A burden shared: the financial, psychological, and health-related consequences borne by family members and caregivers of people with cancer in India.

In India, approximately 1.4 million new cases of cancer are recorded annually, with 26.7 million people living with cancer in 2021. Providing care for family members with cancer impacts caregivers' health and financial resources. Effects on caregivers' health and financial resources, understood as family and caregiver "financial toxicity" of cancer, are important to explore in the Indian context, where family members often serve as caregivers, in light of cultural attitudes towards family. This is reinforced by other structural issues such as grave disparities in socioeconomic status, barriers in access to care, and limited access to supportive care services for many patients. Effects on family caregivers' financial resources are particularly prevalent in India given the increased dependency on out-of-pocket financing for healthcare, disparate access to insurance coverage, and limitations in public expenditure on healthcare. In this paper, we explore family and caregiver financial toxicity of cancer in the Indian context, highlighting the multiple psychosocial aspects through which these factors may play out. We suggest steps forward, including future directions in (1) health services research, (2) community-level interventions, and (3) policy changes. We underscore that multidisciplinary and multi-sectoral efforts are needed to study and address family and caregiver financial toxicity in India.

Financial toxicity in cancer care in India: a systematic review.

Although financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and outcome among the Indian population. In this study, we systematically reviewed the prevalence, determinants, and consequences of financial toxicity among patients with cancer in India. 22 studies were included in the systematic review. The determinants of financial toxicity include household income, type of health-care facility used, stage of disease, area of residence, age at the time of diagnosis, recurrent cancer, educational status, insurance coverage, and treatment modality. Financial toxicity was associated with poor quality of life, accumulation of debts, premature entry into the labour market, and non-compliance with therapy. Our findings emphasise the need for urgent strategies to mitigate financial toxicity among patients with cancer in India, especially in the most deprived sections of society. The qualitative evidence synthesised in this systematic review could provide a basis for the development of such interventions to reduce financial toxicity among patients with cancer.

Clinical Trial Access in Low- and Middle-Income Countries: A Case Study on India.

The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for 64% of global cancer deaths and 80% of disability-adjusted-life-years lost. Despite this, only 5% of the global cancer resources are spent in LMICs causing a high mortality-to-income ratio. Despite the burgeoning number of clinical trials in the HICs, there are several reasons to conduct clinical trials in LMICs. In this commentary, we discuss the problem of access to clinical trials in LMICs using India as a case study.

Adjuvant bisphosphonate therapy in early-stage breast cancer-Treating the soil to kill the seed.

Bisphosphonates alter the tumor microenvironment, possibly preventing cancer cell growth in the bone. Analyses of data from numerous clinical trials and a large individual patient-level data meta-analysis have suggested an anti-tumor effect for bisphosphonates in patients with early-stage breast cancer who are postmenopausal. The absolute benefit from the use of bisphosphonates on breast cancer-related mortality reduction mirrors that seen with the use of anthracycline-based chemotherapy versus a first-generation chemotherapy regimen (CMF). In this review, we discuss the evidence base for the use of adjuvant bisphosphonates in early-stage breast cancer and provide recommendations for clinical use.

More options for adjuvant treatment of HER2-positive breast cancer: How to choose wisely?

Human epidermal growth factor receptor 2-positivity (HER2) has a prognostic and predictive role in breast cancer. Trastuzumab, an anti-HER2 therapy, has a crucial role in a curative setting in Stage I, II and III breast cancer. In recent years, more anti-HER2 agents have been tested in clinical trials. Newer dosing strategies and combination approaches give us a plethora of options to treat a patient with early-stage and locally advanced breast cancer. It has led to the possibility of providing a risk-adapted treatment for patients with HER2-positive breast cancer. In order to reduce overtreatment and protect patients from adverse effects, a deescalation framework can be used in patients at lower risk for recurrence. Similarly, in those with greater risk for recurrence, escalation of therapy can be considered with the goal of achieving a cure. In this narrative review, we aim to provide a critical appraisal of the recent research findings in the management of early-stage and locally advanced breast cancer.

Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy.

BACKGROUND: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options. METHODS: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT. RESULTS: A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2-3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease. CONCLUSIONS: CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.

Prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer.

Cessation of chemotherapy in the last few weeks of life could be an important quality-of-care benchmark. Proportion of metastatic breast cancer patients who receive end-of-life chemotherapy is not well described. We aimed to determine the prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer. A retrospective cohort study using a prospectively collated database of patients with metastatic breast cancer who died between January 1, 2010, and September 30, 2014, was conducted. End-of-life chemotherapy (EOLC) use was defined as receipt of chemotherapy within 2 weeks of death (EOLC2) and receipt of chemotherapy within 4 weeks of death (EOLC4). Patients who did not receive any chemotherapy in the last 4 weeks before death were categorized as non-EOLC. We identified 274 patients with metastatic breast cancer, of whom 28 received EOLC2 (10.2%) and 62 received EOLC4 (22.6%). In comparison with non-EOLC, patients receiving EOLC4 were younger and had greater disease burden. Patients in EOLC4 group received more number of lines of chemotherapy. In a multivariable analysis, younger age at metastatic disease and greater number of metastatic organ systems involved were predictors of end-of-life chemotherapy use. Prevalence of the use of end-of-life chemotherapy in our cohort was higher than previously described. More end-of-life chemotherapy was used in younger women, and those with greater disease burden. Earlier initiation of end-of-life discussions may be targeted to such patients.

Bisphosphonates in breast cancer.

Bisphosphonates are osteoclast inhibitors, currently being used in oncology to prevent or delay bone morbidity in cancer. Oral and intravenous formulations of bisphosphonates have been found to be efficacious in preventing skeletal-related events such as bone pain, pathologic fractures, spinal cord compression and hypercalcemia of malignancy, in patients with bone metastatic breast cancer. Bisphosphonates are also used to prevent bone loss associated with anti-estrogen therapy using aromatase inhibitors. In addition to its role in preventing bone resorption, several pre-clinical studies have noted an anti-tumor role as well. Recent research effort has particularly focused on investigating an adjuvant role for bisphosphonates in early breast cancer. Recently, few randomized trials have found a beneficial effect for adjuvant use of the aminobisphosphonate, zoledronate, in older patients who are post-menopausal. This review article will summarize the various clinical studies investigating the role of bisphosphonates in breast cancer.

The use of adjuvant bisphophonates in the treatment of early-stage breast cancer.

Adjuvant treatment of breast cancer has resulted in significant improvement in breast cancer-related outcomes. In addition to chemotherapy and endocrine therapy, the bone-protective agents known as bisphosphonates have been extensively investigated for their putative antitumor effect. Backed by strong preclinical data from in vitro and in vivo models, several randomized clinical trials have evaluated the role of bisphosphonates in an adjuvant setting. The recent NSABP B-34 (National Surgical Adjuvant Breast and Bowel Project protocol B-34) and AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) studies found no disease-free survival benefit with clodronate and zoledronate, respectively, whereas the ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12) study found improvement in disease-free survival with zoledronate. Data from these trials suggested a beneficial effect of bisphosphonates in older, postmenopausal women and in premenopausal women treated with ovarian suppression. Given the acceptable toxicity profile of bisphosphonates, these agents could be a useful adjunct to adjuvant chemotherapy or endocrine treatment for early-stage breast cancer in a carefully selected subset of patients. This review aims to critically synthesize the results of clinical trials of adjuvant bisphosphonates in early-stage breast cancer, and to provide guidelines for the use of these agents in early-stage breast cancer.

Guiding Principles for Community Building in Global Oncology.

With the escalating incidence and prevalence of cancer worldwide disproportionately affecting low- and middle-income countries, there is an urgent need for the global oncology community to foster bidirectional partnerships and an equitable exchange of knowledge, resources, and expertise. A dedicated Global Oncology Community of Practice (CoP) can serve as a self-organizing, grassroots approach for members, with common goals and values, to coordinate efforts, maximize impact, and ensure sustainable outcomes. It is imperative, however, when outlining goals and priorities to adhere to an ethical and appropriate framework during community building efforts to avoid perpetuating inequities and power imbalances. This article reviews the core guiding principles for ASCO's Global Oncology CoP which includes responsibility, amplification, accessibility, sustainability, and decolonization.

Local Sociocultural Practice Specific Financial Toxicity Assessment Tool for Cancer: An Emerging Need.

It is relevant to study the financial toxicity of cancer to address it. However, the existing tools fail to capture the financial destruction of cancer on patients and their families in resource-limited countries. The authors discuss the need for a new tool in this article.

Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Long-term treatment with intravenous bisphosphonates in metastatic breast cancer: a retrospective study.

Bisphosphonates are important therapies used to reduce the risk of skeletal-related events in patients with bone metastases from breast cancer (BC). This retrospective cohort study evaluated the incidence of osteonecrosis of the jaw (ONJ) and renal impairment in women (n = 221) with bone metastases from BC treated with intravenous bisphosphonates from January 1999 to June 2008. In the long-term cohort, 159 patients received pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) for ≥24 months. The comparator group consisted of patients treated with intravenous bisphosphonates for 12-23 months (n = 62). After 39 months' median follow-up, six of 159 patients developed ONJ (3.8%; median 38.5 treatment cycles and 44 months' exposure) in the long-term cohort. Of patients who developed ONJ, 50% resumed intravenous bisphosphonates after a 12-month treatment holiday. Renal impairment developed in 19 patients in the long-term cohort (11.9%; median 26 treatment cycles and 26 months' exposure). Of these 19 patients, 11 (57.9%) recovered baseline renal function and seven (36.7%) showed partial recovery. After modification of the intravenous bisphosphonate regimen, 17 of 19 patients (89.4%) resumed therapy. Of the 62 patients in the comparator cohort, one patient developed ONJ (1.6%) and six developed renal impairment (9.7%). Similar incidence rates of ONJ and renal impairment were observed for the long-term and comparator cohorts. Times to ONJ or renal impairment also were similar across intravenous bisphosphonate type. Long-term (≥24 months) intravenous bisphosphonate use in metastatic BC is well tolerated, with low incidences of ONJ and renal impairment.

A novel strategy to downstage breast cancer: impact of a phone helpline.

Breast cancer incidence rates in India are rising. The majority of breast cancers are still diagnosed in later stages. There is also a burden of neglected cancers in India, where patients neglect their symptoms due to fear, ignorance, financial insecurity and lack of access to medical care. This results in greater morbidity and mortality from breast cancer. Systematic screening programs have been tested in an Indian setting, with limited success. An effective strategy to downstage breast cancer is an area of unmet need. We aimed to explore the effectiveness of an anonymous nurse-led telephone helpline in identifying patients with possible breast malignancies and to encourage them to seek healthcare. We created a telephone helpline system by training junior public health nurses (JPHNs) to provide counselling to women who may call with breast-related symptoms. We then created a short video message on the initiative and disseminated it using social media platforms. During the 1-year study period, 434 calls were received from individuals who reported having some breast symptoms. Among them, 28% (122 callers) had never consulted a doctor for their symptoms. 78 callers consulted a nearby doctor upon the advice of the JPHN. Among them, 14 callers (18%) were advised by the doctor to undergo investigations to rule out malignancy, while 64 (82%) of them were found to have some benign/normal breast conditions. 3 (21%) out of the 14 patients who underwent further evaluation were eventually diagnosed with breast cancer. Our study provides evidence that an anonymous nurse-led telephone helpline can be an effective strategy to reduce the incidence of neglected breast cancers and downstage the diagnoses.