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Advances in cancer biology and sequencing technology have enabled the selection of targeted and more effective treatments for individual patients with various types of solid tumour. However, only three molecular biomarkers have thus far been demonstrated to predict a response to targeted therapies in patients with gastric and/or gastro-oesophageal junction (G/GEJ) cancers: HER2 positivity for trastuzumab and trastuzumab deruxtecan, and microsatellite instability (MSI) status and PD-L1 expression for pembrolizumab. Despite this lack of clinically relevant biomarkers, distinct molecular subtypes of G/GEJ cancers have been identified and have informed the development of novel agents, including receptor tyrosine kinase inhibitors and monoclonal antibodies, several of which are currently being tested in ongoing trials. Many of these trials include biomarker stratification, and some include analysis of circulating tumour DNA (ctDNA), which both enables the noninvasive assessment of biomarker expression and provides an indication of the contributions of intratumoural heterogeneity to response and resistance. The results of these studies might help to optimize the selection of patients to receive targeted therapies, thus facilitating precision medicine approaches for patients with G/GEJ cancers. In this Review, we describe the current evidence supporting the use of targeted therapies in patients with G/GEJ cancers and provide guidance on future research directions.Despite considerable progress in the development of targeted therapies, only three biomarkers are currently used to guide the treatment of patients with gastric or gastro-oesophageal junction cancers using approved targeted therapies. Nonetheless, owing to advances in our understanding of tumour biology and sequencing technologies, several novel therapies are expected to soon become available. In this Review, the authors describe current and future biomarker-guided therapies for patients with G/GEJ cancers.

Purpose Our study provides data on depression and anxiety in long-term cancer survivors, in men, women and various age groups, as well as identifies associated factors and coping-related resources. Methods We present data obtained from 1002 cancer survivors across a large variety of tumour entities 5 years (cohort 1) and 10 years (cohort 2) after diagnosis, in a cross-sectional study. We analysed depression (PHQ-9) and anxiety (GAD-7) symptomatology in comparison with two large age- and sex-matched samples randomly selected from the general population. Results Moderate to severe depression and anxiety were reported in 17% and 9% of cancer survivors, respectively. There were no significant differences between the 5 years and 10 years after diagnosis cohorts ( p  = 0.232). In both cohorts, we found higher depression and anxiety in women than in men ( p  < 0.001), and lower depression and anxiety in elderly patients ( p  < 0.001). Cancer survivors younger than 60 years of age were more depressed and anxious than the general population ( p  < 0.001). The variables, financial problems (Beta = 0.16, p  < 0.001), global quality of life (Beta = − 0.21, p  < 0.001) and cognitive function (Beta = − 0.30, p  < 0.001), had the strongest association with depression and anxiety. Conclusions For the prevention of depression and anxiety in long-term cancer survivors, individual treatment of physical and psychological symptoms is as important as social support and professional counselling. Post-treatment, cognitive limitations should be carefully assessed in long-term cancer survivorship to distinguish them from symptoms of a mental disorder, especially since younger cancer survivors of working age and female survivors seem to be more affected by depression and anxiety.

HGF-mediated activation of MET results in a complex genetic programme referred to as invasive growth, consisting of a series of processes, including proliferation, invasion, and angiogenesis, that occur under normal physiological conditions during embryonic development and pathologically during oncogenesis.1 The HGF/MET axis is activated in a range of cancers including gastric cancer, and is associated with an aggressive phenotype and poor prognosis.2 One approach of pathway-selective anticancer drug development is antagonism of ligand-receptor interaction. [...]a small proportion of patients in this trial (35% in the rilotumumab group and 38% in the placebo group) received post-protocol therapy.

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes.Peritoneal surface malignancies have heterogeneous origins, including primary peritoneal tumours and metastases of other cancers, for example, digestive tract, reproductive tract, lung, breast and kidney tumours. This Primer reviews the epidemiology, mechanisms and diagnosis of these diseases, and discusses treatment options, patient quality of life and upcoming innovations.

BackgroundZolbetuximab plus first-line EOX (epirubicin, oxaliplatin, capecitabine; ZOL/EOX) significantly prolonged progression-free survival and overall survival in the FAST trial vs EOX alone. We report the patient-reported outcomes (PROs) of FAST in patients with advanced gastroesophageal adenocarcinoma.MethodsPatients were randomized to ZOL/EOX or EOX alone. Patients could receive ≤ 8 EOX cycles and remained on zolbetuximab until disease progression. PROs were collected using the EORTC QLQ-C30 and QLQ-STO22 before drug administration at day 1/cycle 1, day 1/cycle 5, end of EOX treatment, and q12w thereafter until disease progression. Time to deterioration (TTD), defined as the first meaningful worsening from baseline, in the individual QLQ-C30/QLQ-STO22 scores was analyzed. Longitudinal changes in scores from baseline were analyzed using a mixed-effects model for repeated measures (MMRM).ResultsThe per protocol population included 143 (ZOL/EOX: 69; EOX: 74) patients. Baseline QLQ-C30 and STO22 scores were comparable between arms and denoted intermediate-to-high quality of life (QoL), intermediate-to-low global health status (GHS) and low symptom burden. Descriptive analyses showed no differences between arms until end of EOX but maintenance therapy with zolbetuximab was associated with better QoL and less symptom burden thereafter. TTD for most scores favored ZOL/EOX over EOX and reached statistical significance for GHS (p = 0.008). MMRM results support TTD findings; no statistically significant differences were observed between arms in any score except for nausea and vomiting (p = 0.0181 favoring EOX).ConclusionsZOL/EOX allowed patients to maintain good QoL and low symptom burden for longer than EOX alone.

Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov, number NCT01041404. 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18·6 months (IQR 11–25) in the trastuzumab plus chemotherapy group and 17·1 months (9–25) in the chemotherapy alone group. Median overall survival was 13·8 months (95% CI 12–16) in those assigned to trastuzumab plus chemotherapy compared with 11·1 months (10–13) in those assigned to chemotherapy alone (hazard ratio 0·74; 95% CI 0·60–0·91; p=0·0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia (157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not differ between groups. Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. F Hoffmann-La Roche.

Understanding mild to moderate symptoms of coronavirus disease 2019 (Covid-19) is important in order to identify active cases early and thus counteract transmission. In March 2020, Leipzig University Hospital established an outpatient clinic for patients potentially infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Confirmed cases with mild to moderate symptoms self-isolated at home and were followed-up by daily telephone calls for at least 14 days. Symptoms and course of illness of these patients are reported here. From March 20 to April 17, 2020, 1460 individuals were tested for SARS-CoV-2 by naso- or oropharyngeal swab for real-time polymerase chain reaction (RT-PCR). Covid-19 was confirmed in 91 (6.2%) patients, of which 87 were included in the final analysis. Patients presented for testing after a mean of 5.9 days (IQR = 2.0-8.5). The median age was 37.0 years (IQR = 28.5-53), and 48 (55.2%) were female. Five (5.7%) patients required hospital admission during the course of illness. Most frequently reported symptoms were fatigue (n = 64, 74%), cough (n = 58, 67%), and hyposmia/hypogeusia (n = 44, 51%). In contrast to previous reports, fever occurred in less than a third of patients (n = 25, 29%). By day 14, more than half of the patients had recovered completely (n = 37/70, 52.9%). Fever seems to be less common in patients of relatively young age diagnosed with mild to moderate Covid-19. This suggests that body temperature alone may be an insufficient indicator of SARS-CoV-2 infection.

Distress is highly prevalent among patients with cancer, but supportive care needs often go unmet. Digital therapeutics hold the potential to overcome barriers in cancer care and improve health outcomes. This study conducted a randomized controlled trial to investigate the efficacy of Mika, an app-based digital therapeutic designed to reduce distress across the cancer trajectory. This nationwide waitlist randomized controlled trial in Germany enrolled patients with cancer across all tumor entities diagnosed within the last 5 years. Participants were randomized into the intervention (Mika plus usual care) and control (usual care alone) groups. The participants completed web-based assessments at baseline and at 2, 6, and 12 weeks. The primary outcome was the change in distress from baseline to week 12, as measured by the National Comprehensive Cancer Network Distress Thermometer. Secondary outcomes included depression, anxiety (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and quality of life (Clinical Global Impression-Improvement Scale). Intention-to-treat and per-protocol analyses were performed. Analyses of covariance were used to test for outcome changes over time between the groups, controlling for baseline. A total of 218 patients (intervention: n=99 and control: n=119) were included in the intention-to-treat analysis. Compared with the control group, the intervention group reported greater reductions in distress (P=.03; ηp²=0.02), depression (P<.001; ηp²=0.07), anxiety (P=.03; ηp²=0.02), and fatigue (P=.04; ηp²=0.02). Per-protocol analyses revealed more pronounced treatment effects, with the exception of fatigue. No group difference was found for quality of life. Mika effectively diminished distress in patients with cancer. As a digital therapeutic solution, Mika offers accessible, tailored psychosocial and self-management support to address the unmet needs in cancer care. German Clinical Trials Register (DRKS) DRKS00026038; https://drks.de/search/en/trial/DRKS00026038.

Our study provides data on sexual satisfaction among long-term cancer survivors 5 and 10 years after diagnosis, and identifies factors detrimental (e.g. psychosocial and physical symptom burden) or beneficial (e.g. social support) to survivors’ sexual satisfaction. We measured sexual satisfaction among cancer survivors recruited via the local clinical cancer registry across a wide range of tumor sites 5 years (cohort 1) and 10 years (cohort 2) after diagnosis. We further assessed chronic comorbidity index (CCI) and symptom scales (EORTC QLQ-C30), depression (PHQ-9) and anxiety (GAD-7), satisfaction with partnership (PFB), quality of life (EORTC QLQ-C30), and social support (OSSS). 924 patients (5‐year cohort = 608/10‐year cohort = 316) participated in the study (53% men, 80% cohabiting, mean age 66 years, range 18–85). We found that nearly half of the respondents perceived their sexual life as less satisfying than before cancer. High sexual satisfaction was associated with a low chronic comorbidities index ( r  = − 0.27, p  < .001),  less fatigue ( r  = − 0.35, p <.001), less nausea/vomiting ( r  = − 0.13, p <.001) and less pain ( r  = − 0.23, p <.001),  r  ; less depression ( r  = − 0.24, p  < .001), less anxiety( r  = − 0.23, p  < .001); a high level of social support ( r  = 0.16, p  < .001), a high level of satisfaction with their relationship ( r  = 0.24, p  < .001), and high quality of life ( r  = 0.33, p  < .001). Sexual satisfaction may be affected by both psychosocial and physical symptom burden, with the latter having a greater impact on sexual satisfaction. It is essential for health care providers that sexual health issues are understood, evaluated, and treated, including those of long-term cancer survivors.