Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

Safety and Efficacy of Procarbazine and Lomustine Chemotherapy as a Salvage Treatment for Recurrent Adult Glioma

PurposeWhile procarbazine, lomustine, and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma, whether vincristine included in this regimen is beneficial is uncertain due to its potential toxicity and uncertain efficacy. In this study, we evaluated the safety and efficacy of PC chemotherapy in contrast with those of PCV chemotherapy. MethodsUsing electronic medical records, all patient with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary’s Hospital or St. Vincent’s Hospital were examined retrospectively. A total of 59 patients met our eligibility criteria. Among them, 15 patients received PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). ResultsThe PC group presented a significantly lower hematology toxicity (anemia: 6.7% vs. 45.5%; p = 0.02 and thrombocytopenia: 20.0% vs. 70.4%; p < 0.001). Also, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s), or total cessation of chemotherapy, were significantly less frequent (26.7% vs. 68.2%; p = 0.012). The overall survival of PC group was significantly longer than that of PCV group (396 vs. 232 days; p = 0.042), while there was no significant difference in progression-free survival between two groups (284.5 vs. 131 days; p = 0.077). ConclusionThis is the first comparative study to suggest that PC chemotherapy leads to less toxicity than PCV chemotherapy without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are needed to validate our findings.

PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

CTNI-20. PCV CHEMOTHERAPY ALONE IS ASSOCIATED WITH BETTER CLINICAL COURSE IN OLIGODENDROGLIOMA WHO GRADE II

BACKGROUND Current treatment guidelines for oligodendrogliomas (OD) recommend watch-and-wait strategies after gross total resection and radiation with subsequent chemotherapy (procarbazine, CCNU and vincristine (PCV)) after incomplete resection. The value of chemotherapy alone as an option to delay the risk of late cognitive deficits is not well defined yet. Here, we retrospectively investigated long-term outcome in OD WHO II with respect to initial therapy and tumor volume in magnetic resonance imaging (MRI). METHODS A total of 142 patients with OD WHO (World Health Organization) II according to WHO 2016 were retrospectively included. Patients either had watch and wait (W&W) after histological sampling through stereotactic biopsy (n=59) or tumor resection (n=27) or else stereotactic biopsy with subsequent temozolomide (TMZ) (n=26) or PCV (n=30). Pre- and post-therapeutic T2 tumor volumes were obtained. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of secondary malignization after 10 years (MR-10yrs) were correlated with clinical and volumetric data. RESULTS PFS was significantly longer in the PCV cohort compared to TMZ (9.1 vs. 3.6 years, p = 0.04), even after matching patients according to age and initial tumor volume (9.1 vs 4.7 yrs, p = 0.03). PFS in the W&W cohort was 5.1 years and 4.4 years in those receiving tumor resection only. MR-10yrs was 4% in PCV cohort, 18% in the W&W cohort and 52% in the resection only cohort (p = 0.01). In the W&W cohort, patients treated with PCV at first relapse had a longer PR-PFS than those treated with TMZ (in years, 7.2 vs 4.0, p = 0.04). Multivariate analysis confirmed initial PCV therapy (p = 0.01) and initial T2 tumor volume (p = 0.02) to be prognostic. CONCLUSION In oligodendrogliomas WHO II PCV chemotherapy alone is superior in terms of PFS and rate of secondary malignization compared to TMZ chemotherapy alone or tumor resection only.

Short-term outcomes associated with temozolomide vs. PCV chemotherapy for 1p/19q-codeleted WHO grade III anaplastic oligodendrogliomas: a national evaluation

PURPOSEThe optimal chemotherapy regimen between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV) remains uncertain for newly-diagnosed anaplastic oligodendroglioma (AO). We therefore addressed this question using a national database.METHODSPatients newly-diagnosed with 1p/19q-codeleted W.H.O. grade III AO between 2010-2016 were identified from the National Cancer Database. Predictors of receiving first-line single-agent TMZ vs. multi-agent PCV were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression.RESULTS1,360 AO patients were identified: 74.5% (n=1,013) treated with TMZ, 9.6% (n=131) with PCV, and 15.9% (n=216) with no chemotherapy in the first-line setting. In multivariable logistic analysis, PCV utilization increased from 2010 to 2016 (OR=1.38/year, 95%CI: 1.22-1.56, p<0.001) and was less commonly utilized in privately insured patients (OR=0.38 vs. uninsured, 95%CI: 0.15-0.97, p=0.04). In survival analyses (33.1% reached endpoint), there was no difference in unadjusted OS between TMZ (5yr-OS 60.1%, 95%CI: 55.9-64.1) and PCV (5yr-OS 61.1%, 95%CI: 45.6-73.5; p=0.42). There remained no OS difference between TMZ and PCV in the 75.9% (n=1,032) of AO patients that also received radiotherapy (p=0.51), in the Cox regression analysis adjusted by age, extent of resection, and radiotherapy (TMZ vs. PCV HR=1.31, 95%CI: 0.83-2.08, p=0.24), and in subgroup analyses that incorporate KPS or MGMT status.CONCLUSIONSIn a national database of AOs managed in the ‘real-world’ setting, there is no difference in the short-term mortality between first-line TMZ and PCV chemotherapy. These findings provide preliminary data while we await the long-term results from the CODEL trial.

P14.13 Incidence of pseudoprogression in high-grade IDH-mutant gliomas

BACKGROUND Pseudoprogression (PsP) is a well-known concern in IDH-wildtype glioblastomas. The aim of the present study was to describe its incidence in high-grade IDH-mutant gliomas. MATERIAL AND METHODS We retrospectively analyzed the characteristics of a consecutive series of high-grade IDH-mutant gliomas treated with radiotherapy (RT) with or without chemotherapy between March 2009 and September 2017. PsP was defined as a new enhanced lesion that occurred after RT and subsequently disappeared or remained stable during follow-up for a least 6 months. RESULTS The study population consisted of 38 anaplastic IDH-mutant and 1p/19q codeleted oligodendrogliomas, 34 IDH-mutant anaplastic astrocytomas and 18 IDH-mutant glioblastomas. Treatment consisted of radiotherapy alone (n=8, 9%), radiotherapy and PCV chemotherapy (n=63, 70%) and temozolomide radiochemotherapy (n=19, 21%). After a median follow-up of 3.5 years (range 1–8 years), 24 patients (28%) presented a PsP that occurred after a median delay of 10 months after radiotherapy (2 to 32 months). PsP was more frequent in patients treated with RT+PCV than in those treated with RT+TMZ (34% vs 10%, p=0.05). During the first two years after RT completion, 19 patients (21%) presented a PsP and 15 patients (17%) a true progression. At last follow-up, 1 patient (4%) in the PsP group had died compared to 10 patients (16%) in the group of patients without PsP. CONCLUSION PsP is a frequent issue in IDH-mutant high-grade gliomas. Its timing of onset is delayed compared to the timing of PsP onset reported in IDH-wildtype glioblastomas. The association between the use of PCV chemotherapy and PsP requires validation in an independent series.