The studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS)... Show moreThe studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS) studies, unbiased cohorts were used within the international Grand Challenge PRECISION consortium, funded by Cancer Research UK and KWF Dutch Cancer Society. DCIS is graded as low-, intermediate-, or high-grade depending on how abnormal the DCIS-cells look like. However, we showed that pathologists often disagree on grade. To overcome this limitation, we found that almost all DCIS scored as non-high-grade by the majority of pathologists express the estrogen receptor (ER) and are negative for the growth factor receptor HER2, whereas high-grade DCIS is mixed in expression for ER and HER2. We also provided insights in the recurrence risks of DCIS after treatment. See also https://cancergrandchallenges.org/teams/precision.The studies on Invasive Breast Cancer (IBC) were performed on a hospital-based cohort. We found for example substantial variation in tumour response evaluation for HER2-positive IBC after pre-operative chemotherapy due to different guidelines used. For accurate outcome analysis, reducing such variation is mandatory. Therefore, we are working on reaching international consensus of response evaluation. Show less
Bone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors... Show moreBone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors, including the symptoms, the location and extent of the lesion, the wishes and expectations of the patient, and the expected remaining survival. Survival estimation of patients with symptomatic long bone metastases is crucial to prevent over- and undertreatment. This thesis aimed to develop a prognostic model for estimating survival in patients with cancer and symptomatic metastases of the long bones, evaluate current (surgical) treatment modalities and trends, and provide rationale for future prospective randomized trials. As a result, the OPTIModel was developed: an easy-to-use prognostic model that categorises patients into four clinically relevant survival categories based on only three variables (tumour type, Karnofsky Performance Score, visceral/brain metastases). To enable easy use of the model, an app was created (OPTIModel). Futhermore, this thesis shows that almost all treatments of pathologic fractures are based on expert opinion and small, retrospective cohorts, as opposed to large, prospective (randomized) trials, which is interesting in an era of evidence based medicine. This confirms the need of a prospective, multicenter cohort, which was designed and implemented accordingly. Show less
The frequently diagnosed lumbar disc herniation can disappear by natural course, but still leads to high low back surgery rates. The optimal period of conservative care, before surgery is executed,... Show moreThe frequently diagnosed lumbar disc herniation can disappear by natural course, but still leads to high low back surgery rates. The optimal period of conservative care, before surgery is executed, was unknown. It is surprising that scientific evidence was lacking which justified “early” surgery. Surgery, after 6-12 weeks of sciatica, was compared to prolonged conservative care in 283 patients in a randomized study. Primary outcomes were perceived recovery, leg pain intensity and functioning. Early surgery resulted in a 2 times faster recovery rate, compared to prolonged conservative care. From the latter group 39 percent of patients could not evade surgery. Within one year, however, both groups presented similar recovery rates and outcome. The impossibility to sit, because of sciatica, seemed to be a good argument to decide for early surgery. Intense pain and disability were predictors for delayed surgery. Compared to men, females exhibited a 3 times higher odds to develop chronic pain. The higher medical costs of early surgery were fully compensated by quick resumption of working capacity. From a medical point of view one may favor a prolonged wait-and-see strategy but our western society urges patients to decide for early surgery to resume daily activities. Show less
