Time course of serum cytokines in patients receiving proton or combined photon/proton beam radiation for resectable but medically inoperable non-small-cell lung cancer.
OBJECTIVE
We prospectively measured the levels of basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, and procollagen III peptide (P III P) in serum from non-small-cell lung cancer patients treated with photons combined with protons or protons alone. These factors were quantified because they may be extremely important in the development of side effects, and the treated volume integral dose may be crucial in inducing them.


METHODS
Of the 12 participating patients, 6 with squamous cell carcinoma (SCC) and 3 with adenocarcinoma received combined photon/proton beam radiation, whereas 2 with SCC and 1 with large-cell carcinoma (LCC) received only proton radiation. Mean age was 73.6 years. There were 4 male and 8 female patients with a mean smoking history of 87.0 packyears. Nine patients had Stage I, 2 had Stage II, and 1 had stage IIIA lung cancer. Serum samples were obtained at baseline and on Days 15, 30, 45, 60, 90, 120, 150, 180, and 210 after initiation of radiation therapy. Injury scores for pneumonitis and fibrosis based on computed tomography (CT) scans were assigned.


RESULTS
The percentage of lung volume irradiated was significantly less for patients treated with protons alone compared with those receiving photon plus proton therapy (p < 0.001). Injury scores were also lower for proton only treatment (p = 0.039). When evaluated collectively, bFGF, TNF-alpha, and IL-6 concentrations were significantly higher in the photon/proton group (p < 0.05 or less); radiation regimen, but not time after treatment initiation, was a significant factor in their levels. P III P level was also higher in the photon/proton patients (p < 0.001) and both radiation regimen (p = 0.027) and time after treatment (p = 0.019) had an impact.


CONCLUSIONS
Although significant changes occurred in some of the measured cytokines and P III P, it was the difference in the volume integral dose that occurred when protons were used alone vs. mixed photon/proton therapy that correlated with the incidence of pneumonitis and/or fibrosis. However, it cannot be ruled out that differences in cytokine levels before radiotherapy initiation may have contributed to the outcome.
Department of Radiation Medicine, School of Medicine, Loma Linda University and Medical Center, Chan Shuh Pavilion, 11175 Campus Street, Loma Linda, CA 92354, USA. dgridley@dominion.llumc.edu
Daila S
DS
Gridley
Reiner B
RB
Bonnet
David A
DA
Bush
Christian
C
Franke
Gregory A
GA
Cheek
Jerry D
JD
Slater
James M
JM
Slater
D000230:Adenocarcinoma / Q000097:blood / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000532:radiotherapy; D024061:Collagen Type III / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017785:Photons / Q000627:therapeutic use; D011446:Prospective Studies; D061766:Proton Therapy; D017564:Radiation Pneumonitis / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015415:Biomarkers; D024061:Collagen Type III; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2