Profiling of circulating glial cells for accurate blood-based diagnosis of glial malignancies.

Here, we describe a blood test for the detection of glial malignancies (GLI-M) based on the identification of circulating glial cells (CGCs). The test is highly specific for GLI-M and can detect multiple grades (II-IV) and subtypes including gliomas, astrocytomas, oligodendrogliomas, oligoastrocytomas and glioblastomas, irrespective of gender and age. Analytical validation of the test was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Real-world performance characteristics of the test were evaluated in four clinical (observational) studies. The test has high analytical sensitivity (95%), specificity (100%) and precision (coefficient of variation [CV] = 13.7% for repeatability and CV = 23.5% for within laboratory precision, both at the detection threshold) and is not prone to interference from common drugs and serum factors. The ability of the test to detect and differentiate GLI-M from non-malignant brain tumours (NBT), brain metastases from primary epithelial malignancies (EPI-M) and healthy individual donors (HD) was evaluated in four clinical cohorts. Across these clinical studies, the test showed 99.35% sensitivity (95% confidence interval [CI]: 96.44%-99.98%) and 100% specificity (95% CI: 99.37%-100%). The performance characteristics of this test support its clinical utility for diagnostic triaging of individuals presenting with intracranial space-occupying lesions (ICSOL).

Dosimetric comparison of Linac-based (BrainLAB®) and robotic radiosurgery (CyberKnife ®) stereotactic system plans for acoustic schwannoma.

A dosimetric comparison of linear accelerator (LA)-based (BrainLAB) and robotic radiosurgery (RS) (CyberKnife) systems for acoustic schwannoma (Acoustic neuroma, AN) was carried out. Seven patients with radiologically confirmed unilateral AN were planned with both an LA-based (BrainLAB) and robotic RS (CyberKnife) system using the same computed tomography (CT) dataset and contours. Gross tumour volume (GTV) was contoured on post-contrast magnetic resonance imaging (MRI) scan [planning target volume (PTV) margin 2 mm]. Planning and calculation were done with appropriate calculation algorithms. The prescribed isodose in both systems was considered adequate to cover at least 95% of the contoured target. Plan evaluations were done by examining the target coverage by the prescribed isodose line, and high- and low-dose volumes. Isodose plans and dose volume histograms generated by the two systems were compared. There was no statistically significant difference between the contoured volumes between the systems. Tumour volumes ranged from 380 to 3,100 mm(3). Dose prescription was 13-15 Gy in single fraction (median prescribed isodose 85%). There were no significant differences in conformity index (CI) (0.53 versus 0.58; P = 0.225), maximum brainstem dose (4.9 versus 4.7 Gy; P = 0.935), 2.5-Gy volume (39.9 versus 52.3 cc; P = 0.238) or 5-Gy volume (11.8 versus 16.8 cc; P = 0.129) between BrainLAB and CyberKnife system plans. There were statistically significant differences in organs at risk (OAR) doses, such as mean cochlear dose (6.9 versus 5.4 Gy; P = 0.001), mean mesial temporal dose (2.6 versus 1.7 Gy; P = 0.07) and high-dose (10 Gy) volume (3.2 versus 5.2 cc; P = 0.017). AN patients planned with the CyberKnife system had superior OAR (cochlea and mesial temporal lobe) sparing compared with those planned with the Linac-based system. Further evaluation of these findings in prospective studies with clinical correlation will provide actual clinical benefit from the dosimetric superiority of CyberKnife.

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study.

Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 - 3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α - strong and TERT - strong" and the "HIF-1α - weak and TERT - weak" patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.

Long-term outcome of high-dose-rate brachytherapy and perioperative brachytherapy in early mobile tongue cancer.

PURPOSE: To evaluate long-term outcome of high-dose-rate brachytherapy and perioperative brachytherapy in early mobile tongue cancer. MATERIAL AND METHODS: Seventy-three patients with clinically staged T1/T2 N0 M0 of mobile tongue cancer were studied retrospectively. Between January 2000 and September 2010, 47 patients underwent high-dose-rate brachytherapy (HDR-BT) alone and 26 patients underwent perioperative brachytherapy (PB). Endpoints were overall survival, disease-free survival, loco-regional control, and late side effects. RESULTS: Median age was 52 years and median follow-up was 74 months (range, 60-180). There were no local recurrences in the PB group. Overall survival at 6 years was 74.7% vs. 92.3% in HBR BT and PB group, respectively (p = 0.032). Disease-free survival at 6 years was 55.3% vs. 92.3% respectively in HDR-BT and PB (p = 0.002). Disease-free survival at 6 years in tumor histologic grade 1/2 patients was 76.3 months versus 40% in grade 3 patients. Nodal recurrence-free rate at 6 years was 67.5% with HDR-BT only, and 96.2% with PB (p = 0.007). In HDR BT only group, nodal recurrence-free rate at 6 years in T1 patients was 89.8% versus 29.4% in T2 patients. 16% and 7% patients developed soft tissue necrosis and osteoradionecrosis, respectively. Multivariate Cox proportional hazards analysis revealed significant correlation of local recurrence with tumor grade (p = 0.029), nodal recurrence with T-stage (p = 0.007), and disease-free survival with age (p = 0.003) and T stage (p = 0.026). CONCLUSIONS: HDR-BT alone gives acceptable loco-regional control in T1 tumors. T2 stage tumors should not be treated by brachytherapy alone in view of high failure rates in nodal regions and should undergo either neck dissection or nodal irradiation. Perioperative brachytherapy is investigational and can be considered in patients who are at high-risk for local recurrence in patients undergoing surgery alone.

Body Mass Index as a Prognostic Marker in Glioblastoma Multiforme: A Clinical Outcome.

PURPOSE: Correlation of body mass index (BMI) with clinical outcome in patients with glioblastoma is not well documented. Hence, we studied the association between survival and pretreatment BMI in glioblastoma patients. METHODS AND MATERIALS: In this retrospective study, only patients with histopathology-confirmed glioblastoma were included. Their BMIs were calculated from height and weight measurements and recorded in medical records at their first examination. Treatment plans for all patients consisted of concurrent radiation therapy and temozolomide, followed by maintenance therapy with temozolomide. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards models were used to estimate the mortality risk associated with BMI as a continuous and categorical variable. A BMI of 18.5 to 24.9 kg/m2 was classified as normal, 25.0 to 29.9 kg/m2 as overweight, and ≥30.0 kg/m2 as obese. RESULTS: Data from 392 patients treated from January 2008 through June 2016 were analyzed. At a median follow-up of 48.6 months, the median OS was 13.5 months in normal subjects, 15.4 months in overweight subjects, and 15.1 months in obese subjects. A total of 81% of the patients died. The hazard ratios for overweight and obese patients were 0.70 (95% confidence interval, 0.54-0.92; P = .009) and 0.66 (95% confidence interval, 0.45-0.98; P = .04), respectively, when adjusted for age, Karnofsky performance score, and extent of resection. Sex, diabetes, and hypertension had no significant interactions. CONCLUSIONS: Patients with elevated BMIs had significantly better OS in our series of patients. The mechanism of this interaction needs to be explored further to understand this association.

Pre-radiotherapy Haemoglobin Level is A Prognosticator in Locally Advanced Head and Neck Cancers Treated with Concurrent Chemoradiation.

INTRODUCTION: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. AIM OF THE STUDY: Primary end point: To analyse the Pre-Radiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. MATERIALS AND METHODS: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. INCLUSION CRITERIA: HNSCC patients of Stage III/IVA aged ≥18 years and ≤ 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. EXCLUSION CRITERIA: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. RESULTS: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of <10.7 g/dl in 38 (42%) patients and ≥10.7 in 53 (58%) patients; Pre-RT Hb level was <12 g/dl in 67 (74%) patients and ≥12 in 24 (26%) patients. Tumour sites were - Nasopharynx 7 (8 %), Oral Cavity 18 (20 %), Oropharynx 32 (35 %), Hypopharynx 23 (25 %) and Larynx 11 (12 %). Twenty five (27%) had Grade 2 mucositis and 66 (73%) had Grade 3 mucositis. Fifty eight (64%) patients completed treatment with NO breaks and 33 (36%) with treatment breaks for ≥5 days. Pre-radiotherapy haemoglobin ≥ 10.7 g/dl (p < 0.001), ECOG performance status (p = 0.0002), Treatment interruptions for > 5 days (p = <0.0001), Mucositis reaction (p = <0.0001) showed statistical significance with outcome of response. CONCLUSION: The study found that performance status, pre-RT haemoglobin level, radiotherapy interruptions > 5 days and non-development of grade III mucositis was found to be significantly associated with good loco-regional control. Haemoglobin level ≥10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power.

A Report on the Clinical Outcome after High-Dose Rate (HDR) Brachytherapy as Monotherapy in Early Prostate Cancer.

BACKGROUND: To report the clinical outcome after a single implant, high dose rate (HDR) brachytherapy in early prostate cancer. MATERIALS AND METHODS: All clinically localized prostate cancer patients who underwent high-dose rate (HDR) brachytherapy as monotherapy (no external beam radiotherapy) from February 2006 to September 2011 were analyzed prospectively. Acute and chronic toxicity were assessed as per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. Biochemical recurrence was analyzed using the Kaplan Meir method. A log-rank analysis was done to compare the factors affecting the outcome. RESULTS:  Forty-four patients with organ-confined prostate cancer opted for HDR brachytherapy between February 2006 to September 2011 with a median follow-up of 68 months  The five-year biochemical recurrence-free survival (bRFS) rate was 91%. Late Grade 2 genitourinary (GU) toxicity was observed in 9% of patients. The predictors of late Grade 2 GU toxicity were urethra V125 ≥ 0.2 cc (urethral volume receiving ≥ 125% of the prescribed dose) and PTV 150 ≥ 35% ( planning target volume receiving ≥ 150% of the prescribed dose) with p-value = 0.001 and 0.002, respectively. Erectile function was preserved in 72% of the patients who had Grade 0-1 erectile dysfunction before brachytherapy. CONCLUSION: HDR brachytherapy in early prostate cancer results in high local control rates with minimal side-effects.

Stereotactic radiosurgery results in three cases of intramedullary spinal cord arteriovenous malformations.

BACKGROUND CONTEXT: Intramedullary spinal cord arteriovenous malformations (AVMs) are rare and have an unfavorable prognosis. We report our experience of treating three symptomatic patients with stereotactic radiosurgery (SRS). The standard treatment for these lesions are embolization or microsurgical resection. There are only a few reports of efficacy of radiosurgery in these cases. PURPOSE: To study the efficacy of radiosurgery in intramedullary spinal cord AVM patients, who failed or refused conventional treatment. STUDY SETTING: This study reports the results of SRS in 3 cases of intramedullary spinal cord AVMs. PATIENT SAMPLE: Three symptomatic patients diagnosed with intramedullary spinal cord AVMs. Two patients underwent embolization previously and one was newly diagnosed. OUTCOME MEASURES: The AVM obliteration was assessed by yearly high-resolution magnetic resonance imaging (MRI). Clinical examination was carried out every 6 months. METHODS: Three symptomatic patients with intramedullary spinal cord AVMs were treated with SRS using the cyberknife system from January 2010 to May 2011. All the three patients presented with acute neurologic symptoms. Two patients were treated previously with embolization. As per protocol, patients underwent a plain computed tomography (CT), CT angiography, high-resolution MRI, and conventional spinal angiography for radiotherapy planning. The mean target volume was 4.05 cc. The prescribed dose was 21 Gy in three fractions on consecutive days. No special immobilization was done during treatment. Continuous image guidance of the treated area was done using the specialized spine tracking software. Follow-up was done by yearly clinical examination and high-resolution spine MRI after SRS. RESULTS: Mean follow-up was 36 months. Follow-up MRI revealed absence of flow voids, suggesting complete obliteration of the AVM in two patients, with significant improvement in neurologic and functional symptoms. The third patient did not show any clinical improvement or deterioration. There was no incidence of hemorrhage after SRS in any patient and the treatment was well tolerated without any significant complications. CONCLUSIONS: Stereotactic radiosurgery for intramedullary spinal AVMs appears to be well tolerated and effective in selected cases.