Dose-effect relations for early local pulmonary injury after irradiation for malignant lymphoma and breast cancer.
OBJECTIVE
To quantify the influence of treatment- and patient-related factors on the severity of early local pulmonary injury and to establish whether regional differences are present for local dose-effect relations for early radiation-induced pulmonary injury.


METHODS
Forty-two patients with malignant lymphoma and 40 breast cancer patients were examined prior to and 3 months after radiotherapy. The lymphoma patients were irradiated with mantle fields to an average dose of 38 Gy and the breast cancer patients were irradiated with internal mammary node fields with or without tangential breast fields to an average dose of 50 Gy. Dose-effect relations for local perfusion, ventilation and density changes were determined using correlated single photon emission computed tomography (SPECT) and CT data. A multivariate analysis was performed to study the influence of irradiated volume, chemotherapy (CMF and MOPP/ABV), smoking, age and gender. In addition, dose-effect relations for different regions in the lung were determined.


RESULTS
A similar and almost linear increase of early functional changes as a function of radiation dose was observed for perfusion and ventilation, whereas the shape of the dose-effect relation and the magnitude of early structural changes were different for density. For the three end-points studied, regional differences in radiosensitivity could not be demonstrated. For the posterior lung region compared to the anterior lung region, however, a difference was observed, which could be attributed to a gravity-related effect in the measuring procedure. Local structural changes (density) were significantly smaller for smokers (P = 0.002) and young patients (P = 0.007), whereas the CMF chemotherapy regimen given after radiotherapy (P = 0.017) significantly increased the amount of functional changes (perfusion). The magnitude of local pulmonary changes was independent of the irradiated volume, the MOPP/ABV chemotherapy regimen and gender.


CONCLUSIONS
The dose-effect relations for early radiation-induced local pulmonary changes were independent of the irradiated volume, MOPP/ABV, gender and lung region. CMF, smoking and age influenced the magnitude of early pulmonary changes and should be taken into account in dose-escalation protocols.
Theuws
J C
JC
Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Kwa
S L
SL
Wagenaar
A C
AC
Boersma
L J
LJ
Damen
E M
EM
Muller
S H
SH
Baas
P
P
Lebesque
J V
JV
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008223:Lymphoma / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011832:Radiation Injuries; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed