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Tuesday, April 16, 2019

Oncology

The new IJMPO: The phoenix is ready to fly
Padmaj S Kulkarni, Jyoti Bajpai

Indian Journal of Medical and Paediatric Oncology 2019 40(1):1-1



The "Phoenix" rises from its ashes
Gouri Shankar Bhattacharyya

Indian Journal of Medical and Paediatric Oncology 2019 40(1):2-2



What should I Do? What should my patients Do?
Purvish M Parikh, Padmaj Kulkarni

Indian Journal of Medical and Paediatric Oncology 2019 40(1):3-4



Liquid biopsy when MEAT is not the treat
K Govind Babu

Indian Journal of Medical and Paediatric Oncology 2019 40(1):5-6



Editorial - T790M mutation and clinical outcomes with genuine osimertinib
Purvish M Parikh

Indian Journal of Medical and Paediatric Oncology 2019 40(1):7-8



Indian council of medical research consensus document for the management of pancreatic cancer
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

Indian Journal of Medical and Paediatric Oncology 2019 40(1):9-14



Selective cyclin-dependent kinase 4/6 inhibitors as anticancer drugs: Moving beyond hormone receptor-positive breast cancer
Tamojit Chaudhuri, K Govind Babu, KC Lakshmaiah, Lokanatha Dasappa, Linu Abraham Jacob, MC Suresh Babu, AH Rudresha, KN Lokesh, LK Rajeev

Indian Journal of Medical and Paediatric Oncology 2019 40(1):15-20

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.


Role of pretreatment fluorodeoxyglucose positron emission tomography quantitative parameters in prognostication of head-and-neck squamous cell carcinoma
Narayana Subramaniam, Deepak Balasubramanian, P Shanmuga Sundaram, Samskruthi Murthy, Krishnakumar Thankappan, Subramania Iyer

Indian Journal of Medical and Paediatric Oncology 2019 40(1):21-27

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. 


The prevalence of BRAF V600E mutation in hairy cell leukemia: A systematic review and meta-analysis study
Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi, Nasrin Iranshahi

Indian Journal of Medical and Paediatric Oncology 2019 40(1):28-31

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.


Human leukocyte antigen-matched unrelated donor search experience for hematological disorder patients requiring transplant: scenario for Indian patients
Vikash Chandra Mishra, Pranav Dorwal, Hina Solanki, Tarun Kohli, Aseem Kumar Tiwari, Vimarsh Raina, Girish Sharma

Indian Journal of Medical and Paediatric Oncology 2019 40(1):32-34

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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