Health-related quality of life (HRQoL), cognitive function, and psychological status represent an important focus during the treatment of glioblastoma patients. Nevertheless, few randomized, ...prospective clinical trials have analyzed these factors, and very little is known in the real-clinical world. We evaluated these characteristics in glioblastoma patients treated with standard first-line therapy outside clinical trials.
In total, 111 newly, histologically diagnosed glioblastoma patients treated at our oncology center with radiotherapy and temozolomide were prospectively enrolled. No patient was enrolled in an experimental clinical trial. We assessed HRQoL, cognitive function, and psychological status before starting treatment, at the end of radiotherapy, and every 3 months until 9 months after the end of radiotherapy using EORTC QLQ-C30, BN20, MMSE, and HADS questionnaires.
Global health status, physical, cognitive, and social functioning remained unchanged throughout the study period. A statistically significant change was found in emotional functioning as well as a clinically meaningful amelioration in role functioning between the baseline assessment and 9 months after radiotherapy. Patients older than 65 years reported greater impairment on the bladder control scale than younger patients. When considering tumor location, global health status, communication deficit, and drowsiness, scores were significantly different between the right and left hemispheres. Female patients had a clinically relevant lower score for physical functioning at baseline and 3 months after radiation therapy. Female patients also had a clinically relevant lower depression score at 9 months after radiation therapy.
In routine neurooncology practice, HRQoL, cognitive function, and psychological status did not worsen during first-line treatment in glioblastoma patients receiving standard radiotherapy and temozolomide treatment. However, some patient subgroups, such as elderly and female patients, may have different experiences with treatment, and further investigation is required.
The aim of this study was to evaluate clinical results and prognostic factors in a cohort of patient with oligometastatic esophagogastric adenocarcinoma treated with stereotactic radiation therapy ...(SRT).
This retrospective study included patients affected by 1-3 metastases treated with SRT from 2013 to 2021. Local control (LC), overall survival (OS), progression-free survival (PFS), time to polymetastatic dissemination (TTPD) and time to systemic therapy change/initiation (TTS) were evaluated.
Between 2013 and 2021, 55 patients were treated with SRT on 80 oligometastatic sites. Median follow-up was 20 months. Nine patients had local progression. 1 and 3 years LC was respectively 92 and 78%. 41 patients experienced further distant disease progression, median PFS was 9.6 months, 1 and 3 years PFS was respectively 40 and 15%. 34 patients died, median OS was 26.6 months, 1 and 3 years OS was respectively 78 and 40%. During follow-up, 24 patients changed or initiated a new systemic therapy; median TTS time was 9 months. 27 patients experienced poliprogression, 44% after 1 year and 52% after 3 years. Median TTPD was 8 months. The best local response (LR), tyming of metastases and PS were related with prolonged PFS on multivariate analysis. LR was correlated with OS at multivariate analysis.
SRT represents a valid treatment for oligometastatic esophagogastric adenocarcinoma. CR correlated with PFS and OS, while metachronous metastasis and a good PS correlated with a better PFS.
In selected gastroesopagheal oligometastatic patients, SRT can prolong OS Local response to SRT, metachronous timing of metastases and better PS improve PFS.Local response correlates with OS.
Background.
Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α‐ketoglutarate into 2‐hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine ...could predict the presence of IDH1/2 mutations in patients with glioma.
Materials and Methods.
All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry.
Results.
A total of 84 patients were enrolled: 38 with R132H‐IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high‐grade glioma and 17 had low‐grade glioma. Among the 46 patients with IDH1 wild‐type glioma, 35 and 11 had high‐ and low‐grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high‐grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high‐grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment.
Conclusion.
Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.
The use of 2‐hydroxyglutarate (2HG) to predict the presence of isocitrate dehydrogenase (IDH)1/2 mutations in patients with glioma was explored. The ratio of the 2HG levels in the plasma and urine was significantly different between patients with and without an IDH1 mutation.
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Anaplastic Astrocytoma(AA) is a malignant, diffusely infiltrating, primary brain tumor. According to the WHO 2016 classification of central-nervous-system tumors, AA has been ...described as a glial tumor with no co-deletion of 1p/19q, and is divided into IDH mutated tumor, characterized by better prognosis, and IDH wild-type form, with worse prognosis. The standard of care is maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Several efforts have been made to evaluate, according to molecular selection, which is the best post-surgical treatment. At recurrence, the treatment remains challenging and some trials are ongoing to evaluate new potential drugs, alone or in combination with chemotherapy. We performed a description of the status of the art on diagnosis, molecular characteristics and treatment of AA. In particular, we focused our details on new drugs; indeed, a deeper knowledge of the molecular characteristics of gliomas could lead to to development of active personalized treatments according with precision medicine.
•In elderly glioblastoma patients a short course of radiation therapy is suggested.•Literature lacks in the definition of elderly if older than 65 years, or 70 years.•Aim of this study was to explore ...if differences exist between these two cohorts.•Outcome comparison was performed using a propensity score matched analysis.•The PSM analyses showed a similar outcome.
The standard of care for elderly, newly-diagnosed glioblastoma patients consists, if feasible, of surgical resection followed by a short course of radiation therapy (RT) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT). To date, the literature lacks of consistence in the definition of elderly, if older than 65 years, or 70 years. Aim of this study was to explore whether differences exist between these two cohorts, comparing outcomes using a propensity score matched analysis (PSM).
Two hundred twenty-one elderly newly diagnosed glioblastoma patients were included. All patients received surgery followed by RT with concurrent and adjuvant TMZCHT. The RT dose prescribed was 60 Gy/30 fractions for patients 65–69-year-old or 40.5 Gy/15 fractions for ≥70-year-old. After 1:1 matching there were 86 patients in each group. Distribution of covariates was adequately balanced in the matched data set.
After PSM median PFS time, 1,2,3-year PFS rates were 10 months, 33.3%, 13.1%, and 6.6% for the 65–69-year group, 9 months, 34.7%, 11% and 4.8% for the ≥70-year group (p = 0.530). Median OS time, and 1,2,3-year OS rates were 14 months, 54.1%, 23.4%, 13.9% for the 65–69-year old group, and 12 months, 49.3%, 21.5%, 10% for the ≥70-year group (p = 0.357). No differences were recorded in relation to different groups of age.
The PSM analyses showed a similar outcome in 65–69-year old patients compared to older ones notwithstanding a more burdensome RT schedule. Hypofractionated RT treatment has to be considered also in this group of younger elderly, newly-diagnosed GBM patients.
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2043
Background: Pem, an immune checkpoint inhibitor, demonstrated to be active in various neoplasms with MMRd. No data exists about its efficacy in MMRd glioma PTS. Methods: MMRd HGG ...relapsed after receiving RT and CT were treated with Pem. MMR status was analyzed by immunohistochemistry, including the MLH1, MSH2, MSH6, and PMS2 markers. MMRd was defined as presence of a weak (wMMRd) or absent (aMMRd) signal for at least one MMR protein. Other inclusion criteria were: ECOG PS 0-2, histologically confirmed glioma, dexamethasone ≤4 mg. Pem was administrated at 200 mg every 3 weeks until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeks according to the RANO criteria. OS and PFS were evaluated by Kaplan-Meier curves. Results: among 167 glioma PTS, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, all PTS had microsatellite stability. Tumor histologies included 5 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2 deficiency was found in 6 cases , MSH6 deficiency in 9 cases, PMS2 and MLH1 deficiency in 2 cases. Median number of prior lines of chemotherapy was 1 (range 1-5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showed progressive disease (PD). PTS with anaplastic gliomas showed a statistically significant association with SD (p=0.03, OR=3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6 (deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1-13.8), PFS 2.4 ms (95% CI 1.8-2.9). OS was 2.8 ms and 5.6 ms (p=0.9), PFS was 1.8 ms and 3.1 ms (p=0.5) in PTS with wMMRd and aMMRd, respectively. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6-10.2) and 1.8 ms (95% CI 0.2-3.4), p=0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p=0.04), respectively. Grade ≥3 adverse events were reported in 8% of PTS. Conclusions: a subgroup of recurrent MMRd HGG might benefit from Pem, especially anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. The enrollment and analyses for identifying additional molecular predictive factors are ongoing.
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2539
Background: MGMT methylation (MGMTmet) status represents an important prognostic factor for glioblastoma (GBM) patients (PTS). Quantitative pyrosequencing approach has proven to be ...feasible for MGMTmet testing but its value is still unclear. We performed a large, multicentre, retrospective study to identify the association between MGMTmet values and clinical outcome. Methods: from 9 Italian neuro-oncology centres, we collected consecutive GBM PTS with assessment of MGMTmet by pyrosequencing approach evaluating CpG islands from 75 to 84. Other inclusion criteria were: histological diagnosis of GBM, ECOG PS ≤2, therapy with RT+TMZ. Kaplan-Meier method was used to estimate the survival curves, time-dependent ROC curve for defining the optimal cut-off value of mean percentage of MGMTmet in terms of 2y-OS, Cox regression for multivariable analysis, and restricted cubic spline to investigate the non-linear association between methylation values and OS. Results: 681 PTS were enrolled; median age was 60 ys; ECOG PS was 0 in 292 PTS, 1 in 306 PTS, 2 in 83 PTS; 391 PTS (58%) had a complete resection. 8% of PTS received a second surgery. IDH was mutated in 6%. 2y-OS was 31.6%, median OS was 17.4 ms. Median MGMTmet was 3.5% (IQR 0-22%). ROC curve identified a cutoff of 15% of MGMTmet in terms of 2y-OS (sens 78%, spec 57%, AUC = 0.67). 2y-OS was 19.7% and 53.7% for PTS with MGMTmet < and ≥15%, respectively (p < 0.0001). At multivariable analysis, MGMTmet < 15% was associated with impaired survival (HR 2.7, 95% CI 2.1-3.4; p < 0.00001), adjusting for age, KPS, type of surgery and second surgery. A non-linear association between MGMT methylation and survival was identified (non-linear term: p < 0.0001), with lower values of MGMT methylation associated with lower survival; indeed, estimated median OS was lowest (14 months, 2ys-OS: 17.4%) with MGMTmet of 4%, 21ms (2yr-OS: 40.9%) with MGMTmet of 20%, 27ms (2yr-OS: 40.9%) when MGMTmet was 40%, then leveled around 30ms (2yr-OS: 54.5-59.8%) when MGMTmet was > 40%. Conclusions: this study represents one of the largest trials analyzing MGMTmet by pyrosequencing approach. Lower values of MGMTmet were associated with impaired survival and the relationship was non-linear. Noteworthy, we identified a strong prognostic value of MGMTmet which could be used as stratification factor in prospective clinical trials
Abstract
BACKGROUND
Treatment for GBM elderly PTS is still a challenge in neuro-oncology. Clinical tools, including CGA, are needed for improving treatment decision and outcome. The aim of this study ...was to evaluate CGA as a prognostic tool in terms of PFS and OS in elderly GBM PTS.
METHODS
We performed a retrospective analysis of elderly PTS ≥ 65 years, treated at Veneto Institute of Oncology between January 2011 and January 2018, with newly histologically diagnosed GBM and receiving a baseline CGA after 3–4 weeks from surgery. CGA included the following domains: age, activities and instrumental activities of daily living (ADL, IADL), cognitive status (MMSE), mood (GDS), nutritional status (MNA), number of drugs, comorbidity (cumulative Illness Rating Scale-CIRS), presence of geriatric syndromes, presence of caregiver. PTS were classified according to Balducci’s criteria into Fit or Unfit (Frail and Vulnerable).
RESULTS
113 PTS were enrolled: 72(64%) were male, KPS were ≥ 70 in 90 PTS(80%); 37 PTS(33%) had a radical surgery, 63% partial surgery and 4% received a biopsy. 90 PTS(80%) received Stupp treatment, 16 (14%) temozolomide or radiotherapy alone and, only 7(6%) received no treatment. MGMT methylation status was analyzed in 96 PTS: 44% were metMGMT. According to CGA evaluation: 40 PTS(35.4%) were classified as Fit and 73 PTS(64.6%) Unfit. PFS was 11.2(95% CI 6.0–16.4) and 7.2(95% CI 5.8–8.6) months for Fit and Unfit PTS (p=0.1). On multivariate analysis, adjusted for type of surgery, MGMT methylation status and type of therapy, PFS was significantly different between the two groups (HR=0.6, 95% CI 0.2–0.9; p=0.04). OS was 16.4(95% CI 14.6–18.2) and 10.6(95% CI 8.3–12.8) ms for Fit and Unfit PTS (p=0.04); on multivariate analysis the HR was 0.51(95% CI 0.2–0.9; p=0.04). CONCLUSIONS: CGA demonstrated significant outcome prediction in terms of OS and PFS, regardless of therapy and it could be a useful treatment decision-tool.
The optimal treatment of recurrent glioblastoma (GBM) in elderly patients is unclear. Fotemustine (FTM) is a third-generation nitrosourea showing efficacy in gliomas and it has been used with ...different schedules in adult patients. We performed, for the first time anywhere, a mono-institutional retrospective study to analyze the clinical outcome of an alternative fotemustine schedule in elderly patients with recurrent GBM. Retrospectively, we analyzed all GBM patients 65 years or older previously treated with the combination of radiation therapy and temozolomide (TMZ), receiving an alternative FTM schedule as second-line treatment at our Oncological Center from October 2011 to October 2014 with an ECOG PS ≤ 2. FTM was administrated at 80 mg/m
2
every 2 weeks for five consecutive administrations (induction phase), and then every 4 weeks at 80 mg/m
2
as maintenance. We enrolled 44 patients, 33 males and 11 females; average age was 70 years. ECOG PS was 0–1 in 80 % of the patients. 38 patients relapsed during temozolomide (TMZ) therapy. MGMT methylation status was analyzed in 34 patients and MGMT was methylated in 53 % of the patients. The median progression free survival (PFS) and overall survival (OS) from FTM treatment was 4.1 months (95 % CI 3.1–5.2) and 7 months (95 % CI 5.2–8.4), respectively. Patients with MGMT methylated status and patients who relapsed after completing TMZ therapy had a longer PFS and OS from the beginning of FTM. Thrombocytopenia was the most frequent grade 3–4 haematological toxicity (9 %). The alternative schedule of FTM may be an active and safe treatment for elderly patients with recurrent glioblastoma, especially patients with methylated MGMT and who relapsed after completing temozolomide therapy.
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