Arnoud C. Kappelle

Increased Risk of Ischemic Stroke After Radiotherapy on the Neck in Patients Younger Than 60 Years

PURPOSEnTo estimate the risk of ischemic stroke in patients irradiated for head and neck tumors.nnnPATIENTS AND METHODSnThe incidence of ischemic stroke was determined in 367 patients with head and neck tumors (162 larynx carcinomas, 114 pleomorphic adenomas, and 91 parotid carcinomas) who had been treated with local radiotherapy (RT) at an age younger than 60 years. Relative risk (RR) of ischemic stroke was determined by comparison with population rates from a stroke-incidence register, adjusted for sex and age. Other risk factors for stroke (hypertension, smoking, hypercholesterolemia, diabetes mellitus [DM]) were registered. The median follow-up time after RT was 7.7 years (3,011 person-years of follow-up).nnnRESULTSnFourteen cases of stroke occurred (expected, 2.5; RR, 5.6; 95% confidence interval [CI], 3.1 to 9.4): eight in patients with laryngeal carcinoma (expected,1.56; RR, 5.1; 95% CI, 2.2 to 10.1), four in pleomorphic adenoma patients (expected, 0.71; RR, 5.7; 95% CI, 1.5 to 14.5), and two in parotid carcinoma patients (expected, 0.24; RR, 8.5, 95% CI, 1.0 to 30.6). Five of six strokes in patients irradiated for a parotid tumor occurred at the ipsilateral side. Analysis of other risk factors for cerebrovascular disease showed hypertension and DM to cause an increase of the RR after RT. After more than 10 years follow-up, the RR was 10.1 (95% CI, 4.4 to 20.0). The 15-year cumulative risk of stroke after RT on the neck was 12.0% (95% CI, 6.5% to 21.4%).nnnCONCLUSIONnThis is the first study to demonstrate an increased risk of stroke after RT on the neck. During medical follow-up, preventive measures should be taken to reduce the impact of the risk factors for cerebrovascular disease, to decrease stroke in these patients.

Cognitive Rehabilitation in Patients With Gliomas: A Randomized, Controlled Trial

PURPOSEnPatients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas.nnnPATIENTS AND METHODSnOne hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health-related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up.nnnRESULTSnAt the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months.nnnCONCLUSIONnThe CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.

Increased Risk of Stroke and Transient Ischemic Attack in 5-Year Survivors of Hodgkin Lymphoma

BACKGROUNDnInformation on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored potential pathogenic mechanisms.nnnMETHODSnWe performed a retrospective cohort study among 2201 five-year survivors of Hodgkin lymphoma treated before age 51 between 1965 and 1995. We compared incidence rates of clinically verified stroke and TIA with those in the general population. We used multivariable Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided.nnnRESULTSnAfter a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population, after prolonged follow-up. The cumulative incidence of ischemic stroke or TIA 30 years after Hodgkin lymphoma treatment was 7% (95% CI = 5% to 8%). Radiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (hazard ratio = 2.5, 95% CI = 1.1 to 5.6 vs without radiotherapy). Treatment with chemotherapy was not associated with an increased risk. Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease, whereas smoking and overweight were not.nnnCONCLUSIONSnPatients treated for Hodgkin lymphoma experience a substantially increased risk of stroke and TIA, associated with radiation to the neck and mediastinum. Physicians should consider appropriate risk-reducing strategies.

PCV chemotherapy for recurrent glioblastoma multiforme

The authors evaluated response, time to progression (TTP), survival, prognostic factors, and toxicity in 63 patients with a recurrent glioblastoma multiforme treated with procarbazine, lomustine, and vincristine (PCV) chemotherapy. Complete and partial response was observed in two (3%) and five patients (8%). In 16 patients (25%), stable disease was observed. Median TTP and survival were 13 and 33 weeks. Age < 40 years and Karnofsky Performance Status ≥ 90 were associated with longer TTP and survival. PCV treatment was generally well tolerated.

Malignant tumors of the nasal cavity and paranasal sinuses: long-term outcome and morbidity with emphasis on hypothalamic-pituitary deficiency.

PURPOSEnTo evaluate the long-term outcome after surgery and radiotherapy for patients with sinonasal cancer and assess late toxicity, with special emphasis on hypothalamic-pituitary dysfunction.nnnMETHODS AND MATERIALSnA retrospective analysis of 168 patients treated for sinonasal cancer in a single institute between 1986 and 2006. A more detailed analysis was performed on a subgroup of 76 patients with adenocarcinoma or squamous cell carcinoma treated with curative intent. Long-term survivors were evaluated for late toxicity by a multidisciplinary team using the late effects of normal tissues (LENT SOMA) scoring system. Additional endocrinologic tests were performed for assessment of hypothalamic-pituitary function.nnnRESULTSnFive-year actuarial local control and overall survival rates were 62% and 35% for all patients and 64% and 42% for the subgroup with squamous cell carcinoma and adenocarcinoma. In multivariate analysis, T stage was the only significant factor predicting local relapse (79% at 5 years for T1-T3 vs. 53% for T4; p = 0.006). Sinonasal mucosal melanomas had the highest rate of regional failure (33% at 5 years). Thirteen of 21 patients (62%) evaluated at the late morbidity clinic had hormonal disturbances, of whom 5 (24%) had definitive evidence of hypopituitarism with multiple hormonal deficiencies.nnnCONCLUSIONnLocal failure is the dominant cause of treatment failure for patients with sinonasal cancer, with T4 stage the only independent predictor. Because of a high rate of radiation-induced hypopituitarism, we recommend endocrinologic surveillance for these patients.

Development of a model with which to predict the life expectancy of patients with spinal epidural metastasis

The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable.

Decreased Risk of Stroke Among 10-Year Survivors of Breast Cancer

PURPOSEnTo assess treatment-specific risk of cerebrovascular events in early breast cancer (BC) patients, accounting for cerebrovascular risk factors.nnnPATIENTS AND METHODSnWe studied the incidence of cerebrovascular accidents (CVA; stroke and transient ischemic attack [TIA]) in 10-year survivors of early BC (n = 4,414) treated from 1970 to 1986. Follow-up was 96% complete until January 2000. Treatment-specific incidence of CVA was evaluated by standardized incidence ratios (SIRs) based on comparison with general population rates and by Cox proportional hazards regression.nnnRESULTSnAfter a median follow-up of 18 years, 164 strokes and 109 TIAs were observed, resulting in decreased SIRs of 0.8 (95% CI, 0.6 to 0.9) for stroke and 0.8 (95% CI, 0.7 to 1.0) for TIA. Significantly increased risk of stroke was found in women who had received hormonal treatment (HT; tamoxifen) and in women who had hypertension or hypercholesterolemia, with hazard ratios (HRs) of 1.9, 2.1, and 1.6, respectively. Patients irradiated on the supraclavicular area and/or internal mammary chain (IMC) did not experience a higher risk of stroke (HR = 1.0; 95% CI, 0.7 to 1.6) or TIA (HR = 1.4; 95% CI, 0.9 to 2.5) compared with patients who did not receive radiotherapy or who were irradiated on fields other than the supraclavicular area or IMC.nnnCONCLUSIONnLong-term survivors of BC experience no increased risk of cerebrovascular events compared with the general population. HT is associated with an increased risk of stroke. Radiation fields including the carotid artery do not seem to increase the risk of stroke compared with other fields.

Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox?

AbstractObjective: The goal of our study was to investigate the inverse correlation between number of genetic aberrations and malignancy grade in ependymal tumors at the ploidy level.nMethods: we examined seven myxopapillary ependymomas (mpEs) (WHO grade I), 28 spinal and cerebral ependymomas (Es) (WHO grade II), and 18 cerebral anaplastic ependymomas (aEs) (WHO grade III) using image DNA cytometry. The ploidy status was correlated with clinicopathological characteristics and with the results obtained by comparative genomic hybridization (CGH) analysis that we performed in about half of these tumors.nResults: mpEs were exclusively located in the spinal cord and aEs in the cerebrum only, whereas Es were located in both the spinal cord and brain. We found aneuploidy or tetraploidy to be common in the group of mpEs (6 out of 7) and much less frequent in Es (6 out of 28) and aEs (4 out of 18). Three-year postoperative survival was 100% for mpEs, 100% for spinal Es, 92% for cerebral Es, and 33% for aEs. Our CGH results in a selection of these tumors revealed the highest number of genetic aberrations in the mpEs (average 16; n = 2), a lower number in Es (average 12; n = 11) and the lowest number in aEs (average 5; n = 6). Interestingly, in the group of Es and aEs, a high number of genetic aberrations as detected by CGH was not correlated with aneuploidy or tetraploidy. Three patients, all with mpEs had local seeding.nConclusion: These results underline that mpEs are distinctly different from Es and aEs at the genetic level and that extensive genomic alterations and aneuploidy in ependymal tumors are not in itself an indicator of malignant behavior.

Outcome of Carotid Artery Stenting for Radiation-Induced Stenosis

PURPOSEnPatients who have been irradiated at the neck have an increased risk of symptomatic stenosis of the carotid artery during follow-up. Carotid angioplasty and stenting (CAS) can be a preferable alternative treatment to carotid endarterectomy, which is associated with increased operative risks in these patients.nnnMETHODS AND MATERIALSnWe performed a prospective cohort study of 24 previously irradiated patients who underwent CAS for symptomatic carotid stenosis. We assessed periprocedural and nonprocedural events including transient ischemic attack (TIA), nondisabling stroke, disabling stoke, and death. Patency rates were evaluated on duplex ultrasound scans. Restenosis was defined as a stenosis of >50% at the stent location.nnnRESULTSnPeriprocedural TIA rate was 8%, and periprocedural stroke (nondisabling) occurred in 4% of patients. After a mean follow-up of 3.3 years (range, 0.3-11.0 years), only one ipsilateral incident event (TIA) had occurred (4%). In 12% of patients, a contralateral incident event was present: one TIA (4%) and two strokes (12%, two disabling strokes). Restenosis was apparent in 17%, 33%, and 42% at 3, 12, and 24 months, respectively, although none of the patients with restenosed vessels became symptomatic. The length of the irradiation to CAS interval proved the only significant risk factor for restenosis.nnnCONCLUSIONSnThe results of CAS for radiation-induced carotid stenosis are favorable in terms of recurrence of cerebrovascular events at the CAS site.

External Beam Radiotherapy With Endocavitary Boost for Nasopharyngeal Cancer: Treatment Results and Late Toxicity After Extended Follow-Up

PURPOSEnTo evaluate the long-term outcome after treatment of nasopharyngeal carcinoma and assess late toxicity in a multidisciplinary clinic.nnnMETHODS AND MATERIALSnA retrospective analysis of 117 patients treated for nasopharyngeal cancer in a single institute between 1985 and 2002 was performed. Fifty-one long-term survivors were evaluated for late toxicity by a multidisciplinary team comprising a radiation oncologist, otolaryngologist, neurologist, and oral and maxillofacial surgeon.nnnRESULTSnThe 5-year local control rate for T1 to T2 and T3 to T4 tumors was 97% and 76%, respectively. Five-year disease-free survival and overall survival were 82% and 88% for Stage I to IIb disease and 46% and 52% for Stage III to IVb, respectively. Late morbidity evaluation revealed Radiation Therapy Oncology Group (RTOG) Grade III to IV toxicity in 71% of patients. A high incidence of cranial nerve palsies (47%) and mandibular osteolysis (82%) was found, although these complications had limited clinical impact.nnnCONCLUSIONSnThe multidisciplinary late morbidity clinic revealed an unexpected high incidence of cranial nerve palsies and mandibular osteolysis and overall an RTOG Grade III to IV toxicity in 71% of patients treated for nasopharyngeal cancer. External beam radiotherapy with endocavitary brachytherapy produces excellent rates of local control for T1 to T2 tumors, but the high incidence of late toxicity suggests an overtreatment.