Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients

Bubendorf, Lukas; Alain, S.; Wagner, Urs; Sauter, Guido; Moch, Holger; Willi, Niels; Gasser, Thomas C.; Mihatsch, Michael J.

doi:10.1053/hp.2000.6698

Cited by 1,582 publications

(1,161 citation statements)

References 17 publications

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“…2,3,22,23 In addition, autopsies of patients dying of prostate cancer indicated that up to 90% had evidence of metastatic bone disease. 24 Our results indicated that having a bone metastasis was associated with mortality among men with prostate cancer. The association appeared to be stronger for bone metastasis complicated by SRE than for bone metastasis without SRE.…”

Section: Discussionmentioning

confidence: 54%

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Sathiakumar

Delzell

Morrisey

et al. 2011

Prostate Cancer Prostatic Dis

193

148

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Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having bone metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with bone metastasis with or without SRE, compared with men without bone metastasis. Among 126 978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had bone metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with bone metastasis. HRs for risk of death were 6.6 (95% CI ¼ 6.4-6.9) and 10.2 (95% CI ¼ 9.8-10.7), respectively, for men with bone metastasis but no SRE and for men with bone metastasis plus SRE, compared with men without bone metastasis. Bone metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for bone metastasis plus SRE than for bone metastasis without SRE.

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Section: Discussionmentioning

confidence: 54%

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Sathiakumar

Delzell

Morrisey

et al. 2011

Prostate Cancer Prostatic Dis

193

148

View full text Add to dashboard Cite

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“…We also discovered a significant correlation between ERK5 cytoplasmic expression and the presence of bone metastases (P ¼ 0.0044), a key cause of morbidity (Bubendorf et al, 2000;Rubin et al, 2000). It is therefore of interest that IL-6, a cytokine previously implicated in bony metastasis (Okamoto et al, 1997;Adler et al, 1999), was found to activate ERK5 function in multiple myeloma cells (Carvajal-Vergara et al, 2005).…”

Section: Discussionmentioning

confidence: 59%

Aberrant expression of extracellular signal-regulated kinase 5 in human prostate cancer

et al. 2007

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Abnormal intracellular signaling contributes to carcinogenesis and may represent novel therapeutic targets. mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) overexpression is associated with aggressive prostate cancer. In this study, we examined the role of extracellular signal-regulated kinase (ERK5, an MAPK and specific substrate for MEK5) in prostate cancer. ERK5 immunoreactivity was significantly upregulated in high-grade prostate cancer when compared to benign prostatic hyperplasia (Po0.0001). Increased ERK5 cytoplasmic signals correlated closely with Gleason sum score (Po0.0001), bony metastases (P ¼ 0.0044) and locally advanced disease at diagnosis (P ¼ 0.0023), with a weak association with shorter disease-specific survival (P ¼ 0.036). A subgroup of patients showed strong nuclear ERK5 localization, which correlated with poor diseasespecific survival and, on multivariant analysis, was an independent prognostic factor (Po0.0001). Analysis of ERK5 expression in matched tumor pairs (before and after hormone relapse, n ¼ 26) revealed ERK5 nuclear expression was significantly associated with hormoneinsensitive disease (P ¼ 0.0078). Similarly, ERK5 protein expression was increased in an androgen-independent LNCaP subline. We obtained the following in vitro and in vivo evidence to support the above expression data: (1) cotransfection of ERK5wt and MEK5D constructs in PC3 cells results in predominant ERK5 nuclear localization, similar to that observed in aggressive clinical disease; (2) ERK5-overexpressing PC3 cells have enhanced proliferative, migrative and invasive capabilities in vitro (Po0.0001), and were dramatically more efficient in forming tumors, with a shorter mean time for tumors to reach a critical volume of 1000 mm 3 , in vivo (Po0.0001); (3) the MEK1 inhibitor, PD184352, blocking ERK1/2 activation at low dose, did not suppress proliferation but did significantly decrease proliferation at a higher dose required to inhibit ERK5 activation. Taken together, our results establish the potential importance of ERK5 in aggressive prostate cancer.

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“…Each year, nearly 20,000 new cases of spinal metastases are diagnosed in North America with an annual prevalence of around 100,000 cases 2, 3, 4. Bone metastases are common in many different solid tumors with up to 90 percent of patients with breast or prostate cancer having osseous disease in autopsy studies 5, 6. Pathologic fractures in the spine from metastases are painful and debilitating resulting in poor quality of life, which is an important consideration in the setting of recent life‐prolonging advances in systemic treatment for metastatic disease 7, 8, 9, 10.…”

Section: Introductionmentioning

confidence: 99%

Volumetric modulated arc therapy treatment planning of thoracic vertebral metastases using stereotactic body radiotherapy

Mallory

Pokhrel

Badkul

et al. 2018

J Applied Clin Med Phys

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Purpose/ObjectivesTo retrospectively evaluate the plan quality, treatment efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for thoracic spine metastases using stereotactic body radiotherapy (SBRT).Materials/MethodsSeven patients with thoracic vertebral metastases treated with noncoplanar hybrid arcs (NCHA) (1 to 2 3D‐conformal partial arcs +7 to 9 IMRT beams) were re‐optimized with VMAT plans using three coplanar arcs. Tumors were located between T2 and T7 and PTVs ranged between 24.3 and 240.1 cc (median 48.1 cc). All prescriptions were 30 Gy in 5 fractions with 6 MV beams treated using the Novalis Tx linac equipped with high definition multileaf collimators (HDMLC). MR images were fused with planning CTs for target and OAR contouring. Plans were compared for target coverage using conformality index (CI), homogeneity index (HI), D90, D98, D2, and Dmedian. Normal tissue sparing was evaluated by comparing doses to the spinal cord (Dmax, D0.35, and D1.2 cc), esophagus (Dmax and D5 cc), heart (Dmax, D15 cc), and lung (V5 and V10). Data analysis was performed with a two‐sided t‐test for each set of parameters. Dose delivery efficiency and accuracy of each VMAT plan was assessed via quality assurance (QA) using a MapCHECK device. The Beam‐on time (BOT) was recorded, and a gamma index was used to compare dose agreement between the planned and measured doses.Results VMAT plans resulted in improved CI (1.02 vs. 1.36, P = 0.05), HI (0.14 vs. 0.27, P = 0.01), D98 (28.4 vs. 26.8 Gy, P = 0.03), D2 (32.9 vs. 36.0 Gy, P = 0.02), and Dmedian (31.4 vs. 33.7 Gy, P = 0.01). D90 was improved but not statistically significant (30.4 vs. 31.0 Gy, P = 0.38). VMAT plans showed statistically significant improvements in normal tissue sparing: Esophagus Dmax (22.5 vs. 27.0 Gy, P = 0.03), Esophagus 5 cc (17.6 vs. 21.5 Gy, P = 0.02), and Heart Dmax (13.1 vs. 15.8 Gy, P = 0.03). Improvements were also observed in spinal cord and lung sparing as well but were not statistically significant. The BOT showed significant reduction for VMAT, 4.7 ± 0.6 min vs. 7.1 ± 1 min for NCHA (not accounting for couch kicks). VMAT plans demonstrated an accurate dose delivery of 95.5 ± 1.0% for clinical gamma passing rate of 3%/3 mm criteria, which was similar to NCHA plans.Conclusions VMAT plans have shown improved dose distributions and normal tissue sparing compared to NCHA plans. Significant reductions in treatment time could potentially minimize patient discomfort and intrafraction movement errors. VMAT planning for SBRT is an attractive option for the treatment of metastases to thoracic vertebrae, and further investigation using alternative fractionation schedules is warranted.

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Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients

Cited by 1,582 publications

References 17 publications

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Aberrant expression of extracellular signal-regulated kinase 5 in human prostate cancer

Volumetric modulated arc therapy treatment planning of thoracic vertebral metastases using stereotactic body radiotherapy

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