Tumor marker response to SARS-CoV-2 infection among patients with cancer.

BACKGROUND: Inflammatory responses from benign conditions can cause non-cancer-related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS-CoV-2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID-19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID-19. However, available data excludes cancer patients, so little is known about the effect of COVID-19 on tumor markers among cancer patients. METHODS: We conducted a case series and identified patients with a positive SARS-CoV-2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19-9, CA 125, or CA 27-29 laboratory test. Cancer patients with documented COVID-19 infection and at least one pre- and two post-infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID-19 infection, and tumor marker values. RESULTS: Seven patients were identified with a temporary elevation of tumor marker values during the post-COVID-19 period. Elevation in tumor marker occurred within 56 days of COVID-19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post-infectious period among all patients. CONCLUSION: We report temporary elevations of cancer tumor markers in the period surrounding COVID-19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research.

Developing, Implementing, and Validating a Social Toxicity Assessment Tool of Cancer.

PURPOSE: The social impact of cancer on patients and their family is well known. Yet, unlike with physical and financial toxicities, no validated tools are available to measure this impact. This study aimed at developing, validating, and implementing a novel social toxicity assessment tool for patients with cancer diagnosis (STAT-C). METHODS: Questions were generated through multiple steps including focus groups of patients, their families, and oncology care professionals. These steps along with relevant literature resulted in the development of an initial 20-item questionnaire. Content validity and relevance of the tool were assessed using Content Validity Index for individual items and Content Validity Index for the entire scale. Following expert examination, the constructed STAT-C tool consisted of 14 items grouped into three domains-social relations, social activities, and economic impact. Based on the total possible score for the survey in 150 patients for all the items, three levels of a socioeconomic toxicity were determined-severe social toxicity, mild social toxicity, and no social toxicity. RESULTS: The 14 items were marked as relevant, and the Content Validity Index for individual items ranged between 0.80 and 1.00. An overall average Content Validity Index for the entire scale of 0.87 showed high content validity of the constructed tool. Exploratory factor analysis revealed retention of 13 items of the constructed STAT-C Tool, which loaded across three factors that mapped groupings into measures of social relations, social activities, and economic impact domains. CONCLUSION: Our study revealed that STAT-C is a valid, reliable tool, and well captures and measures unique and pertinent social toxicity constructs for Arabic-speaking patients. The tool should enable oncology professionals to deliver better patient-centered care as a component of a comprehensive approach.

A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.

Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, immunotherapy has been ineffective in this disease thus far and treatment remains centered around cytotoxic chemotherapy. Here, we present a case of a patient with pancreatic adenocarcinoma harboring both high microsatellite instability (MSI-H) and HER2 amplification. After an initial response to standard-of-care chemotherapy with FOLFIRINOX followed by progression, she was treated with dual immune checkpoint blockade, which resulted in a period of disease control. This was complicated by the development of autoimmune hypophysitis and an incidental finding of brain metastasis on magnetic resonance imaging (MRI). Her extracranial disease progressed while receiving stereotactic radiosurgery, with findings of lymphangitic spread in her lungs, and her treatment was changed to gemcitabine/nab-paclitaxel with trastuzumab. This resulted in a degree of extracranial disease control, though she experienced progressive brain metastases despite radiation and therapeutic switch to lapatinib and trastuzumab. Ultimately, the patient developed leptomeningeal disease which was not controlled by intrathecal trastuzumab. Given the rarity of central nervous system metastasis, HER2 amplification, and MSI in pancreatic cancer, this patient's presentation represents a confluence of multiple unique features. This case highlights the clinical value of up-front next-generation sequencing in metastatic pancreatic cancer and the ability of pancreatic cancer with actionable molecular variants to develop atypical sites of disease and adaptive resistance.

Developing an Educational Intervention to Address Financial Hardship in Cancer Patients.

OBJECTIVE: To develop an educational intervention to empower patients to manage their financial health better. PARTICIPANTS AND METHODS: This study was conducted from September 1, 2017, to January 31, 2019. Focus groups were held with social workers, case managers, and patient financial service staff and interviews were conducted with patients and caregivers to inform the content, delivery format, and timing of an intervention for mitigating financial hardship from treatment (phase 1). Based on qualitative data, theories of adult learning, and a review of the literature, we created an educational presentation to be delivered in a classroom setting. Two patient focus groups were then held for feedback on the presentation (phase 2). RESULTS: In phase 1, both patients and allied health care staff providers believed that an educational intervention about financial aspects of care early during treatment would help them cope and plan better. Participants' suggestions for the intervention's content included billing information, insurance, authorization processes, employment policies related to health care and disability benefits, and alternative financial resources. Based on these suggestions, a preliminary educational presentation was developed with 3 main themes: insurance issues, employment issues, and financial health. Phase 2 focus group participants suggested refinement of the presentation, including targeting specific groups, adding graphics, and more information about resources. CONCLUSION: Our study provides the basis for a patient-centered education module for emotional, instrumental, and informational support for financial distress for use in a clinical setting.

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis.

Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. Results: The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month follow-up visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL (p = 0.037) and 6.2 mg/dL (p = 0.008), respectively, from baseline values. Conclusion: PCSK-9 inhibitors should be used cautiously with a follow-up liver function test.

Progression-Free Survival in Patients Receiving Chemotherapy Alone (C) or Chemotherapy with Bevacizumab (CB) for First-Line Treatment of KRAS Mutant Metastatic Colorectal Cancer in Community Oncology Settings.

PURPOSE: Bevacizumab is a standard first-line (L1) treatment for metastatic colorectal cancer (mCRC) patients regardless of RAS status. This retrospective study examined treatment patterns and outcomes in a community oncology sample of KRAS mutant mCRC patients treated with chemotherapy (C) or C plus bevacizumab (CB) in L1. METHODS: This study used medical records from the Vector Oncology Data Warehouse. Eligible patients were confirmed KRAS mutant mCRC and received L1 C or CB. Kaplan-Meier analysis assessed L1 progression-free survival (PFS) and overall survival (OS). Cox regression models examined the interaction of tumor location (R/L) with treatment. RESULTS: CB (n = 264) compared to C (n = 109) patients were younger, less likely performance status (PS) impaired, and more likely with liver metastases. Median unadjusted PFS was 10.41 months (95% CI 9.0-11.3) in CB and 7.66 months (95% CI 6.5-9.1) in C patients (p = 0.174). Median unadjusted OS was 26.91 months (95% CI 24.3-29.3) in CB and 23.33 months (95% CI 19.7-29.2) in C patients (p = 0.571). For patients with right- vs. left-sided tumors, C (but not CB)-treated patients had higher adjusted risk for progression (HR = 1.715, 95% CI 1.108, 2.653; p = 0.015). CONCLUSIONS: CB- vs. C-treated KRAS mutant mCRC patients may have a meaningful PFS benefit. Patients with right-sided tumors treated with C were at higher risk for disease progression than patients with left-sided tumors. Tumor location had no significant effect on outcomes in the CB cohort.

Feasibility and Acceptability of a Best Supportive Care Checklist among Clinicians.

CONTEXT: Best supportive care (BSC) is often not standardized across sites, consistent with best evidence, or sufficiently described. We developed a consensus-based checklist to document BSC delivery, including symptom management, decision making, and care planning. We hypothesized that BSC can be feasibly documented with this checklist consistent with consolidated standards of reporting trials. OBJECTIVE: To determine feasibility/acceptability of a BSC checklist among clinicians. METHODS: To test feasibility of a BSC checklist in standard care, we enrolled a sample of clinicians treating patients with advanced cancer at four centers. Clinicians were asked to complete the checklist at eligible patient encounters. We surveyed enrollees regarding checklist use generating descriptive statistics and frequencies. RESULTS: We surveyed 15 clinicians and 9 advanced practice providers. Mean age was 41 (SD = 7.9). Mean years since fellowship for physicians was 7.2 (SD = 4.5). Represented specialties are medical oncology (n = 8), gynecologic oncology (n = 4), palliative care (n = 2), and other (n = 1). For "overall impact on your delivery of supportive/palliative care," 40% noted improved impact with using BSC. For "overall impact on your documentation of supportive/palliative care," 46% noted improvement. Impact on "frequency of comprehensive symptom assessment" was noted to be "increased" by 33% of providers. None noted decreased frequency or worsening impact on any measure with use of BSC. Regarding feasibility of integrating the checklist into workflow, 73% agreed/strongly agreed that checklists could be easily integrated, 73% saw value in integration, and 80% found it easy to use. CONCLUSION: Clinicians viewed the BSC checklist favorably illustrating proof of concept, minor workflow impact, and potential of benefit to patients.

Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: a case series.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) may cause acute kidney injury and proximal tubular dysfunction. However, no detailed studies document urinary phosphate wasting as a marker of TDF-induced tubulopathy. METHODS: Records of HIV-infected patients with presumed TDF toxicity were reviewed. We describe the characteristics and clinical course of 15 patients who had documented elevated (>20%) fractional excretion of phosphate (FEphos). RESULTS: Patients were predominantly Caucasian and male (73 and 80%, respectively), with a mean age of 56 years (range 38-76). Of the 15 patients, 11 had a estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73(2) at time of TDF initiation. The mean duration of TDF therapy prior to diagnosis of TDF toxicity was 64 months. Mean FEphos was 34% (range 20-62). The mean eGFR at TDF initiation was 104 mL/min/1.73 m(2) [standard deviation (SD) 17.0] with a gradual decline to 69 mL/min/1.73 m(2) (SD 19.0) by the time of TDF discontinuation. Of 10 patients with repeated FEphos after TDF discontinuation, 9 had improvement of their FEphos. Of these individuals, 6 had normalization of their FEphos. Estimated GFR improved in 12 patients after discontinuation of TDF, though importantly, none returned to their baseline eGFR. CONCLUSIONS: Urinary phosphate wasting is a sensitive marker for TDF-induced proximal tubulopathy and is associated with unrecognized and permanent renal function decline. Tubular dysfunction can develop after years of TDF therapy in those with normal kidney function at the time of drug initiation. This suggests that continuing vigilance be maintained in all those on TDF.