Quality of life in chordoma survivors: results from the Chordoma Foundation Survivorship Survey.

OBJECTIVE: Chordomas are rare malignant bone tumors whose location in the skull base or spine, invasive surgical treatment, and accompanying adjuvant radiotherapy may all lead patients to experience poor quality of life (QOL). Limited research has been conducted on specific demographic and clinical factors associated with decreased QOL in chordoma survivors. Thus, the aim of the present study was to investigate several potential variables and their impact on specific QOL domains in these patients as well the frequencies of specific QOL challenges within these domains. METHODS: The Chordoma Foundation (CF) Survivorship Survey was electronically distributed to chordoma survivors subscribed to the CF Chordoma Connections forum. Survey questions assessed QOL in three domains: physical, emotional/cognitive, and social. The degree of impairment was assessed by grouping the participants into high- and low-challenge groups designated by having ≥ 5 or < 5 symptoms or challenges within a given QOL domain. Bivariate analysis of demographic and clinical characteristics between these groups was conducted using Fisher's exact test and the Mann-Whitney U-test. RESULTS: A total of 665 chordoma survivors at least partially completed the survey. On bivariate analysis, female sex was significantly associated with increased odds of significant emotional (p = 0.001) and social (p = 0.019) QOL burden. Younger survivors (age < 65 years) were significantly more likely to experience significant physical (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) QOL burden. Skull base chordoma survivors had significantly higher emotional/cognitive QOL burden than spinal chordoma survivors (p = 0.022), while the converse was true for social QOL challenges (p = 0.0048). Survivors currently in treatment were significantly more likely to experience significant physical QOL challenges compared with survivors who completed their treatment > 10 years ago (p = 0.0074). Fear of cancer recurrence (FCR) was the most commonly reported emotional/cognitive QOL challenge (49.6%). Only 41% of the participants reported having their needs met for their physical QOL challenges as well as 25% for emotional/cognitive and 18% for social. CONCLUSIONS: The authors' findings suggest that younger survivors, female survivors, and survivors currently undergoing treatment for chordoma are at high risk for adverse QOL outcomes. Additionally, although nearly half of the participants reported a FCR, very few reported having adequate emotional/cognitive care. These findings may be useful in identifying specific groups of chordoma survivors vulnerable to QOL challenges and bring to light the need to expand care to meet the QOL needs for these patients.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series. Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

Quality of Life in Chordoma Co-Survivors: Results from the Chordoma Foundation Survivorship Survey.

BACKGROUND: Chordomas are a rare form of aggressive bone cancer and are associated with poor quality of life (QOL). The present study sought to characterize demographic and clinical characteristics associated with QOL in chordoma co-survivors (caregivers of patients with chordoma) and assess whether co-survivors access care for QOL challenges. METHODS: The Chordoma Foundation Survivorship Survey was electronically distributed to chordoma co-survivors. Survey questions assessed emotional/cognitive and social QOL, with significant QOL challenges being defined as experiencing ≥5 challenges within either of these domains. The Fisher exact test and Mann-Whitney U test were used to analyze bivariate associations between patient/caretaker characteristics and QOL challenges. RESULTS: Among the 229 respondents to our survey, nearly half (48.5%) reported a high number (≥5) of emotional/cognitive QOL challenges. Co-survivors younger than 65 years were significantly more likely to experience a high number of emotional/cognitive QOL challenges (P < 0.0001), whereas co-survivors >10 years past the end of treatment were significantly less likely to experience a high number of emotional/cognitive QOL challenges (P = 0.012). When asked about access to resources, a lack of knowledge of resources to address their emotional/cognitive and social QOL issues (34% and 35%, respectively) was the most common response. CONCLUSIONS: Our findings suggest that younger co-survivors are at high risk for adverse emotional QOL outcomes. In addition, more than one third of co-survivors did not know about resources to address their QOL issues. Our study may help guide organizational efforts to provide care and support to patients with chordoma and their loved ones.

A comparative analysis of the Hospital Frailty Risk Score in predicting postoperative outcomes among intracranial tumor patients.

OBJECTIVE: In recent years, frailty indices such as the 11- and 5-factor modified frailty indices (mFI-11 and mFI-5), American Society of Anesthesiologists (ASA) physical status classification, and Charlson Comorbidity Index (CCI) have been shown to be effective predictors of various postoperative outcomes in neurosurgical patients. The Hospital Frailty Risk Score (HFRS) is a well-validated tool for assessing frailty; however, its utility has not been evaluated in intracranial tumor surgery. In the present study, the authors investigated the accuracy of the HFRS in predicting outcomes following intracranial tumor resection and compared its utility to those of other validated frailty indices. METHODS: A retrospective analysis was conducted using an intracranial tumor patient database at a single institution. Patients eligible for study inclusion were those who had undergone resection for an intracranial tumor between January 1, 2017, and December 31, 2019. ICD-10 codes were used to identify HFRS components and subsequently calculate risk scores. In addition to several postoperative variables, ASA class, CCI, and mFI-11 and mFI-5 scores were determined for each patient. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC), and the DeLong test was used to assess for significant differences between AUROCs. Multivariate models for continuous outcomes were constructed using linear regression, whereas logistic regression models were used for categorical outcomes. RESULTS: A total of 2518 intracranial tumor patients (mean age 55.3 ± 15.1 years, 53.4% female, 70.4% White) were included in this study. The HFRS had a statistically significant greater AUROC than ASA status, CCI, mFI-11, and mFI-5 for postoperative complications, high hospital charges, nonroutine discharge, and 90-day readmission. In the multivariate analysis, the HFRS was significantly and independently associated with postoperative complications (OR 1.14, p < 0.0001), hospital length of stay (coefficient = 0.50, p < 0.0001), high hospital charges (coefficient = 1917.49, p < 0.0001), nonroutine discharge (OR 1.14, p < 0.0001), and 90-day readmission (OR 1.06, p < 0.0001). CONCLUSIONS: The study findings suggest that the HFRS is an effective predictor of postoperative outcomes in intracranial tumor patients and more effectively predicts adverse outcomes than other frailty indices. The HFRS may serve as an important tool for reducing patient morbidity and mortality in intracranial tumor surgery.

Substance Use Disorders Are Independently Associated with Hospital Readmission Among Patients with Brain Tumors.

BACKGROUND: Research on the effects of substance use disorders (SUDs) on postoperative outcomes within neurosurgical oncology has been limited. Therefore, the present study sought to quantify the effect of having a SUD on hospital length of stay, postoperative complication incidence, discharge disposition, hospital charges, 90-day readmission rates, and 90-day mortality rates following brain tumor surgery. METHODS: The present study used data from patients who received surgical resection for brain tumor at a single institution between January 1, 2017, and December 31, 2019. The Mann-Whitney U test was used for bivariate analysis of continuous variables and Fisher exact test was used for bivariate analysis of categorical variables. Multivariate analysis was conducted using logistic regression models. RESULTS: Our study cohort included a total of 2519 patients, 124 (4.9%) of whom had at least 1 SUD. More specifically, 90 (3.6%) patients had an alcohol use disorder, 27 (1.1%) had a cannabis use disorder, and 12 (0.5%) had an opioid use disorder. On bivariate analysis, 90-day hospital readmission was the only postoperative outcome significantly associated with a SUD (odds ratio 2.21, P = 0.0011). When controlling for patient age, sex, race, marital status, insurance, brain tumor diagnosis, 5-factor modified frailty index score, American Society of Anesthesiologists score, and surgery number, SUDs remained significantly and independently associated with 90-day readmission (odds ratio 1.82, P = 0.013). CONCLUSIONS: In patients with brain tumor, SUDs significantly and independently predict 90-day hospital readmission after surgery. Targeted management of patients with SUDs before and after surgery can optimize patient outcomes and improve the provision of high-value neurosurgical care.

Social determinants of health and the prediction of 90-day mortality among brain tumor patients.

OBJECTIVE: Within the neurosurgical oncology literature, the effect of structural and socioeconomic factors on postoperative outcomes remains unclear. In this study, the authors quantified the effects of social determinant of health (SDOH) disparities on hospital complications, length of stay (LOS), nonroutine discharge, 90-day readmission, and 90-day mortality following brain tumor surgery. METHODS: The authors retrospectively reviewed the records of brain tumor patients who had undergone resection at a single institution in 2017-2019. The prevalence of SDOH disparities among patients was tracked using International Classification of Diseases Ninth and Tenth Revisions (ICD-9 and ICD-10) codes. Bivariate (Mann-Whitney U-test and Fisher's exact test) and multivariate (logistic and linear) regressions revealed whether there was an independent relationship between SDOH status and postoperative outcomes. RESULTS: The patient cohort included 2519 patients (mean age 55.27 ± 15.14 years), 187 (7.4%) of whom experienced at least one SDOH disparity. Patients who experienced an SDOH disparity were significantly more likely to be female (OR 1.36, p = 0.048), Black (OR 1.91, p < 0.001), and unmarried (OR 1.55, p = 0.0049). Patients who experienced SDOH disparities also had significantly higher 5-item modified frailty index (mFI-5) scores (p < 0.001) and American Society of Anesthesiologists (ASA) classes (p = 0.0012). Experiencing an SDOH disparity was associated with a significantly longer hospital LOS (p = 0.0036), greater odds of a nonroutine discharge (OR 1.64, p = 0.0092), and greater odds of 90-day mortality (OR 2.82, p = 0.0016) in the bivariate analysis. When controlling for patient demographics, tumor diagnosis, mFI-5 score, ASA class, surgery number, and SDOH status, SDOHs independently predicted hospital LOS (coefficient = 1.22, p = 0.016) and increased odds of 90-day mortality (OR 2.12, p = 0.028). CONCLUSIONS: SDOH disparities independently predicted a prolonged hospital LOS and 90-day mortality in brain tumor patients. Working to address these disparities offers a new avenue through which to reduce patient morbidity and mortality following brain tumor surgery.

Preclinical and Clinical Development of Therapeutic Antibodies Targeting Functions of CD47 in the Tumor Microenvironment.

CD47 is a ubiquitously expressed cell surface glycoprotein that functions as a signaling receptor for thrombospondin-1 and as the counter-receptor for signal regulatory protein-α (SIRPα). Engaging SIRPα on macrophages inhibits phagocytosis, and CD47 thereby serves as a physiological marker of self. However, elevated CD47 expression on some cancer cells also protects tumors from innate immune surveillance and limits adaptive antitumor immunity via inhibitory SIRPα signaling in antigen presenting cells. CD47 also mediates inhibitory thrombospondin-1 signaling in vascular cells, T cells, and NK cells, and blocking inhibitory CD47 signaling on cytotoxic T cells directly increases tumor cell killing. Therefore, CD47 functions as an innate and adaptive immune checkpoint. These findings have led to the development of antibodies and other therapeutic approaches to block CD47 functions in the tumor microenvironment. Preclinical studies in mice demonstrated that blocking CD47 can limit the growth of hematologic malignancies and solid tumors and enhance the efficacy of conventional chemotherapy, radiation therapy, and some targeted cancer therapies. Humanized CD47 antibodies are showing promise in early clinical trials, but side effects related to enhanced phagocytic clearance of circulating blood cells remain a concern. Approaches to circumvent these include antibody preloading strategies, development of antibodies that recognize tumor-specific epitopes of CD47, SIRPα antibodies, and bivalent antibodies that restrict CD47 blockade to specific tumor cells. Preclinical and clinical development of antibodies and related biologics that inhibit CD47/SIRPα signaling are reviewed, including strategies to combine these agents with various conventional and targeted therapeutics to improve patient outcome for various cancers.