Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: A quantitative dosimetric study

Purpose: To analyze the failure patterns for patients with high-grade astro cytomas treated with high-dose conformal radiotherapy (CRT) using a quantit ative technique to calculate the dose received by the CT- or MR-defined rec urrence volume and to assess whether the final target volume margin used in the present dose escalation study requires redefinition before further esc alation. Methods and Materials: Between 4/89 and 10/95, 71 patients with high-grade supratentorial astrocytomas were entered in a phase I/II dose escalation st udy using 3-D treatment planning and conformal radiotherapy. All patients w ere treated to either 70 or 80 Gy in conventional daily fractions of 1.8-2. 0 Gy. The clinical and planning target volumes (CTV, PTV) consisted of succ essively smaller volumes with the final PTV defined as the enhancing lesion plus 0.5 cm margin. As of 10/95, 47 patients have CT or MR evidence of dis ease recurrence/progression. Of the 47 patients, 36 scans obtained at the t ime of recurrence were entered into the 3-D radiation therapy treatment pla nning system. After definition of the recurrent tumor volumes, the recurren ce scan dataset was registered with the pretreatment CT dataset so that the actual dose received by the recurrent tumor volumes during treatment could be accurately calculated and then analyzed dosimetrically using dose-volum e histograms. Recurrences were divided into several categories: 1) "central ," in which 95% or more of the recurrent tumor volume (V-recur) was within D-95, the region treated to high dose (95% of the prescription dose); 2) "i n-field," in which 80% or more of V-recur was within the D-95 isodose surfa ce; 3) "marginal," when between 20 and 80% of V-recur was inside the D-95 s urface; 4) "outside," in which less than 20% of V-recur was inside the D-95 surface. Results: In 29 of 36 patients, a solitary lesion was seen on recurrence sca ns. Of the 29 solitary recurrences, 26 were central, 3 were marginal, and n one were outside. Multiple recurrent lesions were seen in seven patients: t hree patients had multiple central and/or in-field lesions only, three pati ents had central and/or in-field lesions with additional small marginal or outside lesions, and one patent had 6 outside and one central lesion. Since total recurrence volume was used in the final analysis, 6 of the 7 patient s with multiple recurrent lesions were classified into central/in-field cat egory. Conclusion: Analysis of the 36 evaluable patients has shown that 32 of 36 p atients (89%) failed with central or in-field recurrences, 3/36 (8%) had a significant marginal component to the recurrence, whereas only 1/36 (3%) co uld be clearly labeled as failing mainly outside the high-dose region. Seve n patients had multiple recurrences, but only 1 of 7 had large-volume recur rences outside the high-dose region. This study shows that the great majori ty of patient recurrences that occur after high-dose (70 or 80 Gy) conforma l irradiation are centrally located: only 1/36 patients (with 7 recurrent l esions) had more than 50% of the recurrence volume outside the region previ ously treated to high dose. Further dose escalation to 90 Gy (and beyond) t hus seems reasonable, based on the same target volume definition criteria. (C) 1998 Elsevier Science Inc.