New Horizons for Personalised Treatment in Gastroesophageal Cancer

Gastric and gastroesophageal junction adenocarcinoma (GEA) is still responsible for a huge health burden worldwide, being the second most common cause of cancer-related death globally [...]

Metastatic gastroesophageal cancer in older patients – is this patient cohort represented in clinical trials?

Background Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. Methods A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. Results Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18–94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65–80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7–60%). Conclusions Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

Innovative strategies in metastatic gastric cancer: a short review

SummaryRecent innovative advances, especially concerning immunotherapeutic agents and targeted therapies, have changed the face of modern oncology. The year 2020 represents a milestone in the treatment of gastroesophageal cancer because several trials showed promising survival benefits, at least for a specific subgroup of patients. Not only immunotherapeutic agents, but also targeted therapies seem to be beneficial, particularly when the target is well defined and the threshold value is selected appropriately. Thus, many new innovative treatment strategies are underway and might lead to a further paradigm change in the therapy of patients with advanced gastric tumors. This review gives a concise overview of these new therapeutic options and recently approved strategies as well as ongoing studies.

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Material and Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months; hyperthyroid, n = 50: 23.1 months; hypothyroid, n = 70: 47.9 months; p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months; with, n = 67: 51.3 months; p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months; p = 0.045). Conclusions: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

ASCO 2021–Gastroesophageal tumor highlights

SummaryThe oncological community witnessed several practice-changing clinical reports in this years’ annual congress of the American Society of Clinical Oncology (ASCO). Many immunotherapeutic agents were shown to be beneficial for upper gastrointestinal tumors. For advanced squamous cell carcinoma, immunotherapy and chemotherapy combinations revealed by the CheckMate 648 and ESCORT-1st trials have been implemented into the clinical practice. The updates on the CheckMate 649 and CheckMate 577 trials again underlined the significant clinical contribution of nivolumab in advanced and localized gastroesophageal cancer, respectively. However, this effect seems to be dependent to PD-L1 expression. Not only immunotherapy trials, but also targeted therapy studies such as the FIGHT trial investigating the anti-FGFR2b monoclonal antibody bemarituzumab attracted huge interest, not only due to extension of survival in experimental group, but also due to the innovative design of this trial. This review summarizes the highlights regarding gastroesophageal tumors at the ASCO 2021 congress.

Initial Experience in Staging Primary Oesophageal/Gastroesophageal Cancer with 18F-FDG PET/MRI

Background18F-Fluorodesoxyglucose Positron-emission tomography magnetic resonance imaging (18F-FDG PET/MRI) may improve cancer staging by combining sensitive cancer detection with high contrast resolution and detail. We compared the diagnostic performance of 18F-FDG PET/MRI to 18F-Fluorodesoxyglucose Positron-emission tomography computed tomography (18F-FDG PET/CT )for staging oesophageal/gastroesophageal cancer.Following ethical approval and informed consent, participants with newly diagnosed primary oesophageal/gastroesophageal cancer were enrolled. Exclusions included prior/concurrent malignancy. Following 324±28 MBq 18F-FDG administration and 60-minute uptake, PET/CT was performed; immediately followed by integrated PET/MRI from skull base to mid-thigh. PET/CT was interpreted by two dual-accredited nuclear medicine physicians; PET/MRI by a dual-accredited nuclear medicine physician/radiologist and cancer radiologist in consensus. Per-participant staging was compared with the tumour board consensus staging using the McNemar test, with statistical significance at 5%. Results 22/26 participants (20 male; mean±SD age 68.8±8.7 years) completed 18F-FDG PET/CT and PET/MRI. Compared to the tumour board, the primary tumour was staged concordantly in 55% (12/22) with PET/MRI and 36% (8/22) with PET/CT; the nodal stage was concordant in 45% (10/22) with PET/MRI and 50% (11/22) with PET/CT. There was no statistical difference in PET/CT and PET/MRI staging performance (p>0.05, for T and N staging). The staging of distant metastases was concordant with the tumour board in 95% (21/22) with both PET/MRI and PET/CT. Of participants with distant metastatic disease, PET/MRI detected additional metastases in 30% (3/10). ConclusionIn this preliminary study, compared to 18F-FDG PET/CT, 18F-FDG PET/MRI showed non-significant higher concordance with T-staging, but no difference with N or M-staging. Additional metastases detected by 18F-FDG PET/MRI may be of additive clinical value.

PD-1/PD-L1 Inhibitors versus Chemotherapy for Previously Treated Advanced Gastroesophageal Cancer: A Meta-Analysis of Randomized Controlled Trials

Patients with advanced gastroesophageal cancer refractory to the previous regimen of chemotherapy suffered from poor prognosis without many effective treatment options. Immune checkpoint inhibitors (ICIs) provide promising efficacy, but the relevant clinical trials have offered controversial data. We performed this meta-analysis to compare the efficacy and safety of inhibitors against programmed cell death receptor 1 (PD-1) and its ligand PD-L1 versus chemotherapy as second or third-line therapy in patients with advanced gastroesophageal cancer. Six randomized controlled trials (RCTs) including 2,648 patients were included. The meta-analysis results indicated that both ORR (RR = 1.39, 95% CI: 0.85∼2.25, P = 0.188) and PFS (HR = 1.14, 95% CI: 0.88∼1.46, P = 0.316) were not significantly improved by ICIs compared with chemotherapy. However, the OS was significantly prolonged (HR = 0.85, 95% CI: 0.75–0.97, P = 0.018) in the ICIs group compared with chemotherapy. Subgroup analysis showed that ICIs provide statistically significant OS benefits over chemotherapy in PD-L1-positive, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and aged 65 or older patients. Compared with chemotherapy, the TRAEs risk of ICIs was reduced by 33% (RR = 0.67, 95% CI: 0.62–0.73, P ≤ 0.001). And the risk of grades 3–5 of TRAEs was reduced by 60% (RR = 0.40, 95% CI: 0.33–0.49, P ≤ 0.001). Compared to chemotherapy, ICIs appeared to improve OS and were better tolerated in previously treated patients with advanced esophageal cancer. We recommend PD-1/PD-L1 inhibitors as an optimal treatment option for positive PD-L1 expression, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and ≥65 years of age patients.