Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Patterns of Bone Sarcomas as a Second Malignancy in Relation to Radiotherapy in Adulthood and Histologic Type


There were 1,284,537 adult cancer patients in the cohort who survived for 5 years or longer, with an average follow-up time of 13 years after the first cancer diagnosis. About 25% of cancer survivors received radiotherapy as part of the initial treatment of their first cancer, and more than 90% of these received some form of external beam radiation. Few patients had a first cancer that was staged as distant (3–4%), and this proportion was similar in both radiotherapy and nonradiotherapy groups (Table 1). Compared with the overall cohort, patients who developed second bone sarcomas (n = 159) were slightly younger at initial cancer diagnosis and were more likely to have previously received radiotherapy. Furthermore, in the group of patients who developed a second bone sarcoma after previous radiotherapy, there was a higher percentage of females (67%) and distant-staged first cancers (11%) than in the cohort as a whole.

Table 1.
Descriptive statistics of 1,284,537 five-year adult cancer survivorsa according to previous radiotherapy and development of bone sarcoma as a second malignancy (SEER 9 registries: 1973–2008)

Cases of second bone sarcomas Cohort
Characteristic RT No RT RT No RT
N 70b 89 327,532 957,005
Mean latency, y 10.7 11.8 NA NA
Mean age at first cancer, y 54.1 54.0 58.2 55.7
Stage of first cancer
 % Local/regional 64 73 75 80
 % Distant 11 2 3 4
 % Unknownc 24 25 22 16
Gender
 % Male 33 45 44 40
 % Female 67 55 56 60


https://aacrjournals.org/cebp/article/2 ... Malignancy

Disseminated tumor cells (DTCs) spread systemically yet distinct patterns of metastasis indicate a range of tissue susceptibility to metastatic colonization. Distinctions between permissive and suppressive tissues are still being elucidated at cellular and molecular levels.

Suppressive and Permissive Actions of Glucocorticoids: A Way to Control Innate Immunity and to Facilitate Specificity of Adaptive Immunity?

Activation of Hematopoietic Stem/Progenitor Cells Promotes Immunosuppression Within the Pre–metastatic Niche

Abstract
Metastatic tumors have been shown to establish microenvironments in distant tissues that are permissive to disseminated tumor cells. Hematopoietic cells contribute to this microenvironment, yet the precise initiating events responsible for establishing the pre-metastatic niche remain unclear. Here, we tracked the developmental fate of hematopoietic stem and progenitor cells (HSPC) in tumor-bearing mice. We show that a distant primary tumor drives the expansion of HSPCs within the bone marrow and their mobilization to the bloodstream. Treatment of purified HSPCs cultured ex vivo with tumor-conditioned media induced their proliferation as well as their differentiation into immunosuppressive myeloid cells. We furthered tracked purified HSPCs in vivo and found they differentiated into myeloid-derived suppressor cells in early metastatic sites of tumor-bearing mice. The number of CD11b+Ly6g+ cells in metastatic sites was significantly increased by HSPC mobilization and decreased if tumor-mediated mobilization was inhibited. Moreover, pharmacologic mobilization of HSPCs increased metastasis, whereas depletion of Gr1+ cells abrogated the metastasis-promoting effects of HSPC mobilization. Finally, we detected elevated levels of HSPCs in the circulation of newly diagnosed cancer patients, which correlated with increased risk for metastatic progression. Taken together, our results highlight bone marrow activation as one of the earliest steps of the metastatic process and identify circulating HSPCs as potential clinical indicators of metastatic niche formation. Cancer Res; 76(6); 1335–47. ©2015 AACR.

Hematopoietic stem cells are immature cells that develop into all types of blood cells. Progenitor cells are descendants of stem cells that further differentiate into specialized cell types.

https://aacrjournals.org/cancerres/arti ... itor-Cells