H. Yu

Posttreatment Immune Parameters Predict Cancer Control and Pneumonitis in Stage I Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy

&NA; Stereotactic ablative body radiotherapy can increase the total number of cytotoxic CD8+ T lymphocytes and regulatory T cells among peripheral lymphocytes. Increased cytotoxic CD8+ T‐cell level was an independent prognostic factor for longer progression‐free survival in stage I non–small‐cell lung cancer. Proportion of lung receiving 20 Gy of radiotherapy and mean lung dose are independent predictors of symptomatic radiation pneumonitis (grade 2 or higher); neither pretreatment nor posttreatment T lymphocyte subset level was significantly related to symptomatic radiation pneumonitis (grade 2 or higher). Purpose: Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non–small‐cell lung cancer (NSCLC) patients treated with SABR. Patients and Methods: Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression‐free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan‐Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model. Results: At a median follow‐up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05‐1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16‐3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8+ T‐cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01‐1.28; P = .01). Conclusion: A higher posttreatment cytotoxic CD8+ T‐cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen‐specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients.

Magnetic resonance (MR) imaging for tumor staging and definition of tumor volumes on radiation treatment planning in nonsmall cell lung cancer: A prospective radiographic cohort study of single center clinical outcome

Abstract We investigate the impact of magnetic resonance (MR) on the staging and radiotherapy planning for patients with nonsmall cell lung cancer (NSCLC). A total of 24 patients with NSCLC underwent MRI, which was fused with radiotherapy planning CT using rigid registration. Gross tumor volume (GTV) was delineated not only according to CT image alone (GTVCT), but also based on both CT and MR image (GTVCT/MR). For each patient, 2 conformal treatment plans were made according to GTVCT and GTVCT/MR, respectively. Dose-volume histograms (DVH) for lesion and normal organs were generated using both GTVCT and GTVCT/MR treatment plans. All patients were irradiated according to GTVCT/MR plan. Median volume of the GTVCT/MR and GTVCT were 105.42 cm3 and 124.45 cm3, respectively, and the mean value of GTVCT/MR was significantly smaller than that of GTVCT (145.71 ± 145.04 vs 174.30 ± 150.34, P < 0.01). Clinical stage was modified in 9 patients (37.5%). The objective response rate (ORR) was 83.3% and the l-year overall survival (OS) was 87.5%. MR is a useful tool in radiotherapy treatment planning for NSCLC, which improves the definition of tumor volume, reduces organs at risk dose and does not increase the local recurrence rate.

[Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation â©with Concurrent Twice-daily Radiotherapy for Patients â©with Limited-stage Small Cell Lung Cancer].

BACKGROUND Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer. METHODS Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity. RESULTS From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively. CONCLUSIONS The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).
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