{"paper_id":"41265221-836a-42ad-b299-9bcd4cb54a39","body_text":"Do Patients with a Poor Karnofsky Performance Status Scale Profit from Tumour Volume Reduction? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Do Patients with a Poor Karnofsky Performance Status Scale Profit from Tumour Volume Reduction? Melanie Barz, Julia Gerhardt, Stefanie Bette, A. Kaywan Aftahy, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-113874/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Purpose: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤ 60%. Methods : We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤ 60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. Results : 123 patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. 75 of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm 3 (IR 15.0–56.5cm 3 ) and 3.1 ± 23.8 cm 3 (IR 0.2–15.0 cm 3 ), respectively. The median KPSS was 60% (range 20–60%) preoperatively and 50% (range 0–80%) postoperatively. The median OS was 123 ± 220 days (IR 52–395 days). Age (p<0.001, HR: 1.045 [95% CI 1.022–1.068]), postoperative tumour volume (p=0.02, HR: 1.016 [95% CI 1.002–1.029]) and MGMT promotor status (p=0.016, HR: 0.473 [95% CI 0.257–0.871]) were statistically significant in multivariate analysis. Conclusion: Patients with a preoperative KPSS of ≤ 60% benefit from low postoperative residual tumour volumes. Age and MGMT-methylation status were also significant prognostic parameters in this patient cohort. Neurology Neurosurgery Karnofsky Performance Status Scale Glioblastoma Surgery EOR Figures Figure 1 Figure 1 Figure 2 Figure 2 Figure 3 Figure 3 Figure 4 Figure 4 Figure 5 Figure 5 Introduction In 1949, Karnofsky and Burchena described their instrument, the Karnofsky Performance Scale (KPS) score, as a numerical scale for quantifying patients’ status in relation to the degree of their independence in daily activities and self-care. Originally, it was used for patients with systemic malignancies and divided them according to their level of activity and medical requirements. Patients are scored into 11 categories from 0 to 100, where, for example, a KPSS of 70% means the patient is able to care for himself but is unable to carry out daily activities[ 13 ]. After it had been proven successful in patients with systemic cancer, more and more research groups started to evaluate the KPS score for brain cancer[ 24 , 22 , 14 ]. Previously published studies could show a significant correlation between the preoperative KPS score and the outcome after glioma surgery[ 4 , 15 ]. In most studies, only patients suffering from a glioblastoma with a KPSS of ≥ 70% were included[ 19 , 6 ]. For example, those studies analysed prognostic factors such as tumour size, GRT and adjuvant therapy modalities postoperatively. However, in our clinical daily work, patients with a noticeably lower KPSS are represented as well. It should be noticed that this can be due to clinic symptomology as seizures, acute mental status changes or focal neurologic deficits caused by tumour size and/or location itself. Therefore, the following study intends to show whether it is worthwhile for patients with a KPSS 60% or below to achieve tumour volume reduction. Patients And Methods This retrospective, non-interventional bicentric study was approved by the local medical ethics committee (5625-12) and is in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments[ 9 ]. Patient Population We retrospectively assessed 968 patients with a histologically confirmed glioblastoma WHO IV with a preoperative Karnofsky Performance Status Scale (KPSS) of ≤ 60%, who were treated surgically between September 2006 and March 2016 in two neurosurgical departments. According to interdisciplinary neuro-oncological consensus, patients were assigned to surgery with the intent of complete resection or to biopsy to confirm the histopathological diagnosis. We retrospectively reviewed pre- and postoperative KPSS, date of initial tumour diagnosis, date of death/last contact, age, sex, adjuvant treatment and histopathological findings from the patients’ medical charts. Also, we performed histopathological analysis according to the WHO criteria of 2016[ 17 ] and quantitatively assessed methylation of the O6-methylguanin-DNA-methyltransferase (MGMT) promoter status. We assessed KPSS with regards to hospital admission and five days after surgery. Then, we calculated the overall survival (OS) from the date of surgery until the date of death or censored for the date of the last patient contact. Only patients with complete magnetic resonance imaging data were included to calculate pre- and postoperative contrast-enhancing tumour volumes. Patients with recurrent tumour or incomplete data were excluded (Fig. 1). Imaging All patients received preoperative and early postoperative MRI (within 72 hours after surgery). In centre A, we performed imaging using three different 3 T MRI scanners: Philips Achieva; Philips Ingenia (Philips Medical Systems, The Netherlands B.V.); and Siemens Verio (Siemens Healthcare, Erlangen, Germany). Images included T1w sequences with and without contrast agent, FLAIR (Fluid attenuated inversion recovery) sequences, T2 gradient echo sequences, diffusion-weighted imaging or diffusion-tensor imaging, whereas we calculated isotropic diffusion-weighted images and apparent diffusion coefficient (ADC) maps automatically. Tumour volumes of the contrast-enhancing tumour on pre- and early postoperative MR images using iPlannet® Cranial 3.0.1 were manually segmented by two neurosurgeons (5 and 10 years of experience) and two neuroradiologists (3 years and 6 years of experience). In centre B, we conducted MR imaging with a 3.0 T MRI scanner (Biograph mMR, Siemens Healthcare, Erlangen, Germany). One neurosurgeon (14 years of experience) and one medical student assessed the volumes of the contrast-enhancing tumour through manual segmentation via iPlannet® Cranial 3.0.1 (iPlannet® 3.0 cranial planning software, Brainlab AG, Munich, Germany). The postoperative tumour volumes of patients who underwent biopsies were considered identical to the preoperative tumour volumes. Statistical Evaluation We conducted our data analysis using IBM SPSS Statistics Version 24.0 (SPSS Inc., IBM Corp., Armonk, NY, USA). In the descriptive data analysis, we show non-normally distributed data as median and interquartile range (IR), normally distributed variables as mean and standard deviation. We compared the OS distributions using the Kaplan-Meier estimates (log-rank) and a Cox regression model for multivariate survival analysis. We considered differences with an error probability of less than 0.05 to be statistically significant. Results Patients and Clinical Data 123/968 patients (58 females/65 males) with a mean age of 67.4 ± 13.4 years; (range 21–90 years) met our inclusion criteria: surgical treatment for glioblastoma, preoperative KPSS of ≤ 60%, preoperative and early postoperative MRI, complete medical documentations with date of initial tumour diagnosis, date of death/last contact, age, sex, adjuvant treatment and histopathological findings (Table 1). The median preoperative tumour volume of all patients was 33.0 ± 31.3 cm (IR 15.0–56.5 cm 3) and the median postoperative tumor volume was 3.1 ± 23.8 cm 3 (IR 0.2–15.0 cm 3 ) postoperatively. Complete resection of contrast-enhancing tumours on postoperative MRI was achieved in 24 (19.5%) of all patients. MGMT-methylation status was available in 80 patients (65%), of whom 26 (32.5%) presented with a methylated MGMT-promotor status. Surgical resection with intent for maximum/complete resection was performed in 75/123 patients (61%) (34/75 females and 41/75 males; mean age 64.4 ± 13.7 years (21–87 years). The median tumour volume was 35.2 ± 31.3 cm 3 (IR 19.7–65.3 cm 3 ) preoperatively and 0.5 ± 2.8 cm 3 (IR 0–2.3 cm 3 ) postoperatively. Complete resection of the contrast-enhancing tumour on postoperative MR imaging was seen in 24/75 patients (32%). In this group, we assessed MGMT-methylation status in 52/75 patients (69.3%). We observed methylation of MGMT in 19/52 patients (36.5%) and no methylation of MGMT in 33/52 patients (63.5%). Fifty-eight of 75 (77.3%) patients underwent postoperative adjuvant treatment; three of 58 patients (5.1%) underwent monotherapy with temozolomide, 27/58 (46.6%) received radiation therapy only and 28/58 (48.3%) received a combined therapy according to the Stupp regime. The remaining 48 patients (38.7%) (23/48 females, 25/48 males) with a mean age of 72.1 ± 11.6 years (34–90 years) underwent biopsy for tumour histopathological diagnosis. The median tumour volume in these patients was 26.3 ± 30.9 cm 3 (IR 8.1–51.7 cm 3 ). MGMT-methylation status was available in 28 patients (58.3%) with 21/28 (75%) unmethylated MGMT promotor status. After confirming histopathological diagnosis of glioblastoma via biopsy, 8/48 (16.7%) received combined radio-/chemotherapy, 3/48 (6.3%) received chemotherapy with temozolomide only, 21/48 (43.7%) received radiotherapy alone and 16/48 (33.3%) did not receive any adjuvant therapy. Karnofsky Performance Status Scale (KPSS) The median KPSS of the entire patient cohort was 60% (20–60%) preoperatively and 50% (0–80%) postoperatively. Seventeen patients (22.67%) who had undergone surgical tumour resection had an improved KPSS at time of discharge from the hospital, 25 patients (33.3%) remained unchanged and 33 patients (44.0%) worsened. There was no difference in the median KPSS between patients receiving surgical resection compared to patients receiving biopsy only. In the biopsied group, we recorded a median preoperative KPSS of 60% (range 40–60%) and median postoperative KPSS of 50% (range 0–70%). Patients who were treated by surgical resection showed a median preoperative KPSS of 60% (range 20–60%) and 50% (range 0–80%) postoperatively. Overall Survival (OS) Median OS was 123 days (IR 52–395 days). At the time of the study, 102/123 patients (82.9%) had died, and 21/123 (17.1%) were still alive or censored for their last date of contact. In-hospital mortality was seen in 3/123 (2.4%). Two of these patients received biopsy and one surgical tumour resection. Patients who received a biopsy showed a median OS of 90 days (IR 41.5–173.8 days), whereas patients who underwent surgical resection showed a median OS of 193 days (IR 80–475 days). Univariate Model Surgical resection compared against biopsy (p < 0.001) and complete resection of contrast enhancement (p = 0.03) showed a significant impact on OS in the univariate analysis using Kaplan-Meier estimates (Figs. 2–5). Multivariate Model Cox regression, including all treated patients, showed age at the time of surgery (p < 0.001, HR: 1.045 [95% CI 1.022–1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002–1.029]) and methylation status (p = 0.016 HR: 0.473 [95% CI 0.257–0.871]) as statistical significant predictors of OS. Preoperative tumour volume (p = 0.996, HR: 1.000 [95% CI 0.992–1.009]), preoperative KPSS (p = 0.068 HR: 1.023 [95% CI 0.998–1.049]) and postoperative KPSS (p = 0.237 HR: 0.987 [95% CI 0.965–1.009]) were not significant in the multivariate analysis. Discussion In this cohort of GBM patients with a preoperative KPS ≤ 60%, postoperative tumour volume, age at the time of surgery and MGMT-methylation status were significant predictors of OS in the multivariate analysis. In contrast, preoperative tumour volume and KPSS had no significant impact on OS. Nevertheless, as already understood from other studies, we could also show that extent of resection is an important factor in OS in patients with glioblastoma[ 16 , 10 , 3 , 2 ]. In general, patients with poor preoperative KPSS usually do not receive aggressive surgical therapy. Therefore, data on these patients are very limited. In our cohort, 56/123 (45.5%) showed an improved or unchanged postoperative KPSS with a median of 50%. Adjuvant treatment such as radiation therapy or chemotherapy is usually only offered to patients with a KPSS ≥ 70%[ 20 , 12 ]. Consequently, these patients are usually considered ineligible for adjuvant oncological treatment even after tumour resection. Malakhov et al. could show that 51.2% of the patients presenting with KPSS < 60 and receiving chemoradiation had improved survival compared to RT alone[ 18 ]. However, the majority of our patient cohort (77.6%) who underwent surgical resection received adjuvant therapy. Considering the early postoperative assessment of KPSS in this study, secondary improvement is to be expected. Patients undergoing a biopsy were older and had smaller preoperative tumour volumes than patients, who were selected for surgical tumour resection. Only 16.7% of the patients who received a biopsy underwent adjuvant treatment regimes. Reduced preoperative KPSS is an important prognostic factor in patients with glioblastoma[ 21 , 23 ]. Age, comorbidities and neurological deficits have an impact on KPSS and, in conclusion, on OS[ 1 , 5 , 23 ]. Postoperative deterioration of the performance status scale is usually multifactorial, with the reasons being edema, haemorrhage, postoperative delirium, ischemic events or direct surgical lesions of eloquent brain structures[ 8 ]. In our opinion, the KPSS does not offer sufficient information about quality of life and therefore should not be overrated concerning the selection of patients undergoing surgery. For example, patients with preoperative neurological deficits such as hemiparesis due to surrounding edema might have a KPSS of 60% or below and might therefore not be selected for surgical therapy. However, as we know today, the surrounding edema will disappear a few days after surgery, and the patients are able to recover for adjuvant treatment. The KPSS should therefore be considered with care. The decision for or against aggressive surgical therapy should be made individually by experienced neurosurgeons within the framework of an interdisciplinary neuro-oncology board. Limitations of the Study This study has limitations. First, the retrospective non-randomized design is the main limitation. Second, molecular status was not available for all patients in our cohort study, as the MGMT-methylation status of patients with glioblastoma is known to be one of the strongest predictors concerning survival prognosis[ 7 , 11 ]. Conclusion Even glioblastoma patients with a poor preoperative KPSS seem to profit from low postoperative residual tumour volumes. Age at the time of surgery and MGMT-methylation status had a significant influence on OS in our series. We therefore suggest considering surgical resection even in patients with a KPSS of ≤ 60% after careful selection based on an interdisciplinary neuro-oncological board decision and counselling of patients and their relatives. Declarations Author contributions: Conceptualization: Jens Gempt, Melanie Barz, Julia Gerhardt, Marco Scardelly Methodology: Melanie Barz, Stefanie Bette Formal analysis and investigation: Melanie Barz, Julia Gerhardt, A. Kaywan Aftahy, Felix Behling, Irina Gepfner-Tuma Writing- original draft preparation: Melanie Barz, Julia Gerhardt Writing- review and editing: Insa Janssen, Yu-Mi Ryang, Jens Gempt, Bernhard Meyer, Friederike Schmidt-Graf, Benedikt Wiestler, Thomas Huber Funding acquisition: no funding Resources: no other resources Supervision: Bernhard Meyer, Jens Gempt, Stephanie E. Combs ETHICAL STATEMENT Funding There was no funding Conflict of Interest JG, BM and SB work as consultants for Brainlab (Brainlab AG, Feldkirchen). YMR receives financial research grants from BrainLAB, Carl Zeiss Medical, DepuySynthes, Icotec, Medtronic, Silony, Spineart and Ulrich Medical. Furthermore, YMR works as a consultant for BrainLAB and Icotec. TH worked as a medical consultant for Brainlab AG (Munich, Germany) until 2016 and is head of scientific collaborations at Smart Reporting GmbH (Munich, Germany)—all unrelated to the present study. In addition, BM works as a consultant for Medtronic, Spineart, Icotec, Relievant and Depuy/Synthes. In these firms, BM acts as a member of the advisory board. Furthermore, BM reports a financial relationship with Medtronic, Ulrich Medical, Brainlab, Spineart, Icotec, Relievant and Depuy/Synthes. He received personal fees and research grants for clinical studies from Medtronic, Ulrich Medical, Brainlab, Icotec and Relievant. All this occurred independently of the submitted work. BM holds the royalties/patent for Spineart. All named potential conflicts of interest are unrelated to this study. Ethical Approval This retrospective, non-interventional bicentric study was approved by the local medical ethics committee (5625-12) and is in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments[9]. Informed Consent All patients sign a generally valid declaration of consent for participation in retrospective studies upon admission. References Arvold ND, Reardon DA. Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging. 2014;9:357–67. doi: 10.2147/CIA.S44259 . Bette S, Barz M, Wiestler B, Huber T, Gerhardt J, Buchmann N, Combs SE, Schmidt-Graf F, Delbridge C, Zimmer C, Kirschke JS, Meyer B, Ryang YM, Ringel F, Gempt J. Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection. Ann Surg Oncol. 2018;25:558–64. doi: 10.1245/s10434-017-6253-0 . 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Tables Table 1: Baseline tumour and patient characteristics; normally distributed variables shown as mean ± standard deviation, non-normally distributed as median (interquartile range); KPSS (Karnofsky Performance Status Scale) Demographic data Age 67.4 ± 13.4 years, range 21-90 years Female 58/123 (47.2%) Male 65/123 (52.85%) Surgical data & tumor burden Biopsy 48/123 (39%) - Median preoperative tumor volume 26.3 ± 30.9 cm 3 (IR 8.1-51.7 cm 3 ) - Median postoperative tumor volume 26.3 ± 30.9 cm 3 (IR 8.1-51.7 cm 3 ) Resection 75/123 (61%) - Median preoperative tumor volume 35.2 ± 31.3 cm 3 (IR 19.7-65.3 cm 3 ) - Median postoperative tumor volume 0.5 ± 2.8cm 3 (IR 0-2.3 cm 3 ) Karnofsky Performance Status Scale Median preoperative KPSS 60% (20-60%) Median postoperative KPSS 50% (0-80%) Overall survival Median overall survival 123 ± 219.9 days (IR 52-395 days) Median overall survival after biopsy 90 ± 141 days (IR 41.5-173.8 days) Median overall survival after surgery 193 ± 340.2 days (IR 80-475 days) MGMT-methylation status MGMT- methylation status available 81/123 (65.9%) MGMT-methylated 26/81 (32.1%) MGMT-unmethylated 55/81 (67.9%) Cite Share Download PDF Status: Under Revision Version 1 posted Review # 1 received at journal 23 Dec, 2020 Editorial decision: Major revision 23 Dec, 2020 Review # 2 received at journal 22 Dec, 2020 Reviewer # 2 agreed at journal 03 Dec, 2020 Reviewers invited by journal 30 Nov, 2020 Reviewer # 1 agreed at journal 30 Nov, 2020 Editor invited by journal 18 Nov, 2020 Editor assigned by journal 02 Nov, 2020 Submission checks completed at journal 02 Nov, 2020 First submitted to journal 31 Oct, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-113874\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research article\",\"associatedPublications\":[],\"authors\":[{\"id\":5150782,\"identity\":\"bdecf750-f42f-4327-bcbc-becfe12ce297\",\"order_by\":0,\"name\":\"Melanie Barz\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYFAC5gYGBgMwYmD4ABZJIKSFEaGFcUYC0VoYIFqYeYjRotve2Pi5oMCGwZz97OPPtj8ORzOwJx/Aq8XszMFm6RkGaQyWPekGxjkJh3MbeJ7ht8bsRmKDNI/BYQaDA2kMyWAtEjkG+LXcf9j8m8fgP4PB+WcMhy3AWvI/ELCFsQ1oywEGgxtpjM0MEFvw6gD6JbHNmscgmcdyxjNmxp609Nw2nmcEHHb88OHbPH/s5Mz505g//LCxzu1nT36A3xoo4IGz2IhSPwpGwSgYBaMALwAAf89FV2gg3q4AAAAASUVORK5CYII=\",\"orcid\":\"https://orcid.org/0000-0001-8734-9309\",\"institution\":\"Klinikum rechts der Isar der Technischen Universitat Munchen Neuro-Kopf-Zentrum\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Melanie\",\"middleName\":\"\",\"lastName\":\"Barz\",\"suffix\":\"\"},{\"id\":5150783,\"identity\":\"58d52df7-4ddc-4e09-bf1d-0da99440db35\",\"order_by\":1,\"name\":\"Julia Gerhardt\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Helios Klinikum Berlin, Department of Neurosurgery\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Julia\",\"middleName\":\"\",\"lastName\":\"Gerhardt\",\"suffix\":\"\"},{\"id\":5150784,\"identity\":\"b45af5c9-98f1-4d13-abb6-791e226ac6a0\",\"order_by\":2,\"name\":\"Stefanie Bette\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universitätsklinikum Augsburg, Department of neuroradiology\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Stefanie\",\"middleName\":\"\",\"lastName\":\"Bette\",\"suffix\":\"\"},{\"id\":5150785,\"identity\":\"75bfb005-5195-4e81-bb08-843ee9dd1a1f\",\"order_by\":3,\"name\":\"A. Kaywan Aftahy\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München, Department of neurosurgery\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"A.\",\"middleName\":\"Kaywan\",\"lastName\":\"Aftahy\",\"suffix\":\"\"},{\"id\":5150786,\"identity\":\"e9b0cbf3-2b10-4de3-8dc4-3803890ea702\",\"order_by\":4,\"name\":\"Thomas Huber\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universitätsklinikum Mannheim: Universitatsklinikum Mannheim\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Thomas\",\"middleName\":\"\",\"lastName\":\"Huber\",\"suffix\":\"\"},{\"id\":5150787,\"identity\":\"bf88b472-6dd0-4ab3-b0fc-d54a0119b66e\",\"order_by\":5,\"name\":\"Stephanie E. Combs\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Stephanie\",\"middleName\":\"E.\",\"lastName\":\"Combs\",\"suffix\":\"\"},{\"id\":5150788,\"identity\":\"4d0e21b8-30d1-40da-a04a-cc81c81a4ddd\",\"order_by\":6,\"name\":\"Yu-Mi Ryang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"HELIOS Klinikum Berlin-Buch\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu-Mi\",\"middleName\":\"\",\"lastName\":\"Ryang\",\"suffix\":\"\"},{\"id\":5150789,\"identity\":\"0a6a7834-b957-4ff6-adae-ffa2f2906771\",\"order_by\":7,\"name\":\"Benedikt Wiestler\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Benedikt\",\"middleName\":\"\",\"lastName\":\"Wiestler\",\"suffix\":\"\"},{\"id\":5150790,\"identity\":\"3b4d2101-3d07-44a8-a838-dfd3ba4c60a1\",\"order_by\":8,\"name\":\"Marco Skardelly\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Universitätsklinikum Tübingen: Universitatsklinikum Tubingen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Marco\",\"middleName\":\"\",\"lastName\":\"Skardelly\",\"suffix\":\"\"},{\"id\":5150791,\"identity\":\"e6383de6-942c-46a9-88e0-a481d51dbcdf\",\"order_by\":9,\"name\":\"Irina Gepfner-Tuma\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Irina\",\"middleName\":\"\",\"lastName\":\"Gepfner-Tuma\",\"suffix\":\"\"},{\"id\":5150792,\"identity\":\"5230c460-a9d7-4ae9-99ad-548d75552537\",\"order_by\":10,\"name\":\"Felix Behling\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Felix\",\"middleName\":\"\",\"lastName\":\"Behling\",\"suffix\":\"\"},{\"id\":5150793,\"identity\":\"b9c1af08-32fb-4ad9-893d-fb8fdedea202\",\"order_by\":11,\"name\":\"Friederike Schmidt-Graf\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Friederike\",\"middleName\":\"\",\"lastName\":\"Schmidt-Graf\",\"suffix\":\"\"},{\"id\":5150794,\"identity\":\"ce258508-deb6-417f-88d0-e8c86aba059f\",\"order_by\":12,\"name\":\"Bernhard Meyer\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Bernhard\",\"middleName\":\"\",\"lastName\":\"Meyer\",\"suffix\":\"\"},{\"id\":5150795,\"identity\":\"7b9593f4-554d-479b-8ca6-ad5908b8d3c9\",\"order_by\":13,\"name\":\"Jens Gempt\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Technische Universität München: Technische Universitat Munchen\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jens\",\"middleName\":\"\",\"lastName\":\"Gempt\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2020-11-22 20:39:41\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-113874/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-113874/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":3922266,\"identity\":\"3248595d-8fe2-436f-8abe-4321f8e7b87e\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:27\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":17429,\"visible\":true,\"origin\":\"\",\"legend\":\"Flowchart of patient-selection process.\",\"description\":\"\",\"filename\":\"1.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/e37ad4f4557c18d55255aac3.PNG\"},{\"id\":3922247,\"identity\":\"e2dfb755-7278-4f3b-99dc-8b4d3bb9a74b\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:20\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":17429,\"visible\":true,\"origin\":\"\",\"legend\":\"Flowchart of patient-selection process.\",\"description\":\"\",\"filename\":\"1.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/3c779055d3b4a7eb0ce58447.PNG\"},{\"id\":3922267,\"identity\":\"7102e37d-bad0-44a4-b632-9df0cc9b3fe2\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:27\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":21440,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in complete/incomplete resection\",\"description\":\"\",\"filename\":\"2.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/3ecf576fcfff4f4bf4e56fc7.PNG\"},{\"id\":3922249,\"identity\":\"e41d955c-7688-45d1-a796-823da8d27aa1\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:21\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":21440,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in complete/incomplete resection\",\"description\":\"\",\"filename\":\"2.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/4dade3cb0a96fc5c66740f31.PNG\"},{\"id\":3922268,\"identity\":\"0c5eb2fa-089b-469f-abe0-8e1e96c0b574\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:27\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":21701,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in biopsy/resection\",\"description\":\"\",\"filename\":\"3.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/10fe241f126c925fea51c5ca.PNG\"},{\"id\":3922251,\"identity\":\"a05614de-5192-4603-be78-4d816a933e1e\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:21\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":21701,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in biopsy/resection\",\"description\":\"\",\"filename\":\"3.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/d07b52b2bc1e113fd78ced17.PNG\"},{\"id\":3922269,\"identity\":\"26f59175-32aa-4a10-835e-1465d39db73a\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:27\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":22059,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in MGMT-methylated/MGMT-unmethylated\",\"description\":\"\",\"filename\":\"4.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/e47e3f3d98799a637db52598.PNG\"},{\"id\":3922252,\"identity\":\"59c5d74a-ee69-4b4d-9373-cc955d127d92\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:21\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":22059,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in MGMT-methylated/MGMT-unmethylated\",\"description\":\"\",\"filename\":\"4.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/b5afd0d7f8690f82f09c1826.PNG\"},{\"id\":3922270,\"identity\":\"f13967f7-9854-48cb-bca8-0a1538f67198\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:27\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":20098,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in STUPP regime/RTX alone: A) Complete cohort B) Resection C) Biopsy\",\"description\":\"\",\"filename\":\"5.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/2a5b06bb33637b1e94c1cc20.PNG\"},{\"id\":3922253,\"identity\":\"e4f81530-1ecb-47a2-9a2c-75e25b19d863\",\"added_by\":\"auto\",\"created_at\":\"2020-12-01 16:31:21\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":20098,\"visible\":true,\"origin\":\"\",\"legend\":\"Overall survival, categorized in STUPP regime/RTX alone: A) Complete cohort B) Resection C) Biopsy\",\"description\":\"\",\"filename\":\"5.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/b76f46d173d2422df8f6ff29.PNG\"},{\"id\":13620952,\"identity\":\"1b5f1993-bdb8-416f-84f2-b94b878b245d\",\"added_by\":\"auto\",\"created_at\":\"2021-09-17 07:08:09\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":497373,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-113874/v1/7070e9da-1184-42c3-99fb-5e49cc71440a.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"\\u003cp\\u003eDo Patients with a Poor Karnofsky Performance Status Scale Profit from Tumour Volume Reduction?\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\" \\u003cp\\u003eIn 1949, Karnofsky and Burchena described their instrument, the Karnofsky Performance Scale (KPS) score, as a numerical scale for quantifying patients\\u0026rsquo; status in relation to the degree of their independence in daily activities and self-care. Originally, it was used for patients with systemic malignancies and divided them according to their level of activity and medical requirements. Patients are scored into 11 categories from 0 to 100, where, for example, a KPSS of 70% means the patient is able to care for himself but is unable to carry out daily activities[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. After it had been proven successful in patients with systemic cancer, more and more research groups started to evaluate the KPS score for brain cancer[\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Previously published studies could show a significant correlation between the preoperative KPS score and the outcome after glioma surgery[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. In most studies, only patients suffering from a glioblastoma with a KPSS of \\u0026ge;\\u0026thinsp;70% were included[\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. For example, those studies analysed prognostic factors such as tumour size, GRT and adjuvant therapy modalities postoperatively. However, in our clinical daily work, patients with a noticeably lower KPSS are represented as well. It should be noticed that this can be due to clinic symptomology as seizures, acute mental status changes or focal neurologic deficits caused by tumour size and/or location itself. Therefore, the following study intends to show whether it is worthwhile for patients with a KPSS 60% or below to achieve tumour volume reduction.\\u003c/p\\u003e \"},{\"header\":\"Patients And Methods\",\"content\":\" \\u003cp\\u003eThis retrospective, non-interventional bicentric study was approved by the local medical ethics committee (5625-12) and is in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatient Population\\u003c/h2\\u003e \\u003cp\\u003eWe retrospectively assessed 968 patients with a histologically confirmed glioblastoma WHO IV with a preoperative Karnofsky Performance Status Scale (KPSS) of \\u0026le;\\u0026thinsp;60%, who were treated surgically between September 2006 and March 2016 in two neurosurgical departments. According to interdisciplinary neuro-oncological consensus, patients were assigned to surgery with the intent of complete resection or to biopsy to confirm the histopathological diagnosis. We retrospectively reviewed pre- and postoperative KPSS, date of initial tumour diagnosis, date of death/last contact, age, sex, adjuvant treatment and histopathological findings from the patients\\u0026rsquo; medical charts. Also, we performed histopathological analysis according to the WHO criteria of 2016[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e] and quantitatively assessed methylation of the O6-methylguanin-DNA-methyltransferase (MGMT) promoter status. We assessed KPSS with regards to hospital admission and five days after surgery. Then, we calculated the overall survival (OS) from the date of surgery until the date of death or censored for the date of the last patient contact. Only patients with complete magnetic resonance imaging data were included to calculate pre- and postoperative contrast-enhancing tumour volumes. Patients with recurrent tumour or incomplete data were excluded (Fig.\\u0026nbsp;1).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eImaging\\u003c/h2\\u003e \\u003cp\\u003eAll patients received preoperative and early postoperative MRI (within 72 hours after surgery). In centre A, we performed imaging using three different 3\\u0026nbsp;T MRI scanners: Philips Achieva; Philips Ingenia (Philips Medical Systems, The Netherlands B.V.); and Siemens Verio (Siemens Healthcare, Erlangen, Germany). Images included T1w sequences with and without contrast agent, FLAIR (Fluid attenuated inversion recovery) sequences, T2 gradient echo sequences, diffusion-weighted imaging or diffusion-tensor imaging, whereas we calculated isotropic diffusion-weighted images and apparent diffusion coefficient (ADC) maps automatically. Tumour volumes of the contrast-enhancing tumour on pre- and early postoperative MR images using iPlannet\\u0026reg; Cranial 3.0.1 were manually segmented by two neurosurgeons (5 and 10\\u0026nbsp;years of experience) and two neuroradiologists (3\\u0026nbsp;years and 6\\u0026nbsp;years of experience).\\u003c/p\\u003e \\u003cp\\u003eIn centre B, we conducted MR imaging with a 3.0\\u0026nbsp;T MRI scanner (Biograph mMR, Siemens Healthcare, Erlangen, Germany). One neurosurgeon (14\\u0026nbsp;years of experience) and one medical student assessed the volumes of the contrast-enhancing tumour through manual segmentation via iPlannet\\u0026reg; Cranial 3.0.1 (iPlannet\\u0026reg; 3.0 cranial planning software, Brainlab AG, Munich, Germany). The postoperative tumour volumes of patients who underwent biopsies were considered identical to the preoperative tumour volumes.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Evaluation\\u003c/h2\\u003e \\u003cp\\u003eWe conducted our data analysis using IBM SPSS Statistics Version 24.0 (SPSS Inc., IBM Corp., Armonk, NY, USA). In the descriptive data analysis, we show non-normally distributed data as median and interquartile range (IR), normally distributed variables as mean and standard deviation.\\u003c/p\\u003e \\u003cp\\u003eWe compared the OS distributions using the Kaplan-Meier estimates (log-rank) and a Cox regression model for multivariate survival analysis. We considered differences with an error probability of less than 0.05 to be statistically significant.\\u003c/p\\u003e \\u003c/div\\u003e \"},{\"header\":\"Results\",\"content\":\" \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatients and Clinical Data\\u003c/h2\\u003e \\u003cp\\u003e123/968 patients (58 females/65 males) with a mean age of 67.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.4 years; (range 21\\u0026ndash;90\\u0026nbsp;years) met our inclusion criteria: surgical treatment for glioblastoma, preoperative KPSS of \\u0026le;\\u0026thinsp;60%, preoperative and early postoperative MRI, complete medical documentations with date of initial tumour diagnosis, date of death/last contact, age, sex, adjuvant treatment and histopathological findings (Table\\u0026nbsp;1). The median preoperative tumour volume of all patients was 33.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;31.3\\u0026nbsp;cm (IR 15.0\\u0026ndash;56.5\\u0026nbsp;cm\\u003csup\\u003e3)\\u003c/sup\\u003e and the median postoperative tumor volume was 3.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.8\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 0.2\\u0026ndash;15.0\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e) postoperatively. Complete resection of contrast-enhancing tumours on postoperative MRI was achieved in 24 (19.5%) of all patients. MGMT-methylation status was available in 80 patients (65%), of whom 26 (32.5%) presented with a methylated MGMT-promotor status.\\u003c/p\\u003e \\u003cp\\u003eSurgical resection with intent for maximum/complete resection was performed in 75/123 patients (61%) (34/75 females and 41/75 males; mean age 64.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.7\\u0026nbsp;years (21\\u0026ndash;87\\u0026nbsp;years). The median tumour volume was 35.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;31.3\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 19.7\\u0026ndash;65.3\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e) preoperatively and 0.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.8\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 0\\u0026ndash;2.3\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e) postoperatively. Complete resection of the contrast-enhancing tumour on postoperative MR imaging was seen in 24/75 patients (32%). In this group, we assessed MGMT-methylation status in 52/75 patients (69.3%). We observed methylation of MGMT in 19/52 patients (36.5%) and no methylation of MGMT in 33/52 patients (63.5%).\\u003c/p\\u003e \\u003cp\\u003eFifty-eight of 75 (77.3%) patients underwent postoperative adjuvant treatment; three of 58 patients (5.1%) underwent monotherapy with temozolomide, 27/58 (46.6%) received radiation therapy only and 28/58 (48.3%) received a combined therapy according to the Stupp regime. The remaining 48 patients (38.7%) (23/48 females, 25/48 males) with a mean age of 72.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;11.6\\u0026nbsp;years (34\\u0026ndash;90\\u0026nbsp;years) underwent biopsy for tumour histopathological diagnosis. The median tumour volume in these patients was 26.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;30.9\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 8.1\\u0026ndash;51.7\\u0026nbsp;cm\\u003csup\\u003e3\\u003c/sup\\u003e). MGMT-methylation status was available in 28 patients (58.3%) with 21/28 (75%) unmethylated MGMT promotor status. After confirming histopathological diagnosis of glioblastoma via biopsy, 8/48 (16.7%) received combined radio-/chemotherapy, 3/48 (6.3%) received chemotherapy with temozolomide only, 21/48 (43.7%) received radiotherapy alone and 16/48 (33.3%) did not receive any adjuvant therapy.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eKarnofsky Performance Status Scale (KPSS)\\u003c/h2\\u003e \\u003cp\\u003eThe median KPSS of the entire patient cohort was 60% (20\\u0026ndash;60%) preoperatively and 50% (0\\u0026ndash;80%) postoperatively. Seventeen patients (22.67%) who had undergone surgical tumour resection had an improved KPSS at time of discharge from the hospital, 25 patients (33.3%) remained unchanged and 33 patients (44.0%) worsened. There was no difference in the median KPSS between patients receiving surgical resection compared to patients receiving biopsy only. In the biopsied group, we recorded a median preoperative KPSS of 60% (range 40\\u0026ndash;60%) and median postoperative KPSS of 50% (range 0\\u0026ndash;70%). Patients who were treated by surgical resection showed a median preoperative KPSS of 60% (range 20\\u0026ndash;60%) and 50% (range 0\\u0026ndash;80%) postoperatively.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eOverall Survival (OS)\\u003c/h2\\u003e \\u003cp\\u003eMedian OS was 123 days (IR 52\\u0026ndash;395 days). At the time of the study, 102/123 patients (82.9%) had died, and 21/123 (17.1%) were still alive or censored for their last date of contact. In-hospital mortality was seen in 3/123 (2.4%). Two of these patients received biopsy and one surgical tumour resection. Patients who received a biopsy showed a median OS of 90 days (IR 41.5\\u0026ndash;173.8 days), whereas patients who underwent surgical resection showed a median OS of 193 days (IR 80\\u0026ndash;475 days).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eUnivariate Model\\u003c/h2\\u003e \\u003cp\\u003eSurgical resection compared against biopsy (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001) and complete resection of contrast enhancement (p\\u0026thinsp;=\\u0026thinsp;0.03) showed a significant impact on OS in the univariate analysis using Kaplan-Meier estimates (Figs.\\u0026nbsp;2\\u0026ndash;5).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eMultivariate Model\\u003c/h2\\u003e \\u003cp\\u003eCox regression, including all treated patients, showed age at the time of surgery (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001, HR: 1.045 [95% CI 1.022\\u0026ndash;1.068]), postoperative tumour volume (p\\u0026thinsp;=\\u0026thinsp;0.02, HR: 1.016 [95% CI 1.002\\u0026ndash;1.029]) and methylation status (p\\u0026thinsp;=\\u0026thinsp;0.016 HR: 0.473 [95% CI 0.257\\u0026ndash;0.871]) as statistical significant predictors of OS. Preoperative tumour volume (p\\u0026thinsp;=\\u0026thinsp;0.996, HR: 1.000 [95% CI 0.992\\u0026ndash;1.009]), preoperative KPSS (p\\u0026thinsp;=\\u0026thinsp;0.068 HR: 1.023 [95% CI 0.998\\u0026ndash;1.049]) and postoperative KPSS (p\\u0026thinsp;=\\u0026thinsp;0.237 HR: 0.987 [95% CI 0.965\\u0026ndash;1.009]) were not significant in the multivariate analysis.\\u003c/p\\u003e \\u003c/div\\u003e \"},{\"header\":\"Discussion\",\"content\":\" \\u003cp\\u003eIn this cohort of GBM patients with a preoperative KPS\\u0026thinsp;\\u0026le;\\u0026thinsp;60%, postoperative tumour volume, age at the time of surgery and MGMT-methylation status were significant predictors of OS in the multivariate analysis. In contrast, preoperative tumour volume and KPSS had no significant impact on OS. Nevertheless, as already understood from other studies, we could also show that extent of resection is an important factor in OS in patients with glioblastoma[\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn general, patients with poor preoperative KPSS usually do not receive aggressive surgical therapy. Therefore, data on these patients are very limited. In our cohort, 56/123 (45.5%) showed an improved or unchanged postoperative KPSS with a median of 50%. Adjuvant treatment such as radiation therapy or chemotherapy is usually only offered to patients with a KPSS\\u0026thinsp;\\u0026ge;\\u0026thinsp;70%[\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Consequently, these patients are usually considered ineligible for adjuvant oncological treatment even after tumour resection. Malakhov et al. could show that 51.2% of the patients presenting with KPSS\\u0026thinsp;\\u0026lt;\\u0026thinsp;60 and receiving chemoradiation had improved survival compared to RT alone[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. However, the majority of our patient cohort (77.6%) who underwent surgical resection received adjuvant therapy. Considering the early postoperative assessment of KPSS in this study, secondary improvement is to be expected. Patients undergoing a biopsy were older and had smaller preoperative tumour volumes than patients, who were selected for surgical tumour resection. Only 16.7% of the patients who received a biopsy underwent adjuvant treatment regimes.\\u003c/p\\u003e \\u003cp\\u003eReduced preoperative KPSS is an important prognostic factor in patients with glioblastoma[\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Age, comorbidities and neurological deficits have an impact on KPSS and, in conclusion, on OS[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Postoperative deterioration of the performance status scale is usually multifactorial, with the reasons being edema, haemorrhage, postoperative delirium, ischemic events or direct surgical lesions of eloquent brain structures[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn our opinion, the KPSS does not offer sufficient information about quality of life and therefore should not be overrated concerning the selection of patients undergoing surgery. For example, patients with preoperative neurological deficits such as hemiparesis due to surrounding edema might have a KPSS of 60% or below and might therefore not be selected for surgical therapy. However, as we know today, the surrounding edema will disappear a few days after surgery, and the patients are able to recover for adjuvant treatment. The KPSS should therefore be considered with care.\\u003c/p\\u003e \\u003cp\\u003eThe decision for or against aggressive surgical therapy should be made individually by experienced neurosurgeons within the framework of an interdisciplinary neuro-oncology board.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLimitations of the Study\\u003c/h2\\u003e \\u003cp\\u003eThis study has limitations. First, the retrospective non-randomized design is the main limitation. Second, molecular status was not available for all patients in our cohort study, as the MGMT-methylation status of patients with glioblastoma is known to be one of the strongest predictors concerning survival prognosis[\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e].\\u003c/p\\u003e \\u003c/div\\u003e \"},{\"header\":\"Conclusion\",\"content\":\" \\u003cp\\u003eEven glioblastoma patients with a poor preoperative KPSS seem to profit from low postoperative residual tumour volumes. Age at the time of surgery and MGMT-methylation status had a significant influence on OS in our series. We therefore suggest considering surgical resection even in patients with a KPSS of \\u0026le;\\u0026thinsp;60% after careful selection based on an interdisciplinary neuro-oncological board decision and counselling of patients and their relatives.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eConceptualization: Jens Gempt, Melanie Barz, Julia Gerhardt, Marco Scardelly\\u003c/p\\u003e\\n\\u003cp\\u003eMethodology: Melanie Barz, Stefanie Bette\\u003c/p\\u003e\\n\\u003cp\\u003eFormal analysis and investigation: Melanie Barz, Julia Gerhardt, A. Kaywan Aftahy, Felix Behling, Irina Gepfner-Tuma\\u003c/p\\u003e\\n\\u003cp\\u003eWriting- original draft preparation: Melanie Barz, Julia Gerhardt\\u003c/p\\u003e\\n\\u003cp\\u003eWriting- review and editing: Insa Janssen, Yu-Mi Ryang, Jens Gempt, Bernhard Meyer, Friederike Schmidt-Graf, Benedikt Wiestler, Thomas Huber\\u003c/p\\u003e\\n\\u003cp\\u003eFunding acquisition: no funding\\u003c/p\\u003e\\n\\u003cp\\u003eResources: no other resources\\u003c/p\\u003e\\n\\u003cp\\u003eSupervision: Bernhard Meyer, Jens Gempt, Stephanie E. Combs\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eETHICAL STATEMENT\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eFunding\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThere was no funding\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eConflict of Interest\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eJG, BM and SB work as consultants for Brainlab (Brainlab AG, Feldkirchen).\\u003c/p\\u003e\\n\\u003cp\\u003eYMR receives financial research grants from BrainLAB, Carl Zeiss Medical, DepuySynthes, Icotec, Medtronic, Silony, Spineart and Ulrich Medical. Furthermore, YMR works as a consultant for BrainLAB and Icotec.\\u003c/p\\u003e\\n\\u003cp\\u003eTH worked as a medical consultant for Brainlab AG (Munich, Germany) until 2016 and is head of scientific collaborations at Smart Reporting GmbH (Munich, Germany)\\u0026mdash;all unrelated to the present study.\\u003c/p\\u003e\\n\\u003cp\\u003eIn addition, BM works as a consultant for Medtronic, Spineart, Icotec, Relievant and Depuy/Synthes. In these firms, BM acts as a member of the advisory board. Furthermore, BM reports a financial relationship with Medtronic, Ulrich Medical, Brainlab, Spineart, Icotec, Relievant and Depuy/Synthes. He received personal fees and research grants for clinical studies from Medtronic, Ulrich Medical, Brainlab, Icotec and Relievant. All this occurred independently of the submitted work. BM holds the royalties/patent for Spineart.\\u003c/p\\u003e\\n\\u003cp\\u003eAll named potential conflicts of interest are unrelated to this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eEthical Approval\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis retrospective, non-interventional bicentric study was approved by the local medical ethics committee (5625-12) and is in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments[9].\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eInformed Consent\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll patients sign a generally valid declaration of consent for participation in retrospective studies upon admission.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eArvold ND, Reardon DA. Treatment options and outcomes for glioblastoma in the elderly patient. 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CNS Oncol. 2017;6:19\\u0026ndash;28. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.2217/cns-2016-0023\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSacko A, Hou MM, Temgoua M, Alkhafaji A, Marantidou A, Belin C, Mandonnet E, Ursu R, Doridam J, Coman I, Levy-Piedbois C, Carpentier AF. Evolution of the Karnosky Performance Status throughout life in glioblastoma patients. J Neurooncol. 2015;122:567\\u0026ndash;73. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s11060-015-1749-6\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011;115:3\\u0026ndash;8. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3171/2011.2.JNS10998\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStark AM, Stepper W, Mehdorn HM. Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC. Eur J Cancer Care (Engl). 2010;19:39\\u0026ndash;44. doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1111/j.1365-2354.2008.00956.x\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStark AMSW, Mehdorn HM. Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC. Eur J Cancer Care (Engl). 2010;1:39\\u0026ndash;44.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eTable 1:\\u003c/strong\\u003e Baseline tumour and patient characteristics; normally distributed variables shown as mean \\u0026plusmn; standard deviation, non-normally distributed as median (interquartile range); KPSS (Karnofsky Performance Status Scale)\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\"\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDemographic data\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eAge\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e67.4 \\u0026plusmn; 13.4 years, range 21-90 years\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eFemale\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e58/123 (47.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMale\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e65/123 (52.85%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eSurgical data \\u0026amp; tumor burden\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eBiopsy\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e48/123 (39%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e-\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp; Median preoperative tumor volume\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e26.3 \\u0026plusmn; 30.9 cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 8.1-51.7 cm\\u003csup\\u003e3\\u003c/sup\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e-\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp; Median postoperative tumor volume\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e26.3 \\u0026plusmn; 30.9 cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 8.1-51.7 cm\\u003csup\\u003e3\\u003c/sup\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eResection\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e75/123 (61%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e-\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp; Median preoperative tumor volume\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e35.2 \\u0026plusmn; 31.3 cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 19.7-65.3 cm\\u003csup\\u003e3\\u003c/sup\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e-\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp; Median postoperative tumor volume\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e0.5 \\u0026plusmn; 2.8cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 0-2.3 cm\\u003csup\\u003e3\\u003c/sup\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eKarnofsky Performance Status Scale\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMedian preoperative KPSS\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e60% (20-60%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMedian postoperative KPSS\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e50% (0-80%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eOverall survival\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMedian overall survival\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e123 \\u0026plusmn; 219.9 days (IR 52-395 days)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMedian overall survival after biopsy\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e90 \\u0026plusmn; 141 days (IR 41.5-173.8 days)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMedian overall survival after surgery\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e193 \\u0026plusmn; 340.2 days (IR 80-475 days)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eMGMT-methylation status\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMGMT- methylation status available\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e81/123 (65.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMGMT-methylated\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e26/81 (32.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd width=\\\"274\\\"\\u003e\\n\\u003cp\\u003eMGMT-unmethylated\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd width=\\\"330\\\"\\u003e\\n\\u003cp\\u003e55/81 (67.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-neurology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"nurl\",\"sideBox\":\"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/nurl\",\"title\":\"BMC Neurology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Karnofsky Performance Status Scale, Glioblastoma, Surgery, EOR\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-113874/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-113874/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePurpose:\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cem\\u003e \\u003c/em\\u003eMedian overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤ 60%.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eMethods\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cem\\u003e: \\u003c/em\\u003eWe retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤ 60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eResults\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cem\\u003e: \\u003c/em\\u003e123 patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. 75 of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 15.0–56.5cm\\u003csup\\u003e3\\u003c/sup\\u003e) and 3.1 ± 23.8 cm\\u003csup\\u003e3\\u003c/sup\\u003e (IR 0.2–15.0 cm\\u003csup\\u003e3\\u003c/sup\\u003e), respectively. The median KPSS was 60% (range 20–60%) preoperatively and 50% (range 0–80%) postoperatively. The median OS was 123 ± 220 days (IR 52–395 days). \\u003c/p\\u003e\\u003cp\\u003eAge (p\\u0026lt;0.001, HR: 1.045 [95% CI 1.022–1.068]), postoperative tumour volume (p=0.02, HR: 1.016 [95% CI 1.002–1.029]) and MGMT promotor status (p=0.016, HR: 0.473 [95% CI 0.257–0.871]) were statistically significant in multivariate analysis.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConclusion:\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cem\\u003e \\u003c/em\\u003ePatients with a preoperative KPSS of ≤ 60% benefit from low postoperative residual tumour volumes. Age and MGMT-methylation status were also significant prognostic parameters in this patient cohort.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Do Patients with a Poor Karnofsky Performance Status Scale Profit from Tumour Volume Reduction?\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2020-12-01 16:31:19\",\"doi\":\"10.21203/rs.3.rs-113874/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2020-12-24T00:00:00+00:00\",\"index\":1,\"fulltext\":\"Recommendation: Major revisions required\\nForm responses:\\n---\\n\\nComments to Author:\\n---\\nThis study reports survival outcomes of 123 patients with newly-diagnosed gliobastoma and pre-operative KPS \\u003c= 60. Few studies report on the impact of pre-operative KPS, as pre-chemo/RT KPS is more frequently used to determine treatment decisions. This study is analogous to a prior report by Uzaka (pmid 22976140), however the current study is multi-center, includes more patients, and does not mix patients with low KPS and the elderly.\\n1) Post-operative KPS is measured at 5 days after surgery. The postoperative KPS 4 weeks after surgery or immediately before adjuvant therapy would be more clinically informative.\\n2) It is unclear if the analysis of patients based on postoperative tumor volume includes patients who underwent biopsy alone. These patients should likely be excluded.\\n3) The study above by Uzaka et al. should be referenced.\\n4) If any quality of life metrics are available, these data would be useful in understanding the utility of aggressive resection* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\\n* Declaration of competing interests: **I declare that I have no competing interests**\\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\\n* Is the presentation of the work clear?: **Yes**\\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\\n\"},{\"type\":\"decision\",\"content\":\"Major revision\",\"date\":\"2020-12-24T00:00:00+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2020-12-23T00:00:00+00:00\",\"index\":2,\"fulltext\":\"Recommendation: Major revisions required\\nForm responses:\\n---\\n\\nComments to Author:\\n---\\nThe authors present a retrospective series of 123 patients who underwent biopsy versus resection of WHO Grade IV gliomas who had poor pre-operative KPS (scores 60 or less). The authors suggest that lower post-operative tumors volumes, younger age and MGMT promoter methylation status are associated with improved outcomes for these patients. \\nAs the authors point out in their discussion, pre-operative performance status in the setting of a large tumor causing significant mass effect, peritumoral edema can be improved by surgical resection in carefully selected patients and should not be an a priori contraindication to surgery and potentially adjuvant post-operative treatment. \\nWhile I think this is an interesting study, I do not feel that the current manuscript is publishable in the current format and major revisions should be considered. \\n\\n(1) The title of the work and the main point that the authors seem to investigate is whether cytoreductive surgery for patients with poor performance status and a GBM positively impacts survival. The authors compare biopsy versus surgical resection on KM analysis and show a survival advantage but then seem to combine patients undergoing biopsy/surgery in their multivariate analysis. It thus no surprise that patients with decreased post-operative tumor volumes did better on multivariate analysis. There is clearly a difference between the biopsy and surgical cohorts here that has not been adequately described/compared. Why did only 16.7% of patients in the biopsy arm receive STUPP regimen compared to 48.3% in the surgical cohort (when there seemed to be no apparent difference in pre-operative KPS and post-operative KPS?) Were there differences in age, medical comorbidities, leptomeningeal spread of these patients? Did the KPS improve further in the surgical cohort over time compared to the biopsy cohort? Were the tumor locations similar between the two cohorts? \\n(2) It seems inappropriate to look at tumor volume on multivariate analysis for all patients (biopsy and resection combined). The real question the authors should be comparing here is whether or not surgical resection remains superior to biopsy when all other factors are adjusted for. Looking at tumor volumes on multivariate analysis makes sense if only those receiving surgery are analyzed. \\n(3) The authors measure performance status prior to surgery and 5 days post-operatively. The performance status 5 days after surgery seems to early to inform the ability for patients to receive post-operative adjuvant therapy. It would be helpful to understand that the 30 day post-operative performance status is. \\n(4) The authors give descriptive data on individuals receiving post-operative adjuvant therapy. It 77% of patients in the surgical arm underwent some form of adjuvant therapy. Data should be given on how many patients completed the intended adjuvant therapy. \\n(5) The authors list that the overall survival is 90 days for those receiving a biopsy and 193 days for those undergoing surgical resection (page 5 lines 164-166). Figure 3 shows the KM curves for patients receiving surgery versus biopsy. The median survival for the surgery cohort seems to be closer to 300-400 days and the median survival in the biopsy arm seems more than 90 days. Are the data listed on page 5 the median survival from the KM curves? If so, the scales appear to be inaccurate. \\n(6) In general the authors do not adequately cite figures 2-5 in the manuscript. There is no legend for any of the figures and the number at risk is not included. It is unclear whether the authors included those undergoing biopsy or not in figure 2. \\n(7) The authors do little explanation of the findings in figure 5 in the manuscript. According to this figure, the median survival for all patients (biopsy and surgical cohorts) is over 500 days (16.7 months) for those who undergo STUPP protocol. This data seems to suggest that patients with a KPS of 60 or less (regardless of surgery vs. biopsy) have a median survival similar to patients with good performance status who complete maximal safe resection/chemotherapy/radiation. \\n(8) The authors should list median survival in months. The axes on their Kaplan Meier curves should be uniform and list months\\n(9) The baseline demographics of patients should be expanded. Hydrocephalus, presence of seizures, tumor locations etc. should be included\\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\\n* Declaration of competing interests: **'I declare that I have no competing interests**\\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. 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