QUANTITATIVE EFFECT OF COMBINED CHEMOTHERAPY AND FRACTIONATED RADIOTHERAPY ON THE INCIDENCE OF RADIATION-INDUCED LUNG DAMAGE - A PROSPECTIVE CLINICAL-STUDY

Purpose: The objective of this work was to assess the incidence of rad iological changes compatible with radiation-induced lung damage as det ermined by computed tomography (CT), and subsequently calculate the do se effect factors (DEF) for specified chemotherapeutic regimens. Metho ds and Materials: A prospective, clinical study was conducted to deter mine the response of normal lung tissue to combined chemotherapy and r adiotherapy. Radiation treatments were administered once daily, 5 days -per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bl eomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOP P (nitrogen mustard, vincristine, procarbazine, and prednisone) follow ed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosph amide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predeterm ined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung densit y within the irradiated volume. The radiation dose to lung was calcula ted using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect m odels, the estimated single dose (ED) and the normalized total dose (N TD). Results: A total of 102 patients were entered and 70 completed th e study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% fo r the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoe ffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1. 03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. Conclusion: Quantitative dose effect factor s (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those re ceiving radiotherapy alone. The addition of ABVD or CAV appeared to re duce the tolerance of lung to radiation.