Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations

BackgroundWith the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.MethodsMedical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.ResultsA total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions >20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.ConclusionsA high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.

Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

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.

Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update

Multi-locus Inherited Neoplasia Allele Syndrome (MINAS) refers to individuals with germline pathogenic variants in two or more cancer susceptibility genes(CSGs). With increased use of exome/genome sequencing it would be predicted that detection of MINAS would become more frequent. Here we review recent progress in knowledge of MINAS. A systematic literature search for reports of individuals with germline pathogenic variants in 2 or more of 94 CSGs was performed. In addition, participants with multiple primary tumours who underwent genome sequencing as part of the Rare Disease arm of the UK 100,000 Genomes Project were interrogated to detect additional cases. We identified 385 MINAS cases (211 reported in the last 5 years, 6 from 100,000 genomes participants). Most (287/385) cases contained at least one pathogenic variant in either BRCA1 or BRCA2. 108/385 MINAS cases had multiple primary tumours at presentation and a subset of cases presented unusual multiple tumour phenotypes. We conclude that, as predicted, increasing numbers of individuals with MINAS are being have been reported but, except for individuals with BRCA1/BRCA2 MINAS, individual CSG combinations are generally rare. In many cases it appears that the clinical phenotype is that which would be expected from the effects of the constituent CSG variants acting independently. However, in some instances the presence of unusual tumour phenotypes and/or multiple primary tumours suggests that there may be complex interactions between the relevant MINAS CSGs. Systematic reporting of MINAS cases in a MINAS database (e.g. https://databases.lovd.nl/shared/diseases/04296) will facilitate more accurate prognostic predictions for specific CSG combinations.

Multiple Primary Malignancies in Patients with Gynecologic Cancer

Objective: To investigate the prevalence and oncologic outcomes of patients with multiple primary malignant tumors (MPMT) with gynecologic cancer. Methods: This retrospective study included 1929 patients diagnosed with gynecologic cancer at a tertiary medical center between August 2005 and April 2021. The clinical data included cancer location, age at primary malignancy diagnosis, interval between primary and secondary cancer, stage of cancer, family history of cancer, genetic testing, dates of last follow-up, recurrence, and death. Results: The prevalence of MPMT with gynecologic cancer in patients was 8.6% and the mean diagnostic period between primary and secondary cancer was 60 months. Furthermore, 20 of the 165 patients with MPMT had multiple primary gynecologic cancers (MPGC), whereas 145 had gynecologic cancer coexisting with non-gynecologic cancer (GNC). Endometrial-ovarian cancer (60%) was the most common coexisting cancer in the MPGC group, whereas the most common non-gynecologic cancer in the GNC group was breast cancer (34.5%). There were 48 patients with synchronous cancer and 117 patients with metachronous cancer. The incidence of synchronous cancer was higher in the MPGC group than in the GNC group (p = 0.037). Significantly more patients had early-stage ovarian cancer in the MPGC group than in the GNC group (p = 0.031). The overall recurrence and mortality rates were 15.8% and 8.5%, respectively, in patients with MPMT. Conclusion: Synchronous cancer incidence was significantly higher in the MPGC than in the GNC group. Early-stage ovarian cancer was more highly diagnosed in patients with MPGC than in those with GNC. A systematic examination after primary cancer diagnosis could facilitate the early diagnosis of secondary primary malignancy, thereby improving patient prognosis.

Clinicopathologic Characteristics and Outcomes of Simultaneous Multiple Primary Lung Cancer

Background. Simultaneous multiple primary lung cancer has been detected increasingly nowadays with the development of image technology. However, the clinicopathologic characteristics and outcomes are not clear. Methods. All consecutive patients diagnosed as simultaneous multiple primary lung cancer according to Martini–Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 in our center were enrolled. The clinicopathologic characteristics and outcomes were compared between patients with the same histological type and different histological types. Results. A total of 336 patients were enrolled, consisting of 297 (88.4%) patients with the same histological type and 39 (11.6%) patients with different histological types. Compared to patients with the same histological type, patients with different histological types were more commonly males (87.2% vs. 34.0%; p < 0.001 ) with an older age (65 [62–69] vs. 59 [52–65] yrs; p < 0.001 ) at diagnosis. Also, patients with different histological types showed worse respiratory function and more advanced stage according to TNM staging. The 1-, 2-, and 3-year overall survival of overall patients was 97.7%, 96.1%, and 92.2%, and the 1-, 2-, and 3-year recurrence-free survival of overall patients was 96.8%, 92.9% and 85.7%, respectively. Importantly, patients with different histological types showed worse overall survival ( p < 0.001 ) and recurrence-free survival ( p = 0.002 ) than patients with same histological type. The multivariable Cox proportional hazard model revealed that presence of different histological types was significant predictor for worse overall survival (adjusted hazard ratio: 10.00; 95% confidence interval: 2.92–34.48; p < 0.001 ) and recurrence-free survival (adjusted hazard ratio: 2.59; 95% confidence interval: 1.14–5.88; p = 0.023 ). Conclusions. Although relatively less common in simultaneous multiple primary lung cancer, patients with different histological types showed worse clinical characteristics and outcomes.

Multiple Primary Cancer and Survival after Lumpectomy with or without Radiotherapy for Ductal Carcinoma in Situ: A Propensity- Score-Matching Study

Background: Radiotherapy combined with breast-conserving surgery is widely performed in patients with ductal carcinoma in situ (DCIS). This research was conducted to evaluate the use of radiotherapy to reduce the risk of multiple primary cancer (MPC) and mortality in DCIS patients.Methods: 108,416 patients first diagnosed with DCIS between 1998 and 2015 who received lumpectomy in the Surveillance, Epidemiology, and End Results (SEER) 18 database were included. Age, race, year of diagnosis, laterality, pathologic grade, surgery, radiation, estrogen receptor status, progesterone receptor status, tumor size and vital status were extracted. A comparison of lumpectomy vs. lumpectomy plus radiotherapy was performed using 1:1 propensity score-based matching.Results: Of the 108,416 patients, 39,039 patients were treated with lumpectomy alone, and 69,377 were treated with lumpectomy and radiotherapy. The adjusted hazard ratio (HR) for death was 0.801 and 0.7444 for occurrence of MPC in the lumpectomy and radiotherapy vs. lumpectomy alone groups, respectively. Conclusion: Lumpectomy plus radiotherapy is associated with a significant reduction in mortality and risk of MPC, mainly second primary BC. Younger patients, Black women with high-grade tumors were likely to benefit most. Radiotherapy reduced the risk of occurrence rather than the mortality of MPC patients to reduce the overall mortality.