ONCOLOGIE

CENTRUM ONCOLOGIE

ARTIKELS

ABSTRACT 1

The prognostic value of patient-reported health-related quality of life and geriatric assessment in predicting early

death in 6769 older (≥ 70 years) patients with different

cancer tumors.

Quinten C, Kenis C, Decoster L, Debruyne P, et al. Journal of Geriatric Oncology, 2020, DOI: 10.1016/j. jgo.2020.03.017

OBJECTIVE We aimed to determine the prognostic value of baseline Health-Related Quality Of Life (HRQOL) and geriatric assessment (GA) to predict three-month mortality in older patients with cancer undergoing treatment.

MATERIALS/METHODS Logistic regressions analysed HRQOL, as measured with the EORTC Global Health Status (GHS) scale, and geriatric information prognostic for early mortality controlling for oncology variables. The assessment was established with the odds ratio (OR), 95% confidence interval (CI) and level of significance set at p < 0.05. Discriminative power was evaluated with area under the curve (AUC).

RESULTS In total, 6769 patients were included in the study, of whom 1259 (18.60%) died at three months. Our model showed higher odds of early death for patients with lower HRQOL (GHS, OR 0.98, 95% CI 0.98–0.99; p < 0.001), a geriatric risk profile (G8 Screening Tool, 1.94, 1.14–3.29; p = 0.014), cognitive decline (Mini Mental State Examination, 1.41, 1.15–1.72; p = 0.001), being at risk for malnutrition (Mini Nutritional Assessment–Short Form, 1.54, 1.21–1.98; p = 0.001), fatigue (Visual Analogue Scale for Fatigue, 1.45, 1.16–1.82; p = 0.012) and comorbidities (Charlson Comorbidity index, 1.23, 1.02–1.49; p = 0.033). Additionally, older age, poor ECOG PS and being male increased the odds of early death, although the magnitude differed depending on tumor site and stage, and treatment (all p < 0.05). Predictive accuracy increased with 3.7% when including HRQOL and GA in the model.

CONCLUSION The results suggest that, in addition to traditional clinical measures, HRQOL and GA provide additional prognostic information for early death, but the odds differ by patient and tumor characteristics. ABSTRACT 2

Underrepresentation of vulnerable older patients with cancer in phase II and III oncology registration trials: a case-control study.

Tack L, Ketelaars L, Martens E, Stellamans K, Van Eygen K, Werbrouck P, Vergauwe P, Debruyne P, et al. Journal of Geriatric Oncology, 2020, 11(2), 320-326

Zie Inwendige ziekten/gastro-enterologie pagina 25.

ABSTRACT 3

PSMA expression on neovasculature of solid tumors.

Van de Wiele C, De Jonge P, Debruyne P, Borms M, Beels L, Maes A, et al. Histology and Histopathology, 2020, 35(9), 919-927

Zie Nucleaire geneeskunde pagina 59.

ABSTRACT 4

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors.

Haaker L, Tryssesoone L, Renders I, Debruyne P, et al. Urologic oncology, 2020, 38(8), DOI: 10.1016/j. urolonc.2020.04.031

OBJECTIVE Papillary renal cell carcinoma (papRCC) is a rare (10%-15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors.

MATERIALS/METHODS A multicentric, retrospective analysis of patient records was conducted. BM were detected by computed tomography and/or bone scintigraphy. The International Metastatic RCC Database Consortium (IMDC) score was calculated at start of first agent VEGFR-TKI treatment.

RESULTS Forty-nine patients were included. Best objective response was partial response in 20%, stable disease in 60% and early progressive disease in 20% of patients. Median PFS (mPFS) was 6.0 months and median OS (mOS) 14.0 months after start of first agent VEGFR-TKI. The IMDC score

correlated with mOS: 77.5 months in good, 17.0 months in intermediate and 8.0 months in poor risk patients (P = 0.002). Patients with BM had a poorer outcome compared to patients without BM: mPFS was 4.0 vs. 7.0 months (P = 0.006) and mOS 7.5 vs. 19.0 months (P = 0.002). On bivariate analysis, the presence of BM was independently associated with PFS (P = 0.02) and OS (P = 0.049), independent of the IMDC risk groups.

CONCLUSION In m-papRCC patients treated with first agent VEGFR-TKIs, the presence of BM is an unfavorable prognostic factor, associated with shorter PFS and OS.

ABSTRACT 5

Developing and evaluating a participatory arts programme for cancer patients and their caregivers.

Tack L, Meersman M, Vanneste H, Van Eygen K, Stellamans K, Derijcke S, Vergauwe P, Debruyne P, et al. Acta Clinica Belgica, 2020, DOI: 10.1080/17843286.2020.1773653

Zie Inwendige ziekten/gastro-enterologie pagina 23.

ABSTRACT 6

Quality of blood samples collected at home does not affect clinical decision making for the administration of systemic cancer treatment.

Cool L, Callewaert N, Pottel H, Van Eygen K, et al. Scandinavian Journal of Clinical and Laboratory Investigation, 2020, 80(3), 215-221

Zie Klinisch laboratorium pagina 27.

ABSTRACT 7

Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study.

Helsen N, Maes A, Beels L, Debruyne P, Goethals L, et al. European Journal of Nuclear Medicine and Molecular Imaging, 2020, 47(5), 1075-1082

Zie Nucleaire geneeskunde pagina 59. ABSTRACT 8

One-stage laparoscopic parenchymal sparing liver resection for bilobar colorectal surgical.

D’Hondt M, Parmentier I, De Meyere C, Pironet Z, Vansteenkiste F, et al. Endoscopy, 2021, Mar 8, DOI: 10.1007/ s00464-021-08366-5

Zie Abdominale chirurgie pagina 7.

ABSTRACT 9

The financial impact of SBRT for oligometastatic disease: a population-level analysis in Belgium.

Nevens D, Kindts I, Defourny N, et al. Radiotherapy and Oncology, 2020, 145, 215-222

INTRODUCTION There is a steady rise in Stereotactic Body RadioTherapy (SBRT) utilization in oligometastatic disease (OMD). This may generate important financial consequences for radiotherapy budgets.The National Institute for Health and Disability Insurance of Belgium (NIHDI) initiated a coverage with evidence development (CED) project for innovative radiotherapy, including SBRT, in 2011. A cost calculation and budget estimation for SBRT in the OMD setting was carried out.

MATERIALS/METHODS Predictive growth scenarios for future uptake of SBRT for OMD in Belgium were developed using demographics and CED data. The provider cost of SBRT for OMD in Belgium was calculated using the Time-Driven Activity-Based Costing (TD-ABC) model developed by ESTRO-HERO, alimented with national data on resources, treatments and operational parameters, and compared to the new reimbursement. Combining these, the future financial impact of this novel treatment indication for healthcare providers and payers in Belgium was evaluated.

RESULTS The number of 428 OMDs treated with SBRT in Belgium in 2017 is expected to increase between 484 and 2073 courses annually by 2025. A provider cost of €4360 per SBRT was calculated (range: €3488–€5654), whereas the reimbursement covers between €4139 and €4654. Large variations in potential extra provider costs by 2025 ensue from the different scenarios, ranging between €1,765,993

and €9,038,754.Provider costs and reimbursement show good agreement.

CONCLUSION Although the financial impact of SBRT for OMD in Belgium is forecasted to remain acceptable, even in extreme scenarios, further clinical trials and real-life clinical and financial monitoring with prospective data gathering are necessary to refine the data.

ABSTRACT 10

Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document.

Lievens Y, Guckenberger M, Gomez D, Kindts I, et al. Radiotherapy Oncology, 2020, 148, 157-166

INTRODUCTION Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence.

MATERIALS/METHODS A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature.

RESULTS Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed.

CONCLUSION While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.

ABSTRACT 11

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial.

King M, Link E, Whelan T, Stellamans K, et al. Lancet Oncology, 2020, 21(5), 685-698

INTRODUCTION BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-lowrisk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.

MATERIALS/METHODS The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm

randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy.

Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236.

RESULTS Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021).

Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy.

CONCLUSION Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending.

ABSTRACT 12

PEACE V – Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial.

De Bruycker A, Spiessens A, Dirix P, Liefhooghe N, et al. BMC Cancer, 2020, 20(1), 406

INTRODUCTION Pelvic nodal recurrences are being increasingly diagnosed with the introduction of new molecular imaging techniques, like choline and PSMA PET-CT, in the restaging of recurrent prostate cancer (PCa). At this moment, there are no specific treatment recommendations for patients with limited nodal recurrences and different locoregional treatment approaches are currently being used, mostly by means of metastasis-directed therapies (MDT): salvage lymph node dissection (sLND) or stereotactic body radiotherapy (SBRT). Since the majority of patients treated with MDT relapse within 2 years in adjacent lymph node regions, with an estimated median time to progression of 12-18 months, combining MDT with whole pelvic radiotherapy (WPRT) may improve oncological outcomes in these patients. The aim of this prospective multicentre randomized controlled phase II trial is to assess the impact of the addition of WPRT to MDT and short-term androgen deprivation therapy (ADT) on metastasis-free survival (MFS) in the setting of oligorecurrent pelvic nodal recurrence.

MATERIALS/METHODS Patients diagnosed with PET-detected pelvic nodal oligorecurrence (≤5 nodes) following radical local treatment for PCa, will be randomized in a 1:1 ratio between arm A: MDT and 6 months of ADT, or arm B: WPRT added to MDT and 6 months of ADT. Patients will be stratified by type of PET-tracer (choline, FACBC or PSMA) and by type of MDT (sLND or SBRT). The primary endpoint is MFS and the secondary endpoints include clinical and biochemical progression-free survival (PFS), prostate cancer specific survival, quality of life (QoL), toxicity and time to castration-resistant prostate cancer (CRPC) and to palliative ADT. Estimated study completion: December 31, 2023.

CONCLUSION This is the first prospective multicentre randomized phase II trial assessing the potential of combined WPRT and MDT as compared to MDT alone on MFS for patients with nodal oligorecurrent PCa. ABSTRACT 14

Quality of blood samples collected at home does not affect clinical decision making for the administration of systemic cancer treatment.

Cool L, Callewaert N, Pottel H, Van Eygen K, et al. Scandinavian Journal of Clinical and Laboratory Investigation, 2020, 80(3), 215-221

Zie Klinisch laboratorium pagina 27.

ABSTRACT 13

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy.

Dirix P, Strijbos M, Van den Mooter T, Liefhooghe N, et al. Future Oncology, 2020, DOI: 10.2217/fon-2020-0056

ABSTRACT Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT.