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Metastasis Pattern and Survival Analysis in Primary Small Bowel Adenocarcinoma: A SEER-Based Study.

ABSTRACT: Background: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal tumor with high malignancy. The aim of this study was to comprehensively evaluate the distant metastasis pattern and establish nomograms predicting survival for SBA. Methods: From 2010 to 2015, patients diagnosed with SBA were identified based on the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was applied to compare survival differences between metastasis patterns. Then, univariate and multivariate cox analyses were applied to screened out independent prognostic factors of cancer-specific survival (CSS) and overall survival (OS), and identify the risk factors for metastasis of SBA. To assess the discrimination and calibration of nomograms, the concordance index (C-index), calibration curves, receiver-operating characteristic curve (ROC), and decision curve analysis (DCA) were calculated. Results: Kaplan-Meier curves revealed that metastasis patterns were significantly correlated with CSS (p < 0.001) and OS (p < 0.001). Then, the metastasis pattern was showed to be an independent prognostic factor of OS and CSS in patients with SBA, as well as age, grade, T stage, N stage, surgery, retrieval of regional lymph nodes, and chemotherapy. Combining these factors, we constructed prognostic nomograms, which suggested that the metastasis pattern made the greatest contribution to the survival of patients with SBA. Nomograms for OS and CSS had a C-index of 0.787 and 0.793, respectively. Calibration curves showed an excellent agreement between probability and actual observation in the training and validation cohort. Decision curve analysis also exhibited its clinical value with an improved net benefit. In addition, the models we constructed had better prognostic accuracy and clinical utility than traditional TNM staging based on C-index and ROC. Further, Cox regression analysis showed that old age, poor differentiation, N2, and not receiving chemotherapy were the risk factors for prognosis in patients with metastatic SBA. Conclusion: As an independent prognostic factor, the metastasis pattern exhibited the greatest predictive effect on OS and CSS for patients with SBA. Adjuvant chemotherapy had a positive effect on the survival of patients with SBA. Nomograms for predicting 3-and 5-year OS and CSS of patients with SBA were constructed, which could identify patients with higher risk and might be superior in predicting the survival of patients with SBA than TNM staging.

SUBMITTER: Gu Y

PROVIDER: S-EPMC8691381 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The appeal to enroll patients with primary breast and lung cancer in clinical trials is increasing, but survival of these two primary cancers remains to be elucidated. This study analyzed the prognosis of primary breast duct carcinoma with subsequent lung adenocarcinoma (BCLA) and primary breast duct carcinoma with prior lung adenocarcinoma (LABC). Cohorts of 3,515 patients with BCLA and 654 patients with LABC were identified from the Surveillance, Epidemiology, and End Results database. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer (mTPC1), or mTPC2 groups when the interval times between breast and lung cancer were within 6 months, between 7 and 60 months, or over 60 months, respectively. The propensity score matching program (PSM) was applied to determine the survival of BCLA/LABC relative to single breast/lung cancer. Cox proportional hazard regression model and competing risk modes were performed to identify confounders associated with all-cause and cancer-specific death, respectively. Survival of patients with LABC/BCLA relative to single breast/lung cancer was accessed via median survival time. The survival of patients with BCLA/LABC was generally poor compared with the survival of those with single breast cancer. The PSM-estimated HR in the sTPC group with BCLA and in the mTPC1 and mTPC2 groups with LABC were 0.75 (95% CI 0.62-0.90), 0.52 (95% CI 0.27-0.98), and 0.36 (95% CI 0.20-0.65), respectively, whereas the SHRs were 0.80 (95% CI 0.66-0.97), 0.68 (95% CI 0.34-1.34), and 0.46 (95% CI 0.27-0.80), respectively, compared with those in the single lung cancer group. By contrast, the survival rates of the remaining patients did not differ. The median survival times since secondary malignancy were 42, 23, and 20 months in the sTPC, mTPC1, and mTPC2 groups with BCLA, respectively, and 18, 60, and 180 months in those with LABC, respectively. For patients with BCLA, the adjusted Cox regression suggested incidences of all-cause deaths in mTPC1group were statically higher than those in sTPC group, whereas the incidences of all-cause and cancer-specific death in the mTPC1 and mTPC2 groups were statistically lower than those in the sTPC group. The prognosis of patients with breast cancer and subsequent lung cancer of over 18 months was not significantly different than that of single lung cancer, which supported the profound appeal to increase the involvement of these two primary cancers in potential beneficial clinical trials. For patients with lung cancer and prior breast cancer of within 6 months and subsequent breast cancer of over 18 months, prognosis was improved relative to single lung cancer. Therefore, additional attention is needed to eliminate the potential bias may when these patients are recruited in the clinical trials.

Project description:ImportanceSmall-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking.ObjectiveTo perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations.Design, setting, and participantsProspective analysis was performed of clinical samples from patients with SBA (n?=?317), colorectal cancer (n?=?6353), and gastric carcinoma (n?=?889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions.ResultsOf the 7559 patients included in analysis, 4138 (54.7%) were male; the median age was 56 (range, 12-101) years. The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P?<?.001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P?<?.001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P?<?.001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P?<?.001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P?<?.001). BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases. The ERBB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high tumor mutational burden (9.5% [30 of 317]) were all enriched in SBA. Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs. Targetable alterations in several additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also identified in all 3 series.Conclusions and relevanceThis study presents to our knowledge the first large-scale genomic comparison of SBA with colorectal cancer and gastric carcinoma. The distinct genomic differences establish SBA as a molecularly unique intestinal cancer. In addition, genomic profiling can identify potentially targetable genomic alterations in the majority of SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden in SBA suggests a potential role for immunotherapy.

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Metastasis Pattern and Survival Analysis in Primary Small Bowel Adenocarcinoma: A SEER-Based Study.

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