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We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-β1 (TGF-β1) were measured before and 2 weeks after CRT. The median follow-up was 32.9 months (range: 12.4–40.6 months). The pre-treatment sMICA (p < 0.001) and TGF-β1 (p < 0.001) levels were significantly increased in HNSCC patients, compared to healthy controls. In HNSCC patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3 pg/mL, respectively, while the median pre-CRT and post-CRT TGF-β1 levels were 57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated TGF-β1, and five patients (16.7%) exhibited persistently elevated sMICA and TGF-β1. Patients with persistently elevated sMICA and TGF-β1 after CRT experienced an earlier tumor progression (p = 0.030), and poor overall survival (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently elevated sMICA and TGF-β1 levels after CRT are at higher risk of tumor progression or death. [ABSTRACT FROM AUTHOR]

We investigated the combined effects of ataxia telangiectasia and Rad3-related (ATR) inhibition, ablative radiotherapy, and immune checkpoint inhibitor (ICI) therapy against lung cancer. ATR inhibitor was administered combined with ablative radiotherapy to assess its radiosensitizing effect on lung cancer cells. Treatment response and survival were evaluated in vivo using A549 xenograft flank tumor and synchronous LLC lung and flank tumor mouse models. Mice received ablative radiotherapy (12 Gy/d for 2 d), ATR inhibitor, and ICI. The tumor microenvironment was assessed in irradiated flank and non-irradiated lung tumors. Programmed death-ligand 1 expression was upregulated after irradiation. ATR inhibition attenuated this upregulation. ATR inhibitor pretreatment decreased cell survival after irradiation by inhibiting DNA double-strand break repair, inducing mitotic cell death, and altering cell cycle progression. ATR inhibition enhanced radiation-induced damage-associated molecular patterns determined by high mobility group box 1 quantification and activated the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Combined ATR inhibition and ablative radiotherapy inhibited tumor growth and improved survival in mice. Adding ICI therapy further enhanced local antitumor effects, reducing the metastatic lung tumor burden and remodeling the tumor microenvironment through immunogenic cell death induction and enhanced immune cell infiltration. Triple therapy increased immune cell infiltration in distant non-irradiated lung tumors and stimulated the generation of protective T-cell immunity in splenocytes. Safety analysis showed minimal toxicity. ATR inhibition enhanced the efficacy of ablative radiotherapy and immunotherapy in lung cancer. These findings underscore the importance of combination therapies for enhancing systemic antitumor immune responses and outcomes., (© 2024. The Author(s).)

Purpose: To examine the survival outcomes and late toxicity profiles of three-dimensional conformal radiation therapy (3DCRT) vs. intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma (NPC)., Methods: Three hundred and seventy-four patients with newly diagnosed, non-metastatic, NPC who were curatively treated with 3DCRT between 2004 and 2006 and 481 patients treated with IMRT between 2007 and 2009 were analyzed. Patients were categorized as having advanced-stage disease (stage III, IVA, and IVB disease; n = 709) or early-stage disease (stage I and II; n = 146). The median follow-up time was 90.3 months for patients treated with 3DCRT and 86.3 months for patients treated with IMRT., Results: For early-stage patients, the outcomes of IMRT vs. 3DCRT were similar considering locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). For advanced-stage patients, IMRT was associated with better LRC compared with 3DCRT (5-year LRC rate: 85.6% vs. 76.6%, respectively; p = 0.035) and OS (5-year OS rate: 82.3% vs. 71.8%, respectively; p = 0.002), whereas DMFS was similar for both treatments (5-year DMFS rate: 80.9% vs. 79.0%, respectively; p = 0.324). Furthermore, the IMRT technique was more beneficial for patients with T4 disease. Late toxicities occurred more frequently in patients treated with 3DCRT than in those treated with IMRT (grade ≥3 neck fibrosis: 6.7% vs. 3.7%, respectively, p = 0.036; radiographic temporal lobe necrosis: 10.2% vs. 4.4%, respectively, p < 0.001)., Conclusions: Compared with 3DCRT, IMRT offered better LRC in patients with advanced-stage non-metastatic NPC, which corresponded with better OS.

Background/aims: To evaluate the clinical, pathologic, and imaging findings of solid pseudopapillary neoplasm (SPN) of the pancreas in order to differentiate benign from malignant pancreatic neoplasms., Methodology: We retrospectively identified 23 patients with 24 SPNs confirmed by pathology at National Taiwan University Hospital between January, 2001 and March, 2012. All computed tomography and magnetic resonance imaging were reviewed by two radiologists in consensus. Each tumor was analyzed for location of tumor, tumor margin, proportion of solid component, capsule morphology, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, and enhancement pattern., Results: SPN of the pancreas demonstrated variable degrees of hemorrhagic degeneration and calcification. Focal discontinuity of capsule was consistently observed in five malignant tumors (p = 0.004). There were no statistical differences between benign and malignant tumors based on location of tumor, tumor margin, proportion of solid component, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, or enhancement pattern, Conclusion: Among the various imaging features, we found that focal discontinuity of the capsule may suggest malignancy.