Prospective Phase II Study of Radiotherapy Dose Escalation in Grade 4 Glioma Using 68Ga-Pentixafor PET Scan.

AIMS: Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68Ga-Pentixafor PET scan. High 68Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain. MATERIALS AND METHODS: This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range. RESULTS: Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis. CONCLUSIONS: The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of 68Ga-pentixafor PET scan for radiation dose escalation should be further explored. CLINICAL TRIAL NUMBER: CTRI/2019/05/019146.

Embryonal tumors with multilayered rosettes: A tertiary care centre experience.

BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) is an extremely rare and highly aggressive tumor. It includes three distinct entities i.e, embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL). Here, we present our institutional experience of seven ETMR cases treated over a period of five years. MATERIALS AND METHODS: Patients' records from 2015 to 2019 were reviewed manually and electronically to retrieve the data. Clinicopathological and outcome details of ETMR cases were entered in a predesigned proforma. RESULTS: A total of seven cases of ETMR were registered from 2015 to 2019 with a median age at presentation of four years (range 3-7 years). All patients underwent surgery. However, only three patients completed the planned adjuvant treatment, comprising of focal radiotherapy (RT) alone, craniospinal irradiation (CSI) alone and CSI followed by six cycles of chemotherapy in one patient each respectively. Two patients commenced CSI but deteriorated during RT and thereafter needed best supportive care. Two patients could not be started on any adjuvant treatment. Unfortunately, six patients succumbed to their disease within one year of their diagnosis. Only one patient who received both CSI and adjuvant chemotherapy is alive at 15 months of diagnosis. CONCLUSION: ETMR is a rare and aggressive entity. Majority of the patients die within one year of the diagnosis despite multimodality treatment.

Effect of prophylactic granulocyte-colony stimulating factor (G-CSF) on acute hematological toxicity in medulloblastoma patients during craniospinal irradiation (CSI).

OBJECTIVES: Haematological toxicity and treatment breaks are common during cranio-spinal irradiation (CSI) due to irradiation of large volume of bone marrow. We conducted this study to see the effect of prophylactic granulocyte colony stimulating factor (GCSF) in reducing treatment breaks. PATIENTS AND METHODS: The study was conducted over a period of 15 months from August 2017 to November 2018. Histopathologically proven Medulloblastoma patients received prophylactic GCSF during CSI. Acute hematological toxicities and treatment breaks were noted and effect of age and pretreatment blood counts were analyzed by SPSS (Statistical Package for Social Sciences) version 23. RESULTS: A total of 28 patients were included in the study. During CSI, hematological toxicity leading to treatment breaks was observed in 11 (39.3 %) patients, of which grade 3 and 2 toxicities were seen in ten and one patients respectively. Younger age (<10 years) at diagnosis was significantly associated with the development of hematological toxicity (p = 0.028, Chi-Square). No correlation was found with pre-treatment blood counts. CONCLUSION: Prophylactic use of GCSF may be effective in preventing radiation induced hematological toxicity and treatment breaks.

Dosimetric evaluation and clinical outcome in post-operative patients of carcinoma vulva treated with intensity-modulated radiotherapy.

BACKGROUND: To compare dosimetric parameters of intensity-modulated radiation therapy (IMRT) with 3D conformal radiotherapy (3DCRT) in post-operative patients of vulvar cancer and to assess clinical outcome and toxicity with IMRT. MATERIALS AND METHODS: A total of 8 post-operative patients of vulvar cancer were treated with IMRT. All patients were also planned by 3DCRT for comparison with IMRT. The two plans were compared in terms of conformity index, homogeneity index, tumor control probability (TCP) and normal tissue complication probability (NTCP) for the planning target volume and organs at risk (OAR). RESULTS: IMRT resulted in significantly lesser doses to rectum, bladder, bowel and femoral head as compared with 3DCRT plans. Mean conformity and homogeneity indices were better and within range with IMRT. The TCP was comparable between the two treatment plans and NTCP for rectum, bladder, bowel and femoral head was significantly less with IMRT as compared with 3DCRT. Treatment was well-tolerated and none of the patients developed Grade 3 or higher toxicity. CONCLUSION: IMRT yielded superior plans with respect to target coverage, homogeneity and conformality while lowering dose to adjacent OAR as compared with 3DCRT. Thus, IMRT offers a reduction in NTCP while maintaining TCP.

Spatial mislocalization of EEG electrodes -- effects on accuracy of dipole estimation.

OBJECTIVE: The estimation of cortical current activity from scalp-recorded potentials is a complicated mathematical problem that requires fairly precise knowledge of the location of the scalp electrodes. It is expected that spatial mislocalization of electrodes will introduce errors in this estimation. The present study uses simulated and real data to quantify these errors for dipole current sources in a spherical head model. METHODS: A 3-dimensional digitizer was used to locate the positions of 31 scalp electrodes placed on the head according to the 10-20 system in 10 normal subjects. Dipole localizations were performed on auditory evoked potentials (AEPs) collected from these subjects. RESULTS: Computer simulations with several dipole source configurations suggest that errors in locations and orientations on the order of 5 mm and 5 degrees, respectively, are possible for electrode mislocalizations of about 5 degrees. In actual experimental settings, digitized electrode positions were typically mislocalized by an average of about 4 degrees from their standard 10-20 positions on a spherical model. These differences in electrode positions translated to mean differences of about 8 mm in dipole locations and 5 degrees in dipole orientations. CONCLUSIONS: Dipole estimation errors due to electrode mislocalizations are within the limits of errors due to other modeling approximations and noise.

Distributed source imaging of alpha activity using a maximum entropy principle.

OBJECTIVE: We present a method based on the distributed dipole source model to localize sources of spontaneous human brain activity, such as the alpha rhythm. The proposed method relies on the generalized maximum entropy principle and is implemented in frequency-domain. METHODS: Several computer simulation studies of synchronous and asynchronous distributed dipole sources were carried out to test the validity of the method. The method was also applied to spontaneous electroencephalographic (EEG) recordings from human subjects to estimate the sources of alpha activity. The locations of these sources were registered with actual magnetic resonance images for anatomical visualization. RESULTS: The simulation studies suggest the validity of the proposed method and its capability to detect distributed and fairly deep synchronous dipole sources. Results of human studies with 6 subjects suggest that the generators of alpha rhythm are mainly concentrated over the posterior regions of the cortex. CONCLUSION: The proposed distributed source imaging method is a promising technique for localizing rhythmic brain activity.

Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness.

Experience-related changes in central nervous system (CNS) activity have been observed in the adult brain of many mammalian species, including humans. In humans, late-onset profound unilateral deafness creates an opportunity to study plasticity in the adult CNS consequent to monaural auditory deprivation. CNS activity was assessed by measuring long-latency auditory evoked potentials (AEPs) recorded from teens and adults with late-onset (post-childhood) profound unilateral deafness. Compared to monaurally stimulated normal-hearing subjects, the AEPs recorded from central electrode sites located over auditory cortical areas showed significant increases in inter-hemispheric waveform cross-correlation coefficients, and in inter-hemispheric AEP peak amplitude correlations. These increases provide evidence of substantial changes from the normal pattern of asymmetrical (contralateral > ipsilateral amplitude) and asynchronous (contralateral earlier than ipsilateral) central auditory system activation in the normal-hearing population to a much more symmetrical and synchronous activation in the unilaterally deaf. These cross-sectional analyses of AEP data recorded from the unilaterally deaf also suggest that the changes in cortical activity occur gradually and continue for at least 2 years after the onset of hearing loss. Analyses of peak amplitude correlations suggest that the increased inter-hemispheric symmetry may be a consequence of changes in the generators producing the N (approximately 100 ms peak latency) potential. These experience-related changes in central auditory system activity following late-onset profound unilateral deafness thus provide evidence of the presence and the time course of auditory system plasticity in the adult brain.

Spatio-temporal EEG source localization using simulated annealing.

The estimation of multiple dipole parameters in spatio-temporal source modeling (STSM) of electroencephalographic (EEG) data is a difficult nonlinear optimization problem due to multiple local minima in the cost function. A straightforward iterative optimization approach to such a problem is very susceptible to being trapped in a local minimum, thereby resulting in incorrect estimates of the dipole parameters. In this paper, we present and evaluate a more robust optimization approach based on the simulated annealing algorithm. The complexity of this approach for the STSM problem was reduced by separating the dipole parameters into linear (moment) and nonlinear (location) components. The effectiveness of the proposed method and its superiority over the traditional nonlinear simplex technique in escaping local minima were tested and demonstrated through computer simulations. The annealing algorithm and its implementation for multidipole estimation are also discussed. We found the simulated annealing approach to be 7-31% more effective than the simplex method at converging to the true global minimum for a number of different kinds of three-dipole problems simulated in this work. In addition, the computational cost of the proposed approach was only marginally higher than its simplex counterpart. The annealing method also yielded similar solutions irrespective of the initial guesses used. The proposed simulated annealing method is an attractive alternative to the simplex method that is currently more common in dipole estimation applications.

Triple procedure of penetrating keratoplasty, extra capsular cataract extraction and posterior chamber I.O.L. implantation.

Ten cases of triple procedure of PKP, ECCE with IOL implantation have been presented and there results discussed.

Role of neoadjuvant concurrent chemoradiation in locally advanced unresectable pancreatic cancer: a feasibility study at tertiary care centre.

BACKGROUND: Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease. The objective of the present study was to assess the effect of neoadjuvant chemoradiation therapy (NACRT) on tumor response, down staging and resection, toxicity and any survival advantage. MATERIALS AND METHODS: A prospective pilot study was carried out from January 2009 to June 2011 in which 15 patients of locally advanced unresectable pancreatic cancer were included. All patients were treated with NACRT protocol with oral Capecitabine and 3D conformal radiotherapy (3DCRT) of 30 Gy in 10 fractions. The patients were restaged 3 to 4 weeks after the completion of NACRT and explored for resection. RESULTS: Out of 15 patients, fourteen were evaluable. Four patients underwent surgery, 5 had partial response but remained unresectable, 2 patients had stable disease and 3 had progressive disease. Most of the toxicities were slight and were in grade 1 to 2. None of the patients developed grade 3 or 4 gastrointestinal or hematological toxicity. The median survival was 15 months for resected patients and 8.6 months for unresected patients, respectively. The 2 year actuarial overall survival was 34.6%. CONCLUSION: All patients with locally unresectable pancreatic cancer should be offered chemoradiation therapy, in hopes of down staging the tumor for possible resection and achieving higher survival.

Dose escalation by intensity-modulated radiotherapy boost after whole pelvic radiotherapy in postoperative patients of carcinoma cervix with residual disease.

AIMS: External beam radiotherapy followed by brachytherapy is the standard treatment for patients with carcinoma cervix. However, for patients who come from peripheral hospitals after incomplete surgery, whole pelvic radiotherapy (WPRT) followed by boost with either vaginal vault brachytherapy if suitable or further external beam radiotherapy is recommended. This study was conducted to evaluate if it was possible to give a higher tumour dose using intensity-modulated radiotherapy for that group of patients who were not suitable for high dose rate vaginal vault brachytherapy because of gross disease after WPRT. MATERIALS AND METHODS: A prospective study was carried out from 2005 to 2010 in which 25 postoperative patients of cervical carcinoma with gross residual disease after WPRT of 46 Gy/23 fractions/4.5 weeks were included. Nine patients were treated with 20 Gy to the planning target volume and 30 Gy to the clinical target volume in 10 fractions; 16 patients were treated with 30 Gy to the planning target volume and 35 Gy to the clinical target volume in 15 fractions. The end points of this study were local control, survival and treatment-related toxicity. RESULTS: The median follow-up was 38 months. The 3 year local control, progression-free survival and overall survival rates were 76, 74 and 67%, respectively. Late grade 2 rectal toxicity was seen in 11 patients. Grade 2 bladder toxicity occurred in two patients and grade 3 bowel toxicity in two patients. No other grade 3 or higher toxicity was seen. CONCLUSION: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. It is possible to escalate the tumour dose by intensity-modulated radiotherapy boost after WPRT in postoperative cervical carcinoma patients with gross residual disease with low incidence of severe toxicity and excellent local control.

Wilson's disease in the Commonwealth of Dominica, a case report.

The first case reported in Dominica of Wilson's disease is described. This is possibly the first successfully treated case in the West Indies. Wilson's disease, though rare, may occur in an unexpected setting.

Stereo pairs of bright-field micrographs via Wiener-type inverse filtering.

In a three-dimensional (3-D) image data set obtained through optical sectioning, each two-dimensional (2-D) segment is blurred by out-of-focus information from neighbouring focal planes superimposed on the in-focus segments from that plane. Instead of attempting to remove this redundant information over the full 3-D data set, we have developed a technique for restoring stereoscopic views. In this paper we describe the implementation of a Wiener-type inverse filtering method for generating stereo pairs of bright-field micrographs. A theoretical optical transfer function valid under certain simplifying approximations has been used in implementing this filtering technique. In developing this method the slice theorem of computed tomography is used. In this way the image reconstruction problem is reduced to one of processing 2-D arrays rather than 3-D arrays and the problem of restoring missing Fourier components within the missing-cone region is circumvented. Limited experimentation with real micrographs shows that the approach provides images that display an effective increased depth of field and 3-D attributes of the specimen, even though some of the underlying assumptions on which this method is based are difficult to verify explicitly. The method can be implemented with a relatively fast execution time on 386-SX computers.