title: The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population.
abstract: OBJECTIVE
  To analyze patterns of failure in patients (pts) with high-risk posterior fossa primitive neuroectodermal tumors (PF-PNETs) treated with combined modality therapy on a large, randomized multiinstitutional study.
  
  
  METHODS
  One hundred eighty-eight prospectively staged pts with PF-PNET confirmed by central pathology review, with high-risk features, were treated on Children's Cancer Group Study 921 (CCG-921), comparing two chemoradiotherapy regimens. Patterns of initial sites of failure were analyzed, specifically evaluating the impact of Chang M-stage.
  
  
  RESULTS
  Progression-free survival (PFS) correlated with the presence or absence of metastatic disease (p < 0.001), with 5-year PFS of 68 +/- 5.8% for M0 vs. 43 +/- 6.8% for M+ pts. The cumulative incidence functions (CIF) of recurrence were different (p = 0.005) and at 5 years were 29 +/- 4.7% for M0 pts and 48 +/- 5.5% for M+ pts. Involvement of the PF at time of initial failure as measured by CIF correlated with M-stage (p = 0.047) and occurred in 18 +/- 3.9% of M0 pts and 8 +/- 2.9% of M+ pts overall; PF as the only site of relapse also correlated with M-stage (p = 0.019) and was seen in 6 +/- 2.5 and 0% of M0 and M+ pts, respectively, at 5 years. Relapse in the spine and/or cerebrospinal fluid (CSF) at initial recurrence was correlated with M-stage (p < 0.002), with 5-year cumulative incidences of 14 +/- 3.7%, 26 +/- 8.2%, 40 +/- 15%, and 40 +/- 7.7% for M0, M1, M2, and M3 pts, respectively. Isolated spine/CSF recurrence correlated with M-stage (p = 0.034) and occurred in 2 +/- 1.5% of M0 and 9 +/- 3.2% of M+ pts by 5 years. The median time to relapse for pts who failed was 1.2 years (range 0.2-5.3). Ninety percent of all relapses occurred by 3 years.
  
  
  CONCLUSIONS
  Original sites of disease are at the highest risk for relapse, but the entire neuraxis remains at significant risk, despite combined-modality treatment. M-Stage was prognostic for spine/CSF relapse as well as PFS and may be an important tool in guiding therapy. A more aggressive approach to local control in the neuraxis is warranted, especially in M+ patients.
authors.affiliation: Department of Human Oncology, School of Medicine, University of Wisconsin, Madison, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Yao
authors.forename: M P
authors.initials: MP
authors.lastname: Mehta
authors.forename: J M
authors.initials: JM
authors.lastname: Boyett
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Donahue
authors.forename: L B
authors.initials: LB
authors.lastname: Rorke
authors.forename: P M
authors.initials: PM
authors.lastname: Zeltzer
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003388:Cranial Fossa, Posterior; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy*; D013997:Time Factors; D017211:Treatment Failure