Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro When did the glioblastoma start growing, and how much time can be gained from surgical resection? A model based on the pattern of glioblastoma growth in vivo Anne Line Stensjøen a,b, ⁎ , Erik Magnus Berntsen c,d , Asgeir Store Jakola b,e,f , Ole Solheim b,g,h a Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway b Department of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway c Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway d Department of Radiology and Nuclear Medicine, St. Olavs University Hospital, Trondheim, Norway e Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden f Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, Gothenburg, Sweden g Department of Neuromedicine and Movement science, NTNU - Norwegian University of Science and Technology, Trondheim, Norway h National Advisory Unit for Ultrasound and Image Guided Therapy, St. Olavs University Hospital, Trondheim, Norway ARTICLE INFO Keywords: Tumor growth Extent of resection Glioblastoma Tumor initiation ABSTRACT Objectives: Observational data on the natural course of tumor growth in humans is sparse, and mathematical models of tumor growth are often needed to answer questions related to growth. In this study, a theoretical model of glioblastoma growth was used to investigate two questions often asked by patients and clinicians. First, when did the tumor start growing? Second, how much survival time can be gained from various extents of surgical resection (EOR)?. Patients and methods: A gompertzian growth curve was fitted from observational data of pre-treatment growth from 106 glioblastoma patients based on repeated volume segmentations. The curve was used to find the the- oretical time since tumor initiation. In addition, as a proxy for the potential survival gain from surgery, the number of days until re-growth would reach the preoperative tumor volume were calculated for different extents of resection. Results: The estimated age of the glioblastomas at diagnosis was median 330 days, but ranging from 156 days to 776 days, depending on the tumor volume at diagnosis. The median survival gains from 50%, 75%, 90%, 95% and 99% EOR were, 1.4, 2.5, 3.6, 4.3, and 5.6 months, respectively. However, survival benefit from surgery also depends on lesion volume. In theory, 100 days may be gained from 95% EOR in a 10 mL lesion or a 50% EOR in a 90 ml lesion. Conclusion: In conclusion, we postulate that glioblastoma might originate median 330 days before the diagnosis, assuming the same growth pattern and biology from day one. The theoretical survival benefit of glioblastoma resection is much higher with higher EORs, suggesting that the last milliliters of resection matter the most. Our data also suggest that gain from resection is higher in larger lesions, suggesting that lesion volume may be taken into account in clinical decision-making. 1. Introduction A common question from patients who are diagnosed with brain tumors is “for how long do you think I have had this tumor?” By raising this question, patients indirectly seek insight into the aggressiveness of the disease and its natural course. For both the patient and the surgeon, a subsequent question may be “what can be gained from surgical re- section?” These questions are linked, since if no cure is possible, more time can usually be gained from cytoreductive surgery of slow-growing tumors than from resection of rapid growing cancers. However, these questions are difficult to answer, especially on an individual level. Although there is level 2b evidence (Oxford Centre for Evidence- based Medicine) supporting that complete radiological resection im- proves survival of glioblastoma [1], the impact of lower grades of re- section on survival is still much debated, and various extent of resection (EOR) thresholds with supposed impact on survival have been reported https://doi.org/10.1016/j.clineuro.2018.04.028 Received 30 January 2018; Received in revised form 17 April 2018; Accepted 22 April 2018 ⁎ Corresponding author at: Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, N-3004 Drammen, Norway. E-mail address: alinesten@gmail.com (A.L. Stensjøen). Clinical Neurology and Neurosurgery 170 (2018) 38–42 Available online 24 April 2018 0303-8467/ © 2018 Elsevier B.V. All rights reserved. T