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   Table of Contents - Current issue
Coverpage
January-June 2022
Volume 5 | Issue 1
Page Nos. 1-70

Online since Friday, September 2, 2022

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EDITORIAL  

The enigmatic cell of origin of chronic lymphocytic leukemia p. 1
Anurag Mehta, Shrinidhi Nathany
DOI:10.4103/jco.jco_13_22  
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ORIGINAL ARTICLES Top

Dr. Kanhu’s COSID index: An acronym for plan evaluation in SRS & SBRT Highly accessed article p. 4
Kanhu Charan Patro, Ajitesh Avinash, Arya Pradhan, Chittaranjan Kundu, Partha Sarathi Bhattacharyya, Venkata Krishna Reddy Pilaka, Mrityunjaya Muvvala, Arunachalam Chithambara, Ayyalasomayajula Anil Kumar, Srinu Aketi, Parasa Prasad, Venkata Naga Priyasha Damodara, Veera Surya Premchand Kumar Avidi, Mohanapriya Atchaiyalingam, Keerthiga Karthikeyan
DOI:10.4103/jco.jco_34_21  
Background: A major parameter in the workflow of radiation treatment is the plan evaluation. In order to achieve high dose to target, minimum dose to the critical structures and accurate delivery of treatment, various qualitative and quantitative parameters need to be assessed during plan evaluation. Material and Methods: Here we propose an acronym COSID to describe the five major indices that need to be evaluated during a stereotactic treatment plan. Results: The stereotactic radiation plan evaluation include good target coverage, minimum dose to the organs at risk (OAR), homogeneity and conformity of dose to the target. As very high dose is being delivered in stereotactic radiotherapy in one or small number of fractions, certain other parameters such as the dose fall of beyond the target and the complexity of plan must to be addressed. The proposed COSID index is an acronym for these parameters such as Coverage Index, OAR Index, Spillage Index, Imaging Index and Delivery Index. Conclusion: The paper highlights the five important parameters that need to be assessed while evaluating a Stereotactic Radiosurgery (SRS) or Stereotactic Radiotherapy (SRT) plan.
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FAST-Forward trial in breast cancer: A prospective pilot study addressing dosimetric and practice feasibility in Indian scenario p. 8
A Mohanapriya, Kanhu Charan Patro, Sanjukta Padhi, Chittaranjan Kundu, Partha Sarathi Bhattacharyya, Venkata Krishna Reddy Pilaka, M Mrityunjaya Rao, AC Prabu, Ayyalasomayajula Anil Kumar, Srinu Aketi, P Prasad, Venkata Naga Priyasha Damodara, V S Premchand Kumar Avidi, K Keerthiga, Arya Pradhan, Ajitesh Avinash
DOI:10.4103/jco.jco_39_21  
Aims: To evaluate the dosimetry and practice feasibility in patients of breast carcinoma undergoing postoperative radiotherapy (RT) to the whole breast (WB) as per the FAST-Forward trial protocol. Materials and Methods: A total of 10 patients aged more than 18 years with histopathology proved early stage invasive carcinoma of breast after breast conservation surgery (BCS) were considered for receiving adjuvant RT to the WB with a total dose of 26 Gy in five fractions at a rate of 5.2 Gy per fraction delivered over 5 days. Boost to the tumor bed with a dose of 10 Gy in four fractions was delivered to the BCS cavity with adequate margin as per protocol. Targets were contoured according to the ESTRO guidelines. Heart and ipsilateral lung were considered as organs at risk. Target coverage and dose to the heart and ipsilateral lung were evaluated by dose–volume histograms. All patients were evaluated clinically for acute toxicity such as skin reaction and breast pain weekly once during RT, at the completion of RT, and at 3 months of follow-up. Results: Out of 10 patients, eight patients had right-sided breast carcinoma. As per protocol, we were able to achieve a dose constraint to ipsilateral lung in only three patients (V30%(7.8Gy) ≤ 17%). The range of excess dose variations in remaining seven patients was between 0.4% and 4.5%. Dose constraint to the heart has been achieved in all right-sided breast cancer patients (V25%(6.5Gy) ≤ 5). In left-sided breast cancer patients, an excess range of dose variation was between 0.8% and 2%. Only one patient developed grade III skin reaction at the end of RT (Common Toxicology Criteria for Acute Effects Grade 1). Conclusion: The FAST-Forward trial protocol (26 Gy in five fractions) can be effectively delivered in patients with postoperative invasive early stage breast cancer. The hurdle we faced was lung dose constraint, which was difficult to achieve in certain patients.
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Step-by-step stereotactic radiotherapy planning of brain metastasis in a surgically resected setting: A guide to radiation oncologists: Dr Kanhu’s ROSE case [Radiation Oncology from Simulation to Execution] p. 13
Kanhu C Patro, Ajitesh Avinash, Arya Pradhan, Suresh Tatineni, Chittaranjan Kundu, Partha S Bhattacharyya, Venkata K. R. Pilaka, Mrityunjaya M Rao, Arunachalam C Prabu, Ayyalasomayajula A Kumar, Srinu Aketi, Parasa Prasad, Venkata N. P. Damodara, Veera S. P. K. Avidi, Mohanapriya Atchaiyalingam, Keerthiga Karthikeyan
DOI:10.4103/jco.jco_45_21  
Background: Surgical resection of brain metastasis is followed by adjuvant radiation in order to reduce the risk of local recurrence. Traditionally, adjuvant radiation was practiced in the form of whole brain radiation therapy that was associated with adverse neurocognitive outcomes and poor quality of life of the patients. In the recent times, stereotactic radiosurgery (SRS) is being practiced as the standard of care for treating brain metastasis cavity with good local control and improved the patient’s quality of life by sparing the normal tissues of adverse effects of radiation. Here, we describe procedure details for stereotactic planning of surgically resected brain metastasis. Materials and Methods: The step-by-step procedure for stereotactic planning of brain metastasis cavity has been described using a clinical scenario of brain metastasis. Results: The stereotactic radiation planning of brain metastasis cavity starts with the basic history and relevant evaluation of symptoms. Magnetic resonance imaging (MRI) of the brain is the imaging modality of choice. The radiation planning of brain metastasis cavity starts with computed tomography (CT) simulation and MRI of brain that should be done in a prescribed format to achieve uniformity in radiation planning. After CT and MRI image fusion, contouring of target, organs at risk (OAR), and radiation planning should be done. The plan evaluation includes target and OAR coverage index, conformity, homogeneity and gradient index, and beam arrangement. After radiation plan evaluation, treatment is delivered after quality assurance and dry run. Conclusion: The paper highlights the sequential process of radiation planning for SRT of brain metastasis cavity, starting from simulation, planning, evaluation of plan, and treatment.
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Mortality audit of 19 patients with cancer and SARS-CoV-2 positivity p. 21
Kaberi Kakati, Tashnin Rahman, Debabrata Barman, Mouchumee Bhattacharyya, Bibhuti Bhusan Borthakur, Rashmisnata Barman, Apurba Kalita, Amal Chandra Kataki, Manigreeva Krishnatreya
DOI:10.4103/jco.jco_3_22  
Introduction: Coronavirus disease-2019 (COVID-19) has disrupted cancer care services globally. The main objective of this study was to review the cause of deaths in admitted patients with cancer with positive report for severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2). Materials and Methods: The present review of the cause of deaths was conducted in a tertiary care cancer center in the North East India. In our institute, all cancer patients requiring admission for surgery, chemotherapy, and other daycare procedures require testing for SARS-CoV-2. Results: From 9 July 2020 to 16 May 2021, 119 cancer patients with SARS-CoV-2 positive report or COVID-19 have been admitted to our institute COVID ward. A total of 19 cancer patients with COVID-19 succumbed. Of 19 deaths, 13 (68.4%) patients were men and 6 (31.6%) patients were women. The age range was from 27 years to 74 years (median =55 years). Vomiting alone or with diarrhea was the most common symptom requiring admission after testing (4/19, 21.0%), followed by bleeding from the primary tumor site (3/19, 15.7%). Conclusion: The antecedent and underlying cause of deaths in 19 (100%) patients was cancer. SARS-CoV-2 infection should not be a hindrance to cancer treatment and management.
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Assessment of psychological and physical distress among Indian adolescents and young adults with solid cancer using the NCCN Distress Thermometer and Rotterdam Symptom Checklist p. 25
Shiv Prasad Shrivastava, Aditya Elhence, Prutha Jinwala, Shashank Bansal, Prakash Chitalkar, Shweta Bhatnagar, Rajesh Patidar, Vikas Asati, Pradeep Kumar Reddy
DOI:10.4103/jco.jco_2_22  
Purpose: The incidence of cancer has increased in India with a visible impact on the young population (aged 15–39 years). The present study aims to evaluate psychological and physical distress and symptom burden in Indian adolescents and young adults (AYAs) with solid cancer using the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) and Rotterdam Symptom Checklist (RSCL). Materials and Methods: This prospective, cross-sectional (n = 259) study included AYAs (aged 15–39 years) with histological diagnosis of solid organ malignancy. Patients’ demographic and clinical information were collected. The symptom burden of patients was assessed using the NCCN DT score and RSCL over the trajectory of three time points. Results: Of the 259 patients, 63% were women and 37% men; the median age was 34 years. In total, 71 (27%) were ≤24 years old and 188 (73%) were >24 years old. Bone sarcoma (39%) and germ cell tumor (31%) were the common subtypes in AYA patients aged ≤24 years and breast cancer (21%) in >24 years of age. The distress scores in both the groups were highest at diagnosis (T1) followed by that measured at 1 (T2) and 3 months (T3) after diagnosis. Among AYA patients >24 years old, worry, nervousness, sadness, transportation, and sleep were the top 5 identified problems and in ≤24 years old, the top identified problems were worry, financial support, sleep, nervousness, and sadness. Conclusion: The principle factors related to distress that were identified in Indian AYAs with cancer were: worry, nervousness, sadness, and sleep. The DT and RSCL are useful screening tools for the assessment of psychological and physical distress in AYAs cancer. Early identification of distress burden with the DT and effective interventions in patients with cancer could improve outcomes including survival. Regular screening for psychological distress and substance-cessation counseling will aid in early interventions, thereby improving outcomes in AYAs with cancer in India.
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REVIEW ARTICLES Top

Role of axitinib and other tyrosine kinase inhibitors in the management of metastatic renal cell carcinoma p. 35
Sagar Bhagat, Nishtha Khatri, Saiprasad Patil, Hanmant V Barkate
DOI:10.4103/jco.jco_5_22  
The selection of chemotherapeutic agents in the management of metastatic renal cell carcinoma is a challenge as it has to strike a delicate balance between adverse effects and patient affordability based on the individual risk stratification. In this narrative review, authors have discussed about the various tyrosine kinase inhibitors available and the preference for axitinib as the first-line drug when used as a single agent or in combination with immunotherapeutic agents. This review article has been written based on a literature search of relevant articles conducted from September 2020 to December 2020 across PubMed and Google Scholar.
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Chronic lymphocytic leukemia: Current approach to lab diagnosis p. 39
Devasis Panda, Narender Tejwani, Anurag Mehta
DOI:10.4103/jco.jco_12_22  
Chronic lymphocytic leukemia (CLL) is the most common type of clinically encountered chronic lymphoproliferative disorder (CLPD). The disease was first found in 19th century and was described as asymptomatic leukemia which peacefully coexists with the host. The disease has an indolent clinical course and often picked up when complete blood count is done for an unrelated medical indication. CLL is a disease of elderly and the incidence increases as the age increases. However, Indian patient present early as compared to USA and Europe. There is a slight male preponderance reported worldwide. CLL is often preceded by a non-clinical phase called monoclonal B cell lymphocytosis (MBL) to which is closely related both immunophenotypically and spectrum of molecular aberrations. Recently describe low count MBL however appears to be a distinctive disease of unknown significance as there is not sufficient data to prove that they pose a higher risk of progression to MBL/CLL. Their genetic profile also is very different from MBL/CLL. The symptomatic cases may present with symptoms related to disease progression like cytopenias due to hematopoietic cells replacement or lymph node enlargement or liver/spleen enlargement. The symptoms may also be related to secondary autoimmune phenomena like autoimmune hemolytic anemia and autoimmune thrombocytopenia. The disease diagnoses mostly rely on the use of multi-parametric flowcytometry and peripheral blood morphology. The peripheral smear shows the presence of small cell lymphocytosis with numerous smudge cells. The flowcytometric immunophenotyping show loss of Pan-B cell markers like surface immunoglobulin, CD79b, CD22, and FMC-7. The expression of these markers is either negative or dimmer when compared to normal mature B cells. CD20 expression is also dim as compared to normal mature B cells. Along with the loss of Pan-B cell markers, there is a gain of CD5 (A T cell markers) and CD23. CD200 has emerged as a very useful marker to differentiate this neoplasm from Mantle cell lymphoma which characteristically is CD5 positive, does not show loss of Pan-B cell markers and is negative or Dim positive for CD200. The other differential diagnosis remains other causes of small cell CLPDs like hairy cells, marginal zone lymphomas, lympho-plasmacytic lymphoma, and follicular lymphomas. These cases can be easily differentiated when morphology is combined with flow cytometric findings. In difficult cases, one can use Matutes score where a score of 4 or 5 will indicate a diagnosis of CLL.
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A peek into the world of CLL genomics p. 46
Anurag Mehta, Himanshi Diwan, Sakshi Mattoo
DOI:10.4103/jco.jco_6_22  
Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults in the Western Hemisphere. The divergent course of CLL has instigated a deeper look into CLL genetics. Consequently, many prognostic and predictive biomarkers have emerged. This is a brief review of the CLL genetics, including genes involved in drug resistance.
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Somatic hypermutation in CLL: From bench to bedside p. 52
Shrinidhi Nathany, Anurag Mehta, Himanshi Diwan, Dushyant Kumar, Sakshi Mattoo, Surender Dhanda, Manoj K Panigrahi, Manoj Kumar
DOI:10.4103/jco.jco_9_22  
Chronic lymphocytic leukemia (CLL) is a molecularly heterogeneous disease with a clonal proliferation of B lymphocytes. Immunoglobulin (Ig) sequence analysis is widely employed for prognostic stratification, and European Recommendation in CLL (ERIC) has laid down recommendations for testing and analysis of the same. immunoglobulin heavy chain variable region (IGHV) gene somatic hypermutation has been established as one of the most sensitive prognostic markers in CLL risk stratification, irrespective of the clinical stage or presence of any other alterations. Therapeutic decisions are now based on whether the IGHV is mutated—mCLL (mutated CLL) or unmutated, i.e., uCLL (unmutated CLL). Despite clear-cut clinical observations and differences in both therapeutic response and prognosis of IGHV unmutated group, the exact reason behind this is still elusive. IGHV mutation status has made it to the frontline in both clinical decision-making and the diagnostic battery of CLL testing. This is a focused comprehensive review on the structure, molecular biology, testing recommendations, and prognostic impact of IGHV mutation testing in CLL.
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CLL management in 2022: Indian settings Highly accessed article p. 58
Narendra Agarwal, Megha Verma
DOI:10.4103/jco.jco_8_22  
Chronic lymphocytic leukemia (CLL) is being increasingly recognised in our adult population. Though typically a disease of elderly, many young patients are also being diagnosed especially in Indian subcontinent. It shows a heterogenous clinical course. The diagnosis is established by complete blood counts, blood smears morphology, and immunophenotyping. The diagnosis is made with identification of clonal B-cell population. The clinical staging systems includes results of physical examination and peripheral blood counts. In addition, there are various biological and genetic markers for further prognostic information. The clinical staging and genetic findings guide us for assessing the need to treat and for selection of therapies. The CLL international prognostic index combines the genetic, biological, and clinical variables for risk stratification of patients with CLL. Only selected patients warrant therapy at the time of diagnosis. In the current settings with availability of newer targeted therapies and chemotherapy, clinicians and patients can together choose amongst the available therapeutic regimens. The targeted therapy includes the Bruton kinase inhibitors including Ibrutinib, acalabrutinib and Bcl2 directed therapy with Venetoclax. These therapies can be used as single agent therapy or in combination. Though in west, therapy has majorly shifted to targeted therapy from chemotherapy, we in India are still in the transition phase. Future challenges: Potentially curative treatment regimen of finite duration is being investigated. More studies are needed for improving the outcomes of poor risk group with del17p, Tp53 deletion and in refractory cases. The optimal sequencing of targeted therapies also needs to be determined.
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RESIDENTS CORNER Top

The eyes only see what the mind is prepared to comprehend: A rare case p. 63
Himanshi Diwan, Sunil Pasricha, Anila Sharma, Anurag Mehta
DOI:10.4103/jco.jco_7_22  
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CASE REPORT Top

Breast to bone: Acral metastasis p. 67
Abhay K Kattepur, GN Manjunath, Sreeramulu Patrapalli Nadipanna, Krishna Raj, D Aswathappa
DOI:10.4103/jco.jco_10_22  
Metastasis of the acral bones is a rare phenomenon in breast cancer. Fibular metastasis is extremely uncommon and is usually associated with disseminated disease. We herein describe an elderly woman who presented with a metachronous fibular metastasis as a sign of oligo-recurrent metastatic breast cancer. The patient was treated with palliative radiotherapy with satisfactory outcomes. A brief review of the literature follows.
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