Re-irradiation for high-grade gliomas: Has anything changed?

García-Cabezas, Sonia; Campo, Eleonor Rivin del; Solivera-Vela, J.; Palacios-Eito, Amalia

doi:10.5306/wjco.v12.i9.767

Cited by 14 publications

(9 citation statements)

References 113 publications

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“…It was not possible to analyze the survival benefit of repeat radiotherapy in our study due to the small number of patients receiving this treatment. Repeat radiotherapy is currently considered safe for rGB management, but the heterogeneity of studies in terms of patient characteristics and radiotherapy regimen makes it difficult to draw any firm conclusions about the efficacy of this treatment option for rGB patients [ 32 , 38 , 39 ]. For systemic treatments, OS2 did not differ significantly between patients receiving bevacizumab plus nitrosourea and those treated with nitrosourea alone (median OS2: 8.8 vs. 10.6 months) or bevacizumab alone (median OS2: 8.8 vs. 9.9 months).…”

Section: Discussionmentioning

confidence: 99%

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Clavreul

Autier

Lemée

et al. 2022

Cancers

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Safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) is universally accepted as the first-line treatment for glioblastoma (GB), but no standard of care has yet been defined for managing recurrent GB (rGB). We used the French GB biobank (FGB) to evaluate the second-line options currently used, with a view to defining the optimal approach and future directions in GB research. We retrospectively analyzed data for 338 patients with de novo isocitrate dehydrogenase (IDH)-wildtype GB recurring after TMZ chemoradiotherapy. Cox proportional hazards models and Kaplan–Meier analyses were used to investigate survival outcomes. Median overall survival after first surgery (OS1) was 19.8 months (95% CI: 18.5–22.0) and median OS after first progression (OS2) was 9.9 months (95% CI: 8.8–10.8). Two second-line options were noted for rGB patients in the FGB: supportive care and treatments, with systemic treatment being the treatment most frequently used. The supportive care option was independently associated with a shorter OS2 (p < 0.001). None of the systemic treatment regimens was unequivocally better than the others for rGB patients. An analysis of survival outcomes based on time to first recurrence (TFR) after chemoradiotherapy indicated that survival was best for patients with a long TFR (≥18 months; median OS1: 44.3 months (95% CI: 41.7–56.4) and median OS2: 13.0 months (95% CI: 11.2–17.7), but that such patients constituted only a small proportion of the total patient population (13.0%). This better survival appeared to be more strongly associated with response to first-line treatment than with response to second-line treatment, indicating that the recurring tumors were more aggressive and/or resistant than the initial tumors in these patients. In the face of high rates of treatment failure for GB, the establishment of well-designed large cohorts of primary and rGB samples, with the help of biobanks, such as the FGB, taking into account the TFR and survival outcomes of GB patients, is urgently required for solid comparative biological analyses to drive the discovery of novel prognostic and/or therapeutic clinical markers for GB.

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Section: Discussionmentioning

confidence: 99%

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Clavreul

Autier

Lemée

et al. 2022

Cancers

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“…SRS RGBM as the repeated irradiation following the first RT course is deemed as one of the most promising method for treatment of such patients allowing for improving their survival. Nevertheless, the randomized clinical trials are required for elucidating the optimal treatment strategy (García-Cabezas et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Due to up-to-date improved techniques of radiotherapy, novel visualization techniques, and increasing radiobiological knowledge of brain tissues, the repeated irradiation became possible for this complicated category of patients. The decision is taken on an individual basis taking into account the nature of the recurrence, the previous treatment, the performance status as well as the preferences of the patient and the expected quality of life (García-Cabezas et al, 2021). Several aspects of reirradiation of GBM patients are awaiting their decision, in particular, criteria for selecting of the most favorable candidates for such a treatment and accounting for the factors that affect positively the survival.…”

Section: Ukrainian Scientific Medical Youth Journalmentioning

confidence: 99%

Survival after stereotactic radiosurgery of recurrent glioblastomas in patients with radical resection of primary tumor

Gryazov

Glavatskyi

Zemskova

et al. 2022

USMYJ

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glioblastoma (GBM) is an aggressive tumor with high rate of recurrence and estimated survival of 15-18 months after diagnosis. Factors associated with longer survival of GBM patients are age < 50 years, high performance status and radical resection of the primary tumor. The optimal treatment for recurrence/ progression of GBM has not yet been determined and remains a challenging issue. Stereotactic radiosurgery (SRS) is considered today as a therapeutic option for effective treatment of recurrent malignant gliomas. The aim of this retrospective study was to analyze the survival after SRS of the recurrent GBM in a cohort of 59 patients, which had a radical resection of the primary tumor. The cohort consisted of 59 patients (28 / 47.5% of women and 31 / 52.5% of men); the average age was 51 years (interval 24 - 81). SRS was performed by means of linear accelerator "Trilogy" (USA) (6 MeV) from 2014 to 2020 at the State Institution "Romodanov Neurosurgery Institute". In all cases, the diagnosis of grade 4 GBM according to the WHO classification was confirmed after neurosurgical procedures of the primary tumor. All 59 patients underwent the maximal safe removal of the primary tumor: in the vast majority of cases (54 / 91.5%) - in the perifocal area; in 5 / 8.5% of cases - subtotal. In all 59 cases, patients received adjuvant radiation therapy (total dose 60 Gy in 30 fractions); in 33 / 55.9% of cases radiotherapy was combined with concomitant alkylating chemotherapy (CHT) (Temozolomide 75 mg / m2). In 31 / 52.5% of patients, maintenance alkylating CHT was continued (Temozolomide 150-200 mg / m2). In most cases (51 / 86.4%) recurrent GBM (RGBM) was diagnosed by clinical and radiological signs; in 8 / 13.6% of patients - after repeated surgery. Overall survival (OS), recurrence/progression free survival (RFS) and survival after recurrence (SAR) represented the end-points of the study. The effect of the following quantitative and categorical factors (covariates) on the survival was studied: sex, age, performance status, combination of adjuvant RT with alkylating chemotherapy, neurosurgical procedures of RGBM, type of GBM recurrence, total dose of irradiation (BED11) and SRS dose (BED11), number of SRS fractions, volume of target in SRS, duration of RFS. The effect of RFS was studied in three independent groups: group I – RFS < 10 months; group II – RFS from 10 to 20 months; group III – RFS > 20 months. The survival was analyzed by Kaplan-Meier (KM) method. Log-rank test was used for analysis of the survival according to the binary predictors. The effect of several categorical factors on survival was analyzed by Pearson Chi-square test. The effect of the quantitative covariates on survival was studied by regression analysis in Cox proportional risk model. Hazard ratio was calculated with 95 % confidential intervals (CI). The analysis revealed the following. Median OS following SRS RGBM was 26.3 months (95 % CІ 17 – 45.5), median RFS was 12.9 months (95 % CІ 8.4 – 25.6), median SAR – 9.8 months (95 % CІ 6.7 – 24.4). Two-year OS in our study was 56 %. 6-month survival after SRS –77 %; one-year survival after SRS – 39 %, and two-year survival after SRS – 28 %. The significant impact of performance status (p = 0.00159), duration of recurrence-free period (p = 0.02711) and surgical resection of RGBM (р = 0.009391) on the OS was demonstrated. The best OS was shown for the patients with Karnofsky score 90, recurrence occurring after more than 20 months and previous surgical resection of RGBM. The effects of other factors on OS were not demonstrated. Such factors as age, sex, performance status, adjuvant RT with сoncomitant alkylating CHT, surgical resection of RGBM, type of recurrence, number of SRS fractions, BED11 in SRS RGBM, BED11 for overall courses of irradiation, SRS target volume demonstrated no effect on SAR. SRS is non-invasive method for RGBM treatment that allows for improving the survival without significant radiation toxicity. Primary biological properties of the tumor seem to be of priority in determining the survival of RGBM patients. Although irradiation of GBM is advantageous regarding the improvement of the survival, one could also speculate that re-irradiation of the recurrent malignant glioma triggers some changes in its biology neutralizing the potential effect of the survival factors that had predictive value before re-irradiation.

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“…Adult experiences have much enriched literature with re-RT series [15][16][17] but paediatric experiences are instead scarce. The differences revealed after molecular characterization between adult and paediatric HGG[18] render re-treatment and its results di cult to apply in these different contexts.…”

Section: Discussionmentioning

confidence: 99%

How ten-years of reirradiation for paediatric high-grade glioma can shed light on first line treatment

Massimino

Vennarini

Barretta

et al. 2022

Preprint

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Purpose. Recurrence incidence for paediatric/adolescent high-grade glioma(HGG) exceeds 80%. Reirradiation(reRT) palliates symptoms and delays further progression. Strategies for reRT are scarce: we retrospectively analysed our series to develop rational future approaches.Methods. We re-evaluated MRI+RT plans of 21 relapsed HGG-patients, accrued 2010-2021, aged under 18 years. All underwent surgery and RT+chemotherapy at diagnosis. Pathologic/molecular re-evaluation allowed classification based on WHO 2021 criteria in 20/21 patients. Survival analyses and association with clinical parameters were performed. Results. Relapse after 1st RT was local in 12(7 marginal), 4 disseminated, 5 local+disseminated. Re-RT obtained 8 SD, 1 PR, 1PsPD, 1 mixed response, 10 PD; neurological signs/symptoms improved in 8. Local reRT was given to 12, followed again by 6 local(2 marginal) and 4 local+disseminated second relapses in 10/12 re-evaluated. The 4 with dissemination had 1 whole brain, 2 craniospinal irradiation(CSI), 1 spine reRT and further relapsed with dissemination and local+dissemination in 3/four assessed. Five local+disseminated tumours had 3 CSI, 1 spine reRT, further progressing locally(2), disseminated(1), n.a.(1). Three had a third RT; three were alive at 19.4, 29, 50.3 months after diagnosis. Median times to progression/survival after re-RT were 3.7 months (0.6-16.2 months)/6.9 months (0.6-17.9 months), improved for longer interval r between 1st RT and re-RT(P=0.017) and for non-PD after reRT(P< 0.001). First marginal relapse showed potential association with dissemination after re-RT(P= 0.081) Conclusions. This is the biggest series of re-RT in paediatric HGG. Considering the dissemination relapse incidence observed, our results could prompt the investigation of first RT fields in a randomized trial.

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Re-irradiation for high-grade gliomas: Has anything changed?

Cited by 14 publications

References 113 publications

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Survival after stereotactic radiosurgery of recurrent glioblastomas in patients with radical resection of primary tumor

How ten-years of reirradiation for paediatric high-grade glioma can shed light on first line treatment

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