Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience

Abstract

Recurrent diffuse intrinsic pontine gliomas (DIPG) are traditionally treated with palliative care since no effective treatments have been described for these tumors. Recently, clinical studies have been emerging, and individualized treatment is attempted more frequently. However, an informative way to compare the treatment outcomes has not been established, and historical control data are missing for recurrent disease. We conducted a retrospective chart review of patients with recurrent DIPG treated between 1998 and 2010. Response progression-free survival and possible influencing factors were evaluated. Thirty-one patients were identified who were treated in 61 treatment attempts using 26 treatment elements in 31 different regimens. The most frequently used drugs were etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic acid (13). Seven patients had repeat radiation therapy to the primary tumor. Response was recorded after 58 treatment attempts and was comprised of 0 treatment attempts with complete responses, 7 with partial responses, 20 with stable diseases, and 31 with progressive diseases The median progression-free survival after treatment start was 0.16 years (2 months) and was found to be correlated to the prior time to progression but not to the number of previous treatment attempts. Repeat radiation resulted in the highest response rates (4/7), and the longest progression-free survival. These data provide a basis to plan future clinical trials for recurrent DIPG. Repeat radiation therapy should be tested in a prospective clinical study.

Figure 1

Progression free survival times in patients treated for recurrent DIPG. The different patterns of the bars indicate if the first evaluation after starting the treatment showed stable disease (hateched) or progressive disease (solid) or partial response (white). Patietns with censored time (event not known yet) are excluded from this figure.

Figure 2

Event free survival time in recurrent DIPG in relation o previous time to progression in the same patients after the previous treatment attempt. The two number were weakly correlated. The lines indicate the deviation of the observed EFS from the predicted EFS based on the regression analysis. The length of these lines were defined as EFS-gain and used as measure for treatment success. With points far above the regression line suggesting effective treatment., and point below less than average outcomes.

Figure 3

Kaplan Meier Estimate EFS curves for recurrent DIPG separated by the number of treatments the pateitn had previously. The lines do not separates as assumed, with the fifth line of treatment appearing superior to the second.

Figure 4

event free survival of patient treated with repeat radiation to the primary tumor in comparison to patients treated with a variety of other protocols.