Table 2. Some of the research studies (completed, ongoing and planned) to bridge the knowledge gap of geriatric oncology in India.

Research/Study category	Study	Sample size, and time frame of the study	Key question	Status of the study	Key results	Impact
Epidemiologic research	Epidemiology and demographic profile of older Indian persons with cancer*	266,640 patients from 16 institutes across India; Jan 2019 to Dec 2020	- What proportion of Indian patients with cancer are aged 60 years and over? - What are the common types of cancers in older patients with cancer?	Study is complete; Manuscript in process of submission	- 36.4% of adult Indian patients with cancer were aged 60 years and over. - Common malignancies included gastrointestinal malignancies (23.9%), head-and-neck (18.8%), breast (10.5%), genitourinary (10.5%), lung (10.22%), haematological (8.8%).	- This study will help plan various policies, focus areas and other initiatives
Tool (GA tools) validation	CARG score validation in patients receiving curative intent therapy [64]	N = 270; 2021	Does the CARG score reliably predict grade 3 to 5 chemotherapy toxicities in geriatric patients treated with curative intent chemotherapy?	Completed, published	- 52% of patients had at least one grade 3–5 toxicity. - Risk of toxicities based on the CARG risk score: Low risk-42% - Intermediate risk-51% - High risk-79%; p < 0.001	CARG chemotherapy risk prediction score is valid and reliable in older Indian patients with cancer receiving curative intent therapy.
	G8 and VES-13 as screening tools and predictors of survival [65]	N = 308; Jun 2018 to Nov 2020	-What is the diagnostic accuracy of the G8/VES-13 screening tools to detect an abnormal GA? - What is the optimal cut-off value of G8 for older Indian patients with cancer? - Is an abnormal G8 associated with shorter survival?	Completed, published	G8 (cutoff ≤14): Sensitivity: 84.4% Specificity 17.6% - VES-13 (cut-off >3): Sensitivity: 34.9% Specificity: 82.4% - G8 ≤14 was not associated with abnormal GA (p = 0.736), or worse survival outcomes. - G8 <12 was associated with an abnormal GA (p < 0.001), and predicted for worse survival.	- G8 cut-off <12 is appropriate in older Indian patients with cancer. - G8 <12 is predictive of non-oncological vulnerabilities and shorter survival. - Lowering G8 cutoff to 12 translated to a 35% reduction in the number of patients undergoing a GA. This may help in optimal resource utilisation.
	TUG as a predictor of mortality [57]	N = 851; Jun 2018 to Jan 2022	- Is the TUG score associated with overall survival in older Indian patients with cancer? - What is the optimal cut-off for TUG in older Indian patients with cancer?	Completed, published	- TUG predicted mortality (HR, 1.058; 95% CI, 1.039–1.078). - Median overall survival of patients with TUG <12 seconds was 13.9 months (95% CI, 11.2 to 16.5), compared to 8.5 months (95% CI, 6.6 to 10.3) in those with a TUG ≥12 seconds (p = 0.002). -TUG cut-off score >10 seconds: AUC-ROC sensitivity: 62.3%, specificity 80.6%.	TUG can be a reliable tool in a busy outpatient setting to identify vulnerable patients who require a detailed GA. -TUG ≥10 seconds was a good predictor of impaired mobility.
	CARG-IND: Multicentric, double-blinded, prospective observational cohort study to validate the CARG score as a predictor of ≥grade 3 chemotherapy toxicities in older Indian patients with cancer receiving chemotherapy [66]*	N = 588; Started Dec 2022, ongoing	- Does the CARG score accurately predict the incidence of grade 3–5 chemotherapy-induced toxicities in older patients with cancer receiving systemic therapy?	Active recruitment ongoing	Pending	- Results of this study will help guide optimal systemic therapy decision-making in older patients with cancer receiving chemotherapy, including palliative intent therapy.
	Assessment of PIMs in older Indian patients with cancer [67]	N = 352; 2018 to 2021	- Which is the most reliable screening tool for assessment of PIM use in older adults with cancer?	Completed; manuscript submitted	- 5 PIM tools were compared and assessed: Beers-2015, STOPP and START-2014, PRISCUS-2010, FORTA-2018, and EU (7)-PIM list-2015 - EU (7)-PIM list had the least bias of 0.7% and the narrowest limits of agreement of 0.43 (−0.21 to 0.22). - PIM use was significantly higher in patients with diabetes (p = 0.013) and in patients taking >7 medications (p < 0.001)	- EU (7)-PIM list-2015 should be the tool of choice for assessing PIMs in older Indian patients with cancer. - However, high degrees of discordance were noted between the various tools used to assess PIMs, emphasising the need for local tools to be developed.
	GA as a predictor of survival in older Indian patients with cancer [68]	N = 897; Jun 2018 to Jan 2022	- Do the results of the GA correlate with survival in older Indian patients with cancer? - Which individual domains of the GA are predictive of survival?	Completed, manuscript submitted	- 85% of patients were frail (>1 impaired domain in GA) - GA was predictive of OS; - Median OS in fit patients was 24.3 (95% CI, 18.2-not reached) months, versus 11.2 (10.1–12.8) months in the frail patients; HR, 0.54; 95% CI, 0.41–0.72, p < 0.001 - Function, nutrition and cognition were individually predictive of survival on the multivariate analysis.	- GA is prognostic for survival in older Indian patients with cancer. - GA is prognostic even in patients thought to be the fittest, i.e., PS 0 and 1. - GA must be done in all older Indian patients planned for cancer-directed therapy.
Implementation research	SCOPE-C; version 1: The Screening of the older PErsons with cancer, Version 1-development and validation of a new screening tool for older adults with cancer in resource-limited settings [54, 55]	N = 419; May 2013 to Feb 2016	- Can a targeted assessment be performed in older patients with cancer in resource-limited settings like India where there is paucity of evidence in this field? - Can the SCOPE-C screening tool be converted into a prognostic one by providing score cut offs predictive of survival at 24 weeks?	Completed and published	- SCOPE-C consisting of 13 questions with sub-parts (35 items in total) was developed and validated on a sample of 100 subjects. - Cronbach's alpha: 0.93 and the intra-class correlation co-efficient was 0.94. - Time to administer the tool: 25 minutes - Male sex, functional decline, cognitive impairment, malnutrition, and treatment modality were independently associated with survival. - Individual scores on SCOPE-C V.1 correlated with 24-week survival - Cutoff score of 64 had a 72.2% sensitivity and 77.3% specificity for better prognosis.	- SCOPE-C is valid and reliable. - Preliminary assessment with SCOPE-C may help streamline care in resource-limited settings.
Descriptive/observational research	Impact of the GA on systemic therapy plan [60]	N = 617; Jun 2018 to Sept 2021	- In older patients with cancer, do the results of a GA lead to a change in the cancer-directed systemic therapy plan?	Completed, and published	- Systemic therapy plan was changed in 239 (38.7%) patients following the GA. - Most common change was treatment deintensification in 198 (32.1%) patients.	- GA is very important to optimally plan therapy in older Indian patients with cancer. - GA must be done before starting therapy in all older Indian patients with cancer.
	PIM use and polypharmacy [59]	N = 285; Jun 2018 to Oct 2020	- What is the the prevalence of polypharmacy, and PIM use in older Indian patients with cancer?	Completed, and published	- Polypharmacy (>4 medicines) noted in 55% patients - Excessive polypharmacy (>9 medicines) in 13%. - Polypharmacy noted in 70% patients with lung cancer, versus 45% for other malignancies, p < 0.001. - Unindicated medications such as vitamins and calcium taken by 20% patients - Alternative medicines (ayurvedic/homeopathic/naturopathic) taken by 23% - 80% of the patients were on PIMs, commonly proton-pump inhibitors (33%) and tramadol (30%).	- Polypharmacy and PIM use are common problems in older Indian patients with cancer. - We are in the process of implementing a widespread safe medication prescribing program based on this study.
	ECOG PS as representative of deficits in older Indian patients with cancer [6]	N = 594; May 2018 to Jan 2021	- Does the ECOG PS correlate with the individual GA components and with the burden of deficits as estimated in the GA?	Completed, and published	- ECOG PS ≥1 was predictive of abnormalities in >2 geriatric domains; AUC = 0.69 (95% CI, 0.64–0.74), sensitivity = 95.4%, specificity = 18.4% - With each 1 unit increase in ECOG PS, odds of having ≥2 geriatric abnormalities increased by 4.69 (95% CI, 2.53–8.68). - Median number of impaired geriatric domains based on PS: PS 0 = 1 (IQR, 1–2); PS 1 = 2 (IQR, 1–3); PS 2 = 3 (IQR, 2–4); PS 3 = 4 (IQR, 3–4). - ECOG PS correlated moderately well with deficits in cognition (AUC = 0.66 (95% CI, 0.61–0.72)), function and falls (AUC = 0.73 (95% CI, 0.69–0.77)), and psychological domains (AUC = 0.65 (95% CI, 0.60–0.70)) and poorly correlated with nutritional status (AUC = 0.63 (95% CI, 0.58–0.68)) and comorbidities (AUC = 0.55 (95% CI, 0.49–0.61)).	- Older patients with cancer with an ECOG PS ≥1 are very likely to harbor non-oncological vulnerabilities, and should therefore undergo a GA.
	Inflammatory markers and correlation with survival [69]	N = 787; Jun 2018 to Nov 2021	- Can the NLR, lymphocyte monocyte ratio (LMR) and platelet lymphocyte ratio (PLR) be used to predict overall survival in older Indian patients with cancer?	Completed, manuscript in process	- High NLR (OS: 9.1 versus 16.9 months; HR: 1.5, 95% CI; 1.3–1.8) and high PLR (OS: 9.3 versus 17.1 months; HR: 1.6, 95% CI; 1.3–2.0) were predictors of poor OS, - High LMR (OS: 14.2 versus 10.3 months; HR = 0.8, 95% CI; 0.7–0.9) was a predictor or better OS, even after adjusting for age, sex and primary tumour.	- With simple blood tests like the complete blood count, inlflammatory markers like NLR, PLR and LMR can be used to help prognosticate older Indian patients with cancer. - In combination with other clinicopathologic features, these may be used to help generate an individualised care plan for older Indian patients with cancer.
	Utilisation of technology among older Indian patients with cancer [70]	N = 309; Apr 2021 to Oct 2021	- How many older patients with cancer and their caregivers use mobile phones, Internet and social media applications? - Does the use of technology have any association with various factors?	Completed, and published	- 81% patients had mobile phones. - 25% patients used the Internet - 21% patients used some form of social media (10%: Whatsapp only; 11%: Whatsapp and Facebook) - 99% caregivers used mobile phones - 75% caregivers used E-mail and social media applications. - Women and those with no education, poor vision, and impaired cognition were less likely to own a mobile phone. - People with no education and impaired cognition were less likely to use Internet and social media.	- Although the use of Internet and social media applications was low among our patients, the high utilisation of technology by the caregivers supports the vision of technology use to provide healthcare at the doorstep. - Development of an online GA screening tool would likely be possible given the almost universal use of technology by caregivers, which could help bridge some of the limitations, including time taken for evaluation, requirement of additional staff and bridge the gap between health care provider and older Indian patients with cancer.
	Vaccination uptake in older Indian patients with cancer [71]	- What is the uptake of pneumococcal, influenza, and coronavirus- 2019 (COVID-19) vaccines among older patients with cancer? - Are there any factors associated with vaccination uptake?	N = 1,762; Feb 2020 to Jan 2022	Completed, and published	- 0.68% patients had received pneumococcal vaccine - 0.7% had received influenza vaccine. - 83.3% had received at least one dose of the COVID-19 vaccine. - Factors associated with COVID-19 vaccine uptake: education, marital status, geographic zone and primary tumour site.	- Fewer than one in 100 older Indian persons with cancer receive routine immunisation with influenza and pneumococcal vaccines. - The uptake of COVID-19 vaccination in older Indian persons with cancer is over 80% - Similar strategies as those used to increase COVID-19 vaccination should be employed to increase the uptake of routine vaccinations.
	Real-world experience on the use of immune checkpoint inhibitors (ICIs) for solid tumours in older adults with cancer [72]	What are the treatment-related outcomes and toxicities of ICIs in older Indian patients with cancer?	N = 150; Aug 2014 to Feb 2021	Completed, and published	- Common indications for ICI: NSCLC (52.7%) and HNSCC (17.3%). -Nivolumab was commonest ICI used in 119 (79.4%) patients. - ICIs were used in the palliative setting in 144 (96%) patients. - Median number of ICI cycles: 5 (IQR, 3.0–9.5). - ORR to ICIs: 30%, clinical benefit rate: 52%. -Median PFS: 4.23 months (95% CI, 1.38–7.08) months - Median OS: 8.6 months (95% CI, 4.9–12.2) - Baseline PS was the most significant prognostic factor for PFS and OS in the multivariate analysis.	- ICIs are well tolerated in older Indian patients with cancer, with no new safety concerns. - ICI’s appear to be efficacious in older Indian patients with cancer. - Additional prospective studies to assess the role of ICIs, and the contribution of immunosenescence are needed.
	Financial toxicity among older Indian patients with cancer [73]	- What is the level of financial toxicity in older Indian persons with cancer? - Is there a correlation betweem financial toxicity and QoL? - What factors are associated with financial toxicity?	N = 498; Jun 2022 to Jan 2023	Completed, manuscript in process	- Source of funding for cancer-therapy: family members (53.9%), insurance (14.7%), self pay (12%). - 12.4% had to borrow money, 4.3% had taken a loan, 2.6% sold their assets for the purposes of treatment. - Moderate-severe financial burden on COST-FACIT present in 33.1%, whereas 66.9% experienced no or mild burden. - High financial toxicity was associated with lower socioeconomic status (OR: 4.69, 95% CI 2.47–8.91, p < 0.001), poor financial well-being (OR: 9.35, 95% CI 5.52–16.46, p < 0.001) and poor score on Financial QoL (OR: 5.16, 95% CI 3.39–7.86, p < 0.001)	- There is high prevalence of financial burden in older Indian patients with cancer - Financial toxicity is associated with poor socioeconomic status, poor financial well-being and poor financial QoL. - Recognition of financial toxicity is important to optimally plan and choose the most appropriate therapy options.
	ReproGeri study: Representation of older Indian patients with cancer in interventional clinical trials at the Tata Memorial Hospital [74]	- What is the representation of older Indian patients with cancer in interventional clinical trials at the Tata Memorial Hospital, Mumbai? - How many studies have eligibility criteria that limit the enrollment of older Indian persons with cancer?	N = 21,443; 2005 to 2022	Completed, manuscript in process	- 149 interventional clinical trials at the TMC - Median age of all enrolled patients: 51 years (IQR, 43–59). - Of all patients enrolled in interventional clincal trials: 23.5% were >60 years, and 4.8% were >70 years. - In the same timeframe, 30.6% of adult patients registered in the hospital were aged >60 years. - In 2.84% studies, an upper age limit was part of eligibility criteria - In 26.2% studies, ECOG PS 2 was an exclusion criterion - In 63.8% trials, uncontrolled comorbidities were exclusion criteria.	- There is an underrepresentation of older Indian adults with cancer in interventional clinical trials. - Increasing the representation of older adults with cancer in clinical research is critical to establishing the optimal cancer-directed therapy in this group of vulnerable individuals.
Therapeutic/interventional research	Optimising chemotherapy in the first line for older patients with advanced non-small cell lung cancer (Phase III randomised non-inferiority study) [75]	- Can a lower dose of standard cytotoxic chemotherapy in older persons with advanced non-small cell lung cancer result in lower toxicity, while maintaining survival?	N = 308; Active enrolment ongoing	Enrolling	Pending	- If a lower dose of chemotherapy is found to be non-inferior as compared to full dose chemotherapy, this will help improve the risk-benefit ratio, and will enhance the patients’ therapeutic experience.
	CARGO: A randomised phase III clinical trial evaluating the non-inferiority of reduced dose chemotherapeutic regimens based on CARG risk scores compared to standard doses in older patients with advanced esophageal, esophagogastric, gastric, and biliary tract cancers [76]	- Does a chemotherapy dose reduction based on the CARG chemotherapy risk score lead to similar OS as full dose standard chemotherapy in older patients with advanced biliary tract, esophageal, esophago-gastric, and gastric cancers?	N = 410	Enrolling	Pending	- If the study proves that dose reduction based on the CARG risk prediction score leads to non-inferior survival, this may result in the uniform use of reduced chemotherapy doses in older patients with cancer, thus improving the therapeutic index.
	GOCoG: Geriatric oncology multidomain intervention study to prevent cognitive impairment among older Indian patients with cancer receiving chemotherapy: a randomised controlled trial (GOCoG)	- Can a 3-month multidomain intervention (cognitive training + exercise) decrease the chemotherapy-related cognitive decline in older Indian patients with cancer receiving chemotherapy, compared to usual care?	N = 364	Submitted to the ethics committee of the Tata Memorial Hospital, Mumbai; awaiting approval	Pending	If the intervention succeeds in improving the chemotherapy-related cognitive decline in older Indian patients with cancer, this will have a significant impact on the patients in terms of: - QoL - functional status - independence - decision-making capacity - treatment compliance
	Effects of prehabilitation on outcomes in older Indian patients with cancer: a randomised controlled study	-Will a short-term multimodal prehabilitation program with exercise, respiratory training, nutrition consultation, anxiety reduction anemia correction optimisation of comorbidities and medicines, and smoking cessation reduce postoperative complications and length of hospital stay in older Indian patients with cancer?	Protocol being planned	Protocol being submitted to the ethics committee of Tata Memorial Hospital, Mumbai	Pending	- If the study is positive, it will support the implementation of prehabilitation in all older patients planned for radical cancer-directed surgery. - A reduction in post-operative complications and a decrease in the length of hospital stay will be important and will help improve the therapeutic ratio of surgery.
	Phase III open label superiority randomised trial comparing concurrent chemoradiotherpay to radiation therapy alone in older patients with locally advanced HNSCC	- Does the addition of concurrent chemotherapy to radical intent radiation improve oncologic outcomes in older patients with locally advanced HNSCC	Protocol being planned	Protocol being submitted to the ethics committee of Tata Memorial Hospital, Mumbai	Pending	The results of this study will help us to decide the optimal regimen for patients with locally advanced HNSC planned for non-surgical curative therapy options.
	Optimal assessment of renal function in older Indian patients with cancer [77]	- Which equation for calculating the estimated GFR can most accurately estimate the renal function in older Indian patients with cancer?	N = 276; Jun 2021 to Nov 2022	Completed, manuscript in process	- GFR was estimated with six formulae: Cockcroft-Gault (CG); six variable MDRD; six variable MDRD; CKD-EPI creatinine; CKD-EPI cystatin; CKD-EPI creatinine-cystatin; BIS 1; and BIS 2 equations. - GFR was also measured by 99mTc-DTPA plasma technique (Gates’ method). - Serum cystatin estimated by sandwich ELISA - BIS 2 equation had the least bias (0.854) and narrowest 95% LoA (−31.23 to 32.94) had the highest agreement with ‘gold standard’. - BIS 2 performed consistently well across ages (60–70, 71–80, 81–90) and BMI categories (≤18.5, 18.6–24.9, ≥25)	- Equations derived using cystatin C in general, and BIS 2 in particular, have highest predictive accuracy for GFR estimation in older patients with cancer. - Accurate assessment of renal function is essential particularly in patients receiving renally cleared or nephrotoxic chemotherapy.
Patient-and cergiver-centric research	Caregiver burden experienced by the caregivers of our older patients with cancer [78]	- What is the burden experienced by caregivers of our older patients with cancer?	N = 127; Jun 2020 to Dec 2020	Completed, published	- Caregiver burden was assessed using the Zarit Burden Interview - Median caregiver burden score: 12 (IQR, 6–20) - Caregiver burden was little/none in 76.4%, mild-moderate in 19.7%, moderate-severe in 3.1%, and severe in 0.8% - Psychological issues in the patient and the caregivers’ educational level significantly impacted the caregiver burden scores.	- Caregiver burden was low in our study - By identifying the cohort of patients most likely to have higher caregiver burden, targeted interventions could be planned to help these caregivers, and lessen the burden.
	Patients’ expectations from therapy, and disclosure of diagnosis/prognosis [79]	- Do older Indian patients with cancer wish to know the details of their diagnosis and prognosis? - What are patients' goals from cancer-directed therapy?	N = 319; 2018 to 2021	Completed, manuscript in progress	- 83% patients wished to know about their diagnosis and prognosis. - In 19% cases, the caregivers did not want the disease-related details to be disclosed to the patients. - 85% patients in the curative setting expected a complete cure - 63% patients in the palliative setting valued an improved QoL.	- Recognising patients’ and caregivers’ perspectives is of paramount importance in shared decision making. - It is important to understand that two-thirds of the patients being treated with palliative intent therapy valued a maintained QoL over a prolonged life.
	QoL in older Indian patients with cancer [80]	- How are the different QoL domains affected in treatment-naïve older patients with cancer?	N = 360; July 2015 to Jun 2017	Completed, published	- Fatigue was reported in 68.9% patients, loss of appetite in 66.4% and pain in 50%. - Poor functioning (score <50) was seen in 66%) patients in the global QoL domain (overall health and QoL in the preceding one week), in 68.9% in the role functioning domain, in 55.5% in the physical functioning domain, and in 74.3% in the emotional functioning domain. -Financial constraints were reported by 66.4% patients.	- Understanding the QoL issues in older patients with cancer, particularly with regards to which individual domains are likely to be affected will help in planning early interventions, targeted at improving the QoL of these patients.

^*Collaborative multicentric study

Acronyms: CARG = Cancer and Ageing Research Group; TUG = Timed Up and Go test; PIM = Potentially inappropriate medicines; GA = Geriatric assessment; QoL = Quality of life; ECOG PS = Eastern Cooperative Oncology Group; PS = performance status; AUC = Area under the curve; CI = Confidence interval; OS = Overall survival; HR = Hazard ratio; COST-FACIT = COmprehensive Score for financial Toxicity‐Functional Assessment of Chronic Illness Therapy; OR = Odds ratio; GFR = Glomerular filtration rate; IQR = Interquartile range; NSCLC = Non-small-cell lung cancer; HNSCC = Head and neck squamous cell carcinoma; IQR = Interquartile range; CI = Confidence interval