Shreerang Bhide

Institute of Cancer Research, Londinium, England, United Kingdom

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Publications (6)22.48 Total impact

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    ABSTRACT: Fatigue during head and neck radiotherapy may be related to radiation dose to the central nervous system (CNS). The impact of patient, tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal cancer patients undergoing chemoradiotherapy. Radiation dose to the following retrospectively-delineated CNS structures; brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia (BG) and clinical variables were related to incidence of ⩾ grade 2 fatigue in 40 patients. Sixty per cent of patients reported fatigue during and following radiotherapy. Dmean and D2 to the BG and Dmean to the pituitary gland were significantly associated with fatigue during radiation (P<0.01). Dmean to the cerebellum was associated with fatigue following radiotherapy and at any time (P<0.01). After adjusting for clinical factors, an association remained between fatigue during radiotherapy and mean dose and D2 to the pituitary gland and BG (P=0.012, 0.036, 0.009 and 0.018) and mean dose to the cerebellum following radiation and at any time (P=0.042 and 0.029). Disruption of connections between BG, cerebellum, and higher cortical centres or disruption of pituitary-regulated hormonal balance may be implicated in the pathophysiology of radiation-related fatigue.
    Radiotherapy and Oncology 08/2013; · 4.52 Impact Factor
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    ABSTRACT: BACKGROUND: Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. METHODS: To test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. RESULTS: Correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. CONCLUSIONS: In summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue.
    BMC Cancer 08/2012; 12(1):368. · 3.33 Impact Factor
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    ABSTRACT: Irradiation of tumors in the larynx and pharynx is often technically challenging in patients with a short neck or high shoulders. Shoulder retraction devices can sometimes resolve this problem and allow irradiation via lateral beam directions. This study aimed to measure the proportion of patients who would benefit from such an approach and to quantify the magnitude of the benefit obtained. Twenty patients were studied. Simulator images were obtained before and after intervention. The additional exposure of the cervical spine was measured. Patient comfort and acceptability were assessed with a questionnaire. Improvement of exposure of the cervical spine was observed in 80% of patients. In 20%, there was either no difference or the position was worse. Shoulder retraction exposed a mean of 8.4-10.2 mm more of the cervical spine. Patients in general reported the device as comfortable. The use of a shoulder retraction device produced clinically significant improvements in exposure of the tissues of the cervical spine and neck and should be considered in patients being irradiated for tumors arising in the larynx or hypopharynx.
    Medical dosimetry: official journal of the American Association of Medical Dosimetrists 02/2012; 37(3):293-5. · 1.26 Impact Factor
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    ABSTRACT: To test combination treatment schedules of reovirus and radiation in human and murine tumor cells in vitro and in vivo. In vitro cytotoxicity and cell cycle effects of reovirus given alone and combined with radiotherapy were assessed by colorimetric, tissue culture infectious dose 50, and fluorescence-activated cell sorting-based assays. Interactions between the agents were evaluated using combination index analysis. The effect of different schedules of reovirus and radiotherapy on viral replication and cytotoxicity was tested in vitro and the combination was assessed in three tumor models in vivo. Characterization of reovirus cytotoxicity in a panel of cell lines yielded a range of sensitivities. Combined reovirus and radiotherapy yielded statistically significantly increased cytotoxicity, particularly in cell lines with moderate susceptibility to reovirus alone. The enhanced cytotoxicity of the combination occurred independently of treatment sequence or schedule. Radiation did not affect viral replication and only reduced reoviral cytotoxicity after clinically irrelevant single doses (>50 Gy). Combination index analysis revealed synergy between radiation (3-10 Gy) and reovirus at multiplicities of infection between 0.001 and 1. Combination treatment significantly increased apoptosis in tumor cells relative to either single-agent treatment. In vivo studies using xenograft and syngeneic tumors showed enhanced activity of the combination relative to reovirus or radiation alone (P < 0.001). Combining reovirus and radiotherapy synergistically enhances cytotoxicity in a variety of tumor cells in vitro and in vivo. These results offer strong support for translational clinical trials of reovirus plus radiotherapy that have been initiated in the clinic.
    Clinical Cancer Research 02/2008; 14(3):912-23. · 7.84 Impact Factor
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    ABSTRACT: To determine whether a computer-assisted target volume delineation (CAT) system using a deformable image registration approach can reduce the variation of target delineation among physicians with different head and neck (HN) IMRT experiences and reduce the time spent on the contouring process. We developed a deformable image registration method for mapping contours from a template case to a patient case with a similar tumor manifestation but different body configuration. Eight radiation oncologists with varying levels of clinical experience in HN IMRT performed target delineation on two HN cases, one with base-of-tongue (BOT) cancer and another with nasopharyngeal cancer (NPC), by first contouring from scratch and then by modifying the contours deformed by the CAT system. The gross target volumes were provided. Regions of interest for comparison included the clinical target volumes (CTVs) and normal organs. The volumetric and geometric variation of these regions of interest and the time spent on contouring were analyzed. We found that the variation in delineating CTVs from scratch among the physicians was significant, and that using the CAT system reduced volumetric variation and improved geometric consistency in both BOT and NPC cases. The average timesaving when using the CAT system was 26% to 29% for more experienced physicians and 38% to 47% for the less experienced ones. A computer-assisted target volume delineation approach, using a deformable image-registration method with template contours, was able to reduce the variation among physicians with different experiences in HN IMRT while saving contouring time.
    International Journal of Radiation OncologyBiologyPhysics 09/2007; 68(5):1512-21. · 4.52 Impact Factor
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    ABSTRACT: Head and neck squamous cell carcinoma with occult primary site represents a controversial clinical problem. Conventional total mucosal irradiation (TMI) maximizes local control, but at the expense of xerostomia. IMRT has been shown to spare salivary tissue in head and cancer patients. This study has been performed to investigate the potential of IMRT to perform nodal and TMI and also allow parotid gland sparing in this patient group. Conventional radiotherapy (CRT) and IMRT plans were produced for six patients to treat the ipsilateral (involved) post-operative neck (PTV1) and the un-operated contralateral neck and mucosal axis (PTV2). Plans were produced with and without the inclusion of nasopharynx in the PTV2. The potential to improve target coverage and spare the parotid glands was investigated for the IMRT plans. There was no significant difference in the mean doses to the PTV1 using CRT and IMRT (59.7 and 60.0 respectively, p = 0.5). The maximum doses to PTV1 and PTV2 were lower for the IMRT technique as compared to CRT (P = 0.008 and P < 0.0001), respectively, and the minimum doses to PTV1 and PTV2 were significantly higher for IMRT as compared to CRT (P = 0.001 and P = 0.001), respectively, illustrating better dose homogeneity with IMRT. The mean dose to the parotid gland contralateral to PTV1 was significantly lower for IMRT (23.21 +/- 0.7) as compared to CRT (50.5 +/- 5.8) (P < 0.0001). There was a significant difference in parotid dose between plans with and without the inclusion of the nasopharynx. IMRT offers improved dose homogeneity in PTV1 and PTV2 and allows for parotid sparing.
    Medical Dosimetry 01/2007; 32(3):188-95. · 1.01 Impact Factor