Traveling the prostate cancer timeline in chase of treatment paradigms: Can we cure the incurable?

BJMO - volume 16, issue 7, november 2022

C. Berghen MD, PhD, G. De Meerleer MD, PhD, K. Rans MD, S. Joniau MD, PhD


When prostate cancer (PCa) patients are diagnosed as ‘incurable’, most patients still have many years to live and often undergo a continuum of burdensome and expensive systemic treatments that can impair quality of life. Due to the active promotion of new systemic therapies in the treatment of metastatic and/or castrationrefractory PCa patients, other treatment modalities such as modern radiotherapy (RT) have been considered as therapies that relieve symptoms, without offering any possibility of cure or additional quality of life-adjusted life years. This PhD thesis investigated whether the implementation of modern RT in previously non-RT indications could prove otherwise. To achieve this, the PCa timeline was followed in search of treatment paradigms, and re-introduced RT in different disease settings. Firstly, the addition of elective para-aortic lymph node radiotherapy was investigated in patients diagnosed with locally advanced pN1 prostate cancer, with local treatment of the prostate (bed) and pelvic lymph nodes, along with 24 months of ADT, in the prospective multicentric PART study. Secondly, a large retrospective study was performed, focused on patients with oligorecurrent prostate cancer who were treated with metastasis-directed therapy (MDT). Finally, the use of MDT was investigated in patients diagnosed with oligoprogressive metastatic castration-resistant prostate cancer (mCRPC), while continuing otherwise successful ongoing systemic treatment. Will this approach lead to a substantial postponement of next-line systemic treatment (NEST)?

(BELG J MED ONCOL 2022;16(7):363–6)

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Role and usefulness of an outpatient clinic for patients on oral anticancer therapy: 5-year experience in a general hospital in Belgium and review of the literature

BJMO - volume 16, issue 3, may 2022

K. Eeckhaut MSN , M. Baert PharmD, N. Kizilmese PharmD, S. Thevelin PhD, PharmD, T. Hendrickx PharmD


Oral anticancer therapy (OACT) is increasingly used for the treatment of cancer patients in the outpatient setting. Even for outpatients, clinical pharmacists (CPs) can provide in-depth patient education to ensure correct medication intake and effective management of adverse drug events (ADEs). It is currently unclear if this type of medication counselling can improve the care of outpatients on OACT. In 2010, a multidisciplinary outpatient clinic for patients on OACT (Raadpleging voor patiënten op Orale antitumorale Therapie Sint-Lucas, ROTS) was initiated at Sint-Lucas general hospital in Belgium. The ROTS outpatient service focuses on providing specialised counselling, support, and follow-up (by visit, phone, or mail) to provide a costeffective therapy and improve patients’ adherence in close collaboration with all healthcare providers (HPs). The CPs provided different interventions in the outpatient clinic. This report aims to evaluate the role and usefulness of this outpatient service. Specific objectives included a) number and type of interventions to assure safe, effective and cost-effective drug therapy, b) survey for adherence and satisfaction about counselling for patients, and c) satisfaction survey for physicians about the collaboration. Over a first five year period, a total of 2,974 interventions were performed on 181 patients, mainly consisting of ADE assessment and management, medication reconciliation and review, and adherence review and reinforcement, mostly by direct contact with the patients or remote via e-mail or telephone. In a recent survey, patients and HPs perceived these interventions as very useful, and the satisfaction rate about the provided information and ADEs management was high. In conclusion, our approach to setting up an outpatient service is well accepted by patients and HPs, showing the feasibility of integrating clinical pharmacy services in the multidisciplinary approach to the treatment of cancer patients.

(BELG J MED ONCOL 2022;16(3):133–41)

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Paving the way for immunotherapy in pancreatic cancer by exploring a novel combination immunotherapy consisting of a CD40 agonist and interleukin-15

BJMO - volume 15, issue 3, may 2021

E.L.J.M Smits PhD, G. Roeyen MD, PhD, J.R.M. Van Audenaerde PhD, M. Peeters MD, PhD


Pancreatic Ductal Adenocarcinoma (PDAC) has the worst 5-year survival of all cancer types. Treatment options for these patients are limited and consist mainly of chemotherapy. However, the unique tumour microenvironment with its dense, fibrotic shield causes resistance to current and novel therapies. Tackling this stromal shield is therefore deemed crucial for making progress in PDAC treatment. We investigated in this thesis the potential of Natural Killer (NK) cells to address this high medical need. Firstly, our systematic review revealed strong evidence of their importance in PDAC and how the tumour renders them into a suppressed and less functional state. Based on this information, we sought to stimulate NK cells in such way that they attack both tumour and surrounding stroma. We show that, upon stimulation with IL-15, NK cells are capable of killing both pancreatic cancer and stellate cells, the drivers of the stromal reaction, in a contact-dependant manner. Increased expression of NKG2D and TIM-3 receptors was partially responsible for this enhanced killing. Furthermore, in our search to potentiate IL-15 stimulation, we combined this with an immune priming CD40 agonist and demonstrated profound anti-tumour effects and prolonged survival in PDAC mouse models. Increased intra-tumoral cytotoxic T cells, NK cells and reduced T regulatory cells combined with increased cross-presenting dendritic cells in the tumour draining lymph nodes are the main effectors of the observed anti-tumour effects. Summarised, our data provide a strong rationale for NK cell-driven cancer immunotherapy where immune stimulation is combined with immune priming. Initiation of an early-phase clinical trials with this novel combination immunotherapy for PDAC patients is warranted.

BELG J MED ONCOL 2021;15(3):128-31

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Optimising target volume definition and treatment accuracy in oesophageal cancer

BJMO - volume 15, issue 2, march 2021

M. Machiels MD, PhD


On May 29th, 2020, M. Machiels defended her PhD thesis entitled ‘Optimising target volume definition and treatment accuracy in oesophageal cancer‘. The research was carried out at the Amsterdam UMC, location AMC under supervision of promotor prof. C.R.N. Rasch, MD, PhD, with dr. M.C.C.M. Hulshof, MD, PhD and Mrs. T. Alderliesten, PhD as co-promoters. Important findings are listed below. Full thesis is available at: http://hdl.handle.net/11245.1/2e692172-00cf-4565-b45c-04d1dffb951a.

(BELG J MED ONCOL 2021;15(2):83-6)

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Optimisation of the liquid biopsy workflow: From research to clinical practice

BJMO - volume 15, issue 1, january 2021

C. Rolfo MD, PhD, G. Roeyen MD, PhD, J. Jacobs PhD, K. Zwaenepoel PhD, L. Sorber PhD, P. Pauwels MD, PhD


The general aim of this thesis was to determine the optimal workflow of circulating cell-free nucleic acid- (cfNA) based liquid biopsy for implementation in routine clinical practice. We started by evaluating several pre-analytical variables of the liquid biopsy workflow. We examined several cfDNA isolation kits, determined the optimal centrifugation protocol for both cfDNA and cfRNA, and determined the cfDNA stabilising efficiency of (specialised) blood collection tube (BCT). Next, we focused on the clinical applicability of liquid biopsy in non-small cell lung cancer (NSCLC). Based on this work, we specified recommendations regarding (pre-) analytical and biological variables to ensure successful liquid biopsy analysis.

(BELG J MED ONCOL 2021;15(1):48-50)

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Overcoming intrinsic and acquired resistance to EGFR-targeting agents in cancer treatment: focus on identification of predictive biomarkers and novel therapeutic strategies

BJMO - volume 14, issue 4, june 2020

A. Wouters PhD, F. Lardon PhD, I. De Pauw PhD, JB. Vermorken MD, PhD, M. Peeters MD, PhD


Targeted therapies that inhibit oncogenic signalling pathways are the key for precision medicine in cancer treatment. Research over the past decades has revealed that deregulated or increased signalling of the epidermal growth factor receptor (EGFR) plays an integral role in the development of various cancer types, including colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC). After initially promising results of EGFR-targeted therapies, it became clear that therapeutic resistance is a major clinical problem. Moreover, as an increasing number of patients are currently considered as candidates for treatment with EGFR-targeted therapy, identification of predictive biomarkers is extremely important. The objective of this PhD project was to unravel and overcome resistance to the EGFR-targeting agent cetuximab in CRC and HNSCC. Hereby, we focused on the identification of drug resistance mechanisms, novel drug targets and therapeutic strategies as well as predictive biomarkers.

The present study demonstrated that afatinib, a second-generation irreversible inhibitor of EGFR, HER2 and HER4, has the potential to overcome cetuximab resistance in CRC and HNSCC cell lines. Therefore, these data support the hypothesis that afatinib may be a promising therapeutic agent to treat CRC and HNSCC patients experiencing intrinsic or acquired cetuximab resistance. Furthermore, we found that increased phosphorylation of Akt seems to be characteristic for acquired cetuximab resistance in HNSCC. Although further confirmation in tumour samples of HNSCC patients is imperative, Akt appears a novel drug target to improve outcome after cetuximab treatment as well as a potential predictive biomarker for EGFR-targeted therapies in HNSCC patients. In this view, we encourage further studies that focus on targeting Akt in combination with cetuximab, as this may be a promising strategy to overcome drug resistance in HNSCC patients. These findings can form a solid basis for further experiments with advanced in vitro and in vivo models.

(BELG J MED ONCOL 2020;14(4):155–8)

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Geriatric oncology: targeting older patients with cancer

BJMO - volume 14, issue 3, may 2020

C. Kenis PhD, H. Wildiers MD, PhD, J. De Grève MD, PhD, L. Decoster MD, PhD


As the cancer population ages, treatment decisions in the older patients should not only be guided by the tumour characteristics but also by patient characteristics. The performance of a comprehensive geriatric assessment as well as a health related quality of life evaluation are important in order to deliver the optimal personalised care in older patients with cancer. The current PhD thesis focused on the use of screening tools, geriatric assessment and interventions as well as on health-related quality of life in older patients with cancer.

(BELG J MED ONCOL 2020;14(3):106–8)

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