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   Table of Contents - Current issue
Coverpage
April-June 2021
Volume 4 | Issue 2
Page Nos. 193-431

Online since Wednesday, June 30, 2021

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MUSINGS  

Effect of sorcery on myeloid blasts p. 193
Suvir Singh
DOI:10.4103/crst.crst_43_21  
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Drug pricing: A major barrier to access to cancer care in India Highly accessed article p. 195
Venkatraman Radhakrishnan
DOI:10.4103/crst.crst_66_21  
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Onco awareness in pandemic times p. 198
Ajith Cherian
DOI:10.4103/crst.crst_370_20  
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Art of publication: A beginner's guide to understanding the non-linear dynamics between research and publication p. 200
Biplab Sarkar
DOI:10.4103/crst.crst_65_21  
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Bathinda to Bikaner: My experience of the “cancer train” p. 208
Amol Patel
DOI:10.4103/crst.crst_95_21  
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ORIGINAL ARTICLES Top

COVID-19 vaccine uptake and vaccine hesitancy in Indian patients with cancer: A questionnaire-based survey Highly accessed article p. 211
Vanita Noronha, George Abraham, Suresh Kumar Bondili, Annu Rajpurohit, Rakesh P Menon, Shreya Gattani, Mehak Trikha, Rajanigandha Tudu, Kishore Kumar Kota, Ajay Kumar Singh, Prahalad Elamarthi, Goutam Santosh Panda, Rahul Kumar Rai, Madala Ravi Krishna, Sravan Kumar Chinthala, Minit Jalan Shah, Devanshee Shah, Atul Tiwari, Deep Nareshbhai Vora, Arnav Hemant Tongaonkar, George John, Akshay Patil, Nandini Sharrel Menon, Vijay Maruti Patil, Amit Joshi, Shripad Banavali, Rajendra A Badwe, Kumar Prabhash
DOI:10.4103/crst.crst_138_21  
Background: Patients with cancer are at a higher risk of severe forms of coronavirus disease 2019 (COVID-19) and mortality. Therefore, widespread COVID-19 vaccination is required to attain herd immunity. Objectives: We aimed to evaluate the uptake of the COVID-19 vaccine in Indian patients with cancer and to collect information regarding vaccine hesitancy and factors that contributed to vaccine hesitancy. Materials and Methods: This was a questionnaire-based survey conducted between May 7, 2021 and June 10, 2021 in patients aged 45 years and over, with solid tumors. The primary end points of the study were the proportion of Indian patients with cancer aged 45 years and older who had not received the COVID-19 vaccine, and the reasons why these patients had not received the COVID-19 vaccine. Our secondary end points were the proportion of patients with a history of COVID-19 infection, and the proportion of the patients who had vaccine hesitancy. Additionally, we attempted to assess the factors that could impact vaccine hesitancy. Results: A total of 435 patients were included in the study. Of these, 348 (80%) patients had not received even a single dose of the COVID-19 vaccine; 66 (15.2%) patients had received the first dose, and 21 (4.8%) had received both the doses. Approximately half (47.1%) of the patients reported that they took the COVID-19 vaccine based on the advice from a doctor. The reasons for not taking the COVID-19 vaccine could be considered as vaccine hesitancy in 259 (77%) patients. The two most common reasons were fear in 124 (38%) patients (fear of side-effects and of the impact of the vaccine on the cancer/therapy) and lack of information in 87 (26.7%) patients. On the multivariate analysis, the two factors found to be significantly associated with vaccine hesitancy were a lower educational level (OR, 1.78; 95% CI, 1–3.17; P = 0.048) and a lack of prior advice regarding the COVID-19 vaccine (OR, 2.80; 95% CI, 1.73–4.53; P < 0.001). Conclusion: Vaccine hesitancy is present in over half of our patients, and the most common reasons are a fear of the vaccine impacting the cancer therapy, fear of side-effects, and lack of information. Widespread vaccination can only be attained if systematic programs for education and dissemination of information regarding the safety and efficacy of the COVID-19 vaccine are given as much importance as fortification of the vaccination supply and distribution system.
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COVID-19 vaccination status in Indian patients with cancer: An observational study Highly accessed article p. 219
Ullas Batra, Shrinidhi Nathany, Nitin Bansal, Mansi Sharma
DOI:10.4103/crst.crst_131_21  
Background: Patients with cancer are at an increased risk of severe coronavirus disease-2019 (COVID-19). Hence, safe and efficacious vaccination against COVID-19 may play a crucial role in conferring protection to this group of patients. Objectives: As there are no dedicated trials testing the safety and efficacy of COVID-19 vaccines in immunocompromised individuals or patients with cancer, we conducted this study to assess the vaccination status of Indian patients with cancer. Materials and Methods: This single-center observational study was conducted in the Department of Medical Oncology at the Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India, between March and June 2021. Patients with cancer were interviewed telephonically to obtain information related to their vaccination status. The primary endpoint was the proportion of patients with cancer who received a COVID-19 vaccine. The Chi-squared test and McNemar's test were used to determine the associations between the different variables and the vaccination status. Results: Of the 752 patients included in the study, 219 (29.1%) had received at least one dose of the COVID-19 vaccine. Of these, 34 (15.5%) patients subsequently developed COVID-19. They were treated in domiciliary care and did not require hospitalization. Of the 533 patients (70.9%) who were not vaccinated, 117 (21.9%) tested positive for COVID-19 and 14 (11.9%) succumbed to the disease. Conclusion: Our study suggests that there is probably a lack of awareness or fear related to vaccination, which should be addressed to avoid COVID-19-related cancer mortality.
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Optimal dose of bevacizumab in recurrent glioma: A retrospective study p. 224
Hollis Dsouza, Gunjesh Kumar Singh, Nandini Menon, Anuja Abhyankar, Ameya Puranik, Abhishek Mahajan, Amit Janu, Devanshi Kalra, Ochin Dale, Litty Varghese, Sridhar Epari, Abhishek Chatterjee, Rahul Krishnatry, Tejpal Gupta, Rakesh Jalali, Vijay M Patil
DOI:10.4103/crst.crst_41_21  
Background: Recurrent gliomas have a dismal prognosis. They can be treated with re-surgery and re-irradiation. Bevacizumab as a single agent or in combination with chemotherapy is an alternative treatment option. However, in our country, a considerable proportion of patients cannot afford the approved 10 mg/kg dose. Objective: This study was aimed at evaluating the efficacy of low-dose bevacizumab in recurrent gliomas. Methods: Patients with recurrent gliomas presenting to our Neuro-Medical Oncology unit between July 1, 2015, and November 30, 2018, were retrospectively analyzed. The patients were divided into two groups, those treated with ≤5 mg/kg of bevacizumab (low dose) and those treated with >5–10 mg/kg (standard dose) of bevacizumab. The status of isocitrate dehydrogenase (IDH) and O[6]-methylguanine-DNA methyltransferase was recorded. The primary endpoint of the study was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and adverse events. Results: A total of 68 patients were treated with bevacizumab, of which 23 (33.8%) received the low-dose regimen. At a median follow-up of 26.2 months, there was no difference in the median PFS (low-dose group: 3.60 months; 95% confidence interval [CI], 2.5–7.47 vs. standard-dose group: 3.67 months; 95% CI, 2.17–4.53) (P = 0.18) and median OS (low-dose group: 7.33 months; 95% CI, 3.97–9.10 vs. standard-dose group: 5.47 months; 95% CI, 4.67–6.2) (P = 0.27). In addition, the adverse events were not significantly different between the two groups. Conclusion: Low-dose bevacizumab may be effective in the treatment of recurrent gliomas and should be compared with standard dose in prospective randomized studies.
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Changing trends of invasive mediastinal evaluation in India: A questionnaire-based survey p. 231
Jashma Chandveettil, Abhay K Kattepur, Nizamudheen Mangalasseri Pareekutty, Ratheesan Kumbakara, Satheesan Balasubramania
DOI:10.4103/crst.crst_89_21  
Background: The utilization of mediastinoscopy for mediastinal staging or evaluation has been on the wane, because of the increasing use of methods such as endoscopic ultrasound (EUS)/endobronchial ultrasound (EBUS). The choice of one modality over the other is based on individual preferences, expertise, cost, and the disease in question. Objectives: This study was aimed at assessing the changing trends in the practice of mediastinoscopy and endoscopic techniques across India. Materials and Methods: This online, questionnaire-based survey was conducted at the Malabar Cancer Center, Kerala, India, between September 2019 and January 2020. Surgical oncologists, thoracic surgeons, and pulmonologists treating patients with lung cancer in the National Cancer Grid, India-affiliated institutions were enrolled. A total of 20 questions directed at determining the experience of the healthcare professionals, type of institutions where they practiced, the volume of patients with lung cancers being treated by them, and the temporal changes in the utility of mediastinoscopy and EBUS/EUS over the past 2 years were included in the questionnaire. The survey was conducted using Google Forms. Descriptive and inferential statistics were used for data analysis. A P < 0.05 was considered statistically significant. Results: A total of 347 clinicians were invited to participate in the survey, of which 70 responded. A total of 62 (88.6%) respondents recommended invasive mediastinal staging in patients with lung cancer with positive mediastinal nodes on positron emission tomography (PET). In addition, 39 (55.7%) respondents believed that invasive staging is required even in those with a negative mediastinum on PET; 58 (82.9%) respondents were of the opinion that EBUS is the investigation of choice for suspicious mediastinal nodes, while 8 (11.4%) preferred mediastinoscopy. Conclusion: Endoscopic techniques have superseded mediastinoscopy for invasive mediastinal evaluation across the country.
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Impact of sex of the patient on efficacy and safety of cancer immunotherapy: A retrospective audit p. 238
Akhil Kapoor, Vanita Noronha, Vijay M Patil, Amit Joshi, Nandini Menon, Abhishek Mahajan, Amit Janu, Kumar Prabhash
DOI:10.4103/crst.crst_111_21  
Background: It has been established that women usually mount a stronger immune response than men of the same age. Data for the efficacy of immune checkpoint inhibitors (ICIs) based on the patient's' sex are scarce. Objectives: We aimed to evaluate the impact of the patients' sex on the efficacy and toxicity of ICIs. Materials and Methods: Aretrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors between August 2015 and November 2018 was performed at the Tata Memorial Hospital in Mumbai, India. The categorical and continuous variables were evaluated using descriptive statistics. The Kaplan–Meier estimator was used to analyze the progression-free survival (PFS) and overall survival (OS). Results: Atotal of 155 patients were included in the study, of which 36 (23.2%) were female and 119 (76.8%) were male. The median PFS was 2.8 months (95% confidence interval [CI], 1.4–4.2) for the male patients and 1.9 months (95% CI, 1.0–2.8) for the female patients (hazard ratio [HR], 1.06; 95% CI, 0.69–1.66; P = 0.764). The median OS was 5.9 months (95% CI, 1.5–10.2) for the male patients and 4.2 months (95% CI, 1.1–7.3) for the female patients (HR, 1.27; 95% CI, 0.77–2.12; P = 0.342). The rates of all toxicities, except for pneumonitis, were similar between the male and female patients. All-grade pneumonitis occurred in a total of 7 (5.8%) male patients, while it was not reported in any female patients. All-grade immune-related adverse effects occurred in 24 (20.2%) male and 4 (18.1%) female patients (P = 0.216). Conclusions: This study shows that the efficacy and toxicity of ICIs are similar in the male and female patients. However, future trials with a balanced number of male and female patients are required to ensure an unbiased estimation of the efficacy and safety of ICIs.
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Extended RAS mutations (KRAS and NRAS) in patients with colorectal cancers in eastern India: An observational study p. 244
Koushik Chatterjee, Pratyusha Mukherjee, Jeaul Hoque, Manitirthankar Das, Subhayan Saha
DOI:10.4103/crst.crst_102_21  
Background: All treatment guidelines currently mandate KRAS and NRAS mutation analysis as a pretreatment workup of colorectal cancers (CRCs), in view of their prognostic and predictive significance. Objectives: In this study, we aimed to assess the prevalence of the extended-spectrum of KRAS and NRAS mutations in patients with CRCs from Kolkata, in eastern India. Materials and Methods: This retrospective observational study was conducted from January 2017 to January 2020 in patients registered for treatment at the IPGMER and SSKM Hospitals, in Kolkata, India. Patients diagnosed with CRCs with adenocarcinoma histology were included in the study. The formalin-fixed paraffin-embedded tumor tissues of the patients were assessed for the extended-spectrum of KRAS and NRAS mutations using a real-time polymerase chain reaction. The cut-off used for “Tumor Not Present” (TNP) reporting was 15%. These mutations were then mapped with the tumor location. Data were analyzed in a de-identified manner, using simple descriptive statistical methods. The two-tailed Fisher's exact test was used to determine any statistically significant association between variables. Results: TNP was reported in 13 (8.12%). A total of 147 patients with CRC were included in the study. Extended RAS mutations were found in 59 (40.1%) patients. KRAS and NRAS were found to be mutated in 55 (37.4%) and 4 (2.7%) patients, respectively. The most common mutation in KRAS was in G12 in exon 2 (34, 61.8%). Followed by Q61 in exon 3 (8, 14.5%) and A146 in exon 4 (8, 14.5%). Half of the NRAS mutations were in codons 12–13 in exon 2 and half were in codon 61 in exon 3. Dual KRAS mutations were observed in one patient, while two patients had both a KRAS and an NRAS mutation. Extended RAS, KRAS, and NRAS mutations were numerically more common in right-sided CRCs (47.2%, 43.4%, and 3.8%, respectively) than in left-sided CRCs (37.2%, 34%, and 2.1%, respectively). The rectum had numerically higher extended RAS and KRAS mutations but lower NRAS mutations (43.1%, 41.37%, and 1.72% respectively) as compared to the colon (37.36%, 34.06%, and 3.29% respectively). Conclusions: Extended RAS mutations are present in about 40% of the patients with CRC in eastern India, with KRAS (37.4%) mutations more prevalent than NRAS (2.7%) mutations. The right-sided CRCs have predictably more RAS mutations than the left.
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Knowledge, perception, and attitude of the general population toward cancer and cancer care: A cross-sectional study p. 251
Maya Padmanabhan, Satheesan Balasubramanian, EK Muhammed Sha, Riyas Malodan
DOI:10.4103/crst.crst_31_21  
Background: Despite the advances in the field of oncology, the diagnosis of cancer is often considered a death sentence, owing to the misconceptions and myths about cancer treatment. Moreover, improvements in health literacy and awareness about cancer have also not been able to change the attitude of people toward cancer-related health behaviors. Objective: In this study, we aimed to evaluate the knowledge, perception, and attitude of the general population toward cancer and cancer care. Materials and Methods: This cross-sectional study was conducted at Malabar Cancer Center, a tertiary cancer center in Kerala, India, between June 2017 and February 2018. A survey was conducted in the general population in the northern part of Kerala in the districts of Kannur, Kasargod, and Wayanad during a medical camp. People who were aged above 18 years and could read the Malayalam language were included in the study. The participants were administered a questionnaire comprising 26 questions, and the knowledge, perception, and attitude of the general population toward cancer and cancer care were evaluated. Results: A total of 487 people responded to the survey. Of these, 354 (72.7%) were women and 133 (27.3%) were men. The mean age of the cohort was 43.7 years. About 74% of the participants disagreed that all cancers can be treated using the same treatment modalities. A total of 84% of the participants agreed that cancer can be detected early with screening. Almost 95% of the participants were aware of the importance of cancer screening and strongly recommended establishing cancer screening clinics in government setups. Conclusion: There is a positive attitude among the general public toward cancer. Almost all the people surveyed were interested in attending cancer awareness programs, believed in the role of screening and felt that establishing cancer screening programs would be useful. This may help provide a road map for cancer policy-makers.
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Novel artificial intelligence algorithm for automatic detection of COVID-19 abnormalities in computed tomography images p. 256
K S S Bharadwaj, Vivek Pawar, Vivek Punia, M L V Apparao, Abhishek Mahajan
DOI:10.4103/crst.crst_28_21  
Background: Chest computed tomography (CT) is a readily available diagnostic test that can aid in the detection and assessment of the severity of the coronavirus disease 2019 (COVID-19). Given the wide community spread of the disease, it can be difficult for radiologists to differentiate between COVID-19 and non-COVID-19 pneumonia, especially in the oncological setting. Objective: This study was aimed at developing an artificial intelligence (AI) algorithm that could automatically detect COVID-19-related abnormalities from chest CT images and could serve as a diagnostic tool for COVID-19. In addition, we assessed the performance and accuracy of the algorithm in differentiating COVID-19 from non-COVID-19 lung parenchyma pathologies. Materials and Methods: A total of 1581 chest CT images of individuals affected with COVID-19, individuals affected with non-COVID-19 pathologies, and healthy individuals were included in this study. All the digital images of COVID-19-positive cases were obtained from web databases available in the public domain. About 60% of the data were used for training and validation of the algorithm, and the remaining 40% were used as a test set. A single-stage deep learning architecture based on the RetinaNet framework was used as the AI model for image classification. The performance of the algorithm was evaluated using various publicly available datasets comprising patients with COVID-19, patients with pneumonia, other lung diseases (underlying malignancies), and healthy individuals without any abnormalities. The specificity, sensitivity, and area under the receiver operating characteristic curve (AUC) were measured to estimate the effectiveness of our method. Results: The semantic and non-semantic features of the algorithm were analyzed. For the COVID-19 classification network, the sensitivity, specificity, accuracy, and AUC were 0.92 (95% confidence interval [CI]: 0.85–0.97), 0.995 (95% CI: 0.984–1.0), 0.972 (95% CI: 0.952–0.988), and 0.97 (95% CI: 0.945–0.986), respectively. For the non-COVID classification network, the sensitivity, specificity, and accuracy were 0.931 (95% CI: 0.88–0.975), 0.94 (95% CI: 0.90–0.974), and 0.935 (95% CI: 0.90, 0.965), respectively. Conclusion: The AI algorithm developed in our study can detect COVID-19 abnormalities from CT images with high sensitivity and specificity. Our AI algorithm can be used for the early detection and timely management of patients with COVID-19.
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ORIGINAL ARTICLE-REAL WORLD DATA Top

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India p. 262
Swati Bhayana, Manas Kalra, Pallavi Sachdeva, Anupam Sachdeva
DOI:10.4103/crst.crst_98_21  
Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objectives: This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Materials and Methods: This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Results: A total of 650 tests for COVID-19 were performed for 181 children; 22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support; all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusions: Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.
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ORIGINAL ARTICLE: GERIATRIC ONCOLOGY SECTION Top

Immune checkpoint inhibitors in older patients with solid tumors: Real-world experience from India p. 270
George Abraham, Kunal N Jobanputra, Vanita Noronha, Vijay M Patil, Nandini S Menon, Shreya C Gattani, Kumar Prabhash
DOI:10.4103/crst.crst_86_21  
Background: Older patients with cancer are underrepresented in most immunotherapy trials. Therefore, there is an urgent and unmet need for real-world data on the efficacy and safety of immune checkpoint inhibitors (ICIs) in older patients with cancer. Objectives: This study was aimed at analyzing the demographic pattern, treatment-related outcomes, and toxicities of ICIs in older patients with solid tumors. Materials and Methods: This retrospective study was conducted in the Department of Medical Oncology of the Tata Memorial Hospital, a tertiary cancer care center in Mumbai, India. Patients aged ≥ 60 years with histologically confirmed malignancies of the thoracic, head and neck and genitourinary systems who were treated with ICIs between August 2014 and February 2021, and had received at least 2 cycles of ICI were enrolled in the study. Data related to the demographic profile and pattern of care were obtained from the electronic medical records and physical patient files. Patient management was decided in a multidisciplinary tumor board meeting. The primary endpoint of the study was overall survival (OS). The secondary endpoints were objective response rate (ORR), progression-free survival (PFS), and rate of immune-related adverse events. Results: There were 150 patients included in the study. The most common indications for ICI use were non-small-cell lung cancer (52.7%) and head and neck squamous cell carcinoma (17.3%). Nivolumab was the most common ICI used in 119 (79.4%) patients. ICIs were used in the palliative setting in 144 (96%) patients. A total of 76 (50.6%) patients received ICIs as second-line therapy. The median number of cycles of ICI received was 5 (interquartile range, 3.0–9.5). The ORR to ICIs was 30%, and the clinical benefit rate was 52%. ICIs were discontinued due to toxicities in 4 (2.7%) patients. The median PFS and OS were 4.23 (95% confidence interval [CI], 1.38–7.08) months and 8.6 (95% CI, 4.9–12.2) months, respectively. Baseline performance status was the most significant prognostic factor for PFS and OS in the multivariate analysis. In addition, age, male sex, and comorbid conditions such as chronic kidney disease negatively impacted the OS. Conclusion: Our study shows that ICIs are efficacious and well tolerated in older Indian patients with solid tumors. There is an emerging need for larger prospective studies on ICIs with the incorporation of geriatric assessment scores in this vulnerable patient population.
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POETRY IN ONCOLOGY Top

An ode to a cancer patient from a plastic surgeon p. 277
Dushyant Jaiswal
DOI:10.4103/crst.crst_62_21  
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PATIENT/CAREGIVER CORNER Top

Miracles happen p. 278
Taher Bohra
DOI:10.4103/crst.crst_3_21  
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REVIEW ARTICLE - GUIDELINES Top

Treatment of advanced non-small-cell lung cancer: First line, maintenance, and second line– Indian consensus statement update(Under the aegis of Lung Cancer Consortium Asia, Indian Cooperative Oncology Network, Indian Society of Medical and Pediatric Oncology, Molecular Oncology Society, and Association of Physicians of India) Highly accessed article p. 279
Kumar Prabhash, Amish Vora, Sewanti Limaye, Tarini Prasad Sahoo, Ullas Batra, Shekhar Patil, Vijay M Patil, Vanita Noronha, Bharat Bhosale, Nirmal Vivek Raut, Narayanankutty Warrier, Bharat Vaswani, Govind Babu, Adwaita Gore, Nitesh Rohatgi, Shailesh Bondarde
DOI:10.4103/crst.crst_61_21  
The management of patients with advanced non-small-cell lung cancer (NSCLC) is becoming increasingly complex, with the identification of driver mutations/rearrangements and the development and availability of appropriate targeted therapies. In 2018, a group of medical oncologists with expertise in treating lung cancers used data from the published literature and experience to arrive at practical consensus recommendations for the treatment of advanced NSCLC for use by the community oncologists. These recommendations were subsequently published in 2019, with a plan to be updated annually. This article is an update to the 2019 consensus statement. For updating the consensus statement, a total of 25 clinically relevant questions on the management of patients with NSCLC on which consensus would be sought were drafted. The PubMed database was searched using the following terms combined with the Boolean operator “AND:” (lung cancer, phase 3, non-small cell lung cancer AND non-small-cell lung cancer [MeSH Terms]) AND (clinical trial, phase 3 [MeSH Terms]) AND (clinical trial, phase iii [MeSH Terms]). In addition, “carcinoma, non-smallcell lung/drug therapy” (MeSH Terms), “lung neoplasms/drug therapy” (MeSH), clinical trial, phase III (MeSH Terms) were used to refine the search. The survey results and literature were reviewed by the core members to draft the consensus statements. The expert consensus was that molecular testing is a crucial step to be considered for patients with NSCLC at baseline, and in those who progress on first-line chemotherapy and have not undergone any prior testing. For mutations/rearrangement-negative patients who progress on first-line immunotherapy, doublet or single-agent chemotherapy with docetaxel and/or gemcitabine and/or ramucirumab should be considered. Patients who progress on the newer anaplastic lymphoma kinase inhibitors should be considered for second-line therapy with lorlatinib or systemic chemotherapy. Maintenance therapy with pemetrexed is preferred for NSCLC with non-squamous histology and should be avoided in NSCLC with squamous histology.
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REVIEW ARTICLES Top

Impact of the COVID-19 pandemic on patients with cancer and cancer survivors: A narrative review p. 315
Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava
DOI:10.4103/crst.crst_109_21  
The coronavirus disease-2019 (COVID-19) pandemic has impacted the healthcare system. Patients with cancer have been severely affected by the pandemic and have not been able to utilize the required healthcare services in a timely manner. This review is aimed at assessing the clinical and psychological impact of the COVID-19 pandemic on patients with cancer and cancer survivors. A comprehensive literature search was performed for this review in the PubMed database and Google Scholar database using the keywords, “COVID-19,” “cancer,” and “impact” in the title. Of a total of 30 relevant studies, 27 articles were included in the review. In addition, the World Health Organization website was extensively searched for relevant information. For patients with cancer who are affected by COVID-19, it has been advocated that post recovery from COVID-19, the therapeutic management of cancer should resume at the earliest to minimize cancer-related mortality. The COVID-19 pandemic has caused massive disruptions in the prevention, screening, diagnosis, and management of cancer. Therefore, minimizing the effect of the COVID-19 infection and improving the healthcare services offered to the patients with cancer by strengthening the healthcare system is the need of the hour.
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Vocal fold leukoplakia – An underestimated premalignant lesion of the larynx: A narrative review p. 321
Santosh Kumar Swain, Dattatreya Kar
DOI:10.4103/crst.crst_16_21  
Vocal fold leukoplakia is the clinical term for a whitish patch on the vocal fold mucosa. It is caused by prolonged tobacco smoking, consumption of alcohol, and excessive drying or vocal abuse. Histopathologically, it displays varying degrees of dysplasia and hyperkeratosis. The presence of dysplastic cells in the vocal fold leukoplakia denotes a premalignant lesion. The common clinical presentations of vocal fold leukoplakia include hoarseness of voice, foreign-body sensation, and irritation in the throat. The prognosis of this lesion is uncertain, and it can vary from a non-dysplastic leukoplakia to a squamous cell carcinoma. Early diagnosis and treatment of vocal fold leukoplakia are often challenging, and its management includes excision of the lesion, close follow-up, and avoiding exposure to risk factors such as tobacco smoking and alcohol consumption. For this review, we identified 134 articles from the Scopus, PubMed, Cochrane, and Medline databases and Google Scholar using the search terms, “vocal fold leukoplakia,” “premalignant diseases of the larynx,” “laryngeal keratosis,” “vocal cord leukoplakia,” “glottis,” and “precancerous lesions of glottis.” A total of 52 articles were included in the review. We aimed to assess the epidemiology, etiopathology, clinical presentation, diagnosis, and the current treatment options of vocal fold leukoplakia.
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REVIEW ARTICLE-BIOMARKER SERIES Top

BRAF in lung cancer: A narrative review p. 328
Mansi Sharma, Shrinidhi Nathany, Ullas Batra
DOI:10.4103/CRST.CRST_85_21  
Testing for the presence of oncogenic driver mutations in non-small-cell lung cancer (NSCLC) is a therapeutic mandate, and hence, in-depth knowledge of all the targetable biomarkers is essential. Apart from the well-known driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1, mutations in BRAF comprise an important molecular subtype of NSCLC, which is amenable to targeted therapy. In this review, we have described the molecular biology, detection methods, and various treatment modalities available for patients with NSCLC harboring BRAF mutations. We searched the PubMed, Embase, Scopus, and My Cancer Genome databases using the keywords, “BRAF,” “NSCLC,” “vemurafenib,” “dabrafenib,” and “trametinib.” A total of 44 articles were included in the review. Although targeted therapies have been successfully used in the management of advanced NSCLCs with BRAF mutations, it is necessary for clinicians to be mindful of the nuances of BRAF testing and interpretation of the results. Judicious use of BRAF inhibitors, either in the first or second line, can lead to improved survival in this subgroup of patients. In addition, immunotherapeutic agents may have a role in BRAF-mutant NSCLCs, in contrast to other oncogene-addicted NSCLCs where they are contraindicated.
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DRUG REVIEW Top

Olaparib: A narrative drug review p. 335
Vibhor Sharma, Aparna Sharma
DOI:10.4103/CRST.CRST_107_21  
Olaparib is an oral anticancer drug that inhibits the poly adenosine diphosphate-ribose polymerase protein (PARP). It is approved for use in advanced ovarian, breast, pancreatic, and prostate cancers. For this review, we comprehensively searched the PubMed database and Google for randomized trials and meta-analyses using the keywords “breast cancer,” “pancreatic cancer,” “ovarian cancer,” “prostate cancer,” and “olaparib.” A total of 78 randomized studies, meta-analyses, and other studies were identified, of which 70 were finally included. In this review, we have attempted to elucidate the history, pharmacokinetics, pharmacodynamics, adverse event profile, and special scenarios nvolving the use of olaparib. In addition, we have briefly reviewed the existing literature for its use in ovarian, pancreatic, breast, and prostate cancers.
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RESIDENT CORNER Top

Throwback to when it all started p. 347
Alok K Shetty
DOI:10.4103/crst.crst_84_21  
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The intimidating experience of becoming a surgeon p. 350
Saneya Pandrowala
DOI:10.4103/crst.crst_73_21  
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Pregnancy through the pandemic: From the diary of a pregnant doctor in the times of COVID-19 p. 352
Ruchi Singh
DOI:10.4103/crst.crst_100_21  
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EULOGY Top

Dr. V. Shanta (March 11, 1927–January 19, 2021) p. 354
Venkatraman Radhakrishnan
DOI:10.4103/crst.crst_135_21  
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EDITORIALS Top

Bevacizumab in progressive or recurrent glioblastoma: A quest for the optimal dosage p. 356
Ahitagni Biswas
DOI:10.4103/crst.crst_128_21  
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Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers p. 360
Arvind Krishnamurthy
DOI:10.4103/crst.crst_129_21  
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Biomarkers for response to immune checkpoint inhibitors: Where do we stand? p. 363
Satvik Khaddar, Bal Krishna Mishra
DOI:10.4103/crst.crst_139_21  
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Exploring RAS mutations in Indian patients with colorectal cancer: Have we seen it all? p. 365
Omshree Shetty
DOI:10.4103/crst.crst_142_21  
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Immune checkpoint inhibitors in older patients with cancer: A new era in cancer therapy p. 368
Shalabh Arora, Lalit Kumar
DOI:10.4103/crst.crst_126_21  
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Socio-cultural tailoring of the comprehensive geriatric assessment tool for low- and middle-income countries: The need of the hour p. 370
Ravi Mehrotra, Suzanne Tanya Nethan, Kavita Yadav
DOI:10.4103/crst.crst_64_21  
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MOLECULAR TUMOR BOARD Top

HER2 alterations in non-small-cell lung cancer – Druggable or undruggable? p. 374
Suresh Kumar Bondili, Ravindra Nandhana, Vanita Noronha, Swayamprabha Pawar, Nandini Menon, Omshree Shetty, Anuradha Chougule, Abhishek Mahajan, Rajiv Kumar, Vijay M Patil, Amit Joshi, Kumar Prabhash
DOI:10.4103/crst.crst_81_21  
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IMAGE CHALLENGE Top

Finding unusual pathology in usual clinical presentation: Huge implications for therapy p. 385
Somnath Roy, Ipsita Dhal, Akhil Kapoor
DOI:10.4103/crst.crst_68_21  
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Patterned abrasions p. 389
George Abraham, Alok Shetty, Pavankumar Biraris, Anil Tibdewal, Maheema Bhaskar, Amit Janu, Sandeep P Tandon
DOI:10.4103/crst.crst_101_21  
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STATISTICAL RESOURCE Top

Basics of statistics - 5: Sample size calculation (iii): A narrative review for the use of computer software, tables, and online calculators p. 394
HS Darling
DOI:10.4103/crst.crst_88_21  
Sample size calculation is essential for every analytical study aiming to obtain evidence-based results. This review describes the basics of the use of computer software for sample size calculation with the help of a few simple hypothetical examples. Published studies reporting on sample size calculation were identified from the PubMed and MEDLINE databases. In addition, relevant books were reviewed. Of the 125 articles identified from the database search, five articles fulfilling the eligibility criteria were included in this narrative review. This article describes the appropriate sample size calculation approach to be used in different scenarios using examples mimicking real-world clinical situations. In addition, each example describes an alternate method for sample size calculation to verify the result for ease of understanding. This will enable the confirmation of the accuracy of the calculated sample size to avoid incorrect estimation. Overall, the use of computer software, tables, and online calculators makes sample size calculation convenient, accurate, flexible, and easily reproducible.
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LETTERS TO EDITOR Top

Novel TBP-RET (TATA.binding protein-rearranged during transfection) fusion in a rare case of Skene gland adenocarcinoma: Sequencing unicorns p. 398
Kyaw Z Thein, Jie Wu, Vivek Subbiah
DOI:10.4103/crst.crst_117_21  
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Authors' reply to Thien et al. p. 400
Suresh Kumar Bondili, Anuradha Chougule, Pratik Chandrani, Vanita Noronha
DOI:10.4103/crst.crst_136_21  
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Second-line nivolumab for patients with metastatic renal cell carcinoma in India: A call for expanding global access to clinical trials p. 401
Nicholas J Salgia, Ameish Govindarajan, Sumanta Kumar Pal
DOI:10.4103/crst.crst_78_21  
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Neoadjuvant cabozantinib in metastatic and locally advanced renal cell carcinoma p. 403
Arya Mariam Roy, Andrew Briggler
DOI:10.4103/crst.crst_91_21  
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Polypharmacy and inappropriate medication use in older patients with cancer: An unaddressed and ubiquitous problem p. 404
Suvir Singh, Rintu Sharma
DOI:10.4103/crst.crst_69_21  
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Polypharmacy: Common yet unaddressed issue in geriatric oncology p. 405
Sabeena K Choudhary, A Sreevalli, Linu Abraham Jacob
DOI:10.4103/crst.crst_82_21  
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Authors' reply to Choudhary et al. and Singh et al. p. 407
Vanita Noronha, Vikram Gota, Kumar Prabhash
DOI:10.4103/crst.crst_125_21  
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Cancer-related cognitive impairment in survivors of acute lymphoblastic leukemia p. 408
Bhausaheb Bagal, Dipalee Borade, George John
DOI:10.4103/crst.crst_76_21  
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Addressing neuropsychological issues in cancer survivors: A step beyond treatment, the need of the hour p. 409
Shweta Bansal
DOI:10.4103/crst.crst_80_21  
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Authors' reply to Bagal et al. and Bansal p. 410
Jisha Abraham, Venkatraman Radhakrishnan, Surendran Veeraiah
DOI:10.4103/crst.crst_108_21  
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Burden of cancer: The unaddressed epidemic in India p. 411
Parth Sharma
DOI:10.4103/crst.crst_71_21  
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Author reply to Sharma p. 412
Roopali Goyanka
DOI:10.4103/crst.crst_94_21  
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Man proposes, COVID disposes! p. 413
Abhay Kattepur, Mahesh Goel, Shraddha Patkar
DOI:10.4103/crst.crst_79_21  
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Authors' reply to Kattepur et al. p. 414
Ravikant Singh, Chanda Rai, Rohit Ishan
DOI:10.4103/crst.crst_106_21  
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Skin metastasis of lung cancer: There's more to it than meets the eye p. 415
Saurabh Karmakar, Priya Sharma, H Ameet
DOI:10.4103/crst.crst_97_21  
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Authors' reply to Karmakar et al. p. 416
Sandip Ganguly, Joydeep Ghosh, Bivas Biswas
DOI:10.4103/crst.crst_114_21  
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Comprehensive molecular profiling: The saga of mutations and novel therapeutics p. 417
Tejaswini Mohan
DOI:10.4103/crst.crst_67_21  
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Authors' reply to Mohan p. 419
Akhil Kapoor, Pratik Chandrani
DOI:10.4103/crst.crst_99_21  
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Clinical utility of the NTRK gene fusion in current clinical practice p. 420
Minit Shah, George Abraham, Nandini Menon
DOI:10.4103/crst.crst_122_21  
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Authors' reply to Shah et al. p. 422
Shrinidhi Nathany, Ullas Batra
DOI:10.4103/crst.crst_130_21  
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Pharmacy satisfaction in patients with primary brain tumors receiving systemic therapy: A cross-sectional study p. 423
Nandini Menon, Peelay Zoya Ravish, Gunjesh Kumar Singh, Akhil Rajendra, Vijay M Patil
DOI:10.4103/crst.crst_38_21  
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Chemotherapeutic dose intensity and frailty: A subtle equilibrium p. 425
Suvir Singh, Rintu Sharma
DOI:10.4103/crst.crst_104_21  
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Importance of individualizing aerobic exercise regimens for patients with cancer p. 426
Chidiebere Emmanuel Okechukwu
DOI:10.4103/crst.crst_103_21  
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Inferior outcomes with plerixafor mobilization for autologous transplantation in myeloma: Probably not applicable to resource-constrained settings p. 428
Suvir Singh, Rintu Sharma
DOI:10.4103/crst.crst_74_21  
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ERRATUM Top

Erratum: Impact of COVID-19 lockdown on patients with cancer in North Bihar, India: A phone-based survey p. 430

DOI:10.4103/2590-3233.320316  
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