Claire L. Donohoe

Effective post-treatment surveillance in cancer is designed to drive early detection and treatment of recurrence; however, surveillance protocols following curative-intent treatment for esophagogastric adenocarcinoma (EGA) remain poorly defined, with no consensus across existing guidelines. Historically, a lack of evidence regarding optimal surveillance approaches has been underpinned by limited treatment efficacy in recurrent or metastatic disease. However, recent advances in chemotherapy, immunotherapy, and targeted approaches, as well as the management of oligometastatic disease, have transformed the therapeutic landscape, making early detection of recurrence increasingly actionable. The rising incidence of EGA in younger patients adds further urgency to understanding long-term surveillance and survivorship needs. While ongoing clinical trials seek to address this question, emerging technologies, including liquid biopsy, next-generation sequencing (NGS), and artificial intelligence (AI), promise to further advance surveillance strategies. This review explores the rationale for post-treatment surveillance in EGA and examines future technologies that will shape surveillance strategies into the future.

BACKGROUND Cancer remains a leading cause of morbidity and mortality worldwide. Given its substantial burden, quality of life has become a key outcome in cancer care and research. Patient-reported outcome measures (PROMs) are commonly used to assess quality of life. Although qualitative research is essential for establishing PROM content validity, patient narratives are less often collected and analysed systematically once PROMs are implemented. Adding open-ended responses to quantitative PROM data may provide policy-relevant insights into what patients themselves prioritise. OBJECTIVE This study has aimed to identify the factors that people living with or beyond cancer across Europe perceive as having the greatest impact on their quality of life. METHODS Following a pan-European validation study of the newly developed EUonQoL-Kit – a set of questionnaires designed to assess the quality of life of people living with or beyond cancer in Europe – the responses to the final open-ended question “Having completed the questionnaire, what do you feel most impacts your quality of life?” were collected. Responses underwent qualitative thematic analysis using a coding framework iteratively developed and interpreted by researchers and people with lived experience of cancer involved as ‘co-researchers’. RESULTS Of the 4,284 cancer patients and survivors participating in the EUonQoL-Kit validation study, 3,350 (78.2%) provided a response to the final open-ended question. Factors perceived as having the greatest impact on quality of life were categorised into 23 distinct themes, covering six overarching domains: Physical health, Psychological wellbeing, Social health, Overall health, Healthcare experience and Environment. The most frequently reported factors included physical symptoms, overall health, relationships and connectivity, emotions and feelings, and impact of care pathway. CONCLUSIONS This study provides a comprehensive overview of the factors that impact quality of life most in people living with or beyond cancer across Europe. Combining structured PROMs with open-ended patient input may support more patient-centred quality of life measurement and interpretation and help align care and policy priorities with what matters most to patients.

Summary: Impaired long-term health-related quality of life (HRQL) is a growing concern for disease-free survivors post-esophagectomy. Post-prandial discomfort, neuroglycopenic symptoms, and dumping are common and often linked to reactive hypoglycemia (RH), a condition not yet prospectively studied in this cohort. This study used continuous glucose monitoring (CGM) and detailed diaries to investigate the incidence of symptomatic and asymptomatic RH events in consecutive, disease-free patients post-esophagectomy. Disease-free patients (6–36 months post-esophagectomy, non-diabetic) were recruited. Continuous glucose readings were collected at 15-minute intervals for 7 days using a FreeStyle Libre sensor. Participants completed detailed food and symptom diaries, and validated quality of life and symptom questionnaires. Sensor data were analyzed to detect reactive hypoglycemic events, and symptoms were correlated with glucose readings. Thirty-two patients provided complete data. Almost all participants (96.9%, n = 31) had at least one blood glucose measurement <3.9 mmol/L, with 65.6% (n = 21) recording severe hypoglycemia (<3.0 mmol/L). These events are significantly more prevalent than in healthy reference populations (P < 0.001). The mean total number of hypoglycemic events (defined as interstitial blood glucose <3.9 mmol/L for <15 minutes) was 9.26 (±5.81) over 7 days. Symptomatic RH events (occurring 60–300 minutes post-meal) were experienced by 37.5% of participants (mean 1.25 ± 0.45 events), while asymptomatic events were far more frequent (mean 5.97 ± 4.32). Symptomatic RH included both neuroglycopenic (42%) and abdominal symptoms. Screening questionnaires did not accurately identify all RH cases. Importantly, RH was not associated with impaired HRQL or altered body composition. RH is highly prevalent in disease-free survivors post-esophagectomy, far exceeding general population norms. CGM is a valuable tool for diagnosis, detecting a high rate of both symptomatic and asymptomatic events. Future work should investigate whether dietary modification can reduce these clinically significant RH events.

The concept of love, defined as a multidimensional ethical commitment to human dignity encompassing empathy, compassion, and respect, should be explicitly integrated into the medical curriculum. This commitment is considered the “secret of quality” (Donabedian) and a necessary counterbalance to the reductive, metrics-driven model of modern healthcare. Acknowledging the risk of love becoming a narcissistic illusion (Lacanian critique), its implementation requires strict professional boundaries, “Self-as-Instrument” training via reflective practice and humanistic assessment over measurable metrics.

Summary: In the absence of a mechanical stricture, oropharyngeal dysphagia following esophageal cancer surgery, and swallowing physiology more broadly, is poorly understood. This study investigated oropharyngeal dysphagia within the first year following curative open esophageal resection. A prospective cohort study was conducted (January 2022 to January 2024) at the National Esophageal Cancer Centre in Ireland. Participants were recruited between 6 to 12 months post-esophagectomy. A standardized videofluoroscopy was completed. Outcome measures included the Dynamic Imaging Grade of Swallowing Toxicity (DIGESTv2), Modified Barium Swallow Impairment Profile (MBSImP), and Penetration-Aspiration Scale (PAS). Functional Oral Intake Scale (FOIS) was used to identify oral intake status. To evaluate the trajectory of oropharyngeal dysphagia, long-term data were compared to previously published acute data findings. Seventeen participants (12 males; mean age 65 years, range 46–80) were included. The cohort comprised transthoracic (2-stage n = 7, 3-stage n = 3) and transhiatal (n = 7) resections. 11 participants (65%) had persistent oropharyngeal dysphagia (DIGESTv2), and 2 (12%) continued to aspirate greater than 6-months, both of whom had a transhiatal resection. 10 (59%) continued to modify their diet (abnormal FOIS <7). MBSImP revealed impaired initiation of swallow (82%), anterior hyoid excursion (82%), tongue base retraction (100%), pharyngeal residue (100%) and neo-esophageal clearance (82%). When comparing acute to longer term data, there was a statistically significant difference in aspiration based on PAS (P = 0.016), but not dysphagia based on the DIGESTv2 (P = 0.500). Oropharyngeal dysphagia is prevalent within the first year following open esophageal cancer surgery. The study informs the need for structured guidelines and a swallowing care pathway.

HER2 (human epidermal growth factor receptor 2) is a receptor tyrosine kinase which is overexpressed in ~20% of patients with oesophagogastric adenocarcinoma (EGA). HER2 represents a targetable transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family, which plays a crucial role in cell proliferation, survival, and differentiation. HER2 significantly influences the tumour microenvironment (TME) through various mechanisms, creating a niche that supports tumour progression, immune evasion, and therapeutic resistance. In HER2-positive EGA, aberrant signalling pathways, such as PI3K/AKT and MAPK/ERK, enhance tumour cell survival and proliferation, whilst upregulation of angiogenic factors like VEGF fosters vascularization, meeting a tumour’s metabolic demands and facilitating its proliferation. HER2 also modulates the tumour immune microenvironment (TIME) by downregulating MHC molecules and recruiting immunosuppressive cells, including regulatory T-cells (T-reg) and tumour-associated macrophages (TAMs), which release cytokines that further inhibit anti-tumour immune responses. Together, these factors foster a pro-inflammatory, immunosuppressive microenvironment that underpins resistance to HER2-targeted therapies. As more HER2-directed treatments become available, such as trastuzumab–deruxtecan (T-DXd), gaining a deeper understanding of the multifaceted influence of HER2 on the TME in EGA will be crucial for the development of improved targeted treatments that can overcome these challenges and lead to advancements in targeted treatment for HER2-overexpressing EGA. This review provides a comprehensive overview of the impact of HER2 on the TME in EGA and highlights the challenge it represents as well as the opportunity for novel therapeutic development and the implications for patients in terms of clinicopathological outcomes.

Summary: Background: Oropharyngeal dysphagia and aspiration in the early post-esophagectomy period is rarely studied. This study investigated its prevalence, nature and severity, differences across surgical subgroups, and predictors of risk. Methods: A prospective cohort study was conducted (January 2022–January 2024) at the National Esophageal Cancer Centre. Data was collected on post-operative day (POD) 4 or 5. Swallowing evaluations included videofluoroscopy [Dynamic Imaging Grade of Swallowing Toxicity v2(DIGESTv2), Modified Barium Swallow Impairment Profile (MBSImP), Penetration-Aspiration Scale (PAS)]. Functional Oral Intake Scale (FOIS) was used to identify oral intake status. Results: N = 30 (25 males) were recruited, mean age (range) of 65 (46-80y), n = 13 2-stage, n = 8 3-stage, and n = 9 transhiatal resections. At POD 4/5, 60% (18/30) showed signs of aspiration, with no differences across surgical groups (P = 0.114). Dysphagia per the DIGESTv2 was present in 83% (25/30) of patients, with severe dysphagia in 23% (7/30). MBSImP assessment revealed reduced tongue base retraction (82%), pharyngeal residue (100%) and impaired neo-esophageal clearance (100%). Predictors of aspiration were: pre-operative abnormal FOIS (score < 7) (OR = 7.00, 95%CI 1.2–38.4; P = 0.024), and > 65 years (OR = 7.80, 95%CI 1.47–41.6; P = 0.016). Predictors for oropharyngeal dysphagia were: abnormal pre-operative FOIS (score < 7) (OR = 7.42, 95%CI 1.22–45.45; P = 0.029); age > 65 years (OR = 11.00, 95%CI 1.99–58.8; P = 0.006) and neoadjuvant treatment (OR = 7.20, 95%CI 1.08–47.96, P = 0.041). Conclusion: Oropharyngeal dysphagia and aspiration are prevalent in the early period after esophageal cancer surgery. These data should inform an increased input from speech and language specialists in the assessment and management of post-operative patients, and overall caution in the implementation and progression of early per orum intake.

The curative treatment for esophageal cancer (EC) is esophagectomy, a procedure which modifies the capacity to normally metabolize food. Post-esophagectomy, individuals may struggle with food intake, malabsorption, weight loss, and gastrointestinal issues, negatively impacting their quality of life (QOL). Despite the increasing survival rate of EC patients, little is still known about their dietary intake pattern over the course of long-term survivorship. This study aims to explore the nutritional intake of EC survivors, comparing it to the general Irish population and recommended standards. Male EC survivors were recruited from St James’s Hospital and completed a detailed food diary over 7 days. Diaries were analyzed using nutritics and nutrient intakes were compared to the National Adult Nutrition Survey cohort. A modified World Cancer Research Fund (WCRF) score was created to assess adherence to the WCRF recommendations for cancer prevention. QOL scores were calculated using the European Organization for Research and Treatment of Cancer guidelines. Twenty-eight participants completed food diaries. EC survivors had significantly lower intakes of energy, protein, fat, carbohydrate, fiber, sugar, Vitamin E, and alcohol compared to the general population. Participants scored 2.99/6 on the WCRF score, with particularly poor adherence to fruit/vegetable, fiber, and red/processed meat guidelines. While 10.7% of the cohort were obese, 57.1% experienced >10% weight loss in >6 months. QOL results indicated deficits in physical and functional capacity among EC survivors compared to population norms. EC survivors have numerous nutritional deficits, alongside reduced physical and functional status. It is evident that continued dietary advice is needed long-term in EC survivorship to optimize diet quality, thus reducing the risk of cancer recurrence and all-cause mortality and improving QOL.