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Background Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies. Methods To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy. Results PD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival ( P = 0.019). Conclusion Tumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

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Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

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Purpose Intensity‐modulated radiation therapy (IMRT) utilizes many small fields for producing a uniform dose distribution. Therefore, there are many field junctions in the target region, and resulting dose uncertainties are accumulated. However, such accumulation of the dose uncertainty has not been implemented in the current practice of IMRT dose verification. The purpose of this study is to develop a method to predict the gamma passing rate (GPR) using a dose uncertainty accumulation model. Methods Thirty‐three intensity‐modulated (IM) beams for head‐and‐neck cases with step‐and‐shoot techniques were used in this study. The treatment plan was created using the XiO treatment planning system (TPS). The IM beam was produced by the ONCOR Impression Plus linear accelerator. MapCHECK was used to measure the dose distribution. The distribution of a dose uncertainty potential (DUP) was generated by in‐house software that accumulated field shapes weighted by a segmental monitor unit, followed by Gaussian folding. The width of the Gaussian was determined from the width of the lateral penumbra. The dose difference between the calculated and measured doses was compared with the estimated DUP at each point. The GPR of each beam was predicted for 2%/2‐mm, 3%/2‐mm, and 3%/3‐mm tolerances by its own DUP histogram and a GPR‐vs‐DUP correlation of other beams using the leave‐one‐out cross‐validation method. The predicted GPR was compared with the measured GPR to evaluate the performance of this prediction method. The criteria for the predicted GPR corresponding to a measured GPR ≥ 90% were estimated to examine the feasibility of estimating the measured GPR by this GPR prediction method. Results The DUP was confirmed to have proportionality to the standard deviation (SD) of the dose difference. The SDs of the difference between the measured and predicted GPRs were 3.1, 1.7, and 1.4% for 2%/2‐mm, 3%/2‐mm, and 3%/3‐mm tolerances, respectively. The criteria of the predicted GPR corresponding to the measured GPR ≥ 90% were 94.1 and 95.0% with confidence levels of 99 and 99.9%, respectively. Conclusion In this study, we confirmed the good proportionality between the dose difference and the estimated DUP. The results showed a feasibility to predict the dose difference from DUP as estimated by a DUP accumulation model. The predicted GPR developed in this study showed good accuracy for planar dose distributions of head and neck IMRT. The prediction method developed in this study is considered to be feasible as a substitute for the current practice of measurement‐based verification of the dose distribution with gamma analysis.

In this study, fatal RP tended to be more common in the patients with subclinical ILD. In particular, the presence of extensive fibrosis on CT may be a contraindication for thoracic RT.