Evaluation of dose calculation accuracy of various algorithms in lung equivalent inhomogeneity: Comparison of calculated data with Gafchromic film measured results.

AIM: To evaluate dose calculation accuracy of various algorithms in lung equivalent inhomogeneity comprising tumor within it and comparison with Gafchromic film data. MATERIALS AND METHODS: Gafchromic film measured central axis absorbed dose in lung insert (-700 Hounsfield unit [HU]), in racemosa wood cylindrical inhomogeneity (-725 HU) and at three surfaces of tumor (-20 HU) created in cylindrical inhomogeneity, put in the cavity of computerized imaging reference systems (CIRS) thorax phantom were compared with convolution (CON), superposition (SP), fast SP (FSP), and X-ray voxel Monte Carlo (XVMC) algorithms calculated dose using 6 MV beams of field size 2 cm × 2 cm, 3 cm × 3 cm, 4 cm × 4 cm, 5 cm × 5 cm, and 8 cm × 8 cm. RESULTS: XVMC was in good agreement with film measured results for all selected field sizes except 3 cm × 3 cm. SP under estimated by 5.7% at the center of the lung insert while deviation up to 6% was found at the cent of wood inhomogeneity in 2 cm × 2 cm. Except CON, increase in dose from proximal to the central surface of the tumor and then dose falloff from central to the distal surface for field size 2 cm × 2 cm to 4 cm × 4 cm was recorded. The change in film measured percentage depth dose from 2 cm × 2 cm to 3 cm × 3 cm field sizes was found -8% however for consecutive field size(s) larger than 3 cm × 3 cm this difference was less. CON and FSP produced overestimated results. CONCLUSION: Out of four algorithms, XVMC found consistent with measured data. The electronic disequilibrium within and at the interface of inhomogeneity make the accurate dose predictions difficult. These limitations results in deviations from the expected results of the treatments.

Performance Evaluation of Algorithms in Lung IMRT: A comparison of Monte Carlo, Pencil Beam, Superposition, Fast Superposition and Convolution Algorithms.

BACKGROUND: Inclusion of inhomogeneity corrections in intensity modulated small fields always makes conformal irradiation of lung tumor very complicated in accurate dose delivery. OBJECTIVE: In the present study, the performance of five algorithms via Monte Carlo, Pencil Beam, Convolution, Fast Superposition and Superposition were evaluated in lung cancer Intensity Modulated Radiotherapy planning. MATERIALS AND METHODS: Treatment plans for ten lung cancer patients previously planned on Monte Carlo algorithm were re-planned using same treatment planning indices (gantry angel, rank, power etc.) in other four algorithms. RESULTS: The values of radiotherapy planning parameters such as Mean dose, volume of 95% isodose line, Conformity Index, Homogeneity Index for target, Maximum dose, Mean dose; %Volume receiving 20Gy or more by contralateral lung; % volume receiving 30 Gy or more; % volume receiving 25 Gy or more, Mean dose received by heart; %volume receiving 35Gy or more; %volume receiving 50Gy or more, Mean dose to Easophagous; % Volume receiving 45Gy or more, Maximum dose received by Spinal cord and Total monitor unit, Volume of 50 % isodose lines were recorded for all ten patients. Performance of different algorithms was also evaluated statistically. CONCLUSION: MC and PB algorithms found better as for tumor coverage, dose distribution homogeneity in Planning Target Volume and minimal dose to organ at risks are concerned. Superposition algorithms found to be better than convolution and fast superposition. In the case of tumors located centrally, it is recommended to use Monte Carlo algorithms for the optimal use of radiotherapy.

EGFR and HER-2/neu Expression in Gallbladder Carcinoma: An Institutional Experience.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignancy of the biliary tract in India. Despite the recent advancement in the understanding of the cancer biology, the disease still remains a therapeutic challenge with poor prognosis and low survival. Surgery is the primary modality of treatment and rest of the modalities are basically adjuvant in nature. This study was performed to evaluate the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 HER-2/neu) expression in GBC. METHODS: The present study was prospective and done in tertiary super-specialty institute of northern India. This was a pilot study, and at the time of completion, 29 samples were found suitable which were later submitted for EGFR and HER-2/neu evaluation. The sample includes both cases of GBC (n=18) and cholecystitis (n=11) as control. (Table 1) After performing necessary processing, slides were incubated with primary antibody (EGFR) ready to use (RTU) BioGenex, India and HER-2/neu dilution 1:600, Dakopatts (Denmark). Then slides were incubated with secondary antibody (Real Envision Detection Kit, Dakopatts, Denmark). Finally in mounted slides, cell membrane staining was used to assess positivity for EGFR and HER-2/neu. RESULTS: EGFR was positive in 21/29 (72.41%) overall, out of which 14/18 (77.78%) positive in cases and 7/11 (63.64%) positive in control. (Table 1, 3)(Figure 2). For HER-2/neu, it was positive in 21/29 (72.41%) overall, just like in EGFR mentioned above, but positive 12/18 (66.67%) in cases and 9/11 (81.82%) in control respectively. CONCLUSION: Despite the efforts by many investigators, GBC continues to represent a major challenge in oncology. Surgical resection remains the only curative treatment for this disease. The roles of radiation, chemoradiation, and chemotherapy in neoadjuvant and adjuvant settings remained to be defined in prospective studies. With further studies based on molecular understanding and developing new targeted therapies, we will be in better position to manage GBC and increase the survival rate.

Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation.

AIMS: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical chemoradiation (CT-RT). MATERIALS AND METHODS: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9*2 and CYP2C9*013, leading to poor metabolizers (PMs) by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO) criteria. RESULTS AND ANALYSIS: The frequency of heterozygous genotypes of both CYP2C9*2 (27.8%) and CYP2C9*3 (25%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9*2 or CYP2C9*013. Further, majority of the cases assessed for response (n = 436) carrying variant alleles of CYP2C9*2 (69.6%) or CYP2C9*3 (65.2%) were found to respond poorly to cisplatin-based radical CT-RT. CONCLUSION: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.

Aneurysmal bone cyst: An unusual presentation of back pain.

Aneurysmal bone cyst (ABC) is a rare benign tumor comprising 1.4% of all primary bone tumors. It commonly involves humerus, femur, tibia, and pelvic bones. Spinal involvement is rare. The pathological appearance of the lesion is one of the blown out distension with fluid filled cavities from which it gains the name aneurysmal bone cyst. The World Health Organization has defined it as an expanding lesion with blood filled cavities separated by septa of trabecular bone or fibrous tissue containing osteoclast giant cells. We describe the case of a 20-year-old Asian male who presented with backache and pain in right leg. Radiology was suggestive of an ABC involving the posterior elements of the lumbar vertebra. Excision was performed. We discuss this unusual case, reviewing the current literature on biological behavior and management of aneurysmal bone cyst.

Cellular and molecular mechanism of ofloxacin induced apoptotic cell death under ambient UV-A and sunlight exposure.

Ofloxacin (OFLX) is a racemic mixture of levofloxacin which revealed phototoxicity in patients exposed with sunlight after medication. Here, we have been addressed the possible cellular and molecular mechanisms of OFLX induced apoptosis under ambient UV-A and sunlight exposure using HaCaT cell line as a model. The results showed that Photodegradation and three photo-products formation of OFLX by LC-MS/MS under ambient intensities of UV-A (1.5 and 2.2 mW/cm(2)) and sunlight. OFLX produced (1)O2, O2(.-), and OH radicals via type-II- and type-I-dependent reaction mechanism, which corroborated by its specific quenchers. 2'-dGua degradation in photochemical and % tail DNA formation in cell line using comet test advocated the genotoxic potential of OFLX. Photocytotoxic assays (MTT and NRU) revealed the considerable decline in cell viability by OFLX. OFLX triggered apoptosis, proved by cell cycle, Annexin V/PI double staining along with acridine orange (AO)/ethidium bromide (EB), and Hoechst staining as well as caspase-3 activity by colorimetric assay. OFLX induced lysosomal disruption and mitochondrial membrane destabilization confirmed through fluorescence staining with AO/JC-1. OFLX significantly upregulated the expression of p21 and bax genes. In conclusion, the study revealed that photosensitized OFLX induced apoptosis via ROS-mediated DNA damage, destabilization of lysosomal and mitochondrial membrane, and upregulation of p21, bax, and caspase-3 genes.

Role of type-II pathway in apoptotic cell death induction by photosensitized CDRI-97/78 under ambient exposure of UV-B.

Novel trioxane 97/78, developed by Central Drug Research Institute (CDRI), Lucknow has shown promising antimalarial activity. Clinical experience of anti-malarial drugs registered the occurrence of phototoxicity in patients exposed with sunlight subsequent to medication. Photodegradation study has identified one photo-product up to 4h under UV-B/Sunlight by LC-MS/MS. UV-B irradiated 97/78 compound produced ¹O2 via type-II dependent reaction mechanism, corroborated by its specific quencher. 2'-dGuO degradation and % tail development in photochemical as well as comet test, advocated the genotoxic potential of 97/78. The photocytotoxicity assays (MTT and NRU) on HaCaT cell line revealed the considerable decline in cell viability by 97/78. Cell cycle and Annexin V/PI double stain along with AO/EB demonstrated the G2/M phase arrest and apoptosis. Significant caspase-3 activity was measured in photoexcited 97/78 by colorimetric assay. Fluorescence stain with AO/JC-1 confirmed the lysosomal disruption and mitochondrial membrane destabilization by UV-B irradiated 97/78. Gene expression by RT-PCR showed significant upregulation of p21 and pro-apoptotic Bax, but no change observed in Bcl-2. In conclusion, the study highlights ROS mediated DNA damage, lysosomal and mitochondrial destabilization via upregulation of Bax and activation of caspase-3 which further leads to apoptosis.

Efficacy of plain radiographs, CT scan, MRI and ultra sonography in temporomandibular joint disorders.

The complexity of structure and functions of the Temporomandibular Joint (TMJ) make the diagnosis of its diseases/disorders difficult. Remarkable progress made in the field of imaging of this joint led us to compare four imaging modalities viz. plain radiographs, CT scan, MRI and ultrasound. We found that MRI was most specific and sensitive for interpretation of soft tissue and inflammatory conditions in the joint, whereas CT examination produced excellent image for osseous morphology and pathology. Plain X-rays are useful for destructive bony changes and sonography is a good in aid in diagnosing disc derangement and is very economical.

Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck.

BACKGROUND: Squamous cell carcinoma of head and neck (SCCHN) is a major concern of health risk in developing countries, such as India. Apart from genetic configuration, environmental and lifestyle factors, as well as poor oral hygiene, provide free radical-generating environment, which may contribute to the development of cancer through DNA damage. MATERIALS AND METHODS: Here we ascertained the various oxidative stress determinants in diagnosed SCCHN patients with health risk addictions. This study further evaluated the incremental effects inflicted by these lifestyle factors on redox status. The study included 100 consenting SCCHN patients and 90 matched healthy controls. Salivary total antioxidant capacity (TAC), glutathione (GSH), free radicals: such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) along with oxidative DNA adduct (8-OHdG) were monitored. RESULTS: Our findings indicated altered salivary oxidant-antioxidant status in SCCHN. A substantial rise in ROS (~2.0 folds) and RNS (~1.4 folds), together with significant lowering in TAC (~1.2 folds) and GSH (~1.7 folds) was observed. The 8-OHdG levels were also found to be considerably higher (P < 0.001) in salivary cell's DNA of these patients. CONCLUSIONS: Our results demonstrate significant redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN.

Primary intraparenchymal brain melanoma: a case report.

Primary intraparenchymal brain melanocytic lesions are very rare and arise from leptomeninges in the superficial cortex with invariably poor clinical outcome. We report a case of a 45-year old male who presented with an intraparenchymal brain lesion without meningeal involvement, radiologicallly consistent with primary brain tumor. However, the pathology of excisional biopsy proved to be melanoma on histopathology and immunohistochemistry. Treatment consisted of limited surgery followed by local radiotherapy with the patient had no significant clinical improvement, and was managed conservatively with steroids along with chemotherapy. The patient died due to diffuse intracranial dissemination within 4 months from completion of radiotherapy.

Deep vein and artery thrombosis associated with cetuximab-based chemoradiotherapy.

Molecular targeted agents have lower hematological toxicity. However, specific side-effects such as allergic rashes, skin reactions and high cost limit their use. We report a case of 35-year-old male patient with carcinoma of left tonsil treated with concurrent cetuximab and radiotherapy. After four weeks of treatment, the patient developed sudden onset of pain in the left calf region radiating to the left foot. Doppler study of the left lower limb revealed complete thrombosis of superficial femoral, popliteal and proximal tibial arteries and veins and no flow in anterior tibial artery and lower posterior tibial artery. Emergency embolectomy was done. After 48 h of observation, no improvement was noted. A repeat Doppler examination showed similar finding. Ultimately a left lower limb amputation was done. We report simultaneous arterio-venous thrombosis associated with cetuximab-based chemoradiotherapy. Oncologists should be aware of this possible complication to undertake early intervention.

Association and treatment response to capecitabine-based chemoradiotherapy with CYP2C9 polymorphism in head and neck cancer.

AIMS: The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemoradiotherapy. MATERIALS AND METHODS: One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. RESULTS: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.3%) and CYP2C9FNx013 (20.1%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (134) carrying variant alleles of both CYP2C9FNx012 (65.3%) or CYP2C9FNx013 (70.58%) were found to respond poorly to the radio-chemotherapy. CONCLUSIONS: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment schedule.

Metastatic medulloblastoma at diagnosis.

Medulloblastoma is an aggressive tumor of the brain. It is the most common and the most malignant embryonal tumor of the pediatric central nervous system and a rare tumor of adults. We are reporting a rare presentation of adult classic subtype of medulloblastoma which was central in location with metastases in the suprasellar region at the time of diagnosis.

Training the trainees in radiation oncology with telemedicine as a tool in a developing country: a two-year audit.

Purpose. The estimated new cancer patient load in the Indian state of Uttar Pradesh is 0.1-0.12 million per year. Approximately two thirds of these require treatment by a radiation oncologist. Radiation oncologists: cancer patient ratio in this state is 1 : 2000 as compared to the recommended 1 : 250. This problem is compounded by the poor infrastructure of radiation oncology departments in the state which is suboptimal for teaching, training of resident doctors, and treatment in most barring a few departments. To bridge some gap in the sociodemographics stated above and enhancement of training of residents, we submitted a project for establishment of a telemedicine facility in our department to the Department of Science and Technology, Government of India. We present the design, implementation, and a two-year audit of our tele-education activities. Materials and Methods. After the sanction of the project, we established telemedicine linkage with another medical institute in the city located 25 kms away in 2007. After implementation of the project, academic sessions designed for trainee residents in our department were shared with the remote end. A record of these activities and a feedback of the activities were audited at the end of 2 years of implementation of this project. Results. Regular videoconferencing sessions comprising of lectures on clinical oncology, medical physics, and radiobiology were held. Feedback from the users revealed satisfaction with the content of the academic sessions for the purpose of MD training. Conclusions. Distance education in radiation oncology is an important tool for training of the trainee residents.

Use of positioning stents in lingual carcinoma patients subjected to radiotherapy.

To evaluate the short-term efficacy of oral positioning stents in minimizing the adverse oral effects of external beam radiation therapy in patients suffering from lingual carcinoma, 48 subjects were selected for this study. Half of the patients (n = 24) were given positioning stents while the other half (n = 24) formed the control group. Subjects were evaluated for oral radiation toxicity effects using the Radiation Therapy Oncology Group's 045 head and neck cancer adverse events grading tool from the National Cancer Institute's Common Toxicity Criteria for Adverse Events over a period of 60 days. The control group showed a significant increase in palatal mucositis, xerostomia, and salivary changes compared to the study group.

Quantitative tumor volume VS TNM staging: the impact on prognosis in head and neck cancer.

OBJECTIVES: To evaluate the prognostic value of tumor volume (TV) by clinical method (CM) and Computerized Tomography (CT) scan in head and neck (H and N) cancer. MATERIALS AND METHODS: Total 25 patients' (pts) pretreatment tumor volume (PT TV) was assessed clinically by cuboid volume method. Afterwards contrast enhanced computerized tomography (CECT) images of the pts were transferred to workstation by DICOM software. The computerized tomography tumor volume (CT TV) was obtained on Radworks 6.0, using mouse control cursor. After assessment, the patients were given 3 cycles of neoadjuvant chemotherapy followed by radiotherapy by conventional method on Co-60 Theratron 780 C. After 1 month of treatment, TV was again measured. STATISTICAL METHOD: Statistical analysis was done on MSTAT statistical analysis software. Two-tailed student t test, chi square test and test for two proportions for significance had been used. RESULTS: Large variations in tumor volume were found both in intra as well as inter T-stages. As the tumor size increases with T stages, the difference in measurement of TV by both methods decreases. CT TV results pre as well as post-treatment were more consistent than clinical method. CONCLUSION: The use of TV as a prognostic factor by CT scan seems to be more useful parameter than the CM. TV should be included in the TNM (tumor, node, and metastasis) classification after setting the strict guidelines for tumor delineation, to solve the discrepancy of treatment outcome in the same clinical stage.

Expression profiling of G2/M phase regulatory proteins in normal, premalignant and malignant uterine cervix and their correlation with survival of patients.

BACKGROUND: Cell regulatory G2/M phase proteins are the key regulators of mitosis and have been reported with abnormal expressions in various malignancies. AIM: To determine the expressions of these proteins in neoplastic uterine cervix tissue. MATERIALS AND METHODS: This study evaluates the G2/M phase regulatory protein expression of Cyclin B1, Aurora-B, Pololike kinase 1 (PLK1) and LIM kinase1 (LIMK1) in tissues of 25 normal (control), 16 dysplastic (dysplasia) and 34 neoplastic (cancer) patients of uterine cervix. The expressions of different proteins were obtained by using Western Blot technique. STATISTICAL ANALYSIS: One way analysis of variance (ANOVA), Pearson correlation, Kaplan-Meier and other tests are used for analysis. RESULTS AND CONCLUSION: The level of expression of LIMK1 in cervical cancer patients was found to be significantly higher (P < 0.01) than both the controls and dysplasia. The expression of Aurora B and PLK1 in cervical cancer patients was also found to be significantly higher ( P < 0.05) than controls but it did not differ with dysplasia. However, the expression of Cyclin B1 was similar among cervical cancer patients, dysplasia and controls ( P> 0.05). The expression of all the above proteins showed significant ( P < 0.01) and inverse relation with the survival of cancer patients. Among the selected candidate proteins, it was LIMK1 that showed the most positive correlation with the aggressiveness of the disease and negative correlation (r= -0.64; P < 0.01) with the survival of patients.

Exploring new potentials and generating hypothesis for management of locally advanced head neck cancer: analysis of pooled data from two phase II trials.

BACKGROUND: To study the long term results of two phase II concurrent chemoradiotherapy protocols and conduct pooled data analysis with special emphasis on nodal density. MATERIALS AND METHODS: In the period from April 2001 to May 2003, phase II Mitomycin C (MMC) and late chemo-intensification (LCI) protocols were started in the same institute, enrolling 69 and 74 patients respectively. Long term results for these individual trials are reported along with pooled data analysis. RESULTS: Median follow-up time for whole group, MMC protocol and LCI protocol was 43.8 months (SD619.8), 55 months (SD 618.5) and 47.5 months (SD 620.9) respectively. LRFS, DFS and OS at five years for whole group was 59.4, 43.5 and 47.1% respectively, for MMC protocol was 59.9, 45.5 and 49.5% respectively and for LCI, protocol was 53.6%, 41.5% and 44.4% respectively. Subgroup analysis revealed that MMC protocol was more effective than LCI protocol in terms of DFS and OS in patients with hypo dense nodes while opposite was true for Isodense nodes. Multivariate analysis revealed nodal density as an independent variable that had an impact on treatment outcome. Risk of death in patients with hypo dense nodes was 2.91 times that of Isodense nodes. CONCLUSIONS: Innovative and pragmatic approach is required to address locally advanced head neck cancer. Long term results for MMC and LCI protocols are encouraging. Integrating the basic concepts of these protocols may help develop new protocols, which will facilitate the search for the optimal solution.

Ovarian adenocarcinoma in a young female with skin and umbilical metastasis.

We report the case of ovarian carcinoma with skin and umbilical metastasis in a 30-year-old female. The computed tomography (CT) scan of the abdomen showed a right ovarian mass with anterior abdominal wall metastasis. The CT-guided fine needle aspiration cytology (FNAC) from the ovarian mass showed adenocarcinoma. FNAC from the umbilical and skin metastasis also showed adenocarcinoma. Because of the unresectability of the mass, the patient was put on taxol-based chemotherapy, which she took for two cycles, and then died of progressive disease after three months.