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Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617.

ABSTRACT: 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.

SUBMITTER: Jin JY

PROVIDER: S-EPMC8699524 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThere are currently two recommended radiation strategies for clinical stage III NSCLC: a lower "preoperative" (45-54 Gy) and a higher "definitive/nonsurgical" (60-70 Gy) dose. We sought to determine if definitive radiation doses should be used in the preoperative setting given that many clinical stage III patients planned for surgery are ultimately managed with chemoradiation alone.MethodsUsing the National Cancer Database data from 2006 to 2016, we performed a comparative effectiveness analysis of stage III N2 patients who received chemoradiotherapy. Patients were stratified into subgroups across 2 parameters: (1) radiation dose: lower (45-54 Gy) and higher (60-70 Gy); and (2) the use of surgery (i.e., surgical and nonsurgical treatment approaches). Long-term survival and perioperative outcomes were evaluated using multivariable Cox proportional hazards and logistic regression models.ResultsA cohort of 961 patients received radiation before surgery including 321 who received a higher dose and 640 who received a lower dose. A higher preoperative dose revealed similar long-term mortality risk (hazard ratio = 0.99, 95% confidence interval: 0.82-1.21, p = 0.951) compared with a lower dose. There was no significant association between radiation dose and 90-day mortality (p = 0.982), 30-day readmission (p = 0.931), or prolonged length of stay (p = 0.052) in the surgical cohort. A total of 17,904 clinical-stage IIIA-N2 patients were treated nonsurgically, including 15,945 receiving higher and 1959 treated with a lower dose. A higher dose was associated with a reduction in long-term mortality risk (hazard ratio = 0.64, 95% confidence interval: 0.60-0.67, p < 0.001) compared with a lower dose.ConclusionsFor clinical stage III NSCLC, the administration of 60 to 70 Gy of radiation seems to be more effective than the lower dose for nonsurgical patients without compromising surgical safety for those that undergo resection. This evidence supports the implementation of 60 to 70 Gy as a single-dose strategy for both preoperative and definitive chemoradiotherapy.

Project description:BackgroundStage III Non-small cell lung cancer (NSCLC) is a heterogenous disease with novel treatment options. Recently, immunotherapy has attracted a lot of attention for advanced NSCLC.ObjectiveThe objective of our study was to assess the efficacy and safety of neoadjuvant immuno-chemotherapy for resectable stage III NSCLC.MethodsWe analyzed 11 stage III primary NSCLC surgical cases who had undergone standard lobectomy or bronchial sleeve resection and lymph node dissection between December 2020 and July 2021. The data analyzed included basic clinical features, serum levels of key biomarkers, clinical efficacy in the perioperative period, postoperative pathological results, postoperative complications and the incidence rates of Immune-Related Adverse Events.ResultsEleven patients were enrolled in our study with a mean age of 67.7 ± 4.8 years, and 10 patients being men with former or current smoking history. Squamous carcinoma (10/11, 91.1%) was the most common cancer type. Six patients had stage IIIa, five had stage IIIb. All patients received two or three cycles of neoadjuvant immuno-chemotherapy, with the median duration between the last treatment and surgery being 39 days (range, 32-46 days). All patients underwent R0 resection with ten patients undergoing single-port video-assisted thoracoscopic surgery. The median operative time was 170 min (range, 120-240 min). Only three (3/11, 27.3%) patients experienced mild postoperative complications and the mean hospital stay time was 6.9 days (range, 4-15 days). Nine (9/11, 81.8%) patients experienced major pathological response of which seven (7/11, 63.6%) was complete pathological response in postoperative results. The pathological stage was downgraded in 10 (10/11, 91.1%) patients, and although the incidence of Immune-Related Adverse Events was slightly higher (8/11, 72.7%), most events were grade 1-2 and did not delay surgery.ConclusionOur study demonstrated that neoadjuvant immuno-chemotherapy is feasible and relatively safe for resectable stage III primary NSCLC patients. We hope this new neoadjuvant immuno-chemotherapy model can improve overall survival and open a new era for stage III primary NSCLC patients.

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Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617.

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