On the margins.

Top Line: Do reduced clinical target volume (CTV) margins increase marginal recurrences for glioblastoma multiforme (GBM)?

The Study: The ideal CTV margin for GBM is debated. Guidelines recommend a 1-2 cm margin acknowledging that many high volume centers tend towards the lower end of that spectrum with some using even smaller margins. This large retrospective retrospective study analyzed 207 GBM recurrences from two Italian centers. All patients were treated with radiation and concurrent temozolomide followed by adjuvant temozolomide. Radiation dose was either 60 Gy in 30 fractions or 59.4 Gy in 33 fractions. A single volume approach was used based on the ESTRO-ACROP guidelines with a 2 cm CTV expansion from the T1 enhancing (plus resection cavity) GTV. Most commonly, a 3 mm PTV margin was used. The authors generated new, reduced margin CTVs consisting of a 1 cm expansion from the original GTV with the same 3-5 mm PTV margins. They then defined “in-field” recurrence as >80% of the recurrent tumor overlapping the 95% isodose line, “marginal” recurrence as 20-80% overlap, and “distant” recurrence as <20% overlap. Using the original plans with 2 cm CTV margins, 87% of recurrences were in-field, 2% were marginal, and 11% were distant. This included 2% with simultaneous in-field and distant recurrence. Using the reduced CTV margins, 86% of recurrences were in-field, 1% were marginal, and 13% were distant. In other words, there was no difference in patterns of recurrence with a reduction in the CTV margin to 1 cm. In one sense, we don’t know if there would have been more marginal recurrences had a smaller volume been used for the actual treatment. But this does show that the majority of in-field recurrences with a large CTV margin are not at the edges of that volume. They are within 1 cm of the GTV. There were big differences, though, in dosimetry. The median CTV volume was nearly halved using a 1 cm margin (137cc v 235cc). There were also significant reductions in V20-V50 of normal brain and reduced dose to the hippocampi.

TBL: In this large retrospective series of GBM recurrences, most occurred within 1 cm of the GTV. A smaller 1 cm CTV margin would likely have covered these volumes while slashing normal brain dose. | Minniti, Radiother Oncol 2022