Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy

Nguyen, Ludovic; Touch, Socheat; Nehme-Schuster, H.; Antoni, D.; Eav, Sokha; Clavier, Jean-Baptiste; Bauer, N.; Vigneron, C.; Schött, Roland; Kehrli, P.; Noël, Georges

doi:10.3390/cancers5031177

Cited by 18 publications

(12 citation statements)

References 41 publications

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“…CLIO-ICT synergized with temozolomide in vivo , thereby revealing a novel therapeutic combinatorial regimen for targeting GBMs. Current GBM therapies include surgical resection followed by radiation therapy with concurrent temozolomide (TMZ) treatment (41). However 90% of GBM patients develop tumor recurrence (42).…”

Section: Discussionmentioning

confidence: 99%

A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

Mohanty

Chen

et al. 2017

Molecular Cancer Therapeutics

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Glioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.

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Section: Discussionmentioning

confidence: 99%

A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

Mohanty

Chen

et al. 2017

Molecular Cancer Therapeutics

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“…However, the optimal treatment strategy for older patients remains controversial. Although the addition of RT, compared to best supportive care, may be associated with better survival outcomes and equivalent quality of life outcomes in the elderly, the optimal RT dose fractionation and the benefit of chemotherapy in this population is an area of active investigation .…”

Section: Introductionmentioning

confidence: 99%

Hypofractionated short‐course radiotherapy in elderly patients with glioblastoma multiforme: an analysis of the National Cancer Database

et al. 2017

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For elderly patients with glioblastoma multiforme (GBM), randomized trials have shown similar survival with hypofractionated short‐course radiotherapy (SCRT) compared to conventionally fractionated long‐course radiotherapy (LCRT). We evaluated the adoption of SCRT along with associated factors and survival in a national patient registry. Using the National Cancer Data Base (NCDB), we identified patients aged ≥70 years with GBM, diagnosed between 1998 and 2011, who received SCRT (34–42 Gy in 2.5–3.4 Gy fractions), or LCRT (58–63 Gy in 1.8–2.0 Gy fractions). Crude and adjusted hazard ratios (HR) were calculated using Cox regression modeling. 4598 patients were identified, 304 (6.6%) in the SCRT group and 4294 (93.4%) in the LCRT group. Median follow‐up was 8.4 months. Median age was 78 versus 75 years, respectively (P < 0.0001). Patients who received SCRT had higher Charlson–Deyo comorbidity scores versus LCRT (score of ≥2: 16.9% vs. 10.8%, respectively; P = 0.006), and were more likely to be female (53.0% vs. 44.6%, P = 0.005). Patients who received SCRT were less likely to undergo chemotherapy (42.8% vs. 79.3%, P < 0.0001), more likely to undergo biopsy only (34.5% vs. 19.5%, P < 0.0001), and more likely to receive treatment at academic/research programs (49.2% vs. 37.2%, P = 0.0001). Median survival was 4.9 months versus 8.9 months, respectively (P < 0.0001). The survival detriment with SCRT persisted on multivariable analysis [HR 1.51 (95% CI: 1.33–1.73, P < 0.0001)], adjusting for age, gender, race, comorbidities, diagnosis year, facility type, surgery, and chemotherapy. In conclusion, hypofractionated SCRT was associated with worse survival compared to conventionally fractionated LCRT for elderly patients with GBM. Patients who received SCRT were older with worse comorbidities, and were less likely to undergo chemotherapy or resection.

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“…Only a few studies have reported on the use of hypofractionated RT in combination with TMZ [21,39,40]. We recently conducted a phase 2 trial on the efficacy of an abbreviated RT course (40 Gy in 15 fractions over 3 weeks) plus concomitant and adjuvant TMZ chemotherapy for up to 12 cycles in 70 patients aged C70 years with newly diagnosed GBM [39].…”

Section: Combined Chemoradiationmentioning

confidence: 99%

Radiation therapy for older adults with glioblastoma: radical treatment, palliative treatment, or no treatment at all?

Minniti

Enrici

2014

J Neurooncol

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The incidence of glioblastoma in older adults has increased over the last few decades. Current treatment includes surgery, radiotherapy, and chemotherapy, but optimal disease management remains a matter of debate. Both standard (60 Gy in 30 daily fractions) and hypofractionated radiotherapy (30-40 Gy in 10-15 daily fractions) have been employed with a similar survival benefit. Recent randomized studies indicate that chemotherapy with the alkylating agent temozolomide is a safe and effective therapeutic option for patients aged 60 years or older with newly diagnosed glioblastoma, suggesting that it should be a sufficient treatment for patients presenting with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter gene. The addition of concomitant temozolomide chemotherapy, adjuvant temozolomide chemotherapy, or both to postoperative radiotherapy, which is the standard treatment for adults with glioblastoma, has been associated with a survival benefit for older patients with a good performance status; however, aggressive treatment in this population may be associated with a high risk of neurological toxicity and deterioration of quality of life. Survival stratification according to age, MGMT promoter methylation status, and neurological status may be useful for clinical decision making and designing randomized trials for adequately evaluating the optimal combination of radiotherapy and chemotherapy for older patients with glioblastoma.

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Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy

Cited by 18 publications

References 41 publications

A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival

Hypofractionated short‐course radiotherapy in elderly patients with glioblastoma multiforme: an analysis of the National Cancer Database

Radiation therapy for older adults with glioblastoma: radical treatment, palliative treatment, or no treatment at all?

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