Search

Objectives: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC). Methods: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC. Results: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR). Conclusions: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC. [ABSTRACT FROM AUTHOR]

Objective: At present, the incidence of synchronous multiple primary lung cancer (SMPLC) is increasing, and the treatment is still a challenge. This study aims to investigate the appropriate surgical procedure for treating bilateral primary lung cancer simultaneously. Methods: A retrospective analysis was conducted on clinical data from 32 patients who underwent simultaneous bilateral lung cancer surgery in our team. This data included patient characteristics, pulmonary function indicators, surgical procedures, operation duration, chest tube removal time, postoperative hospital stay, and postoperative complications. Results: Out of the 32 patients, 15 were male, and 17 were female, with an average age of 56.4 ± 8.8 years. The average maximum diameter of the main and minor tumors was 1.8 ± 1.0 cm and 1.0 ±.5 cm, respectively. All surgeries were performed thoracoscopically through intercostal approach. The procedure for the minor tumor was performed first, followed by the main tumor operation after turning over. One case was converted to thoracotomy during the main tumor operation because of bleeding. Postoperative complications occurred in one patient. No instances of respiratory insufficiency or failure were observed after the operation, and there were no perioperative deaths or readmissions within 90 days. Conclusion: Simultaneous bilateral thoracoscopic surgery is deemed a secure and feasible option for eligible patients with bilateral primary lung cancer, and it is advisable to commence the operation on the minor tumor first. [ABSTRACT FROM AUTHOR]

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC. [ABSTRACT FROM AUTHOR]

Introduction: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. Method: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. Results: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. Conclusions: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with multiple primary lung cancers staged from IA to IB based on tumor size. Methods: Clinicopathological and follow-up data of 122 patients with multiple primary lung cancers diagnosed at stages IA-IB and surgically treated at the Department of Thoracic Surgery, Shenzhen people's Hospital from January 2019 to December 2021 were retrospectively analyzed. The study involved 42 males and 80 females. STAS status was used to divide them into two groups (87 cases in STAS (-) and 35 cases in STAS (+)). A logistic regression analysis, univariate and multivariate Cox regression analysis, and Kaplan-Meier curves (K-M) were used to determine how STAS affected recurrence-free survival (RFS) in patients. Results: STAS (+) had a significantly higher recurrence rate than STAS (-). STAS was predicted by smoking history (P = 0.044), main tumor diameter (P = 0.02), and solid nodules on chest CT (P = 0.02). STAS incidence was not significantly different between lobectomy and sublobar resection groups (P = 0.17). Solid nodules on CT, tumor diameter, vascular invasion, pleural invasion, and STAS were significant predictors of recurrence in the univariate Cox regression analysis. Tumor diameter, pleural invasion and STAS were significant prognostic factors for recurrence in the multivariate Cox regression analysis. Furthermore, STAS (+) group was at greater risk of recurrence than STAS (-) group (34% vs. 0%, P < 0.05)。. Conclusion: Stage IA-IB multiple primary lung cancer patients with STAS (+) had a higher recurrence rate and a shorter overall survival rate. [ABSTRACT FROM AUTHOR]

Purpose: Surgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice. Methods: A retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups. Results: A total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2–3 cm (P < 0.05). Conclusion: The OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2–3 cm tumor size, lobar resection is more advantageous than sublobar resection. [ABSTRACT FROM AUTHOR]

AIM: To explore the effect of microRNA-184 (miR-184) on compensatory lung growth (CLG) after lobectomy in multiple primary lung cancer (MPLC) and its mechanism. METHODS: (l) Lung tissue samples (na= 16) from MPLC patients and patients with good recovery after lobectomy (CLG) were collected, and the expression of miR-184 was measured by RT-qPCR. (2) Human alveolar epithelial cells were divided into NC-mimic group, miR-184 mimic group, OE-NC group, tissue inhibitor of metalloproteinase-2 (TIMP-2) overexpression (OE-TIMP-2) group, and miR-184 mimic+OE-TIMP-2 group according to the transfection (n=3). The expression of miR-184, TIMP-2 mRNA and matrix metalloproteinase-14 (MMP-14) mRNA was measured by RT-qPCR, and the protein expression of TIMP-2 and MMP-14 was determined by Western blot. The proliferation of the cells was measured by CCK-8 and colony formation assays. (3) C57BL/6J mice were divided into pneumonectomy (PNX) group and PNX+miR-184 mimic group (n=5). The flexiVent system was used to measure the vital capacity and lung compliance of the mice. Lung volume was measured by water displacement method, and lung tissue changes were observed by HE staining. RESULTS: The expression of miR-184 was significantly higher in the patients with better recovery after lobectomy (P<0.01). Overexpression of miR-184 promoted the proliferation of human alveolar epithelial cells and the recovery of lung function in mice after PNX. In terms of mechanism, miR-184 showed targeted binding with TIMP-2, and overexpression of miR-184 promoted the expression of MMP-14 by inhibiting TIMP-2, thereby promoting the proliferation of human alveolar epithelial cells and the recovery of mouse lung function after PNX. CONCLUSION: miR-184 promotes CLG after PNX through the TIMP-2/MMP-14 axis. [ABSTRACT FROM AUTHOR]

Introduction: With the advancements in early diagnosis, more and more patients with multiple primary lung cancer (MPLC) have been identified. However, the progression of MPLC involves complex changes in cell composition and metabolic function, which remains largely controversial. Objective: Our study aims to comprehensively reveal the cellular characteristics and inter‐cellular connections of MPLC. Methods: We performed scRNA‐seq from 23 samples of six MPLC patients, combined with bulk whole‐exome sequencing. We performed trajectory analysis to investigate the transition of different cell types during the development of MPLC. Results: A total of 1 67 397 cells were sequenced derived from tumour and adjacent tissues of MPLC patients, and tumour, normal, immune and stromal cells were identified. Two states of epithelial cells were identified, which were associated with immune response and cell death, respectively. Furthermore, both CD8+ naïve and memory T cells participated in the differentiation of CD8+ T cells. The terminal states of CD8+ T cells were exhausted T cells and cytotoxic T cells, which positively regulated cell death and were implicated in the regulation of cytokine production, respectively. Two main subpopulations of B cells with distinct functions were identified, which participate in the regulation of the immune response and antigen presentation, respectively. In addition, we found a specific type of endothelial cells that were abundant in tumour samples, with an increasing trend from normal to tumour samples. Conclusions: Our study showed the comprehensive landscape of different cells of MPLC, which might reveal the key cellular mechanisms and, therefore, may provide new insights into the early diagnosis and treatment of MPLC. [ABSTRACT FROM AUTHOR]

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field. [ABSTRACT FROM AUTHOR]

Background: An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of elec- tromagnetic navigation bronchoscopy (ENB)-guided thoracoscopic sublobectomy for stage IA SMPLC. Methods: Patients with SMPLC who underwent ENB-guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted. Results: Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7 cm (range from 0.5 to 1.1 cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p < 0.01) and negatively correlated with the distance from the nodule to the pleura (p = 0.02). All nodules were completely resected. Operation time, drainage volume on the third postoperative day, and catheter time were significantly correlated with the resected lesion numbers (p = 0.009, p = 0.004, and p = 0.01, respectively). Conclusions: ENB-guided uniportal video-assisted thoracoscopic sublobectomy provides accurate preoperative localization and avoids unnecessary lung resection of patients with stage IA SMPLC. However, complete resection of multilocation nodules (more than four lesions) increases the risk of postoperative complications. A new combined treatment strategy for SMPLC should be explored. [ABSTRACT FROM AUTHOR]

Background: Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth.Methods: This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed.Results: There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08-1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94-6.30) predicted small nodule interval growth.Conclusion: We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment. [ABSTRACT FROM AUTHOR]

Background: Endobronchial microwave ablation via flexible catheter offers the potential for local therapy for inoperable peripheral lung cancer. The study aimed to evaluate the feasibility and safety of navigation bronchoscopy‐guided water‐cooled microwave ablation catheter for nonsurgical peripheral lung cancer. Methods: This was a prospective single arm pilot study. Patients with early stage or multiple primary peripheral lung cancer who were nonsurgical candidates for surgery were enrolled in the study. Bronchoscopic microwave ablation was performed via a flexible water‐cooled microwave ablation antenna under the guidance of navigation bronchoscopy. Radial probe endobronchial ultrasound combined with fluoroscopy was used to confirm the position. Treatment outcomes were evaluated based on follow‐up chest CT and positron emission tomography scans. Primary endpoints were technical success and safety. Secondary endpoints were complete ablation rate, 2‐year local control rate, and progression‐free survival. Results: Thirteen patients were enrolled in the study from April 2018 to July 2019. A total of 19 sessions of microwave ablation were performed on 14 tumors under the guidance of navigation bronchoscopy. The technical success was 100%. Treatment‐related complications occurred in two patients. The complete ablation rate was 78.6% (11/14). The 2‐year local control rate was 71.4%. Median progression‐free survival was 33 months for all patients. Conclusions: In this pilot study, bronchoscopic microwave ablation appears to be feasible with acceptable occurrence of complication in the treatment of peripheral lung cancer under the guidance of navigation bronchoscopy. [ABSTRACT FROM AUTHOR]

The incidence of lung cancer in Xuanwei area of Yunnan Province ranks first in China,which is a typical air pollution related lung cancer. In recent years,Xuanwei lung cancer incidence rate continues to grow rapidly,showing a clear phenomenon of family aggregation. The incidence of lung cancer in the Xuanwei area is earlier than that of adenocarcinoma and multiple primary lung cancer. Hypertension,diabetes and other cancers are common. The gene mutation spectrum and genetic background of family lung cancer patients are unique. Xuanwei family lung cancer is an ideal object to study the environment,genetics and occurrence of lung cancer. This paper reviews the research progress of family lung cancer in Xuanwei area of Yunnan Province. [ABSTRACT FROM AUTHOR]

Multiple primary lung cancer (MPLC) is considered relatively rare. This report presents an unusual case of multiple pulmonary nodules in a 74-year-old man who presented with three independent synchronous tumors in the right upper lobe. The tumors were diagnosed as peripheral squamous cell carcinoma (SCC), adenocarcinoma, and pulmonary mixed squamous cell and glandular papilloma (mixed papilloma). Mixed papilloma is an extremely rare, benign pulmonary tumor with a typical papillary appearance, showing squamous and glandular epithelial differentiation. The histological and immunohistochemical features of each tumor were analyzed. In addition, molecular pathological examination for epidermal growth factor receptor (EGFR) showed no mutation in two primary cancers. Mixed papilloma showed no BRAF V600E mutation or HPV infection. The present case report provides a clinicopathological understanding of an instance in which three tumors of different pathological types are present in the same lung lobe. Furthermore, it provides a literature review regarding multiple lung nodules, focusing on the clinicopathological diagnosis, clinical treatment, and prognostic assessment of these nodules. This is the first case report of mixed papilloma arising in MPLC. [ABSTRACT FROM AUTHOR]

Background: To explore the genetic and immunophenotyping heterogeneities between patients with intrapulmonary metastasis (IPM) or multiple primary lung cancer (MPLC). Methods: Whole exome sequencing (WES) and transcriptome sequencing (RNA‐seq) were performed on the tissue and blood samples of IPM and MPLC patients to comprehensively analyze the clonal evolution, molecular typing and immunophenotyping. Results: There was no significant difference in genetic mutation, tumor mutational burden (TMB) value and mutant allele tumor heterogeneity (MATH) value between IPM and MPLC patients. Notably, the loss of heterozygosity (LOH) of human leukocyte antigen (HLA) appeared in all IPM patients, while there was also no significant difference between the two groups. In addition, expression of immune checkpoint‐related genes including CTLA‐4, BTLA, TIGIT and HAVCR2 in the MPLC group was significantly higher than those in IPM group. At the same time, 86 differentially expressed genes (DEGs) were observed between IPM and MPLC patients with transcriptome sequencing, of which 56 DEGs were upregulated and 30 were downregulated in the IPM group compared with the MPLC group. The cluster analysis revealed that the 86 DEGs could be distinguished in IPM and MPLC samples. Moreover, only the infiltration levels of CD56dim natural killer cells in the IPM group was significantly higher than that in the MPLC group, and the infiltration levels of the remaining 27 immune cell subsets were similar in both groups. Conclusions: IPM and MPLC are roughly similar in genetic and immune characteristics indicating that genomics alone may not be able to effectively distinguish between IPM and MPLC, which still needs to be comprehensively evaluated with clinical manifestations, imaging, and pathological characteristics. [ABSTRACT FROM AUTHOR]

Estimated to comprise approximately 10% of lung cancer cases, multiple pulmonary lesions pose a diagnostic and therapeutic challenge in thoracic oncology. Distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) directly affects tumor staging and clinical management. In equivocal cases in which the lesions are histopathologically indistinguishable, targeted sequencing can provide key additional evidence for differential diagnosis. Herein, we describe an unusual patient who presented with seven lung lesions that consisted of primary tumors and metastatic lesions, each showing distinct clonality status based on histomolecular findings. Specifically, the 45-year-old female never-smoker underwent a surgery that removed one invasive lepidic predominant adenocarcinoma and five microinvasive adenocarcinomas. Next-generation sequencing revealed three of the lesions to carry a clonal driver mutation EGFR p.L858R, supporting an IMP diagnosis. EGFR p.L858R was not detected in two other surgical specimens, which instead harbored respective oncogenic BRAF p.G469A and an uncommon EGFR p.G779F. These results led to diagnosis of the two lesions as primary tumors of lineages different from that of the metastases. The patient had achieved a recurrence-free survival of 21 months as of the latest follow-up. In this rare case that presented with evidence of both MPLC and IPM, targeted sequencing proved valuable in facilitating the diagnostic workup. [ABSTRACT FROM AUTHOR]

Background: In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP. Case presentation: Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months. Conclusion: Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: The best surgical approach for second primary lung cancer remains a subject of debate. The purpose of this study was to review the postoperative complications after second surgery for second primary lung cancer and to investigate the outcomes based on these complications. Methods: The clinical data of 105 consecutive patients who underwent pulmonary resection for multiple primary lung cancers between January, 1996 and December, 2017, were reviewed according to the Martini–Melamed criteria. Results: After the second surgery, low body mass index (BMI) (< 18.5 kg/m2) (P = 0.004) and high Charlson comorbidity index (CCI) (P = 0.002) were independent predictors of postoperative complications. Survival analysis revealed the 5-year overall survival rates of 74.5% and 61.4% for patients without postoperative complications and those with postoperative complications (P = 0.044), respectively, but the 5-year cancer-specific survival rates of 82.5% and 80.0% (P = 0.926), respectively. During this period, there were significantly more respiratory-related deaths of patients with complications than of those without complications (P = 0.011). Conclusion: Surgical intervention is feasible and potentially effective for second primary lung cancer but may not achieve positive perioperative and long-term outcomes for patients with a low BMI or a high CCI. Treatment options should be considered carefully for these patients. [ABSTRACT FROM AUTHOR]

Multiple primary lung cancer (MPLC) is defined as two or more primary lung cancers occurring in the same patient and can be classified as synchronous multiple primary lung cancer (sMPLC) and metachronous multiple primary lung cancer (mMPLC). Due to various clinicopathological characteristics and genetic features, MPLC is increasingly encountered in clinical practice. The distinction between MPLC and intrapulmonary metastasis (IM) is of great importance to clinical treatment and prognosis. However, there are currently no golden diagnostic criteria for MPLC due to tumor heterogeneity. Here, we report the case of a patient with four lung cancers (tumor 1, named T1, in the right middle lobe seven years earlier; tumor 2, named T2, in the left lower lobe; tumor 3 and tumor 4, named T3 and T4, in the left upper lobe) and two tumors (T1 and T2) which shared the mutation in epidermal growth factor receptor (EGFR) L858R/T790M based on targeted multigene sequencing, which indicate that these two tumors might have originated from a common ancestor. However, based on previously published guidelines, these three tumors (T2T4) were diagnosed as mMPLC. [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate the genetic features of multiple lung cancer (MLC) and identify effective molecular markers for diagnosis using next generation sequencing (NGS). The present data may also inform patient treatment and prognosis. A total of 35 lesions were obtained from 17 patients with MLC. Based on lesion histology and NGS, 13 cases of multiple primary lung cancer (MPLC) were identified and 4 cases were classified as intrapulmonary metastasis (IPM). All 4 patients with IPM exhibited an epidermal growth factor receptor (EGFR) mutation and synchronous mutation of at least one tumor suppressor gene. The frequency and percentage of EGFR mutations, accompanied with tumor suppressor genes, were significantly higher in patients with IPM compared with MPLC. Furthermore, a high EGFR-heterogeneity score and male sex were risk factors of IPM occurrence. There were significant differences in mean EGFR mutation abundance alone, mutations of tumor suppressor genes and mutations of EGFR combined with tumor suppressor genes between patients with adenocarcinoma (ADC) and adenocarcinoma in situ (AIS). In conclusion, histological characteristics combined with genetic alterations may be an effective method for the diagnosis of MPLC and IPM, and NGS may serve as a useful diagnostic tool. MLC exhibited unique molecular characteristics, including higher rates of EGFR mutations, EGFR driver mutations accompanied with tumor suppressor gene mutations and the absence of anaplastic lymphoma kinase mutations, which may help distinguish between patients with MPLC or IPM. The present study hypothesized that the mean frequency of EGFR mutations, mutations of tumor suppressor genes and mutations of both EGFR and tumor suppressor genes may serve an important role in the development of AIS to ADC. The results of the present study highlight the potential underlying mechanisms of lung ADC development, which may assist with future elucidation of effective treatments to prevent the progression of lung cancer. [ABSTRACT FROM AUTHOR]

Background: Routine clinical and pathological examinations usually cannot fully conclusively determine the relationship between different lesions of lung cancer. Detailed genetic analysis of tumor samples may supply important additional information and identify second primary lung cancers.Case Presentation: In the present study, we report a case of synchronous multiple primary lung cancer (MPLC) composed of two distinct pathological subtypes with epidermal growth factor receptor (EGFR) gene mutations L858R of the acinar adenocarcinoma subtype and EML4-ALK rearrangement of the squamous cell carcinoma.Conclusion: The present report highlights the clinical importance of molecular cancer biomarkers detection to guide management decisions in MPLC cases. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) based on deep learning, convolutional neural networks and big data has been increasingly effective in the diagnosis and treatment of multiple primary pulmonary nodules. In comparison to previous imaging systems, AI measures more objective parameters such as three‐dimensional (3D) volume, probability of malignant nodules, and possible pathological patterns, making the access to the properties of nodules more objective. In our retrospective study, a total of 53 patients with synchronous and metachronous multiple pulmonary nodules were enrolled of which 33 patients were confirmed by pathological tests to have primary binodules, and nine to have primary trinodules. A total of 15 patients had only one focus removed. The statistical results showed that the agreement in the AI diagnosis and postoperative pathological tests was 88.8% in identifying benign or malignant lesions. In addition, the probability of malignancy of benign lesions, preinvasive lesions (AAH, AIS) and invasive lesions (MIA, IA) was totally different (49.40±38.41% vs 80.22±13.55% vs 88.17±17.31%). The purpose of our study was to provide references for the future application of AI in the diagnosis and follow‐up of multiple pulmonary nodules. AI may represent a relevant diagnostic aid that shows more accurate and objective results in the diagnosis of multiple pulmonary nodules, reducing the time required for interpretation of results by directly displaying visual information to doctors and patients and together with the clinical conditions of MPLC patients, offering plans for follow‐up and treatment that may be more beneficial and reasonable for patients. Despite the great application potential in pneumosurgery, further research is needed to verify the accuracy and range of the application of AI. [ABSTRACT FROM AUTHOR]

A preoperative chest computed tomography examination of the right breast in a 52‐year‐old woman with breast cancer revealed multiple nodules in both lungs. The nodule in the apical segment of the upper lobe of the right lung was larger, at a diameter of approximately 2.1 cm. The patient underwent resection of the right breast, followed by thoracoscopic wedge resection of four pulmonary nodules. Hematoxylin and eosin staining and immunohistochemistry showed that the nodules in the apical and anterior segments of the upper lobe and the paravertebral nodule in the lower lobe of the right lung were primary adenocarcinoma, and the subpleural nodule in the lower lobe of the right lung was infiltrated with inflammatory cells. Exon sequencing was conducted in the resected tissue samples and blood specimens. According to the characteristics of the somatic mutations, the nodule in the apical segment of the upper lobe of the right lung was primary lung adenocarcinoma, the nodule in the anterior segment of the upper lobe and the paravertebral nodule in the lower lobe of the right lung were intrapulmonary metastatic cancer, and the subpleural nodule in the lower lobe of the right lung indicated early stage tumor progression. This case provides new evidence that conducting gene detection in multiple tissue samples from patients who have undergone resection may assist to determine the relationship among multiple nodules in the lung to exclude lung metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Multiple primary lung cancer may present in synchronous or metachronous form. Synchronous multiple primary lung cancer is defined as multiple lung lesions that develop at the same time, whereas metachronous multiple primary lung cancer describes multiple lung lesions that develop at different times, typically following treatment of the primary lung cancer. Patients with previously treated lung cancer are at risk for developing metachronous lung cancer, but with the success of computed tomography and positron emission tomography, the ability to detect both synchronous and metachronous lung cancer has increased.Case Presentation: We present a case of a 63-year-old Hispanic man who came to our hospital for evaluation of chest pain, dry cough, and weight loss. He had recently been diagnosed with adenocarcinoma in the right upper lobe, with a poorly differentiated carcinoma favoring squamous cell cancer based on bronchoalveolar lavage of the right lower lobe for which treatment was started. Later, bronchoscopy incidentally revealed the patient to have an endobronchial lesion that turned out to be mixed small and large cell neuroendocrine lung cancer. Our patient had triple synchronous primary lung cancers that histologically were variant primary cancers.Conclusions: Triple synchronous primary lung cancer management continues to be a challenge. Our patient's case suggests that multiple primary lung cancers may still occur at a greater rate than can be detected by high-resolution computed tomography. [ABSTRACT FROM AUTHOR]

Background Distinguishing synchronous multiple primary lung cancers (SMPLCs) from intrapulmonary metastases is important. The objective of this study was to determine long-term survival in patients who underwent surgical resection for synchronous multiple lung cancers and identify additional criteria that may be useful to distinguish patients with SMPLCs from those with more advanced disease. Methods The medical records of patients with lung cancer who underwent planned resection for synchronous multiple lung cancers from 2007 to 2012 at our institutions were reviewed retrospectively. A comprehensive histologic assessment was used to determine whether the tumors were metastases or separate synchronous primary tumors. Results A total of 51 patients with synchronous multiple lung cancers underwent surgical resection. Twenty-nine patients had ipsilateral synchronous multiple lung cancers, and 22 had bilateral synchronous multiple lung cancers. No perioperative death occurred. The survival analysis of all 51 patients with synchronous multiple lung cancers who underwent planned resection of all lesions showed 3- and 5-year overall survival rates of 86% and 67%, respectively, The median overall survival was not reached. The comprehensive histologic assessment identified six patients with intrapulmonary metastasis and 45 patients with SMPLCs. Intrapulmonary metastases were associated with decreased survival. Among patients with SMPLCs, the epidermal growth factor receptor mutation distribution shown high concordant frequency rate of 35% (5/14). Conclusions Survival after surgical resection of synchronous multiple lung cancers in different lobes was promising. A comprehensive histologic assessment was useful for differentiating SMPLCs from intrapulmonary metastases. [ABSTRACT FROM AUTHOR]

Background: The incidence of adenocarcinomas as multiple primary lung cancers (MPLCs) is increasing. How to determine the treatment strategies of MPLCs, especially second primary lung adenocarcinomas (SPLACs), and the prognostic factors associated with it are unclear. Methods: The clinical records of patients undergoing surgery for second adenocarcinomas based on Martini-Melamed criteria between 2001 and 2014 were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards model. Results: A total of 115 patients with SPLACs were identified based on Martini-Melamed criteria. With respect to the second resections, three subgroups with low- (adenocarcinoma in situ, n=6; minimally invasive adenocarcinoma, n=19), intermediate- (lepidic, n=9; acinar, n=40; papillary, n=23), and high-grades (solid, n=9; micropapillary, n=2; invasive mucinous, n=7) were assigned. The 5-year overall survival (OS) rates from the time of the first and the second resections were 86.5% and 69.5%, respectively. Cox multivariate analysis identified computed tomography (CT) morphology of SPLACs (ground glass opacity predominant versus solid predominant; hazard ratio [HR]=0.42; P=0.036), histologic classification (same/similar vs different; HR=0.06; P,0.001), pathologic stage of the primary (stage I vs II; HR=0.20; P=0.015) and second tumors (stage I vs IIIa; HR=0.21; P=0.002), and histologic grade of SPLACs (low- vs high-grade, HR=0.05, P=0.016; intermediate- vs high-grade, HR=0.37, P=0.027) as significantly favorable prognostic factors for OS. Conclusion: In addition to pathologic stage of the initial tumors and histologic classification, pathologic stage and CT morphology of SPLACs were identified as predictors of survival. The histologic grade of SPLACs based on the new adenocarcinoma classification could provide additional prognostic information. [ABSTRACT FROM AUTHOR]

Background With the development of imaging technology, an increasing number of multiple primary lung cancers (MPLC) are diagnosed in recent years. However, there is still ambiguity in the stage classification rules for patients with MPLC. Our purpose was to access the prognosis of synchronous and metachronous MPLC. Methods A systematic literature search was performed on four databases (EBSCO, Pubmed, OVID and Springer) to obtain relevant articles. We used published hazard ratios (HRs) of overall survival (OS) if available or estimates from the published survival data. Results There were 1796 patients with MPLC in 22 relevant studies, who were eligible for analysis. We found that the OS of patients with synchronous MPLC was inferior to the one of metachronous MPLC patients when starting from the diagnosis of the first metachronous tumor (HR 3.36, 95% CI 2.39–4.74; p < 0.001). However, there was no difference when starting from the diagnosis of the second metachronous tumor (HR 1.19, 95% CI 0.86–1.66; p = 0.29). From further analysis we found the OS of patients with MPLC was superior to that of patients with intrapulmonary metastasis (HR 2.66, 95% CI 1.30–5.44; p = 0.007). Besides, we found no difference in OS between synchronous (HR 1.39, 95% CI 0.98–1.96; p = 0.06) and metachronous (HR 1.05, 95% CI 0.75–1.47; p = 0.77) patients, in spite of the histology. In terms of unilateral and bilateral MPLC patients, the OS had no difference either (HR 1.30, 95% CI 1.00–1.69; p = 0.05). Conclusion We found that MPLC had better OS than the lung cancer patients with intrapulmonary metastasis. And despite the tumor-free interval, the OS for metachronous MPLC was as good as that for synchronous MPLC. Furthermore, there was no difference of OS in different subgroups, including histology and position. [ABSTRACT FROM AUTHOR]

The incidence of synchronous multiple primary lung cancer (MPLC) is increasing. However, present diagnostic methods are unable to satisfy the individualized treatment requirements of patients with MPLC. The present study aimed to establish a quantitative mathematical model and analyze its diagnostic value for distinguishing between MPLC and cases of the histologically similar disease, intrapulmonary metastasis (IPM). The sum value of the differential expression ratios of four proteins, namely p53, p16, p27 and c-erbB2, was evaluated by immunohistochemically-staining specimens of primary cancers, second separate cancers, metastatic lymph nodes and metastatic cancers. The sum value of the differential expression ratio of the four proteins from the primary tumor and the lymph-node metastasis or metastatic cancer was <90 in the 11 patients with a single metastatic cancer and in the 30 patients with lymph-node metastasis, but was >90 in the 14 patients with different histological types of MPLC. Therefore, a quantitative differentially-expressed gene mathematical model was established as follows: Sum of the differential expression ratios = p16T1 - T + p27T1 - T2 + C-erbB2T1 - T2 + p53T1 - T2, where T1 is the primary cancer and T2 is the lymph node metastasis, metastatic cancer or the second separate cancer. The quantitative differentially-expressed gene mathematical model is considered to be a useful tool for distinguishing between MPLC and IPM. [ABSTRACT FROM AUTHOR]

BACKGROUND Surgical resection has been the standard treatment for early stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. For this report, the authors explored the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. METHODS Patients with MPLC who received SABR (50 grays [Gy] in 4 fractions or 70 Gy in 10 fractions) for the second tumor were reviewed. Four-dimensional, computed tomography-based, planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. RESULTS For the 101 patients who received SABR, at a median follow-up of 36 months and with a median overall survival (OS) of 46 months, the 2-year and 4-year in-field local control rates were 97.4% and 95.7%, respectively. The 2-year and 4-year OS rates were 73.2% and 47.5%, respectively; and the progression-free survival (PFS) rates were 67% and 58%, respectively. Patients who had metachronous tumors had better OS and PFS than patients who had synchronous tumors (2-year OS: 80.6% metachronous vs 61.5% synchronous; 4-year OS: 52.7% vs 39.7%, respectively; P = .047; 2-year PFS: 84.7% vs 49.4%, respectively; 4-year PFS: 75.6% vs 30.4%, respectively; P = .0001). For patients who either underwent surgery or received SABR for an index tumor, the incidence of grade ≥3 radiation pneumonitis was 3% (2 of 71 patients); however, this increased to 17% (5 of 30 patients) for those who received conventional radiotherapy for an index tumor. Other grade ≥3 toxicities included grade 3 chest wall pain (3 of 101 patients; 3%) and grade 3 skin toxicity (1 of 101 patients; 1%). CONCLUSIONS SABR achieves promising long-term tumor control and survival and may be a potential curative treatment for early stage MPLC. Cancer 2013;119:3402-10. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives To review the literature and report our experience with the use of stereotactic body radiation therapy (SBRT) to treat multiple primary lung cancers (MPLCs). Methods A retrospective review of 18 patients with 36 separate MPLC lesions (6 synchronous pairs and 12 metachronous pairs) was performed. Of these 18 patients, 16 were not surgical candidates and 2 declined to have surgery. Of the 36 lesions treated, 27 received SBRT, 6 had received prior fractionated RT, and 3 had prior surgical resection. Radiotherapy doses for SBRT ranged from 48 to 56 Gy (Median = 50 Gy) in 4 to 13 fractions (Median = 5 fractions) and treatment plans used 4D-CT simulation scans in all patients. Results The median follow-up was 20 months after initial SBRT. We observed local control in 22 of 27 (81.5%) of the lesions treated with SBRT. The actuarial overall survival at 2 years from completion of initial SBRT course was 62%. Metastatic disease occurred in 3 of the 6 deceased patients. Clinically evident pneumonitis was observed in 3 of the 18 pts (17%), which resolved completely with steroid therapy. Conclusions SBRT appears to be a safe and effective treatment for MPLC both solely or after prior fractionated RT or surgical resection. SBRT for MPLC is a reasonable treatment option for patients who are not optimal candidates for surgery or who decline surgery. [ABSTRACT FROM AUTHOR]

Introduction: To review outcomes of medically inoperable patients treated with stereotactic body radiation therapy (SBRT) for multiple primary lung cancer (MPLC). Methods: We retrospectively reviewed the charts of 10 patients (21 lesions) treated with SBRT for synchronous (seven), metachronous (one) or synchronous/metachronous lung cancers. All patients were male, medically inoperable and had a median age of 66 years. Eight patients had bilateral disease and two had unilateral disease. All patients had a histological diagnosis in at least one of the two lesions and four patients (44.4%) had both lesions biopsied. There were 18 T1 lesions and three T2 lesions. SBRT was in three fractions of 20 Gy or five fractions of 11-12 Gy to each lesion. Results: Mean and median follow up were 18.8 and 15.5 months, respectively. At analysis, six patients (60.0%) are alive, and five of these living patients (83.3%) have no evidence of disease recurrence or progression. Four patients (44.4%) developed distant metastatic disease. Twenty lesions (95.2%) achieved in-field local control. No patients experienced acute pulmonary complications and only two patients (22.2%) experienced late grade I lung toxicity as per the Radiation Therapy Oncology Group toxicity criteria. Conclusion: SBRT for MPLC in medically inoperable patients is a safe, feasible and effective treatment approach. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Patients with multiple primary lung cancers (MPLC) present a therapeutic dilemma, particularly when they are at high risk for surgical resection. We evaluated the role of stereotactic body radiation therapy (SBRT) in the treatment of MPLC. Materials and methods: A prospective thoracic SBRT registry was explored for patients with either synchronous or metachronous MPLC treated with SBRT for one or both of their tumors. Sixty-three patients were identified and clinical data were analyzed. Results: Fifteen patients had synchronous lesions and 48 patients had metachronous lesions. Seventy-six lesions were treated with SBRT. Median follow-up was 24months for living patients. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort was 15.5 and 20months, respectively. Patients with metachronous MPLC had a significantly higher 2year PFS (53.3% vs. 0%, p =0.0466) compared to patients with synchronous MPLC. Likewise, 2year OS was also superior for patients with metachronous versus synchronous MPLC (68.1% vs. 27.5%, p =0.0014). Six tumors (7.9%) recurred within the radiation field. There were no grade ⩾3 toxicities. Conclusions: SBRT for patients with MPLC appears to be a safe and effective local treatment alternative to surgery, particularly for medically inoperable patients. Patients with metachronous MPLC have encouraging survival rates, and thus local therapy appears justified. However, patients with synchronous MPLC have poor OS and PFS despite having excellent local control, and thus the utility of local therapy in this population requires further study. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study is to clarify the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of epidermal growth factor receptor (EGFR) and K-ras. Methods: We analyzed 82 multifocal lung adenocarcinomas from 36 patients who underwent surgical resection. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and analyzed for EGFR and K-ras mutations. We determined the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. The actuarial survival time was estimated and the prognostic factors were evaluated for 31 patients with synchronous multifocal lung adenocarcinomas. Results: EGFR and K-ras mutations were detected in 36 (44%) and 19 (23%) of the 82 tumors, respectively. EGFR mutations had occurred randomly in 20 (91%) of the 22 patients with at least one EGFR mutated tumor. K-ras mutations had occurred randomly in 14 (93%) of the 15 patients with at least one K-ras mutated tumor. Combining the results for the EGFR and K-ras mutation patterns, the clonality status of multifocal lung adenocarcinomas could be determined in 30 (83%) of the 36 patients. No statistically significant difference in the actuarial survival of the patient subgroups stratified according to the clonality status, which was based on the presence of EGFR and K-ras mutations, was observed. Conclusions: Both EGFR and K-ras mutations frequently occur randomly in multifocal lung adenocarcinomas. Combined mutation pattern analyses of EGFR and K-ras may be useful for making decisions regarding treatment strategies for patients with multifocal lung adenocarcinomas. [Copyright &y& Elsevier]

Simple Summary: With the wide application of computed tomography and lung cancer screening, the incidence of multiple primary lung cancer, that is, the occurrence of two or more primary malignant lung tumors in a patient, has been increasingly reported. The optimal strategy for the diagnosis and treatment of multiple primary lung cancers is controversial. Surgery remains the main treatment modality, whereas other treatment methods, including radiotherapy and local ablation, are also feasible, particularly for inoperable patients. Next-generation sequencing and novel therapies, such as targeted agents and immune-checkpoint inhibitors, have provided new insights into this topic. With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Due to recent advances in imaging, the incidence of patients presenting with bilateral lung lesions is increasing. A single contralateral lung lesion can be an isolated metastasis or a synchronous second primary lung cancer. For the revision of the TNM in 2009, the International Association for the Study of Lung Cancer Staging Committee proposes that patients with contralateral lung nodules remain classified as M1 disease. In this retrospective study, the survival after resection of synchronous bilateral lung cancer is evaluated. Methods: From our database of bronchial carcinoma, all patients with bilateral synchronous lung lesions between 1990 and 2007 were retrieved. We analysed 57 patients in which, after functional assessment and thorough staging, the decision was taken to treat the disease with bilateral resection. All these files were retrospectively reviewed. Twenty-one patients were excluded from this analysis because only one side was resected (n =15) or one of the lesions was non-neoplastic on final pathology (n =6). Results: Thirty-six patients underwent bilateral resection for synchronous multiple primary lung cancer. All resections were performed as sequential procedures. In 23 patients, one side was anatomically resected (2 pneumonectomies) and the contralateral side was resected by limited resection. In 10 patients a bilateral lobectomy was performed, and 3 patients had bilateral limited resections. Postoperative mortality was 2.8%. Eighteen patients had a tumour with a different histological pattern, confirmed by comparing both specimens by an experienced senior pathologist. The median survival after resection of synchronous bilateral lung cancer in our series was 25.4 months with a 5-year survival rate of 38%. There was no significant difference in survival between patients with different versus same histology. This survival is much higher compared to the survival of assumed stage IV disease. Conclusions: Our study shows that selected patients with bilateral lung cancer may benefit from an aggressive approach, with acceptable morbidity and mortality, and rewarding long-term survival. Patients with a single contralateral lung lesion should not be treated as disseminated disease (stage IV). After extensive searching for metastatic spread, bilateral surgical resection should be considered in fit patients. [Copyright &y& Elsevier]

Abstract: Objective: T4-disease for non-small cell lung cancer (NSCLC) includes different conditions: mediastinal invasion, neoplastic pleural cytology, and multifocal disease in the same lobe; regarding the last category, no strict criteria allow to differentiate satellite nodules from synchronous multiple primary tumours. Methods: Retrospective study of 56 patients who underwent a complete resection from 1985 to 2006 of a NSCLC graded pT4N0 due to multifocal disease. A small nodule (<1cm) closed to the primary tumour, in a same pulmonary segment with an identical histology was considered as a satellite nodule (pT4sn). Multiple tumours, sized more than 1cm, with an identical histology, located in the same lobe but in different segment were considered as synchronous cancers (pT4sc). Results: There were 44 males and 12 females: 35 patients were graded T4sn and 21 patients T4sc. The median age was 62.5 years. The two groups were similar for sex, age, tobacco consumption, ASA score, NYHA, Charlson''s index, spirometric parameters, cardiovascular comorbidity and history of previous extra-thoracic malignancies. All had a complete anatomic resection with mediastinal lymphadenectomy. Thirty-day mortality rate was 3.6%. Overall 5-year and 10-year survival rates were 48.2% and 29.9%, respectively. There was a non-significant trend for a worse survival in T4sn group patients when compared to that of T4sc group patients: 42.9% vs 52.3% at 5 years, and 25% vs 34.9% at 10 years (p =0.62). Conclusions: Multifocal T4 stage IIIB disease is a heterogeneous category where overall prognosis is far better than those of other T4 subgroups. Survival rates associated with pT4sn and pT4sc look roughly similar because of the small size of the subgroups usually submitted to comparison in most series. In the present experience, respective survival figures diverge, suggesting different biological behaviours. [Copyright &y& Elsevier]

The article deals on patients with particular forms of non-small cell lung cancer (NSCLC) that require special considerations. This includes patients with Pancoast tumors, satellite nodules in the same lobe, metachronous multiple primary lung cancers, and chest wall involvement. In patients with a Pancoast tumor, a multimodality approach seems to be optimal, involving chemoradiotherapy and surgical resection. In general, patients with early stage NSCLC are treated primarily with surgery.

A case of triple primary lung cancers--squamous cell carcinoma, adenocarcinoma and large-cell carcinoma--is presented. Surgical treatment comprised, respectively, left pneumonectomy, partial resection of the right upper lobe and completion right upper lobectomy. The postoperative courses were uneventful and the patient remains well, with no sign of recurrence, 20 months after the third operation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Is lobectomy really more effective than sublobar resection in the surgical treatment of second primary lung cancer? by A. Zuin and colleagues in a 2013 issue.

A response from the authors of the article "Is lobectomy really more effective than sublobar resection in the surgical treatment of second primary lung cancer?" in a 2013 issue is presented.

OBJECTIVES Sublobar resection for early-stage lung cancer is still a controversial issue. We sought to compare sublobar resection (segmentectomy or wedge resection) with lobectomy in the treatment of patients with a second primary lung cancer. METHODS From January 1995 to December 2010, 121 patients with second primary lung cancer, classified by the criteria proposed by Martini and Melamed, were treated at our Institution. We had 23 patients with a synchronous tumour and 98 with metachronous. As second treatment, we performed 61 lobectomies (17 of these were completion pneumonectomies), 38 atypical resections and 22 segmentectomies. Histology was adenocarcinoma in 49, squamous in 38, bronchoalveolar carcinomas in 14, adenosquamous in 8, large cells in 2, anaplastic in 5 and other histologies in 5. RESULTS Overall 5-year survival from second surgery was 42%; overall operative mortality was 2.5% (3 patients), while morbidity was 19% (22 patients). Morbidity was comparable between the lobectomy group, sublobar resection and completion pneumonectomies (12.8, 27.7 and 30.8%, respectively, P = 0.21). Regarding the type of surgery, the lobectomy group showed a better 5-year survival than sublobar resection (57.5 and 36%, respectively, P = 0.016). Compared with lobectomies, completion pneumonectomies showed a significantly less-favourable survival (57.5 and 20%, respectively, P = 0.001). CONCLUSIONS From our experience, lobectomy should still be considered as the treatment of choice in the management of second primary lung cancer, but sublobar resection remains a valid option in high-risk patients with limited pulmonary function. Completion pneumonectomy was a negative prognostic factor in long-term survival. [ABSTRACT FROM AUTHOR]