Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab.

PURPOSE: Systemic chemotherapy including monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma (GBM). Most patients tolerated these regimens well with known side effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ- or system- specific toxicities from chemotherapy agents have never been examined by postmortem study. This is the largest cohort used to address this issue in glioma patients. METHODS: Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression. RESULTS: Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. CONCLUSION: There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma tumor progression with infiltration to brain stem and aspiration pneumonia.

Health-related quality of life in Hodgkin lymphoma: a systematic review.

PURPOSE: Hodgkin Lymphoma (HL) is highly curable with well-established treatment regimens; however, the impact on patient's health-related quality of life (HRQL) from diagnosis through survivorship is unclear. This systematic review aimed to describe the available literature on HRQL in HL, assess the quality of these studies, identify gaps in the literature and recommend further areas of research. METHODS: Following PRISMA guidelines, we performed a systematic review to include studies assessing the HRQL in HL patients. Articles identified through database searches were screened and data extracted. Quality was evaluated using a 6-point scale, adapted from published HRQL systematic reviews. RESULTS: Sixty five articles published between 1986 and 2015 met inclusion criteria. These included 53 (82 %) cross-sectional studies; 12 (18 %) longitudinal studies, including three embedded in randomized trials; and three additional longitudinal studies that began assessment at diagnosis. Study sample sizes of HL patients varied considerably with only five (42 %) longitudinal studies including more than 50 patients. Multidimensional HRQL was assessed in 45 studies, single HRQL domains in 22 studies, and symptoms, including fatigue, in 28 studies. CONCLUSIONS: The majority of studies employed a cross-sectional design, enrolling HL survivors at least 10 years after the completion of therapy. Emphasis on HRQL following therapy may inform initial treatment decisions and long-term survivorship goals. We recommend that future research include prospective, longitudinal randomized designs across both treatment and time.

Providing Survivorship Care for a Young Adult With a History of Blood Cancer.

Adolescents and young adults (AYAs) with a history of cancer are at an increased risk for late effects from their cancer treatment and have higher rates of long-term morbidity and mortality compared to their age-matched peers. As a result, this vulnerable population needs attentive follow-up care, end-organ surveillance, and secondary cancer screening; however, a history of cancer can often become buried on a problem list or not addressed at all. This case report illustrates an AYA survivor of classic Hodgkin lymphoma who relocates to a new city and establishes care with a new primary care provider (PCP). The PCP's awareness of a prior cancer diagnosis and the previous treatment regimen is a critical component in providing comprehensive care. In this case, the PCP's first step is to reach out and collaborate with oncology providers to gather an accurate treatment summary and then consult evidence-based guidelines to develop a plan of care. Based on the patient's previous treatment with chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine, the PCP orders recommended testing, reviews results, and provides subsequent counseling on health promotion and psychosocial wellness. This case illustrates strategies healthcare providers can use to provide coordinated, evidence-based care for AYA cancer survivors.

Financial distress and medical financial hardship among young adult survivors of blood cancer.

BACKGROUND: The long-term financial impact of cancer care has not been adequately addressed in young adults. As part of a remote intervention study, we describe medical financial distress and hardship among young adult survivors of blood cancer at study entry. METHODS: Young adults were recruited from 6 US hospitals. Using a Research Electronic Data Capture link, young adults confirmed their eligibility-namely, currently 18 to 39 years of age, blood cancer diagnosis 3 or more years ago, off active treatment, and not on parent's insurance. Following consent, the baseline assessment was sent. The primary outcome measure, the Personal Financial Wellness Scale, measured financial distress (scored as severe, 1-2; high, 3-4; average, 5-6; and low to no, 7-10). Medical financial hardship encompassed material hardship, psychological impact, and coping behaviors. Descriptive summary statistics and linear regression were used. RESULTS: Among the 126 participants, 54.5% came from minority racial or ethnic groups. Median time since diagnosis was 10 years (interquartile range = 6-16 years), with 56% having received a diagnosis when they were between 18 and 39 years of age. The overall mean (standard deviation) Personal Financial Wellness Scale score was 5.1 (2.4), but 49% reported severe or high distress. In multivariable analysis, female sex, Hispanic ethnicity, and lower income were strongly associated with worse Personal Financial Wellness Scale scores. Among participants with severe financial distress (n = 26), 72% reported 2 or more household material hardships, had worse scores across all psychological domains, and altered survivorship care because of cost (68%). CONCLUSIONS: Nearly half of long-term young adult cancer survivors reported severe or high levels of financial distress. Individuals with severe or high distress also reported more medical financial hardship than other participants. This finding highlights the need for ongoing financial intervention in this vulnerable population. CLINICALTRIALS.GOV: NCT05620979.

Adolescent and Young Adult Survivorship Care: Emerging from the COVID-19 Pandemic Stronger Through Teleoncology.

The Adolescent and Young Adult (AYA) survivorship clinic at Tufts Medical Center transitioned to telehealth appointments when ambulatory clinics closed at the onset of the COVID-19 pandemic in early 2020. This review analyzes 195 survivorship telehealth visits for 90 patients, diagnosed with cancer younger than the age of 40 years. This cohort, seen during the Massachusetts State of Emergency, exemplifies the success and acceptance of telehealth among AYA survivors. The clinic's long-term goal is to advocate for telehealth as a standard in AYA survivorship care; however, telehealth faces increasing barriers as modifications to address the pandemic are amended or lifted.

Evaluating the role of financial navigation in alleviating financial distress among young adults with a history of blood cancer: A hybrid type 2 randomized effectiveness-implementation design.

BACKGROUND: Young adulthood (YA) is a complex phase of life, marked by key developmental goals, including educational and vocational attainment, housing independence, maintenance of social relationships, and financial stability. A cancer diagnosis during, or prior to, this phase of life can compromise the achievement of these milestones. Studies of adults with cancer have demonstrated that >70% report experiencing financial side-effects, which are associated with increased mortality, diminished health-related quality of life, and forgone medical care. The goal of this project is to evaluate financial distress of YA-aged survivors of blood cancers, and the impact of financial navigation on alleviating this distress. METHODS: This three-arm, multi-site, hybrid type 2 randomized effectiveness-implementation design (EID) study will be conducted through remote consent, remote data capture and telephone-based/virtual financial navigation. Participants will be aged 18-39, and more than three years from their blood cancer diagnosis. In this six-month intervention, the study will compare the primary outcome of financial distress in three arms: (1) usual care (2) participant-initiated, ad hoc navigation, and (3) study-directed proactive navigation. The study will be evaluated via the five-component Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) outcome strategy with a mixed-methods approach through quantitative assessment of participant-reported financial distress using the Personal Financial Wellness Scale™, as the primary outcome measure, and qualitative assessment through interviews. CONCLUSION: The study will address many unanswered questions regarding financial navigation within the YA survivor population and will inform the most successful strategies to mitigate financial distress in this vulnerable population.

The Creation of a Comprehensive Adolescent and Young Adult Cancer Survivorship Program: "Lost in Transition" No More.

Purpose: The Reid R. Sacco AYA Cancer Program set out to improve survivorship care for AYA-aged patients (15-39 years) of pediatric or AYA cancer. This article discusses the steps in establishing the clinic, including the creation of a database on cancer history, exposures, and attendant risks of late effects. Results from the database tell the broader story of AYAs who seek care within a dedicated survivorship clinic. Methods: The database was created with REDCap® (Research Electronic Data Capture), a secure web-based, HIPAA compliant application for research and clinical study data. Data were abstracted and analyzed by trained members of the program team. Results: A total of 144 patients were seen for their initial survivorship visit between January 2013 and September 2019. Regarding physical health, two-thirds of the patients presented with an established late effect, one third with an established medical comorbidity, and 11% (n = 16) with secondary cancer related to their oncologic treatment. In assessing mental health, a significant cohort reported a known affective disorder (32%, n = 46) with one quarter already taking a psychotropic medication. Despite the transient nature of AYAs, 85% of patients remained in care within the long-term follow-up clinical model. Conclusions: Data presented illustrate how multilayered and complex survivorship care needs can be, as patients enter the clinic with complicated pre-existing psychosocial issues, significant late effects, and comorbidities. This study reinforces the value of a clinical database to better understand AYA survivors with the ultimate goal of optimizing and coordinating care.

Development of Phase-Specific Breast Cancer Survivorship Care Plans.

INTRODUCTION: Phase-specific survivorship care plans (SCPs) have the potential to be powerful tools in providing individualized, comprehensive survivorship care, particularly in terms of care coordination and transition, if used as dynamic documents. MATERIALS AND METHODS: We designed an initial follow-up care plan (FCP) to be used at the conclusion of curative therapy, as well as distinct, phase-specific FCPs for periodic use at 5-year and 10-year time points in the survivorship course. These FCPs incorporate the 4 essential components of survivorship care outlined by the Institute of Medicine: prevention, surveillance, intervention for consequences of cancer treatment, and coordination among health care providers. RESULTS: Phase-specific SCPs were designed by a multidisciplinary team with expertise in breast health, survivorship, and cancer care delivery across diverse practice settings. The FCPs were formulated to align with national guidelines and emergent, peer-reviewed literature, and reflect evolving recommendations regarding the duration of adjuvant hormone therapy. The SCPs were pilot-tested and successfully integrated into the existing work flow of the electronic medical records at each practice site. CONCLUSION: Phase-specific SCPs were developed to incorporate new knowledge about evolving treatment recommendations, screening guidelines, and updated genetic information to encourage timely discussions relevant to the specific stage of survivorship.

Schwannoma Formation in Childhood Cancer Survivors Exposed to Total Body Irradiation: Case Series.

Childhood cancer survivors are at risk for ongoing health risks related to their initial treatment. One potential long-term complication following radiation is the development of secondary tumors, including peripheral nerve tumors, such as schwannomas. We present three adolescent and young adult (AYA)-aged survivors of pediatric cancer (22-40 years), followed in our AYA survivorship clinic. Each was found to have a schwannoma many years following total body irradiation for a childhood primary malignancy. We highlight a late effect of low-dose total body irradiation as well as the importance of long-term monitoring in this population.