[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: Aims:
Treatment intensification either by using concurrent chemoradiotherapy (CCRT) or altered fractionation radiotherapy (AFRT) improves outcomes of locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The superiority of one approach over the other, however, remains to be firmly established. The aim of the present study was to compare outcomes of CCRT versus AFRT in the definitive non-surgical management of locoregionally advanced HNSCC for evidence-based decision making.
Materials and methods:
An electronic search of Medline via PubMed was conducted with no language, year, or publication status restrictions. The Cochrane Central Register of Controlled Trials (CENTRAL) and Database of Abstracts of Reviews of Effectiveness (DARE) were also searched electronically. Only randomised controlled trials assigning HNSCC patients randomly to conventionally fractionated CCRT or AFRT alone were included. Data were extracted independently by two reviewers and pooled using the Cochrane methodology for meta-analysis and expressed as a hazard ratio with 95% confidence intervals. Overall survival was the primary outcome of interest, whereas disease-free survival, locoregional control and toxicity were secondary end points.
Five randomised controlled trials (involving 1117 patients and 627 deaths) directly comparing conventionally fractionated CCRT with AFRT alone were included. The risk of bias in included studies was low for efficacy outcomes, but high for toxicity outcomes. The overall pooled hazard ratio of death was 0.73 (95% confidence interval = 0.62-0.86), which significantly favoured conventionally fractionated CCRT over AFRT alone (P < 0.0001). Similarly, disease-free survival (hazard ratio = 0.79, 95% confidence interval = 0.68-0.92; P = 0.002) and locoregional control (hazard ratio = 0.71, 95% confidence interval = 0.59-0.84; P < 0.0001) were significantly improved with CCRT. There were no significant differences in the incidence of severe acute toxicity (dermatitis and mucositis) between the two approaches of treatment intensification. Late xerostomia was significantly increased with CCRT. Significant haematological toxicity and nephrotoxicity were seen exclusively with chemotherapy.
There is moderate quality evidence that conventionally fractionated CCRT improves survival outcomes compared with AFRT alone in the definitive radiotherapeutic management of locoregionally advanced HNSCC. No form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy.
[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