Initial PCV Chemotherapy Followed by Radiotherapy Is Associated With a Prolonged Response But Late Neurotoxicity in 20 Diffuse Low-Grade Glioma Patients

Abstract

BackgroundStudy RTOG 9802 in high-risk diffuse low-grade gliomas (DLGGs) showed the potential synergistic effect on survival of the procarbazine, CCNU, and vincristine (PCV) radiotherapy (RT) combination. Limited data on long-term neurocognitive impact and quality of life (QoL) have yet been reported.Patients and MethodsWe described a monocentric series of patients treated at first line by the combination of PCV immediately followed by RT between January 01, 1982 and January 01, 2017. Radiological data were collected and included volume, velocity of diametric expansion (VDE), and MRI aspects. Long-term neurocognitive and QoL were analyzed.ResultsTwenty patients fulfilled the eligibility criteria. The median response rate was 65.1% (range, 9.6%–99%) at the time of maximal VDE decrease corresponding to a median volume reduction of 79.7 cm3 (range, 3.1 to 174.2 cm3), which occurred after a median period of 7.2 years (range, 0.3–21.9) after the end of RT. An ongoing negative VDE was measured in 13/16 patients after the end of RT, with a median duration of 6.7 years (range, 9 months–21.9 years). The median follow-up since radiological diagnosis was 17.5 years (range, 4.8 to 29.5). Estimated median survival was 17.4 years (95% CI: 12; NR). After a long-term follow-up, substantial neurotoxicity was noticed with dementia in six progression-free patients (30%), leading to ventriculo-peritoneal shunt procedures in three, and premature death in five. Thirteen patients (65%) were unable to work with disability status. Successive longitudinal neurocognitive assessments for living patients showed verbal episodic memory deterioration.ConclusionsPCV-RT combination seems to have not only an oncological synergy but also a long-term neurotoxic synergy to consider before initial therapeutic decision.

Repeated Awake Surgical Resection(s) for Recurrent Diffuse Low-Grade Gliomas: Why, When, and How to Reoperate?

“…Conversely, if the regrowth is slow after the initial resection, then postponing adjuvant therapies can be proposed, especially concerning radiotherapy ( 67 ). Indeed, irradiation of the white matter tracts has a risk to generate delayed cognitive deteriorations ( 68 , 69 ). Moreover, radiotherapy-induced alterations in the brain microenvironment also contribute to recurrent glioma aggressiveness ( 70 ).…”

A Personalized Longitudinal Strategy in Low-Grade Glioma Patients: Predicting Oncological and Neural Interindividual Variability and Its Changes over Years to Think One Step Ahead

“…Combination of RT with procarbazine, CCNU (lomustine), and vincristine (PCV) resulted in prolonged OS in comparison with RT alone [ 83 ]. However, due to its possible negative impact on long-term cognition [ 94 ], this regimen has not imposed itself as the gold-standard treatment after surgery, especially in the European Low-Grade Glioma Network, in which Temozolomide is largely used as first-line treatment after surgical resection for high-risk LGG patients, or at progression [ 95 ]. Interestingly, predictive factors of chemosensitivity have been identified, especially 1p19q co-deletion and MGMT methylation, to select patients who can benefit from upfront treatment with Temozolomide, with the aim to defer radiation therapy to enable long-lasting preservation of quality of life [ 96 ].…”

“…Radiotherapy: As evidenced by many studies involving objective neuropsychological evaluation performed within 18 months [ 152 , 153 ] and after long-term follow-up following brain RT [ 94 , 154 ], there is a high risk of inducing permanent cognitive decline with a negative impact on QoL, including possible dementia, even if the glioma is still under control [ 94 ]. Importantly, as well as possibly inhibiting hippocampal neurogenesis, radiation-induced impairment of cognitive abilities is mainly related to white matter tract damage [ 155 , 156 , 157 ].…”

The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma

“…In addition, vincristine inhibits the synthesis of proteins and nucleic acids, blocking the utilization of glutamic acid [8]. The PCV regimen in combination with radiotherapy achieves an antineoplastic effect, but this combination of drugs has a pronounced neurotoxicity that exceeds the neurotoxicity of each of the components [9].…”