The prognostic analysis of non-small cell lung cancer with unexpected pleural cavity dissemination

doi:10.21203/rs.3.rs-2482337/v1

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The prognostic analysis of non-small cell lung cancer with unexpected pleural cavity dissemination

https://doi.org/10.21203/rs.3.rs-2482337/v1

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Background: The prognosis of advanced non-small cell lung cancer (NSCLC) is poor. At present, incidental pleural cavity dissemination during operation is still unavoidable. The clinicopathological features and the best way to deal with incidental pleural cavity dissemination during operation has not been determined.

Methods: 58 NSCLC patients with pleural cavity disseminated incidentally found during surgery were included in our retrospective research from December 2012 to August 2018 according to the 8th edition of TNM staging. None of these had distant metastasis.

Results: Univariate and multivariate analysis revealed that targeted therapy was the only predictor of prognosis. Among patients receiving lymph node sampling or dissection, univariate analysis revealed that more advanced stage, lymph node metastasis, and higher proportion of metastatic lymph nodes were associated with worse progression-free survival (PFS). Smoking, more advanced stage, higher proportion of metastatic lymph nodes and no targeted therapy were significantly associated with worse overall survival (OS). Multivariate analysis recognized targeted therapy as the only predictor of prognosis. In patients not receiving targeted therapy, pleural cavity infusion chemotherapy seemed to be beneficial both to PFS and OS, but without statistical significance. Multivariate analysis found that lymph node metastasis was the only predictor of PFS, but no predictor of OS.

Conclusions: Targeted therapy is the best treatment for NSCLC patients with incidentally pleural cavity dissemination if there was target gene mutation. Pleural cavity infusion chemotherapy has potential survival benefit for patients without target gene mutations. Lymph node metastasis is not beneficial to the prognosis of patients with pleural cavity dissemination.

advanced non-small cell lung cancer

pleural cavity dissemination

targeted therapy

lymph node metastasis

primary tumor resection

Targeted therapy is the best treatment for non-small cell lung cancer (NSCLC) patients with incidentally pleural cavity dissemination if there was target gene mutation. Patients couldn't benefit from primary tumor resection and lymph node sampling or dissection.

Studies have shown the prognostic benefit of targeted drugs and primary tumor resection in those patients. However, there is still no consensus on the necessity of lymph node sampling or dissection and pleural cavity infusion chemotherapy. In our study, we explore the appropriate treatment to those patients.

We found that targeted therapy is the best therapeutic modality in NSCLC with pleural cavity dissemination. Resection of the primary tumor focus is not helpful for improving the prognosis. Lymph node sampling or dissection was associated with worse progression-free survival (PFS) in patients with pleural cavity dissemination. Pleural cavity infusion chemotherapy seemed to help improve PFS, but with only a limited degree.

Lung cancer has the third highest morbidity, second only to breast cancer and prostate cancer, with the highest mortality worldwide and non-small cell lung cancer (NSCLC) account for 85% of the incidence of lung cancer[1, 2]. The lung cancer 75% of the patients were in locally advanced stage or advanced stage at the time of diagnosis, and lost the opportunity of surgery, while the 5-year survival rate of advanced lung cancer was lower than 5%[3]. Advanced lung cancer includes a special form of pleural dissemination (PD), that is, the tumor breaks through the visceral pleura and enters the thoracic cavity for implantation and metastasis. PD is generally divided into two types, dry and wet PD. Wet PD can usually be diagnosed before operation. However, although some dry PD can be found by preoperative examination, it is still common to find PD during operation. Moreover, even if chest computed tomography (CT) could predict the existence of pleural or fissural nodules[4], the metabolism of these nodules from positron emission tomography (PET) is not completely related to the nodule metastatic status, and surgical treatment may still be performed. In a word, PD during operation is accidental. According to the recommendation of NCCN, cases with PD are classified as IVa stage, and surgery is not suitable for this situation. At present, for the treatment of advanced NSCLC with target gene mutation, such as epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement, targeted therapy is the first-line treatment[5, 6]. If there is no target gene mutation, chemotherapy or immunotherapy should be considered[3]. Radiotherapy is also helpful for local control of tumors[7]. However, literatures have shown the prognostic benefit of surgery in this type of IVa stage disease[8, 9]. So the clinicopathological features of PD cases have not been finally determined and there is still no consensus for the best treatment methods in NSCLC patients with disseminated lesions accidentally found during operation. Whether the clinicopathological features and treatment of patients with PD is different from other types of advanced stage NSCLC needs further discussion.

We retrospectively reviewed medical records of all patients who were diagnosed with NSCLC and underwent surgery in the thoracic surgery department of Peking Union Medical College Hospital from December 2012 to August 2018. The inclusion criteria were as follows: primary NSCLC with pathological stage of IVa stage according to the 8th edition of TNM staging; all patients receiving systematic examination, such as PET or the other whole-body examinations, including head enhanced MRI, thoracoabdominal CT, abdominal ultrasound, whole-body bone imaging, etc; no distant metastatic lesions were found; pleural cavity dissemination was found during operation. Exclusion criteria: small cell carcinoma; patients only receiving thoracotomy; distant metastasis was found preoperatively; patients with medical history of other tumors.

All patients received surgery, such as sampling of pleural dissemination sites and the resection of primary tumor including lobectomy and sublobectomy. After the surgery, there were professional pathologists for pathological examination. In our study, the definition of locally advanced stage includes TxN2-3M1a T4N0M1a and T3-4N1M1a. We recommended all patients undergo genetic test, and if there was a target gene mutation, targeted therapy was recommended. If there was no target gene mutation, chemotherapy is under consideration. All patients received regular follow-up postoperatively every 3 months. Patients who didn’t return to the hospital were determined as censored.

Statistical analysis: Chi-square test was used to analyze categorical variables, and t test was used to analyze continuous variables to compare the differences in clinicopathological characteristics and treatment methods. X-tile software was used to determine the best cut off value for continuous variables. Progression free survival (PFS) is the time from the date of surgery to progression or the last follow-up. Overall survival (OS) is the time from the time of surgery to death or the last follow-up. Survival was analyzed using the Kaplan-Meier method and compared using the log rank test. Univariate and multivariate Cox proportional hazards models were used to determine prognostic factors. A significant difference was defined as a p-value less than 0.05. SPSS 19.0 was used for statistical analysis.

58 cases were recruited for analysis. The median follow-up time is 2214 days. The median survival time is 1687 days while the median PFS time is 738 days. Univariate survival analysis (Table 1, Fig. 1) revealed that the extent of surgery (lobectomy, sublobectomy, or biopsy of pleural dissemination sites) had no effect on PFS. Short-term pleural cavity infusion chemotherapy (PCIC) seemed to be effective for PFS, but of no statistical significance. Patients with lymph node metastasis had worse PFS (5-year PFS 24.8% vs 15.2%, P = 0.054). The PFS of those who underwent lymph node dissection was worse than that of those who did not (5-year PFS 25.1% vs 0%, P = 0.038). Patients who received targeted drug therapy had better PFS than those who didn’t (5-year PFS 30.9% vs 6.2%, P = 0.023). Multivariate survival analysis revealed that targeted therapy was the only predictor of PFS. As for OS (Table 2, Fig. 2), the extent of surgery, the PCIC, the status of lymph node metastasis, the lymph node dissection, had no significant effect on OS. The targeted therapy was the only predictor of OS (5-year OS 66.5%vs 23.8%, p = 0.000). The Kaplan-Meier analysis clarified the great benefit of targeted therapy in patients with PD.

Table 1

The univariate and multivariate progression-free survival analysis of 58 non-small cell lung cancer patients with pleural cavity dissemination.
	Univariate survival analysis		Multivariate survival analysis
Characteristic	HR	p	HR	p
Gender Female Male	0.782(0.430–1.420)	0.419
Age ≥65 years old < 65 years old	1.080(0.559–2.086)	0.818
Smoking history No Yes	0.963(0.523–1.773)	0.904
Size ≥3cm < 3cm	1.029(0.563–1.879)	0.926
Pathological stage (except pleural cavity metastasis) Not locally advanced Locally advanced	0.667(0.364–1.220)	0.188
Surgical type Without primary tumor resection With primary tumor resection	1.355(0.696–2.640)	0.372
Pleural cavity infusion chemotherapy No Yes	1.638(0.852–3.149)	0.139
Pathological subtypes Not acinar dominant adenocarcinoma Acinar dominant adenocarcinoma	1.118(0.615–2.033)	0.714
Lymph node dissection No Yes	0.445(0.207–0.956)	0.038	0.688(0.271–1.749)	0.432
Definite lymph node metastasis N/A or no Yes	0.551(0.300–1.010)	0.054	0.638(0.303–1.343)	0.237
Adjuvant treatment Not Targeted therapy Targeted therapy	2.020(1.102–3.702)	0.023	1.960(1.055–3.640)	0.033
HR: hazard ratio

Table 2

The univariate and multivariate overall survival analysis of 58 non-small cell lung cancer patients with pleural cavity dissemination.
	Univariate survival analysis		Multivariate survival analysis
Characteristic	HR	p	HR	p
Gender Female Male	0.714(0.354–1.439)	0.344
Age ≥65 years old < 65 years old	1.342(0.631–2.855)	0.443
Smoking history No Yes	0.767(0.378–1.559)	0.462
Size ≥3cm < 3cm	1.583(0.790–3.172)	0.192
Pathological stage (except pleural cavity metastasis) Not locally advanced Locally advanced	0.510(0.241–1.079)	0.073	0.551(0.260–1.167)	0.119
Surgical type Without primary tumor resection With primary tumor resection	1.538(0.725–3.263)	0.259
Pleural cavity infusion chemotherapy No Yes	1.672 (0.781–3.577)	0.181
Pathological subtypes Not acinar dominant adenocarcinoma Acinar dominant adenocarcinoma	1.149(0.571–2.313)	0.697
Lymph node dissection No Yes	0.602(0.260–1.395)	0.232
Lymph node metastasis N/A or no Yes	0.592(0.295–1.185)	0.134
Adjuvant treatment Not Targeted therapy Targeted therapy	3.598(1.745–7.420)	0.000	3.468(1.679–7.161)	0.001
HR: hazard ratio

The pleural metastasis was not the unique type of metastasis that influenced prognosis. The lymph node metastasis also might influence the prognosis. Although our previous research results seemed to demonstrated that the status of lymph node metastasis had no influence on prognosis, not all of 58 patients received lymph node sampling or dissection. After filtering patients who didn’t receive lymph node sampling or dissection, 32 cases were finally included for further survival analysis. In this part, the proportion of metastatic lymph nodes describes the seriousness of lymph node metastasis. The mean number of lymph node dissection is 18.34 ± 2.910. The X-tile software recommended the cut off value of the proportion of metastatic lymph nodes was 0.11.

Univariate survival analysis (Table 3, Fig. 3) revealed that more advanced stage was associated with worse PFS (P = 0.041). The PFS of patients with lymph node metastasis was worse than those without lymph node metastasis (5-year PFS 45.0% vs 15.2%, P = 0.039). PFS of those who underwent lymph node dissection was worse than those who did not (5-year PFS 32.1% vs 0%, P = 0.052). Patients with lower proportion of metastatic lymph nodes had better PFS than those with higher proportion of metastatic lymph nodes (47.7% vs 10%, P = 0.003). Patients receiving targeted drugs had better PFS than those not receiving targeted therapy (5-year PFS 33.3% vs 11.7%, P = 0.016). However, the advanced stage, the extent of pulmonary resection and PCIC had no effect on PFS. Multivariate survival analysis revealed that the targeted therapy was the only predictor of PFS. As for OS (Table 4, Fig. 4), nonsmokers had better prognosis (5-year OS 63.2% vs 23.1%, p = 0.027). Advanced stage was associated with worse OS (5-year OS 70.0% vs 36.4%, p = 0.042). Patients with higher proportion of metastatic lymph nodes had worse OS than those with lower proportion of metastatic lymph nodes (35.0% vs 66.7%, p = 0.039). Patients receiving targeted drugs had better OS than those not receiving targeted therapy (73.3% vs 23.5%, p = 0.001). In contrast, the extent of pulmonary resection and the PCIC, the status of lymph node metastasis and the sampling or dissection of lymph nodes didn’t influence OS. Multivariate survival analysis revealed that non-smoking and the targeted therapy were predictors of OS.

Table 3

The univariate and multivariate progression-free survival analysis of 32 non-small cell lung cancer patients receiving lymph node sampling or dissection with pleural cavity dissemination.
	Univariate survival analysis		Multivariate survival analysis
Characteristic	HR	p	HR	p
Gender Female Male	0.501(0.221–1.137)	0.092	0.253(0.046–1.396)	0.115
Smoking history No Yes	0.474(0.209–1.073)	0.067	1.032(0.212–5.027)	0.969
Pathological stage (except pleural cavity metastasis) Not locally advanced Locally advanced	0.383(0.148–0.989)	0.041	4.037E4(0.000-2.585E85)	0.911
Surgical type Without primary tumor resection With primary tumor resection	1.293(0.440–3.800)	0.640
Pleural cavity infusion chemotherapy No Yes	1.458(0.598–3.555)	0.404
Pathological subtypes Not acinar dominant adenocarcinoma Acinar dominant adenocarcinoma	0.884(0.393–1.991)	0.766
Lymph node dissection No Yes	0.426 (0.176–1.034)	0.052	0.537(0.196–1.473)	0.227
Lymph node metastasis No Yes	0.356(0.129–0.982)	0.039	0.365(0.026–5.162)	0.456
The proportion lymph node metastasis ≤ 0.11 > 0.11	0.253(0.098–0.656)	0.003	0.000(0.000-7.246E75)	0.905
Adjuvant treatment Not Targeted therapy Targeted therapy	1.915(0.841–4.358)	0.116	3.209(1.236–8.329)	0.017
HR: hazard ratio

Table 4

The univariate and multivariate overall survival analysis of 32 non-small cell lung cancer patients receiving lymph node sampling or dissection with pleural cavity dissemination.
	Univariate survival analysis		Multivariate survival analysis
Characteristic	HR	p	HR	p
Gender Female Male	0.466(0.182–1.191)	0.103
Smoking history No Yes	0.372(0.150–0.924)	0.027	0.313(0.119–0.823)	0.019
Pathological stage (except pleural cavity metastasis) Not locally advanced Locally advanced	0.298(0.086–1.029)	0.042	0.428(0.041–4.430)	0.477
Surgical type Without primary tumor resection With primary tumor resection	1.072(0.311–3.693)	0.913
Pleural cavity infusion chemotherapy No Yes	1.089(0.391–3.037)	0.870
Pathological subtypes Not acinar dominant adenocarcinoma Acinar dominant adenocarcinoma	0.898(0.363–2.221)	0.816
Lymph node dissection No Yes	0.601(0.236–1.535)	0.282
Lymph node metastasis No Yes	0.368(0.107–1.270)	0.100
The proportion lymph node metastasis ≤ 0.11 > 0.11	0.328(0.108–0.997)	0.039	0.640(0.080–5.112)	0.674
Adjuvant treatment Not Targeted therapy Targeted therapy	4.665(1.657–13.132)	0.001	5.959(2.007–17.698)	0.001
HR: hazard ratio

Patients with pleural metastasis could receive excellent survival benefit from targeted therapy. However, what is the better treatment in patients without targeted gene mutation and appropriate drugs? To determine this question, further subgroup analysis was performed. A total of 24 patients didn’t receive targeted therapy. Female had better PFS than male did. The prognosis of patients with lymph node metastasis was statistically significantly worse than those without lymph node metastasis. Patients with advanced stage had worse PFS, but without statistical significance. Lymph node dissection was meaningless. PCIC seemed to be helpful, but was not statistically significant to PFS. Multivariate analysis revealed that only lymph node metastasis was the independent predictor of PFS. As for OS, female had better OS than male. Patients seemed to benefit from PCIC but without significance. Multivariate analysis recognized the gender as the only predictor of OS.

NSCLC with PD is an advanced-stage type with poor prognosis[10]. The treatment exploring of those patients with PD has been still ongoing. Previous studies have elucidated the essential role of surgical resection in patients with PD[11]. Chen, et al confirmed the effectiveness of wait-and-see strategy for patients with PD[12]. Some preclinical study demonstrated the treatment value of near infrared photoimmunotherapy[13]. In conclusion, PD is a special type of advanced lung cancer, and its optimal treatment still needs further exploration.

Targeted therapy is the best therapeutic modality in NSCLC with PD. If there is corresponding gene mutation, the first choice is targeted therapy, which can greatly improve PFS and OS. For patients with EGFR activation mutation or ALK rearrangement, the use of tyrosine kinase inhibitors has completely changed the treatment of advanced NSCLC[14]. In our study, the 5-year OS rate and PFS rate of patients with PD was 48.1% and 20.5%, which was better than the prognosis of patients with other types of advanced lung cancer[15]. Meanwhile, the 5-year OS rate and PFS rate of patients without targeted therapy was 23.8% and 6.2%, which was also prior to the prognosis of patients with general advanced lung cancer. PD is a special type of metastasis causing the advanced staging, which differs from the metastatic type of lymph node metastasis or distant metastasis, such as brain or bone metastasis, whose prognosis is different from that of patients with other metastatic types. That is to say, NSCLC patients with PD has independent clinicopathological characteristics and prognosis.

Resection of the primary tumor focus is not helpful to improve the prognosis. In our institute, compared with simple biopsy of metastatic nodules, the resection of primary tumor, no matter wedge resection or lobectomy, has no effect on better PFS and OS. We speculate that although the primary lesion has been removed, there are still secondary metastatic lesions in the thoracic cavity, and there is still a persistent risk of progression or metastasis, which will affect the prognosis. Previous published articles demonstrated the potential surgical value of NSCLC with PD in selected patients, but only limited to patients without mediastinal lymph node metastasis[16, 17]. Li, et al. conducted a retrospective study enrolling 105 patients and revealed that surgery significantly prolonged survival in the non-targeted therapy group (median survival time 39.8 vs 14.2 months, P = 0.002)[18].The most accepted surgical modes were lobectomy and segmentectomy. Li, et al. enrolled 43 patients and found that patients in the tumor resection group had better PFS (3-year survival: 44.5% vs 0%; P = 0.009) and OS (3-year survival: 82.9% vs 38.5%; P = 0.013) than the open-close group did. However, there was no significant survival difference between sublobar resection and lobectomy for the main tumor resection[19]. Fan, et al obtained a similar conclusion[20]. Another retrospective study conducted by Li, et al. showed the prognostic benefit of surgery except for those with pericardial effusion or N3 disease[21]. Furthermore, patients who underwent lobe/bilobectomy had significantly better OS than those who underwent sublobar resection[21]. However, our study didn’t find the survival benefit from surgery, no matter PFS or OS, possibly due to the excellent prognostic contribution from targeted therapy and the small sample size of those without targeted therapy.

PCIC seems to help improve PFS. Inspite of the survival analysis of 58 patients or the survival analysis of patients who did not receive targeted drug therapy, two survival curves of whether receiving PCIC or not were obviously separated. However, patients might only benefit a limited degree from PCIC. In addition, our data volume is exactly small, so we failed to obtain statistically significant benefits. In 1995, Matsuzaki, et al proved the potential prognostic value of intrapleural perfusion hyperthermo-chemotherapy for patients with pleural dissemination who have had their primary lesions removed[22]. Moreover, PCIC is a safety, effective and promising approach[23] with controllable side effects[24]. At the same time, the length of hospitalization between two groups was not different. So PCIC could be considered in patients with occasional PD during operation or postoperatively.

Lymph node sampling or dissection was not helpful for the prognosis of patients with pleural cavity dissemination, and was even associated with worse PFS in univariate survival analysis. Multivariate analysis also did not find the impact of lymph node or sampling or dissection on the prognosis, which indicates that lymph node sampling or dissection is not necessary in patients with PD. In addition, univariate analysis showed that lymph node metastasis was associated with worse PFS, and had no significant effect on OS. Previous study showed that lymph node involvement was an independent prognostic factor for M1a patients[25]. Earlier in 1994, Akaogi, et al revealed that the presence of N2 disease was a poor prognostic sign in lung cancer with PD[26]. Iida, et al conducted a national study and found that better node status and macroscopic complete resection were beneficial to patients with pleural carcinomatosis[27]. PD is only a type of metastasis while there is still a possibility of no lymph node involved affecting prognosis in another way[28]. In my study, when the proportion of lymph node metastasis is lower, the prognosis is better. We wouldn't say that the 0.11 cutoff value is a referential indicator, but the lower the ratio of lymph node metastasis was, the better survival the patients had.

Our research has many limitations. First of all, this is a retrospective clinical study with many potential biases. In addition, the number of our samples is small. Although we have collected data from a single center for 8 years, only 58 patients were finally included after screening, and not all patients had lymph node sampling or dissection, which is not conducive to the selection of prognostic factors. In future, we can design a prospective, multicenter clinical study to determine the clinical interventions that affect the prognosis, such as PCIC.

To summarize, our research shows that targeted therapy is the best treatment for NSCLC patients with PD if there was target gene mutation. Primary focus resection and lymph node sampling or dissection are not helpful for both PFS and OS. PCIC has potential survival benefit for patients without target gene mutations. Lymph node metastasis is harmful to the prognosis of patients with PD.

NSCLC	non-small cell lung cancer
PD	pleural dissemination
CT	computed tomography
PET	positron emission tomography
PFS	progression-free survival
OS	overall survival
PCIC	pleural cavity infusion chemotherapy

Ethics approval and consent to participate: The approval for the retrospective study was obtained from Institutional Review Board of Peking Union Medical College Hospital, Beijing, China. This retrospective study waived from requiring informed consent approved by the Institutional Review Board of Peking Union Medical College Hospital, Beijing, China. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Consent for publication: Not applicable.

Availability of data and materials: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that there were no conflicts of interests and funding support.

Funding: This work was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-011).

Author contributions: Li contributed to study conception and design. Guo contributed to administrative support. Ren contributed to data collection. Wang contributed to statistic analysis and interpretation. All authors read and approved the final manuscript.

Acknowledgments: None.

Siegel, R.L., et al., Cancer statistics, 2022. CA Cancer J Clin, 2022. 72(1): p. 7-33.
Xia, C., et al., Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl), 2022. 135(5): p. 584-590.
Miller, M. and N. Hanna, Advances in systemic therapy for non-small cell lung cancer. Bmj, 2021. 375: p. n2363.
Kim, Y.K., et al., Dry pleural dissemination in non-small cell lung cancer: prognostic and diagnostic implications. Radiology, 2011. 260(2): p. 568-74.
Moore, S. and P. Wheatley-Price, EGFR Combination Therapy Should Become the New Standard First-Line Treatment in Advanced EGFR-Mutant NSCLC. J Thorac Oncol, 2021. 16(11): p. 1788-1792.
Cameron, L.B., et al., Targeted therapy for advanced anaplastic lymphoma kinase (<I>ALK</I>)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev, 2022. 1(1): p. Cd013453.
Shang, S., et al., Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates. Cancer Commun (Lond), 2021. 41(11): p. 1086-1099.
Wang, Z., et al., Development and External Validation of a Nomogram for Predicting Cancer-Specific Survival of Non-Small Cell Lung Cancer Patients With Ipsilateral Pleural Dissemination. Front Oncol, 2021. 11: p. 645486.
Li, H., et al., New horizons in non-small-cell lung cancer patients with ipsilateral pleural dissemination (M1a): review of the literature. Ann Transl Med, 2021. 9(11): p. 959.
Eberhardt, W.E., et al., The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol, 2015. 10(11): p. 1515-22.
Ichinose, Y., et al., Prognosis of resected non-small cell lung cancer patients with carcinomatous pleuritis of minimal disease. Lung Cancer, 2001. 32(1): p. 55-60.
Chen, Y., et al., Wait-and-See Treatment Strategy Could be Considered for Lung Adenocarcinoma with Special Pleural Dissemination Lesions, and Low Genomic Instability Correlates with Better Survival. Ann Surg Oncol, 2020. 27(10): p. 3808-3818.
Sato, K., et al., Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience. Theranostics, 2015. 5(7): p. 698-709.
Tan, A.C. and D.S.W. Tan, Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations. J Clin Oncol, 2022. 40(6): p. 611-625.
Wei, S., et al., Cathepsin F and Fibulin-1 as novel diagnostic biomarkers for brain metastasis of non-small cell lung cancer. Br J Cancer, 2022. 126(12): p. 1795-1805.
David, E.A., et al., The Role of Thoracic Surgery in the Therapeutic Management of Metastatic Non-Small Cell Lung Cancer. J Thorac Oncol, 2017. 12(11): p. 1636-1645.
Okamoto, T., et al., Pulmonary resection for lung cancer with malignant pleural disease first detected at thoracotomy. Eur J Cardiothorac Surg, 2012. 41(1): p. 25-30.
Li, H., et al., Primary tumor resection of non-small cell lung cancer patients with ipsilateral pleural dissemination (M1a) in the era of targeted therapy. Thorac Cancer, 2020. 11(11): p. 3213-3222.
Li, C., et al., Lung adenocarcinoma with intraoperatively diagnosed pleural seeding: Is main tumor resection beneficial for prognosis? J Thorac Cardiovasc Surg, 2018. 155(3): p. 1238-1249.e1.
Fan, L., et al., Surgical Resection of Primary Tumors Provides Survival Benefits for Lung Cancer Patients With Unexpected Pleural Dissemination. Front Surg, 2021. 8: p. 679565.
Li, H., et al., Primary tumour resection in non-small-cell lung cancer patients with ipsilateral pleural dissemination (M1a): a population-based study. Eur J Cardiothorac Surg, 2019. 55(6): p. 1121-1129.
Matsuzaki, Y., et al., Intrapleural perfusion hyperthermo-chemotherapy for malignant pleural dissemination and effusion. Ann Thorac Surg, 1995. 59(1): p. 127-31.
Feng, X., et al., Therapeutical effect of intrapleural perfusion with hyperthermic chemotherapy on malignant pleural effusion under video-assisted thoracoscopic surgery. Int J Hyperthermia, 2018. 34(4): p. 479-485.
Sakaguchi, H., et al., Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion. Lung Cancer, 2017. 104: p. 70-74.
Dai, C., et al., Does Lymph Node Metastasis Have a Negative Prognostic Impact in Patients with NSCLC and M1a Disease? J Thorac Oncol, 2016. 11(10): p. 1745-54.
Akaogi, E., et al., Pleural dissemination in non-small cell lung cancer: results of radiological evaluation and surgical treatment. J Surg Oncol, 1994. 57(1): p. 33-9.
Iida, T., et al., Surgical Intervention for Non-Small-Cell Lung Cancer Patients with Pleural Carcinomatosis: Results From the Japanese Lung Cancer Registry in 2004. J Thorac Oncol, 2015. 10(7): p. 1076-82.
Mordant, P., et al., Surgery for metastatic pleural extension of non-small-cell lung cancer. Eur J Cardiothorac Surg, 2011. 40(6): p. 1444-9.

No competing interests reported.

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The prognostic analysis of non-small cell lung cancer with unexpected pleural cavity dissemination

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