Portal de Periódicos da CAPES

Ultra-Short Courses of Adjuvant Breast Radiotherapy: Promised Land or Primrose Path?

2012; Elsevier BV; Volume: 82; Issue: 2 Linguagem: Inglês

10.1016/j.ijrobp.2011.07.034

1879-355X

Atif J. Khan, Douglas W. Arthur, Roger Dale, Bruce G. Haffty, Frank A. Vicini,

BRCA gene mutations in cancer

In accelerated partial breast irradiation (APBI), the most commonly used fractionation schemes include 340 or 385 cGy delivered in a twice-daily administration. A further extension of the APBI literature has been the recent interest in extremely short courses of adjuvant radiotherapy, usually delivered by intraoperative radiotherapy techniques. This newer area of single-fraction radiotherapy approaches remains highly contentious. In particular, the recently reported TargetedIntraoperativeRadiotherapy(TARGIT)trial(1)has been the subject of both praise and scorn, and a critical examination of the trial data and the underlying hypotheses is warranted. Short-term outcomes of the related Italian Electron Intraoperative Therapy (ELIOT) approach have also been reported (2). Although the assumptions of linear–quadratic formalism are likely to hold true in the range of 2 to 8 Gy, equating different schedules beyond this range becomes an entirely inexact science. A major problem of current single-fraction approachesis that thetreatment doses are chosen empirically or are based on tolerability or on the physical dose delivery characteristics of the chosen technology rather than true radiobiologic rationale. The TARGIT approach uses an intraoperative spherical applicator to deliver a single dose of 20 Gy at the applicator surface with 50-kV x-rays, resulting in a dose of 5 Gy at 1 cm. The TARGIT trialists have extensively advocated their treatmentandthetheoreticalbasisforthestrategy.InitialfindingsoftheTARGIT-Atrialwererecentlypublished(1).Atotal of 2,232 women were randomized either to fractionated whole-breast radiotherapy (with or without a boost) or to targeted intraoperative radiotherapy at a dose of 20 Gy at the applicator surface. Patients were grouped into two strata: the prepathology stratum included patients who had their first definitivelumpectomyandTARGITatthesamesitting,whereas the postpathology stratum consisted of patients who were takenbacktotheoperatingroomfortheTARGITtreatmentafter final pathology had been reviewed. The median age of patientswas 63years (interquartilerange,57–69 years ),86% of tumorswereunder2cm,and84%wereGrade1or2;over90% ofpatientswereER positive.Thetrial didallow node-positive patients; 83% of patients were node negative. Approximately 80% of patients received systemic therapy. Curiously, the medianfollow-upoftheentiregroupisnotreportedbutappearsto beapproximately24monthsfromthemanuscriptfigures.At4 years, there were 6 local recurrences in the intraoperative group and 5 in the external beam radiotherapy (EBRT) group. There was no significant difference in the Kaplan-Meier estimates for local failure at 4 years (1.20% vs. 0.95%, p = 0.41). Toxicity events were low and comparable in both arms. Although the report indicates that 14% of patients assignedtotheTARGITarmwentontoalsoreceiveEBRTbecause of permanent pathology findings, the denominator for thispercentageincludedpatients inthepostpathologystratum whoalreadyhadpathologicconfirmationofsuitability.Inaletter to the editor, in response to queries, the authors subsequently acknowledged that 21% of patients in the prepathology stratum were triaged for additional EBRT (3). Because of its prominence, a critical review of the TARGITassumptions is warranted. The biologic rationale for intraoperative single-fraction radiotherapy, as advanced by the TARGIT trialists, circumvents the potential constraints imposed by conventional radiobiology by invoking a new and currently undefined biologic parameter, that of the lumpectomy cavity microenvironment. In support of their hypothesis, the authors have reported the results of translational experiments performed with wound fluid harvested from TARGIT-treated and untreated patients, and these results appear tooffertantalizingevidencethatradiotherapy abrogates the proliferative cascade induced by surgical wound healing