ABSTRACT
Background. Molecular diagnostics appear promising for early, non-invasive detection of invasive fungal disease (IFD) in immunocompromised patients. Our clinical lab developed and validated cell free DNA (cfDNA) fungal polymerase chain reaction (PCR) assays (Table 1), which have been in clinical use since November 2020 and were recently included in an institutional pediatric clinical care pathway for prolonged febrile neutropenia. We aimed to evaluate the performance of these plasma cfDNA fungal PCR assays in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. Methods. We initiated an observational study of inpatient oncology and HSCT patients who had plasma mold panel (+/- Candida panel) cfDNA fungal PCR obtained as part of an IFD evaluation at our freestanding quaternary care children's hospital. The primary outcome was IFD clinical diagnosis (proven, probable, possible, unlikely) as per EORTC/MSG+ definitions within one month of the cfDNA fungal PCR, which was assigned independently by two physicians, with a third physician utilized in cases of discrepancy. Patient demographics, hospital course, imaging results, and clinical laboratory data were ed and maintained in an encrypted REDCap © database. Results. In a preliminary analysis of October 2021-March 2022 data, there were 21 IFD evaluations for 18 patients (Table 2). Most oncology evaluations were for prolonged febrile neutropenia, while many HSCT were non-neutropenic, but on enhanced immunosuppression with new clinical concerns (e.g., respiratory symptoms, persistent fever). Plasma cfDNA detected a mold or yeast consistent with the clinical presentation in 100% of the five proven/probable cases (Figures 1 & 2). All 14 possible IFD cases had a negative cfDNA fungal PCR. Proven cases are designated with blue icon, while the probable case is orange. All five cases were in oncology patients who did not have history of hematopoietic stem cell transplant. Cell free DNA (cfDNA) fungal polymerase chain reaction (PCR) results include the organism identified, followed by the cycle threshold (Ct) in parenthesis. Maximum Ct for the assay is 45. Abbreviations: AG: Aspergillus galactomannan index (Ref <0.5);ALL: acute lymphoblastic leukemia. BAL: bronchoalveolar lavage;1,3-BDG: 1,3-beta-D-glucan (Ref <60 pg/ml);cfDNA: cell freedeoxyribonucleic acid;CNS: central nervous system;EORTC/MSG: European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group & the National Institute of Allergy&Infectious Diseases Mycoses Study Group;L-AmB: liposomal amphotericin B;SARS-CoV-2: severe acute respiratory syndrome associated with coronavirus 2. Conclusion. Upfront plasma cfDNA fungal PCR successfully detected a relevant mold or yeast with short turnaround time in 100% of cases that were later classified as proven/probable. This appears promising for early, noninvasive diagnosis that enables prompt optimization of antifungal and surgical management, particularly for mucormycosis cases. Additional data may permit consideration of Mucorales agents PCR as a new EORTC/MSG mycologic criteria. (Table Presented).
ABSTRACT
Background: The COVID-19 pandemic has affected oncology practice in a variety of ways. We sought to evaluate the impact on pediatric oncology parent and young adult (YA) patient experiences, concerns, and perceived stress. Methods: We conducted a cross-sectional Internet-based survey of parents and YA patients in the pediatric oncology and survivorship clinics at Stanford between June-December 2020. Patients were recruited in person by clinic staff or through the electronic patient health portal. Surveys (available in English and Spanish) included the NIH Perceived Stress Scale (PSS-10) and investigator-developed questions evaluating clinical practice changes, concerns about health and cancer care, and pandemic-related challenges. Bivariate analyses evaluated associations between demographic, clinical, and pandemic-related factors and (a) concern about the pandemic affecting health and cancer care, and (b) perceived stress. Results: Among 81 participants (66 parents, mean age 41.6 ± SD 9.6;15 YAs, mean age 21.9 ± 8.4 years), 37% selfidentified as Hispanic/Latino, 36% non-Hispanic white, and 21% Asian. Twenty-eight percent were on treatment and 47% had completed treatment (79% < 5 years prior). Thirty percent reported cancer-related appointment changes, largely rescheduling (75%) and/or switching to telehealth (42%). Nearly half (45%) of parents and 27% of YAs reported feeling 'very' or 'extremely' concerned about the pandemic affecting their child's/their health or cancer care. Race/ethnicity emerged as the only demographic feature that was significantly associated with high concern (p = 0.018), with 57% of Hispanic/Latino and only 21% of non-Hispanic white respondents reporting high levels of concern. Specific concerns included fear of severe infection, immunosuppression, and whether infection would change treatment and compromise effectiveness. Parents and YAs reported 'a lot' or 'a great deal' of challenges in their personal/family life (61%) and work/professional life (48%). Among these were having less support from friends/family (35%), reduced wages/work hours (31%), and job loss (20%) with 20% reporting ≥ 3 challenges. On the PSS-10, stress in the past month was high for parents (mean 30 ± 4) and YAs (mean 31 ± 5.1) on a scale of 0-40. Risk factors for higher stress included: male gender (p = 0.028), less support from family/friends (p = 0.002), and experiencing ≥ 3 pandemic-related challenges (p = 0.013). Conclusions: Our findings confirm the prevalent worry and stress that pediatric oncology patients and families are experiencing during the COVID-19 pandemic. Better communication about cancer care service changes may help to alleviate some concerns. Supportive care resources may also help patients and families cope with psychosocial stressors, particularly among at-risk groups.