P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy

Hypothesis: P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT). Study Design: Re trospective analysis of p53 and Ki-67 status from the CRT arm of a randomiz ed, controlled trial (n = 50) and from patients receiving the same treatmen t but not enrolled in the trial (n = 55). Methods: P53 and Ki-67 status wer e established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells st ained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained fo r Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive m odels were calculated for each outcome. Results: Neither marker predicted t umor response to treatment. P53+ status was associated with tumor recurrenc e (P = .003) and locoregional recurrence (P = .003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free sur vival (P = .004), lower disease-specific survival (P = .04), lower overall survival with primary site preservation (P = .03), and lower disease-specif ic survival with primary site preservation (P = .003). Multivariate analysi s revealed that p53+ status was significantly related to a lower recurrence -free survival (P = .01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P = .02, RR = 3.41). Ki-67+ status was n ot related to any variables. However, multivariate analysis revealed that K i-67+ was significantly related to a lower overall survival (P = .05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associate d with a lower incidence of tumor recurrence (P = .02), lower locoregional recurrence (P =.01), and fewer second primary lesions (P = .04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P = .02), higher disease-specific survival with primary site preservation (P = .02), and higher overall survival with prima ry site preservation (P = .02). Multivariate analysis revealed that p53-/Ki -67- status was significantly related to a higher overall survival with sit e preservation (P = .01, RR = 2.78). Conclusions: P53 and Ki-67 status appe ar to be related to the various survival end points considered in this stud y. However, this relation does not seem to be sufficient to warrant treatme nt modifications. Closer follow-up may be justified in both p53+ and Ki67patients to detect recurrence or a second primary at an earlier stage, poss ibly improving survival.