finally integrated into our electronic health record (pilot: 2016, full: May 2017). We compared diagnoses and prescribed treatments for new patients who were given a headache diagnosis, looking at trends in the proportion of patients given specific diagnoses (migraine, etc.) versus the non-specific diagnosis, "headache." Next, we conducted a prospective cohort study to test for association between provider use of the form and the presence of a specific diagnosis, then for an association between specific diagnosis and prescription of migraine treatment. RESULTS: Between July 2011 and December 2022 the proportion of new headache patients who were given a diagnosis of migraine increased 9.7% and non-specific headache diagnoses decreased 21.0%. In the EHR cohort (June 2017-December 2022, n = 15,122), use of the provider form increased the rate of specific diagnosis to 87.2% (1839/2109) compared to 75.5% (5708/7560) without a patient questionnaire, nearly doubling the odds of making a specific diagnosis (odds ratio [OR] 1.90, 95% confidence interval [CI]: 1.65-2.19). Compared to those given only a non-specific headache diagnosis who were prescribed a migraine therapy 53.7% (1766/3286) of the time, 75.3% (8914/11836) of those given a specific diagnosis received a migraine therapy, more than doubling the odds of prescription (OR 2.39, 95% CI: 2.20-2.60). CONCLUSIONS: Interventions to improve specificity of diagnosis were effective and led to increased rates of prescription of migraine treatments. These results have been sustained over several years. This headache questionnaire was adapted into the Foundation system of EpicCare, so it is broadly available as a clinical and research tool for institutions that use this EHR software.

SARS-CoV-2 Seropositivity and Seroconversion in Patients Undergoing Active Cancer-Directed Therapy.

PURPOSE: Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. We aimed to gauge the effectiveness of these measures at the University of Pennsylvania. METHODS: We conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between May 21, 2020, and October 8, 2020. Participants completed questionnaires and had up to five serial blood collections. RESULTS: Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95% CI, 0.0 TO 4.1%) over 14.8 person-years of follow up, with a median of 13 health care visits per patient. CONCLUSION: These results suggest that patients with cancer receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.

CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

Rates of COVID-19-Related Outcomes in Cancer Compared With Noncancer Patients.

Cancer patients are a vulnerable population postulated to be at higher risk for severe coronavirus disease 2019 (COVID-19) infection. Increased COVID-19 morbidity and mortality in cancer patients may be attributable to age, comorbidities, smoking, health care exposure, and cancer treatments, and partially to the cancer itself. Most studies to date have focused on hospitalized patients with severe COVID-19, thereby limiting the generalizability and interpretability of the association between cancer and COVID-19 severity. We compared outcomes of SARS-CoV-2 infection in 323 patients enrolled in a population-based study before the pandemic (n = 67 cancer patients; n = 256 noncancer patients). After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer was independently associated with higher odds of hospitalization (odds ratio = 2.16, 95% confidence interval = 1.12 to 4.18) and 30-day mortality (odds ratio = 5.67, 95% confidence interval = 1.49 to 21.59). These associations were primarily driven by patients with active cancer. These results emphasize the critical importance of preventing SARS-CoV-2 exposure and mitigating infection in cancer patients.

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

SARS-CoV-2 seropositivity and seroconversion in patients undergoing active cancer-directed therapy.

Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. To gauge the effectiveness of these measures at the University of Pennsylvania, we conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between 5/21/2020 and 10/8/2020. Participants completed questionnaires and had up to five serial blood collections. Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95%CI 0.0-4.1%) over 14.8 person-years of follow up, with a median of 13 healthcare visits per patient. These results suggest that cancer patients receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.

Rates of COVID-19-related Outcomes in Cancer compared to non-Cancer Patients.

Cancer patients are a vulnerable population postulated to be at higher risk for severe COVID-19 infection. Increased COVID-19 morbidity and mortality in cancer patients may be attributable to age, comorbidities, smoking, healthcare exposure, and cancer treatments, and partially to the cancer itself. Most studies to date have focused on hospitalized patients with severe COVID-19, thereby limiting the generalizability and interpretability of the association between cancer and COVID-19 severity. We compared outcomes of SARS-CoV-2 infection in 323 patients enrolled prior to the pandemic in a large academic biobank (n=67 cancer patients and n=256 non-cancer patients). After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer was independently associated with higher odds of hospitalization (OR 2.16, 95% CI 1.12-4.18) and 30-day mortality (OR 5.67, CI 1.49-21.59). These associations were primarily driven by patients with active cancer. These results emphasize the critical importance of preventing SARS-CoV-2 exposure and mitigating infection in cancer patients.

Opportunity Costs of Receiving Palliative Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: The median overall survival (OS) for metastatic pancreatic ductal adenocarcinoma (mPDAC) is < 1 year. Factors that contribute to quality of life during treatment are critical to quantify. One factor-time spent obtaining clinical services-is understudied. We quantified total outpatient time among patients with mPDAC receiving palliative systemic chemotherapy. METHODS: We conducted a retrospective analysis using four patient-level time measures calculated from the medical record of patients with mPDAC receiving 5-fluorouracil infusion, leucovorin, oxaliplatin, and irinotecan; gemcitabine/nab-paclitaxel; or gemcitabine within the University of Pennsylvania Health System between January 1, 2011 and January 15, 2019. These included the total number of health care encounter days (any day with at least one visit) and total visit time. Total visit time represented the time spent receiving care (care time) plus time spent commuting and waiting for care (noncare time). We performed descriptive statistics on these outpatient time metrics and compared the number of encounter days to OS. RESULTS: A total of 362 patients were identified (median age, 65 years; 52% male; 78% white; 62% received gemcitabine plus nab-paclitaxel). Median OS was 230.5 days (7.6 months), with 79% of patients deceased at the end of follow-up. On average, patients had 22 health care encounter days, accounting for 10% of their total days survived. Median visit time was 4.6 hours, of which 2.5 hours was spent commuting or waiting for care. CONCLUSION: On average, patients receiving palliative chemotherapy for mPDAC spend 10% of survival time on outpatient health care. More than half of this time is spent commuting and waiting for care. These findings provide an important snapshot of the patient experience during ambulatory care, and efforts to enhance efficiency of care delivery may be warranted.

Impact of KRAS and TP53 Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With STK11-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: The STK11 gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non-small-cell lung cancer (NSCLC) and STK11 mutations often have other co-mutations. We evaluated the impact of KRAS and TP53 co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors STK11 mutations. METHODS: We conducted a retrospective review of patients with metastatic NSCLC and STK11 mutations treated at the University of Pennsylvania. STK11 mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between STK11 co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). RESULTS: From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an STK11 mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an STK11 mutation alone, 19 had STK11/KRAS, 18 had STK11/TP53, and seven had STK11/KRAS/TP53. Patients with STK11/KRAS co-mutations had a worse median PFS (2.4 months) compared with STK11 alone (5.1 months; log-rank P = .048), STK11/TP53 (4.3 months; log-rank P = .043), and STK11/KRAS/ TP53 (13 months; log-rank P = .03). Patients with STK11/KRAS co-mutation experienced shorter median OS (7.1 months) compared with STK11 alone (16.1 months; log-rank P < .001), STK11/TP53 (28.3 months; log-rank P < .001), and STK11/KRAS/TP53 (22 months; log-rank P = .025). CONCLUSION: Among patients with advanced NSCLC and STK11 mutations treated with first-line systemic therapy, co-mutation with KRAS was associated with significantly worse PFS and OS. By contrast, co-mutation of STK11 with TP53 conferred a better prognosis.

Evidence for and Against Green Tea and Turmeric in the Management of Chronic Lymphocytic Leukemia.

Complementary and alternative medicine (CAM) is a diverse group of medical and health care systems, practices, and products that are not generally considered part of conventional medicine. Chronic lymphocytic leukemia (CLL) is the most common leukemia diagnosed in the western hemisphere, and 16.5% to 66% of patients have reported using CAM. Most patients use spiritual/mind-body techniques and high doses of vitamins and herbs (most commonly polyphenols, including teas). We have reviewed the reported data on green tea and turmeric use in CLL patients.