2018 Sep 4. https://www.ncbi.nlm.nih.gov/pubmed/30182159
Full article:
http://sci-hub.tw/http://link.springer.com/10.1007/s11060-018-2989-z
PURPOSE/OBJECTIVES:
We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.
RESULTS:
A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT (fractionated stereotactic radiotherapy). Patient characteristics were as follows: median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months.
For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only).
In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively.
In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively.
Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75).
CONCLUSIONS:
The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.
The gross tumor volume (GTV) was defined as peripherally enhancing tissue on T1 post-contrast MRI. Surrounding edema was not purposely included in the treatment volume. The planning target volume (PTV) was the GTV with no margin. The PTV was treated to a median dose of 35 Gy delivered in 10 fractions (Supplemental Fig. 1). The constraints for normal critical structures include: brainstem max dose<30 Gy; optic nerve max dose<25 Gy, chiasm max dose<25 Gy for patients previously irradiated near critical structures and max doses less than 35 Gy for patients not previously irradiated near critical organs at risk.
Full article:
http://sci-hub.tw/http://link.springer.com/10.1007/s11060-018-2989-z
PURPOSE/OBJECTIVES:
We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.
RESULTS:
A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT (fractionated stereotactic radiotherapy). Patient characteristics were as follows: median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months.
For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only).
In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively.
In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively.
Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75).
CONCLUSIONS:
The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.
The gross tumor volume (GTV) was defined as peripherally enhancing tissue on T1 post-contrast MRI. Surrounding edema was not purposely included in the treatment volume. The planning target volume (PTV) was the GTV with no margin. The PTV was treated to a median dose of 35 Gy delivered in 10 fractions (Supplemental Fig. 1). The constraints for normal critical structures include: brainstem max dose<30 Gy; optic nerve max dose<25 Gy, chiasm max dose<25 Gy for patients previously irradiated near critical structures and max doses less than 35 Gy for patients not previously irradiated near critical organs at risk.
Selection bias means we can't fairly compare overall survival from diagnosis of this group with historical controls. As it says in the discussion:
ReplyDelete"The patient group examined likely exhibits selection bias
as they were healthy enough to receive multiple treatment
modalities at recurrence, which is often not present in many
patients with a poorer performance status and limits the
accuracy of comparison with historical controls."
Also, 26% of patients in this study had anaplastic astrocytomas, and most likely half or over half of those would have had IDH1 mutation. I would only look at the GBM cohort within this study. Mixing up grade 3 and 4 gliomas where no IDH1 status is available only confuses matters.
There are some inconsistencies in the paper. In the abstract and results, it says median survival from recurrence for the entire group of 118, was 13.8 months. Then in the discussion it says "median survival time from recurrence in our cohort of patients was 14.7 months" - a discrepancy of nearly 1 month from what is stated in the abstract and results sections. And then it says in the discussion median survival from recurrence in the GBM-only group was 13.8 months, whereas the abstract and results stated 11.9 months for the GBM only group. I'm not sure how peer review failed to notice this.
Another limitation, as acknowledged by the authors: "is the inability to determine whether the second treatment modality was added due to progression on BEV or FSRT alone or as a planned sequential regimen."
If all the patients had undergone BEV and FSRT as part of a planned sequential regimen, this would have been closer to a prospective trial, and all patients could have been included in an analysis (including those who were not well enough to receive the second part of the planned treatment) versus historical controls. But that was not the case, and selection bias (only patients who were well enough to receive two salvage therapies could be included) favors this group compared to general historical controls that allowed patients receiving less than two salvage regimens.
My comments are not an argument against sequential BEV + FSRT, or FSRT + BEV. But I'm not sure what this study proves, given the selection biases inherent in the analysis, except that the sequence of BEV -> FSRT versus FSRT -> BEV doesn't seem to matter a great deal.