Impact of Radiation Dose to Circulating Immune Cells on Tumor Control and Survival in Esophageal Cancer

Author(s):  
Shang Cai ◽  
Yawen Fan ◽  
Qi Guo ◽  
Yanze Sun ◽  
Peifeng Zhao ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6193
Author(s):  
Jian-Yue Jin ◽  
Chen Hu ◽  
Ying Xiao ◽  
Hong Zhang ◽  
Rebecca Paulus ◽  
...  

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanyan Long ◽  
Yan Liang ◽  
Shujie Li ◽  
Jing Guo ◽  
Ying Wang ◽  
...  

Abstract Background and purpose Stereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm). Materials and methods A systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity. Results After a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively. Conclusion The study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.


2020 ◽  
Vol 146 ◽  
pp. 180-186 ◽  
Author(s):  
Cai Xu ◽  
Jian-Yue Jin ◽  
Ming Zhang ◽  
Amy Liu ◽  
Jun Wang ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e000487 ◽  
Author(s):  
Dora Lucia Vallejo Ardila ◽  
Katrina A Walsh ◽  
Theodora Fifis ◽  
Rita Paolini ◽  
Georgios Kastrappis ◽  
...  

BackgroundIt is now recognized that many anticancer treatments positively modulate the antitumor immune response. Clinical and experimental studies have shown that inhibitors of the classical renin–angiotensin system (RAS) reduce tumor progression and are associated with better outcomes in patients with colorectal cancer. RAS components are expressed by most immune cells and adult hematopoietic cells, thus are potential targets for modulating tumor-infiltrating immune cells and can provide a mechanism of tumor control by the renin–angiotensin system inhibitors (RASi).AimTo investigate the effects of the RASi captopril on tumor T lymphocyte distribution in a mouse model of colorectal liver metastases.MethodsLiver metastases were established in a mouse model using an autologous colorectal cancer cell line. RASi (captopril 750 mg/kg) or carrier (saline) was administered to the mice daily via intraperitoneal injection, from day 1 post-tumor induction to endpoint (day 15 or 21 post-tumor induction). At the endpoint, tumor growth was determined, and lymphocyte infiltration and composition in the tumor and liver tissues were analyzed by flow cytometry and immunohistochemistry (IHC).ResultsCaptopril significantly decreased tumor viability and impaired metastatic growth. Analysis of infiltrating T cells into liver parenchyma and tumor tissues by IHC and flow cytometry showed that captopril significantly increased the infiltration of CD3+ T cells into both tissues at day 15 following tumor induction. Phenotypical analysis of CD45+ CD3+ T cells indicated that the major contributing phenotype to this influx is a CD4 and CD8 double-negative T cell (DNT) subtype, while CD4+ T cells decreased and CD8+ T cells remained unchanged. Captopril treatment also increased the expression of checkpoint receptor PD-1 on CD8+and DNT subsets .ConclusionCaptopril treatment modulates the immune response by increasing the infiltration and altering the phenotypical composition of T lymphocytes and may be a contributing mechanism for tumor control.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 29-29
Author(s):  
Styliani Mantziari ◽  
Pierre Allemann ◽  
Michael Winiker ◽  
Marguerite Messier ◽  
Nicolas Demartines ◽  
...  

Abstract Background Current guidelines recommend the use of neoadjuvant chemo-radiation (NCR) for the treatment of locally advanced esophageal cancer, both types, adenocarcinoma (AC) and squamous cell carcinoma (SCC). So far, the optimal dose of radiotherapy to achieve a maximal tumor response within an acceptable toxicity is not yet determined. The aim of this study was to assess the impact of preoperative radiation dose on postoperative outcomes and long-term survival. Methods Consecutive patients operated in two European tertiary centers for AC or SCC, treated with NCR and surgery from 2000–2016 were assessed. Specific postoperative complications (i.e. anastomotic leakage, atrial fibrillation), histological tumor regression grade (TRG, Mandard score), overall and disease-free survival were compared among three patients groups: group A (41.4Gy), group B (45Gy), and group C (50.4Gy). The x2 or Fisher test were used for categorical variables and ANOVA for continuous variables. Survival analysis was done with the Kaplan-Meier method and log-rank test. Results There were 294 patients included; 41.5% (n = 122) had AC and 58.5% (n = 172) SCC. Overall, 9.2%/27 patients received 41Gy, 57.8%/170 patients 45Gy and 33%/97 patients received 50.4Gy. Carboplatin-Paclitaxel was the most frequently used chemotherapy for group A (62.9%), and 5FU-Cisplatin for groups B (69.4%) and C (51.5%). Postoperative anastomotic leakage was lower for group B (7.1%) compared to group A (22.2%) and C (13.4%) (P = 0.036), as was the occurrence of atrial fibrillation (11.8% group B, 33.3% group A and 19.6% group C, P = 0.013). Complete or excellent response (TRG 1–2) was significantly better for group B (58.2%), followed by group C (49.5%) and A (25.9%) patients (P = 0.012). Median overall survival was 48, 27 and 29 months for group A, B and C (P = 0.498), and median disease-free survival was 13, 27 and 18 months (P = 0.411), respectively. Conclusion Preoperative radiotherapy dose of 45Gy with 5FU-Cisplatin was associated with a better histological response and less postoperative adverse outcomes compared to 41Gy and 50.4Gy, with no significant differences in long-term recurrence and survival. The role of the type of chemotherapy and histological tumor type are important co-factors affecting outcome and must be further assessed. Disclosure All authors have declared no conflicts of interest.


2018 ◽  
Vol 154 (6) ◽  
pp. S-1291-S-1292
Author(s):  
Mickey S. Ising ◽  
Jaimin Trivedi ◽  
Katy Marino ◽  
Adam Rojan ◽  
Neal Dunlap ◽  
...  

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