Synchronous Multiple Lung Research Articles

High Discrepancy of Driver Mutations in Patients with NSCLC and Synchronous Multiple Lung Ground-Glass Nodules

The aim of this study was to investigate the discordance rates of eight known driver mutations among multiple matched intrapulmonary ground-glass nodules (GGNs) in non-small-cell lung cancer (NSCLC) patients. Tumors from 35 patients with multiple lesions resected, including confirmed NSCLC and at least one GGN, were analyzed for mutations in EGFR, KRAS, HER2, BRAF, and PIK3CA together with fusions in ALK, ROS1, and RET. From 35 patients, a total of 72 lesions (60 were GGNs) were analyzed. These included nine adenocarcinoma in situ, nine minimal invasive adenocarcinoma, and 54 invasive adenocarcinoma. Among them, 33 tumor lesions (45.8 %) were found harboring EGFR mutations: 13 tumors with exon 19 deletion, 18 with L858R on exon 21, and two with both exon 19 del and L858R mutation. There were 5 tumors (6.9 %) harboring EML4-ALK fusion, four HER2 mutations (5.6%), three KRAS mutations (4.2%), one ROS1 fusion and one BRAF mutation. When we used the matched tumors to determine the intertumor discrepancy, only six out of 30 patients harbored identical mutations. The discordance rate of driver mutations was 80% (24 of 30) in those patients harboring at least one of the detected driver mutations. The median disease-free survival was 41.2 months (95% confidence interval: 35.8-52.6 months) and the median overall survival was "still not reached" in this cohort. We found a high discrepancy of driver mutations among NSCLC patients with GGNs and a favorable prognosis after multiple lesions resection, which support surgical resection in this situation as a reasonable approach.

Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions.

We reviewed the medical record of a series of patients with synchronous multiple lung cancers (SMLC), in an attempt to identify the optimal treatment strategy for multiple ground-glass opacities (GGOs). From 2004 to 2010, 1223 patients underwent complete resection of non-small cell lung cancer. Among these, there were 67 patients (5.5%) with SMLC with at least 1 of the nodules showing GGO appearance. SMLC was divided into the main cancer (MC) which was a main target based on its tumor size or radiological invasiveness and sub-nodules. According to consolidation/tumor ratio (CTR) on thin-section computed tomography, 67 cases were classified into GG-group (MC showing GGO-dominant lesion; CTR≤0.5) and GS-group (MC showing solid-dominant lesion; CTR>0.5). There were 24 patients in the GG-group (36%) and 43 patients in the GS-group (64%). Surgical resections included 11 sublobar resections (SLs), 32 lobectomies, 19 lobectomy+SLs, and 4 bilobectomies. There were 39 patients with a total of 118 unresected GGOs after the initial surgery. Among them, the frequency of growth was 8% on a per-nodule basis with the median tumor doubling time of 1373 days, and new GGOs emerged in 15 patients (23%). Multivariate analysis demonstrated that larger size of MC and the GS-group was associated with poor prognosis, whereas growth of the residual GGOs, the development of new GGOs, or whether or not all GGOs were treated did not affect survival. The 5-year OS proportions were 95.8% for the GG-group and 68.0% for the GS-group (p=0.009), and 92.4% for a MC of ≤25 mm and 53.6% for a MC of >25 mm (p=0.008). Survival of patients with multifocal GGOs is strongly affected by radiological findings of the MC. Strict surgical control for MC could be most important.

Outcomes of stereotactic body radiotherapy (SBRT) treatment of multiple synchronous and recurrent lung nodules.

BackgroundStereotactic body radiotherapy (SBRT) is evolving into a standard of care for unresectable lung nodules. Local control has been shown to be in excess of 90% at 3 years. However, some patients present with synchronous lung nodules in the ipsilateral or contralateral lobe or metasynchronous disease. In these cases, patients may receive multiple courses of lung SBRT or a single course for synchronous nodules. The toxicity of such treatment is currently unknown.MethodsBetween 2006 and 2012, 63 subjects with 128 metasynchronous and synchronous lung nodules were treated at the Mayo Clinic with SBRT. Demographic patient data and dosimetric data regarding SBRT treatments were collected. Acute toxicity (defined as toxicity < 90 days) and late toxicity (defined as toxicity > = 90 days) were reported and graded as per standardized CTCAE 4.0 criteria. Local control, progression free survival and overall survival were also described.ResultsThe median age of patients treated was 73 years. Sixty five percent were primary or recurrent lung cancers with the remainder metastatic lung nodules of varying histologies. Of 63 patients, 18 had prior high dose external beam radiation to the mediastinum or chest. Dose and fractionation varied but the most common prescriptions were 48 Gy/4 fractions, 54 Gy/3 fractions, and 50 Gy/5 fractions. Only 6 patients demonstrated local recurrence. With a median follow up of 12.6 months, median SBRT specific overall survival and progression free survival were 35.7 months and 10.7 months respectively. Fifty one percent (32/63 patients) experienced acute toxicity, predominantly grade 1 and 2 fatigue. One patient developed acute grade 3 radiation pneumonitis at 75 days. Forty six percent (29/63 patients) developed late effects. Most were grade 1 dyspnea. There was one patient with grade 5 pneumonitis.ConclusionMultiple courses of SBRT and SBRT delivery after external beam radiotherapy appear to be feasible and safe. Most toxicity was grade 1 and 2 but the risk was approximately 50% for both acute and late effects.

Prognostic Nomogram to Predict Survival After Surgery for Synchronous Multiple Lung Cancers in Multiple Lobes

In the absence of metastatic disease, surgery for synchronous non-small-cell lung cancers involving multiple lobes can be curative. However, there currently exists no reliable prognostic instrument for this patient population after surgery. We undertook an analysis to examine the prognostic significance of adenocarcinoma histology and developed a prognostic nomogram. This study was a pooled analysis of six previously reported datasets. Patients without extra-thoracic metastasis who underwent surgical resection of synchronous lung cancers in multiple lobes were included. Those with small cell cancer, carcinoid tumor, or exclusively carcinoma in situ were excluded. A multivariable Cox proportional hazards regression model was fitted to identify independent survival predictors for nomogram development. Data from 467 patients were analyzed. Adenocarcinoma was a sole histology in 253 patients (54.2%). Those with exclusively adenocarcinoma histology had a better median survival than their counterparts: 67.4 versus 36.2 months, (p < 0.001). Multivariable analysis incorporating histology, sex, age, maximal T-size, highest N-stage, and laterality demonstrated that having exclusively adenocarcinoma histology independently predicted an improved survival: hazard ratio 0.61 (95% confidence interval: 0.48, 0.78). Other favorable survival predictors were N0, T-size less than or equal to 3 cm, bilateral cancers, age less than 70 years, and women sex. The developed nomogram was well calibrated and demonstrated a moderate to good discrimination with a bootstrap-corrected Harrell C-statistic of 0.70. Several unique features among patients with resected synchronous multiple lung cancers, including the presence of exclusively adenocarcinoma histology, are of prognostic significance. A simple nomogram incorporating these factors can be utilized to predict patient survival with acceptable accuracy.

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.

小細胞癌を含む同時性多発肺癌に対して右肺全摘術による完全切除を行った1例

小細胞癌を含む同時性多発肺癌に対して右肺全摘術による完全切除を行った1例

A Case of Synchronous Multiple Lung Cancer Diagnosed by TBLB and EBUS-TBNA

A Case of Synchronous Multiple Lung Cancer Diagnosed by TBLB and EBUS-TBNA

A Case of Synchronous Multiple Lung Cancer Diagnosed by Transbronchial Aspiration Biopsies of the Right #11i Lymph Node and Transbronchial Biopsies of a Left B^3c Tumor

A Case of Synchronous Multiple Lung Cancer Diagnosed by Transbronchial Aspiration Biopsies of the Right #11i Lymph Node and Transbronchial Biopsies of a Left B^3c Tumor

Clinicopathology and Genetic Profile of Synchronous Multiple Small Adenocarcinomas: Implication for Surgical Treatment of an Uncommon Lung Malignancy

Synchronous multiple small adenocarcinomas are detected more frequently than in the past; however, the genetic profile, treatment, and prognosis of patients remain unclear. For treatment decisions and prognostic applications, we evaluated epidermal growth factor receptor (EGFR), p53, and KRAS somatic mutations in synchronous multiple small lung adenocarcinomas. The presence of EGFR, p53, and KRAS somatic mutations was determined in 64 synchronous multiple lung adenocarcinomas ≤2cm in maximal dimension. Mutational analysis was performed on DNA extracted from paraffin-embedded tumors. Five-year disease-free survival (DFS) was 86.1%, and overall survival was 95.8%. EGFR, p53, and KRAS mutations were detected in 41 (64.1%), 8 (12.5%), and 4 (6.3%) patients, respectively. The high frequency of genetic mutations resulted in a high discrimination rate of tumor clonality (68.8%; 44/64) in the study group. Fourteen (31.8%) patients were assessed as having the same clonality, whereas 30 (68.2%) patients had different clonality, which further supported the concept of field cancerization. Multivariate analysis showed lymph node metastasis (p=0.003) and smoking (p=0.011) were significantly correlated with tumor relapse. Surgical method, clonality, and tumor location were not correlated with tumor relapse. Whether these tumors are different or the same clonal, sublobar resection of each lesion can achieve long-term DFS and is the treatment of choice for synchronous multiple small lung adenocarcinomas. Patients with lymph node metastasis are at risk of relapse and adjuvant chemotherapy is indicated.

EGFR陽性肺癌とALK陽性肺癌が併存した同時性多発肺癌の2例

EGFR陽性肺癌とALK陽性肺癌が併存した同時性多発肺癌の2例

A case of multiple synchronous lung adenocarcinomas with differing EGFR mutations

We report a case of four synchronous lung cancers, each with a different epidermal growth factor receptor (EGFR) mutation in the tyrosine kinase domain. Bilateral double lung cancer was diagnosed clinically, and a left upper lobectomy and partial left S6 resection were performed. Right S1 segmental resection was performed later. Pathological examination revealed three lung adenocarcinomas in the left lung (S1 + 2, S3, and S6) and one in the right. Three different mutations of EGFR were identified with the polymerase chain reaction and direct sequencing of DNA from the three left lung tumors. The EGFR mutation on the right also differed from that of the left lung tumors.

Predictors of survival after resections of synchronous lung cancers located in mutiple lobes: A multi-institutional pooled analysis.

7024 Background: Surgical resection is a treatment option for patients with multiple primary lung cancers. However, for synchronous disease, it is often difficult to differentiate this condition from metastatic disease, especially when cancers are distributed in multiple lobes or in both lungs. Some people believe that surgery should be avoided when patients have bilateral cancers or when all cancers have the same histology. To date, however, available evidences are limited by small sample size. Methods: Studies (published 2008-2011) of curative resection for patients with synchronous (&lt; 2-year interval) multiple lung cancers located in ≥ 2 lobes, but without radiographic evidence of distant metastasis, were identified from literature. Corresponding authors were contacted and individual patient data were obtained. Patients with multiple cancers, but localized only to one lobe, were not included. Databases were pooled and multi-variable Cox Proportional Hazard models were fit to adjust for confounders. Results: There were 467 patients included from 6 studies. Median overall survival was 52.0 months (95% CI: 45.6-63.7). Postoperative (30-day) mortality rate was 1.9%. In a multivariable model, study site or having pneumonectomy did not independently impact on survival. However, age, gender, nodal stage, tumor location, and histological similarity were independent predictors of survival. Advanced age increased mortality (p=0.012). Male sex increased mortality compared with female: HR 1.64 (95% CI: 1.23-2.19, p=0.0008). N2 or N1 increased mortality over N0: HR 1.85 (95% CI 1.29-2.66, p=0.0008) and 1.97 (1.43-2.73, p=0.0001), respectively. Unilateral location increased mortality over bilateral location: HR 1.62 (95% CI 1.23-2.13, p=0.0002). Different histology increased mortality over similar histology: HR 1.45 (95% CI 1.11-1.90, p=0.0069). Conclusions: In this largest multi-institutional database of resected multiple lung cancers of multiple lobes to date, we found no evidence of inferior survival among patients having bilateral cancers or having all cancers with the same histology. In fact, the survival among such patients appears superior to their counterparts.

Multiple Segmentectomy for Synchronous Multiple Small Peripheral Lung Cancers: Report of Two Cases

Treatment strategies for synchronous, multiple peripheral lung cancers remain controversial. Bilobectomy for multiple lung cancers could cause pulmonary function impairment. We report two patients with synchronous multiple peripheral non-small cell lung cancers, who underwent multiple segmentectomy simultaneously. This is the first report of consecutive segmentectomy of two segments.

Prognosis in Patients with Non-Small Cell Lung Cancer and Satellite Tumors

Aim of the study was to identify factors affecting survival in patients with lung cancer and satellite tumors (ST). Between 2001 and 2008, there were 102 patients with synchronous multiple lung cancers among the 1355 lung resections performed in lung cancer patients. Satellite tumors were found to be near the primary lung cancer (PLC) in 29 patients. Complete resection was achieved in all patients, and the 5-year survival rate was 52 %. The independent "T" stages of the PLCs and STs did not affect survival ( P = 0.98 and P = 0.54, respectively). A distance between the PLC and ST longer or shorter than 2, 3, or 4 cm also did not affect survival ( P = 0.78, P = 0.57, and P = 0.62, respectively). The survival of patients treated with adjuvant therapy was significantly higher than that of patients who did not receive adjuvant therapy ( P = 0.0043). Satisfactory survival was achieved after surgical therapy for non-small cell lung cancer associated with ST. While the PLC and ST characteristics and the distance between tumors did not affect survival rates, the introduction of adjuvant chemotherapy with/without radiotherapy positively affected survival.

Relationship between Tumor Size and Survival among Patients with Resection of Multiple Synchronous Lung Cancers

Relationship between Tumor Size and Survival among Patients with Resection of Multiple Synchronous Lung Cancers

Relationship between Tumor Size and Survival among Patients with Resection of Multiple Synchronous Lung Cancers

Multiple synchronous non-small cell lung cancers (NSCLCs) without extrathoracic metastasis are relatively uncommon. Some patients are treated as metastatic disease by chemotherapy alone; others are treated as multiple primary cancers by surgery. For those undergoing surgery, limited information exists on the relationship between tumor size and survival. We retrospectively reviewed medical records of patients with resection of at least two synchronous NSCLC located in > or =2 lobes during 1997-2008. Those with only satellite nodules in single lobe were excluded. Cox proportional hazard model was used to examine the prognostic significance of tumor size in the context of other clinical parameters including tumor stage, nodal stage, age, gender, laterality, histology, and pneumonectomy. There were 116 patients: 57 patients had cancers distributed in one lung and 59 in both lung. Overall, 186 thoracotomies were performed, with a 90-day mortality rate of 2.6%. The median overall survival was 65.1 months (95% confidence interval [CI]: 49.2-83.7). The median size of the largest tumor and the median sum of tumor sizes were 3.0 and 4.5 cm, respectively. Both were a significant predictor of survival: hazard ratios per centimeter increase where 1.17 (95% CI: 1.06-1.30, p = 0.003) and 1.15 (95% CI: 1.05-1.26, p = 0.003), respectively. Multivariable regression analysis identified tumor size and lung function as independent survival predictors. Among patients with resected multiple synchronous NSCLC, tumor size is an independent predictor of survival. The size of the largest tumor performs slightly better than the sum of tumor sizes in the survival prediction; however, both are much better than the American Joint Committee on Cancer stage for this purpose.

Surgical treatment of synchronous multiple lung cancer located in a different lobe or lung: high survival in node-negative subgroup☆

The International Association for Study of Lung Cancer Staging Committee proposes for the next revision of TNM (tumour, nodes, metastases) classification that additional nodules in a different lobe of the ipsilateral lung moves from an M1 designation to T4, while additional nodule(s) in the contralateral lung should be classified as M1a, because of poorer survival. We analysed the survival after surgery of patients presenting with synchronous lung cancers located in a different lobe or lung. A database of 1551 patients operated on for non-small-cell lung cancer (NSCLC) between 1990 and 2007 was evaluated for unilateral (other lobe) (n=15) and bilateral (n=28) synchronous multiple lung cancers. The relationships among the location of tumours, histology, date of surgery (before and after 2000), lymph node metastasis, type of surgery, adjuvant therapy and survival were analysed. The 5-year survival for all synchronous multiple lung cancers (n=43) was 34%, with a median survival of 32 months. Postoperative mortality was 7%. On univariate analysis, only lymph node metastasis and surgery before the year 2000 affected the overall survival adversely, and both prognostic factors maintained a statistical significance on multivariate analysis. The 5-year survivals were 57% and 0% for patients without (n=25) and with (n=18) lymph node metastasis, respectively (p=0.004), and were 43% and 18% for patients operated upon after (n=27) and before (n=16) the year 2000, respectively (p=0.01), perhaps reflecting a better selection process related to the extensive use of positron emission tomography (PET) scanning. The 5-year survival was not different between bilateral (43%) and unilateral (27%) synchronous lung cancers (p=n.s.). Our data support complete surgical resection of synchronous multiple lung cancers in patients with node-negative NSCLC. Even patients with bilateral lung cancer should not be treated as metastatic disease. Provided there is no evidence of node and distant metastasis, after an extensive preoperative work-up, including PET scanning and mediastinoscopy, bilateral surgical resection should be performed in fit patients.

Peritoneal disseminated recurrence and lung metastasis after surgery for stage IA uterine papillary serous carcinoma of the endometrium: a case report

We describe a case of synchronous peritoneal dissemination and multiple lung metastases after surgery for stage IA primary uterine papillary serous carcinoma (UPSC) of the endometrium, revealed by an uncontrollable retention of ascites. She was initially treated with a hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy after initial presentation. Tumor recurrence, diagnosed 12 months later, has been treated with six cycles of Paclitaxel 175 mg/m(2) and Carboplatin [area under the curve 5 (Calvert Formula)] every 3 weeks and showed an advantage of this regimen. Early recurrences of the stage IA UPSC can occur and continued close surveillance is recommended. We report herein the case about this entity.

Problems in Pathologic Staging of Lung Cancer

Abstract Context.—Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy. Objective.—To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms. Data Sources.—Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and...

Problems in Pathologic Staging of Lung Cancer

Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy. To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms. Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and intrapulmonary metastasis of non-small cell carcinoma of the lung (pT4 or pM1 according to their location); and the role of the recent American Joint Committee on Cancer terminology for the classification of lymph nodes (isolated tumor cells, micrometastases, and metastases). The variety of practical problems that can arise during the assessment of important prognostic and predictive features such as resection margin status and evaluation of lymphovascular invasion are reviewed. A brief discussion of the assessment of the effects of neoadjuvant therapy on resected lung neoplasms is also included.