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Durable recurrence-free survival after pneumonectomy for late lung metastasis from rectal cancer: case report with genetic and epigenetic analyses.

ABSTRACT: Treatment of pulmonary recurrence from colorectal cancer involving the main bronchus usually entails palliation using interventional bronchoscopy, because the prognosis is generally very poor. Surgical experience has clarified that in this setting pneumonectomy should only be performed in carefully selected patients showing favorable prognostic profiles (defined by low carcinoembryonic antigen serum levels pre-thoracotomy), solitary and completely resectable pulmonary metastasis, and long disease-free intervals. In the few long-term survivors after pneumonectomy for late-recurrent colorectal cancer, the disease has a relatively indolent metastatic course and genetic and epigenetic profiling may provide further insight regarding tumor evolution.We describe a rare case of late hilar-endobronchial and lymph nodal recurrence of rectal cancer, sequential to hepatic metastasectomy, that we successfully treated with pneumonectomy and chemotherapy (leucovorin, 5-fluorouracil and oxaliplatin regimen); the patient achieved 7-year relapse-free survival after lung metastasectomy and 24-year overall survival after primary rectal cancer resection. To our knowledge, this is the longest survival reported after sequential liver resection and pneumonectomy for recurrent colorectal cancer. In our case the primary rectal cancer and its recurrences showed identical immunohistochemical patterns. The primary rectal cancer and the matched metastases (hepatic, pulmonary and lymph nodal) demonstrated no KRAS, NRAS, BRAF and PIK3CA mutations, a microsatellite stable phenotype, and no tumor protein p53 alterations or recurrent copy number alterations on chromosome 8. High genetic concordances between the paired primary tumor and metastases suggest that the key tumor biological traits remained relatively conserved in the three metastatic sites. Minor differences in gene specific hypermethylation were observed between the primary tumor and lung and nodal metastases. These differences suggest that epigenetic mechanisms may be causally involved in the microenvironmental regulation of cancer metastasis.The exceptionally long survival of the patient in our case study involving favorable clinical features was related to an excellent response to surgery and adjuvant chemotherapy; however, genetic or epigenetic factors that remain unidentified cannot be excluded as contributory factors. Our findings support the concept of a common clonal origin of the primary cancer and synchronous and late metastases, and suggest that aberrant DNA methylation may regulate tumor dormancy mechanisms.

SUBMITTER: Imperatori A

PROVIDER: S-EPMC4522059 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Durable recurrence-free survival after pneumonectomy for late lung metastasis from rectal cancer: case report with genetic and epigenetic analyses.

Imperatori Andrea A Rotolo Nicola N Dominioni Lorenzo L Nardecchia Elisa E Cattoni Maria M Cimetti Laura L Riva Cristina C Sessa Fausto F Furlan Daniela D

BMC cancer 20150801

<h4>Background</h4>Treatment of pulmonary recurrence from colorectal cancer involving the main bronchus usually entails palliation using interventional bronchoscopy, because the prognosis is generally very poor. Surgical experience has clarified that in this setting pneumonectomy should only be performed in carefully selected patients showing favorable prognostic profiles (defined by low carcinoembryonic antigen serum levels pre-thoracotomy), solitary and completely resectable pulmonary metastas ...[more]

PMID: 26231173

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Project description:Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p = 0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p < 0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk.

Project description:BackgroundRectal cancer is usually treated by surgery, but recurrence or metastasis seriously affect the quality of life and survival of patients. Identifying the risk factors for postoperative recurrence or metastasis of rectal cancer has important guiding value for the treatment of rectal cancer. However, the research on risk factors of postoperative recurrence or metastasis of rectal cancer has not been unified.MethodsThe data of all patients undergoing rectal cancer surgery in The Fifth People's Hospital of Shanghai, Fudan University, from 2016 to 2020 were collected and analyzed. A total of 185 patients were included for statistical analysis and were divided into a recurrence or metastasis group and a non-recurrence or metastasis group. Patients were followed up according to National Comprehensive Cancer Network (NCCN) guidelines by enhanced CT or MRI, and colonoscopy. The cut-off of the research was recurrence, metastasis, or death. Logistic regression analysis and Cox regression analysis were used to analyze the risk factors related to postoperative recurrence or metastasis of rectal cancer, and the survival curve was drawn.ResultsMultiple logistic regression analysis showed involvement of the mesorectal fascia (MRF) [OR (odds ratio) =2.9, 95% confidence interval (CI): 1.16-7.29, P=0.023], nerve and vascular invasion (OR =1.7, 95% CI: 1.08-2.59, P=0.022), intraoperative blood transfusion (OR =3.7, 95% CI: 1.45-9.40, P=0.006), and Dukes staging (OR =2.3, 95% CI: 1.26-4.35, P=0.007) were independent risk factors for postoperative recurrence or metastasis of rectal cancer. Involvement of mesenteric fascia infiltration (OR =11.5, 95% CI: 1.49-88.79, P=0.019) and Dukes stage (OR =3.0, 95% CI: 1.46-6.26, P=0.003) were independent risk factors for liver metastasis, while nerve and vascular invasion (OR =2.4, 95% CI: 1.19-5.00, P=0.015) was an independent risk factor for pulmonary metastasis.ConclusionsPostoperative recurrence or metastasis of rectal cancer is related to many factors. These findings have clinical guiding value and significance for the follow up and prognosis of patients with rectal cancer after surgery. Large-scale prospective clinical studies are needed.

Dataset Information

Durable recurrence-free survival after pneumonectomy for late lung metastasis from rectal cancer: case report with genetic and epigenetic analyses.

Publications

Durable recurrence-free survival after pneumonectomy for late lung metastasis from rectal cancer: case report with genetic and epigenetic analyses.

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