BackgroundNumerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal p...Show moreBackgroundNumerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials.MethodsIn this multimethod analysis, data from 1801 women participating in the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials were used for statistical analyses and causal inference. The cohort included 714 patients with intermediate-risk endometrial cancer, 427 patients with high-intermediate risk endometrial cancer, and 660 patients with high-risk endometrial cancer. Associations of age with clinicopathological and molecular features were analysed using non-parametric tests. Multivariable competing risk analyses were performed to determine the independent prognostic value of age. To analyse age as a causal prognostic variable, a deep learning causal inference model called AutoCI was used.FindingsMedian follow-up as estimated using the reversed Kaplan-Meier method was 12·3 years (95% CI 11·9–12·6) for PORTEC-1, 10·5 years (10·2–10·7) for PORTEC-2, and 6·1 years (5·9–6·3) for PORTEC-3. Both overall recurrence and endometrial cancer-specific death significantly increased with age. Moreover, older women had a higher frequency of deep myometrial invasion, serous tumour histology, and p53-abnormal tumours. Age was an independent risk factor for both overall recurrence (hazard ratio [HR] 1·02 per year, 95% CI 1·01–1·04; p=0·0012) and endometrial cancer-specific death (HR 1·03 per year, 1·01–1·05; p=0·0012) and was identified as a significant causal variable.InterpretationThis study showed that advanced age was associated with more aggressive tumour features in women with endometrial cancer, and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone. Show less
Bosch, S. van den; Takes, R.P.; Ridder, M. de; Bree, R. de; Al-Mamgani, A.; Schreuder, W.H.; ... ; Kaanders, J.H.A.M. 2024
BackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable... Show moreBackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life.Methods/designThis is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment.DiscussionIf this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care. Show less
Jong, M.A. de; Adegeest, E.; Bérenger-Currias, N.M.L.P.; Mircea, M; Merks, R.M.H.; Semrau, S. 2023
Introduction: Diagnosing Meniere's disease (MD) by its characteristics such as episodes of vertigo, fluctuating hearing loss, and tinnitus with aural fullness remains challenging. Available tests... Show moreIntroduction: Diagnosing Meniere's disease (MD) by its characteristics such as episodes of vertigo, fluctuating hearing loss, and tinnitus with aural fullness remains challenging. Available tests evaluating the presence of endolymphatic hydrops (EH) are often expensive or time assuming. An in-office quick and simple non-invasive diagnostic test is multifrequency tympanometry (MFT). It can measure conductance at 2 kHz probe tones, which was demonstrated to reflect variations in cochlear pressure. Previous studies investigating MFT as a diagnostic test for MD showed conflicting outcomes possibly biased by their retrospective design. Methods: We prospectively collected MFT results (Y width) in patients with dizziness and compared MFT test results in affected (group 1) and unaffected (group 2) ears of 37 MD subjects and in control ears of 33 non-MD subjects (group 3). Results: The mean value of the Y width in affected ears was 315.6 +/- 70.2 daPa compared to 292.3 +/- 98.6 daPa in unaffected ears in MD subjects and 259.4. +/- 60.6 daPa in the non-MD group. A positive test result (i.e., a Y width of 235 daPa or more) was found in 35 ears in the MD group, 21 times involving the affected ear and 14 times involving the unaffected ear, compared to 16 in the non-MD group. No significant differences between the three groups could be demonstrated (p > 0.05). We found a sensitivity of 58.3% and specificity of 66.3% for detecting EH in an affected ear in MD subjects. Conclusion: There is a trend towards increased conductance tympanometry in affected ears. However, we noticed a high false positive rate of MFT and do not support standardized use of MFT as an additional diagnostic tool for detecting EH in MD patients. A negative test result on the contrary is unlikely related to EH. Show less
Hendriksma, M.; Heijnen, B.J.; Verbist, B.M.; Jong, M.A. de; Langeveld, A.P.M.; Benthem, P.P.G. van; Sjogren, E.V. 2022
Objective: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. Methods: A... Show moreObjective: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. Methods: A cross-sectional study was performed on patients who were treated with radiotherapy for T2N0 glottic carcinoma. Four questionnaires were used to measure different aspects of functional outcome. In addition, objective evaluation and perceptual analysis were performed. Results: Fourteen patients were included in this study. The median time between the start of radiotherapy and assessment was 42 months (range, 26-143 months). Patients reported high-level functioning, with low symptom scores and good swallowing function, and showed a median dysphonia grade of 1.5. The median Voice Handicap Index-30 score was 17.5. Conclusion: Patients with T2N0 glottic carcinoma treated with radiotherapy had good long-term quality of life, with low symptom scores, good swallowing functioning and slightly elevated voice outcome parameters. Show less
Hendriksma, M.; Heijnen, B.J.; Verbist, B.M.; Jong, M.A. de; Langeveld, A.P.M.; Benthem, P.P.G. van; Sjgren, E.V. 2022
ObjectiveTo evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour–node stage T2N0 glottic carcinoma, stratified for tumour extension.MethodsA cross... Show moreObjectiveTo evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour–node stage T2N0 glottic carcinoma, stratified for tumour extension.MethodsA cross-sectional study was performed on patients who were treated with radiotherapy for T2N0 glottic carcinoma. Four questionnaires were used to measure different aspects of functional outcome. In addition, objective evaluation and perceptual analysis were performed.ResultsFourteen patients were included in this study. The median time between the start of radiotherapy and assessment was 42 months (range, 26–143 months). Patients reported high-level functioning, with low symptom scores and good swallowing function, and showed a median dysphonia grade of 1.5. The median Voice Handicap Index-30 score was 17.5.ConclusionPatients with T2N0 glottic carcinoma treated with radiotherapy had good long-term quality of life, with low symptom scores, good swallowing functioning and slightly elevated voice outcome parameters. Show less
Steenbeek, M.P.; Harmsen, M.G.; Hoogerbrugge, N.; Jong, M.A. de; Maas, A.H.E.M.; Prins, J.B.; ... ; Hullu, J.A. de 2021
IMPORTANCE Most women with a BRCA1/2 pathogenic variant undergo premature menopause with potential short- and long-term morbidity due to the current method of ovarian carcinoma prevention: risk... Show moreIMPORTANCE Most women with a BRCA1/2 pathogenic variant undergo premature menopause with potential short- and long-term morbidity due to the current method of ovarian carcinoma prevention: risk-reducing salpingo-oophorectomy (RRSO). Because the fallopian tubes play a key role in ovarian cancer pathogenesis, salpingectomy with delayed oophorectomy may be a novel risk-reducing strategy with benefits of delaying menopause.OBJECTIVE To compare menopause-related quality of life after risk-reducing salpingectomy (RRS) with delayed oophorectomy with RRSO in carriers of the BRCA1/2 pathogenic variant.DESIGN, SETTING, AND PARTICIPANTS A multicenter nonrandomized controlled preference trial (TUBA study), with patient recruitment between January 16, 2015, and November 7, 2019, and follow-up at 3 and 12 months after surgery was conducted in all Dutch university hospitals and a few large general hospitals. In the Netherlands, RRSO is predominantly performed in these hospitals. Patients at the clinical genetics or gynecology department between the ages of 25 and 40 years (BRCA1) or 25 to 45 years (BRCA2) who were premenopausal, had completed childbearing, and were undergoing no current treatment for cancer were eligible.INTERVENTIONS Risk-reducing salpingo-oophorectomy at currently recommended age or RRS after completed childbearing with delayed oophorectomy. After RRSO was performed, hormone replacement therapy was recommended for women without contraindications.MAIN OUTCOMES AND MEASURES Menopause-related quality of life as assessed by the Greene Climacteric Scale, with a higher scale sum (range, 0-63) representing more climacteric symptoms. Secondary outcomes were health-related quality of life, sexual functioning and distress, cancer worry, decisional regret, and surgical outcomes.RESULTS A total of 577 women (mean [SD] age, 37.2 [3.5] years) were enrolled: 297 (51.5%) were pathogenic BRCA1 variant carriers and 280 (48.5%) were BRCA2 pathogenic variant carriers. At the time of analysis, 394 patients had undergone RRS and 154 had undergone RRSO. Without hormone replacement therapy, the adjusted mean increase from the baseline score on the Greene Climacteric Scale was 6.7 (95% CI, 5.0-8.4; P < .001) points higher during 1 year after RRSO than after RRS. After RRSO with hormone replacement therapy, the difference was 3.6 points (95% CI, 2.3-4.8; P < .001) compared with RRS.CONCLUSIONS AND RELEVANCE Results of this nonrandomized controlled trial suggest that patients have better menopause-related quality of life after RRS than after RRSO, regardless of hormone replacement therapy. An international follow-up study is currently evaluating the oncologic safety of this therapy. Show less
Background: Local recurrence after radiotherapy for T2 glottic carcinoma remains an issue and identifying patients at risk for relapse is, therefore, important. This study aimed to assess the... Show moreBackground: Local recurrence after radiotherapy for T2 glottic carcinoma remains an issue and identifying patients at risk for relapse is, therefore, important. This study aimed to assess the oncological outcomes and prognostic factors in a consecutive series of patients treated with radiotherapy for T2N0 glottic carcinoma. Methods: Patients with T2N0 glottic carcinoma treated with radiotherapy were included in this retrospective study. Five- and ten-year local control (LC), overall survival (OS), disease-specific survival (DSS), and laryngeal preservation (LP) rates were calculated with the Kaplan-Meier method. The impact of prognostic variables was evaluated with the log-rank test. Results: Ninety-four patients were included for analysis. LC, OS, DSS, and LP rates were 70.5, 63.7, 86.0, and 74.7%, respectively at five years and 65.8, 41.0, 75.6, and 72.4% at 10 years. In total, 46 scans were included in the analyses. Vertical involvement of the anterior commissure on imaging showed a significant impact on LC. Conclusions: In accordance with previously described surgical risk factors, we identified vertical involvement of the anterior commissure on imaging as a prognostic factor for radiation failure. Show less
Loon, Y. van; Hendriksma, M.; Heijnen, B.J.; Kamp, V.A.H. van de; Hakkesteegt, M.M.; Bohringer, S.; ... ; Sjogren, E.V. 2019
Objective: For early glottic carcinoma, the 2 main treatment modalities are radiotherapy (RT) and transoral CO2 laser microsurgery (TLM). The aim of this study was to investigate treatment... Show moreObjective: For early glottic carcinoma, the 2 main treatment modalities are radiotherapy (RT) and transoral CO2 laser microsurgery (TLM). The aim of this study was to investigate treatment preferences and considerations in patients with early glottic carcinoma (T1-T2) who were given a choice between TLM and RT.Subjects and Methods: Patients with early glottic cancer (suspected or confirmed extended T1 or limited T2) were counseled by an ENT-surgeon. A subset of 32 patients was also counseled by a radiotherapist. Treatment choice and considerations were recorded and analyzed.Results: Of 175 patients, 168 patients (96%) chose TLM, and 7 patients (4%) chose RT. The most common reason for choosing TLM was shorter treatment and more treatment options in case of recurrence. Subanalysis showed that additional counseling by the radiotherapist did not seem to affect our patients' preferences for TLM in this group.Conclusions: The majority of patients in our study prefer TLM to RT when given a choice. Reasons given indicate that optimizing future treatment options and practical considerations seemed more important to our patients than primary functional outcome. Further research is needed to study patient-related and physician-related factors to gain more insight into this complicated process of shared decision making. Show less
Jong, M.A. de; Hysi, P.; Spector, T.; Niessen, W.; Koudstaal, M.J.; Wolvius, E.B.; ... ; Bohringer, S. 2018
