One year of procarbazine lomustine and vincristine is poorly tolerated in low grade glioma: a real world experience in a national neuro-oncology centre

Abstract Background Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice. Methods We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities. Results Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia. Conclusion Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.

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One Year of Procarbazine Lomustine and Vincristine is Poorly Tolerated in Low Grade Glioma: A Real World Experience in a National Neuro-Oncology Centre

10.21203/rs.3.rs-115879/v1 ◽

2020 ◽

Author(s):

Rachel Keogh ◽

Razia Aslam ◽

Maeve Hennessy ◽

Zac Coyne ◽

Bryan Hennessy ◽

...

Keyword(s):

Clinical Practice ◽

Dose Intensity ◽

Low Grade Glioma ◽

Randomised Control Trial ◽

Low Grade ◽

One Year ◽

Oncology Centre ◽

Dose Modifications ◽

Experienced Grade ◽

Grade Iii

Abstract BackgroundFollowing optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, one year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after six months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice. MethodsWe conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities. ResultsOverall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥ 40 years. Overall, 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all six cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia. ConclusionToxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.

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Comment on: the role of biopsy in the management of patients with presumed diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline

Journal of Neuro-Oncology ◽

10.1007/s11060-016-2086-0 ◽

2016 ◽

Vol 128 (1) ◽

pp. 173-173 ◽

Cited By ~ 1

Author(s):

Christoph Schwartz ◽

Friedrich-Wilhelm Kreth

Keyword(s):

Systematic Review ◽

Clinical Practice ◽

Clinical Practice Guideline ◽

Practice Guideline ◽

Low Grade Glioma ◽

Low Grade ◽

Evidence Based

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Evidence-based clinical practice parameter guidelines for the treatment of adults with diffuse low grade glioma: introduction and methods

Journal of Neuro-Oncology ◽

10.1007/s11060-015-1847-5 ◽

2015 ◽

Vol 125 (3) ◽

pp. 449-456 ◽

Cited By ~ 7

Author(s):

Jeffrey J. Olson ◽

Steven N. Kalkanis ◽

Timothy C. Ryken

Keyword(s):

Clinical Practice ◽

Low Grade Glioma ◽

Low Grade ◽

Evidence Based ◽

Practice Parameter

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Update on the evidence-based clinical practice parameter guidelines for the treatment of adults with diffuse low grade glioma: the role of initial chemotherapy

Journal of Neuro-Oncology ◽

10.1007/s11060-016-2137-6 ◽

2016 ◽

Vol 128 (3) ◽

pp. 487-489 ◽

Cited By ~ 1

Author(s):

Mateo Ziu ◽

Jeffrey J. Olson

Keyword(s):

Clinical Practice ◽

Low Grade Glioma ◽

Low Grade ◽

Evidence Based ◽

Practice Parameter

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EASE: Clinical Implementation of Automated Tumor Segmentation and Volume Quantification for Adult Low-Grade Glioma

Frontiers in Medicine ◽

10.3389/fmed.2021.738425 ◽

2021 ◽

Vol 8 ◽

Author(s):

Karin A. van Garderen ◽

Sebastian R. van der Voort ◽

Adriaan Versteeg ◽

Marcel Koek ◽

Andrea Gutierrez ◽

...

Keyword(s):

Clinical Practice ◽

Automatic Segmentation ◽

Low Grade Glioma ◽

Tumor Segmentation ◽

Low Grade ◽

Clinical Implementation ◽

Volumetric Assessment ◽

Ensure Patient Safety ◽

Volume Measurements ◽

The Individual

The growth rate of non-enhancing low-grade glioma has prognostic value for both malignant progression and survival, but quantification of growth is difficult due to the irregular shape of the tumor. Volumetric assessment could provide a reliable quantification of tumor growth, but is only feasible if fully automated. Recent advances in automated tumor segmentation have made such a volume quantification possible, and this work describes the clinical implementation of automated volume quantification in an application named EASE: Erasmus Automated SEgmentation. The visual quality control of segmentations by the radiologist is an important step in this process, as errors in the segmentation are still possible. Additionally, to ensure patient safety and quality of care, protocols were established for the usage of volume measurements in clinical diagnosis and for future updates to the algorithm. Upon the introduction of EASE into clinical practice, we evaluated the individual segmentation success rate and impact on diagnosis. In its first 3 months of usage, it was applied to a total of 55 patients, and in 36 of those the radiologist was able to make a volume-based diagnosis using three successful consecutive measurements from EASE. In all cases the volume-based diagnosis was in line with the conventional visual diagnosis. This first cautious introduction of EASE in our clinic is a valuable step in the translation of automatic segmentation methods to clinical practice.

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Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma

Journal of Clinical Oncology ◽

10.1200/jco.2003.01.009 ◽

2003 ◽

Vol 21 (4) ◽

pp. 646-651 ◽

Cited By ~ 184

Author(s):

Jennifer A. Quinn ◽

David A. Reardon ◽

Allan H. Friedman ◽

Jeremy N. Rich ◽

John H. Sampson ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Objective Response ◽

Malignant Gliomas ◽

Progression Free Survival ◽

Chemical Conversion ◽

Low Grade Glioma ◽

Low Grade ◽

Grade 3 ◽

Experienced Grade

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

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P03.09 Real world management and prognosis of glioma patients:SYSUCC report from China

Neuro-Oncology ◽

10.1093/neuonc/noz126.090 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii26-iii27

Author(s):

D Li ◽

Y Chen ◽

C Guo ◽

Q Yang ◽

S Wu ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Cancer Center ◽

Low Grade ◽

High Grade ◽

Who Grade ◽

Low Grade Gliomas ◽

Pathological Subtype ◽

High Grade Gliomas ◽

Grade Iii

Abstract Background: The conventional way of patient treatment should be following guidelines. While in clinical practice, patients received treatments very often away from suggested guideline. In this report, we reviewed glioma patients received real world treatment at Sun Yat-sen University Cancer Center (SYSUCC) and results of this patient series. Methods: Total of 1215 glioma patients received surgery at SYSUCC from 2000 to 2017 were enclosed for analysis. The pathologic diagnosis of patients has followed WHO classification (initially 2007 standard, than 2016 standard). Results: A total of 1001 newly diagnosed brain glioma patients were analyzed, including 90 cases WHO grade I, 307 grade II, 239 grade III and 365 grade IV. The median age of onset was 14 (1–75), 35 (2–69), 41 (8–82) and 50 (2–86) years old, respectively, for grade I, II, III and IV glioma patients. Tumor total resection was achieved in 567 patients (57.5%). Among all patients, 331 high-grade gliomas (54.8%) and 159 low-grade glioma (40.1%) received radiotherapy, whereas 285 high-grade gliomas (47.1%) and 80 low-grade tumors (20.2%) received chemotherapy. Among high-grade gliomas, the median OS of glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglial tumors were 17.7 months (15.7–19.7 months), 33.7 months (24.0–43.4 months) and 110.6 months (43.5–177.7 months), respectively, whereas the median OS of low-grade gliomas was not reach. The 5-year survival rate of grade I, II, III and IV gliomas was 94.7%, 73.7%, 45.1% and 18.6%, respectively. Multivariate analysis identified that onset age, Karnofsky performance status, tumor location, preoperative seizure, pathological subtype, resection extent and post-surgical treatment were independent predictors of OS for patients with high-grade gliomas. Patients received post-surgical radiotherapy and (or) chemotherapy had better survival than those without adjuvant treatment (grade III: 53.3 vs. 20.6 months, p =0.012; grade IV: 22.9 vs. 12.3 months, p < 0.001). For low-grade gliomas, patients’ age, Ki-67 index, tumor subtype and resection extent were associated with clinical outcomes. Conclusions: Glioma patients received treatments do not always following guidelines in clinical practice. Although standard care for patients may beneficial for prognosis, personalized treatment may more acceptable for patients and even resulting better outcome which should keep in mind in routine clinical practice.

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