Publications

INTRODUCTION: Healthy habits such as regular physical activity, a balanced diet and tobacco abstinence are associated with better health-related quality of life (HRQoL) in cancer survivors. However, there is limited evidence on this relationship in Latin American countries, where socioeconomic and cultural factors may influence adherence to healthy behaviours.

OBJECTIVES: To evaluate the relationship between adherence to healthy lifestyle recommendations and HRQoL in cancer survivors in Uruguay.

MATERIALS AND METHODS: A cross-sectional study was conducted with 241 early-stage cancer survivors treated at two hospitals in Uruguay. Adherence to healthy habits was assessed using a questionnaire based on the American Cancer Society recommendations. HRQoL was measured using the RAND-36 questionnaire. Categorical variables were analysed using the chi-square test, while continuous variables were analysed using Student's t-test or the Mann-Whitney test. The correlation between SF-36 dimensions and healthy habits was assessed using Spearman's coefficient.

RESULTS: The median age was 66.7 years and 55.2% were women. The most common cancers were breast (31.1%), colorectal (28.2%) and prostate (26.6%). A total of 62.7% of participants adhered to three or more healthy habits. Adherent patients showed significantly higher HRQoL scores, particularly in physical function (62.68 versus 45.67, p < 0.001), energy/fatigue (64.83 versus 45.89, p < 0.001) and emotional well-being (69.43 versus 53.02, p < 0.001). Adherence to multiple healthy habits was significantly correlated with improvements in physical and mental domains, with energy/fatigue showing the strongest correlation (rs = 0.66, p < 0.001).

CONCLUSION: Adherence to healthy habits has a cumulative positive impact on the HRQoL of cancer survivors. This study highlights the need to design comprehensive interventions to promote healthy behaviours in this population, contributing to the global evidence on cancer care and underscoring its importance in developing countries.

Merkel cell carcinoma (MCC) is a rare and aggressive tumour of the skin, characterised by a high rate of local recurrence and lymph node involvement. We present the case of a 58-year-old woman who developed a 5-cm tumour on the right lower eyelid, leading to ocular occlusion. Magnetic resonance imaging revealed an exophytic lesion in the right orbit, and a biopsy confirmed the diagnosis of MCC. After complete surgical resection and cervical emptying, the patient was treated with adjuvant radiotherapy. The final diagnosis was MCC, stage pT3 pN1 M0. The periocular location and tumour size were determinants in the treatment decision.

BACKGROUND: Palliative care research (PCR) plays a critical role in improving the quality of life for patients with serious illness, yet its global distribution and focus areas remain uneven. Understanding the trends and impact of PCR over the past decade can inform future research priorities and policy development.

METHODS: We conducted a bibliometric analysis of publications indexed in the Web of Science related to PCR between 2013 and 2022. Articles were identified using a comprehensive filter based on title keywords and specialist journals, and were further classified by research domain, disease area and study type.

RESULTS: The volume of PCR publications has grown over the past decade, increasing from 0.29% of all biomedical research outputs in 2013-14 to 0.62% in 2021-22. Countries with the highest levels of PCR output-primarily European and Anglophone nations-also ranked highly on the Economist Intelligence Unit's Quality of Death Index. Using eight different bibliometric indicators, we assessed the impact of countries' PCR outputs; while rankings varied by metric, European countries such as the Netherlands, Belgium, the United Kingdom and Ireland consistently performed strongly. Cancer emerged as the dominant disease focus, although many studies also addressed co-morbid conditions including COVID-19 in recent years. A significant proportion of PCR also examined the impact of illness on patients' families and caregivers.

CONCLUSION: The findings highlight cancer as a major area of focus and need within PCR. However, research outputs remain disproportionately concentrated in high-income countries, revealing a persistent gap in low- and middle-income settings.

RECOMMENDATIONS: To address the growing global burden of cancer and serious illness, palliative care should be integrated as a core component of national cancer control plans. This integration must be supported by a targeted research agenda that emphasises implementation and scaling of palliative care models, particularly in low- and middle-income countries. Policymakers and research funders should prioritise holistic, patient-centred approaches and ensure that impact measurement reflects meaningful outcomes for patients and families.

BACKGROUND: Head and neck squamous cell carcinoma is often treated with radiotherapy, frequently combined with chemotherapy, to improve overall survival (OS). Despite advancements, locoregional control (LRC) remains a significant challenge, with 15%-50% of patients experiencing locoregional recurrence, negatively impacting OS and quality of life. Hypoxia within tumor cells is a critical factor contributing to treatment failure, necessitating higher radiation doses to achieve similar therapeutic effects as in normoxic cells. This study aims to investigate the role of dose escalation using [18F] fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET CT) to target hypoxic sub-volumes in head and neck cancer (HNC) to improve LRC.

METHODS: The dose-escalated hypoxia-adjusted radiotherapy trial is an open-label, parallel, randomised, single-centre, phase II study. Patients with HNC will undergo [18F]. FMISO PET CT to identify hypoxic regions. Normoxic patients will be labeled as Arm 1 and will not be part of the primary assessment. Patients with hypoxia will be stratified into two arms (2 and 3). Arm 2 will receive standard radiotherapy of 70 Gy in 2 Gy fractions, while Arm 3 will receive an additional boost to the hypoxic sub-volumes, delivering a total of 80 Gy (Phase 2). All patients in Arms 2 and 3 will also receive concurrent chemotherapy with cisplatin. Patients will be monitored weekly for treatment tolerance, with acute adverse events recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. The primary endpoint is LRC, defined as the time from randomisation to the first histopathologically confirmed relapse of locoregional disease. Secondary endpoints include OS, locoregional relapse-free survival, acute and late toxicity and patient-reported outcomes assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires.

DISCUSSION: This study addresses a critical gap in the management of HNC by targeting hypoxic regions within tumours, potentially improving LRC and, consequently, OS. The use of [18F] FMISO PET CT for identifying hypoxic sub-volumes allows for tailored radiation dose escalation, which could overcome the radioresistance associated with hypoxia. By comparing outcomes among standard radiotherapy (Arm 2) and dose-escalated treatment (Arm 3), this trial aims to establish a more effective therapeutic strategy for HNC patients.

TRIAL REGISTRATION: This trial is registered with the Clinical Trials Registry of India (CTRI/2024/04/065373), registered on 08th April 2024 on ctri.nic.in and clinicaltrials.gov (NCT06087614) registered on 18th September 2023 on clinicaltrials.gov.

BACKGROUND: Advanced laryngeal carcinoma (LC) has a poor prognosis with limited treatment options. Managing oligometastasis is challenging, and there are currently no standard recommendations.

METHODS: We reported a case of a 64-year-old male with locally advanced LC who developed oligometastatic disease in the bones and liver 21 months after concurrent cisplatin-based chemoradiotherapy. Initially, due to negative PD-L1 expression, the patient was treated docetaxel, cisplatin and cetuximab combination. Chemotherapy after 10 months, new hepatic progression was confirmed by biopsy. Given the asymptomatic, single-site progression in a cirrhotic liver, microwave ablation was performed. Isolated bone progressions were treated with stereotactic body radiation therapy at 2 and 4 months, and nivolumab replaced cetuximab.

RESULTS: The patient has shown no evidence of disease progression for 22 months, with excellent tolerance.

CONCLUSION: The synergy between nivolumab and local therapies appears promising for managing oligometastasis in laryngeal cancer.

Metastatic castration-resistant prostate cancer (mCRPC) remains a formidable clinical challenge despite advancements in therapy. This narrative review explores the role of artificial intelligence (AI), machine learning and deep learning in addressing therapeutic resistance in mCRPC. AI-driven approaches leverage integrated datasets encompassing genomics, proteomics and clinical parameters to uncover molecular mechanisms, predict treatment responses and identify biomarkers of resistance. These methodologies promise personalised treatment strategies tailored to individual patient profiles. However, data heterogeneity and regulatory considerations are challenges that hinder the translation of AI insights into clinical practice. By synthesising current literature, this review examines the progress, potential and limitations of AI applications in combating therapeutic resistance in mCRPC, highlighting implications for future research and clinical implementation.

BACKGROUND: Zambia faces the double burden of rising cancer incidence and a disproportionate volume of mortality from delayed presentations. The Ministry of Health Zambia acknowledged cancer research as a key pillar of cancer control in the National Cancer Control Strategic Plan 2022-2026, but there remains a paucity of country-specific evidence to inform strategies, implementation, monitoring and evaluation of research activities. Our study aimed to map and critically analyse the existing cancer research landscape to inform national planning.

METHODS: We adopted a two-stage mixed-method research. First, we conducted a systematic review, including 76 Zambian cancer studies published between 2012 and 2022, adhering to PRISMA guidance. Second, we conducted an in-person modified consensus meeting in Ndola, Zambia attended by 31 domestic and international stakeholders, to co-develop priorities and strategies based on gaps and facilitators identified through the systematic review.

RESULTS: The year-on-year cancer research output in Zambia had risen and diversified beyond cervical cancer but prevention, palliative care and health economic studies were lacking. Delay in deciding to seek care was most studied (n = 17, 63.0%), especially in cervical cancer. Research activities were mostly retrospective (n = 47/76, 61.8%) with only one randomised controlled trial identified. Greater than 90% (n = 10/11, 90.9%) of the most prolific research funders were international, predominantly from the United States and the United Kingdom, and Zambian researchers were under-represented as first and last authors at 43% (n = 33/76) and 45% (n = 34/76), respectively. The existing national cervical cancer registry, active global collaboration and adoption of technology were facilitators to be leveraged to build research capacity through multi-level, stakeholder-specific strategies.

CONCLUSION: To strengthen research capacity, sustained commitment to priorities through the implementation of co-developed strategies is required at individual, organisational and institutional levels. This paradigm shift is necessary to deliver evidence-based cancer care tailored to the needs of Zambians with emphasis on value and quality.

PURPOSE: To evaluate discrete wavelet transform (DWT) features as quantitative biomarkers of macular cone function from pattern electroretinography (PERG) in macular-predominant inherited retinal diseases (mpIRDs).

METHODS: In total, 486 PERG recordings from 123 participants were obtained from the PERG-Institute of Applied Ophthalmobiology open-access data set and analyzed. Twenty mother wavelets were screened with an energy-to-entropy ratio criterion; six (haar, sym2, sym4, db4, coif1, fk4) were retained for feature generation. After feature cleaning and correlation pruning, a final set of 141 features was obtained and averaged per participant to avoid visit bias. Group separation was assessed with nonparametric statistics. Inverse-DWT signal reconstruction was performed with the sym2 wavelet to algorithmically determine time-frequency indices needed to preserve N35, P50, and N95 peaks. The smallest set of indices that achieved this was retained.

RESULTS: Sym2-D6-2 (38-75 ms, 13-27 Hz) emerged as the top discriminative feature (res = 0.644, common-language effect size = 0.875) and correlated strongly with the clinical macular cone marker |P50-N35| (rcorr = 0.95) across 67 normal participants (262 recordings). Compared with |P50-N35|, the same index showed tighter, nonoverlapping group distributions, a higher diagnostic area under the curve (0.875 vs. 0.835), and a larger effect size (res = 0.644 vs. 0.576).

CONCLUSIONS: DWT-derived time-frequency features, particularly sym2-D6-2, provide robust, multidimensional biomarkers of macular cone function. These quantitative endpoints hold promise for monitoring disease progression and evaluating therapeutics in mpIRDs.

TRANSLATIONAL RELEVANCE: Sym2-D6-2 provides an objective metric of macular cone function that could serve as a quantitative endpoint in mpIRD trials.