Hematological adverse events in the management of glioblastoma.

BACKGROUND: Hematological adverse events (HAEs) are common during treatment for glioblastoma (GBM), usually associated with temozolomide (TMZ). Their clinical value is uncertain, as few investigations have focused on outcomes for HAEs during GBM treatment. METHODS: We combined data from two randomized clinical trials, RTOG 0525 and RTOG 0825, to analyze HAEs during treatment for GBM. We investigated differences between chemoradiation and adjuvant therapy, and by regimen received during adjuvant treatment. RESULTS: 1454 patients participated in these trials, of which 1154 (79.4%) developed HAEs. During chemoradiation, 44.4% of patients developed HAEs (54% involving more than one cell line), and were most commonly lymphopenia (50.6%), and thrombocytopenia (47.5%). During adjuvant treatment, 45% of patients presented HAEs (78.6% involving more than one cell line), and were more commonly leukopenia (62.7%), and thrombocytopenia (62.3%). Median overall survival (OS) and progression free survival (PFS) were longer in patients with HAEs (OS 19.4 months and PFS 9.9 months) compared to those with other or no adverse events (OS 14.1 months and PFS 5.9 months). There was no significant difference in survival between grade 1 and/or 2 versus grade 3 and/or 4 HAEs. History of HAEs during chemoradiation was a protective factor for presentation of HAEs during adjuvant therapy. CONCLUSION: HAEs are common during GBM treatment, and often involve more than one cell line (more likely during adjuvant therapy). HAEs may be associated with prolonged OS and PFS, particularly during adjuvant therapy. HAEs during chemoradiation was a protective factor for HAEs during adjuvant therapy.

Acute encephalitis, myoclonus and Sweet syndrome after mRNA-1273 vaccine.

A patient presented with fever, generalised rash, confusion, orofacial movements and myoclonus after receiving the first dose of mRNA-1273 vaccine from Moderna. MRI was unremarkable while cerebrospinal fluid showed leucocytosis with lymphocyte predominance and hyperproteinorrachia. The skin evidenced red, non-scaly, oedematous papules coalescing into plaques with scattered non-follicular pustules. Skin biopsy was consistent with a neutrophilic dermatosis. The patient fulfilled the criteria for Sweet syndrome. A thorough evaluation ruled out alternative infectious, autoimmune or malignant aetiologies, and all manifestations resolved with glucocorticoids. While we cannot prove causality, there was a temporal correlation between the vaccination and the clinical findings.

Primary central nervous system tumor treatment and survival in the United States, 2004-2015.

INTRODUCTION: Brain tumor treatment and survival information is generally limited in large-scale cancer datasets. We provide a clinical investigation of current patterns of care and survival estimates for central nervous system (CNS) tumors treated in the United States. METHODS: We analyzed the National Cancer Database from 2004-2015 for all patients with diagnosis of primary CNS tumors. We describe patient demographics, treatment modality, and analyzed survival estimates. RESULTS: 512,168 patient tumor records were examined. The most common histology was meningioma (43.6%), followed by glioblastoma (22.0%), and nerve sheath tumors (10.6%). Patients had a median age of 60 years, with a female (57.9%), white (85.0%), and non-Hispanic (87.8%) predominance. Tumors were reported as World Health Organization (WHO) grade I for 55.9% of the patients, grade II for 5.9%, grade III for 4.4%, grade IV for 24.3%, and grade unknown or not applicable for 9.4%. Overall, 56% underwent surgical procedures, 30.4% received radiation, and 20.6% received chemotherapy. Radiation plus chemotherapy and surgery was the most common treatment modality in high-grade tumors (40.5% in WHO grade III and 49.3% in WHO grade IV), while surgery only or watchful waiting was preferred in low-grade tumors. Older age, male gender, non-Hispanic origin, higher number of comorbidities, and lower socioeconomic status were identified as risk factors for mortality. CONCLUSIONS: Our analysis provides long-term survival estimates and initial treatment decisions for patients with CNS tumors in hospitals throughout the United States. Age, comorbidities, gender, ethnicity, and socioeconomic characteristics were determinants of survival.

Initial management of meningiomas: Analysis of the National Cancer Database.

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma. RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in community facilities, had higher Charlson-Deyo score, and a lower rate of private insurance. Watchful waiting was the most common treatment modality (46.7%), followed by surgery only (40%). Grade II and III patients were more likely to receive therapy. Watchful waiting increased from 35.2% in 2004 to 51.4% in 2014. Younger age, male gender, private insurance, and treatment in academic facilities were determinants for receipt of surgery and/or radiation. Median survival was 12.6 years, higher in histologically confirmed cases (13.1 years). Older patients, Blacks, males, those that received radiation plus surgery, and were treated in community facilities had an increased risk of mortality. CONCLUSIONS: Over half of patients were diagnosed by imaging, suggesting a higher role of clinical determinants over histological confirmation in treatment decisions. Watchful waiting as initial management is increasing. Our survival analysis favored histological confirmation. Patients receiving radiation and surgery had an increased risk of mortality.

Multiple sclerosis outcomes after cancer immunotherapy.

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes. METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution. RESULTS: We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; two patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors. CONCLUSIONS: Reported MS relapses after ICI are rare, but the adverse events described include rapid neurologic progression and death. Larger and prospective studies are warranted to assess disability and long-term outcomes and outweigh the risks of starting immunotherapy in patients with MS.

Association Between Sarcopenia and AFP Level in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Sarcopenia is one of the most common complications of cirrhosis. Liver transplantation (LT) is the treatment of choice for patients with early-stage hepatocellular carcinoma (HCC) that are unsuitable for resection. METHODS: We performed a retrospective analysis of 163 patients transplanted at our institution with HCC from 1998 to 2016. Sarcopenia was diagnosed based on the skeletal muscle mass on computed tomography imaging using SliceOmatic 5.0 software at L3 level (≤52.4 cm2/m2 in males and ≤38.5 cm2/m2 in females). RESULTS: From the 163 patients who underwent LT for HCC, 119 had available computed tomography scan. From those, 61 were identified as sarcopenic by lumbar skeletal muscle index (LSMI), of which 53 patients were male (86.9%) with a median age of 59 y (56-64). The most common etiologies of cirrhosis were hepatitis C virus infection (55.7%) and alcohol liver disease (46.7%). A multivariable analysis was performed to find predictors of sarcopenia. Alpha-fetoprotein level >100 mg/dL (OR, 6.577; 95% CI: 1.370-51.464; P = 0.034) and gender (male) (OR, 5.878; 95% CI: 1.987-20.054; P = 0.002) were independently associated with the presence of sarcopenia in this cohort. Patients in the lowest quartile for LSMI had prolonged length of stay compared to the rest of the patients (P = 0.029). CONCLUSIONS: Alpha-fetoprotein level >100 mg/dL is associated with almost 6-fold increased risk of sarcopenia in patients with HCC undergoing LT. Patients in the lowest quartile of the LSMI are associated with 70% increased risk of prolonged length of stay in this cohort.

Patterns and disparities of care in glioblastoma.

BACKGROUND: Glioblastoma is an aggressive disease with a defined standard of care offering crucial survival benefits. Disparities in care may influence treatment decisions. This study seeks to evaluate potential patterns in care delivery using the National Cancer Database (NCDB). METHODS: We evaluated the NCDB from 1998 to 2011 for patients diagnosed with glioblastoma older than 20 years of age in order to describe current hospital-based demographics, rates of treatment modality by age, race, gender, likelihood of receiving treatment, and survival probabilities. RESULTS: From 1998 to 2011, 100672 patients were diagnosed with glioblastoma in the United States. Of these, 54% were younger than 65 years of age, while 20% were 75 years of age or older. The most common type of treatment was surgery (73%), followed by radiation (69%) and chemotherapy (50%). Eleven percent of patients did not receive any form of therapy. Patients receiving no form of treatment were more likely to be older, female, black, or Hispanic. Tumors that did not involve brainstem, ventricles, or the cerebellum were associated with more aggressive treatment and better overall survival. The median survival was 7.5 months. The use of concomitant surgical resection, chemotherapy, and radiation demonstrated greater survival benefit. CONCLUSIONS: Median survival for glioblastoma is significantly less than reported in clinical trials. Sociodemographic factors such as age, gender, race, and socioeconomic status affect treatment decisions for glioblastoma. The elderly are greatly undertreated, as many elderly patients receive no treatment or significantly less than standard of care.

Outcomes in patients with portal hypertension undergoing gastrointestinal surgery: A propensity score matched analysis from the NSQIP dataset.

BACKGROUND/AIM: We aim to study the impact of PH in patients undergoing gastrointestinal surgery (GI). METHODS: We queried the ACS-NSQIP database from 2005 through 2010 for patients undergoing GI surgery with PH. Esophageal varices (EV) diagnosis was used as a surrogate of PH. RESULTS: A total of 192,296 patients underwent GI surgery, of which 379 had PH. Regression analyses revealed that patients with PH had a 6-fold (95% CI 4.6-7.9) increase in 30-day mortality, a 3-fold (95% CI 2.5-3.7) increase in morbidity, a 3.2-fold (95% CI 2.6-3.9) increase in critical care complications (CCC), and a 6.5-day (95% CI 5.1-7.8) increase in hospital LOS. After PSM, the impact of PH on the outcomes remained. These differences were significant regardless of the emergent or elective status of the procedure. AUC analysis demonstrated that MELD and MELDNa + score greater than 10.5 was the most predictive of peri-operative mortality in elective PH cases. CONCLUSIONS: PH is associated with an increased risk of poor surgical outcomes in patients undergoing elective and emergent gastrointestinal surgery.

Comprehensive evaluation of treatment and outcomes of low-grade diffuse gliomas.

BACKGROUND: Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma. RESULTS: We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most common primary site location was the cerebrum (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3% chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy + chemotherapy (6.7%). Radiation was more common in treatment of elderly patients, 1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline location. Median survival was 11 years with younger age, 1p/19q co-deletion, and cerebrum location offered survival advantage. CONCLUSIONS: Tumor location, 1p/19q co-deletion, and age were the main determinants of treatment received and survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting in the majority of the patients (86.1% versus 8.1%). Survival of low-grade gliomas is higher than previously reported in the majority of clinical trials and population-based analyses. Our analysis provides a real world estimation of treatment decisions, use of molecular data, and outcomes.

Dose-dense temozolomide for recurrent high-grade gliomas: a single-center retrospective study.

There are limited treatment modalities after high-grade gliomas recurrence. MGMT depletion modulated by dose-dense temozolomide (ddTMZ) remains a debated therapy for initial TMZ responders. Patients were selected retrospectively from our practice with diagnosis of high-grade gliomas (WHO grade III or IV), and were followed since the start of ddTMZ until death or change of therapy. Twenty-one patients were reviewed, with a median age of 47 (25-61) years and a median of 5.8 (1.5-38.8) cycles of ddTMZ. The majority were males (71.4%). Sixty-six percent received 21 on/28 off ddTMZ schedule, 28.6% daily, and 1 patient received a 7 days on/7 days off schedule. IDH mutation status was available for 18 (85.7%) patients, with 7 (33.3%) IDH mutant and 11 (52.5%) IDH wild type. MGMT methylation was assessed in 6 (28.6%) of the patients, being MGMT methylated in 3 (14.3%) patients, and non-methylated in 3 (14.3%) patients. The majority of patients (57.1%) were receiving ddTMZ in addition to other forms of therapy, including either bevacizumab (38.1%) or tumor-treating fields (TTFields) (19.1%). Overall ddTMZ was well tolerated, with few adverse events reported. The estimated median overall survival after ddTMZ start was 11 months. Median progression-free survival (PFS) was 6 months. Outcomes did not vary between patients receiving ddTMZ alone or those using TTFields or bevacizumab as concomitant therapy, but there was a trend to longer survival with the use of concomitant TTFields. Our results demonstrate benefit of ddTMZ after previous treatment with standard TMZ dosing with no apparent increase in treatment-related toxicities. In summary, ddTMZ should be considered in TMZ responsive patients and warrants further investigation.

Re-transplantation for Hepatic Artery Thrombosis: A National Perspective.

BACKGROUND: Hepatic artery thrombosis (HAT) is a major complication after liver transplantation that commonly requires re-transplantation. METHODS: We queried the UNOS dataset for all patients transplanted between 1995 and 2015 for HAT. RESULTS: We identified 623 patients who underwent re-transplantation for HAT with a mean age of 51.25 + 10.4 years. The mean BMI was 26.72 kg/m2, and mean MELD score was 19.62 + 9.09. There was a higher proportion of male patients, with higher prevalence of pre-transplant portal vein thrombosis (7.4 vs. 5.4%, p = 0.04), lower incidence of hepatitis C virus infection (29.5 vs. 35.8%, p = 0.002), and shorter waiting time (61 vs. 111 days, p = 0.001) in the HAT group compared to those re-transplanted for other indications. The perioperative 90-day mortality was lower in patients re-transplanted for HAT (16 vs. 20%, p = 0.02). Patients undergoing re-transplantation for HAT had 13% decreased graft survival and 13% increased long-term survival. After case-control matched analysis, graft survival and patient survival were significantly better in the HAT group. Late re-transplantation (>30 days) for HAT was linked to decreased graft and patient survival when compared to those undergoing early re-transplantation (within 30 days). CONCLUSIONS: Improved outcomes were seen in patients undergoing re-transplantation for HAT compared to patients who underwent re-transplantation for other indications. Those re-transplanted late after HAT (>30 days) were associated with worse outcomes when compared to early re-transplantation.

Characteristics and survival outcomes associated with the lack of radiation in the treatment of glioblastoma.

Radiation increases survival in glioblastoma (GBM); however, 30% do not receive this treatment. We sought to identify characteristics associated with not receiving radiation and the impact on outcomes. We analyzed the Surveillance, Epidemiology, and End Results program (SEER) 18 registries 2000-2013 research database on 30,479 GBM cases that were aged 20 years and older. In total, 21,179 received radiation as first course of therapy, while 8218 did not with 5178 (63%) being 65 years and older. Early decisions on surgery often predicted radiation therapy with 61% having only a biopsy or no surgery at diagnosis. Radiation use as upfront therapy has slowly increased over time at a rate of 0.4% per year; still 25% did not receive radiation in 2013. Cases treated with radiation were more likely to be younger, underwent surgery, lived in a metropolitan area, had higher socioeconomic status, and were in a couple-based relationship. An increased survival in GBM was associated with the use of upfront radiation along with younger age, being of race other than white, undergoing surgery, and a more recent diagnosis. Not receiving radiation therapy adversely affects survival. A trend toward an increased use of radiation was observed although many young adults still do not receive this treatment. Decreased usage of radiation in the elderly and in biopsy-only surgeries was anticipated, but race, gender, and poverty were also statistically significant. Clinicians should be aware of this underutilization, and an increased usage of radiation should improve outcomes for glioblastoma.

National cancer database analysis of outcomes in pediatric glioblastoma.

Glioblastoma in children is an aggressive disease with no defined standard therapy. We evaluated hospital-based demographic and survival patterns obtained through the National Cancer Database to better characterize children with glioblastoma. Our study identified 1173 patients from 0 to 19 years of age between 1998 and 2011. Comparisons were made among demographics, clinical characteristics, treatment, and survival variables. Fifty-four percent of patients were over 10 years of age. Approximately 80% of patients underwent either partial or complete resection. Adjuvant therapy was used variably, and its use increased with patient age. Forty-eight percent of patients received the combination of surgery, radiation, and chemotherapy, and 4% did not receive any treatment. As expected, patients ≤5 years of age had better 5-year survival than those ages 6-10 (P = 0.01) or 11-19 years (P = 0.0077). Other factors associated with poor survival included black race and central tumor location. Better outcomes were associated with treatment that included surgery, radiotherapy, and chemotherapy compared to any other treatment combinations. Radiotherapy had no impact on survival in the 0 to 10-year-old age group, but was associated with improved survival for patients 11-19 years. We report an extensive demographic and survival analysis of pediatric glioblastoma. The observed differences likely reflect variances in tumor biology and likelihood of treatment receipt. Improved survival was associated with the use of surgery, radiotherapy, and chemotherapy. Radiation therapy was not associated with survival in patients younger than 10 years of age.

Brain tumors associated with psychogenic non-epileptic seizures: Case series.

OBJECTIVE: The association of psychogenic non-epileptic seizures (PNES) with primary or secondary brain tumors has not been well described in the literature. We aim to discuss their association, and their impact in brain tumor treatment. PATIENTS AND METHODS: We identified four patients retrospectively from our practice. The diagnosis of PNES was based on clinical suspicion and standard EEG, supplemented with video-EEG recording in 2 patients. RESULTS: The initial diagnosis of brain tumor was associated with a new onset seizure prior to diagnosis. The majority of the patients presented with ES followed by recurrent PNES during the course of their disease. Patients were treated with multiple anti-epileptic drugs, requiring frequent schedule adjustments. The preferred tumor treatment modality was chemotherapy, followed by surgical resection. The patients were offered psychological consultation achieving partial control of their events. These patients manifested recurrent disabling clinical events that required multiple medical consultations. None of these patients presented clinical evidence of tumor progression at the time of PNES presentation. CONCLUSION: A high index of suspicion and early psychological consultation referral will likely mitigate the quality of life impact of PNES in these patients.

Impact of super obesity on perioperative outcomes after hepatectomy: The weight of the risk.

BACKGROUND: We evaluated perioperative outcomes in super obese patients (body mass index >50 kg/m2) undergoing liver resection using the American College of Surgeons National Surgical Quality Improvement Program. METHODS: Patients undergoing hepatectomy recorded in the American College of Surgeons National Surgical Quality Improvement Program dataset from 2005 to 2015 were analyzed. Out of 21,228 hepatectomies in the National Surgical Quality Improvement Program dataset, 146 were performed on super obese patients. RESULTS: Seventy-two percent of the super obese patients were female with a median age of 50.6 years, and 10% were classified as American College of Surgeons Class ≥III. In this group, 69.2% were hypertensive, 38.4% were diabetics, and 17.8% had dyspnea. The median operation time was 248 minutes in the super obese group, greater than any other body mass index class. Twenty-two percent of these patients required perioperative transfusion, although 74% underwent partial hepatectomies. Body mass index >50 kg/m2 significantly increased morbidity in patients undergoing hepatectomies, almost 2-fold. Infectious complications increased by 86%, and the risk of developing critical care complications increased by 63%. CONCLUSION: Our data show that super obesity (body mass index >50 kg/m2) is the strongest independent predictor of perioperative morbidity. These patients also are at much greater risk of infectious complications and critical care complications. Future studies should be conducted using weight loss strategies in extreme obese patients to reduce their risk of life-threatening complications after hepatectomy.

Liver Transplantation for the Treatment of Complicated Iatrogenic Biliary Injuries: A National Review from the UNOS Data Set.

BACKGROUND: Liver transplantation (LT) is rarely indicated in the management of iatrogenic bile duct injuries (IBDI), but occasionally, it becomes the only remaining therapy. The purpose of this study is to evaluate potential complications of IBDI and their impact on perioperative mortality, graft, and patient survival after LT. METHODS: The United Network for Organ Sharing database was queried for all LT performed in the United States between 1994 and 2014. Of the 101 238 liver transplants performed, 61 were related to IBDI. We performed a case matched analysis in a 5:1 ratio. RESULTS: The median age for patients with IBDI was 50.16 ± 11.7 years with a mean Model End-Stage Liver Disease score of 22.6 ± 9.8. Patients receiving LT for IBDI were more likely women (54.1%, P = 0.001), had lower incidence of hepatitis C virus infection (4.9%, P = 0.001) and longer cold ischemic time (P = 0.001). The mean body mass index was 25.5 ± 5.2 in patients transplanted for IBDI. IBDI was recognized as the strongest independent predictor associated with eightfold increased risk of early graft loss (P = 0.001; odds ratio, 8.4) and a 2.9-fold increased risk of 30-day mortality after LT in a case matched analysis (P = 0.03). CONCLUSIONS: IBDI is an uncommon but challenging indication for LT. These patients have significantly increased rates of early graft loss. IBDI is an independent factor related to increased risk of perioperative death after LT. Further studies are needed to determine the causes of perioperative complications and identify potential modifiable factors to improve outcomes in patients undergoing transplantation for IBDI.