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January-March 2021
Volume 17 | Issue 1
Page Nos. 1-294

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REVIEW ARTICLES  

Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management Highly accessed article p. 1
Siddharth A Shah, Anand Shyamlal Gupta, Piyush Kumar
DOI:10.4103/jcrt.JCRT_488_18  
Cannabis was extensively utilized for its medicinal properties till the 19th century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug. Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors – cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol. Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system. Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss. THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals). Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer's disease), and alcohol addiction and hence should be exploited for potential benefits. The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.
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Role of intraluminal brachytherapy as a palliative treatment modality in unresectable cholangiocarcinomas p. 10
Kiran Chigurupalli, Apoorv Vashistha
DOI:10.4103/jcrt.JCRT_836_19  
Cholangiocarcinoma, a primary malignant tumor of the bile ducts mainly originates from cholangiocytes. The incidence of biliary tract tumours is high in Asian countries, mainly in Thailand, India, Japan and Korea. These tumor relapse frequently and can metastsize to distant organs. Biliary stenting either by percutaneous transhepatic biliary drainage is widely used procedure used to attain symptomatic relief. Radiation therapy can be used to prevent the tumor growth in or surrounding the stent, maintaining its patency. External beam radiation therapy and intraluminal brachytherapy are the two methods by which tumoricidal doses could be delivered. Intraluminal brachytherapy can help in delivering high to the tumor while not exceeding the normal tissue tolerance of surrounding organs. In the present article we try to emphasize on the role of intra luminal brachytheraphy for palliation in advanced unresectable cholangiocarcinomas.
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Rare mediastinal masses – imaging review p. 13
Sujata Patnaik, Amaresh Rao Malempati, Megha Uppin, Rammurti Susarla
DOI:10.4103/jcrt.JCRT_587_19  
Mediastinal masses span a wide histopathological and radiological spectrum. Apart from primary thymic/thyroid masses and lymphomas, all other mediastinal masses can be considered rare tumors. Chest radiography and Computed tomography (CT) are helpful to characterize the mass and can reach a diagnosis or a close differential diagnosis. MRI in special situations can depict the pericardial/vascular invasion better, and diffusion studies can recognize benign from the malignant mass. The imaging details of 15 histopathologically proven cases of rare mediastinal tumors are described. Neuroblastoma (NB) (n = 3) was the most common among the rare masses. Three were sarcomas, one liposarcoma, one synovial sarcoma, one spindle-cell tumor and one Hemangiopericytoma (HPC). Lymphoma presenting as a single mass, neuroendocrine tumor (NET) of the anterior mediastinum, paraganglioma of the posterior mediastinum (one each) were seen.The imaging features of these rare mediastinal masses have to be kept in mind for appropriate diagnosis.
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Oxidative stress and its role in cancer Highly accessed article p. 22
Marija Dragan Jelic, Aljosa D Mandic, Slobodan M Maricic, Branislava U Srdjenovic
DOI:10.4103/jcrt.JCRT_862_16  
Reactive oxygen species (ROS) can damage lipids, nucleic acids, and proteins, thereby altering their functions. When a balance between production of ROS and antioxidative defense is disturbed, state of oxidative stress occurs. Oxidative stress leads to many diseases. There are few biomarkers that are used for better understanding how oxidative stress is involved in cancer pathophysiology. This review focuses on 8-hidroxy-2-deoxyguanosine (8-OHdG) and antioxidative enzymes as biomarkers for measurement of oxidative stress in different types of cancer. This review also deals with the product of lipid peroxidation, malondialdehyde (MDA), and across a variety of cancers. To address this aim, analysis of studies of breast, prostate, lung, colon, cervical, ovarian, brain, bladder, renal, thyroid cancer, and chronic lymphocytic leukemia has been conducted. In general, levels of antioxidative enzymes are mostly lower in cancer patients, while 8-OHdG and MDA are higher. Further research is needed, with focus on correlation levels of these biomarkers and advancement of the disease. Moreover, all studies explored the idea of those biomarkers as a useful tool in determining the levels of oxidative stress. Some of the studies proposed their potential in defining the stage of tumor progression.
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Deciphering the “Collagen code” in tumor progression Highly accessed article p. 29
Archana Anshuman Gupta, Supriya Kheur, Sangeeta J Palaskar, Bindiya R Narang
DOI:10.4103/jcrt.JCRT_489_17  
Invasion and metastasis are the fundamental properties of tumor biology and the root causes of cancer death. With the elucidation of genetic and epigenetic mechanisms, it has been postulated that cancer is a disease of imbalance. It is not merely a disease of tumor cells but also the body's mismanagement of those tumor cells. Tumor microenvironment plays an important role in tumor progression via the co-evolution of tumor cells and tumor stroma. Hence, exploring the complex mechanisms of tumor progression from perspectives of tumor stroma has become a new frontier. The major component of tumor stroma, the extracellular matrix (ECM), acts as a key regulator of cell and tissue function. Conventionally, the role of ECM was considered primarily as a physical scaffold that binds cells and tissues together. However, recent studies revealed the biochemical and biophysical signaling properties of the ECM as well that affect cell adhesion and migration, tissue morphogenesis and repair, and angiogenesis and cancer. The most abundant constituent of ECM, collagen, accounts for the major function of ECM, which can be associated with increased malignancy. The present review summarizes the dynamic interplay between collagen and tumor cells. It focuses on changes in physicochemical-biological properties of collagen. A new paradigm has been formulated that collagen can no more be considered playing a passive role over which tumor progression and metastasis takes place. Rather, its active role in the promotion of tumor progression and metastasis should be explored.
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ORIGINAL ARTICLES Top

Cancer in patients of and above 90 years: A hospital-based retrospective study p. 33
Amal Chandra Kataki, Jagannath Dev Sharma, Manoj Kalita, Nizara Baishya, Mouchumee Bhattacharyya, Manigreeva Krishnatreya
DOI:10.4103/jcrt.JCRT_28_18  
Background and Objective: Cancers in a nonagenarian patient are rarely seen, and there is always a moral dilemma for the family members and patient of whether to opt for the treatment or not. The main objective was to identify the survival differences between treated and not treated nonagenarian cancer patients. Materials and Methods: This was a retrospective study of Hospital-Based Cancer Registry data from 2010 to 2016. The data of all nonagenarian cancer patients were analyzed for gender distribution, leading sites of cancer, stage distribution, types of treatment received, and survival. The survival was calculated from the date of the first diagnosis. Kaplan–Meier analysis was done to present the survival. Results: Of 60,087 patients, 146 (0.2%) patients were of 90 years and above. Hypopharynx in males (20.5%) and tongue (20.5%) in females were the top cancer sites, 60% patient data were in Stages III and IV, 37 (25.3%) patients received treatment, and 86% patients were treated by radiotherapy. The overall survival (OS) was 14.3%. OS in the treatment group was 21.3% versus 7.7% (P = 0.001) in the no treatment group. The unadjusted hazard ratio for no treatment group was 3.8 (P = 0.003, confidence interval = 1.5–9.7). Conclusion: Selected nonagenarian cancer patients from our population with a good performance status should receive curative treatments in all possible ways.
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Human apoptosis antibody array-membranes studying the apoptotic effect of marine bacterial exopolysaccharides in HepG2 cells p. 38
Salma M Abdelnasser, Shaymaa M M. Yahya, Wafaa F Mohamed, Magdy A Gadallah, Hala M Abu Shady, Manal G Mahmoud, Mohsen M S. Asker
DOI:10.4103/jcrt.JCRT_391_19  
Background: Hepatocellular carcinoma (HCC) is considered as the third leading cause of cancer-related deaths, in spite of great advances in its treatment. The carbohydrate polymers, exopolysaccharides (EPSs), showed anticancer activity in diverse cancers. Objective: The purpose of this study is to investigate a panel of 43 apoptotic proteins to assess the possible apoptotic induction effect of bacterial EPSs showing promising cytotoxic effects in HepG2 cells in our previous study, in an attempt to introduce exopolysaccharides as new source for cancer treatment. Materials and Methods: Apoptosis-related proteins panel were examined through the analysis of Human Apoptosis Antibody Array-Membrane (43 targets). Results: EPS-6 induces apoptosis through upregulation of different pro-apoptotic proteins as cytochrome C (9.52 fold) and tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R1) (153.49 fold). EPS-RS induces apoptosis through up regulation of second mitochondria-derived activator of caspases (SMAC) (15.75 fold) and the six insulin-like growth factors binding proteins (IGFBP-1 through – 6) (76.81 fold, 7.68 fold, 55.15 fold, 4.9 × 107 fold, 29.69 fold, and 28.92 fold), respectively. Conclusion: Our results suggested that EPS-6 and EPS-RS could be considered as promising agents in hepatocellular carcinoma treatment.
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Evaluation of newly identified Ikaros family zinc finger 1 loci in colorectal cancer p. 46
Bhanu Sharma, Ruchi Shah, Rajeshwer Singh Jamwal, Sonali Verma, Amrita Bhat, Gulam Rasool Bhat, Divya Bakshi, Supinder Singh, Shabab Angurana, Audesh Bhat, Samantha Vaishnavi, Rakesh Kumar
DOI:10.4103/jcrt.JCRT_844_20  
Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). Materials and Methods: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. Results: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34–2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011–4.76) at 95% CI, P > 0.05. Conclusions: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.
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Outcomes of patients with anal cancer treated with volumetric-modulated arc therapy or intensity-modulated radiotherapy and concurrent chemotherapy p. 51
Serap Yucel, Huseyin Kadioglu, Zeynep Gural, Zuleyha Akgun, Esra Kaytan Saglam
DOI:10.4103/jcrt.JCRT_774_16  
Aims: To evaluate the results of chemoradiation with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) for the treatment of anal canal cancer patients at three institutions that had advanced devices. Materials and Methods: A retrospective analysis was performed for patients treated with 5-fluorouracil and mitomycin-based chemotherapy and IMRT or VMAT for anal cancer from 2011 to 2013. Complete response (CR) rates, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and toxicities were investigated. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, Version 3.0. Results: Fifteen patients were included in the analysis. The majority of patients had T2 (53.3%) and N0 (40%) disease according to the staging system that was developed by the American Joint Committee on Cancer. CR was observed in 14 patients (93%), and the median follow-up was 26 months (13–42 months). The 3-year CFS, DFS, and OS were 86%, 86%, and 88%, respectively. Acute Grade 3 toxicities were observed as 6% of hematological, 26% of gastrointestinal, and 26% of dermatological. Conclusion: Early results confirm that IMRT or VMAT for anal cancer treatment reduces acute toxicities while maintaining high control rates.
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A comparison of radiotherapy treatment planning techniques in patients with rectal cancers by analyzing testes doses p. 56
Evrim Duman, Yılmaz Bilek, Gokay Ceyran
DOI:10.4103/jcrt.JCRT_328_19  
Purpose: To evaluate the target volume (TV) and critical organ doses with priority of testes with the comparison of conformal radiotherapy (CRT), dynamic intensity-modulated radiotherapy (DIMRT), and volumetric modulated arc therapy (VMAT) techniques. Materials and Methods: CRT, DIMRT, and VMAT techniques were generated on computed tomography images in prone position of 10 male patients with distal rectal cancer. Conformity index (CI), heterogeneity index (HI), treatment time, and monitor units were examined; dose-volume-histograms (DVHs) for the TV and the organs at risk (OARs) were evaluated. Results: Target dose coverage of all treatment plans was similar. HI and CI values for DIMRT and VMAT were closer to “1” compared to CRT. DVH parameters for OARs were decreased with DIMRT and VMAT compared to CRT. The percent volume (Vx) of 3 Gy dose of testes was 62.01% (±25.45%), 42.68% (±16.42%), and 35.89% (±14.97%) in the CRT, DIMRT, and VMAT techniques, respectively. V3 of testes decreased with VMAT compared to CRT and DIMRT (P = 0.008 and P = 0.051, respectively). Conclusion: Modern radiotherapy techniques are superior to conformal techniques in planning quality parameters and sparing OARs. DIMRT and VMAT could be considered instead of CRT in the desire to preserve fertility of patients with rectal cancer.
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In vitro cytotoxicity of cardamom oil, lemon oil, and jasmine oil on human skin, gastric, and brain cancer cell line Highly accessed article p. 62
Chetan Manjunath, Nitin Mahurkar
DOI:10.4103/jcrt.JCRT_915_17  
Objective: The main objective of the study was to evaluate the cytotoxicity of selected essential oils on human skin, gastric, and brain cancer cell lines using microculture tetrazolium test. Materials and Methods: Phytochemical analysis, as well as acute oral toxicity tests, was carried out in female albino mice with cardamom oil, lemon oil, and jasmine oil according to the Organization for Economic Co-operation and Development guidelines 425. Anticancer activities of the above test drugs were performed using human cancer cell lines. The studies were carried out at Skanda Life Sciences Pvt. Ltd., Bengaluru. Results: Phytochemical analysis has shown the presence of carbohydrates and flavonoids in cardamom oil. While lemon oil has shown the presence of carbohydrates, flavonoids, steroids, terpenoids, and tannins, jasmine oil has shown the presence of carbohydrates, alkaloids, flavonoids, steroids, terpenoids, and glycosides. Toxicity studies showed that cardamom oil, lemon oil, and jasmine oil were all found to be safe up to 2000 mg/kg body weight. Results have shown that lemon oil exhibited the strongest cytotoxicity toward three human cancer cell lines, namely skin cancer (A431), gastric cancer (MKN-45), and brain cancer (U-87 MG) cell lines, with higher IC50 values of 62.82 μg/ml, 220.9 μg/ml, and 440.1 μg/ml compared to standard. Jasmine oil exhibited the strongest cytotoxicity toward skin cancer and brain cancer cell lines, whereas cardamom oil has shown stronger cytotoxicity only toward skin cancer cell line but did not show any level of inhibition of growth of brain and gastric cancer cells. Conclusion: Our study reveals that lemon oil, jasmine oil, and cardamom oil possess potent antitumor activity compared to standard. At different concentrations, lemon oil has shown statistically significant (***P < 0.0001) anticancer activity toward all the three human cancer cell lines. While jasmine oil has shown statistically significant (***P < 0.0001) anticancer activity toward skin and brain cancer cell line, cardamom oil has also shown statistically significant (***P < 0.0001) anticancer activity but only toward skin cancer cell line.
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The role of volumetric method in the assessment of chemotherapy response and predicting survival in malignant pleural mesothelioma p. 69
Furkan Erturk Urfali, Selma Metintas, Atila Gurgen, AK Guntulu, Ragip Ozkan, Muzaffer Metintas
DOI:10.4103/jcrt.JCRT_217_19  
Background: Malignant pleural mesothelioma (MPM) is a pleural tumor with high mortality rate and short-term survival expectancy after diagnosis. Assessment of the response to chemotherapy, which is the first choice in treatment of MPM, is important for the transition to alternative chemotherapy protocols and immunotherapy. There is no clarity in the response to chemotherapy treatment. Objective: Our study aims to compare the assessment of chemotherapy response using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and volumetric measurements and to correlate with median survival. Materials and Methods: Thirty-two patients (16 females and 16 males) were included in the study, and their ages ranged from 28 to 78 years. Chemotherapy response was determined by both mRECIST and volumetric approach. Tumor volume was measured by linear interpolation and semi-automatic segmentation. Log-rank multiple cutoff analysis was used to determine appropriate cutoff values of volumetric response criteria. Results: According to both mRECIST and volumetric approach, median survival times in partial response, stable disease, and progressive disease groups were 24, 15, and 9 months, respectively. The survival times of the three groups were different (logrank: 17.76; P < 0.001) by mRECIST. The survival of the progressive disease group was shorter than that of the other groups (logrank: 18.91; P < 0.001) by volumetric approach. Conclusions: In the assessment of chemotherapy response, even though classifications obtained according to the mRECIST criteria and volumetric measurements are statistically compatible, we think that the measurement of the volumetric values will increase the standardization. In our study, threshold values for volumetric measurements were determined; however, these values should be supported by large-scale multicenter studies.
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Systemic treatment options for growing teratoma syndrome: A single-center experience with a comprehensive review of the literature p. 75
Yusuf Acikgoz, Oznur Bal, Yakup Ergun, Berna Oksuzoglu, Birol Yildiz, Mutlu Doğan
DOI:10.4103/jcrt.JCRT_568_19  PMID:33328389
Background: Growing teratoma syndrome (GTS) is a very uncommon phenomena. Given its lower prevalence, there is little data about clinichopathological features and management of GTS. Literature about disease mostly composed of case reports. In this study, we aimed to report patients characteristics and treatment modalities in our center within a relatively large cohort. Patients and Methods: We retrospectively reviewed the clinical records 21 patients who fulfilled criteria of GTS. Survival analysis was performed by using the Kaplan-Meier method with the Long-rank test. p<0.05 was considered statistically significant. Results: The median age at diagnosis was 25 (range 17-51). A total of 12 patients could have undergone surgery. Of patients who underwent surgery, 5 patients remained fully disease free, and 7 patients had experienced disease recurrences. Nine patients had unresectable disease, and treated with either platin-based chemotherapy or interferone α2b. Of those, 5 patients eventually had undergone autologous stem cell transplantation (ASCT) with surprisingly promising response rates. One patient had complete response and three patients had partial response. One patient died soon after ASCT due to infectious complication. Conclusion: GTS is an unique entity with regard to its clinicopathological features and available treatment options as we mentioned in the text. Despite various agents reported to have efficacy in case reports, surgery remains as the mainstay of treatment. According to result of our study, ASCT and platin-based chemotherapy regimens may be feasible options for patients with unresectable disease.
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Dosimetric comparison of single-arc/partial-arc volumetric modulated arc therapy and intensity-modulated radiotherapy for peripheral and central lung cancer p. 80
Melek Akcay, Durmus Etiz, Kerem Duruer, Ozge Bozdogan, Alaattin Ozen
DOI:10.4103/jcrt.JCRT_221_19  
Aim: The aim of this study is to compare the differences between intensity-modulated radiotherapy (IMRT) and single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in locally advanced-stage non-small cell lung cancer (NSCLC). Materials and Methods: Locally advanced 22 patients with NSCLC were evaluated retrospectively. Each patient underwent radiation therapy with either IMRT or SA-VMAT or 2PA-VMAT technique. Homogeneity index, conformity number, and dosimetric parameters were evaluated. Results: Ten peripheral and 12 central lung tumors were evaluated. In the entire patient group, tV5-10-60, total mean lung dose (tMLD), iV5-10-30-50-60, iMLD, and esophagus Dmean and Dmax were lower in IMRT technique, cV5-10-20-30, kMLD, and medulla spinalis Dmax were lower in PA-VMAT technique, whereas iMLD is the highest in the SA-VMAT technique. In peripheral tumors, tV5-10-60, iV5-10-20-30-40-60, iMLD, and esophagus Dmean were lower in IMRT technique and kV5-10 was lower in the 2PA-VMAT technique. In central tumors, tV5-10, tMLD, iV5-60, iMLD, and esophagus Dmean and Dmax were lower in IMRT technique, whereas cV10-20 and medulla spinalis Dmax were lower in 2PA-VMAT, and all contralateral lung doses are high in the SA-VMAT technique (all P < 0.05). Conclusion: IMRT and VMAT techniques have different advantages in locally advanced lung cancer, and the use of those two techniques as a hybrid can provide a single collection of these advantages.
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“Christie Regimen” palliative radiotherapy in advanced head-and-neck cancer: A single-center experience p. 88
Anurita Srivastava, Narayan Adhikari, Deepak Raj Sonkar, Kishore Singh, Arun Kumar Rathi
DOI:10.4103/jcrt.JCRT_229_20  
Background: Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes. Aims and Objectives: To assess the outcomes of hypofractionated “Christie” palliative radiotherapy regimen in advanced HNSCC Materials and Methods: Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria. Results: Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 – 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 – 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization. Conclusion: Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting.
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The esophageal dose–volume parameters for predicting Grade I–II acute esophagitis correlated with weight loss and serum albumin decrease in lung cancer radiotherapy p. 94
Zumrut Arda Kaymak Cerkesli, Emine Elif Ozkan, Alper Ozseven
DOI:10.4103/jcrt.JCRT_410_19  
Introduction: Acute esophagitis (AE) is a commonly encountered side effect of curative thoracic radiotherapy (CTRT) for lung cancer patients. Nevertheless, its identification for widely used scoring systems depends on patients' statements. It is aimed to evaluate the correlation between the esophagus doses during CTRT and Grade 1–2 AE, weight change, and change in serum albumin (Alb) levels. Subjects and Methods: The data collected from 124 lung cancer patients treated with ≥60 Gy CTRT were evaluated retrospectively. Weight and serum Alb level difference of each patient, throughout CTRT, were calculated. The percentage of the esophagus volume receiving ≥5 Gy (V5), V10, V35, V50, and V60; the absolute esophagus volume receiving ≥60 Gy (V60(cc)); the length of esophagus receiving ≥60 Gy (L60); the average esophagus dose (Dmean); and the maximum esophagus dose (Dmax) were the dose parameters calculated. The correlations were performed by Spearman's rank correlation coefficient. Results: Grade 1 and Grade 2 AE were reported in 62 and 25 patients, respectively. All of the dose parameters were correlated with Grade 1–2 AE (P < 0.001) and weight loss (P < 0.001 for all, except Dmax P = 0.018). Decrease in serum Alb level was significantly correlated with all the parameters, but V5 and V10. Receiver operating characteristic curve analysis was performed for five parameters with the highest correlation coefficient (V35, V50, V60(%), V60(cc), and Dmean), and the cutoff values were 39.5%, 28.17%, 2.21%, 0.5cc, and 26.04 Gy, respectively. Conclusions: The correlation of the dose parameters that might be effective on Grade 1–2 AE with the weight loss and Alb loss was investigated, and the cutoff values corresponding to the best sensitivity and specificity were identified.
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Hippocampal sparing for brain tumor radiotherapy: A retrospective study comparing intensity-modulated radiotherapy and volumetric-modulated arc therapy p. 99
Gulsen Pinar Soydemir, Nazli Bilici, Elif Eda Tiken, Ayben Yentek Balkanay, Ali Firat Sisman, Didem Karacetin
DOI:10.4103/jcrt.JCRT_32_19  
Context: Radiotherapy may have side effects on the brain, such as radiation necrosis, cognitive impairment, and a high chance of tumor recurrence, which has been considered the most common cause of treatment failure. Aims: Using intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques, we aimed to test the potential outcome of sparing the contralateral hippocampus (CLH) in radiotherapy for brain tumors by comparing dosimetric parameters. Settings and Design: A prospective clinical comparative study. Subjects and Methods: Using IMRT and VMAT, sparing CLH in radiotherapy of brain tumors was tested in ten patients, and various dosimetric parameters were compared. The treatment plans were accepted only if they met the set of planning objectives defined in the protocol. Results: The dose delivered to 95% of the CLH volume (CLH D95), and the mean (CLH Dmean) and max (CLH Dmax) doses were found to be significantly highest in the standard IMRT (P = 0.002, <0.001, and < 0.001, respectively). The lowest CLH D95, CLH Dmean and CLH Dmax for the hippocampus were detected in sparing VMAT planning than in the other plans (P < 0.05). None of the post hoc comparisons for CLH D95 was different among any of the plans, whereas the mean dose to CLH was statistically different among all paired comparisons (P < 0.008). The maximum dose to CLH was also statistically different among all paired plans (P < 0.008), except the dose difference between standard VMAT and IMRT plans. Conclusions: Although VMAT planning is troublesome and time-consuming, the advantage of sparing the hippocampus is beneficial, preserving the hippocampus and cognitive functions during radiotherapy.
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Malignant peripheral nerve sheath tumor with analysis of various prognostic factors: A single-institutional experience p. 106
Mohit R Sharma, Ketul Sureshbhai Puj, Abhijeet A Salunke, Shashank J Pandya, Jahnavi S Gandhi, Ankita R Parikh
DOI:10.4103/jcrt.JCRT_854_19  
Context: Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft-tissue sarcoma. Aims: The aim of this study was to analyze various prognostic factors and treatment outcome of patients with MPNST. Settings and Design: This was a retrospective study. Subjects and Methods: Ninety-two patients, who presented with MPNST at a tertiary care cancer center from 2011 to 2018, were included in this study. The median follow-up of all living patients was 33 months. Neurofibromatosis 1 (NF1) was seen in 12 (13%) patients. Sixty (65.2%) patients received curative-intent treatment. Statistical Analysis Used: Kaplan–Meier method was used for survival analysis. Log-rank test was used for univariate analysis, and multivariate analysis was done by Cox proportional hazard ratio method. Results: The 5-year overall survival (OS) of all patients was 47.2% and the 5-year disease-free survival (DFS) of operated patients was 41.5%. On univariate analysis, association with NF1 (P = 0.009), grade (P = 0.017), and margin status (P = 0.002) had a significant effect on DFS, whereas association with NF1 (P = 0.025), metastatic disease on presentation (P < 0.0001), palliative intent of treatment (P < 0.0001), grade (P = 0.049), and margin status (P = 0.036) had a significant effect on OS. On multivariate analysis for patients who were treated with curative-intent treatment, grade (P = 0.015), and margin status (P = 0.028) had a significant effect on DFS, whereas association with NF1 (P = 0.00026) and location of tumor (P = 0.040) had a significant effect on OS. Conclusions: The presence of distant metastasis, palliative intent of treatment, association with NF1, location of the tumor in the head and neck, high tumor grade, and positive margin status were the risk factors associated with poor survival for the patients with MPNST. Wide local excision with negative resection margin is the highly recommended treatment.
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Translational relevance of baseline peripheral blood biomarkers to assess the efficacy of anti-programmed cell death 1 use in solid malignancies p. 114
Hrishi Varayathu, Vinu Sarathy, Beulah Elsa Thomas, Suhail Sayeed Mufti, Lalram Sangi, Satheesh Chiradoni Thungappa, Priyank Tripathi, Radheshyam Naik
DOI:10.4103/jcrt.JCRT_910_20  
Background: This study is an overall clinical analysis of anti-programmed cell death 1 (PD1) antibodies used in a single institution, emphasizing the role of baseline peripheral blood markers as a prognostic or predictor biomarker of immunotherapy. Methods: Sixty-one patients were retrospectively analyzed from hospital medical records. The endpoint of this study was death from any cause and the survival time was calculated from the date of start of immunotherapy to the date of death. Descriptive and survival statistics was performed using SPSS version 23. Cutoff values for baseline biomarkers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NER], and lymphocyte-to-monocyte ratio [LMR]) were obtained using cutp function of Evaluate Cutpoints software (R survMisc package). Pearson and Pearman correlation coefficients were used to examine the relationship of peripheral blood biomarkers. Results: Nighty-eight percent of the study population had Stage IV disease and total median overall survival postanti-PD1 therapy was 10.7 months. Patients receiving more than 5 doses of anti-PD1 therapy (12.6 m vs. 4.4 m, P < 0.001) and used in front lines (18.9 m vs. 10.7 m vs. 10.1 m vs. 2.8 m in first line, second line, third line, and >3 lines, respectively, P = 0.049) were found to have an impact in overall survival. Pembrolizumab showed a better survival compared to nivolumab (17.4 m vs. 8.2 m, P = 0.049) in our study. Among baseline biomarkers assessed, NLR (cutoff − 2.81, P = 0.003) and LMR (cutoff – 5.76, P = 0.017) has shown a statistically significant relationship with immunotherapy response. NER (cutoff − 24.32, P = 0.051) and PLR (cutoff – 190.8, P = 0.072) were also found to exhibit a strong relationship with anti-PD1 therapy response. NLR exhibits a statistically significant positive correlation with PLR (r = 0.917 P < 0.001) and NER (r = 0.400 P = 0.014). Conclusion: Real-life data analysis of anti-PD1 use for solid cancers highlights that baseline NLR, PLR, NER, and LMR have a significant role as immunotherapy biomarkers. However, larger studies are required to further prove the specificity and sensitivity.
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Anticancer potential of ascorbic acid and inorganic selenium on human breast cancer cell line MCF-7 and colon carcinoma HCT-116 Highly accessed article p. 122
Magdah A Ganash
DOI:10.4103/jcrt.JCRT_989_17  
Background and Objectives: Till now, cancer is a major health problem and one of the main causes of mortality worldwide. Ascorbic acid and selenium are the two most popular dietary supplements used to prevent cancer proliferative, therefore, the work aims to study the antitumor effect of ascorbic acid and selenium on HCT116 and MCF7 cell lines. Materials and Methods: In the present study, the cytotoxic effect of different concentrations of ascorbic acid and selenium on human breast cancer cell line (MCF7 cells) and human colon carcinoma (HCT116) was studied. Results: Viability % of HCT116 cell line and MCF7 cell line decreased with increasing ascorbic acid concentrations (1–4 mM). The 50% inhibitory concentration (IC50) of five dilutions of each concentration of ascorbic acid was evaluated in the current study. IC50 was 0.18, 0.17, 0.16, and 0.16 mM for HCT116 cell line and was 0.86, 1.34, 1.74, and 0.47 mM for MCF7 cell line at 1, 2, 3, and 4 mM, respectively. Cell viability decreased depending on the selenium concentrations ranging from 20 to 100 mM. Selenium effect showed less cytotoxicity on MCF7 compared to HCT116 cells at all tested concentrations where the cell viability at 20, 40, 60, 80, and 100 mM selenium was 33.74, 29.48, 26.08, 54.53, and 20.89 for HCT116 cell and was 79.53, 76.01, 59.42, 54.53, and 51.98 for MCF7 cell, respectively. Ascorbic acid induced apoptosis by promoting the release of lactate dehydrogenase (LDH) in HCT116 and MCF7 cells, but reduced release of LDH was observed in selenium treatment but increased when it added to ascorbic acid because of a possible synergistic action that may produce an enhanced anticarcinogenic effect. Conclusion: The present study documented that a combination of ascorbic acid and selenium produces an additive chemopreventive effect on carcinogenesis.
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Super-selective intra-arterial platinum-based chemotherapy concurrent with low-dose-rate plaque brachytherapy in the treatment of retinoblastoma: A simulation study p. 130
Hesameddin Mostaghimi, Foad Goli Ahmadabad, Hadi Rezaei
DOI:10.4103/jcrt.JCRT_340_19  
Objective: Retinoblastoma is the most common cancer among children under 5 years of age. The common conventional methods for the treatment of retinoblastoma include chemotherapy and brachytherapy (BT). This study investigated the concurrent use of BT with 125I and 103Pd sources and chemotherapy with platinum-based chemotherapy drugs for retinoblastoma. Materials and Methods: The absorbed doses in different parts of the eye were measured with and without platinum. Platinum concentrations of 5, 7.5, 10, and 15 mg/g were evaluated, and the dose enhancement factors (DEFs) were calculated for different cases. Results: For the 125I source, the DEFs at the tumor apex were 1.49, 1.67, 1.81, and 1.97 at concentrations of 5, 7.5, 10, and 15 mg/g, respectively. The DEF decreased dramatically beyond the apex at 0.85 cm from tumor base and was 0.87, 0.82, 0.76, and 0.63 for the abovementioned concentrations, respectively. For the 103Pd source, the DEFs were 1.15, 1.24, 1.21, and 1.07, respectively, at the apex and 0.76, 0.65, 0.56, and 0.39, respectively, beyond the apex. Conclusions: Our results showed that the concurrent use of low-dose-rate plaque BT and platinum-based chemotherapy significantly increased the tumor-absorbed dose and decreased the absorbed dose in areas outside the tumor and the treatment time.
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Herbal supplement usage among cancer patients: A questionnaire-based survey p. 136
Thirunavukkarasu Kanimozhi, Kalluru Hindu, Yuvaraj Maheshvari, Y Gulab Khushnidha, Mahendrian Kumaravel, K Satish Srinivas, M Manickavasagam, Kalachaveedu Mangathayaru
DOI:10.4103/jcrt.JCRT_612_18  
Background: Herbal supplements (HS) are one of the most commonly used complementary and alternative medicines in cancer. Reduced therapeutic efficacy of prescription anticancer agents through unwarranted herb–drug interactions is a major efficacy/safety concern. In view of the rising cancer prevalence in India along with a high degree of reliance and cultural acceptability in favor of traditional medicine drugs, prevalence data exclusively of HS usage during cancer treatment are of considerable epidemiological significance. Methodology: This questionnaire-based prospective observational study aimed at estimating the prevalence of HS among cancer patients during treatment at our tertiary care medical center. Taken on a population of 220 patients within a period of 9 months, data were generated by a customized validated questionnaire and the same processed by IBM SPSS Statistics for Windows, version XXIV, Armonk, NY: IBM Corp. Differences between HS use and nonuse with respect to demographic, disease, and treatment characteristics were assessed by Chi-square test. For examining the latter variables as possible predictors of HS usage, they were entered into bivariate logistic regression with odds ratio and confidence intervals calculated for each. Results: Out of 220 patients, 57 (26%) were HS users and 163 (74%) were nonusers. Majority of the users (42.1%) were on self-prepared folklore herbal medicine postdiagnosis of cancer (57.9%), the most common reason cited being symptom palliation (35.1%) on the advice of friends and family (64.9%). Fear of disapproval was the most common reason cited (68.4%) for not disclosing HS usage to the physician. Conclusion: Chemotherapy and unemployment are predictors of HS usage, and there is a significant association between occupation status and HS usage. This first study on HS prevalence among South Indian population proposes the need for a more robust evidence base for understanding all aspects of HS use in cancer.
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Optimal time management on linear accelerator: A logical model to reduce patient waiting time p. 142
Avinash H Udayashankar, Shibina Noorjahan, Nirmala Srikantia, Ravindra Babu Kamunuri, Niranjan Immanuel, Sandeep Muzumder, SH Chandramouli, Mazhar H Shariff
DOI:10.4103/jcrt.JCRT_841_18  
Introdction: Optimal time management is of utmost importance in the radiotherapy department. Inappropriate allocation of time slots leads to prolonged waiting times and decreased patient satisfaction during external beam radiotherapy. The present study tests a logical model to improve the waiting time for the patients. Materials and Methods: The treatment time, waiting time, and causes of delay were studied from November 4, 2014, to July 24, 2015. New rules were framed for treatment slot allocation from December 26, 2014. The treatment slots were classified based on the treatment technology (three-dimensional conformal radiotherapy and intensity-modulated radiotherapy) with inclusion of “buffer slots” and patient education. The results were compared before and after rules. Results: A total of 1032 time slots were analyzed, of which 225 “before rules” and 807 “after rules,” respectively. There was a significant reduction in the average waiting time for treatment in on-time patients (median [interquartile range (IQR)] of 25.2 min [31.75] vs. 3 min [3.5]; P< 0.00001) as well as in late-coming patients (median [IQR] of 38.2 min [13.795] vs. 21.11 min [12.75]; P= 0.00006). 59.7% (71 patients) of the treatment was delayed “before rules” as opposed to 32.2% (137 patients) “after rules” in on-time patients. Due to better patient education, there was a significant improvement in the patient punctuality toward the allotted time. Conclusion: The treatment slots classified based on the teletherapy technique with buffer slots, and patient education helps in better time management on linear accelerator. This methodology significantly reduces waiting time and thereby the number of patients having delay in the treatment.
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Implementation of a visual feedback system for motion management during radiation therapy p. 148
Jamema Swamidas, John Rose, Supriya Chopra, Siji N Paul, Kishore Joshi, Subhajit Panda, Reena Ph, Jai Prakash Agarwal
DOI:10.4103/jcrt.JCRT_95_18  
Purpose: To describe the details of an in-house video goggles feedback system assembled from several commercially available components. The objective of this paper is to share our experience with this system, provide details on the equipment needed, system assembly, patient set up and user settings on some components. Materials and Methods: The system consisted of goggles (FPView3DHD, ITV, USA), RJ45(Registered Jack) to Digital Visual Interface (DVI) converter (Tripplite), DVI to HDMI converters, Local Area Network(LAN) cable, HDMI and power extender cables. The video coaching system was implemented both in CT simulator (GE Discovery)) and in treatment delivery machine True Beam v2.1 Varian Medical Systems (VMS, Palo Alto), which was integrated with respiratory motion management (RPM V 1.7.5) system. Results: The video feedback system is in clinical use since Aug 2017, so far, we have treated 13 patients, with approximately 150 fractions. The performance of the device was found to be satisfactory. All the patients were coached for DIBH and the usage of the goggles, which includes wearing the goggles, display details of the monitor, and the threshold levels of the breathing wave cycle. The patients understand the instructions very well and hence regulate the breathing cycle, which improves the treatment accuracy and efficiency. Conclusion: Video feedback system for motion management, for patients undergoing radiotherapy was implemented successfully both in CT simulator and in linear accelerator.
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Observational study of cone beam computed tomography based interfractional urinary bladder filling variation during image guided radiation therapy in pelvic malignancies p. 152
Manjari Shah, Sandeep Agarwal, Rashi Agarwal, Bala Subramanian, Sweety Gupta, Sudarsan De, Shiv Mishra
DOI:10.4103/jcrt.JCRT_626_18  
Background: Organ motion is an important factor that limits the precision of radiation treatment. Bladder filling variation has significant impact on the position of target volumes in pelvic malignancies. Aims and Objective: This study was an effort to maintain a consistent urinary bladder volume after following a bladder protocol, which was then analyzed by in-room cone-beam computed tomography (CBCT) imaging. Material and Methods: A total number of 26 patients/300 scans, i.e. 26 planning scan and 274 CBCT were analyzed. The bladder volumes and bladder wall dimension were analyzed comprehensively, thus adding considerable understanding to the bladder wall motions. Result: The mean bladder volume for all 26 patients was 183.07 cc with standard deviation of 90.43 cc. The mean +/- standard deviation of transverse, anteroposterior and longitudinal diameter was 8.35+/- 1.03, 6.69+/-1.05 and 5.59+/-1.79 cm. Conclusion: This study showed considerable reduction of margin could be done on the lateral side, as there is less displacement on transverse diameter and more liberal margins should be considered in anteroposterior dimension and longitudinal dimensions. This study has reached the conclusion that bladder-filling protocol is necessary to maintain the consistent bladder volume, but it is too preliminary to state that it will translate into reduction of margin.
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Assessment and implication of rectal filling on vaginal motion in postoperative carcinoma endometrium patients during image guided radiotherapy p. 157
Rashi Agrawal, Soobuhi Jafar, Prekshi Choudhary, D Anbalagan, Dinesh Singh, Sandeep Agarwal
DOI:10.4103/jcrt.JCRT_1113_19  
Aim: While delivering radiotherapy it is utmost important to minimize target motion to decrease margins in postoperative gynaecological patients. Hence certain bladder and rectum filling protocols are followed by each institute. During cone beam computed tomography (CBCT) verification, we observed that this motion was more affected by rectal filling. To verify, we retrospectively analysed the vaginal movement and its relation with bladder and rectum filling. Materials and Methods: We evaluated CBCTs of 15 patients of carcinoma endometrium. Bladder and rectum both were contoured offline on each scan. To assess the motion of vagina, two reference points were selected. Posterior movement of bladder and anterior movement of rectum were noted on these points on each scan. Results: Total 150 scans (135 KV-CBCT scans and 15 planning computed tomography) of 15 patients were studied. Stepwise regression analysis reported that bladder wall changes has a nonsignificant relationship with bladder volume among all the individuals. The significant rectal wall changes both at Point X and Y were observed in six patients and only at Point X in three patients. Rest of the patients showed no significant relationship in their CBCT scans. Thus 60% patients showed significant relation between rectal volume and rectal wall changes. Conclusion: Hence we suggest to advice our patients more regarding volume of rectum to decrease vaginal motion. Bladder volume is needed to decrease the dose to small intestine. However prospective data with large number of patients in the study is required to confirm these findings.
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Role of WT1, B-cell lymphoma 2, Ki-67 (Mib1), and Her2/Neu as diagnostic and prognostic immunomarkers in ovarian serous and endometroid carcinoma p. 164
Santosh Kumar Mondal, Bijan Basak, Saptarshi Bhattacharya, Utpal Kumar Panda
DOI:10.4103/jcrt.JCRT_311_19  
Background: Ovarian cancer is the fifth common cause of death due to cancer in women. It constitutes 3% of all cancers in females and 15%–20% of genital malignancy. Most of the ovarian cancers are serous type followed by the endometrioid type. Sometimes, glands of these two carcinomas are indistinguishable histologically. It also becomes difficult to differentiate these two types when they are poorly differentiated. Aims: The aim of this study was to find differences in immunomarker expressions between serous and endometrioid carcinomas and the association of their staining patterns with other clinicopathological prognostic factors. Materials and Methods: Immunohistochemical staining for WT1, B-cell lymphoma 2 (Bcl2), Ki67 (MIB1), and Her2/Neu were done in paraffin-embedded tissues of histologically diagnosed 38 cases of ovarian serous and endometrioid carcinomas and staining patterns were correlated with other clinicopathological prognostic factors. Results: Of these 38 cases (21 serous and 17 endometrioid), 24 cases were in Stage I/II and 14 cases Stage III/IV. On the other hand, 16 cases were in low grade, 12 cases intermediate grade, and 10 cases high grade. Twenty of 21 serous carcinomas were strongly positive for WT1, whereas most of the endometrioid carcinomas were negative. Ki67 (MIB1) labeling index and Her2/Neu were higher in both higher grade and stages. On the contrary, the intensity of Bcl2 staining was lower in higher grades and stages lesions. Conclusions: The use of WT1 may be useful in resolving diagnostic dilemma between serous and endometrioid carcinoma, especially in difficult cases. Ki67, Bcl2, and Her2/Neu may be used as prognostic markers.
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Dose–volume analysis of acute gastrointestinal complications in cervical cancer undergoing definitive concurrent chemoradiation p. 170
Anup Kumar, Rajanigandha Tudu, Rashmi Singh, Payal Raina
DOI:10.4103/jcrt.JCRT_313_19  
Context: Definitive concurrent chemoradiation with brachytherapy is the prime modality of treatment of cervical cancer. The small bowel is one of the critical organs responsible for gastrointestinal complications. Aims: This study aims to analyze the relation of small bowel dosimetric parameters with the incidence of acute gastrointestinal complications. Subjects and Methods: The study analyzed 40 patients of stage IIB–IVA who underwent concurrent chemoradiation with three-dimensional conformal radiotherapy and weekly cisplatin from June 2017 to June 2018. The small bowel was contoured as the organ of risk. Dose–volume histogram parameters of the small bowel subjected to analysis were mean dose, maximum dose, the total volume of organ receiving 20 Gy, 40 Gy, and 45 Gy (V20-45), and the volume of V20-45 to total volume (V20-45 ratio). Gastrointestinal toxicity was graded using CTCAE version 5.0 criteria. Association between dosimetric parameters and incidence of 1–2 gastrointestinal complications were evaluated. Results: A total of forty patients treated with concurrent chemoradiation were analyzed. Seven patients reported Grade 1, whereas three patients reported Grade 2 gastrointestinal complications. None of the patients reported Grade 3 or higher gastrointestinal complication. Patients with gastrointestinal complications had greater V30-45 and mean dose as compared to those without gastrointestinal complication. Conclusions: Dosimetric parameters of small bowel should be evaluated to reduce the incidence of gastrointestinal complications.
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Endoscopic and clinical correlation with dose to sigmoid colon in carcinoma cervix patients treated with radical radiotherapy p. 174
Jyosthna Elagandula, TR Arulponni
DOI:10.4103/jcrt.JCRT_817_19  
Context: Sigmoid colon, due to its close proximity to central tandem in intracavitary brachytherapy (BT), is at risk of receiving high dose, the clinical significance of which is not documented. Aim: This study was designed to assess the dose received by sigmoid colon following radical treatment and to correlate clinically with the sigmoid mucosal changes seen on sigmoidoscopy. Settings and Design: This is a prospective study. Subjects and Methods: Thirty histologically proven carcinoma cervix patients treated with radical radiotherapy were accrued. A baseline sigmoidoscopy was done and repeated at 6 months following completion of BT. The dose–volume parameters (DVP) were used to calculate the dose received by the sigmoid colon and correlate with symptoms along with the sigmoid mucosal changes. Statistics: The following were the statistical methods used: frequency; percentages; and descriptive statistics such as mean ± standard deviation, Chi-square test, Kolmogorov–Smirnov test, and independent sample t-test. P < 0.05 was considered statistically significant. Results: The dose of the sigmoid colon in patients with a sigmoidoscopy score of ≥2 was significantly high compared to that of patients with a score of <2 for DVP such as D0.1cc, D1cc, D2cc, D5cc, and mean dose, whereas max dose was not significantly high. Conclusions: The dose received by the sigmoid colon is directly proportional to the mucosal changes and hence possibly a higher morbidity. Tighter dose–volume constraints, better optimization techniques, and close follow-up sigmoidoscopy will help in the prevention and early treatment of long-term morbidity.
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Role of various screening techniques in detecting preinvasive lesions of the cervix among symptomatic women and women having unhealthy cervix p. 180
Prasanta Kumar Nayak, Subarna Mitra, Sarita Agrawal, Nighat Hussain, Pushpawati Thakur, Byasdev Mishra
DOI:10.4103/jcrt.JCRT_30_19  
Introduction: Cervical cancer which is preventable, occurs due to humanpapiloma virus infection and results in a preinvasive condition called cervical intraepithelial neoplasm (CIN) before the development of cancer. Majority of the patients with CIN or early stage of cervical cancer present with symptoms such as abnormal vaginal discharge or bleeding, and unhealthy looking cervix. Selectively screening these symptomatic patients, can detect more number of positive cases and also most effective screening technique for these selective patients can be advocated. Materials and Methods: All married women between 21 and 65 years attending gynecology outpatient department of a tertiary care health center in Central India and having unhealthy cervix or abnormal vaginal discharge were included. All women were subjected to Pap smear, visual inspection under acetic acid (VIA), visual inspection under Lugol's iodine (VILI) and colposcopy. Biopsy was taken in all cases. Diagnostic value of each screening method was determined in terms of sensitivity, specificity, positive predictive value and negative predictive value. Results: Out of 352 patients, around 20% of them were found to have abnormal cytology. The sensitivity and specificity of Pap smear was found to be 34% and 94%. But colposcopy has high sensitivity and low specificity, i.e., 99% and 31%, respectively. On the other hand the sensitivity and specificity of VIA and VILI are comparable i.e., 65% and 45% and 64% and 48% respectively. Pap smear shows high positive predictive value among all, i.e., 85% and colposcopy shows 58% for the same. Conclusion: Pap smear carries low sensitivity but high positive predictive value. As compared to Pap smear, VIA and VILI are more sensitive and are of low cost. Colposcopy can be considered as a preferred method of screening due to its extremely high sensitivity.
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Retrospective analysis of surgically treated cases of squamous cell carcinoma vulva p. 186
Seema Singhal, Sunesh Kumar, DN Sharma, Juhi Bharti, Jyoti Meena, Anshu Yadav
DOI:10.4103/jcrt.JCRT_9_19  
Context: Vulvar carcinoma accounts for 3%–5% of gynecologic malignancies. The past three decades has observed changes in the trends of clinical characteristics and treatment modalities used in managing this disease. Aims: The aim of the present study is to analyze the clinic-pathological characteristics and survival of women with squamous cell carcinoma vulva who underwent primary surgical management. Settings and Design: This was a retrospective observational study. Subjects and Methods: Case records of 30 consecutive patients with squamous cell carcinoma of vulva during the period of 2010–2016 were retrospectively reviewed and their clinical profile, treatment details, complications, and survival were analyzed. Statistical Analysis Used: Kaplan–Meier survival analysis, followed by logrank test, was used for survival outcome, and Cox proportional hazard model was used to assess significant risk factors. Results: The mean age of patients was 58 ± 12.9 years. The most common symptom was growth over vulva (73.3%), itching (63.3%), and nonhealing vulval ulcer (26.6%). The most common site for disease was labia majora. The surgical treatments ranged from wide local excision to radical vulvectomy. Postoperative adjuvant therapy was required for 16 patients. The median (95% confidence interval [CI]) overall survival was 27 (21.7–32.2) months. Five-year survival probability for early-stage disease (I + II) was 49% (95% CI: 12.9, 78.4) and for advanced disease (III + IV) was 24.8% (95% CI: 4.8, 42.6). Lymph node-positive status was found to have a significant impact on survival (hazard ratio of 4.9 [95% CI: 1.15–21.02, P = 0.02]). Conclusions: Despite advances in detection and management modalities, the survival for vulval malignancies has not improved.
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Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources: 60Co and 192Ir p. 191
Suresh Yadav, OP Singh, S Choudhary, Dinesh Kumar Saroj, Veenita Yogi, Brijesh Goswami
DOI:10.4103/jcrt.JCRT_199_19  
Background: Iridium-192 (192Ir) has been a widely accepted radioisotope for high-dose-rate (HDR) brachytherapy. Recently, Cobalt-60 (60Co) radioisotope with a longer half-life (5.26 years) has been gaining popularity due to economic and logistical reasons as compared with the traditional 192Ir. Aim: This study aimed to evaluate and compare the integral dose (ID) to the target and organs at risk (OARs) with two HDR brachytherapy sources in brachytherapy treatment of carcinoma uterine cervix to find appropriate HDR radioisotopes for clinical benefit. Materials and Methods: This is a retrospective analysis of 52 computed tomography image-based brachytherapy plans of 52 patients who have received intracavitary treatment with 192Ir HDR source. For each patient plan, one additional set of plan was created using 60Co source in place of 192Ir source keeping the same dwell position, and again dose was optimized. The volume and mean dose for target, OARs, and volume structures of 400%, 200%, 150%, 100%, and 50% were recorded for the estimation and comparison of ID. Results: The mean ID to high-risk clinical target volume was significantly higher by 5.84% in 60Co plan than that in 192Ir plan. For OARs, the mean ID to the rectum was significantly higher by 2.60% in 60Co plan as compared to 192Ir plan, whereas for bladder and sigmoid colon, it was lower in 60Co plan than that in 192Ir plan. The mean ID of central dose volume structures of 400%, 200%, 150%, 100%, and 50% was higher by 12.97%, 9.77%, 8.16%, 6.10%, and 3.22%, respectively, in 60Co plan than that of 192Ir plan. Conclusion: The results of our study concluded that 192Ir HDR radioisotope should be preferred for intracavitary brachytherapy due to its ideal physical characteristics for better clinical outcomes.
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Chemoradiation in locally advanced Ca Cx: Effect on NGAL levels p. 198
Rakesh Dhankhar, Sandeep Chhabra, Kiran Dahiya, Veena Singh Ghalaut, Sunder Singh, Keerti Gupta
DOI:10.4103/jcrt.JCRT_569_18  
Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to be unregulated in many cancers and to suppress tumor suppressor genes like p53 leading to cell proliferation. Studies to report its relationship with carcinoma cervix (Ca Cx) are still scant. Materials and Methods: Serum NGAL levels were analyzed in 30 patients of histopathologically proven locally advanced Ca Cx at the time of diagnosis and 3 weeks after standard chemoradiation by enzyme-linked immunosorbent assay. These patients underwent either brachytherapy or supplementary external beam radiotherapy (EBRT) depending on the response of treatment. The results were analyzed statistically by applying Student's paired t-test. Results: No statistically significant difference (P > 0.05) was observed in patients of Ca Cx before and after treatment or when compared stage wise, histopathological grade wise, or response wise. But the levels were found to increase when duration of treatment was ≥8 weeks (P = 0.040) and to decrease significantly when duration of treatment was <8 weeks (P = 0.0052). The NGAL levels also increased significantly after treatment in patients who received EBRT and supplementary radiotherapy (P = 0.019) while the pre- and post-treatment difference in NGAL levels was not statistically significant in patients who received EBRT + intracavitary brachytherapy (P > 0.05). Conclusion: As the duration as well as modality of treatment is quite important in Ca Cx, shorter duration associated with better results and lower NGAL levels, NGAL might prove to be a useful biomarker although further studies are needed to support the claim.
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Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation p. 204
Geeta S Narayanan, MS Ganesh, Rishabh Kumar
DOI:10.4103/jcrt.JCRT_177_19  
Objectives: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. Materials and Methods: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2–IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83–90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. Results: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2 = 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2 = 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. Conclusion: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.
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Effects of Vitamin E on the immune system and tumor growth during radiotherapy p. 211
Yeun-Hwa Gu, Ki-Mun Kang, Takenori Yamashita, Jin Ho Song
DOI:10.4103/jcrt.JCRT_706_18  
Purpose: The purpose of this study is to evaluate the effects of Vitamin E (VE) on the immune system and tumor growth during radiotherapy (RT) in mice model. Methods: C57BL/6NCrSlc mice were randomly distributed in four groups (control, VE alone, RT alone, and VE + RT). In the VE and VE + RT groups, VE was administered in the diet at 500 mg/kg. Radiation was delivered at 2 Gy in a single fraction on the whole body or at 6 Gy in three fractions locally in the RT and VE + RT groups. Changes in leukocytes and T lymphocytes were counted and compared between the four groups. To evaluate the effects on tumor growth, Ehrlich carcinoma cells were injected into the thighs of mice, and tumor volumes and growth inhibition rates were compared. Results: The number of leukocytes was increased in the VE group compared with that in the control group. The magnitude of leukocyte recovery after RT was also increased by VE. This change was affected largely by alterations in lymphocytes and monocytes rather than that in granulocytes. Both CD4+ and CD8+ T lymphocytes were positively affected by VE. The tumor growth was inhibited not only by RT but also by VE alone. If RT was delivered with VE, tumor growth was markedly inhibited. Conclusion: VE could increase the number of leukocytes, primarily lymphocytes, even after RT was delivered. VE also inhibited the tumor growth in addition to RT. Thus, VE may be a useful radioprotective supplement in radiotherapy without inducing tumor growth.
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Prevalence of anxiety and depression in cancer patients during radiotherapy: A rural Indian perspective p. 218
Neelam Sharma, Abhishek Purkayastha
DOI:10.4103/jcrt.JCRT_277_19  
Objective: This cross-sectional, quantitative epidemiological study was aimed at finding the prevalence of depression in cancer patients and correlation of anxiety and depression with various factors such as age, sex, and type of malignancy while coming for treatment to the radiotherapy department of a tertiary cancer hospital, at the onset, midway, and at the end of radiotherapy treatment using the Hospital Anxiety and Depression Scale (HADS). Materials and Methods: A total of 100 consecutive cancer patients referred for definitive radiotherapy were included. All patients were administered the HADS. The percentage of respondents with anxiety increased significantly after initiating RT and maximum scores were recorded at the end of treatment. The association between anxiety scores and various factors such as age, site, and sex during various phases of RT was found using Chi-square test. Results: At the beginning of Radiotherapy (RT), 61% of our patients reported abnormal scores while this percentage increased to almost 89% at the end of treatment, the comparison between the scores at the beginning and at the end reach a statistical significance (P < 0.0005) while the comparison between the scores at the start and midway led to (P < 0.011). According to the subsite, maximum prevalence of anxiety and depression was seen in patients having head and neck malignancies while older age again was a significant factor leading to the symptoms of anxiety and depression. Conclusion: The diagnosis of cancer carries with it a significant amount of psychological morbidity, both subjectively experienced and objectively observed. Cancer treatments such as chemotherapy and radiotherapy further aggravate anxiety by becoming additional stressors.
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Overexpression of Beclin1 gene leads to reduction of telomerase activity in MDCK cells and enhances apoptosis p. 225
Fatemeh Taji, Asghar Abdoli, Kazem Baesi, Farzaneh Sheikholeslami, Homa Mohseni Kouchesfahani
DOI:10.4103/jcrt.JCRT_265_17  
Background: Telomeres through maintaining chromosomal integrity have key roles in the cell life span. The autophagy is typically a pro-survival process and important for maintaining cellular homeostasis. Conversely, in some conditions, autophagy acts as caspase-independent cell death program. Beclin1 gene plays a principal role in the initiation of autophagy. Objective: The aim of this study was to evaluate the effect of autophagy induction via recombinant Beclin1 on telomerase activity and programmed cell death (apoptosis) in MCDK cells. Materials and Methods: The recombinant Beclin1-pcDNA3.1(-) was transfected into MDCK cells. Next, the autophagy information was detected by LC3II staining as autophagy marker using flow cytometry. The telomerase activity was measured by telomeric repeat amplification protocol method in MDCK cells. To detection of the cell death in MDCK cells, apoptosis assay was done through Annexin V staining method. Results: The results of flow cytometry analysis indicated that following overexpression of Beclin1 gene, the percentage of the LC3II was 16.08% compared with control group (0.48%). Following induction of autophagy, telomerase activity reduced 10 folds in comparison with the control group. The rate of apoptosis in transfected MDCK cells increased up to 12.74%. Conclusion: Crosstalk between telomerase, autophagy, and apoptosis may determine the fate of the cancer cell aging. Hence, manipulation of autophagy may create a novel area to design new compounds and combination therapy to shorten the cancer cell survival.
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Choosing a career in radiation oncology in India: A survey among young radiation oncologists p. 231
Anindya Mukherjee, Kazi Sazzad Manir, Praloy Basu, Suman Mallik, Jyotirup Goswami
DOI:10.4103/jcrt.JCRT_779_19  
Background: Radiation oncology in India is much debated as a career option to take up. This survey among young radiation oncologists (YROs), the first of its kind, attempts to assess the career expectations and concerns that affect most of us. Materials and Methods: This survey was conducted using the online survey tool of SurveyMonkey in October 2018. The Association of Radiation Oncologists of India (AROI) members' database was used to send the survey link over E-mail to recipients (AROI life member after 2004). Results: Out of 1685 invitees, 492 (29.19%) recipients took the survey. Most (69.14%) of the respondents were males who worked as senior residents and junior consultants and employed in private hospitals and state-level teaching institutes. Postspecialization (MD/DNB) experience was mostly <3 years (56.52%). Most of YROs worked in Tier-I city (48.9%) mostly in telecobalt-based facilities. Most of our respondents (73.01%) aspired to work in academic teaching hospital/research institute, and the primary concern was academics/research (39.88%) followed by income (23.31%). There was a similar distribution of respondents with respect to their desire to shift to medical oncology. There was marked dissatisfaction over remuneration, job openings, job security, and poor scope of career improvement. 56.50% of respondents believed that they need to move abroad to improve their quality of life. However, 76.69% of respondents still felt very passionate about their professional choice. Finally, 61.97% of professionals believed that this survey will correctly reflect the present scenario among YROs. Conclusions: The survey portrays a mixed picture as expected. Major policy changes are required to improve the infrastructure and job opportunities of this profession.
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Study of volumetric and dosimetric changes during fractionated radiotherapy in head and neck cancers: A single centre experience p. 235
Viney Kumar, Vipul Nautiyal, Ravi Kant, Meenu Gupta, Saurabh Bansal, Mushtaq Ahmad
DOI:10.4103/jcrt.JCRT_350_20  
Aims and Objective: The assessment of volumetric and dosimetric changes in the head-and-neck cancer during fractionated radiotherapy by intensity-modulated radiotherapy (IMRT) technique. Materials and Methods: A single-center prospective observational hospital-based study with a sample size of 20 cases of the head-and--neck squamous cell carcinoma over 1 year treated with chemoradiotherapy 66–70 Gy/33–35#@2 Gy/fraction with weekly cisplatin 35 mg/m2. After contouring of target volumes (TVs) and organs at risk (OARs) in initial computed tomography (CT) scan, all patients were planned and treated by the IMRT technique. We re-delineated the TVs and OARs in the second (CT15#) and third (CT30#) planning CT scan, and the initial plan was implemented in the re-CT scan dataset with the same optimization and doses. The volumetric and dosimetric changes during fractionated radiotherapy of TVs and OARs were evaluated and compared. Nonparametric Wilcoxon–signed-rank test was used to compare the means between each plan. Results: For all 20 patients, plans were compared for volumetric and dosimetric parameters on repeat CT scans. The mean variation in gross tumor volume (GTV) and planning TV (PTV) was significant after 15 and 30 fractions of radiotherapy. On dosimetric evaluation, there was a significant increase in doses to GTV and OARs (parotid, spinal cord, and cochlea) with a significant P value. However, doses to the OARs were not exceeded the maximum tolerance limit. Conclusion: This prospective single-center study concluded that two repeat imaging, along with re-planning improved TV coverage and decreased doses to the normal tissue. Larger studies with more sample sizes are required to set the criteria for replanning.
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Hypericin induces apoptosis in K562 cells via downregulation of Myc and Mdm2 p. 242
Hamid Zaferani Arani, Maedeh Olya, Asra Sadat Mirahmadi, Hossein Saleki, Hesam Adin Atashi, Hadi Zare Marzouni, Mohammad Hoseinian, Mohammad Amin Javidi, Amirhossein Zabolian
DOI:10.4103/jcrt.JCRT_826_19  
Background: Nowadays, some studies have shown the effect of hypericin on cancer cells. However, considering the cytotoxicity of this plant and signs of anticancer activity in the plant, unfortunately, there is still no proper treatment for leukemia cancer cells. Therefore, the present study aims to evaluate the anticancer effect of hypericin in the treatment of leukemia cancer and its possible mechanism of action. Methods: In this study, the K562 cell line was treated with different concentrations of hypericin for 24 and 48 h. Detection of cell death was performed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide assay. The rate of cell apoptosis was measured by Annexin V/propidium iodide assay using flow cytometry. The expression of Bax, Bcl2, Myc, Mdm2, and P53 genes was evaluated by real-time polymerase chain reaction test, and immunocytochemistry (ICC) analysis was used for further evaluation of P53. Results: The results showed that hypericin has a dose-dependent cytotoxic effect on the K562 (in much less dose compared with cisplatin). According to flow cytometry results, cell apoptosis after exposure to hypericin for 24 h was 53%, and ICC analysis on p53 confirmed this. Furthermore, after 24 h of exposure to hypericin with IC50 concentration, the expression of P53 and Bax genes increased and the expression of the Bcl2, Myc, and Mdm2 gene decreased. Conclusion: The results showed that hypericin exerts its cytotoxicity on K562 cancer cells by downregulating Mdm2 and Myc. Based on the data acquired from the present study and many investigations till now, hypericin can be a good option for leukemia cancer cells treatment.
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CASE REPORTS Top

An urban legend: Malignant transformation caused by radiotherapy in patients with presacral ganglioneuroma. The necessity and first-time administration of radiotherapy. Case report and literature review p. 248
Sema Yilmaz Rakici, Vaner Koksal, Recep Bedir, Sibel Goksel
DOI:10.4103/jcrt.JCRT_380_18  
Ganglioneuromas (GNs) are well-differentiated, rare benign tumors of neural crest origin and are, for the most part, considered to be the benign equivalent of neuroblastomas. There are very few cases of GN reported to be at presacral location in the literature. The standard form of treatment is the total surgical excision. However, total resection of GN is not always possible depending on the neuron, from which it originates, and its localization. Moreover, adjuvant radiotherapy (RT) or chemotherapy is not recommended even though patients are still symptomatic after subtotal resection. This view is based on the urban legend that it undergoes a malignant transformation although it is a benign tumor. Moreover, there are no data indicating that the GN cases reported in the literature have undergone RT. Therefore, articles about the suspicion that GN may undergo spontaneous or malignant transformation after RT are absolutely controversial. Based on our case, we present here, we believe that we will explain the valid necessity of application of RT that we administered for the first time and that with the clarification of this controversial topic, a significant gap will be closed in the literature.
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Successful treatment results of external radiotherapy without brachytherapy in advanced uterine cervical cancer p. 255
Soo Jung Gong, Su Jung Shim
DOI:10.4103/jcrt.JCRT_43_20  
In advanced uterine cervical cancer, external radiotherapy with intracavitary brachytherapy has been established as a curative treatment method. However, in an environment where brachytherapy is difficult to perform, there has been an attempt to use only external radiotherapy. We report the results of eight patients over 65 years of age with advanced uterine cervical cancer who refused brachytherapy and obtained successful results through external radiotherapy alone.
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Four synchronous primary tumors in a male patient p. 258
Yazan Abdeen, Mohammad Al-Amer, Eric Taft, Moh'd Al-Halawani
DOI:10.4103/jcrt.JCRT_187_18  
Multiple primary malignancies are defined as two or more primary malignant tumors diagnosed in one individual; they are further classified to synchronous or metachronous based on the period between each cancer diagnosis and the other. The diagnosis of four synchronous cancers is exceedingly rare. We report a case of a 72-year-old man, diagnosed with synchronous quadruple cancers, Hurthle cell carcinoma and papillary carcinoma of the thyroid, as well as squamous cell carcinoma and carcinoid tumor of the lung.
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Drug-induced infiltrative lung disease with weekly paclitaxel in breast cancer: Case series p. 262
Renu Raghupathi, Channappa Patil, Pravesh Dhiman
DOI:10.4103/jcrt.JCRT_1225_16  
Drug-induced infiltrative lung disease (DI-ILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. Common chemotherapeutic drugs causing DI-ILD include bleomycin, mitomycin C, bis (2-chloroethyl)-l-nitrosourea, cyclophosphamide, busulfan, and methotrexate. Taxanes and trastuzumab are also associated with lung injury. Estimated incidence of paclitaxel-induced lung injury is 0.73%–12%. Although cases of paclitaxel-induced lung injury have been reported previously, we found only one published case report of fatal lung injury caused by paclitaxel use. We are reporting the largest case series of seven patients who developed paclitaxel-induced lung injury along with review of literature.
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Antitumor effects of sodium selenite on acute lymphocytic leukemia p. 266
Ayesha Siddiqa, Rimsha Munir, Muhammad Faisal
DOI:10.4103/jcrt.JCRT_147_17  
Selenium is obligatory for proper functioning of body as it is the part of enzyme protection system. Its both organic and inorganic forms are thought to be active as an antitumor agent. We trialed the different dosages (0 × 106 M, 2.7 × 106 M, 5.4 × 106 M, and 8.1 × 106 M) of sodium selenite given to the acute lymphocytic leukemia cell lines incubated for 24, 48, and 72 h. The ratios of dead cells to live cells when treated with sodium selenite were very high as compared to the control with no treatment. This dosage-dependent apoptosis increased with the incubation time.
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Synchronous occurrence of myelodysplastic syndrome and a bleeding jejunal gastrointestinal stromal tumor in a patient with obscure gastrointestinal bleed p. 269
Bharadhwaj Ravindhran, H Harish Kumar, GC Raghunandan, Rakesh Ramesh
DOI:10.4103/jcrt.JCRT_18_18  
The coexistence of gastrointestinal (GI) stromal tumors (GISTs) and other malignancies, both synchronous or metachronous, has been discussed extensively in literature. It has also been described that the frequency of malignancies among patients with GIST is significantly higher than that in the general population. We present a case report of a patient with synchronous occurrence of myelodysplastic syndrome (MDS) and a GIST who presented with chronic fatigue and an episode of syncope and was found to have obscure GI bleed. Laboratory investigations revealed severe anemia, marrow picture was suggestive of MDS, and magnetic resonance imaging of the abdomen revealed a proximal small bowel neoplasm. She underwent resection of the diseased segment and anastomosis. The histopathology of the specimen confirmed the diagnosis of a GIST arising from the jejunum. She was started on imatinib on postoperative day 21 and is presently well preserved and on regular follow-up. The possibility of small bowel neoplasm, especially GIST, must be considered in patients diagnosed with chronic anemia secondary to obscure GI bleed and the possibility of a synchronous GIST, although uncommon must be considered in patients with myeloproliferative disorders and leukemia.
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Complete androgen insensitivity syndrome with intra-abdominal seminoma in a phenotypic female: A rare presentation p. 272
Savita Arora, Neha Sharma, Arun Kumar Rathi, Kishore Singh, Kavita Sehrawat
DOI:10.4103/jcrt.JCRT_302_18  
Androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder which causes alterations in androgen receptor gene leading to hormone resistance, which may present clinically under three phenotypes: complete AIS (CAIS), partial AIS, or mild AIS. The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea. We report a case of a 35-year-old woman who was diagnosed with CAIS and presented with malignant transformation of the undescended testis. The histopathology confirmed the presence of seminoma. In this case report, we reviewed the literature which describes the biochemical and endocrinological abnormalities leading to the syndrome. It also highlights the potential for malignant changes of the undescended testes, diagnosis, and therapeutic management.
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First-line treatment of NRAS-mutated metastatic melanoma with a MEK inhibitor Highly accessed article p. 276
Angelika Bickel, Stefan Diem, Lukas Flatz, Björn Stinn, Marco Siano
DOI:10.4103/jcrt.JCRT_50_18  
Until recently, standard treatment for advanced melanoma comprised basically dacarbazine and interleukin-2, leading to low response rates and significant toxicity. These days, new treatments such as immunotherapy (anti-CTLA4 and anti-PD1 antibodies) and targeted therapy with BRAF/MEK-inhibitor combinations for patients harboring a BRAF mutation are available. In BRAF wild-type patients harboring an NRAS mutation, not fit for immunotherapy treatment options are still dismal. We describe an 84-year-old patient with widespread metastatic melanoma. He presented in July 2015 with a cerebral hemorrhage under anticoagulation for atrial fibrillation. Computed tomography revealed extensive metastatic disease (liver, lung, bones, lymph nodes, heart, and brain). Molecular testing was negative for BRAF but showed the presence of an NRAS mutation in exon 3 (pQ61K [c.181C>A]). The patient received as first-line treatment two cycles of cobimetinib showing a good partial remission and manageable side effects.
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Aggressive-fungating retinal hemangioblastoma p. 279
Sudha Girish Menon, Girish Menon Ramachandran, Mridula Jacob, Ajay Hegde, Kanthilatha Pai
DOI:10.4103/jcrt.JCRT_718_18  
Retinal hemangioblastomas are one of the most common and early manifestations of Von Hippel–Lindau disease. Early detection is the key in their management. When left untreated, these benign neoplasms may continue to grow and result in scleral infiltration and extraocular extension warranting enucleation of the globe.
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An unknown chromosomal aberration in a patient with chronic lymphocytic leukemia: Extra isochromosome 4q p. 282
Emine Ikbal Atli, Hakan Gurkan, Ahmet Muzaffer Demir
DOI:10.4103/jcrt.JCRT_236_17  
The genetic characterization of chronic lymphocytic leukemia (CLL) has made significant progress over the past few years. Chromosomal abnormalities are detected in up to 80% of patients. Determination of new chromosomal disorders is important in the pathogenesis and treatment facilities. A patient was diagnosed with CLL Stage 2 on 2012 and followed since then by hematology clinic. She was 63 years old. Mature, small lymphocytes, and smudge cell was found in the patient's peripheral blood smear. Bone marrow (BM) biopsy made and hypercellularity showing infiltration of atypical cells with CD5+, CD20+, and CD23+ were determined. Hypoplasia is detected in myeloid/erythroid series, and Stage 2 reticular fibers proliferation were detected. The patient was followed up without medication. While follow-up of patient's white blood cell: 57300, hemoglobin: 5.36, and PLT: 99700 are determined in May 2014. According to the patient's flow results, CD5+, CD23+, and FMC7+ were detected. Mature, small lymphocytes and smudge cell was found in the patient's peripheral blood smear. In ultrasonography imaging, multiple laps were found in the abdomen and multiple neck lymph nodes were detected. The patient BM aspiration was performed in 2014, and hypercellularity was found to contain 54% of atypical lymphocytes in the BM. Fluorescence in situ hybridization (FISH) analysis made two times in 2014. At first, FISH analysis patient's rate of 18% in RB1/13q14.2/13qter revealed a deletion of the gene regions. Patient's FISH result was reported as normal (for RB1/13q14.2/13qter) after 5 months at second analysis. Cytogenetic analysis is made from the patient's BM at the same time. According to the results of karyotyping and FISH, 47, XX, isochromosome 4q (+i4q) is determined. According to literature, extra isochromosome 4q is reported by our case for the first time in CLL. She was diagnosed with Stage 4 CLL and FISH treatment was initiated. Our patient showed disease progression compared to previous results. Hence, we offer that this evidence can be considered regarding triggering the disease's progression or as a result of disease progression i4q was occurred.
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Primary diffuse large B-cell lymphoma masquerading as uterine fibroid: A pathologistsf diagnosis p. 288
Aarti Tyagi, Andleeb Abrari, Urmi Mukherjee
DOI:10.4103/jcrt.JCRT_499_18  
Lymphoma involving the uterus is rare, and the diagnosis is usually difficult due to the rarity and nonspecific presentation. The treatment is often delayed and difficult because there is no standard treatment. We report our experience with a case of diffuse large B-cell lymphoma (DLBCL) involving the uterus. A 40-year-old female presented to our hospital posthysterectomy for suspected fibroid. Computed tomography scan and the tissue biopsy along with the immunoprofile revealed uterine DLBCL. She was treated with chemotherapy followed by radiation therapy and showed the complete response to the treatment, and thus, the clinicians should be aware of this rare disease for prompt diagnosis.
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LETTERS TO THE EDITOR Top

Characteristics of BRAF V600K versus V600E: Effect of molecular weight change in melanoma p. 291
Beuy Joob, Viroj Wiwanitkit
DOI:10.4103/jcrt.JCRT_433_18  
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Microsatellite instability in colorectal cancer from causes to detection p. 292
Meysam Mosallaei, Miganoosh Simonian, Rasool Salehi
DOI:10.4103/jcrt.JCRT_913_18  
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Rapidly developing facial and intertriginous hyperpigmentation with acral erythema after docetaxel infusion p. 293
Melek Karakurt Eryilmaz, Gokhan Tazegul, Betül Ünal, Fatma Yalçin Müsri, Halil Göksel Güzel, Hasan Şenol Coşkun
DOI:10.4103/jcrt.JCRT_385_17  
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