Proefschriften

Dr. Karlijn H.J. Groenen

Titel proefschrift : Spinal (in)stability in metastatic bone disease. Experimental, computational and clinical perspectives.
Universiteit : faculteit der Geneeskunde van de Radboud Universiteit Nijmegen.
Promotor : prof. dr. ir. N.J.J. Verdonschot.
Co-promotoren : dr. E.J.M. Tanck, dr. Y.M. van der Linden.
Promotiedatum: 17 april 2018.



Samenvatting: 

Increasing cancer incidence rates together with prolonged survival will result in more cancer patients being confronted with the clinical consequences of spinal bone metastases. Estimating current or future spinal instability or stability plays an important role in treatment decisions on whether to use non‐invasive local therapies such as radiotherapy or to perform stabilizing surgical interventions, or combinations of these. However, is mostly done by relying on the clinical experience of involved physicians. The goal of this work was to improve the assessment of spinal (in)stability in patients suffering from metastatic spinal bone disease. 

Link naar proefschrift:
“Spinal (in)stability in metastatic bone disease. Experimental, computational and clinical perspectiveshttp://hdl.handle.net/2066/187343


Dr. Joanne M. van der Velden

Titel proefschrift : Towards personalized treatment for patients with bone metastases.
Universiteit : faculteit der Geneeskunde van de Universiteit Utrecht.
Promotoren : prof. dr. H.M. Verkooijen, prof. dr. J.J.W. Lagendijk.
Co-promotoren : dr. J.J. Verlaan, dr. Y.M. van der Linden.
Promotiedatum:4 april 2018.


Samenvatting:

Many patients with cancer develop bone metastases with pain as an important symptom impacting on quality of life. Conventional radiotherapy is the standard local treatment, effective in a small majority of patients (61%). In patients with spinal instability, radiotherapy might be less effective. We found an association between spinal stability and a complete pain response after radiotherapy, supporting this hypothesis. Furthermore, the VERTICAL trial was initiated to quantify the effect of SBRT in patients with bone metastases. SBRT involves high precision, high dose delivery to the target volume while sparing healthy tissues. Accurate and consistent delineation of the target volume is therefore crucial in SBRT. In our delineation study, considerable differences in interpretation of the tumor volumes were found. The use of MRI result in the highest inter-observer agreement. After spinal SBRT, a serious adverse effect is the occurrence of compression fractures. A simultaneous integrated boost (SIB) approach was proposed, designed to spare bone surrounding the metastasis to mitigate this risk. 

Link naar proefschrift: “Towards personalized treatment for patients with bone metastaseshttps://www.narcis.nl/publication/RecordID/oai:dspace.library.uu.nl:1874/363195/uquery/Towards personalized treatment for patients with bone metastases/id/1/Language/NL   


Dr. Paulien G. Westhoff

Titel proefschrift : Quality of life in painful bone metastases: results from the Dutch bone metastasis study.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotor : prof. dr. C.A.M. Marijnen.
Co-promotoren : dr. A. de Graeff, dr. Y.M. van der Linden.
Promotiedatum: 21 februari 2018.
 


Samenvatting:

This thesis focuses on several aspects of quality of life in patients with painful bone metastases, treated with palliative radiotherapy within the randomized Dutch Bone Metastasis Study. The detailed course of quality of life after treatment was studied, as was the relation between a pain response and quality of life. Also prognostic factors predicting a pain response, psychological distress, side-effects and survival were studied.

Link naar proefschrift: “Quality of life in painful bone metastases: results from the Dutch bone metastasis studyhttp://hdl.handle.net/1887/61149


Dr. Yuchuan Qiao

Titel proefschrift : Fast optimization methods for image registration in adaptive radiation therapy.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotor : prof. dr. ir. B.P.F. Lelieveldt.
Co-promotor : dr. ir. M. Staring.
Promotiedatum: 1 november 2017.



Samenvatting:

In this thesis we developed several stochastic optimization methods for fast image registration, leading to a 5-10 fold speedup over previous approaches. All proposed methods are implemented using C++ and integrated in the open source registration package elastix. We also exploited the usage of high performance computation resources -- the life science grid (lsgrid) to perform over $10^6$ registrations, which significantly reduced computation time for large scale computational tasks. As we have evaluated the proposed method in the application of online adaptive IMPT for prostate cancer, we expect that these methods can achieve the desirable performance for use in clinical practice.

Link naar proefschrift: “Fast optimization methods for image registration in adaptive radiation therapyhttp://hdl.handle.net/1887/59448

 

Dr. Rinse M. Bakker

Titel proefschrift : Sexual rehabilitation after treatment for gynaecological cancer.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotoren : prof. dr. C.L. Creutzberg, prof. dr. J.B.M.Z. Trimbos.
Co-promotor : dr. M.M. ter Kuile.
Promotiedatum:  16 mei 2017.
 


Samenvatting:

In this thesis, quantitative and qualitative evidence was gathered in an attempt to improve and extend the current sexual health care of gynaecological cancer survivors. Although surgery has a major impact on sexual functioning, vaginal changes and symptoms have been shown to be more profound after intensive radiotherapy. Therefore, the studies in this thesis were especially focused on gynaecological cancer survivors who received radiotherapy, and mainly concerned cervical cancer patients; a relatively young patient population often treated with intensive external-beam radiation therapy (EBRT) in combination concurrent chemotherapy, and intrauterine and vaginal brachytherapy (BT), although the results are equally relevant to other gynaecological cancer patients treated with EBRT with or without BT. In order to assess what type of patient education and/or support would be needed to minimise the impact of gynaecological cancer treatment on sexual functioning, and to improve the survivors’ sexual recovery we followed several approaches: assessment of survivors’ experience with sexual distress after treatment, and unmet needs for psychosexual counselling and support; it was explored how survivors and professionals could best deal with treatment-induced vaginal changes; and, partly based on the previous findings, a sexual rehabilitation intervention was developed and evaluated in a pilot study.

Link naar proefschrift:Sexual rehabilitation after treatment for gynaecological cancer” https://openaccess.leidenuniv.nl/handle/1887/49750


Dr. Ellen Stelloo

Titel proefschrift : Molecular alterations in endometrial cancer: implications for clinical management.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotoren : prof. dr. V.T.H.B.M. Smit, prof. dr. C.L. Creutzberg.
Co-promotor : dr. T. Bosse.
Promotiedatum : 20 april 2017.
 


Samenvatting:

Over the last decades, advances have been made in the treatment of endometrial cancer. The clinicopathological risk stratification for postoperative therapy has considerably reduced overtreatment by refining indications and introducing treatment with fewer side effects. Despite refinement in the use of postoperative radiation therapy in EC, over- and under- treatment remain a clinical problem. This may be caused by the limited accuracy of the clinicopathological risk stratification to select patients of higher risk of recurrence. The lack of reproducibility of pathologists to diagnose tumor type and grade may also limit the accuracy of the clinicopathological risk stratification. Expert gyneco-pathology review and a two-tiered grading system will lead to more accurate and reproducible diagnoses. Nonetheless, there is pressing need to understand tumor behavior and design tailored treatments to further improve risk stratification. The identification of molecular markers predictive of recurrence risk or treatment benefit beyond current clinicopathological factors would represent a major advance. The aims of this thesis were to gain insight in the molecular alterations of endometrial cancer and to identify prognostic markers in endometrial cancer to refine clinicopathological risk assessment and direct adjuvant therapy.

Link naar proefschrift: “Molecular alterations in endometrial cancer: implications for clinical management” https://openaccess.leidenuniv.nl/handle/1887/48189

        

Dr. Lisette M. Wiltink

Titel proefschrift : Long-term effects and quality of life after treatment for rectal cancer.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotor : prof. dr. C.A.M. Marijnen.
Co-promotor : dr. R.A. Nout.
Promotiedatum : 8 maart 2017.
                              


Samenvatting:

In this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with rectal cancer were included between 1996 and 1999. These patients were randomly assigned to total mesorectal excision (TME) or to short-course preoperative radiotherapy (5x5 Gy) followed by TME surgery.

Link naar proefschrift: “Long-term effects and quality of life after treatment for rectal cancer” https://openaccess.leidenuniv.nl/handle/1887/46445

         

Dr. Loes C.E.M. Derikx

Titel proefschrift : Femoral fracture risk prediction in metastatic bone disease.
Universiteit : faculteit der Geneeskunde van de Radboud Universiteit Nijmegen.
Promotoren : prof. dr. ir. N.J.J. Verdonschot, prof. dr. I. Jonkers.
Co-promotoren : dr. E.J.M. Tanck, dr. Y.M. van der Linden.
Promotiedatum : 19 november 2015.
 


Link naar proefschrift: “Femoral fracture risk prediction in metastatic bone diseasehttp://hdl.handle.net/2066/145312

 

Dr. Marjan van Hezewijk

Titel proefschrift : Tailoring follow-up in early-stage breast cancer.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotoren : prof. dr. C.A.M. Marijnen, prof. dr. C.J.H. van de Velde.
Co-promotor : dr. A.N. Scholten.
Promotiedatum : 13 mei 2015.
 


Samenvatting:

In this thesis the feasibility of tailored follow-up for early-stage breast cancer patients is evaluated. In order to do so, we first determined the risk of loco-regional recurrence (LRR) dependent on local treatment in a large cohort of low-risk breast cancer patients, treated with adequate modern systemic therapy. In the second part we evaluated both patients’ and professionals’ needs and preferences for breast cancer follow-up and we reviewed the literature on cost effectiveness of known follow-up schedules. Finally we prospectively examined whether the implementation of a tailored follow-up programme, based on a prognostic index for LRR, is feasible and acceptable to patients and professionals. The results show that in general, implementation of minimised tailored follow-up seems feasible, but professionals tend to more frequent follow-up. Patients accept less intensive follow-up schedules and follow-up by a nurse practitioner. Given the low risk of LRR, tailoring should not only be done based on this risk, but individually, based on the presence of treatment related side effects, either physical or psychosocial. If patients do not experience side effects, annual planned mammography and telephone contact coordinated by a single professional, preferably a specialised nurse, suffice in case of easily accessible information and on demand visits.

Link naar proefschrift: “Tailoring follow-up in early-stage breast cancer” https://openaccess.leidenuniv.nl/handle/1887/32965

 

Dr. Laurien A. Daniëls

Titel proefschrift: Late effects after treatment for Hodgkin lymphoma.
Universiteit: faculteit der Geneeskunde van de Universiteit Leiden.
Promotor: prof. dr. C.L. Creutzberg.
Co-promotor: dr. A.D.G. Krol.
Promotiedatum : 14 oktober 2014.
 

Samenvatting :

Although modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has become increasingly evident that the historically used extensive treatment fields can potentially lead to numerous long-term adverse effects, often presenting clinically with a delay of more than 10-15 years. Epidemiological studies have shown an increased risks of second malignancies in HL survivors. HL survivors treated with mediastinal radiotherapy also have increased risk of late cardiac complications such as myocardial infarction, which might be due to radiation-induced coronary artery stenosis. All these adverse effects can severely impact health-related quality of life.

 This thesis investigates the long-term sequelae that HL survivors may encounter. The long-term risk of secondary skin cancers after radiotherapy in HL survivors was evaluated, and compared to the risks in the general Dutch population. The feasibility of screening for coronary artery disease by means of computed tomography coronary angiography (CTA) in HL survivors was investigated, and also satisfaction with information provision and the psychological burden of screening. Furthermore, the prevalence of fatigue in HL survivors compared with the general Dutch population, and associations with predisposing factors were assessed.

Link naar proefschrift: “Late effects after treatment for Hodgkin lymphoma” https://openaccess.leidenuniv.nl/handle/1887/29128

         

Dr. Jan J. Meeuse

Titel proefschrift : Aspects of pain in measurement, management and health care utilization.
Universiteit : faculteit der Medische Wetenschappen van de Universiteit Groningen.
Promotoren : prof. dr. R.O.B. Gans.
Co-promotoren : dr. Y.M. van der Linden, prof. dr. A.K.L. Reyners.
Promotiedatum : 11 september 2013.

Samenvatting :

This thesis describes various aspects of pain. It aims to contribute to improve pain measurement, treatment, and the relationship between pain and health care consumption. To develop an instrument for patients who are not able to indicate their pain intensity, the association between heart rate variability with pain intensity was studied in 75 healthy volunteers. Although changes occurred in heart rate variability during pain, these changes were not correlated with the perceived pain intensity. Radiotherapy is effective for painful bone metastases. Since pain relief is not always immediate and is sometimes preceded by an increase in pain, we examined whether radiotherapy is useful in patients with a short life expectancy. In a sub-analysis of 274 patients from the Dutch Bone Metastases Study, who deceased within 12 weeks after radiotherapy, 45% showed a decrease in pain. Nonetheless, in 60% of them the pain remained moderate to severe. The hypothesis that people experience less pain if they are distracted, e.g. by music, was studied in 245 patients who underwent sigmoidoscopy. Whether or not you listen to music did not affect the perceived pain intensity. Care during the last weeks of life is preferably provided at the patients’ home, according to the Dutch model. In a sub-analysis of the Dutch Bone Metastases Study we found, that during these weeks an increase in GP contacts was not accompanied with a reduction in hospital based care. A transmural multidisciplinary palliative team may help to avoid unnecessary hospital visits.

Link naar nieuwsbericht verdediging proefschrift: “Aspects of pain in measurement, management and health care utilization” https://www.rug.nl/about-us/news-and-events/events/phd-ceremonies/2013/28-meeuse

          

Dr. Remi A. Nout

Titel proefschrift : Post-operative radiation therapy in endometrial carcinoma : reducing overtreatment and improving quality of life.
Universiteit : faculteit der Geneeskunde van de Universiteit Leiden.
Promotoren : prof. dr. C.L. Creutzberg, prof.dr. C.A.M. Marijnen.
Co-promotor : prof. dr. V.T.H.B.M. Smit.
Promotiedatum : 17 april 2013.
 

Samenvatting :

This thesis describes the results of the first and second Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials. The 15-year results of PORTEC-1 confirm the importance of the prognostic factors age, grade and depth of myometrial invasion for selection of patients with high-intermediate risk (HIR) features. Postoperative pelvic external beam radiotherapy (EBRT) reduces the risk of loco-regional recurrence (mainly due to a decrease in vaginal recurrences), without a survival benefit compared to no additional therapy. The PORTEC-2 trial has shown that EBRT and vaginal brachytherapy (VBT) offer excellent rates of vaginal control and similar overall survival for HIR patients, while VBT has a clearly more favourable health related quality of life profile, with results similar to an age-matched norm population. EBRT is associated with a higher risk of long-lasting bowel symptoms that impact on patients’ daily lives and physical functioning. Therefore, VBT is the treatment of choice for HIR patients. Finally, a pilot study in PORTEC-2 patients showed that the presence of multiple activated oncogenic pathways was the most powerful independent prognostic factor for decreased disease free survival, indicating that molecular prognostic factors refine the currently used system for risk classification.

Link naar proefschrift: “Post-operative radiation therapy in endometrial carcinoma : reducing overtreatment and improving quality of life” https://openaccess.leidenuniv.nl/handle/1887/20755