Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.
OBJECTIVE
The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered.


METHODS
Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred.


RESULTS
Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities.


CONCLUSIONS
It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.
Anscher
M S
MS
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. anscher@radonc.duke.edu
Marks
L B
LB
Shafman
T D
TD
Clough
R
R
Huang
H
H
Tisch
A
A
Munley
M
M
Herndon
J E
JE
Garst
J
J
Crawford
J
J
Jirtle
R L
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000097:blood*
D015415:Biomarkers; D016212:Transforming Growth Factor beta