Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: a prospective clinical study

• Published in: International journal of radiation oncology, biology, physics Vol. 28; no. 3; p. 563
• Main Authors: Mah, K, Keane, T J, Van Dyk, J, Braban, L E, Poon, P Y, Hao, Y
• Format: Journal Article
• Language: English
• Published: United States 01-02-1994
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bleomycin - administration & dosage; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - radiotherapy; Carcinoma, Small Cell - therapy; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Dacarbazine - administration & dosage; Doxorubicin - administration & dosage; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - therapy; Fluorouracil - administration & dosage; Hodgkin Disease - drug therapy; Hodgkin Disease - radiotherapy; Hodgkin Disease - therapy; Humans; Incidence; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Lung Neoplasms - therapy; Mechlorethamine - administration & dosage; Prednisone - administration & dosage; Procarbazine - administration & dosage; Prospective Studies; Radiation Pneumonitis - diagnostic imaging; Radiation Pneumonitis - epidemiology; Radiation Pneumonitis - etiology; Tomography, X-Ray Computed; Vinblastine; Vincristine - administration & dosage
• ISSN: 0360-3016
• DOI: 10.1016/0360-3016(94)90180-5

The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens.
A prospective, clinical study was conducted to determine the response of normal lung tissue to combined chemotherapy and radiotherapy. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, 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 predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD).
A total of 102 patients were entered and 70 completed the study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% for 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 isoeffect 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.
Quantitative dose effect factors (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation.