Cancer Trials Ecosystem in India-Ready for Prime Time?

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

Challenges and Outcomes of the First Stem Cell Transplant Program in Tanzania, East Africa.

Introduction: Due to the significant resources involved in creating HSCT programs there is a significant disparity in the availability of this treatment modality between the developed and developing countries. This manuscript details the process and the outcomes of the first HSCT program in East Africa which was started at Muhimbili National Hospital (MNH) in Dar-es-Salaam, Tanzania. Materials and Methods: Information and data were collected on the processes which had been implemented for starting the HSCT program at MNH. The details of the collaborations, training, infrastructure development, and acquisition of the biomedical equipment, as well as the actual process for HSCT, as well as the outcomes of treatment are described. Observations. The project has been detailed in 4 stages for ease of description: Stage 1: Preparatory work which was performed by the Government of Tanzania, as well as the administrators and clinicians from MNH (July 2017-September 2021). Stage 2: Exploratory gap analysis by the teams from MNH and International Haematology Consortium of HCG Hospital, India (HCG-IHC) in October 2021. Stage 3: Activities for closure of gaps (November 2021). Stage 4: Stem Cell Transplantation Camps (November 2021 to March 2022). 11 peripheral blood stem cell transplants were done in two camps, November 2021 (5 patients), and February 2022 (6 patients). 10 patients underwent autologous peripheral blood stem cell transplantation for multiple myeloma and 1 for lymphoma. The median duration of hospital stay was 19 ± 6 days. The median time for neutrophil engraftment, it was on 8.8 ± 0.8 days, and for platelet engraftment was 9.6 ± 2.4 days. Progression-free survival was 100%, and there was no mortality. Conclusion: Commonalities in the socioeconomic challenges in developing countries can be leveraged to create robust HSCT programs in other developing countries.

Recurrent squamous cell carcinoma of the skin treated with immunotherapy.

Squamous cell carcinoma (SCC) has a good prognosis, while metastatic tumors have aggressive behavior. Immunotherapy has become a standard line of treatment in metastatic cancers; pembrolizumab has shown promising results and improved quality of life in recurrent and metastatic cancers. We report a case of recurrent SCC of the skin with extensive disease and a known case of human immunodeficiency virus. He completed standard lines of treatment and currently on immunotherapy. After 3 cycles of immunotherapy plus chemotherapy, he got a complete metabolic response. Our experience showed palliative benefits and increased quality of life.

Use of home telemedicine for critical illness rehabilitation: an Indian success story.

One-fifth of healthcare beneficiaries in developed nations get discharged from hospitals to physician supervised skilled nursing care facilities. In low-income and middle-income countries like India, postdischarge skilled nursing facilities are at a very nascent stage and largely underequipped in terms of infrastructure, skilled nursing and physician staff to manage complicated patients. Hence the responsibility of management of such patients lies largely with their families. We present a case where a 26-year-old man with Duchenne Muscular Dystrophy who became ventilator dependent following major surgeries was weaned off his ventilator and rehabilitated back to his prehospital state. This was done at his home with visiting nurses and rehabilitation services under telemedicine supervision by a critical care specialist. Use of telemedicine services could be a viable and cost-effective option to ensure adherence to evidence-based medicine and standardisation of care in resource limited countries such as India.

Effect of Long-term Yoga Practice on Psychological outcomes in Breast Cancer Survivors.

AIM: Breast cancer has become a pandemic with an ever-increasing incidence. Although better diagnostics and treatment modalities have reduced mortality, a large number of survivors face cancer and treatment-related long-term symptoms. Many survivors are taking up yoga for improving the quality of life (QoL). The present study attempts to evaluate predictors of psychological states in breast cancer survivors with long-term yoga experience. MATERIALS AND METHODS: A case-control study recruited early breast cancer survivors, 30-65 years, completing treatment > 6 months before recruitment, and grouped them based on prior yoga experience (BCY, n = 27) or naïve (BCN, n = 25). Demography, cancer history, diet, exercise habits, and yoga schedule were collected and tools to assess stress, anxiety, depression, general health, and QoL were administered. Multivariate linear regression was done to identify predictors of psychological variables. RESULTS: BCY had significantly lower stress, anxiety, depression, better general health, and QoL (P < 0.001). Global QoL and trait anxiety were significantly predicted by Yoga practice; depression was predicted by yoga practice, annual income, and sleep quality; state anxiety was predicted by Yoga practice and income; and stress was predicted by Yoga practice and sleep quality. CONCLUSION: Results indicate that breast cancer survivors, doing yoga, have better psychological profiles and are able to deal with demanding situations better. The psycho-oncogenic model of cancer etiology suggests that a better psychological state in survival has the potential to improve prognosis and survival outcomes and Yoga may be a suitable practice for staying cancer-free for a longer time.

Effects of Yoga in Managing Fatigue in Breast Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: Cancer-related fatigue is widely prevalent in cancer patients and affects quality of life in advanced cancer patients. Fatigue is caused due to both psychologic distress and physiological sequel following cancer progression and its treatment. In this study, we evaluate the effects of yogic intervention in managing fatigue in metastatic breast cancer patients. METHODS: Ninety-one patients with metastatic breast cancer were randomized to receive integrated yoga program (n = 46) or supportive therapy and education (n = 45) over a 3-month period. Assessments such as perceived stress, fatigue symptom inventory, diurnal salivary cortisol, and natural killer cell counts were carried out before and after intervention. Analysis was done using an intention-to-treat approach. Postmeasures for the above outcomes were assessed using ANCOVA with respective baseline measure as a covariate. RESULTS: The results suggest that yoga reduces perceived stress (P = 0.001), fatigue frequency (P < 0.001), fatigue severity (P < 0.001), interference (P < 0.001), and diurnal variation (P < 0.001) when compared to supportive therapy. There was a positive correlation of change in fatigue severity with 9 a.m. salivary cortisol levels. CONCLUSION: The results suggest that yoga reduces fatigue in advanced breast cancer patients.

Effect of Yoga on Sleep Quality and Neuroendocrine Immune Response in Metastatic Breast Cancer Patients.

BACKGROUND: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK) cell counts in patients with metastatic cancer. METHODS: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive "integrated yoga based stress reduction program" (n = 45) or standard "education and supportive therapy sessions" (n = 46) over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. RESULTS: There was a significant decrease in scales of symptom distress (P < 0.001), sleep parameters (P = 0.02), and improvement in quality of sleep (P = 0.001) and Insomnia Rating Scale sleep score (P = 0.001) following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003) alone following intervention. There was a significant improvement in NK cell percent (P = 0.03) following intervention in yoga group compared to control group. CONCLUSION: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.

Role of Yoga in Cancer Patients: Expectations, Benefits, and Risks: A Review.

BACKGROUND: The diagnosis and treatment of cancer poses severe psychologic distress that impacts functional quality of life. While cancer directed treatments are directed purely against tumor killing, interventions that reduce treatment related distress and improve quality of life are the need of the hour. Yoga is one such mind body intervention that is gaining popularity among cancer patients. METHOD: Several research studies in the last two decades unravel the benefits of yoga in terms of improved mood states, symptom reduction, stress reduction and improved quality of life apart from improving host factors that are known to affect survival in cancer patients. However, several metaanalysis and reviews show equivocal benefits for yoga. In this review, we will study the Yoga interventions in cancer patients with respect to expectations, benefits and risks and analyse the principles behind tailoring yoga interventions in cancer patients. RESULTS: The studies on Yoga show heterogeneity with varied types of Yoga Interventions, duration, exposure, practices and indications. It also elucidates the situational context for reaping benefits and cautions against its use in several others. However, there are several reviews and bibliometric analysis of effects of yoga; most of them have not enlarged the scope of their review to cover the basic principles behind use of these practices in cancer patients. CONCLUSION: This review offers insight into the principles and practice of yoga in cancer patients.

Glioblastoma with signet ring cell morphology: A diagnostic challenge.

Glioblastoma (WHO Grade IV), the most frequent malignant brain tumor, can have varied morphologic variations like epithelial/glandular structures, granular cells, and lipidized cells. Glioblastoma with signet ring cell morphology is very unusual and can mimic a metastatic carcinoma. These rare tumors may be just a morphological variant or may signify a different carcinogenic pathway.

Relationship between p53 overexpression, human papillomavirus infection, and lifestyle in Indian patients with head and neck cancers.

Exposure to pollutants in the environment, tobacco and alcohol consumption, poor oral hygiene and opportunistic viral infections are important aetiological factors in head and neck cancers. In this study, we evaluate the complex interrelationships between these factors and molecular events such as p53 overexpression in causation of head and neck cancers. Tissue samples from 110 patients with histopathologically confirmed carcinoma of head and neck were analyzed from our tissue biorepository with patient consent. Data pertaining to their dietary habits, tobacco and alcohol consumption were abstracted. P53 overexpression was analysed by immunohistochemistry and HPV (high-risk genotype) were studied by Chromogenic in situ Hybridization using an ultra sensitive DNA probe. Chi-square analysis was done to determine relationships between proportions of dependent and independent variables. Bivariate relationships were determined between these variables using Spearman's rank correlation. Linear regression analysis was used to determine the best predictor variable influencing p53 expression. Tobacco consumption especially smoking cigarettes and all forms of tobacco consumption put together and HPV infection significantly influenced p53 overexpression. Forty-five percent of the studied cohort was positive for HPV. Regression analysis showed interaction between tobacco and HPV infection to be a primary predictor (ß = 0.31, p = 0.02) for p53 expression. Tobacco in any form: chewing, smoking and snuffing, along with HPV infection is significantly associated with p53 overexpression. There is a high prevalence of HPV infection (45%) in Indian patients suggesting its possible role in the aetiology of head and neck cancer.

An uncommon case of an adult with del(5)(q) in acute lymphoblastic leukemia.

Del(5)(q) is a common chromosomal abnormality with favourable prognosis in Myelodysplastic Syndrome (MDS) and Acute myeloid leukemia (AML). However, del(5)(q) is also seen rarely in Acute lymphoblastic leukemia (ALL) and its significance remains poorly understood. We present here, a case report of diagnosis of an adult 75 year old patient of ALL with a cytogenetic abnormality of del(5)(q32). His clinical features, morphology and immunophenotyping findings were suggestive of T-ALL. Relevant literature has been reviewed and discussed.

Effects of yoga program on quality of life and affect in early breast cancer patients undergoing adjuvant radiotherapy: a randomized controlled trial.

OBJECTIVES: This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer outpatients undergoing adjuvant radiotherapy at a cancer centre. METHODS: Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days. Assessments included European Organization for Research in the Treatment of Cancer-Quality of Life (EORTCQoL C30) functional scales and Positive and Negative Affect Schedule (PANAS). Assessments were done at baseline and after 6 weeks of radiotherapy treatment. RESULTS: An intention to treat GLM repeated measures ANOVA showed significant difference across groups over time for positive affect, negative affect and emotional function and social function. There was significant improvement in positive affect (ES = 0.59, p = 0.007, 95%CI 1.25 to 7.8), emotional function (ES = 0.71, p = 0.001, 95%CI 6.45 to 25.33) and cognitive function (ES = 0.48, p = 0.03, 95%CI 1.2 to 18.5), and decrease in negative affect (ES = 0.84, p<0.001, 95%CI -13.4 to -4.4) in the yoga group as compared to controls. There was a significant positive correlation between positive affect with role function, social function and global quality of life. There was a significant negative correlation between negative affect with physical function, role function, emotional function and social function. CONCLUSION: The results suggest a possible role for yoga to improve quality of life and affect in breast cancer outpatients.

Relationship between molecular markers and treatment response in a retrospective cohort of Indian patients with primary carcinoma of the larynx.

p53 Mutations and over expression have been shown to predict treatment response in head and neck cancer patients. Failure of organ sparing therapy has been attributed to cisplatin and radiotherapy resistance in carcinoma of the larynx patients. In this study, we evaluate the relationships between p53 over expression/mutations, bcl(2) expression and ploidy status in a retrospective cohort of responder and non-responder carcinoma of the larynx patients. Tissue samples from 22 patients with histopathologically confirmed carcinoma of the larynx and matched for age, stage, node status and treatment regimen, were analysed from our tissue biorepository. Differences in the above molecular markers were analysed between the responders and non-responders to conventional treatment. p53 and bcl(2) over expression was checked by IHC and p53 mutation by PCR and direct sequencing. DNA ploidy and S-phase fractions were also analysed. Chi square analysis was used to identify changes in proportions of these markers in responders and non-responders and likelihood ratio test was done to determine the best predictor biological marker for treatment response. Bivariate relationships were determined between these variables using Spearman's rank correlation. Node negativity at time of diagnosis (p=0.05), p53 mutation (p=0.02) and bcl(2) negativity (p=0.05) are some of the factors that are known to influence treatment response in our study. p53 over expression, S-phase fractions and ploidy status did not seem to influence treatment response. There was a significant inverse correlation between stage of cancer (p=0.03) and node positivity (p=0.06) with bcl(2) positivity. There was an inverse correlation between mutation category to treatment response (p=0.01). The results suggest p53 mutations to be a promising marker in predicting treatment response in carcinoma of the larynx patients.

Effects of a yoga program on cortisol rhythm and mood states in early breast cancer patients undergoing adjuvant radiotherapy: a randomized controlled trial.

UNLABELLED: Objectives. This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer outpatients undergoing adjuvant radiotherapy at a cancer center. METHODS: Eighty-eight stage II and III breast cancer outpatients are randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to radiotherapy treatment. Assessments include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety, depression, and stress collected before and after 6 weeks of radiotherapy. RESULTS: Analysis of covariance reveals significant decreases in anxiety (P < .001), depression (P = .002), perceived stress (P < .001), 6 a.m. salivary cortisol (P = .009), and pooled mean cortisol (P = .03) in the yoga group compared with controls. There is a significant positive correlation between morning salivary cortisol level and anxiety and depression. CONCLUSION: Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy.

Cutaneous fibrosis induced by docetaxel: a case report.

BACKGROUND: Docetaxel is a taxoid antineoplastic agent approved for use in the treatment of metastatic breast carcinoma. The current study reports an unusual case of generalized cutaneous fibrosis in a 39-year-old white female after treatment with 18 cycles of docetaxel for metastatic breast carcinoma. METHODS: Cutaneous fibrosis represents a rare and unique reaction associated with the cyclic use of docetaxel. The reaction is manifested by a distinct sequence of events involving pronounced edema followed by the rapid development of cutaneous fibrosis in dependent areas. RESULTS: Cessation of therapy results in dramatic reversal of the fibrotic process. CONCLUSIONS: This case report further substantiates the belief that docetaxel represents one of a very limited number of agents that appear capable of giving rise to scleroderma-like features.