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Abstract
Background: 99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS).

Methods: Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed.

Results: Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2-3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3 cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis.

Conclusion: The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.

Affiliations

Vanessa Murad # 1, Minseok Suh # 1 2, Hongyoon Choi 3 4 5, Gi Jeong Cheon 1 2 6 7 8, Kwon Joong Na 9 7, Young Tae Kim 9 7
1Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
2Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea.
3Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea. chy1000@snu.ac.kr.
4Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea. chy1000@snu.ac.kr.
5Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea. chy1000@snu.ac.kr.
6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
7Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea.
8Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
9Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
#Contributed equally.