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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/m2). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. Methods: Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. Results: In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio [OR] 1.10, 95% CI 0.48–2.54), nor overweight (OR 0.96, 95% CI 0.71–1.29), or obesity (OR 0.84, 95% CI 0.56–1.26) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Univariable and multivariable Cox regression modelling did not identify an effect of weight on the development of metachronous CPM. Neither underweight (HR 0.162, 95% CI 0.02–1.16), nor overweight (HR 1.07, 95% CI 0.82–1.39), or obesity (HR 1.02, 95% CI 0.73–1.16) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Conclusion: CRC patients who are overweight or obese are not more at risk for the presence of synchronous CPM nor development of metachronous CPM than their normal-weight counterparts. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM. [ABSTRACT FROM AUTHOR]

– This population-based study aimed to investigate incidence, risk factors, treatment, and survival of synchronous peritoneal metastases (PM) of hepatobiliary origin. – All Dutch patients diagnosed with hepatobiliary cancer between 2009 and 2018 were selected. Factors associated with PM were identified with logistic regression analyses. Treatments for patients with PM were categorized into local therapy, systemic therapy, and best supportive care (BSC). Overall survival (OS) was investigated using log-rank test. – In total, 12 649 patients were diagnosed with hepatobiliary cancer of whom 8% (n = 1066) were diagnosed with synchronous PM (12% [n = 882/6519] in biliary tract cancer [BTC] vs. 4% [n = 184/5248] in hepatocellular carcinoma [HCC]). Factors that were positively associated with PM were the female sex (OR 1.18, 95% CI 1.03–1.35), BTC (OR 2.93, 95% CI 2.46–3.50), diagnosis in more recent years (2013–2015: OR 1.42, 95% CI 1.20–1.68; 2016–2018: OR 1.48, 95% CI 1.26–1.75), T3/T4 stage (OR 1.84, 95% CI 1.55–2.18), N1/N2 stage (OR 1.31, 95% CI 1.12–1.53) and other synchronous systemic metastases (OR 1.85, 95% CI 1.62–2.12). Of all PM patients, 723 (68%) received BSC only. Median OS was 2.7 months (IQR 0.9–8.2) in PM patients. – Synchronous PM were found in 8% of all hepatobiliary cancer patients and occurred more often in BTC than in HCC. Most patients with PM received BSC only. Given the high incidence and dismal prognosis of PM patients, extended research in hepatobiliary PM is needed to achieve better outcome in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The genetic characteristics and mismatch repair (MMR) status of the primary tumor and corresponding metastases in colorectal cancer (CRC) are generally considered to be highly concordant. This implies that either the primary or metastatic tumor can be used for testing gene mutation and MMR status. However, whether this is also true for CRC and their ovarian metastases is currently unknown. Ovarian metastases generally show a poorer response to systemic therapy compared to other metastatic sites. Differences in biomarker status between primary CRC and ovarian metastases could possibly explain this difference in therapy response. Methods: The study cohort was selected from CRC patients treated in two Dutch hospitals. Eligible patients with CRC and ovarian metastasis who were surgically treated between 2011 and 2018 were included. CRC and corresponding ovarian metastatic tissues were paired. Gene mutation status was established using next-generation sequencing, while the MMR status was established using either immunohistochemistry or microsatellite instability analysis. Results: Matched samples of CRC and ovarian metastasis from 26 patients were available for analysis. A biomarker concordance of 100% was detected. Conclusion: Complete biomarker concordance was found between MMR proficient CRC and their matching ovarian metastasis. Biomarker testing of MMR proficient CRC tissue appears to be sufficient, and additional testing of metastatic ovarian tissue is not necessary. Differences in therapy response between ovarian metastases and other metastases from CRC are thus unlikely to be caused by differences in the genetic status. [ABSTRACT FROM AUTHOR]

This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started. Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009–2012), startup (2013–2016), and matured-network (2017–2020) periods. Nationwide, 13.981patients were diagnosed between 2009 and 2020, of whom 1.624 were diagnosed in the network. Of patients diagnosed in the network's expert hospitals, 36.7% received ablation and/or resection versus 28.3% in nonexpert hospitals (p < 0.01). The odds ratio (OR) of receiving ablation and/or resection for patients diagnosed in expert versus nonexpert hospitals increased from 1.38 (p = 0.581, pre-network), to 1.66 (p = 0.108, startup), to 2.48 (p = 0.090, matured-network). Nationwide, the same trend occurred (respectively OR 1.41, p = 0.011; OR 2.23, p < 0.001; OR 3.20, p < 0.001). Patients diagnosed in expert hospitals were more likely to receive ablation and/or resection for SCLM than patients diagnosed in non-expert hospitals. This difference increased over time despite the startup of a multi-hospital network. Establishing a multi-hospital network did not have an effect on reducing the existing unequal odds of receiving specialized treatment. Specialized oncology treatments are increasingly provided through multi-hospital networks. However, scant empirical evidence on the effectiveness of these networks exists. This study analyzes whether a regional multi-hospital network was able to improve equal access to specialized oncology treatments. [ABSTRACT FROM AUTHOR]

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra‐ovarian metastases only. Three‐year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score‐matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3‐year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria. [ABSTRACT FROM AUTHOR]

Simple Summary: Although relatively rare, locally advanced or recurrent rectal cancer (LARC and LRRC) can metastasize. Patients whose advanced rectal cancer has metastasized to the peritoneum face a very poor prognosis. In selected patients, the prognosis might be improved by undergoing very intense treatment. This multimodality treatment, consisting of intraoperative radiotherapy (IORT), cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), is aimed at attaining a microscopic radical resection of the rectal tumor and its peritoneal metastases (PM), as this is the only option for long-term survival. The present study reports on 30 consecutive patients who have undergone this multimodality treatment. The results in terms of complications and survival are comparable to the results described in the literature on IORT and CRS-HIPEC as separate treatment entities. Thus, this multimodality treatment can be considered a treatment option for highly selected patients, provided that it is performed in a tertiary referral center. Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1–38.7), and median OS was 31.0 months (Interquartile Range 15.9–144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are at risk of significant treatment burden. Multiple studies have reported on patient-reported outcome (PRO) measurements of these patients. However, outcomes are difficult to interpret as no comparison has been made between CRS-HIPEC and conventional surgery. The present study compares several PROs at three different timepoints between patients with colorectal peritoneal metastases treated with CRS-HIPEC and colorectal cancer (CRC) patients treated with conventional surgery. PROs were obtained from two Dutch prospective trials. Despite a more extensive procedure with greater risk of morbidity, CRS-HIPEC in patients with colorectal peritoneal metastases did not have a greater negative impact on PROs than conventional surgery in patients with CRC. Furthermore, systemic therapy did not affect these PROs. These findings may facilitate future patient counseling and shared decision making in clinical practice. Purpose—To compare patient-reported outcomes (PROs) of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for colorectal peritoneal metastases to PROs of colorectal cancer (CRC) patients undergoing conventional surgery. Methods—Data were extracted from the CAIRO6 trial (CRS-HIPEC group) and the PROCORE study (conventional surgery group). Nine predefined PROs (derived from the EORTC QLQ-C30 questionnaire) were compared at baseline, in the early postoperative period and one year postoperatively, with correction for treatment with systemic therapy using linear mixed modeling. Results—In total, 331 patients were included: 71 in the CRS-HIPEC group and 260 in the conventional surgery group. All predefined PROs (fatigue, diarrhea, C30 summary score, Global Health Status, physical, role, emotional, cognitive, and social functioning) did not differ significantly between the groups at all three timepoints, and differential effects over time for all PROs did not differ significantly between the groups. Significant worsening of fatigue, C30 summary score, physical and role functioning (both groups), and cognitive and social functioning (conventional surgery group only) was present in the early postoperative period. All scores returned to baseline at one year postoperatively, except for physical and cognitive functioning in the conventional surgery group. Emotional functioning improved postoperatively in both groups compared to baseline. Conclusion—Despite a more extensive procedure with greater risk of morbidity, CRS-HIPEC in patients with colorectal peritoneal metastases did not have a greater negative impact on PROs than conventional surgery in patients with CRC. Further, systemic therapy did not affect these PROs. These findings may facilitate future patient counseling and shared decision making in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis. Currently, research has been ongoing to develop new treatment options for CRC patients with PM. DNA/RNA alterations identification in the primary tumor might help identify patients who are at high risk for developing PM postoperatively. These patients could benefit from preventive or early treatment. The aim of this systematic review is to create an overview of studies which analyzed genomic DNA and RNA expression alteration correlated to PM with the goal of identifying potentially predictive biomarkers. We included 32 studies investigating primary colorectal tumors of 18,906 patients. Only BRAF mutations were reported as significantly associated with PM in 10 of 17 studies. As no specific biomarkers in the primary tumors of CRC patients could have been identified, further research with comprehensive genomic profiling is still desirable. Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required. [ABSTRACT FROM AUTHOR]

Background: CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment.Methods: In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m2). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen's D ≥ 0.50) of statistically significant differences.Results: Twenty patients underwent 59 procedures (median 3 [range 1-6]). Several PROs solely worsened 1 week after the first procedure (index value - 0.10, p < 0.001; physical functioning - 20, p < 0.001; role functioning - 27, p < 0.001; social functioning - 18, p < 0.001; C30 summary score - 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure.Conclusions: Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure.Trial Registration: Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: In female colorectal cancer patients, a mean proportion of synchronous and/or metachronous ovarian metastases of 3.4% was described. Previous literature showed that young or premenopausal women (≤ 55 years of age) may be more frequently affected. Once ovarian metastases are diagnosed, the prognosis of the patient is generally dismal, with 5-year survival varying from 12 to 27%. The present study is aimed at determining the proportion of young or premenopausal women diagnosed with colorectal cancer who presented with or developed ovarian metastases by reviewing the current literature on this topic. Methods: This review was performed by querying MEDLINE and EMBASE databases using a combination of terms: "colorectal neoplasms, colorectal cancer, ovarian neoplasms, Krukenberg tumor, young adult, young age, premenopause." Studies that indicated ovarian metastases, either synchronous or metachronous (or a combination of the two), in young women were retrieved and analyzed. Results: The review identified 14 studies encompassing 3379 young or premenopausal female colorectal cancer patients. In this selected group of patients, a mean proportion of ovarian metastases of 4.6% [95% CI: 4.0;5.4] was found. Conclusions: This review showed that approximately one in twenty young female colorectal cancer patients will present with or develop ovarian metastases. Since outcome of this specific oncological pathology is often dismal, this finding is clinically relevant. It demonstrates the need to develop strategies to lower the incidence of ovarian metastases with adequate treatment and counseling of these patients. [ABSTRACT FROM AUTHOR]

Introduction: The peritoneum is a predilection site for gastric cancer metastases. Current standard treatment for gastric cancer patients with synchronous peritoneal metastases is palliative systemic therapy. However, its efficacy is largely unknown. The aim of this study was to investigate the incidence, treatment and survival patterns of gastric cancer patients with synchronous peritoneal metastases in the Netherlands. Methods: All newly diagnosed gastric adenocarcinoma patients with synchronous peritoneal metastases between 1999 and 2017 were selected from the Netherlands Cancer Registry (NCR). Incidence, treatment and survival patterns were analyzed. Results: In total, 3,773 patients were identified from the NCR. The incidence of synchronous peritoneal metastases in gastric cancer patients increased from 18% in 2008 to 27% in 2017. The use of systemic therapy increased from 15% in 1999–2002 to 43% in 2013–2017 (p < 0.001). The median survival of the entire cohort did not significantly increase over time. Median survival of patients treated with systemic therapy increased from 7.4 months in 1999–2002 to 9.4 months in 2013–2017 (p = 0.005). In contrast, median survival of patients not treated with systemic therapy decreased from 3.3 months in 1999–2002 to 2.1 months in 2013–2017 (p < 0.001). Some clinical and pathological data such as the extent of the peritoneal metastases were not available. Conclusion: Synchronous peritoneal metastases are increasingly diagnosed in gastric cancer patients. In recent years, more patients were treated with systemic treatment and survival of these patients increased. However, as survival of the entire group did not improve over time, the effect of systemic therapy remains unknown. [ABSTRACT FROM AUTHOR]

Objectives: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. Methods: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. Results: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. Discussion and Conclusion: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision. [ABSTRACT FROM AUTHOR]

Background: Approximately 20-30% of patients with pT4 colon cancer develop metachronous peritoneal metastases (PM). Due to restricted accuracy of imaging modalities and absence of early symptoms, PM are often detected at a stage in which only a quarter of patients are eligible for curative intent treatment. Preliminary findings of the COLOPEC trial (NCT02231086) revealed that PM were already detected during surgical re-exploration within two months after primary resection in 9% of patients with pT4 colon cancer. Therefore, second look diagnostic laparoscopy (DLS) to detect PM at a subclinical stage may be considered an essential component of early follow-up in these patients, although this needs confirmation in a larger patient cohort. Furthermore, a third look DLS after a negative second look DLS might be beneficial for detection of PM occurring at a later stage.Methods: The aim of this study is to determine the yield of second look DLS and added value of third look DLS after negative second look DLS in detecting occult PM in pT4N0-2 M0 colon cancer patients after completion of primary treatment. Patients will undergo an abdominal CT at 6 months postoperative, followed by a second look DLS within 1 month if no PM or other metastases not amenable for local treatment are detected. Patients without PM will subsequently be randomized between routine follow-up including 18 months abdominal CT, or an experimental arm with a third look DLS provided that PM or incurable metastases are absent at the 18 months abdominal CT. Primary endpoint is the proportion of PM detected after a negative second look DLS and will be determined at 20 months postoperative.Discussion: Second look DLS is supposed to result in 10% occult PM, and third look DLS after negative second look DLS is expected to detect an additional 10% of PM compared to routine follow-up alone in patients with pT4 colon cancer. Detection of PM at an early stage will likely increase the proportion of patients eligible for curative intent treatment and subsequently improve survival, given the uniformly reported direct association between the extent of peritoneal disease and survival.Trial Registration: ClinicalTrials.gov: NCT03413254 , January 2018. [ABSTRACT FROM AUTHOR]

Background. A large proportion of patients with pancreatic cancer presents with metastatic disease. We conducted a population-based study to evaluate trends in treatment and survival of patients with metastatic pancreatic cancer. Methods. We included all patients diagnosed with pancreatic cancer between 1993 and 2010 in the South of the Netherlands (N = 3099). Multivariable logistic regression analysis was conducted to evaluate trends in treatment with chemotherapy. Crude overall survival according to period of diagnosis was analyzed, and independent risk factors for death were identified. Results. Forty-eight percent of the patients (N = 1494) were diagnosed with metastatic disease. The percentage of patients being diagnosed with metastatic disease increased during the study period from 35% in 1993-1996 to 59% in 2009-2010 (p < 0.0001). Overall, 18% of these patients received chemotherapy. The prescription of palliative chemotherapy almost tripled from 10% to 27% (p < 0.0001). Treatment largely depended on age, ranging from 38% among patients aged < 50 years [compared to 60-69 years: adjusted odds ratio (ORadj) 2.5 (95% CI 1.4-4.2)] to 1% among patients aged ≥ 80 years [compared to 60-69 years: ORadj 0.04 (95% CI 0.0-0.2)]. Patients were more likely to receive chemotherapy if they had a high socioeconomic status [ORadj 2.0 (95% CI 1.3-3.1)], and if diagnosis was pathologically verified [no verification vs. verification: ORadj 0.3 (95% CI 0.2-0.5)]. The administration of chemotherapy varied widely between 10 hospitals (5-34%, p < 0.0001). The median overall survival of patients with metastatic pancreatic cancer remained 9-11 weeks. Conclusion. A growing proportion of pancreatic cancer patients presented with metastatic disease. Usage of palliative chemotherapy increased over time, but median survival remained 9-11 weeks. In the near future, it should be evaluated if the recently introduced regimens have an impact on population-based survival. [ABSTRACT FROM AUTHOR]

Background: This study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients. Methods: All patients operated on with curative intent for colorectal cancer ( Tany Nany Mo ) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included ( N = 5671). By means of active followup by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years. Results: Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10-29 months). Male gender (HR = 1.2, 95%CI 1.03-1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32-1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42-3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72-5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17-1.62), and a positive (HR = 2.1, 95%CI 1.68-2.71) and unknown (HR = 1.7, 95%CI 1.34-2.22) resection margin were predictors for metachronous metastases. Conclusions: Different patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options. [ABSTRACT FROM AUTHOR]

The article presents research on the incidence and prognosis of synchronous peritoneal carcinomatosis. A population-based data on synchronous peritoneal carcinomatosis and its development predictors is evaluated. The predictors of the carcinomatosis were analyzed using multivariable logistic regression analysis. It concludes that synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients.

Simple Summary: Physical activity is linked to longer survival among non-metastasized colorectal cancer patients. It is unclear if physical activity is also beneficial for survival among patients with metastatic colorectal cancer. We researched this question in our study of 293 patients with metastatic colorectal cancer. We found that participants who reported higher levels of physical activity at diagnosis lived longer compared to patients who reported low activity levels. Furthermore, adherence to the physical activity guidelines for cancer survivors was related to prolonged survival. Our findings suggest that patients with metastatic colorectal cancer also benefit from being physically active. Future studies are needed to investigate whether improving exercise levels after diagnosis of metastasis is also beneficial and what kind of exercise interventions are most optimal for possibly improving survival time of patients with metastatic colorectal cancer. Regular physical activity (PA) is associated with improved overall survival (OS) in stage I–III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299–0.807, p value = 0.005) and 0.485 (95% CI 0.303–0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278–0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224–0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412–0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS. [ABSTRACT FROM AUTHOR]

The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assists in designing potentially more effective treatment protocols and clinical trials. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In total, 60 articles were included in this study. The selected articles were screened on the HIPEC parameters. Recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. [ABSTRACT FROM AUTHOR]

Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35–0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25–3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36–0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36–0.80)). The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making. • A large nationwide cohort study of 2697 small intestinal adenocarcinomas (SIAs). • The incidence of duodenal adenocarcinomas almost doubled with no improvement in OS. • Despite adjuvant chemotherapy prolonging OS, only 13.8% of eligible patients were treated. • In the first-line setting CAPOX prolonged OS compared to FOLFOX and capecitabine. • A metastasectomy in patients with one distant metastasis was associated with OS. [ABSTRACT FROM AUTHOR]

Background In the Netherlands, surgery for peritoneal metastases of colorectal cancer (PMCRC) is centralised, whereas PMCRC is diagnosed in all hospitals. This study assessed whether hospital of diagnosis affects treatment selection and overall survival (OS). Methods Between 2005 and 2015, all patients with synchronous PMCRC without systemic metastases were selected from the Netherlands Cancer Registry. Treatment was classified as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), systemic therapy or other/no treatment. Hospitals of diagnosis were classified as: (1) non-teaching or academic/teaching hospital and (2) HIPEC centre or referring hospital. Referring hospitals were further classified based on the frequency of CRS/HIPEC as high-, medium- or low-frequency hospital. Multivariable regression analyses were used to assess the independent influence of hospital categories on the likelihood of CRS/HIPEC and OS. Results A total of 2661 patients, diagnosed in 89 hospitals, were included. At individual hospital level, CRS/HIPEC and systemic therapy ranged from 0% to 50% and 6% to 67%, respectively. Hospital of diagnosis influenced the likelihood of CRS/HIPEC: 33% versus 13% for HIPEC centres versus referring hospitals (odds ratio (OR) 3.66 [2.40−5.58]) and 11% versus 17% for non-teaching hospitals versus academic/teaching hospitals (OR 0.60 [0.47–0.77]). Hospital of diagnosis affected median OS: 14.1 versus 9.6 months for HIPEC centres versus referring hospitals (hazard ratio (HR) 0.82 [0.67–0.99]) and 8.7 versus 11.5 months for non-teaching hospitals versus academic/teaching hospitals (HR 1.15 [1.06–1.26]). Compared with diagnosis in medium-frequency referring hospitals, median OS was increased in high-frequency referring hospitals (12.6 months, HR 0.82 [0.73−0.91]) and reduced in low-frequency referring hospitals (8.1 months, HR 1.12 [1.01–1.24]). Conclusion Treatment disparities among hospitals of diagnosis and their impact on survival indicate suboptimal treatment selection for PMCRC. [ABSTRACT FROM AUTHOR]

Purpose To determine the impact of the implementation of novel systemic regimens and locoregional treatment modalities on survival at population level in colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs). Methods All consecutive CRC patients with synchronous PM (<3 months) between 1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer Registry. Trends in treatment and overall survival were assessed in four time periods. Multivariable regression analysis was used to analyse the impact of systemic and locoregional treatment modalities on survival. Results A total of 37,036 patients were diagnosed with primary CRC between 1995 and 2014. Synchronous PM was diagnosed in 1,661 patients, of whom 55% had also metastases at other sites (n = 917) and 77% received anticancer therapy (n = 1,273). Treatment with systemic therapy increased from 23% in 1995–1999 to 56% in 2010–2014 (p < 0.0001). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was applied since 2005 and increased from 10% in 2005–2009 to 23% in 2010–2014. Surgery for lymphatic or haematogenous metastases increased from 2% to 10% in these periods. Median overall survival of the complete cohort improved from 6.0 months in 1995–2000 to 12.5 months in 2010–2014 (p < 0.0001), with a doubling of survival for both PM alone and PM with other involved sites. The influence of year of diagnosis on survival (hazard ratio, 2010–2014 versus 1995–1999; 0.5, 95% confidence interval: 0.43–0.62; p < 0.0001) disappeared after including systemic therapy and locoregional treatment modalities in subsequent multivariable models. Conclusion CRC patients presenting with PM are increasingly offered a multidisciplinary treatment approach, resulting in an increased overall survival for the entire cohort. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Until recently, peritoneal metastases (PM) were regarded as an untreatable condition, regardless of the organ of origin. Currently, promising treatment options are available for selected patients with PM from colorectal, appendiceal, ovarian or gastric carcinoma. The aim of this study was to investigate the incidence, treatment and survival of patients presenting with PM in whom the origin of PM remains unknown. Methods: Data from patients diagnosed with PM of unknown origin during 1984–2010 were extracted from the Eindhoven Cancer Registry. European age-standardised incidence rates were calculated and data on treatment and survival were analysed. Results: In total 1051 patients were diagnosed with PM of unknown origin. In 606 patients (58%) the peritoneum was the only site of metastasis, and 445 patients also had other metastases. Chemotherapy usage has increased from 8% in the earliest period to 16% in most recent years (p =.016). Median survival was extremely poor with only 42days (95% confidence interval (CI) 39–47days) and did not change over time. Median survival of patients not receiving chemotherapy was significantly worse than of those receiving chemotherapy (36 versus 218days, p <.0001). Conclusion: The prognosis of PM of unknown origin is extremely poor and did not improve over time. Given the recent progress that has been achieved in selected patients presenting with PM, maximum efforts should be undertaken in order to diagnose the origin of PM as accurately as possible. Potentially effective treatment strategies should be further explored for patients in whom the organ of origin remains unknown. [Copyright &y& Elsevier]