Free breathing gated delivery (FBGD) of lung radiation therapy: analysis of factors affecting clinical patient throughput.

PURPOSE: Accurate radiation targeting and delivery within the chest and abdomen is greatly affected by the respiratory cycle. Prior methods to minimize respiratory effect include breath-hold and abdominal compression techniques; these are subject to error secondary to variable inspiration/expiration volumes, or by the nature of many cancer patients having inherently poor respiratory function. However, advanced technology called free breathing gated delivery (FBGD) allows patients to breath normally during treatment. The photon beam is on only during a particular prescribed percentage of the respiratory cycle where the target tumor volume is minimized. Consequently, by using an intermittent beam, the time required to treat a patient is increased. No previous study has described the patient throughput ramifications of FBGD. PATIENTS AND METHODS: At Emory clinic, a gated treatment delivery system was inaugurated into clinical use beginning in June 2004. As of 12/31/2004, 15 patients have completed treatment with FBGD. The majority of patients had lung cancer (n=12) with single cases of adrenal metastasis, thymoma, and atypical carcinoid. Over 900 gated treatment fields (approximately 375 treatment sessions) were reviewed on an IRB-approved retrospective protocol. Records from the record-and-verify (R&V) system were queried using automated database mining software to obtain the treatment room time, treatment field time, beam-on time (BOT), dose rate, and monitor units (MU) for each treatment. The presence or absence of a dynamic wedge was also noted, as was the prescribed percent of the respiratory cycle treated. For comparison purposes, 13 non-gated lung cancer patients (lesions were not moving with respiration) were selected from the R&V database. RESULTS: Patients receiving FBGD required significantly more time for treatment delivery. The time required for FBGD was, on average, 5.5 times greater (range 1.2-12.2) than calculated BOT without gating. Time was further increased with the use of a dynamic wedge, which occurred in 45% (28/62) of the planned fields. The use of MV imaging also increased the time for FBGD treatment sessions by more than 7.5 min on average. CONCLUSIONS: FBGD uniformly increases the time required for RT delivery, and MV imaging and dynamic wedging even more so. Even though this technology more accurately targets tumor volumes while sparing normal tissue, the patient throughput issue may deter this technology from being implemented into busy clinical practices.

High dose fractionated ionizing radiation inhibits prostate cancer cell adhesion and beta(1) integrin expression.

BACKGROUND: The effect of ionizing radiation on extracellular matrix (ECM)-mediated cellular functions is an important area of research for translational science. Mechanisms of tumor cell ability to proliferate, migrate, and survive appear dependent on integrin-mediated adhesion to the ECM; however, the exact role therapeutic radiation plays in altering signaling pathways and promoting cell death within remains less well established. METHODS: To examine these effects on prostate carcinoma cell lines, cells were irradiated at sub-lethal doses. We have studied two human prostate cancer cell lines (PC3 and DU-145) irradiated with different fractionated radiation schedules. Three groups were compared to non-irradiated controls. Group A was given a single dose of 5 Gy. Group B was given 5 Gy the first week and then 10 Gy the second week for a total of 15 Gy. Group C was given 5 Gy the first week, and then 10 Gy the second and third week for a total of 25 Gy. Cells were analyzed at their prescribed total dose. At 48 hr post irradiation, cells were detached from culture dishes and were subsequently used for adhesion assays and immunoblotting analysis. RESULTS: Our findings revealed that two prostate carcinoma cell lines, PC3 and DU-145, had a reduced cellular adhesion to fibronectin (FN) compared to the non-irradiated control groups. Both prostate cancer cell lines showed decreased adhesion to FN and reduced beta(1) integrin protein levels at a total dose of 25 Gy, but not at the doses of 15 and 5 Gy. In a parallel analysis, at the maximum total dose of 25 Gy, both PC3 and DU-145 demonstrated a significant decrease in cell proliferation. CONCLUSIONS: High dose radiation treatment of prostate cancer cell lines inhibits integrin expression. Our study suggests that promoting a synergistic decrease in adhesion could bring additional therapeutic benefit to patients treated with radiation therapy.