Deleting Suppressor of Cytokine Signaling-3 in chondrocytes reduces bone growth by disrupting mitogen-activated protein kinase signaling.

OBJECTIVE: To investigate the impact of deleting Suppressor of Cytokine Signaling (SOCS)-3 (SOCS3) in chondrocytes during murine skeletal development. METHOD: Mice with a conditional Socs3 allele (Socs3fl/fl) were crossed with a transgenic mouse expressing Cre recombinase under the control of the type II collagen promoter (Col2a1) to generate Socs3Δ/Δcol2 mice. Skeletal growth was analyzed over the lifespan of Socs3Δ/Δcol2 mice and controls by detailed histomorphology. Bone size and cortical bone development was evaluated by micro-computed tomography (micro-CT). Growth plate (GP) zone width, chondrocyte proliferation and apoptosis were assessed by immunofluorescence staining for Ki67 and TUNEL. Fibroblast growth factor receptor-3 (FGFR3) signaling in the GP was assessed by immunohistochemistry, while the effect of SOCS3 overexpression on FGFR3-driven pMAPK signaling in HEK293T cells was evaluated by Western blot. RESULTS: Socs3Δ/Δcol2 mice of both sexes were consistently smaller compared to littermate controls throughout life. This phenotype was due to reduced long bone size, poor cortical bone development, reduced Ki67+ proliferative chondrocytes and decreased proliferative zone (PZ) width in the GP. Expression of pMAPK, but not pSTAT3, was increased in the GPs of Socs3Δ/Δcol2 mice relative to littermate controls. Overexpression of FGFR3 in HEK293T cells increased Fibroblast Growth Factor 18 (FGF18)-dependent Mitogen-activated protein kinase (MAPK) phosphorylation, while concomitant expression of SOCS3 reduced FGFR3 expression and abrogated MAPK signaling. CONCLUSION: Our results suggest a potential role for SOCS3 in GP chondrocyte proliferation by regulating FGFR3-dependent MAPK signaling in response to FGF18.

A nomogram for predicting the risk of neck node metastasis in pathologically node-negative oral cavity carcinoma.

OBJECTIVE: To generate a nomogram for predicting the risk of neck node metastasis in pathologically node-negative patients using a combination of variables comprising of protein expression, ultrastructural alterations and clinicopathological parameters. MATERIALS AND METHODS: Surgically removed oral tumours (n = 103) were analysed for the expression of desmosomal and hemidesmosomal assembly proteins by immunohistochemistry and ultrastructural alterations by transmission electron microscopy (TEM). Protein expression, ultrastructural alterations and clinicopathological variables were used to construct nomogram from the training set in 75 patients. Clinical utility of the nomogram was validated in a discrete set of 28 patients. RESULTS: Univariate and multivariate analyses were performed on the training set, and obtained significant variables comprising of integrin ß4 expression (p = .027), number of hemidesmosomes (p = .027)/desmosomes (p = .046), tumour differentiation grade (p = .033) and tumour thickness (p = .024) were used for construction of the nomogram. The area under the curve was calculated for both training 0.821 (95% CI 0.725-0.918) and validation sets 0.880 (95% CI 0.743-1.000). The nomogram demonstrated a predictive accuracy of 73.3% and 78.6% with the sensitivity of 81.4% and 83.3% in the training and validation sets, respectively. CONCLUSIONS: The nomogram constructed on postsurgical tumour samples will be a value addition to histopathology for the detection of neck node metastasis in pathologically node-negative patients.

Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas.

OBJECTIVE: To investigate the clinical significance of vimentin expression at early and late events of tobacco/areca nut-associated oral tumorigenesis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was carried out on paraffin-embedded tissues of oral mucosa normal (n = 10), inflammatory lesions (n = 19), leukoplakia (n = 52), submucous fibrosis (n = 71) and tumours/cut margins (n = 227 each), using anti-vimentin antibody, and the expression profile was correlated with patients' clinical parameters. Immunofluorescence, Western blot and RT-PCR analysis were also carried out wherever adequate and fresh tissues were available. RESULTS: Aberrant vimentin expression was seen in hyperplastic, dysplastic and fibrotic tissues, which showed statistically significant correlation with the histopathological grade of dysplasia (P = 0.001) and fibrosis (P = 0.009). Vimentin expression also showed statistically significant correlation with tumour size (P = 0.048), clinical stage (P = 0.013), regional lymph node metastases (P = 0.001), local recurrence (P = 0.001) and survival (P = 0.021) of patients with oral squamous cell carcinoma (OSCC). Its expression in invasive fronts statistically correlated with development of nodal metastasis and local recurrence. CONCLUSIONS: Our results suggest possible role of vimentin in early events of tobacco/areca nut-associated oral tumorigenesis, which may prove useful to predict the malignant potential of high-risk oral lesions. Further, association between vimentin expression in invasive fronts and aggressive phenotype of tumours may help clinicians to choose the appropriate treatment modality for OSCC management.

Impact of oral health education on oral hygiene knowledge, practices, plaque control and gingival health of 13- to 15-year-old school children in Bangalore city.

OBJECTIVES: To assess effectiveness of an oral health education (OHE) programme on oral hygiene knowledge, practices, plaque control and gingival health of 13- to 15-year-old school children in Bangalore city. METHODS: Three schools were randomly selected and assigned to experimental I, experimental II and control groups. At baseline, a 20-item questionnaire was used to assess the oral hygiene knowledge and practices. Clinical examinations (Turesky-Gilmore-Glickman modification of Quigley Hein plaque index; Loe-Silness gingival index) were performed by 2 examiners. OHE was provided by the investigator for experimental groups I (lecture using a PowerPoint presentation) and II (lecture using a PowerPoint presentation with toothbrushing demonstration). Control group did not receive any intervention. Reinforcement was provided for experimental groups at 3 and 6 months. At end of 9 months, questionnaire was administered and clinical examinations were performed. Data were analysed using chi-square, anova and post hoc Tukey's tests. RESULTS: Nine months post-intervention, there was significant improvement in oral hygiene knowledge and practices in experimental groups. There were significant reductions in mean plaque index and gingival index scores in the experimental groups. The control group did not show any significant improvement. CONCLUSION: Active involvement of school children with reinforcement of OHE can improve oral hygiene knowledge, practices and gingival health and decrease plaque levels.

Imaging of Neck Nodes in Head and Neck Cancers - a Comprehensive Update.

Cervical lymph node metastases from head and neck squamous cell cancers significantly reduce disease-free survival and worsen overall prognosis and, hence, deserve more aggressive management and follow-up. As per the eighth edition of the American Joint Committee on Cancer staging manual, extranodal extension, especially in human papillomavirus-negative cancers, has been incorporated in staging as it is important in deciding management and significantly impacts the outcome of head and neck squamous cell cancer. Lymph node imaging with various radiological modalities, including ultrasound, computed tomography and magnetic resonance imaging, has been widely used, not only to demonstrate nodal involvement but also for guided histopathological evaluation and therapeutic intervention. Computed tomography and magnetic resonance imaging, together with positron emission tomography, are used widely for the follow-up of treated patients. Finally, there is an emerging role for artificial intelligence in neck node imaging that has shown promising results, increasing the accuracy of detection of nodal involvement, especially normal-appearing nodes. The aim of this review is to provide a comprehensive overview of the diagnosis and management of involved neck nodes with a focus on sentinel node anatomy, pathogenesis, imaging correlates (including radiogenomics and artificial intelligence) and the role of image-guided interventions.

Is routine neck dissection warranted at salvage laryngectomy?

BACKGROUND: There is controversy regarding management of the neck at salvage laryngectomy. The aim of this study was to perform an analysis to determine the incidence of occult node positivity in this group and analyse factors affecting it. METHOD: A retrospective analysis of 171 patients who underwent salvage total laryngectomy between 2000 and 2015 for recurrent or residual disease following definitive non-surgical treatment and were clinico-radiologically node negative at the time salvage laryngectomy was carried out. RESULTS: A total of 171 patients with laryngeal or hypopharyngeal cancers underwent concurrent neck dissection at laryngectomy. There were 162 patients (94.7 per cent) who underwent bilateral neck dissection, and 9 patients (5.3 per cent) who underwent ipsilateral neck dissection. The occult lateral nodal metastasis rate was 10.5 per cent. Of various factors, initial node positive disease was the only factor predicting occult metastasis on univariable and multivariable analysis (p = 0.001). CONCLUSION: Risk of occult metastasis is high in patients who have node positive disease before starting radiotherapy. This group should be offered elective neck dissection.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Impaired inhibitory control is associated with higher-order repetitive behaviors in autism spectrum disorders.

BACKGROUND: Impairments in executive cognitive control, including a reduced ability to inhibit prepotent responses, have been reported in autism spectrum disorders (ASD). These deficits may underlie patterns of repetitive behaviors associated with the disorder. METHOD: Eighteen individuals with ASD and 15 age- and IQ-matched healthy individuals performed an antisaccade task and a visually guided saccade control task, each with gap and overlap conditions. Measures of repetitive behaviors were obtained using the Autism Diagnostic Inventory-Revised (ADI-R) and examined in relation to neurocognitive task performance. RESULTS: Individuals with an ASD showed increased rates of prosaccade errors (failures to inhibit prepotent responses) on the antisaccade task regardless of task condition (gap/overlap). Prosaccade error rates were associated with the level of higher-order (e.g. compulsions, preoccupations) but not sensorimotor repetitive behaviors in ASD. CONCLUSIONS: Neurocognitive disturbances in voluntary behavioral control suggest that alterations in frontostriatal systems contribute to higher-order repetitive behaviors in ASD.

PET-CT in recurrent head neck cancers: a study to evaluate impact on patient management.

BACKGROUND AND OBJECTIVES: PET-CT has shown promise in the management of head neck cancers. However, there have been only few studies evaluating its impact on management of patients with recurrent cancers in the presence of available clinicoradiologic methods of assessment. We conducted this study to assess the same in patients with suspected recurrent head and neck cancer. METHODS: Case histories were presented to two oncologists, who were blinded to PET-CT reports. Treatment plans were made by these oncologists based on clinical findings and other conventional imaging. These plans were then compared to the actual treatment received by patients after PET-CT. Any change was recorded as "change in management." RESULTS: Forty-nine patients with suspected recurrent head and neck cancer were evaluated in the study. Overall, there was a 38.7% change in management because of the addition of PET-CT to conventional methods of assessment. Eight patients (16.3%) had a major change in therapy while in 11 patients (22.4%), diagnostic procedures like endoscopies, biopsies and examination under anesthesia were avoided. CONCLUSION: In our study, PET-CT had a significant impact on the management of patients with suspected recurrent head neck cancer.

An Audit for Radiotherapy Planning and Treatment Errors From a Low-Middle-Income Country Centre.

AIMS: To report the findings of an audit for radiotherapy errors from a low-middle-income country (LMICs) centre. This would serve as baseline data for radiotherapy error rates, their severity and causes, in such centres where modern error reporting and learning processes still do not exist. MATERIALS AND METHODS: A planned cross-sectional weekly audit of electronic radiotherapy charts at the radiotherapy planning and delivery step for all patients treated with curative intent was conducted. Detailed analysis was carried out to determine the step of origin of error, time and contributing factors. They were graded as per indigenous institutional (TMC) radiotherapy error grading (TREG) system and the contributing factors identified were prioritised using the product of frequency, severity and ease of detection. RESULTS: In total, 1005 consecutive radically treated patients' charts were audited, 67 radiotherapy errors affecting 60 patients, including 42 incidents and 25 near-misses were identified. Transcriptional errors (29%) were the most common type. Most errors occurred at the time of treatment planning (59.7%), with "plan information transfer to the radiation oncology information system" being the most frequently affected sub-step of the radiotherapy process (47.8%). More errors were noted at cobalt units (52/67; 77.6%) than at linear accelerators. Trend analysis showed an increased number of radiotherapy incidents on Fridays and near-misses on Mondays. Trend for increased radiotherapy errors noted in the evening over other shifts. On severity grading, most of the errors (54/60; 90%) were clinically insignificant (grade I/II). Inadequacies and non-adherence towards standard operating procedures, poor documentation and lack of continuing education were the three most prominent causes. CONCLUSION: Preliminary data suggest a vulnerability of LMIC set-up to radiotherapy errors and emphasises the need for the development of longitudinal prospective processes, such as voluntary reporting and a continued education system, to ensure robust and comprehensive safe practises on par with centres in developed countries.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Invasion of the mandible in gingivobuccal complex cancers: Histopathological analysis of routes of tumour entry and correlation with preoperative assessment.

OBJECTIVES: To determine the most accurate imaging modality predicting mandibular invasion in gingivobuccal (GB) complex cancers. To determine patterns of invasion and routes of tumour entry into the mandible by detailed histopathologic analysis. MATERIAL AND METHODS: Prospective observational study of GB Complex cancers juxtaposed with the mandible clinically necessitating some form of mandibular resection. Orthopantomogram (OPG), Multi Detector Computed Tomography (MDCT), DENTA scan and Single Photon Emission Computed Tomography scan (SPECT) were performed after which the patient was subjected to surgery. Histopathological assessment was systematically performed with serial cuts of the mandibular segment. RESULTS: Of 70 patients, MDCT was the most accurate with area under curve (AUC) of 0.833. OPG, DENTA and SPECT had AUC of 0.714, 0.786 and 0.738 respectively. Mean calculated difference of involved height was -0.025 cm by MDCT (p value 0.87), -0.2 cm by OPG (p value 0.09) and 0.12 by DENTA scan (p value 0.41). Mean difference of involved length was -0.51 cm (p value 0.08) and -1.02 cm (p value 0.04) for MDCT and OPG respectively. 50% of tumour invasion was through the occlusal route while large tumours demonstrated multiple routes of entry. CONCLUSION: -Gingivobuccal complex cancers are homogenous with respect to mandibular invasion, preferred route of tumour entry being the occlusal surface. -Multidetector CT scan is fairly accurate in detecting mandibular involvement and predicting extent of involvement. -Oncological safety can be achieved by positioning the bone cuts corresponding to the adjacent soft tissue margins in segmental mandibulectomy.

Validation of the University of Washington quality of life questionnaires for head and neck cancer patients in India.

UNLABELLED: Quality of life (QOL) is a multidimensional construct capturing the subjective wellbeing of patients in physical, emotional, functional and social domains. Available work on post treatment QOL have only been made in western literature and less in Indian literature. AIMS: To translate the UW-QOL into both Hindi and Marathi and psychometrically validate the translation in HandN cancer patients in Indian population. SETTINGS AND DESIGN: A prospective study was done at the Tata Memorial Hospital for patients who were treated for H and N cancers. MATERIALS AND METHODS: 147 patients were enrolled from January to April 2005. The study was carried out in two phases. Patients were given translated versions of the UW-QOL and EORTC QOL questionnaires pre-operatively, 15 days post-operatively and then three months post-operatively. RESULTS: Both the Hindi and Marathi translations had strong internal consistency (Cronbach's alpha=0.7971 and 0.7839). UW-QOL composite scores correlated well with the global questions on overall QOL in both the Hindi (r=0.69) and Marathi (r=0.66) translations and also with T-stage. QOL scores were worse three months post-operatively than pre-operatively and for patients undergoing surgery that violated the mucosa. A strong correlations was observed (r>0.50) between all similar domains on the UW-QOL and EORTC HandN35 except the saliva item on the Marathi translation, where r< 0.50, but P-values were significant. CONCLUSIONS: The Marathi and Hindi versions of the UW-QOL appear to be valid and reliable instruments for assessing the QOL in Indian population and will be a vital tool for achieving greater insight into the short- and the long term QOL.

In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy.

CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

Depth of invasion is the most significant histological predictor of subclinical cervical lymph node metastasis in early squamous carcinomas of the oral cavity.

AIMS: Cervical node metastasis is the single most important prognostic factor in head and neck squamous carcinomas. Taking a homogenous patient population, applying stringent selection criteria, and standard pathological evaluation methods, this retrospective study aims to establish histological predictors of subclinical cervical node metastasis in early (T1-T2/N0) squamous carcinomas of the oral cavity, thereby identifying a subset of patients who are at an increased risk for cervical node metastasis. METHODS: Forty-eight previously untreated patients with clinically T1 or T2, and N0, squamous carcinomas of the oral cavity who were treated with primary excision of the tumour and elective neck node dissection were selected. Various histological factors including T size, gross and microscopic tumour depth and thickness, grade of differentiation, pattern of invasion, inflammatory response, perineural and lymphovascular invasion were studied. The statistical significance of various parameters as predictors of subclinical node metastasis was determined using logistic regression analysis. RESULTS: Of all the parameters studied, microscopic tumour depth and thickness were the only significant factors (P value=0.026 and 0.046, respectively) which correlated with cervical node metastasis, on univariate analysis. Tumour depth emerged as a single most significant predictor on multivariate analysis. Majority of patients with node metastasis had a tumour depth of more than or equal to 5 mm. CONCLUSION: Depth is the most significant predictor of cervical node metastasis in early squamous carcinomas of the oral cavity. Patients with a tumour depth of more than or equal to 5 mm are at an increased risk of harbouring node metastasis, hence should be taken up for elective node dissection.

A technique to identify and preserve the spinal accessory nerve during neck dissection.

INTRODUCTION: Preservation of the spinal accessory nerve during neck dissection should be the rule rather than the exception. Despite the presence of many described techniques to locate the nerve, a tedious dissection is often required; as a consequence, it remains vulnerable to damage. METHOD: We describe a novel method, not previously reported, based on identifying a constant vein which crosses the nerve. This aids in the nerve's early identification. CONCLUSION: Our method enables the surgeon to locate the nerve precisely and to avoid damage to it, thereby maximizing post-operative function.

Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders.

Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD.

Barriers in conducting clinical trials in oncology in the developing world: A cross-sectional survey of oncologists.

BACKGROUND: Several obstacles impede oncologists from performing clinical trials in the developing world. This study aimed to identify these barriers in order of importance and suggest possible remedial measures. MATERIALS AND METHODS: Design - cross-sectional survey. Two part questionnaire capturing experience of oncologists in practice and conducting trials (Part 1) and perceived barriers pertaining to investigator (training, time), patient (strict follow-up protocol), infrastructure (funds) and professional environment (encouragement from seniors) (Part 2) were administered to oncologists in two different settings: (1) Online portal (Survey Monkey) (2) In person during a national conference (Best of American Society of Clinical Oncology). Responses were captured on a Likert scale (1-5). RESULTS: (436/3021) 14.04% responded. A total of 313 (71.8%) had experience in conducting trials, but these were mainly industry-sponsored or small nonpractice changing studies. Lack of patient follow-up was the most significant barrier (inter quartile range [IQR] 4-5) followed by inadequate training, time and funds (IQR 2-5) and lack of encouragement (IQR 2-4) in decreasing order of frequency. Lack of adequate training was a barrier across all specialties (113 [71.97%] radiation oncologists, 71 [60.68%] medical oncologists and 73 [71.56%] surgical oncologists). More than half of the respondents without experience in clinical trials worked in academic institutions (50.48%). They perceived time constraint as a barrier more than their counterparts into private practice (175/242 [72.31%] vs. 119/177 [66.47%] respectively). CONCLUSION: Inability to maintain patient follow-up, lack of protected time and funds, inadequate training were the most significant barriers. Most of these can be addressed.