Serum amyloid a as a predictive marker for radiation pneumonitis in lung cancer patients.

PURPOSE: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. METHODS AND MATERIALS: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. RESULTS: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. CONCLUSIONS: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy.

BACKGROUND: To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. METHODS: Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8-16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45-72 Gy). The median estimated biological effective dose at 10 Gy (BED10) was 71.8 Gy (range, 65.3-119.0 Gy), and that at 3 Gy (BED3) was 123.8 Gy (range, 112.5-233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm3 (range: 2.5-178.1 cm3). RESULTS: The median follow-up period was 25.8 months (range, 3.0-60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2 months versus >50 months (not reached) in the patients without EPD (p < 0.001). Those patients with smaller GTV (≦27.9 cm3) had a better survival than those with larger GTV (>27.9 cm3): >40 months versus 12.85 months (p = 0.047). The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed ≧grade 3 radiation pneumonitis. CONCLUSION: Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than lesion number in predicting survival.

Upfront gefitinib/erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer: a mono-institutional experience.

BACKGROUND: Upfront tyrosine kinase inhibitor (TKI) has proved effective for selective advanced lung cancer patients in Taiwan. We hypothesized that early integration of radiotherapy during TKI treatment would decrease the chance of drug resistance and prolong progression-free survival (PFS). METHODS: This study included 25 patients with stage IIIb or IV non-squamous cell, non-small cell lung cancer (NSqCLC) who responded to upfront TKI treatment. Multi-target radiotherapy was administered during the TKI treatment course. Tomotherapy comprising a hypofractionated schedule with a dose of 40-50 Gy in 16-20 fractions was used for individual metastatic lesions. RESULTS: The patients' median follow-up duration was 30 months (range, 9-62 months). Of the 23 patients who had stage IV disease, 9 had oligometastases (≤5 gross target volumes) and 14 were in the more advanced stages of the disease. Twelve patients received more than 1 cycle of radiotherapy (median, 3; range, 2-6) with TKI being the only systemic treatment before they were salvaged with chemotherapy. The overall response rate after radiotherapy was 84.0%, and the median PFS was 16 months. The 3-year overall survival rate was 62.5% (95% confidence interval [CI], 39.1-85.8%). Toxicities were generally tolerated but it is necessary to prevent radiation-induced pneumonitis. CONCLUSION: We showed that combined first-line TKI therapy and early multi-target radiotherapy are very effective in selected patients that respond to TKI, when the status of mutations in the epidermal growth factor receptor (EGFR) are not known before the treatment. Our data may aid expansion of the effectiveness of TKI treatment through radiotherapy in Asian patients with stage IV NSqCLC.