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   Table of Contents - Current issue
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January-June 2019
Volume 2 | Issue 1
Page Nos. 1-133

Online since Monday, September 9, 2019

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MUSINGS  

On being a surgeon and a mother Highly accessed article p. 1
Sabita Jiwnani
DOI:10.4103/CRST.CRST_23_19  
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ORIGINAL ARTICLES Top

Outcomes in rhabdomyosarcoma: Experience from a tertiary cancer center in India p. 4
LP Bhaskar Bhuvan, Venkatraman Radhakrishnan, Anand Raja, Selvaluxmy Ganesarajah, Tenali Gnana Sagar
DOI:10.4103/CRST.CRST_14_19  
Background: Rhabdomyosarcoma (RMS) is an embryonal tumor seen commonly in children. There is a paucity of literature on RMS from India. The present study was conducted to look at the disease characteristics and outcome of RMS patients treated at our center. Methods: This was a retrospective study that included patients with RMS of all age groups treated at our center between 2001 and 2016. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan–Meier method. Results: The study included 70 patients with a median age of 7 years (1–70 years) and 42/70 (60%) were male. The common sites of disease were parameningeal in 31 (44%) and extremity in 17 (24%) patients. Metastasis at presentation was seen in 22/70 (31%) patients. Embryonal (66%) followed by alveolar (9%) and pleomorphic (4%) were the common histologic subtype. The risk stratification showed good-risk in 13 (18%), intermediate-risk in 35 (50%), and high-risk in 22 (32%) patients. The median duration of follow-up was 70.4 months (Confidence interval: 26.1–114.8 months). The median EFS and OS in the study were 11 months and 21 months, respectively. The factors associated with better OS were male gender (P = 0.038), nonmetastatic disease (P = 0.028), good- and intermediate-risk subgroup (P = 0.002), complete surgical excision (P = 0.002), and radiotherapy (P = −0.002). Conclusion: Outcomes in RMS remain dismal with most patients presenting with advanced disease. Multimodality management with chemotherapy, surgery, and radiotherapy in patients with nonmetastatic disease improves outcome.
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Clinical management and prognostic outcome of intracranial ventricular tumors: A study of 134 cases p. 10
CK Kriankumar, Ravindra Pramod Deshpande, Y B. V K. Chandrasekhar, I Satish Rao, Manas Panigrahi, Phanithi Prakash Babu
DOI:10.4103/CRST.CRST_19_19  
Introduction: Ventricular tumors are known to have a relatively rare occurrence and are underlined by complex pathophysiology. Methods: We retrospectively analyzed the clinicopathological details of 134 patients with intracranial ventricular lesions over a 5-year period. The patients were selected on the basis of diagnosed lesions by magnetic resonance imaging and further histopathology study. We have assessed the clinicopathological details from the database. Results: The median age of patients was 30 years (range: 1–73 years). In 47% of the cases, the lesions were located in the anterior third ventricle; glioma (n = 43) and colloidal cysts (n = 41) were the most common lesions. Presenting symptoms included seizures and features of hydrocephalus in 38.8% of patients. Open microsurgical (81.6%) and endoscopic (18.4%) surgery were performed. An open microsurgical approach was the main surgical treatment with operative mortality of 0.86% and permanent morbidity of 6.7%. Sixteen of the 27 patients in the endoscopic group underwent endoscopic third ventriculostomy (ETV) with biopsy. Survival was affected by the type of lesion. The progression-free survival was highest in the patients with neurocytoma and lowest in the patients with glioma (P = 0.01). Twenty-three patients received adjuvant radiation therapy. The decision regarding radiation therapy was made on the basis of individual lesion, histopathological type, and proliferative index. The mean overall survival was 34 months. Conclusions: Management of intraventricular tumors requires multimodality treatment including open microscopic surgery, neuroendoscopy, and radiation therapy as per the tumor pathology and hydrocephalus status. Simultaneous endoscopic biopsy with ETV can avoid major open surgery and mitigate the possible postsurgical complications.
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Determination of ROS1 positivity by immunohistochemistry in a multicentric cohort of 426 non-small-cell lung cancer cases in India p. 16
Jugnu Jain, Deepthi Chinta, Umeshnandan B Jayaraman, Neha Pathak, Manpreet Kaur, Soma Chatterjee, Meenakshi Swain, Vijay Anand Reddy
DOI:10.4103/CRST.CRST_12_19  
Introduction: ROS1 is a receptor tyrosine kinase of the insulin receptor family that acts as a driver oncogene in 1%–2% of non-small cell lung carcinoma (NSCLC) patients via a gene translocation between ROS1 and other genes, the most common one being CD74. Histologic and clinical features that are associated with ROS1 translocations include never smokers, younger age, and adenocarcinoma (AC) histology. The identification of ROS1 fusion is important because it responds to targeted therapies such as crizotinib that can greatly improve the survival of the patient. The goal of this study was to determine the percentage of population harboring ROS1 mutation in India. Materials and Methods: ROS immunohistochemistry (IHC) method was optimized using Cell Signalling Technology, ROS antibody (ROS1 clone D4D6 rabbit mAb), and appropriate positive and negative controls in a fully automated procedure using Ventana automated stainer. Approximately 2000 retrospective lung cancer cases from six different Apollo hospitals were identified. The formalin-fixed paraffin-embedded blocks and corresponding diagnostic and demographic data were retrieved. A total of 426 cases with confirmed diagnosis of NSCLC were then tested by IHC for ROS1. Results: Given the retrospective nature of the cancer cases and diagnostic data being used for the study, there was high attrition in the availability of the blocks and data. Among the 2000 cases examined, there were 604 cases that were initially reported as lung cancer in the hospital medical records and for whom corresponding blocks were available, but blocks for only 485 cases had sufficient tumor content, as judged by hematoxylin and eosin staining and microscopic examination, to enable testing for ROS1 staining. Of these 485 cases, 225 were confirmed AC cases. A single case stained positive for ROS1 among the 225 AC cases. The percentage is calculated to be 0.44% based on this single positive case. No positive case was observed in squamous cell carcinomas or other cancers of the lung such as neuroendocrine tumors, germ cell tumors, and adenoid cystic tumors. Conclusion: The percentage positivity for ROS1 in the study comprising 225 Indian NSCLC AC cases appeared similar to the 0.3%–1.6% range reported for smokers and lower than 0.9%–1.7% positivity reported in mixed patient populations.
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Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of a Phase III randomized trial to compare the benefit of gefitinib versus pemetrexed/carboplatin for epidermal growth factor receptor-mutated non-small cell lung cancer p. 21
Vijay Patil, Vanita Noronha, Amit Joshi, Anuradha Chougule, Atanu Bhattacharjee, Alok Goel, Vikas Talreja, Nandini Menon, Anant Ramaswamy, Ashay Karpe, Nikhil Pande, Arun Chandrasekharan, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash
DOI:10.4103/CRST.CRST_17_19  
Background:> In an open-label, Phase III randomized study, gefitinib was found to be superior to pemetrexed-platinum in terms of progression-free survival in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. In this analysis, we have assessed the efficacy of gefitinib over pemetrexed-platinum using quality-adjusted time without symptoms or toxicity (Q-TWiST) of treatment analysis method. Methods: The overall survival in each arm was partitioned into the following three health states: time spent in Grade 2 or above toxicity after randomization and before progression (TOX state), time spent after randomization and before progression without Grade 2 or above toxicity (TWiST state), and time spent after progression (REL state). The mean Q-TWiST was calculated for each arm using utility coefficients of 0.65 for TOX, 0.71 for TWiST, and 0.67 for REL states. The difference in Q-TWiST and the 95% confidence interval (CI) of the difference were calculated using a nonparametric bootstrap.P= 0.05 was considered statistically significant. Results: The mean TOX duration (37.6 vs. 16.2 days,P < 0.001) and TWiST duration (211.7 vs. 162.2 days, P = 0.002) were higher in the gefitinib arm. The mean REL state duration was higher in the pemetrexed-carboplatin arm (164.4 vs. 74.3 days,P < 0.001). The mean Q-TWiST was 224.6 days in the gefitinib arm versus 235.9 days in the pemetrexed-carboplatin arm. The difference was 11.3 days; 95% CI, 6.920–29.564,P= 0.224. Conclusion: The mean Q-TWiST of patients in the gefitinib arm was similar to that of patients in the pemetrexed-carboplatin arm. These results challenge the superiority of sequencing gefitinib followed by chemotherapy over pemetrexed-carboplatin followed by gefitinib in terms of Q-TWiST.
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Clinical–radiological features of methotrexate-induced subacute leukoencephalopathy in patients with acute lymphoblastic leukemia: 'Panda eye sign' on diffusion weighted-magnetic resonance imaging p. 28
Abhishek Mahajan, Hasmukh Jain, Vijai Simha, Tanvi Vaidya, GV Santhosh Kumar, Anurag Gupta, Bhausaheb Bagal, Manju Sengar
DOI:10.4103/CRST.CRST_22_19  
Background and Purpose: Subacute leukoencephalopathy in ALL is a rare complication after high dose methotrexate (HDMTX) administration and recognizing this self-remitting entity has important therapeutic implications. We did a retrospective study to evaluate the role of magnetic resonance imaging (MRI) in diagnosing this entity and asses the incremental value of diffusion weighted MR (DW-MRI). Materials and Methods: We did a retrospective analysis of adult ALL patients being treated with the modified Berlin-Frankfurt-Münster (BFM)-90 protocol at our center between January 2014 and January 2015 and identified those who developed neurotoxicity after HDMTX. All these patients underwent a contrast enhanced CT and contrast enhanced MRI of brain with DW-MRI within 48 hours of presentation. Results: Eleven patients were identified from a cohort of 239 patients (~5%). They presented with focal neurological deficits within ~14 days after HDMTX that resolved completely with conservative measures. The CT scans were normal in all these patients. A consistent finding seen in all these cases was the occurrence of restricted diffusion in the region of the centrum semiovale on DW-MRI. On diffusion maps, symmetrical areas of hyperintensity resembled Panda eyes and mean apparent diffusion coefficient cut-off of our series was 0.000453 x 10–3 +/- 0.000120 cm2/sec. Conclusion: CT brain and conventional MR imaging have no significant role to play in diagnosing this entity however restricted diffusion in the centrum semiovale is a consistent imaging finding and the 'panda eye sign' as seen on DW imaging can be considered diagnostic for methotrexate induced subacute leukoencephalopathy and this sign can help in timely establishment of the diagnosis and appropriate management.
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PATIENT/CAREGIVER CORNER Top

My journey: Hell to well p. 34
Srisharada Krishnan
DOI:10.4103/CRST.CRST_28_19  
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REVIEW ARTICLES Top

Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management p. 36
Akhil Rajendra, Vanita Noronha, Amit Joshi, Vijay Maruti Patil, Nandini Menon, Kumar Prabhash
DOI:10.4103/CRST.CRST_51_19  
Non-small-cell lung cancer (NSCLC) constitutes 85% of patients diagnosed with lung cancer. In metastatic cases, its treatment classically consists of systemic cytotoxic chemotherapy, which resulted in a median overall survival of 7.9 months. However, over the last decade, improved understanding of driver mutations, especially identification of epidermal growth factor receptor (EGFR) mutation, has changed the treatment landscape of these patients. Our understanding of EGFR mutations has improved tremendously, and we now have three generations of EGFR tyrosine kinase inhibitors, have identified secondary resistance mutations, and have developed agents targeting these resistance mutations, making precision medicine a reality. We review these developments and try to propose an optimal approach toward the management of these patients with EGFR-mutated NSCLC.
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Low doses in immunotherapy: Are they effective? p. 54
Vijay M Patil, Vanita Noronha, Amit Joshi, Anuja Abhyankar, Nandini Menon, Shripad Banavali, Sudeep Gupta, Kumar Prabhash
DOI:10.4103/CRST.CRST_29_19  
Checkpoint inhibitors are versatile immunomodulatory agents, and they are being approved for the treatment of an increasing number of cancers, based on the demonstration of clinical benefits. While they have changed the landscape of treatment of many cancers, they remain inaccessible to most patients, especially in low-income countries because of their prohibitive costs. Conventionally, chemotherapy drug doses are decided based on the maximum tolerable dose in phase 1 studies, but this dose-finding methodology is not applicable to targeted therapies where dose-limiting toxicity is not reached at doses much higher than sufficiently active doses. This review article focuses on how lower doses of immunotherapy drugs could be as efficacious as the currently recommended doses, thus decreasing the financial burden.
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SYSTEMATIC REVIEW Top

Depth of tumor infiltration as a prognosticator in pT1-2 cN0 oral squamous cell carcinoma thereby need for elective neck dissection – A meta-analysis p. 61
Mohammad Akheel, Rinku K George, Amit Jain, Qutubuddin Chahwala, Ashmi Wadhwania
DOI:10.4103/CRST.CRST_24_19  
Aim: The aim of the study is to identify the cutoff value for depth of infiltration that predicts the risk of lymph node metastasis in the neck in surgically treated patients affected by pT1/pT2 cN0 oral squamous cell carcinoma (OSCC). Materials and Methods: Meta-analysis of six articles, including 938 patients, was performed from a PubMed search of the last 15 years. Results: The mean depth of infiltration in N0 neck was 4.42 mm, standard deviation (SD) 0.66 (95% confidence interval [CI], 3.89–4.95), while the mean depth of infiltration in N+ neck was 6.95 mm, SD 1.36 (95% CI, 5.86–8.04). One sample t-test done to analyze the level of significance between the cutoff depth of infiltration for N0 and N+ was found to be significant,P= 0.002. Receiver operating characteristic analysis was done to find the cutoff depth of infiltration in all N0 necks which was 4.5 mm with odds ratio 9.32, sensitivity of 84.7% in N+ necks which makes elective neck dissection an important surgical option for good prognosis of OSCC. Conclusion: Tumor infiltration depth is an important prognosticator in pT1/pT2 cN0 necks. Tumors with depth of infiltration >4.5 mm radiologically or clinically should undergo an elective neck dissection to improve the prognosis of OSCC.
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EDITORIALS Top

ROS1 rearrangement testing: Is immunohistochemistry changing the horizon? p. 66
Anuradha Choughule, H D'Souza
DOI:10.4103/CRST.CRST_32_19  
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Improving outcomes in Rhabdomyosarcoma-The way ahead p. 69
Badira Cheriyalinkal Parambil, Subramaniam Ramanathan
DOI:10.4103/CRST.CRST_47_19  
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Challenges in the management of intraventricular tumors in the current era p. 72
Rahul Krishnatry
DOI:10.4103/CRST.CRST_39_19  
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Head-and-neck dermatofibrosarcoma protuberans: Where does imatinib 'fit in'? p. 74
Avinash Vijaykumar Pandey, Anjana Singh
DOI:10.4103/CRST.CRST_46_19  
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INTERESTING ONGOING TRIALS Top

Induction therapy in newly diagnosed multiple myeloma: Current research scenario and questions for the future p. 76
Bhausaheb Bagal, Avinash Bonda
DOI:10.4103/CRST.CRST_42_19  
The outcomes of patients with newly diagnosed multiple myeloma (NDMM) have substantially improved over the last decade. Besides improved staging, diagnostic and prognostic tools leading to better risk-stratified approaches, a major contributing factor has been better induction regimens. The major emphasis of the current clinical research is on the development of induction regimens capable of producing a deep and durable remission as measured by minimal residual disease negativity, which correlates with a better overall survival. This review explores the current changing landscape of induction therapy in NDMM and discusses implications for the current clinical practice.
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PROFESSIONAL RESOURCE Top

Radical Chemo-radiation (CRT) Protocols for Head and Neck Squamous Cell Carcinomas (HNSCC) p. 83
Kushal Gupta
DOI:10.4103/CRST.CRST_38_19  
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IMAGE CHALLENGE Top

Delirium and seizures in a patient with head-and-neck squamous cell carcinoma on docetaxel, cisplatin, and 5-fluorouracil p. 105
Satvik Khaddar, Vijay M Patil, Vanita Noronha, Amit Joshi, Nandini Menon, Kumar Prabhash
DOI:10.4103/CRST.CRST_35_19  
A 33 year male, case of locally advanced carcinoma left buccal mucosa treated with docetaxel, cisplatin and 5-fluorouracil as neoadjuvant therapy developed acute onset delirium, seizures and agitation on fifth day of first cycle of chemotherapy. Although CT brain revealed no abnormality, MRI brain showed symmetric areas of diffusion restriction with T2/FLAIR hyperintensity involving periventricular region (lateral ventricles), centrum semiovale and corpus callosum. His clinical symptoms normalized after one week of stopping therapy. What is the diagnosis, and how should the patient be managed?
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STATISTICAL RESOURCE Top

Testing and interpreting assumptions of COX regression analysis p. 108
Sampada Dessai, Vijay Patil
DOI:10.4103/CRST.CRST_40_19  
The COX regression analysis is like any statistical test that is based on multiple assumptions. This is a guide for how to test the assumptions and how to interpret the results.
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REAL WORLD DATA Top

Dermatofibrosarcoma protuberans of head and neck: Clinical outcome of nine cases treated with imatinib p. 112
Lakhan Kashyap, Vanita Noronha, Vijay Patil, Amit Joshi, Abhishek Mahajan, Neha Mittal, Kumar Prabhash
DOI:10.4103/CRST.CRST_36_19  
Background: Dermatofibrosarcoma protuberans (DFSP) of head and neck is rare and presents a unique challenge as surgery may be associated with poor cosmetic and functional outcomes or inadequate surgical margins. There is a paucity of data regarding the use and effectiveness of imatinib in head and neck DFSP. We retrospectively analyzed head and neck DFSP cases treated with imatinib. Patients and Methods: Data of nine head and neck DFSP cases treated with imatinib were retrieved from our hospital electronic medical records. Demographic and toxicity data were presented using descriptive statistics and simple percentages; survival was calculated using the Kaplan–Meier method. Results: The median age was 40 years (range, 22–47 years) with almost equal male to female distribution. The site of primary tumor was scalp in seven patients, face and neck in one patient each. One-third of the patients had metastatic disease; sites of metastases included lung, lymph node, soft tissue, and brain. Fibrosarcomatous variant was present in four patients. Eight patients underwent wide local excision for the primary tumor. Three patients each received imatinib in the neoadjuvant, adjuvant, and palliative setting. The response rate to imatinib in the neoadjuvant and palliative setting was 66.7% and 33.3%, respectively. Four patients received adjuvant radiotherapy (RT) after surgery for recurrent disease and one patient received palliative hemostatic RT to the local site. The median duration of follow-up was 84 months (range, 2–148 months), and median recurrence free survival was 82 months (interquartile range, 74–83 months). All patients were alive until last follow-up. Conclusions: Head and neck DFSP requires multimodality management with incorporation of neoadjuvant imatinib and adjuvant RT to achieve favorable clinical outcomes.
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LETTERS TO EDITOR Top

Coexistence of epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation in non-small cell lung cancer: Do we know the treatment sequence? p. 119
Vikas T Talreja, Vanita Noronha, Amit Joshi, Vijay Patil, Abhishek Mahajan, Kumar Prabhash
DOI:10.4103/CRST.CRST_26_19  
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Osimertinib in G719A mutated non-small cell lung cancer with leptomeningeal metastases p. 121
Avinash Pandey, Anjana Singh, Shivkant Singh, Amit Kumar
DOI:10.4103/CRST.CRST_27_19  
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Tobacco use among adolescent school-going children: Extent of problem and solutions for the future p. 124
Shivakumar Thiagarajan
DOI:10.4103/CRST.CRST_25_19  
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Reducing dexamethasone premedication with paclitaxel p. 126
Nirmal Vivek Raut
DOI:10.4103/CRST.CRST_31_19  
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Author response to: Reducing dexamethasone premedication with paclitaxel p. 128
Vanita Noronha, Deborah Enting, Ravi Thippeswamy, Amit Joshi, Vijay Maruti Patil, Kumar Prabhash
DOI:10.4103/CRST.CRST_53_19  
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Hypothyroidism in head and neck cancer: A surrogate of better radiation delivery? p. 129
Kaustav Talapatra, Rohit Avinash Vadgaonkar
DOI:10.4103/CRST.CRST_30_19  
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Quality of life in patients with multiple myeloma p. 131
Avinash Bonda
DOI:10.4103/CRST.CRST_33_19  
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Lets talk about sex...to our cancer patients p. 132
Kunal Dholakia, Gagan Prakash
DOI:10.4103/CRST.CRST_34_19  
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