Cisplatin-based chemoradiation decreases telomerase-specific CD4 TH1 response but increases immune suppressive cells in peripheral blood.

BACKGROUND: The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. Here, we investigated the systemic immune effects of CRT in patients with lung or head and neck cancer. MATERIALS AND METHODS: Peripheral blood mononuclear cells were collected at baseline and 1 month after treatment from blood samples of 29 patients treated with cisplatin-based chemoradiotherapy for lung or head and neck cancer. Circulating anti-tumor Th1 response was assessed by the ELISpot assay using a mixture of human leucocyte antigen (HLA) class II restricted peptides derived from telomerase (TERT). Phenotyping of circulating immunosuppressive cells (Treg and MDSC) was performed by flow cytometry. RESULTS: A significant increase of circulating Treg was observed in 60% of patients after CRT The mean rate of Treg was 3.1% versus 4.9% at baseline and after CRT respectively, p = 0.0015). However, there was a no significant increase of MDSC rate after CRT. In contrast, a decrease of tumor-specific Th1 response was documented in 7 out of 10 evaluated patients. We found high frequency of pre-existing tumor-specific Th1 response among patients with objective response after CRT compared to non-responders. CONCLUSION: Cisplatin-based CRT promotes expansion of Treg and decrease of circulating anti-tumor Th1 response in peripheral blood. The balance towards a sustained specific anti-tumor T-cell response appears to be associated with response to CRT.

Elevated Baseline Neutrophil Count Correlates with Worse Outcomes in Patients with Muscle-Invasive Bladder Cancer Treated with Chemoradiation.

BACKGROUND: The role of inflammation in the development and prognosis of bladder cancer (BC) is now established. We evaluated the significance of neutrophil-to-lymphocyte ratio (NLR) and neutrophil count (PNN) in patients with localized BC treated with chemoradiation. METHODS: Clinical characteristics and baseline biological data were retrospectively collected. We tested the association between NLR, PNN, and overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and ninety-four patients were included. Median PNN was 4000.0/mm3 [1500.0-16,858.0] and median NLR was 2.6 [0.6-19.2]. In patients with NLR > 2.6, median OS and PFS were lower (OS: 25.5 vs. 58.4 months, p = 0.02; PFS: 14.1 vs. 26.7 months, p = 0.07). Patients with PNN > 4000/mm3 had significantly lower OS (21.8 vs. 70.1 months, p < 0.001) and PFS (13.7 vs. 38.8 months, p < 0.001). Contrary to NLR, PNN > 4000/mm3 was associated with shorter OS and PFS in multivariate analysis. CONCLUSIONS: Elevated PNN at baseline was associated with worse OS and PFS. NLR was not an independent prognostic factor.

Dosimetric feasibility of stereotactic irradiation of primary prostate cancer at 5x9 Gy with a method of urethral sparing.

OBJECTIVE: The most commonly used dose for prostate cancer stereotactic body radiotherapy (SBRT) is 5 × 7.25 Gy. The aim of this study was to evaluate the dosimetric feasibility of a 5 × 9 Gy SBRT regimen while still limiting the dose to the urethra to 5 × 7.25 Gy. This dosimetric study is part of the groundwork for a future Phase III randomized trial. METHODS: The prostate, the urethra and the tumors were delineated on 20 dosimetric CT-scans with MRI-registration. The planning target volume (PTVp) was defined as a 5 mm expansion (3 mm posteriorly) of the prostate. The planning at risk volume (PRVu) was defined as a 2 mm expansion of the urethra. The tumors were delineated on the MRI (GTVt) and a 3 mm-margin was added to create a tumoral planning target volume (PTVt). IMRT plans were optimized to deliver 5 × 9 Gy to the PTVp, limiting the dose to the PRVu to 5 × 7.25 Gy. Results are presented using average (range) values. RESULTS: PTVp doses were D98% = 36.2 Gy (35.6-36.8), D2% = 46.9 Gy (46.5-47.5) and mean dose = 44.1 Gy (43.8-44.5). The dose to the PRVu was within tolerance limits for all 20 patients: V34.4Gy = 99.8% (99.2-100) and D5% = 38.7 Gy (38.6-38.8). Dose coverage of PTV-PRVu was D95% = 40.6 Gy (40.5-40.9), D5% = 46.6 Gy (46.2-47.2) and mean dose = 44.6 Gy (44.3-44.9). Dose to the PTVt reached 44.6 Gy (41.2-45.9). Doses to the OAR were respected, except V36Gy ≤1 cc for the rectum. CONCLUSION: A SBRT dose-escalation to 5 × 9 Gy on the prostate while sparing the urethra + 2 mm at 36.25 Gy is feasible without compromising dose coverage to the tumor. This radiation regimen will be used for a Phase-III trial. ADVANCES IN KNOWLEDGE: In prostate SBRT, dose optimization on the urethra is feasible and could decrease urinary toxicities.