[68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients

1001 Background: Metastasis is the main cause of cancer-related death. Single disseminated tumor cells (DTC) can be detected by sensitive immunocytochemical and molecular technologies, but it is still unclear whether these cells are viable and biologically active. Methods: We applied a novel enzyme-linked immunospot assay (‘EPISPOT‘) that reveals a fingerprint of specific proteins secreted from single viable epithelial tumor cells. The membrane of ELISPOT plates were coated with monoclonal antibodies against the tumor-associated marker proteins mucin-1 (MUC1) for breast cancer and prostate-specific antigen (PSA) for prostate cancer. In addition, dual fluorescent EPISPOT assays were developed to characterize MUC1+ and PSA+ cells (i.e. CK19, FGF2 secretion). Results: Even in the absence of overt metastases (stage M0), the EPISPOT assay revealed viable tumor cells in the peripheral blood of 65% of prostate cancer patients (n=31) and the bone marrow of 54% of breast cancer patients (n=37). Respective samples from non-carcinoma controls were EPISPOT- negative, whereas 80 to 100% of samples from metastatic patients (stage M1, n=40) were positive. The number of EPISPOT-positive cells in M0-patients ranged from 2 to 197 in the blood of prostate cancer patients and 1 to 262 in the bone marrow of breast cancer patients, while M1- patients showed significantly higher counts (prostate cancer, 1–684; breast cancer, 4–813). Interestingly, subsets of MUC1- or PSA-secreting cells expressed a breast stem cell-like phenotype (MUC1-/CK19+) or secreted FGF-2 as factor relevant for the growth of DTC, respectively. Conclusions: A significant fraction of cancer patients harbor viable and biologically active tumor cells in their blood and bone marrow, even in the absence of overt metastases. The multiparameter EPISPOT assay helps to identify these putative metastatic precursor cells. No significant financial relationships to disclose.

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Dose to Bone Marrow Using IMRT Techniques in Prostate Cancer Patients

Strahlentherapie und Onkologie ◽

10.1007/s00066-005-1360-4 ◽

2005 ◽

Vol 181 (3) ◽

pp. 172-178 ◽

Cited By ~ 18

Author(s):

Eduard Gershkevitsh ◽

Catharine H. Clark ◽

John Staffurth ◽

David P. Dearnaley ◽

Klaus-Rüdiger Trott

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Patients

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Expression of BCL-2 Oncoprotein and P53 Protein Accumulation in Bone Marrow Metastases of Androgen Independent Prostate Cancer

The Journal of Urology ◽

10.1016/s0022-5347(01)65204-2 ◽

1997 ◽

Vol 157 (2) ◽

pp. 569-574 ◽

Cited By ~ 87

Author(s):

Timothy J. McDonnel ◽

Nora M. Navone ◽

Patricia Troncoso ◽

Louis L. Pisters ◽

Claudio Conti ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

P53 Protein ◽

Protein Accumulation ◽

Bone Marrow Metastases ◽

Androgen Independent

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Prognostic Significance of Disseminated Tumor Cells in the Bone Marrow of Prostate Cancer Patients Treated With Neoadjuvant Hormone Treatment

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.0441 ◽

2008 ◽

Vol 26 (30) ◽

pp. 4928-4933 ◽

Cited By ~ 51

Author(s):

Jens Köllermann ◽

Steffen Weikert ◽

Martin Schostak ◽

Carsten Kempkensteffen ◽

Klaus Kleinschmidt ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Radical Prostatectomy ◽

Hormone Therapy ◽

Cancer Patients ◽

Tumor Cells ◽

Prognostic Significance ◽

Specific Antigen ◽

Disseminated Tumor Cells ◽

Significant Prognostic Factor

Purpose To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy. Patients and Methods Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients’ outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months. Results DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014). Conclusion The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.

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Radiation Induced Bone Marrow Toxicity in Prostate Cancer Patients, Treated With Adjuvant, Salvage or Radical Radiation Therapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2015.07.1143 ◽

2015 ◽

Vol 93 (3) ◽

pp. E236-E237

Author(s):

T.M. Niazi ◽

N. Awj ◽

L. Azoulay ◽

B. Bahoric ◽

Y. Hui ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Radiation Therapy ◽

Cancer Patients ◽

Bone Marrow Toxicity ◽

Radiation Induced ◽

Radical Radiation

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Effect of prior therapy and bone marrow metastases on progenitor cell content of blood stem cell harvests in breast cancer patients

Biology of Blood and Marrow Transplantation ◽

10.1053/bbmt.2002.v8.pm12064364 ◽

2002 ◽

Vol 8 (5) ◽

pp. 268-272 ◽

Cited By ~ 5

Author(s):

Ahmet Demirkazik ◽

Anne Kessinger ◽

James Lynch ◽

Elizabeth Reed ◽

Stefano Tarantolo ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Stem Cell ◽

Cancer Patients ◽

Progenitor Cell ◽

Blood Stem Cell ◽

Breast Cancer Patients ◽

Cell Content ◽

Prior Therapy ◽

Bone Marrow Metastases

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Clinical Outcome of Patients with Myelophthisic Anemia Arising From Advanced Gastric Cancer.

Blood ◽

10.1182/blood.v114.22.5095.5095 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5095-5095

Author(s):

Ji Yeon Kwon ◽

Han Jo Kim ◽

Kyoung Ha Kim ◽

Se-Hyung Kim ◽

Sang-Cheol Lee ◽

...

Keyword(s):

Gastric Cancer ◽

Bone Marrow ◽

Clinical Outcome ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Median Survival ◽

Palliative Chemotherapy ◽

Bone Marrow Involvement ◽

Bone Marrow Metastases ◽

Gastric Cancer Patients

Abstract Abstract 5095 Background Although it is not common to encounter patients with myelophthisic anemia arising from advanced gastric cancer, clinical features and optimal treatment are not yet to be elucidated. Prognosis for gastric cancer patients with bone marrow metastases is extremely poor. The current study was performed to evaluate clinical outcome of patients with myelophthisic anemia arising from advanced gastric cancer. Methods We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases between September 1986 and February 2009 at Soonchunhyang University Hospital. Results The median age was 46 years (range 24-61 yeras). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients showed thrombocytopenia, anemia, and elevation of lactate dehydrogenase. Sixteen patients (61.5%) were received palliative chemotherapy with a median of 4 cycles. (range, 1-13 cycles). Median survival durations after bone marrow metastases for entire patients were 37 days (95% CI, 12.5-61.5 days). The median survival times from bone marrow involvement were 11 days in the best supportive care group (range 9.5-12.5 days) and 121 days (range 94.7-147.3 days) in the palliative chemotherapy group (p <0.001). Patients died of tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and DIC (1 patient, 4%). There were no chemotherapy related deaths. Conclusion It is difficult to decide whether to proceed with aggressive treatment for gastric cancer patients with bone marrow metastases because of the hematologic findings, e.g. anemia, thrombocytopenia, and DIC. However, this study suggests that palliative chemotherapy should be actively considered in patients with myelophthisic anemia arising from advanced gastric cancer. Disclosures No relevant conflicts of interest to declare.

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