Indications for Treatment: Is Observation or Chemotherapy Alone a Reasonable Approach in the Management of Low-Grade Gliomas?

Abstract

The treatment of newly diagnosed low grade gliomas (LGG) remains controversial. Recently published results from the long-term follow up of Radiation Therapy Oncology Group (RTOG) trial 9802 demonstrated medically meaningful and statistically significant survival prolongation by adding chemotherapy with procarbazine, lomustine, and vincristine (PCV) after radiotherapy vs. radiotherapy alone for “high” risk patients (median 13.3 vs. 7.8 years, HR 0.59, p=0.03). However, in the 17 years since that trial was launched there have been advances in the understanding of LGG biology and patient heterogeneity, an increased recognition of late neuro-cognitive injury from early radiotherapy and the emergence of temozolomide as an alternative chemotherapy to PCV. These and other changes in the treatment landscape make the applicability of results from RTOG 9802 to all patients less clear. Moreover, in some patients, especially those at the lowest risk for early disease progression, deferred radiotherapy in favor of active surveillance or chemotherapy alone may remain reasonable treatment approaches.

Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?

“…25,26 does not necessarily follow, as previously reported. [31][32][33][34] We conclude that evidence-based practice in the field of diffuse low-grade glioma cannot be derived from the standard methodology of randomized clinical trials. This is not surprising, considering the very long survival of patients with this disease and the numerous parameters (age, clinical, epileptic and cognitive status, patient's way of life, histology, molecular biology, radiological kinetics, extent of resection, response to each chemotherapy line and radiation sequence) that have to be integrated to update decision making all along the course of the management.…”

Salinomycin exhibits anti-angiogenic activity against human glioma in vitro and in vivo by suppressing the VEGF-VEGFR2-AKT/FAK signaling axis

“…Glioma is highly aggressive and is associated with a very poor prognosis, and the median survival rate is ~12–15 months ( 30 , 31 ). Even though the current clinical treatments for glioma have achieved satisfactory results, adjuvant chemotherapy after surgical resection and radiotherapy are still irreplaceable ( 32 – 34 ). This forms a rationale for the development of novel chemotherapeutic agents for the treatment of glioma.…”

Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network

“…The Radiation Therapy Oncology Group (RTOG) 9802 trial demonstrated a clear survival benefit of PCV following RT in patients with “high-risk” DLGG. 4 However, this result did not necessarily influence practice 10,11,16,25 as clinicians still largely propose TMZ to patients, in the absence of studies comparing both regimens and considering the ease of administration of TMZ and the toxicity of PCV.…”