The effect of patient-specific factors on radiation-induced regional lung injury.
OBJECTIVE
To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion.


METHODS
Fifty patients (32 lung carcinoma, 7 Hodgkin's disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and > or = 24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose-response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction = coefficient 1 x dose + coefficient 2 x dose2). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-beta), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients.


RESULTS
None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used.


CONCLUSIONS
Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient-specific factors will impact on how the summation of regional injury translates into whole organ injury. Refinements in our methods to generate and compare SPECT scans are needed.
Garipagaoglu
M
M
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Munley
M T
MT
Hollis
D
D
Poulson
J M
JM
Bentel
G C
GC
Sibley
G
G
Anscher
M S
MS
Fan
M
M
Jaszczak
R J
RJ
Coleman
R E
RE
Marks
L B
LB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000528:radiation effects*; D012907:Smoking / Q000503:physiopathology