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   Table of Contents - Current issue
January-March 2019
Volume 40 | Issue 1
Page Nos. 1-158

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The new IJMPO: The phoenix is ready to fly Highly accessed article p. 1
Padmaj S Kulkarni, Jyoti Bajpai
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The “Phoenix” rises from its ashes Highly accessed article p. 2
Gouri Shankar Bhattacharyya
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What should I Do? What should my patients Do? p. 3
Purvish M Parikh, Padmaj Kulkarni
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Liquid biopsy when MEAT is not the treat p. 5
K Govind Babu
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Editorial - T790M mutation and clinical outcomes with genuine osimertinib p. 7
Purvish M Parikh
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Indian council of medical research consensus document for the management of pancreatic cancer p. 9
Shailesh V Shrikhande, Savio G Barreto, Bhawna Sirohi, Munita Bal, Raj Kumar Shrimali, Raju T Chacko, Vikram Chaudhari, Vikram Bhatia, Suyash Kulkarni, Tanvir Kaur, RS Dhaliwal, Goura Kishor Rath
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Selective cyclin-dependent kinase 4/6 inhibitors as anticancer drugs: Moving beyond hormone receptor-positive breast cancer p. 15
Tamojit Chaudhuri, K Govind Babu, KC Lakshmaiah, Lokanatha Dasappa, Linu Abraham Jacob, MC Suresh Babu, AH Rudresha, KN Lokesh, LK Rajeev
The cyclin D-cyclin-dependent kinase (CDK) 4/6 pathway controls the cell cycle machinery by regulating the G1-to-S-phase transition. Dysregulation of this pathway, resulting in increased cellular proliferation, is frequently observed in a variety of human cancers. Activation of cyclin D-CDK 4/6 pathway can occur through different mechanisms, including gene amplification/rearrangement, loss of negative regulatory factors, epigenetic modifications, and point mutations of different components of this pathway. Quite conspicuously, CDK 4/6 inhibitors have emerged as promising anticancer agents in various tumors in which CDK 4/6 has a pivotal role in the G1-to-S-phase cell cycle transition. The clinical use of first-generation, nonselective pan-CDK inhibitors was not progressed beyond early phase trials, due to unacceptable toxicity and lack of efficacy noted with these agents. The emergence of selective CDK 4/6 inhibitors, including ribociclib, abemaciclib, and palbociclib, has enabled us to effectively target cyclin D-CDK 4/6 pathway, at the cost of acceptable toxicity. The results of landmark Phase III trials investigating palbociclib and ribociclib in advanced hormone receptor (HR)-positive breast cancer have demonstrated a substantial clinical benefit with a well-tolerated toxicity profile. Mechanisms of acquired resistance to selective CDK 4/6 inhibitors are beginning to emerge. Clearly, a detailed understanding of these resistance mechanisms is very much essential for the rational development of post-CDK 4/6 inhibitor therapeutic strategies. Extending the use of selective CDK 4/6 inhibitors beyond HR-positive breast cancer is a challenging task and will likely require identification of clinically meaningful biomarkers to predict response and the use of combination approaches to optimize CDK 4/6 targeting.
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Role of pretreatment fluorodeoxyglucose positron emission tomography quantitative parameters in prognostication of head-and-neck squamous cell carcinoma p. 21
Narayana Subramaniam, Deepak Balasubramanian, P Shanmuga Sundaram, Samskruthi Murthy, Krishnakumar Thankappan, Subramania Iyer
In spite of the good organ preservation strategies available for locally advanced head-and-neck squamous cell carcinoma (HNSCC), failure rates have been reported to be as high as 35%–50%. There has been an increasing interest in predicting response to treatment, to aid early intervention and better outcomes. Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is a standard modality for posttreatment evaluation; however, it is still underutilized as a pretreatment investigative modality. Several articles have described quantitative parameters in pretreatment FDG-PET to prognosticate patients and determine the likelihood of response to treatment; however, they are still not used commonly. This article was a review of the literature available on pretreatment FDG-PET quantitative parameters and their value in predicting failure. A thorough review of literature from MEDLINE and EMBASE was performed on pretreatment quantitative parameters in HNSCC. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were reliable parameters to predict response to organ preservation therapy, disease-free survival, and overall survival. Maximum SUV (SUVmax) was an inconsistent parameter. MTV and TLG may help predict poor response to organ preservation to initiate early surgical salvage or modify therapeutic decisions to optimize clinical outcomes. Routine use may provide additional information over SUVmax alone.
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The prevalence of BRAF V600E mutation in hairy cell leukemia: A systematic review and meta-analysis study p. 28
Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi, Nasrin Iranshahi
Background: BRAF V600E mutations were recently identified in the leukemic cells from patients with hairy cell leukemia (HCL) that this mutation in exon 15 is considered the disease-defining mutation in HCL. Objectives: This meta-analysis aimed to report the prevalence of BRAF V600E mutation in HCL patients. Methods: Three databases including PubMed, Scopus, and Web of Science up to 2017 were searched for the prevalence of BRAF mutation in HCL patients. A random effects meta-analysis was performed using the Comprehensive Meta-Analysis software version 2.0 with the event rate (ER) and 95% confidence interval (95% CI). Results: Out of 552 articles identified from the search, 11 were included included and were analyzed for meta-analysis study. The studies in meta-analysis included 437 patients with HCL, of which 353 (80.8%) patients had BRAF V600E mutation. The pooled ER of the studies was 81.5% (95% CI: 69.5%–89.5%). The Begg's test did not show publication bias, but the Egger's test showed publication bias. Conclusions: With regard to the mentioned limitations, the prevalence of BRAF mutation in HCL patients was >80%. In future studies, considering sex, age, and other variables can exactly show the correlation between these variables with the detection of BRAF mutation.
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Human leukocyte antigen-matched unrelated donor search experience for hematological disorder patients requiring transplant: scenario for Indian patients p. 32
Vikash Chandra Mishra, Pranav Dorwal, Hina Solanki, Tarun Kohli, Aseem Kumar Tiwari, Vimarsh Raina, Girish Sharma
Introduction: Human leukocyte antigen (HLA)-matched unrelated donor (MUD) is the source of MUD transplantation (MUDT) for about 70% of patients who do not have matched related donor. To facilitate MUD search globally, there are 75 stem cell registries with more than 28 million donors registered (as of January 2017). Out of these donors, India has an insignificant representation of approximately 0.23 million. Further, Indians express high genetic variations, making it difficult to find MUD for an Indian patient. Aims and Objectives: The aim of this study is to analyze the MUD search for hematological disorder patients requiring transplant. An attempt was made to observe the MUD scenario for Indian patients requiring MUDT from accessible stem cell registries. Methods: A total of 558 patients approached Genebandhu registry and Chimera Transplant Research Foundation for MUD search over a period of 4 years requiring MUDT were included in this study. High resolution of HLA-A, -B, -C, -DRB1, and -DQB1 was used to perform MUD search through proprietary software called Prometheus and Bone Marrow Donors Worldwide (BMDW) search tool. Results: Out of 558 patients, MUD was located only for 135 (24.19%) patients. Out of these 135 patients, 91 (16.30%) patients found an MUD in global database and only 44 (7.88%) patients within India. Conclusion: This study demonstrates that building a large Indian database will not only help in increasing the chances of finding an MUD for maximum number of patients within India but also provide cost-effective treatment, in a society where cost is a vital factor.
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Clinicopathological spectrum of BCR-ABL-Negative myeloproliferative neoplasms with correlation with janus-associated kinase 2 mutation p. 35
Roopa Dixith, A Sara, Navatha Vangala, Shantveer G Uppin, Megha S Uppin, A MV R Narendra, Tara Roshni Paul
Background: Non chronic myelogenous leukemia (non-CML)/BCR-ABL-negative myeloproliferative neoplasms (MPNs) include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (apart from chronic neutrophilic leukemia and chronic eosinophilic leukemia, which are rare). They are uncommon clonal disorders of adults, with an incidence ranging from 0.5 to 3/100,000 persons, BCR-ABL negative, and characterized by the activation of Janus-associated kinase 2 (JAK2). Very few studies have been reported from India. Aims and Objectives: The aims and objectives of this study were to analyze the clinicopathological spectrum and to determine the frequency of JAK2 mutation in patients of non-CML/BCR-ABL negative MPNs. Materials and Methods: Clinical and morphological features and frequency of JAK2 mutation in patients with PV, ET, and PMF were studied at a tertiary care hospital. The material was retrieved from the hematopathology records and reviewed. Results: JAK2V617F mutation was found in 10 of 14 cases (71%) of MPNs, 100% in PV, 50% in ET, and 71% of idiopathic myelofibrosis. The presence of JAK2V617F mutation was associated with a higher hemoglobin level (P < 0.05), a higher TLC (P < 0.05), and higher age (P < 0.05). Results showed that there are morphologic differences, and megakaryocytic morphology represents a useful clue for the differential diagnosis of these three BCR-ABL-negative MPN subtypes. Conclusion: The JAK2 V617F mutation was detected in 71% of patients with MPN disorders. Peripheral blood mutation screening for JAK2 V617F should be incorporated into the initial evaluation of patients suspected to have MPNs. Differences in megakaryocytic morphology provide the histomorphological hallmark of BCR-ABL-negative MPN subtypes.
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Clinical profile and outcomes of Non-Hodgkin's lymphoma in children: A report from a tertiary care hospital from India p. 41
Jagdish Prasad Meena, Aditya Kumar Gupta, Mansingh Parihar, Rachna Seth
Background: Non-Hodgkin's lymphoma (NHL) is an aggressive malignancy. Its outcome has improved over the past decades. Although it accounts for 8%–10% of all childhood cancers, very less information about its clinical presentation and outcomes is available from India. Our objective was to study the clinical presentation and outcomes in children (<15 years) with NHL at our center. Methodology: We retrospectively analyzed 26 children diagnosed with NHL at our center from August 2008 to June 2014 and followed them up to May 2017. Results: The median age at the time of diagnosis was 7.7 years (2.5–13 years). Abdominal distension and an abdominal lump were the most common presenting features occurring in 75%, followed by fever (73.8%) and weight loss (46.2%). Most patients had advanced-stage (Stage III/IV, 92.3%) disease at presentation. The primary presentation was extranodal in 57.7%, nodal in 26.9%, and combined in 15.4%. Burkitt's lymphoma (BL) was the most common subtype (46.2%), followed by T-lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma. Three patients did not take treatment. The median follow-up of patients was 48 months (36–99 months). Nineteen patients achieved remission and four had progressive disease. Significantly better event-free survival (EFS) was found with younger age and lower stage of presentation. The EFS did not significantly differ with sex, group of disease, lactate dehydrogenase levels, and presenting features. Conclusions: Our cohort of patients with NHL showed characteristics similar to those reported from other developing countries. NHL occurred at a younger age, with a higher incidence of BL. The outcome for patients aged >10 years was poor. The outcome of NHL was comparable to that of other centers in the world.
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Role of neoadjuvant chemotherapy in breast cancer patients: Systematic review and meta-analysis p. 48
Mona Pathak, SV S Deo, Sada Nand Dwivedi, Vishnubhatla Sreenivas, Bhaskar Thakur, Pramod Kumar Julka, GK Rath
Background: The present systematic review and meta-analysis critically assessed the impact of neoadjuvant chemotherapy (NACT) in comparison to ACT in breast cancer patients in terms of oncological and functional outcomes. Methods: Randomized controlled trials comparing NACT with ACT in breast cancer patients were identified through Medline and Cochrane Register of Controlled Trials on January 21, 2016. Cochrane risk of bias assessment tool was used to assess the risk of bias. Meta-analysis was performed using fixed-effects or random-effects method depending on heterogeneity (I2). Grading of the evidences was also done. Subgroup meta-analysis on the basis of total preoperative chemotherapy or sandwich chemotherapy was also performed. Results: The present meta-analysis shows increased breast-conserving surgery (BCS) rate (n = 9, risk ratio [95% confidence interval (CI)] = 1.19 [1.03–1.37]) with NACT. Further, NACT was found equally effective regarding overall survival (n = 15, hazard ratio [HR] [95% CI] = 0.98 [0.89–1.08]), disease-free survival (DFS) (n = 14, HR [95% CI] = 1.01 [0.86–1.18]), and distant metastasis (n = 13, HR [95% CI] = 0.97 [0.82–1.16]). Although locoregional recurrence (LRR) rate was noted to be significantly higher in NACT group (n = 15, HR [95% CI] = 1.23 [1.06–1.43]), its significance disappeared (n = 13, HR [95% CI] = 1.17 [0.98–1.40]) by excluding the trials where surgery was not provided for patients with complete tumor response. After excluding such trials, preoperative NACT was associated with increased BCS with similar LRR in ACT group. Discussion: NACT has no major impact on breast cancer survival. However, it is associated with increased BCS rates. NACT downgrades tumor size facilitating more BCSs without increasing LRR. The evidences were graded for all outcomes as high except DFS and BCS as moderate.
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Octamer 4 expression and lymph node metastasis in ductal carcinoma of breast: Are they associated? p. 63
Sangita A Vanik, Shakti Kumar Yadav, Aarzoo Jahan, Sonam Kumar Pruthi, Namrata Sarin, Ratna Chopra, Sompal Singh
Purpose: Octamer 4 (Oct-4) is a transcription factor which is required for the self-renewal and pluripotency of embryonic stem cells and germ cells. In this study, we tried to examine the association of expression of Oct-4 with lymph node metastasis in ductal carcinoma of the breast. Methods: The study was conducted on a total of 45 cases of invasive ductal carcinoma of breast, no special type. Oct-4 expression was studied on paraffin-embedded sections by immunohistochemistry. Results: Oct-4 expression was seen in 22.2% of cases. No statistically significant association was found between the expression of Oct-4 and histological type, tumor size, histological grade, and lymph node metastasis. Of Oct-4 positive tumor, 80% of cases showed lymph node metastasis, as compared to 62.85% without Oct-4 expression. However, the association was statistically insignificant. Conclusion: Oct-4 expression can be a promising biomarker of carcinogenesis, metastatic potential, and prognosis of carcinoma breast. However, the study with larger sample size is needed to establish the clinicopathological potential of this biomarker.
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Triple-negative breast cancer: Pattern of recurrence and survival outcomes p. 67
Shyny Reddy Chintalapani, Stalin Bala, Meher Lakshmi Konatam, Sadashivudu Gundeti, Siva Prasad Kuruva, Monalisa Hui
Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer which is defined as the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 overexpression by immunohistochemistry. As the survival data on TNBC in the Indian population are scant, this study was done to analyze the clinicopathological features and clinical outcomes of TNBC patients. Materials and Methods: Data from medical records of patients with breast cancer between 2009 and 2014 were retrieved, and patients with TNBC were identified and analyzed for demographic and clinicopathological features. Survival analyses were performed using the Kaplan–Meier method for disease-free survival (DFS) and overall survival (OS). Results: A total of 1024 breast cancer patients were registered at our institute during the study period, of which 198 were TNBCs accounting for 19.3% of all breast cancers. Median age at the diagnosis was 50 years (range, 22–78 years). Lymph nodal positivity in TNBC was associated with larger tumor size (P = 0.003) and higher tumor grade (P = 0.01). At a median follow-up of 48 months (range, 12–88), 36 (19.1%) patients had recurrence of the disease, whereas 28 (14%) patients were lost to follow-up. Lung (52.7%) was the most common site of recurrence followed by bone (25%) and brain (11.1%). Three-year DFS and OS were 63.2% and 65.6%, respectively. On univariate analysis, nodal status, size of tumor, and lymphovascular invasion were found to have a significant impact on OS and DFS. On multivariate analysis, only nodal status was significant for DFS and OS (P < 0.001 and P = 0.001, respectively). Conclusions: TNBCs have a rapid clinical course, and early recurrences are common inspite of timely medical intervention which reflects the aggressive tumor biology. This warrants further studies on intensification of chemotherapy and identification and development of targeted therapy aimed at decreasing recurrences and improving survival in this patient population.
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T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer p. 73
Ravi Jaiswal, Rakesh Pinninti, M VT Krishna Mohan, A Santa, Pavan Kumar Boyella, Lavanya Nambaru, Sudha S Murthy, K Veeriah Chowdary, Senthil Rajappa
Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors TKIs) are highly effective in EGFR-mutant advanced lung cancer. The most common resistance mechanism to EGFR-TKI is the development of T790M mutation in Exon 20. Osimertinib, a highly selective EGFR-TKI, has been approved for use in patients who progress on the first-line TKI and harbor the T790M mutation. Objective: The primary objective is to prospectively study the incidence of T790M mutation in patients who progress on the first-line EGFR-TKI. Secondary objectives include clinical characteristics that predict for T790M mutation and outcomes with osimertinib. Materials and Methods: This single-center, prospective observational study included 90 patients who progressed on first-line EGFR TKI. All patients had DNA extracted from tissue re-biopsy or plasma circulating tumor DNA (re-biopsy was not feasible or inadequate). T790M mutation was detected using amplification refractory mutation system-polymerase chain reaction, and patients harboring T790M mutation were started on osimertinib (80 mg once daily) until progression or unacceptable side effects. Results: At progression, T790M mutation was detected in 47/90 patients (52.2%). On binary logistic regression model analysis, variables that were independently predictive of the development of T790M were younger age (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.14–16.6, P = 0.031); nonerlotinib TKI use (OR 8.3, 95% CI 1.24–55.8, P = 0.029); and pure adenocarcinoma histology (OR 6.2, 95% CI 1.60–24.7, P = 0.008). Forty-six patients were started on osimertinib. The overall response rate and median progression-free survival were 65.21% and 12.45 months (standard deviation [SD] 1.03, 95% CI 10.41–14.48), respectively. Osimertinib was well tolerated with most toxicities being Grade 1 and 2 diarrhea and skin rash. Conclusions: In our prospective cohort, half of all patients had a T790M mutation at progression on the first-line EGFR TKI. Tissue biopsy is feasible in the majority of patients. Clinical outcomes with osimertinib were consistent with those reported.
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Experience with using fosfestrol for treating metastatic castrate-resistant prostate cancer in resource-limited setting p. 79
Jayachandran Perumal Kalaiyarasi, Venkatraman Radhakrishnan, Trivadi S Ganesan, Anand Raja, Prasanth Ganesan, Manikandan Dhanushkodi, Tenali Gnana Sagar
Background: Fosfestrol is a low-cost estrogen analog that is useful in the management of metastatic prostate cancer in resource-challenged settings. It acts by altering the pituitary axis, adrenal secretion, and 5-alpha reductase activity. Patients and Methods: The outcomes of metastatic castration-resistant prostate cancer patients treated with fosfestrol in our center between June 2012 and December 2015 were analyzed retrospectively. Fosfestrol was given orally at a dose of 120 mg thrice daily. Event was defined as the discontinuation of fosfestrol due to tumor progression or drug toxicity or death due to any cause. The event-free survival (EFS) and overall survival (OS) were calculated by the Kaplan–Meier method. Results: The analysis included 47 patients with a median age of 65 years. Initial Gleason score was available for 41 of 47 patients, of which 17% (7), 39% (16), and 44% (18) were low risk, intermediate risk, and high risk, respectively. The most common site of metastasis was bone (98%). Of 47 patients, 32 (68%) received fosfestrol as the second line of treatment after progression on complete androgen blockade, 14/47 (30%) received it as the third line, and 1/47 received it as the fourth line of treatment. The median prostate-specific antigen (PSA) value at the start of fosfestrol and the nadir PSA value were 43.7 ng/ml and 13.1 ng/ml, respectively. Ninety-one percent (n = 43) of patients had not been previously treated with chemotherapy (docetaxel). Response of PSA of >50% was observed in 55% (n = 26) of patients. The median EFS and median OS after the start of fosfestrol were 6.8 and 14.7 months, respectively, with a median follow-up of 10.9 months. Only two patients developed Grade 3 toxicity, both of whom had diarrhea. Conclusions: In resource-challenged settings, oral fosfestrol is an effective, cheap, and safe option for the management of metastatic prostate cancer progressing after first-line complete androgen blockade.
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Comparison of cervical cancer screening by visual inspection with acetic acid versus cervical-cytology in pregnancy p. 85
Saritha Shamsunder, Deepika Pannu, Geetika Khanna, Ananya Banerjee, Vijay Zutshi, Sunita Malik
Aims: The aim of this study was to compare visual inspection with acetic acid (VIA) with cervical cytology for cervical cancer screening in pregnant women. Settings and Design: A prospective cohort study was conducted after institutional ethical committee approval in a tertiary care hospital in Northern India. Pregnant women of gestational age <28 weeks were randomly recruited from the antenatal clinic. Subjects and Methods: All eligible women had a Pap smear followed by VIA; colposcopy was performed if either test was positive. Swede score was used for grading of the acetowhite lesion; biopsy was planned if Swede score was ≥8. Statistical Analysis Used: The sensitivity, specificity, and predictive values for both screening methods were compared with colposcopy as the reference standard. Results: There were 370 low-risk pregnant women in the age group of 20–36 years in the study with a mean parity was 2.1, and the median period of gestation of 14.6 weeks. Abnormal Pap cytology was seen in 5.9% (n = 22) of patients; the abnormalities were ASCUS in 13 (59%), LSIL in 4 (18.2%), and AGC-NOS in 5 (22.7%) patients. VIA positivity was found in 8.4% (n = 31). The positive predictive value was 31.8% for cervical cytology and 48.4% for VIA (P = 0.001). No invasive lesion was detected. Positive predictive value of VIA was significantly higher than Pap cytology for detection of abnormal lesions. Conclusions: VIA is a cost-effective method with better predictive value than Pap smear for cervical cancer screening in pregnant women.
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Trends in gallbladder cancer incidence in the high- and low-risk regions of India p. 90
Prachi Ravindra Phadke, Sharayu Sitaram Mhatre, Atul Madhukar Budukh, Rajesh Prabhakar Dikshit
Background: Gallbladder cancer (GBC), a common cancer surrounding the Gangetic belt of India, accounts for 80%–90% of biliary tract cancers. GBC incidence shows striking geographical variation in India. Materials and Methods: We used the data from the National Cancer Registry Programme for the year 2001–2014 to study the time trends of GBC in the high- and low-risk geographical regions of India. Annual percentage change (APC) in age-adjusted incidence rates was computed by log-linear regression model. Results: Among females, a statistically significant increase in trend was observed in Cachar (APC: 7.0, P = 0.02), Delhi (APC: 4.0, P = 0.04), and Kamrup (APC: 4.3, P = 0.02) marked under high-risk region and in Bengaluru (APC: 5.7, P = 0.04) and Pune (APC: 3.4, P = 0.04) marked under low-risk region. Among males, increasing but statistically nonsignificant trends were observed in Cachar, Dibrugarh, Kamrup, Nagpur, and Sikkim, whereas decreasing trends were observed in Bengaluru, Barshi, Bhopal, and Kolkata. Aurangabad showed a statistically significant decrease in trend (APC: −14.5, P < 0.001) among males. Conclusion: The time trend and pattern of GBC have striking differences within the country as well as in state. Further large-scale region-wise studies are needed to find the risk factors of GBC.
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Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in oral cavity cancers p. 94
Akshat Malik, Aseem Mishra, Manish Mair, Swagnik Chakrabarti, Apurva Garg, Hitesh Singhvi, Prashant Chopda, Burhanuddin Qayyumi, Nupoor Sawarkar, Yash Mathur, Rathan Shetty, Sudhir Nair, Deepa Nair, Pankaj Chaturvedi
Background: Various studies have associated inflammation with carcinogenesis. But still, the role of inflammatory markers in oral cancer has not been evaluated extensively. Most of the existing studies have been done on patients of varied sites, and their sample size is also scarce. In this study, we have evaluated the impact of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on various clinicopathological factors and survival. Methodology: This was a retrospective analysis of prospectively collected data of 400 patients with oral squamous cell cancer. The pretreatment neutrophil and lymphocyte and platelet counts were recorded, and NLR and PLR were calculated for all patients. The NLR and PLR tertiles were correlated with the incidence of various clinicopathological factors and overall survival. Results: The median follow-up of the cohort was 36 months. The mean survival of the cohort was 41.7 months. PLR was associated with higher incidence of adverse clinicopathological factors. There was a trend of decreased overall survival with increasing NLR tertile. It was found to be significant only for the group which received adjuvant chemoradiotherapy (P 0.01). Patients with higher PLR values have been found to have a lower overall survival (P 0.006). Conclusion: NLR and PLR can be used to predict survival and outcomes in patients oral cavity cancer. PLR is a good predictor for adverse clinicopathological factors and survival. NLR can predict survival only in the subset of patients who have received chemotherapy.
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Effectiveness of filgrastim and polyethylene glycol-filgrastim in the treatment of postchemotherapy neutropenia in children: Phase I clinical trial p. 101
Saeed Yousofian, Ghasem Miri-Aliabad, Azadeh Kiumarsi, Tayeb Ramim
Background: One of the most common side effects of chemotherapy in cancer patients is neutropenia that can result in hospitalization. The purpose of this study was to evaluate the efficacy and tolerability of polyethylene glycol (PEG)-filgrastim compared with filgrastim in the recovery of neutropenia. Methods: This study was a Phase I clinical trial conducted among patients with acute lymphoblastic leukemia aged <16 years who were referred to the Ali Asghar Hospital, Tehran, Iran, from April 2012 until October 2013. Eleven patients were selected, and filgrastim and PEG-filgrastim were injected subcutaneously at a dose of 5–10 μg/kg/day for 7 days and 100 μg/kg as a single dose, respectively. Absolute neutrophil count (ANC) was checked 7 days after the last injection in the two groups. Results: The mean age of the patients was 8.82 ± 4.36 years (3–15 years). Six boys (54.5%) and five girls (45.5%) participated in the study. ANC increase among patients treated with PEG-filgrastim or filgrastim was analyzed separately, and the results showed statistically significant differences between the study groups (P = 0.038). Conclusions: According to the findings, it can be concluded that the PEG-filgrastim is better than filgrastim alone to improve neutropenia induced by chemotherapy in patients with acute lymphoblastic leukemia.
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Drug utilization evaluation of anticancer drugs in a charitable hospital p. 105
Maneesha Mathew, Uday Venkat Mateti, Neethu Saj, Malona Lilly Philip, Vijith Shetty
Background: Evaluating the prescribing patterns of anticancer and supportive care drugs is necessary for ensuring effectiveness and patient's quality of life. Aim: This study aims to evaluate the prescribing patterns in patients receiving chemotherapy. Settings and Design: A prospective observational study was conducted in the Department of Medical Oncology at Justice K. S. Hegde Charitable Hospital. Methods: The study was conducted for 8 months from September 2017 to April 2018. Cancer patients who were above 18 years and are on chemotherapy along with supportive care medications were enrolled. Statistical Analysis: Data were analyzed using descriptive statistics. Continuous data were expressed as mean ± standard deviation, and the nominal data were expressed as frequency and percentages. Results: Among 230 patients, majority of patients were in the age group of 45–60 years (47%), females (51.7%), Stage III (51.3%), solid tumor (85.5%), breast cancer (21.7%), doublet regimen (60.4%), who received doxorubicin and cyclophosphamide (36%) in breast cancer while paclitaxel and carboplatin (16.52%) were mostly prescribed among the different cancer types. The most commonly prescribed supportive care medications were dexamethasone (100%), ranitidine (100%), filgrastim (67.4%), tramadol and paracetamol (23.91%), and levofloxacin (9.56%). The percentage of drugs prescribed from the National List Essential Medicine and the World Health Organization (WHO) model list was 80.84% and 78.92%, respectively. Conclusion: According to the WHO core prescribing indicators, the average number of drugs per prescription was 9.63. Majority of the cancer patients were prescribed with paclitaxel and carboplatin (16.52%); dexamethasone and ranitidine (100%) were coadministered in all patients during their chemotherapy cycles.
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Emotional exhaustion in cancer clinicians: A mixed methods exploration Highly accessed article p. 111
Rhea Daruvala, Maupali Ghosh, Francesca Fratazzi, Siti Adibah Norzan, Anirban Laha, Rosina Ahmed, Samiran Panda, Soumitra Shankar Datta
Objectives: The aim of the current study was to explore the associations of emotional exhaustion in oncology clinicians and perceptions of doctors about their work–life balance in a developing country. Methods: The current study used quantitative semi-structured interviews and qualitative in-depth interviews to explore emotional exhaustion and burnout in doctors in a tertiary care cancer center. Sociodemographic details, Maslach Burnout Inventory, and Patient Health Questionnaire were used for the quantitative analysis. Results: Increased work pressure (adjusted odds ratio [AOR]: 5.39, 95% confidence interval [CI]: 2.01–14.47, P < 0.01), reduced job-related satisfaction (AOR: 3.56, 95% CI: 1.37–9.25, P < 0.01), being a woman (AOR: 3.4, 95% CI: 1.2–9.5, P < 0.01), and having higher anxiety and depression scores (AOR: 2.89, 95% CI: 1.11–7.46, P = 0.03) were independently associated with higher levels of emotional exhaustion. In the qualitative interviews, many doctors felt working in oncology a satisfying as well as stressful experience. Dealing with palliative and end-of-life situations and counseling patients and their family members about various treatment options contributed to the stress. Male and female clinicians viewed work–life balance differently. Female doctors charted a larger area of influence for which they felt responsible in work and life. Conclusion: Increased work pressure, reduced job satisfaction, and increased affective symptoms contribute to emotional exhaustion in oncology clinicians, and the risk increases especially in female doctors. Having gender-sensitive and employee-friendly policies will likely help in having a nurturing work environment.
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Medical oncology in India: Workload, infrastructure, and delivery of care p. 121
Manju Sengar, Adam Fundytus, Wilma M Hopman, Hemant Malhotra, Sudeep Gupta, CS Pramesh, Nazik Hammad, Richard Sullivan, Verna Vanderpuye, Bostjan Seruga, Gilberto Lopes, Michael D Brundage, Christopher M Booth
Background: The growing burden of cancer within India has implications across the health system including operational delivery of cancer care and planning for human health resources. Here, we report the Indian results of a global survey of medical oncology (MO) workload in comparison to medical oncologists (MOs) in other low-middle- income countries (LMICs). Methods: An online survey was distributed through a snowball method through national oncology societies to chemotherapy-prescribing physicians in 22 LMICs. The survey was distributed to Indian MOs by the Indian Society of Medical and Pediatric Oncology and the National Cancer Grid of India. The workload was measured as the annual number of new cancer patient consults seen per oncologist. Results: One hundred and forty-seven oncologists from LMICs completed the survey; 82 from India and 65 from other LMICs. About 59% (48/82) of Indian MOs reported working exclusively in the private health system compared to 23% (15/65) of MOs in other LMICs (P < 0.001). The median number of annual consults per MO was 475 in India compared with 350 in other LMICs. The proportion of MOs seeing >1000 new consults/year was 24% (20/82) in India and 20% (13/65) in other LMICs (P = 0.530). The median number of patients seen in a full-day clinic was 35 in India and 25 in other LMCs (P = 0.003); 26% of Indian MO reported seeing >50 patients per day. Compared to other LMICs, Indian MOs worked more days/week (median 6 vs. 5, P < 0.001) and hours/week (median 51–60 vs. 41–50, P = 0.004) and had less annual leave for vacation (3 weeks vs. 4, P = 0.017). Conclusion: Indian MOs have higher clinical volumes and workload than MOs in other LMICs and substantially higher workload than MOs in high-income countries. Indian health policymakers should consider alternative models of care and increasing MO workforce supply to address the growing burden of cancer.
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How can we doctors protect ourselves - Managing medicolegal aspects p. 128
Sujit Nilegaonkar, Padmaj Kulkarni
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Why we treat: The tale of a budding oncologist! p. 129
Shruti S Gandhi, Padmaj Kulkarni
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Drug review: Carfilzomib p. 130
Prasanth Ganesan
Carfilzomib is a second generation proteasome inhibitor approved for use in relapsed/ refractory multiple myeloma. The mechanism of action, usage, toxicity and key trials involving this agent are briefly reviewed here.
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Drug review: Fosaprepitant p. 132
Venkatraman Radhakrishnan
Chemotherapy-induced nausea and vomiting (CINV) is a significant contributor to the treatment morbidity experienced by patients with cancer. With effective prophylactic anti-emetics given prior to administration of moderately or highly emetogenic chemotherapy (MEC or HEC) it is expected that 70-80% of patients will have no CINV. Fosaprepitant is an intravenous prodrug of aprepitant that acts as an anti-emetic by blocking the neurokinin (NK-1) receptor. Fosaprepitant in combination with dexamethasone and 5-HT3 antagonist like ondansetron has been shown to be effective in preventing CINV in patients receiving MEC or HEC. The current review discusses the pharmacology and clinical indications for the use of fosaprepitant. The evidence for the effectiveness of fosaprepitant in the prevention of CINV and the commonly observed adverse events with its administration is discussed in this review.
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Conflict of interest: Have we learned anything? p. 136
Maheboob Basade
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Early-onset unusual second cancers – More nightmare in a resource-constrained setting: A report from Lagos, Nigeria p. 137
Adeseye Michael Akinsete, Zainab Aramide Akere, A Nicholas Awolola, Edamisan Olusoji Temiye, Adebola O Akinsulie
Second cancers are not quite common in the pediatric age group, and they are described as histologically distinct cancers from the initial cancer. This study aimed to report the occurrence of second cancers among a cohort of children treated for cancers in Lagos, Nigeria. The report was compiled from the Department of Pediatrics, Lagos University Teaching Hospital, between January 2015 and June 2017. Ethical approval was obtained from the hospital's Research and Ethics Committee. Parental consent was also obtained to publish the reports. A total of one hundred and seventy nine children were treated in the period under review for various malignancies and all those on follow up were included. Two children developed second cancers within 15 months of completing treatment. Extensive genetic testing and surveillance is advocated for children treated in resource-limited settings.
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A novel in-frame 231bp deletion mutation in ABL1 kinase activation loop p. 141
Prashant Ajit Deshpande, Gajanan Bhanudas Padmawar, Venkatesh S Ekbote
Tyrosine kinase domain (TKD) mutation is one of the most common causes for tyrosine kinase inhibitors' resistance in patients with chronic myeloid leukemia (CML). Mutations in the exon 7 of ABL1 gene are one of the most common TKD mutations, especially in the Indian population, but they are frequently underreported, and their clinical significance is not clear. We are reporting a novel ABL1 exon 7 mutation in a previously diagnosed and treated patient CML who presented at the blast crisis stage. Cytogenetic studies showed multiple copies of Philadelphia (Ph) chromosome along with isochromosome 17. Kinase domain mutation studies showed a novel 231bp in-frame deletion mutation (p. 372_448del) in the activation loop of BCR-ABL1 chimeric protein. The given mutation would result in a complete loss of activation loop, including DFG domain-regulating activation status of the catalytic domain. This mutation, along with cytogenetic abnormalities, could have contributed to progression to blast crisis.
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Strongyloides stercoralis hyperinfection complicated by secondary infections in a case of transformed diffuse large B-cell lymphoma p. 144
Hemant J Vira, Hollis D'Souza, Vivek G Bhat, Avinash Bonda
We report Strongyloides stercoralis hyperinfection complicated by secondary infections in a case of transformed diffuse large B-cell lymphoma. The hyperinfection was followed by a sequela of candidemia and infection of the peritoneal fluid that was associated with the leakage of gut flora from the bowel damaged by the migration of larvae. This phenomenon has seldom been reported in a case of hematolymphoid cancer such as transformed diffuse large B-cell lymphoma. The complications arising due to S. stercoralis hyperinfection are associated with a high fatality rate in immunocompromised patients, and this should be taken into account in the diagnosis and management of this condition.
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Gastric lymphoma and gastric tuberculosis: A diagnostic dilemma p. 147
Atul Jain, Pradhuman Yadav, Subhajeet Dey, Tanweer Karim
Gastric outlet obstruction may be caused by a heterogeneous group of diseases that include both benign and malignant conditions. Primary gastric lymphoma (3%–5% of all gastrointestinal malignancies) and primary gastric tuberculosis (TB) (0.4%–2%) are very rare and resemble each other in clinical presentation with diagnostic dilemma between them. Do the two entities exist concomitantly or precede each other is still a topic of debate in the literature. Here, we present a case of primary gastric TB and gastric lymphoma in the same patient.
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Methotrexate and mucositis: A merry-go-round for oncologists p. 150
Kundan Mishra, Aditya Jandial, Anil Kumar, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra
High-dose methotrexate is the backbone of various regimens for treating lymphoid malignancies. Mucositis is a well-known, dose-related side effect of methotrexate. Prophylactic measures such as folinic acid rescue are useful but do not prevent mucositis in all the cases. Once severe mucositis (WHO Grade IV) sets in, mortality is very high. The index case highlights the natural course of methotrexate-induced mucositis and the need for swift and preemptive intervention.
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Indian national guidelines for stem cell research (2017): Summary p. 153
Sandeep Lahiry, Rajasree Sinha
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Carboplatin dosing in real life: Beyond estimating glomerular filtration rate and the virtue of simplicity! p. 155
Valliappan Muthu, Kuruswamy Thurai Prasad, Navneet Singh
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Retraction: Radiofrequency ablation of osteoid osteoma in common and technically challenging locations in pediatric population p. 158

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