ABSTRACT
PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.
Subject(s)
Central Nervous System Neoplasms , Pandemics , Humans , Retrospective Studies , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/therapy , Patient Care Team , Referral and ConsultationABSTRACT
BACKGROUND: Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes. MATERIALS AND METHODS: A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected. RESULTS: Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131). CONCLUSION: This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.
Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Brain Neoplasms , Cholangiocarcinoma , Humans , Proto-Oncogene Proteins B-raf/genetics , Biliary Tract Neoplasms/genetics , Mutation , Brain Neoplasms/genetics , Retrospective Studies , Cholangiocarcinoma/pathology , Bile Duct Neoplasms/drug therapyABSTRACT
PURPOSE: The aim of this study was to determine outcomes and prognostic factors for patients with primary and locally recurrent extra-abdominal desmoid tumors who underwent percutaneous cryoablation, and to compare with patients treated with surgery. METHODS: Group characteristics were compared using Fisher's exact test, and propensity score matching was performed using the nearest-neighbor approach. Kaplan-Meier and log-rank analyses were used to evaluate the variation in first local recurrence and disease control, while multivariate Cox regression was used to identify factors associated with first local recurrence. All statistical tests were two-sided and a p-value of 0.05 was considered statistically significant. RESULTS: Twenty-two cryoablation patients were matched with 33 surgical patients (n = 55). Median follow-up after cryoablation was 16.3 months versus 14.9 months after surgery. Two-year local recurrence-free survival (LRFS) was 59% after cryoablation and 71% after surgery, and median LRFS was 26.6 months after cryoablation but was not reached after surgery. Two-year disease control for all patients was 85%, however median disease control was not reached in either the cryoablation or surgery groups. There was no significant difference in LRFS or disease control between matched cryoablation and surgical patients. No local recurrences occurred after the first cryoablation in patients with zero or one of the following risk factors: tumor size > 5 cm, age ≤ 25 years, or locally recurrent disease. All patients with two or more of these risk factors recurred locally after the first cryoablation. CONCLUSION: Percutaneous cryoablation of primary and locally recurrent extra-abdominal desmoid tumors provides freedom from first local recurrence and long-term disease control comparable with surgery.
Subject(s)
Catheter Ablation , Cryosurgery , Fibroma , Fibromatosis, Aggressive , Adult , Fibromatosis, Aggressive/surgery , Humans , Risk FactorsABSTRACT
Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.
Subject(s)
Glioblastoma , Glioma , Humans , Glioma/genetics , Glioma/surgery , Mutation , Protein Kinase Inhibitors , Receptor, Fibroblast Growth Factor, Type 3/genetics , Microtubule-Associated ProteinsABSTRACT
BACKGROUND: Meningiomas are the most common primary central nervous system tumors. Potential risk factors include obesity, height, history of allergy/atopy, and autoimmune diseases, but findings are conflicting. This study sought to assess the role of the different risk factors in the development of meningioma in adolescents/young adults. METHODS: The cohort included 2,035,915 Jewish men and women who had undergone compulsory physical examination between 1967 and 2011, at age 16 to 19 years, prior to and independent of actual military enlistment. To determine the incidence of meningioma, the military database was matched with the Israel National Cancer Registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according to sex, body mass index (BMI), height, and history of allergic or autoimmune disease. RESULTS: A total of 480 subjects (328 females) were diagnosed with meningioma during a follow-up of 40,304,078 person-years. Median age at diagnosis was 42.1 ± 9.4 years (range 17.4-62.6). On univariate analysis, female sex (p < 0.01) and height (p < 0.01) were associated with risk of meningioma. When the data were stratified by sex, height remained a significant factor only in men. Spline analysis of the male subjects showed that a height of 1.62 m was associated with a minimum disease risk and a height of 1.85+ meters, with a significant risk. CONCLUSIONS: This large population study showed that sex and adolescent height in males (> 1.85 m) were associated with an increased risk of meningioma in adulthood.
Subject(s)
Body Height , Meningeal Neoplasms/epidemiology , Meningioma/epidemiology , Adolescent , Adult , Female , Follow-Up Studies , Humans , Incidence , Israel/epidemiology , Male , Middle Aged , Prospective Studies , Registries , Risk Assessment/statistics & numerical data , Risk Factors , Sex Factors , Young AdultSubject(s)
Meningeal Neoplasms , Meningioma , Humans , Animals , Dogs , Meningioma/genetics , Meningeal Neoplasms/geneticsABSTRACT
BACKGROUND: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. CASE PRESENTATION: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). CONCLUSIONS: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.
Subject(s)
Brain Neoplasms/secondary , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/pathology , Brain Neoplasms/surgery , Female , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/radiotherapy , Gastrointestinal Neoplasms/surgery , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/radiotherapy , Gastrointestinal Stromal Tumors/surgery , Humans , Middle Aged , Prognosis , Proto-Oncogene MasABSTRACT
BACKGROUND: Examine the potential effects of health disparities in survival of glioblastoma (GB) patients. METHODS: We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS). RESULTS: We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.
Subject(s)
Brain Neoplasms/epidemiology , Brain Neoplasms/therapy , Glioblastoma/epidemiology , Glioblastoma/therapy , Healthcare Disparities , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Insurance, Health , Karnofsky Performance Status , Male , Middle Aged , Prognosis , Racial Groups , Retrospective Studies , Socioeconomic Factors , Survival Analysis , Young AdultABSTRACT
BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.
Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Cohort Studies , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Male , Radiotherapy , Retrospective Studies , Temozolomide/therapeutic use , Treatment OutcomeABSTRACT
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days-19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Neoplasms/drug therapy , Nervous System Diseases/etiology , Adult , Aged , Antineoplastic Agents, Immunological/therapeutic use , Fatal Outcome , Female , Humans , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/mortality , Nervous System Diseases/pathology , Retrospective Studies , Time Factors , Young AdultABSTRACT
BACKGROUND: Iliac vein stenting is increasingly being used in the treatment of chronic venous insufficiency caused by nonthrombotic iliac vein lesions (NIVL). We have noticed that many stents do not deploy to the expected stent area (ESA) as designated by the manufactured stent diameter (MSD). The purpose of this study was to identify factors predictive of Wallstent® underexpansion in the iliocaval venous system. METHODS: Retrospective analysis of all patients with NIVL who were treated with iliac vein stenting using Wallstents® was performed. None of the patients in this study underwent pre-or post-stenting balloon angioplasty. Multiway analysis of variance and multiple linear regression analysis were performed to examine the effects of gender, age, stent laterality, location of stenosis, and CEAP (clinical, etiology, anatomy, and pathophysiology) score at presentation on the proportion of observed stent area (OSA) to ESA. RESULTS: Two-hundred three patients (64 male and 139 female; mean age: 68 ± 13.9 years) underwent 242 treatments between December 2012 and January 2016. Disease severity based on CEAP score were: C1 (0), C2 (0), C3 (n = 59, 24%), C4 (n = 148, 61%), C5 (n = 4, 2%), and C6 (n = 31, 13%). On average, stents deployed to 69.58% of the ESA (range, 23.87123.35%). Multiple linear regression analysis showed a significant negative correlation between increasing MSD and ESA achieved. Regression coefficients for differences in percent difference between ESA and OSA based on MSD were as follows: 16 mm (−15.0, P = 0.1519), 18 mm (−21.0, P = 0.0077), 20 mm (−23.2, P = 0.0059), and 2022 mm (−35.3, P < 0.0001). No significant difference in stent underexpansion was detected based on gender, age, stent laterality, location of stenosis, or CEAP score. CONCLUSIONS: Larger MSD is associated with greater magnitude of stent underexpansion. These findings may have implications for future venous stent designing.
Subject(s)
Angioplasty, Balloon/instrumentation , Iliac Vein , Prosthesis Failure , Stents , Venous Insufficiency/therapy , Aged , Aged, 80 and over , Angioplasty, Balloon/adverse effects , Chronic Disease , Constriction, Pathologic , Female , Humans , Iliac Vein/diagnostic imaging , Iliac Vein/physiopathology , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Risk Factors , Treatment Outcome , Venous Insufficiency/diagnostic imaging , Venous Insufficiency/physiopathologyABSTRACT
Background Dialysis access-associated steal syndrome is a major complication of arteriovenous fistula creation whereby the low-resistance venous conduit shunts arterial inflow through the anastomosis, resulting in clinically significant distal artery insufficiency. Herein, we describe a case of severe steal phenomenon with gangrene of a digit following placement of an arteriovenous fistula that was treated with a novel, entirely endovascular technique. To our knowledge, this was the first totally endovascular approach to dialysis access-associated steal syndrome. Methods Catheterization of the right subclavian, axillary, and brachial arteries was performed. A short 5-Fr sheath was exchanged for a long destination 6-Fr sheath and placed in the proximal brachial artery. An arteriogram showed no stenosis of the arterial system, but did show substantial steal phenomenon with inflow to the arteriovenous fistula, instead of the forearm. We placed a stent graft in the brachial artery across the anastomosis such that the graft covered 3/4 of the length of the opening of the anastomosis. Results Immediately after placement of the stent graft the clinical picture improved dramatically. Patient was followed for 15 months after this procedure until her demise for unrelated causes without ever experiencing dialysis access-associated steal syndrome and with a patent and functional arteriovenous fistula. Conclusion We present a patient with severe dialysis access-associated steal syndrome complicated by third fingertip gangrene, which was successfully treated using a completely endovascular technique. This novel endovascular approach enabled a high-risk patient to avoid open surgery, preserve her limb, and maintain the function of her arteriovenous fistula.
Subject(s)
Arteriovenous Fistula/surgery , Arteriovenous Shunt, Surgical , Renal Dialysis , Upper Extremity/surgery , Aged, 80 and over , Arteriovenous Shunt, Surgical/methods , Brachial Artery/surgery , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Female , Humans , Renal Dialysis/adverse effects , Treatment Outcome , Upper Extremity/blood supply , Veins/physiopathology , Veins/surgeryABSTRACT
The purpose of this study is to determine whether a custom Google Maps application can optimize site selection when scheduling outpatient interventional radiology (IR) procedures within a multi-site hospital system. The Google Maps for Business Application Programming Interface (API) was used to develop an internal web application that uses real-time traffic data to determine estimated travel time (ETT; minutes) and estimated travel distance (ETD; miles) from a patient's home to each a nearby IR facility in our hospital system. Hypothetical patient home addresses based on the 33 cities comprising our institution's catchment area were used to determine the optimal IR site for hypothetical patients traveling from each city based on real-time traffic conditions. For 10/33 (30%) cities, there was discordance between the optimal IR site based on ETT and the optimal IR site based on ETD at non-rush hour time or rush hour time. By choosing to travel to an IR site based on ETT rather than ETD, patients from discordant cities were predicted to save an average of 7.29 min during non-rush hour (p = 0.03), and 28.80 min during rush hour (p < 0.001). Using a custom Google Maps application to schedule outpatients for IR procedures can effectively reduce patient travel time when more than one location providing IR procedures is available within the same hospital system.
Subject(s)
Maps as Topic , Mobile Applications , Outpatients , Radiology, Interventional , Travel/statistics & numerical data , Humans , Software , TimeABSTRACT
Treatment response and survival after bevacizumab failure remains poor in patients with glioblastoma. Several recent publications examining glioblastoma patients treated with bevacizumab have described specific radiographic patterns of disease progression as correlating with outcome. This study aims to scrutinize these previously reported radiographic prognostic models in an independent data set to inspect their reproducibility and potential for clinical utility. Sixty four patients treated at MD Anderson matched predetermined inclusion criteria. Patients were categorized based on previously published data by: (1) Nowosielski et al. into: T2-diffuse, cT1 Flare-up, non-responders and T2 circumscribed groups (2) Modified Pope et al. criteria into: local, diffuse and distant groups and (3) Bahr et al. into groups with or without new diffusion-restricted and/or pre-contrast T1-hyperintense lesions. When classified according to Nowosielski et al. criteria, the cT1 Flare-up group had the longest overall survival (OS) from bevacizumab initiation, with non-responders having the worst outcomes. The T2 diffuse group had the longest progression free survival (PFS) from start of bevacizumab. When classified by modified Pope at al. criteria, most patients did not experience a shift in tumor pattern from the pattern at baseline, while the PFS and OS in patients with local-to-local and local-to-diffuse/distant patterns of progression were similar. Patients developing restricted diffusion on bevacizumab had worse OS. Diffuse patterns of progression in patients treated with bevacizumab are rare and not associated with worse outcomes compared to other radiographic subgroups. Emergence of restricted diffusion during bevacizumab treatment was a radiographic marker of worse OS.
Subject(s)
Bevacizumab/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Glioblastoma/diagnostic imaging , Glioblastoma/drug therapy , Magnetic Resonance Imaging , Adult , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/drug effects , Brain Neoplasms/pathology , Disease Progression , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Glioblastoma/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Reproducibility of Results , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.
Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Glioblastoma/diagnosis , Glioblastoma/genetics , Isocitrate Dehydrogenase/genetics , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/genetics , Adult , Aged , Clinical Trials as Topic , Disease-Free Survival , Humans , Middle Aged , Mutation , Retrospective Studies , Young AdultABSTRACT
The risk of venous thromboembolism (VTE) is high for patients with brain tumors (11-20 %). Glioblastoma (GBM) patients, in particular, have the highest risk of VTE (24-30 %). The Khorana scale is the most commonly used clinical scale to evaluate the risk of VTE in cancer patients but its efficacy in patients with GBM remains unclear. The aim of this study is to estimate the frequency of VTE in GBM patients and identify potential risk factors for the development of VTE during adjuvant chemotherapy. Furthermore, we intend to examine whether the Khorana scale accurately predicts the risk of VTE in GBM patients. We retrospectively reviewed the medical records of GBM patients treated at MD Anderson during the years 2005-2011. The study cohort included 440 patients of which 64 (14.5 %) developed VTE after the start of adjuvant treatment. The median time to develop VTE was 6.5 months from the start of adjuvant treatment. On multivariate analysis male sex, BMI ≥ 35, KPS ≤ 80, history of VTE and steroid therapy were significantly associated with the development of VTE. The Khorana scale was found to be an invalid VTE predictive model in GBM patients due to poor specificity. Of the 64 patients who developed a VTE, 36 were treated with anticoagulation, 2 with an IVC filter, and 21 with both. Complications (intracranial hemorrhage, bleeding in other organs and thrombocytopenia) secondary to anticoagulation were reported in 16 % (n = 10). VTE is common in patients with GBM. Our results did not validate the Khorana scale in GBM patients. Additional studies identifying which GBM patients are at highest risk for VTE are needed to enable further evaluation of VTE preventive measures in this selected group.
Subject(s)
Brain Neoplasms/epidemiology , Glioblastoma/epidemiology , Venous Thromboembolism/epidemiology , Adult , Aged , Aged, 80 and over , Brain Neoplasms/therapy , Chemotherapy, Adjuvant , Female , Glioblastoma/therapy , Humans , Male , Middle Aged , Risk Factors , Sensitivity and Specificity , Venous Thromboembolism/therapy , Young AdultABSTRACT
Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Wound Healing/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Electronic Health Records/statistics & numerical data , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Gliosarcoma is classified by the World Health Organization as a variant of glioblastoma. These tumors exhibit biphasic histologic and immunophenotypic features, reflecting both glial and mesenchymal differentiation. Gliosarcomas can be further classified into primary (de novo) tumors, and secondary gliosarcomas, which are diagnosed at recurrence after a diagnosis of glioblastoma. Using a retrospective review, patients seen at MD Anderson Cancer Center between 2004 and 2014 with a pathology-confirmed diagnosis of gliosarcoma were identified. 34 patients with a diagnosis of gliosarcoma seen at the time of initial diagnosis or at recurrence were identified (24 primary gliosarcomas (PGS), 10 secondary gliosarcomas (SGS)). Molecular analysis performed on fourteen patients revealed a high incidence of TP53 mutations and, rarely, EGFR and IDH mutations. Median overall survival (OS) for all patients was 17.5 months from the diagnosis of gliosarcoma, with a progression free survival (PFS) of 6.4 months. Comparing PGS with SGS, the median OS was 24.7 and 8.95 months, respectively (from the time of sarcomatous transformation in the case of SGS). The median OS in SGS patients from the initial diagnosis of GB was 25 months, with a PFS of 10.7 months. Molecular analysis revealed a higher than expected rate of TP53 mutations in GS patients and, typical of primary glioblastoma, IDH mutations were uncommon. Though our data shows improved outcomes for both PGS and SGS when compared to the literature, this is most likely a reflection of selection bias of patients treated on clinical trials at a quaternary center.