[Show abstract][Hide abstract] ABSTRACT: To estimate dose-response relationship using dynamic quantitative (99m)Tc-pertechnate scintigraphy in head-neck cancer patients treated with parotid-sparing conformal radiotherapy.
Dynamic quantitative pertechnate salivary scintigraphy was performed pre-treatment and subsequently periodically after definitive radiotherapy. Reduction in salivary function following radiotherapy was quantified by salivary excretion fraction (SEF) ratios. Dose-response curves were modeled using standardized methodology to calculate tolerance dose 50 (TD50) for parotid glands.
Salivary gland function was significantly affected by radiotherapy with maximal decrease in SEF ratios at 3-months, with moderate functional recovery over time. There was significant inverse correlation between SEF ratios and mean parotid doses at 3-months (r = -0.589, p < 0.001); 12-months (r = -0.554, p < 0.001); 24-months (r = -0.371, p = 0.002); and 36-months (r = -0.350, p = 0.005) respectively. Using a post-treatment SEF ratio <45% as the scintigraphic criteria to define severe salivary toxicity, the estimated TD50 value with its 95% confidence interval (95%CI) for the parotid gland was 35.1Gy (23.6-42.6Gy), 41.3Gy (34.6-48.8Gy), 55.9Gy (47.4-70.0Gy) and 64.3Gy (55.8-70.0Gy) at 3, 12, 24, and 36-months respectively.
There is consistent decline in parotid function even after conformal radiotherapy with moderate recovery over time. Dynamic quantitative pertechnate scintigraphy is a simple, reproducible, and minimally invasive test of major salivary gland function.
[Show abstract][Hide abstract] ABSTRACT: Medulloblastoma, the most common primary pediatric malignant brain tumor is a molecularly heterogeneous disease with different developmental origins, distinct phenotypes, diverse biological behaviour, and contrasting clinical outcomes. The current clinico-radiological risk-classification fails to take account of this heterogeneity and existent prognostic variability. It is widely accepted that dysregulation of normal developmental processes constitute a key mechanism of tumorigenesis in at least a subset of medulloblastomas. Several attempts at biological classification have successfully identified distinct subgroups with subgroup-specific gene signatures, demographics, histologic subtypes, and rates of metastases. Several research groups have classified medulloblastoma into molecular subgroups using a variety of different genomic approaches and platforms such as gene expression profiling, microRNA profiling and methylation arrays. Recently, a consensus has emerged that classifies medulloblastoma into four distinct molecular sub-groups named as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4 respectively. However, such integrative approaches have limited applicability in the clinic due to the need of fresh-frozen tissues and elaborate molecular biology tools. In parallel, some groups have proposed and validated traditional antibody-based approaches using immunohistochemistry on archival specimen for rapid and reliable molecular subgrouping to be applied in any basic neuropathology laboratory. Heterogeneity within each of these four consensus subgroups has also been demonstrated that needs to be considered in the design of future clinical trials. There is a compelling need to integrate integrate molecular biomarkers with clinico-pathologic outcome indicators to refine risk-stratification as well as develop novel molecularly targeted agents for optimizing therapeutic index and personalizing therapy.
[Show abstract][Hide abstract] ABSTRACT: To evaluate current focal high precision radiotherapy (RT) techniques to spare hippocampi most optimally, in view of mounting clinical evidence to preserve neurocognition.
Computed tomography/magnetic resonance imaging (CT/MRI) datasets of 10 patients with benign/low-grade brain tumors, treated with focal conformal RT were replanned with helical tomotherapy (Tomo), intensity-modulated radiotherapy (IMRT) with high definition multileaf collimator (HD-MLC), and forward planning stereotactic conformal radiotherapy (SCRT). The primary planning objective was to encompass 99% of planning target volume (PTV) by 95% of prescribed dose (54 Gy/30#). Assessments included target coverage (TC), homogeneity index (HI), and maximum (max) and minimum (min) dose. Hippocampal dose was assessed with mean, maximum, minimum, median dosem and various dose levels.
Mean V 95 for PTV coverage in Tomo, IMRT, and SCRT were 99.7, 99.4, and 98.3%, respectively. PTV coverage was significantly better in Tomo and IMRT compared to SCRT (P = 0.03). Tomotherapy (HI ≤ 0.06) and IMRT (HI ≤ 0.06) plans were more homogenous than SCRT (HI > 0.7) (P = 0.00). Right hippocampus mean dose with Tomo (20Gy) was 18.5% less than SCRT (30 Gy); but for left hippocampus, difference decreased to 3.3% (Tomo-32.2Gy and SCRT-34Gy). At 30% dose level, 9% more volume of right hippocampus was treated in IMRT and 20% in SCRT when compared to Tomo plan. At 80% dose, 6 and 12% more volumes were treated with IMRT and SCRT, respectively, in comparison to Tomo plan. For left hippocampus all three techniques were comparable.
Tomotherapy and Linear accelerator (LINAC)-based IMRT achieved significantly better PTV coverage than forward planned SCRT. Tomo as compared to SCRT and IMRT plans showed trend towards significant sparing of the contralateral hippocampus, in eccentrically located tumors.
Journal of cancer research and therapeutics 04/2015; 11(2):358-63. DOI:10.4103/0973-1482.157310 · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.
Indian Journal of Cancer 12/2014; 51(3):231-235. DOI:10.4103/0019-509X.146734 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The purpose of this study was to determine the incidence of hypothyroidism after chemoradiation in head and neck squamous cell cancer (HNSCC). Methods
One hundred twenty-two patients treated with 3-dimensional conformal radiotherapy (3DCRT; 70 Gy/35#) or intensity-modulated radiation therapy (IMRT; 66 Gy/30#) in 2 identical simultaneous randomized trials were studied. Thyroid function was assessed at baseline and every 3 to 6 monthly thereafter. Development of subclinical (thyroid-stimulating hormone [TSH] >4.67 IU/mL) or biochemical (T4 <4.5 g/dL) hypothyroidism was noted. Multivariate analyses were done to determine the factors associated with hypothyroidism. ResultsAt a median of 41 months, 55.1% of the patients developed hypothyroidism (39.3% subclinical, 15.7% biochemical). The IMRT arm had higher subclinical hypothyroidism (51.1% vs 27.3%; p = .021) peaking around 1 year postradiotherapy in both arms. Younger age, hypopharynx/larynx primary, node positivity, higher dose/fraction (IMRT arm), and D100 were statistically significant factors for developing hypothyroidism. Conclusion
Postradiotherapy hypothyroidism peaks at 1 year. Higher dose per fraction possibly led to greater incidence of hypothyroidism in the IMRT cohort. (c) 2014 Wiley Periodicals, Inc. Head Neck 36: 1573-1580, 2014
Head & Neck 11/2014; 36(11). DOI:10.1002/hed.23482 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Hemangioblastomas (HBs) are rare WHO grade I neoplasms of uncertain histogenesis. Most are sporadic and association with von Hippel-Lindau disease (VHL) is uncommon.
Materials and methods:
Histomorphological and immunohistochemical evaluation of 24 cases of HBs was done.
Age range was 15-68 yrs (median: 30 yrs) with male:Female of 1.2:1 (M-13; F-11). Cerebellum was commonest location (n = 20), one each was seen in brain stem, cervical spinal cord, fourth ventricle and frontal lobe, respectively. VHL association was noted in 5 cases. Four cases were recurrent in nature of which 3 were in association with vHL. Histologically, reticular variant was the predominant subtype (n = 15), 5 were of cellular variant and 4 were mixed. Nuclear pleomorphism, nuclear cytoplasmic inclusions, cytoplasmic vacuolation were noted in the stromal cells in varying proportions. Immunohistochemical evaluation was successful in only 11 cases and of which 8 showed stromal cell positivity for alpha-inhibin. CD56 (NCAM), Nestin and synaptophysin positivity was seen in 6, 7 and 4 cases, respectively. Nestin positivity was noted in stromal cells only and no reactivity with the endothelial cells seen. S-100 protein and NSE positivity was seen in 8 and 10 cases, respectively. Glial fibrillary acidic protein (GFAP) showed two distinct patterns of immunoreactivity - scattered stromal cell positivity (n:5) and pattern of reactive astrogliosis positivity (n:10). CD44 positivity was noted in 5 cases. VEGF and EGFR positivity was seen in 5 cases each. None of the cases showed positivity for epithelial membrane antigen and no stromal cells in any of the cases showed positivity for CD34 and CD31.
HBs can occur in throughout the neuroaxis. Cerebellum is the commonest site of occurrence for HBs and uncommonly can occur in the supratentorial compartment and spinal cord. Its association with vHL is uncommon and no histological or immunohistochemical correlation was identified with the same.
Indian Journal of Pathology and Microbiology 10/2014; 57(4):542-548. DOI:10.4103/0377-4929.142645 · 0.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To study the impact of multiparametric MRI and (18)F-FDG-PET on the outcome of children with diffuse intrinsic pontine gliomas (DIPG).
Materials and methods:
Imaging data from a phase-II prospective therapeutic study in children with newly diagnosed DIPG were considered for evaluation. They included baseline MRI with contrast enhancement before treatment. Functional imaging included MR spectroscopy, MR perfusion and FDG-PET studies. All patients (n = 20) had baseline MRI and 11 patients had FDG-PET. Response was assessed by MRI and PET 4 weeks after therapy. Baseline imaging findings were correlated with survival. Presence or absence of adverse parameters on MRI (heterogeneous contrast enhancement, hyperperfusion or increased choline:NAA ratio) was used to develop a cumulative radiological prognostic index (RPI). Sensitivity and specificity of each imaging modality in tumour grading was estimated.
The cumulative RPI was able to classify the patients into different grades and was predictive of overall survival (p = 0.02). MR perfusion also predicted survival (p = 0.039). Sensitivity and specificity of MRI and FDG-PET to detect low-grade gliomas were low to moderate (33-66%), but moderate to high in detecting high-grade gliomas (50-100%). Baseline FDG uptake on PET scan did not correlate with survival (p = 0.7).
Cumulative RPI was able to classify tumours into different grades and predicted clinical outcome. At baseline, MR hyperperfusion indicated a shorter survival for DIPG patients. Sensitivity and specificity of imaging modalities to detect low-grade gliomas were poor.
[Show abstract][Hide abstract] ABSTRACT: SUMMARY Glioblastomas are organized hierarchically with a small number of glioblastoma stem cells that have unique self-renewal capacity and multilineage potency. The subventricular zone (SVZ) constitutes the largest neural stem cell niche in the adult human brain; it may also act as a reservoir of glioblastoma stem cells that can initiate, promote or repopulate a tumor. Incidental irradiation of SVZ has been shown to potentially influence outcomes suggesting that aggressively targeting the stem cell niche may offer a ray of hope in glioblastoma. The following review provides a summary of the experimental evidence supporting the origin and location of the putative glioblastoma stem cell in the SVZ, and offers a critical appraisal of the growing body of clinical evidence correlating SVZ dosimetry with outcomes in glioblastoma.