2345P - The possibility of programmed death-ligand 1-related immune modulation in neoadjuvant thermoradiotherapy for rectal cancer

Background

The expression of programmed death ligand 1 (PDL1) and CD8-positive T lymphocytes (CD8T) in tumor tissue is known to be influenced by radiotherapy (RT). This type of immune modulation is likely enhanced by hyperthermia (HT), which has been studied preclinically. We describe the immunogenic effects of additive HT in neoadjuvant treatment for rectal cancer.

Methods

Clinical data were reviewed for consecutive 32 patients who received neoadjuvant treatment and did not achieve total regression considering paired tumor tissue analysis from 2012 to 2017. On obtained pre- and post-treatment tumor tissue for each patient, further immunohistochemistry was done to examine the expression of PDL1 and CD8T. The majority of the patients were male (78.1%) and the median age was 57 years. Sixteen patients (50.0%) received HT twice weekly with 40 Gy RT (RHT group) and the others (50.0%) underwent standard 50.4 Gy RT (RT group). Age, initial clinical stage, and pathologic differentiation did not differ between the two groups. The median follow-up period was 68 months (range, 14−107 months).

Results

Both groups showed no significant difference in T- and N-downstaging ratio. Near total regression was experienced by 4 (25.0%) and 7 (43.8%) patients in the RHT and RT groups, respectively. The increase in PDL1 positivity was 0.95±2.17% (p=0.076) in the RHT group and 0.52±0.95% (p=0.257) in the RT group, while CD8T positivity increase was remarkable in both groups (RHT group: 27.97±18.26% (p<0.001); RT group: 22.50±13.14% (p<0.001)). The RHT group showed a relatively high propensity for both overall survival (median 72.0 versus 63.2 months, p=0.130) and local recurrence-free survival (median 69.1 versus 59.7 months, p=0.136). In multivariate analysis, higher level of post-treatment PDL1 positivity (>0.57%) and its increment (>0.35%) had a greater impact on disease-free survival (p=0.027 and p=0.008) and distant metastasis-free survival (p=0.063 and p=0.020).

Conclusions

Post-treatment PDL1 positivity status may have an effect on the prognosis. Even with relatively poor tumor regression, HT-combined low-dose RT did not impair survival, indicating that HT might be involved in the PDL1-related immune mechanism.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.