Synchronous Multiple Primary Lung Cancer Research Articles

Double primary non-small cell lung cancer with synchronous small cell lung cancer N2 nodes: a case report.

Synchronous multiple primary lung cancer (SMPLC) is rare and very hard to distinguish from metastatic disease. Recent studies indicate the presence of this entity in the lung, with no mention to the involvement of the mediastinum. An extremely rare case of a 68-year-old male with double primary non-small cell lung cancer (NSCLC) in the left upper lobe and N2 positive nodes for small cell lung cancer (SCLC) is presented. Modern diagnostic criteria as well as aggressive curative strategies are encouraged, in order to achieve better survival rates for such patients.

Synchronous, Multiple Primary Lung Cancers: A Report of Three Cases

Multiple primary lung cancers (MPLC) are named synchronous if determined simultaneously with the index tumor, and metachronous if the second tumor is diagnosed with an accepted time after the first tumor. It is important for both the rate of survival and treatment alternatives to differentiate synchronous MPLCs from the metastases of the primary lung tumors, and also from the multiple pulmonary metastases of the extra pulmonary tumors. In this study, clinical characteristics, diagnosis and treatment processes of three synchronous MPLC cases diagnosed in our department were assessed.

A novel differential diagnostic model for multiple primary lung cancer: Differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis.

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.

Prognosis of synchronous and metachronous multiple primary lung cancers: systematic review and meta-analysis.

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. 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. 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). 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.

Synchronous Triple Primary Lung Cancer: A Rare Case with Radiologic-Pathologic Correlation

According to the diagnostic criteria of Martini and Melamed (1), synchronous multiple primary lung cancers are physically distinct, separate, and originate from different carcinomas insitu or show different histologic types without involvement of common lymphatics or extrapulmonary metastases. Multiple synchronous primary lung cancer is rare with a low and variable incidence rate of 1–16% (2). Furthermore, the reported incidence of synchronous triple lung cancers is approximately 0.02% (3). We reported the case of a patient with synchronous triple and histologically different primary lung cancers. Furthermore, we determined the correlation of the radiologic features with pathology.

EComment. Does the histological features of synchronous multiple primary lung cancers influence the surgical planning in patients undergoing curative surgery?

eComment. Does the histological features of synchronous multiple primary lung cancers influence the surgical planning in patients undergoing curative surgery?

Does the extent of resection affect survival in patients with synchronous multiple primary lung cancers undergoing curative surgery?

A best evidence topic was written according to a structured protocol. The question addressed was whether the extent of pulmonary resection affects survival in patients with synchronous multiple primary lung cancers undergoing curative surgery. A total of 724 papers were identified using the reported searches, of which 14 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. All studies were retrospective. Eight of 14 studies found no difference in terms of median, overall or progression-free survival when a sublobar resection in the form of a wedge resection or segmentectomy was performed for at least one of the synchronous lesions. Two studies demonstrated a negative impact on survival when lobectomy or bilobectomy was not performed for each lesion. Five papers reviewed the role of pneumonectomy in this category of patients and four of them demonstrated that such an extended resection has a significantly negative impact on survival, while, in one study, although pneumonectomy when compared with sublobar resections and photodynamic therapy had decreased long-term survival, this difference did not reach statistical significance. The use of lung-sparing resections (wedge resection or segmentectomy) of at least one lesion (if technically feasible) is advised for patients with synchronous multiple primary lung cancers. Most studies do not demonstrate any differences in immediate or long-term survival with two anatomical resections. Embarking for anatomical lung resections in the form of lobectomies should be done only in those cases where there are no concerns about postoperative pulmonary reserve. The performance of a pneumonectomy should be avoided, especially for bilateral synchronous lesions, unless it is absolutely necessary.

Single-staged uniportal VATS major pulmonary resection for bilateral synchronous multiple primary lung cancers.

It is difficult to make diagnosis and treatment decision for patient with bilateral multiple pulmonary foci. Surgical resection can offer sufficient specimens for diagnostic differentiation and the greatest chance for long-term survival in patient with presumptive synchronous multiple primary lung cancers (SMPLC). Since uniportal video-assisted thoracoscopic surgery (VATS) is a less invasive technique and has been attempted in lung cancer surgery, we transferred it into the management of SMPLC. In this paper, we report two cases of bilateral SMPLC managed through single-staged uniportal VATS with major pulmonary resection. This successful attempt provides an optimized idea to accomplish simplified mini-invasive diagnosis and synchronous treatment using the less invasive uniportal VATS technique for the management of SMPLC, especially for those with multiple bilateral lesions.

Synchronous double primary lung cancer: a report of three cases.

The incidence of synchronous multiple primary lung cancers is on the rise due to improvements in computed tomography (CT) scanning and increasing use of positron emission tomography scanning and other diagnostic modalities. We report three cases of synchronous double primary lung cancer (DPLC) diagnosed based on CT findings, results of bronchoscopy and histological study. All patients had a long-term history of heavy smoking. Squamous cell carcinoma and small cell carcinoma were the most common histological types in these cases. DPLC frequently involves the upper lobes of left or right lung. Future molecular biological studies on DPLC should be warranted to shed light on the mechanisms underlying the pathogenesis of DPLC and the role of targeted therapy in this condition.

Invited Commentary

The article by Yu and colleagues [1Yu Y.C. Hsu P.K. Yeh Y.C. et al.Surgical results of synchronous multiple primary lung cancers: similar to the stage-matched solitary primary lung cancers?.Ann Thorac Surg. 2013; 96: 1966-1974Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar] concerning synchronous primary lung cancers highlights several points that are important for the diagnosis, staging, and treatment of multiple lung cancers. To begin, there is a lack of clarity concerning synchronous tumors as to whether they represent lung cancers identified on presentation, or one cancer with subsequent further interval growth of another malignant nodule within a 2-year period [2Martini N. Melamed M. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 7T: 606-612Google Scholar]. This is important for CT lung cancer screening programs in which 20% of patients are identified and followed with nodules [3Bach P.B. Mirkin J.N. Oliver T.K. et al.Benefits and harms of CT screening for lung cancer. A systematic review.JAMA. 2013; 307: 2418-2429Crossref Scopus (957) Google Scholar]. Some of these nodules, if malignant, may also be multicentric on presentation or develop at a later date. It is possible that synchronous tumors from these groups possess different biologic behaviors [4Greenberg A.K. Lu F. Goldberg J.D. et al.CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort.PLOS one. 2012; 7: e39403Crossref PubMed Scopus (32) Google Scholar]. This study involves a significant number of nonsmoking participants; it is important to note that this might represent a geographic trend that could be associated with specific somatic mutations. These factors might reflect evidence for a gender survival bias, reported elsewhere in a published pooled analysis of prognostic survival factors for synchronous lung cancers [5Tanetyanon T. Finley D.J. Fabian T. et al.Prognostic factors for survival after complete resections of synchronous lung cancers in multiple lobes: pooled analysis based on individual patient data.Ann Oncol. 2013; 24: 89-94Google Scholar]. Age, size, and location are also identified as risk factors for survival. It is not unreasonable to expect age and location (extent of surgical resection) to effect survival; it is also possible that tumor size is associated with lymphovascular and nodal metastases, negatively effecting survival. The authors note that the specific tumor histologic pattern will effect overall survival as has been shown by further subtyping ground-glass nodules [6Shrager J. Approach to the patient with multiple lung nodules.Thorac Surg Clin. 2013; 23: 257-266Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. Furthermore, routine histology performed on multiple lung nodules, without analysis of clonality by genomic or mutational testing, might not adequately differentiate metastatic from multicentric tumors [7Dacic S. Dilemmas in lung cancer staging.Arch Pathol Lab Med. 2012; 136: 1194-1197Crossref PubMed Scopus (8) Google Scholar]. This differentiation could be of critical importance in separating multiple early stage IA cancers from metastatic stage IV disease, thus effecting treatment decisions. The results of this study imply that synchronous lung tumors, in the absence of multiple disease sites and without metastatic nodal involvement, regardless of clonality, have equivalent survival with early stage lung cancer. The authors suggest that more data are needed to support or refute adjuvant treatment following the removal of synchronous lung tumors. The role of stereotactic body radiation therapy as a treatment modality in combination with surgery remains to be established. In summary, this article reflects the need for a sophisticated multidisciplinary approach to lung cancer. This approach would encompass advanced diagnostic testing and collaboration between oncologists and surgeons for best personalized care. Surgical Results of Synchronous Multiple Primary Lung Cancers: Similar to the Stage-Matched Solitary Primary Lung Cancers?The Annals of Thoracic SurgeryVol. 96Issue 6PreviewTreatment for synchronous multiple primary lung cancers (SMPLC) remains controversial. Some surgeons treat SMPLC like advanced lung cancer, whereas other surgeons treat SMPLC as separate primary lung cancers. In this study, survival of SMPLC patients and matched-stage solitary primary lung cancer (SPLC) patients after surgical treatment were compared. Full-Text PDF

Surgical Results of Synchronous Multiple Primary Lung Cancers: Similar to the Stage-Matched Solitary Primary Lung Cancers?

Treatment for synchronous multiple primary lung cancers (SMPLC) remains controversial. Some surgeons treat SMPLC like advanced lung cancer, whereas other surgeons treat SMPLC as separate primary lung cancers. In this study, survival of SMPLC patients and matched-stage solitary primary lung cancer (SPLC) patients after surgical treatment were compared. Prospective medical records between 2001 and 2011 were retrospectively reviewed. A total of 1,995 patients underwent pulmonary resection for lung cancer in a tertiary referral center. Only 97 patients met the modified criteria of Martini and Melamed for SMPLC. The median follow-up time was 38.3 months. The 3-year and 5-year overall survival rates were 83.1% and 69.6%, respectively. In the univariate analysis, males, smokers, and tumor size greater than 3 cm demonstrated significantly worse survival. After multivariate analysis, only tumor size (p= 0.018; hazard ratio 3.199) was identified as an independent predictor of survival. In addition, there was no significant difference in overall survival between the matched-stage SMPLC and SPLC without mediastinal lymph node involvement. Subgroup analysis in the multiple synchronous adenocarcinoma (n= 78) group demonstrated no significant difference between similar and different comprehensive histologic subtyping with respect to overall survival (61.3% versus 68.8%, p= 0.474). The surgical results for SMPLC were compatible and acceptable with those for SPLC even with similar histologic subtyping, instead of T4 or M1 stages in the current TNM classification system. Preoperatively, tumor size was the only independent prognostic factor for SMPLC with surgical intervention.

Discordant tumor response in the treatment of ALK-rearranged non-small cell lung cancer leads to the diagnosis of synchronous multiple primary lung cancer

The advent of targeted molecular therapy against the EML4-ALK fusion gene is the latest therapeutic intervention for a subset of patients with non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) is an orally available small molecule tyrosine kinase inhibitor proven in clinical trials to significantly impact progression free survival and overall response rate. We present a case of a 56-year-old male with NSCLC whose lack of a positive treatment response to this therapy led to the clinical suspicion and identification of the underdiagnosed entity known as synchronous multiple primary lung cancer (SMPLC).

同時性同一肺葉内多発肺癌を含む異時性3臓器4重複癌の1切除例

同時性同一肺葉内多発肺癌を含む異時性3臓器4重複癌の1切除例

Synchronous Bronchioloalveolar and Squamous Cell Lung Cancer With Different 18F-FDG Avidity on PET/CT

We report a case of synchronous multiple primary lung cancer diagnosed by 18F-FDG PET/CT. A 78-year-old man underwent staging FDG PET/CT that demonstrated intense tracer uptake in the primary, and a second lesion with low uptake. Histopathologic evaluation revealed synchronous squamous cell and bronchioloalveolar carcinoma, representing 2 distinct primaries. FDG PET/CT may identify and diagnose synchronous multiple primary lung cancer on the basis of different morphologic and metabolic features of distinct tumor entities. Moreover, pulmonary lesions with low FDG avidity may still represent malignant disease, even in the context of biopsy-proven FDG-avid lung cancer.

A case of resected synchronous multiple primary lung cancer comprising adenocarcinoma and carcinoid (cancer-in-cancer)

We performed surgical resection of synchronous multiple primary lung cancer, comprising adenocarcinoma and carcinoid components. The latter tumor was located within the central scar tissue formed by the adenocarcinoma (cancer-in-cancer). The patient was a 67-year-old Japanese woman who had a nodular lesion in the right S1 on chest computed tomography. Lung cancer was diagnosed intraoperatively by rapid needle aspiration cytology, and right upper lobectomy with mediastinal lymph node dissection was performed. Histological examination of the resected specimen revealed cancer-in-cancer, consisting of adenocarcinoma and a carcinoid tumor. The carcinoid component was localized within the central fibrous scar of the dominant adenocarcinoma component.

Stereotactic body radiation therapy in the treatment of multiple primary lung cancers

Background and purposePatients 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 methodsA 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. ResultsFifteen 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. ConclusionsSBRT 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.

Early clinical diagnosis of synchronous multiple primary lung cancer

The diagnosis of synchronous multiple primary lung cancer (SMPLC) remains a formidable challenge. The aim of the present study was to identify useful clues for the clinical diagnosis of SMPLC, in particular for the early stages. The medical records of 10 patients diagnosed with SMPLC with different histological types were analyzed retrospectively. Chest computed tomography (CT) findings showed two pulmonary lesions in all patients. The two lesions displayed malignant characteristics of primary lung cancer. The levels of a number of tumor markers, including carcinoembryonic antigen, neuron-specific enolase, cytokeratin fragment 21-1, squamous cell carcinoma and CA125 increased in 2 patients. Auxiliary examinations of other physical sites in these patients did not show signs of neoplasm metastasis. Two tumors were separately staged and appropriate treatment was carried out based on the revised stage, which provided more benefits for SMPLC patients. The diagnosis of SMPLC might be delayed or mistaken owing to its similarity to neoplasm metastasis. A high index of awareness is required for the early diagnosis of this disease. The malignant characteristics of primary lung cancer in various lesions may be valuable clues for the diagnosis of SMPLC. Alterations in the levels of tumor markers may be a poor diagnostic tool for the detection of SMPLC. Separate biopsies for different pulmonary masses should be performed for clinical staging as soon as possible and reasonable treatment based on the stage should also be selected.

Treatment outcomes for patients with synchronous multiple primary non-small cell lung cancer

Introduction The development of synchronous multiple primary non-small cell lung cancer (NSCLC) is not rare. Nevertheless, the diagnosis, treatment and outcome are controversial. The purposes of this study were to assess the treatment outcomes for patients with synchronous multiple primary NSCLC and to analyze the factors related to this outcome. Methods We retrospectively analyzed clinical characteristics and treatment outcomes of 32 patients with synchronous multiple primary NSCLC who underwent surgical resection between 1995 and 2008. Results A total of 68 separate tumors were identified in 32 patients. Fifteen (46.9%) patients underwent lobectomy or pneumonectomy with mediastinal lymph node dissection, and 17 (53.1%) patients underwent at least one limited resection or photodynamic therapy. The rate of immediate postoperative mortality was 9.4% ( N = 3). The five-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% and 60.9%, respectively. Small tumor size, similar histology, pN0, and pT1 were associated with better PFS in univariable analyses. Female gender, young age, non-smoker, FEV1/FVC ≥70%, small tumor size, similar histology, and highest pT1 were associated with better OS in univariable analyses. Conclusions An aggressive surgical approach offers the greatest chance for long-term survival in patient with synchronous multiple primary NSCLC and several clinical factors were associated with survivals. However, the decision of aggressive surgical treatments for synchronous MPLC should be made carefully in the patients with old age and underlying comorbidities due to poor OS and increased surgical mortality.

Survival and prognostic factors in surgically resected synchronous multiple primary lung cancers

The presence of synchronous multiple primary non-small-cell lung cancers (SMPLC) is a rare condition and the optimal treatment remains unclear. In this study, the survival of surgically treated SMPLC patients and the factors affecting survival were analyzed. Between 2001 and 2008, 26 consecutive patients diagnosed with SMPLC, who had all of their tumors resected, were retrospectively evaluated. Patients, who had bronchoalveolar carcinoma or carcinoid tumors and satellite nodules, were excluded. Prognostic factors were analyzed using univariate and multivariate analyses. The tumors were unilateral in 14 and bilateral in 12 patients. In total, 38 procedures were performed. A complete resection was achieved in 35 (92.1%) procedures. The in-hospital mortality rate was 7.6% (two patients). The overall 5-year survival rate was 49.7%, and the median survival time was 40 months. The 5-year survival rate was 40.6% for unilateral and 62.8% for bilateral SMPLC patients (p = 0.47). Histopathologic tumor type, N1 nodal disease, tumor (T) status, and older age did not influence survival. There was no survival disadvantage for patients, upon whom a sublobar resection had been performed. There was a trend toward poorer survival in patients upon whom a pneumonectomy had been performed (p = 0.12). The 3-year survival rate for patients, who received adjuvant chemotherapy and/or radiotherapy (66.7%), was better than other patients (56.3%). In the multivariate analysis, we found a trend toward poor survival in patients, who received a pneumonectomy, and a trend toward better survival in patients, who received adjuvant therapy (p = 0.05 and p = 0.06). The survival of SMPLC patients, who were treated surgically, was satisfactory. Pneumonectomy was a poor prognostic factor, whereas adjuvant therapy was a good prognostic factor.

Clinical study of synchronous multiple primary cancer involving the lung

Ten cases of synchronous multiple primary cancer involving the lung were experienced in our hospital during the period from January 1962 to May 1987. The incidence rate was 1.3% of all hospitalized cases of primary lung cancer. The counterpart organs were thyroid gland (4 cases), stomach (2 cases), colorectum (2 cases) and lung (2 cases). Three of four thyroid cancer cases were resected at the same time of pulmonary resection, whereas the stomach and colorectal cancer cases underwent two stage operation. Lung perfusion scintigraphy was very useful in determining the operative method for synchronous multiple primary lung cancer. The 5-year survival rate of all cases of synchronous multiple primary cancer involving the lung was 26.3%, with no hospital death. Surgical treatment is recommended for such cases when both cancers are expected to be resected completely.