Gene expression analysis of retinoblastoma tissues with clinico-histopathologic correlation Murali M S Balla, Rohini M Nair, Imran Khan, Ravi Kiran Reddy Kalathur, Santosh G Honavar, Javed Ali Mohammed, Paturu Kondaiah, Geeta K Vemuganti Journal of Radiation and Cancer Research 2019 10(2):85-95 Purpose: Retinoblastoma (Rb) is the most common intraocular malignant tumor, which is not only unique but also has unraveled many novel aspects of tumor-suppressor genes. Genetic mutations of Rb, loss of phosphorylation, and many other factors resulted in uncontrolled cell division of the retinal cells resulting in tumor progression. In this study, we have analyzed the gene expression patterns of unilateral tumors (n = 11) in comparison to the normal-appearing retina (n = 2) from Rb patients who underwent enucleation for advanced Rb. With recent advances in the knowledge of the role of stem cells in these tumors, it is important to evaluate and understand the self-renewal signaling involved in these tumors. Here, in this study, we particularly aimed at evaluating the aberrant self-renewal signaling pathways in human Rb tumors and genes which show differential expression in cases with and without histologic risk factors (HRF). Materials and Methods: Freshly unfixed eyeballs (n = 11) were obtained. Normal-appearing retinas were pooled together (n = 2) and used as a control for microarray experiments. Total RNA was isolated from tumors and control tissues, and expression of genes was evaluated by hybridizing to expression arrays. Using real-time polymerase chain reaction (PCR), the results, thus, obtained were validated (for expression of N-Myc, HMGA2, LIN-28b, and Activin receptor 1C [ACVR1C]) in tissues compared to two control retinas latter obtained from enucleated Rb eyeballs without tumor. Furthermore, immunohistochemistry (IHC) was done on retrospective (n = 19) cases to confirm the expression of ACVR1C. Results: In Rb tumors, 5593 genes were upregulated and 4864 genes were downregulated (P ≤ 0.05 and fold change ≥1.5 folds). Changes in N-Myc, HMGA2, LIN28b, and ACVR1C expression detected by microarray were validated by real-time PCR. The analysis shows significant up-regulation of HMGA2 and its downstream regulator LIN-28b, which is involved in self-renewal pathway of fetal neural stem cells. ACVR1C is one of the markers, which shows differential expression between histological subtypes of tumors as evident in IHC. CBLB (P ≤ 0.05) and MAPK 8 (P ≤ 0.05) were shown to be highly upregulated in tumors without HRF compared to cases with HRF. Conclusions: This study showed up-regulation of genes involved in neural stem cell self-renewal and marginally in notch signaling. While other stem cell pathways such as Wnt and sonic hedgehog (SHH) pathways were upregulated in these tumors. Targeting these self-renewal pathways would aid in eliminating the resistant cells in this tumor and thus may help in treating the recurrence. Genes such as CBLB, MAPK 8, and ACVR1C can be used as potential biomarkers in this tumor to prognosticate cases with or without HRFs and differentiation of the tumors.

The effect of breast phantom, and geometry on dose distribution in breast brachytherapy using the strut-adjusted volume implant and contura applicators Maryam Papie, Sedigheh Sina, Reza Faghihi Journal of Radiation and Cancer Research 2019 10(2):96-103 Context: Accelerated partial breast irradiation using brachytherapy is a postlumpectomy treatment to reduce cancer recurrence and a choice for people in the early-stage breast cancer. Although accurate dosimetry is necessary to obtain successful clinical outcomes, the usual commercial treatment planning systems use a simple water phantom to simulate the patient. Hence, the precise attenuated radiation and also the scattering effects occurred in real situations may be dosimetrically ignored. Aims: The purpose of this study is to use Monte Carlo simulation to obtain the effect of phantom material and geometry corrections on dose distribution of the strut-adjusted volume implant (SAVI) and Contura high-dose-rate brachytherapy applicators of breast cancer. Settings and Design: Contura with four lumens surrounding the central one and also SAVI with eight peripheral source channels are separately simulated into the breast phantoms. 192Ir high dose rate sources are located on dwell positions in each applicator. Subjects and Methods: The applicators were simulated inside three different phantom geometry and materials. The dose distribution and dose-volume histograms for each phantom were obtained for typical treatment. Gamma index evaluation is performed to examine the dose distribution according to the water phantom for each trial. Results: According to the results for SAVI and Contura applicators, breast material correction shows about 1% deviations from the calculations for water in most points of the breast. Maximum differences are not >3% that are found near the skin. Conclusion: Deviations from the water phantom in both SAVI and Contura treatments show good conformity especially in Contura and it seems that no serious dosimetric correction is necessary for simple water phantom. Although the results for SAVI were not observed with great deviations from water, areas with high-gradient dose need to be precisely considered.

Primary Central Nervous System Lymphoma: An Experience of a Regional Cancer Center from India Budhi Singh Yadav, Rohit Mahajan, Suresh Chander Sharma, Ankita Gupta, Shikhar Kumar Journal of Radiation and Cancer Research 2019 10(2):104-107 Background: Primary central nervous system lymphoma (PCNSL) is a rare malignant non-Hodgkin's lymphoma and it accounts for 1% of all intracranial tumors. Only a few PCNSL studies have been reported from India, and hence, we conducted the retrospective study in our institute to analyze the main clinical features at diagnosis and the treatment results in PCNSL. Materials and Methods: We retrospectively reviewed the medical records of 32 patients with PCNSL who were treated from 2003 to 2014. A complete history was recorded, and the physical examination included neurological assessment. Baseline investigations such as complete blood count, blood biochemistry, chest X-ray, HIV serology, and two-dimensional echocardiography were also done. Contrast-enhanced computed tomography (CT) of the brain or magnetic resonance imaging, positron-emission tomography (if affordable), cerebrospinal fluid (CSF) analysis for cytology, histopathological diagnosis (following stereotactic or open biopsy), CT of the thorax and abdomen, and bone marrow biopsy were done. All patients received whole-brain radiotherapy (WBRT) (36–50 Gy) followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen for six cycles. Clinical features and the treatment results were analyzed. Results: A total of 32 patients with PCNSL were studied. The median age was 50 years (range: 32–70 years). Male: female ratio was 2.5:1. All the 32 patients were histologically diffuse large B-cell lymphoma. The most common presenting symptom was headache in 20 (62.5%) patients. The area of involvement was mainly cerebral hemispheres in 22 (68.8%) patients. Multifocal involvement was seen in 22 (68.8%) patients. CSF cytology was negative in all patients. All patients received WBRT (36–50 Gy) followed by CHOP regimen for six cycles. All patients were compliant to radiation as well as chemotherapy. On a median follow-up of 18 months, the median overall survival was 14 months (range: 1–80). Conclusions: Breaking the blood–brain barrier with radiotherapy followed by CHOP chemotherapy results in reasonable outcome in patients of PCNSL, especially in the Indian setting where general built and tolerance is low- to high-dose methotrexate regimens. Newer chemotherapy regimens or targeted therapies need to be evaluated to further improve the survival.

In-house-developed phantoms for organ dose measurements using bovine tissues: A comparison study with CT-Expo simulation software Michael Onoriode Akpochafor, Akintayo Daniel Omojola, Rachel Ibhade Obed, Samuel Olaolu Adeneye, Oluwadare Joseph Adewa, Mary-Ann Etim Ekpo Journal of Radiation and Cancer Research 2019 10(2):108-116 Background: Estimating organ dose from computed tomography (CT) procedures is still ongoing. The aim is to reduce induced cancer risk associated with over dose. Aim and Objectives: The aim of this study was to estimate organ dose using CT-Expo software, to compare obtained values with thermoluminescent dosimeter (TLD) measurements from validated in-house phantoms, and to compare the CT-Expo results with other related studies. Materials and Methods: Four CT diagnostic centers denoted as A, B, C, and D were randomly selected for this study. A CT-Expo software (version 2.5 Germany) was used. A preliminary study was carried out to determine organ dose from the in-house phantoms using bovine tissues. The CT dose parameters used with the in-house phantoms were retrieved from the CT monitor and were used with CT-Expo worksheet to estimate organ dose as well. Results: The CT-Expo mean organ dose to the brain, eye lens, esophagus, and thyroid were 29.05 ± 10.78, 35.65 ± 15.1, 12.45 ± 10.13, and 4.25 ± 2.78 mGy, respectively; to the heart and lungs were 13.08 ± 9.84 and 11.5 ± 7.26 mGy, respectively; and to the liver, stomach, and kidney were 14.42 ± 9.07, 12.78 ± 7.97, and 11.73 ± 7.92 mGy, respectively. There was no statistically significant difference between the TLD measurements and CT-Expo (P = 0.361). The relative difference between CT-Expo and TLD measurements for brain, eye lens, heart, lungs, kidney, liver, and stomach were ≤21%. Investigated organ doses from the software were between 4.25 and 35.65 mGy. There was no difference in mean organ dose when compared to the studies in Thailand, Tanzania, Japan, USA (cadavers 1 and 2), and Nigeria. Conclusion: Large percentage differences were noticed in the thyroid and esophagus which was as a result of the software not recognizing them as organs in the head/neck but rather as organs in the chest; however, there was no difference in organ dose between the CT-Expo and TLD measurement from the in-house-validated phantom.

Radiographic assessment of protective aprons and dose simulation to personnel Akintayo Daniel Omojola, Michael Onoriode Akpochafor, Samuel Olaolu Adeneye, Ukeme Pius Aniekop Journal of Radiation and Cancer Research 2019 10(2):117-123 Background: Studies have shown that protective aprons are carelessly handled after working hours. This, in turn, leads to crack, tear, hole, and creases on the apron, which may lead to distortion in the attenuating property and hence reduction in efficiency. Aim and Objective: The aim of the study was to carry out the radiographic assessment of four protective aprons (denoted A–D), to check for tear, crack, or pressure marks and to simulate what the equivalent dose rate, dose/procedure, percentage absorbance, and transmission factor (TF) would be if a physician is to perform hysterosalpingogram (HSG), for which he/she will be averagely exposed twice/procedure. Materials and Methods: This study used a functional mobile X-ray unit, four protective aprons, a measuring tape, an electronic dosimeter and a locally designed phantom as materials. The first phase involved the radiographic exposure of the protective aprons. The second phase involved the use of a plastic phantom to produce scatter, a wooden T-stand to hold the apron, which was positioned 1.6 m diagonally from the X-ray collimator. This position was assumed to be where a physician would stand during the procedure. Results: Two out of the four aprons were defective (50%). One out of the four aprons was rejected because it exceeded the 670 mm[2] criteria for acceptance. The mean estimated dose/procedure was 65.69–347.56 μSv, and the estimated mean dose per year for 0.25, 0.35, and 0.50 mm protective aprons was 35,592, 9689, and 7900 μSv/year, respectively. TF for 0.25, 0.35, and 0.50 mm protective aprons was 20.4–23.2, 5.3–6.9, and 3.7%–6.3%, respectively. Absorbance for 0.35 and 0.50 mm protective aprons was ≥94%. There was no statistically significant difference in mean percentage absorbance for 0.25 mm protective aprons, compared to other studies (P = 0.981). Conclusion: Estimated equivalent skin dose per year to a physician with 0.25, 0.35, and 0.50 mm protective aprons was below 500 mSv/year, and the mean percentage absorbance for 0.25 mm protective aprons was seen to be below 90%.

High-dose rate surface mold brachytherapy in a case of squamous cell carcinoma of lower eyelid: A case report from a rural cancer center of Maharashtra Vandana Shailendra Jain, Vidyasagar Kushwah, P Waghmare Chaitali, B Sarje Mukund Journal of Radiation and Cancer Research 2019 10(2):124-127 Squamous cell carcinoma (SCC) of skin is an uncontrolled growth of cells of epithelium commonly seen in males in fifth to sixth decade of life. Risk factors include fair skin, blonde hair, exposure to sunlight (ultraviolet B), immunosuppression, human papillomavirus, and genetics. Surface mold brachytherapy (SMB) is a well-established treatment for early stage head and neck cancers involving accessible sites. It has evolved from the radium era to low-dose rate and now to high-dose rate intensity-modulated interventional brachytherapy. We present a 50-year-old male patient with squamous carcinoma of the left lower eyelid and was operated for the same. Histopathology was well-differentiated SCC with all positive margins. The patient was then treated by SMB and evaluated for toxicity, local control, and survival.