Metastatic dissemination patterns of different primary tumors to the spine and other bones

Onken, Julia; Fekonja, Lucius S.; Wehowsky, Romy; Hubertus, Vanessa; Vajkoczy, Peter

doi:10.1007/s10585-019-09987-w

Cited by 27 publications

(29 citation statements)

References 31 publications

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“…These results suggest that the mechanism of organotropic metastasis is clearly different. Our results suggest that loss of adherens junction integrity, which is generally accepted as the rst step in PM formation, is more important in PM than in metastases to other sites such as bone, which occurs mostly through hematogenous spreading [24].…”

Section: Discussionmentioning

confidence: 69%

Clinical Significance of CLDN18.2 Expression in Diffuse-Type Metastatic Gastric Cancer

Kim

Shin

Park

et al. 2020

Preprint

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Background Isoform 2 of the tight junction protein claudin-18 (CLDN18.2) is a potential target of gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC).Methods We evaluated CLDN18.2, RhoGAP, and E-cadherin expression by performing two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line, platinum-based chemotherapy between March 2015 and February 2017.Results CLDN18.2 and E-cadherin expression was significantly reduced in patients with peritoneal metastasis (PM) compared with those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), while it was significantly higher in patients who never exhibited PM from diagnosis to death than in those who did (p=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin were expressed at significantly higher levels in patients with bone metastasis than in those without it (p=0.010 and 0.001, respectively). We identified a positive correlation between the expression of CLDN18.2 and E-cadherin (p < 0.001), RhoGAP and CLDN18.2 (p=0.004), and RhoGAP and E-cadherin (p=0.001). CDLN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival.Conclusions CLDN18.2 expression was reduced in PM but significantly intact in bone metastasis. Furthermore, a positive correlation was identified between the expression of CLDN18.2 and other adherens junction molecules, which has clinical implications for mDGC and PM pathogenesis.

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Section: Discussionmentioning

confidence: 69%

Clinical Significance of CLDN18.2 Expression in Diffuse-Type Metastatic Gastric Cancer

Kim

Shin

Park

et al. 2020

Preprint

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“…Several concepts regarding the prognosis of HR+/HER2-metastatic patients have been considered important in evaluating survival after recurrence [11], and the current study was performed based on post-recurrent characteristics, especially the metastatic site. Previous studies have shown that first metastatic sites (single, multiple, liver, or other visceral metastases) are significantly related to survival after recurrence in HR+/HER2-patients [10][11][12][13], but there has been clinical diversity in the metastatic distribution patterns of both single metastasis and multiple metastases [25][26][27]. Therefore, we studied the prognosis of HR+/HER2-patients with single and multiple metastases separately.…”

Section: Discussionmentioning

confidence: 99%

“…Metastatic breast cancer represents a biologically heterogeneous population with diverse metastatic patterns exhibiting highly unpredictable clinical behaviors [25][26][27]. Prognosis varies significantly among patient subtypes [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Multiple metastases are considered a poor prognostic factor [10][11][12][13][14][15][16][17][18]. The prognosis of patients with multiple metastases may vary with the metastatic organ sites due to the heterogeneity [25][26][27], but there has been no report investigating prognosis by each relevant metastatic site involved in multiple metastases. In the current study, multiple metastases not involving liver or brain metastasis had no significant relationship with prognosis after recurrence, whereas multiple metastases including liver or brain metastasis was a strong independent prognostic factor for worse outcomes in HR+/HER2patients.…”

Section: Discussionmentioning

confidence: 99%

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New insights into patterns of first metastatic sites influencing survival of patients with hormone receptor-positive, HER2-negative breast cancer: a multicenter study of 271 patients

Yamamura

Kamigaki

Fujita

et al. 2020

Preprint

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Background: The initial therapeutic strategy for hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer is based on the first metastatic site, but little evidence is available regarding the influence of metastatic distribution patterns of first metastatic sites on prognosis. In this study, we aimed to identify the metastatic distribution patterns of first metastatic sites that significantly correlate with survival after recurrence. Methods: We performed a retrospective review of records from 271 patients with recurrent metastatic HR+/ HER2- breast cancer diagnosed between January 2000 and December 2015. We assessed survival after recurrence according to the metastatic distribution patterns of first metastatic sites and identified significant prognostic factors among the patients with single and multiple metastases. Results: Prognosis was significantly better in patients with single metastasis than those with multiple metastases (median overall survival after recurrence: 5.86 years vs. 2.50 years, p<0.001). No metastatic organ site with single metastasis was significantly associated with prognostic outcome, though single metastasis with diffuse lesions was an independent risk factor for worse prognosis (HR: 3.641; 95% CI: 1.856-7.141), and more easily progressed to multiple metastases (p=0.002). Multiple metastases including liver metastasis (HR: 3.145; 95% CI: 1.802-5.495) or brain metastasis (HR: 3.289; 95% CI: 1.355-7.937) were regarded as a significant independent poor prognostic factor, but multiple metastases not involving liver or brain metastasis were not significantly related to prognosis after recurrence. Conclusions: Single metastasis with diffuse lesions could more easily disseminate systemically and progress to multiple metastases, leading to poor prognosis similar to multiple metastases. The metastatic distribution patterns of first metastatic sites may be important clinical clues for achieving optimal initial treatment for recurrent metastatic HR+/HER2- breast cancer. Our findings indicate that reconsideration of the determinant factors of therapeutic strategies for first recurrence may be needed.

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“…Die Zeitspanne von der initialen Tumordiagnose bis zur Entwicklung einer metastatischen Wirbelsäule beträgt in 50 % der Fälle ein Jahr, mit einem zweiten Gipfel nach 5 Jahren (knapp 20 %). Verzögerte Metastasen im Bereich der Wirbelsäule nach > 5 Jahren beobachtet man beim Mammakarzinom, Melanom, Prostatakarzinom und Nierenzellkarzinom [2].…”

Section: Introductionunclassified

In Zukunft werden Spinale Metastasen nur noch in Tumorzentren versorgt: Pro

Vajkoczy

2020

Die Wirbelsäule

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ZusammenfassungIn den vergangenen Jahren beobachten wir einen zunehmenden Anstieg in der Inzidenz metastatischer Absiedlungen in die Wirbelsäule. Dies liegt an der zunehmenden Kontrolle der Primärtumoren durch fortgeschrittene operative und effektivere, adjuvante Therapiemaßnahmen. Mit zunehmendem Erfolg und zunehmender Komplexität der Behandlung onkologischer Primärfälle innerhalb von zertifizierten Tumorzentren erfolgt die Behandlung dieser Patienten zunehmend regionalisiert/zentralisiert. Im Falle von sekundären Absiedlungen in die Wirbelsäule/spinaler Metastasierung steht damit das flächendeckende Angebot wirbelsäulenchirurgischer Institutionen und die zentralisierte Behandlung onkologischer Fälle in Tumorzentren in zunehmendem Widerspruch. Hier werden die Argumente für eine Zentralisierung der chirurgischen Versorgung spinaler Metastasen in Zentren der spinalen Maximalversorung mit Anschluss an onkologische Spitzenzentren zusammengefasst.

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Metastatic dissemination patterns of different primary tumors to the spine and other bones

Cited by 27 publications

References 31 publications

Clinical Significance of CLDN18.2 Expression in Diffuse-Type Metastatic Gastric Cancer

Clinical Significance of CLDN18.2 Expression in Diffuse-Type Metastatic Gastric Cancer

New insights into patterns of first metastatic sites influencing survival of patients with hormone receptor-positive, HER2-negative breast cancer: a multicenter study of 271 patients

In Zukunft werden Spinale Metastasen nur noch in Tumorzentren versorgt: Pro

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