Pneumocephalus resulting from traumatic pneumothorax and brachial plexus avulsion.

Background: Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus caused by traumatic pneumothorax and brachial plexus avulsion. Case Presentation: A 20-year-old male was admitted to our hospital following a motorcycle accident with complete paralysis of the right upper limb. 2 days later, follow-up computed tomography revealed a slight right pneumothorax, pneumomediastinum around the neck, and intracranial air without skull fracture. Air migrates into the subarachnoid space through a dural tear caused by a brachial plexus avulsion. The pneumocephalus immediately improved after the insertion of a chest drain. Conclusion: Pneumothorax combined with brachial plexus avulsion could lead to pneumocephalus. Immediate chest drainage might be the best way to stop the migration of air; however, care should be taken to not worsen cerebrospinal fluid leakage.

Penetrating cardiac injury caused by multiple rib fractures following high-energy trauma: Usefulness of the exploratory video-assisted thoracoscopic surgery.

Background: Penetrating cardiac injuries are usually fatal and associated with poor survival rates. Case Presentation: A 69-year-old man was injured in a motor vehicle accident and suffered from left hemothorax and multiple rib fractures near the heart. A comprehensive assessment raised suspicions of lacerated pericardium and myocardial injury. Consequently, a thoracoscopy was performed 9 h after injury. A penetrating cardiac injury was detected and surgically treated via video-assisted thoracoscopic surgery. The patient recovered uneventfully and was discharged on postoperative day 16. Conclusion: Exploratory video-assisted thoracoscopic surgery may play a key role in the primary diagnosis of patients with high-energy chest traumas with cardiac injury and simultaneously allow for the appropriate surgical interventions.

Time dependency and unique etiology of barotrauma in COVID-19: A retrospective cohort study with landmark analysis and pathological approach.

BACKGROUND: Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. METHODS AND FINDINGS: We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group's 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group's survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. CONCLUSIONS: Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction.

Predictive performance of PD-L1 tumor proportion score for nivolumab response evaluated using archived specimens in patients with non-small cell lung cancer experiencing a postoperative recurrence.

OBJECTIVES: Postoperative recurrence in patients with non-small-cell lung carcinoma (NSCLC) is a major issue for life expectancy. Programmed cell death ligand 1 (PD-L1) expression on tumor cells is important in the prognosis of NSCLC. However, the predictive ability of PD-L1 evaluated with archived surgical specimens for nivolumab treatment have remained unknown. This study was aimed to analyze the predictive ability of the PD-L1 tumor proportion score (TPS) for nivolumab response in patients with NSCLC experiencing a postoperative recurrence using archived surgical specimens. MATERIALS AND METHODS: This retrospective cohort study involved patients with advanced NSCLC (N = 78) treated with nivolumab between April 2016 and September 2018. They were categorized into postoperative recurrence (N = 24) and non-postoperative recurrence (N = 54) groups. The predictive ability of PD-L1 TPS for response to nivolumab treatment in these two groups was determined using receiver operating characteristic (ROC) analysis. Additionally, we evaluated the predictive ability of PD-L1 TPS using rebiopsy specimens collected from the recurrent lesions in six patients of the postoperative recurrence group. RESULTS: PD-L1 TPS exhibited lower predictive performance in the postoperative recurrent group (area under the curve [AUC] = 0.58) compared with that in the non-post operative recurrent group (AUC = 0.81). Furthermore, PD-L1 TPS was significantly increased in rebiopsy specimens. The predictive performance of PD-L1 TPS in these specimens was higher (AUC = 0.90) than that in the archived surgical specimens. CONCLUSION: The study revealed that archived surgical specimens are inadequate for assessing the predictive ability of PD-L1 for nivolumab response, while rebiopsy specimens are adequate.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection. METHODS: We retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors. RESULTS: Overall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor. CONCLUSION: This study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis. Trial registration The study was approved by the Kobe City Medical Center General Hospital's ethics board (No. 20112) on August 20, 2020.

Chest wall pseudotumor: a case of non-tuberculous mycobacterial infection.

BACKGROUND: Non-tuberculous mycobacterial (NTM) infections are increasing worldwide, making them an international public health problem. Surgical management is often indicated for localized infectious disease; however, most surgeons are unaware of the potential risks of transmission during surgery. CASE PRESENTATION: An 88-year-old Asian female was referred to our hospital for a tumor in the right lateral thoracic region. One month prior, she had a feeling of fullness and complained of localized pain and warmth in the right lateral thoracic wall. Pain and warmth gradually resolved without intervention; however, the fullness was getting worse. Computed tomography (CT) scan showed a mass of approximately 65 × 30 mm with an osteolytic change, involving the right 8th rib. Based on the rapid growth rate and CT findings, we strongly suspected a malignant chest wall tumor, and en bloc tumor resection with the 8th rib was performed. When the specimen was cut, a large amount of viscous pus was drained and its culture showed growth of Mycobacterium avium. Microscopically, the non-caseating epithelioid cell granuloma extended into the rib, infiltrating the bone cortex. On follow-up 1 month after discharge, there were no signs of infection or other adverse events associated with the surgery. CONCLUSIONS: Herein, we report about a patient with a mass diagnosed as an NTM abscess involving the rib cage, which was confused with a malignant tumor and eventually diagnosed following surgical excision. This report emphasizes the need to be aware of the possibility of NTM infection and take appropriate precautions if the patient has a rapidly growing mass in the chest wall.

Tumor-to-Tumor Metastasis: Pulmonary Carcinoid Metastasizing to Solitary Fibrous Tumor.

BACKGROUND Tumor-to-tumor metastasis is an uncommon phenomenon in which a primary tumor metastasizes into another tumor. CASE REPORT An 81-year-old Asian woman was referred to our hospital for evaluation and treatment of a solid mass in the right middle lung lobe that had rapidly enlarged for 1.5 years compared to that observed over the last 5 years. On computed tomography (CT), the mass was 68×60 mm, and 2 different tumors appeared to exist in the upper portion of the mass. Blood examination findings revealed high serum levels of progastrin-releasing peptide and neuron-specific enolase. Based on the radiographic course of the tumor and elevated levels of tumor markers, we suspected that a new malignant tumor, such as a neuroendocrine tumor, had developed dorsally adjacent to the benign tumor. CT-guided percutaneous needle biopsy of the lung indicated a solitary fibrous tumor (SFT), which did not lead to the diagnosis of another tumor adjacent to the original tumor. Therefore, a right middle lobectomy was performed. The resected specimen contained 2 different tumors: an SFT and a typical carcinoid without mitosis or necrosis. On microscopic examination, they were separated from each other by normal alveolar tissue. In addition, a typical carcinoid was also observed inside the SFT lesion, completely enclosed by the SFT tissue. These findings suggested that the carcinoid metastasized to the SFT in the same lung lobe. CONCLUSIONS To the best of our knowledge, this is the first case of a pulmonary typical carcinoid metastasizing to an intraparenchymal SFT.

Association Between Formalin Fixation Time and Programmed Cell Death Ligand 1 Expression in Patients With Non-Small Cell Lung Cancer.

BACKGROUND/AIM: The expression of programmed cell death ligand 1 (PD-L1) determined by immunohistochemistry (IHC) may be associated with tissue formalin fixation time in non-small cell lung cancer (NSCLC) samples. We investigated the association between the PD-L1 expression and formalin fixation time, and clarified the optimal duration of fixation for accurate PD-L1 evaluation. MATERIALS AND METHODS: We collected 55 tumor specimens from resected NSCLC patients. The samples were halved and immediately fixed in 10% buffered formalin for 12-24 h (normal fixation), or 96-120 h (prolonged fixation). Each specimen was stained using two assay systems (22C3 and SP263) for PD-L1. RESULTS: The mean PD-L1 tumor proportion score was not significantly different between normal and prolonged fixation groups for either 22C3 or SP263 (normal fixation: 18.8%; prolonged fixation: 16.3%, p=0.277; normal fixation: 16.2%; prolonged fixation: 17.6%, p=0.560, respectively). CONCLUSION: Formalin fixation duration for up to 120 h does not affect PD-L1 IHC expression. PD-L1 tumor proportion score of tumor specimens can be evaluated by IHC even if these have been fixed in formalin outside the recommended duration in clinical practice.

Comparison of PD-L1 Assays in Non-small Cell Lung Cancer: 22C3 pharmDx and SP263.

BACKGROUND/AIM: While the PD-L1 22C3 pharmDx assay is an FDA-approved diagnostic assay for pembrolizumab use, not every pathology laboratory has the Dako Autostainer to use this assay. Since Ventana BenchMark platforms are more common, the Ventana SP263 assay can be used to inform treatment decisions involving nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC). However, some studies have shown discordant results between the two assays. This study aimed was to compare PD-L1 expression using these two assays. MATERIALS AND METHODS: A total of 100 samples from consecutive cases of resected NSCLC were tested using the two PD-L1 assays. RESULTS: The agreement rates of the two assays were 88-97% at various cut-offs. There was no significant difference between 22C3 and SP263 in tumour proportion score (p=0.455). CONCLUSION: The SP263 assay can be used in the place of the 22C3 assay for PD-L1 testing, for guiding therapy with PD-1 axis inhibitors in NSCLC.

Salvage Pulmonary Operations Following Stereotactic Body Radiotherapy for Small Primary and Metastatic Lung Tumors: Evaluation of the Operative Procedures.

Stereotactic body radiotherapy is an alternative treatment option for small-sized, primary lung cancers and pulmonary metastatic diseases. In the case of local relapse after stereotactic body radiotherapy, salvage pulmonary resection is considered cautiously. However, no study has described the difficulty of the salvage operations. This study aimed to assess the difficulty associated with salvage operative procedures. Eight patients who developed local relapse after stereotactic body radiotherapy and had undergone salvage pulmonary operations were enrolled in this study (stereotactic body radiotherapy group). Additionally, 439 patients who underwent video-assisted thoracoscopic lobectomy without previous stereotactic body radiotherapy were enrolled as the standard operative control group (non-stereotactic body radiotherapy group). In the stereotactic body radiotherapy group, 1 of the 8 patients had undergone lobectomy with composite resection of the third and fourth ribs. Of the 8 patients, 6 had undergone video-assisted thoracoscopic lobectomy and 1 had been inoperable because of rapid tumor progression. The operation time and the incision length of the utility port were apt to be longer in the stereotactic body radiotherapy group than in the non-stereotactic body radiotherapy group. On the contrary, the duration of drain placement and the length of hospital stay after the operation were not different. Thus, the salvage pulmonary operations were performed in the usual video-assisted thoracoscopic lobectomy approach, but slightly complicated than the standard video-assisted thoracoscopic lobectomy. Although to decide the indication of salvage operation might be difficult, it could be a feasible treatment option in local relapse after stereotactic body radiotherapy.

Sleeve lobectomy for lung adenocarcinoma treated with neoadjuvant afatinib.

Afatinib, the second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been postulated to be associated with improved inhibition of EGFR-dependent tumor growth compared with first-generation EGFR-TKIs for advanced non-small cell lung cancer (NSCLC). We present a case of lung adenocarcinoma (cT3N0M0) treated with neoadjuvant afatinib and sleeve lobectomy. Because of the location of the tumor, reduced FEV1 value, and the presence of EGFR mutation, the patient was planned to be prescribed afatinib (30 mg daily) for 3 weeks as neoadjuvant therapy and underwent sleeve lobectomy to avoid pneumonectomy as much as possible. Although the patient presented with grade 3 diarrhea and dose reduction of afatinib to 20 mg daily was needed, several image findings showed a partial response of the tumor on Day 20. Oral administration of afatinib was discontinued on Day 22. A right upper sleeve lobectomy combined with partial resection of lower lobe was performed after oral administration of afatinib on Day 24. The patient's postoperative course was uneventful and she has been free of recurrence for 26 months. This strategy could reduce the risk of pneumonectomy with acceptable side effects. The treatment, clinical course and pathological findings of the patient are discussed.

Programmed Cell Death Ligand 1 Expression in Non-Small-cell Lung Cancer Patients With Interstitial Lung Disease: A Matched Case-control Study.

BACKGROUND: Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have demonstrated antitumor activity, and immunohistochemical analysis of PD-L1 expression has been used to identify the response in patients with non-small-cell lung cancer (NSCLC). Recently, considerable interest has ensued toward extending the benefit of these inhibitors to high-risk patients, such as those with NSCLC and interstitial lung disease (ILD). However, no studies have compared PD-L1 expression in NSCLC patients with and without ILD. Therefore, we conducted a case-control study to evaluate PD-L1 expression and stromal CD8+ lymphocyte density in these patients. MATERIALS AND METHODS: The data from patients with pathologic stage I or II NSCLC who had undergone surgery from January 2007 to January 2016 were analyzed. RESULTS: We identified 62 patients with pathologic stage I or II NSCLC and ILD. We compared these patients with 1:1-matched cohort. In both groups with and without ILD, approximately 60% were PD-L1+. Tumor cell PD-L1 expression was similar between the groups (median, 1%; interquartile range, 0%-5%; vs. median, 1%; interquartile range, 0%-5%; P = .49). The proportion of patients with positive (≥ 1%) and strongly positive (≥ 50%) PD-L1 expression was also similar between the 2 groups (P = .46 and P = 1.00, respectively). Additionally, the CD8+ lymphocyte density did not differ between patients with and without ILD. CONCLUSION: PD-L1 expression and stromal CD8+ lymphocyte density were comparable between the NSCLC patients with and without ILD. PD-1 axis inhibitors might be effective for NSCLC patients with ILD.

Reduced Tumour Proportion Scores for Programmed Cell Death Ligand 1 in Stored Paraffin Tissue Sections.

BACKGROUND/AIM: We evaluated the effects of storage of formalin-fixed, paraffin-embedded (FFPE) sections on the tumour proportion score (TPS) for programmed cell death ligand 1 (PD-L1), as indicator in non-small cell lung cancer (NSCLC) tissues of treatment efficacy. MATERIALS AND METHODS: NSCLC postoperative specimens with PD-L1 TPS ≥50% were obtained and cut into five serial sections. One section was stained immediately, and four were stored at 4°C for 2, 4, 6, or 8 weeks. Slides were subjected to PD-L1 immunohistochemistry using the anti-PD-L1 clone 28-8. PD-L1 TPS were blindly evaluated by two independent pathologists. RESULTS: Twelve specimens (60 slides) were evaluated. After slide storage for 2, 4, 6, and 8 weeks, a TPS of <50% was obtained in five (41%), four (33%), seven (58%), and eight (67%) patients, respectively. CONCLUSION: TPS values for PD-L1 were reduced by long-term slide storage of FFPE specimens. Sectioned slides should be stained for PD-L1 without delay.

Thoracoscopic Surgery for a Congenital Bronchoesophageal Fistula With Pulmonary Sequestration in an Adult Woman.

A congenital bronchoesophageal fistula with pulmonary sequestration is rare in adults. Here, we report the case of an adult woman having congenital bronchoesophageal fistula with intralobar pulmonary sequestration who successfully underwent thoracoscopic resection and showed a good postoperative course.

KRAS mutation-positive mucinous adenocarcinoma originating in the thymus.

Thymic carcinoma is a rare, aggressive disease with a low 5-year survival rate. The most common histological neoplastic thymic tumor subtype is squamous cell. We describe an interesting case of a 39-year-old woman who presented with mucinous adenocarcinoma that originated in the thymus and was treated via radical resection and venoplasty of the superior vena cava (SVC). Macroscopically, the resected tumor contained a solid region and multiple cysts with abundant mucin. Microscopic examination showed a papillary growth pattern of goblet cells with round nuclei. Based on the histopathological and immunohistochemical findings and other inspections, the tumor was eventually diagnosed as a mucinous adenocarcinoma of the thymus. It was classified as Masaoka-Koga stage III owing to tumor invasion into the left brachiocephalic vein and pericardium. Polymerase chain reaction identified a Kirsten rat sarcoma viral oncogene homolog (KRAS) G12V mutation in the tumor. There were no mutations in the epidermal growth factor (EGFR) gene or a fusion gene of the echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK). A year later, multiple lung metastases were detected, and the patient underwent chemotherapy. She is alive 34 months after the initial surgery. This is the first report of a KRAS mutation-positive mucinous adenocarcinoma originating in the thymus. The treatment, diagnosis, and pathological findings of the patient are discussed.

Alteration of PD-L1 expression and its prognostic impact after concurrent chemoradiation therapy in non-small cell lung cancer patients.

Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (P = 0.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (P < 0.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.

Natural history and clinical characteristics of multiple pulmonary nodules with ground glass opacity.

BACKGROUND AND OBJECTIVE: Ground glass nodules (GGNs) are frequently encountered in the lungs. We report the natural history and characteristics of multiple GGNs, and propose a management plan for patients with multiple GGNs. METHODS: We retrospectively analysed patients with GGNs that met the following criteria: (i) GGN diameter of 3 cm or less, (ii) ground glass opacity proportion of 50% or more and (iii) observation without treatment for ≥6 months. We evaluated size changes in computed tomography images. Two end points, 'incidence of growth at 36 months' and 'time to growth' were analysed using logistic regression models and Cox proportional hazards model. RESULTS: Between April 2008 and December 2014, 187 patients fulfilled the inclusion criteria (78 (42%) had multiple lesions). Among the multiple-GGN patients, the median observation period was 45.5 months, 25 patients (32%) experienced GGN progression at 36 months and 4 patients (5.1%) after 36 months. Between the multiple and single GGNs, there were no significant differences in growth incidence at 36 months (P = 0.1), after 36 months (P = 0.6) or in time to growth (P = 0.3). Among patients with multiple GGNs who experienced one GGN growth, 41% of patients experienced residual GGN growth afterwards. CONCLUSION: Patients with multiple GGNs showed a tendency to growth within the first 36 months, and a significant proportion of patients experienced multiple GGN progression. We suggest that the optimal observation period for patients with multiple GGNs is 36 months, but careful observation is needed after a lesion begins to grow.

Giant cell tumor of the rib with direct invasion into the thoracic spine.

Giant cell tumors of bone are relatively rare, benign, but locally aggressive osteolytic skeletal neoplasms of young adults. They usually affect the epiphyses of long bones, especially around the knee joint, and are rarely seen in the ribs. The mainstay of therapy is surgical resection. Herein, we report a case of successful resection in a patient who presented with primary giant cell tumor of the rib, directly invading the thoracic spine. Computed tomography and magnetic resonance imaging were helpful for assessing the depth of tumor invasion. Radical resection of the tumor and reconstruction of the vertebrae with preserved allograft bone were performed. No respiratory or neurological problems occurred, and the patient remained well 2 years after surgery.

The prognostic value of serum CA 19-9 for patients with advanced lung adenocarcinoma.

BACKGROUND: This study aimed to assess the prognostic accuracy of serum CA 19-9 in patients with advanced lung adenocarcinoma. METHODS: We retrospectively reviewed data of 246 patients who were diagnosed at our institute with advanced (stage IIIB or IV) lung adenocarcinoma between March 2006 and December 2012. We excluded patients who received no chemotherapy, or for whom we had no data on pre-treatment tumor markers. We also evaluated 116 consecutive resected specimens from patients with clinical stage I lung adenocarcinoma pathologically. RESULTS: The 76 (31 %) patients who were CA 19-9+ had shorter overall survival (OS) than CA 19-9- group (12.5 vs 26.2 months, P = 0.005). Cox's multivariate regression analysis identified Eastern Cooperative Oncology Group Performance Status 0 or 1 (P < 0.001), mutated epidermal growth factor receptor (EGFR) status (P < 0.001), stage IIIB (P < 0.001), CYFRA 21-1- (P < 0.001), CA 19-9- (P = 0.005) and use of platinum doublet therapy (P = 0.034) as independent predictors of longer OS. We stratified patients by CA 19-9 and CYFRA 21-1 as double positive (CA 19-9+/CYFRA 21-1+, n = 59), single positive (either CA19-9+ or CYFRA 21-1+, n = 113), or double negative (CA 19-9-/CYFRA 21-1-, n = 74). Their respective OS were 10.0, 23.3 and 31.8 months (P < 0.001). Pathological analysis also correlated CA 19-9 expression with malignant features such as vessel invasion, pleural invasion, cancer invasive factors and mucin production. CONCLUSIONS: CA 19-9 and CYFRA 21-1 are independent prognostic markers in patients with advanced lung adenocarcinoma. Combined use of CA 19-9 and CYFRA 21-1 provides further prognostic information in patients with advanced lung adenocarcinoma.