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   Table of Contents - Current issue
Coverpage
July-December 2022
Volume 2 | Issue 2
Page Nos. 57-145

Online since Monday, February 6, 2023

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EDITORIAL  

Closing the cancer care gap: Addressing inequalities in oncology Highly accessed article p. 57
US Vishal Rao
DOI:10.4103/jpo.jpo_3_23  
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REVIEW ARTICLES Top

Liquid biopsy: Decoding cancer in blood Highly accessed article p. 58
Abhishek Mohanty
DOI:10.4103/jpo.jpo_17_22  
The molecular landscape of the tumors has been typically established using the surgical or biopsy tissue samples resulting in a sampling bias offering only a single snapshot of tumor heterogeneity from the tissue-based tumor profiles. A rapid understanding of such a bias over the years has helped in procuring a precise portrait of the tumors. This practice has positioned the employability of currently employed molecular analysis of the circulating markers in blood and several other body fluids, such as urine, saliva, and pleural effusions, using liquid biopsies. The genomic profiling of the circulating markers such as circulating circulating tumor DNA (ctDNA), circulating tumor cells, or even RNA, proteins, and lipids as part of exosomes has not only guided the monitoring of response to treatment but also the drug resistance and minimal residual disease. The tumor educated platelets (TEPs) and their biological mechanisms driving the influencing of platelets by tumor cells are beginning to unearth TEPS as dynamically predominant components of liquid biopsy. Here, the biology, methodology, and clinical applications of liquid biopsy biomarkers are highlighted. The article puts forth how technological advances have catapulted cancer diagnosis via liquid biopsy in the last decade to obtain a tumor-derived genetic information for its exploitation toward personalized patient care so that liquid biopsy can come into routine clinical practice.
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Omics approaches in cancer management: Focussing on biobanks as emerging platforms for biomarker-based precision oncology Highly accessed article p. 67
Abhishek Mohanty, Daniel Catchpoole
DOI:10.4103/jpo.jpo_18_22  
Biobanks provide a platform for innovative biomedical research of cancer etiology, progression, and prognosis and have improvised translational and personalized medicine to a great extent. They form the cornerstone, providing resources for future investigations and helping us understand the effects of genetic, environmental, and lifestyle factors on human morbidity, mortality, and health. Time 2009 published ten ideas changing the world right now with biobanks providing linkage to clinical, pathologic, and epidemiologic data of emphasizing its role in discovering and developing biomarkers in new therapeutic drugs. In this review, we highlight the emergence of biobanks as definitive platforms for biomarker discovery-based precision oncology as well as its potential to facilitate bench-to-bedside oriented and multiomics-based translational cancer research.
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Molecular mechanisms of oral submucous fibrosis and oral cancer: A review p. 75
Ashwini Dhopte, Hiroj Siddharth Bagde
DOI:10.4103/jpo.jpo_23_22  
Chewing betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSMF), a potentially malignant oral premalignant condition (OPMD). BQ constituents including areca nut (AN), trauma by coarse AN fibre, catechin, copper, alkaloids, increased reactive oxygen species, inflammation, and cytotoxicity are hypothesised to be the causative factors. They may stimulate tissue inflammation, fibroblast proliferation and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links, and impede collagenphagocytosis, ultimately leading to the formation of oral squamous cell carcinoma (OSMF) and oral cancer. Through modulation of transforming growth factor1, plasminogen activator inhibitor1, cystatin, lysyl oxidase, tissue inhibitors of metalloproteinases, and matrix metalloproteinases, BQ componentinduced alterations in extracellular matrix turnover facilitate these events. In addition, genetic predisposition plays a role in many disease processes. Understanding the molecular pathways underlying BQinduced OSMF and oral cancer can aid in the future prevention and treatment of disease.This paper provides a comprehensive review of the molecular processes involved in BQ-induced OSMF and oral cancer, as well as future preventative prospects.
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Multifaceted role of mesenchymal stem cell in oral cancer: A review p. 83
Lynn Johnson, Hiroj Bagde
DOI:10.4103/jpo.jpo_22_22  
Oral cancer is among the top 10 most prevalent forms of cancer worldwide, characterized by a highly diverse group of tumors and the absence of specific biomarkers and poor prognosis. It is evident that oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer in developing nations, particularly in Southeast Asia and southern Africa. Despite recent advances in the treatment modalities, including surgery, chemotherapy, and radiotherapy, the mortality rate of OSCC (mainly due to lymphatic involvement and metastasis) continues to rise, presenting both patients and healthcare systems with a challenge. It has been shown that tumors are heterogeneous due to the presence of different kinds of cancer cells. In addition to these populations of cells, cancer stem cells (CSCs) contribute substantially to the initiation and progression of cancer. The CSCs are also capable of self-renewal and differentiation, similar to their stem cell counterparts. The mesenchymal SCs (MSCs) are a specific population of CSCs which differentiate into mesodermal cells. The characteristics of MSCs include self-renewal, rapid proliferation, multipotent differentiation, and low immunogenicity. Furthermore, because MSCs are particularly prone to delivering therapeutic agents and transferring genetic material to injured tissues and tumors, they are excellent candidates for use as cell carriers. There has been a significant amount of research regarding the potential pro-or antitumorigenic effect of MSCs on the progression and initiation of tumors. The interaction between tumor cells and MSCs within the tumor microenvironment plays an important role in tumor progression. It is important to note that MSCs are recruited to the site of wound healing in order to repair damaged tissues, a process that is also related to tumorigenesis. Alternatively, resident or migrating MSCs may favor tumor angiogenesis and make the tumor more aggressive. The interaction between MSCs and cancer cells is fundamental to the development, progression, and metastasis of cancer. Therefore, an interesting topic is the relationship between cancer cells and MSCs, since contrasting reports about their respective influences have been reported. In this review, we discuss recent findings related to conflicting results on the influence of MSCs in cancer development and its management.
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ORIGINAL ARTICLES Top

Evaluation of the effect of yoga on symptom burden and quality of life impairment in head-and-neck cancer patients receiving radiotherapy p. 95
Meenakshi Chobe, Amritanshu Ram, Raghavendra Rao, Shivaji Chobe
DOI:10.4103/jpo.jpo_2_23  
Introduction: Psychological stress has been implicated in the onset and exacerbations of several diseases, including cancer. Psychosocial factors have been associated with a higher cancer incidence, poorer survival, and higher cancer mortality. The present study aimed to see the relationship of symptom burden and quality of life (QoL) impairment in head-and-neck cancer (HNC) patients undergoing radiotherapy with perceptions of yoga intervention. Methodology: The present study was a one-time survey conducted on 53 patients with HNC. The main outcome variables of the study were symptom severity and burden, which were assessed by The MD Anderson Symptom Inventory (MDASI) QoL impairment by using the European Organization for Research and Treatment in Cancer H and N 35 questionnaire and survey questions were prepared and administered to elicit the perceptions of patients toward a yoga. Results: The mean age of the study population was 56.5 ± 12.34 years. The perceived benefit of yoga among the yoga practitioners was 66%, and on the other hand, the perceived benefit of conventional treatment among nonyoga practitioners was only 23%. The HNC patients performing yoga along with conventional treatment experienced significantly less distress as compared to the nonyoga practitioners. Conclusion: The study has shown that the yoga practitioners experience less psychological distress as compared to the nonyoga practitioners and their perceived benefits were higher. Yoga also reinforced beliefs in conventional treatment. This may be probably useful in improving compliance with conventional treatment. Therefore, adding yoga to the conventional treatment can prove to be an important and useful adjunct.
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Evaluation of morphological, clinical, and prognostic significance of nucleophosmin gene mutation in de novo acute myeloid leukemia: A retrospective study p. 102
Sudarshan Venkat Pandit, Nilesh Wasekar, Girish Badarkhe, Rajat Bajaj, Yasam Venkata Ramesh, Raj Nagarkar
DOI:10.4103/jpo.jpo_2_22  
Introduction: Nucleophosmin 1 (NPM1) is a molecular chaperone protein. Mutation of NPM1 gene is identified to be one of the most predominant molecular abnormalities in acute myeloid leukemia (AML). Among the genetic mutations, NPM1 along with FMS-like tyrosine kinase 3 (FLT3) mutations lead to poor prognosis and unfavorable outcomes in patients with AML. Methods: This was a retrospective study conducted for 2 years at a leading cancer care center in India. A total of 10 patients were identified to be NPM1 positive in 50 identified AML patients. Results: In 10 NPM1-positive patients, eight patients were female. All were adults with a median age of 39.3 years. The majority of the patients were presented with Auer rod (7/10) and intranuclear cup-like inclusions (7/10) with increased number of blasts in peripheral blood smear (77.88%). Lymphadenopathy was absent in all patients. Morphological analysis has shown blast cells with a cup shape and prominent nucleoli with indentation. Whereas, immunophenotyping analysis has shown lower positivity of cluster of differentiation 34 (12%) and lack of human leukocyte antigen-DR expression (34%). Conclusion: The presence of NPM1 mutations alone without FLT3 mutations in patients with AML was observed to have a better prognosis of the disease. Early identification of such mutations by morphological and immunophenotyping analysis can play a vital role in treatment initiation at the earliest for better prognosis and clinical outcomes without much delay.
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Holistic approach to improve quality of life in head-and-neck cancer patients using CARER model of supportive care: A prospective study p. 108
Samara Mahindra, Paul George, Vishal Rao
DOI:10.4103/jpo.jpo_1_23  
Aim: To describe a model (CARER) of supportive care for head-and-neck cancer (HNC) patients and survivors. Methods: Primary data were collected from HNC patients from November 2018 to February 2019. An intervention-based CARER protocol was prescribed to 25 HNC patients. Data on movement and meditation, emotional status, spiritual and mental well-being were assessed in patients at baseline and end line (6 weeks). CARER assessed the patients and caregiver's satisfaction through a questionnaire rating on a scale of 1 to 5 (1-worst and 5-best). Student's independent t-test was used to assess differences between various scores at different time points, and P < 0.05 was considered statistically significant. Results: All patients received the CARER 45 program (mean age 56.0 ± 14.0 years) with 100% compliance. When compared to baseline, onco-nutrition score improved significantly at the end line (5.5 vs. 8.7, P < 0.05). Similarly, significant improvement was observed in onco-movement and meditation (5.9 vs. 6.9, P < 0.05) and onco-mental well-being scores (6.2 vs. 7.5, P < 0.05). Conclusion: Our study supports the utilization of holistic care using CARER model for patients living with and beyond cancer. Furthermore, this study offers potential support for further research on CARER model to influence future policy and funding decisions.
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Prostate-specific Membrane Antigen Positron Emission Tomography (PSMA-PET) and Gleason grading system based Artificial Intelligence (AI) model in diagnosis and staging of prostate cancer p. 113
Dinesh M Siddu, Anil Pawar, G Lohith, Krithikaa Sekar
DOI:10.4103/jpo.jpo_15_22  
Introduction: Prostate cancer is the second-most commonly occurring cancer and the fifth major cause of death among men worldwide. Early diagnosis and treatment planning are very crucial in reducing the mortality rate due to prostate cancer. Gleason grading is the most used prostate cancer prognosis tool by doctors for a long time. It is used to determine the aggressiveness of the cancer for planning treatment options. The process requires very trained pathologists to look at multiple biopsy samples under the microscope and assign a grade to the cancer based on its severity. Methods: In this work, we are adding Gleason grading capabilities to prostate-specific membrane antigen positron emission tomography/ computed tomography (PSMA PET-CT) scans for tumor habitats and classify them as aggressive or indolent type. Tagging habitats with Gleason grade to categorize them as aggressive or indolent type helps in biopsy planning to extract the right tissue samples and tagging helps to target aggressive tumors during radiation therapy. We have developed a machine learning-based model to automatically classify tumor habitat regions of interest from PSMA PET and CT imaging data into Gleason grade groups of indolent and aggressive. Results: The 68Ga-PSMA PET-CT scans are very effective in detecting the presence of different habitats within the tumor with distinct volumes, each with a specific combination of flow, cell density, necrosis, and edema. Habitat distribution through tumor heterogeneity analysis in patients with prostate cancers can be enabled to discriminate between cancers that progress quickly and those that are more indolent. Conclusion: We have developed an AI model to classify habitat tumors present in the gross tumor volume into indolent and aggressive types based on the ground truth generated using Gleason grade groups on pathology samples by Healthcare Global Cancer Hospital, Bangalore, India. Habitat analysis helps radiotherapists to target active tumor cells within gross tumor volume and helps in selecting the right tissue for performing biopsy. The currently developed model is performing with an overall accuracy of 90% on test data.
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Expression of breast cancer gene 2 in oral squamous cell carcinoma and its correlation with the metastatic potential: A retrospective study p. 120
Niharika Hitendra Mistry, Suchitra Rajesh Gosavi, Akshay Dhobley, Shubhangi Mishra, Pooja Kherde
DOI:10.4103/jpo.jpo_25_22  
Background: Breast cancer gene 2 (BRCA2), a tumor suppressor gene, has been extensively evaluated in various cancers and correlated with metastatic potentials. However, to the best of our knowledge, the correlation has not been reflected in the literature in patients with oral squamous cell carcinoma (OSCC). Any positive correlation may yield the protein as an exploitable marker for the prediction of metastasis and target for chemotherapy in patients with OSCC. Materials and Methods: This observational retrospective study was conducted on 54 tissue samples, 18 samples each of normal oral mucosa, and of OSCC with and without cervical lymph node metastasis. The study samples were immunohistochemically stained with BRCA2 antibody. The staining index was calculated as a product of the percentage of positive cells per high-power field (HPF) (A) and the staining intensity (B). Results: Based on intergroup comparisons, it was found that the percentage of positive cells/HPF, staining intensity, and staining index were higher in OSCCs with cervical lymph node metastasis and lower in normal oral mucosa samples. It was found that a large number of the normal oral mucosa samples (n = 13) did not show any BRCA2 immunoreactivity and a large number of the OSCC samples with cervical lymph node metastasis displayed high BRCA2 immunoreactivity (n = 15). Conclusion: Overexpression of BRCA2 is linked to the presence of metastases in patients with OSCC and has the potential to be utilised as a marker to predict the outcome of the patient's treatment. The findings may be used in the future to develop targeted therapies, depending on the direction that future research follows.
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Molecular profiling of large B-Cell lymphomas : A retrospective observational pilot study p. 125
Amrit Kaur Kaler, Shaila , R Ashwini, R Veena, Sachin Jadav, Baby Dharman, Ramesh Patil, Gautam Balaram, Prassana Kumari, Mithua Ghosh, Shruthi Sudarshan, BS Ajai Kumar
DOI:10.4103/jpo.jpo_19_22  
Background: Large B-cell non-Hodgkin's lymphoma (NHL) comprises of a heterogeneous group of lymphomas with a high-grade morphology and aggressive nature. The diagnosis has gradually evolved from morphological characterization to classification of this group based on ancillary techniques such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular studies. Diffuse large B-cell lymphomas (DLBCL), not otherwise specified (NOS) is the most common B-cell NHL reported and a new diagnostic entity termed high-grade B-cell lymphoma harboring an MYC rearrangement with a BCL2 and/or BCL6 have been introduced by the WHO in 2017. MYC and BCL2/BCL6 proteins expression on IHC due to mutations leading to nuclear factor kappa B pathway activation is considered as double-expressor lymphoma (DEL). Materials and Methods: Sixty-two patients diagnosed with DLBCL, NOS on histopathology were subjected to IHC markers such as (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT, and Myc) and classified into activated B-cell and germinal center B-cell based on Hans' Algorithm. The samples were consequently subjected to tissue FISH for the detection of MYC, BCL2, and BCL6 gene translocations and classified as double-hit lymphoma (DHL)/triple-hit lymphoma (THL). The FISH results were subsequently compared for IHC expression of c-myc, Bcl2, and Bcl6. The staging, international prognostic index (IPI) scoring and lactate dehydrogenase levels were compared with progression-free survival (PFS) of 15 months among DHL/THL and DEL/TEL. Results: The median age of presentation among DLBCL-NOS patients is 58 years, while males (66.7%) were affected more commonly than females (33.3%). The majority of the patients presented with nodal involvement (71%) while extranodal involvement was seen in 29% cases. Hans' algorithm showed a significant P value with the IHC expression of BCL2, BCL6 and C-MYC. IHC and FISH correlation for BCL2 and BCL6 showed 100% sensitivity and 100% negative predictive value. IHC and FISH for c-MYC showed concordant results with a significant P < 0.03. The clinicopathological results of S/D/THL showed association with higher stage disease, higher IPI scoring, and high Ki-67 index with inferior PFS. Conclusions: IHC MYC is a sensitive screening modality for MYC translocation and can be used for the identification of rearrangement in lower socioeconomic areas. Based on clinicopathological studies, all patients with DLBCL must undergo MYC FISH testing as these patients behave as high-grade lymphomas. Hence, a new entity DLBCL with MYC rearrangement without BCL-2/6 rearrangements maybe considered as a novel entity and to be studied in future cohorts.
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CASE REPORTS Top

Secondary plasma cell leukemia: A case series and review of the literature p. 133
Sudarshan Venkat Pandit, Nilesh Wasekar, Girish Badarkhe, Rajat Bajaj, Yasam Venkata Ramesh, Raj Nagarkar
DOI:10.4103/jpo.jpo_1_22  
Secondary plasma cell leukemia is a rare, aggressive plasma cell disorder with a poor prognosis. Early detection and prompt treatment can increase overall survival. In the current case series, we are reviewing the literature and retrospectively reporting the data of patients who presented to our center over a 3-year period with this rare condition. All of our patients were kept on induction chemotherapy following their initial diagnosis utilizing drug combinations that included cyclophosphamide, bortezomib, and dexamethasone (VTD chemotherapy). Further chemotherapy regimens were added during the later phases, including carfilzomib, pomalidomide, and dexamethasone as well as bortezomib, doxorubicin, and dexamethasone based on the outcome of the patient's response. This case study series emphasizes the significance of early disease detection and prompt supportive and targeted therapy.
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BRAF/Mitogen-activated extracellular signal-related kinase inhibitors induced sarcoid-like reaction in patients with refractory localized conjunctival melanoma: A rare case report p. 138
Susan Kennedy, Karina Kulakova, John Crown
DOI:10.4103/jpo.jpo_14_22  
We present a rare case of a patient with refractory localized conjunctival melanoma (CM) who was treated with BRAF/mitogen-activated extracellular signal-related kinase inhibitors in the absence of systemic metastasis. The patient had complete remission and developed a local sarcoid-like reaction. To our knowledge, this is the first report of this complication in a patient with locally advanced CM which emphasizes the local complication of BRAF inhibition.
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SHORT COMMUNICATION Top

Acute myeloid leukemia with nucleophosmin 1 mutation: Clonal hematopoiesis with indeterminate potential or oncogenic potential? p. 143
Amrit Kaur Kaler, Nikhil Rabade, Kiran Ghodke, Yash Tiwarekar, Smita Umarji, Kaveri Gadgi, Ankita Nikam, Samrudhi Rane, Shuchi Singhal, Varsha Vadera, Sameer Tulpule
DOI:10.4103/jpo.jpo_20_22  
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