Advanced Centre for Treatment, Research and Education in Cancer

Population-based cancer registry (PBCR) of Bhutan was established in Jigme Dorji Wangchuk National Referral Hospital (JDWNRH) in 2014 with the support of the Ministry of Health (Bhutan) and IARC Regional Hub, Tata Memorial Centre (TMC), Mumbai, India. This PBCR provides nationwide coverage (0.7 million population). We aim to present the cancer patterns in Bhutan for the years 2014-2022 using PBCR data. Trained registry staff collect cancer patient information by visiting various sources such as hospitals and diagnostic facilities. Data is entered into CanReg5 software. Data quality and consistency are checked by the IARC Regional Hub-TMC, Mumbai. The age-specific rate and age-adjusted rate were calculated using CanReg5 software. In the 9-year period (2014-2022), the PBCR registered 5906 incidence cancer cases, of which 2659 (45%) were males and 3247 (55%) were females. The age-adjusted incidence rate for males and females was 88.3 and 113.2 per 100,000 population, respectively. Age-adjusted mortality rates for males and females were 42.7 and 44.6 per 100,000 population, respectively. The leading cancer sites among males are stomach, esophagus, liver, lung, and rectum, and for females, cervix uteri, stomach, breast, lung, and thyroid. Cancer registry will play a pivotal role in boosting and monitoring screening program initiatives in Bhutan. Through effective linkages, it will build a robust database providing a cancer profile of the Bhutanese population which can be employed to devise effective cancer control activities in Bhutan.

Abstract Aging causes a progressive loss of tissue homeostasis, with stem cell exhaustion as a major hallmark. Age-associated decline in organ function is widely perceived as emanating from progressive accumulation of cellular damage in adult tissues. However, whether aging trajectories are established early on during development remains an open question. Here, we demonstrate that genetic modulation of cellular aging pathways in larval adult midgut progenitors (AMPs), which serve as the precursors of adult intestinal stem cells and differentiated epithelial cells, dictates the long-term trajectory of intestinal aging in Drosophila . Accelerated cellular aging by genetic perturbation employing Toll or Imd pathway overactivation or elevation of reactive oxygen species (ROS) using ND42 (mitochondrial complex I) knockdown in the AMPs results in aberrant progenitor proliferation, skewed lineage allocation, epithelial barrier dysfunction, and genomic instability. These alterations are accompanied by marked destabilization of AMP islet architecture and widespread changes in age-related molecular signatures, as revealed by bulk transcriptomic analysis. In contrast, decelerated cellular aging mediated by Foxo or Atg8a overexpression results in a decrease in enteroendocrine population and the intestinal barrier remained unaffected. Intriguingly, early-life activation of immune and oxidative stress signaling manifested later in the adult gut as elevated enteroendocrine differentiation, highlighting lasting effects on intestinal regenerative capacity and lineage balance. Together, our findings demonstrate that cellular aging is tightly regulated early on in development and its perturbation can cause developmental disruption hampering adult gut homeostasis, establishing AMPs as key developmental determinants that regulate the trajectory of intestinal aging in Drosophila .

Carica papaya leaf extract (CPLE) is known to increase platelet counts (PCs) in certain infections. Patients were randomly assigned in a 2:1 ratio to the CPLE or placebo arm and continued treatment until the PC improved to 75,000 × 109/L or above, a platelet transfusion was required, or upto D+10. The primary outcome was to evaluate whether CPLE improves PC faster compared with placebo in a significant proportion of patients with a modified intention-to-treat protocol. Between March 2020 and October 2024, 219 patients were randomly assigned, of whom 198 patients (CPLE arm: 129; placebo arm: 69) were analyzed for outcomes. The primary end point with modified intention-to-treat analysis showed a statistically significant increase in PC to ≥75,000 × 109/L in a greater proportion of patients by D+4 compared with placebo (59% v 44%; P = .042). The primary outcome of increasing PC >75,000 × 109/L at D+4 was significantly improved by CPLE (83/129, 64% v 33/69, 48%; P = .034) compared with placebo as per protocol analysis. There was no grade 3 or grade 4 treatment-related adverse events associated with CPLE. About 43% of patients in the placebo arm versus 25% of patients in the CPLE arm needed dose reductions or delays in their subsequent chemotherapy treatment for patients with grade 2 chemotherapy-induced thrombocytopenia (CIT) at the baseline (P 0.033) and not significant in grade 3 CIT. CPLE is a potential therapeutic intervention to improve CIT faster and to a greater extent than placebo in this phase III randomized trial without any safety concerns. It could be potentially used as a secondary prophylaxis to maintain the chemotherapy intensity.

This retrospective study evaluated predictors of early versus late recurrence in 277 patients with oral squamous cell carcinoma (OSCC) who underwent surgical treatment between 2017 and 2020. Using receiver operating characteristic analysis, an 8-month disease-free survival cutoff effectively stratified patients into early (DFS < 8 months) and late (DFS ≥ 8 months) recurrence groups. Early recurrence was associated with significantly poorer overall survival (mean OS 24.03 months) compared to late recurrence (mean OS 35.26 months). Multivariate logistic regression identified adjuvant therapy status and type, bone involvement, positive pathological nodal stage, and perineural invasion as independent predictors of early recurrence. Local recurrences demonstrated better survival outcomes than regional or distant failures. The findings underscore the prognostic significance of recurrence timing and highlight the need for risk-adapted surveillance and tailored adjuvant strategies in high-risk OSCC patients.

Abstract Growing evidence suggests that early-life stress history can shape biological aging, yet the pathways through which this lifelong vulnerability manifests remain unclear. Using a maternal separation (MS) rodent model of early-life stress, we show that MS history evokes persistent cognitive, inflammatory, neurovasculature and bioenergetic changes that can accelerate aging trajectories. MS animals exhibit premature decline in object recognition memory in middle-aged life, accompanied by elevated peripheral inflammation, blood-brain barrier (BBB) compromise, heightened neuroinflammasome and microglial reactivity, and deteriorated mitochondrial health in the hippocampus. Notably, we demonstrate that adult-onset systemic supplementation with Nicotinamide (NAM), a NAD + precursor, prevents the emergence of peripheral and central inflammatory signatures, protects BBB integrity, maintains hippocampal mitochondrial health and mitigates cognitive decline in middle-aged MS animals. Collectively, these findings provide mechanistic insights into how early-life stress shapes brain aging, while highlighting NAM supplementation as a gerotherapeutic strategy to prevent premature aging driven by early adversity.

Abstract Introduction Young patients with left-sided breast cancer face a higher long-term risk of major cardiac events due to incidental cardiac radiation exposure and cardio-toxic systemic therapy agents. Photon-based radiotherapy delivering a mean heart dose (MHD) of &amp;lt;font face=“Symbol”&amp;gt;Ź&amp;lt;/font&amp;gt;3 Gy is associated with at least a 2% increase in the risk of major cardiac events (Kirby et al., 2023). This study aimed to stratify patients based on their risk and identify those most likely to benefit from proton beam therapy (PBT), a modality recently introduced at our tertiary care cancer center. Objective To identify patients with left-sided breast cancer who are most likely to benefit from proton beam therapy based on predicted cardiac exposure. Methodology We reviewed records of 737 patients with stage I to III or oligometastatic breast cancer treated with adjuvant radiotherapy at our center in 2023. A dosimetric audit was performed for all left-sided cases. Radiotherapy was delivered using IMRT or field-in-field 3DCRT, with or without DIBH. Fractionation regimens included 40 Gy in 15 fractions, 26 Gy in 5 fractions, and 28.5 Gy in 5 weekly fractions with boost when indicated. Patients were categorized according to the UK PARABLE trial criteria, which stratify cardiac dose thresholds based on age and the presence of risk factors. Statistical analysis was performed using IBM SPSS Version 28.0. Associations between groups were assessed using the Chi-square test, with a significance threshold of p &amp;lt; 0.05. Results The data for 444 patients was analyzed; 69.3% were under the age of 55. Cardiac comorbidities (22.3%) and diabetes (19.8%) were the most prevalent risk factors, while COPD (1.6%) and smoking (5.6%) were less common. Most patients (84.5%) had a BMI below 30.Fourteen patients (3.1%) did not achieve the age- and risk-adjusted desired MHD using photon techniques and could potentially benefit from proton therapy. Among those with risk factors, 6.5% did not meet their MHD thresholds. In contrast, only 1.1% of patients without risk factors failed to achieve the desired MHD. (Table 1) Younger patients (below 4 years) were disproportionately represented among those not achieving target MHD, particularly those with comorbidities. Conclusion Proton therapy may offer significant benefit to a subset of left-sided breast cancer patients at high cardiac risk, particularly younger individuals with comorbidities or unfavorable anatomy who are unable to achieve guideline-recommended mean heart dose thresholds with photon techniques. Risk-adapted selection for PBT is a promising strategy to optimize cardiac sparing in this population.As PBT is a limited and high-cost resource, such data-driven selection is essential for equitable and cost-effective use, ensuring access for those most likely to benefit. Citation Format: R. Sangle, R. Krishnamurthy, K. Bhandarwar, P. Sharma, N. Sharma, S. Nair, G. Yadav, T. Wadasadawala, R. Pathak, S. Kale, P. Sahoo, S. Gadge, R. Sarin. Personalizing Radiotherapy for Left-Sided Breast Cancer: Identifying Candidates for Proton Beam Therapy Based on Cardiac Risk [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-07-12.