Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

Niewald, Marcus; Berdel, Christian; Fleckenstein, Jochen; Licht, Norbert; Ketter, Ralf; Rübe, Christian

doi:10.1186/1748-717x-6-141

Cited by 45 publications

(37 citation statements)

References 23 publications

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“…Hematologic toxicity related to concurrent and adjuvant temozolomide was emphasized in the EORTC/NCIC trial [2], with rates of severe thrombocytopenia and neutropenia of 7 %, similar to our study. Most reports on treatment tolerance among glioblastoma patients have included only the elderly [11][12][13]22] or focused on hematologic toxicity [14,23,24], with minimal data on morbidity leading to hospitalization. A recent population-wide study of glioblastoma patients reported readmission diagnoses 30 days after surgery, but included only elderly patients (age C 66) predominantly in the pretemozolomide era, and did not capture toxicities during CRT [22].…”

Section: Discussionmentioning

confidence: 99%

“…Disease-and treatment-related morbidity leading to hospitalization is particularly relevant [5,6], given that inpatient admission is associated with reduced quality of life among patients with incurable cancer including glioblastoma [7,8], as well as growing calls to reduce readmissions from quality-of-care and costcontainment perspectives [9,10]. Prior studies have reported on treatment tolerance specifically in the elderly glioblastoma population [11][12][13][14], and randomized trials have profiled adverse events among patients eligible for clinical trial inclusion [2]. However, little is known about the general glioblastoma population with regard to specific toxicities experienced by patients over the course of their disease, as well as the incidence, predictors, or reasons for hospitalization.…”

Section: Introductionmentioning

confidence: 99%

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Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

et al. 2015

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Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

et al. 2015

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“…The patients receiving only adjuvant treatment seemed to fare no worse than those in the concomitant treatment group. This could probably be explained by the lesser toxicity of the former during initial treatment 51,52…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma patients in Slovenia from 1997 to 2008

Smrdel¹,

Kovač²,

Popović³

et al. 2014

Radiology and Oncology

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BackgroundGlioblastoma is the most common primary brain tumour. It has a poor prognosis despite some advances in treatment that have been achieved over the last ten years. In Slovenia, 50 to 60 glioblastoma patients are diagnosed each year. In order to establish whether the current treatment options have any influence on the survival of the Slovenian glioblastoma patients, their data in the period from the beginning of the year 1997 to the end of the year 2008 have been analysed.Patients and methodsAll patients treated at the Institute of Oncology Ljubljana from 1997 to 2008 were included in the retrospective study. Demographics, treatment details, and survival time after the diagnosis were collected and statistically analysed for the group as a whole and for subgroups.ResultsFrom 1997 to 2008, 527 adult patients were diagnosed with glioblastoma and referred to the Institute of Oncology for further treatment. Their median age was 59 years (from 20 to 85) and all but one had the diagnosis confirmed by a pathologist. Gross total resection was reported by surgeons in 261 (49.5%) patients; good functional status (WHO 0 or 1) after surgery was observed in 336 (63.7%) patients, radiotherapy was performed in 422 (80.1%) patients, in 317 (75.1%) of them with radical intent, and 198 (62.5 %) of those received some form of systemic treatment (usually temozolomide). The median survival of all patients amounted to 9.7 months. There was no difference in median survival of all patients or of all treated patients before or after the chemo-radiotherapy era. However, the overall survival of patients treated with radical intent was significantly better (11.4 months; p < 0.05). A better survival was also noticed in radically treated patients who received additional temozolomide therapy (11.4 vs. 13.1 months; p = 0.014). The longer survival was associated with a younger age and a good performance status as well as with a more extensive tumour resection. In patients treated with radical intent, having a good performance status, and receiving radiotherapy and additional temozolomide therapy, the survival was significantly longer, based on multivariate analysis.ConclusionsWe observed a gradual increase in the survival of glioblastoma patients who were treated with radical intent over the last ten years. Good functional surgery, advances in radiotherapy and addition of temozolomide all contributed to this increase. Though the increased survival seems to be more pronounced in certain subgroups, we have still not been able to exactly define them. Further research, especially in tumour biology and genetics is needed.

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“…In addition, there was a 28% rate of grade 3–4 hematologic toxicity 26. A German study of 46 GBM patients with mean age 59 years who received concurrent chemoradiation highlights that hematologic toxicity may be persistent, with the mean duration of thrombocytopenia in that series being just over 2 months 27. Another Italian report on 58 GBM patients aged 65 years or older receiving concurrent and adjuvant TMZ reported a 25% rate of grade 3–4 mental status toxicity during the adjuvant TMZ phase, at a median time of approximately 6 months after completion of chemoradiation, although it is not clear whether this was attributable to combined RT/TMZ treatment as opposed to underlying disease progression 28.…”

Section: Standard Gbm Treatment: Applicable To the Elderly?mentioning

confidence: 99%

Treatment options and outcomes for glioblastoma in the elderly patient

Arvold¹,

Reardon²

2014

CIA

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Age remains the most powerful prognostic factor among glioblastoma (GBM) patients. Half of all patients with GBM are aged 65 years or older at the time of diagnosis, and the incidence rate of GBM in patients aged over 65 years is increasing rapidly. Median survival for elderly GBM patients is less than 6 months and reflects less favorable tumor biologic factors, receipt of less aggressive care, and comorbid disease. The standard of care for elderly GBM patients remains controversial. Based on limited data, extensive resection appears to be more beneficial than biopsy. For patients with favorable Karnofsky performance status (KPS), adjuvant radiotherapy (RT) has a demonstrated survival benefit with no observed decrement in quality of life. Concurrent and adjuvant temozolomide (TMZ) along with RT to 60 Gy have not been prospectively studied among patients aged over 70 years but should be considered for patients aged 65–70 years with excellent KPS. Based on the recent NOA-08 and Nordic randomized trials, testing for O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation should be performed routinely immediately after surgery to aid in adjuvant treatment decisions. Patients aged over 70 years with favorable KPS, or patients aged 60–70 years with borderline KPS, should be considered for monotherapy utilizing standard TMZ dosing for patients with MGMT-methylated tumors, and hypofractionated RT (34 Gy in ten fractions or 40 Gy in 15 fractions) for patients with MGMT-unmethylated tumors. The ongoing European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial will help clarify the role for concurrent TMZ with hypofractionated RT. For elderly patients with poor KPS, reasonable options include best supportive care, TMZ alone, hypofractionated RT alone, or whole brain RT for symptomatic patients needing to start treatment urgently. Given the balance between short survival and quality of life in this patient population, optimal management of elderly GBM patients must be made individually according to patient age, MGMT methylation status, performance score, and patient preferences.

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Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

Cited by 45 publications

References 23 publications

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

Glioblastoma patients in Slovenia from 1997 to 2008

Treatment options and outcomes for glioblastoma in the elderly patient

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