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Pattern of distant metastases at presentation in newly diagnosed non-small cell cancer

Background: Extrathoracic metastases (ETMs) are common in nonsmall cell lung cancer (NSCLC) at presentation. Objective: Our study was to detect the percentage distribution of ETMs in various organs at presentation in patients with NSCLC. Methodology: Between January 2017 and November 2018 inpatient records of all NSCLC was retrospectively analysed for ETMs. Results: We included 71 patients of NSCLC. ETMs were diagnosed in 35.2% (25/71) of the patients at presentation. 18 fluorodeoxy glucose positron emission tomography combined with Computed tomography (FDG PET/CT) played crucial role in detecting unexpected ETMs. Brain was the most common organ involved in extrathoracic metastases. Conclusions: Distant metastases at presentation are usual in NSCLC and FDG-PET CT is the key imaging modality to be done in all patients of NSCLC to detect unexpected ETMs.


Introduction
Majority of the lung cancer patients at presentation have either locally advanced disease or distant metastasis. Matsuda et al. Little et al. and Bain reported that 40-50% of NSCLC patients at presentation have distant metastasis at the time of diagnosis [1][2][3]. In this study we aim to determine the percentage of NSCLC patients with extrathoracic metastases and the pattern of distribution at presentation.

Materials and Methods
Post ethical committee approval, we retrospectively analysed inpatient records of newly diagnosed primary lung cancer between January 2017 and November 2018. Only histologically and or cytologically proven Non-small cell lung cancer (NSCLC) patients were enrolled. Secondary and Lymphoproliferative lung cancers were excluded. Lung cancers were staged as per 8 th edition of The Union Internationale Contre le Cancer (UICC) and American Joint Committee on Cancer (AJCC). As per this TNM classification M Category is classified in M0: no distant metastasis; M1a: malignant pleural or pericardial effusion or pleural or pericardial nodule or separate tumour nodule(s) in contralateral lobe; M1b: single extrathoracic metastasis; M1c: multiple extrathoracic metastases (1 or > 1 organ). The various radiological investigation used to stage the disease were Contrast enhanced Computed Tomography (CECT) of Chest, Ultrasonography (USG) of Chest, Ultrasonography of whole abdomen, 18 Fluoro deoxy glucose positron emission tomography combined with Computed tomography(FDG PET CT) and Magnetic resonance imaging of Brain (MRI). Fibreoptic Bronchoscopy where relevant was used for diagnosis. Pleural fluid and regional lymph node sampling was done to either diagnose or stage the disease where appropriate.

Results
The study included 71 patients of bronchogenic carcinoma. The disease was staged as per 8 th AJCC Lung Cancer classification (Table 1). TNM stage I to IIIA was combined due to fewer patients. FDG-PET CT was done in all the patients to detect extrathoracic metastases. Majority of the patients (n=38, 53.5%) were with M1 disease ( Table 2). ETM (M1b & M1c) at presentation were observed in 35.2% of the patients ( Table 2). The various sites involved in extrathoracic metastases (M1b & M1c) at presentation were noticed with brain being most commonly involved (Table 3). FDG-PET CT detected 9 patients with unexpected ETM with most common site being brain. ETMs frequently occurred in adenocarcinoma subtype of histology.    [7][8][9]. In our study based on the 8 th AJCC TNM classification the percentage of patient who had distant or extrathoracic metastases i.e. M1b and M1c at presentation was 35.2% (25/71) [ Table 2]. If patients with M1a disease were also included then this was 53.5% (38/71)[ Table 2]. The various sites of extrathoracic metastases (M1b & M1c) at presentation were noticed in following frequency brain (17%), followed by liver (14%), adrenal glands(6%), axillary lymph node (4%), bone excluding spine (3%) and renal, pancreas and subcutaneous tissue had 1% each (Table 3). Single organ extrathoracic metastases were seen in brain, 8 patients; liver, 6 patients; and axillary lymph nodes, 2 patients. The remaining 9 patient had multifocal extrathoracic metastases. The localized M1a in the form of pleural effusion and contralateral lobe nodule were observed in 13 patients.
The brain metastasis were observed in 12 patients with cerebral metastasis, 5 patients; cerebellar metastasis, 4 patients; and remaining 3 patients with both. The liver metastases were observed in 10 patients with single lesion in 3 patients and remaining 7 patients with multiple lesions. The extrathoracic metastases were more commonly observed in adenocarcinoma subtype of lung cancer. Brain and Liver metastasis was most commonly observed in patient with adenocarcinoma. The patients with bone or brain metastasis are mostly symptomatic and help in further evaluation with specific imaging studies. While majority of patients with adrenal gland, liver, renal and pancreatic metastases are asymptomatic and even biochemical investigation do not indicate the presence of metastasis. Further the organ involved with metastasis at presentation can have impact on the overall survival. Gorg C et al., and Yamamoto et al., observed in their study that NSCLC with liver metastasis do not respond well to chemotherapy [10][11]. Whereas Tamura et al., observed that patients with brain metastasis had better overall survival which can be attributed to stereotactic radiation therapy and use of epidermal growth factor receptor tyrosine kinase inhibitors [12].

Conclusions
ETM are not uncommon at presentation and thus Whole body FDG-PET CT Scan is a must for detection of extrathoracic metastases in NSCLC and prevent underestimation of tumor stage.

Conflicts of Interests:
None declared.