Peritoneal metastases from gastric cancer in a nationwide cohort: Incidence, treatment and survival.

The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic: A population-based observational study.

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1-12 2020: pre-COVID-19, weeks 12-20 2020: 1st peak, weeks 21-41 2020: recovery, weeks 42-53 2020: 2nd peak, weeks 1-20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77-0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72-0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p < .001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.

Measurement of metabolite levels and treatment-induced changes in hepatic metastases of gastro-esophageal cancer using 7-T phosphorus magnetic resonance spectroscopic imaging.

Methods for early treatment response evaluation to systemic therapy of liver metastases are lacking. Tumor tissue often exhibits an increased ratio of phosphomonoesters to phosphodiesters (PME/PDE), which can be noninvasively measured by phosphorus magnetic resonance spectroscopy (31P MRS), and may be a marker for early therapy response assessment in liver metastases. However, with commonly used 31P surface coils for liver 31P MRS, the liver is not fully covered, and metastases may be missed. The objective of this study was to demonstrate the feasibility of 31P MRS imaging (31P MRSI) with full liver coverage to assess 31P metabolite levels and chemotherapy-induced changes in liver metastases of gastro-esophageal cancer, using a 31P whole-body birdcage transmit coil in combination with a 31P body receive array at 7 T. 3D 31P MRSI data were acquired in two patients with hepatic metastases of esophageal cancer, before the start of chemotherapy and after 2 (and 9 in patient 2) weeks of chemotherapy. 3D 31P MRSI acquisitions were performed using an integrated 31P whole-body transmit coil in combination with a 16-channel body receive array at 7 T, with a field of view covering the full abdomen and a nominal voxel size of 20-mm isotropic. From the 31P MRSI data, 12 31P metabolite signals were quantified. Prior to chemotherapy initiation, both PMEs, that is, phosphocholine (PC) and phosphoethanolamine (PE), were significantly higher in all metastases compared with the levels previously determined in the liver of healthy volunteers. After 2 weeks of chemotherapy, PC and PE levels remained high or even increased further, resulting in increased PME/PDE ratios compared with healthy liver tissue, in correspondence with the clinical assessment of progressive disease after 2 months of chemotherapy. The suggested approach may present a viable tool for early therapy (non)response assessment of tumor metabolism in patients with liver metastases.

Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

BACKGROUND: This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. METHODS: This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. RESULTS: Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). CONCLUSION: Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

MR Elastography of the Pancreas: Bowel Preparation and Repeatability Assessment in Pancreatic Cancer Patients and Healthy Controls.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. PURPOSE: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. STUDY TYPE: Prospective. POPULATION: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. FIELD STRENGTH/SEQUENCE: 3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo. ASSESSMENT: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. STATISTICAL TESTS: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant. RESULTS: Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094). DATA CONCLUSION: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer: Results from the randomized CRITICS trial.

BACKGROUND AND OBJECTIVE: This study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC). METHODS: A post-hoc analysis of the CRITICS-trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy-related toxicity and compliance were compared. RESULTS: Data from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor-positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes. CONCLUSIONS: Positive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.

Genome-wide and panel-based cell-free DNA characterization of patients with resectable esophageal adenocarcinoma.

Circulating tumor DNA (ctDNA) holds promise in resectable esophageal adenocarcinoma (EAC) to predict patient outcome but is not yet sensitive enough to be clinically applicable. Our aim was to combine ctDNA mutation data with shallow whole-genome sequencing (sWGS)-derived copy number tumor fraction estimates (ichorCNA) to improve pathological response and survival prediction in EAC. In total, 111 stage II/III EAC patients with baseline (n = 111), post-neoadjuvant chemoradiotherapy (nCRT) (n = 68), and pre-surgery (n = 92) plasma samples were used for ctDNA characterization. sWGS (<5× coverage) was performed on all time-point samples, and copy number aberrations were estimated using ichorCNA. Baseline and pre-surgery samples were sequenced using a custom amplicon panel for mutation detection. Detection of baseline ctDNA was successful in 44.3% of patients by amplicon sequencing and 10.5% by ichorCNA. Combining both, ctDNA could be detected in 50.5% of patients. Baseline ctDNA positivity was related to higher T stage (cT3, 4) (p = 0.017). There was no relationship between pathological response and baseline ctDNA positivity. However, baseline ctDNA metrics (variant allele frequency > 1% or ichorCNA > 3%) were associated with a high risk of disease progression [HR = 2.23 (95% CI 1.22-4.07), p = 0.007]. The non-clearance of a baseline variant or ichorCNA > 3% in pre-surgery samples was related to early progression [HR = 4.58 (95% CI 2.22-9.46), p < 0.001]. Multi-signal analysis improves detection of ctDNA and can be used for prognostication of resectable EAC patients. Future studies should explore the potential of multi-modality sequencing for risk stratification and treatment adaptation based on ctDNA results. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Open communication between patients and relatives about illness & death in advanced cancer-results of the eQuiPe Study.

OBJECTIVE: To assess the degree of openness of communication about illness and death between patients with advanced cancer and their relatives during the last three months of the patient's life, and its association with relatives' characteristics and bereavement distress. METHODS: We used data from bereaved relatives of patients with advanced cancer from the prospective, longitudinal, multicenter, observational eQuipe study. Univariate and multivariable linear regression analyses were used to assess the association between the degree of openness of communication (measured using the validated Caregivers' Communication with patients about Illness and Death scale), the a priori defined characteristics of the relatives, and the degree of bereavement distress (measured using the Impact of Event Scale). RESULTS: A total of 160 bereaved relatives were included in the analysis. The average degree of open communication about illness and death between patients with advanced cancer and their relatives was 3.86 on a scale of 1 to 5 (SE=0.08). A higher degree of open communication was associated with a lower degree of bereavement distress (p=0.003). No associations were found between the degree of open communication and the relatives' age (p=0.745), gender (p=0.196), level of education (p>0.773), (religious) worldview (p=0.435), type of relationship with the patient (p>0.548), or level of emotional functioning before the patient's death (p=0.075). CONCLUSIONS: Open communication about illness and death between patients and relatives seems to be important, as it is associated with a lower degree of bereavement distress. Healthcare professionals can play an important role in encouraging the dialogue. However, it is important to keep in mind that some people not feel comfortable talking about illness and death.

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic: A retrospective population-based study.

BACKGROUND: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. AIM: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. DESIGN: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, >1 emergency room contact, >1 hospitalization, hospitalization >14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. PARTICIPANTS: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. RESULTS: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74-0.88 and OR 0.92; 95% CI 0.87-0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. CONCLUSIONS: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.

Effects of prognostic communication strategies on emotions, coping, and appreciation of consultations: An experimental study in advanced cancer.

OBJECTIVES: We aimed to investigate effects of prognostic communication strategies on emotions, coping, and appreciation of consultations in advanced cancer. METHODS: For this experimental study, we created 8 videos of a scripted oncological consultation, only varying in prognostic communication strategies. Disease-naive individuals (n = 1036) completed surveys before and after watching 1 video, while imagining being the depicted cancer patient. We investigated effects of the type of disclosure (prognostic disclosure vs. communication of unpredictability vs. non-disclosure) and content of disclosure (standard vs. standard and best-case vs. standard, best- and worst-case survival scenarios; numerical vs. word-based estimates) on emotions, coping, and appreciation of consultations. Moderating effects of individual characteristics were tested. RESULTS: Participants generally reported more satisfaction (p < .001) after prognostic disclosure versus communication of unpredictability and less uncertainty (p = .042), more satisfaction (p = .005), and more desirability (p = .016) regarding prognostic information after numerical versus word-based estimates. Effects of different survival scenarios were absent. Prognostic communication strategies lacked effects on emotions and coping. Significant moderators included prognostic information preference and uncertainty tolerance. SIGNIFICANCE OF RESULTS: In an experimental setting, prognostic disclosure does not cause more negative emotions than non-disclosure and numerical estimates are more strongly appreciated than words. Oncologists' worries about harming patients should not preclude disclosing (precise) prognostic information, yet sensitivity to individual preferences and characteristics remains pivotal.

Conditional relative survival in nonmetastatic esophagogastric cancer between 2006 and 2020: A population-based study.

Conditional relative survival (CRS) is useful for communicating prognosis to patients as it provides an estimate of the life expectancy after having survived a certain time after treatment. Our study estimates the 3-year relative survival conditional on having survived a certain period for patients with esophageal or gastric cancer. Patients with nonmetastatic esophageal or gastric cancer diagnosed between 2006 and 2020 treated with curative intent (resection with or without [neo]adjuvant therapy, or chemoradiotherapy) were selected from the Netherlands Cancer Registry. CRS was calculated since resection or last day of chemoradiotherapy. The probability of surviving an additional 3 years (ie, 3-year CRS), if the patients survived 1, 3 and 5 years after diagnosis was 62%, 79%, 87% and 69%, 84%, 90% for esophageal and gastric cancer, respectively. The 3-year CRS after having survived 3 years for patients with esophageal cancer who underwent a resection (n = 12 204) was 91%, 88%, 77% and 60% for pathological Stage 0, I, II and III, and for patients with esophageal cancer who received chemoradiotherapy (n = 4158) was 51% and 66% for clinical Stage II and III, respectively. The 3-year CRS after having survived 3 years for patients with gastric cancer who underwent a resection (n = 6531) was 99%, 90%, 73% and 59% for pathological Stage 0, I, II and III, respectively. Despite poor prognosis of patients with esophageal or gastric cancer, life expectancy increases substantially after patients have survived several years after treatment. Our study provides valuable information for communication of prognosis to patients during follow-up after treatment.

SOURCE beyond first-line: A survival prediction model for patients with metastatic esophagogastric adenocarcinoma after failure of first-line palliative systemic therapy.

Prior models have been developed to predict survival for patients with esophagogastric cancer undergoing curative treatment or first-line chemotherapy (SOURCE models). Comprehensive clinical prediction models for patients with esophagogastric cancer who will receive second-line chemotherapy or best supportive care are currently lacking. The aim of our study was to develop and internally validate a new clinical prediction model, called SOURCE beyond first-line, for survival of patients with metastatic esophagogastric adenocarcinoma after failure of first-line palliative systemic therapy. Patients with unresectable or metastatic esophageal or gastric adenocarcinoma (2015-2017) who received first-line systemic therapy (N = 1067) were selected from the Netherlands Cancer Registry. Patient, tumor and treatment characteristics at primary diagnosis and at progression of disease were used to develop the model. A Cox proportional hazards regression model was developed through forward and backward selection using Akaike's Information Criterion. The model was internally validated through 10-fold cross-validations to assess performance. Model discrimination (C-index) and calibration (slope and intercept) were used to evaluate performance of the complete and cross-validated models. The final model consisted of 11 patient tumor and treatment characteristics. The C-index was 0.75 (0.73-0.78), calibration slope 1.01 (1.00-1.01) and calibration intercept 0.01 (0.01-0.02). Internal cross-validation of the model showed that the model performed adequately on unseen data: C-index was 0.79 (0.77-0.82), calibration slope 0.93 (0.85-1.01) and calibration intercept 0.02 (-0.01 to 0.06). The SOURCE beyond first-line model predicted survival with fair discriminatory ability and good calibration.

Trends in best-case, typical and worst-case survival scenarios of patients with non-metastatic esophagogastric cancer between 2006 and 2020: A population-based study.

New treatment options and centralization of surgery have improved survival for patients with non-metastatic esophageal or gastric cancer. It is unknown, however, which patients benefitted the most from treatment advances. The aim of this study was to identify best-case, typical and worst-case scenarios in terms of survival time, and to assess if survival associated with these scenarios changed over time. Patients with non-metastatic potentially resectable esophageal or gastric cancer diagnosed between 2006 and 2020 were selected from the Netherlands Cancer Registry. Best-case (20th percentile), upper-typical (40th percentile), typical (median), lower-typical (60th percentile) and worst-case (80th percentile) survival scenarios were defined, and regression analysis was used to investigate the change in survival time for each scenario across years. For patients with esophageal cancer (N = 24 352) survival time improved on average 12.0 (until 2011), 1.5 (until 2018), 0.7, 0.4 and 0.2 months per year for the best-case, upper-typical, median, lower-typical and worst-case scenario, respectively. For patients with gastric cancer (N = 9993) survival time of the best-case scenario remained constant, whereas the upper-typical, median, lower-typical and worst-case scenario improved on average with 1.0 (until 2018), 0.5, 0.2 and 0.2 months per year, respectively. Subgroup analyses showed that, survival scenarios improved for nearly all patients across treatment groups and for patients with squamous cell carcinomas or adenocarcinomas. Survival improved for almost all patients suggesting that in clinical practice the vast majority of patients benefitted from treatment advances. The clinically most meaningful survival advantage was observed for the best-case scenario of esophageal cancer.

Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Stroma-targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and tumor-suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA-sequencing reads from patient-derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta-analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co-cultures and assessed in existing and novel single-cell gene expression analysis from control, pancreatitis, pancreatitis-recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC.

Delayed Versus Immediate Start of Chemotherapy in Asymptomatic Patients With Advanced Cancer: A Meta-Analysis.

BACKGROUND: Due to increased use of imaging, advanced stages of cancer are increasingly being diagnosed in an early, asymptomatic phase. Traditionally, chemotherapy is started immediately in these patients. However, a strategy wherein chemotherapy is withheld until symptoms occur may be beneficial for patients in terms of quality of life (QOL). A systematic review regarding optimal timing of chemotherapy including survival and QOL is lacking. METHODS: We systematically searched PubMed, EMBASE, and Cochrane for studies investigating the timing of start of chemotherapy in asymptomatic patients with advanced cancer. Overall survival (OS) was abstracted as primary, QOL, and toxicity as secondary outcomes. A meta-analysis was performed on OS. QOL was described using the global health status derived from the EORTC-QLQ-C30 questionnaire and toxicity as grade 3-4 adverse events. RESULTS: Overall, 919 patients from 4 randomized controlled trials and 1 retrospective study were included. The included studies investigated colorectal cancer (n = 3), ovarian cancer (n = 1), and gastric cancer (n = 1). Pooled analysis demonstrated no significant differences in OS between delayed and immediate start of chemotherapy (pooled HR: 1.05, 95% CI, 0.90-1.22, P = .52). QOL, evaluated in 3 studies, suggested a better QOL in the delayed treatment group. Toxicity, evaluated in 2 studies, did not differ significantly between groups. CONCLUSION: This meta-analysis confirms the need for prospective studies on timing of start of chemotherapy in asymptomatic patients with advanced cancer. The limited evidence available suggests that delayed start of chemotherapy, once symptoms occur, as compared to immediate start in asymptomatic patients does not worsen OS while it may preserve QOL.

Prevalence and Predictors of Physician-Patient Discordance in Prognostic Perceptions in Advanced Cancer.

BACKGROUND: Discordance between physicians' and patients' prognostic perceptions in advanced cancer care threatens informed medical decision-making and end-of-life preparation, yet this phenomenon is poorly understood. We sought to: (1) describe the extent and direction of prognostic discordance, patients' prognostic information preferences in cases of prognostic discordance, and physicians' awareness of prognostic discordance; and (2) examine which patient, physician, and caregiver factors predict prognostic discordance. MATERIALS AND METHODS: Oncologists and advanced cancer patients (median survival ≤12 months; n = 515) from 7 Dutch hospitals completed structured surveys in a cross-sectional study. Prognostic discordance was operationalized by comparing physicians' and patients' perceptions of the likelihood of cure, 2-year mortality risk, and 1-year mortality risk. RESULTS: Prognostic discordance occurred in 20% (likelihood of cure), 24%, and 35% (2-year and 1-year mortality risk) of physician-patient dyads, most often involving patients with more optimistic perceptions than their physician. Among patients demonstrating prognostic discordance, the proportion who preferred not knowing prognosis varied from 7% (likelihood of cure) to 37% (1-year mortality risk), and 45% (2-year mortality risk). Agreement between physician-perceived and observed prognostic discordance or concordance was poor (kappa = 0.186). Prognostic discordance was associated with several patient factors (stronger fighting spirit, self-reported absence of prognostic discussions, an information source other than the healthcare provider), and greater physician-reported uncertainty about prognosis. CONCLUSION: Up to one-third of the patients perceive prognosis discordantly from their physician, among whom a substantial proportion prefers not knowing prognosis. Most physicians lack awareness of prognostic discordance, raising the need to explore patients' prognostic information preferences and perceptions, and to tailor prognostic communication.

Prognostic Value of T-Cell Density in the Tumor Center and Outer Margins in Gastric Cancer.

Tumor-infiltrating lymphocytes are associated with the survival of gastric cancer patients. T-cell densities in the tumor and its periphery were previously identified as prognostic T-cell markers for resectable gastric cancer. Immunohistochemistry for 5 T-cell markers, CD3, CD45RO, CD8, FOXP3, and granzyme B was performed on serial sections of N = 251 surgical resection specimens of patients treated with surgery only in the D1/D2 trial. Positive T cells were digitally quantified into tiles of 0.25 mm2 across 3 regions: the tumor center (TC), the inner invasive margin, and the outer invasive margin (OIM). A classification and regression tree model was employed to identify the optimal combination of median T-cell densities per region with cancer-specific survival (CSS) as the outcome. All statistical tests were 2-sided. CD8OIM was identified as the most dominant prognostic factor, followed by FOXP3TC, resulting in a decision tree containing 3 prognostically distinct subgroups with high (Hi) or low (Lo) density of the markers: CD8OIMHi, CD8OIMLo/FOXP3TCHi, and CD8OIMLo/FOXP3TCLo. In a multivariable Cox regression analysis, which included pathological T and N stages, Lauren histologic types, EBV status, microsatellite instability, and type of surgery, the immune subgroups were independent predictors for CSS. CSS was lower for CD8OIMLo/FOXP3TCHi (HR: 5.02; 95% CI: 2.03-12.42) and for CD8OIMLo/FOXP3TCLo (HR: 7.99; 95% CI: 3.22-19.86), compared with CD8OIMHi (P < .0001). The location and density of both CD8+ and FOXP3+ T cells in resectable gastric cancer are independently associated with survival. The combination of CD8OIM and FOXP3TC T-cell densities is a promising stratification factor that should be validated in independent studies.

Gastrointestinal Symptoms After Resection of Esophagogastric Cancer: A Longitudinal Study on Their Incidence and Impact on Patient-Reported Outcomes.

BACKGROUND: This study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities. PATIENTS AND METHODS: Patients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed ≥ 2 questionnaires from the time intervals prior to resection and 0-3, 3-6, 6-9, and 9-12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately. RESULTS: The study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0-3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9-12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity. CONCLUSIONS: This study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship.

Metabolic profiling of colorectal cancer organoids: A comparison between high-resolution magic angle spinning magnetic resonance spectroscopy and solution nuclear magnetic resonance spectroscopy of polar extracts.

Patient-derived cancer cells cultured in vitro are a cornerstone of cancer metabolism research. More recently, the introduction of organoids has provided the research community with a more versatile model system. Physiological structure and organization of the cell source tissue are maintained in organoids, representing a closer link to in vivo tumor models. High-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) is a commonly applied analytical approach for metabolic profiling of intact tissue, but its use has not been reported for organoids. The aim of the current work was to compare the performance of HR MAS MRS and extraction-based nuclear magnetic resonance (NMR) in metabolic profiling of wild-type and tumor progression organoids (TPOs) from human colon cancer, and further to investigate how the sequentially increased genetic alterations of the TPOs affect the metabolic profile. Sixteen metabolites were reliably identified and quantified both in spectra based on NMR of extracts and HR MAS MRS of intact organoids. The metabolite concentrations from the two approaches were highly correlated (r = 0.94), and both approaches were able to capture the systematic changes in metabolic features introduced by the genetic alterations characteristic of colorectal cancer progression (e.g., increased levels of lactate and decreased levels of myo-inositol and phosphocholine with an increasing number of mutations). The current work highlights that HR MAS MRS is a well-suited method for metabolic profiling of intact organoids, with the additional benefit that the nondestructive nature of HR MAS enables subsequent recovery of the organoids for further analyses based on nucleic acids or proteins.

Emotional distress in cancer survivors from various ethnic backgrounds: Analysis of the multi-ethnic HELIUS study.

PURPOSE: Insight into emotional distress of cancer survivors from ethnic minority groups in Europe is scarce. We aimed to compare distress levels of survivors from ethnic minorities to that of the majority population, determine whether the association between having cancer (yes vs. no) and distress differs among ethnic groups and investigate sociocultural correlates of distress. METHODS: Cross-sectional data were derived from HELIUS, a multi-ethnic cohort study conducted in the Netherlands. Of 19,147 participants, 351 were diagnosed with cancer (n = 130 Dutch, n = 75 African Surinamese, n = 53 South-Asian Surinamese, n = 43 Moroccan, n = 28 Turkish, n = 22 Ghanaian). Distress (PHQ-9, MCS-12) and correlates were assessed by self-report. Cancer-related variables were derived from the Netherlands Cancer Registry. RESULTS: Survivors were on average 7 years post-diagnosis. Survivors from South-Asian Surinamese, Moroccan, Turkish and Ghanaian origin reported more distress than survivors from Dutch origin (effect sizerange : 0.44-1.17; adjusted models). The association between having cancer or not with distress differed in direction between Dutch and the non-Dutch ethnic groups: Non-Dutch cancer patients tended to have more distress than their cancer-free peers, whereas Dutch cancer patients tended to have less distress than their cancer-free peers. For Moroccan and Turkish patients, the acculturation style of separation/marginalization, compared to integration/assimilation, was associated with higher depressive symptoms. In analyses pooling data from all ethnic minorities, lower health literacy, lower emotional support satisfaction and younger age at the time of migration were associated with higher depressive symptoms. Lower health literacy, fewer emotional support transactions, and more frequent attendance at religious services were associated with worse mental health. CONCLUSION: Cancer survivors from ethnic minorities experience more distress than those from the majority population. Culturally sensitive supportive care should be considered.