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Lymphocyte mutagen sensitivity correlates significantly with gender, histology, and radiation toxicity in lung cancer patients
I. J. Radiation
232
240
l Biology
l Physics
Volume 48. Number 3. Supplement,
2000
Th orascopic wedge resection and radiotherapy for TlNO non-small cell lung cancer (NSCLC) in high risk patients: Preliminary analysis of a cancer and leukemia group B and Eastern Cooperative Oncology Group phase II trial
H. Shennib,’ J. A. Bogart,’ M. R. Green’ ‘Cancer
Oncology
und Leukemia
J. Herndon,’
L. Kohman.’
D. J. Sugarbaker,’
R. J. Keenan,’
T. J. Fitzgerald,’
A. T. Turrisi,’
Group B. Chicago, IL, ‘Easter-n Coope,rmti~w Oncology Gmup
Purpose: Evaluate the feasibility of video assisted radiotherapy for patients with pulmonary dysfunction
thorascopic wedge resection and stage lA NSCLC.
(VAR) followed
by local external
beam
Materials & Methods: 58 eligible high risk patients from CALGB and ECOG institutions underwent attempted VAR for peripheral lung lesions 5 3cm between September 1995 and September 1999. A preoperative pathologic diagnosis of cancer wah not required for study entry. High risk was defined as any of the following: FEVl < 40% predicted, PaC02 >55 mmHg. DC0 < 50% predicted, or V02 max
24 1
Lymphocyte mutagen lung cancer patients
sensitivity
correlates significantly
with gender, histology, and radiation
toxicity in
J. F. Kelly, X. Wu. R. Komaki, C. W. Stevens, Z. Liao, M. Detry, S. E. Honn, M. L. Bondy, M. R. Spitz
Purpose: Bleomycin and ionizing radiation both produce intracellular damage through the generation of free oxygen radicals, so bleomycin’s mechanism of action is considered radiomimetic. Additionally. bleomycin-induced chromosomal breakage in lymphocyte cultures has been shown to be a significant independent risk factor for lung cancer. To investigate whether this mutagen sensitivity assay has predictive value in lung cancer patients undergoing radiotherapy, we prospectively analyzed bleomycin-induced chromosome breaks in lymphocytes obtained prior to treatment. Materials and Methods: One-hundred and twenty-three previously untreated patients with pathologically confirmed lung carcinoma had peripheral blood drawn between 1993-98. All patients received radiation as part of their therapy. Lymphocyte cultures were treated with 0.03 units bleomycin/ml for 5 hr. During the last hour, Colcemid was added to accumulate arrested mitosea in metaphase. Chromosome breaks in 50 metaphases/sample were counted and expressed as the average number of breaks/cell. Mean values were correlated with patients’ pretreatment characteristics, acute treatment-related toxicity as scored by RTOG criteria. and survival. Results: The mean number of breaks per cell was 0.79 2 0.41 (2 SD). There was a significant correlation between male gender and bleomycin sensitivity compared with female gender and sensitivity (0.90 2 0.42 vs. 0.69 f 0.38, p = 0.002). Patients with regional lymphatic involvement or distant spread at diagnosis exhibited more breaks than those with early or limited disease. Patienta with adenocarcinoma and large cell carcinoma were significantly less mutagen-sensitive than other histologies (0.70 t 0.34 vs. 0.87 % 0.46. p = 0.037). In terms of acute radiation-related toxicity, there was no significant difference in mutagen sensitivity between 39 patients without complications (0.72 -t 0.45) and 69 patients with dysphagia (0.77 2 0.34). However, 15 patients with complications other than dysphagia (e.g. pneumonitis) were more bleomycin sensitive (106 2 0.53, p = 0.03 1). No overall correlation between mutagen sensitivity and survival was found, but more DNA breaks were seen in the patients who had tumor relapse within 120 days of completing therapy (106 5 0.56) compared with those who relapsed after 120 days (0.71 t- 0.29). Conclusion: Bleomycin-induced chromosomal breakage is a significant correlate of gender, histology, and radiation-related toxicity in this cohort of 123 lung cancer patients. We continue to collect pretreatment blood samples from newly diagnosed lung cancer patients scheduled to receive definitive radiotherapy with or without chemotherapy to further correlate mutagen sensitivity with known prognosric factors and with acute and late effects of treatment.
232
240
l Biology
l Physics
Volume 48. Number 3. Supplement,
2000
Th orascopic wedge resection and radiotherapy for TlNO non-small cell lung cancer (NSCLC) in high risk patients: Preliminary analysis of a cancer and leukemia group B and Eastern Cooperative Oncology Group phase II trial
H. Shennib,’ J. A. Bogart,’ M. R. Green’ ‘Cancer
Oncology
und Leukemia
J. Herndon,’
L. Kohman.’
D. J. Sugarbaker,’
R. J. Keenan,’
T. J. Fitzgerald,’
A. T. Turrisi,’
Group B. Chicago, IL, ‘Easter-n Coope,rmti~w Oncology Gmup
Purpose: Evaluate the feasibility of video assisted radiotherapy for patients with pulmonary dysfunction
thorascopic wedge resection and stage lA NSCLC.
(VAR) followed
by local external
beam
Materials & Methods: 58 eligible high risk patients from CALGB and ECOG institutions underwent attempted VAR for peripheral lung lesions 5 3cm between September 1995 and September 1999. A preoperative pathologic diagnosis of cancer wah not required for study entry. High risk was defined as any of the following: FEVl < 40% predicted, PaC02 >55 mmHg. DC0 < 50% predicted, or V02 max
24 1
Lymphocyte mutagen lung cancer patients
sensitivity
correlates significantly
with gender, histology, and radiation
toxicity in
J. F. Kelly, X. Wu. R. Komaki, C. W. Stevens, Z. Liao, M. Detry, S. E. Honn, M. L. Bondy, M. R. Spitz
Purpose: Bleomycin and ionizing radiation both produce intracellular damage through the generation of free oxygen radicals, so bleomycin’s mechanism of action is considered radiomimetic. Additionally. bleomycin-induced chromosomal breakage in lymphocyte cultures has been shown to be a significant independent risk factor for lung cancer. To investigate whether this mutagen sensitivity assay has predictive value in lung cancer patients undergoing radiotherapy, we prospectively analyzed bleomycin-induced chromosome breaks in lymphocytes obtained prior to treatment. Materials and Methods: One-hundred and twenty-three previously untreated patients with pathologically confirmed lung carcinoma had peripheral blood drawn between 1993-98. All patients received radiation as part of their therapy. Lymphocyte cultures were treated with 0.03 units bleomycin/ml for 5 hr. During the last hour, Colcemid was added to accumulate arrested mitosea in metaphase. Chromosome breaks in 50 metaphases/sample were counted and expressed as the average number of breaks/cell. Mean values were correlated with patients’ pretreatment characteristics, acute treatment-related toxicity as scored by RTOG criteria. and survival. Results: The mean number of breaks per cell was 0.79 2 0.41 (2 SD). There was a significant correlation between male gender and bleomycin sensitivity compared with female gender and sensitivity (0.90 2 0.42 vs. 0.69 f 0.38, p = 0.002). Patients with regional lymphatic involvement or distant spread at diagnosis exhibited more breaks than those with early or limited disease. Patienta with adenocarcinoma and large cell carcinoma were significantly less mutagen-sensitive than other histologies (0.70 t 0.34 vs. 0.87 % 0.46. p = 0.037). In terms of acute radiation-related toxicity, there was no significant difference in mutagen sensitivity between 39 patients without complications (0.72 -t 0.45) and 69 patients with dysphagia (0.77 2 0.34). However, 15 patients with complications other than dysphagia (e.g. pneumonitis) were more bleomycin sensitive (106 2 0.53, p = 0.03 1). No overall correlation between mutagen sensitivity and survival was found, but more DNA breaks were seen in the patients who had tumor relapse within 120 days of completing therapy (106 5 0.56) compared with those who relapsed after 120 days (0.71 t- 0.29). Conclusion: Bleomycin-induced chromosomal breakage is a significant correlate of gender, histology, and radiation-related toxicity in this cohort of 123 lung cancer patients. We continue to collect pretreatment blood samples from newly diagnosed lung cancer patients scheduled to receive definitive radiotherapy with or without chemotherapy to further correlate mutagen sensitivity with known prognosric factors and with acute and late effects of treatment.