Synchronous Lung Cancer Research Articles

Multi-modality radical intent treatment in synchronous oligometastatic non-small cell lung cancer: how many patients complete the full treatment regime recommended by the MDT?

Multi-modality radical intent treatment in synchronous oligometastatic non-small cell lung cancer: how many patients complete the full treatment regime recommended by the MDT?

Women With Synchronous or Metachronous Lung and Ovarian Cancer: A Multi-Institutional Report.

Double diagnosis of lung cancer (LC) and ovarian cancer (OC) is rare. Here, we describe patients with synchronous/metachronous LC and OC to identify common clinical and pathological patterns. Clinical, pathological and molecular data of patients diagnosed and treated at 30 European Institutions from 2008 to 2018 were retrieved and analysed. Whenever tissue was available, centralized pathology revision was performed. A total of 19 cases were found; one was excluded at pathology revision. Most LCs were adenocarcinomas (15/18) and most OCs were high-grade serous (15/18) carcinomas. Of the 9 patients analysed, 7 carried oncogene-addicted LC (4 EGFR, 1 B-RAF and 2 ALK) and five out of 7 carried BRCA mutations. One patient with a germline-BRCA1 mutation received olaparib, resulting in a durable response of both malignancies. Median overall survival was 33 months. In our series, most synchronous/metachronous LCs and OCs showed genetic alterations. Further analyses with wide NGS panel could shed light on the biological mechanisms driving their occurrence.

Ten-year follow-up of a patient after segmentectomy and lobectomy for synchronous bilateral peripheral lung cancer

Ten-year follow-up of a patient after segmentectomy and lobectomy for synchronous bilateral peripheral lung cancer

Synchronous Oligometastatic Lung Cancer Deserves a Dedicated Management

Oligometastatic stage IV non-small lung cancer (NSCLC) patients have a 5-year overall survival of 30% versus 4% to 6% in historical cohorts of stage IV NSCLC patients. We reviewed data and patterns of care of patients affected by oligometastatic NSCLC in our center between 2001 and2017. We retrospectively reviewed clinical and pathological files of all patients with lung cancer and synchronous isolated adrenal or brain metastases, or both, treated by locally ablative treatments (surgery or radiotherapy, or both) of both primary cancer and distant metastasis. Statistical analysis was performed to assess the effect on overall survival of patient- and tumor-related characteristics and therapeutic approaches. Overall survival was assessed by the Kaplan-Meier method. Survival rates were compared by log-rank test. Significance was accepted at a level of p of less than 0.05. Our department treated 51 patients affected by NSCLC and synchronous brain metastasis (n= 41), adrenal metastasis (n= 9), or both (n= 1). Median survival was 42 months (95% confidence interval, 22.3 to 63.7). Overall survival was 62% at 2 years and 34.4% at 5 years. A univariate and multivariate analysis the positive prognostic factors for survival was cessation of smoking (p= 0.006) and lymphovascular and perineural spreading in the tissues (p= 0.024). In selected oligometastatic synchronous NSCLC patients, a multimodality approach encompassing radical treatment of the primary tumor and ablative treatment of concurrent metastases is recommended, with encouraging results. Smoking cessation is a part of the treatment sequence.

Synchronous multiple lung cancer consisting of squamous cell carcinoma and adenocarcinoma with de novo T790M EGFR gene mutation

Synchronous multiple lung cancer consisting of squamous cell carcinoma and adenocarcinoma with de novo T790M EGFR gene mutation

Radiopathologic correlation of collision lung cancer with ground-glass opacity

Pulmonary collision tumors have been described as a special entity of synchronous multiple lung cancer. There have been no reports detailing the chronological changes in primary collision lung cancers on chest computed tomography. We report a case of ground-glass lung nodules gradually colliding with each other. The collision tumors of the lung were composed of minimally invasive adenocarcinoma and adenocarcinoma in situ with epidermal growth factor mutations. Immunohistochemically, the Ki-67 labeling indices were different in the 2 components. Ki-67 staining was useful to distinguish the 2 components. The 2 dominant ground-glass tumors grew slowly with radiologic and pathologic heterogeneity.

Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis

In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer‐related oncogenes using next‐generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.

1482P - Localablative treatment for synchronous oligometastatic lung cancer: A propensity score analysis of 180 patients

1482P - Localablative treatment for synchronous oligometastatic lung cancer: A propensity score analysis of 180 patients

P2.09-21 Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report

P2.09-21 Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report

P2.09-16 Heterogeneity Analyses of MSLCs—Especially in the EGFR Mutation-Positive Ones

Multiple synchronous lung cancers (MSLCs) are diagnosed as multiple tumor nodules in the same or different lung lobes. MSLCs present a clinical dilemma whether they are primary tumors or metastases. Recent studies showed that MSLCs shared an identical germline genetic background and environmental exposure in the same individual patient, however, different tumor nodules showed highly different heterogeneity, even in all the EGFR mutation-positive focuses. Therefore, we performed this study to further analyze MSLCs as to estimate the pathology and molecule heterogeneity among these nodules. Tumor samples were obtained from nine patients diagnosed with MSLCs. Immunohistochemistry were performed by professional pathologists. Whole-exome sequencing (WES) was conducted by IlluminaNovaseq with sequencing depth of 200X. NeoTyping was used to describe the dispersion of sequencing data among MSLCs of the same patient. We found different tumor nodules showed obviously pathological and molecular heterogeneities in the same individual (Figure 1). More different dispersion was observed among the nodules with more different pathologies in the same patient. The dispersion of 20%, 50% and 100% were observed in MSLCs with the same driver genes (such as EGFR exon21 L858R and L861Q) of lung adenocarcinoma, different evolutional stages (AAH, MIA and IA) and completely different pathologies (adenocarcinoma and squamous cancer), respectively. All the sequencing data showed MSLCs had different gene information, even in all the EGFR mutation-positive nodules, maybe similar, but not the same, which supported that each nodule in one patient was independent with others. MSLCs could be independent with each other due to their pathological and molecular heterogeneities, even for EGFR mutation-positive nodules which hold the same driver gene, but different mutation site in just one patient. WES should be an effective way to recognize this heterogeneous characteristic, which would be helpful for the whole precise management of one MSLC patient.

Local ablative treatment for synchronous single organ oligometastatic lung cancer—A propensity score analysis of 180 patients

IntroductionLocal ablative treatment (LAT) improves outcome in lung cancer with oligometastatic disease (OMD) and potentially leads to long term survival. The aim of this retrospective study was to evaluate and quantify the additional benefit of LAT in synchronous OMD and to further identify prognostic factors for survival. Patients and methodsA propensity score-matched pairs analysis was performed on a set of patient and disease variables in 180 patients, treated for synchronous single organ OMD including non small-cell and neuroendocrine lung cancer with ≤4 metastases between 2000 and 2016 in 3 lung cancer centers in Berlin, Germany. Patients either received LAT for all sites of disease (intervention group) by means of surgery or stereotactic radiotherapy, or standard chemotherapy, if necessary combined with a local treatment with palliative intent (control group). ResultsMedian follow-up time was 32.2 and 18.8 months for the intervention and control group, respectively. Substantial benefits in median progression-free survival (PFS, 25.1 vs. 8.2 months; HR, 0.30; 95% CI, 0.21–0.43; p < 0.001) and overall survival (OS, 60.4 vs. 22.5 months; HR, 0.42; 95% CI, 0.28–0.62; p < 0.001) were associated with LAT. Histology of adenocarcinoma and T1a primaries also predicted a favorable prognosis concerning PFS and OS. More favorable nodal stage (N0-2 vs. 3) and solitary metastases were associated with an extended PFS, whereas initial ECOG-PS (0–1 vs. 2) predicted OS. ConclusionsLAT was the strongest predictor for PFS and OS in OMD with ≤4 metastases. Survival in the control group identifies OMD as a subset of lung cancer with a generally more favorable prognosis.

Targeted Sequencing Analysis of Pulmonary Adenocarcinoma with Multiple Synchronous Ground-Glass/Lepidic Nodules

IntroductionLung adenocarcinoma (ADC) with synchronous ground-glass/lepidic (GG/L) nodules is considered a distinct disease entity in multiple synchronous lung cancers. Few studies have performed next-generation sequencing analysis of these synchronous sequential lesions, and genetic alterations of GG/L nodules must be further investigated. MethodsWe performed targeted sequencing in ADC with synchronous atypical adenomatous hyperplasia (AAH), ADC in situ, or minimally invasive ADC from 16 patients. Next-generation sequencing was performed by using a customized panel including 154 cancer-associated genes. ResultsMultiple synchronous lesions in the same patient showed different mutation profiles, and some shared identically mutated genes. In five patients harboring EGFR-mutant ADC, their synchronous GG/L nodules had EGFR mutation; however, none was observed in EGFR wild-type ADC. The average numbers of exonic mutations were 4.2, 5.4, 4.0, and 5.4 in AAH, ADC in situ, minimally invasive ADC, and ADC, respectively. In each lesion type, various mutations, including LDL receptor related protein 1B gene (LRP1B), KRAS, EGFR, and BRAF were observed in AAH, and EGFR mutations were the most frequently observed in ADC. In all, 80% of mutations with a variant allele frequency of 20% or higher, which contained driver gene mutations, were identified in ADC. Intratumoral heterogeneity of the genetic profile was found between the lepidic and invasive areas of ADC, but the driver gene mutations were similar. ConclusionsThis study suggests that ADC and synchronous GG/L nodules are genetically independent tumors. Intratumoral genetic heterogeneity of ADC was present, but driver gene mutations were homogeneously distributed. Driver gene mutations with a high variant allele frequency were identified in the invasive tumor. These findings support the relevance of molecular characterization of lung ADC and synchronous GG/L nodules.

Androgen deprivation therapy is associated with decreased second primary lung cancer risk in the United States veterans with prostate cancer.

OBJECTIVESWe investigated whether androgen deprivation therapy (ADT) in prostate cancer patients was associated with a decreased risk for second primary lung cancer in US veterans.METHODSProstate cancer diagnoses in the US Veterans Affairs Cancer Registry between 1999 and 2008 were identified. Use of hormonal therapy and diagnoses of second primary lung cancer were determined from the registry. Synchronous prostate and lung cancers, defined as 2 diagnoses made within 1 year, were excluded from the analysis. Cancer-free survival was estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazard models.RESULTSAmong the 63,141 identified patients with prostate cancer, 18,707 subjects were eligible for the study. Hormonal therapy was used in 38% of patients and the median follow-up period was 28 months. ADT use was associated with longer lung cancer-free survival in prostate cancer patients (log-rank p=0.01). After adjusting for age, race, smoking and prostate cancer stage, ADT use was associated with decreased lung cancer risk by 15, 21, and 24% after 1, 2, and 3 years, respectively.CONCLUSIONSADT in prostate cancer patients may be associated with decreased second primary lung cancer risk among US veterans.

Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Primer for Radiologists.

The past 2 decades have seen a rapid growth in use of stereotactic body radiation therapy (SBRT) for the management of non-small cell lung cancer (NSCLC). Not only is SBRT the reference standard for treatment of early-stage node-negative NSCLC in medically inoperable patients, it is also currently challenging the role of surgery for early-stage operable disease. SBRT is also used to treat recurrent disease and has a role in the management of multiple synchronous lung cancers. Imaging changes after SBRT differ from the changes after conventional radiation therapy in many ways, the knowledge of which is pertinent for accurate image interpretation. Posttreatment response assessment and detection of recurrent disease are heavily reliant on radiologic assessment, and often the decision to treat recurrent disease is based on the imaging findings themselves. This article provides a comprehensive review of the concepts of SBRT and the current indications for its use in the treatment of early-stage NSCLC, as well as a discussion of the CT findings seen after SBRT compared with the changes after conventional radiation therapy. Radiologic findings that are suggestive of recurrent disease and the imaging pitfalls are also highlighted. Finally, the rare complications after SBRT are described. SBRT is a major component of the changing treatment paradigms for early- and late-stage NSCLC. The imaging findings after SBRT often determine the next steps in a patient's clinical management. Therefore, radiologists must be familiar with the uses of this therapy and its radiologic appearance to be able to effectively contribute to the care of patients with NSCLC. ©RSNA, 2018.

Abstract 3680: Comparative mutational evaluation for multiple lung cancer by multiplex oncogene mutation analysis

Abstract [Background] In the treatment of synchronous or metachronous multiple lung cancer (MLC), determination whether multiple primary lung cancer (MP) or intrapulmonary metastases (IM) is very important to make an appropriate management. Clinical or pathological diagnoses have been adopted to distinguish whether MLC were MP or IM, however, the accuracy of these approaches seemed to be insufficient. On the other hand, recent evolution of high-throughput sequencing made it possible to perform comprehensive gene mutation analysis in cancer cells. The aims of this study were to investigate mutational profiles of synchronous or metachronous MLC, and to compare multiplex gene mutation analysis of MP or IM among paired tumors with clinical or pathological evaluations. [Methods] We performed targeted sequencing for 20 lung cancer related oncogenes using next-generation sequencing technology in 82 tumors from 37 patients (18 patients with synchronous MLC and 19 patients with metachronous MLC) who underwent surgical resection in our department from July 2002 to April 2013. Then, classification of MP or IM was made by clinical, pathological, and gene mutational evaluation. [Results] Among paired tumors, matching of mutation was observed in 20 (54%) cases (nine cases with completely matched and 11 cases with partially matched), which were diagnosed as IM by mutational evaluation. In pathologically suggested IM cases (n=7), six (86%) patients were interpreted as IM by mutational evaluation, and most of them (n=5) had multiple matched mutations, which suggested the clonality between paired tumors strongly. In pathologically suggested MP cases (n=17), the mutational diagnosis was discordant in eight (47%) patients. Among these cases, four paired tumors had multiple matched mutation, suggesting the pathological diagnosis in these cases might be incorrect. In addition, careful interpretation was required when the paired tumors harboring frequent mutation including TP53 or EGFR because such mutation may match accidentally. [Conclusion] Our findings suggest that multiplex mutational analysis of synchronous or metachronous MLC could complement the pathological diagnosis in differentiation whether MP or IM. In the cases with pathologically equivocal or those with discordant between pathological diagnosis and mutational evaluation, the frequency and the number of matched mutation may be helpful for the differentiation. Citation Format: Yuta Takahashi, Kazuhiko Shien, Shuta Tomida, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Takahiro Yoshioka, Hidejiro Trigoe, Hiroki Sato, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka. Comparative mutational evaluation for multiple lung cancer by multiplex oncogene mutation analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3680.

Bilateral synchronous multiple lung nodules: Surgical experience from two cases

Synchronous multiple lung cancer (SMPLC) has been increasingly detected as a result of improved imaging techniques, though the incidence of SMPLC is rare. Surgery is currently the only treatment offering potential cure and long-term survival in patients with SMPLC, and complete resection is widely accepted as the first choice of procedure for this type. However, due to the rarity of this clinical scenario, many surgeons lack experience in surgical treatment of SMPLC. Here, we present two cases whose SMPLC was successfully managed with aggressive surgical therapy through video-assisted thoracoscopic surgery.

Synchronous bilateral lung adenocarcinomas associated with vulvar rhabdomyosarcoma in a 15-year-old girl

Abstract Pediatric malignancies are thought to be risk factors of second malignant neoplasms. However, lung cancer associated with rhabdomyosarcoma is extremely rare. When multiple pulmonary lesions are observed in cancer patients, resection is necessary to distinguish them from metastatic lesions. We report an extremely rare case of synchronous bilateral multiple lung cancers showing ground glass nodules (GGNs) associated with rhabdomyosarcoma in a 15-year-old girl with vulvar rhabdomyosarcoma. When we identify GGNs in adolescents with a history of rhabdomyosarcoma, we should consider lung cancer as a differential diagnosis in addition to pulmonary metastasis usually showing solid nodule. In the present case with tiny lesions, surgical resection using lipiodol-marking helped to ensure both an early diagnosis and curative treatment.

The Value of Prognostic Factors for Survival in Synchronous Multifocal Lung Cancer: A Retrospective Analysis of 164 Patients

We reviewed patients treated for synchronous multifocal lung cancers (SMLCs) to analyze outcomes and evaluate valuable prognostic factors. From January 2010 to June 2016, 3,031 patients underwent lung cancer resection at Jinling Hospital and Suzhou Hospital affiliated to Nanjing Medical University, and 164 (5.4%) had SMLC. The Kaplan-Meier method was used for survival analysis, and a multivariable Cox proportional hazards regression model was used for identification of independent survival predictors. The overall survival and progression-free survival rates with SMLC were 72.6% and 61.0%, respectively. A statistically significant difference existed for overall survival and progression-free survival between synchronous multiple primary lung cancer and intrapulmonary metastases according to Martini criteria. There was no statistical difference among the subgroups categorized by the TNM classification. Furthermore, small tumor size showed a benefit for overall survival and progression-free survival. Patients whose tumors were 0.8 cm or smaller had a 5-year survival rate of 100%. Tumor size, lymphatic metastases, and histologic differentiation were identified by univariate and multivariate regression analysis as independent survival predictors. Survival of patients with SMLC is strongly correlated with the tumor size, differentiation, and lymphatic metastases but not with clinical TNM stage. The Martini criteria based on histologic subtyping has certain predictive value to survival. In comparison, tumor size is of greater value for prognosis. Both of the criteria above are much better than the TNM classification. The 5-year survival rate of 100% in patients with tumors sized 0.8 cm or smaller is extremely valuable for predicting survival after surgical resection.

123 Distinct Molecular Mutations in Synchronous Lung Cancers

123 Distinct Molecular Mutations in Synchronous Lung Cancers

P2.16-020 Surgical Strategy for Synchronous Multiple Lung Cancer with Ground Glass Opacity

With the recent advances of diagnostic imaging modalities such as high-resolution computed tomography (HRCT), the detection rate of multiple synchronous lung cancer with ground-glass opacity (GGO) has increased. In clinical practice, preoperative pathological diagnosis of GGO lesions by transbronchial biopsy is difficult. It is necessary to develop the optimal surgical strategy that achieves both accurate diagnosis and curative resection. We recently encountered three cases of synchronous multiple lung cancer with GGO.