OBJECTIVE: Our purpose is to evaluate the patterns of organ metastasis and the prognosis in lung adenosquamous carcinoma patients with organ metastasis.
METHODS: We collected the data from the surveillance epidemiology and end results database, covering the period of 2000-2018. Cox regression, Kaplan-Meier and log-rank analyses were performed.
RESULTS: Totally, 2698 patients were enrolled, comprising 851 (31.54%) patients diagnosed with organ metastasis and 2017 (68.46%) patients without organ metastasis. Patients with distant organ metastasis show a significant decrease in median overall survival. In addition to the aforementioned factors, age over 70 years, male, main bronchus, advanced T stage, larger tumour size, absence of primary tumour surgery and lack of radiotherapy have all been identified as prognostic indicators associated with a poorer outcome. In terms of treatment options, patients with organ metastasis can benefit from chemotherapy and primary tumour surgery. Moreover, in patients with organ metastasis, those who received a combination treatment of surgery, chemotherapy and radiotherapy displayed the most favourable prognosis, with a median overall survival of 17 months.
CONCLUSIONS: We identified the prognostic indicators for organ metastasis in patients with lung adenosquamous carcinoma. Highly selected patients who undergo a combination treatment of surgery, chemotherapy and radiotherapy may experience the greatest survival benefit.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally. Metastasis is associated with a poor prognosis, yet the underlying molecular mechanism(s) remained largely unknown. In this study, a total of 85 CRC patients were included and the primary tumor lesions were evaluated by next-generation sequencing using a targeted panel for genetic aberrations. Patients were sub-divided according to their metastasis pattern into the non-organ metastases (Non-OM) and organ metastases (OM) groups. By comparing the genetic differences between the two groups, we found that mutations in FBXW7 and alterations in its downstream NOTCH signaling pathway were more common in the Non-OM group. Moreover, correlation analysis suggested that FBXW7 mutations were independent of other somatic alterations. The negative associations of alterations in FBXW7 and its downstream NOTCH signaling pathway with CRC organ metastasis were validated in a cohort of 230 patients in the TCGA CRC dataset. Thus, we speculated that the genomic alterations of FBXW7/NOTCH axis might be an independent negative indicator of CRC organ metastases.

UNASSIGNED: The incidence rate of lung large cell neuroendocrine carcinoma (LCNEC) in lung cancer is low, but the malignancy is high and the prognosis is poor. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine the population distribution of organ metastasis in LCNEC, conduct survival analysis, judge prognostic factors, and provide direction for follow-up diagnosis and treatment.
UNASSIGNED: By logging into the SEER database, the data of lung LCNEC were retrieved and the target population was selected. According to the presence or absence of organ metastasis (bone, brain, liver, and lung), we divided the target population into the no organ metastasis group (n = 1,202) and the organ metastasis group (n = 870). By analyzing the clinicopathological data of patients and using the survival function, the corresponding median survival time was obtained, and the influencing factors of each group were analyzed. Then, the significant influencing factors were analyzed by multivariate Cox regression analysis to screen out the independent influencing factors.
UNASSIGNED: In the overall sample group, multivariate Cox regression analysis showed that sex, age, primary site surgery, bone metastasis, brain metastasis, liver metastasis, radiotherapy, and chemotherapy were independent prognostic factors. The 1-year survival rate was 13.8% in the bone metastasis group, 19.1% in the brain metastasis group, 13.8% in the liver metastasis group, and 20.3% in the intrapulmonary metastasis group. In the organ metastasis group, multivariate Cox regression analysis showed that sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age at diagnosis were independent factors affecting the prognosis.
UNASSIGNED: In the overall sample of LCNEC, bone metastasis, brain metastasis, and liver metastasis all reduced the overall survival time, while the effect of intrapulmonary metastasis on the overall survival time was not statistically significant. Sex, chemotherapy, radiotherapy sequence with surgery, primary site surgery, liver metastasis, and age were independent factors affecting the prognosis of the LCNEC organ metastasis group. Women, chemotherapy, and radiotherapy sequence with surgery were favorable factors, while old age, liver metastasis, and male were unfavorable factors.

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 or Akt2 dramatically decreased metastatic colonization of lungs by inducing apoptosis or inhibiting invasion, respectively. Importantly, transient pharmacologic inhibition of Akt activity with MK-2206 or AZD5363 inhibitors did not prevent colonization of lung tissue by TNBC cells. Knockdown of AMPKα1, AMPKα2, or AMPKα1/2 also had no effect on metastatic colonization of lungs. Taken together, these findings demonstrate that transient decrease in AMPK isoforms expression alone or in combination with Akt1 in circulating tumor cells does not synergistically reduce TNBC metastatic lung colonization. Our results also provide evidence that Akt1 and Akt2 expression serve as a bottleneck that can challenge colonization of lungs by TNBC cells.

UNASSIGNED: The aim of this study was to investigate the potential associations of the sites and the number of specific metastases with survival in patients newly diagnosed with cervical cancer.
UNASSIGNED: Medical records of patients with organ metastases of newly diagnosed cervical cancer at Zhejiang Cancer Hospital from October 2006 to December 2016 were reviewed retrospectively. Survival times were compared using the Kaplan-Meier method. Variables associated with survival were identified using univariate and multivariate Cox proportional hazards models.
UNASSIGNED: A total of 99 patients with newly diagnosed organ metastatic cervical cancer were identified. Median follow-up was 11.6 months (range, 0.5-114.7 months). Median overall survival (OS) time was 11.7 months from diagnosis, with 1, 2, and 5-year OS rates of 48.2%, 22.8%, and 12.6%, respectively. The most common site of organ metastasis was bone (36.8%), followed by lung (32.8%) and liver (24%). In univariate analysis, OS rates were better for bone metastasis than visceral metastasis (P=0.013), oligometastasis than non-oligometastasis (P=0.003) and single organ metastasis than multiple organ metastases (P=0.016), while that for liver metastasis was poorer than non-liver metastases (P<0.001). In multivariate analysis, liver metastasis (hazard ratio [HR] =4.02; 95% confidence interval [CI], 1.15-14.05, P=0.029) was significantly and independently related to poor overall survival.
UNASSIGNED: Our data revealed the site of metastasis is associated with overall survival of patients with newly diagnosed organ metastatic cervical cancer, with liver metastasis signifying particularly poor overall survival. Individualized treatments should be administered to patients depending on the specific metastatic sites.

BACKGROUND: The clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer.
METHODS: We retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival.
RESULTS: A total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6-114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort.
CONCLUSIONS: In this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.

The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).