Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death ...1 (PD-1) inhibitor) in patients with advanced rare cancers.
In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).
A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.
The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population.
NCT02721732.
Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI ...variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM.
We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image.
Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively).
Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.
Purpose
Primary central nervous system lymphoma (PCNSL) in patients living with HIV (PLWH) is a distinct entity; however, the management is adopted from patients without HIV. The study aims to ...examine the differences in presentation, treatment, and outcomes of PCNSL patients with or without HIV.
Methods
We retrospectively compared the characteristics of 144 patients with PCNSL with and without HIV, and analyzed factors associated with overall and progression-free survival. Results were compared to the Central Brain Tumor Registry of the United States (CBTRUS) and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) system.
Results
Among all patients with PCNSL, 19% had HIV. PLWH were younger (38 vs. 63 years;
p
< 0.01) and more likely to be African American (59% vs. 7%;
p
< 0.01) and male (74% vs. 49%;
p
= 0.02) than patients without HIV. PLWH were more likely to have multiple lesions (67% vs. 43%;
p
= 0.02), hemorrhage (59 vs. 37%;
p
= 0.03), and peripheral rim enhancement (57% vs. 7%;
p
< 0.01) on imaging; to receive palliative care (15% vs. 2%) or whole brain radiation (63% vs. 3%); and less likely to receive chemotherapy (22% vs. 95%) (
p
< 0.01). Twenty-four patients, none PLWH, underwent stem cell transplant. Not receiving transplant was an independent factor in mortality and disease progression. Our cohort of patients, compared to the national database, were younger (60 vs. 65 years), 58% were white vs. 75%, and had longer median overall survival 43 vs. 25 months.
Conclusion
Epidemiology, imaging, and treatment options for patients with PCNSL with and without HIV differ, but HIV was not an independent factor of mortality or disease progression. More efforts are needed to improve access to research and treatment options for PLWH with PCNSL.
Invasion of tumor cells into adjacent brain parenchyma is a major cause of treatment failure in glioblastoma. Furthermore, invasive tumors are shown to have a different genomic composition and ...metabolic abnormalities that allow for a more aggressive GBM phenotype and resistance to therapy. We thus seek to identify those genomic abnormalities associated with a highly aggressive and invasive GBM imaging-phenotype.
We retrospectively identified 104 treatment-naïve glioblastoma patients from The Cancer Genome Atlas (TCGA) whom had gene expression profiles and corresponding MR imaging available in The Cancer Imaging Archive (TCIA). The standardized VASARI feature-set criteria were used for the qualitative visual assessments of invasion. Patients were assigned to classes based on the presence (Class A) or absence (Class B) of statistically significant invasion parameters to create an invasive imaging signature; imaging genomic analysis was subsequently performed using GenePattern Comparative Marker Selection module (Broad Institute).
Our results show that patients with a combination of deep white matter tracts and ependymal invasion (Class A) on imaging had a significant decrease in overall survival as compared to patients with absence of such invasive imaging features (Class B) (8.7 versus 18.6 months, p < 0.001). Mitochondrial dysfunction was the top canonical pathway associated with Class A gene expression signature. The MYC oncogene was predicted to be the top activation regulator in Class A.
We demonstrate that MRI biomarker signatures can identify distinct GBM phenotypes associated with highly significant survival differences and specific molecular pathways. This study identifies mitochondrial dysfunction as the top canonical pathway in a very aggressive GBM phenotype. Thus, imaging-genomic analyses may prove invaluable in detecting novel targetable genomic pathways.
The integration of imaging characteristics and genomic data has started a new trend in approach toward management of glioblastoma (GBM). Many ongoing studies are investigating imaging phenotypical ...signatures that could explain more about the behavior of GBM and its outcome. The discovery of biomarkers has played an adjuvant role in treating and predicting the outcome of patients with GBM. Discovering these imaging phenotypical signatures and dysregulated pathways/genes is needed and required to engineer treatment based on specific GBM manifestations. Characterizing these parameters will establish well-defined criteria so researchers can build on the treatment of GBM through personal medicine.
Radiomics is a new area of research in the field of imaging with tremendous potential to unravel the hidden information in digital images. The scope of radiology has grown exponentially over the last ...two decades; since the advent of radiomics, many quantitative imaging features can now be extracted from medical images through high-throughput computing, and these can be converted into mineable data that can help in linking imaging phenotypes with clinical data, genomics, proteomics, and other "omics" information. In cancer, radiomic imaging analysis aims at extracting imaging features embedded in the imaging data, which can act as a guide in the disease or cancer diagnosis, staging and planning interventions for treating patients, monitor patients on therapy, predict treatment response, and determine patient outcomes.
Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false ...positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.
Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. ...MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules.
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