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SOURCE-PANC: A Prediction Model for Patients With Metastatic Pancreatic Ductal Adenocarcinoma Based on Nationwide Population-Based Data

Héctor G. van den Boorn, Willemieke P.M. Dijksterhuis, Lydia G.M. van der Geest, Judith de Vos-Geelen, Marc G. Besselink, Johanna W. Wilmink, Martijn G.H. van Oijen, and Hanneke W.M. van Laarhoven

Background: A prediction model for overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (PDAC) including patient and treatment characteristics is currently not available, but it could be valuable for supporting clinicians in patient communication about expectations and prognosis. We aimed to develop a prediction model for OS in metastatic PDAC, called SOURCE-PANC, based on nationwide population-based data. Materials and Methods: Data on patients diagnosed with synchronous metastatic PDAC in 2015 through 2018 were retrieved from the Netherlands Cancer Registry. A multivariate Cox regression model was created to predict OS for various treatment strategies. Available patient, tumor, and treatment characteristics were used to compose the model. Treatment strategies were categorized as systemic treatment (subdivided into FOLFIRINOX, gemcitabine/nab-paclitaxel, and gemcitabine monotherapy), biliary drainage, and best supportive care only. Validation was performed according to a temporal internal–external cross-validation scheme. The predictive quality was assessed with the C-index and calibration. Results: Data for 4,739 patients were included in the model. Sixteen predictors were included: age, sex, performance status, laboratory values (albumin, bilirubin, CA19-9, lactate dehydrogenase), clinical tumor and nodal stage, tumor sublocation, presence of distant lymph node metastases, liver or peritoneal metastases, number of metastatic sites, and treatment strategy. The model demonstrated a C-index of 0.72 in the internal–external cross-validation and showed good calibration, with the intercept and slope 95% confidence intervals including the ideal values of 0 and 1, respectively. Conclusions: A population-based prediction model for OS was developed for patients with metastatic PDAC and showed good performance. The predictors that were included in the model comprised both baseline patient and tumor characteristics and type of treatment. SOURCE-PANC will be incorporated in an electronic decision support tool to support shared decision-making in clinical practice.

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Beyond Median Overall Survival: Estimating Trends for Multiple Survival Scenarios in Patients With Metastatic Esophagogastric Cancer

Marieke Pape, Steven C. Kuijper, Pauline A.J. Vissers, Laurens V. Beerepoot, Geert-Jan Creemers, Hanneke W.M. van Laarhoven, and Rob H.A. Verhoeven

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.

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Chemotherapy-Induced Peripheral Neuropathy in Patients With Gastroesophageal Cancer

Merel J.M. van Velzen, Marieke Pape, Mirjam A.G. Sprangers, Jessy Joy van Kleef, Bianca Mostert, Laurens V. Beerepoot, Marije Slingerland, Elske C. Gootjes, Ronald Hoekstra, Lonneke V. van de Poll-Franse, Nadia Haj Mohammad, and Hanneke W.M. van Laarhoven

Background: Chemotherapy for various stages of gastroesophageal cancer (GEC) is often neurotoxic. Chemotherapy-induced peripheral neuropathy (CIPN) impairs health-related quality of life (HRQoL). This study investigates the incidence and severity of CIPN and its association with HRQoL in patients with GEC. Patients and Methods: Patients who received chemoradiotherapy or chemotherapy for GEC were identified from the Netherlands Cancer Registry. Patient-reported data (measured using the EORTC QLQ-CIPN20 and EORTC QLQ-C30) were collected through the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) at baseline and at 3, 6, 9, 12, 18, and 24 months after treatment initiation. Linear mixed effects models were constructed to assess CIPN and the correlation between CIPN and HRQoL was analyzed using Spearman’s correlation. Results: A total of 2,135 patients were included (chemoradiotherapy: 1,593; chemotherapy with curative intent: 295; palliative chemotherapy: 247). In all 3 treatment groups, CIPN significantly increased during treatment (adjusted mean score of CIPN at 6 months: chemoradiotherapy, 8.3 [baseline: 5.5]; chemotherapy with curative intent, 16.0 [baseline: 5.6]; palliative therapy, 25.4 [baseline: 10.7]). For chemoradiotherapy, the adjusted mean score continued to increase after treatment (24 months: 11.2). For chemotherapy with curative intent and palliative therapy, the adjusted mean score of CIPN decreased after treatment but did not return to baseline values. CIPN was negatively correlated with HRQoL in all treatment groups, although significance and strength of the correlation differed over time. Conclusions: Because of the poor prognosis of GEC, it is essential to consider side effects of (neurotoxic) treatment. The high prevalence and association with HRQoL indicate the need for early recognition of CIPN.

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Cachexia and Dietetic Interventions in Patients With Esophagogastric Cancer: A Multicenter Cohort Study

Willemieke P.M. Dijksterhuis, Anouk E.J. Latenstein, Jessy Joy van Kleef, Rob H.A. Verhoeven, Jeanne H.M. de Vries, Marije Slingerland, Elles Steenhagen, Joos Heisterkamp, Liesbeth M. Timmermans, Marian A.E. de van der Schueren, Martijn G.H. van Oijen, Sandra Beijer, and Hanneke W.M. van Laarhoven

Background: Cachexia is common in patients with esophagogastric cancer and is associated with increased mortality. Nutritional screening and dietetic interventions can be helpful in preventing evolvement of cachexia. Our aim was to study the real-world prevalence and prognostic value of pretreatment cachexia on overall survival (OS) using patient-reported weight loss, and to explore dietetic interventions in esophagogastric cancer. Materials and Methods: Patients with esophagogastric cancer (2015–2018), regardless of disease stage, who participated in the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) and completed patient-reported outcome measures were included. Data on weight loss and dietetic interventions were retrieved from questionnaires before start of treatment (baseline) and 3 months thereafter. Additional patient data were obtained from the Netherlands Cancer Registry. Cachexia was defined as self-reported >5% half-year body weight loss at baseline or >2% in patients with a body mass index (BMI) <20 kg/m2 according to the Fearon criteria. The association between cachexia and OS was analyzed using multivariable Cox proportional hazard analyses adjusted for sex, age, performance status, comorbidities, primary tumor location, disease stage, histology, and treatment strategy. Results: Of 406 included patients, 48% had pretreatment cachexia, of whom 65% were referred for dietetic consultation at baseline. The proportion of patients with cachexia was the highest among those who received palliative chemotherapy (59%) or best supportive care (67%). Cachexia was associated with decreased OS (hazard ratio, 1.52; 95% CI, 1.11–2.09). Median weight loss after 3-month follow-up was lower in patients with cachexia who were referred to a dietician at baseline compared with those who were not (0% vs 2%; P=.047). Conclusions: Nearly half of patients with esophagogastric cancer have pretreatment cachexia. Dietetic consultation at baseline was not reported in more than one-third of the patients with cachexia. Because cachexia was independently associated with decreased survival, improving nutritional screening and referral for dietetic consultation are warranted to prevent further deterioration of malnutrition and mortality.

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First- and Second-Line Palliative Systemic Treatment Outcomes in a Real-World Metastatic Pancreatic Cancer Cohort

Esther N. Pijnappel, Willemieke P.M. Dijksterhuis, Lydia G. van der Geest, Judith de Vos-Geelen, Jan Willem B. de Groot, Marjolein Y.V. Homs, Geert-jan Creemers, Nadia Haj Mohammad, Marc G. Besselink, Hanneke W.M. van Laarhoven, Johanna W. Wilmink, and for the Dutch Pancreatic Cancer Group

Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor survival rate, which can be improved by systemic treatment. Consensus on the most optimal first- and second-line palliative systemic treatment is lacking. The aim of this study was to describe the use of first- and second-line systemic treatment, overall survival (OS), and time to failure (TTF) of first- and second-line treatment in metastatic PDAC in a real-world setting. Patients and Methods: Patients with synchronous metastatic PDAC diagnosed between 2015 and 2018 who received systemic treatment were selected from the nationwide Netherlands Cancer Registry. OS and TTF were evaluated using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: The majority of 1,586 included patients received FOLFIRINOX (65%), followed by gemcitabine (18%), and gemcitabine + nab-paclitaxel (13%) in the first line. Median OS for first-line FOLFIRINOX, gemcitabine + nab-paclitaxel, and gemcitabine monotherapy was 6.6, 4.7, and 2.9 months, respectively. Compared to FOLFIRINOX, gemcitabine + nab-paclitaxel showed significantly inferior OS after adjustment for confounders (hazard ratio [HR], 1.20; 95% CI, 1.02–1.41), and gemcitabine monotherapy was independently associated with a shorter OS and TTF (HR, 1.98; 95% CI, 1.71–2.30 and HR, 2.31; 95% CI, 1.88–2.83, respectively). Of the 121 patients who received second-line systemic treatment, 33% received gemcitabine + nab-paclitaxel, followed by gemcitabine (31%) and FOLFIRINOX (10%). Conclusions: Based on population-based data in patients with metastatic PDAC, treatment predominantly consists of FOLFIRINOX in the first line and gemcitabine with or without nab-paclitaxel in the second line. FOLFIRINOX in the first line shows superior OS compared with gemcitabine with or without nab-paclitaxel.

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Patient Satisfaction and Quality of Life Before and After Treatment of Pancreatic and Periampullary Cancer: A Prospective Multicenter Study

Tara M. Mackay, Lennart B. van Rijssen, Jurr O. Andriessen, Mustafa Suker, Geert-Jan Creemers, Ferry A. Eskens, Ignace H. de Hingh, Lonneke V. van de Poll-Franse, Mirjam A.G. Sprangers, Olivier R. Busch, Johanna W. Wilmink, Casper H. van Eijck, Marc G. Besselink, Hanneke W. van Laarhoven, and on behalf of the Dutch Pancreatic Cancer Group

Background: This study sought to assess patient satisfaction and quality of life (QoL) before and after treatment of pancreatic and periampullary cancer. Methods: We conducted a prospective multicenter study of patients treated for pancreatic and periampullary cancer. General patient satisfaction was measured using the EORTC satisfaction with care questionnaire (IN-PATSAT32) at baseline and 3 months after treatment initiation, with a 10-point change on the Likert scale considered clinically meaningful. QoL was measured using the EORTC Core Quality of Life Questionnaire (QLQ-C30). The influence of treatment (curative and palliative) on patient satisfaction and QoL was determined. Results: Of 100 patients, 71 completed follow-up questionnaires. General satisfaction with care decreased from 74.3 before treatment to 61.9 after treatment (P<.001), whereas global QoL increased from 68.4 to 71.4 (P=.39). Clinically meaningful reductions were also observed for the reported interpersonal skills of doctors (from 73.4 to 63.3) and exchange of information within the care team (from 63.5 to 52.5). Satisfaction scores were lower for patients treated with curative intent than for those treated with palliative intent regarding interpersonal skills of doctors (P=.01), information provision by doctors (P=.004), information provision by nurses (P=.02), availability of nurses (P=.004), exchange of information within the care team (P=.01), and hospital access (P=.02). In multivariable analysis, clinicopathologic or QoL factors were not independently associated with general patient satisfaction. Conclusions: Satisfaction with care, but not QoL, decreased after pancreatic cancer treatment. Improvements in communication and interpersonal skills are needed to maintain patient satisfaction after treatment.

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Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study

Niels A.D. Guchelaar, Bo J. Noordman, Marion W. Welten, Myron T. van Santen, Micha J. de Neijs, Stijn L.W. Koolen, Rob H.A. Verhoeven, Esther Oomen-de Hoop, Pieter C. van der Sluis, Sjoerd M. Lagarde, Hanneke W.M. van Laarhoven, Ignace H.J.T. de Hingh, Geert-Jan Creemers, Bianca Mostert, Bas P.L. Wijnhoven, and Ron H.J. Mathijssen

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.

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Relationship Between Quality of Life and Survival in Patients With Pancreatic and Periampullary Cancer: A Multicenter Cohort Analysis

Tara M. Mackay, Anouk E.J. Latenstein, Mirjam A.G. Sprangers, Lydia G. van der Geest, Geert-Jan Creemers, Susan van Dieren, Jan-Willem B. de Groot, Bas Groot Koerkamp, Ignace H. de Hingh, Marjolein Y.V. Homs, Evelien J.M. de Jong, I. Quintus Molenaar, Gijs A. Patijn, Lonneke V. van de Poll-Franse, Hjalmar C. van Santvoort, Judith de Vos-Geelen, Johanna W. Wilmink, Casper H. van Eijck, Marc G. Besselink, Hanneke W.M. van Laarhoven, and for the Dutch Pancreatic Cancer Group

Background: A relationship between quality of life (QoL) and survival has been shown for several types of cancer, mostly in clinical trials with highly selected patient groups. The relationship between QoL and survival for patients with pancreatic or periampullary cancer is unclear. Methods: This study analyzed QoL data from a prospective multicenter patient-reported outcome registry in patients with pancreatic or periampullary carcinoma registered in the nationwide Netherlands Cancer Registry (2015–2018). Baseline and delta QoL, between baseline and 3-month follow-up, were assessed with the Happiness, EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30), and QLQ-PAN26 questionnaires. The relationship between QoL and survival was assessed using Cox regression models, and additional prognostic value of separate items was assessed using Nagelkerke R 2 (explained variance). Results: For the baseline and delta analyses, 233 and 148 patients were available, respectively. Most were diagnosed with pancreatic adenocarcinoma (n=194; 83.3%) and had stage III disease (n=77; 33.0%), with a median overall survival of 13.6 months. Multivariate analysis using baseline scores indicated several scales to be of prognostic value for the total cohort (ie, happiness today, role functioning, diarrhea, pancreatic pain, and body image; hazard ratios all P<.05) and for patients without resection (ie, overall satisfaction with life, physical and cognitive functioning, QLQ-C30 summary score, fatigue, pain, constipation, diarrhea, and body image; hazard ratios all P<.05). Except for diarrhea, all QoL items accounted for >5% of the additional explained variance and were of added prognostic value. Multivariate analysis using delta QoL revealed that only constipation was of prognostic value for the total cohort, whereas no association with survival was found for subgroups with or without resection. Conclusions: In a multicenter cohort of patients with pancreatic or periampullary carcinoma, QoL scores predicted survival regardless of patient, tumor, and treatment characteristics. QoL scores may thus be used for shared decision-making regarding disease management and treatment choice.

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SOURCE: Prediction Models for Overall Survival in Patients With Metastatic and Potentially Curable Esophageal and Gastric Cancer

Héctor G. van den Boorn, Ameen Abu-Hanna, Nadia Haj Mohammad, Maarten C.C.M. Hulshof, Suzanne S. Gisbertz, Bastiaan R. Klarenbeek, Marije Slingerland, Laurens V. Beerepoot, Tom Rozema, Mirjam A.G. Sprangers, Rob H.A. Verhoeven, Martijn G.H. van Oijen, Koos H. Zwinderman, and Hanneke W.M. van Laarhoven

Background: Personalized prediction of treatment outcomes can aid patients with cancer when deciding on treatment options. Existing prediction models for esophageal and gastric cancer, however, have mostly been developed for survival prediction after surgery (ie, when treatment has already been completed). Furthermore, prediction models for patients with metastatic cancer are scarce. The aim of this study was to develop prediction models of overall survival at diagnosis for patients with potentially curable and metastatic esophageal and gastric cancer (the SOURCE study). Methods: Data from 13,080 patients with esophageal or gastric cancer diagnosed in 2015 through 2018 were retrieved from the prospective Netherlands Cancer Registry. Four Cox proportional hazards regression models were created for patients with potentially curable and metastatic esophageal or gastric cancer. Predictors, including treatment type, were selected using the Akaike information criterion. The models were validated with temporal cross-validation on their C-index and calibration. Results: The validated model’s C-index was 0.78 for potentially curable gastric cancer and 0.80 for potentially curable esophageal cancer. For the metastatic models, the c-indices were 0.72 and 0.73 for esophageal and gastric cancer, respectively. The 95% confidence interval of the calibration intercepts and slopes contain the values 0 and 1, respectively. Conclusions: The SOURCE prediction models show fair to good c-indices and an overall good calibration. The models are the first in esophageal and gastric cancer to predict survival at diagnosis for a variety of treatments. Future research is needed to demonstrate their value for shared decision-making in clinical practice.