Dosimetric Evaluation of Radiation Treatment Planning for Simultaneous Integrated Boost Technique Using Monte Carlo Simulation.

Monte Carlo (MC) techniques have been recognized as the gold standard for the simulation of radiation transport in radiotherapy. The aim of the study is to perform dosimetric evaluation of Simultaneous Integrated Boost (SIB) radiation treatment planning using MC simulation approach. The geometrical source modeling and simulation of 6 MV Flattening Filter Free (FFF)beam from TrueBeam linear accelerator have been carried out to simulate Volumetric Modulated Arc Therapy (VMAT) plans using MC simulation software PRIMO. All the SIB plans have been generated using VMAT techniques for patients with locally advanced postoperative head-and-neck squamous cell carcinoma in Eclipse Treatment Planning System (TPS) retrospectively. TPS plans have been compared against their respective MC-simulated plans in PRIMO. The quality assessments of plans have been performed using several dose volume parameters, plan quality indices, and methods of gamma analysis. Dmean, D50%, and D2% received by planning target volume (PTV), PTV60, and PTV52 have been found significantly lower in TPS-generated plans compared to MC-simulated plans. D100%, D98%, and D95% received by PTV60 exhibit good agreement. However, PTV52 shows a significant deviation between TPS and MC plans. The mean organ-at-risk doses have been found significantly lower in TPS plans compared to MC plans. TPS and MC plans have been found in close agreement within gamma acceptance criteria of 3% Dose Difference (DD) and 3 mm Distance to Agreement (DTA). Dose distributions computed using MC simulation techniques are reliable, accurate, and consistent with analytical anisotropic algorithm. Plan quality indices have been found slightly compromised in MC-simulated plans compared with TPS-generated plans appeared to be a true representation of real dose distribution obtained from MC simulation technique. Validation using MC simulation approach provides an independent secondary check for ensuring accuracy of TPS-generated plan.

Determination of an inflection point for a dosimetric analysis of unflattened beam using the first principle of derivatives by python code programming.

BACKGROUND: Practice of Unflattened or Flattening filter free (FFF) beam has become the high dose standard in radiotherapy (RT), such as stereotactic radio-surgery (SRS) and stereotactic radiotherapy (SRT). The removal of a flattening filter (FF) from the path of a photon beam alters the characteristics of FFF beam. Since the conventional route for dosimetric analysis of FF beam cannot be applied to FFF beam, the procedure of analyzing beam characteristics for FFF beam based on inflection points (IPs) is used. IP is a point where the concavity change observed corresponds to its change in sign (±) of the second derivative. AIM: The objective of the study is to determine IPs for dosimetric analysis of the FFF beam profile. METHODS AND MATERIALS: In this study, IPs are determined through the python code programming based on the mathematical first principle of the derivative. They are compared with IPs estimated by the conventional graphical manual method using Microsoft Excel (MS). IPs and their dependent dosimetric parameters determined by both mathematical and graphical manual methods are compared. RESULT: Percentage differences between the IPs determined by both methods, for 6MVFFF inline and crossline beam profile are found to be 2.7% and 0.8% respectively. Similarly, the average penumbra differences for 6MVFFF inline and crossline beam profile are found to be 0.15 mm and 0.9 mm, respectively. However, differences in the field width between both methods are found insignificant. CONCLUSION: Graphical manual method is very time-consuming, tedious and user dependent. However, the mathematical method through python code programming is more precise, faster and independent of individual users.

Factor analysis of symptom profile in early onset and late onset OCD.

This study aimed to assess the factor structure of early and late onset OCD. Additionally, cluster analysis was conducted in the same sample to assess the applicability of the factors. 345 participants were assessed with Yale Brown Obsessive Compulsive Scale symptom checklist. Patients were classified as early onset (onset of symptoms at age ≤ 18 years) and late onset (onset at age > 18 years) OCD depending upon the age of onset of the symptoms. Factor analysis and cluster analysis of early-onset and late-onset OCD was conducted. The study sample comprised of 91 early onset and 245 late onset OCD subjects. Males were more common in the early onset group. Differences in the frequency of phenomenology related to contamination related, checking, repeating, counting and ordering/arranging compulsions were present across the early and late onset groups. Factor analysis of YBOCS revealed a 3 factor solution for both the groups, which largely concurred with each other. These factors were named as hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual and religious factor (factor-3). To conclude this study shows that factor structure of symptoms of OCD seems to be similar between early-onset and late-onset OCD.

Dosimetric impact of setup errors in head and neck cancer patients treated by image-guided radiotherapy.

To assess and analyze the impact of setup uncertainties on target volume coverage and doses to organs at risk (OAR) in head and neck cancer (HNC) patients treated by image-guided radiotherapy (IGRT). Translational setup errors in 25 HNC patients were observed by kilovoltage cone beam computed tomography (kV CBCT). Two plans were generated. Plan one - the original plan which was the initially optimized and approved plan of the patient. All patients were treated according to their respective approved plans at a defined isocenter. Plan two - the plan sum which was the sum of all plans recalculated at a different isocenter according to setup errors in x, y, and z-direction. Plan sum was created to evaluate doses that would have been received by planning target volume (PTV) and OARs if setup errors were not corrected. These 2 plans were analyzed and compared in terms of target volume coverage and doses to OARs. A total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The systematic (mean) and random errors (standard deviation) combined for 25 patients in x, y, and z directions were 0.15 cm, 0.21 cm, and 0.19 cm and 0.09 cm, 0.12 cm, and 0.09 cm, respectively. The study showed that there was a significant difference in PTV coverage between 2 plans. The doses to various OARs showed a nonsignificant increase in the plan sum. The correction of translational setup errors is essential for IGRT treatment in terms of delivery of planned optimal doses to target volume.

Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5.

Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Sildenafil, vardenafil, tadalafil and avanafil are FDA approved drugs in market as PDE5 inhibitors for treating erectile dysfunction. In the present study a lead molecule 4-ethoxy-N-(6-hydroxyhexyl)-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide, that is, compound-4a, an analog of pyrazolopyrimidinone scaffold has been identified as selective PDE5 inhibitor. A series of compounds was synthesized by replacing N-methylpiperazine moiety (ring-C) of sildenafil structure with different N-substitutions towards sulfonamide end. Compound-4a showed lower IC50 value (1.5 nM) against PDE5 than parent sildenafil (5.6 nM) in in vitro enzyme assay. The isoform selectivity of the compound-4a against other PDE isoforms was similar to that of the Sildenafil. In corroboration with the in vitro data, this molecule showed better efficacy in in vivo studies using the conscious rabbit model. Also compound-4a exhibited good physicochemical properties like solubility, caco-2 permeability, cLogP along with optimal PK profile having no significant CYP enzyme inhibitory liabilities. Discovery of these novel bioactive compounds may open a new alternative for developing novel preclinical candidates based on this drugable scaffold.

Improving the accuracy of target volume delineation by combined use of computed tomography, magnetic resonance imaging and positron emission tomography in head and neck carcinomas.

OBJECTIVE: Conformal radiation therapy mandates accurate delineation of target volumes, which requires incorporation of modern imaging modalities like magnetic resonance imaging (MRI) and positron emission tomography (PET) in addition to conventionally used computed tomography (CT). This can resolve discrepancies in target delineation in head and neck carcinomas resulting in better local control. We hereby report the comparison of Gross Tumor Volumes (GTVs) (primary) drawn using PET, CT and MRI and their concordance indices. METHODS AND MATERIAL: Twenty five patients with head and neck cancer were taken into this study. MRI, PET and CT planning scans were done as per standard guidelines. Three sets of primary GTVs namely GTV- PET, GTV-CT and GTV-MRI were contoured on fused images. All the three volumes and concordances among the volumes were analyzed. RESULT: The mean GTV-CT, GTV-PET and GTV-MRI volumes were 29.65 cc ± 31.27, 32.05 cc ± 33.75 and 24.85 cc ± 25.28 respectively. There was a significant difference in the GTV-MRI & GTV-CT volumes (P = 0.023) and GTV-PET & GTV-MRI volumes (P = 0.049). However, there was no significant difference in the GTV-PET & GTV-CT volume (P = 0.468). The mean CI (PET-MRI), CI (CT-MRI) and CI (PET-CT) was 0.42, 0.46 and 0.47 respectively, which depicts a moderate concordance. CONCLUSION: PET and MRI are useful imaging tools in head and neck malignancies and should be used in conjunction with CT scan for improved target volume delineation.

Retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients: A single institutional study.

AIM: To present a retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients at our institute. METHODS: Thirty-one patients of head and neck cancer who presented with a locoregional recurrence from April 2007 to April 2012 underwent salvage reirradiation. Median dose of first-time radiation was 70 Gy. Median duration of gap between the first and second course of radiation was 45.6 months. The median dose of reirradiation was 60 Gy. Conformal radiotherapy technique in the form of intensity modulated radiotherapy was used in 60% (17) of patients. Fourteen patients received concurrent chemotherapy or immunotherapy. RESULTS: After a median follow-up of 20.6 months, 12 patients were alive with no evidence of disease. The 3-year disease-free survival and overall survival were 28.7 and 48.5%, respectively. Acute and late toxicities were reported in 29 and 61% of patients, respectively. Severe grade 3 and 4 late complications were observed in nine patients but none of them led to mortality. CONCLUSION: Reirradiation appears to be both feasible and well tolerated in patients treated with previous radiotherapy for recurrent and second primary head and neck cancer. Careful case selection for reirradiation based on patient's performance status and tumor characteristics is essential.

Factors associated with suicidal ideations and suicidal attempts in patients with obsessive compulsive disorder.

Aim of this study was to evaluate the prevalence of suicidal ideations (SI) and to study the risk factors for SI and suicide attempt in patients with OCD. One hundred and thirty patients with OCD were assessed on Yale-Brown Obsessive­Compulsive Scale and Symptom Checklist, Beck Depression Inventory, Beck Hopelessness Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, Buss­Durkee Hostility Inventory, Barratt Impulsiveness Scale, Family Interview for Genetic Studies, Brown Assessment of Beliefs Scale and DSM-IV insight criteria for OCD. Of the 130 patients, 60 (46.1%) had current SI and 81 (62.3%) patients had life time SI. Of the 60 patients with current SI, 30 had current depression as assessed on SCID-CV. More than half (48 out of 81; 59.25%) of the patients with lifetime SI had lifetime comorbid depression. Ten patients had history of lifetime suicide attempts. Current SI in patients without current depression were associated with female gender, presence of comorbid psychiatric illness, contamination obsessions and cleaning/washing compulsions. To conclude this study suggests that SI are highly prevalent in patients with OCD and although depression may be a contributory factor for suicidal ideations in patients with OCD, but it is not the sole risk factor for suicidal ideations.

Functional convergence spasm.

Convergence spasm (CS) means intermittent episodes of convergence, miosis and accommodation with disconjugate gaze mimicking abducens palsy. The organic causes range from metabolic to host of neurological and ophthalmic diseases that we describe. It was first described as a presentation of psychogenic disorders by von Graefe as early as in 1856. Nonetheless, patients exhibiting this sign are often subjected to plethora of unnecessary, sophisticated and invasive diagnostic procedures. Such functional cases were treated with either cycloplegic/placebo eye drop or amytal abreaction. Though epidemiological studies suggest that conversion disorder is equally prevalent in industrialized nations and developing countries, a few cases of functional CS are reported from West including Asia, that to, decade(s) before and none from India, to the best of our knowledge. We illustrate a case of functional CS with photograph after consent from patient and its successful treatment.

Serum zinc as a prognostic indicator in locally advanced cancer cervix patients receiving chemo-irradiation: A pilot study.

OBJECTIVE: To evaluate the prognostic significance of serum Zinc (S.Zn) in locally advanced cancer cervix (LACC) patients treated with chemo-irradiation. MATERIALS AND METHODS: S.Zn values in 34 females with histopathologically (HP) proven LACC (>/= stage II B) were prospectively measured using atomic absorption spectrophotometer pre- and post-treatment. Thirty-four age- and sex-matched healthy individuals were also evaluated for the parameter during the course of the study. After completion of treatment, the patients were divided into 2 groups based on the response, 1 - Complete response (CR) and 2 - Partial/No response (PR/NR). These groups were compared based on the observations of the studied parameter. RESULTS: The mean post-treatment S.Zn values were significantly higher in group 1 as compared to group 2 (P < 0.05). CONCLUSION: In our study, patients achieving CR had higher mean levels of S.Zn compared to patients achieving PR/NR. We advocate further in-depth studies to evaluate the role of S.Zn in the prognosis of LACC patients treated with chemo-irradiation.

A patient with Tramadol dependence and predictable provoked epileptic seizures.

Tramadol is an atypical, centrally acting synthetic analgesic with propensity for provoked seizures as well as abuse potential. The index case of Tramadol dependence discussed in this case report developed multiple epileptic seizures with high doses of Tramadol, used as a sexual enhancer by him, and later he learned to prevent the seizures by self-medicating with Alprazolam. The authors further emphasize on the regulation of Tramadol prescription.

The scenario of presentation of young females in a rural cancer hospital of North India: An initial experience.

A total of 51 cases of young females aged between 18-35 years were prospectively studied for the presentation in a Rural Charitable Cancer hospital in north India during the period August 2011 to April 2012. Breast related symptoms comprised 27 (52.94%) cases, out of which 10 (19.60%) were proven malignant. Other cases seen were Gynecological (Gyn) 8 (15.68%), Head and Neck (H and N) 5 (9.80%), Gastrointestinal (GI) 4 (7.84%), Lymphomas 3 (5.88%) and 2 (3.92%) cases each of Bone Tumors and Central Nervous System (CNS) tumors. Breast related symptoms constituted the major presentation in young females (aged 18-35 years) in our Rural Cancer Hospital. This high percentage of Breast related symptoms points towards the increasing trend of Breast malignancies possibly overtaking cancer cervix in rural India, as already in the urban settlements of India as well as the increasing awareness in the females of rural India regarding early symptoms of carcinoma Breast.

Anxiolytic activity of Nymphaea alba Linn. in mice as experimental models of anxiety.

OBJECTIVE: The aim of the present work was to evaluate the anxiolytic effect of an ethanolic extract of Nymphaea alba Linn. in mice. MATERIALS AND METHODS: The elevated plus maze test (EPMT), light and dark test (L and DT) and open field test (OFT) were used to assess the anxiolytic activity of the ethanolic extract of N. alba Linn. in mice. In addition, aggressive behavior and motor coordination was also assessed by foot shock induced aggression test (FSIAT) and rota rod test (RRT). Diazepam 1 mg/kg served as a standard anxiolytic drug, administered orally. RESULTS: The ethanolic extract of N. alba (100 and 200 mg/kg, p.o.) significantly increased the percentage of time spent and number of entries in open arm in EPMT. In L and DT, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. In FSIAT, N. alba extract attenuated aggressive behavior related to anxiolytic activity, such as number of vocalization, leaps, rearing, biting/attacks and facing each other in paired mice. Furthermore, the extract produced skeletal muscle relaxant effect assessed by RRT. CONCLUSION: The results of the present study suggest that an ethanolic extract of N. alba may possess anxiolytic activity and provide a scientific evidence for its traditional claim.