Ehab Y. Hanna

Bio: Ehab Y. Hanna is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Medicine & Head and neck cancer. The author has an hindex of 52, co-authored 340 publications receiving 9248 citations. Previous affiliations of Ehab Y. Hanna include Cleveland Clinic & University of Michigan.

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Abstract: Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.

Sex Discrimination: How Do We Tell the Difference between Male and Female Faces?:

Abstract: People are remarkably accurate (approaching ceiling) at deciding whether faces are male or female, even when cues from hair style, makeup, and facial hair are minimised. Experiments designed to explore the perceptual basis of our ability to categorise the sex of faces are reported. Subjects were considerably less accurate when asked to judge the sex of three-dimensional (3-D) representations of faces obtained by laser-scanning, compared with a condition where photographs were taken with hair concealed and eyes closed. This suggests that cues from features such as eyebrows, and skin texture, play an important role in decision-making. Performance with the laser-scanned heads remained quite high with 3/4-view faces, where the 3-D shape of the face should be easiest to see, suggesting that the 3-D structure of the face is a further source of information contributing to the classification of its sex. Performance at judging the sex from photographs (with hair concealed) was disrupted if the photographs were inverted, which implies that the superficial cues contributing to the decision are not processed in a purely 'local' way. Performance was also disrupted if the faces were shown in photographic negatives, which is consistent with the use of 3-D information, since negation probably operates by disrupting the computation of shape from shading. In 3-D, the 'average' male face differs from the 'average' female face by having a more protuberant nose/brow and more prominent chin/jaw. The effects of manipulating the shapes of the noses and chins of the laser-scanned heads were assessed and significant effects of such manipulations on the apparent masculinity or femininity of the heads were revealed. It appears that our ability to make this most basic of facial categorisations may be multiply determined by a combination of 2-D, 3-D, and textural cues and their interrelationships.

Endoscopic resection of sinonasal cancers with and without craniotomy: oncologic results

Abstract: Objective To evaluate the oncologic outcomes of patients with sinonasal cancer treated with endoscopic resection. Design Retrospective review. Setting Tertiary care academic cancer center. Patients All patients with biopsy-proved malignant neoplasm of the sinonasal region who were treated with endoscopic resection between 1992 and 2007 were included in the study, and their charts were reviewed for demographics, histopathologic findings, treatment details, and outcome. Main Outcome Measures Oncologic outcomes, including disease recurrence and survival. Results Of a total of 120 patients, 93 (77.5%) underwent an exclusively endoscopic approach (EEA) and 27 (22.5%) underwent a cranioendoscopic approach (CEA) in which the surgical resection involved the addition of a frontal or subfrontal craniotomy to the transnasal endoscopic approach. Of the 120 patients, 41% presented with previously untreated disease, 46% presented with persistent disease that had been partially resected, and 13% presented with recurrent disease after prior treatment. The most common site of tumor origin was the nasal cavity (52%), followed by the ethmoid sinuses (28%). Approximately 10% of the tumors had an intracranial epicenter, most commonly around the olfactory groove. Tumors extended to or invaded the skull base in 20% and 11% of the patients, respectively. An intracranial epicenter (P .99). The cerebrospinal fluid leak resolved spontaneously in 3 patients, and the fourth patient underwent successful endoscopic repair. With a mean follow-up of 37 months, 18 patients (15%) experienced local recurrence, with a local disease control of 85%. Regional and distant failure occurred as the first sign of disease recurrence in 6% and 5% of patients, respectively. The 5- and 10-year disease-specific survival rates were 87% and 80%, respectively. Disease recurrence and survival did not differ significantly between the EEA group and the CEA group. Conclusions To the best of our knowledge, this is the largest US series to date of patients with malignant tumors of the sinonasal tract treated with endoscopic resection. Our results suggest that, in well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal cancer results in acceptable oncologic outcomes.

Endoscopic Resection of Sinonasal Cancers With and Without Craniotomy

Abstract: differentbetweentheEEAgroupandtheCEAgroup.Approximatelytwo-thirds(63%)ofthepatientstreatedwith EEAhadalower(T1-2)diseasestage,while95%ofpatients treatedwithCEAhadahigher(T3-4)diseasestage(P.001). The most common tumor types were esthesioneuroblastoma(17%),sarcoma(15%),adenocarcinoma(14%),melanoma(14%),andsquamouscellcarcinoma(13%).Other, less common tumors included adenoid cystic carcinoma (7%),neuroendocrinecarcinoma(4%),andsinonasalundifferentiatedcarcinoma(2%).Microscopicallypositivemarginswerereportedin15%ofpatients.Ofthe120patients, 50% were treated with surgery alone, 37% received postoperative radiation therapy, and 13% were treated with surgery, radiation therapy, and chemotherapy. The overallsurgicalcomplicationratewas11%forthewholegroup. Postoperativecerebrospinalfluidleakageoccurredin4of 120patients(3%)andwasnotsignificantlydifferentbetween theCEAgroup(1of27patients)andtheEEAgroup(3of 93patients)(P.99).Thecerebrospinalfluidleakresolved spontaneouslyin3patients,andthefourthpatientunderwentsuccessfulendoscopicrepair.Withameanfollow-up of 37 months, 18 patients (15%) experienced local recurrence,withalocaldiseasecontrolof85%.Regionalanddistantfailureoccurredasthefirstsignofdiseaserecurrence in6%and5%ofpatients,respectively.The5-and10-year disease-specific survival rates were 87% and 80%, respectively. Disease recurrence and survival did not differ significantly between the EEA group and the CEA group. Conclusions:Tothebestofourknowledge,thisisthelargest US series to date of patients with malignant tumors of thesinonasaltracttreatedwithendoscopicresection.Our resultssuggestthat,inwell-selectedpatientsandwithappropriateuseofadjuvanttherapy,endoscopicresectionof sinonasalcancerresultsinacceptableoncologicoutcomes. ArchOtolaryngolHeadNeckSurg.2009;135(12):1219-1224

Assessing quality of life in patients with head and neck cancer: cross-validation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Head and Neck module (QLQ-H&N35).

Abstract: Objective To evaluate the reliability and validity of a new, disease-specific quality-of-life measure for patients with head and neck cancer: the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire—QLQ-H&N35. Design Cross-sectional study using questionnaire data and medical chart review. Setting Academic tertiary care otolaryngology clinic. Participants One hundred twenty ambulatory patients, including 30 patients with advanced head and neck cancer in each of the following stages of treatment: (1) prior to treatment, (2) during active treatment, (3) within 6 months of completing treatment, and (4) more than 6 months after completing treatment. In addition, (5) a comparison group of 40 patients without malignant disease was included (total sample, N=160). Main Outcome Measures Scores on EORTC Quality of Life Core Questionnaire (QLQ-C30) and head and neck module (QLQ-H&N35), Profile of Mood States, and Impact of Events Scale. Results The QLQ-H&N35 demonstrated acceptable reliability (internal consistency). It successfully discriminated between cancer patients and the comparison group, and among subgroups of cancer patients at different phases of treatment (construct validity). The instrument was sensitive to the effects of radiation treatment and to site of disease. Its low-to-moderate correlations with the EORTC core questionnaire indicated that the QLQ-H&N35 provided unique information (discriminant validity). Scores were significantly associated with a number of demographic variables. Conclusion Results support the use of this disease-specific measure to assess quality of life among patients with advanced head and neck cancer.

The biogenesis, biology and characterization of circular RNAs.

Abstract: Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

Nonviral Vectors for Gene Delivery

Abstract: The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less