Abstract
Background
In the literature there is some evidence that the incidence of metastases may increase after radiation treatment.
Methods
In order to investigate whether radiation-induced changes in the lymphatic drainage may alter the rate of lymph node metastasis, the center part of the left hind foot of rats was irradiated with a dose of 1 x 55 Gy before inoculation of tumor cells into the irradiated part of the footpad at different time intervals. Cells of 2 different tumor lines were employed. A rarely metastasising rhabdomyosarcoma, R-l, to look for a possible enhancement of lymphatic metastases, and a readily metastasising mammary carcinoma, Cl-2, in case of a possible decrease in the rate of lymphatic metastasis from tumors growing in pre-irradiated footpads.
Results
The incidence of regional lymph node metastasis decreased for R-l tumors growing in pre-irradiated footpads, but not for Cl-2 tumors. Furthermore, the average time required for lymph node metastasis to attain a reference volume of 100 mm3 is not significantly influenced by pre-irradiation of the footpad. No difference was observed in average times for doubling in volume of lymph node metastases originating from primary tumors in pre-irradiated footpads. Abscopal effects after footpad irradiation may cause a 50-fold increase in size of regional lymph nodes and, therefore, histological examination is essential for verification of lymph node metastases.
Conclusions
Damage to the lymphatic system to be expected in the irradiated footpad did not enhance the incidence of regional metastasis of R-1 tumors. A reduced rate of lymphatic metastasis contradicts earlier findings of enhanced lymphatic metastasis development of R-l tumors, growing in pre-irradiated gastrocnemius muscles. The influence of irradiation on regional metastasis formation seems to be “tumor bed” dependent for R-l tumors.
Zusammenfassung
Hintergrund
In der Literatur finden sich Hinweise, da\ die lokale Strahlenbehandlung eines PrimÄrtumors unter UmstÄnden die Metastasierungsrate erhöht.
Methodik
Untersucht wurde an zwei syngenen Tumormodellen der Ratte, ob durch eine Anderung der Lymphdrainage als Folge einer lokalen Vorbestrahlung des Tumorbetts eine Zunahme der lymphogenen Metastasierung verursacht wird. Zu verschiedenen Zeitpunkten nach Bestrahlung des linken Mittelfu\es mit 55 Gy Einzeldosis wurden Tumorzellen lokal injiziert. Das gering metastasierende Rhabdomyosarkom R-l sollte hierbei dem Nachweis einer eventuellen Erhöhung der Metastasierungsrate dienen, das extrem metastasierungsfreudige Mammakarzinom Cl-2 zur Erfassung einer eventuellen Erniedrigung der Metastasierungsrate.
Ergebnisse
Die HÄufigkeit regionaler Metastasen nahm beim R-1-Tumor ab, nicht jedoch beim Cl-2-Karzinom. Die durchschnittlich benötigte Zeit zum Erreichen eines Lymphknotenmetastasenvolumens von 100 mm3 war im wesentlichen von einer Vorbestrahlung des Tumorbetts unabhÄngig, ebenso die Verdopplungszeit von 100 auf 200 mm3. Als “abscopal effect” wurde eine bis zu 50fache Vergrö\erung der homolateralen poplitealen Lymphknoten nach Fu\bestrahlung ohne Tumorzellinjektion beobachtet, was auf die klinische Bedeutung einer histologischen Absicherung hinweist.
Schlu\folgerungen
Die anzunehmende lokale SchÄdigung der. LymphgefÄ\e aufgrund der Vorbestrahlung bedingte keine Erhöhung der regionalen Metastasierungsrate im Fall des R-1-Tumors. Die beobachtete Erniedrigung der Rate steht im Widerspruch mit früheren Befunden nach einer Implantation in den vorbestrahlten Gastroknemiusmuskel und deutet auf eine vom jeweiligen Tumorbett abhÄngige Strahlenwirkung.
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References
Anderson P, Dishe S. Local tumor control and the subsequent incidence of distant metastatic disease. Int J Radiat Oncol Biol Phys 1981;7:1645–8.
Baker D, Elkon D, Lim ML, et al. Does local X-irradiation of a tumor increase the incidence of metastases? Cancer 1981;48:2394–8.
Barendsen GW, Broerse JJ. Experimental radiotherapy of a rat rhabdomyosarcoma with 15-MeV neutrons and 300-kV X-rays. I. Effects of single exposures. Eur J Cancer 1969;5:373–91.
Carmel RJ, Brown JM. The effect of cyclophosphamide and other drugs on the incidence of pulmonary metastases in mice. Cancer Res 1977;37:145–51.
De la Monte SM, Hutchins GM, Moore GW. Altered metastatic behaviour of small cell carcinoma of the lung after chemotherapy and radiation. Cancer 1988;61:2176–82.
De Ruiter J, Cramer SJ, Lelieveld P, et al. Comparison of metastatic disease after local tumor treatment with radiotherapy or surgery in various tumor models. Eur J Cancer Clin Oncol 1982;18:281–9.
Dörr W. Ansätze zur konservativen Behandlung von Strahlenfolgen. Strahlenther Onkol 1997;173:480–3.
Frost P, Kerbel RS, Hunt B, et al. Selection of metastatic variants with identifiable karyotypic changes from a non-metastatic murine tumor after treatment with 2’-deoxy-5-azacytidine or hydroxyurea: Implications for the mechanisms of tumor progression. Cancer Res 1987:47:2690–5.
Hebel R, Stromberg MW. Anatomy of the laboratory rat. Baltimore: Williams & Wilkins, 1976.
Heisel MA, Laug WE, Stowe SM, et al. Effects of X-irradiation on artificial blood vessel wall degeneration by invasive tumor cells. Cancer Res 1984;44:2441–5.
Hermens AF. Variations in the cell kinetics and the growth rate in an experimental tumor during natural growth and after irradiation. Thesis. Amsterdam: Municipal University, 1973.
Hermens AF. To what extent may nonmalignant cells in or near tumors influence tumor responses resulting from therapy?, In: RF Kallman, ed. Rodent Tumor Models in Experimental Cancer therapy. Chapter 39. New York: Pergamon Press, 1987:179–88.
Host H, Brennhovd IO. Combined surgery and radiation therapy versus surgery alone in primary mammary carcinoma: I The effect of orthovoltage radiation. Acta Radiat Ther Phys Biol 1975;14:25–32.
Iwamoto Y, Fujita Y, Sugioka Y. YIGSR, a synthetic laminin peptide, inhibits the enhancement by cyclophosphamide of experimental lung metastasis of human fibrosarcoma cells, din. Exp. Metastas 1992;10:183–9.
Kundu N, Shaozeng Z, Fulton AM. Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mamma carcinoma, Clin Exp Metastas 1995;13:16–22.
Lund C, Jorgensen K, Hjelm-Hansen M, et al. Laryngeal carcinoma: III Treatment results in relation to microscopic score. Acta Radiol Oncol 1979;18:497–508.
MÄnnel DN, Orosz P, Hafner H, et al. Mechanisms involved in metastasis enhanced by inflammatory mediators. Circ Shock 1994;44:9–13.
Milas L, Hunter N, Peters, LJ. The tumor bed effect: dependence of tumor take, growth rate and metastasis on the time interval between irradiation and tumor cell transplantation. Int J Radiat Oncol Biol Phys 1987:13:379–83.
Milas, L, Hirata H, Hunter N, et al. Effect of radiation-induced injury of tumorbed stroma on metastatic spread of murine sarcomas and carcinomas. Cancer Res 1988:48:2116–20.
Nathanson SD, Haas GP, Bobrowski R, et al. Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice. Int J Radiat Oncol Biol Phys 1986:13:243–9.
Orr FW, Adamson IYR, Young L. Promotion of pulmonary metastasis in mice by bleomycin-induced endothelial injury. Cancer Res 1986:46:891–7.
Ramani P, Balkwill FR. Enhanced metastases of a mouse carcinoma after in vitro treatment with murine interferon gamma. Int J Cancer 1987:40:830.
Rappaport DS, Brown JM. Influence of localised pre-inoculation irradiation of the foot on lymphatic metastasis from a primary tumor growing in the foot. Radiat Res 1979:78:108–21.
Rappaport DS, Brown JM. A study of the mechanism by which localised pre-inoculation irradiation enhances the rate of lymphatic spread. Radiat Res 1980;83:566–78.
Rosen EM, Vinter DW, Goldberg ID. Hypertrophy of cultured bovine aortic endothelium following irradiation. Radiat Res 1989:117:395–408.
van der Planken HJM, Quartel FW de, Hermens AF. Lymph node metastasis accompanying regrowth after irradiation of an experimental rhabdomyosarcoma in the rat. In: Radiation Research: Proceedings of the 8th International Congress of Radiation Research, Edinburgh, 19-24 July 1987: Vol. I. London: Taylor & Francis, 1987:277:E31–10V.
Volpe JPG, Basic I, Milas L. Metastatic abilities of murine sarcomas and carcinomas. II. Relationship to cell volume and DNA index. Clin Exp Metastas 1990;8:193–202.
von Essen CF. Radiation enhancement of metastasis: a review. Clin Exp Metastas 1991;9:77–104.
Wright JA, Turley EA, Greenberg AH. Transforming growth factor beta and fibroblast growth factor as promoters of tumor progression to malignancy. Crit Rev Oncogenes 1993;4:473–92.
Yokoyama I, Hayashi S, Sato E, et al. Enhancement of tumor proliferation by cyclosporine A in early phase of experimental hepatic metastasis. Jap J Cancer Res 1994;85:704–9.
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van der Planken, H.J.M., Hermens, A.F. Lymphatic metastasis from tumors transplanted into the pre-irradiated footpad of the rat. Strahlentherapie und Onkologie 175, 32–38 (1999). https://doi.org/10.1007/BF02743459
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DOI: https://doi.org/10.1007/BF02743459