Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

The issues and challenges with cancer biomarkers.

A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers.

Advances in Radiation Oncology: Current Status and Future Directions in India.

Radiation therapy is one of the core components of the comprehensive cancer care. Several new advancements in the radiation physics, radiation biology, and technical upgradation have led us in to a new era of radiation oncology. The access to quality radiation therapy treatment however remains a concern, and this mini-review emphasizes on these issues and also focuses on the future directions for radiation oncology in India.

Cancer immunotherapy: Recent advances and challenges.

Immunotherapy is a treatment that uses specific components of a person's immune system to fight diseases. This is usually done by stimulating or assisting one's immune system is attacking the offending agent - for instance, in the case of cancer - the target of immunotherapy will be cancer cells. Some types of immunotherapy are also called biologic therapy or biotherapy. One of the fundamental challenges that a living cell encounters are to accurately copy its genetic material to daughter cells during every single cell cycle. When this process goes haywire, genomic instability ensues, and genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Genomic instability arising out of DNA structural changes (indels, rearrangements, etc.,) can give rise to mutations predisposing to cancer. Cancer prevention refers to actions taken to mitigate the risk of getting cancer. The past decade has encountered an explosive rate of development of anticancer therapy ranging from standard chemotherapy to novel targeted small molecules that are nearly cancer specific, thereby reducing collateral damage. However, a new class of emerging therapy aims to train the body's defense system to fight against cancer. Termed as "cancer immunotherapy" is the new approach that has gained worldwide acceptance. It includes using antibodies that bind to and inhibit the function of proteins expressed by cancer cells or engineering and boosting the person's own T lymphocytes to target cancer. In this review, we summarized the recent advances and developments in cancer immunotherapy along with their shortcoming and challenges.

Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.

An updated account on molecular heterogeneity of acute leukemia.

The progress in the field of personalized therapy has been the backbone for the improved mortality and morbidity figure in cancer especially with reference to acute leukemia. The same has been supported by evolving research and development in the field of genomics. The newer discoveries of mutations and the account of already discovered mutations have been playing a pivotal role to refine management strategy. Here, in this review, we are giving an account of relevant mutations and their potential role in the pathogenesis of acute leukemia. The article discusses the old and newly discovered mutations in acute myeloid/lymphoblastic leukemia. The various pathways and cross-talks between the mutations have been briefly described to develop insight towards their contributory and consequent role in the neoplastic process. The article is to sensitize the students, clinicians, and researchers towards the recent updates and development in genomics of acute leukemia.

A systematic review of clinical and laboratory parameters of 3,000 COVID-19 cases.

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.

Indian Council of Medical Research consensus document on hepatocellular carcinoma.

This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Demography, Pattern of Care, and Survival in Patients with Xanthoastrocytoma: A Systematic Review and Individual Patient Data Analysis of 325 Cases.

Objectives Xanthoastrocytoma (XA) is a low-grade glial tumor seen in young adults and there is lack of robust data on treatment of this rare tumor. In this systematic review and individual patient's data analysis, we aimed to look into the demography, pattern of care, survival outcomes, and prognostic factors in patients with both Grade II and III XA. Methods A comprehensive search was conducted with the Medical Subject Heading terms: "Xanthoastrocytoma; Pleomorphic Xanthoastrocytoma; Anaplastic Xanthoastrocytoma; Xanthoastrocytoma AND treatment; and Anaplastic Xanthoastrocytoma AND survival" to find all possible publications. Results A total of 325 individual patients from a total of 138 publications pertaining to XA were retrieved. Median age of the entire cohort was 19 years. About 56.1% of the patients underwent a gross total resection (GTR) and 31.4% underwent a subtotal resection. Nearly, 76.6% of the patients had a Grade II tumor and adjuvant radiation was delivered in 27.4% of the patients. Estimated 2- and 5-year progression-free survival (PFS) were 68.5 and 51.2%, respectively. Age, grade, and extent of surgery were significant factors affecting PFS. Estimated 2- and 5-year overall survival (OS) was 88.8 and 78%, respectively. The median OS for Grade II and Grade III tumors were 209 and 49 months, respectively. Age and extent of surgery were significant factors affecting OS. Conclusion XA is a disease of young adults with favorable prognosis. Younger patients (<20 years), patients who undergo a GTR, and patients with a lower grade tumor have a better treatment outcome.

Environmental and occupational determinants of lung cancer.

Lung cancer has become a global problem, from a rare disease to an emerging public health issue. The current data of GLOBOCAN 2018, indicates that this disease has recorded highest mortality among all types of cancer. The etiological factors of lung cancer have become more multiplex because of increasing industrialization and environmental pollution around the world, especially in India. There is a rise in incidence of lung cancer among non-smokers and this can be attributed to environmental and occupational exposure to various kinds of hazardous substances. Target mutations are high in Lung cancer among non-smokers when compared to smokers. Some developed countries have guidelines and policies for prevention and control of risk factors focusing on these issues. Intervention aiming for primary prevention can be an important and cost-effective tool in developing countries to deal with increasing incidence of lung cancer. There is a need to define high risk group among non-smokers after taking into account environmental and occupational determinants as important risk factors. Research on etiology of lung cancer and prevention provides evidence to work on global incidence and prevalence of lung cancer, and for designing cost effective lung cancer prevention strategies. Research in the area of lung cancer prevention should be considered to recognize the areas where action is required to prevent environment and occupation related lung cancer. The government and occupational health and safety organizations have taken many steps in the last few years that can help to protect workers from these exposures. But the dangers are still there, so there is a need to do more to limit these exposures around workplace. This whole situation guides us to advocate population-based intervention along with policy implementation.

Feasibility of lung cancer screening in developing countries: challenges, opportunities and way forward.

Lung cancer is the leading cause of all cancer deaths worldwide, comprising 18.4% of all cancer deaths. Low-dose computed tomography (LDCT) has shown mortality benefit in various trials and now a standard tool for lung cancer screening. Most researches have been carried out in developed countries where lung cancer incidence and mortality is very high. There is an increasing trend in lung cancer incidence in developing countries attributed to tobacco smoking and various environmental and occupational risk factors. Implementation of lung cancer screening is challenging, so organised lung cancer screening is practically non-existent. There are numerous challenges in implementing such programs ranging from infrastructure, trained human resources, referral algorithm to cost and psychological trauma due to over-diagnosis. Pulmonary tuberculosis and other chest infections are important issues to be addressed while planning for lung cancer screening in developing countries. Burden of these diseases is very high and can lead to over-diagnosis in view of cut off of lung nodule size in various studies. Assessment of high risk cases for lung cancer is difficult as various forms of smoking make quantification non-uniform and difficult. Lung cancer screening targets only high risk population unlike screening programs for other cancers where entire population is targeted. There is a need of lung cancer screening for high risk cases as it saves life. Tobacco control and smoking cessation remain the most important long term intervention to decrease morbidity and mortality from lung cancer in developing countries. There is no sufficient evidence supporting the introduction of population-based screening for lung cancer in public health services.

Urinary Dysfunction Assessment in Long-Term Survivors of Carcinoma Cervix Using LENT SOMA Scale: An Indian Study Addressing Quality of Life Issues

Background: Carcinoma cervix is the second most common type of cancer in the world. With the increasing proportion of women surviving carcinoma of the cervix, quality of life has been an important clinical issue. Since there are very few studies from India, this study is to assess urinary dysfunction issues in patients of carcinoma cervix treated with multimodality therapy using the LENT SOMA scores. Methods: The study was prospective and patients treated between 1995 - 2007 on follow up were included in this study after ethical clearance. A total of 85 patients were accrued comprising 6 stage IB, 6 stage II A, 25 stage II B, 2 stage IIIA, 45 stage III B and 1 stage IV A disease. Sixty-six patients were treated with radiotherapy in which 46 patients received chemoradiotherapy and 19 had surgery prior to post-operative radiotherapy. The mean age was 47.81 years with a range of 25-68 years. Completion of LENT SOMA scale and Statistical analysis was done. Results: Mean score for BU (Bladder/Urethra) was highest (0.0758) in fifth year of treatment whereas UK (Ureter/Kidney score was highest (0.0408) after 4 years. Bladder score was more in 60-69 years of age and in stage IIIB patients of cervical cancers. Bladder morbidity was more in patients who received chemoradiotherapy and in patients who received radiotherapy with boost where Bladder and Urethra morbidity was more in patients who were treated with Extended Field radiation. Conclusions: The LENT SOMA system was acceptable and feasible to use and gave us an insight into the morbidity in our patients and to develop effective management plans to reduce the post treatment symptoms and improve quality of life.

A short geriatric assessment tool for the older person with cancer in India-Development and psychometric validation.

INTRODUCTION: With rise in incidence and prevalence of cancers in the ageing population, the need for an age sensitive comprehensive assessment measure has been felt. Comprehensive Geriatric Assessment (CGA) is often difficult to implement due to time and logistic constraints. A brief assessment tool encompassing the specific domains of the CGA would be a better way to assess older adults with cancer. These tools exist but have not necessarily been culturally adapted. The main aim of the study was to develop a culturally relevant short geriatric assessment tool and explore its psychometric properties. METHODOLOGY: An initial item pool was formed after review of the literature and study of the existing scales. This draft tool was then pre and pilot tested to finalize the items and check the feasibility of application. The final tool was validated by exploratory factor analysis on a sample of 100 older patients with cancer. RESULTS: After pre and pilot study on fifteen and thirty older patients with cancer respectively, this tool consisting of a total of 38 items spread over eight domains was developed and validated on a sample of 100 subjects. Due to co-linearity, three items were deleted after exploratory factor analysis, bringing the final item number to35. The Cronbach's alpha was 0.93 and the intra-class correlation co-efficient (ICC) was 0.94. Thus, the final tool had 13 questions with sub-parts (35 items in total). The time taken to administer the tool was around 25 min. CONCLUSION: The tool developed is valid and reliable and can be used for the initial assessment and further care planning of older Indian patients with cancer.

Impact of Cancer Awareness Drive on Generating Awareness of and Improving Screening for Cervical Cancer: A Study Among Schoolteachers in India.

PURPOSE: Cervical cancer is the second most common cancer in India. Our study assessed the level and impact of awareness programs in the adoption of safe practices in prevention and early detection. METHODS: This assessment was part of a Pink Chain Campaign, the mission of which is to fight cancer. During cancer awareness events from 2013 to 2015 at various women's colleges in different parts in India, a pretest related to cervical cancer was followed by an awareness program. A post-test was conducted 6 months and 1 year later. RESULTS: A total of 872 of 985 teachers participated in the study, for a response rate of 88.5%. Mean age of the population was 42.4 years. There was a significant increase in the level of knowledge regarding cervical cancer at 6 months, which was sustained at 1 year. Regarding cervical cancer screening, knowledge and practice of the Papanicolaou (Pap) test as a screening test for cervical cancer among teachers were changed significantly at 6 months and 1 year. More than 75% of teachers were educated by physicians about the Pap test. At the time of the post-test, there was a significant change in alcohol and smoking habits. The main reasons for not undergoing a screening test were ignorance (50%), lethargic attitude (44.8%), and lack of time (34.6%). CONCLUSION: The level of knowledge of cervical cancer was poor. A significant increase in the level of knowledge of cervical cancer among the population was found after this study. To inculcate safe lifestyle practices, awareness programs should be conducted more widely and frequently.

Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial).

INTRODUCTION: Maximal safe surgical resection followed by adjuvant chemoradiation has been standard for newly diagnosed glioblastoma multiforme (GBM). Hypofractionated accelerated radiotherapy (HART) has the potential to improve outcome as it reduces the overall treatment time and increases the biological effective dose. METHODS: Between October 2011 and July 2017, a total of 89 newly diagnosed GBM patients were randomized to conventional fractionated radiotherapy (CRT) or HART. Radiotherapy was delivered in all patients with a three-dimensional conformal radiotherapy technique in CRT arm (60 Gy in 30 fractions over 6 weeks @ 2 Gy/per fraction) or simultaneous integrated boost intensity modulated radiotherapy in HART arm (60 Gy in 20 fractions over 4 weeks @ 3 Gy/per fraction to high-risk planning target volume (PTV) and 50 Gy in 20 fractions over 4 weeks @ 2.5 Gy/per fraction to low-risk PTV). The primary endpoint of the trial was overall survival (OS). RESULTS: After a median follow-up of 11.4 months (Range: 2.9-42.5 months), 26 patients died and 39 patients had progression of the disease. Median OS for the entire cohort was 23.4 months. Median OS in the CRT and HART arms were 18.07 months (95% CI 14.52-NR) and 25.18 months (95% CI 12.89-NR) respectively, p = 0.3. Median progression free survival (PFS) for the entire cohort was 13.5 months (Range: 11.7-15.7 months). In multivariate analysis patients younger than 40 years of age, patients with a gross total resection of tumor and a mutated IDH-1 had significantly better OS. PFS was significantly better for patients with a gross total resection of tumor and a mutated IDH-1. All patients included in the trial completed the planned course of radiation. Only two patients required hospital admission for features of raised intracranial tension. One patient in the HART arm required treatment interruption. CONCLUSION: HART is comparable to CRT in terms of survival outcome. HART arm had no excess treatment interruption and minimal toxicity. Dose escalation, reduction in overall treatment time, is the advantages with use of HART.

Trends in Lung Cancer Incidence in Delhi, India 1988-2012: Age-Period-Cohort and Joinpoint Analyses

Introduction: Lung cancer (LC) has been one of the most commonly diagnosed cancers worldwide, both in terms of new cases and mortality. Exponential growth of economic and industrial activities in recent decades in the Delhi urban area may have increased the incidence of LC. The primary objective of this study was to evaluate the time trend according to gender. Method: LC incidence data over 25 years were obtained from the population based urban Delhi cancer registry. Joinpoint regression analysis was applied for evaluating the time trend of age-standardized incidence rates. The age-period-cohort (APC) model was employed using Poisson distribution with a log link function and the intrinsic estimator method. Results: During the 25 years, 13,489 male and 3,259 female LC cases were registered, accounting for 9.78% of male and 2.53% of female total cancer cases. Joinpoint regression analysis revealed that LC incidence in males continued to increase during the entire period, a sharp acceleration being observed starting from 2009. In females the LC incidence rate remained a plateau during 1988-2002 and thereafter increased. The cumulative risks for 1988-2012 were 1.79% and 0.45%. The full APC (IE) model showed best fit for an age-period-cohort effect on LC incidence, with significant increase with age peaking at 70-74 years in males and 65-69 years in females. A rising period effect was observed after adjusting for age and cohort effects in both genders and a declining cohort effect was identified after controlling for age and period effects. Conclusion: The incidence of LC in urban Delhi showed increasing trend from 1988-2012. Known factors such as environmental conservation, tobacco control, physical activity awareness and medical security should be implemented more vigorously over the long term in our population.