Johan Menten
Catholic University Leuven (Belgium), Oncology, Faculty Member
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Purpose Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long - term side effects are of considerable concern. A... more
Purpose Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long - term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. Methods We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. Results We included 169 patients with a median age of 51 years (range 22–84). Every patient received fractionated radiotherapy using photons with a median dose of 56 Gy (range 54–56) in fractions of 2 Gy (range 1.8–2). The median follow-up was 5.3 years (range 0.1–14). The cumulative stroke incidence function showed an incidence of 11.6% after 9 years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p < 0.001). 5-year local control and overall survival rates were respectively 97.4% and 91.2%. Other late grade III/IV toxicities occurred in 16.0% (27/169) of patients. Conclusion Our study shows a higher incidence of stroke in patients who received radiotherapy for their benign meningioma compared to the general population.
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1560 Background: Temozolomide (TemodalR, TMZ) is an active alkylating agent for the treatment of gliomas. Conventional dosing of TMZ consists of an oral dose of 150–200 mg/m2/day for 5 consecutive days every 28 days. Extended daily dosing... more
1560 Background: Temozolomide (TemodalR, TMZ) is an active alkylating agent for the treatment of gliomas. Conventional dosing of TMZ consists of an oral dose of 150–200 mg/m2/day for 5 consecutive days every 28 days. Extended daily dosing of TMZ might be more active because of the depletion of the AGAT repair protein. TMZ administered for 21 consecutive days (at a dose of 100 mg/m2/day) every 28 days, is being tested in a multicenter Belgian phase II study for the treatment of recurrent anaplastic (oligo)astrocytoma. We report the toxicity that was associated with this regimen at the occasion of the first interim monitoring of the adverse events. Methods: For the monitoring of toxicity (CTCAEv3.0), the protocol requested a weekly clinical and hematological evaluation during the first 8 wks and every 2 wks thereafter. An interim analysis was carried out for the toxicity seen during the first 67 administered treatment cycles. Results: 17 patients (pts) were recruited into this study (4 F, 13 M; median age 4...
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LBA2 Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed glioblastoma (GB) showed increased overall survival (OS) with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Pts were 18-71 (median... more
LBA2 Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed glioblastoma (GB) showed increased overall survival (OS) with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Pts were 18-71 (median 56) years; however, a trend of decreasing benefit from the addition of TMZ with increasing age was noted. Recent RCTs in elderly GB detected non-inferiority of 40 Gy/15 v 60 Gy/30 RT and superior survival was noted for MGMT-methylated pts treated with TMZ alone. However, whether the addition of TMZ to RT improves survival in elderly pts remained unanswered. Methods: We conducted a global randomized phase III clinical trial for patients ≥ 65 yrs with histologically confirmed newly diagnosed GB, ECOG 0-2, randomized 1:1 to receive 40Gy/15 RT v 40Gy/15 RT with 3 weeks of concomitant TMZ plus monthly adjuvant TMZ until progression or 12 cycles. Stratification was by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. Results: 562 pts were randomized, 281 on each arm; median age 73 yrs (range 65-90), male 61%, PS 0/1 77%, resection 68%. RT+TMZ significantly improved OS over RT alone (median 9.3m v 7.6m, HR 0.67, 95%CI 0.56-0.80, p &lt; 0.0001) and significantly improved PFS (median 5.3m v 3.9m, HR 0.50, 95%CI 0.41 – 0.60, p &lt; 0.0001). Tissue from 462 pts was provided and adequate for MGMT analysis in 354 to date. In MGMT methylated patients (n = 165) OS for RT+TMZ v RT was 13.5 m and 7.7m respectively (HR: 0.53 (95% C.I. 0.38, 0.73, p = 0.0001). In MGMT unmethylated patients (n = 189) OS for RT + TMZ v RT was 10.0m vs 7.9m respectively (HR 0.75 (95% C.I. 0.56 – 1.01, p = 0.055). QoL analyses showed no differences in functional domains of QLQC30 and BN20 but were worse in the RT/TMZ arm for nausea, vomiting, and constipation. Systemic therapy after PD was reported in 39% on RT+TMZ v 41% on RT. Conclusions: The addition of concomitant and adjuvant TMZ to hypofractionated RT for elderly pts with GB significantly improves OS and PFS in all patients and is well tolerated. Patients with MGMT methylated tumors benefit the most from the addition of TMZ to RT where median OS is nearly doubled. Clinical trial information: NCT00482677.
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To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All... more
To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All patients were in complete remission after combined modality treatment with IV and intrathecal high-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT). An extensive neuropsychological assessment, including QOL measures, was conducted in 19 patients with PCNSL. The results were compared with matched control subjects with systemic hematologic malignancies treated with systemic chemotherapy or non-CNS radiotherapy. In addition, a neuroradiologic evaluation was carried out in 18 patients with PCNSL. Cognitive impairment was found in 12 patients with PCNSL (63%) despite a complete tumor response. Four patients (21%) showed severe cognitive deficits, and the percentage of impaired test indices correlated with age. In comparison, only two control subjects (11%) showed cognitive dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in contrast to 81% of the control subjects, resumed work. White matter abnormalities were observed in 14 patients with PCNSL, and 14 had cortical atrophy. Cortical atrophy correlated with cognitive functioning, age, and Karnofsky performance score. Group differences in cognitive status and QOL could not be explained by anxiety, depression, or fatigue. Combined modality treatment for primary CNS lymphoma is associated with cognitive impairment even in patients aged &lt;60 years.
Research Interests: Cognitive Science, Chemotherapy, Medicine, Brain, Humans, and 15 moreInternal Medicine, Female, Male, Clinical Sciences, Atrophy, Adult, Methotrexate, Cognition disorders, Case Control Studies, Cohort Studies, Cerebral White Matter, Combined Modality Therapy, Methylprednisolone, Hospital Anxiety, and hydrocortisone
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2547 Background: Lymphopenia (LMP) may lead to worse outcomes for patients with glioblastoma (GBM). This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on LMP, as well as the... more
2547 Background: Lymphopenia (LMP) may lead to worse outcomes for patients with glioblastoma (GBM). This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on LMP, as well as the association of LMP with overall survival. Methods: CCTG clinical trial CE.6 randomized elderly GBM patients (≥ 65 yrs) to short course radiation alone (RT) or short course radiation with temozolomide (RT + TMZ). In this study LMP (mild-mod: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0 criteria, and measured at baseline, 1 wk and 4 wks post-RT. Pre-selected key factors for the analysis included age, sex, ECOG, extent of resection, MGMT methylation, MMSE, and steroid use. Multinomial logistic regression models were used to identify factors associated with LMP and multivariable Cox regression models were used to study effect of LMP on survival. Results: A total of 562 patients were included for analysis (281 RT vs 281 RT+TMZ). At baseline, both ...
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Introduction Breast cancer patients with a high-risk tumor (for example Triple Negative Breast Cancer) who achieve a pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) have a better outcome compared to patients... more
Introduction Breast cancer patients with a high-risk tumor (for example Triple Negative Breast Cancer) who achieve a pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) have a better outcome compared to patients with residual disease at surgery. This study investigated Breast Cancer Free Survival (BCFS) and predictors for distant relapse despite pCR. Methods Monocentric retrospective study of 243 consecutive breast cancer patients who achieved pCR (ypT0/is ypN0/N0(i+)) after treatment with NACT in UZ Leuven between 01/2000 and 08/2017. 58% had stage III breast cancer, 40% Triple Negative Breast Cancer (TNBC) and 47% HER2 pos breast cancer. BCFS was defined as any breast cancer related event (local, contra-lateral, regional, metastatic) that first appeared. Primary endpoints were frequency of BCFS and predictors for metastatic relapse: patient demographics (age, body mass index (BMI)) and tumor characteristics (TNM stage, histological type, hormonal receptor status). Secondary endpoints were breast cancer specific survival (BCSS) and overall survival (OS). Statistical analysis was performed using the Statistical Package for the Social Sciences software (SPSS, version 25). The Kaplan Meier method was used for survival analysis. Results Of 1167 breast cancer patients undergoing neoadjuvant treatment, 243 patients (20,8%) achieved pCR and were included. Median follow up was 57 months (range 9-252 months). 22 (9.1%) developed tumor progression; 20 (8.2%) metastatic and 2 (0.8%) contralateral. First metastatic site was the brain in 11/20 patients (55%) and 14/22 (64%) died of breast cancer. Higher clinical tumor stage at diagnosis predicted metastatic relapse (stage I-II 2.9%; stage III 12.1%). Patients with a BMI ≤25 kg/m2 had less metastatic relapse than patients with BMI &gt;25kg/m2 (3.8% versus 12.0%), better OS (94.6% vs 88.0%) and BCSS (97.7 vs 91.7%). Neither tumor type (TNBC 8.2%; HER2-pos 8.1%; HR-pos/HER2 neg 9.3%) nor younger age &lt; 36yrs (3.3% versus 8.9%) was prognostic for post-pCR relapse. There is a lower OS (mean 174m versus 231m, 95% CI 158-190m, median 208m) and BCSS (mean 191m versus 253m, 95% CI 182-200m) in cN1-3 versus cN0 disease at diagnosis. Conclusion Despite NACT-induced pCR, a small proportion (9.1%) will develop a metastatic relapse after a median follow-up of 57 months. We found that a higher stage at diagnosis and a higher BMI were prognostic for worse BCFS while age &lt;36 y and negative hormonal receptor status were not prognostic. cN+ at diagnosis and a BMI &gt;25 predict worse OS and BCSS. Citation Format: Borremans K, Berteloot P, Van Nieuwenhuysen E, Han S, Hoste G, Wildiers H, Punie K, Smeets A, Nevelsteen I, Floris G, Van Ongeval C, Keupers M, Prevos R, Van Limbergen E, Menten J, Weltens C, Janssen H, Vergote I, Neven P. Breast cancer recurrence and predictors for recurrence despite pathologic complete response following neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-04.
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ObjectivesPalliative sedation for existential suffering (PS-ES) is considered a controversial practice to control refractory suffering at the end of life. This study aims to explore Belgian palliative care physicians’ perceptions... more
ObjectivesPalliative sedation for existential suffering (PS-ES) is considered a controversial practice to control refractory suffering at the end of life. This study aims to explore Belgian palliative care physicians’ perceptions regarding the ethics of PS-ES.MethodsThis nationwide qualitative study follows a Grounded Theory approach. We conducted semistructured interviews with 25 palliative care physicians working in 23 Belgian hospitals and hospices (Flanders, Brussels, Wallonia). We analysed the data using the Qualitative Analysis Guide Of Leuven and we followed the Consolidated Criteria for Reporting Qualitative Research guidelines.ResultsThe data revealed that Belgian palliative care physicians have difficulty characterising ES and distinguishing it from other types of suffering. They express mixed attitudes towards PS-ES and employ a wide range of ethical arguments in favour and against it, which are mainly linked to the four principles of biomedical ethics.ConclusionSince the...
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Case description: We report on an 72-year-old male patient with a history of treated RCC who presented after 40 months with a classic but severe triad of Hakim and Adams due to hydrocephalus related to a choroid plexus mass in the... more
Case description: We report on an 72-year-old male patient with a history of treated RCC who presented after 40 months with a classic but severe triad of Hakim and Adams due to hydrocephalus related to a choroid plexus mass in the trigonum of the both lateral ventricles. Because of the severity of symptoms we decided to first treat the symptoms of normal pressure hydrocephalus. Follow-up imaging showed clear disease progression unilateral in the right sided trigonum. Consequently the patient was referred to surgery to remove the right-sided lesion. The left-sided lesion was not resected. The histopathological examination was consisted with a RCC metastasis. The patient was referred for additional systemic treatment.
