Background: The concept of expecting radiosensitive tumors in patients genetically hypersensitive to radiation is not widely accepted. Here, we aim to assess whether the tumors of patients with increased lymphocyte apoptotic response with head and neck cancer have a better outcome than their normoresponsive counterparts.
Methods: Seventy-five patients with head and neck cancer treated with curative radiation therapy (RT) were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aiming at assessing the value of CD8 T-lymphocyte apoptosis in predicting intrinsic radiosensitivity. Male to female ratio was 60/15, and median age was 59 years (35-85 ). Median radiation dose was 66 Gy (60-74.4 ) administered in median 41 days (37-58 ). Dose per fraction was 2 Gy in the majority of the patients (n = 70). Prior to RT, all patients were tested using a rapid (48 h) apoptosis assay where fresh blood samples were irradiated with 8-Gy X rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by gradual degradation of DNA (sub-G1 peak on the DNA histogram). Acute (CTC v2.0) and late (RTOG/EORTC) toxicities were graded in all patients. Median follow-up period was 31 months (23-43 ).
Results: Following in vitro 8-Gy irradiation, median radiation-induced CD8 apoptosis was 20.88% (5.69-57.00%). Radiation-induced CD8 apoptosis significantly predicted grade 2 and 3 late effects. The area under the curve of the receiver-operated characteristic curve (sensitivity versus 1-specificity) of CD8 apoptosis was 0.83. Median time to locoregional relapse was 30 months (1-43 months). There were 13 locoregional relapses among the 37 patients showing CD8 apoptosis below the median compared to 5 of 38 who were above (p = 0.02). Two-year estimated locoregional relapse rate was 31% (95% CI: 17-45%) versus 14% (95% CI: 3-25%), respectively (p = 0.03).
Conclusions: In patients with head and neck cancer treated with definitive or postoperative RT, in vivo apoptotic response of CD8 lymphocytes depends on genetic radiosensitivity, and the tumor follows the same genetic radiosensitivity of normal tissues. However, these findings should be confirmed prospectively, and future dose escalation studies could be stratified using the apoptosis assay.