Erasmus MC Cancer Institute Research Articles

The development of brain metastases in patients with different therapeutic strategies for metastatic renal cell cancer.

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single-center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty-six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty-five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM-free survival since ECM diagnosis was significantly longer (p = .02) in previously treated patients (29.0 [IQR 12.6-57.0] months) compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM-free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC.

Feasibility and Relevance of Incorporating Genetic Testing By Next-Generation Sequencing for Acute Myeloid Leukemia Patients Treated in Low- and Middle-Income Countries

Background: The outcome of the treatment for acute myeloid leukemia (AML) in low- and middle-income countries (LMIC) is significantly worse than in high-income ones due to several factors, including higher non-relapse mortality from infections and limited access to hematopoietic stem-cell transplantation (HSCT). In this resource-constrained setting, AML-risk stratification is based exclusively on cytogenetics, which has longer turn-around time and higher failure rates compared to next-generation sequencing (NGS). Here, we report the benefit of adding a simplified NGS gene panel to improve risk stratification for 279 adult Brazilian patients with AML (male=146, female=136; mean age=50 years; range 18-65) included in International Consortium of Acute Leukemia (ICAL) 2015 Study. Material & Methods: Samples from 10 ICAL centers were shipped to the National Central Lab at the University of São Paulo at Ribeirão Preto Medical School, Brazil (located zero to 1420 kilometers from centers). All patient samples were assessed by conventional cytogenetics and molecular tests by RT-PCR for RUNX1::RUNX1T1 and CBFB::MYH11 , PCR and fragment analysis for NPM1 and FLT3-ITD allelic ratio, and Skyline AML profiler assay for CEBPA double mutant. We retrospectively searched for mutations in the ASXL1, CEBPA, FLT3, IDH1, IDH2, NPM1, RUNX1, TP53 genes using NGS in 53 out of the 279 samples. The tests were performed in the Illumina iSeq100 Sequencing System using reagents and methodology developed under the supervision of the Erasmus MC Cancer Institute (Valk Laboratory) as part of the activities of the ICAL Laboratory Subcommittee. Training, including bioinformatics analysis, was provided virtually and through a short-term visiting program (ASH Visitor Training Program) to Erasmus MC. Datasets with genetic testing results obtained locally were sent and reanalyzed at Erasmus MC and discussed in bi-monthly meetings. Risk stratification was determined either by cytogenetics only or by cytogenetic and molecular analysis according to the ELN 2017 proposal. Overall survival (OS) was defined from date of diagnosis to last follow up or death and compared by Kaplan-Meier and Log-Rank test followed by Benjamini-Hochberg p-value adjustment method, using R 4.3.1. Results: conventional cytogenetics was informative in 68% (190/279) of the cases, and based on those results 32 (16.8%), 116 (61%) and 42 (22.1%) patients were stratified into favorable, intermediate and adverse categories, respectively. However, no significant difference in the OS was detected according to cytogenetic risk. When genetic testing by NGS was added, 54 (27.3%), 98 (49.5%) and 46 (23.2%) patients were assigned into favorable, intermediate and adverse categories, respectively. Twenty-six (48%) patients had risk re-classified as a consequence of the NGS results. Moreover, two out of four patients whose risk stratification could not be assigned due to insufficient metaphasis were classified based on NGS results. Of note, the median OS of the favorable group was significantly longer (not reached) than that of intermediate and of the adverse groups (6 months), ( p<0.0001), but no difference was detected between the latter two. We also assessed whether genetic testing by NGS would change the risk category of AML patients previously classified based on conventional cytogenetics in association with the evaluation of gene rearrangements, NPM1, FLT3 and CEBPA mutational analysis by methods other than NGS. NGS results changed the category of 3 out of 54 patients. Our results indicate the feasibility of developing a simplified platform of genetic testing for AML based on NGS in LMIC, which was able to improve the identification of favorable-risk patients and may help to better allocate resources.

NCMP-01. TREATMENT STRATEGIES IN PATIENTS WITH RENAL CELL CANCER AND BRAIN METASTASES

Abstract BACKGROUND Brain metastases (BM) significantly impact quality of life and survival in patients with metastatic renal cell cancer (mRCC). Based on the International Metastatic RCC Database Consortium (IMDC) risk classification, treatment strategies for patients with mRCC vary from systemic treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and/or immune checkpoint inhibitors (ICIs) to active surveillance (AS). Here, we describe the impact of treatment strategies on survival in patients with RCC and BM. METHODS We conducted a single-center, retrospective cohort study at Erasmus MC Cancer Institute (Rotterdam, Netherlands). All consecutive patients with RCC BM between 2011-2022 were included. Primary outcome was the BM-free survival, i.e. the time between diagnosis of extracranial metastases (ECM) and BM. Secondary outcome was overall survival (OS). RESULTS 46 patients with RCC BM were included: 25 (54.3%) had received prior systemic treatment for ECM, and 21 (45.7%) were treatment naive at diagnosis of BM. IMDC scores (favorable 12% resp. 0%, intermediate 48% resp. 64%, poor 24% resp. 0%, unknown 16% resp. 36%) were not significantly different (p=0.07) between these groups. In 39 (84.8%) of 46 patients, BM were metachronous ( >1 month) after ECM. In these patients (n=39), the median BM-free survival was 22.3 (IQR 5.7-46.7) months and was significantly longer (p=0.02) in previously treated patients (29.0 [IQR 12.6-57.0] months) as compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). However, median OS since ECM diagnosis (39.1 [IQR 16.5-111.5] months) was not significantly different (p=0.62) between previously treated and treatment naive patients. CONCLUSION Patients with RCC who received systemic treatment for ECM prior to BM diagnosis, had a longer BM-free survival as compared to patients without previous systemic treatment. These results emphasize the need for careful evaluation of AS in patients with mRCC, even in patients with a favorable prognostic profile.

Application of the ESHO-QA guidelines for determining the performance of the LCA superficial hyperthermia heating system

Purpose This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility. Materials and methods The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging. Results A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS. Conclusions The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.

8q Gain Has No Additional Predictive Value in SF3B1MUT Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1MUT Uveal Melanoma

Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 (SF3B1)-mutated (SF3B1MUT) tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of SF3B1MUT UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and SF3B1MUT UM. Retrospective cohort study. Patients diagnosed with UM who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included. Fifty-nine patients with SF3B1MUT tumors and 211 patients with BRCA1 associated protein 1 (BAP1)-mutated (BAP1MUT) tumors were included in this study. Copy number status and gene expression were assessed using either a single nucleotide polymorphism array, fluorescence in situ hybridization, and karyotyping, or a combination of these techniques. Disease-free survival was determined and a cut-off of 60 months was used to define early-onset metastatic disease. Disease-free survival. Forty-eight patients with SF3B1MUT UM (81%) had chromosome 8q gain (3 copies, 78%; 4 copies, 22%). Kaplan-Meier analysis of SF3B1MUT UM did not indicate a difference in survival in patients with or without gain of 8q (P= 0.99). Furthermore, the number of 8q copies was not associated with survival when comparing early (P= 0.97) versus late (P= 0.23) metastases group. In contrast, the presence of 8q gain (86%) was correlated with a decreased survival in BAP1MUT UM (P= 0.013). We did not find a correlation between 8q gain and early-onset metastasis in SF3B1MUT tumors. Gain of 8q has no additional predictive value in SF3B1MUT tumors. In contrast, 8q gain is predictive of a worse prognosis in patients with BAP1MUT tumors. Thus, gain of chromosome 8q has additional predictive value for BAP1MUT tumors, but not for SF3B1MUT tumors. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

P11.64.A TREATMENT STRATEGIES BEFORE THE DIAGNOSIS OF BRAIN METASTASIS IN PATIENTS WITH RENAL CELL CANCER (RCC)

Abstract BACKGROUND Metastatic renal cell cancer (mRCC) is known for its variable disease course and can be categorized according to the International Metastatic RCC Database Consortium (IMDC) criteria. As patients with mRCC who have a favorable IMDC score and/or a low tumor burden usually have an indolent disease course, watchful waiting is often considered in daily clinical practice. However, it is unknown whether watchful waiting impacts the development of brain metastasis (BM). Therefore, we investigated variables that may affect the interval between first diagnosis of mRCC and BM (BM-free interval) in patients with RCC and BM. MATERIAL AND METHODS A single-center, retrospective cohort study was performed at the Erasmus MC Cancer Institute (Rotterdam, the Netherlands). All consecutive patients with a diagnosis of RCC and BM between 01-01-2011 and 31-07-2022 were included. The primary outcome was the BM-free interval. Secondary outcomes were intracranial progression-free survival (iPFS), progression-free survival (PFS) and overall survival (OS), since diagnosis of BM. Subgroups included patients with and without systemic treatment prior to the diagnosis of BM. Kaplan-Meier (Logrank test) and Cox Proportional Hazards Model (Likelihood ratio test) analyses were performed with significance considered at p-values <0.05. RESULTS A total of 46 patients with RCC and BM were included; 80% was male and 89.1% had a clear cell RCC subtype. In 84.8% of patients, BMs were diagnosed metachronous (>1 month) after the diagnosis of extracranial metastasis (ECM) and 80.4% of patients had symptomatic BM at BM diagnosis. After the diagnosis of BM, the median iPFS was 7.6 (IQR 3.5-12.2) months, the median PFS was 3.7 (IQR 2.3-8.7) months and the median OS was 10.1 (IQR 5.1-22.8) months. Prior to the diagnosis of BM, 25 (54.3%) patients had received systemic therapy, whereas 21 (45.7%) patients were treatment naïve. The median BM-free interval was 22.3 (IQR 5.7-46.7) months. The median BM-free interval was significantly shorter for treatment naïve patients (6.8 [IQR 1.0-7.0] months) as compared to patients who received previous systemic therapy (29.0 [IQR 12.6-57.0]; p=0.02). In multivariate analysis, a longer BM-free interval was significantly associated with nephrectomy (HR 0.10 [95%CI 0.03-0.31]) and systemic treatment prior to BM diagnosis (HR 0.10 [95%CI 0.03-0.30]). CONCLUSION In this cohort of patients with RCC BM, patients who had not received systemic treatment for ECM were earlier diagnosed with BM than patients who had received prior systemic treatment. Although the retrospective nature of this small selective cohort is a limitation, these results indicate that watchful waiting should be carefully considered for patients with mRCC.

Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial

BackgroundMalignant peritoneal mesothelioma (MPM) is an aggressive malignancy with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes, but recurrence rates remain high. Dendritic cell-based...

The transition from transrectal to transperineal prostate biopsy without antibiotic prophylaxis: Cancer detection rates and complication rates.

Currently, transperineal prostate biopsy (TPB) is preferred over transrectal biopsy (TRB) because of less infectious complications and improved clinically significant prostate cancer (csPCa) detection. However, literature on omitting antibiotic prophylaxis (AP) is limited. Furthermore, previous studies did not include invasive cribriform growth/intraductal carcinoma (CR/IDC) in the definition of csPCa. Therefore, we compared the infectious complication rates between TPB without AP and TRB with AP, and we compared the csPCa detection rates between TPB and TRB including CR/IDC in the definition of csPCa. We included 729 men who were referred to Erasmus MCCancer Institute between 2013-2019 for MRI/TRUS fusion-guided prostate biopsy. Up to 2019, TRB was performed with AP, thereafter TPB was performed without AP. Data on complications were collected prospectively. We compared csPCa detection rates between the biopsy routes using multivariable logistic regressions for men without previous PCa diagnosis and mixed logistic regression for men on active surveillance. To compare the csPCa detection rates in anterior and apical lesions, and the complications rates between the biopsy routes, we used the chi-square test. Overall, we found no difference in csPCa detection between TPB and TRB (odds ratio 1.0, 95%-confidence interval (CI) 0.62-1.76, p = 0.9; for men on active surveillance: odds ratio 1.05, 95%-CI 0.58-1.88, p = 0.9). This was confirmed in anterior and apical lesions although absolute numbers were low. TPB reduced infectious complications with fever compared to TRB (1.1% vs 5.1%, difference = 4.0%, 95%-CI 1.0-7.9, p = 0.010). TPB has no different csPCa detection rate from TRB taking CR/IDC into account. TPB is, however, preferable because of less infectious complications, even if AP is omitted.

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse.

Simple SummaryMore than 40% of patients initially diagnosed with ‘low risk’ (stage I–II) melanoma eventually develop melanoma recurrence or die as a result of melanoma. While the current standard of care at diagnosis for these patients is watchful waiting, they may benefit from adjuvant systemic treatment. The primary aim of this retrospective study was to assess the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict sentinel node metastasis, to identify patients with stage I–II melanoma at risk of disease relapse. This study included Swedish and Dutch patients (18 years of age or older) with a melanoma of the skin without sentinel node metastasis. Using the non-invasive CP-GEP model, the patients could be divided into two groups: high (413 patients) or low risk (122 patients) of recurrence. While these results are promising, optimization of the CP-GEP model is recommended before implementing the model in clinical practice.Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I–II melanoma) is watchful waiting, while >40% of patients with stage IB–IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I–II melanoma at risk of disease relapse. Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (The Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only. Results: In total, 535 patients (stage I–II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4–96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3–84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41–6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a ‘low risk’ of recurrence (96.8% 5-year RFS (95%CI 91.6–98.8), n = 130), 49% as ‘intermediate risk’ (88.4% 5-year RFS (95%CI 83.6–91.8), n = 261), and 26% as ‘high risk’ (61.1% 5-year RFS (95%CI 51.9–69.1), n = 137). Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I–II melanoma into two groups differentiated by RFS.

Use of Merlin Assay to identify patients with a low-risk for SN metastasis in a prospective multicenter Dutch study of a primary melanoma gene-signature (CP-GEP model) to predict sentinel node status during COVID-19.

9571 Background: Approximately 70%-85% of patients who undergo sentinel lymph node biopsy (SLNb) show no nodal metastasis in the sentinel node (SN). The clinicopathological and gene expression profile (CP-GEP) model ( Merlin Assay) was developed and validated to identify patients that may forgo the SLNb surgery due to their low risk for for nodal metastasis This study was initiated during the first wave of Covid-19 pandemic to allow for surgical triage on SLNb and evaluate the implementation of the Merlin assay in clinical practice. Methods: This study was conducted in four designated melanoma centers in the Netherlands. Patients (age &gt; 18y) with newly diagnosed melanoma of the skin, eligible to undergo SLNb were screened for study inclusion. Main exclusion criteria was prior history of primary melanoma ( &gt; T1b) in the past 5 years. After enrollment, tissue sections of the primary melanoma were centrally reviewed at the Erasmus MC Cancer Institute to determine Breslow thickness at primary diagnosis. FFPE tumor tissue was dispatched for molecular analysis of eight target genes known to play a role in cancer development. In combination with age, Breslow thickness, and GEP outcome, risk of having nodal metastasis was calculated. Results were binary presented as 'CP-GEP low risk' and 'CP-GEP high risk'. SLNb status was used as gold standard for comparison. Results: A total of 177 patients were analyzed using the CP-GEP model. Median age was 64 years (IQR 52-73) Median Breslow thickness was 1.4mm (IQR 1.0-2.4). Of all patients 28.2% was diagnosed with T1, 40.7% with T2 and 20.9% with T3 melanoma. Corresponding positivity rate was 7%, 14% and 29% respectively. A total of 24 out of 177 patients had a positive SLNb. Median turn-around time from inclusion to CP-GEP result was 15 days. Overall 37.1.% of patients had a CP-GEP low risk profile. The CP-GEP model had a NPV of 94.6%. Conclusions: This is the first prospective multicenter implementation study for the Merlin assay. Results are in line with previous validation studies. The CP-GEP model could accurately identify patients at low risk for SN metastasis. Implementation in clinical practice is feasible based on current turn-around time. In the future, using the Merlin assay to deselect patients for SLNB may allow for a reduction of surgery in patients with melanoma.

Personalised selection of experimental treatment in patients with advanced solid cancer is feasible using whole-genome sequencing

BackgroundBiomarker-guided therapy in an experimental setting has been suggested to improve patient outcomes. However, trial-specific pre-screening tests are time and tissue consuming and complicate the personalised treatment of patients eligible for early-phase clinical trials. In this study the feasibility of whole-genome sequencing (WGS) as a one-test-for-all for guided inclusion in early-phase trials was investigated.MethodsPhase I Molecular Tumor Board (MTB) at the Erasmus MC Cancer Institute reviewed patients with advanced cancer without standard-of-care treatment (SOC) options for a ‘fresh-frozen’ (FF) tumour biopsy for WGS based on clinical-pathological features. Clinical grade WGS was performed by Hartwig Medical Foundation. MTB matched the patient with a trial, if available.ResultsFrom September 2019–March 2021, 31 patients with highly diverse tumour types underwent a tumour biopsy for WGS. The median turnaround time (TAT) was 15 days [10–42 days]. At least one actionable event was found in 84% of the patients (26/31). One-third of the patients (11/31) received matched experimental treatment.ConclusionsWGS on fresh FF biopsies is a feasible tool for the selection of personalised experimental therapy in patients with advanced cancer without SOC options. WGS is now possible in an acceptable TAT and thus could fulfil the role of a universal genomic pre-screening test.

EHA-ESMO Guidelines for the Diagnosis, Treatment, and Follow-up of Multiple Myeloma

ON DAY 6 of the European Hematology Association (EHA) Virtual Congress 2021, Pieter Sonneveld, Professor of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands, chaired the European Society for Medical Oncology and EHA (ESMO-EHA) joint session on clinical practice guidelines for the diagnosis, treatment, and follow-up of multiple myeloma.

Intraoperative Assessment of the Resection Specimen Facilitates Achievement of Adequate Margins in Oral Carcinoma.

BackgroundInadequate resection margins in oral cavity squamous cell carcinoma have an adverse effect on patient outcome. Intraoperative assessment provides immediate feedback enabling the surgeon to achieve adequate resection margins. The goal of this study was to evaluate the value of specimen-driven intraoperative assessment by comparing the margin status in the period before and the period after the introduction of specimen-driven assessment as a standard of care (period 2010–2012 vs period 2013–2017).MethodsA cohort of patients surgically treated for oral squamous cell carcinoma at the Erasmus MC Cancer Institute, Rotterdam, between 2010–2012 was studied retrospectively and compared to results of a prospectively collected cohort between 2013–2017. The frequency, type and results of intraoperative assessment of resection margins were analyzed.ResultsOne hundred seventy-four patients were included from 2010–2012, 241 patients were included from 2013–2017. An increase in the frequency of specimen-driven assessment was seen between the two periods, from 5% in 2010–2012 to 34% in 2013–2017. When performing specimen-driven assessment, 16% tumor-positive resection margins were found in 2013–2017, compared to 43% tumor-positive resection margins overall in 2010–2012. We found a significant reduction of inadequate resection margins for specimen-driven intraoperative assessment (p < 0.001). Also, tumor recurrence significantly decreased, and disease-specific survival improved when performing specimen-driven intraoperative assessment.ConclusionsSpecimen-driven intraoperative assessment improves resection margins and consequently, the outcome of oral cancer patients. We advocate this method as standard of care.

Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.37–0.73, p < 0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p = 0.19). In pretreated patients no significant effect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p = 0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p = 0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p < 0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this effect was only observed in patients that were not treated with chemotherapy.

A qualitative research on co-creating care pathways for Sarcoma and GIST by stimulating reflection

Introduction Care Pathway Management intends to enhance the quality of care by restructuring care services. As recipients of care, patients have relevant experiential knowledge on the provision of care, but they are rarely involved in Care Pathway Management due to various barriers. This study aims to acquire insights into how patients can be meaningfully involved in Care Pathway Management. Methods A case study was conducted to assess the implementation of patient involvement in the co-creation of the care pathways of Soft Tissue Sarcoma and Gastrointestinal Stromal Tumour at Erasmus MC Cancer Institute (the Netherlands), using the Interactive Learning and Action methodology. Within the pathways, seven patients and eight health professionals were involved. To overcome expected and encountered barriers to involving patients, reflection was stimulated on the care pathways and the development process. Qualitative data were collected via interviews, participatory observations and informal conversations. For analysis, a patient involvement evaluation framework and criteria for knowledge co-creation were used. Results Patients indicated specific improvements for current pathways regarding communication, the assistance of a nurse and integrated care. However, the co-creation process encountered several barriers, including limited opportunities to overcome patients’ knowledge gap on medical care services, limited time and uncertainties about responsibilities. Moreover, participatory reflection to enhance the co-creation process was constrained by power imbalances between patients and health professionals and health professionals’ restricted perceptions of their role. Discussion To enhance the meaningful involvement of patients in Care Pathway Management, constraints in joint reflection on the co-creation process must be overcome.

Histopathological growth patterns and positive margins after resection of colorectal liver metastases

BackgroundHistopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether the non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. MethodsAll patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. ResultsOf all patients (n = 1302) included for analysis, 13% (n = 170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11–2.87, p = 0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08–1.23 p < 0.001). Both positive resection margins (HR: 1.41, 95% CI: 1.13–1.76, p = 0.002) and non-dHGP (HR: 1.57, 95% CI: 1.26–1.95, p < 0.001) were independently associated with worse overall survival. ConclusionPatients with non-dHGP are at higher risk of positive resection margins. Despite this association, both positive resection margins and non-dHGP are independent prognostic indicators of worse overall survival.

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

IntroductionCardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for...

Impact of Older Age on the Exposure of Paclitaxel: a Population Pharmacokinetic Study.

Limited available data suggest that older patients are more prone to develop paclitaxel-induced toxicity than their younger peers. It remains unclear whether this is related to age-dependent pharmacokinetics (PK) of paclitaxel. Primary objective of this study was to determine the influence of older age on the PK of paclitaxel. PK data of patients aged ≥70years who received paclitaxel intravenously at the Netherlands Cancer Institute (NKI) and the Radboud University Medical Center between September 2012 and May 2017 were collected. These prospectively collected data were pooled with previously published databases from multiple clinical trials conducted at the NKI and Erasmus MC Cancer Institute. A previously developed 3-compartment population PK model with saturable distribution and elimination was used to describe paclitaxel plasma concentration-time data. Hereafter, influence of age on paclitaxel PK was assessed in a previously established full covariate model. In total, paclitaxel PK data from 684 patients were available, consisting of 166 patients ≥70years (24%). Median age of the cohort was 61years (range 18 to 84years). The impact of age, either treated as a continuous or dichotomous covariate (<70 versus ≥70years), on the elimination of paclitaxel was only marginal but statistically significant (both p < 0.001 with no clinically relevant decrease in interindividual variability). For a typical patient, maximal elimination capacity decreased by only 5% for a 10-year increment of age. In this extensive multi-center dataset, which included a considerable number of older patients, older age had no clinically relevant impact on paclitaxel PK.

Optimizing prognostication in patients with synchronous liver metastases from rectal cancer treated according to the liver-first approach.

Background: Patients with rectal cancer (RC) and synchronous rectal liver metastases (sRLM) can be treated according to the liver-first approach. A proportion of patients does not complete the full treatment trajectory. This study aims to evaluate currently available prognostic factors in patients treated according to the liver-first protocol. It also aims to improve prognostication for non-completion of the treatment sequence in this highly selected patient population. Methods: Retrospective analysis of all patients treated for RC with sRLM at the Erasmus MC Cancer Institute according to the liver-first protocol. Results: In total 132 consecutive patients were included in this study, of which 90 patients (68%) completed the full treatment trajectory. Logistic regression showed that two well-known clinicopathological factors (RLM size > 5cm, bilobar RLM) were associated with not completing full treatment trajectory. Receiver operating characteristic (ROC) analysis identified the optimal cut-offs for preoperative CEA (37 ug/L), size (2.65 cm) and number (5) of RLM. The use of optimal cut-offs improved performance of the logistic regression model, as the area under the curve (AUC) increased from 0.62 to 0.73. Conclusion: The study identified optimal cut-off points for currently available clinicopathological factors, which improved prognostication in this selected patient group. The obtained Results can be used for counselling but, cannot be used to exclude patients from treatment according the liver first protocol.

Optimizing prognostication in patients with synchronous liver metastases from rectal cancer treated according to the liver-first approach

Background: Patients with rectal cancer (RC) and synchronous rectal liver metastases (sRLM) can be treated according to the liver-first approach. A proportion of patients does not complete the full treatment trajectory. This study aims to evaluate currently available prognostic factors in patients treated according to the liver-first protocol. It also aims to improve prognostication for non-completion of the treatment sequence in this highly selected patient population. Methods: Retrospective analysis of all patients treated for RC with sRLM at the Erasmus MC Cancer Institute according to the liver-first protocol. Results: In total 132 consecutive patients were included in this study, of which 90 patients (68%) completed the full treatment trajectory. Logistic regression showed that two well-known clinicopathological factors (RLM size > 5cm, bilobar RLM) were associated with not completing full treatment trajectory. Receiver operating characteristic (ROC) analysis identified the optimal cut-offs for preoperative CEA (37 ug/L), size (2.65 cm) and number (5) of RLM. The use of optimal cut-offs improved performance of the logistic regression model, as the area under the curve (AUC) increased from 0.62 to 0.73. Conclusion: The study identified optimal cut-off points for currently available clinicopathological factors, which improved prognostication in this selected patient group. The obtained results can be used for counselling but, cannot be used to exclude patients from treatment according the liver first protocol.