A new randomized prospective study has compared conventional and hypofractionated chemoradiotherapy regimens in patients with newly diagnosed glioblastoma multiforme (GBM). The study, published in the Journal of Cancer Research and Therapeutics in June 2023, found that a hypofractionated radiotherapy (RT) regimen was not inferior to conventional RT in terms of treatment response and progression-free survival.
The study was conducted at the Regional Cancer Centre in Bikaner, India. Fifty patients with histologically-proven postoperative newly diagnosed GBM were enrolled between December 2018 and March 2020. Patients were randomly assigned to receive either conventional chemoradiotherapy (arm A) or hypofractionated chemoradiotherapy (arm B), with 25 patients in each arm.
Patients in the conventional arm received a total dose of 60 Gy in 30 fractions (2 Gy per fraction) over 6 weeks. Those in the hypofractionated arm received 50 Gy in 20 fractions (2.5 Gy per fraction) over 4 weeks. All patients received concurrent chemotherapy with temozolomide (TMZ) at 75 mg/m2 daily during radiotherapy. This was followed by adjuvant TMZ at 150 mg/m2 for 5 days every 4 weeks for 6 cycles in both arms.
The primary objective was to compare the efficacy of hypofractionated RT versus conventional RT in terms of disease-free survival (DFS). Secondary objectives included assessment of treatment-related toxicities and tumor response.
Inclusion criteria were age 15-65 years, operated cases of GBM, Karnofsky performance status (KPS) of 70 or higher, normal hematological, renal and liver function, no previous RT for GBM, and no concurrent malignancies. The median age was 35 years in arm A and 43 years in arm B. Most patients had involvement of multiple lobes and a KPS of 90.
Treatment response was evaluated by contrast-enhanced CT or MRI at 1, 3, 6 and 12 months after completion of chemoradiotherapy. At the 3-month follow-up, partial response was observed in 64% of patients in arm A versus 60% in arm B. Stable disease was seen in 36% and 40% respectively. The difference in response rates was not statistically significant (p=0.768).
At 6 months, the progression-free survival (PFS) rate was 84% in arm A versus 80% in arm B (p=0.71). The 12-month PFS was 60% in arm A and 52% in arm B (p=0.69). While arm A showed slightly higher PFS rates, the differences were not statistically significant.
Importantly, the toxicity profiles were similar between the two arms. There were no grade 3 or 4 non-hematological toxicities observed in either group. The most common side effects included nausea, vomiting, headache, fatigue, seizures and alopecia, predominantly of grade 1-2 severity.
The authors concluded that the hypofractionated RT regimen was not inferior to conventional RT in terms of overall response and 6-month PFS, with comparable toxicity profiles. They suggest hypofractionation could be considered as an alternative approach in appropriate GBM patients.
This study adds to the growing body of evidence supporting hypofractionated RT regimens in GBM. Previous research has shown promising results with shortened RT courses. For instance, the HART-GBM trial published in 2018 found comparable survival outcomes and toxicity between hypofractionated and conventional RT with concurrent TMZ. A 2017 study by Perry et al. demonstrated improved survival with the addition of TMZ to short-course RT in elderly GBM patients.
The potential clinical impact of these findings is significant. A shortened RT course could offer several advantages for patients with GBM: 1. Reduced treatment burden: Fewer hospital visits and a shorter overall treatment time may improve quality of life for patients with limited life expectancy. 2. Improved resource utilization: Shorter RT courses could allow treatment of more patients with the same resources, potentially reducing wait times. 3. Cost-effectiveness: Fewer fractions may lead to reduced healthcare costs associated with RT delivery. 4. Biological rationale: Some radiobiological models suggest hypofractionation may be more effective against rapidly proliferating tumors like GBM.
However, it is important to note the limitations of this study when interpreting its results: 1. Small sample size: With only 25 patients per arm, the study may have been underpowered to detect small differences in outcomes. 2. Short follow-up: The 12-month follow-up period may not be sufficient to assess long-term outcomes and late toxicities. 3. Single-center design: Results from a single institution may not be generalizable to all patient populations and treatment settings. 4. Lack of overall survival data: While PFS was reported, overall survival outcomes were not presented, which is a critical endpoint in GBM studies. 5. Potential selection bias: The inclusion of patients with KPS ≥70 may have selected for a relatively fit patient population, potentially limiting generalizability to all GBM patients.
Despite these limitations, the study provides valuable data supporting the feasibility and potential non-inferiority of hypofractionated RT in GBM. The results are consistent with other studies in the field and add to the growing evidence base for this approach.
The findings may be particularly relevant for certain subgroups of GBM patients. Elderly patients or those with poor performance status may especially benefit from a shortened treatment course. Additionally, in resource-limited settings or during situations that necessitate minimizing hospital visits (such as the recent COVID-19 pandemic), hypofractionated regimens could be an attractive option.
However, before widespread adoption of hypofractionated RT as a standard approach in GBM, larger multi-center randomized trials with longer follow-up and overall survival endpoints are needed. Such studies should also aim to identify subgroups of patients most likely to benefit from hypofractionation and explore potential combinations with novel systemic therapies.
It is worth noting that ongoing research in GBM is also exploring other strategies to improve outcomes, including dose-escalated RT, particle therapy, immunotherapy combinations, and targeted molecular agents. The optimal integration of hypofractionated RT within these evolving treatment paradigms remains an area of active investigation.
In conclusion, this study provides encouraging data on the use of hypofractionated RT in newly diagnosed GBM. While not practice-changing on its own, it adds to the growing evidence supporting this approach and may inform the design of larger definitive trials. As the field continues to evolve, personalized treatment strategies that balance efficacy, toxicity, and patient preference will be crucial in improving outcomes for patients with this challenging disease.
For now, the decision to use hypofractionated versus conventional RT in GBM should be made on a case-by-case basis, considering factors such as patient age, performance status, tumor characteristics, and patient preference. Ongoing and future studies will help further refine the role of hypofractionation in the multimodal management of GBM.
References
Khatri NK, Kumar HS, Sharma N, Jakhar SL, Dhaka S. Comparative study of concurrent conventional chemoradiotherapy versus hypofractionated chemoradiotherapy in newly diagnosed glioblastoma multiforme postoperative patients. J Cancer Res Ther. 2023;19(5):1126-1130. doi:10.4103/jcrt.jcrt_594_21
