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BACKGROUND: Survival of gastric cancer in the Western world remains poor. We conducted a retrospective population-based study to evaluate trends in incidence, treatment and outcome of gastric adenocarcinoma. METHODS: All patients diagnosed with gastric adenocarcinoma during 1990-2007 in the Dutch Eindhoven Cancer Registry area were included (n=4,797). Trend analyses were conducted for incidence, mortality, tumour and patient characteristics, treatment and crude overall survival, according to tumour location (cardia versus non-cardia). Temporal changes in the odds of undergoing surgery and the risk of death were analysed by means of multivariable regression methods. RESULTS: Age-standardised incidence decreased among males (24-12 per 100,000 inhabitants) and females (10-6); mortality rates decreased at a similar pace. The proportion of cardia tumours remained stable. Stage distribution worsened over time among patients with cardia (stages I and II: 32% in 1990-1993 and 22% in 2006-2007, p=0.005) and non-cardia (stage IV: 33% in 1990-1993 and 40% in 2006-2007, p=0.0003) cancer. Chemotherapy rates increased in all settings. Five-year survival worsened over time for patients with non-cardia tumours. Age and stage had significant influence on survival after stratification for tumour localisation. After adjustments for relevant factors (i.e. stage), the risk of death decreased since the late 90s for patients with a cardia tumour (hazard ratio 0.8, p=0.01). CONCLUSION: The absence of improvement in survival rates indicates the need for earlier detection and prospective studies to evaluate new therapy regimens with standardised surgery and pathology. [ABSTRACT FROM AUTHOR]

Background: The CRC-PIPAC-II study prospectively assessed bidirectional therapy (BT) consisting of first-line palliative systemic therapy and electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC-OX) in patients with unresectable colorectal peritoneal metastases (CPM). This study describes the exploration of patient-reported outcomes (PROs)., Methods: In this phase II trial, 20 patients with isolated CPM were treated with up to three cycles of BT, each cycle consisting of two to three courses of systemic therapy, followed by ePIPAC-OX (92 mg/m 2 ). Patients were asked to complete the EuroQoL EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CR29 questionnaires at baseline, during the first cycle of BT, and one and four weeks after each consecutive BT cycle. PRO scores were calculated and compared between baseline and each subsequent time point using linear-mixed modeling (LMM). PROs were categorized into symptom scales and function scales. Symptom scales ranged from 0 to 100, with 100 representing the maximum symptom load. Function scales ranged from 0 to 100, with 100 representing optimal functioning., Results: Twenty patients underwent a total of 52 cycles of bidirectional therapy. Most PROs (29 of 37, 78%) were not significantly affected during trial treatment. In total, only eight PROs (22%) were significantly affected during trial treatment: Six PROs (index value, global health status, emotional functioning, C30, appetite, and insomnia) showed transient improvement at different time points. Two PROs transiently deteriorated: pain initially improved during the first BT cycle [- 16, p < 0.001] yet worsened temporarily one week after the first two BT cycles (+ 20, p < 0.001; + 17, p = 0.004; respectively). Abdominal pain worsened temporarily one week after the first BT cycle (+ 16, p = 0.004), before improving again four weeks after treatment ended (- 10, p = 0.004). All significant effects on Pros were clinically significant and all deteriorations in PROs were of temporary nature., Discussion: Patients undergoing BT for unresectable CPM had significant, but reversible alterations in several PROs. Most affected PROs concerned improvements and only two PROs showed deteriorations. Both deteriorated PROs returned to baseline after trial treatment and were of a temporary nature. These outcomes help to design future studies on the role of ePIPAC in the palliative setting., (© 2024. The Author(s).)

Background: HER2 targeting in esophageal adenocarcinoma (EAC) has shown potential, but often fails to show durable response. Given the contributions of the tumor immune microenvironment (TIME) to therapeutic responses, we aimed to chart the TIME characteristics of HER2 positive tumors., Methods: 84 biopsies were taken from the TRAP cohort (neoadjuvant chemoradiotherapy (nCRT) according to CROSS with trastuzumab and pertuzumab; n = 40; HER2 + n = 40) and a control cohort with nCRT only (n = 44; HER2- n = 40, HER2 + n = 4) before treatment. Biopsies were analysed using targeted gene expression analysis (Nanostring immune-oncology panel, 750 genes). Differential gene expression was assessed between HER2 positive (n = 44) vs. negative biopsies (n = 40), and non-responders (n = 17) vs. responders (n = 23) to anti-HER2 treatment. Statistical significance was determined as p-value <0.05, adjusted for multiple testing correction., Results: 83 biopsies were eligible for analyses following quality control (TRAP cohort n = 40; control cohort n = 43); there were no significant differences in clinical characteristics between the TRAP vs. control the cohort or HER2 positive vs. HER2 negative biopsies. HER2 expression was found to associate with epithelial markers (EPCAM p < 0.001; E-cadherin p < 0.001). Moreover, HER2 expression was associated with a lower expression of immune cell infiltration, such as NK-cells (p < 0.001) and CD8 T-cells (p < 0.001), but also lower expression of immune exhaustion markers (PDCD1LG2, CTLA4; p < 0.001). In non-responders to anti-HER2 treatment, baseline biopsies showed increased expression of immune exhaustion markers, as well as hypoxia and VEGF signalling., Discussion: HER2 expression was associated with epithelial tumor characteristics. The HER2 positive TIME showed reduced immune cell infiltration but also lower expression of inhibitory signals associated with immune exhaustion, questioning the mechanism behind potential clinical benefit of co-administration of anti-HER2 agents and checkpoint inhibitors. As limited response was associated with increased VEGF signalling, studies could investigate potential synergism of targeting VEGF and HER2., Competing Interests: Declaration of competing interest All authors completed the disclosure of conflict of interest. The following authors declared a potential conflict of interest. M. Slingerland reports an advisory role for Lilly, AstraZeneca and BMS. N. Haj Mohammad reports an advisory role for BMS, Merck, Servier, Elli Lilly, and AstraZeneca, and has received honoraria for lectures from Servier and BMS with fees paid to the institution. G.K. Hospers reports a consultancy/advisory role for Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, Pierre Fabre, and has received research grants from Bristol-Myers Squibb, Seerave. L. Beerepoot reports an advisory role for Servier, Ipsen, Medtalks and Travel Congress Management, and reports a leadership role for Ciebom NVMO and cieOOM NVMO. M.F. Bijlsma has received research funding from Celgene, Frame Therapeutics and Lead Pharma, and has acted as a consultant to Servier and Olympus. H.W.M. van Laarhoven reports an advisory role for AMphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, Daiichy-Sankyo, Dragonfly, MSD, Myeloid, Servier, has received research funding, medication supply and/or research support from Auristone, Incyte, Merck, ORCA and Servier, and has had a speaker role at Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management BV. All fees were paid to the institution., (Copyright © 2024. Published by Elsevier Inc.)

Background: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.1679 T > G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. The goal of this study was to identify additional genetic variants, both inside and outside DPYD, that may contribute to fluoropyrimidine toxicity., Methods: Biospecimens and data from the Alpe-DPD study were used. Exon sequencing was performed to identify risk variants inside DPYD. In silico and in vitro analyses were used to classify DPYD variants. A genome-wide association study (GWAS) with severe fluoropyrimidine-related toxicity was performed to identify variants outside DPYD. Association with severe toxicity was assessed using matched-pair analyses for the exon sequencing and logistic, Cox, and ordinal regression analyses for GWAS., Results: Twenty-four non-synonymous, frameshift, and splice site DPYD variants were detected in ten of 986 patients. Seven of these variants (c.1670C > T, c.1913 T > C, c.1925 T > C, c.506delC, c.731A > C, c.1740 + 1G > T, c.763 - 2A > G) were predicted to be deleterious. The carriers of either of these variants showed a trend towards a 2.14-fold (95% CI, 0.41-11.3, P = 0.388) increased risk of severe toxicity compared to matched controls (N = 30). After GWAS of 942 patients, no individual single nucleotide polymorphisms achieved genome-wide significance (P ≤ 5 × 10 -8 ), however, five variants were suggestive of association (P < 5 × 10 -6 ) with severe toxicity., Conclusions: Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity., (© 2024. The Author(s).)

Background: Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting., Methods: Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics., Results: In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52-0.91, and HR, 0.68; 95% CI, 0.51-0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53-2.83)., Conclusions: There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD)., Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD., Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18 F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended., Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment., Competing Interests: Declaration of Competing Interest Dr. van Laarhoven reports a consultant or advisory role: Amphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, Daiichy-Sankyo, Dragonfly, MSD, Myeloid, Servier; Research funding, medication supply, and/or other research support: Auristone, Incyte, Merck, ORCA, Servier; Speaker role: Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management B.V. Dr. Muijs reports institutional grants from: Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, KWF, all outside the submitted work. Dr. van Hillegersberg has a consulting and advisory role at Intuitive Surgical, Medtronic, Olympus and J&J Ethicon. Dr. de Manzoni reports personal fees from Lilly, outside the submitted work. Dr. Gani reports travel grants from Elekta and departmental research cooperation, outside the submitted work. Dr. Smyth is supported by the NIHR Biomedical Research Centre at Oxford (the views expressed in this Article are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health) and resports personal fees/grants from: Astra Zeneca, Beigene, BMS, Amal Therapeutics, Amgen, Daiichi Sankyo, Merck, Servier, Novartis, Pfizer, Roche, and Zymeworks, all outside the submitted work. Dr. Haj Mohammad reports consulation fees from: Merck, BMS, Eli Lilly, Astra Zeneca, and research funding from Servier, all outside the submitted work. Dr. Adenis reports grants and personal fees from Bayer, personal fees and non-financial support from MSD, personal fees from: BMS, Novartis, Pierre-Fabre, non-financial support from Servier, grants from Sanofi, all outside the submitted work. Dr. Lordick reports grants from: BMS and Gilead, personal fees from: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Incyte, Merck, MSD, Roche, Servier, all outside the submitted work. Dr. Slingerland reports an advisory role at BMS and Lilly. Dr. van Berge Henegouwen received researcher-initiated grant from Stryker and is consultant for Alesi Surgical, Johnson and Johnson, Medtronic, BBraun and Viatris. Dr Nilsson reports advisory roles for BMS and Medtronic. Dr. Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc; and also educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). Dr. Tabernero declares institutional financial interest in form of financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK. Dr. Nieuwenhuijzen reports advisory/speaker roles from Medtronic and Lilly. All remaining authors have declared no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease)., Methods: All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard., Results: A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits., Conclusion: The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: While shared decision making (SDM) is advocated for ethical reasons and beneficial outcomes, SDM might also negatively affect patients with incurable cancer. The current study explored whether SDM, and an oncologist training in SDM, are associated with adverse outcomes (i.e., patient anxiety, tension, helplessness/hopelessness, decisional uncertainty, and reduced fighting spirit)., Design: A secondary analysis of a randomized clinical trial investigating the effects of SDM interventions in the context of advanced cancer. The relations between observed SDM (OPTION12), specific SDM elements (4SDM), oncologist SDM training, and adverse outcomes were analyzed. We modeled adverse outcomes as a multivariate phenomenon, followed by univariate regressions if significant., Results: In total, 194 patients consulted by 31 oncologists were included. In a multivariate analysis, observed SDM and adverse outcomes were significantly related. More specifically, more observed SDM in the consultation was related to patients reporting more tension ( P  = 0.002) and more decisional uncertainty ( P  = 0.004) at 1 wk after the consultation. The SDM element "informing about the options" was especially found to be related to adverse outcomes, specifically to more helplessness/hopelessness ( P  = 0.002) and more tension ( P  = 0.016) at 1 wk after the consultation. Whether the patient consulted an oncologist who had received SDM training or not was not significantly related to adverse outcomes. No relations with long-term adverse outcomes were found., Conclusions: It is important for oncologists to realize that for some patients, SDM may temporarily be associated with negative emotions. Further research is needed to untangle which, when, and how adverse outcomes might occur and whether and how burden may be minimized for patients., Highlights: Observed shared decision making was related to more tension and uncertainty postconsultation in advanced cancer patientsHowever, training oncologists in SDM did not affect adverse outcomes.Further research is needed to untangle which, when, and how adverse outcomes might occur and how burden may be minimized., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LFvdW received research funding from the Dutch Cancer Society. DWB–vdH received research funding from ZonMw. HWMvL received research funding and/or medication supply from Bayer, BMS, Celgene, Janssen, Incyte, Eli Lilly, MSD, Nordic Pharma, Philips, Roche, and Servier; has a consultant or advisory role at Amphera, AstraZeneca, Beigene, BMS, Daiichy-Sankyo, Dragonfly, Eli Lilly, MSD, Nordic Pharma, and Servier; and has a speaker role at Astellas, Benecke, Daiichy-Sankyo, JAAP, Medtalks, Novartis, and Travel Congress Management BV. FYFdV received research funding from Foundation STOPbraintumors.org, BMS, Novartis, and EORTC Sponsor drive clinical research; participates on the advisory board for Bristol Myers Squibb; and servers on the other following boards and committees: faculty member, ESMO CNS tumors, quality of care commission of the Dutch Society of Medical Oncology, and quality assurance commission of EORTC. IH received research funding from the Dutch Cancer Society. The other authors declare that they have no competing interests. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided entirely by grants from the Dutch Cancer Society (DCS-UVA 2013-5949, UVA 2014-7000) and ZonMw (844001514). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: Dutch Cancer Society, LFvdW; ZonMw, DWB–vdH.

Purpose: DPYD -guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis., Methods: Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G>A and c.2846A>T) or 50% ( DPYD *2A and c.1679T>G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression., Results: In total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G>A, 25 DPYD *2A, 13 c.2846A>T, and-when pooled-93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) were not negatively affected by DPYD -guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) was found in c.1236G>A variant carriers, whereas no differences were found for DPYD *2A and c.2846A>T carriers., Conclusion: In this exploratory analysis, DPYD -guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers receiving a reduced starting dose.

Objective: Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory., Methods: A prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis., Results: 409 relatives completed ≥1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient' sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning., Conclusions: Relatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning., (© 2023 John Wiley & Sons Ltd.)

Background: The importance of sex and gender as modifiers of health and disease is increasingly recognized. The aim of this study was to analyze gender differences in incidence, tumor characteristics, treatment and relative survival (RS) in colorectal cancer (CRC)., Methods: Observational population-based study including patients diagnosed with CRC in the Netherlands between 2010 and 2020. Stratified by localization (colon/rectum) and age (18-55/56-70/≥71years), gender differences in incidence, tumor characteristics, treatment and RS were analyzed. Multivariable regression was used to analyze the influence of gender on treatment and RS., Results: The age-standardized incidence per 100,000 person-years of colon and rectal cancer is higher among men than women (colon: 41.2 versus 32.4, rectum: 22.8 versus 12.6). Besides differences in patient- and tumor characteristics, differences in treatment allocation and RS were observed. Most strikingly, women aged ≥ 71 years with stage IV colon cancer are less often treated with systemic therapy (31.3 % versus 28.4 %, adjusted odds ratio (OR) 0.63, 95 % CI 0.48-0.83) and more often receive best supportive care only (47.6 % versus 40.0 %, adjusted OR 1.58, 95 % CI 1.19-2.11)., Conclusion: Statistically significant and clinically relevant gender differences in incidence, patient- and tumor characteristics and treatment allocation are observed in patients with CRC. Reasons for differences in treatment allocation deserve further investigation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AW is principal investigator of the EORC-Trial 1203 “INNOVATION”, which is supported by an educational grant from Roche to EORTC, neither AW nor her institution receives any financial compensation for this work. AW also fulfils advisory and consulting roles paid to the institution and reimbursed in part for Merck, Lily, Pierre Fabre Pharma, Hauffmann-La Roche, Sanofi, Daichi Sankyo, Dragonfly Therapeutics, Servier, Bristol-Myers Squibb, Aklepios and Astellas Pharma, all outside the submitted work. RV has received a research grant from BMS and has served as a consultant for Daiichi Sankyo. The other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR., Methods: Patients who underwent neoadjuvant treatment and surgery for locally recurrent rectal cancer with curative intent between January 2004 and June 2020 at a tertiary referral hospital were analysed. Primary outcomes included overall survival, disease-free survival, metastasis-free survival, and local re-recurrence-free survival, stratified according to whether the patient had a pCR., Results: Of a total of 345 patients, 51 (14.8 per cent) had a pCR. Median follow-up was 36 (i.q.r. 16-60) months. The 3-year overall survival rate was 77 per cent for patients with a pCR and 51.1 per cent for those without (P < 0.001). The 3-year disease-free survival rate was 56 per cent for patients with a pCR and 26.1 per cent for those without (P < 0.001). The 3-year local re-recurrence-free survival rate was 82 and 44 per cent respectively (P < 0.001). Surgical procedures (for example soft tissue, sacrum, and urogenital organ resections) and postoperative complications were comparable between patients with and without a pCR., Conclusion: This study showed that patients with a pCR have superior oncological outcomes to those without a pCR. It may therefore be safe to consider a watch-and-wait approach in highly selected patients, potentially improving quality of life by omitting extensive surgical procedures without compromising oncological outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer., Methods: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%)., Results: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement)., Conclusion: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. van Laarhoven reports grants or advisory/speaker role from: Astellas, BMS, Dragonfly, Lilly, Merck, Novartis, Nordic Pharma, Servier; research funding or medical supply from: Bayer, BMS, Celgene, Janssen, Incyte, Lilly, Merck, Nordic Pharma, Philips, Roche, Servier; and has received unrestricted research funding (non-commercial) from: Dutch Cancer Society, NWO/ZonMw, European Research Council, MaagLeverDarm Stichting. Dr. Muijs reports institutional grants from: Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, KWF, all outside the submitted work. Dr. van Hillegersberg has a consulting and advisory role at Intuitive Surgical. Dr. de Manzoni reports personal fees from Lilly, outside the submitted work. Dr. Gani reports travel grants from Elekta and departmental research cooperation, outside the submitted work. Dr. Smyth reports personal fees/grants from: Astra Zeneca, Beigene, BMS, Amal Therapeutics, Amgen, Daiichi Sankyo, Merck, Servier, Novartis, Pfizer, Roche, and Zymeworks, all outside the submitted work. Dr. Haj Mohammad reports consulation fees from: Merck, BMS, Eli Lilly, Astra Zeneca, and research funding from Servier, all outside the submitted work. Dr. Adenis reports grants and personal fees from Bayer, personal fees and non-fianciel support from MSD, personal fees from: BMS, Novartis, Pierre-Fabre, non-financial support from Servier, grants from Sanofi, all outside the submitted work. Dr. Lordick reports grants from: BMS and Gilead, personal fees from: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Incyte, Merck, MSD, Roche, Servier, all outside the submitted work. Dr. Slingerland reports an advisory role at BMS and Lilly. Dr. van Berge Henegouwen received researcher-initiated grant from Stryker and is consultant for Alesi Surgical, Johnson and Johnson, Medtronic, Braun and Mylan. Dr Nilsson reports advisory roles for BMS and Medtronic. All remaining authors have declared no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess perception of prognosis in patients with advanced cancer, its association with patient's characteristics and health-related quality of life (HRQoL)., Methods: In a multicentre observational cohort study (eQuiPe), conducted on patients with advanced cancer, perceived prognosis, coping strategies, and HRQoL were assessed. Clinical data were obtained from the Netherlands Cancer Registry. Patients with vs. without a perception of prognosis, patients who perceived their prognosis as limited (< 1 year) vs. longer (> 1 year), and patients who did not want to know their prognosis vs. those who did not know for other reasons were compared., Results: Of 1000 patients with advanced cancer, 29% perceived their prognosis as > 1 year, 13% < 1 year, and 4% non-life threatening. Thirty-six percent did not know their prognosis and another 15% did not want to know. Patients without a perception were older, lower educated, coped differently (less accepting, planning, active; more denial), and received treatment more often (p < 0.05). Global QoL was lower in patients with vs. without a perceived prognosis (66 (SD21) vs. 69 (SD19), p = 0.01), specifically in patients who perceived a limited rather than a longer prognosis (57 (SD22) vs. 70 (SD19), p < 0.01). Global QoL of patients who did not want to know their prognosis was comparable to patients who did not know for other reasons (71 (SD19) vs. 69 (SD19), p = 0.22)., Conclusion: More than half of the patients with advanced cancer have no perception of their prognosis. Patients with a perceived prognosis have lower HRQoL, but only in patients who perceived their prognosis as limited (< 1 year) and were probably closer to the end of life, which more likely determines their poorer HRQoL, rather than prognostic perception. Ignorance of prognosis is not associated with lower HRQoL, however, should not hamper appropriate palliative care., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease., (© 2023. The Author(s).)

Background: In recent years, clinical trials have shown improved survival of patients with metastatic esophageal or gastric cancer. The number of patients participating in clinical trials is limited, and survival improvements observed from clinical trials are unrepresentative for the full population. The aim of our study was to assess trends in survival for the best-case, typical, and worst-case scenarios in patients with metastatic esophageal or gastric cancer., Methods: We selected patients with metastatic esophageal or gastric cancer diagnosed between 2006 and 2020 from the nationwide Netherlands Cancer Registry. Survival was calculated for different percentiles of the survival curve for each incidence year (eg, the 10th percentile [p10] represents the top 10% of patients with the best survival): p10 (best-case), p25 (upper-typical), p50 (median), p75 (lower-typical), and p90 (worst-case). Weighted linear regression analyses were performed to test whether changes in survival were significant., Results: The overall median survival between 2006 and 2020 remained unchanged for patients with esophageal cancer (n=10,448; from 5.2 to 5.2 months, respectively; P=.06) and improved for patients with gastric cancer (n=10,512; from 3.5 to 4.3 months, respectively; P=.001). For patients with esophageal cancer, survival for the best-case scenario (p10; best 10% of patients) significantly improved from 17.2 to 21.0 months (P=.006). For patients with gastric cancer, survival significantly improved for the best-case scenario (p10) from 15.9 to 23.5 months (P<.001) and the upper-typical scenario (p25) scenario improved from 7.9 to 9.9 months (P<.001)., Conclusions: Despite significant survival improvements in clinical trials, survival improvements were not observed for the majority of patients treated in daily clinical practice. An increase in survival was only observed for patients with the best prognosis.

Purpose: When deliberating palliative cancer treatment, insight into patients' attitudes toward striving for quality of life (QL) and length of life (LL) may facilitate goal-concordant care. We investigated the (1) attitudes of patients with advanced cancer toward striving for QL and/or LL and whether these change over time, and (2) characteristics associated with these attitudes (over time)., Methods: We performed a secondary analysis of a randomized controlled trial on improving shared decision making (SDM), without differentiation between intervention arms. Patients (n = 173) with advanced cancer, a median life expectancy of < 12 months without anticancer treatment, and a median survival benefit of < 6 months from systemic therapy were included in seven Dutch hospitals. We used audio-recorded consultations and surveys at baseline (T0), shortly after the consultation (T2), at 3 and 6 months (T3 and T4). Primary outcomes were patients' attitudes toward striving for QL and LL (Quality Quantity Questionnaire; T2, T3, and T4)., Results: Overall, patients' attitudes toward striving for QL became less positive over 6 months ( P < .01); attitudes toward striving for LL did not change on group level. Studying individual patients, 76% showed changes in their attitudes toward striving for QL and/or LL at some point during the study, which occurred in various directions. More helplessness/hopelessness ( P < .001), less fighting spirit ( P < .05), less state anxiety ( P < .001), and more observed SDM ( P < .05) related to more positive attitudes toward striving for QL. Lower education, less helplessness/hopelessness, more fighting spirit, and more state anxiety ( P < .001) related to more positive attitudes toward striving for LL., Conclusion: Oncologists may explore patients' attitudes toward striving for QL and LL repeatedly and address patients' coping style and emotions during SDM to facilitate goal-concordant care throughout the last phase of life., Competing Interests: Hanneke W.M. Van LaarhovenConsulting or Advisory Role: Bristol Myers Squibb, Servier, Dragonfly Therapeutics, MerckResearch Funding: Bristol Myers Squibb (Inst), Bayer Schering Pharma (Inst), Celgene (Inst), Janssen-Cilag (Inst), Lilly (Inst), Nordic Group (Inst), Philips Healthcare (Inst), Roche (Inst), Merck Sharp & Dohme (Inst), Servier (Inst), Merck KGaA (Inst), Incyte (Inst)Travel, Accommodations, Expenses: AstraZeneca Petronella B. OttevangerConsulting or Advisory Role: AstraZeneca (Inst), GlaxoSmithKline (Inst), Nykode (Inst) Serge E. DohmenOther Relationship: Roche Filip Y.F.L. de VosResearch Funding: Novartis (Inst), Bristol Myers Squibb (Inst), Agios (Inst)No other potential conflicts of interest were reported.

Objective: The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors., Method: A prospective, longitudinal, multicenter, observational study on quality of care and quality of life of patients with advanced cancer and their relatives was conducted (eQuiPe). The association between EF of relatives during bereavement and the following factors was investigated: gender, type of relationship, educational level, pre-bereavement emotional and social functioning and global quality of life, social support pre- and during bereavement, anticipatory complicated grief, support of healthcare professionals during bereavement, age of patient and bereaved relative and duration of survival after primary cancer diagnosis., Results: 150 bereaved relatives completed the bereavement questionnaire. In 41% of the bereaved relatives EF was ≤71, indicating clinically relevant low EF. Multivariable logistic regression showed that females experienced more often emotional problems (OR = 2.82). Emotional functioning pre-bereavement (OR = 0.96) and social support during bereavement (OR = 0.97) were associated with low EF during bereavement., Conclusions: Almost half of the bereaved relatives of patients with advanced cancer experienced low EF and this was associated with low EF pre-bereavement and low social support during bereavement. Support for relatives should be initiated before the patient's death. Future research is needed to investigate the impact of such support on relatives' wellbeing during bereavement., (© 2022 John Wiley & Sons Ltd.)

Background: This study aimed to investigate the agreement between magnetic resonance tumour regression grade (mrTRG) and pathological regression grade (pTRG) in patients with locally recurrent rectal cancer (LRRC). Also, the reproducibility of mrTRG was investigated., Methods: All patients with LRRC who underwent a resection between 2010 and 2018 after treatment with induction chemotherapy and neoadjuvant chemo(re)irradiation in whom a restaging MRI was available were retrospectively selected. All MRI scans were reassessed by two independent radiologists using the mrTRG, and the pTRG was reassessed by an independent pathologist. The interobserver agreement between the radiologists as well as between the radiologists and the pathologist was assessed with the weighted kappa test. A subanalysis was performed to evaluate the influence of the interval between imaging and surgery., Results: Out of 313 patients with LRRC treated during the study interval, 124 patients were selected. Interobserver agreement between the radiologists was fair (k = 0.28) using a two-tier grading system (mrTRG 1-2 versus mrTRG 3-5). For the lead radiologist, agreement with pTRG was moderate (k = 0.52; 95 per cent c.i. 0.36 to 0.68) when comparing good (mrTRG 1-2 and Mandard 1-2) and intermediate/poor responders (mrTRG 3-5 and Mandard 3-5), and the agreement was fair between the other abdominal radiologist and pTRG (k = 0.39; 95 per cent c.i. 0.22 to 0.56). A shorter interval (less than 7 weeks) between MRI and surgery resulted in an improved agreement (k = 0.69), compared with an interval more than 7 weeks (k = 0.340). For the lead radiologist, the positive predictive value for predicting good responders was 95 per cent (95 per cent c.i. 71 per cent to 99 per cent), whereas this was 56 per cent (95 per cent c.i. 44 per cent to 66 per cent) for the other radiologist., Conclusion: This study showed that, in LRRC, the reproducibility of mrTRG among radiologists is limited and the agreement of mrTRG with pTRG is low. However, a shorter interval between MRI and surgery seems to improve this agreement and, if assessed by a dedicated radiologist, mrTRG could predict good responders., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Aim: This study aims to assess the quality of life and quality of care as experienced by patients with advanced cancer and their relatives while taking their interdependency into account., Methods: A prospective multicentre observational study (eQuiPe study) was conducted. Quality of life scores (EORTC QLQ-C30) was compared to a matched normative population and logistic regression analyses were conducted to assess the relation between high emotional functioning (EF, measured with the EORTC QLQ-C30) and experienced quality of care (IN-PATSAT32, CQ-index PC)., Results: In total, 1103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower EF than the normative population (78 versus 87, p < .001). Compared to patients, relatives reported clinically relevantly lower EF (69 versus 78, p < .001). Being more satisfied with care in general (p < .05) and clarity about the key health-care provider (p < .05) was positively associated with high EF in patients. For relatives, experienced continuity of care (p < .01) and information for the patient (p < .05) were positively associated with high EF. The EF of patients (p < .001) and relatives (p < .001) were positively associated with each other and continuity of care as perceived by relatives was positively associated with high EF in patients (p < .01)., Conclusions: Patients with advanced cancer reported low levels of EF but their relatives reported even lower levels of EF. Experienced integrated organisation and satisfaction with care were positively related to EF. The interdependent relation between patients' and relatives' EF and their care experiences suggests that a family-centred approach can optimise palliative cancer care., Trial Registration: The eQuiPe study is registered as NTR6584 in the Netherlands Trial Register., Competing Interests: Conflict of interest statement The authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Biological sex, gender and age have an impact on the incidence and outcome in patients with metastatic pancreatic cancer. The aim of this study is to investigate whether biological sex, gender and age are associated with treatment allocation and overall survival (OS) of patients with metastatic pancreatic cancer in a nationwide cohort., Methods: Patients with synchronous metastatic pancreatic cancer diagnosed between 2015 and 2019 were selected from the Netherlands Cancer Registry (NCR). The association between biological sex and the probability of receiving systemic treatment were examined with multivariable logistic regression analyses. Kaplan Meier analyses with log-rank test were used to describe OS., Results: A total of 7470 patients with metastatic pancreatic cancer were included in this study. Fourty-eight percent of patients were women. Women received less often systemic treatment (26% vs. 28%, P=0.03), as compared to men. Multivariable logistic regression analyses with adjustment for confounders showed that women ≤55 years of age, received more often systemic treatment (OR 1.82, 95% CI 1.24-2.68) compared to men of the same age group. In contrast, women at >55 years of age had a comparable probability to receive systemic treatment compared to men of the same age groups. After adjustment for confounders, women had longer OS compared to men (HR 0.89, 95% CI 0.84-0.93)., Conclusion: This study found that women in general had a lower probability of receiving systemic treatment compared to men, but this can mainly be explained by age differences. Women had better OS compared to men after adjustment for confounders., Competing Interests: AW has received non-financial support from Roche and has received institutional support from Abbvie, Daichi Sankyo, IPSEN, Lily, Merck, MSD, Pierre Fabre, Servier. JV-G has received non-financial support from Servier, and has received institutional research funding from Servier. All outside the submitted work. JWW has served as a consultant for Shire, Servier and Celgene and reports grands from Servier, Halozyne, Novartis, Celgene, Astra Zeneca, Pfizer, Roche, Amgen and Merck. HWMvL has served as a consultant for BMS, Celgene, Lilly, Merck, Nordic, and Servier and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips, Roche and Servier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pijnappel, Schuurman, Wagner, de Vos-Geelen, Geest, de Groot, Koerkamp, de Hingh, Homs, Creemers, Cirkel, van Santvoort, Busch, Besselink, van Eijck, Wilmink and van Laarhoven.)

Aim: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan., Patients and Methods: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1∗28 and UGT1A1∗93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction. The primary endpoint was incidence of febrile neutropenia in the first two cycles of treatment. Toxicity in UGT1A1 PMs was compared to a historical cohort of UGT1A1 PMs treated with full dose therapy, and to UGT1A1 non-PMs treated with full dose therapy in the current study. Secondary endpoints were pharmacokinetics, feasibility, and costs., Results: Of the 350 evaluable patients, 31 (8.9%) patients were UGT1A1 PM and received a median 30% dose reduction. The incidence of febrile neutropenia in this group was 6.5% compared to 24% in historical UGT1A1 PMs (P = 0.04) and was comparable to the incidence in UGT1A1 non-PMs treated with full dose therapy. Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: +32%). Cost analysis showed that genotype-guided dosing was cost-saving with a cost reduction of €183 per patient., Conclusion: UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving. Therefore, UGT1A1 genotype-guided dosing of irinotecan should be considered standard of care in order to improve individual patient safety., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HLMcL declares the following potential conflicts of interest: Board of Directors: Vyant Bio; Co-Founder: Clariifi LLC; Advisor: EviCore, Total Dx Connect, and Viecure. All remaining authors declare no potential conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes., Methods: All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post-treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1-2), partial (TRG 3) or poor (TRG 4-5). The PET/CT and TRG categories were compared, and possible confounders were analysed., Results: A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post-treatment PET/CT and surgery negatively influenced the predictive value., Conclusion: Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Background: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort., Methods: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups., Results: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553)., Conclusion: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM., (© 2021. The Author(s).)

Background: Studies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals., Methods: Between 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM., Results: After participation in the uMDTM more patients were discussed in an MDTM (80%-89%,p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%-82%,p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%-61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%-34%,p = 0.034) and the use of best supportive care decreased (21%-15%,p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%-30%,p = 0.025)., Conclusions: Implementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival., Competing Interests: Declaration of competing interest None declared. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer., Methods: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS., Results: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning., Conclusion: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models., (© 2021. The Author(s).)

Background: Population-based predictive factors for the effectiveness of second-line palliative systemic therapy in gastro-oesophageal cancer are not available. This study investigates the predictive value of effectiveness of first-line treatment for second-line treatment outcomes in gastro-oesophageal cancer in a real-world setting., Methods: Patients with metastatic gastro-oesophageal cancer diagnosed in 2010-2017 who were treated with second-line therapy after disease progression on first-line therapy were identified from the Netherlands Cancer Registry. Patients were divided into four groups as per duration of time to treatment failure (TTF) of the first line (0-3, 3-6, 6-9 and >9 months), and the association with overall survival (OS) and second-line TTF was assessed using Kaplan-Meier curves and two-sided multivariable regression models., Results: Median OS since the start of the second line of patients (n = 611) with first-line TTF of 0-3, 3-6, 6-9 and >9 months was 4.0, 4.1, 5.5 and 7.1 months, respectively (P < 0.001). Median second-line TTF of patients with first-line TTF of 0-3, 3-6, 6-9 and >9 months was 2.8, 2.4, 3.0 and 4.5 months, respectively (P < 0.001). Patients with first-line TTF of >9 months showed a longer OS than patients with first-line TTF of 0-3 months (adjusted hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.46-2.47), 3-6 months (adjusted HR 1.88; 95% CI 1.47-2.39) and 6-9 months (adjusted HR 1.31; 95% CI 1.04-1.65). Results for second-line TTF were similar., Conclusions: This study shows a positive correlation between effectiveness of first-line therapy and outcomes of second-line therapy in gastro-oesophageal cancer. Physicians should take duration of the first line into account when considering second-line palliative systemic therapy., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HWMvL reports grants from Roche, has served as a consultant for BMS, Celgene, Lilly, and Nordic and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips, and Roche. NHM has served as a consultant for BMS, Lilly and MSD. RHAV reports grants from Roche and BMS. The other authors have no interests to declare., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)