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Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy

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Abstract

Over the past two decades, it has been established that cancer patients with oligometastases, i.e., only a few detectable metastases confined to one or a few organs, may benefit from an aggressive local treatment approach such as the application of high-precision stereotactic body radiotherapy (SBRT). Specifically, some studies have indicated that achieving long-term local tumor control of oligometastases is associated with prolonged overall survival. This motivates investigations into which factors may modify the dose-response relationship of SBRT by making metastases more or less radioresistant. One such factor relates to the uptake of the positron emission tomography tracer 2-deoxy-2-[18F]fluoro-D-glucose (FDG) which reflects the extent of tumor cell glycolysis or the Warburg effect, respectively. Here we review the biological mechanisms how the Warburg effect drives tumor cell radioresistance and metastasis and draw connections to clinical studies reporting associations between high FDG uptake and worse clinical outcomes after SBRT for oligometastases. We further review the evidence for distinct metabolic phenotypes of metastases preferentially seeding to specific organs and their possible translation into distinct radioresistance. Finally, evidence that obesity and hyperglycemia also affect outcomes after SBRT will be presented. While delivered dose is the main determinant of a high local tumor control probability, there might be clinical scenarios when metabolic targeting could make the difference between achieving local control or not, for example when doses have to be compromised in order to spare neighboring high-risk organs, or when tumors are expected to be highly therapy-resistant due to heavy pretreatment such as chemotherapy and/or radiotherapy.

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Notes

  1. We apply the standard oncological definition of “cure” which is a five-year disease-free interval after therapy.

  2. While SBRT refers to extracranial sites, the analogous, highly conformal radiation technique for treating individual brain tumors is usually called radiosurgery. This will not be the subject of this review.

  3. BED denotes the biologically effective dose which is calculated as \(\textrm{BED}= nd\left(1+\frac{d}{\alpha /\beta}\right)\), with n being the number of fractions, d the single fraction dose and α/β was assumed to be 10 Gy.

References

  1. Dillekås, H., Rogers, M. S., & Straume, O. (2019). Are 90% of deaths from cancer caused by metastases? Cancer Medicine, 8(12), 5574–5576. https://doi.org/10.1002/cam4.2474

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jones, H. B. (1956). Demographic consideration of the cancer problem. Transactions of the New York Academy of Sciences, 18(4), 298–333. https://doi.org/10.1111/j.2164-0947.1956.tb00453.x

    Article  CAS  PubMed  Google Scholar 

  3. Edlich, R. F., Shea, M. A., Foker, J. E., Grondin, C., Castaneda, A. R., & Varco, R. L. (1966). A review of 26 years’ experience with pulmonary resection for metastatic cancer. Diseases of the Chest, 49(6), 587–594. https://doi.org/10.1378/chest.49.6.587

    Article  CAS  PubMed  Google Scholar 

  4. Mountain, C. F., McMurtrey, M. J., & Hermes, K. E. (1984). Surgery for pulmonary metastasis: A 20-year experience. Annals of Thoracic Surgery, 38(4), 323–330. https://doi.org/10.1016/S0003-4975(10)62280-1

    Article  CAS  PubMed  Google Scholar 

  5. Foster, J. H. (1978). Survival after liver resection for secondary tumors. The American Journal of Surgery, 135(3), 389–394. https://doi.org/10.1016/0002-9610(78)90072-7

    Article  CAS  PubMed  Google Scholar 

  6. van Dongen, J. A., & van Slooten, E. A. (1978). The surgical treatment of pulmonary metastases. Cancer Treatment Reviews, 5, 29–48.

    Article  PubMed  Google Scholar 

  7. Hellman, S., & Weichselbaum, R. R. (1995). Oligometastases. Journal of Clinical Oncology, 13(1), 8–10.

    Article  CAS  PubMed  Google Scholar 

  8. Kendal, W. S. (2014). Oligometastasis as a predictor for occult disease. Mathematical Biosciences, 251(1), 1–10. https://doi.org/10.1016/j.mbs.2014.02.006

    Article  PubMed  Google Scholar 

  9. Gutiontov, S. I., Pitroda, S. P., Tran, P. T., & Weichselbaum, R. R. (2021). (Oligo)metastasis as a spectrum of disease. Cancer Research, 81(10), 2577–2583. https://doi.org/10.1158/0008-5472.can-20-3337

  10. Tree, A. C., Khoo, V. S., Eeles, R. A., Ahmed, M., Dearnaley, D. P., Hawkins, M. A., Huddart, R. A., Nutting, C. M., Ostler, P. J., & van As, N. J. (2013). Stereotactic body radiotherapy for oligometastases. Lancet Oncology, 14(1), e28–e37. https://doi.org/10.1016/S1470-2045(12)70510-7

    Article  PubMed  Google Scholar 

  11. Otake, S., & Goto, T. (2019). Stereotactic radiotherapy for oligometastasis. Cancers, 11, 133. https://doi.org/10.3390/cancers11020133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ruers, T., Van Coevorden, F., Punt, C. J. A., Pierie, J.-P. E. N., Borel-Rinkes, I., Ledermann, J. A., Poston, G., Bechstein, W., Lentz, M.-A., Mauer, M., Folprecht, G., Van Cutsem, E., Ducreux, M., & Nordlinger, B. (2017). Local treatment of unresectable colorectal liver metastases: Results of a randomized phase ii trial. Journal of the National Cancer Institute, 109(9), 1–10. https://doi.org/10.1093/jnci/djx015

    Article  Google Scholar 

  13. Iyengar, P., Kavanagh, B. D., Wardak, Z., Smith, I., Ahn, C., Gerber, D. E., Dowell, J., Hughes, R., Abdulrahman, R., Camidge, D. R., Gaspar, L. E., Doebele, R. C., Bunn, P. A., Choy, H., & Timmerman, R. (2014). Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. Journal of Clinical Oncology, 32(34), 3824–3830. https://doi.org/10.1200/JCO.2014.56.7412

    Article  PubMed  Google Scholar 

  14. Gomez, D. R., Tang, C., Zhang, J., Blumenschein, G. R., Hernandez, M., Jack Lee, J., Ye, R., Palma, D. A., Louie, A. V., Camidge, D. R., Doebele, R. C., Skoulidis, F., Gaspar, L. E., Welsh, J. W., Gibbons, D. L., Karam, J. A., Kavanagh, B. D., Tsao, A. S., Sepesi, B., et al. (2019). Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: Long-term results of a multi-institutional, phase II, randomized study. Journal of Clinical Oncology, 37(18), 1558–1565. https://doi.org/10.1200/JCO.19.00201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Palma, D. A., Olson, R., Harrow, S., Gaede, S., Louie, A. V., Haasbeek, C., Mulroy, L., Lock, M., Rodrigues, G. B., Yaremko, B. P., Schellenberg, D., Ahmad, B., Senthi, S., Swaminath, A., Kopek, N., Liu, M., Moore, K., Currie, S., Schlijper, R., et al. (2020). Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the SABR-COMET Phase II randomized trial. Journal of Clinical Oncology, 38(25), 2830–2838. https://doi.org/10.1200/JCO.20.00818

    Article  PubMed  PubMed Central  Google Scholar 

  16. MacDermed, D. M., Weichselbaum, R. R., & Salama, J. K. (2008). A rationale for the targeted treatment of oligometastases with radiotherapy. Journal of Surgical Oncology, 98(3), 202–206. https://doi.org/10.1002/jso.21102

    Article  PubMed  Google Scholar 

  17. Widder, J., Klinkenberg, T. J., Ubbels, J. F., Wiegman, E. M., Groen, H. J. M., & Langendijk, J. A. (2013). Pulmonary oligometastases: Metastasectomy or stereotactic ablative radiotherapy? Radiotherapy and Oncology, 107(3), 409–413. https://doi.org/10.1016/j.radonc.2013.05.024

    Article  PubMed  Google Scholar 

  18. Lodeweges, J. E., Klinkenberg, T. J., Ubbels, J. F., Groen, H. J. M., Langendijk, J. A., & Widder, J. (2017). Long-term outcome of surgery or stereotactic radiotherapy for lung oligometastases. Journal of Thoracic Oncology, 12(9), 1442–1445. https://doi.org/10.1016/j.jtho.2017.05.015

    Article  PubMed  Google Scholar 

  19. Phillips, R., Shi, W. Y., Deek, M., Radwan, N., Lim, S. J., Antonarakis, E. S., Rowe, S. P., Ross, A. E., Gorin, M. A., Deville, C., Greco, S. C., Wang, H., Denmeade, S. R., Paller, C. J., Dipasquale, S., DeWeese, T. L., Song, D. Y., Wang, H., Carducci, M. A., et al. (2020). Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncology, 6(5), 650–659. https://doi.org/10.1001/jamaoncol.2020.0147

    Article  PubMed  PubMed Central  Google Scholar 

  20. Klement, R. J., Abbasi-Senger, N., Adebahr, S., Alheid, H., Allgaeuer, M., Becker, G., Blanck, O., Boda-Heggemann, J., Brunner, T., Duma, M., Eble, M. J., Ernst, I., Gerum, S., Habermehl, D., Hass, P., Henkenberens, C., Hildebrandt, G., Imhoff, D., Kahl, H., et al. (2019). The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: A combined analysis of 388 patients with 500 metastases. BMC Cancer, 19, 173. https://doi.org/10.1186/s12885-019-5362-5

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yamamoto, T., Niibe, Y., Aoki, M., Shintani, T., Yamada, K., Kobayashi, M., Yamashita, H., Ozaki, M., Manabe, Y., Onishi, H., Yahara, K., Nishikawa, A., Katsui, K., Oh, R.-J., Terahara, A., & Jingu, K. (2020). Analyses of the local control of pulmonary oligometastases after stereotactic body radiotherapy and the impact of local control on survival. BMC Cancer, 20, 997. https://doi.org/10.1186/s12885-020-07514-9

    Article  PubMed  PubMed Central  Google Scholar 

  22. Takeda, A., Yokosuka, N., Ohashi, T., Kunieda, E., Fujii, H., Aoki, Y., Sanuki, N., Koike, N., & Ozawa, Y. (2011). The maximum standardized uptake value (SUVmax) on FDG-PET is a strong predictor of local recurrence for localized non-small-cell lung cancer after stereotactic body radiotherapy (SBRT). Radiotherapy and Oncology, 101(2), 291–297. https://doi.org/10.1016/j.radonc.2011.08.008

    Article  PubMed  Google Scholar 

  23. Clarke, K., Taremi, M., Dahele, M., Freeman, M., Fung, S., Franks, K., Bezjak, A., Brade, A., Cho, J., Hope, A., & Sun, A. (2012). Stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC): Is FDG-PET a predictor of outcome? Radiotherapy and Oncology, 104(1), 62–66. https://doi.org/10.1016/j.radonc.2012.04.019

    Article  PubMed  Google Scholar 

  24. Abelson, J. A., Murphy, J. D., Trakul, N., Bazan, J. G., Maxim, P. G., Graves, E. E., Quon, A., Le, Q.-T., Diehn, M., & Loo, B. W. (2012). Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy. Lung Cancer, 78(3), 219–224. https://doi.org/10.1016/j.lungcan.2012.08.016

    Article  PubMed  Google Scholar 

  25. Mazzola, R., Fersino, S., Alongi, P., Di Paola, G., Gregucci, F., Aiello, D., Tebano, U., Pasetto, S., Ruggieri, R., Salgarello, M., & Alongi, F. (2018). Stereotactic body radiation therapy for liver oligometastases: Predictive factors of local response by 18F-FDG-PET/CT. British Journal of Radiology, 91(1088), 20180058. https://doi.org/10.1259/bjr.20180058

    Article  PubMed  PubMed Central  Google Scholar 

  26. Oikonomou, A., Khalvati, F., Tyrrell, P. N., Haider, M. A., Tarique, U., Jimenez-Juan, L., Tjong, M. C., Poon, I., Eilaghi, A., Ehrlich, L., & Cheung, P. (2018). Radiomics analysis at PET/CT contributes to prognosis of recurrence and survival in lung cancer treated with stereotactic body radiotherapy. Scientific Reports, 8, 4003. https://doi.org/10.1038/s41598-018-22357-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rahmim, A., Bak-Fredslund, K. P., Ashrafinia, S., Lu, L., Schmidtlein, C. R., Subramaniam, R. M., Morsing, A., Keiding, S., Horsager, J., & Munk, O. L. (2019). Prognostic modeling for patients with colorectal liver metastases incorporating FDG PET radiomic features. European Journal of Radiology, 113(February), 101–109. https://doi.org/10.1016/j.ejrad.2019.02.006

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dissaux, G., Visvikis, D., da-ano, R., Pradier, O., Chajon, E., Barillot, I., Duvergé, L., Masson, I., Abgral, R., Santiago Ribeiro, M. J., Devillers, A., Pallardy, A., Fleury, V., Mahé, M. A., de Crevoisier, R., Hatt, M., & Schick, U. (2020). Pretreatment 18F-FDG PET/CT radiomics predict local recurrence in patients treated with stereotactic body radiotherapy for early-stage non-small cell lung cancer: A multicentric study. Journal of Nuclear Medicine, 61(6), 814–820. https://doi.org/10.2967/jnumed.119.228106

    Article  CAS  PubMed  Google Scholar 

  29. Carles, M., Fechter, T., Radicioni, G., Schimek-Jasch, T., Adebahr, S., Zamboglou, C., Nicolay, N. H., Martí-Bonmatí, L., Nestle, U., Grosu, A. L., Baltas, D., Mix, M., & Gkika, E. (2021). FDG-PET radiomics for response monitoring in non-small-cell lung cancer treated with radiation therapy. Cancers, 13(4), 814. https://doi.org/10.3390/cancers13040814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Apostolova, I., Wedel, F., & Brenner, W. (2016). Imaging of tumor metabolism using positron emission tomography (PET). In T. Cramer & C. A. Schmitt (Eds.), Metabolism in Cancer (1st ed., pp. 177–205). Springer International Publishing. https://doi.org/10.1007/978-3-319-42118-6_8

    Chapter  Google Scholar 

  31. El Naqa, I. (2014). The role of quantitative PET in predicting cancer treatment outcomes. Clinical and Translational Imaging, 2(4), 305–320. https://doi.org/10.1007/s40336-014-0063-1

    Article  Google Scholar 

  32. Warburg, O., Posener, K., & Negelein, E. (1924). Über den Stoffwechsel der Carcinomzelle. Biochemische Zeitschrift, 152, 309–343.

    CAS  Google Scholar 

  33. Warburg, O., Wind, F., & Negelein, E. (1926). Über den Stoffwechsel der Tumoren im Körper. Klinische Wochenschrift, 5, 829–838.

    Article  CAS  Google Scholar 

  34. Warburg, O., Wind, F., & Negelein, E. (1927). The metabolism of tumors in the body. The Journal of General Physiology, 8(6), 519–530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pedersen, P. L. (1978). Tumor mitochondria and the bioenergetics of cancer cells. Progress in Experimental Tumor Research, 22, 190–274. https://doi.org/10.1159/000401202

    Article  CAS  PubMed  Google Scholar 

  36. Carew, J. S., & Huang, P. (2002). Mitochondrial defects in cancer. Molecular Cancer, 1, 9. https://doi.org/10.1186/1476-4598-1-9

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wallace, D. C. (2005). Mitochondria and cancer: Warburg addressed. Cold Spring Harbor Symposia on Quantitative Biology, 70, 363–374. https://doi.org/10.1101/sqb.2005.70.035

    Article  CAS  PubMed  Google Scholar 

  38. Xia, M. F., Zhang, Y. Z., Jin, K., Lu, Z. T., Zeng, Z., & Xiong, W. (2019). Communication between mitochondria and other organelles: A brand-new perspective on mitochondria in cancer. Cell & Bioscience, 9, 27. https://doi.org/10.1186/s13578-019-0289-8

    Article  Google Scholar 

  39. Seyfried, T. N., & Chinopoulos, C. (2021). Can the mitochondrial metabolic theory explain better the origin and management of cancer than can the somatic mutation theory? Metabolites, 11, 572. https://doi.org/10.3390/metabo11090572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Seyfried, T. N., Arismendi-Morillo, G., Mukherjee, P., & Chinopoulos, C. (2020). On the origin of ATP synthesis in cancer. iScience, 23(11), 101761. https://doi.org/10.1016/j.isci.2020.101761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Seyfried, T. N., & Shelton, L. M. (2010). Cancer as a metabolic disease. Nutrition and Metabolism, 7, 7. https://doi.org/10.1186/1743-7075-7-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Seyfried, T. N. (2015). Cancer as a mitochondrial metabolic disease. Frontiers in Cell and Development Biology, 3, 43. https://doi.org/10.3389/fcell.2015.00043

    Article  Google Scholar 

  43. Kim, J. W., & Dang, C. V. (2006). Cancer’s molecular sweet tooth and the Warburg effect. Cancer Research, 66(18), 8927–8930. https://doi.org/10.1158/0008-5472.CAN-06-1501

    Article  CAS  PubMed  Google Scholar 

  44. Kim, J. W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006). HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism, 3(3), 177–185. https://doi.org/10.1016/j.cmet.2006.02.002

    Article  CAS  PubMed  Google Scholar 

  45. Semenza, G. L. (2010). HIF-1: Upstream and downstream of cancer metabolism. Current Opinion in Genetics and Development, 20(1), 51–56. https://doi.org/10.1016/j.gde.2009.10.009

    Article  CAS  PubMed  Google Scholar 

  46. Courtnay, R., Ngo, D. C., Malik, N., Ververis, K., Tortorella, S. M., & Karagiannis, T. C. (2015). Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Molecular Biology Reports, 42(4), 841–851. https://doi.org/10.1007/s11033-015-3858-x

    Article  CAS  PubMed  Google Scholar 

  47. Gallagher, E. J., & LeRoith, D. (2011). Minireview: IGF, insulin, and cancer. Endocrinology, 152(7), 2546–2551. https://doi.org/10.1210/en.2011-0231

    Article  CAS  PubMed  Google Scholar 

  48. Klement, R. J., & Fink, M. K. (2016). Dietary and pharmacological modification of the insulin/IGF-1 system: exploiting the full repertoire against cancer. Oncogenesis, 5, e193. https://doi.org/10.1038/oncsis.2016.2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nussinov, R., Wang, G., Tsai, C. J., Jang, H., Lu, S., Banerjee, A., Zhang, J., & Gaponenko, V. (2017). Calmodulin and PI3K signaling in KRAS cancers. Trends in Cancer, 3(3), 214–224. https://doi.org/10.1016/j.trecan.2017.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Klement, R. J. (2019). The influence of ketogenic therapy on the 5 R’s of radiobiology. International Journal of Radiation Biology, 95(4), 394–407. https://doi.org/10.1080/09553002.2017.1380330

    Article  CAS  PubMed  Google Scholar 

  51. Meister, A. (1983). Selective modification of glutathione metabolism. Science, 220(4596), 472–477.

    Article  CAS  PubMed  Google Scholar 

  52. Sattler, U. G., & Mueller-Klieser, W. (2009). The anti-oxidant capacity of tumour glycolysis. International Journal of Radiation Biology, 85(11), 963–971. https://doi.org/10.3109/09553000903258889

    Article  CAS  PubMed  Google Scholar 

  53. Meijer, T. W. H., Kaanders, J. H. A. M., Span, P. N., & Bussink, J. (2012). Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clinical Cancer Research, 18(20), 5585–5594. https://doi.org/10.1158/1078-0432.CCR-12-0858

    Article  CAS  PubMed  Google Scholar 

  54. Quennet, V., Yaromina, A., Zips, D., Rosner, A., Walenta, S., Baumann, M., & Mueller-klieser, W. (2006). Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice. Radiotherapy and Oncology, 81(2), 130–135. https://doi.org/10.1016/j.radonc.2006.08.012

    Article  CAS  PubMed  Google Scholar 

  55. Sattler, U. G. A., Meyer, S. S., Quennet, V., Hoerner, C., Knoerzer, H., Fabian, C., Yaromina, A., Zips, D., Walenta, S., Baumann, M., & Mueller-Klieser, W. (2010). Glycolytic metabolism and tumour response to fractionated irradiation. Radiotherapy and Oncology, 94(1), 102–109. https://doi.org/10.1016/j.radonc.2009.11.007

    Article  CAS  PubMed  Google Scholar 

  56. Mailloux, R. J., & Harper, M.-E. (2011). Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radical Biology & Medicine, 51(6), 1106–1115. https://doi.org/10.1016/j.freeradbiomed.2011.06.022

    Article  CAS  Google Scholar 

  57. Vozza, A., Parisi, G., de Leonardis, F., Lasorsa, F. M., Castegna, A., Amorese, D., Marmo, R., Calcagnile, V. M., Palmieri, L., Ricquier, D., Paradies, E., Scarcia, P., Palmieri, F., Bouillaud, F., & Fiermonte, G. (2014). UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proceedings of the National Academy of Sciences, 111(3), 960–965. https://doi.org/10.1073/pnas.1317400111

    Article  CAS  Google Scholar 

  58. Lemos, D., Oliveira, T., Martins, L., de Azevedo, V. R., Rodrigues, M. F., Ketzer, L. A., & Rumjanek, F. D. (2019). Isothermal microcalorimetry of tumor cells: Enhanced thermogenesis by metastatic cells. Frontiers in Oncology, 9, 1430. https://doi.org/10.3389/fonc.2019.01430

    Article  PubMed  PubMed Central  Google Scholar 

  59. Liu, C. H., Huang, Z. H., Dong, X. Y., Zhang, X. Q., Li, Y. H., Zhao, G., Sun, B. S., & Shen, Y. N. (2020). Inhibition of uncoupling protein 2 enhances the radiosensitivity of cervical cancer cells by promoting the production of reactive oxygen species. Oxidative Medicine and Cellular Longevity, 2020, 5135893. https://doi.org/10.1155/2020/5135893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sun, A., Johansson, S., Turesson, I., Dau, A., & Sörensen, J. (2012). Imaging tumor perfusion and oxidative metabolism in patients with head-and-neck cancer using 1- [ 11C]-acetate PET during radiotherapy: Preliminary results. International Journal of Radiation Oncology Biology Physics, 82(2), 554–560. https://doi.org/10.1016/j.ijrobp.2010.11.007

    Article  PubMed  Google Scholar 

  61. Dong, M., Liu, J., Sun, X., & Xing, L. (2017). Prognositc significance of SUVmax on pretreatment 18F-FDG PET/CT in early-stage non-small cell lung cancer treated with stereotactic body radiotherapy: A meta-analysis. Journal of Medical Imaging and Radiation Oncology, 61(5), 652–659. https://doi.org/10.1111/1754-9485.12599

    Article  PubMed  Google Scholar 

  62. Dosani, M., Yang, R., McLay, M., Wilson, D., Liu, M., Yong-Hing, C. J., Hamm, J., Lund, C. R., Olson, R., & Schellenberg, D. (2019). Metabolic tumour volume is prognostic in patients with non-small-cell lung cancer treated with stereotactic ablative radiotherapy. Current Oncology, 26(1), e57–e63. https://doi.org/10.3747/co.26.4167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lu, J., Tan, M., & Cai, Q. (2015). The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Letters, 356(2), 156–164. https://doi.org/10.1016/j.canlet.2014.04.001

    Article  CAS  PubMed  Google Scholar 

  64. Payen, V. L., Porporato, P. E., Baselet, B., & Sonveaux, P. (2016). Metabolic changes associated with tumor metastasis, part 1: Tumor pH, glycolysis and the pentose phosphate pathway. Cellular and Molecular Life Sciences, 73(7), 1333–1348. https://doi.org/10.1007/s00018-015-2098-5

    Article  CAS  PubMed  Google Scholar 

  65. Lu, J. (2019). The Warburg metabolism fuels tumor metastasis. Cancer and Metastasis Reviews, 38(1–2), 157–164. https://doi.org/10.1007/s10555-019-09794-5

    Article  CAS  PubMed  Google Scholar 

  66. Huysentruyt, L. C., & Seyfried, T. N. (2010). Perspectives on the mesenchymal origin of metastatic cancer. Cancer and Metastasis Reviews, 29(4), 695–707. https://doi.org/10.1007/s10555-010-9254-z

    Article  PubMed  Google Scholar 

  67. Seyfried, T. N., & Huysentruyt, L. C. (2013). On the origin of cancer metastasis. Critical Reviews in Oncogenesis, 18(1–2), 43–73. https://doi.org/10.1615/CritRevOncog.v18.i1-2.40

    Article  PubMed  PubMed Central  Google Scholar 

  68. Guerra, F., Guaragnella, N., Arbini, A. A., Bucci, C., Giannattasio, S., & Moro, L. (2017). Mitochondrial dysfunction: A novel potential driver of epithelial-to-mesenchymal transition in cancer. Frontiers in Oncology, 7, 295. https://doi.org/10.3389/fonc.2017.00295

    Article  PubMed  PubMed Central  Google Scholar 

  69. Gatenby, R. A., Smallbone, K., Maini, P. K., Rose, F., Averill, J., Nagle, R. B., Worrall, L., & Gillies, R. J. (2007). Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer. British Journal of Cancer, 97(5), 646–653. https://doi.org/10.1038/sj.bjc.6603922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chen, K. H., Tung, P. Y., Wu, J. C., Chen, Y., Chen, P. C., Huang, S. H., & Wang, S. M. (2008). An acidic extracellular pH induces Src kinase-dependent loss of β-catenin from the adherens junction. Cancer Letters, 267(1), 37–48. https://doi.org/10.1016/j.canlet.2008.03.005

    Article  CAS  PubMed  Google Scholar 

  71. Rozhin, J., Sameni, M., Ziegler, G., & Sloane, B. F. (1994). Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Research, 54(24), 6517–6525.

    CAS  PubMed  Google Scholar 

  72. Bourguignon, L. Y. W., Singleton, P. A., Diedrich, F., Stern, R., & Gilad, E. (2004). CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion. Journal of Biological Chemistry, 279(26), 26991–27007. https://doi.org/10.1074/jbc.M311838200

    Article  CAS  PubMed  Google Scholar 

  73. Li, X., Yu, X., Dai, D., Song, X., & Xu, W. (2016). The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters. Oncotarget, 7(17), 23141–23155. https://doi.org/10.18632/oncotarget.8153

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kato, Y., Lambert, C. A., Colige, A. C., Mineur, P., Noël, A., Frankenne, F., Foidart, J. M., Baba, M., Hata, R. I., Miyazaki, K., & Tsukuda, M. (2005). Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling. Journal of Biological Chemistry, 280(12), 10938–10944. https://doi.org/10.1074/jbc.M411313200

    Article  CAS  PubMed  Google Scholar 

  75. Lin, S., Sun, L., Lyu, X., Ai, X., du, D., Su, N., Li, H., Zhang, L., Yu, J., & Yuan, S. (2017). Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: A positive metabolic feedback loop. Oncotarget, 8(66), 110426–110443. https://doi.org/10.18632/oncotarget.22786

    Article  PubMed  PubMed Central  Google Scholar 

  76. Miranda-Gonçalves, V., Lameirinhas, A., Macedo-Silva, C., Lobo, J., C. Dias, P., Ferreira, V., Henrique, R., & Jerónimo, C. (2020). Lactate increases renal cell carcinoma aggressiveness through sirtuin 1-dependent epithelial mesenchymal transition axis regulation. Cells, 9(4), 1053. https://doi.org/10.3390/cells9041053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Stern, R., Shuster, S., Neudecker, B. A., & Formby, B. (2002). Lactate stimulates fibroblast expression of hyaluronan and CD44: The Warburg effect revisited. Experimental Cell Research, 276(1), 24–31. https://doi.org/10.1006/excr.2002.5508

    Article  CAS  PubMed  Google Scholar 

  78. Sullivan, W. J., Mullen, P. J., Schmid, E. W., Flores, A., Momcilovic, M., Sharpley, M. S., Jelinek, D., Whiteley, A. E., Maxwell, M. B., Wilde, B. R., Banerjee, U., Coller, H. A., Shackelford, D. B., Braas, D., Ayer, D. E., de Aguiar Vallim, T. Q., Lowry, W. E., & Christofk, H. R. (2018). Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization. Cell, 175(1), 117–132.e21. https://doi.org/10.1016/j.cell.2018.08.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Walenta, S., Wetterling, M., Lehrke, M., Schwickert, G., Sundfør, K., Rofstad, E. K., & Mueller-Klieser, W. (2000). High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Research, 60(4), 916–921.

    CAS  PubMed  Google Scholar 

  80. Walenta, S., Salameh, A., Lyng, H., Evensen, J. F., Mitze, M., Rofstad, E. K., & Mueller-Klieser, W. (1997). Correlation of high lactate levels in head and neck tumors with incidence of metastasis. The American Journal of Pathology, 150(2), 409–415.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Brizel, D. M., Schroeder, T., Scher, R. L., Walenta, S., Clough, R. W., Dewhirst, M. W., & Mueller-Klieser, W. (2001). Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics, 51(2), 349–353.

    Article  CAS  PubMed  Google Scholar 

  82. Walenta, S., Van Chau, T., Schroeder, T., Lehr, H. A., Kunz-Schughart, L. A., Fuerst, A., & Mueller-Klieser, W. (2003). Metabolic classification of human rectal adenocarcinomas: A novel guideline for clinical oncologists? Journal of Cancer Research and Clinical Oncology, 129(6), 321–326. https://doi.org/10.1007/s00432-003-0450-x

    Article  PubMed  Google Scholar 

  83. Dupuy, F., Tabariès, S., Andrzejewski, S., Dong, Z., Blagih, J., Annis, M. G., Omeroglu, A., Gao, D., Leung, S., Amir, E., Clemons, M., Aguilar-Mahecha, A., Basik, M., Vincent, E. E., St.-Pierre, J., Jones, R. G., & Siegel, P. M. (2015). PDK1-dependent metabolic reprogramming dictates metastatic potential in breast cancer. Cell Metabolism, 22(4), 577–589. https://doi.org/10.1016/j.cmet.2015.08.007

    Article  CAS  PubMed  Google Scholar 

  84. Montero-Calle, A., Gómez de Cedrón, M., Quijada-Freire, A., Solís-Fernández, G., López-Alonso, V., Espinosa-Salinas, I., Peláez-García, A., Fernández-Aceñero, M. J., Ramírez de Molina, A., & Barderas, R. (2022). Metabolic reprogramming helps to define different metastatic tropisms in colorectal cancer. Frontiers in Oncology, 12, 903033. https://doi.org/10.3389/fonc.2022.903033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jekabsons, M. B., Merrell, M., Skubiz, A. G., Thornton, N., Milasta, S., Green, D., Chen, T., Wang, Y. H., Avula, B., Khan, I. A., & Zhou, Y. D. (2023). Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cells. Cancer & Metabolism, 11, 4. https://doi.org/10.1186/s40170-023-00303-5

    Article  Google Scholar 

  86. Kamarajugadda, S., Stemboroski, L., Cai, Q., Simpson, N. E., Nayak, S., Tan, M., & Lu, J. (2012). Glucose oxidation modulates anoikis and tumor metastasis. Molecular and Cellular Biology, 32(10), 1893–1907. https://doi.org/10.1128/mcb.06248-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kim, N. H., Cha, Y. H., Lee, J., Lee, S. H., Yang, J. H., Yun, J. S., Cho, E. S., Zhang, X., Nam, M., Kim, N., Yuk, Y. S., Cha, S. Y., Lee, Y., Ryu, J. K., Park, S., Cheong, J. H., Kang, S. W., Kim, S. Y., Hwang, G. S., et al. (2017). Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nature Communications, 8, 4374. https://doi.org/10.1038/ncomms14374

    Article  CAS  Google Scholar 

  88. Lee, S. Y., Jeon, H. M., Ju, M. K., Kim, C. H., Yoon, G., Han, S. I., Park, H. G., & Kang, H. S. (2012). Wnt/snail signaling regulates cytochrome c oxidase and glucose metabolism. Cancer Research, 72(14), 3607–3617. https://doi.org/10.1158/0008-5472.CAN-12-0006

    Article  CAS  PubMed  Google Scholar 

  89. Wang, P., Valentijn, A. J., Gilmore, A. P., & Streuli, C. H. (2003). Early events in the anoikis program occur in the absence of caspase activation. Journal of Biological Chemistry, 278(22), 19917–19925. https://doi.org/10.1074/jbc.M210337200

    Article  CAS  PubMed  Google Scholar 

  90. Røsland, G. V., Dyrstad, S. E., Tusubira, D., Helwa, R., Tan, T. Z., Lotsberg, M. L., Pettersen, I. K. N., Berg, A., Kindt, C., Hoel, F., Jacobsen, K., Arason, A. J., Engelsen, A. S. T., Ditzel, H. J., Lønning, P. E., Krakstad, C., Thiery, J. P., Lorens, J. B., Knappskog, S., & Tronstad, K. J. (2019). Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC. Cancer & Metabolism, 7, 6. https://doi.org/10.1186/s40170-019-0197-8

    Article  Google Scholar 

  91. Avella, D., Manjunath, Y., Singh, A., Deroche, C. B., Kimchi, E. T., Staveley-O’Carroll, K. F., Mitchem, J. B., Kwon, E., Li, G., & Kaifi, J. T. (2020) 18F-FDG PET/CT total lesion glycolysis is associated with circulating tumor cell counts in patients with stage I to IIIA non-small cell lung cancer. Translational Lung Cancer Research, 9(3), 515–521. https://doi.org/10.21037/tlcr.2020.04.10

  92. Minn, A. J., & Massagué, J. (2011). Invasion and Metastasis. In V. T. DeVita Jr., T. S. Lawrence, & S. A. Rosenberg (Eds.), Primer of the Molecular Biology of Cancer (1st ed., pp. 143–162). Lippincott Wiliams & Wilkins.

    Google Scholar 

  93. Epstein, T., Gatenby, R. A., & Brown, J. S. (2017). The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand. PLoS One, 12(9), e0185085. https://doi.org/10.1371/journal.pone.0185085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chen, J., Cao, S., Situ, B., Zhong, J., Hu, Y., Li, S., Huang, J., Xu, J., Wu, S., Lin, J., Zhao, Q., Cai, Z., Zheng, L., & Wang, Q. (2018). Metabolic reprogramming-based characterization of circulating tumor cells in prostate cancer. Journal of Experimental & Clinical Cancer Research, 37(1), 127. https://doi.org/10.1186/s13046-018-0789-0

    Article  CAS  Google Scholar 

  95. Schild, T., Low, V., Blenis, J., & Gomes, A. P. (2018). Unique metabolic adaptations dictate distal organ-specific metastatic colonization. Cancer Cell, 33(3), 347–354. https://doi.org/10.1016/j.ccell.2018.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ortiz-Prado, E., Dunn, J. F., Vasconez, J., Castillo, D., & Viscor, G. (2019). Partial pressure of oxygen in the human body: a general review. American Journal of Blood Research, 9(1), 1–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Stresing, V., Baltziskueta, E., Rubio, N., Blanco, J., Arriba, M., Valls, J., Janier, M., Clézardin, P., Sanz-Pamplona, R., Nieva, C., Marro, M., Dmitri, P., & Sierra, A. (2013). Peroxiredoxin 2 specifically regulates the oxidative and metabolic stress response of human metastatic breast cancer cells in lungs. Oncogene, 32(6), 724–735. https://doi.org/10.1038/onc.2012.93

    Article  CAS  PubMed  Google Scholar 

  98. Cejas, P., López-Gómez, M., Aguayo, C., Madero, R., de Castro Carpeño, J., Belda-Iniesta, C., Barriuso, J., Moreno García, V., Larrauri, J., López, R., Casado, E., Gonzalez-Barón, M., & Feliu, J. (2009). KRAS mutations in primary colorectal cancer tumors and related metastases: A potential role in prediction of lung metastasis. PLoS One, 4(12), e8199. https://doi.org/10.1371/journal.pone.0008199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tie, J., Lipton, L., Desai, J., Gibbs, P., Jorissen, R. N., Christie, M., Drummond, K. J., Thomson, B. N. J., Usatoff, V., Evans, P. M., Pick, A. W., Knight, S., Carne, P. W. G., Berry, R., Polglase, A., McMurrick, P., Zhao, Q., Busam, D., Strausberg, R. L., et al. (2011). KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clinical Cancer Research, 17(5), 1122–1130. https://doi.org/10.1158/1078-0432.CCR-10-1720

    Article  CAS  PubMed  Google Scholar 

  100. Wang, Z., Zheng, X., Wang, X., Chen, Y., Li, Z., Yu, J., Yang, W., Mao, B., Zhang, H., Li, J., & Shen, L. (2021). Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: Next generation sequencing and clinical implications. Annals of Translational Medicine, 9(12), 967–967. https://doi.org/10.21037/atm-21-2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yang, L., Shen, C., Estrada-Bernal, A., Robb, R., Chatterjee, M., Sebastian, N., Webb, A., Mo, X., Chen, W., Krishnan, S., & Williams, T. M. (2021). Oncogenic KRAS drives radioresistance through upregulation of NRF2-53BP1-mediated non-homologous end-joining repair. Nucleic Acids Research, 49(19), 11067–11082. https://doi.org/10.1093/nar/gkab871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mazzola, R., Fiorentino, A., di Paola, G., Giaj Levra, N., Ricchetti, F., Fersino, S., Tebano, U., Pasetto, S., Ruggieri, R., Salgarello, M., & Alongi, F. (2017). Stereotactic ablative radiation therapy for lung oligometastases: Predictive parameters of early response by 18FDG-PET/CT. Journal of Thoracic Oncology, 12(3), 547–555. https://doi.org/10.1016/j.jtho.2016.11.2234

    Article  PubMed  Google Scholar 

  103. Chin, A. L., Kumar, K. A., Guo, H. H., Maxim, P. G., Wakelee, H., Neal, J. W., Diehn, M., Loo, B. W., Jr., & Gensheimer, M. F. (2018). Prognostic value of pretreatment FDG-PET parameters in high-dose image-guided radiotherapy for oligometastatic non–small-cell lung cancer. Clinical Lung Cancer, 19(5), e581–e588. https://doi.org/10.1016/j.cllc.2018.04.003

    Article  PubMed  Google Scholar 

  104. Greco, C., Pares, O., Pimentel, N., Louro, V., Morales, J., Nunes, B., Castanheira, J., Oliveira, C., Silva, A., Vaz, S., Costa, D., Zelefsky, M., Kolesnick, R., & Fuks, Z. (2019). Phenotype-oriented ablation of oligometastatic cancer with single dose radiation therapy. International Journal of Radiation Oncology Biology Physics, 104(3), 593–603. https://doi.org/10.1016/j.ijrobp.2019.02.033

    Article  PubMed  Google Scholar 

  105. Wulf, J., Guckenberger, M., Haedinger, U., Oppitz, U., Mueller, G., Baier, K., & Flentje, M. (2006). Stereotactic radiotherapy of primary liver cancer and hepatic metastases. Acta Oncologica, 45(7), 838–847. https://doi.org/10.1080/02841860600904821

    Article  PubMed  Google Scholar 

  106. Stintzing, S., Hoffmann, R.-T., Heinemann, V., Kufeld, M., Rentsch, M., & Muacevic, A. (2010). Radiosurgery of liver tumors: value of robotic radiosurgical device to treat liver tumors. Annals of Surgical Oncology, 17(11), 2877–2883. https://doi.org/10.1245/s10434-010-1187-9

    Article  PubMed  Google Scholar 

  107. Takeda, A., Kunieda, E., Ohashi, T., Aoki, Y., Koike, N., & Takeda, T. (2011). Stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer and other primary cancers in comparison with primary lung cancer. Radiotherapy and Oncology, 101(2), 255–259. https://doi.org/10.1016/j.radonc.2011.05.033

    Article  PubMed  Google Scholar 

  108. Singh, D., Chen, Y., Hare, M. Z., Usuki, K. Y., Zhang, H., Lundquist, T., Joyce, N., Schell, M. C., & Milano, M. T. (2014). Local control rates with five-fraction stereotactic body radiotherapy for oligometastatic cancer to the lung. Journal of Thoracic Disease, 6(4), 369–374. https://doi.org/10.3978/j.issn.2072-1439.2013.12.03

    Article  PubMed  PubMed Central  Google Scholar 

  109. Thibault, I., Poon, I., Yeung, L., Erler, D., Kim, A., Keller, B., Lochray, F., Jain, S., Soliman, H., & Cheung, P. (2014). Predictive factors for local control in primary and metastatic lung tumours after four to five fraction stereotactic ablative body radiotherapy: A single institution’s comprehensive experience. Clinical Oncology (Royal College of Radiologists), 26(11), 713–719. https://doi.org/10.1016/j.clon.2014.06.018

    Article  CAS  Google Scholar 

  110. Andratschke, N., Parys, A., Stadtfeld, S., Wurster, S., Huttenlocher, S., Imhoff, D., Yildirim, M., Rades, D., Rödel, C. M., Dunst, J., Hildebrandt, G., & Blanck, O. (2016). Clinical results of mean GTV dose optimized robotic guided SBRT for liver metastases. Radiation Oncology, 11, 74. https://doi.org/10.1186/s13014-016-0652-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Aoki, M., Hatayama, Y., Kawaguchi, H., Hirose, K., Sato, M., Akimoto, H., Miura, H., Ono, S., & Takai, Y. (2016). Stereotactic body radiotherapy for lung metastases as oligo-recurrence : A single institutional study. Journal of Radiation Research, 57(1), 55–61. https://doi.org/10.1093/jrr/rrv063

    Article  PubMed  Google Scholar 

  112. Binkley, M. S., Trakul, N., Jacobs, L. R., von Eyben, R., le, Q. T., Maxim, P. G., Loo, B. W., Jr., Shultz, D. B., & Diehn, M. (2015). Colorectal histology is associated with an increased risk of local failure in lung metastases treated with stereotactic ablative radiation therapy. International Journal of Radiation Oncology Biology Physics, 92(5), 1044–1052. https://doi.org/10.1016/j.ijrobp.2015.04.004

    Article  PubMed  Google Scholar 

  113. Klement, R. J. (2017). Radiobiological parameters of liver and lung metastases derived from tumor control data of 3719 metastases. Radiotherapy and Oncology, 123(2), 218–226. https://doi.org/10.1016/j.radonc.2017.03.014

    Article  PubMed  Google Scholar 

  114. Osti, M. F., Agolli, L., Valeriani, M., Reverberi, C., Bracci, S., Marinelli, L., de Sanctis, V., Cortesi, E., Martelli, M., de Dominicis, C., Minniti, G., & Nicosia, L. (2018). 30 Gy single dose stereotactic body radiation therapy (SBRT): Report on outcome in a large series of patients with lung oligometastatic disease. Lung Cancer, 122(3), 165–170. https://doi.org/10.1016/j.lungcan.2018.06.018

    Article  CAS  PubMed  Google Scholar 

  115. Guckenberger, M., Wulf, J., Mueller, G., Krieger, T., Baier, K., Gabor, M., Richter, A., Wilbert, J., & Flentje, M. (2009). Dose–Response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: Relevance of 4D dose calculation. International Journal of Radiation Oncology, Biology, Physics, 74(1), 47–54. https://doi.org/10.1016/j.ijrobp.2008.06.1939

    Article  PubMed  Google Scholar 

  116. Filippi, A. R., Badellino, S., Ceccarelli, M., Guarneri, A., Franco, P., Monagheddu, C., Spadi, R., Ragona, R., Racca, P., & Ricardi, U. (2015). Stereotactic ablative radiation therapy as first local therapy for lung oligometastases from colorectal cancer: A single-institution cohort study. International Journal of Radiation Oncology, Biology, Physics, 91(3), 524–529. https://doi.org/10.1016/j.ijrobp.2014.10.046

    Article  PubMed  Google Scholar 

  117. Fode, M. M., & Høyer, M. (2015). Survival and prognostic factors in 321 patients treated with stereotactic body radiotherapy for oligo-metastases. Radiotherapy and Oncology, 114(2), 155–160. https://doi.org/10.1016/j.radonc.2014.12.003

    Article  PubMed  Google Scholar 

  118. Kim, H. S., Heo, J. S., Lee, J., Lee, J. Y., Lee, M. Y., Lim, S. H., Lee, W. Y., Kim, S. H., Park, Y. A., Cho, Y. B., Yun, S. H., Kim, S. T., Park, J. O., Lim, H. Y., Choi, Y. S., Kwon, W. I., Kim, H. C., & Park, Y. S. (2016). The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: A retrospective analysis. BMC Cancer, 16, 120. https://doi.org/10.1186/s12885-016-2141-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sánchez-Muñoz, A., Gallego, E., de Luque, V., Pérez-Rivas, L. G., Vicioso, L., Ribelles, N., Lozano, J., & Alba, E. (2010). Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer. BMC Cancer, 10, 136. https://doi.org/10.1186/1471-2407-10-136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Milano, M. T., Katz, A. W., Zhang, H., & Okunieff, P. (2012). Oligometastases treated with stereotactic body radiotherapy: Long-term follow-up of prospective study. International Journal of Radiation Oncology, Biology, Physics, 83(3), 878–886. https://doi.org/10.1016/j.ijrobp.2011.08.036

    Article  PubMed  Google Scholar 

  121. Klement, R. J., Guckenberger, M., Alheid, H., Allgäuer, M., Becker, G., Blanck, O., Boda-Heggemann, J., Brunner, T., Duma, M., Gerum, S., Habermehl, D., Hildebrandt, G., Lewitzki, V., Ostheimer, C., Papachristofilou, A., Petersen, C., Schneider, T., Semrau, R., Wachter, S., & Andratschke, N. (2017). Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control. Radiotherapy and Oncology, 123(2), 227–233. https://doi.org/10.1016/j.radonc.2017.01.013

    Article  CAS  PubMed  Google Scholar 

  122. Klement, R. J., & Champ, C. E. (2014). Calories, carbohydrates, and cancer therapy with radiation: Exploiting the five R’s through dietary manipulation. Cancer and Metastasis Reviews, 33(1), 217–229. https://doi.org/10.1007/s10555-014-9495-3

    Article  CAS  PubMed  Google Scholar 

  123. Klement, R. J., & Champ, C. E. (2017). Corticosteroids compromise survival in glioblastoma in part through their elevation of blood glucose levels. Brain, 140(1–2), e16. https://doi.org/10.1093/brain/aww324

    Article  PubMed  Google Scholar 

  124. Barua, R., Templeton, A. J., Seruga, B., Ocana, A., Amir, E., & Ethier, J. L. (2018). Hyperglycaemia and survival in solid tumours: A systematic review and meta-analysis. Clinical Oncology, 30(4), 215–224. https://doi.org/10.1016/j.clon.2018.01.003

    Article  CAS  PubMed  Google Scholar 

  125. Montemurro, N., Perrini, P., & Rapone, B. (2020). Clinical risk and overall survival in patients with diabetes mellitus, hyperglycemia and glioblastoma multiforme. A review of the current literature. International Journal of Environmental Research and Public Health, 17, 8501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Huang, Y. J., Chen, Y. T., Huang, C. M., Kuo, S. H., Liao, Y. Y., Jhang, W. Y., Wang, S. H., Ke, C. C., Huang, Y. H., Cheng, C. M., Huang, M. Y., & Chuang, C. H. (2022). HIF-1α expression increases preoperative concurrent chemoradiotherapy resistance in hyperglycemic rectal cancer. Cancers, 14(16), 4053. https://doi.org/10.3390/cancers14164053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Klement, R. J., Koebrunner, P. S., Meyer, D., Kanzler, S., & Sweeney, R. A. (2021). Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients. Clinical Nutrition, 40, 4674–4684. https://doi.org/10.1016/j.clnu.2021.05.015

    Article  PubMed  Google Scholar 

  128. Allen, B. G., Bhatia, S. K., Buatti, J. M., Brandt, K. E., Lindholm, K. E., Button, A. M., Szweda, L. I., Smith, B. J., Spitz, D. R., & Fath, M. A. (2013). Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clinical Cancer Research, 19(14), 3905–3913. https://doi.org/10.1158/1078-0432.CCR-12-0287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Kalman, N. S., Hugo, G. D., Mahon, R. N., Deng, X., Mukhopadhyay, N. D., & Weiss, E. (2018). Diabetes mellitus and radiation induced lung injury after thoracic stereotactic body radiotherapy. Radiotherapy and Oncology, 129(2), 270–276. https://doi.org/10.1016/j.radonc.2018.08.024

    Article  PubMed  Google Scholar 

  130. Huang, X. F., & Chen, J. Z. (2009). Obesity, the PI3K/Akt signal pathway and colon cancer. Obesity Reviews, 10(6), 610–616. https://doi.org/10.1111/j.1467-789X.2009.00607.x

    Article  CAS  PubMed  Google Scholar 

  131. Su, Y.-H., Wu, Y.-Z., Ann, D. K., Chen, J. L.-Y., & Kuo, C.-Y. (2023). Obesity promotes radioresistance through SERPINE1-mediated aggressiveness and DNA repair of triple-negative breast cancer. Cell Death & Disease, 14, 53. https://doi.org/10.1038/s41419-023-05576-8

    Article  CAS  Google Scholar 

  132. Park, J. M., Spielman, D. M., Josan, S., Jang, T., Merchant, M., Hurd, R. E., Mayer, D., & Recht, L. D. (2016). Hyperpolarized 13C-lactate to 13C-bicarbonate ratio as a biomarker for monitoring the acute response of anti-vascular endothelial growth factor (anti-VEGF) treatment. NMR in Biomedicine, 29(5), 650–659. https://doi.org/10.1002/nbm.3509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This paper was motivated by the topic of a brief talk held by the Rainer J. Klement to obtain his habilitation from the Faculty of Medicine at the University of Zurich, Switzerland.

Author information

Authors and Affiliations

  1. Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, 97422, Schweinfurt, Germany

    Rainer J. Klement & Reinhart A. Sweeney

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  1. Rainer J. Klement
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  2. Reinhart A. Sweeney
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Correspondence to Rainer J. Klement.

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RAS and RJK have received travel/accommodation fees for consultant meetings/conferences from Elekta.

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Klement, R.J., Sweeney, R.A. Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy. Cancer Metastasis Rev 42, 927–940 (2023). https://doi.org/10.1007/s10555-023-10110-5

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