Systematic Pan-Cancer Population-Based Analysis Reveals the Incidence and Prognosis of Lung Metastases at Diagnosis

Abstract

Background. Metastasis is one of the most prevalent causes of death in cancer patients and the lungs are among the organs most commonly affected by metastasis. However, analysis of the incidence and prognosis of lung metastasis (LM) based on primary cancer sites is lacking. Methods. We enrolled cancer patients with LM from the Surveillance, Epidemiology, and End Results (SEER) database. The risk factors for LM were determined using multivariate logistics regression. Forest plots were used to compare the impact of with LM versus without LM alone among different primary caner site subgroups. Results. Among 1,525,441 cases, 47,537 presented with LM at initial diagnosis. Multivariate logistics regression revealed that male sex, older age, later T/N stage, unmarried status, and lack of insurance were risk factors for LM. The incidence of LM was 11.91% in bone cancer and 11.19% in pancreatic cancer. In terms of the distribution of primary cancers, 19.22% of LMs originated from the colon and rectum, with 11.63% from the kidneys. The median survival for LM cases was 6 months, with the best survival in testicular cancer (19 months) and bone cancer (12 months). Patients with LM had higher hazard ratio (HR) for mortality compared to those without LM, except for those with primary cancer in the brain ( P = 0.09 ). We stratified patients by primary cancer site, and subgroup analyses showed that LM had a significant negative impact on survival. The most significant was in thyroid cancer (HR = 44.79), followed by melanoma (HR = 24.26), prostate (HR = 16.0), breast (HR = 13.46), endometrial (HR = 12.64), testicular (HR = 12.31), and kidney (HR = 11.33) cancer (all P < 0.001 ). Conclusion. Patients presenting with LM had higher HR for mortality compared to those without LM, except for those with brain tumor. Clinicians should pay more attention to the occurrence of LM, especially in patients with a significantly increased HR for mortality, such as those with thyroid cancer, melanoma, and prostate cancer.

Analysis of prognostic factors of metastatic endometrial cancer based on surveillance, epidemiology, and end results database

“…Lymph node metastasis is the most common type of metastasis (17). Distant organ metastasis is rare (18). Early and accurate diagnosis is particularly important to establish the best treatment plan and prognosis.…”

Ongoing Replication Stress Response and New Clonal T Cell Development Discriminate Between Liver and Lung Recurrence Sites and Patient Outcomes in Pancreatic Ductal Adenocarcinoma

“…Previous efforts to dissect PDAC tumors into subtypes used unbiased approaches with gene expression, proteomics, or metabolomics data to describe mutually exclusive subsets and defining signatures 25,26,28,29,31,33 . We approached the problem differently by classifying tumors based on a well-known clinical outcome associated with metastatic organotropism; specifically, longer-term survival among patients with lung-avid, liver-averse disease and poor outcomes with liver-avid disease 14–16,63 . We generated two new large datasets obtained from only patients with proven adenocarcinoma in the pancreas or Ampulla of Vater tumors that were histologically pancreaticobiliary: 1) a 290 specimen RNA-seq dataset with genomic alterations from tumor-enriched regions from primary and metastatic tumors and 2) TCRB sequencing of 289 blood and 175 matched tumor samples, mostly overlapping with the RNA-seq dataset.…”

“…Previous efforts to dissect PDAC tumors into subtypes used unbiased approaches with gene expression, proteomics, or metabolomics data to describe mutually exclusive subsets and defining signatures 25,26,28,29,31,33 . We approached the problem differently by classifying tumors based on a wellknown clinical outcome associated with metastatic organotropism; specifically, longer-term survival among patients with lung-avid, liver-averse disease and poor outcomes with liver-avid disease [14][15][16]63 .…”

“…Of the ~20% of patients eligible for potentially curative resection of the primary tumor, only 30-35% survive >5 years. However, a subset of PDAC patients (~10%) who develop lung metastases survive significantly longer than patients with metastatic spread to other sites [14][15][16][17] ; in some cases, these patients survive >5 years with untreated, indolent lung metastases 18 . Patients with lung-restricted metastatic PDAC typically have slowly progressing disease, and may benefit from a metastatectomy 19 .…”

The different clonal origins of metachronous and synchronous metastases

“…LPR was calculated for each patient by arranging all metastases in a rising order of diameters and grouping all metastases with similar diameter (with diameter difference ≤ 1 mm on axial chest CT) into a single cluster. The LPR was then calculated with the aid of a computer code (available in supplementary material S2) using the formula: LPR = (∑ c − ∑ i )/(∑ c + ∑ i ) where “c” is the sum number of metastases that can be clustered metastases and “i” the sum number of isolated metastases (Liang et al 2021 ). LPR ≤ 0 suggests dominance of the parallel spreading pathway and LPR > 0 suggests dominance of the linear pathway.…”